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

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Wood Science & Technology (AREA)
  • Mycology (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Epidemiology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Saccharide Compounds (AREA)
  • Air Bags (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

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
US07/789,179 US5545727A (en) 1989-05-10 1991-11-08 DNA encoding fused di-alpha globins and production of pseudotetrameric hemoglobin
US789,179 1991-11-08
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) EP0857489A3 (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

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5449759A (en) * 1987-05-16 1995-09-12 Somatogen, Inc. Hemoglobins with intersubunit desulfide bonds
US6828125B1 (en) * 1989-05-10 2004-12-07 Baxter Biotech Technology, S.A.R.L. DNA encoding fused di-alpha globins and use thereof
US5599907A (en) * 1989-05-10 1997-02-04 Somatogen, Inc. Production and use of multimeric hemoglobins
US6150506A (en) * 1989-05-10 2000-11-21 Baxter Biotech Technology Sarl Modified hemoglobin-like compounds and methods of purifying same
US5844090A (en) * 1994-05-09 1998-12-01 Somatogen, Inc. Modified hemoglobin-like compounds
US5478806A (en) * 1989-11-22 1995-12-26 Enzon, Inc. Enhancement of antitumor therapy with hemoglobin-based conjugates
AU665599B2 (en) * 1991-11-08 1996-01-11 Hemosol Inc. Hemoglobins as drug delivery agents
US5939391A (en) * 1993-03-31 1999-08-17 Pro-Neuron, Inc. Hemoglobin alpha chain peptide fragments useful for inhibiting stem cell proliferation
US6610654B2 (en) 1993-03-31 2003-08-26 Wellstat Therapeutics Corporation Inhibitor of stem cell proliferation and uses thereof
WO1994022915A1 (en) 1993-03-31 1994-10-13 Pro-Neuron, Inc. Inhibitor of stem cell proliferation and uses thereof
IS4198A (en) * 1993-08-13 1995-02-14 Somatogen, Inc Treatment for side effects associated with extracellular hemoglobin administration
US5631219A (en) * 1994-03-08 1997-05-20 Somatogen, Inc. Method of stimulating hematopoiesis with hemoglobin
US6242417B1 (en) 1994-03-08 2001-06-05 Somatogen, Inc. Stabilized compositions containing hemoglobin
WO1997023631A2 (en) * 1995-12-22 1997-07-03 Somatogen, Inc. Globins containing binding domains
US6218513B1 (en) 1995-12-22 2001-04-17 Baxter Biotech Technology Sarl Globins containing binding domains
US5861483A (en) * 1996-04-03 1999-01-19 Pro-Neuron, Inc. Inhibitor of stem cell proliferation and uses thereof
JP2000516455A (en) 1996-08-02 2000-12-12 バクスター バイオテック テクノロジー エス．アー．エール．エル． Methods for controlling beta-dimer formation in hemoglobin
AU4652797A (en) * 1996-09-27 1998-04-17 Board Of Trustees Of The University Of Illinois, The Oxygen-binding heme proteins incorporating circularly-permuted globins
CA2268278A1 (en) * 1996-10-18 1998-04-30 Somatogen, Inc. Methods of reducing the levels of protoporphyrin ix in recombinant hemoglobin preparations
