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1. (WO1992010564) SUSTAINED AND CONTINUOUS PRODUCTION OF HIGH TITERS OF RECOMBINANT VIRAL VECTORS AND TRANSDUCED TARGET CELLS FOR USE IN GENE THERAPY
Latest bibliographic data on file with the International Bureau

Pub. No.: WO/1992/010564 International Application No.: PCT/US1991/009069
Publication Date: 25.06.1992 International Filing Date: 10.12.1991
Chapter 2 Demand Filed: 10.12.1991
IPC:
A61K 48/00 (2006.01) ,C12M 3/06 (2006.01) ,C12N 7/00 (2006.01) ,C12N 9/78 (2006.01) ,C12N 15/867 (2006.01)
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
48
Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
M
APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY
3
Tissue, human, animal or plant cell, or virus culture apparatus
06
with filtration, ultrafiltration, inverse osmosis or dialysis means
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
7
Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
9
Enzymes, e.g. ligases (6.); Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating, or purifying enzymes
14
Hydrolases (3.)
78
acting on carbon to nitrogen bonds other than peptide bonds (3.5)
C CHEMISTRY; METALLURGY
12
BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
N
MICRO-ORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICRO-ORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
15
Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
09
Recombinant DNA-technology
63
Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
79
Vectors or expression systems specially adapted for eukaryotic hosts
85
for animal cells
86
Viral vectors
867
Retroviral vectors
Applicants:
THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, U.S. DEPARTMENT OF COMMERCE [US/US]; 5285 Port Royal Road Springfield, VA 22161, US
CELLCO, INC. [US/US]; 12321 Middlebrook Road Germantown, MD 20874, US
Inventors:
CULVER, Kenneth, W.; US
KNAZEK, Richard, A.; US
BLAESE, R., Michael; US
Agent:
STERN, Marvin, R. ; Fleit, Jacobson, Cohn, Price, Holman & Stern The Jenifer Building 400 Seventh Street, N.W. Washington, DC 20004, US
Priority Data:
627,00813.12.1990US
Title (EN) SUSTAINED AND CONTINUOUS PRODUCTION OF HIGH TITERS OF RECOMBINANT VIRAL VECTORS AND TRANSDUCED TARGET CELLS FOR USE IN GENE THERAPY
(FR) PRODUCTION SOUTENUE ET CONTINUE DE TITRES ELEVES DE VECTEURS VIRAUX RECOMBINES ET CELLULES CIBLES OBTENUES PAR TRANSDUCTION UTILISABLES DANS DES THERAPIES GENETIQUES
Abstract:
(EN) This invention provides improved methods for producing high titers of recombinant viral vectors by culturing producer cells in a hollow fiber bioreactor. The titer of virus in the extra fiber space (EFS) of the hollow fiber bioreactor is sufficient to transduce target cells at a multiplicity of infection sufficient to render the transduced target cells useful for genetic therapy. In a preferred embodiment, target cells are transduced with the EFS medium from a hollow fiber bioreactor in which a producer cell line, which releases packaged retroviral vectors into the EFS, has been cultured. Lymphocytes derived from an adenosine deaminase (ADA)-deficient individual that have been transduced with EFS medium that contains retroviral vectors that include RNA that encodes ADA, express ADA at a rate comparable to that of cells from an individual who does not have ADA deficiency.
(FR) L'invention se rapporte à des procédés améliorés qui servent à produire des titres élevés de vecteurs viraux recombinés et qui, à cet effet, consistent à cultiver des cellules productrices dans un bioréacteur à fibres creuses. Le titre de virus dans l'espace hors fibres (espace EFS) du bioréacteur à fibres creuses est suffisant pour transmettre par transduction des cellules cibles sur une multitude d'infections de façon à rendre les cellules cibles ainsi transmises par transduction utilisables dans des thérapies génétiques. Dans un mode de réalisation préféré, les cellules cibles sont obtenues par transduction au moyen du milieu de l'espace EFS provenant d'un bioréacteur à fibres creuses, dans lequel a été cultivée une lignée de cellules productrices, qui libère dans l'espace EFS des vecteurs rétroviraux enveloppés. Des lymphocytes dérivés d'un individu ayant une carence en adénosine-désaminase (ADA) et ayant été obtenus par transduction à l'aide d'un milieu de l'espace EFS qui contient les vecteurs rétroviraux renfermant l'ARN qui code pour l'ADA, réalisent l'expression de l'ADA à une cadence comparable à celle qu'on obtient avec des lymphocytes provenant d'un individu n'ayant aucune carence en ADA.
Designated States: AU, CA, JP
European Patent Office (AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LU, MC, NL, SE)
Publication Language: English (EN)
Filing Language: English (EN)
Also published as:
EP0564539JPH06500927CA2098510AU1991091246