CA2421588A1 - Tnf receptor-like molecules and uses thereof - Google Patents

Tnf receptor-like molecules and uses thereof Download PDF

Info

Publication number
CA2421588A1
CA2421588A1 CA002421588A CA2421588A CA2421588A1 CA 2421588 A1 CA2421588 A1 CA 2421588A1 CA 002421588 A CA002421588 A CA 002421588A CA 2421588 A CA2421588 A CA 2421588A CA 2421588 A1 CA2421588 A1 CA 2421588A1
Authority
CA
Canada
Prior art keywords
seq
polypeptide
amino acid
set forth
acid sequence
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002421588A
Other languages
French (fr)
Other versions
CA2421588C (en
Inventor
Lars Eyde Theill
Richard Yeh
Scott Michael Silbiger
Gang Yu
Giorgio Senaldi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Amgen Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2421588A1 publication Critical patent/CA2421588A1/en
Application granted granted Critical
Publication of CA2421588C publication Critical patent/CA2421588C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2799/00—Uses of viruses
    • C12N2799/02—Uses of viruses as vector
    • C12N2799/021—Uses of viruses as vector for the expression of a heterologous nucleic acid

Abstract

Novel MK61 polypeptides and nucleic acid molecules encoding the same. The invention also provides vectors, host cells, selective binding agents, and methods for producing MK61 polypeptides. Also provided for are methods for t he treatment, diagnosis, amelioration, or prevention of diseases with MK61 polypeptides.

Claims (93)

1. An isolated nucleic acid. molecule comprising a nucleotide sequence selected from the group consisting of:
(a) the nucleotide sequence as set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID
NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID NO:13, or SEQ
ID NO:15;
(b) the MK61 coding portion of SEQ ID
NO:1, SEQ ID NO: 3, SEQ ID NO: 5, SEQ ID NO: 7, SEQ ID
NO: 9, SEQ ID NO: 11, SEQ ID NO: 13, or SEQ ID NO: 15;
(c) a nucleotide sequence encoding the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(d) a nucleotide sequence which hybridizes under moderately stringent conditions to the complement of (a) or (b), wherein the encoded polypeptide has an activity of the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16; and (e) a nucleotide sequence complementary to any of (a) - (d).
2. An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
(a) a nucleotide sequence encoding a polypeptide that exhibits at least about 70 percent identity to the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, wherein the polypeptide has an activity of the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ
ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(b) a nucleotide sequence encoding an allelic variant or splice variant of the nucleotide sequence set forth in SEQ ID NO:1, SEQ ID NO:3, SEQ ID
NO:5, SEQ ID NO:7, SEQ ID NO:9, SEQ ID NO:11, SEQ ID
NO:13, or SEQ ID NO:15, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(c) a nucleotide sequence of SEQ ID
NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID
NO:9, SEQ ID NO:11; SEQ ID NO:13, or SEQ ID NO:15; (a) or (b) encoding a polypeptide fragment of at least about 25 amino acid residues, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16;
(d) a nucleotide sequence of SEQ ID
NO:1, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:7, SEQ ID
NO:9, SEQ ID NO:11, SEQ ID NO:13, or SEQ ID NO:15, or (a) - (c) comprising a fragment of at least about 16 nucleotides;
(e) a nucleotide sequence which hybridizes under moderately stringent conditions to the complement of any of (a) - (d), wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and (f) a nucleotide sequence complementary to any of (a) - (c).
3. An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of:
(a) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6,. SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16 with at least one conservative amino acid substitution, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16;
(b) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(c) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(d) a nucleotide sequence encoding a polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16 which has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(e) a nucleotide sequence encoding a polypeptide set forth in.SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16 with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(f) a nucleotide sequence of (a) - (e) comprising a fragment of at least about 16 nucleotides;
(g) a nucleotide sequence which hybridizes under. moderately stringent conditions to the complement of any of (a)-(f), wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and (h) a nucleotide sequence complementary to any of (a) - (e).
4. A vector comprising the nucleic acid molecule of claims 1, 2, or 3.
5. A host cell comprising the vector of claim 4.
6. The host cell of claim 5 that is a eukaryotic cell.
7. The host cell of claim 5 that is a prokaryotic cell.
8. A process of producing an MK61 polypeptide comprising culturing the host cell of Claim 5 under suitable conditions to express the polypeptide, and optionally isolating the polypeptide from the culture.
9. An isolated polypeptide produced by the process of claim 8.
10. The process of claim 8, wherein the nucleic acid molecule comprises promoter DNA other than the promoter DNA for the native MK61 polypeptide operatively linked to the nucleotide sequence encoding the MK61 polypeptide.
11. The isolated nucleic acid molecule according to claim 2, wherein the percent identity is determined using a computer program selected from the group consisting of GAP, BLASTP, BLASTN, FASTA, BLASTA, BLASTX, BestFit and the Smith-Waterman algorithm.
12. A process for identifying candidate inhibitors of MK61 polypeptide activity or production comprising exposing a cell according to claim 5, 6 or 7 to the candidate inhibitors, measuring MK61 polypeptide activity or production in said cell, and comparing activity of MK61 in cells exposed to the candidate inhibitor with activity in cells not exposed to the candidate inhibitor.
13. A process for identifying candidate stimulators of MK61 polypeptide activity or production comprising exposing a cell according to claims 5, 6 or 7 to candidate stimulators, measuring MK61 polypeptide activity in said cell, and comparing activity of MK61 in cells exposed to the candidate stimulator with activity in cells not exposed to the candidate stimulator.
14. An isolated polypeptide comprising the amino acid sequence set forth in SEQ ID NO:2, SEQ
ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID
NO:12, SEQ ID NO:14, or SEQ ID NO:16.
15. An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
(a) an amino acid sequence comprising the mature form of the polypeptide set forth in SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID

NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, and optionally further comprising an amino-terminal methionine;
(b) an amino acid sequence for an ortholog of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ
ID NO:8, SEQ ID NO:10; SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, wherein the ortholog has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(c) an amino acid sequence that exhibits at least about 70 percent identity to the amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID
NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID
NO:14, or SEQ ID NO:16, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(d) a fragment of the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID
NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID
NO:14, or SEQ ID NO:16 comprising at least about 25 amino acid residues, wherein the encoded polypeptide has an activity of the polypeptide as set forth in SEQ
ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and (e) an amino acid sequence for an allelic variant or splice variant of either the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16, or at least one of (a)-(c) wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.
16. An isolated polypeptide comprising the amino acid sequence selected from the group consisting of:
(a) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID
NO:16 with at least one conservative amino acid substitution, wherein the encoded polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16;
(b) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID
NO:16 with at least one amino acid insertion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16;
(c) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID
NO:16 with at least one amino acid deletion, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16;

(d) the amino acid sequence set forth in SEQ ID NO: 2 which has a C- and/or N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and (e) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID
NO:16, with at least one modification selected from the group consisting of amino acid substitutions, amino acid insertions, amino acid deletions, C-terminal truncation, and N-terminal truncation, wherein the polypeptide has an activity of the polypeptide set forth in SEQ ID NO:2, SEQ ID NO;4, SEQ ID NO:6, SEQ ID
NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ
ID NO:16.
17. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 38 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine.
18. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 39 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine.
19. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 51 of SEQ ID NO: 2, 4, 6, 8, 10 or 12 is cysteine, serine or alanine.
20. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 60 of SEQ ID.NO: 2, or 6 is cysteine, serine or alanine.
21. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 76 of SEQ ID NO: 2, or 6 is cysteine, serine or alanine.
22. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 41 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine.
23. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 42 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine.
24. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 54 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine.
25. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 63 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine.
26. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 79 of SEQ ID NO: 14 or 16 is cysteine, serine or alanine.
27. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 171 of SEQ ID NO: 2 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine.
28. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 172 of SEQ ID NO: 2 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine.
29. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 178 of SEQ ID NO: 14 or 16 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine.
30. A polypeptide comprising the amino acid sequence of claims 15 or 16 wherein the amino acid at position 180 of SEQ ID NO: 14 or 16 is leucine, norleucine, isoleucine, valine, methionine, alanine or phenylalanine.
31. An isolated polypeptide encoded by the nucleic acid molecule of claims 1, 2, or 3.
32. The isolated polypeptide according to Claim 15 wherein the percent identity is determined using a computer program selected from the group consisting of GAP, BLASTP, BLASTN, FASTA, BLASTA, BLASTX, BestFit and the Smith-Waterman algorithm.
33. An antibody produced by immunizing an animal with a peptide comprising an amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ
ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.
34. An antibody or fragment thereof that specifically binds the polypeptide of any one of claims 14, 15, or 16.
35. The antibody of claim 34 that is a monoclonal antibody.
36. A hybridoma that produces a monoclonal antibody that binds to a peptide comprising an amino acid sequence of SEQ ID NO:2, SEQ ID NO:4, SEQ
ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ
ID NO:14, or SEQ ID NO:16.