AU735459B2 (en) 1997-01-30 2001-07-12 University Of Virginia Patent Foundation Cysteine-depleted peptides recognized by A3-restricted cytotoxic lymphocytes, and uses therefor
US6054427A (en) * 1997-02-28 2000-04-25 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
US5814601A (en) * 1997-02-28 1998-09-29 The Regents Of The University Of California Methods and compositions for optimization of oxygen transport by cell-free systems
JP4512673B2 (en) 1997-05-02 2010-07-28 バクスター バイオテク テクノロジー エス． アー． アール． エル． Hemoglobin variants with increased soluble expression and / or decreased nitric oxide excretion
EP1950298A3 (en) 1997-05-02 2008-12-24 Baxter Biotech Technology S.A.R.L. Hemoglobin mutants with increased soluble expression and/or reduced nitric oxide scavenging
US6780892B1 (en) 1998-10-01 2004-08-24 Temple University—Of the Commonwealth System of Higher Education Polymeric hemoglobin mutants
AU6504199A (en) * 1998-10-01 2000-04-17 Temple University - Of The Commonwealth System Of Higher Education Polymeric hemoglobin mutants
US8128922B2 (en) * 1999-10-20 2012-03-06 Johns Hopkins University Superior molecular vaccine linking the translocation domain of a bacterial toxin to an antigen
EP2292657A1 (en) 1999-11-12 2011-03-09 Baxter Biotech Technology S.A.R.L. Reduced side-effect hemoglobin compositions
US7164035B2 (en) * 2000-01-07 2007-01-16 Newsome David A Zinc-monocysteine complex and method of using zinc-cysteine complexes
JP5087201B2 (en) * 2000-08-03 2012-12-05 ジョンズ・ホプキンス・ユニバーシティ Molecular vaccine with endoplasmic reticulum chaperone polypeptide linked to antigen
US6645767B1 (en) * 2000-10-03 2003-11-11 Carnegie Mellon University Cells engineered to contain genes of interest without expressed bacterial sequences and materials and methods therefor
US8008459B2 (en) * 2001-01-25 2011-08-30 Evolva Sa Concatemers of differentially expressed multiple genes
EP1363660A4 (en) * 2001-02-01 2006-06-21 Univ Johns Hopkins Superior molecular vaccine based on self-replicating rna, suicidal dna or naked dna vector, that links antigen with polypeptide that promotes antigen presentation
MXPA03008022A (en) * 2001-03-09 2003-12-04 Genentech Inc Process for production of polypeptides.
US20040133468A1 (en) * 2002-04-12 2004-07-08 Varghese Kivin G. Method and system for providing interactive adversing cross reference to related application
US7238777B2 (en) * 2001-10-16 2007-07-03 Asahi Kasei Kabushiki Kaisha Agents for adsorption and bridging for adenovirus
JPWO2003040025A1 (en) 2001-11-08 2005-03-03 松下電器産業株式会社 Fine particle film and manufacturing method thereof
US20050164915A1 (en) * 2002-04-01 2005-07-28 Sangart, Inc. Compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin
US20030153491A1 (en) * 2002-01-11 2003-08-14 Winslow Robert M. Methods and compositions for oxygen transport comprising a high oxygen affinity modified hemoglobin
JP3912206B2 (en) * 2002-07-05 2007-05-09 株式会社日立製作所 Fuel pump for in-cylinder direct fuel injection system
JP5253708B2 (en) * 2002-07-22 2013-07-31 エムビーエー ポリマーズ， インコーポレイテッド Mediating electrostatic separation
