CA2121889A1 - Production and use of multimeric hemoglobins - Google Patents

Production and use of multimeric hemoglobins

Info

Publication number
CA2121889A1
CA2121889A1 CA002121889A CA2121889A CA2121889A1 CA 2121889 A1 CA2121889 A1 CA 2121889A1 CA 002121889 A CA002121889 A CA 002121889A CA 2121889 A CA2121889 A CA 2121889A CA 2121889 A1 CA2121889 A1 CA 2121889A1
Authority
CA
Canada
Prior art keywords
hemoglobin
tetramers
tetramer
monodisperse
residue
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
CA002121889A
Other languages
French (fr)
Other versions
CA2121889C (en
Inventor
David C. Anderson
Anthony J. Mathews
Gary L. Stetler
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.)
Baxter Biotech Technology SARL
Original Assignee
Baxter Biotech Technology S.A.R.L.
Rhb1 Acquisition Corp.
David C. Anderson
Anthony J. Mathews
Gary L. Stetler
Somatogen, Inc.
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 Baxter Biotech Technology S.A.R.L., Rhb1 Acquisition Corp., David C. Anderson, Anthony J. Mathews, Gary L. Stetler, Somatogen, Inc. filed Critical Baxter Biotech Technology S.A.R.L.
Publication of CA2121889A1 publication Critical patent/CA2121889A1/en
Application granted granted Critical
Publication of CA2121889C publication Critical patent/CA2121889C/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
    • C07K14/795—Porphyrin- or corrin-ring-containing peptides
    • C07K14/805—Haemoglobins; Myoglobins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
    • A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
    • A61K47/6445—Haemoglobin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • 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
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • C12N15/81—Vectors or expression systems specially adapted for eukaryotic hosts for fungi for yeasts
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/90—Fusion polypeptide containing a motif for post-translational modification
    • C07K2319/92—Fusion polypeptide containing a motif for post-translational modification containing an intein ("protein splicing")domain

Abstract

The present invention relates to multimeric hemoglobin-like proteins wherein two or more tetramers or pseudotetramers are covalently bonded. Between any pair of covalently linked tetramers, the covalent linkage may take the form of a crosslink between two cysteine residues of different polypeptide chain, or of a peptide linker connecting the "carboxy most" residue of a globin-like domain of one tetramer with the "amino most" residue of a similar domain of a second tetramer. Preferably, the multimeric hemoglobin-like protein-containing composition is at least 50% monodisperse, more preferably, at least 95% monodisperse. Although free hemoglobin purified from natural sources may be polymerized by chemical crosslinking to increase halflife via increased molecular weight, and to reduce oncotic pressure, all such preparations are heterogeneous. Monodispersability can be achieved only by laborious purification. The present invention provides means of exerting strict control over the degree of polymerization of hemoglobin tetramers. The ability to strictly control formation of multimers will greatly facilitate purification and characterization of the final product and will reduce the chance of adverse reaction to minor components. It is also believed that a more mono-disperse composition will have greater consistency of clinical effect.
CA002121889A 1991-11-08 1992-11-06 Production and use of multimeric hemoglobins Expired - Fee Related CA2121889C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US789,179 1991-11-08
US07/789,179 US5545727A (en) 1989-05-10 1991-11-08 DNA encoding fused di-alpha globins and production of pseudotetrameric hemoglobin
PCT/US1992/009752 WO1993009143A1 (en) 1991-11-08 1992-11-06 Production and use of multimeric hemoglobins

Publications (2)

Publication Number Publication Date
CA2121889A1 true CA2121889A1 (en) 1993-05-13
CA2121889C CA2121889C (en) 2001-08-21

Family

ID=25146814

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002121889A Expired - Fee Related CA2121889C (en) 1991-11-08 1992-11-06 Production and use of multimeric hemoglobins

Country Status (13)

Country Link
US (7) US5545727A (en)
EP (2) EP0611376B1 (en)
JP (1) JPH07501059A (en)
AT (1) ATE167485T1 (en)
AU (1) AU672960B2 (en)
CA (1) CA2121889C (en)
DE (1) DE69225978T2 (en)
FI (1) FI942138A (en)
HU (1) HUT70309A (en)
IL (2) IL119656A0 (en)
NO (1) NO941703L (en)
SG (1) SG47882A1 (en)
WO (1) WO1993009143A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112662677A (en) * 2021-03-02 2021-04-16 天津师范大学 Chironomus rubripes Hb gene and application thereof in water quality biological monitoring

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Also Published As

Publication number Publication date
FI942138A0 (en) 1994-05-09
WO1993009143A1 (en) 1993-05-13
DE69225978T2 (en) 1999-02-11
EP0857489A2 (en) 1998-08-12
FI942138A (en) 1994-06-29
EP0857489A3 (en) 1998-09-30
HU9401338D0 (en) 1994-08-29
EP0611376A1 (en) 1994-08-24
AU3133793A (en) 1993-06-07
US5844088A (en) 1998-12-01
US5801019A (en) 1998-09-01
IL119656A0 (en) 1997-02-18
US5545727A (en) 1996-08-13
NO941703D0 (en) 1994-05-06
DE69225978D1 (en) 1998-07-23
IL119657A0 (en) 1997-02-18
ATE167485T1 (en) 1998-07-15
SG47882A1 (en) 1998-04-17
US6274331B1 (en) 2001-08-14
HUT70309A (en) 1995-09-28
JPH07501059A (en) 1995-02-02
NO941703L (en) 1994-07-04
US5844089A (en) 1998-12-01
AU672960B2 (en) 1996-10-24
EP0611376B1 (en) 1998-06-17
US5744329A (en) 1998-04-28
US5798227A (en) 1998-08-25
CA2121889C (en) 2001-08-21

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