RU2001119156A - The expression system for factor VIII - Google Patents

The expression system for factor VIII

Info

Publication number
RU2001119156A
RU2001119156A RU2001119156/13A RU2001119156A RU2001119156A RU 2001119156 A RU2001119156 A RU 2001119156A RU 2001119156/13 A RU2001119156/13 A RU 2001119156/13A RU 2001119156 A RU2001119156 A RU 2001119156A RU 2001119156 A RU2001119156 A RU 2001119156A
Authority
RU
Russia
Prior art keywords
cells
stage
factor viii
protein
human
Prior art date
Application number
RU2001119156/13A
Other languages
Russian (ru)
Other versions
RU2249041C2 (en
Inventor
Миунг-Сэм ЧО
Шэм Йуен ЧЭН
Вильям КЕЛСИ
Хелена ЙИ
Original Assignee
Байер Корпорейшн
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 US09/209,916 external-priority patent/US6358703B1/en
Application filed by Байер Корпорейшн filed Critical Байер Корпорейшн
Publication of RU2001119156A publication Critical patent/RU2001119156A/en
Application granted granted Critical
Publication of RU2249041C2 publication Critical patent/RU2249041C2/en

Links

Claims (19)

1. Способ получения клеток, экспрессирующих белок, обладающий прокоагулирующей активностью фактора VIII, включающий следующие последовательные этапы: a) получение клеток исключительно человеческого происхождения, b) взаимодействие клеток стадии а) с вектором в условиях, позволяющих вектору проникнуть в клетки, причем вектор включает селективный маркер и последовательность, кодирующую белок, обладающий прокоагулирующей активностью фактора VIII, оперативно связанную с промотором, c) отбор клеток стадии b) при помощи агента селекции и d) выделение из клеток, полученных на стадии с) отдельных клонов, экспрессирующих большие количества белка, обладающего прокоагулирующей активностью фактора VIII.1. A method of producing cells expressing a protein having procoagulating activity of factor VIII, comprising the following sequential steps: a) obtaining cells of exclusively human origin, b) interaction of the cells of stage a) with the vector under conditions allowing the vector to penetrate the cells, the vector comprising selective marker and sequence encoding a protein having procoagulating activity of factor VIII operably linked to a promoter, c) selection of cells of stage b) using a selection agent and d) isolated and from the cells obtained in step c) of individual clones expressing large amounts of a protein having procoagulating factor VIII activity. 2. Способ по п.1, включающий далее стадию e) адаптации клонов стадии d) к росту в среде, свободной от белков плазмы.2. The method according to claim 1, further comprising stage e) adaptation of the clones of stage d) to growth in a medium free of plasma proteins. 3. Способ по п.1, где клетки стадии а) являются гибридами клеток лимфомы человека и клеток 293 S.3. The method according to claim 1, where the cells of stage a) are hybrids of human lymphoma cells and 293 S. cells. 4. Способ по п.1, где клетки стадии а) являются гибридами клеток 2В8 (АТСС CRL-12569) и клеток 293S.4. The method according to claim 1, where the cells of stage a) are hybrids of 2B8 cells (ATCC CRL-12569) and 293S cells. 5. Способ по п.1, где клетки стадии а) являются клетками НКВ11 (АТСС CRL-12568).5. The method according to claim 1, where the cells of stage a) are NKB11 cells (ATCC CRL-12568). 6. Способ по п.1, где стадии с) и d) выполняются больше, чем один раз.6. The method according to claim 1, where stages c) and d) are performed more than once. 7. Способ по п.1, где последовательность стадии b) кодирует последовательность, представленную на Фиг.1 (SEQ ID NO: 1).7. The method according to claim 1, where the sequence of step b) encodes the sequence shown in Figure 1 (SEQ ID NO: 1). 8. Способ по п.1, где последовательность стадии b) кодирует фактор VIII человека.8. The method according to claim 1, where the sequence of stage b) encodes a human factor VIII. 9. Способ по п.1, где селективный маркер стадии b) - dhfr и агент селекции стадии с) - метотрексат.9. The method according to claim 1, where the selective marker of stage b) is dhfr and the selection agent of stage c) is methotrexate. 