US7998705B2 (en) * 2002-08-06 2011-08-16 FUJIFILM Diosynth Biotechnologies U.S.A., Inc Increased dynamic binding capacity in ion exchange chromatography by addition of polyethylene glycol
CA2509260C (en) 2002-12-31 2012-10-02 Nektar Therapeutics Al, Corporation Maleamic acid polymer derivatives and their bioconjugates
WO2004098526A2 (en) * 2003-05-05 2004-11-18 Johns Hopkins University Anti-cancer dna vaccine employing plasmids encoding signal sequence, mutant oncoprotein antigen, and heat shock protein
SI1678314T1 (en) 2003-10-22 2013-01-31 Keck Graduate Institute Methods of synthesizing heteromultimeric polypeptides in yeast using a haploid mating strategy
WO2005074521A2 (en) * 2004-01-30 2005-08-18 The Trustees Of Columbia University In The City Of New York C-TERMINAL p53 PALINDROMIC PEPTIDE THAT INDUCES APOPTOSIS OF CELLS WITH ABERRANT p53 AND USES THEREOF
AU2005322960A1 (en) * 2005-01-06 2006-07-13 The Johns Hopkins University RNA interference that blocks expression of pro-apoptotic proteins potentiates immunity induced by DNA and transfected dendritic cell vaccines
WO2006081323A2 (en) * 2005-01-26 2006-08-03 The Johns Hopkins University Anti-cancer dna vaccine employing plasmids encoding mutant oncoprotein antigen and calreticulin
WO2006089206A2 (en) * 2005-02-16 2006-08-24 Massachusetts Institute Of Technology Methods to enhance carbon monoxide dehydrogenase activity and uses thereof
US8318474B1 (en) * 2005-05-23 2012-11-27 California Institute Of Technology Engineered yeast cells and uses thereof
WO2008024844A2 (en) * 2006-08-22 2008-02-28 The Johns Hopkins University Anticancer combination therapies
US9085638B2 (en) 2007-03-07 2015-07-21 The Johns Hopkins University DNA vaccine enhancement with MHC class II activators
US20080260765A1 (en) * 2007-03-15 2008-10-23 Johns Hopkins University HPV DNA Vaccines and Methods of Use Thereof
EP2190987B1 (en) * 2007-08-21 2012-11-14 MorphoSys AG Methods for the formation of disulphide bonds
US20090285861A1 (en) * 2008-04-17 2009-11-19 Tzyy-Choou Wu Tumor cell-based cancer immunotherapeutic compositions and methods
EP2571991A1 (en) 2010-05-20 2013-03-27 Evolva SA Method of producing isoprenoid compounds in yeast
US20130137645A1 (en) * 2010-07-19 2013-05-30 Mary S. Rosendahl Modified peptides and proteins
US9814759B2 (en) * 2014-07-02 2017-11-14 Cheer Global Ltd. Pharmaceutical composition comprising recombinant hemoglobin protein or subunit-based therapeutic agent for cancer targeting treatment
US10752672B1 (en) * 2019-02-01 2020-08-25 Cheer Global Limited Recombinant hemoglobins and methods of preparation and use thereof
CN113087787B (en) * 2021-05-19 2023-03-21 广西医科大学第二附属医院(广西医科大学第二临床医学院) Earthworm hemoglobin separation and purification method
WO2023102156A1 (en) 2021-12-03 2023-06-08 Wisconsin Alumni Research Foundation Mutant ace2 proteins and methods of using same
CN116203144B (en) * 2022-05-11 2023-10-27 重庆医科大学附属儿童医院 Method for determining chain ratio of various globin in hemoglobin and application thereof

Family Cites Families (42)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2449885C3 (en) * 1974-10-21 1980-04-30 Biotest-Serum-Institut Gmbh, 6000 Frankfurt Process for the production of chemically modified, long-life hemoglobin preparations as well as the modified hemoglobin preparation produced by this process
US4061736A (en) * 1975-02-02 1977-12-06 Alza Corporation Pharmaceutically acceptable intramolecularly cross-linked, stromal-free hemoglobin
US4001401A (en) * 1975-02-02 1977-01-04 Alza Corporation Blood substitute and blood plasma expander comprising polyhemoglobin
US4001200A (en) * 1975-02-27 1977-01-04 Alza Corporation Novel polymerized, cross-linked, stromal-free hemoglobin
US4053590A (en) * 1975-02-27 1977-10-11 Alza Corporation Compositions of matter comprising macromolecular hemoglobin
US4769326A (en) * 1980-02-29 1988-09-06 The Regents Of The University Of California Expression linkers
US4338397A (en) * 1980-04-11 1982-07-06 President And Fellows Of Harvard College Mature protein synthesis
US4551433A (en) * 1981-05-18 1985-11-05 Genentech, Inc. Microbial hybrid promoters
US4473496A (en) * 1981-09-14 1984-09-25 The United States Of America As Represented By The Secretary Of The Army Intramolecularly crosslinked hemoglobin
DE3144705C2 (en) * 1981-11-11 1983-12-08 Biotest-Serum-Institut Gmbh, 6000 Frankfurt Process for the production of a storage-stable, cross-linked hemoglobin preparation with high oxygen transport capacity, as well as the hemoglobin preparation produced by this process
US4599197A (en) * 1982-12-22 1986-07-08 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4511503A (en) * 1982-12-22 1985-04-16 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4620948A (en) * 1982-12-22 1986-11-04 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4512922A (en) * 1982-12-22 1985-04-23 Genentech, Inc. Purification and activity assurance of precipitated heterologous proteins
US4713339A (en) * 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
US4529719A (en) * 1983-05-04 1985-07-16 Tye Ross W Modified crosslinked stroma-free tetrameric hemoglobin
US4840896A (en) * 1983-11-02 1989-06-20 Integrated Genetics, Inc. Heteropolymeric protein
US4738952A (en) * 1984-04-27 1988-04-19 Synthetic Blood Corporation Substitute for human blood and a method of making the same
GB8412517D0 (en) * 1984-05-16 1984-06-20 Nagai K Recombinant fusion proteins
US4600531A (en) * 1984-06-27 1986-07-15 University Of Iowa Research Foundation Production of alpha-alpha cross-linked hemoglobins in high yield
US4598064A (en) * 1984-06-27 1986-07-01 University Of Iowa Research Foundation Alpha-alpha cross-linked hemoglobins
US4542225A (en) * 1984-08-29 1985-09-17 Dana-Farber Cancer Institute, Inc. Acid-cleavable compound
US4774180A (en) * 1986-02-26 1988-09-27 Massachusetts Institute Of Technology Construction and application of polyproteins
US4584130A (en) * 1985-03-29 1986-04-22 University Of Maryland Intramolecularly cross-linked hemoglobin and method of preparation
DE3515252C2 (en) * 1985-04-27 1994-02-24 Roehm Gmbh Process for the immobilization of dissolved proteins
DE3675588D1 (en) * 1985-06-19 1990-12-20 Ajinomoto Kk HAEMOGLOBIN TIED TO A POLY (ALKENYLENE OXIDE).
US4826811A (en) * 1986-06-20 1989-05-02 Northfield Laboratories, Inc. Acellular red blood cell substitute
US4704692A (en) * 1986-09-02 1987-11-03 Ladner Robert C Computer based system and method for determining and displaying possible chemical structures for converting double- or multiple-chain polypeptides to single-chain polypeptides
US4730936A (en) * 1986-10-10 1988-03-15 The United States Of America As Represented By The Secretary Of The Air Force Gas driven system for preparing large volumes of non-oxidized, pyridoxylated, polymerized stroma-free hemoglobin solution for use as a blood substitute
DE3636590A1 (en) * 1986-10-28 1988-05-26 Braun Melsungen Ag BLOOD REPLACEMENT
WO1988006601A1 (en) * 1987-03-02 1988-09-07 Genex Corporation Gene repressors
GB8710598D0 (en) * 1987-05-05 1987-06-10 Star Medical Diagnostics Ltd Hemoglobin based blood substitute
GB8711614D0 (en) 1987-05-16 1987-06-24 Medical Res Council Proteins
US5049493A (en) * 1987-10-23 1991-09-17 California Institute Of Technology Enhancement of cell growth by expression of a cloned hemoglobin gene
EP0319206A3 (en) * 1987-11-30 1990-04-18 Berlex Laboratories, Inc. Gene amplification
IL87708A (en) * 1988-09-08 1994-04-12 Technion Inst For Research And Hemoglobin-based blood substitute possessing a colloid oncotic pressure substantially similar to human blood and method for the preparation thereof
NL8901174A (en) * 1989-05-10 1990-12-03 Het Hoofd Van De Afdeling Mili HEMOGLOBINE PREPARATION AND USE THEREOF.
ES2093640T3 (en) * 1989-05-10 1997-01-01 Somatogen Inc PRODUCTION OF HEMOGLOBIN AND ITS ANALOGS THROUGH BACTERIA AND YEAST.
US5173426A (en) * 1989-10-06 1992-12-22 Yale University DNAs encoding genetically engineered low oxygen affinity mutants of human hemoglobin
JPH07504645A (en) * 1990-04-16 1995-05-25 アペックス　バイオサイエンス　インコーポレーテッド Expression of recombinant hemoglobin in yeast
DE69132763D1 (en) * 1990-12-20 2001-11-15 Univ Alabama Res Foundation Bi TRANSGENIC, NETWORKED HEMOGLOBIN
US5250665A (en) * 1991-05-31 1993-10-05 The University Of Toronto Innovations Foundation Specifically β-β cross-linked hemoglobins and method of preparation

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

Also Published As

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

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