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Publication numberUS20090093402 A1
Publication typeApplication
Application numberUS 11/929,702
Publication dateApr 9, 2009
Filing dateOct 30, 2007
Priority dateDec 21, 2001
Also published asCA2471363A1, CA2471363C, CA2841097A1, EP1463751A2, EP1463751A4, EP1463751B1, EP1997829A1, EP2261250A1, EP2277888A2, EP2277888A3, EP2277889A2, EP2277889A3, EP2277889B1, EP2277910A1, US7141547, US7238667, US7592010, US7799759, US7847079, US8012464, US8071539, US8211439, US8252739, US8513189, US20050186664, US20060194735, US20060276396, US20070244047, US20070259815, US20080146503, US20080153751, US20080161243, US20080167239, US20080167240, US20080213886, US20090099073, US20110009312, US20120046221, US20130150296, US20140179596, WO2003060071A2, WO2003060071A3
Publication number11929702, 929702, US 2009/0093402 A1, US 2009/093402 A1, US 20090093402 A1, US 20090093402A1, US 2009093402 A1, US 2009093402A1, US-A1-20090093402, US-A1-2009093402, US2009/0093402A1, US2009/093402A1, US20090093402 A1, US20090093402A1, US2009093402 A1, US2009093402A1
InventorsCraig A. Rosen, William A. Haseltine, David J. Ballance, Andrew J. Turner, Steven M. Ruben
Original AssigneeHuman Genome Sciences, Inc., Delta Biotechnology Limited
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Albumin Fusion Proteins
US 20090093402 A1
Abstract
The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and/or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.
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Claims(21)
1-21. (canceled)
22. An albumin fusion comprising an IL-1 receptor antagonist polypeptide fused to albumin, or albumin fragment or variant, wherein said albumin fragment or variant has the ability to prolong the serum half-life of the unfused IL-1 receptor antagonist polypeptide, and wherein said albumin fusion protein has IL-1 receptor antagonist activity.
23. The albumin fusion protein of claim 22, wherein said IL-1 receptor antagonist polypeptide is selected from:
a) a full-length IL-1 receptor antagonist;
b) a fragment of IL-1 receptor antagonist;
c) a variant of IL-1 receptor antagonist; and
d) a mature IL-1 receptor antagonist.
24. The albumin fusion protein of claim 23, wherein said fragment of IL-1 receptor antagonist is an N-terminal deletion mutant, a C-terminal deletion mutant, or an N-terminal and C-terminal deletion mutant.
25. The albumin fusion protein of claim 22, wherein said albumin, or albumin fragment or variant, comprises an amino acid sequence selected from:
a) amino acid residues 1 to 585 of SEQ ID NO:18; and
b) amino acid residues 1 to 387 of SEQ ID NO:18.
26. The albumin fusion protein of claim 22, which further comprises a second IL-1 receptor antagonist polypeptide.
27. The albumin fusion protein of claim 22, wherein said IL-1 receptor antagonist polypeptide is fused at the N-terminus or at the C-terminus of the albumin, or albumin fragment or variant.
28. The albumin fusion protein of claim 22, wherein said IL-1 receptor antagonist polypeptide is separated from said albumin, or albumin fragment or variant, by a linker peptide.
29. The albumin fusion protein of claim 22, further comprising a secretion leader sequence.
30. The albumin fusion protein of claim 22, which is non-glycosylated.
31. The albumin fusion protein of claim 22, which is expressed in yeast.
32. The albumin fusion protein of claim 31, wherein said yeast is a Saccharomyces cerevisiae.
33. The albumin fusion protein of claim 31, wherein said yeast is glycosylation deficient.
34. The albumin fusion protein of claim 31, wherein said yeast is glycosylation and protease deficient.
35. The albumin fusion protein of claim 31, wherein said fusion protein is encoded by a polynucleotide that is codon-optimized for expression in yeast.
36. The albumin fusion protein of claim 22, wherein said fusion protein is expressed by a mammalian cell.
37. The albumin fusion protein of claim 36, wherein said mammalian cell is a COS, CHO (Chinese hamster ovary), or NSO cell.
38. A composition comprising the albumin fusion protein of claim 22 and a pharmaceutically acceptable carrier.
39. A kit comprising the composition of claim 38.
40. A method of treating a patient in need of an IL-1 receptor antagonist polypeptide, comprising the step of administering an effective amount of the albumin fusion protein of claim 22.
41. A nucleic acid molecule comprising a polynucleotide sequence encoding the albumin fusion protein of claim 22.
Description
CROSS REFERENCE TO RELATED APPLICATION

This is a divisional of U.S. application Ser. No. 11/429,276, filed May 8, 2006, which is a continuation of U.S. application Ser. No. 10/775,204, filed Feb. 11, 2004, which is a continuation of International Application No. PCT/US02/40891, filed Dec. 23, 2002, which claims benefit under 35 USC 119(e) of U.S. Provisional Application Nos. 60/341,811, filed Dec. 21, 2001; 60/350,358, filed Jan. 24, 2002; 60/351,360, filed Jan. 28, 2002; 60/359,370, filed Feb. 26, 2002; 60/360,000, filed Feb. 28, 2002; 60/367,500, filed Mar. 27, 2002; 60/370,227, filed Apr. 8, 2002; 60/378,950, filed May 10, 2002; 60/382,617, filed May 24, 2002; 60/383,123, filed May 28, 2002; 60/385,708, filed Jun. 5, 2002; 60/394,625, filed Jul. 10, 2002; 60/398,008, filed Jul. 24, 2002; 60/402,131, filed Aug. 9, 2002; 60/402,708, filed Aug. 13, 2002; 60/411,426, filed Sep. 18, 2002; 60/411,355, filed Sep. 18, 2002; 60/414,984, filed Oct. 2, 2002; 60/417,611, filed Oct. 11, 2002; 60/420,246, filed Oct. 23, 2002; and 60/423,623, filed Nov. 5, 2002. All of the above listed applications are incorporated by reference herein.

REFERENCE TO SEQUENCE LISTING ON COMPACT DISC

This application refers to a “Sequence Listing” listed below, which is provided as an electronic document on three identical compact disc (CD-R), labeled “Copy 1,” “Copy 2,” and “CRF.” These compact discs each contain the file “PF564D1 SEQLIST FINAL.txt” (3,568,877 bytes, created on Apr. 19, 2006), which is incorporated by reference in its entirety. The Sequence Listing may be viewed on an IBM-PC machine running the MS-Windows operating system.

BACKGROUND OF THE INVENTION

The invention relates generally to Therapeutic proteins (including, but not limited to, at least one polypeptide, antibody, peptide, or fragment and variant thereof) fused to albumin or fragments or variants of albumin. The invention encompasses polynucleotides encoding therapeutic albumin fusion proteins, therapeutic albumin fusion proteins, compositions, pharmaceutical compositions, formulations and kits. Host cells transformed with the polynucleotides encoding therapeutic albumin fusion proteins are also encompassed by the invention, as are methods of making the albumin fusion proteins of the invention using these polynucleotides, and/or host cells.

Human serum albumin (HSA, or HA), a protein of 585 amino acids in its mature form (as shown in FIG. 1 (SEQ ID NO:1038)), is responsible for a significant proportion of the osmotic pressure of serum and also functions as a carrier of endogenous and exogenous ligands. At present, HA for clinical use is produced by extraction from human blood. The production of recombinant HA (rHA) in microorganisms has been disclosed in EP 330 451 and EP 361 991.

Therapeutic proteins in their native state or when recombinantly produced, such as interferons and growth hormones, are typically labile molecules exhibiting short shelf-lives, particularly when formulated in aqueous solutions. The instability in these molecules when formulated for administration dictates that many of the molecules must be lyophilized and refrigerated at all times during storage, thereby rendering the molecules difficult to transport and/or store. Storage problems are particularly acute when pharmaceutical formulations must be stored and dispensed outside of the hospital environment.

Few practical solutions to the storage problems of labile protein molecules have been proposed. Accordingly, there is a need for stabilized, long lasting formulations of proteinaceous therapeutic molecules that are easily dispensed, preferably with a simple formulation requiring minimal post-storage manipulation.

SUMMARY OF THE INVENTION

The present invention encompasses albumin fusion proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides comprising, or alternatively consisting of, nucleic acid molecules encoding a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides, comprising, or alternatively consisting of, nucleic acid molecules encoding proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin, that is sufficient to prolong the shelf life of the Therapeutic protein, and/or stabilize the Therapeutic protein and/or its activity in solution (or in a pharmaceutical composition) in vitro and/or in vivo. Albumin fusion proteins encoded by a polynucleotide of the invention are also encompassed by the invention, as are host cells transformed with polynucleotides of the invention, and methods of making the albumin fusion proteins of the invention and using these polynucleotides of the invention, and/or host cells.

In a preferred aspect of the invention, albumin fusion proteins include, but are not limited to, those encoded by the polynucleotides described in Table 2.

The invention also encompasses pharmaceutical formulations comprising an albumin fusion protein of the invention and a pharmaceutically acceptable diluent or carrier. Such formulations may be in a kit or container. Such kit or container may be packaged with instructions pertaining to the extended shelf life of the Therapeutic protein. Such formulations may be used in methods of treating, preventing, ameliorating or diagnosing a disease or disease symptom in a patient, preferably a mammal, most preferably a human, comprising the step of administering the pharmaceutical formulation to the patient.

In other embodiments, the present invention encompasses methods of preventing, treating, or ameliorating a disease or disorder. In preferred embodiments, the present invention encompasses a method of treating a disease or disorder listed in the “Preferred Indication: Y” column of Table 1 comprising administering to a patient in which such treatment, prevention or amelioration is desired an albumin fusion protein of the invention that comprises a Therapeutic protein or portion corresponding to a Therapeutic protein (or fragment or variant thereof) disclosed in the “Therapeutic Protein: X” column of Table 1 (in the same row as the disease or disorder to be treated is listed in the “Preferred Indication: Y” column of Table 1) in an amount effective to treat, prevent or ameliorate the disease or disorder.

In one embodiment, an albumin fusion protein described in Table 1 or 2 has extended shelf life.

In a second embodiment, an albumin fusion protein described in Table 1 or 2 is more stable than the corresponding unfused Therapeutic molecule described in Table 1.

The present invention further includes transgenic organisms modified to contain the nucleic acid molecules of the invention (including, but not limited to, the polynucleotides described in Tables 1 and 2), preferably modified to express an albumin fusion protein of the invention.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1A-D shows the amino acid sequence of the mature form of human albumin (SEQ ID NO:1038) and a polynucleotide encoding it (SEQ ID NO:1037).

FIG. 2 shows the restriction map of the pPPC0005 cloning vector ATCC deposit PTA-3278.

FIG. 3 shows the restriction map of the pSAC35 yeast S. cerevisiae expression vector (Sleep et al., BioTechnology 8:42 (1990)).

FIG. 4 shows the effect of various dilutions of EPO albumin fusion proteins encoded by DNA comprised in Construct ID NOS. (hereinafter CID) 1966 and 1981 and recombinant human EPO on the proliferation of TF-1 cells (see Examples 8 and 9). Cells were washed 3× to remove GM-CSF and plated at 10,000 cells/well for 72 hours in the presence of 3-fold dilutions of CID 1966 protein or CID 1981 protein. Concentrations used were calculated based on the weight of Epo alone, not HSA plus Epo. Recombinant human Epo (rhEpo) was used as the positive control and serially diluted 3 fold from 100 ng/ml to 0.01 ng/ml. Cells were exposed to 0.5 mCi/well of 3H-thymidine for an additional 18 hours. (□) rhEpo; (▾) HSA-Epo 1981; () Epo-HSA 1966.

FIG. 5 is a dose response analysis and shows the effect of various doses of recombinant human EPO and EPO albumin fusion proteins encoded by DNA comprised in CID 1966 and 1981 on the percent change in hematocrit from day 0 to day 7 (see Examples 8 and 9). 48 eight-week old female DBA/2NHsd mice were divided into 12 groups of 4 animals each. Recombinant human Epo (rhEpo) was administered subcutaneously at 0.5, 1.5, 4.5 and 12 μg/kg on days 0, 2, 4, and 6. Epo albumin fusion proteins made from constructs CID 1966 and CID 1981 were administered subcutaneously at 2, 6, 18, and 54 μg/kg on days 0, 2, 4, and 6. The higher doses of the Epo albumin fusion proteins allows a rough equimolar comparison with recombinant human Epo (note that the weight of the fusions is about 4.35 times the weight of non-glycosylated Epo). On days 0 and 7 of the experiment, the animals were bled via a tail vein and the hematocrit was determined by centrifugation. (▪) rhEpo; (◯) CID 1981; (▴) CID 1966.

FIG. 6A shows the effect of various subcutaneous administrations of Epo albumin fusion proteins encoded by DNA comprised in CID 1966 and 1997, respectively, on the percent change in hematocrit from day 0 to day 8 (see Examples 8 and 10). *, p<0.005 compared to rhEpo as determined by Mann-Whitney nonparametric analysis (n=6).

FIG. 6B shows the effect of subcutaneous administrations of Epo albumin fusion proteins encoded by DNA comprised in CID 1997 and 1966 on the percent change in hematocrit from day 0 to day 14 (see Examples 8 and 10). *, p<0.005 compared to rhEpo as determined by Mann-Whitney nonparametric analysis (n=6); **, p<0.05 compared to rhEpo as determined by Mann-Whitney nonparametric analysis (n=6).

FIG. 7 shows the effect of various dilutions albumin fusion proteins encoded by DNA comprised in CID 1981 and 1997, respectively, on the proliferation of TF-1 cells (see Examples 9 and 10). Cells were washed 3× to remove GM-CSF and plated at 10,000 cells/well for 72 hours in the presence of 3-fold dilutions of Epo albumin fusion proteins encoded by CID 1981 or 1997. Equimolar amounts of rhEpo were used as a positive control (4.35 times less protein added since weight of non-glycosylated Epo is 20 kd, while Epo albumin fusion proteins are 87 kd). Cells were exposed to 0.5 μCi/well of 3H-thymidine for an additional 24 hours. (▪) rhEpo Standard; (▴) CID 1981 (CHO); (∘) CID 1997 (NSO).

FIG. 8 shows the effect of various doses of recombinant human EPO (rhEpo) and EPO albumin fusion protein encoded by DNA comprised in construct 1997 (CID 1997) on the percent change in hematocrit from day 0 to day 8 (see Example 10). (▴)=rhEpo, ( )=CID 1997.

FIG. 9 shows the effect of various dilutions of IL2 albumin fusion proteins encoded by DNA comprised in CID 1812 (see Example 15) on CTLL-2 proliferation. 1×104 cells/well were seeded in a 96-well plate in a final volume of 200 ul of complete medium containing the indicated amount of IL2 albumin fusion protein (CID 1812). All samples were run in triplicate. The cells were incubated for 40 hours at 37° C., then 20 ul of Alamar Blue was added and cells incubated for 8 hours. Absorbance at 530/590 was used as a measure of proliferation. EC50=0.386±0.021. (Δ)=CID 1812.

FIG. 10 shows the effect of IL2 albumin fusion protein encoded by DNA comprised in CID 1812 on RENCA tumor growth at day 21 (see Example 15). BALB/c mice (n=10) were injected SC (midflank) with 105 RENCA cells. 10 days later mice received 2 cycles (Day 10 to Day 14 and Days 17-21) of daily (QD) injections of rIL2 (0.9 mg/kg), IL2 albumin fusion protein (CID 1812 protein; 0.6 mg/kg), or PBS (Placebo) or injections every other day (QOD) of CID 1812 protein (0.6 mg/kg). The tumor volume was determined on Day 21 after RENCA inoculation. The data are presented in scatter analysis (each dot representing single animal). Mean value of each group is depicted by horizontal line. *, p=0.0035 between placebo control and CID 1812 protein. The number in parentheses indicates number of mice alive over the total number of mice per group. (◯)=Placebo; ()=IL2; (Δ)=CID 1812 protein (QD); (□)=CID 1812 protein (QOD).

FIG. 11 shows the effect of various dilutions of GCSF albumin fusion proteins encoded by DNA comprised in CID 1642 and 1643 on NFS-60 cell proliferation (see Examples 19 and 20). (▪)=CID 1642; (▴)=CID 1643; (◯)=HSA.

FIG. 12 shows the effect of recombinant human GCSF (Neupogen) and GCSF albumin fusion protein on total white blood cell count (see Example 19). Total WBC (103 cells/ul) on each day are presented as the group mean ±SEM. GCSF albumin fusion protein was administered sc at either 25 or 100 ug/kg every 4 days×4 (Q4D), or at 100 ug/kg every 7 days×2 (Q7D). Data from Days 8 and 9 for GCSF albumin fusion protein 100 ug/kg Q7 are presented as Days 9 and 10, respectively, to facilitate comparison with other groups. Controls were saline vehicle administered SC every 4 days×4 (Vehicle Q4D), or Neupogen administered SC daily×14 (Neupogen 5 ug/kg QD). The treatment period is considered Days 1-14, and the recovery period, Days 15-28.

FIG. 13 shows the effect of various dilutions of IFNb albumin fusion proteins encoded by DNA comprised in CID 2011 and 2053 on SEAP activity in the ISRE-SEAP/293F reporter cells (see Example 25). Proteins were serially diluted from 5e-7 to 1e-14 g/ml in DMEM/10% FBS and used to treat ISRE-SEAP/293F reporter cells. After 24 hours supernatants were removed from reporter cells and assayed for SEAP activity. IFNb albumin fusion protein was purified from three stable clones: 293F/#2011, CHO/#2011 and NSO/#2053. Mammalian derived IFNb, Avonex, came from Biogen and was reported to have a specific activity of 2.0e5 IU/ug.

FIG. 14 illustrates the steady-state levels of insulin mRNA in INS-1 (832/13) cells after treatment with GLP-1 or GLP-1 albumin fusion protein encoded by construct ID 3070 (CID 3070 protein). Both GLP-1 and the CID 3070 protein stimulate transcription of the insulin gene in INS-1 cells. The first bar (black) represents the untreated cells. Bars 2-4 (white) represent cells treated with the indicated concentrations of GLP-1. Bars 5-7 (gray) represent cells treated with the indicated concentrations of CID 3070 protein.

FIG. 15 compares the anti-proliferative activity of IFN albumin fusion protein encoded by CID 3165 (CID 3165 protein) and recombinant IFNa (rIFNa) on Hs294T melanoma cells. The cells were cultured with varying concentrations of either CID 3165 protein or rIFNa and proliferation was measured by BrdU incorporation after 3 days of culture. CID 3165 protein caused measurable inhibition of cell proliferation at concentrations above 10 ng/ml with 50% inhibition achieved at approximately 200 ng/ml. (▪)=CID 3165 protein, (♦)=rIFNa.

FIG. 16 shows the effect of various dilutions of IFNa albumin fusion proteins on SEAP activity in the ISRE-SEAP/293F reporter cells. One preparation of IFNa fused upstream of albumin (♦) was tested, as well as two different preparations of IFNa fused downstream of albumin (▴) and (▪).

FIG. 17 shows the effect of time and dose of IFNa albumin fusion protein encoded by DNA comprised in construct 2249 (CID 2249 protein) on the mRNA level of OAS (p41) in treated monkeys (see Example 31). Per time point: first bar=Vehicle control, 2nd bar=30 ug/kg CID 2249 protein day 1 iv, third bar=30 ug/kg CID 2249 protein day 1 sc, 4th bar=300 ug/kg CID 2249 protein day 1 sc, 5th bar=40 ug/kg recombinant IFNa day 1, 3 and 5 sc.

FIG. 18 shows the effect of various dilutions of insulin albumin fusion proteins encoded by DNA comprised in constructs 2250 and 2276 on glucose uptake in 3T3-L1 adipocytes (see Examples 33 and 35).

FIG. 19 shows the effect of various GCSF albumin fusion proteins, including those encoded by CID #1643 and #2702 (L-171, see Example 114), on NFS cell proliferation. The horizontal dashed line indicates the minimum level of detection.

DETAILED DESCRIPTION

Definitions

The following definitions are provided to facilitate understanding of certain terms used throughout this specification.

As used herein, “polynucleotide” refers to a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one Therapeutic protein X (or fragment or variant thereof); a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, the amino acid sequence of SEQ ID NO:Y (as described in column 6 of Table 2) or a fragment or variant thereof; a nucleic acid molecule having a nucleotide sequence comprising or alternatively consisting of the sequence shown in SEQ ID NO:X; a nucleic acid molecule having a nucleotide sequence encoding a fusion protein comprising, or alternatively consisting of, the amino acid sequence of SEQ ID NO:Z; a nucleic acid molecule having a nucleotide sequence encoding an albumin fusion protein of the invention generated as described in Table 2 or in the Examples; a nucleic acid molecule having a nucleotide sequence encoding a Therapeutic albumin fusion protein of the invention, a nucleic acid molecule having a nucleotide sequence contained in an albumin fusion construct described in Table 2, or a nucleic acid molecule having a nucleotide sequence contained in an albumin fusion construct deposited with the ATCC (as described in Table 3).

As used herein, “albumin fusion construct” refers to a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof); a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof) generated as described in Table 2 or in the Examples; or a nucleic acid molecule comprising, or alternatively consisting of, a polynucleotide encoding at least one molecule of albumin (or a fragment or variant thereof) joined in frame to at least one polynucleotide encoding at least one molecule of a Therapeutic protein (or fragment or variant thereof), further comprising, for example, one or more of the following elements: (1) a functional self-replicating vector (including but not limited to, a shuttle vector, an expression vector, an integration vector, and/or a replication system), (2) a region for initiation of transcription (e.g., a promoter region, such as for example, a regulatable or inducible promoter, a constitutive promoter), (3) a region for termination of transcription, (4) a leader sequence, and (5) a selectable marker. The polynucleotide encoding the Therapeutic protein and albumin protein, once part of the albumin fusion construct, may each be referred to as a “portion,” “region” or “moiety” of the albumin fusion construct.

The present invention relates generally to polynucleotides encoding albumin fusion proteins; albumin fusion proteins; and methods of treating, preventing, or ameliorating diseases or disorders using albumin fusion proteins or polynucleotides encoding albumin fusion proteins. As used herein, “albumin fusion protein” refers to a protein formed by the fusion of at least one molecule of albumin (or a fragment or variant thereof) to at least one molecule of a Therapeutic protein (or fragment or variant thereof). An albumin fusion protein of the invention comprises at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another by genetic fusion (i.e., the albumin fusion protein is generated by translation of a nucleic acid in which a polynucleotide encoding all or a portion of a Therapeutic protein is joined in-frame with a polynucleotide encoding all or a portion of albumin). The Therapeutic protein and albumin protein, once part of the albumin fusion protein, may each be referred to as a “portion”, “region” or “moiety” of the albumin fusion protein (e.g., a “Therapeutic protein portion” or an “albumin protein portion”). In a highly preferred embodiment, an albumin fusion protein of the invention comprises at least one molecule of a Therapeutic protein X or fragment or variant of thereof (including, but not limited to a mature form of the Therapeutic protein X) and at least one molecule of albumin or fragment or variant thereof (including but not limited to a mature form of albumin).

In a further preferred embodiment, an albumin fusion protein of the invention is processed by a host cell and secreted into the surrounding culture medium. Processing of the nascent albumin fusion protein that occurs in the secretory pathways of the host used for expression may include, but is not limited to signal peptide cleavage; formation of disulfide bonds; proper folding; addition and processing of carbohydrates (such as for example, N- and O-linked glycosylation); specific proteolytic cleavages; and assembly into multimeric proteins. An albumin fusion protein of the invention is preferably in the processed form. In a most preferred embodiment, the “processed form of an albumin fusion protein” refers to an albumin fusion protein product which has undergone N-terminal signal peptide cleavage, herein also referred to as a “mature albumin fusion protein”.

In several instances, a representative clone containing an albumin fusion construct of the invention was deposited with the American Type Culture Collection (herein referred to as “ATCC®”). Furthermore, it is possible to retrieve a given albumin fusion construct from the deposit by techniques known in the art and described elsewhere herein. The ATCC® is located at 10801 University Boulevard, Manassas, Va. 20110-2209, USA. The ATCC® deposits were made pursuant to the terms of the Budapest Treaty on the international recognition of the deposit of microorganisms for the purposes of patent procedure.

In one embodiment, the invention provides a polynucleotide encoding an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein. In a further embodiment, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein. In a preferred embodiment, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a serum albumin protein encoded by a polynucleotide described in Table 2. In a further preferred embodiment, the invention provides a polynucleotide encoding an albumin fusion protein whose sequence is shown as SEQ ID NO:Y in Table 2. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment of a Therapeutic protein and a serum albumin protein. In other embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active variant of a Therapeutic protein and a serum albumin protein. In preferred embodiments, the serum albumin protein component of the albumin fusion protein is the mature portion of serum albumin. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein, and a biologically active and/or therapeutically active fragment of serum albumin. In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a Therapeutic protein and a biologically active and/or therapeutically active variant of serum albumin. In preferred embodiments, the Therapeutic protein portion of the albumin fusion protein is the mature portion of the Therapeutic protein. In a further preferred embodiment, the Therapeutic protein portion of the albumin fusion protein is the extracellular soluble domain of the Therapeutic protein. In an alternative embodiment, the Therapeutic protein portion of the albumin fusion protein is the active form of the Therapeutic protein. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

In further embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, a biologically active and/or therapeutically active fragment or variant of a Therapeutic protein and a biologically active and/or therapeutically active fragment or variant of serum albumin. In preferred embodiments, the invention provides an albumin fusion protein comprising, or alternatively consisting of, the mature portion of a Therapeutic protein and the mature portion of serum albumin. The invention further encompasses polynucleotides encoding these albumin fusion proteins.

Therapeutic Proteins

As stated above, a polynucleotide of the invention encodes a protein comprising or alternatively consisting of, at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are associated with one another, preferably by genetic fusion.

An additional embodiment includes a polynucleotide encoding a protein comprising or alternatively consisting of at least a fragment or variant of a Therapeutic protein and at least a fragment or variant of human serum albumin, which are linked with one another by chemical conjugation.