37. A method of detecting or quantitating the amount of MK61 polypeptide in a sample comprising contacting a sample suspected of containing MK61 with the anit-MK61 antibody or antibody fragment of any of claims 33, 34 or 35 and detecting said binding of said antibody or antibody fragment.
38. A selective binding agent or fragment thereof that specifically binds at least one polypeptide wherein said polypeptide comprises the amino acid sequence selected from the group consisting of:
(a) the amino acid sequence set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID
NO:16; and (b) a fragment of at least about 25 amino acids the amino acid sequence set forth in at least one of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ
ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16; and (c) a naturally occurring variant of (a) or (b).
39. The selective binding agent of claim 38 that is an antibody or a fragment thereof.
40. The selective binding agent of claim 38 that is a humanized antibody.
41. The selective binding agent of claim 38 that is a human antibody or a fragment thereof.
42. The selective binding agent of Claim 38 that is a polyclonal antibody or a fragment thereof.
43. The selective binding agent of claim 38 that is a monoclonal antibody or a fragment thereof.
44. The selective binding agent of claim 38 that is a chimeric antibody or a fragment thereof.
45. The selective binding agent of claim 38 that is a complementarity determining region (CDR0-grafted antibody or a fragment thereof.
46. The selective binding agent of claim 38 that is an anti-idiotypic antibody or a fragment thereof.
47. The selective binding agent of claim 38 which is an antibody variable region fragment.
48. The variable region fragment of claim 38 which is a Fab or a Fab' fragment.
49. A selective binding agent or fragment thereof comprising at least one complementarity-determining region with specificity for a polypeptide having the amino acid sequence of SEQ ID
NO:2, SEQ ID NO:4, SEQ ID NO;6, SEQ ID NO:8, SEQ ID
NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.
50, The selective binding agent of claim 38 which is bound to a detectable label.
51. The selective binding agent of claim 38 which is an antagonist or agonist of MK61 polypeptide biological activity.
52. A method for treating, preventing or ameliorating a disease, condition or disorder comprising administering to a patient an effective amount of a selective binding agent according to claim 38.
53. A selective binding agent produced by immunizing an animal with a polypeptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.
54. A hybridoma that produces a selective binding agent capable of binding a polypeptide according to claims 1, 2, or 3.
55. A composition comprising the polypeptide of claims 14, 15, or 16 and a pharmaceutically acceptable formulation agent.
56. The composition of claim 55 wherein the pharmaceutically acceptable formulation agent is a carrier, adjuvant, solubilizer, stabilizer or anti-oxidant.
57. The composition of claim 55 wherein the polypeptide comprises the mature form of the polypeptide as set forth in SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID NO:12, SEQ ID NO:14, or SEQ ID NO:16.
58. A polypeptide comprising a derivative of the polypeptide of claims 14, 15, or 16.
59. The polypeptide of claim 58 which is covalently modified with a water-soluble polymer.
60. The polypeptide of claim 51, wherein the water-soluble polymer is selected from the group consisting of polyethylene glycol, monomethoxy-polyethylene glycol, dextran, cellulose, poly-(N-vinyl pyrrolidone) polyethylene glycol, propylene glycol homopolymers, polypropylene oxide/ethylene oxide co-polymers, polyoxyethylated polyols, and polyvinyl alcohol.
61. A composition comprising a nucleic acid molecule of claims 1, 2 or 3 and a pharmaceutically acceptable formulation agent.
62. The composition of claim 61, wherein said nucleic acid molecule is contained in a viral vector.
63. A viral vector comprising a nucleic acid molecule of any of claims 1, 2, or 3.
64. A polypeptide comprising the polypeptide of any of claims 14, 15, or 16 fused to a heterologous amino acid sequence.
65. The fusion polypeptide of claim 64 wherein the heterologous amino acid sequence is an IgG
constant domain or fragment thereof.
66. A fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 36.
67. A fusion polypeptide comprising the amino acid sequence of SEQ ID NO: 39.
68 A method for treating, preventing or ameliorating a medical condition in a mammal resulting from increased levels of MK61 polypeptide comprising administering to said mammal a therapeutically effective amount of an antagonist selected from the group consisting of selective binding agents, small molecules, peptides, peptide derivatives and antisense oligonucleotides.
69. A method for treating, preventing or ameliorating a medical. condition in a mammal resulting from decreased levels of MK61 polypeptide comprising administering to said mammal a therapeutically effective amount of the polypeptide of any of claims 14, 15, or 16 or the polypeptide encoded by the nucleic acid of army of claims 1, 2, or 3 to said mammal.
70. A method of diagnosing a pathological condition or a susceptibility to a pathological condition in a subject caused by or-resulting from abnormal levels of MK61 polypeptide comprising:
