CA2253287A1 - A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium - Google Patents

A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium

Info

Publication number
CA2253287A1
CA2253287A1 CA002253287A CA2253287A CA2253287A1 CA 2253287 A1 CA2253287 A1 CA 2253287A1 CA 002253287 A CA002253287 A CA 002253287A CA 2253287 A CA2253287 A CA 2253287A CA 2253287 A1 CA2253287 A1 CA 2253287A1
Authority
CA
Canada
Prior art keywords
culture medium
cell culture
chymotrypsins
inhibitor
metal
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
CA002253287A
Other languages
French (fr)
Other versions
CA2253287C (en
Inventor
Lars Adamson
Erik Walum
Johan Dixelius
Kristina Lima Lie
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.)
Swedish Orphan Biovitrum AB
Original Assignee
Pharmacia & Upjohn Ab
Lars Adamson
Erik Walum
Johan Dixelius
Kristina Lima Lie
Pharmacia Aktiebolag
Biovitrum Ab
Biovitrum Ab (Publ)
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
Priority claimed from SE9601855A external-priority patent/SE9601855D0/en
Application filed by Pharmacia & Upjohn Ab, Lars Adamson, Erik Walum, Johan Dixelius, Kristina Lima Lie, Pharmacia Aktiebolag, Biovitrum Ab, Biovitrum Ab (Publ) filed Critical Pharmacia & Upjohn Ab
Publication of CA2253287A1 publication Critical patent/CA2253287A1/en
Application granted granted Critical
Publication of CA2253287C publication Critical patent/CA2253287C/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
    • C07K14/435—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)
    • 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
    • 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
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • C12N15/67—General methods for enhancing the expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P21/00—Preparation of peptides or proteins
    • C12P21/02—Preparation of peptides or proteins having a known sequence of two or more amino acids, e.g. glutathione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Abstract

The present invention relates to a process for reducing the detrimental influence of certain proteases on recombinant human protein and polypeptide molecules, by adding an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium. The invention also relates to a cell culture medium for cultivating cells expressing and secreting a biologically active recombinant human polypeptide containing an inhibitor of metal-dependent proteases or chymotrypsins, or a combination thereof. The invention further relates to use of recombinant factor VIII which has been produced in a cell culture medium according to the present process for the manufacture of a medicament for administration to a patient having the symptoms of hemophilia A. Also, the invention relates to a method for treatment of hemophilia A by administration of a therapeutically effective amount of recombinant factor VIII which has been produced in a cell culture medium according to the present process.
CA002253287A 1996-05-14 1997-05-13 A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium Expired - Fee Related CA2253287C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
SE9601855A SE9601855D0 (en) 1996-05-14 1996-05-14 Process for producing a protein
SE9601855-1 1996-05-14
US1887496P 1996-05-29 1996-05-29
US60/018,874 1996-05-29
PCT/SE1997/000783 WO1997043436A1 (en) 1996-05-14 1997-05-13 A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium

Publications (2)

Publication Number Publication Date
CA2253287A1 true CA2253287A1 (en) 1997-11-20
CA2253287C CA2253287C (en) 2008-02-19

Family

ID=26662616

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002253287A Expired - Fee Related CA2253287C (en) 1996-05-14 1997-05-13 A process for producing a recombinant polypeptide involving the addition of an inhibitor of metal-dependent proteases or chymotrypsins to the cell culture medium

Country Status (13)