10. Способ по п.1, где селективный маркер стадии b) - gs и агент селекции стадии с) - метионин сульфоксиимин.10. The method according to claim 1, where the selective marker of stage b) is gs and the selection agent of stage c) is methionine sulfoxyimine. 11. Способ по п.1, где селективный маркер стадии b) - mdr и агент селекции стадии с) - колхицин.11. The method according to claim 1, where the selective marker of stage b) is mdr and the selection agent of stage c) is colchicine. 12. Способ получения белка, обладающего активностью фактора VIII, включающий выращивание клеток, полученных способом по п.1, в ростовой среде, и дальнейшее выделение из среды белка, обладающего активностью фактора VIII.12. A method of obtaining a protein having a factor VIII activity, comprising growing cells obtained by the method according to claim 1, in a growth medium, and further isolating a protein having a factor VIII activity from the medium. 13. Способ по п.11, где белок является фактором VIII человека.13. The method according to claim 11, where the protein is a human factor VIII. 14. Способ по п.11, где белок имеет аминокислотную последовательность, приведенную на Фиг.1 (SEQ ID NO: 1).14. The method according to claim 11, where the protein has the amino acid sequence shown in Figure 1 (SEQ ID NO: 1). 15. Линия клеток человека, полученная из клеток лимфомы человека и клеток 293S, экспрессирующая на высоком уровне белок, обладающий активностью фактора VIII.15. A human cell line derived from human lymphoma cells and 293S cells expressing at a high level a protein having factor VIII activity. 16. Линия клеток человека по п.14, где линия клеток человека получена из клеток HKB11(ATCCCRL-12568).16. The human cell line of claim 14, wherein the human cell line is derived from HKB11 cells (ATCCCRL-12568). 17. Линия клеток человека, полученная из клеток лимфомы человека и клеток 293S, экспрессирующая на высоком уровне белок, обладающий активностью фактора VIII, при выращивании в среде, свободной от белков плазмы.17. The human cell line obtained from human lymphoma cells and 293S cells, expressing at a high level a protein having the activity of factor VIII, when grown in a medium free of plasma proteins. 18. Клеточная линия по п.16, где клеточная линия получена из клеток НКВ11 (АТСС CRL-12568).18. The cell line according to clause 16, where the cell line is obtained from NKB11 cells (ATCC CRL-12568). 19. Клеточная линия, обозначенная 20В8 (АТСС CRL-12582).19. The cell line designated 20B8 (ATCC CRL-12582).
RU2001119156/13A 1998-12-10 1999-12-08 Method for preparing and isolating protein eliciting activity of factor viii, strain of cells hkb expressing protein eliciting activity of factor viii (variants) RU2249041C2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US09/209,916 1998-12-10
US09/209,916 US6358703B1 (en) 1998-12-10 1998-12-10 Expression system for factor VIII

Publications (2)

Publication Number Publication Date
RU2001119156A true RU2001119156A (en) 2003-07-27
RU2249041C2 RU2249041C2 (en) 2005-03-27

Family

ID=22780858

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2001119156/13A RU2249041C2 (en) 1998-12-10 1999-12-08 Method for preparing and isolating protein eliciting activity of factor viii, strain of cells hkb expressing protein eliciting activity of factor viii (variants)

Country Status (26)

Country Link
US (10) US6358703B1 (en)
EP (1) EP1137797B1 (en)
JP (1) JP4240818B2 (en)
KR (1) KR100616028B1 (en)
AT (1) ATE412765T1 (en)
AU (1) AU761801B2 (en)
BG (1) BG65431B1 (en)
BR (1) BRPI9916069B8 (en)
CA (1) CA2354845C (en)
CZ (1) CZ302330B6 (en)
DE (1) DE69939839D1 (en)
DK (1) DK1137797T3 (en)
ES (1) ES2315026T3 (en)
HU (1) HU228489B1 (en)
IL (2) IL143353A0 (en)
NO (1) NO329544B1 (en)
NZ (1) NZ512234A (en)
PL (1) PL200676B1 (en)
PT (1) PT1137797E (en)
RO (1) RO121604B1 (en)
RU (1) RU2249041C2 (en)
SI (1) SI20644B (en)
SK (1) SK286945B6 (en)
TR (1) TR200101592T2 (en)
UA (1) UA77383C2 (en)
WO (1) WO2000034505A1 (en)

