HK48497A - Modified biological material - Google Patents

Modified biological material Download PDF

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Publication number
HK48497A
HK48497A HK48497A HK48497A HK48497A HK 48497 A HK48497 A HK 48497A HK 48497 A HK48497 A HK 48497A HK 48497 A HK48497 A HK 48497A HK 48497 A HK48497 A HK 48497A
Authority
HK
Hong Kong
Prior art keywords
tissue
cell
complement
species
hcrf
Prior art date
Application number
HK48497A
Other languages
English (en)
French (fr)
Inventor
David J. G. White
Frederick Williams Alan
Original Assignee
Imutran Limited
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26296038&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HK48497(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Priority claimed from GB898922987A external-priority patent/GB8922987D0/en
Priority claimed from GB909017198A external-priority patent/GB9017198D0/en
Application filed by Imutran Limited filed Critical Imutran Limited
Publication of HK48497A publication Critical patent/HK48497A/en

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    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0271—Chimeric vertebrates, e.g. comprising exogenous cells
    • 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
    • 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
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C07K14/4703—Inhibitors; Suppressors
    • 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
    • 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
    • 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
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/108—Swine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/02—Animal zootechnically ameliorated
    • A01K2267/025—Animal producing cells or organs for transplantation
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Environmental Sciences (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Animal Behavior & Ethology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Animal Husbandry (AREA)
  • Physics & Mathematics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Plant Pathology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Transplantation (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Materials For Medical Uses (AREA)

Claims (20)

  1. Verpflanzbare tierische Zelle oder ein solches Gewebe einer Spendergattung;
    wobei die Zelle oder das Gewebe mit einem oder mehreren homologen Komplementrestriktionsfaktoren verbunden ist, die bei einer Empfängergattung verwendet werden können, um die vollständige Aktivierung des Komplements zu verhindern, und wobei die Spendergattung in bezug auf die Empfängergattung eine nicht übereinstimmende Gattung ist,
    zur Verwendung in der Medizin.
  2. Zelle oder Gewebe nach Anspruch 1 zur Verwendung in der Transplantationstherapie.
  3. Zelle oder Gewebe zur Verwendung nach Anspruch 1 oder Anspruch 2, wobei das Gewebe ein Organ ist.
  4. Zelle oder Gewebe zur Verwendung nach Anspruch 3, wobei das Organ ein Herz, eine Lunge, eine Leber, eine Niere, eine Bauchspeicheldrüse oder Schilddrüse ist.
  5. Zelle oder Gewebe zur Verwendung nach Anspruch 1 oder Anspruch 2, wobei das Gewebe Blut oder hämopoetische Zellen, Langerhans-Inseln, Gehirnzellen oder Zellen endocriner Organe umfaßt.
  6. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 5, wobei der HCRF jenen Teil der Komplementaktivierungskaskade beeinflußt, der sowohl dem klassischen als auch dem alternativen Weg gemein ist.
  7. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 6, wobei der HCRF ein natürlicher HCRF ist.
  8. Zelle oder Gewebe zur Verwendung nach Anspruch 6, wobei der HCRF die Komplementaktivierung bei C3 reguliert.
  9. Zelle oder Gewebe zur Verwendung nach Anspruch 8, wobei der HCRF folgendes ist oder dessen Aktivität besitzt:
    Faktor I (früher auch als C3b-Inaktivator oder KAF bekannt);
    Faktor H;
    C4-Bindungsprotein;
    DAF (auch als CD55 bekannt);
    Membran-Cofaktorprotein (MCP; auch als CD46 bekannt und erstmals als gp45-70 beschrieben und ferner als gp66/56 bekannt);
    CR1 (auch als C3b/C4b-Rezeptor oder CD35 bekannt); und/oder
    CR2 (auch als CD21, C3.dg-Rezeptor, 3d/EBV-Rezeptor und p140 bekannt).
  10. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 9, wobei der HCRF die Aktivität eines natürlichen HCRF besitzt, dessen Gen an dem RCA-(Regulator der Komplementaktivierung)-Ort angeordnet ist, der bei der Bande q32 von Chromosom 1 kartiert ist.
  11. Zelle oder Gewebe zur Verwendung nach Anspruch 6, wobei der HCRF die Komplementaktivierung bei C8 und/oder C9 reguliert.
  12. Zelle oder Gewebe zur Verwendung nach Anspruch 11, wobei der HCRF folgendes ist oder dessen Aktivität besitzt:
    C8bp (auch als HRF oder MIP bekannt);
    P-18 (auch als HRF-20, CD59 oder MIRL bekannt); oder
    SP40.40
  13. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 12, wobei der HCRF membrangebunden ist.
  14. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 13, wobei der HCRF derart vorgesehen ist, daß er in der Zellmembran auf dem Spendergewebe integriert ist.
  15. Zelle oder Gewebe zur Verwendung nach Anspruch 14, wobei das Spendergewebe transgen ist, indem es Nucleinsäure enthält und exprimiert, die für einen oder mehrere HCRF kodiert, die in der Empfängergattung verwendet werden können, wenn sie in den Empfänger verpflanzt werden.
  16. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 15, wobei die Empfängergattung der Mensch ist.
  17. Zelle oder Gewebe zur Verwendung nach einem der Ansprüche 1 bis 16, wobei die Empfängergattung das Schwein ist.
  18. Verwendung einer tierischen Zelle oder eines Gewebes, das von einer Spendergattung abgeleitet ist, und einem oder mehreren homologen , Komplementrestriktionsfaktoren (HCRF), die in einer Empfängergattung verwendet werden können, um die vollständige Aktivierung des Komplements zu verhindern; wobei die Spendergattung in bezug auf die Empfängergattung eine nicht übereinstimmende Gattung ist; bei der Herstellung eines Gewebes, das in die Empfängergattung ohne hyperakute Abstoßung verpflanzbar ist.
  19. Verwendung nach Anspruch 18, wobei das Spendertier für den oder jeden HCRF transgen ist und die Zellen oder das Gewebe diesen exprimieren.
  20. Verwendung nach Anspruch 18 oder 19, ferner gekennzeichnet durch jedes der besonderen Merkmale der Ansprüche 3 bis 14, 16 und 17.
HK48497A 1989-10-12 1997-04-17 Modified biological material HK48497A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB898922987A GB8922987D0 (en) 1989-10-12 1989-10-12 Modified biological material
GB909017198A GB9017198D0 (en) 1990-08-06 1990-08-06 Modified biological material

Publications (1)

Publication Number Publication Date
HK48497A true HK48497A (en) 1997-04-25

Family

ID=26296038

Family Applications (1)

Application Number Title Priority Date Filing Date
HK48497A HK48497A (en) 1989-10-12 1997-04-17 Modified biological material

Country Status (27)

Country Link
US (1) US6495735B1 (de)
EP (2) EP0709459A3 (de)
JP (1) JP3302358B2 (de)
KR (2) KR100317106B1 (de)
CN (2) CN1491624A (de)
AT (1) ATE139562T1 (de)
AU (1) AU654116B2 (de)
BG (1) BG61080B1 (de)
CA (1) CA2067235A1 (de)
CY (1) CY1996A (de)
DE (2) DE495852T1 (de)
DK (1) DK0495852T3 (de)
ES (1) ES2060561T3 (de)
FI (1) FI921618A0 (de)
GR (2) GR940300004T1 (de)
HK (1) HK48497A (de)
HU (1) HUT64584A (de)
IE (1) IE75345B1 (de)
IL (2) IL95970A0 (de)
IN (1) IN171948B (de)
MY (1) MY107433A (de)
NO (2) NO303502B1 (de)
NZ (2) NZ248153A (de)
PT (2) PT95580B (de)
RO (1) RO109863B1 (de)
SG (1) SG72614A1 (de)
WO (1) WO1991005855A1 (de)

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US5705732A (en) * 1989-06-12 1998-01-06 Oklahoma Medical Research Foundation Universal donor cells
WO1991002002A1 (en) * 1989-07-21 1991-02-21 Washington University Recombinantly produced human membrane cofactor protein (mcp)
US5846715A (en) * 1990-05-11 1998-12-08 The Austin Research Institute CD46 variants
EP0537171B1 (de) * 1990-05-11 2002-09-18 The Austin Research Institute CD46 Isoformen
EP1041142A3 (de) * 1991-07-15 2007-10-24 Oklahoma Medical Research Foundation Universale Spenderzellen
US6916654B1 (en) * 1992-06-29 2005-07-12 Oklahoma Medical Research Foundation Universal donor cells
FI951325A7 (fi) * 1992-09-22 1995-05-09 Nextran Proteiinien kuljetus membraanien välisellä siirrolla ksenogeenisten el insiirrännäisten esisovittamista varten ja muihin tarkoituksiin
US5627264A (en) * 1994-03-03 1997-05-06 Alexion Pharmaceuticals, Inc. Chimeric complement inhibitor proteins
EP0773993A4 (de) * 1994-08-19 2000-07-05 Gen Hospital Corp Gentechnisch veränderte schweine-zellen
JPH11510698A (ja) 1995-08-04 1999-09-21 ザ ジェネラル ホスピタル コーポレイション トランスジェニックブタ及びヒトｈｌａ遺伝子を有するブタ細胞
US6166288A (en) * 1995-09-27 2000-12-26 Nextran Inc. Method of producing transgenic animals for xenotransplantation expressing both an enzyme masking or reducing the level of the gal epitope and a complement inhibitor
WO1997035886A1 (en) * 1996-03-22 1997-10-02 Imutran Limited Surfaces which prevent or reduce complement activation
US6423316B1 (en) 1997-03-26 2002-07-23 Imperial College Innovative Limited Anticoagulant fusion protein anchored to cell membrane
US6825395B1 (en) 1997-07-14 2004-11-30 Nippon Meat Packers, Inc. Transgenic non-human mammals expressing the human complement inhibitor (DAF/CD55)
CA2298475A1 (en) * 1997-10-31 1999-05-14 Walter Reed Army Institute Of Research Method of inhibiting side effects of pharmaceutical compositions containing amphiphilic vehicles or drug carrier molecules
SE523817C2 (sv) 1999-02-05 2004-05-18 Corline Systems Ab Användning av ett koagulationsförebyggande ämne i samband med transplantation av insulinproducerande celler
GB9905503D0 (en) 1999-03-10 1999-05-05 Adprotech Plc Novel compound formulations and methods of delivery
CA2533259C (en) * 2003-07-21 2014-01-28 Lifecell Corporation Acellular tissue matrices made from galactose .alpha.-1,3-galactose-deficient tissue
ES2767881T3 (es) 2009-08-14 2020-06-18 Revivicor Inc Cerdos multi-transgénicos para el tratamiento de diabetes
US9420770B2 (en) 2009-12-01 2016-08-23 Indiana University Research & Technology Corporation Methods of modulating thrombocytopenia and modified transgenic pigs
AU2011295715B9 (en) 2010-09-03 2017-02-23 Abbvie Stemcentrx Llc Novel modulators and methods of use
ES2680636T3 (es) 2011-02-14 2018-09-10 Revivicor Inc. Cerdos genéticamente modificados para xenotrasplante de xenoinjertos vascularizados y derivados de los mismos
WO2015066668A1 (en) 2013-11-04 2015-05-07 Lifecell Corporation Methods of removing alpha-galactose
CN114686427B (zh) * 2022-05-23 2022-07-29 中国人民解放军总医院第一医学中心 一种脾脏调节型b淋巴细胞及其制备方法与应用

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US4431636A (en) 1982-05-24 1984-02-14 American Cyanamid Company Bis(4-O-polyhexaose-thio)-phenyl ureas and method of use
US5109113A (en) * 1986-05-02 1992-04-28 Genentech, Inc. Membrane anchor fusion polypeptides
JPS62104594A (ja) * 1985-10-31 1987-05-15 Terumo Corp クエン酸塩利用能検査用培地組成物
JPH0742235B2 (ja) * 1985-11-08 1995-05-10 三共株式会社 自己免疫性疾病の予防・治療剤
IL82390A0 (en) * 1986-05-02 1987-10-30 Genentech Inc Nucleic acid and methods for the synthesis of novel daf compositions
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IL89790A (en) * 1988-04-01 2002-05-23 Johns Hopking University Nucleic acid sequences that encode and cells that produce cr1 protein and methods of production and purification
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US5573940A (en) * 1989-06-12 1996-11-12 Oklahoma Medical Research Foundation Cells expressing high levels of CD59

Also Published As

Publication number Publication date
JP3302358B2 (ja) 2002-07-15
CN1491624A (zh) 2004-04-28
HUT64584A (en) 1994-01-28
NO303502B1 (no) 1998-07-20
RO109863B1 (ro) 1995-06-30
IL120795A0 (en) 1997-09-30
FI921618A7 (fi) 1992-04-10
BG61080B1 (bg) 1996-10-31
BG96329A (bg) 1993-12-24
PT101896A (pt) 1998-02-27
IE903649A1 (en) 1991-04-24
AU654116B2 (en) 1994-10-27
PT95580A (pt) 1991-09-13
CN1122719C (zh) 2003-10-01
CY1996A (en) 1997-09-05
IL95970A0 (en) 1992-05-25
ES2060561T3 (es) 1996-08-01
HU9201240D0 (en) 1992-06-29
NO921438L (no) 1992-04-10
ES2060561T1 (es) 1994-12-01
IN171948B (de) 1993-02-13
NO982131D0 (no) 1998-05-11
GR940300004T1 (en) 1994-02-28
JPH05503074A (ja) 1993-05-27
NO982131L (no) 1992-04-10
DE69027535D1 (de) 1996-07-25
DE69027535T2 (de) 1996-11-28
FI921618L (fi) 1992-04-10
NZ235657A (en) 1994-05-26
KR100317106B1 (ko) 2001-12-22
WO1991005855A1 (en) 1991-05-02
CN1051199A (zh) 1991-05-08
AU6539290A (en) 1991-05-16
SG72614A1 (en) 2000-05-23
DK0495852T3 (da) 1996-07-15
EP0709459A3 (de) 1999-01-07
KR920702410A (ko) 1992-09-04
PT101896B (pt) 2003-01-31
DE495852T1 (de) 1994-03-31
FI921618A0 (fi) 1992-04-10
ATE139562T1 (de) 1996-07-15
IE75345B1 (en) 1997-08-27
EP0709459A2 (de) 1996-05-01
NZ248153A (en) 1997-07-27
GR3020741T3 (en) 1996-11-30
NO921438D0 (no) 1992-04-10
MY107433A (en) 1995-12-30
PT95580B (pt) 1999-05-31
EP0495852B1 (de) 1996-06-19
EP0495852A1 (de) 1992-07-29
CA2067235A1 (en) 1991-04-13
US6495735B1 (en) 2002-12-17

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