(a) determining the presence or amount of expression of the polypeptide of any of claims 14, 15, or 16 or the polypeptide encoded by the nucleic acid molecule of any of claims 1, 2 or 3 in a sample;
and (b) comparing the level of MK61 polypeptide in a biological, tissue or cellular sample from normal subjects or the subject at a different time, wherein susceptibility to a pathological condition is based on the presence or amount of expression of the polypeptide.
71. A device comprising:
(a) a membrane suitable for implantation; and (b) cells encapsulated within said membrane, wherein said cells secrete a polypeptide of any of claims 14, 15 or 16, and wherein said membrane is permeable to said protein.
72. A device comprising:
(a) a membrane suitable for implantation; and (b) the MK61 polypeptide encapsulated within said membrane, wherein said membrane is permeable to said polypeptide.
73. A method of identifying a compound which binds to a polypeptide comprising:
(a) contacting the polypeptide of any of claims 14, 15 or 16 with a compound; and (b) determining the extent of binding of the polypeptide to the compound.
74. A method of modulating levels of a polypeptide in an animal comprising administering to the animal the nucleic acid molecule of any of claims 1, 2, or 3.
75. A method of inhibiting MK61 receptor activity in a mammal, comprising administering at least one polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ
ID NO:10, SEQ ID NO:12, SEQ ID NO:14, SEQ ID NO:16, SEQ
ID NO: 36 and SEQ ID NO: 39.
76. A method of inhibiting MK61 ligand activity in a mammal, comprising administering at least one polypeptide having the amino acids sequence selected from the group consisting of SEQ ID NO:2, SEQ
ID NO:4, SEQ ID NO:6, SEQ ID NO:8, SEQ ID NO:10, SEQ ID
NO:12, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO: 36 and SEQ ID NO: 39.
77. A method of stimulating an immune response in a mammal comprising administering a negative regulator of MK61 receptor signaling.
78. The method of claim 77 wherein the negative regulator is selected from the group consisting of a fusion protein, an antibody, a small molecule, a peptide and a peptide derivative.
79. The method of claim 78 wherein the fusion protein comprises the amino acid sequence of SEQ
ID NO: 16, SEQ ID NO: 36 or SEQ ID NO: 39.
80. A method of.inhibiting an immune response comprising administering a positive regulator of MK61 receptor signaling.
81. The method of claim 80 wherein the positive regulator is selected from the group consisting of a fusion protein, an antibody, a small molecule, a peptide and a peptide derivative.
82. A method of stimulating reverse signaling through a cell surface bound MK61 ligand comprising administering a positive regulator of MK61 ligand reverse signaling.
83. The method of claim 84 wherein the positive regulator is selected from the group consisting of a fusion protein, an antibody, a small molecule, a peptide and a peptide derivative.
84. The method of claim 83 wherein the fusion protein comprises the amino acid sequence of SEQ
ID NO: 16, SEQ ID NO: 36 or SEQ ID NO: 39.
85. A method of inhibiting reverse signaling through cell surface bound MK61 ligand comprising administering a negative regulator of MK61 ligand reverse signaling.
86. The method of claim 87 wherein the negative regulator is selected from the group consisting of a fusion protein, an antibody, a small molecule, a peptide and a peptide derivative.
87. A method of treating a B and T cell lymphoproliferative disorder in a mammal comprising administering a therapeutically effective amount of MK61-Fc fusion protein, an anti-MK-61 antibody, an antisense oligonucleotide, a MK61 ligand, or a anti-MK61 ligand antibody to said mammal.
88. The method of claim 87 wherein the lymphoproliferative disorder is leukemia, myeloma, B
lymphoma, or non-hodgkins lymphoma.
89. A method of treating an autoimmune disease comprising administering a therapeutically effective amount of MK61-Fc fusion protein, an anti-MK-61 antibody, an antisense oligonucleotide, a MK61 ligand, or a anti-MK61 ligand antibody to said mammal.
90. The method of claim 89 wherein the autoimmune disease is rheumatoid arthritis, systemic lupus erythematosus (SLE), intestinal bowel disease, or Crohn's disease.
91. A method of treating an inflammatory disease comprising administering a therapeutically effective amount of MK61-Fc fusion protein, an anti-MK-61 antibody, an antisense oligonucleotide, a MK61 ligand, or a anti-MK61 ligand antibody to said mammal.
92. The method of claim 91 wherein the inflammatory disease is rheumatoid arthritis, sepsis, intestinal bowel disease, or Crohn's disease.
93. A polypeptide fragment having an amino acid sequence comprising the cysteine rich domain residues 26-60 of SEQ ID NO: 36.
CA2421588A 2000-09-05 2001-09-05 Tnf receptor-like molecules and uses thereof Expired - Fee Related CA2421588C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US23019100P 2000-09-05 2000-09-05
US60/230,191 2000-09-05
PCT/US2001/027631 WO2002020762A2 (en) 2000-09-05 2001-09-05 Tnf receptor-like molecules and uses thereof