Families Citing this family (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6475725B1 (en) 1997-06-20 2002-11-05 Baxter Aktiengesellschaft Recombinant cell clones having increased stability and methods of making and using the same
US6358703B1 (en) * 1998-12-10 2002-03-19 Bayer Corporation Expression system for factor VIII
US6180108B1 (en) * 1998-12-10 2001-01-30 Bayer Corporation Vectors having terminal repeat sequence of Epstein-Barr virus
DE60115613T2 (en) * 2000-03-22 2006-08-24 Octagene Gmbh PREPARATION OF RECOMBINANT MOUTHES OF BLOOD CREATING FACTOR VIII IN HUMAN CELL LINES
ES2331909T3 (en) * 2001-06-14 2010-01-20 The Scripps Research Institute FACTOR VIII STABILIZED WITH GENETICALLY MODIFIED DISULFIDE LINKS.
CN1767857A (en) * 2003-02-26 2006-05-03 尼克塔治疗亚拉巴马公司 Polymer-factor VIII moiety conjugates
US7485291B2 (en) * 2003-06-03 2009-02-03 Cell Genesys, Inc. Compositions and methods for generating multiple polypeptides from a single vector using a virus derived peptide cleavage site, and uses thereof
US7709224B2 (en) * 2003-06-03 2010-05-04 Biosante Pharmaceuticals, Inc. Compositions and methods for enhanced expression of recombinant polypeptides from a single vector using a peptide cleavage site
AU2005302516A1 (en) * 2004-10-29 2006-05-11 Centocor, Inc. Chemically defined media compositions
WO2006053299A2 (en) 2004-11-12 2006-05-18 Bayer Healthcare Llc Site-directed modification of fviii
AR058568A1 (en) 2005-12-20 2008-02-13 Bristol Myers Squibb Co METHODS TO PRODUCE A COMPOSITION WITH CTLA4-IG MOLECULES FROM A CROP MEANS
KR101398713B1 (en) 2005-12-20 2014-06-12 브리스톨-마이어스 스큅 컴퍼니 Compositions and methods for producing a composition
EP3255152A1 (en) * 2007-12-27 2017-12-13 Baxalta GmbH Cell culture processes
KR101005967B1 (en) * 2008-04-12 2011-01-05 (주)셀트리온 Human host cell for producing recombinant proteins with high quality and quantity
CN102137935A (en) * 2008-06-25 2011-07-27 拜耳医药保健有限公司 Factor VIII muteins with reduced immunogenicity
RU2011110459A (en) 2008-08-21 2012-09-27 Октафарма АГ (CH) RECOMBINANTLY OBTAINED HUMAN FACTOR VIII AND IX
MX2011002316A (en) * 2008-09-03 2011-05-10 Octapharma Ag New protecting compositions for recombinantly produced factor viii.
MX362028B (en) 2009-02-03 2019-01-04 Amunix Pharmaceuticals Inc Extended recombinant polypeptides and compositions comprising same.
CN102427823A (en) * 2009-03-24 2012-04-25 拜耳医药保健有限公司 Factor VIII variants and methods of use
AU2010290077C1 (en) 2009-08-24 2015-12-03 Bioverativ Therapeutics Inc. Coagulation factor IX compositions and methods of making and using same
US20110150843A1 (en) * 2009-10-30 2011-06-23 National Institute Of Immunology Method for the therapeutic correction of hemophilia a by transplanting bone marrow cells
US20130017997A1 (en) * 2010-08-19 2013-01-17 Amunix Operating Inc. Factor VIII Compositions and Methods of Making and Using Same
BR112013028006A2 (en) * 2011-05-13 2016-09-06 Octapharma Ag method for increasing eukaryotic cell productivity in the production of recombinant fviii
BR112014017165B1 (en) 2012-01-12 2023-05-02 Bioverativ Therapeutics Inc CHIMERIC PROTEIN COMPRISING A FACTOR VIII PROTEIN, PHARMACEUTICAL COMPOSITION, AND USES THEREOF
ES2771208T3 (en) * 2012-02-15 2020-07-06 Bioverativ Therapeutics Inc Factor VIII compositions and methods of preparation and use thereof
EP3549953A1 (en) 2012-02-15 2019-10-09 Bioverativ Therapeutics Inc. Recombinant factor viii proteins
WO2017180807A1 (en) 2016-04-15 2017-10-19 Baxalta Incorporated Method and apparatus for providing a pharmacokinetic drug dosing regiment
WO2015023891A2 (en) 2013-08-14 2015-02-19 Biogen Idec Ma Inc. Factor viii-xten fusions and uses thereof
CN106456718A (en) 2014-01-10 2017-02-22 比奥根Ma公司 Factor viii chimeric proteins and uses thereof
EA201890423A1 (en) 2015-08-03 2018-07-31 Биовератив Терапьютикс Инк. SLIGHT PROTEINS OF THE FACTOR IX, METHODS OF THEIR RECEPTION AND APPLICATION
EP3487538A1 (en) 2016-07-22 2019-05-29 Nektar Therapeutics Conjugates of a factor viii moiety having an oxime-containing linkage
US10896749B2 (en) 2017-01-27 2021-01-19 Shire Human Genetic Therapies, Inc. Drug monitoring tool
WO2019055717A1 (en) * 2017-09-13 2019-03-21 Evolve Biosystems, Inc. Oligosaccharide compositions and their use during transitional phases of the mammalian gut microbiome
KR20190086269A (en) * 2018-01-12 2019-07-22 재단법인 목암생명과학연구소 Long-acting recombinant glycoproteins and menufacturing method thereof
AU2019366942A1 (en) * 2018-10-23 2021-06-10 The Children's Hospital Of Philadelphia Compositions and methods for modulating factor VIII function