As used herein, “Therapeutic protein” refers to proteins, polypeptides, antibodies, peptides or fragments or variants thereof, having one or more therapeutic and/or biological activities. Therapeutic proteins encompassed by the invention include but are not limited to, proteins, polypeptides, peptides, antibodies, and biologics. (The terms peptides, proteins, and polypeptides are used interchangeably herein.) It is specifically contemplated that the term “Therapeutic protein” encompasses antibodies and fragments and variants thereof. Thus a protein of the invention may contain at least a fragment or variant of a Therapeutic protein, and/or at least a fragment or variant of an antibody. Additionally, the term “Therapeutic protein” may refer to the endogenous or naturally occurring correlate of a Therapeutic protein.

By a polypeptide displaying a “therapeutic activity” or a protein that is “therapeutically active” is meant a polypeptide that possesses one or more known biological and/or therapeutic activities associated with a therapeutic protein such as one or more of the Therapeutic proteins described herein or otherwise known in the art. As a non-limiting example, a “Therapeutic protein” is a protein that is useful to treat, prevent or ameliorate a disease, condition or disorder. As a non-limiting example, a “Therapeutic protein” may be one that binds specifically to a particular cell type (normal (e.g., lymphocytes) or abnormal e.g., (cancer cells)) and therefore may be used to target a compound (drug, or cytotoxic agent) to that cell type specifically.

For example, a non-exhaustive list of “Therapeutic protein” portions which may be comprised by an albumin fusion protein of the invention includes, but is not limited to, erythropoietin (EPO), IL-2, G-CSF, Insulin, Calcitonin, Growth Hormone, IFN-alpha, IFN-beta, PTH, TR6 (International Publication No. WO 98/30694), BLyS, BLyS single chain antibody, Resistin, Growth hormone releasing factor, VEGF-2, KGF-2, D-SLAM, KDI, and TR2, GLP-1, Extendin 4, and GM-CSF.

Interferon hybrids may also be fused to the amino or carboxy terminus of albumin to form an interferon hybrid albumin fusion protein. Interferon hybrid albumin fusion protein may have enhanced, or alternatively, suppressed interferon activity, such as antiviral responses, regulation of cell growth, and modulation of immune response (Lebleu et al., PNAS USA, 73:3107-3111 (1976); Gresser et al., Nature, 251:543-545 (1974); and Johnson, Texas Reports Biol Med, 35:357-369 (1977)). Each interferon hybrid albumin fusion protein can be used to treat, prevent, or ameliorate viral infections (e.g., hepatitis (e.g., HCV); or HIV), multiple sclerosis, or cancer.

In one embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon alpha-interferon alpha hybrid (herein referred to as an alpha-alpha hybrid). For example, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha D. In a further embodiment, the A/D hybrid is fused at the common BgIII restriction site to interferon alpha D, wherein the N-terminal portion of the A/D hybrid corresponds to amino acids 1-62 of interferon alpha A and the C-terminal portion corresponds to amino acids 64-166 of interferon alpha D. For example, this A/D hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX1ISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHE MIQQIFNLFTTKDSSAAWDEDLLDKFCTELYQQLNDLEACVMQEERVGETPLMNX2D SILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:1326), wherein the X1 is R or K and the X2 is A or V (see, for example, Construct ID #2875). In an additional embodiment, the A/D hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/D hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha D. For example, this A/D hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX1ISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHE MIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEACVMQEERVGETPLMNX2D SILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:1311), wherein the X1 is R or K and the second X2 is A or V (see, for example, Construct ID #2872). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety.

In an additional embodiment, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha F. In a further embodiment, the A/F hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/F hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha F. For example, this A/F hybrid would comprise the amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRXISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHE MIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDMEACVIQEVGVEETPLMNVDSI LAVKKYFQRITLYLTEKKYSPCAWEVVRAEIMRSFSLSKIFQERLRRKE (SEQ ID NO:1321), wherein X is either R or K (see, for example, Construct ID #2874). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety. In a further embodiment, the alpha-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha A fused to interferon alpha B. In an additional embodiment, the A/B hybrid is fused at the common PvuIII restriction site, wherein the N-terminal portion of the A/B hybrid corresponds to amino acids 1-91 of interferon alpha A and the C-terminal portion corresponds to amino acids 93-166 of interferon alpha B. For example, this A/B hybrid would comprise an amino acid sequence: CDLPQTHSLGSRRTLMLLAQMRX1ISLFSCLKDRHDFGFPQEEFGNQFQKAETIPVLHE MIQQIFNLFSTKDSSAAWDETLLDKFYTELYQQLNDLEX2X3X4X5QEVGVIESPLMYE DSILAVRKYFQRITLYLTEKKYSSCAWEVVRAEIMRSFSLSINLQKRLKSKE (SEQ ID NO:1316), wherein the X1 is R or K and X2 through X5 is SCVM or VLCD (see, for example, Construct ID #2873). These hybrids are further described in U.S. Pat. No. 4,414,510, which is hereby incorporated by reference in its entirety.

In another embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon beta-interferon alpha hybrid (herein referred to as a beta-alpha hybrid). For example, the beta-alpha hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon beta-1 fused to interferon alpha D (also referred to as interferon alpha-1). In a further embodiment, the beta-1/alpha D hybrid is fused wherein the N-terminal portion corresponds to amino acids 1-73 of interferon beta-1 and the C-terminal portion corresponds to amino acids 74-167 of interferon alpha D. For example, this beta-1/alpha D hybrid would comprise an amino acid sequence: MSYNLLGFLQRSSNFQCQKLLWQLNGRLEYCLKDRMNFDIPEEIKQLQQFQKEDAAL TIYEMLQNIFAIFRQDSSAAWDEDLLDKFCTELYQQLNDLEACVMQEERVGETPLMN XDSILAVKKYFRRITLYLTEKKYSPCAWEVVRAEIMRSLSLSTNLQERLRRKE (SEQ ID NO:2130), wherein X is A or V. These hybrids are further described in U.S. Pat. No. 4,758,428, which is hereby incorporated by reference in its entirety.

In another embodiment, the interferon hybrid portion of the interferon hybrid albumin fusion protein comprises an interferon alpha-interferon beta hybrid (herein referred to as a alpha-beta hybrid). For example, the alpha-beta hybrid portion of the interferon hybrid albumin fusion protein consists, or alternatively comprises, of interferon alpha D (also referred to as interferon alpha-1) fused to interferon beta-1. In a further embodiment, the alpha D/beta-1 hybrid is fused wherein the N-terminal portion corresponds to amino acids 1-73 of interferon alpha D and the C-terminal portion corresponds to amino acids 74-166 of interferon beta-1. For example, this alpha D/beta-1 hybrid would have an amino acid sequence: MCDLPETHSLDNRRTLMLLAQMSRISPSSCLMDRHDFGFPQEEFDGNQFQKAPAISVL HELIQQIFNLFTTKDSSSTGWNETIVENLLANVYHQINHLKTVLEEKLEKEDFTRGKL MSSLHLKRYYGRILHYLKAKEYSHCAWTIVRVEILRNFYFINRLTGYLRN (SEQ ID NO:2131). These hybrids are further described in U.S. Pat. No. 4,758,428, which is hereby incorporated by reference in its entirety.

In further embodiments, the interferon hybrid portion of the interferon hybrid albumin fusion proteins may comprise additional combinations of alpha-alpha interferon hybrids, alpha-beta interferon hybrids, and beta-alpha interferon hybrids. In additional embodiments, the interferon hybrid portion of the interferon hybrid albumin fusion protein may be modified to include mutations, substitutions, deletions, or additions to the amino acid sequence of the interferon hybrid. Such modifications to the interferon hybrid albumin fusion proteins may be made, for example, to improve levels of production, increase stability, increase or decrease activity, or confer new biological properties.

The above-described interferon hybrid albumin fusion proteins are encompassed by the invention, as are host cells and vectors containing polynucleotides encoding the polypeptides. In one embodiment, a interferon hybrid albumin fusion protein encoded by a polynucleotide as described above has extended shelf life. In an additional embodiment, a interferon hybrid albumin fusion protein encoded by a polynucleotide described above has a longer serum half-life and/or more stabilized activity in solution (or in a pharmaceutical composition) in vitro and/or in vivo than the corresponding unfused interferon hybrid molecule.

In another non-limiting example, a “Therapeutic protein” is a protein that has a biological activity, and in particular, a biological activity that is useful for treating, preventing or ameliorating a disease. A non-inclusive list of biological activities that may be possessed by a Therapeutic protein includes, enhancing the immune response, promoting angiogenesis, inhibiting angiogenesis, regulating endocrine function, regulating hematopoietic functions, stimulating nerve growth, enhancing an immune response, inhibiting an immune response, or any one or more of the biological activities described in the “Biological Activities” section below and/or as disclosed for a given Therapeutic protein in Table 1 (column 2).

As used herein, “therapeutic activity” or “activity” may refer to an activity whose effect is consistent with a desirable therapeutic outcome in humans, or to desired effects in non-human mammals or in other species or organisms. Therapeutic activity may be measured in vivo or in vitro. For example, a desirable effect may be assayed in cell culture. As an example, when EPO is the Therapeutic protein, the effects of EPO on cell proliferation as described in Example 8 may be used as the endpoint for which therapeutic activity is measured. Such in vitro or cell culture assays are commonly available for many Therapeutic proteins as described in the art. Examples of assays include, but are not limited to those described herein in the Examples section or in the “Exemplary Activity Assay” column (column 3) of Table 1.

Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention, such as cell surface and secretory proteins, are often modified by the attachment of one or more oligosaccharide groups. The modification, referred to as glycosylation, can dramatically affect the physical properties of proteins and can be important in protein stability, secretion, and localization. Glycosylation occurs at specific locations along the polypeptide backbone. There are usually two major types of glycosylation: glycosylation characterized by O-linked oligosaccharides, which are attached to serine or threonine residues; and glycosylation characterized by N-linked oligosaccharides, which are attached to asparagine residues in an Asn-X-Ser or Asn-X-Thr sequence, where X can be any amino acid except proline. N-acetylneuramic acid (also known as sialic acid) is usually the terminal residue of both N-linked and 0-linked oligosaccharides. Variables such as protein structure and cell type influence the number and nature of the carbohydrate units within the chains at different glycosylation sites. Glycosylation isomers are also common at the same site within a given cell type.

For example, several types of human interferon are glycosylated. Natural human interferon-α2 is O-glycosylated at threonine 106, and N-glycosylation occurs at asparagine 72 in interferon-α14 (Adolf et al., J. Biochem 276:511 (1991); Nyman T A et al., J. Biochem 329:295 (1998)). The oligosaccharides at asparagine 80 in natural interferon-β1α may play an important factor in the solubility and stability of the protein, but may not be essential for its biological activity. This permits the production of an unglycosylated analog (interferon-β1b) engineered with sequence modifications to enhance stability (Hosoi et al., J. Interferon Res. 8:375 (1988; Karpusas et al., Cell Mol Life Sci 54:1203 (1998); Knight, J. Interferon Res. 2:421 (1982); Runkel et al., Pharm Res 15:641 (1998); Lin, Dev. Biol. Stand. 96:97 (1998)). Interferon-7 contains two N-linked oligosaccharide chains at positions 25 and 97, both important for the efficient formation of the bioactive recombinant protein, and having an influence on the pharmacokinetic properties of the protein (Sareneva et al., Eur. J. Biochem 242:191 (1996); Sareneva et al., Biochem J. 303:831 (1994); Sareneva et al., J. Interferon Res. 13:267 (1993)). Mixed O-linked and N-linked glycosylation also occurs, for example in human erythropoietin, N-linked glycosylation occurs at asparagine residues located at positions 24, 38 and 83 while O-linked glycosylation occurs at a serine residue located at position 126 (Lai et al., J. Biol. Chem. 261:3116 (1986); Broudy et al., Arch. Biochem. Biophys. 265:329 (1988)).

Glycosylation of EPO albumin fusion proteins may influence the activity and/or stability of the EPO albumin fusion proteins. The EPO portion of the albumin fusion protein may contain 3 N-linked sites for glycosylation, each of which can carry one tetra-antennary structure. When the EPO albumin fusion protein is glycosylated, the half-life of the molecule may be increased. In one embodiment, the EPO albumin fusion protein is glycosylated. In another embodiment, the EPO albumin fusion protein is hyperglycosylated.

One type of sugar commonly found in oligosaccharides is sialic acid. Each tetra-antennary structure of the N-linked glycosylation sites of EPO may carry four sialic acid residues. Accordingly, in a preferred embodiment, the EPO albumin fusion protein is glycosylated with a carbohydrate group containing sialic acid. In an additional embodiment, the EPO albumin fusion protein comprises a fully sialylated EPO protein containing four sialic acid residues per tetra-antennerary structure per site with a molar ratio of sialic acid to protein 12:1 or greater. In alternative embodiments, the EPO albumin fusion protein comprises a hypersialylated EPO protein wherein one, two, or three sialic acid residues are attached at each tetra-antennerary structure per site with a molar ratio of sialic acid to protein less than 12:1.

Two types of sialic acid that may be used in the sialylation of the EPO albumin fusion protein are N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc). In a preferred embodiment, hypersialylated EPO albumin fusion proteins contain Neu5Ac. More preferably, the total sialic acid content of hypersialylated EPO albumin fusion proteins is at least 97% Neu5Ac. Most preferred are EPO albumin fusion protein structures with little or no Neu5Gc.

Preferably, the albumin EPO fusion protein has at least 4 moles of sialylation, and more preferably, at least 8-9 moles of sialylation. An additional embodiment comprises an albumin EPO fusion protein with 4 moles of sialylation, 5 moles of sialylation, 6 moles of sialylation, 7 moles of sialylation, 8-9 moles of sialylation, 8 moles of sialylation, 9 moles of sialylation, 10 moles of sialylation, 11 moles of sialylation, or 12 moles of sialylation.

The degree of sialylation of a protein changes the charge of the protein and its retention time on a chromatography column. Therefore, certain chromatography steps used in the purification process may be used to monitor or enrich for hypersialylated EPO albumin fusion proteins. In a preferred embodiment, the amount of sialylation may be monitored by HPLC chromatography. In an additional embodiment, steps in the purification process of EPO albumin fusions may be used to enrich for hypersialylated EPO albumin fusion proteins. In a preferred embodiment the purification steps that may be used to enrich for hypersialylated EPO albumin fusion proteins comprise the butyl-sepharose FF purification step to remove virus particles by high ammonium salt and the hydroxyapatite chromatography at pH 6.8 for the final purification step.

Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention, as well as analogs and variants thereof, may be modified so that glycosylation at one or more sites is altered as a result of manipulation(s) of their nucleic acid sequence, by the host cell in which they are expressed, or due to other conditions of their expression. For example, glycosylation isomers may be produced by abolishing or introducing glycosylation sites, e.g., by substitution or deletion of amino acid residues, such as substitution of glutamine for asparagine, or unglycosylated recombinant proteins may be produced by expressing the proteins in host cells that will not glycosylate them, e.g. in E. coli or glycosylation-deficient yeast. These approaches are described in more detail below and are known in the art.

Therapeutic proteins, particularly those disclosed in Table 1, and their nucleic acid and amino acid sequences are well known in the art and available in public databases such as Chemical Abstracts Services Databases (e.g., the CAS Registry), GenBank, and subscription provided databases such as GenSeq (e.g., Derwent). Exemplary nucleotide sequences of Therapeutic proteins which may be used to derive a polynucleotide of the invention are shown in column 7, “SEQ ID NO:X,” of Table 2. Sequences shown as SEQ ID NO:X may be a wild type polynucleotide sequence encoding a given Therapeutic protein (e.g., either full length or mature), or in some instances the sequence may be a variant of said wild type polynucleotide sequence (e.g., a polynucleotide which encodes the wild type Therapeutic protein, wherein the DNA sequence of said polynucleotide has been optimized, for example, for expression in a particular species; or a polynucleotide encoding a variant of the wild type Therapeutic protein (i.e., a site directed mutant; an allelic variant)). It is well within the ability of the skilled artisan to use the sequence shown as SEQ ID NO:X to derive the construct described in the same row. For example, if SEQ ID NO:X corresponds to a full length protein, but only a portion of that protein is used to generate the specific CID, it is within the skill of the art to rely on molecular biology techniques, such as PCR, to amplify the specific fragment and clone it into the appropriate vector.

Additional Therapeutic proteins corresponding to a Therapeutic protein portion of an albumin fusion protein of the invention include, but are not limited to, one or more of the Therapeutic proteins or peptides disclosed in the “Therapeutic Protein X” column of Table 1 (column 1), or fragment or variable thereof.

Table 1 provides a non-exhaustive list of Therapeutic proteins that correspond to a Therapeutic protein portion of an albumin fusion protein of the invention, or an albumin fusion protein encoded by a polynucleotide of the invention. The first column, “Therapeutic Protein X,” discloses Therapeutic protein molecules that may be followed by parentheses containing scientific and brand names of proteins that comprise, or alternatively consist of, that Therapeutic protein molecule or a fragment or variant thereof. “Therapeutic protein X” as used herein may refer either to an individual Therapeutic protein molecule, or to the entire group of Therapeutic proteins associated with a given Therapeutic protein molecule disclosed in this column. The “Biological activity” column (column 2) describes Biological activities associated with the Therapeutic protein molecule. Column 3, “Exemplary Activity Assay,” provides references that describe assays which may be used to test the therapeutic and/or biological activity of a Therapeutic protein:X or an albumin fusion protein comprising a Therapeutic protein X (or fragment thereof) portion. Each of the references cited in the “Exemplary Activity Assay” column are herein incorporated by reference in their entireties, particularly with respect to the description of the respective activity assay described in the reference (see Methods section therein, for example) for assaying the corresponding biological activity set forth in the “Biological Activity” column of Table 1. The fourth column, “Preferred Indication: Y,” describes disease, disorders, and/or conditions that may be treated, prevented, diagnosed, and/or ameliorated by Therapeutic protein X or an albumin fusion protein comprising a Therapeutic protein X (or fragment thereof) portion. The “Construct ID” column (column 5) provides a link to an exemplary albumin fusion construct disclosed in Table 2 which encodes an albumin fusion protein comprising, or alternatively consisting of the referenced Therapeutic Protein X (or fragment thereof) portion.

TABLE 1
Therapeutic Exemplary Activity Therapeutic
Protein: X Biological Activity Assay Preferred Indication: Y Construct ID Protein: Z
EPO Stimulates cellular Cell proliferation assay Anemia; Anemia in Renal Disease; 1772, 1774, 1781, See Table 2,
(Erythropoietin; differentiation of using a Anemia in Oncology Patients; Bleeding 1783, 1793, 1794, SEQ ID
Epoetin bone-marrow stem erythroleukemic cell Disorders; Chronic Renal Failure; 1925, 1926, 1966, NO: Z for
alfa; Epoetin cells at an early stage line TF-1. (Kitamura et Chronic Renal Failure in Pre-Dialysis 1969, 1980, 1981, particular
beta; Gene- of erythropoiesis; al. 1989 J. Cell. Physiol. Patients; Renal Disease; End-Stage 1994, 1995, 1996, construct.
activated accelerates the 140: 323) Renal Disease; End-Stage Renal Disease 1997, 2047, 2102,
erythropoietin; proliferation and in Dialysis Patients; Chemotherapy; 2283, 2284, 2287,
Darbepoetin- maturation of Chemotherapy in Cancer Patients; 2289, 2294, 2298,
alpha; NESP; terminally Anemia in zidovudine-treated HIV 2310, 2311, 2325,
Epogen; differentiating cells patients; Anemia in zidovudine-treated 2326, 2344, 2363,
Procrit; Eprex; into erythrocytes; patients; Anemia in HIV patients; 2373, 2387, 2414,
Erypo; Espo; and modulates the Anemia in premature infants; Surgical 2441, 2603, 2604,
Epoimmun; level of circulating patients (pre and/or post surgery); 2605, 3194, 3195,
EPOGIN; erythrocytes. Surgical patients (pre and/or post 3196,
NEORECORMON; surgery) who are anemic; Surgical
HEMOLINK; patients (pre and/or post surgery) who
Dynepo; are undergoing elective surgery; Surgical
ARANESP) patients (pre and/or post surgery) who
are undergoing elective, non-cardiac
surgery; Surgical patients (pre and/or
post surgery) who are undergoing
elective, non-cardiac, non-vascular
surgery; Surgical patients (pre and/or
post surgery) who are undergoing
elective, non-vascular surgery; Surgical
patients (pre and/or post surgery) who
are undergoing cardiac and/or vascular
surgery; Aplastic anemia; Refractory
anemia; Anemia in Inflammatory Bowel
Disease; Refractory anemia in
Inflammatory Bowel Disease;
Transfusion avoidance; Transfusion
avoidance for surgical patients;
Transfusion avoidance for elective
surgical patients; Transfusion avoidance
for elective orthopedic surgical patients;
Patients who want to Increase Red Blood
Cells.
G-CSF Stimulates the Proliferation of murine Chemoprotection; Adjunct to 1642, 1643, 2363, See Table 2,
(Granulocyte proliferation and NFS-60 cells Chemotherapy; Inflammatory disorders; 2373, 2387, 2414, SEQ ID
colony- differentiation of the (Weinstein et al, Proc Cancer; Leukemia; Myelocytic leukemia; 2441, 2702, 2637, NO: Z for
stimulating progenitor cells for Natl Acad Sci USA Neutropenia, Primary neutropenias (e.g.; 2700, 2701, 2703, particular
factor; granulocytes and 1986; 83, pp5010-4) Kostmann syndrome); Secondary 2886, 2887, 2888, construct.
Granulokine; monocytes- neutropenia; Prevention of neutropenia; 2889, 2890,
KRN 8601; macrophages. Prevention and treatment of neutropenia
Filgrastim; in HIV-infected patients; Prevention and
Lenograstim; treatment of neutropenia associated with
Meograstim; chemotherapy; Infections associated with
Nartograstim; neutropenias; Myelopysplasia;
Neupogen; Autoimmune disorders; Psoriasis;
NOPIA; Gran; Mobilization of hematopoietic
GRANOCYTE; progenitor cells; Wound Healing;
Granulokine; Autoimmune Disease; Transplants; Bone
Neutrogin; marrow transplants; Acute
Neu-up; myelogeneous leukemia; Lymphoma,
Neutromax) Non-Hodgkin's lymphoma; Acute
lymphoblastic leukemia; Hodgkin's
disease; Accelerated myeloid recovery;
Glycogen storage disease.
GM-CSF Regulates Colony Stimulating Bone Marrow Disorders; Bone marrow 1697, 1699, 2066, See Table 2,
(Granulocyte- hematopoietic cell Assay: Testa, N. G., et transplant; Chemoprotection; Hepatitis and 2067. SEQ ID
macrophage differentiation, gene al., “Assays for C; HIV Infections; Cancer; Lung Cancer; NO: Z for
colony- expression, growth, hematopoietic growth Melanoma; Malignant melanoma; particular
stimulating and function. factors.” Balkwill FR Mycobacterium avium complex; construct.
factor; rhuGM- (edt) Cytokines, A Mycoses; Leukemia; Myeloid Leukemia;
CSF; BI practical Approach, pp Infections; Neonatal infections;
61012; 229-44; IRL Press Neutropenia; Mucositis; Oral Mucositis;
Prokine; Oxford 1991. Prostate Cancer; Stem Cell Mobilization;
Molgramostim; Vaccine Adjuvant; Ulcers (such as
Sargramostim; Diabetic, Venous Stasis, or Pressure
GM-CSF/IL 3 Ulcers); Prevention of neutropenia;
fusion; Acute myelogenous leukemia;
Milodistim; Hematopoietic progenitor cell
Leucotropin; mobilization; Lymphoma; Non-
PROKINE; Hodgkin's lymphoma; Acute
LEUKOMAX; Lymphoblastic Leukemia; Hodgkin's
Interberin; disease; Accelerated myeloid recovery;
Leukine; Transplant Rejection; Xenotransplant
Leukine Rejection.
Liquid;
Pixykine)
Human growth Binds to two GHR Ba/F3-hGHR Acromegaly; Growth failure; Growth 3163, 2983, See Table 2,
hormone molecules and proliferation assay, a hormone replacement; Growth hormone SEQ ID
(Pegvisamont; Induces signal novel specific bioassay deficiency; Pediatric Growth Hormone NO: Z for
Somatrem; transduction through for serum human Deficiency; Adult Growth Hormone particular
Somatropin; receptor dimerization growth hormone. J Clin Deficiency; Idiopathic Growth Hormone construct.
TROVERT; Endocrinol Metab 2000 Deficiency; Growth retardation; Prader-
PROTROPIN; Nov; 85(11): 4274-9 Willi Syndrome; Prader-Willi Syndrome
BIO-TROPIN; Plasma growth in children 2 years or older; Growth
HUMATROPE; hormone (GH) deficiencies; Growth failure associated
NUTROPIN; immunoassay and with chronic renal insufficiency;
NUTROPINAQ; tibial bioassay, Appl Osteoporosis; Postmenopausal
NUTROPHIN; Physiol 2000 osteoporosis; Osteopenia,
NORDITROPIN; Dec; 89(6): 2174-8 Osteoclastogenesis; burns; Cachexia;
GENOTROPIN; Growth hormone Cancer Cachexia; Dwarfism; Metabolic
SAIZEN; (hGH) receptor Disorders; Obesity; Renal failure;
SEROSTIM) mediated cell mediated Turner's Syndrome; Fibromyalgia;
proliferation, Growth Fracture treatment; Frailty, AIDS
Horm IGF Res 2000 wasting; Muscle Wasting; Short Stature;
Oct; 10(5): 248-55 Diagnostic Agents; Female Infertility;
International standard lipodystrophy.
for growth hormone,
Horm Res 1999; 51
Suppl 1: 7-12
Insulin Stimulates glucose Insulin activity may be Hyperglycemia; Diabetes; Diabetes 2250, 2255, 2276, See Table 2,
(Human uptake and promotes assayed in vitro using a Insipidus; Diabetes mellitus; Type 1 2278, 2656, 2668, SEQ ID
insulin; Insulin glycogenesis and [3-H]-glucose uptake diabetes; Type 2 diabetes; Insulin 2669, 2671, 2821, NO: Z for
aspart; Insulin lipogenesis. assay. (J Biol Chem resistance; Insulin deficiency; 2822, 2832, 2877, particular
Glargine; 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- 2878, 2882, 2885, construct.
Insulin lispro; 274(43): 30864-30873). insulin dependent Diabetes Mellitus 2891, 2897, 2930,
Lys-B28 Pro- (NIDDM); Insulin-dependent Diabetes 2931, 2942, 2986,
B29; lyspro; Mellitus (IDDM); A Condition 3025, 3133, 3134,
LY 275585; Associated With Diabetes Including, But 3197, 3198, 2726,
diarginylinsulin; Not Limited To Obesity, Heart Disease, 2727, 2784, 2789
Des-B26- Hyperglycemia, Infections, Retinopathy,
B30-insulin- And/Or Ulcers; Metabolic Disorders;
B25-amide; Immune Disorders; Obesity; Vascular
Insulin Disorders; Suppression of Body Weight;
detemir; Suppression of Appetite; Syndrome X.
LABI;
NOVOLIN;
NOVORAPID;
HUMULIN;
NOVOMIX
30;
VELOSULIN;
NOVOLOG;
LANTUS;
ILETIN;
HUMALOG;
MACRULIN;
EXUBRA;
INSUMAN;
ORALIN;
ORALGEN;
HUMAHALE;
HUMAHALIN)
Interferon alfa Confers a range of Anti-viral assay: Viral infections; HIV Infections; 2249, 2343, 2366, See Table 2,
(Interferon cellular responses Rubinstein S, Familletti Hepatitis; Chronic Hepatitis; Hepatitis B; 2381, 2382, 2410, SEQ ID
alfa-2b; including antiviral, PC, Pestka S. (1981) Chronic Hepatitis B; Hepatitis C; and 3165. NO: Z for
recombinant; antiproliferative, Convenient assay for Chronic Hepatitis C; Hepatitis D; particular
Interferon alfa- antitumor and interferons. J. Virol. Chronic Hepatitis D; Human construct.
n1; Interferon immunomodulatory 37(2): 755-8; Anti- Papillomavirus; Herpes Simplex Virus
alfa-n3; activities; stimulate proliferation assay: Infection; External Condylomata
Peginterferon production of two Gao Y, et al (1999) Acuminata; HIV; HIV Infection;
alpha-2b; enzymes: a protein Sensitivity of an Oncology; Cancer; Solid Tumors;
Ribavirin and kinase and an epstein-barr virus- Melanoma; Malignant Melanoma; Renal
interferon alfa- oligoadenylate positive tumor line, Cancer (e.g., Renal Cell Carcinoma);
2b; Interferon synthetase. Daudi, to alpha Lung Cancer (e.g,. Non-Small Cell Lung
alfacon-1; interferon correlates Cancer or Small Cell Lung Cancer)
interferon with expression of a Colon Cancer; Breast Cancer; Liver
consensus; GC-rich viral Cancer; Prostate Cancer; Bladder
YM 643; transcript. Mol Cell Cancer; Gastric Cancer; Sarcoma; AIDS-
CIFN; Biol. 19(11): 7305-13. Related Kaposi's Sarcoma; Lymphoma;
interferon- T Cell Lymphoma; Cutaneous T-Cell
alpha Lymphoma; Non-Hodgkin's Lymphoma;
consensus; Brain Cancer; Glioma; Glioblastoma
recombinant Multiforme; Cervical Dysplasia;
methionyl Leukemia; Preleukemia; Bone Marrow
consensus Disorders; Bone Disorders; Hairy Cell
interferon; Leukemia; Chronic Myelogeonus
recombinant Leukemia; Hematological Malignancies;
consensus Hematological Disorders; Multiple
interferon; Myeloma; Bacterial Infections;
CGP 35269; Chemoprotection; Thrombocytopenia;
RO 253036; Multiple Sclerosis; Pulmonary Fibrosis;
RO 258310; Age-Related Macular Degeneration;
INTRON A; Macular Degeneration; Crohn's Disease;
PEG- Neurological Disorders; Arthritis;
INTRON; Rheumatoid Arthritis; Ulcerative Colitis;
OIF; Osteoporosis, Osteopenia,
OMNIFERON; Osteoclastogenesis; Fibromyalgia;
PEG- Sjogren's Syndrome; Chronic Fatigue
OMNIFERON; Syndrome; Fever; Hemmorhagic Fever;
VELDONA; Viral Hemmorhagic Fevers;
PEG- Hyperglycemia; Diabetes; Diabetes
REBETRON; Insipidus; Diabetes mellitus; Type 1
ROFERON A; diabetes; Type 2 diabetes; Insulin
WELLFERON; resistance; Insulin deficiency;
ALFERON Hyperlipidemia; Hyperketonemia; Non-
N/LDO; insulin dependent Diabetes Mellitus
REBETRON; (NIDDM); Insulin-dependent Diabetes
ALTEMOL; Mellitus (IDDM); A Condition
VIRAFERON Associated With Diabetes Including, But
PEG; Not Limited To Obesity, Heart Disease,
PEGASYS; Hyperglycemia, Infections, Retinopathy,
VIRAFERON; And/Or Ulcers; Metabolic Disorders;
VIRAFON; Immune Disorders; Obesity; Vascular
AMPLIGEN; Disorders; Suppression of Body Weight;
INFERGEN; Suppression of Appetite; Syndrome X.
INFAREX;
ORAGEN)
Calcitonin Regulates levels of Hypocalcemic Rat Bone Disorders; Fracture prevention; 1833, 1834, 1835, See Table 2,
(Salmon calcium and Bioassay, bone Hypercalcemia; Malignant 1836, 2447, 2513, SEQ ID
Calcitonin phosphate in serum; resorbing assay and the hypercalcemia; Osteoporosis; Paget's 2806, 2915 NO: Z for
(Salcatonin); causes a reduction in pit assay, CT receptor disease; Osteopenia, Osteoclastogenesis; particular
Calcitonin serum calcium--an binding assay, CAMP osteolysis; osteomyelitis; osteonecrosis; construct.
human-salmon effect opposite to that stimulation assay: J periodontal bone loss; osteoarthritis;
hybrid; of human parathyroid Bone Miner Res 1999 rheumatoid arthritis; osteopetrosis;
Forcaltonin; hormone. Aug; 14(8): 1425-31 periodontal, lytic, or metastatic bone
Fortical; disease; osteoclast differentiation
Calcitonin; inhibition; bone disorders; bone healing
Calcitonina and regeneration.
Almirall;
Calcitonina
Hubber;
Calcimar; Calsynar;
Calogen;
Miacalcic;
Miacalcin;
SB205614;
Macritonin;
Cibacalcin;
Cibacalcina;
Cibacalcine;
Salmocalcin;
PowderJect
Calcitonin)
(CAS-21215-
62-3)
Interferon beta Modulates MHC Anti-viral assay: Multiple Sclerosis; Oncology; Cancer; 1778, 1779, 2011, See Table 2,
(Interferon antigen expression, Rubinstein S, Familletti Solid Tumors; Melanoma; Malignant 2013, 2053, 2054, SEQ ID
beta-1a; NK cell activity and PC, Pestka S. (1981) Melanoma; Renal Cancer (e.g., Renal 2492, 2580, 2795, NO: Z for
Interferon beta IFNg production and Convenient assay for Cell Carcinoma); Lung Cancer (e.g,. 2796, 2797. particular
1b; Interferon- IL12 production in interferons. J. Virol. Non-Small Cell Lung Cancer or Small construct.
beta-serine; monocytes. 37(2): 755-8; Anti- Cell Lung Cancer) Colon Cancer; Breast
SH 579; ZK proliferation assay: Cancer; Liver Cancer; Prostate Cancer;
157046; Gao Y, et al (1999) Bladder Cancer; Gastric Cancer;
BCDF; beta-2 Sensitivity of an Sarcoma; AIDS-Related Kaposi's
IF; Interferon- epstein-barr virus- Sarcoma; Lymphoma; T Cell
beta-2; rhIL-6; positive tumor line, Lymphoma; Cutaneous T-Cell
SJ0031; DL Daudi, to alpha Lymphoma; Non-Hodgkin's Lymphoma;
8234; FERON; interferon correlates Brain Cancer; Glioma; Glioblastoma
IFNbeta; with expression of a Multiforme; Cervical Dysplasia;
BETASERON; GC-rich viral Leukemia; Preleukemia; Bone Marrow
AVONEX; transcript. Mol Cell Disorders; Bone Disorders; Hairy Cell
REBIF; Biol. 19(11): 7305-13. Leukemia; Chronic Myelogeonus
BETAFERON; Leukemia; Hematological Malignancies;
SIGOSIX) Hematological Disorders; Multiple
Myeloma; Bacterial Infections;
Chemoprotection; Thrombocytopenia;
Viral infections; HIV Infections;
Hepatitis; Chronic Hepatitis; Hepatitis B;
Chronic Hepatitis B; Hepatitis C;
Chronic Hepatitis C; Hepatitis D;
Chronic Hepatitis D; Human
Papillomavirus; Herpes Simplex Virus
Infection; External Condylomata
Acuminata; HIV; HIV Infection;
Pulmonary Fibrosis; Age-Related
Macular Degeneration; Macular
Degeneration; Crohn's Disease;
Neurological Disorders; Arthritis;
Rheumatoid Arthritis; Ulcerative Colitis;
Osteoporosis, Osteopenia,
Osteoclastogenesis; Fibromyalgia;
Sjogren's Syndrome; Chronic Fatigue
Syndrome; Fever; Hemmorhagic Fever;
Viral Hemmorhagic Fevers;
Hyperglycemia; Diabetes; Diabetes
Insipidus; Diabetes mellitus; Type 1
diabetes; Type 2 diabetes; Insulin
resistance; Insulin deficiency;
Hyperlipidemia; Hyperketonemia; Non-
insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Growth Acts on the anterior Growth hormone- Acromegaly; Growth failure; Growth 1747 and 1748. See Table 2,
hormone pituitary to stimulate releasing peptides hormone replacement; Growth hormone SEQ ID
releasing the production and (GHRPs) are known to deficiency; Pediatric Growth Hormone NO: Z for
factor; Growth secretion of growth release growth Deficiency; Adult Growth Hormone particular
hormone hormone and exert a hormone (GH) in vivo Deficiency; Idiopathic Growth Hormone construct.
releasing trophic effect on the and in vitro by a direct Deficiency; Growth retardation; Prader-
hormone gland. action on receptors in Willi Syndrome; Prader-Willi Syndrome
(Sermorelin anterior pituitary cells. in children 2 years or older; Growth
acetate; Biological activity can deficiencies; Growth failure associated
Pralmorelin; be measured in cell with chronic renal insufficiency;
Somatorelin; lines expressing growth Osteoporosis; Osteopenia,
Somatoliberin; hormone releasing Osteoclastogenesis; Postmenopausal
Geref; Gerel; factor receptor (Mol osteoporosis; burns; Cachexia; Cancer
Groliberin) Endocrinol 1992 Cachexia; Dwarfism; Metabolic
Oct; 6(10): 1734-44, Disorders; Obesity; Renal failure;
Molecular Turner's Syndrome; Fibromyalgia;
Endocrinology, Vol 7, Fracture treatment; Frailty, AIDS
77-84). wasting; Muscle Wasting; Short Stature;
Diagnostic Agents; Female Infertility;
lipodystrophy.
IL-2 Promotes the growth T cell proliferation Cancer; Solid Tumors; Metastatic Renal 1757, 1758, 1812, See Table 2,
(Aldesleukin; of B and T cells and assay “Biological Cell Carcinoma; Metastatic Melanoma; 1813, 1952, 1954, SEQ ID
interleukin-2 augments NK cell activity of recombinant Malignant Melanoma; Melanoma; Renal 2030, and 2031. NO: Z for
fusion toxin; T and CTL cell killing human interleukin-2 Cell Carcinoma; Renal Cancer; Lung particular
cell growth activity. produced in Cancer (e.g,. Non-Small Cell Lung construct.
factor; Escherichia coli. Cancer or Small Cell Lung Cancer);
PROLEUKIN; Science 223: 1412-1415, Colon Cancer; Breast Cancer; Liver
IMMUNACE; 1984. natural Cancer; Leukemia; Preleukemia;
CELEUK; killer (NK) cell and Hematological Malignancies;
ONCOLIPIN CTL cytotoxicity assay Hematological Disorders; Acute Myeloid
2; “Control of Leukemia; Melanoma; Malignant
MACROLIN) homeostasis of CD8+ Melanoma; Non-Hodgkin's Lymphoma;
memory T cells by Ovarian Cancer; Prostate Cancer; Brain
opposing cytokines. Cancer; Glioma; Glioblastoma
Science 288: 675-678, Multiforme; Hepatitis; Hepatitis C;
2000; CTLL-2 Lymphoma; HIV Infection (AIDS);
Proliferation: Gillis et Inflammatory Bowel Disorders; Kaposi's
al (1978) J. Immunol. Sarcoma; Multiple Sclerosis; Arthritis;
120, 2027 Rheumatoid Arthritis; Transplant
Rejection; Diabetes; Type 1 Diabetes
Mellitus; Type 2 Diabetes.
Parathyroid Acts in conjuction Adenylyl cyclase Bone Disorders; Fracture prevention; 1749, 1750, 1853, See Table 2,
hormone; with calcitonin to stimulation in rat Hypercalcemia; Malignant 1854, 1889, 1906, SEQ ID
parathyrin control calcium and osteosarcoma cells, hypercalcemia; Osteoporosis; Paget's 1907, 1914, 1932, NO: Z for
(PTH; phosphate ovariectomized rat disease; Osteopenia, Osteoclastogenesis; 1938, 1941, 1949, particular
Ostabolin; metabolism; elevates model of osteoporosis: osteolysis; osteomyelitis; osteonecrosis; 2021, 2022, 2023, construct.
ALX1-11; blood calcium level; IUBMB Life 2000 periodontal bone loss; osteoarthritis; 2428, 2714, 2791,
hPTH 1-34; stimulates the activity Feb; 49(2): 131-5 rheumatoid arthritis; osteopetrosis; 2965, 2966.
LY 333334; of osteocytes; periodontal, lytic, or metastatic bone
MN 10T; enhances absorption disease; osteoclast differentiation
parathyroid of Ca+/Pi from small inhibition; bone disorders; bone healing
hormone (1-31); intestine into blood; and regeneration.
FORTEO; promotes
PARATHAR) reabsorption of Ca+
and inhibits Pi by
kidney tubules.
Resistin Mediates insulin Ability of resistin to Hyperglycemia; Diabetes; Diabetes 2295, 2296, 2297, See Table 2,
resistance in Type II influence type II Insipidus; Diabetes mellitus; Type 1 2300, and 2309. SEQ ID
diabetes; inhibits diabetes can be diabetes; Type 2 diabetes; Insulin NO: Z for
insulin-stimulated determined using resistance; Insulin deficiency; particular
glucose uptake assays known in the Hyperlipidemia; Hyperketonemia; Non- construct.
art: Pontoglio et al., J insulin dependent Diabetes Mellitus
Clin Invest 1998 May (NIDDM); Insulin-dependent Diabetes
15; 101(10): 2215-22. Mellitus (IDDM); A Condition
Associated With Diabetes Including,
But Not Limited To Obesity, Heart
Disease, Hyperglycemia, Infections,
Retinopathy, And/Or Ulcers; Metabolic
Disorders; Immune Disorders; Obesity;
Vascular Disorders; Suppression of
Body Weight; Suppression of Appetite;
Syndrome X.
TR6 (DcR3; Inhibits Fas Ligand Cellular apoptosis can Fas Ligand or LIGHT induced 1520, 1537, 1545, See Table 2,
Decoy and AIM-2 (TL5, be measured by apoptotic disorders: hepatitis; liver 1546, 1568, 1570, SEQ ID
Receptor 3; LIGHT) mediated annexin staining, failure (including fulminant liver 1622, 1623, 1645, NO: Z for
FASTR) apoptosis. TUNEL staining, failure); graft versus host disease; graft 1700, 1702, 1703, particular
measurement of rejection; myelodysplastic syndrome; 1704, 1891, 1892, construct.
caspase levels. renal failure; insulin dependent 1912, and 1913.
Inhibition of cell diabetes mellitus; rheumatoid arthritis;
growth can also be inflammatory bowel disease;
directly measured, for autoimmune disease; toxic epidermal
example by ALOMAR necrolysis; multiple sclerosis.
Blue staining. Assay
refs: cytotoxicity assay
on human
fibrosarcoma (Epsevik
and Nissen-Meyer,
1986, J. Immunol.
methods).
DeCAF (D- Inhibits DeCAF activity can be B cell and/or T cell mediated immune 1657. See Table 2,
SLAM; proliferation and determined using disorders; Immunodeficiency (e.g., SEQ ID
BCM-like differentiation of B assays known in the Common Variable Immunodeficiency, NO: Z for
membrane cells; Antagonize art, such as for Selective IgA Deficiency) particular
protein; BLyS activity example, those construct.
BLAME (B described in Examples
lymphocyte 32-33 of International
activator Publication No.
macrophage WO0111046.
expressed))
BLyS (B Promotes BLyS activity can be B cell and/or T cell mediated immune 1680, 2095, See Table 2,
Lymphocyte proliferation, determined using disorders, particularly immune system and 2096. SEQ ID
Stimulator; differentiation and assays known in the disorders associated with low B cell NO: Z for
Neutrokine survival of B cells; art, such as, for numbers or low serum particular
alpha; TL7; Promotes example, the immunoglobulin; Immunodeficiency construct.
BAFF; immunoglobulin costimulatory (e.g., Common Variable
TALL-1; production by B proliferation assay and Immunodeficiency, Selective IgA
THANK; cells. other assays disclosed Deficiency). Radiolabeled forms:
radiolabeled by Moore et al., 1999, lymphoma, non-Hodgkins lymphoma,