Publications (2)

Publication Number Publication Date
CA2421588A1 true CA2421588A1 (en) 2002-03-14
CA2421588C CA2421588C (en) 2010-01-26

Family

ID=22864263

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2421588A Expired - Fee Related CA2421588C (en) 2000-09-05 2001-09-05 Tnf receptor-like molecules and uses thereof

Country Status (10)

Country Link
US (3) US7153669B2 (en)
EP (1) EP1317536B1 (en)
JP (1) JP2004508043A (en)
AT (1) ATE431405T1 (en)
AU (2) AU2001288812B2 (en)
CA (1) CA2421588C (en)
DE (1) DE60138715D1 (en)
ES (1) ES2327102T3 (en)
MX (1) MXPA03001930A (en)
WO (1) WO2002020762A2 (en)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003020932A1 (en) * 2001-09-03 2003-03-13 Takeda Chemical Industries, Ltd. Novel secretory proteins and dna thereof
EP1338609A1 (en) * 2002-02-21 2003-08-27 MEMOREC Stoffel GmbH-Medizinisch-Molekulare Entwicklung, Köln A further KDR receptor and the use thereof
US8202701B2 (en) * 2004-10-08 2012-06-19 Georgia Tech Research Corporation Microencapsulation of cells in hydrogels using electrostatic potentials
CN102482321B (en) 2009-06-22 2015-06-17 安姆根有限公司 Refolding proteins using a chemically controlled redox state
JP2012531428A (en) 2009-06-25 2012-12-10 アムジエン・インコーポレーテツド Capture and purification process for proteins expressed in non-mammalian systems
CA2782320A1 (en) 2009-12-02 2011-06-09 Acceleron Pharma Inc. Compositions and methods for increasing serum half-life of fc fusion proteins
EP2646463B1 (en) 2010-12-02 2016-06-29 F.Hoffmann-La Roche Ag Antibody blocking the interaction between igfl1 and tmem149
WO2012170938A1 (en) 2011-06-08 2012-12-13 Acceleron Pharma Inc. Compositions and methods for increasing serum half-life
UY35148A (en) 2012-11-21 2014-05-30 Amgen Inc HETERODIMERIC IMMUNOGLOBULINS
US9708375B2 (en) 2013-03-15 2017-07-18 Amgen Inc. Inhibitory polypeptides specific to WNT inhibitors
EP3712166A1 (en) 2013-09-05 2020-09-23 Amgen Inc. Fc-containing molecules exhibiting predictable, consistent, and reproducible glycoform profiles
MX2016014761A (en) 2014-05-16 2017-05-25 Amgen Inc Assay for detecting th1 and th2 cell populations.
CA3056011A1 (en) 2017-03-14 2018-09-20 Amgen Inc. Control of total afucosylated glycoforms of antibodies produced in cell culture
CN111954719A (en) 2018-03-26 2020-11-17 美国安进公司 Total defucosylated glycoforms of antibodies produced in cell culture
JP2022549329A (en) 2019-09-26 2022-11-24 アムジェン インコーポレイテッド Methods of Producing Antibody Compositions
EP4162257A1 (en) 2020-06-04 2023-04-12 Amgen Inc. Assessment of cleaning procedures of a biotherapeutic manufacturing process
AU2021360897A1 (en) 2020-10-15 2023-05-25 Amgen Inc. Relative unpaired glycans in antibody production methods
CA3222409A1 (en) 2021-06-07 2022-12-15 Amgen Inc. Using fucosidase to control afucosylation level of glycosylated proteins
CA3233279A1 (en) 2021-10-05 2023-04-13 Amgen, Inc. Fc-gamma receptor ii binding and glycan content
WO2023215725A1 (en) 2022-05-02 2023-11-09 Fred Hutchinson Cancer Center Compositions and methods for cellular immunotherapy