Country Link
US (1) US5851800A (en)
EP (1) EP0934424B1 (en)
JP (2) JP2000509994A (en)
AT (2) ATE321141T1 (en)
AU (1) AU716245B2 (en)
CA (1) CA2253287C (en)
DE (2) DE69735510T2 (en)
DK (1) DK0934424T3 (en)
ES (2) ES2260524T3 (en)
NO (2) NO325358B1 (en)
NZ (1) NZ332751A (en)
PT (2) PT934424E (en)
WO (1) WO1997043436A1 (en)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
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US6475725B1 (en) 1997-06-20 2002-11-05 Baxter Aktiengesellschaft Recombinant cell clones having increased stability and methods of making and using the same
EP2921180B1 (en) 1999-02-22 2019-08-14 University of Connecticut Albumin-free factor VIII formulations
AT409379B (en) 1999-06-02 2002-07-25 Baxter Ag MEDIUM FOR PROTEIN- AND SERUM-FREE CELL CULTURE
CA2381173A1 (en) * 1999-08-05 2001-02-15 Baxter Aktiengesellschaft Recombinant stable cell clone, its production and use thereof
WO2001052891A1 (en) * 2000-01-20 2001-07-26 Nippon Organon K. K. Inhibitors for plasmodial invasion into erythrocytes
PL214284B1 (en) * 2002-07-09 2013-07-31 Baxter Healthcare Sa Animal protein free media for cultivation of cells
CN100402660C (en) * 2002-12-23 2008-07-16 布里斯托尔-迈尔斯斯奎布公司 Product quality enhancement in mammalian cell culture processes for protein production
TWI312368B (en) * 2002-12-23 2009-07-21 Bristol Myers Squibb Compan Mammalian cell culture processes for protein production
AU2004234377A1 (en) * 2003-04-25 2004-11-11 Immunex Corporation Inducers of recombinant protein expression
US7255288B2 (en) * 2004-03-08 2007-08-14 Wan Shan Chan Aroma therapy for fountain
US20060094104A1 (en) * 2004-10-29 2006-05-04 Leopold Grillberger Animal protein-free media for cultivation of cells
EP1707634A1 (en) * 2005-03-29 2006-10-04 Octapharma AG Method for isolation of recombinantly produced proteins
PL1974014T3 (en) 2006-01-04 2017-09-29 Baxalta Incorporated Oligopeptide-free cell culture media
WO2008102923A1 (en) * 2007-02-23 2008-08-28 Sk Chemicals Co., Ltd. Process for producing and purifying factor viii and its derivatives
WO2008135498A2 (en) * 2007-05-04 2008-11-13 Novo Nordisk A/S Prevention of protein degradation in mammalian cell cultures
EP1988101A1 (en) 2007-05-04 2008-11-05 Novo Nordisk A/S Improvement of factor VIII polypeptide titers in cell cultures
WO2010054238A1 (en) 2008-11-07 2010-05-14 Baxter International Inc. Factor viii formulations
US9540426B2 (en) * 2009-10-06 2017-01-10 Bristol-Myers Squibb Company Mammalian cell culture processes for protein production
PL2625262T3 (en) 2010-10-05 2016-05-31 Novo Nordisk Healthcare Ag Process for protein production
JP2015531244A (en) 2012-10-15 2015-11-02 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Mammalian cell culture method for producing protein
KR20170049319A (en) 2015-10-28 2017-05-10 주식회사유한양행 Long-acting fgf21 fusion proteins and pharmaceutical composition comprising the same
KR20170049320A (en) 2015-10-28 2017-05-10 주식회사유한양행 Dual function proteins and pharmaceutical composition comprising the same
AU2017358289A1 (en) 2016-11-10 2019-06-20 Yuhan Corporation Pharmaceutical composition for preventing or treating hepatitis, hepatic fibrosis, and hepatic cirrhosis comprising fusion proteins
EA201992516A1 (en) 2017-04-21 2020-04-09 Юхан Корпорейшн METHOD FOR PRODUCING BIFUNCTIONAL PROTEINS AND THEIR DERIVATIVES