BLyS) Science, chronic lymphocytic leukemia,
285(5425): 260-3. multiple myeloma.
Anti-BLyS Agonize or BLyS agonist or B cell and/or T cell mediated immune 1821, 1956, 2501, See Table 2,
single chain antagonize BlyS antagonist activity can disorders; Autoimmune disorders, 2502, 2638. SEQ ID
antibody activity. be determined using particularly autoimmune diseases NO: Z for
(scFvI116A01, assays known in the associated with the production of particular
scFvI050B11, art, such as, for autoantibodies; Rheumatoid Arthritis, construct.
scFvI006D08) example, a modified Systemic Lupus Erythmatosus;
and others. version the Sjögren's Syndrome, cancers
costimulatory expressing Blys as an autocrine growth
proliferation assay factor, e.g. certain chronic lymphocytic
disclosed by Moore et leukemias.
al., 1999, Science,
285(5425): 260-3, in
which BlyS is mixed
or preincubated with
the anti-BlyS antibody
prior to being applied
to the responder B
lymphocytes.
MPIF-1 Inhibits myeloid MPIF-1 activity can be Chemoprotection; Adjunct to 1681, 3166, 3167, See Table 2,
(Myeloid progenitor cells; measured using the Chemotherapy; Inflammatory 3168, SEQ ID
Progenitor and activates myeloprotection assay disorders; Cancer; Leukemia; NO: Z for
Inhibitory monocytes and chemotaxis assay Myelocytic leukemia; Neutropenia, particular
Factor; CK described in U.S. Pat. Primary neutropenias (e.g.; Kostmann construct.
beta-8; No. 6,001,606. syndrome); Secondary neutropenia;
Mirostipen) Prevention of neutropenia; Prevention
and treatment of neutropenia in HIV-
infected patients; Prevention and
treatment of neutropenia associated
with chemotherapy; Infections
associated with neutropenias;
Myelopysplasia; Autoimmune
disorders; Psoriasis; Mobilization of
hematopoietic progenitor cells; Wound
Healing; Autoimmune Disease;
Transplants; Bone marrow transplants;
Acute myelogeneous leukemia;
Lymphoma, Non-Hodgkin's
lymphoma; Acute lymphoblastic
leukemia; Hodgkin's disease;
Accelerated myeloid recovery;
Glycogen storage disease.
KDI Inhibits bone KDI activity can be Multiple sclerosis; Hepatitis; Cancer; 1746. See Table 2,
(Keratinocyte marrow measured using the Viral infections, HIV infections, SEQ ID
Derived proliferation; and antiviral and cell Leukemia. NO: Z for
Interferon; shows antiviral proliferation assays particular
Interferon activity. described in Examples construct.
Kappa 57-63 of International
Precursor) Publication No.
WO0107608.
TNFR2 (p75) Binds both TNFa T-cell proliferation can Autoimmune disease; Rheumatoid 1777 and 1784. See Table 2,
(ENBREL) and TNFb; be measured using Arthritis; Psoriatic arthritis; Still's SEQ ID
mediates T-cell assays known in the Disease; Ankylosing Spondylitis; NO: Z for
proliferation by art. For example, Cardiovascular Diseases; Vasulitis; particular
TNF; reduces signs “Lymphocytes: a Wegener's granulomatosis; construct.
and structural practical approach” Amyloidosis; Systemic Lupus
damage in patients edited by: SL Rowland, Erythematosus, Insulin-Dependent
with moderately to AJ McMichael - Diabetes Mellitus; Immunodeficiency
severly active chapter Disorders; Infection; Inflammation;
rheumatoid arthritis 6, pages 138-160 Inflammatory Bowel Disease; Chrohn's
(RA). Oxford University Disease; Psoriasis; AIDS; Graft
Press (2000); and Rejection; Graft Versus Host Disease.
“Current Protocols on
CD-ROM” section
3.12 Proliferation
Assays for T-cell
Function John Wiley
&Soncs, Inc. (1999).
Keratinocyte Stimulates KGF-2 activity can be Stimulate Epithelial Cell Proliferation; 1785, 1786, 1916, See Table 2,
growth factor 2 epithelial cell measured using the Stimulate Basal Keratinocytes; Wound 1917, 2498, 2499, SEQ ID
(Repifermin; growth. wound healing assays Healing; Stimulate Hair Follicle 2552, 2553, 2584, NO: Z for
KGF-2; and epithelial cell Production; Healing Of Dermal 2607, 2608, 2606, particular
Fibroblast proliferation assays Wounds. Wound Healing; Eye Tissue 2630 construct.
Growth described in U.S. Pat. Wounds, Dental Tissue Wounds, Oral
Factor-10; No. 6,077,692. Cavity Wounds, Diabetic Ulcers,
FGF-10) Dermal Ulcers, Cubitus Ulcers,
Arterial Ulcers, Venous Stasis Ulcers,
Burns Resulting From Heat Exposure
Or Chemicals, or Other Abnormal
Wound Healing Conditions such as
Uremia, Malnutrition, Vitamin
Deficiencies or Complications
Associated With Systemic Treatment
With Steroids, Radiation Therapy or
Antineoplastic Drugs or
Antimetabolites; Promote Dermal
Reestablishment Subsequent To
Dermal Loss; Increase the Adherence
Of Skin Grafts To A Wound Bed;
Stimulate Re-Epithelialization from
The Wound Bed; To Promote Skin
Strength; Improve The Appearance Of
Aged Skin; Proliferate Hepatocytes,
Lung, Breast, Pancreas, Stomach,
Bladder, Small Intestine, Large
Intestine; Sebocytes, Hair Follicles,
Type II Pneumocytes, Mucin-
Producing Goblet Cells, or Other
Epithelial Cells, Endothelial Cells,
Keratinocytes, or Basal Keratinocytes
(and Their Progenitors) Contained
Within The Skin, Lung, Liver, Bladder,
Eye, Salivary Glands, or
Gastrointestinal Tract; Reduce The
Side Effects Of Gut Toxicity That
Result From Radiation, Chemotherapy
Treatments Or Viral Infections;
Cytoprotector, especially of the Small
Intestine Mucosa or Bladder; Mucositis
(Mouth Ulcers); Regeneration Of Skin;
Full and/or Partial Thickness Skin
Defects, including Burns, (e.g.,
Repopulation Of Hair Follicles, Sweat
Glands, And Sebaceous Glands);
Psoriasis; Epidermolysis Bullosa;
Blisters; Gastric and/or Doudenal
Ulcers; Reduce Scarring;
Inflamamatory Bowel Diseases;
Crohn's Disease; Ulcerative Colitis;
Gut Toxicity; Lung Damage; Repair Of
Alveoli And/or Brochiolar Epithelium;
Acute Or Chronic Lung Damage;
Emphysema, ARDS; Inhalation
Injuries; Hyaline Membrane Diseases;
Infant Respiratory Distress Syndrome;
Bronchopulmonary Displasia In
Premature Infants; Fulminant Liver
Failure; Cirrhosis, Liver Damage
caused by Viral Hepatitis and/or Toxic
Substances; Diabetes Mellitus;
Inflammation.
TR2 (and Inhibits B cell Co-stimulation B-cell Herpes; immune disorders; 1788 and 2129. See Table 2,
TR2sv1, proliferation, and proliferation assay and autoimmune disease; graft versus host SEQ ID
TR2SV2; mediates and Ig production assay disease; graft rejection; variable NO: Z for
TNFRSF14; inhibits Herpes (Moore et al., 1999, immunodeficiency; immunodeficiency particular
HVEM; Simplex Virus Science, syndromes; cancer. construct.
Herpes Virus (HSV) infection. 285(5425): 260-3.).
Entry HSV-1 and HSV-2
Mediator; Infectivity Assay:
ATAR) International
Publication No. WO
97/04658
Macrophage Chemotactic for Chemokine activities Inflammatory diseases; wound healing; 1809, 2137, 2474, See Table 2,
derived monocyte-derived can be determined angiogenesis; AIDS infection. 2475, 2476, SEQ ID
chemokine, dendritic cells and using assays known in and 2477. NO: Z for
MDC IL-2-activated the art: Methods in particular
(Ckbeta-13) natural killer cells. Molecular Biology, construct.
2000, vol. 138:
Chemokine Protocols.
Edited by: A. E. I.
Proudfoot,
T. N. C. Wells,
and C. A. Power.
© Humana
Press Inc., Totowa, NJ
HAGDG59 Activates MIP1a Dendritic cell assays Immune disorders; cancer; viral 1830 and 1831. See Table 2,
(Retinal release in Dendritic are well known in the infection; inflammation; sepsis; SEQ ID
short-chain Cells. art. For example, J. arthritis; asthma. NO: Z for
dehydrogenase) Immunol. 158: particular
2919-2925 (1997); J. construct.
Leukoc. Biol. 65:
822-828 (1999).
GnRH Promotes release of GnRH is known to Infertility; Kallmann's syndrome or 1862 and 1863. See Table 2,
(Gonadotropin follicle-stimulating cause the release of other forms of hypergonadotropic SEQ ID
Releasing hormone and follicle stimulating hypergonadism (failure to go through NO: Z for
Hormone) luteinizing hormone hormone (FSH) and/or puberty naturally). particular
from anterior luteinizing hormone construct.
pituitary. (LH) in vivo by a
direct action on
receptors in anterior
pituitary gonadotropes.
GnRH activity can be
determined by
measuring FSH levels
in the medium of
cultured gonadotropes
before and after GnRH
supplementation. For
example, Baker et al.
Biol Reprod 2000
Sep; 63(3): 865-71.
Teprotide Inhibits angiotensin Inhibition of ACE can Hypertension; congestive heart failure. 1866, 1867, 2025, See Table 2,
converting enzyme be determined using and 2026. SEQ ID
(ACE). assays known in the NO: Z for
art. For example, particular
Anzenbacherova et al., construct.
J.Pharma Biomed Anal
2001 Mar; 24(5-6):
1151-6.
Human Involved in Chemokine activities Autoimmune disorders; Immunity; 1933, 1934, 1947, See Table 2,
chemokine inflammation, can be determined Vascular and Inflammatory disorders; 1948, 1955, 1998, SEQ ID
HCC-1 allergy, tissue using assays known in HIV; AIDS; infectious diseases. 2355, 2412, 2449, NO: Z for
(ckBeta-1; rejection, viral the art: Methods in 2837, 2838, 2839, particular
HWFBD) infection, and Molecular Biology, 2840, 2841, 2842, construct.
tumor biology; 2000, vol. 138: 2843, 2844, 2845,
enhances Chemokine Protocols. 2849, 2947, 3066,
proliferation of Edited by: A. E. I. 3105, 3124, 3125,
CD34+ myeloid Proudfoot, T. N. C. 3139, 3152, 3153,
progenitor cells. Wells, and C. A. Power. 3154, 3155, 3156,
© Humana 3169, 3170, 3202,
Press Inc., Totowa, NJ 3203, 3204, 3205,
3206, 3207, 3272
ACE2 Inhibits production Inhibition of Treatment for elevated angiotensin II 1989, 2000, 2001, See Table 2,
inhibitor of angiotensin II angiotensin can be and/or aldosterone levels, which can and 2002. SEQ ID
(DX512) which induces determined using lead to vasoconstriction, impaired NO: Z for
aldosterone assays known in the cardiac output and/or hypertension; particular
production, art. For example, in Cardiovascular Disease; Cardiac construct.
arteriolar smooth vitro using a Failure; Diabetes; Type II Diabetes;
muscle proliferation assay with Proteinuria; Renal disorders,
vasoconstriction, rat cardiac fibroblasts congestive heart failure.
and proliferation of as described in Naunyn
cardiac fibroblasts, Schmiedebergs Arch
Induces Pharmacol 1999
angiogenesis; an May; 359(5): 394-9.
enzyme that
converts
angiotensin I to
angiotensin1-9; also
cleaves des-Arg,
bradykinin and
neurotensin.
TR1 (OCIF; Inhibits Coculture Assay for Osteoporosis; Paget's disease; 2016, 2017, 2085, See Table 2,
Osteoclastogenesis osteoclastogenesis Osteoclastogenesis, osteopenia; osteolysis; osteomyelitis; 2086, 2529, 2530, SEQ ID
inhibitory and bone Bone resorption assay osteonecrosis; periodontal bone loss; 2531, 2532, 2555, NO: Z for
factor; resorption, and using fetal long-bone osteoarthritis; rheumatoid arthritis; 2556, 2557, particular
osteoprotegerin, induces fibroblast organ culture system, osteopetrosis; periodontal, lytic, or and 2558. construct.
OPG; proliferation. dentine resorption metastatic bone disease; osteoclast
tumor assay, and fibroblast differentiation inhibition; bone
necrosis proliferation assays are disorders; bone healing and
factor each described in regeneration; organ calcification;
receptor Kwon et al., FASEB J. vascular calcification.
superfamily 12: 845-854 (1998).
member 11B
precursor;)
Human Chemotactic for Chemokine activities Cancer; Wound healing; Inflammatory 2101, 2240, 2241, See Table 2,
chemokine both activated can be determined disorders; Immmunoregulatory 2245, 2246, 2247, SEQ ID
Ckbeta-7 (CD3+) T cells and using assays known in disorders; Atherosclerosis; and 2248. NO: Z for
nonactivated the art: Methods in Parasitic Infection; Rheumatoid particular
(CD14−) Molecular Biology, Arthritis; Asthma; Autoimmune construct.
lymphocytes and 2000, vol. 138: disorders.
(CD4+) and Chemokine Protocols.
(CD8+) T Edited by: A. E. I.
lymphocytes and Proudfoot, T. N. C.
(CD45RA+) T cells Wells, and C. A. Power.
© Humana
Press Inc., Totowa, NJ
CKbeta4 Attracts and Chemokine activities Cancer; Solid Tumors; Chronic 2141, 2330, 2335, See Table 2,
(HGBAN46; activates can be determined Infection; Autoimmune Disorders; 2336, 2337, 2338, SEQ ID
HE9DR66) microbicidal using assays known in Psoriasis; Asthma; Allergy; and 2348. NO: Z for
leukocytes; Attracts the art: Methods in Hematopoiesis; Wound Healing; Bone particular
CCR6-expressing Molecular Biology, Marrow Failure; Silicosis; Sarcoidosis; construct.
immature dendritic 2000, vol. 138: Hyper-Eosinophilic Syndrome; Lung
cells and Chemokine Protocols. Inflammation; Fibrotic Disorders;
memory/effector T Edited by: A. E. I. Atherosclerosis; Periodontal diseases;
cells; B-cell Proudfoot, T. N. C. Viral diseases; Hepatitis.
chemotaxis; inhibits Wells, and C. A. Power.
proliferation of © Humana
myeloid Press Inc., Totowa, NJ
progenitors;
chemotaxis of
PBMC's.
Leptin Controls obesity in vivo modulation of Hyperglycemia; Diabetes; Diabetes 2146, 2184, 2186, See Table 2,
through regulation food intake, reduction Insipidus; Diabetes mellitus; Type 1 and 2187. SEQ ID
of appetite, in body weight, and diabetes; Type 2 diabetes; Insulin NO: Z for
reduction of body lowering of insulin and resistance; Insulin deficiency; particular
weight, and glucose levels in ob/ob Hyperlipidemia; Hyperketonemia; construct.
lowering of insulin mice, Non-insulin dependent Diabetes
and glucose level. radioimmunoassay Mellitus (NIDDM); Insulin-dependent
(RIA) and activation of Diabetes Mellitus (IDDM); a Condition
the leptin receptor in a Associated With Diabetes Including,
cell-based assay. But Not Limited To Obesity, Heart
Protein Expr Purif Disease, Hyperglycemia, Infections,
1998 Dec; 14(3): 335-42 Retinopathy, And/Or Ulcers; Metabolic
Disorders; Immune Disorders; Obesity;
Vascular Disorders; Suppression of
Body Weight; Suppression of Appetite;
Syndrome X; Immunological
Disorders; Immunosuppression.
IL-1 receptor Binds IL1 receptor 1) Competition for Autoimmune Disease; Arthritis; 2181, 2182, 2183, See Table 2,
antagonist without activating IL-1 binding to IL-1 Rheumatoid Arthritis; Asthma; and 2185. SEQ ID
(Anakinra; the target cells; receptors in YT-NCI or Diabetes; Diabetes Mellitus; GVHD; NO: Z for
soluble inhibits the binding C3H/HeJ cells (Carter Inflammatory Bowel Disorders; particular
interleukin-1 of IL1-alpha and et al., Nature 344: Chron's Disease; Ocular Inflammation; construct.
receptor; IL1-beta; and 633-638, 1990); Psoriasis; Septic Shock; Transplant
IRAP; neutralizes the 2) Inhibition of IL-1- Rejection; Inflammatory Disorders;
KINERET; biologic activity of induced endothelial Rheumatic Disorders; Osteoporosis;
ANTRIL) IL1-alpha and IL1- cell-leukocyte adhesion Postmenopausal Osteoporosis; Stroke.
beta. (Carter et al., Nature
344: 633-638, 1990);
3) Proliferation assays
on A375-C6 cells, a
human melanoma cell
line highly susceptible
to the antiproliferative
action of IL-1 (Murai T
et al., J. Biol. Chem.
276: 6797-6806, 2001).
TREM-1 Mediates activation Secretion of cytokines, Inflammation; Sepsis; bacterial 2226 and 2230. See Table 2,
(Triggering of neutrophil and chemokines, infection; autoimmune diseases; SEQ ID
Receptor monocytes; degranulation, and cell GVHD. NO: Z for
Expressed on Stimulates surface activation particular
Monocytes neutrophil and markers can be construct.
1) monocyte-mediated determined using
inflammatory assays described in
response; Promotes Bouchon et al, J
secretion of TNF, Immunol 2000 May
IL-8, and MCP-1; 15; 164(10): 4991-5.
Induces neutrophil
degranulation,
Ca2+ mobilization
and tyrosine
phosphorylation of
extracellular signal-
related kinase 1
(ERK1), ERK2 and
phospholipase C-
gamma.
HCNCA73 Induces T-cell FMAT can be used to Autoimmune disorders; Inflammation 2244 and 2365. See Table 2,
activation- measure T-cell surface of the gastrointestinal tract; Cancer; SEQ ID
expression of markers (CD69, Colon Cancer; Allergy; Crohn's NO: Z for
CD152 marker; CD152, CD71, HLA- disease. particular
Stimulates release DR) and T-cell construct.
of TNF-a and MIP- cytokine production
1a from immature, (e.g., IFNg
monocyte-derived production). J. of
dendritic cells; Biomol. Screen. 4:
Promotes 193-204 (1999). Other T-
maturation of cell proliferation
dendritic cells. assays: “Lymphocytes:
a practical approach”
edited by: SL Rowland,
AJ McMichael -
Chapter 6,
pages 138-160 Oxford
University Press
(2000); WO 01/21658
Examples 11-14, 16-17
and 33.
VEGF-2 Promotes VEGF activity can be Coronary artery disease; Critical limb 2251, 2252, 2256, See Table 2,
(Vascular endothelial cell determined using ischemia; Vascular disease; and 2257. SEQ ID
Endothelial proliferation. assays known in the proliferation of endothelial cells, both NO: Z for
Growth art, such as those vascular and lymphatic. Antagonists particular
Factor-2; disclosed in may be useful as anti-angiogenic construct.
VEGF-C) International agents; Cancer.
Publication No.
WO0045835, for
example.
HCHNF25 Activates MIP1a Dendritic cell assays Immune disorders; cancer. 2271, 2280, See Table 2,
(jumping Release in are well known in the and 2320. SEQ ID
translocation Dendritic Cells. art. For example, J. NO: Z for
breakpoint) Immunol. 158: particular
2919-2925 (1997); J. construct.
Leukoc. Biol. 65:
822-828 (1999).
HLDOU18 Activates L6/GSK3 Assays for activation Hyperglycemia; Diabetes; Diabetes 2328, 2340, 2350, See Table 2,
(Bone kinase assay. of GSK3 kinase Insipidus; Diabetes mellitus; Type 1 2351, 22359, SEQ ID NO: Z
Morphogenic activity are well diabetes; Type 2 diabetes; Insulin 2362, 2367, 2369, for particular
Protein 9 known in the art. For resistance; Insulin deficiency; 22370, 2473, construct.
(BMP9); example, Biol. Chem. Hyperlipidemia; Hyperketonemia; Non- 2623, 2624,
Growth 379(8-9): (1998) insulin dependent Diabetes Mellitus 2625, 2631,
differentiation 1101-1110.; Biochem (NIDDM); Insulin-dependent Diabetes 2632, 2633.
factor-2 J. 1993 Nov 15; 296 Mellitus (IDDM); A Condition
precursor (Pt 1): 15-9. Associated With Diabetes Including,
(GDF-2 But Not Limited To Obesity, Heart
precursor)) Disease, Hyperglycemia, Infections,
Retinopathy, And/Or Ulcers; Metabolic
Disorders; Immune Disorders; Obesity;
Vascular Disorders; Suppression of
Body Weight; Suppression of Appetite;
Syndrome X.
Glucagon- Stimulates the GLP1 activity may be Hyperglycemia; Diabetes; Diabetes 2448, 2455, 2456, See Table 2,
Like-Peptide 1 synthesis and release assayed in vitro using a Insipidus; Diabetes mellitus; Type 1 2457, 2803, 2804, SEQ ID
(GLP1; of insulin; enhances [3-H]-glucose uptake diabetes; Type 2 diabetes; Insulin 2900, 2904, 2945, NO: Z for
Insulinotropin) the sensitivity of assay. (J Biol Chem resistance; Insulin deficiency; 2964, 2982, 3070, particular
adipose, muscle, and 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- 2802, 3027, 3028, construct.
liver tissues towards 274(43): 30864-30873). insulin dependent Diabetes Mellitus 3045, 3046, 3069,
insulin; stimulates (NIDDM); Insulin-dependent Diabetes 3071, 3072, 3085,
glucose uptake; slows Mellitus (IDDM); A Condition 3086, 3087, 3140,
the digestive process; Associated With Diabetes Including, But 3309
suppresses appetite; Not Limited To Obesity, Heart Disease,
blocks the secretion Hyperglycemia, Infections, Retinopathy,
of glucagon. And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Exendin-4 Stimulates the Exendin-4 activity may Hyperglycemia; Diabetes; Diabetes 2469 and 2470. See Table 2,
(AC-2993) synthesis and release be assayed in vitro Insipidus; Diabetes mellitus; Type 1 SEQ ID
of insulin; enhances using a [3-H]-glucose diabetes; Type 2 diabetes; Insulin NO: Z for
the sensitivity of uptake assay. (J Biol resistance; Insulin deficiency; particular
adipose, muscle, and Chem 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- construct.
liver tissues towards 274(43): 30864-30873). insulin dependent Diabetes Mellitus
insulin; stimulates (NIDDM); Insulin-dependent Diabetes
glucose uptake; slows Mellitus (IDDM); A Condition
the digestive process; Associated With Diabetes Including, But
suppresses appetite; Not Limited To Obesity, Heart Disease,
blocks the secretion Hyperglycemia, Infections, Retinopathy,
of glucagon. And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
T20 (T20 HIV a peptide from Virus inhibition assays HIV; AIDS; SIV (simian 7777, 2672, 2673 See Table 2,
inhibitory residues 643-678 of as described in Zhang immunodeficiency virus) infection. SEQ ID
peptide, the HIV gp41 et al., Sept. 26 2002, NO: Z for
DP178; DP178 transmembrane Sciencexpress particular
HIV inhibitory protein ectodomain (www.sciencexpress.- construct.
peptide) which binds to gp41 org).
in its resting state and
prevents
transformation to the
fusogenic state
T1249 (T1249 a second generation Virus inhibition assays HIV; AIDS; SIV (simian 9999, 2667, 2670, See Table 2,
HIV inhibitory HIV fusion inbitor as described in Zhang immunodeficiency virus) infection 2946 SEQ ID
peptide; T1249 et al., Sept. 26 2002, NO: Z for
anti-HIV Sciencexpress particular
peptide) (www.sciencexpress.- construct.
Interferon Confers a range of org). Anti-viral assay: Viral infections; HIV Infections; 2875, 2872, 2876, See Table 2,
Hybrids, cellular responses Rubinstein S, Familletti Hepatitis; Chronic Hepatitis; Hepatitis B; 2874, 2873. SEQ ID
specifically including antiviral, PC, Pestka S. (1981) Chronic Hepatitis B; Hepatitis C; NO: Z for
preferred: antiproliferative, Convenient assay for Chronic Hepatitis C; Hepatitis D; particular
IFNalpha A/D antitumor and interferons. J. Virol. Chronic Hepatitis D; Human construct.
hybrid (BgIII immunomodulatory 37(2): 755-8; Anti- Papillomavirus; Herpes Simplex Virus
version) activities; stimulate proliferation assay: Infection; External Condylomata
IFNalpha A/D production of two Gao Y, et al (1999) Acuminata; HIV; HIV Infection;
hybrid (PvuII enzymes: a protein Sensitivity of an Oncology; Cancer; Solid Tumors;
version) kinase and an epstein-barr virus- Melanoma; Malignant Melanoma; Renal
IFNalpha A/F oligoadenylate positive tumor line, Cancer (e.g., Renal Cell Carcinoma);
hybrid synthetase. Also, Daudi, to alpha Lung Cancer (e.g., Non-Small Cell Lung
IFNalpha A/B modulates MHC interferon correlates Cancer or Small Cell Lung Cancer)
hybrid antigen expression, with expression of a Colon Cancer; Breast Cancer; Liver
IFNbeta NK cell activity and GC-rich viral Cancer; Prostate Cancer; Bladder
1/alpha D IFNg production and transcript. Mol Cell Cancer; Gastric Cancer; Sarcoma; AIDS-
hybrid IL12 production in Biol. 19(11): 7305-13. Related Kaposi's Sarcoma; Lymphoma;
(IFNbeta- monocytes. T Cell Lymphoma; Cutaneous T-Cell
1/alpha-1 Lymphoma; Non-Hodgkin's Lymphoma;
hybrid) Brain Cancer; Glioma; Glioblastoma
IFNalpha/beta Multiforme; Cervical Dysplasia;
hybrid Leukemia; Preleukemia; Bone Marrow
Disorders; Bone Disorders; Hairy Cell
Leukemia; Chronic Myelogeonus
Leukemia; Hematological Malignancies;
Hematological Disorders; Multiple
Myeloma; Bacterial Infections;
Chemoprotection; Thrombocytopenia;
Multiple Sclerosis; Pulmonary Fibrosis;
Age-Related Macular Degeneration;
Macular Degeneration; Crohn's Disease;
Neurological Disorders; Arthritis;
Rheumatoid Arthritis; Ulcerative Colitis;
Osteoporosis, Osteopenia,
Osteoclastogenesis; Fibromyalgia;
Sjogren's Syndrome; Chronic Fatigue
Syndrome; Fever; Hemmorhagic Fever;
Viral Hemmorhagic Fevers;
Hyperglycemia; Diabetes; Diabetes
Insipidus; Diabetes mellitus; Type 1
diabetes; Type 2 diabetes; Insulin
resistance; Insulin deficiency;
Hyperlipidemia; Hyperketonemia; Non-
insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
B-type stimulates smooth Inhibition of Congestive heart failure; cardiac volume 3119, 8888. See Table 2,
natriuretic muscle relaxation angiotensin can be overload; cardiac decompensation; SEQ ID
peptide (BNP, and vasodilation, determined using Cardiac Failure; Left Ventricular NO: Z for
brain natriuresis, and assays known in the art, Dysfunction; Dyspnea particular
natriuretic suppression of renin- for example using an in construct.
peptide) angiotensin and vitro proliferation assay
endothelin. with rat cardiac
fibroblasts as described
in Naunyn
Schmiedebergs Arch
Pharmacol 1999
May; 359(5): 394-9.
Vasodilation can be
measured in animals by
measuring the
myogenic responses of
small renal arteries in
an isobaric arteriograph
system (see Am J
Physiol Regul Integr
Comp Physiol 2002
Aug; 283(2): R349-
R355). Natriuesis is
determined by
measuring the amount
of sodium in the urine.
α-defensin, Suppression of HIV Virus inhibition assays HIV, AIDS; ARC. 3208, 3209, 3210. See Table 2,
including replication; active as described in Zhang SEQ ID
alpha 1 against bacteria, et al., Sep. 26, 2002, NO: Z for
defensin, alpha fungi, and enveloped Sciencexpress particular
2 defensin, viruses. (www.sciencexpress.- construct.
alpha 3 org).
defensin
(myeloid-
related
defensin;
DEFA1;
neutrophil-
specific
defensin;
CAF)
Phosphatonin Regulation of Blood phosphate levels Hyperphosphatemia; Hyperphosphatemia 3238. See Table 2,
(matrix phosphate can be measured using in chronic renal failure; SEQ ID
extracellular metabolism. methods known in the hypophosphatemia; Osteomalacia; NO: Z for
phospho- art such as the Rickets; X-linked dominant particular
glycoprotein; Hypophosphatemic Rat hypophosphatemic rickets/osteomalacia construct.
MEPE) Bioassay. Zoolog Sci (XLH); autosomal dominant
1995 Oct; 12(5): 607-10. hypophosphatemic rickets/osteomalacia
(ADHR); tumor-induced
rickets/osteomalacia (TIO).
P1pal-12 Regulation of Platelet aggregation can Protection against systemic platelet 3274. See Table 2,
(pepducin, protease-activated be measured using activation, thrombus, heart attack, stroke, SEQ ID
PAR1-based receptor (PAR) signal methods known in the and/or coagulation disorders. NO: Z for
pepducin) transduction and art such as described in particular
thrombin-mediated Nature Medicine 2002 construct.
aggregation of human Oct; 8(10): 1161-1165.
platelets.
P4pal-10 Regulation of Platelet aggregation can Protection against systemic platelet 3275. See Table 2,
(pepducin, protease-activated be measured using activation, thrombus, heart attack, stroke, SEQ ID
PAR4-based receptor (PAR) signal methods known in the and/or coagulation disorders. NO: Z for
pepducin) transduction and art such as described in particular
thrombin-mediated Nature Medicine 2002 construct.
aggregation of human Oct; 8(10): 1161-1165.
platelets.
HRDFD27 Involved in the T-cell proliferation can Chemoprotection; Adjunct to 2361 See Table 2,
proliferation of T be measured using Chemotherapy; Inflammatory disorders; SEQ ID
cells; Production of assays known in the art. Cancer; Leukemia; Myelocytic leukemia; NO: Z for
TNFgamma. For example, Neutropenia, Primary neutropenias (e.g.; particular
“Lymphocytes: a Kostmann syndrome); Secondary construct.
practical approach” neutropenia; Prevention of neutropenia;
edited by: SL Rowland, Prevention and treatment of neutropenia
AJ McMichael - in HIV-infected patients; Prevention and
chapter 6, pages 138-160 treatment of neutropenia associated with
Oxford University chemotherapy; Infections associated with
Press (2000); and neutropenias; Myelopysplasia;
“Current Protocols on Autoimmune disorders; Psoriasis;
CD-ROM” section 3.12 Mobilization of hematopoietic
Proliferation Assays for progenitor cells; Wound Healing;
T-cell Function John Autoimmune Disease; Transplants; Bone
Wiley & Soncs, Inc. marrow transplants;Acute
(1999). myelogeneous leukemia; Lymphoma,
Non-Hodgkin's lymphoma; Acute
lymphoblastic leukemia; Hodgkin's
disease; Accelerated myeloid recovery;
Glycogen storage disease
HWHGZ51 Stimulates an The ability to affect Skeletal diseases and disorders; 2407, 2408 See Table 2,
(CD59; immune response and chondrocyte Musculoskeletal diseases and disorders; SEQ ID
Metastasis- induces inflammation differentiation can be Bone fractures and/or breaks; NO: Z for
associated by inducing measured using Osteoporosis (postmenopausal, senile, or particular
GPI-adhered mononuclear cell, methods known in the idiopathic juvenile); Gout and/or construct.
protein eosinophil and PMN art, such as described in pseudogout; Paget's disease;
homolog) infiltration; Inhibits Bone (1995) Sep; Osteoarthritis; Tumors and/or cancers of
growth of breast 17(3): 279-86. the bone (osteochondromas, benign
cancer, ovarian chondromas, chondroblastomas,
cancer, leukemia, and chondromyxoid fibromas, osteoid
melanoma; osteomas, giant cell tumors, multiple
Overexpressed in myelomas, osteosarcomas,
colon, lung, breast fibrosarcomas, malignant fibrous
and rectal tumors; histiocytomas, chondrosarcomas,
Regulates glucose Ewing's tumors, and/or malignant
and/or FFA update by lymphomas); Bone and joint infections
adipocytes and (osteomyelitits and/or infectious
skeletal muscle; arthritis); Charcot's joints; Heel spurs;
Induces Sever's disease; Sport's injuries; Cancer;
redifferentiation of Solid Tumors; Melanoma; Malignant
chondrocytes Melanoma; Renal Cancer (e.g., Renal
Cell Carcinoma); Lung Cancer (e.g,.
Non-Small Cell Lung Cancer or Small
Cell Lung Cancer) Colon Cancer; Breast
Cancer; Liver Cancer; Prostate Cancer;
Bladder Cancer; Gastric Cancer;
Sarcoma; AIDS-Related Kaposi's
Sarcoma; Lymphoma; T Cell
Lymphoma; Cutaneous T-Cell
Lymphoma; Non-Hodgkin's Lymphoma;
Brain Cancer; Glioma; Glioblastoma
Multiforme; Cervical Dysplasia;
Leukemia; Preleukemia; Bone Marrow
Disorders; Bone Disorders; Hairy Cell
Leukemia; Chronic Myelogeonus
Leukemia; Hematological Malignancies;
Hematological Disorders; Multiple
Myeloma; Kidney diseases and
disorders; Shonlein-Henoch purpura,
Berger disease, celiac disease, dermatitis
herpetiformis, Chron disease; Diabetes;
Diabetes Insipidus; Diabetes mellitus;
Type 1 diabetes; Type 2 diabetes; Insulin
resistance; Insulin deficiency;
Hyperlipidemia; Hyperketonemia; Non-
insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Kidney disorders; Hyperinsulinemia;
Hypoinsulinemia; Immunological
disorders (e.g. arthritis, asthma,
immunodeficiency diseases, AIDS,
rheumatoid arthritis, granulomatous
disease, inflammatory bowl disease,
sepsis, acne, neutropenia, neutrophilia,
psoriasis, hypersensitivities, T-cell
mediated cytotoxicity, host-versus-graft
disease, autoimmunity disorders,
demyelination, systemic lupus
erythematosis, drug induced hemolytic
anemia, rheumatoid arthritis, Sjorgren's
disease, scleroderma)
C17 (cytokine- Inhibits glucose Proliferation of kidney Kidney diseases and disorders; Shonlein- 2489, 2490 See Table 2,
like protein and/or FFA uptake by mesangial cells can be Henoch purpura, Berger disease, celiac SEQ ID
C17) adipocytes; Induces assayed using disease, dermatitis herpetiformis, Chron NO: Z for
proliferation of techniques described in disease; Diabetes; Diabetes Insipidus; particular
kidney mesangial J. Investig. Med. (1998) Diabetes mellitus; Type 1 diabetes; Type construct.
cells; Regulation of Aug; 46(6): 297-302. 2 diabetes; Insulin resistance; Insulin
cytokine production deficiency; Hyperlipidemia;
and antigen Hyperketonemia; Non-insulin dependent
presentation Diabetes Mellitus (NIDDM); Insulin-
dependent Diabetes Mellitus (IDDM); A
Condition Associated With Diabetes
Including, But Not Limited To Obesity,
Heart Disease, Hyperglycemia,
Infections, Retinopathy, And/Or Ulcers;
Metabolic Disorders; Immune Disorders;
Obesity; Vascular Disorders;
Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Kidney disorders; Hyperinsulinemia;
Hypoinsulinemia; Hematopoietic
disorders; Immunological diseases and
disorders; Developmental diseases and
disorders; Hepatic diseases and
disorders; Cancer (particularly
leukemia); Immunological disorders (e.g.
arthritis, asthma, immunodeficiency
diseases, AIDS, rheumatoid arthritis,
granulomatous disease, inflammatory
bowl disease, sepsis, acne, neutropenia,
neutrophilia, psoriasis, hypersensitivities,
T-cell mediated cytotoxicity, host-
versus-graft disease, autoimmunity
disorders, demyelination, systemic lupus
erythematosis, drug induced hemolytic
anemia, rheumatoid arthritis, Sjorgren's
disease, scleroderma)
HDPBQ71 Regulates production Such assays that may Blood disorders and infection (e.g., viral 2515, 2545 See Table 2,
and secretion of be used or routinely infections, tuberculosis, infections SEQ ID
IFNgamma; modified to test associated with chronic granulomatosus NO: Z for
Activation of immunomodulatory disease and malignant osteoporosis); particular
myeloid cells and/or activity of polypeptides Autoimmune disease (e.g., rheumatoid construct.
hematopoietic cells of the invention arthritis, systemic lupus erythematosis,
(including antibodies multiple sclerosis); Immunodeficiency,
and agonists or boosting a T cell-mediated immune
antagonists of the response, and suppressing a T cell-
invention) include the mediated immune response;
assays disclosed in Inflammation and inflammatory
Miraglia et al., J disorders; Idiopathic pulmonary fibrosis;
Biomolecular Neoplastic diseases (e.g., leukemia,
Screening 4: 193-204 lymphoma, melanoma); Neoplasms and
(1999); Rowland et al., cancers, such as, for example, leukemia,
““Lymphocytes: a lymphoma, melanoma, and prostate,
practical approach”” breast, lung, colon, pancreatic,
Chapter 6: 138-160 esophageal, stomach, brain, liver and
(2000); Gonzalez et al., urinary cancer;. Benign dysproliferative
J Clin Lab Anal disorders and pre-neoplastic conditions,
8(5): 225-233 (1995); such as, for example, hyperplasia,
Billiau et al., Ann NY metaplasia, and/or dysplasia; Anemia;
Acad Sci 856: 22-32 Pancytopenia; Leukopenia;
(1998); Boehm et al., Thrombocytopenia; Hodgkin's disease;
Annu Rev Immunol Acute lymphocytic anemia (ALL);
15: 749-795 (1997), and Plasmacytomas; Multiple myeloma;
Rheumatology Burkitt's lymphoma; Arthritis; AIDS;
(Oxford) 38(3): 214-20 Granulomatous disease; Inflammatory
(1999) bowel disease; Sepsis; Neutropenia;
Neutrophilia; Psoriasis; Suppression of
immune reactions to transplanted organs
and tissues; Hemophilia;
Hypercoagulation; Diabetes mellitus;
Endocarditis; Meningitis; Lyme Disease;
Asthma; Allergy
Oscar Regulator of Assay to detect Skeletal diseases and disorders; 2571, 2749 See Table 2,
(osteoclast- osteoclast osteoclast Musculoskeletal diseases and disorders; SEQ ID
associated differentiation; differentiation is Bone fractures and/or breaks; NO: Z for
receptor regulator of innate described in J. Exp. Osteoporosis (postmenopausal, senile, or particular
isoform-3) and adaptive immune Med. (2002) Jan 21; idiopathic juvenile); Gout and/or construct.
responses 195(2): 201-9. pseudogout; Paget's disease;
Osteoarthritis; Tumors and/or cancers of
the bone (osteochondromas, benign
chondromas, chondroblastomas,
chondromyxoid fibromas, osteoid
osteomas, giant cell tumors, multiple
myelomas, osteosarcomas,
fibrosarcomas, malignant fibrous
histiocytomas, chondrosarcomas,
Ewing's tumors, and/or malignant
lymphomas); Bone and joint infections
(osteomyelitits and/or infectious
arthritis); Charcot's joints; Heel spurs;
Sever's disease; Sport's injuries
Tumstatin (T5, Inhibits angiogenesis; A tumor cell Cancer; Solid Tumors; Melanoma; 2647, 2648, 2649, See Table 2,
T7 or T8 Inhibits tumor proliferation assay is Malignant Melanoma; Renal Cancer 2650, 2943, 2944, SEQ ID
peptide; growth; Inhibits described in J. Biol. (e.g., Renal Cell Carcinoma); Lung 3047, 3048 NO: Z for
α3(IV)NC1) protein synthesis Chem. (1997) Cancer (e.g,. Non-Small Cell Lung particular
272: 20395-20401. Cancer or Small Cell Lung Cancer) construct.
Protein synthesis can be Colon Cancer; Breast Cancer; Liver
measured as described Cancer; Prostate Cancer; Bladder
in Science (2002) Jan Cancer; Gastric Cancer; Sarcoma; AIDS-
4; 295(5552): 140-3. Related Kaposi's Sarcoma; Lymphoma;
T Cell Lymphoma; Cutaneous T-Cell
Lymphoma; Non-Hodgkin's Lymphoma;
Brain Cancer; Glioma; Glioblastoma
Multiforme; Cervical Dysplasia;
Leukemia; Preleukemia; Bone Marrow
Disorders; Bone Disorders; Hairy Cell
Leukemia; Chronic Myelogeonus
Leukemia; Hematological Malignancies;
Hematological Disorders; Multiple
Myeloma; Angiogenesis
CNTF (Ciliary Enhances myelin Regulation of myelin Neurological and neural diseases and 2724, 2725, 3171, See Table 2,
neurotrophic formation; Reduces formation can be disorders, particularly diseases and 3172 SEQ ID
factor) photoreceptor assayed as described in disorders associated with myelin and NO: Z for
degredation; J. Neurosci. (2002) demyelination, such as, for example, particular
Regulates calcium Nov. 1; 22(21): 9221-7. ALS, multiple sclerosis, Huntington's construct.
currents disease; Neuronal and spinal cord
injuries; Disorders of the eye, such as,
for example, retinitis pigmentosa,
blindness, color-blindness, macular
degeneration.
Somatostatin Inhibits growth Inhibition of growth Cancer; Metastatic carcinoid tumors; 2798, 2825, 2830, See Table 2,
(Octreotide; hormone, glucagons hormone release in Vasoactive Intestinal Peptide secreting 2831, 2902 SEQ ID
octreotide and insulin; humans by adenomas; Diarrhea and Flushing; NO: Z for
acetate; Suppresses LF somatostatin can be Prostatic disorders and cancers; Breast particular
Sandostating response to GnRH; measured as described cancer; Gastrointestinal disorders and construct.
LAR ®) Decreases splanchnic in J. Clin. Endocrinol. cancers; Cancers of the endocrine
blood flow; Inhibits Metab. (1973) Oct; system; Head and neck paragangliomas;
release of serotonin, 37(4): 632-4. Liver disorders and cancers;
gastrin, vasoactive Inhibition of insulin Nasopharyngeal cancers; Thyroid
intestinal peptide, secretion by disorders and cancers; Acromegaly;
secretin, motilin, and somatostatin can be Carcinoid Syndrome; Gallbladder
pancreatic measured as described disorders, such as gallbladder
polypeptide. in the Lancet (1973) contractility diseases and abnormal bile
Dec. 8; 2(7841): secretion; Psoriasis; Diabetes; Diabetes
1299-1301. Insipidus; Diabetes mellitus; Type 1
diabetes; Type 2 diabetes; Insulin
resistance; Insulin deficiency;
Hyperlipidemia; Hyperketonemia; Non-
insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Kidney disorders; Neurological disorders
and diseases, including Alzheimers
Disease, Parkinson's disease and
dementia; Neuropsychotic disorders,
including Bipolar affective disorder;
Rheumatoid arthritis; Hypertension;
Intracranial hypertension; Esophageal
varices; Graves' disease; Seizures;
Epilepsy; Gastritis; Angiogenesis;
IL-22 (IL22, Stimulates glucose IL-22 activity may be Hyperglycemia; Diabetes; Diabetes 2901, 2903 See Table 2,
interleukin-22; uptake in skeletal assayed in vitro using a Insipidus; Diabetes mellitus; Type 1 SEQ ID
IL17D, IL27) muscle cells; [3-H]-glucose uptake diabetes; Type 2 diabetes; Insulin NO: Z for
increases skeletal assay. (J Biol Chem resistance; Insulin deficiency; particular
muscle insulin 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- construct.
sensitivity. 274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
HCE1P80 Stimulates glucose HCE1P80 activity may Hyperglycemia; Diabetes; Diabetes 2908, 3049, 3050, See Table 2,
uptake in; increases be assayed in vitro Insipidus; Diabetes mellitus; Type 1 3051, 3052 SEQ ID
insulin sensitivity, using a [3-H]-glucose diabetes; Type 2 diabetes; Insulin NO: Z for
uptake assay. (J Biol resistance; Insulin deficiency; particular
Chem 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- construct.
274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
HDRMI82 Stimulates glucose HDRMI82 activity may Hyperglycemia; Diabetes; Diabetes 2909 See Table 2,
uptake; increases be assayed in vitro Insipidus; Diabetes mellitus; Type 1 SEQ ID
insulin sensitivity. using a [3-H]-glucose diabetes; Type 2 diabetes; Insulin NO: Z for
uptake assay. (J Biol resistance; Insulin deficiency; particular
Chem 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- construct.
274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
HDALV07 Modulates insulin Insulin activity may be Diabetes; Diabetes Insipidus; Diabetes 3053, 3055, 3056 See Table 2,
(adiponectin; action assayed in vitro using a mellitus; Type 1 diabetes; Type 2 SEQ ID
gelatin-binding [3-H]-glucose uptake diabetes; Insulin resistance; Insulin NO: Z for
28k protein assay. (J Biol Chem deficiency; Hyperlipidemia; particular
precurson; 1999 Oct 22; Hyperketonemia; Non-insulin dependent construct.
adipose most 274(43): 30864-30873). Diabetes Mellitus (NIDDM); Insulin-
abundant gene dependent Diabetes Mellitus (IDDM); A
transcript; Condition Associated With Diabetes
APM-1; Including, But Not Limited To Obesity,
GBP28; Heart Disease, Hyperglycemia,
ACRP30; Infections, Retinopathy, And/Or Ulcers;
ADIPOQ) Metabolic Disorders; Immune Disorders;
Obesity; Vascular Disorders;
Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Hyperglycemia; Familial combined
hyperlipidemia; Metabolic syndrome;
Inflammatory disorders; Atherogenic
disorders
C Peptide An insulin precursor C-peptide Diabetes; Diabetes Insipidus; Diabetes 3088, 3149 See Table 2,
involved in insulin concentrations can be mellitus; Type 1 diabetes; Type 2 SEQ ID
regulation measured using assays diabetes; Insulin resistance; Insulin NO: Z for
well known in the art, deficiency; Hyperlipidemia; particular
such as the one Hyperketonemia; Non-insulin dependent construct.
described in PNAS Diabetes Mellitus (NIDDM); Insulin-
(1970) Sep; 67(1): dependent Diabetes Mellitus (IDDM); A
148-55 Condition Associated With Diabetes
Including, But Not Limited To Obesity,
Heart Disease, Hyperglycemia,
Infections, Retinopathy, And/Or Ulcers;
Metabolic Disorders; Immune Disorders;
Obesity; Vascular Disorders;
Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Hyperglycemia; Familial combined
hyperlipidemia; Metabolic syndrome
HCBOG68 Controls Activation of cAMP- Treatment of Obesity; treatment of 3106, 3270 See Table 2,
(enteric proliferation/ mediated transcription Diabetes; suppression of body weight SEQ ID
adipokine; Fat differentiation or in adipocytes can be gain; suppression of appetite. NO: Z for
SID; proline metabolism/ assayed using methods Hyperglycemia; Diabetes; Diabetes particular
rich acidic physiology/pathology/ known in the art Insipidus; Diabetes mellitus; Type 1 construct.
protein) of adipocytes and (Berger et al., Gene diabetes; Type 2 diabetes; Insulin
adipose tissue in 66: 1-10 (1998); Cullen resistance; Insulin deficiency;
response to dietary and Malm, Methods in Hyperlipidemia; Hyperketonemia; Non-
conditions. Enzymol 216: 362-368 insulin dependent Diabetes Mellitus
(1992); Henthorn et al., (NIDDM); Insulin-dependent Diabetes
Proc Natl Acad Sci Mellitus (IDDM); A Condition
USA 85: 6342-6346 Associated With Diabetes Including, But
(1988); Reusch et al., Not Limited To Obesity, Heart Disease,
Mol Cell Biol Hyperglycemia, Infections, Retinopathy,
20(3): 1008-1020 And/Or Ulcers; Metabolic Disorders;
(2000); and Klemm et Immune Disorders; Obesity; Vascular
al., J Biol Chem Disorders; Suppression of Body Weight;
273: 917-923 (1998)). Suppression of Appetite; Syndrome X.
Other indications for antibodies and/or
antagonists, include treatment of weight
loss; treatment of AIDS wasting; appetite
stimulant; treatment of cachexia.
PYY (Peptide Decreases appetite; Appetite and food Most preferred: Treatment of Obesity; 3108, 3109, 3281, See Table 2,
YY), including increases satiety; intake can be can be treatment of Diabetes; suppression of 3117, 3118, 3282. SEQ ID
PYY3-36 decreases food measured by methods body weight gain; suppression of NO: Z for
(amino acid intake. known in the art appetite. particular
residues 31-64 (Batterham et al. Hyperglycemia; Diabetes; Diabetes construct.
of full length Nature 2002; Insipidus; Diabetes mellitus; Type 1
PYY, amino 418: 650654) diabetes; Type 2 diabetes; Insulin
acid residues resistance; Insulin deficiency;
3-36 of mature Hyperlipidemia; Hyperketonemia; Non-
PYY) insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Other indications for antibodies,
antagonists: treatment of weight loss;
treatment of AIDS wasting; appetite
stimulant; treatment of cachexia.
WNT10b Inhibits adipogenesis. WNT10b activity can Most preferred: Treatment of Obesity; 3141 See Table 2,
be measured using suppression of body weight gain; SEQ ID
adipogenesis inhibition suppression of appetite. NO: Z for
assays (Ross et al., Other indications: Hyperglycemia; particular
Science 2000; Diabetes; Diabetes Insipidus; Diabetes construct.
289(5481): 950-953 mellitus; Type 1 diabetes; Type 2
diabetes; Insulin resistance; Insulin
deficiency; Hyperlipidemia;
Hyperketonemia; Non-insulin dependent
Diabetes Mellitus (NIDDM); Insulin-
dependent Diabetes Mellitus (IDDM).
WNT11 Promotes WNT11 activity can be Treatment of Cardiovascular disorders; 3142 See Table 2,
cardiogenesis. measured using assays Congestive Heart Failure; Myocardial SEQ ID
known in the art, Infarction. NO: Z for
including cardiogenesis particular
assays (Eisenberg et al., construct.
Dev Dyn 1999
Sep; 216(1): 45-58).
Herstatin Inhibits cancer Herstatin activity can Oncology; Cancer; Solid Tumors; 3143 See Table 2,
proliferation. be measured using cell Melanoma; Malignant Melanoma; Renal SEQ ID
proliferation assays Cancer (e.g., Renal Cell Carcinoma); NO: Z for
known in the art Lung Cancer (e.g,. Non-Small Cell Lung particular
(Doherty et al., PNAS Cancer or Small Cell Lung Cancer); construct.
1999; 96(19): Colon Cancer; Breast Cancer; Liver
10869-10874. Cancer; Prostate Cancer; Bladder
Cancer; Gastric Cancer; Sarcoma; AIDS-
Related Kaposi's Sarcoma; Lymphoma;
T Cell Lymphoma; Cutaneous T-Cell
Lymphoma; Non-Hodgkin's Lymphoma;
Brain Cancer; Glioma; Glioblastoma
Multiforme; Cervical Dysplasia;
Leukemia; Preleukemia; Hairy Cell
Leukemia; Chronic Myelogeonus
Leukemia; Hematological Malignancies;
Hematological Disorders; Multiple
Myeloma.
Adrenomedullin stimulates Vasodilation can be Treatment of Congestive Heart Failure; 3144 See Table 2,
vasodilation; measured using assays Hypertension; Myocardial Infarction; SEQ ID
promotes bone known in the art Septic Shock; Osteoporosis; NO: Z for
growth. (Ashton et al. Postmenopausal osteoporosis; particular
Pharmacology 2000; Osteopenia. construct.
61(2): 101-105. The
promotion of bone
growth can be
measured using assays
known in the art, such
as the osteoblast
proliferation assay
(Cornish et al. Am J
Physiol 1997
Dec; 273(6 Pt 1): E1113-
20).
Nogo Receptor Receptor for the axon The promotion of axon Treatment of Central Nervous System 3184, 3185 See Table 2,
growth inhibitor, regeneration and Damage; Spinal Cord Injury; Peripheral SEQ ID
Nogo. growth can be Nerve Damage; Neurodegenerative NO: Z for
measured using assays Diseases; Parkinson's Disease; particular
known in the art Alzheimer's Disease; Huntington's construct.
(Fournier et al. Nature Disease; Amyotrophic Lateral Sclerosis;
2001; 409(6818): Progressive Supranuclear Palsy;
341-346). Creutzfeld-Jacob Disease; Motor Neuron
Disease.
CART Inhibits food intact Appetite and food Most preferred: Treatment of Obesity; 3232 See Table 2,
(Cocaine- and and fat storage; intake can be can be suppression of body weight gain; SEQ ID
Amphetamine- promotes lipid measured by methods suppression of appetite. NO: Z for
Regulated oxidation. known in the art Other indications: Hyperglycemia; particular
Transcript) (Batterham et al. Diabetes; Diabetes Insipidus; Diabetes construct.
Nature 2002; mellitus; Type 1 diabetes; Type 2
418: 650654) diabetes; Insulin resistance; Insulin
deficiency; Hyperlipidemia;
Hyperketonemia; Non-insulin dependent
Diabetes Mellitus (NIDDM); Insulin-
dependent Diabetes Mellitus (IDDM).
RegIV (Colon Stimulates glucose RegIV activity may be Hyperglycemia; Diabetes; Diabetes 2910. See Table 2,
Specific Gene; uptake; increases assayed in vitro using a Insipidus; Diabetes mellitus; Type 1 SEQ ID
Colon Specific insulin sensitivity. [3-H]-glucose uptake diabetes; Type 2 diabetes; Insulin NO: Z for
Protein) assay. (J Biol Chem resistance; Insulin deficiency; particular
1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non- construct.
274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Cosyntropin Synthetic The activity of Endocrine; Addison's disease; Cushing's SEQ ID:
(Cortrosyn) corticotropin; cosyntropin can be syndrome; pituitary dysfunction; acute NO: 2198
(CAS-16960- stimulates the release assessed in vivo by adrenal crisis
16-0) of cortisol. measuring serum
cortisol levels. (Frank
et al. J. Am. Vet. Med.
Assoc. 1998
212(10): 1569-71).
Pexiganan Disrupts bacterial Pexiganan acetate Treatment of Infectious Diseases; SEQ ID NO:
Acetate membranes. activity can be assessed Treatment of Bacterial Infections. 2199
(CAS-172820- using in vitro
23-4) antibacterial assays
known in the art.
(Zasloff et al.,
Antimicrobial Agents
and Chemotherapy
1999, 43: 782-788).
Pramlintide Slows gastric Appetite and food Treatment of Obesity; treatment of SEQ ID NO:
(Amylin) emptying; decreases intake can be can be Diabetes; suppression of body weight 2200
(CAS-151126- food intake. measured by methods gain; suppression of appetite; treatment
32-8) known in the art of endocrine disorders;
(Batterham et al. Hyperglycemia; Diabetes; Diabetes
Nature 2002; Insipidus; Diabetes mellitus; Type 1
418: 650654) diabetes; Type 2 diabetes; Insulin
resistance; Insulin deficiency;
Hyperlipidemia; Hyperketonemia; Non-
insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Other indications for antibodies,
antagonists: treatment of weight loss;
treatment of AIDS wasting; appetite
stimulant; treatment of cachexia.
Teriparatide Acts in conjuction Adenylyl cyclase Bone Disorders; Fracture prevention; SEQ ID NO:
(CAS-52232- with calcitonin to stimulation in rat Hypercalcemia; Malignant 2201
67-4) control calcium and osteosarcoma cells, hypercalcemia; Osteoporosis; Paget's
phosphate ovariectomized rat disease; Osteopenia, Osteoclastogenesis;
metabolism; elevates model of osteoporosis: osteolysis; osteomyelitis; osteonecrosis;
blood calcium level; IUBMB Life 2000 periodontal bone loss; osteoarthritis;
stimulates the activity Feb; 49(2): 131-5 rheumatoid arthritis; osteopetrosis;
of osteocytes; periodontal, lytic, or metastatic bone
enhances absorption disease; osteoclast differentiation
of Ca+/Pi from small inhibition; bone disorders; bone healing
intestine into blood; and regeneration.
promotes
reabsorption of Ca+
and inhibits Pi by
kidney tubules.
Terlipressin Analog of Terlipressin activity Variceal hemorrhage; cirrhosis; portal SEQ ID NO:
(triglycyl vasopressin; induces can be measured using hypertension; hepatorenal syndrome; 2202
lycine vasoconstriction. assays of Blood-related disorders
vasopressin) vasoconstriction, such
(CAS-14636- as the isolated arterial
12-5) ring preparation.
(Landstrom et al., Hum
Reprod 1999
Jan; 14(1): 151-5).
Ularitide Stimulates Ularitide activity can be Excretory disorders; Acute renal failure; SEQ ID NO:
(CAS-118812- natriuresis, diuresis, assessed by measuring asthma; congestive heart failure; 2203
69-4) and vasodilation. cGMP accumulation in hypertension; pulmonary hypertension;
rat renal cells. cardiovascular disorders
(Valentin et al.,
Hypertension 1993
Apr; 21(4): 432-8).
Aprotinin Serine protease Inhibition of thrombin- Inhibition of fibrinolysis; reduction of SEQ ID NO:
(Trasylol) inhibitor; attenuates induced platelet blood loss during surgery; Treatment of 2204
(CAS-9087- Systemic aggregation can be Inflammation and Immune Disorders.
70-1; CAS- Inflammatory measured using
11061-94-2; Response, methods known in the
CAS-12407- fibrinolysis and art. (Poullis et al., J
79-3) thrombin-induced Thorac Cardiovasc
platelet aggregation. Surg 2000
Aug; 120(2): 370-8).
Aspartocin Antibacteria Aspartocin activity can Treatment of Infectious Diseases; SEQ ID NO:
(CAS-4117- be assessed using in treatment of bacterial infections. 2205
65-1; CAS- vitro antibacterial
1402-89-7) assays known in the art.
(Zasloff et al.,
Antimicrobial Agents
and Chemotherapy
1999, 43: 782-788).
Calcitonin Regulates levels of Hypocalcemic Rat Musculoskeletal; Osteroporosis; Paget's SEQ ID NO:
(Calcimar) calcium and Bioassay, bone disease; hypercalcemia; 2206
(CAS-21215- phosphate in serum; resorbing assay and the Bone Disorders; Fracture prevention;
62-3) causes a reduction in pit assay, CT receptor Malignant hypercalcemia; Osteopenia,
serum calcium--an binding assay, CAMP Osteoclastogenesis; osteolysis;
effect opposite to that stimulation assay: J osteomyelitis; osteonecrosis; periodontal
of human parathyroid Bone Miner Res 1999 bone loss; osteoarthritis; rheumatoid
hormone. Aug; 14(8): 1425-31 arthritis; osteopetrosis; periodontal, lytic,
or metastatic bone disease; osteoclast
differentiation inhibition; bone disorders;
bone healing and regeneration.
Carperitide Stimulates Carperitide activity can Treatment of Heart Failure; SEQ ID NO:
(HANP; natriuresis, diuresis, be assessed in vitro by Cardiovascular disorders; Respiratory 2207
recombinant and vasodilation. measuring cGMP disorders; Acute respiratory distress
human atrial accumulation in a syndrome.
natriuretic number of cell lines,
peptide) including PC12 cells
(CAS-89213- and cultured human
87-6) glomerular cells.
(Medvede et al., Life
Sci 2001 Aug
31; 69(15): 1783-90;
Green et al., J Am Soc
Nephrol 1994
Oct; 5(4): 1091-8).
Desirudin Inhibits thrombin; Desirudin activity can Blood-related disorder; Thrombosis; SEQ ID NO:
(recombinant inhibits blood be assessed using blood thrombocytopenia; hemorrhages. 2208
hirudin; clotting. clotting assays known
Revasc) in the art, such as in
(CAS-120993- vitro platelet
53-5) aggragation assays.
(Glusa, Haemostasis
1991; 21 Suppl 1:
116-20).
Emoctakin proinflammatory Treatment of Inflammation, Immune SEQ ID NO:
(interleukin 8) cytokine disorders, RSV infection. 2209
(CAS-142298-
00-8)
Felypressin Derivative of Felypressin Treatment of pain; to induce local SEQ ID NO:
(CAS-56-59-7) Vasopressin; vasoconstriction anesthesia. 2210
Stimulates activity can be
vasoconstriction; measured using assays
Induces local of vasoconstriction,
anesthesia. such as the isolated
arterial ring
preparation.
(Landstrom et al., Hum
Reprod 1999
Jan; 14(1): 151-5).
Glucagon Induces Glucagon activity may Hypoglycemia; Diabetes; Diabetes SEQ ID NO:
(CAS-16941- hyperglycemia. be assayed in vitro Insipidus; Diabetes mellitus; Type 1 2211
32-5) using a [3-H]-glucose diabetes; Type 2 diabetes; Insulin
uptake assay. (J Biol resistance; Insulin deficiency;
Chem 1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non-
274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X;
Endocrine disorders.
Nagrestipen Inflammation; Immune SEQ ID NO:
(CAS-166089- 2212
33-4)
Pentigetide Respiratory; Allergy; Immune SEQ ID NO:
(Pentyde) 2213
(CAS-62087-
72-3)
Proinsulin Stimulates glucose Insulin activity may be Hyperglycemia; Diabetes; Diabetes SEQ ID NO:
(CAS-67422- uptake and promotes assayed in vitro using a Insipidus; Diabetes mellitus; Type 1 2214
14-4) glycogenesis and [3-H]-glucose uptake diabetes; Type 2 diabetes; Insulin
lipogenesis. assay. (J Biol Chem resistance; Insulin deficiency;
1999 Oct 22; Hyperlipidemia; Hyperketonemia; Non-
274(43): 30864-30873). insulin dependent Diabetes Mellitus
(NIDDM); Insulin-dependent Diabetes
Mellitus (IDDM); A Condition
Associated With Diabetes Including, But
Not Limited To Obesity, Heart Disease,
Hyperglycemia, Infections, Retinopathy,
And/Or Ulcers; Metabolic Disorders;
Immune Disorders; Obesity; Vascular
Disorders; Suppression of Body Weight;
Suppression of Appetite; Syndrome X.
Becaplermin Promotes wound Becaplermin activity Stimulate Epithelial Cell Proliferation; SEQ ID NO:
(Regranex; healing. can be assessed using Stimulate Basal Keratinocytes; Promote 2215
recombinant animal wound healing Wound Healing; Stimulate Hair Follicle
PDGF-BB) models known in the Production; Healing Of Dermal Wounds.
(CAS-165101- art. (Saba et al., Ann Wound Healing; Eye Tissue Wounds,
51-9) Plast Surg 2002 Dental Tissue Wounds, Oral Cavity
Jul; 49(1): 62-6). Wounds, Diabetic Ulcers, Dermal
Ulcers, Cubitus Ulcers, Arterial Ulcers,
Venous Stasis Ulcers, Burns Resulting
From Heat Exposure Or Chemicals, or
Other Abnormal Wound Healing
Conditions such as Uremia,
Malnutrition, Vitamin Deficiencies or
Complications Associated With
Systemic Treatment With Steroids,
Radiation Therapy or Antineoplastic
Drugs or Antimetabolites; Promote
Dermal Reestablishment Subsequent To
Dermal Loss; Increase the Adherence Of
Skin Grafts To A Wound Bed; Stimulate
Re-Epithelialization from The Wound
Bed; To Promote Skin Strength;
Improve The Appearance Of Aged Skin;
Proliferate Hepatocytes, Lung, Breast,
Pancreas, Stomach, Bladder, Small
Intestine, Large Intestine; Sebocytes,
Hair Follicles, Type II Pneumocytes,
Mucin-Producing Goblet Cells, or Other
Epithelial Cells, Endothelial Cells,
Keratinocytes, or Basal Keratinocytes
(and Their Progenitors) Contained
Within The Skin, Lung, Liver, Bladder,
Eye, Salivary Glands, or Gastrointestinal
Tract; Reduce The Side Effects Of Gut
Toxicity That Result From Radiation,
Chemotherapy Treatments Or Viral
Infections; Cytoprotector, especially of
the Small Intestine Mucosa or Bladder;
Mucositis (Mouth Ulcers); Regeneration
Of Skin; Full and/or Partial Thickness
Skin Defects, including Burns, (e.g.,
Repopulation Of Hair Follicles, Sweat
Glands, And Sebaceous Glands);
Psoriasis; Epidermolysis Bullosa;
Blisters; Gastric and/or Doudenal Ulcers;
Reduce Scarring; Inflamamatory Bowel
Diseases; Crohn's Disease; Ulcerative
Colitis; Gut Toxicity; Lung Damage;
Repair Of Alveoli And/or Brochiolar
Epithelium; Acute Or Chronic Lung
Damage; Emphysema, ARDS; Inhalation
Injuries; Hyaline Membrane Diseases;
Infant Respiratory Distress Syndrome;
Bronchopulmonary Displasia In
Premature Infants; Fulminant Liver
Failure; Cirrhosis, Liver Damage caused
by Viral Hepatitis and/or Toxic
Substances; Diabetes Mellitus;
Inflammation; Cancer; Digestive
disorders.
Ghrelin Stimulates release of Appetite and food Endocrine; loss of body weight; loss of SEQ ID NO:
(Genbank growth hormone intake can be can be body weight associated with cancer or 2216
Accession No. from anterior measured by methods anorexia nervosa; loss of appetite;
AB029434) pituitary. Stimulates known in the art excessive appetite; body weight gain;
appetite and reduces (Batterham et al. Obesity; Diabetes; Acromegaly; Growth
fat burning. Nature 2002; failure; Growth hormone deficiency;
418: 650654) Growth failure and growth retardation
Prader-Willi syndrome in children 2
years or older; Growth deficiencies;
Growth failure associated with chronic
renal insufficiency; Postmenopausal
osteoporosis; burns; cachexia; cancer
cachexia; dwarfism; metabolic disorders;
obesity; renal failure; Turner's
Syndrome, pediatric and adult;
fibromyalgia; fracture treatment; frailty,
AIDS wasting
Ghrelin- Inhibits growth Appetite and food Endocrine; Obesity; Diabetes; body
binding hormone release in intake can be can be weight gain; excessive appetite; loss of
antibody response to Ghrelin; measured by methods appetite; loss of body weight.
including inhibits increase in known in the art
antibody appetite. (Batterham et al.
fragment, or Nature 2002;
dominant- 418: 650654)
negative form
of Ghrelin
receptor
NOGO-66 Neurodegenerative disorders; spinal cord SEQ ID NO:
peptide injury; neuronal injury; brain trauma; 2217
fragment stroke; multiple sclerosis; demyelinating
(Genbank disorders; neural activity and
Accession No. neurological diseases; neural cell (e.g.,
NP_008939 neuron, glial cell, and schwann cell)
(amino acids regeneration and/or growth
62-101))
Gastric Increases nutrient Nutrient uptake and Most preferred: loss of body weight, SEQ ID NO:
inhibitory uptake and tryglyceride AIDS wasting, cachexia, loss of apetite. 2218
polypeptide tryglyceride accumulation can be Other: Obesity; Diabetes; insulin
(GIP), accumulation in measured by methods resistance; body weight gain; excessive
including GIP adipocytes, which desribed in Miyawaki appetite.
fragments leads to obesity and et al., Nat. Medicine,
(Genbank insulin resistance. 2002, Vol 8(7): 738-742.
Accession No.
NM_004123)
Gastric Increased use of fat Fat utilization as an Obesity; Diabetes; Insulin resistance;
inhibitory as predominant energy source can be body weight gain.
polypeptide energy source; measured as described
antibody, or decreased in Miyawaki et al., Nat.
antibody accumulation of fat Medicine, 2002, Vol
fragments in adipocytes. 8(7): 738-742.
Gastric Increased use of fat Fat utilization as an Most preferred: Obesity; Diabetes; body SEQ ID NO:
inhibitory as predominant energy source can be weight gain; excessive appetite; insulin 2219
peptide energy source; measured as described resistance. Other: loss of body weight,
receptor or decreased in Miyawaki et al., Nat. AIDS wasting, loss of appetite.
receptor accumulation of fat Medicine, 2002, Vol
fragments or in adipocytes. 8(7): 738-742.
variants
including
soluble
fragments or
variants
(Genbank
Accession
Number
NM_000164)
POMC Activity of POMC- Preferred: resistance to stress; anti- SEQ ID NO:
(proopio- derived fragments are inflammatory activity; analgesic activity; 2220
melanocortin), diverse, and well- increased skin pigmentation; increased
including known in the art. protein catabolism; increased
fragments or See, for example, gluconeogenesis; obesity; diabetes.
variants (such Hadley et al., Ann N Other: decreased protein catabolism,
as, for example, Y Acad Sci 1999 Oct decreased skin pigmentation, Addison's
alpha- 20; 885: 1-21; Dores, disease, Cushing's syndrome
melanocyte Prog Clin Biol Res
stimulating 1990; 342: 22-7;
hormone, Blalock, Ann N Y
αMSH, Acad Sci. 1999 Oct
gamma 20; 885: 161-72).
melanocyte
stimulating
hormone,
γMSH, beta-
melanocyte
stimulating
hormone,
βMSH,
adrenocorticotropin,
ACTH,
beta-
endorphin,
met-
enkephalin)
(Genbank
Accession No.
NM_000930)
HP 467, See U.S. Pat. No. See U.S. Pat. No. Resistance to stress; anti-inflammatory SEQ ID NO:
HP228 6,350,430 6,350,430 activity; analgesic activity; increased 2221
(U.S. Pat. No. skin pigmentation; increased protein
6,350,430) catabolism; increased gluconeogenesis.
NDP See U.S. Pat. No. See U.S. Pat. No. Resistance to stress; anti-inflammatory SEQ ID NO:
(U.S. Pat. No. 6,350,430 6,350,430 activity; analgesic activity; increased 2222
6,350,430) skin pigmentation; increased protein
catabolism; increased gluconeogenesis.
Interleukin-21 Immunomodulator; IL-21 activity can be Autoimmune disorders; Inflammatory 3298 SEQ ID NO:
(IL-21) inhibits interferon assessed by measuring disorders; Treatment of Psoriasis; 2177
gamma production by interferon gamma Rheumatoid Arthritis; Inflammatory
Th1 cells, production in Th1 cells. bowel disease.
(Wurster et al.,: J Exp
Med 2002 Oct
7; 196(7): 969-77)
Interleukin-4 Immunomodulator; IL-4 activity can be Treatment of Psoriasis; Autoimmune 3307 SEQ ID NO:
(IL-4) promotes the assessed by measuring disorders; Rheumatoid Arthritis; 2178
differentiation of T Th1/Th2 cytokine Inflammatory bowel disease;
cells into Th2 responses of isolated Inflammatory disorders.
phenotype. spleen cells in vitro.
(Waltz et al., Horm
Metab Res 2002
Oct; 34(10): 561-9).
Osteoclast Inhibits osteoclast Osteoclast Inhibitory Treatment of Bone Disorders; 3312 SEQ ID NO:
Inhibitory formation. Lectin activity can be Osteoporosis; Fracture prevention; 2181
Lectin assessed using Hypercalcemia; Malignant
(OCIL) osteoclast formation hypercalcemia; Paget's disease;
assays known in the art. Osteopenia, Osteoclastogenesis;
(Zhou et al., J Biol osteolysis; osteomyelitis; osteonecrosis;
Chem 2002 Dec periodontal bone loss; osteoarthritis;
13; 277(50): 48808-15) rheumatoid arthritis; osteopetrosis;
periodontal, lytic, or metastatic bone
disease; osteoclast differentiation
inhibition; bone healing and
regeneration.

TABLE 2
SEQ SEQ SEQ SEQ SEQ
Fu- Con- ID ID ID ID ID
sion struct Expression NO: NO: NO: NO: NO: Leader
No. ID Construct Name Description Vector Y X Z A B Sequence
1 1520 pC4:HSA/TR6.V30-H300 Amino acids V30 to H300 of TR6 pC4 217 1 433 649 650 HSA
(fragment shown as V1 to H271 of
SEQ ID NO: 433) fused downstream
of HSA.
2 1537 pYPG:HSA.TR6coV30-E294 Amino acids V30 to E294 of TR6 pYPGaf 218 2 434 651 652 HSA
(fragment shown as V1 to E265 of
SEQ ID NO: 434) fused downstream
of HSA. DNA encoding TR6 has
been codon optimized.
3 1545 pYPG:HSA.TR6coV30-L288 Amino acids V30 to L288 of TR6 pYPGaf 219 3 435 653 654 HSA
(fragment shown as V1 to L259 of
SEQ ID NO: 435) fused downstream
of HSA. DNA encoding TR6 has
been codon optimized.
4 1546 pYPG:HSA.TR6coV30-R284 Amino acids V30 to R284 of TR6 pYPGaf 220 4 436 655 656 HSA
(fragment shown as V1 to R255 of
SEQ ID NO: 436) fused downstream
of HSA. DNA encoding TR6 has
been codon optimized.
5 1568 pSAC35:HSA-yTR6 TR6 fused downstream of HSA. pSAC35 221 5 437 657 658 HSA/kex2
DNA encoding TR6 has been codon
optimized.
6 1570 pSAC35:TR6-HSA Mature TR6 fused downstream of the pSAC35 222 6 438 659 660 HSA/kex2
HSA/kex2 leader and upstream of the
mature HSA.
7 1622 pC4:synTR6.M1-H300.- Synthetic TR6 fused upstream of pC4 223 7 439 661 662 Native
HSA mature HSA, with 2 extra amino TR6
acids between the TR6 and HSA
portions.
8 1623 pC4:HSA.synTR6.V30-H300 Synthetic mature TR6 fused pC4 224 8 440 663 664 HSA
downstream of FL HSA. Last amino
acid HSA sequence is missing at
BSU36I site.
9 1642 pSAC35:GCSF.T31-P204.- Mature GCSF cloned downstream of pSAC35 225 9 441 665 666 HSA/kex2
HSA the HSA/kex2 leader and upstream of
the mature HSA
10 1643 pSAC35:HSA.GCSF.- Mature GCSF cloned downstream of pSAC35 226 10 442 667 668 HSA/kex2
T31-P204 the mature HSA and HSA/kex2
leader sequence.
11 1645 pSAC35:yTR6(N173Q).- Mutant mature TR6 cloned upstream pSAC35 227 11 443 669 670 HSA/kex2
HSA of mature HSA and downstream of
the HSA/kex2 leader sequence.
12 1657 pC4.HSA:DeCAF.A23-D233 Amino acids A23 to D233 of DeCAF pC4 228 12 444 671 672 HSA
fused downstream of full length
HSA.
13 1680 pYPG:HSA.BLyS.A134-L285 Amino acids A134 to L285 of BLyS pYPGaf 229 13 445 673 674 HSA
fused downstream of FL HSA. Two
extra amino acids (Leu, Glu) have
been added between the therapeutic
protein and HSA portions.
14 1681 pYPG.HSA.MPIF.D45-N120 Amino acids D45 to N120 of MPIF pYPGaf 230 14 446 675 676 HSA
fused downstream of FL HSA. Two
additional amino acids (L and E)
have been added between HSA and
MPIF.
15 1697 pSAC35:HSA.GM- Amino acids A18 to E144 of GM- pSAC35 231 15 447 677 678 HSA
CSF.A18-E144 CSF fused downstream of FL HSA.
16 1699 pSAC35:GM- Amino acids A18 to E144 of GM- pSAC35 232 16 448 679 680 HSA/kex2
CSF.A18-E144:HSA CSF fused upstream of mature HSA
and downstream of HSA/kex2 leader.
17 1700 pSAC35:HSA- Mutant TR6 fused downstream of pSAC35 233 17 449 681 682 HSA/kex2
yTR6(N173Q) mature HSA with HSA/kex2 leader
sequence.
18 1702 pYPG:HSA.ek.TR6co Amino acids V30 to L288 of TR6 pYPGaf 234 18 450 683 684 HSA
V30-L288 (fragment shown as V1 to L259 of
SEQ ID NO: 450) fused downstream
of FL HSA with an enterokinase site
in between. DNA encoding TR6 has
been codon optimized.
19 1703 pYPG:HSA.ek.TR6co Amino acids V30 to R284 of TR6 pYPGaf 235 19 451 685 686 HSA
V30-R284 (fragment shown as V1 to R255 of
SEQ ID NO: 451) fused downstream
of HSA with an enterokinase site in
between. DNA encoding TR6 has
been codon optimized.
20 1704 pYPG:HSA.TR6.V30-E294 Amino acids V30 to E294 of TR6 pYPGaf 236 20 452 687 688 HSA
fused downstream of HSA. Two
additional amino acids (Leu, Glu) are
in between HSA and TR6.
21 1746 pYPG:HSA.ek.KDI.L28-K207 Amino acids L28 to K207 of KDI pYPGaf 237 21 453 689 690 HSA
fused downstream of HSA with an
enterokinase site in between.
22 1747 pSAC35.HSA.hGHRF.- Amino acids Y32 to L75 of hGHRF pSAC35 238 22 454 691 692 HSA
Y32-L75 fused downstream of HSA.
23 1748 pSAC35.hGHRF.Y32-L75.- Amino acids Y32 to L75 of hGHRF pSAC35 239 23 455 693 694 HSA/kex2
HSA (see also SEQ IDNO: 454) fused
upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
24 1749 pSAC35:HSA.PTH.S1-F3 FL HSA fused upstream of amino pSAC35 240 24 456 695 696 HSA
acids S1-F34 of PTH
25 1750 pSAC35:PTH.S1-F34.- Amino acids 1-34 of PTH fused pSAC35 241 25 457 697 698 HSA/kex2
HSA upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
26 1757 pSAC35:IL2.A21-T153.- Mature human IL-2 with a single pSAC35 242 26 458 699 700 HSA/kex2
145C/S.HSA amino acid mutation (C to S at
position 145) cloned downstream of
the HSA/KEX2 leader and upstream
of mature HSA
27 1758 pSAC35:HSA.IL2.A21-T153.- Mature human IL-2 with a single pSAC35 243 27 459 701 702 HSA/kex2
145C/S amino acid mutation (C to S at
position 145) cloned downstream of
HSA with HSA/kex2 leader
sequence.
28 1772 pSAC:EPOco.A28-D192.- Amino acids A28-D192 of EPO pSAC35 244 28 460 703 704 HSA/kex2
HSA variant (where glycine at amino acid
140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence. DNA encoding EPO
has been codon optimized.
29 1774 pSAC:HSA.EPOco.A28-D192. Amino acids A28-D192 of EPO pSAC35 245 29 461 705 706 HSA/kex2
variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of HSA
with HSA/kex2 leader sequence.
DNA encoding EPO has been codon
optimized.
30 1777 pSAC35:TNFR2.L23-D257.- Mature TNFR2 fused downstream of pSAC35 246 30 462 707 708 HSA/kex2
HSA the HSA/kex2 signal and upstream of
mature HSA.
31 1778 pSAC35:IFNβ.M22-N187: Residues M22-N187 of full-length pSAC35 247 31 463 709 710 HSA/kex2
HSA IFNb (shown as M1 to N166 of SEQ
ID NO: 463) fused upstream of
mature HSA and downstream of
HSA/kex2 leader sequence.
32 1779 pSAC35:HSA:IFNβ.- Residues M22-N187 of full-length pSAC35 248 32 464 HSA/kex2
M22-N187 IFNb (shown as M1 to N166 of SEQ
ID NO: 464) fused downstream of
HSA with HSA/kex2 leader
sequence.
33 1781 pSAC:EPOcoA28-D192.- Amino acids A28-D192 of EPO pSAC35 249 33 465 711 712 HSA/kex2
HSA variant (where glycine at amino acid
51N/S, 65N/S, 110N/s 140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence. Glycosylation sites
at amino acid 51, 65, 110 are mutated
from N to S residue. DNA encoding
EPO has been codon optimized.
34 1783 pSAC:HSA.EPOcoA28-D192.- Amino acids A28-D192 of EPO pSAC35 250 34 466 713 714 HSA/kex2
51N/S, 65N/S, 110N/s variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of HSA
with HSA/kex2 leader sequence.
Glycosylation sites at amino acids 51,
65, 110 are mutated from N to S
residue. DNA encoding EPO has
been codon optimized.
35 1784 pSAC35:HSA.TNFR2.- Mature TNFR2 fused downstream of pSAC35 251 35 467 715 716 HSA
L23-D257 FL HSA.
36 1785 pSAC35:KGF2Δ28.A63-S208: Amino acids A63 to S208 of KGF2 pSAC35 252 36 468 717 718 HSA/kex2
HSA fused upstream of mature HSA and
downstream of the HSA/kex2 signal
peptide.
37 1786 pSAC35:HSA.KGF2 Amino acids A63 to S208 of KGF2 pSAC35 253 37 469 719 720 HSA
{D}28.A63-S208 fused downstream of HSA.
38 1788 pSAC35:HSA.TR2.P37-A192 Amino acids P37 to A192 of TR2 pSAC35 254 38 470 721 722 HSA/kex2
fused downstream of HSA with
HSA/kex2 leader sequence.
39 1793 pSAC35:HSA.EPO.A28-D192 Amino acids A28-D192 of EPO pSAC35 255 39 471 HSA/kex2
(N51A, N65A, N110A) variant (where glycine at amino acid
140 has been replaced with an
arginine; see, for example, SEQ ID
NO: 499) fused downstream of HSA
with HSA/kex2 leader sequence.
Glycosylation sites at amino acids
51, 65, 110 are mutated from N to A
residue.
40 1794 pSAC35:HSA.EPO.A28-D192 Amino acids A28-D192 of the EPO pSAC35 256 40 472 HSA/kex2
variant (where glycine at amino acid
140 has been replaced with an
arginine; see, for example, SEQ ID
NO: 499) fused downstream of HSA
with HSA/kex2 leader sequence.
41 1809 pSAC35.MDC.G25-Q93.- Amino acids P26 to Q93 of MDC pSAC35 257 41 473 723 724 HSA/kex2
HSA with an N-terminal methionine, fused
downstream of the HSA/kex2 leader
and upstream of mature HSA.
42 1812 pSAC35:IL2.A21-T153.- Amino acids A21 to T153 of IL-2 pSAC35 258 42 474 725 726 HSA/kex2
HSA fused downstream of the HSA/kex2
leader and upstream of mature HSA.
43 1813 pSAC35:HSA.IL2.A21-T153 Amino acids A21 to T153 of IL-2 pSAC35 259 43 475 727 728 HSA/kex2
fused downstream of HSA with
HSA/kex2 leader sequence.
44 1821 pSAC35:scFv116A01.- BLyS antibody fused upstream of pSAC35 260 44 476 729 730 Modified
HSA mature HSA which lacks the first 8 HSA/kex2,
amino acids and downstream from lacking
the HSA/kex2 signal sequence which the last
lacks the last two amino acids. two amino
acids
45 1830 pSAC35:HSA.KEX2.- Amino acids L19-Q300 of pSAC35 261 45 477 731 732 HSA/kex2
HAGDG59.L19-Q300 HAGDG59 fused downstream of the
HSA/kex2 signal, mature HSA and
KEX2 cleavage site.
46 1831 pSAC35:HAGDG59.- HSA/kex2 signal peptide followed by pSAC35 262 46 478 733 734 HSA/kex2
L19-Q300.HSA amino acids L19-Q300 of HAGDG59
followed by mature HSA.
47 1833 pSAC35:humancalcitonin.- Human Calcitonin (amino acids pSAC35 263 47 479 735 736 HSA/kex2
C1-G33:HSA C98-G130 of SEQ ID NO: 479) fused
upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
48 1834 pSAC35:HSA.humancalcitonin.- Human Calcitonin (amino acids pSAC35 264 48 480 737 738 HSA
C1-G33 C98-G130 of SEQ ID NO: 480) fused
downstream of FL HSA.
49 1835 pSAC35:salmoncalcitonin.- Salmon Calcitonin amino acids pSAC35 265 49 481 739 740 HSA/kex2
C1-G33:HSA C1-G33 fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence.
50 1836 pSAC35:HSA.salmon Salmon Calcitonin amino acids pSAC35 266 50 482 741 742 HSA
calcitonin. C1-G33 C1-G33 fused downstream of HSA.
51 1853 pSAC35:PTH(1-34) Amino acids 1 to 34 of PTH fused pSAC35 267 51 483 743 744 HSA/kex2
N26.HSA upstream of mature HSA and
downstream of HSA/kex2 leader
sequence. Amino acid K26 of PTH
mutated to N26.
52 1854 pSAC35:HSA.PTH(1-34) Amino acids 1 to 34 of PTH fused pSAC35 268 52 484 745 746 HSA
N26 downstream of HSA. Amino acid
K26 of PTH mutated to N26.
53 1862 pSAC35:HSA.GnRH.- Amino acids Q24-G33 of human pSAC35 269 53 485 747 748 HSA/kex2
Q24-G33 gonadotropin releasing hormone
fused downstream of HSA with
HSA/kex2 leader sequence.
54 1863 pSAC35:GnRHQ24-G33.- Amino acids Q24-G33 of human pSAC35 270 54 486 749 750 HSA/kex2
HSA gonadotropin releasing hormone
fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
55 1866 pSAC35:teprotide.HSA Teprotide fused upstream of mature pSAC35 271 55 487 751 752
HSA.
56 1867 pSAC35:HSA.teprotide. Teprotide fused downstream of FL pSAC35 272 56 488 753 754 HSA
HSA.
57 1889 pC4:HSA.PTH.S1-F34 PTH(1-34) fused downstream of pC4 273 57 489 755 756 HSA
HSA.
58 1891 pEE12:HSA.sTR6 Soluble mature TR6 fused pEE12.1 274 58 490 757 758 HSA
downstream of HSA.
59 1892 pEE12:sTR6.HSA Synthetic full length TR6 fused pEE12.1 275 59 491 759 760 TR6
upstream of mature HSA.
60 1906 pC4:PTH.S1-F34.- Amino acids S1 to F34 of PTH fused pC4 276 60 492 761 762 MPIF
HSA (junctioned) upstream of mature HSA and
downstream of MPIF leader
sequence. There are two cloning
junction amino acids (T, S) between
PTH and HSA.
61 1907 pC4:HSA.PTH.S1-F34 Amino acids S1 to F34 fused pC4 277 61 493 763 764 HSA
(junctioned) downstream of FL HSA. The last C-
terminal amino acid (L) residue is
missing for HSA in the cloning
junction between HSA and PTH.
62 1912 pC4:sTR6.HSA Synthetic full length TR6 fused pC4 278 62 494 765 766 Native
upstream of mature HSA. TR6
leader
63 1913 pC4:HSA.synTR6.V30-H300 Amino acids V30 to H300 of pC4 279 63 495 767 768 HSA
(seamless) synthetic TR6 (shown as V1 to H271
of SEQ ID NO: 495) fused
downstream of full-length HSA.
64 1914 pC4:PTH.S1-F34.- Amino acids S1 to F34 of PTH fused pC4 280 64 496 769 770 MPIF
HSA (seamless) downstream of MPIF leader sequence
and upstream of mature HSA.
65 1916 pC4:HSA.KGF2D28.- Amino acids A63 to S208 of full pC4 281 65 497 771 772 HSA
A63-S208 length KGF2 fused downstream of
HSA.
66 1917 pC4:KGF2D28.A63-S208: Amino acids A63 to S208 of KGF2 pC4 282 66 498 773 774 HSA/kex2
HSA fused upstream of mature HSA.
67 1925 pcDNA3.EPO M1-D192.- Amino acids M1 to D192 of EPO pcDNA3 283 67 499 775 776 Native
HSA variant (where glycine at amino acid EPO
140 has been replaced with an leader
arginine) fused upstream of HSA. peptide
D192 of EPO and D1 of mature HSA
are the same amino acids in this
construct.
68 1926 pcDNA3:SPHSA.EPO Amino acids A28 to D192 of EPO pcDNA3 284 68 500 777 778 MPIF
A28-D192 variant (where glycine at amino acid
140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of the MPIF
leader peptide.
69 1932 pEE12.1:HSA.PTH.S1-F34 Amino acids 1 to 34 of PTH fused pEE12.1 285 69 501 779 780 HSA
downstream of full length HSA.
70 1933 pSAC35:HCC-1.T20-N93: Amino acids T20 to N93 of HCC-1 pSAC35 286 70 502 781 782 HSA/kex2
HSA fused upstream of mature HSA and
downstream of the HSA/kex2 leader
sequence.
71 1934 pSAC35:HCC- Amino acids T20 to N93 of HCC-1 pSAC35 287 71 503 783 784 HSA/kex2
1C.O.T20-N93:HSA fused upstream of mature HSA and
downstream of the HSA/kex2 leader
sequence. DNA sequence is codon
optimized for yeast expression.
72 1938 pEE12.1:PTH.S1-F34.- Amino acids S1 to F34 of PTH fused pEE12.1 288 72 504 785 786 MPIF
HSA upstream of mature HSA and
downstream of MPIF leader
sequence.
73 1941 pC4:HSA/PTH84 PTH fused downstream of full length pC4 289 73 505 787 788 HSA
(junctioned) HSA. The last amino acid of HSA
(Leu) has been deleted.
74 1947 pSAC35:d8HCC- Amino acids G28 to N93 of HCC-1 pSAC35 290 74 506 789 790 HSA/kex2
1.G28-N93:HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
75 1948 pSAC35:d8HCC- Amino acids G28 to N93 of HCC-1 pSAC35 291 75 507 791 792 HSA/kex2
1C.O.G28-N93:HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence. DNA sequence is codon
optimized for yeast expression.
76 1949 pC4:PTH.S1-Q84/ PTH fused downstream of the MPIF pC4 292 76 508 793 794 MPIF
HSA (junctioned) leader sequence and upstream of
mature HSA. There are two
additional amino acids between
PTH84 and HSA as a result of the
cloning site.
77 1952 pcDNA3.1:IL2.HSA Full length human IL-2, having a pCDNA3.1 293 77 509 795 796 Native IL-
Cysteine to Serine mutation at amino 2 leader
acid 145, fused upstream of mature
HSA.
78 1954 pC4:IL2.HSA Full length human IL-2, having a pC4 294 78 510 797 798 Native IL-
Cysteine to Serine mutation at amino 2 leader
acid 145, fused upstream of mature
HSA.
79 1955 pSAC35:t9HCC- Amino acids G28 to N93 of HCC-1 pSAC35 295 79 511 799 800 HSA/kex2
1.G28-N93:spcHSA fused upstream of a 16 amino acid
spacer and mature HSA and
downstream of HSA/kex2 leader
sequence.
80 1956 pSAC35:HSA.scFv116A01 Single chain BLyS antibody fused pSAC35 296 80 512 801 802 HSA/kex2
downstream of HSA with HSA/kex2
leader sequence. This construct also
contains a His tag at the 3′ end.
81 1966 pC4:EPO.M1-D192.- Amino acids M1 to D192 of EPO pC4 297 81 513 Native
HSA variant (where glycine at amino acid EPO
Construct is also 140 has been replaced with an leader
named pC4:EPOM1-D192.- arginine) fused upstream of mature peptide
HSA HSA.
82 1969 pC4:MPIFsp.HSA.EPO.- Amino acids A28 to D192 of EPO pC4 298 82 514 MPIF
A28-D192 variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of MPIF
leader sequence and upstream of
mature HSA.
83 1980 pC4:EPO.A28-D192.- Amino acids A28 to D192 of EPO pC4 299 83 515 803 804 HSA
HSA variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of the
HSA leader peptide and upstream of
mature HSA.
84 1981 pC4.HSA-EPO.A28-D192.- Amino acids A28 to D192 of EPO pC4 300 84 516 805 806 HSA
variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of the
full length HSA.
85 1989 pSAC35:activeAC2inhibitor: Active inhibitor of ACE2 (DX512) pSAC35 301 85 517 807 808 HSA/kex2
HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
86 1994 pEE12.1.HSA- Amino acids A28 to D192 of EPO pEE12.1 302 86 518 HSA
EPO.A28-D192. variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of full
length HSA.
87 1995 pEE12.1:EPO.A28-D192.- Amino acids A28 to D192 of EPO pEE12.1 303 87 519 HSA
HSA variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of the
HSA leader peptide and upstream of
mature HSA.
88 1996 pEE12.1:MPIFsp.HSA.- Amino acids A28 to D192 of EPO pEE12.1 304 88 520 MPIF
EPO.A28-D192 variant (where glycine at amino acid
140 has been replaced with an
arginine) fused downstream of MPIF
leader sequence and upstream of
mature HSA.
89 1997 pEE12.1:EPO M1-D192.- Amino acids M1 to D192 of EPO pEE12.1 305 89 521 Native
HSA variant (where glycine at amino acid EPO
140 has been replaced with an leader
arginine) fused upstream of mature
HSA.
90 1998 pC4:CKB1.G28-N93.- Amino acids G28 to N93 of CkBeta1 pC4 306 90 522 809 810 HSA
HSA fused upstream of mature HSA and
downstream of the HSA leader
sequence.
91 2000 pSAC35:HSA:activeAC2 Active inhibitor of ACE2 (DX512) pSAC35 307 91 523 811 812 HSA
inhibitor fused downstream of HSA.
92 2001 pSAC35:inactiveAC2inhibitor: Inactive inhibitor of ACE2 (DX510) pSAC35 308 92 524 813 814 HSA/kex2
HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
93 2002 pSAC35:HSA.inactive Inactive inhibitor of ACE2 (DX510) pSAC35 309 93 525 815 816 HSA
AC2inhibitor fused downstream of HSA.
94 2011 pC4:IFNb-HSA Full length IFNb fused upstream of pC4 310 94 526 817 818 Native
mature HSA. IFNb
leader
95 2013 pC4:HSA-IFNb.M22-N187 Amino acids M22 to N187 of IFNb pC4 311 95 527 HSA
(fragment shown as amino acids M1
to N166 of SEQ ID NO: 527) fused
downstream of HSA.
96 2016 pC4:TR1.M1-L401.- Amino acids M1 to L401 of TR1 pC4 312 96 528 819 820 Native
HSA fused upstream of mature HSA. TR1
Native TR1 signal sequence used. A
Kozak sequence was added.
97 2017 pC4:HSA.TR1.E22-L401 Amino acids E22 to L401 of TR1 pC4 313 97 529 821 822 HSA
fused downstream of HSA.
98 2021 pC4:PTH.S1-Q84/ Amino acids 1-84 of PTH fused pC4 314 98 530 823 824 HSA
HSA (seamless) upstream of mature HSA and
downstream of native HSA leader
sequence.
99 2022 pEE12.1:PTH.S1-Q84.- Amino acids 1-84 of PTH fused pEE12.1 315 99 531 HSA
HSA upstream of mature HSA and
downstream of native HSA leader
sequence.
100 2023 pSAC35.PTH.S1-Q84.- Amino acids 1-84 of PTH fused pSAC35 316 100 532 825 826 HSA/kex2
HSA upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
101 2025 pSAC35:teprotide.spacer.- Teprotide fused upstream of a linker pSAC35 317 101 533 827 828
HSA and mature HSA.
102 2026 pSAC35:HSA.spacer.teprotide Teprotide fused downstream of HSA pSAC35 318 102 534 829 830 HSA
and a linker.
103 2030 pSAC35.ycoIL-2.A21-T153.- Amino acids A21 to T153 of IL-2 pSAC35 319 103 535 831 832 HSA/kex2
HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence. DNA encoding IL-2 has
been codon optimized.
104 2031 pSAC35.HSA.ycoIL- Amino acids A21 to T153 of IL-2 pSAC35 320 104 536 833 834 HSA/kex2
2.A21-T153 fused downstream of HSA with the
HSA/kex2 leader sequence. DNA
encoding IL-2 has been codon
optimized.
105 2047 pC4HSA:SP.EPO Amino acids A28 to D192 of EPO pSAC35 321 105 537 835 836 MPIF
A28-D192.HSA variant (where glycine at amino acid
140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of MPIF leader
peptide.
106 2053 pEE12:IFNb-HSA Full length IFNb fused upstream of pEE12.1 322 106 538 Native
also named mature HSA. IFNb
pEE12.1:IFNβ-HSA leader
107 2054 pEE12:HSA-IFNb Mature IFNb fused downstream of pEE12.1 323 107 539 HSA
HSA.
108 2066 pC4:GM-CSF.M1-E144.- Amino acids M1 to E144 of GM- pC4 324 108 540 837 838 Native
HSA CSF fused upstream of mature HSA. GM-CSF
109 2067 pC4:HSA.GM- Amino acids A18 to E144 of GM- pC4 325 109 541 839 840 HSA
CSF.A18-E144 CSF fused downstream of HSA.
110 2085 pEE12.1:TR1.M1-L401.- Amino acids M1 to L401 of TR1 pEE12.1 326 110 542 Native
HSA fused upstream of mature HSA. TR-1
111 2086 pEE12.1:HSA.TR1.E22-L401 Amino acids E22 to L401 (fragment pEE12.1 327 111 543 HSA
shown as amino acids E1 to L380 of
SEQ ID NO: 543) of TR1 fused
downstream of HSA.
112 2095 pC4:HSA-BLyS.A134 Amino acids A134 to L285 of BLyS pC4 328 112 544 841 842 HSA
fused downstream of HSA.
113 2096 pC4:sp.BLyS.A134-L285.- Amino acids A134 to L285 of BLyS pC4 329 113 545 843 844 Native
HSA (fragment shown as amino acids A1 CKβ8
to L152 of SEQ ID NO: 545) fused
upstream of mature HSA and
downstream of the CKb8 signal
peptide.
114 2101 pcDNA3:SP.Ck7 N-terminal Methionine fused to pcDNA3 330 114 546 845 846 MPIF
Q22-A89.HSA. amino acids Q22 to A89 of Ckβ7
fused upstream of mature HSA and
downstream of MPIF signal peptide.
115 2102 pEE12.1:SP.EPO Amino acids A28 to D192 of EPO pEE12.1 331 115 547 MPIF
A28-D192.HSA variant (where glycine at amino acid
140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of MPIF leader
peptide.
116 2129 pC4:TR2.M1-A192.- Amino acids M1-A192 of TR2 fused pC4 332 116 548 847 848 Native
HSA upstream of HSA. TR2
117 2137 pSAC35.MDC.G25-Q93.- Amino acids G25 to Q93 of MDC pSAC35 333 117 549 849 850 HSA/kex2
HSA. fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
118 2141 HSA-CK-Beta4 Full length CK-beta4 fused pSAC35 334 118 550 851 852 HSA
downstream of HSA.
119 2146 pC4:Leptin.HSA Full length Leptin fused upstream of pC4 335 119 551 853 854 Native
mature HSA. leptin
120 2181 pC4:HSA.IL1Ra(R8-E159) Amino acids R8 to E159 of IL1Ra pC4 336 120 552 855 856 HSA
(plus an added methionine at N-
terminus) fused downstream of HSA.
121 2182 pC4:MPIFsp(M1-A21).- Amino acids R8 to E159 of IL1Ra pC4 337 121 553 857 858 MPIF
IL1Ra(R8-E159).- (plus an added methionine at N-
HSA terminus) fused downstream of the
MPIF leader sequence and upstream
of mature HSA.
122 2183 pSAC35:HSA.IL1Ra Amino acids R8 to E159 of IL1Ra pSAC35 338 122 554 859 860 HSA
(R8-E159) (plus an added methionine at N-
terminus) fused downstream of HSA.
123 2184 pC4:HSA.Leptin.V22-C166 Amino acids V22 to C167 of Leptin pC4 339 123 555 861 862 HSA
fused downstream of HSA.
124 2185 pSAC35:IL1Ra(R8-E159).- Amino acids R8 to E159 of IL1Ra pSAC35 340 124 556 863 864 HSA/kex2
HSA (plus an added methionine at N-
terminus) fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence.
125 2186 pSAC35:Leptin.V22-C166.- Amino acids V22 to C167 of Leptin pSAC35 341 125 557 865 866 HSA/kex2
HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
126 2187 pSAC35:HSA.Leptin.- Amino acids V22 to C167 of Leptin pSAC35 342 126 558 867 868 HSA/kex2
V22-C166 fused downstream of HSA with
HSA/kex2 leader sequence.
127 2226 pcDNA3(+):TREM- Amino acids A21 to P202 of TREM- pCDNA3.1 343 127 559 869 870 MPIF
1(21-202)-HSA 1 fused upstream of mature HSA and
downstream of the MPIF leader
sequence.
128 2230 pC4:TREM-1.M1-P202.- Amino acids M1 to P202 of TREM-1 pC4 344 128 560 871 872 Native
HSA fused upstream of mature HSA. TREM-1
129 2240 pC4:SP.Ck7 Q22-A89.- N-terminal Methionine fused to pC4 345 129 561 873 874 MPIF
HSA. amino acids Q22 to A89 of Ckβ7
fused upstream of mature HSA and
downstream of the MPIF leader
sequence. Contains a linker sequence
between Ckβ7 and HSA.
130 2241 pC4:HSA.Ck7metQ22-A89. N-terminal Methionine fused to pC4 346 130 562 875 876 HSA/kex2
amino acids Q22 to A89 of
Chemokine beta 7 (Ckbeta 7 or CK7)
fused downstream of HSA with
HSA/kex2 leader sequence. Contains
a linker sequence between CkB7 and
HSA.
131 2244 pC4.HCNCA73.HSA HCNCA73 fused upstream of mature pC4 347 131 563 877 878 HCNCA73
HSA.
132 2245 pScNHSA:CK7.Q22-A89 Amino acids Q22 to A89 of Ckβ7 pScNHSA 348 132 564 879 880 HSA/kex2
fused downstream of HSA with
HSA/kex2 leader sequence. Contains
a linker sequence between Ckβ7 and
HSA.
133 2246 pScCHSA.CK7metQ22-A89 N-terminal Methionine fused to pScCHSA 349 133 565 881 882 HSA/kex2
amino acids Q22 to A89 of Ckβ7
fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
134 2247 pSAC35:CK7metQ22-A89.- N-terminal Methionine fused to pSAC35 350 134 566 883 884 HSA/kex2
HSA. amino acids Q22 to A89 of Ckβ7
fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
135 2248 pSAC35:HSA.CK7met N-terminal Methionine fused to pSAC35 351 135 567 885 886 HSA/kex2
Q22-A89. amino acids Q22 to A89 of Ckβ7
fused downstream of HSA with
HSA/kex2 leader sequence. Contains
a linker sequence between Ckβ7 and
HSA.
136 2249 pSAC35:IFNa2-HSA Mature IFNa2 fused upstream of pSAC35 352 136 568 887 888 HSA/kex2
also named: mature HSA and downstream of
pSAC23:IFNα2-HSA HSA/kex2 leader sequence.
137 2250 pSAC35:HSA.INSULIN Mature Insulin wherein the C-peptide pSAC35 353 137 569 889 890 HSA
(GYG) is replaced by the C-domain of IGF-1
also named: fused downstream of HSA. DNA
pSAC35.HSA.INSULING encoding Insulin was codon
(GYG).F1-N62 optimized.
138 2251 pScCHSA:VEGF2.T103-R227. Amino acids T103 to R227 of pScCHSA 354 138 570 891 892 HSA/kex2
VEGF2 fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence.
139 2252 pScNHSA:VEGF2.T103-R227. Amino acids T103 to R227 of pScNHSA 355 139 571 893 894 HSA/kex2
VEGF2 fused downstream of HSA
with HSA/kex2 leader sequence.
140 2255 pSAC35:INSULIN(GYG).- Mature Insulin wherein the C-peptide pSAC35 356 140 572 895 896 HSA/kex2
HSA is replaced by the C-domain of IGF-1
also named fused upstream of mature HSA and
pSAC35.INSULING downstream of HSA/kex2 leader.
(GYG).F1-N62.HSA DNA encoding Insulin was codon
optimized.
141 2256 pSAC35:VEGF2.T103-R227.- Amino acids T103 to R227 of pSAC35 357 141 573 897 898 HSA/kex2
HSA VEGF2 fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence.
142 2257 pSAC35:HSA.VEGF2.- Amino acids T103 to R227 of VEGF- pSAC35 358 142 574 899 900 HSA/kex2
T103-R227 2 fused downstream of HSA with
HSA/kex2 leader sequence.
143 2271 pEE12.1:HCHNF25M1-R104.- Amino acids M1 to R104 of pEE12.1 359 143 575 Native
HSA HCHNF25 fused upstream of mature HCHNF25
HSA.
144 2276 pSAC35:HSA.INSULIN Mature Insulin wherein the C-peptide pSAC35 360 144 576 901 902 HSA
(GGG) is replaced by a synthetic linker fused
also named: downstream of HSA. DNA encoding
pSAC35.HSA.INSULING Insulin was codon optimized.
(GGG).F1-N58
145 2278 pSAC35:insulin(GGG).- Mature Insulin wherein the C-peptide pSAC35 361 145 577 903 904 HSA/kex2
HSA is replaced by a synthetic linker fused
downstream of HSA/kex2 leader and
upstream of mature HSA. DNA
encoding Insulin was codon
optimized.
146 2280 pC4:HCHNF25.HSA HCHNF25 fused upstream of mature pC4 362 146 578 905 906 Native
HSA. HCHNF25
147 2283 pScCHSA:EPOcoA28-D192.- Amino acids A28 to D192 of EPO pScCHSA 363 147 579 907 908 HSA/kex2
51N/Q, 65N/Q, variant (where glycine at amino acid
110N/Q EPO 140 has been replaced with an
arginine) are fused upstream of
mature HSA and downstream of
HSA/kex2 leader sequence.
Glycosylation sites at amino acids 51,
65 and 110 are mutated from N to Q
residue. DNA encoding EPO is
codon optimized.
148 2284 pScNHSA:EPOcoA28-D192.- Amino acids A28 to D192 of EPO pScNHSA 364 148 580 909 910 HSA/kex2
51N/Q, 65N/Q, variant (where glycine at amino acid
110N/Q EPO 140 has been replaced with an
arginine) fused downstream of
mature HSA and HSA/kex2 leader
sequence. Glycosylation sites at
amino acids 51, 65 and 110 are
mutated from N to Q residue. DNA
encoding EPO is codon optimized.
149 2287 pSAC35:EPOcoA28-D192.- Amino acids A28 to D192 of EPO pSAC35 365 149 581 911 912 HSA/kex2
51N/Q, 65N/Q, 110N/Q.- variant (where glycine at amino acid
HSA. 140 has been replaced with an
arginine) fused upstream of mature
HSA and downstream of HSA/kex2
leader sequence. Glycosylation sites
at amino acid 51, 65 and 110 are
mutated from N to Q residue. DNA
encoding EPO is codon optimized.
150 2289 pSAC35:HSA.EPOco Amino acids A28 to D192 of EPO pSAC35 366 150 582 913 914 HSA/kex2
A28-D192.- variant (where glycine at amino acid
51N/Q, 65N/Q, 110N/Q. 140 has been replaced with an
arginine) fused downstream of
mature HSA and HSA/kex2 leader
sequence. Glycosylation sites at
amino acid 51, 65 and 110 are
mutated from N to Q residue. DNA
encoding EPO is codon optimized.
151 2294 pC4:EPO.R140G.HSA Amino acids M1-D192 of EPO fused pC4 367 151 587 915 916 Native
also named upstream of mature HSA. The EPO EPO
pC4.EPO.R1406.HSA sequence included in construct 1997
was used to generate this construct,
mutating arginine at EPO amino acid
140 to glycine. This mutated
sequence matches the wildtype EPO
sequence.
152 2295 pSAC35:humanresistin.- Amino acids K19 to P108 of Resistin pSAC35 368 152 584 917 918 HSA/kex2
K19-P108:HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
153 2296 pSAC35:HSA:humanresistin.- Amino acids K19 to P108 of Resistin pSAC35 369 153 585 919 920 HSA
K19-P108 fused downstream of HSA.
154 2297 pSAC35:humanresistin.- Amino acids K19 to P108 of Resistin pSAC35 370 154 586 921 922 HSA/kex2
K19-P108.stop:HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence. Includes two stops at 3′
end for termination of translation
before the HSA.
155 2298 pEE12.1:EPO.R140G.- Amino acids M1 to D192 of EPO pEE12.1 371 155 587 923 924 Native
HSA fused upstream of mature HSA. The EPO
EPO sequence included in construct
1997 was used to generate this
construct, mutating arginine at EPO
amino acid 140 to glycine. This
mutated sequence matches the
wildtype EPO sequence.
156 2300 pC4:humanresistin.M1-P108: Amino acids M1 to P108 of Resistin pC4 372 156 588 925 926 Native
HSA fused upstream of mature HSA. resistin
157 2309 pEE12.1:humanresistin.- Amino acids M1 to P108 of Resistin pEE12.1 373 157 589 927 Native
M1-P108:HSA fused upstream of mature HSA. resistin
158 2310 pc4:EPOco.M1-D192.- Amino acids M1 to D192 of EPO pC4 374 158 590 928 929 Native
HSA variant fused upstream of mature EPO
HSA. DNA encoding EPO is codon
optimized. The EPO sequence
included in construct 1997 was used
to generate this construct, mutating
arginine at EPO amino acid 140 to
glycine. This mutated sequence
matches the wildtype EPO sequence.
159 2311 pC4:EPO.M1-G27.- Amino acids M1 to D192 of EPO pC4 375 159 591 930 931 Native
EPOco.A28-D192.- fused upstream of mature HSA. DNA EPO
HSA encoding only EPO portion is codon
optimized. The EPO sequence
included in construct 1997 was used
to generate this construct, mutating
arginine at EPO amino acid 140 to
glycine. This mutated sequence
matches the wildtype EPO sequence.
160 2320 pC4:HCHNF25M1-R104.- Amino acids M1 to R104 of pC4 376 160 592 932 933 Native
HSA HCHNF25 fused upstream of mature HCHNF25
HSA.
161 2325 pC4.EPO:M1-D192.- Amino acids M1 to D192 of EPO pC4 377 161 593 Native
HSA.Codon fused upstream of mature HSA. DNA EPO
opt. encoding EPO is codon optimized.
162 2326 pEE12.1.EPO:M1-D192.- Amino acids M1 to D192 of EPO pEE12.1 378 162 594 Native
HSA.Codon fused upstream of mature HSA. DNA EPO
opt. encoding EPO is codon optimized.
163 2328 pC4:HLDOU18.K23-R429.- Amino acids K23 to R429 of pC4 379 163 595 934 935 HSA
HSA HLDOU18 fused upstream of mature
HSA and downstream of native HSA
leader sequence.
164 2330 CK-Beta4-HSA Full length Ckbeta4 fused upstream pSAC35 380 164 596 936 937 Native
of mature HSA. CKβ4
165 2335 pC4:MPIFsp.ck{b}4D31-M96.- Amino acids D31 to M96 of Ckbeta4 pC4 381 165 597 938 939 MPIF
HSA fused upstream of mature HSA and
downstream of MPIF leader
sequence.
166 2336 pC4:MPIFsp.ck{b}4G35-M96.- Amino acids G35 to M96 of Ckbeta4 pC4 382 166 598 940 941 MPIF
HSA fused upstream of mature HSA and
downstream of MPIF leader
sequence.
167 2337 pC4:MPIFsp.ck{b}4G48-M96.- Amino acids G48 to M96 of Ckbeta4 pC4 383 167 599 942 943 MPIF
HSA fused upstream of mature HSA and
downstream of MPIF leader
sequence.
168 2338 pC4:MPIFsp.ck{b}4A62-M96.- Amino acids A62 to M96 of Ckbeta4 pC4 384 168 600 944 945 MPIF
HSA fused upstream of mature HSA and
downstream of MPIF leader
sequence.
169 2340 pC4:HSA.HLDOU18.- Amino acids K23 to R429 of pC4 385 169 601 946 947 HSA
K23-R429 HLDOU18 fused downstream of
HSA.
170 2343 pSAC35.INV- Mature Interferon alpha2 fused pSAC35 386 170 602 948 949 invertase
IFNA2.HSA upstream of mature HSA and
downstream of invertase signal
peptide.
171 2344 pC4.SpIg.EPO:A28-D192.- Amino acids A28 to D192 of EPO pC4 387 171 603 950 951 Mouse Ig
HSA.Codon fused upstream of mature HSA and leader
opt. downstream of mouse Ig leader
sequence. DNA encoding EPO is
codon optimized.
172 2348 pC4:MPIFsp.ck{b}4G57-M96.- Amino acids G57 to M96 of Ckbeta4 pC4 388 172 604 952 953 MPIF
HSA fused upstream of mature HSA and
downstream of MPIF leader
sequence.
173 2350 pC4:MPIFsp.HLDOU18 Amino acids S320 to R429 of pC4 389 173 605 954 955 MPIF
(S320-R429).HSA HLDOU18 fused upstream of mature
HSA and downstream of MPIF leader
sequence.
174 2351 pC4:HSA.HLDOU18 Amino acids S320 to R429 of pC4 390 174 606 956 957 HSA
(S320-R429) HLDOU18 fused downstream of
HSA.
175 2355 pSAC35:MATalpha.d8ckbeta1.- Amino acids G28 to N93 of Ckbeta1 pSAC35 391 175 607 958 959 MFα-1
G28-N93: fused upstream of mature HSA and
HSA downstream of the yeast mating
factor alpha leader sequence.
176 2359 pEE12:HLDOU18.K23-R429.- Amino acids K23 to R429 of pEE12.1 392 176 608 HSA
HSA HLDOU18 fused upstream of mature
HSA and downstream of native HSA
leader sequence.
177 2361 pC4:HRDFD27:HSA HRDFD27 fused upstream of mature pC4 393 177 609 960 961 Native
HSA. HRDFD27
178 2362 pEE12:HSA.HLDOU18.- Amino acids K23 to R429 of pEE12.1 394 178 610 HSA
K23-R429 HLDOU18 fused downstream of
HSA.
179 2363 pC4GCSF.HSA.EPO.- Amino acids M1 to P204 of GCSF pC4 395 179 611 Native
A28-D192 fused upstream of mature HSA GCSF
which is fused upstream of amino
acids A28 to D192 of EPO variant
(where amino acid 140 of EPO is
mutated from glycine to arginine.)
180 2365 pEE12.1.HCNCA73HSA HCNCA73 is fused upstream of pEE12.1 396 180 612 962 963 Native
mature HSA. HCNCA73
181 2366 pSAC35.MAF- Mature IFNa2 fused upstream of PSAC35 397 181 613 964 965 MFα-1
IFNa2.HSA mature HSA and downstream of
yeast mating factor alpha leader
sequence.
182 2367 pEE12.MPIFsp.HLDOU18.- Amino acids S320 to R429 of pEE12.1 398 182 614 966 967 MPIF
S320-R429.- HLDOU18 fused upstream of mature
HSA HSA and downstream of MPIF leader
sequence.
183 2369 pC4:HLDOU18.HSA Amino acids M1 to R429 of pC4 399 183 615 968 969 Native
HLDOU18 fused upstream of mature HLDOU18
HSA.
184 2370 pEE12:HLDOU18.HSA Amino acids M1 to R429 of pEE12.1 400 184 616 Native
HLDOU18 fused upstream of mature HLDOU18
HSA.
185 2373 pC4.GCSF.HSA.EPO.- Amino acids M1 to P204 of GCSF is pC4 401 185 617 Native
A28-D192.R140G fused upstream of mature HSA which GCSF
is fused upstream of amino acids A28
to D192 of EPO, wherein amino acid
140 is glycine. The EPO sequence
included in construct 1997 was used
to generate this construct, mutating
arginine at EPO amino acid 140 to
glycine. This mutated sequence
matches the wildtype EPO sequence.
186 2381 pC4:HSA-IFNa2(C17-E181) Amino acids C17 to E181 of IFNa2 pC4 402 186 618 970 971 HSA
(fragment shown as amino acids C1
to E165 of SEQ ID NO: 618) fused
downstream of HSA.
187 2382 pC4:IFNa2-HSA IFNa2 fused upstream of mature pC4 403 187 619 972 973 Native
HSA. IFNα2
leader
188 2387 pC4:EPO(G140)- Amino acids M1-D192 of EPO fused pC4 404 188 620 Native
HSA-GCSF.T31-P204 upstream of mature HSA which is EPO
fused upstream of amino acids T31 to
P204 of GCSF.
189 2407 pC4:HWHGZ51.M1-N323.- Amino acids M1 to N323 of pC4 405 189 621 974 975 Native
HSA HWHGZ51 fused upstream of mature HWHGZ51
HSA.
190 2408 pEE12.1:HWHGZ51.- Amino acids M1 to N323 of pEE12.1 406 190 622 976 977 Native
M1-N323.HSA HWHGZ51 fused upstream of mature HWHGZ51
HSA.
191 2410 pSAC35INV:IFNa- Mature IFNa2 fused downstream of pSAC35 407 191 623 978 979 invertase
HSA the invertase signal peptide and
upstream of mature HSA.
192 2412 pSAC35:delKEX.d8ckbeta1.- Amino acids G28 to N93 of Ckbeta1 pSAC35 408 192 624 980 981 HSA
G28-N93:HSA fused downstream of the HSA signal minus the
sequence (with the KEX site deleted - KEX site
last 6 amino acids of the leader)
and upstream of mature HSA.
193 2414 pC4.EPO:M1-D192 Amino acids M1 to D192 of EPO pC4 409 193 625 982 983 Native
copt.HSA.GCSF.- fused upstream of mature HSA which EPO
T31-P204 is fused upstream of amino acids T31
also named: to P204 of GCSF. DNA encoding
pC4.EPO:M1-D192 EPO has been codon optimized.
copt.HAS.GCSF.-
T31-P204
194 2428 pN4:PTH.S1-Q84/ Amino acids S1 to Q84 of PTH fused pN4 410 194 626 HSA
HSA upstream of mature HSA and
downstream of the native HSA leader
sequence.
195 2441 pEE12.EPO:M1-D192 Amino acids M1 to D192 of EPO pEE12.1 409 196 628 EPO
copt.HSA.GCSF.- fused upstream of mature HSA which leader
T31-P204 is fused upstream of amino acids T31
also named: to P204 of GCSF. DNA encoding
pEE12.EPO:M1-D192 EPO has been codon optimized.
copt.HAS.GCSF.-
T31-P204
196 2447 pC4:HSA.humancalcitonin.- Amino acids C98 to G130 of SEQ ID pC4 413 197 629 986 987 HSA
C1-G33 NO: 629 fused downstream of HSA.
197 2448 pSAC35:GLP-1(7- Amino acids H98 to R127 of pSAC35 414 198 630 988 989 HSA/kex2
36).HSA preproglucagon (SEQ ID NO: 630)
(hereinafter this specific domain will
be referred to as “GLP-1(7-36)”) is
fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
198 2449 pSAC35:INV.d8CKB1.- Amino acids G28 to N93 of Ckbeta1 pSAC35 415 199 631 990 991 Invertase
G28-N93:HSA fused downstream of the invertase
signal peptide and upstream of
mature HSA.
199 2455 pSAC35:HSA.GLP- GLP-1(7-36) is fused downstream of pSAC35 416 200 632 992 993 HSA/kex2
1(7-36) mature HSA and HSA/kex2 leader
sequence.
200 2456 pSAC35:GLP-1(7- Amino acids H98 to R127 of pSAC35 417 201 633 994 995 HSA/kex2
36(A8G)).HSA Preproglucagon (SEQ ID
NO: 633)(also referred to as “GLP-
1(7-36)”) is mutated at amino acid 99
of SEQ ID NO: 633 to replace the
alanine with a glycine. This
particular GLP-1 mutant will be
hereinafter referred to as “GLP-1(7-
36(A8G))” and corresponds to the
sequence shown in SEQ ID
NO: 1808. GLP-1(7-36(A8G)) is
fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
201 2457 pSAC35:HSA.GLP- GLP-1(7-36(A8G)) (SEQ ID pSAC35 418 202 634 996 997 HSA/kex2
1(7-36(A8G)) NO: 1808) is fused downstream of
mature HSA and HSA/kex2 leader
sequence.
202 2469 pSAC35:HSA.exendin.- Amino acids H48 to S86 of Extendin pSAC35 419 203 635 HSA
H48-S86 fused downstream of full length
HSA.
203 2470 pSAC35:Exendin.H48-S86.- Amino acids H48 to S86 of Extendin pSAC35 420 204 636 HSA/kex2
HSA fused upstream of mature HSA and
downstream of HSA/kex2 leader
sequence.
204 2473 pC4.HLDOU18:HSA: M1-R319 of HLDOU18 (containing pC4 421 205 637 998 999 Native
S320-R429 the furin site RRKR) followed by HLDOU18
residues ‘LE’ followed by mature
HSA followed by ‘LE’ and amino
acids S320 through R429 of
HLDOU18 (fragment shown as SEQ
ID NO: 637).
205 2474 pSAC35.MDC.P26-Q93.- Amino acids P26 to Q93 of MDC pSAC35 422 206 638 1000 1001 HSA/kex2
HSA fused downstream of the HSA/kex2
leader and upstream of mature HSA.
206 2475 pSAC35.MDC.M26-Q93.- Amino acids Y27 to Q93 of MDC pSAC35 423 207 639 1002 1003 HSA/kex2
HSA with an N-terminal methionine, fused
downstream of the HSA/kex2 leader
and upstream of mature HSA.
207 2476 pSAC35.MDC.Y27-Q93.- Amino acids Y27 to Q93 of MDC pSAC35 424 208 640 1004 1005 HSA/kex2
HSA fused downstream of the HSA/kex2
leader and upstream of mature HSA.
208 2477 pSAC35.MDC.M27-Q93.- Amino acids G28 to Q93 of MDC pSAC35 425 209 641 1006 1007 HSA/kex2
HSA with an N-terminal methionine, fused
downstream of the HSA/kex2 leader
and upstream of mature HSA.
209 2489 pSAC35:HSA.C17.A20-R136 Amino acids A20 to R136 of C17 pSAC35 426 210 642 1008 1009 HSA/kex2
fused downstream of mature HSA
with HSA/kex2 leader sequence.
210 2490 pSAC35:C17.A20-R136.- Amino acids A20 to R136 of C17 pSAC35 427 211 643 1010 1011 HSA/kex2
HSA fused downstream of the HSA/kex2
leader and upstream of mature HSA.
211 2492 pC4.IFNb(deltaM22).- Mutant full length INFbeta fused pC4 428 212 644 Native
HSA upstream of mature HSA. First IFNβ
residue of native, mature IFNbeta leader
(M22) has been deleted.
212 2498 pC4:HSA.KGF2D60.- Amino acids G96 to S208 of KGF-2 pC4 429 213 645 1012 1013 HSA
G96-S208 fused downstream of HSA.
213 2499 pC4:KGF2D60.G96-S208: Amino acids G96 to S208 of KGF2 pC4 430 214 646 1014 1015 HSA
HSA fused upstream of mature HSA and
downstream of the HSA signal
peptide.
214 2501 pSAC35:scFvI006D08.- BLyS antibody fused upstream of pSAC35 431 215 647 1016 1017 HSA/kex2
HSA mature HSA and downstream of
HSA/kex2 signal peptide.
215 2502 pSAC35:scFvI050B11.- BLyS antibody fused upstream of pSAC35 432 216 648 1018 1019 HSA/kex2
HSA mature HSA and downstream of
HSA/kex2 leader sequence.
216 2513 pC4:HSA.salmoncalcitonin.- C1 through G33 of salmon calcitonin pC4 1513 1345 1681 1854 1855 HSA
C1-G33 fused downstream of full length
HSA.
217 2515 pC4:HDPBQ71.M1-N565.- M1 through N565 of HDPBQ71 pC4 1514 1346 1682 1856 1857 Native
HSA fused upstream of mature HSA HDPBQ71
218 2529 pC4:TR1.M1-K194. Amino acids M1 to K194 of TR1 pC4 1223 1208 1238 1253 1254 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
219 2530 pC4:TR1.M1-Q193.- Amino acids M1 to Q193 of TR1 pC4 1224 1209 1239 1255 1256 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
220 2531 pC4:TR1.M1-E203.- Amino acids M1 to E203 of TR1 pC4 1225 1210 1240 1257 1258 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
221 2532 pC4:TR1.M1-Q339.- Amino acids M1 to Q339 of TR1 pC4 1226 1211 1241 1259 1260 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
222 2545 pEE12.1:HDPBQ71.- M1 through N565 of HDPBQ71 pEE12.1 1515 1347 1683 Native
M1-N565.HSA fused upstream of mature HSA HDPBQ71
223 2552 pSAC35:KGF2delta33.- Amino acids S69 through S208 of pScCHSA 1516 1348 1684 1858 1859 HSA/kex2
S69-S208.HSA KGF2 fused upstream of HSA.
224 2553 pSAC35:HSA.KGF2delta33.- HSA/kex2 signal peptide followed by pScNHSA 1517 1349 1685 1860 1861 HSA/kex2
S69-S208 HSA peptide followed by amino
acids S69 to S208 of KGF2.
225 2555 pEE12.1:TR1.M1-Q193.- Amino acids M1 to Q193 of TR1 pEE12.1 1227 1212 1242 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
226 2556 pEE12.1:TR1.M1-K194.- Amino acids M1 to K194 of TR1 pEE12.1 1228 1213 1243 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
227 2557 pEE12.1:TR1.M1-E203.- Amino acids M1 to E203 of TR1 pEE12.1 1229 1214 1244 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
228 2558 pEE12.1:TR1.M1-Q339.- Amino acids M1 to Q339 of TR1 pEE12.1 1230 1215 1245 Native
HSA (including native signal sequence) TR1
fused upstream of mature HSA.
229 2571 pC4.OSCAR.R232.HSA M1-R232 of OSCAR fused upstream pC4 1518 1350 1686 1862 1863 Native
of mature HSA. OSCAR
receptor
leader
230 2580 pC4.IFNb(deltaM22, C38S).- IFNb fused upstream of mature HSA. pC4 1519 1351 1687 Native
HSA The IFNb used in this fusion lacks IFNβ
the first residue of the mature form of
IFNb, which corresponds to M22 of
SEQ ID NO: 1687. Also amino acid
38 of SEQ ID NO: 1687 has been
mutated from Cys to Ser.
231 2584 pC4:MPIFsp.KGF2delta28.- MPIF signal sequence followed by pC4 1520 1352 1688 1864 1865 MPIF
A63-S208.HSA A63 through S208 of KGF2 followed
by mature HSA.
232 2603 pC4:HSA(A14)- Modified HSA A14 leader fused pC4 1521 1353 1689 Modified
EPO(A28-D192.- upstream of mature HSA which is HSA
G140) fused upstream of A28 through D192 (A14)
of EPO. Amino acid 140 of EPO is a
‘G’.
233 2604 pC4:HSA(S14)- Modified HSA S14 leader fused pC4 1522 1354 1690 Modified
EPO(A28-D192.- upstream of mature HSA which is HSA
G140) fused upstream of A28 through D192 (S14)
of EPO. Amino acid 140 of EPO is a
‘G’.
234 2605 pC4:HSA(G14)- Modified HSA G14 leader fused pC4 1523 1355 1691 Modified
EPO(A28-D192.- upstream of mature HSA which is HSA
G140) fused upstream of A28 through D192 (G14)
of EPO. Amino acid 140 of EPO is a
‘G’.
235 2606 pC4:HSA#64.KGF2D28.- A63 through S208 of KGF2 fused pC4 1524 1356 1692 1866 1867 Modified
A63-S208 downstream of mature HSA and the HSA #64
modified #64 leader sequence.
236 2607 pC4:HSA#65.KGF2D28.- A63 through S208 of KGF2 pC4 1525 1357 1693 1868 1869 Modified
A63-S208 downstream of mature HSA and the HSA #65
modified #65 leader sequence.
237 2608 pC4:HSA#66.KGF2D28.- A63 through S208 of KGF2 fused pC4 1526 1358 1694 1870 1871 Modified
A63-S208 downstream of mature HSA and the HSA #66
modified #66 leader sequence.
238 2623 pC4:(AGVSG, 14-18) A modified HSA A14 leader pC4 1527 1359 1695 Modified
HSA.HLDOU18.K23-R429 followed by mature HSA and amino HSA
acids K23 through R429 of (A14)
HLDOU18. leader
239 2624 pC4:(SGVSG, 14-18) Modified HSA S14 leader followed pC4 1528 1360 1696 Modified
HSA.HLDOU18.K23-R429 by mature HSA and amino acids K23 HSA
to R429 of HLDOU18. (S14)
leader
240 2625 pC4:(GGVSG, 14-18) A modified HSA G14 leader pC4 1529 1361 1697 Modified
HSA.HLDOU18.K23-R429 sequence followed by mature HSA HSA
and amino acids K23 through R429 (G14)
of HLDOU18. leader
241 2630 pC4:HSA.KGF2D28.- Amino acids A63 to S208 of KGF-2 pC4 1530 1362 1698 1872 1873 HSA
A63-S208#2 fused to the C-terminus of HSA.
242 2631 pEE12.1:(AGVSG, 14-18) A modified HSA A14 leader pEE12.1 1531 1363 1699 Modified
HSA.HLDOU18.K23-R429 sequence followed by mature HSA HSA
and amino acids K23 through R429 (A14)
of HLDOU18. leader
243 2632 pEE12.1:(SGVSG, 14-18) Modified HSA S14 leader followed pEE12.1 1532 1364 1700 Modified
HSA.HLDOU18.K23-R429 by mature HSA and amino acids K23 HSA
to R429 of HLDOU18. (S14)
leader
244 2633 pEE12.1:(GGVSG, 14-18) A modified HSA G14 leader pEE12.1 1533 1365 1701 Modified
HSA.HLDOU18.K23-R429 sequence followed by mature HSA HSA
and amino acids K23 through R429 (G14)
of HLDOU18. leader
245 2637 pSAC35:HSA.GCSF.- HSA/kex2 leader fused upstream of pScNHSA 1534 1366 1702 1874 1875 HSA/kex2
T31-P207 mature HSA followed by T31
through P207 of GCSF (SEQ ID
NO: 1702).
246 2638 pPPC007:116A01.HSA scFv I116A01 with C-terminal HSA pPPC007 1535 1367 1703 1876 1877 scFvI006
fusion, where the mature form of A01
HSA lacks the first 8 amino acids.
247 2647 pSAC35:T7.HSA. The T7 peptide (SEQ ID NO: 1704) pScCHSA 1536 1368 1704 1878 1879 HSA/kex2
of Tumstatin was fused with a C-
terminal HSA and N terminal
HSA/kex2 leader.
248 2648 pSAC35:T8.HSA The T8 peptide (SEQ ID NO: 1705) pScCHSA 1537 1369 1705 1880 1881 HSA/kex2
of Tumstatin is fused upstream to
mature HSA and downstream from
HSA/kex2.
249 2649 pSAC35:HSA.T7 The T7 peptide (SEQ ID NO: 1706) pScNHSA 1538 1370 1706 1882 1883 HSA/kex2
of Tumstatin was fused with a N-
terminal HSA/kex2 signal sequence.
250 2650 pSAC35:HSA.T8 The T8 peptide (SEQ ID NO: 1767) pScNHSA 1539 1371 1707 1884 1885 HSA/kex2
of Tumstatin is fused downstream to
HSA/kex2 signal sequence and
mature HSA.
251 2656 pSac35:Insulin(KR.GGG.- Synthetic gene coding for a single- pScCHSA 1540 1372 1708 1886 1887 HSA/kex2
KR).HSA chain insulin with HSA at C-
terminus. Contains a modified loop
for processing resulting in correctly
disulfide bonded insulin coupled to
HSA.
252 2667 pSAC35:HSA.T1249 T1249 fused downstream of full pSAC35 1178 1179 1180 1181 1182 HSA
length HSA
253 2668 pSac35:HSA.Insulin Synthetic gene coding for insulin pScNHSA 1541 1373 1709 1888 1889 HSA
(KR.GGG.KR) with FL HSA at N-terminus.
Contains a modified loop for
processing resulting in correctly
disulfide bonded insulin coupled to
HSA.
254 2669 pSac35:Insulin(GGG.- Synthetic gene coding for a single- pScCHSA 1542 1374 1710 1890 1891 HSA/kex2
KK).HSA chain insulin with HSA at C-
terminus. Contains a modified loop.
255 2670 pSAC35:T1249.HSA T1249 fused downstream of pSAC35 1183 1179 1180 1184 1185 HSA/kex2
HSA/kex2 leader and upstream of
mature HSA.
256 2671 pSac35:HSA.Insulin Synthetic gene coding for a single- pScNHSA 1543 1375 1711 1892 1893 HSA
(GGG.KK) chain insulin with HSA at N-
terminus. Contains a modified loop
for greater stability.
257 2672 pSAC35:HSA.T20 Amino terminus of T20 (codon pSAC35 1186 1187 1188 1189 1190 HSA
optimized) fused downstream of full
length HSA
258 2673 pSAC35:T20.HSA Amino terminus of T20 (codon pSAC35 1191 1187 1188 1192 1193 HSA/kex2
optimized) fused downstream of
HSA/kex2 leader and upstream of
mature HSA.
259 2700 pSAC35:HSA.GCSF.- C-terminal deletion of GCSF fused pSAC35 1544 1376 1712 1894 1895 HSA/kex2
T31-R199 downstream of mature HSA.
260 2701 pSAC35:HSA.GCSF.- C-terminal deletion of GCSF fused pScNHSA 1545 1377 1713 1896 1897 HSA/kex2
T31-H200 downstream of mature HSA.
261 2702 pSAC35:HSA.GCSF.- HSA/kex2 leader followed by mature pSAC35 1194 1195 1196 1197 1198 HSA/kex2
T31-L201 HSA and amino acids T31-L201 of
GCSF (corresponding to amino acids
T1 to L171 of SEQ ID NO: 1196).
262 2703 pSAC35:HSA.GCSF.- HSA/kex2 leader followed by pScNHSA 1546 1378 1714 1898 1899 HSA/kex2
A36-P204 mature HSA and amino acids
A36-P204 of GCSF.
263 2714 pC4:HSASP.PTH34(2)/ PTH34 double tandem repeats fused pC4 1199 1200 1201 1202 1203 HSA
HSA downstream of HSA leader (with the leader
KEX site deleted - last 6 amino acids minus
of the leader) and upstream of mature Kex site
HSA.
264 2724 pSAC35.sCNTF.HSA HSA/Kex2 fused to CNTF, and then pSAC35 1547 1379 1715 1900 1901 HSA/kex2
fused to mature HSA.
265 2725 pSAC35:HSA.sCNTF HSA/Kex2 fused to mature HSA and pSAC35 1548 1380 1716 1902 1903 HSA/kex2
then to CNTF
266 2726 pSac35.INV.GYGinsulin.- Synthetic gene coding for a single- pSAC35 1549 1381 1717 1904 1905 Invertase
HSA chain insulin with HSA at C-
terminus. The signal peptide of
invertase is used for this construct.
267 2727 pSac35.INV.GYGinsulin Synthetic gene coding for a single- pSAC35 1550 1382 1718 1906 1907 invertase
(delF1).HSA chain insulin with HSA at C-
terminus. Construct uses the
invertase signal peptide and is
lacking the first amino acid (F) of
mature human insulin.
268 2749 pEE12.1.OSCAR.R232.- Amino acids M1 through R232 of pEE12.1 1551 1383 1719 1908 1909 Native
HSA OSCAR fused upstream of mature OSCAR
HSA. leader
269 2784 pSAC35:Insulin(GYG)- Synthetic gene coding for a single- pSAC35 1552 1384 1720 1910 1911 invertase
HSA codon chain insulin with HSA at C-
optimized terminus.
270 2789 pSAC35:Insulin(GGG).- Synthetic gene coding for a single- pSAC35 1553 1385 1721 1912 1913 invertase
HSA (codon chain insulin with HSA at C-
optimized) terminus.
271 2791 pEE12.1:HSAsp.PTH34 Parathyroid hormone is fused in pEE12.1 1554 1386 1722 HSA
(2X).HSA tandem and upstream of mature HSA leader
and downstream from HSA signal minus
peptide (with the KEX site deleted - Kex site
last 6 amino acids of the leader)
272 2795 pC4:HSA(A14)- The mature form of IFNb is fused to pC4 1555 1387 1723 Modified
IFNb.M22-N187 the C-terminus of HSA, which HSA
contains an modified signal peptide, (A14)
designed to improve processing and
homogeneity.
273 2796 pC4:HSA(S14)- The mature form of IFNb is fused to pC4 1556 1388 1724 Modified
IFNb.M22-N187 the C-terminus of HSA, which HSA
contains a modified signal peptide, (S14)
designed to improve processing and
homogeneity.
274 2797 pC4:HSA(G14)- The mature form of IFNb is fused to pC4 1557 1389 1725 Modified
IFNb.M22-N187 the C-terminus of HSA, which HSA
contains an modified signal peptide. (G14)
275 2798 pSAC35:Somatostatin A 14 amino acid peptide of pScCHSA 1558 1390 1726 1914 1915 HSA/kex2
(S14).HSA Somatostatin fused downstream of
HSA/kex2 leader and upstream of
mature HSA.
276 2802 pSAC35:GLP-1(7- GLP-1(7-36(A8G)) (SEQ ID pScNHSA 1559 1391 1727 HSA/kex2
36(A8G)).IP2.HSA NO: 1808) is fused downstream from
the HSA/kex2 leader sequence and
upstream from the intervening
peptide-2 of proglucagon peptide and
upstream from mature HSA.
277 2803 pSAC35:GLP-1(7- GLP-1(7-36(A8G)) (SEQ ID pScCHSA 1231 1216 1246 1261 1262 HSA/kex2
36(A8G))x2.HSA NO: 1808) is tandemly repeated and
fused downstream of the HSA/kex2
signal sequence, and upstream of
mature HSA.
278 2804 pSAC35:coGLP-1(7- GLP-1(7-36(A8G)) (SEQ ID pScCHSA 1232 1217 1247 1263 1264 HSA/kex2
36(A8G))x2.HSA NO: 1808) is tandemly repeated and
fused downstream of the HSA/kex2
signal sequence, and upstream of
mature HSA.
279 2806 pC4:HSA#65.salmoncalcitonin.- Modified HSA leader #65 followed pC4 1560 1392 1728 1916 1917 Modified
C1-G33 by mature HSA and C1-G33 of HSA #65
salmon calcitonin.
280 2821 pSac35.delKex2.Insulin Synthetic gene coding for a single- pScCHSA 1561 1393 1729 Modified
(GYG).HSA chain insulin with HSA at C- HSA/kex2,
terminus. The kex2 site has been lacking
deleted from the HSA/KEX2 signal the Kex2
peptide. site.
281 2822 pSac35.alphaMF.Insulin Synthetic gene coding for a single- pSAC35 1562 1394 1730 1920 1921 MFα-1
(GYG).HSA chain insulin with HSA at C-
terminus. The signal peptide of alpha
mating factor (MFα-1) is used for
this construct.
282 2825 pSAC35:HSA.Somatostatin 14 amino acid peptide of pScNHSA 1563 1395 1731 1922 1923 HSA/kex2
(S14) Somatostatin was fused downstream
of HSA/kex2 leader and mature
HSA.
283 2830 pSAC35:S28.HSA 28 amino acids of somatostatin fused pScCHSA 1564 1396 1732 1924 1925 HSA/kex2
downstream of HSA/kex2 leader and
upstream of mature HSA.
284 2831 pSAC35:HSA.S28 28 amino acids of somatostatin fused pScNHSA 1565 1397 1733 1926 1927 HSA/kex2
downstream of HSA/kex2 leader and
mature HSA.
285 2832 pSAC35:Insulin.HSA Long-acting insulin peptide fused pScCHSA 1566 1398 1734 1928 1929 invertase
(yeast codon upstream of mature HSA.