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0393438T3 (en) 1989-04-21 2005-05-30 Amgen Inc TNF receptor, TNF binding proteins and DNAs encoding it
IL95031A (en) 1989-07-18 2007-03-08 Amgen Inc Method for the production of a human recombinant tumor necrosis factor inhibitor
US5194596A (en) * 1989-07-27 1993-03-16 California Biotechnology Inc. Production of vascular endothelial cell growth factor
US5350836A (en) * 1989-10-12 1994-09-27 Ohio University Growth hormone antagonists
DE4004317A1 (en) 1990-02-13 1991-08-14 Basf Ag NEW 3-SUBSTITUTED PYRIDINE METHANOLS AND FUNGICIDES CONTAINING THEM
US6641809B1 (en) * 1990-03-26 2003-11-04 Bristol-Myers Squibb Company Method of regulating cellular processes mediated by B7 and CD28
US5843789A (en) * 1995-05-16 1998-12-01 Neomecs Incorporated Method of analysis of genomic biopolymer and porous materials for genomic analyses
CA2323830A1 (en) * 1998-03-16 1999-09-23 Millennium Pharmaceuticals, Inc. Methods and compositions for diagnosing and treating chromosome-18p related disorders
US6660843B1 (en) * 1998-10-23 2003-12-09 Amgen Inc. Modified peptides as therapeutic agents
CA2395872A1 (en) 2000-01-31 2001-08-02 Human Genome Sciences, Inc. Nucleic acids, proteins, and antibodies
US6783969B1 (en) * 2001-03-05 2004-08-31 Nuvelo, Inc. Cathepsin V-like polypeptides

Also Published As

Publication number Publication date
US20090325880A1 (en) 2009-12-31
AU8881201A (en) 2002-03-22
ATE431405T1 (en) 2009-05-15
MXPA03001930A (en) 2003-06-19
EP1317536B1 (en) 2009-05-13
JP2004508043A (en) 2004-03-18
WO2002020762A8 (en) 2004-03-04
US20070015219A1 (en) 2007-01-18
US7569387B2 (en) 2009-08-04
ES2327102T3 (en) 2009-10-26
US20020150977A1 (en) 2002-10-17
EP1317536A2 (en) 2003-06-11
US7153669B2 (en) 2006-12-26
CA2421588C (en) 2010-01-26
WO2002020762A3 (en) 2002-08-08
AU2001288812B2 (en) 2007-05-10
DE60138715D1 (en) 2009-06-25
WO2002020762A2 (en) 2002-03-14

Similar Documents

Publication Publication Date Title
CA2421588A1 (en) Tnf receptor-like molecules and uses thereof
JP2004508043A5 (en)
JP2003527117A5 (en)
KR0178384B1 (en) Human, gp130 protein
HK1222415A1 (en) Circovirus sequence associated with porcine wasting disease (pwd) (pwd)
AU2005202316B2 (en) Receptor on the surface of activated T-cells- ACT-4
CA2296737C (en) Ligand for herpes simplex virus entry mediator and methods of use
CA2195955A1 (en) Modulators of body weight, corresponding nucleic acids and proteins, and diagnostic and therapeutic uses thereof
JP2007044044A5 (en)
US8426144B2 (en) Monocyte-derived nucleic acids and related compositions and methods
JP4776845B2 (en) Novel triggering receptors associated with natural cytotoxicity mediated by human natural killer cells and antibodies with identical properties
AU2005214141A1 (en) Protein ligands for NKG2d and UL16 receptors and uses thereof
JP2007054072A5 (en)
WO1995016709A2 (en) Anti-mullerian hormone receptor polypeptides and antibodies thereto
US6998108B1 (en) Antibodies to p30 polypeptides and methods making and using same
CA2393467A1 (en) Chordin-like molecules and uses thereof
JP2004514448A5 (en)
AU2008200700B2 (en) Novel Protein and Process for Producing The Same
WO1998011131A2 (en) Nucleic acid encoding human neuronal calcium channel subunits
US7164003B2 (en) Histamine receptor H4 polynucleotides
CA2288307C (en) Novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells and antibodies that identify the same
JP2006519582A5 (en)
WO1996024846A1 (en) Human t cell inositol 1,4,5-trisphosphate receptor
EP1174502A1 (en) Type 2 dendritic cell precursor derived coding nucleic acids and related compositions and methods
MXPA06009312A (en) Protein ligands for nkg2d and ul16 receptors and uses thereof

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed