WO1998000541A3 - Methods for administration of recombinant gene delivery vehicles for treatment of human disease - Google Patents

Methods for administration of recombinant gene delivery vehicles for treatment of human disease Download PDF

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Publication number
WO1998000541A3
WO1998000541A3 PCT/US1997/011784 US9711784W WO9800541A3 WO 1998000541 A3 WO1998000541 A3 WO 1998000541A3 US 9711784 W US9711784 W US 9711784W WO 9800541 A3 WO9800541 A3 WO 9800541A3
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WO
WIPO (PCT)
Prior art keywords
methods
administration
treatment
gene delivery
delivery vehicles
Prior art date
Application number
PCT/US1997/011784
Other languages
French (fr)
Other versions
WO1998000541A9 (en
WO1998000541A2 (en
Inventor
Douglas J Jolly
Jack R Barber
Stephen M Chang
James G Respess
John R Allen
Mordehcai Boder
Kimberly Chong
La Vega Dan De Jr
Nicholas J Depolo
David Chi-Tang Hsu
Carlos E Ibanez
Denice M Mittelstaedt
Charles E Prussak
Judith Greengard
Robert Lee
Original Assignee
Chiron Corp
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 Chiron Corp filed Critical Chiron Corp
Priority to EP97940534A priority Critical patent/EP0951544A2/en
Publication of WO1998000541A2 publication Critical patent/WO1998000541A2/en
Publication of WO1998000541A3 publication Critical patent/WO1998000541A3/en
Publication of WO1998000541A9 publication Critical patent/WO1998000541A9/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
    • 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
    • C12N15/86—Viral vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/555—Interferons [IFN]
    • C07K14/56—IFN-alpha
    • 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
    • C07K14/575—Hormones
    • C07K14/61—Growth hormone [GH], i.e. somatotropin
    • 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
    • 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
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/7455—Thrombomodulin
    • 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
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8125—Alpha-1-antitrypsin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/8107—Endopeptidase (E.C. 3.4.21-99) inhibitors
    • C07K14/811—Serine protease (E.C. 3.4.21) inhibitors
    • C07K14/8121—Serpins
    • C07K14/8128—Antithrombin III
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1205—Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases
    • C12N9/1211—Thymidine kinase (2.7.1.21)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/644—Coagulation factor IXa (3.4.21.22)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/6464—Protein C (3.4.21.69)
    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C12N9/647—Blood coagulation factors not provided for in a preceding group or according to more than one of the proceeding groups
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21022—Coagulation factor IXa (3.4.21.22)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21069—Protein C activated (3.4.21.69)
    • 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
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/13011—Gammaretrovirus, e.g. murine leukeamia virus
    • C12N2740/13041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/13043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biotechnology (AREA)
  • Toxicology (AREA)
  • Microbiology (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Cell Biology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Virology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Methods are provided for obtaining measurable levels of a protein, nucleic acid molecule, or enzymatic product in a bodily fluid or cells of a human, comprising the step of administering to a human a recombinant retroviral preparation having a titer on HT1080 cells of greater than 105 cfu/ml, wherein the recombinant retroviral preparation is capable of directing the expression of a protein, nucleic acid molecule, or enzyme which generates an enzymatic product, such that measurable levels of the protein, nucleic acid molecule, or enzymatic product may be obtained in the bodily fluid or cells of the human.
PCT/US1997/011784 1996-07-03 1997-07-02 Methods for administration of recombinant gene delivery vehicles for treatment of human disease WO1998000541A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP97940534A EP0951544A2 (en) 1996-07-03 1997-07-02 Methods for administration of recombinant gene delivery vehicles for treatment of human disease

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US64560196A 1996-07-03 1996-07-03
US08/645,601 1996-07-03
US69638196A 1996-08-13 1996-08-13
US08/696,381 1996-08-13
US08/869,309 1997-06-04
US86930997A 1997-06-05 1997-06-05

Publications (3)

Publication Number Publication Date
WO1998000541A2 WO1998000541A2 (en) 1998-01-08
WO1998000541A3 true WO1998000541A3 (en) 1998-03-19
WO1998000541A9 WO1998000541A9 (en) 1998-06-18

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PCT/US1997/011785 WO1998000542A2 (en) 1996-07-03 1997-07-02 Methods for administration of recombinant gene delivery vehicles for treatment of hemophilia
PCT/US1997/011784 WO1998000541A2 (en) 1996-07-03 1997-07-02 Methods for administration of recombinant gene delivery vehicles for treatment of human disease