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6045849B2 (en) 1980-08-25 1985-10-12 林原 健 Method for producing human erythropoietin
US4766075A (en) 1982-07-14 1988-08-23 Genentech, Inc. Human tissue plasminogen activator
GB8308235D0 (en) 1983-03-25 1983-05-05 Celltech Ltd Polypeptides
US4757006A (en) 1983-10-28 1988-07-12 Genetics Institute, Inc. Human factor VIII:C gene and recombinant methods for production
US4703008A (en) 1983-12-13 1987-10-27 Kiren-Amgen, Inc. DNA sequences encoding erythropoietin
KR890002004B1 (en) * 1984-01-11 1989-06-07 가부시끼 가이샤 도오시바 Distinction apparatus of papers
US4965199A (en) 1984-04-20 1990-10-23 Genentech, Inc. Preparation of functional human factor VIII in mammalian cells using methotrexate based selection
US4970300A (en) * 1985-02-01 1990-11-13 New York University Modified factor VIII
US4868112A (en) 1985-04-12 1989-09-19 Genetics Institute, Inc. Novel procoagulant proteins
US5198349A (en) 1986-01-03 1993-03-30 Genetics Institute, Inc. Method for producing factor VIII:C and analogs
ATE63335T1 (en) * 1986-07-11 1991-05-15 Miles Inc PRODUCTION OF RECOMBINANT PROTEIN.
DK175363B1 (en) 1986-09-12 2004-09-13 Genentech Inc Process for Continuous Production of a Desired Heterologous Protein in a Eukaryotic Host Cell, Vector Adding That Ability, and Cells Transformed with the Vector
US5171844A (en) * 1987-06-12 1992-12-15 Gist-Brocades N.W. Proteins with factor viii activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them
SE465222C5 (en) 1989-12-15 1998-02-10 Pharmacia & Upjohn Ab A recombinant human factor VIII derivative and process for its preparation
US5661008A (en) 1991-03-15 1997-08-26 Kabi Pharmacia Ab Recombinant human factor VIII derivatives
US5859204A (en) 1992-04-07 1999-01-12 Emory University Modified factor VIII
DK0874057T3 (en) * 1993-06-10 2004-11-22 Bayer Ag Vector and mammalian cell line with improved production ability
US5952198A (en) * 1995-05-04 1999-09-14 Bayer Corporation Production of recombinant Factor VIII in the presence of liposome-like substances of mixed composition
DE19517194A1 (en) * 1995-05-11 1996-11-14 Giesecke & Devrient Gmbh Device and method for checking sheet material, e.g. Banknotes or securities
MX9504215A (en) 1995-10-05 1997-04-30 Inst Politecnico Nacional Improved process to purify oligopeptides with molecular weights from 1,000 to 10,000 daltons, from leukocyte extracts and their pharmaceutical presentation.
US5922959A (en) * 1996-10-15 1999-07-13 Currency Systems International Methods of measuring currency limpness
US5923413A (en) * 1996-11-15 1999-07-13 Interbold Universal bank note denominator and validator
US5804420A (en) * 1997-04-18 1998-09-08 Bayer Corporation Preparation of recombinant Factor VIII in a protein free medium
CA2312291A1 (en) * 1997-12-05 1999-06-17 The Immune Response Corporation Novel vectors and genes exhibiting increased expression
US6040584A (en) * 1998-05-22 2000-03-21 Mti Corporation Method and for system for detecting damaged bills
US6528286B1 (en) 1998-05-29 2003-03-04 Genentech, Inc. Mammalian cell culture process for producing glycoproteins
US6358703B1 (en) * 1998-12-10 2002-03-19 Bayer Corporation Expression system for factor VIII
US6136599A (en) * 1998-12-10 2000-10-24 Bayer Corporation Human hybrid host cell for mammalian gene expression
US6180108B1 (en) 1998-12-10 2001-01-30 Bayer Corporation Vectors having terminal repeat sequence of Epstein-Barr virus