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149787A (en) * 1984-05-22 1992-09-22 The Blood Center Research Foundation Method for maintaining intact, non-degraded factor VIII/von-Willebrand factor during blood processing
SE8501050D0 (en) * 1985-03-05 1985-03-05 Kabivitrum Ab BIOLOGICALLY ACTIVE FRAGMENTS OF HUMAN ANTIHEMOPHILIC FACTOR AND METHOD FOR PREPARATION THEREOF
US5279939A (en) * 1986-08-18 1994-01-18 Smithkline Beecham Corporation Protein protease inhibitors from streptomyces
US4891356A (en) * 1987-07-15 1990-01-02 Brigham & Women's Hospital Proteinase inhibitors for treatment of gastrointestinal ulcer disease
JPH0387173A (en) * 1987-09-10 1991-04-11 Teijin Ltd Preparation of human active natural type factor viii c and transformant using the same
CA1340740C (en) * 1987-12-08 1999-09-14 Eileen R. Mulvihill Co-expression in eukaryotic cells
JP2769170B2 (en) * 1987-12-08 1998-06-25 ザイモジェネティクス，インコーポレイティド Simultaneous expression in eukaryotic fat
WO1990002175A1 (en) * 1988-08-16 1990-03-08 Novo Nordisk A/S A method of producing polypeptides by culturing eukaryotic cells in the presence of protease inhibitors
DK457788D0 (en) * 1988-08-16 1988-08-16 Nordisk Gentofte PROCEDURE FOR PREPARING A DESIRED POLYPEPTIDE
GB8827305D0 (en) * 1988-11-23 1988-12-29 British Bio Technology Compounds
DK105489D0 (en) * 1989-03-03 1989-03-03 Novo Nordisk As POLYPEPTIDE
SE465222C5 (en) * 1989-12-15 1998-02-10 Pharmacia & Upjohn Ab A recombinant human factor VIII derivative and process for its preparation
ES2180529T3 (en) * 1990-02-26 2003-02-16 Univ Leland Stanford Junior IDENTIFICATION AND EXPRESSION OF DNA SEQUENCES OF AN INSECT STEROID RECEIVER.
US5189178A (en) * 1990-11-21 1993-02-23 Galardy Richard E Matrix metalloprotease inhibitors
US5304603A (en) * 1991-06-18 1994-04-19 The Population Council Leydig cell stimulator
US5661034A (en) * 1991-07-18 1997-08-26 Fuji Yakuhin Kogyo Kabushiki Kaisha Serum-free medium for tissue culture containing tissue inhibitor of metalloproteinases and method for growing cells using the medium
JP3951062B2 (en) * 1991-09-19 2007-08-01 ジェネンテック・インコーポレーテッド Expression of antibody fragments with cysteine present at least as a free thiol in E. coli for the production of bifunctional F (ab ') 2 antibodies
CA2078721A1 (en) * 1991-09-24 1993-03-25 Hiroshi Yonemura Process for preparing human coagulation factor viii protein complex
US5278289A (en) * 1991-11-12 1994-01-11 Johnson Alan J Antihemophilic factor stabilization
US5296471A (en) * 1992-12-22 1994-03-22 Glycomed Incorporated Method for controlling o-desulfation of heparin and compositions produced thereby
AU7524994A (en) * 1993-08-12 1995-03-14 University Of Maryland Thermostable alkaline metalloprotease produced by a hyphomonas, and preparation thereof
US5631159A (en) * 1993-09-22 1997-05-20 Creative Biomolecules, Inc. Lipid-modified serum free media
US5543396A (en) * 1994-04-28 1996-08-06 Georgia Tech Research Corp. Proline phosphonate derivatives

Also Published As

Publication number Publication date
DE69736391T2 (en) 2007-08-16
AU716245B2 (en) 2000-02-24
NZ332751A (en) 2000-06-23
NO985297D0 (en) 1998-11-13
NO20065027L (en) 1999-01-14
JP4896999B2 (en) 2012-03-14
AU2919797A (en) 1997-12-05
ATE334223T1 (en) 2006-08-15
EP0934424B1 (en) 2006-07-26
DE69736391D1 (en) 2006-09-07
ES2260524T3 (en) 2006-11-01
EP0934424A1 (en) 1999-08-11
NO985297L (en) 1999-01-14
NO325633B1 (en) 2008-06-30
JP2009148271A (en) 2009-07-09
US5851800A (en) 1998-12-22
DK0934424T3 (en) 2006-11-20
CA2253287C (en) 2008-02-19
DE69735510D1 (en) 2006-05-11
NO325358B1 (en) 2008-04-07
DE69735510T2 (en) 2006-08-24
PT934424E (en) 2006-12-29
WO1997043436A1 (en) 1997-11-20
JP2000509994A (en) 2000-08-08
ATE321141T1 (en) 2006-04-15
ES2270460T3 (en) 2007-04-01
PT1318198E (en) 2006-08-31

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Effective date: 20140513