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PCT/US1997/011785 WO1998000542A2 (en) 1996-07-03 1997-07-02 Methods for administration of recombinant gene delivery vehicles for treatment of hemophilia

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EP (2) EP0951544A2 (en)
WO (2) WO1998000542A2 (en)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6560220B2 (en) 1997-06-20 2003-05-06 Telefonaktiebolaget L M Ericsson (Publ) Network access device and telecommunications signaling
EP1009444A2 (en) * 1997-09-02 2000-06-21 Chiron Corporation Compositions and methods for treating arthritis utilizing gene therapy
AU1107199A (en) * 1997-10-21 1999-05-10 Chiron Corporation Methods for cancer immunotherapy using retroviral vectors expressing gamma interferon
WO1999029848A1 (en) * 1997-12-05 1999-06-17 The Immune Response Corporation Novel vectors and genes exhibiting increased expression
AU4089899A (en) 1998-05-20 1999-12-06 University Of Tennessee Research Corporation, The Stable envelope proteins for retroviral, viral and liposome vectors and use in gene and drug therapy
WO2000017375A2 (en) * 1998-09-23 2000-03-30 Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw Method to treat haemophilia by in vivo gene therapy with retroviral vectors
IL151857A0 (en) * 2000-03-22 2003-04-10 Octagene Gmbh Production of recombinant blood clotting factors in human cell lines
FR2817559B1 (en) * 2000-12-06 2003-12-12 Genodyssee METHOD FOR DETERMINING ONE OR MORE FUNCTIONAL POLYMORPHISM (S) IN THE NUCLEIC SEQUENCE OF A PRESELECTED FUNCTIONAL "CANDIDATE" GENE AND ITS APPLICATIONS
US7667089B2 (en) * 2004-04-09 2010-02-23 National Chung Hsing University Transgenic mammal secreting B-domain deleted human FVII in its milk
DK2425016T3 (en) 2009-04-29 2015-06-29 Amc Amsterdam MEANS AND METHODS TO REMEDY THE, PREVENT AND / OR diagnose heart failure or EN risk of cardiac failure
CU23896B1 (en) 2010-04-01 2013-05-31 Ct De Ingeniería Genética Y Biotecnología METHOD FOR INHIBITING THE REPLICATION OF HIV IN CELLS OF MAMMALS
EP2390346A1 (en) 2010-05-28 2011-11-30 Universiteit Twente Osteoarthrosis markers
WO2012105826A1 (en) 2011-02-01 2012-08-09 Erasmus University Medical Center Rotterdam Use of micrornas in diagnosis and therapy of aging
SG10201602423TA (en) 2011-09-30 2016-05-30 Bluebird Bio Inc Compounds For Improved Viral Transduction
WO2014041500A2 (en) * 2012-09-12 2014-03-20 Centre For Bioseparation Technology-Vit Double mutant coagulation factor viii and methods thereof
WO2017139561A1 (en) 2016-02-12 2017-08-17 Bluebird Bio, Inc. Vcn enhancer compositions and methods of using the same

Citations (8)

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Publication number Priority date Publication date Assignee Title
WO1991002805A2 (en) * 1989-08-18 1991-03-07 Viagene, Inc. Recombinant retroviruses delivering vector constructs to target cells
WO1993025698A1 (en) * 1992-06-10 1993-12-23 The United States Government As Represented By The Vector particles resistant to inactivation by human serum
WO1995003834A1 (en) * 1993-07-28 1995-02-09 The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services PRE-BINDING OF RETROVIRAL VECTOR PARTICLES WITH COMPLEMENT COMPONENTS TO ENABLE THE PERFORMANCE OF HUMAN GENE THERAPY $i(IN VIVO)
WO1995016784A1 (en) * 1993-12-13 1995-06-22 Transgene S.A. Human interferon expression vectors for treating aids
WO1996004934A1 (en) * 1994-08-17 1996-02-22 Genetic Therapy Inc. Retroviral vectors produced by producer cell lines resistant to lysis by human serum
WO1996021035A2 (en) * 1994-12-30 1996-07-11 Chiron Viagene, Inc. Retroviral delivery of full length factor viii
WO1996021014A2 (en) * 1994-12-30 1996-07-11 Chiron Corporation Production and administration of high titer recombinant retroviruses
WO1997008330A1 (en) * 1995-08-23 1997-03-06 Cancer Research Campaign Technology Limited Expression systems

Patent Citations (8)

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WO1991002805A2 (en) * 1989-08-18 1991-03-07 Viagene, Inc. Recombinant retroviruses delivering vector constructs to target cells
WO1993025698A1 (en) * 1992-06-10 1993-12-23 The United States Government As Represented By The Vector particles resistant to inactivation by human serum
WO1995003834A1 (en) * 1993-07-28 1995-02-09 The Government Of The United States Of America, Represented By The Secretary Of The Department Of Health And Human Services PRE-BINDING OF RETROVIRAL VECTOR PARTICLES WITH COMPLEMENT COMPONENTS TO ENABLE THE PERFORMANCE OF HUMAN GENE THERAPY $i(IN VIVO)
WO1995016784A1 (en) * 1993-12-13 1995-06-22 Transgene S.A. Human interferon expression vectors for treating aids
WO1996004934A1 (en) * 1994-08-17 1996-02-22 Genetic Therapy Inc. Retroviral vectors produced by producer cell lines resistant to lysis by human serum
WO1996021035A2 (en) * 1994-12-30 1996-07-11 Chiron Viagene, Inc. Retroviral delivery of full length factor viii
WO1996021014A2 (en) * 1994-12-30 1996-07-11 Chiron Corporation Production and administration of high titer recombinant retroviruses
WO1997008330A1 (en) * 1995-08-23 1997-03-06 Cancer Research Campaign Technology Limited Expression systems

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Title
BANAPOUR B ET AL: "THE AIDS-ASSOCIATED RETROVIRUS IS NOT SENSITIVE TO LYSIS OR INACTIVATION BY HUMAN SERUM", VIROLOGY, vol. 152, no. 1, 15 July 1986 (1986-07-15), pages 268 - 271, XP000613450 *
COSSET F -L ET AL: "HIGH-TITER PACKAGING CELLS PRODUCING RECOMBINANT RETROVIRUSES RESISTANT TO HUMAN SERUM", JOURNAL OF VIROLOGY, vol. 69, no. 12, 1 December 1995 (1995-12-01), pages 7430 - 7436, XP000569527 *
DEPOLO N ET AL: "Differential sensitivity of retrovectors to human serum inactivation.", KEYSTONE SYMPOSIUM ON GENE THERAPY AND MOLECULAR MEDICINE, STEAMBOAT SPRINGS, COLORADO, USA, MARCH 26-APRIL 1, 1995. JOURNAL OF CELLULAR BIOCHEMISTRY SUPPLEMENT 0 (21A). 1995. 404. ISSN: 0733-1959, 10 March 1995 (1995-03-10) - 4 April 1995 (1995-04-04), XP002051678 *
GREENGARD J S ET AL: "Sustained high level factor VIII antigen expression in immune-competent rabbits following peripheral intravenous injection of retroviral vector.", THIRTY-EIGHTH ANNUAL MEETING OF THE AMERICAN SOCIETY OF HEMATOLOGY, ORLANDO, FLORIDA, USA, DECEMBER 6-10, 1996. BLOOD 88 (10 SUPPL. 1 PART 1-2). 1996. 273A. ISSN: 0006-4971, XP002051681 *
K. CORNETTA ET AL.: "Amphotropic murine leukemia retrovirus is not an acute pathogen for primates", HUMAN GENE THERAPY, vol. 1, no. 1, 1990, MARY ANN LIEBERT, INC. PUBLISHERS, NEW YORK, US, pages 15 - 30, XP002051680 *
K. CORNETTA ET AL.: "Safety issues related to retroviral-mediated gene transfer in humans", HUMAN GENE THERAPY, vol. 2, no. 1, 1991, MARY ANN LIEBERT, INC. PUBLISHERS, NEW YORK, US, pages 5 - 14, XP002051679 *
TAKEUCHI Y ET AL: "TYPE C RETROVIRUS INACTIVATION BY HUMAN COMPLEMENT IS DETERMINED BY BOTH THE VIRAL GENOME AND THE PRODUCER CELL", JOURNAL OF VIROLOGY, vol. 68, no. 12, 1 December 1994 (1994-12-01), pages 8001 - 8007, XP000569528 *

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WO1998000541A2 (en) 1998-01-08
EP0915975A2 (en) 1999-05-19
WO1998000542A2 (en) 1998-01-08
EP0951544A2 (en) 1999-10-27

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