Similar Documents

Publication Publication Date Title
RU2001119156A (en) The expression system for factor VIII
JP2766781B2 (en) Microorganisms capable of producing bovine growth hormone
EP0246279B1 (en) Method for isolation of recombinant polypeptides in biologically active forms
Ohno Evolution by gene duplication
US6229003B1 (en) Production of bovine growth hormone by microorganisms
US5693499A (en) Process for preparing human coagulation factor VIII protein complex
CN102358902B (en) Silkworm fibroin heavy-chain gene mutation sequence and mutation method and application
RU2009139802A (en) ENZYME FOR SYNTHESIS OF METHYLMONONYL-CO-ENZYME A AND ETHYLMALONYL-CO-ENZYME A, AND ITS APPLICATION
WO2000056900A3 (en) Promoter sequences derived from fusarium venenatum and uses thereof
SI20644B (en) Expression system for factor viii
HUP0101136A2 (en) Protein expression in baculovirus vector expression systems
RU2005136013A (en) PHOSPHODYESTERASE 8A
EP0772627A1 (en) Production of biologically active recombinant neurotrophic protein
KR920004571A (en) Gene encoding heparin binding neurotrophic factor (HBNF), expression vectors and host cells comprising the same, and methods for producing and using HBNF
JP2003506077A (en) Recombinant stable cell clone, its production and use
JP2003506015A5 (en)
JP2003506077A5 (en)
AU1941597A (en) Protein having cellulase activities and process for producing the same
CA2298412A1 (en) Identification of human cell lines for the production of human proteins by endogenous gene activation
CA2000309A1 (en) Recombinant pdgf and methods for production
KR890701606A (en) Production of animal lysozyme via secretion from Peachia pastoris and composition for same
EP0247145B1 (en) Multiply-amplifiable vectors for high level expression of exogenous dna
Engelmann Induction of the insect vitellogenin in vivo and in vitro
EP0134085A1 (en) DNA encoding a GRF precursor
Allen et al. Synthesis and cloning of a gene coding for a fusion protein containing mouse epidermal growth factor.: Isolation from transformed Escherichia coli and some physical, chemical and biological characteristics of the growth factor