NO308174B1 - DNA-sekvens som koder for et biologisk aktivt rekombinant menneskefaktor VIII-derivat, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av menneskefaktor VIII-derivat - Google Patents

DNA-sekvens som koder for et biologisk aktivt rekombinant menneskefaktor VIII-derivat, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av menneskefaktor VIII-derivat Download PDF

Info

Publication number: NO308174B1
Authority: NO; Norway
Prior art keywords: factor viii; dna sequence; kda; dna; factor
Prior art date: 1991-03-15

Application number

NO924395A

Other languages

English (en)

Norwegian (no)

Other versions

NO924395D0 (no

NO924395L (no

Inventor

Annelie B Almstedt

Eva Maria Gray

Peter Lind

Catherine Ljung

Helena Inga Sandberg

Jack Spira

Mona Sydow-Bockman

Helena Wiman

Original Assignee

Pharmacia & Upjohn Ab

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.)

1991-03-15

Filing date

1992-11-13

Publication date

2000-08-07

1992-11-13 Application filed by Pharmacia & Upjohn Ab filed Critical Pharmacia & Upjohn Ab

1992-11-13 Publication of NO924395D0 publication Critical patent/NO924395D0/no

1993-01-13 Publication of NO924395L publication Critical patent/NO924395L/no

2000-08-07 Publication of NO308174B1 publication Critical patent/NO308174B1/no

Links

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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
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
Hematology (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Biochemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Gastroenterology & Hepatology (AREA)
Genetics & Genomics (AREA)
Zoology (AREA)
Molecular Biology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Toxicology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Diabetes (AREA)
Biophysics (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Peptides Or Proteins (AREA)
Micro-Organisms Or Cultivation Processes Thereof (AREA)

NO924395A 1991-03-15 1992-11-13 DNA-sekvens som koder for et biologisk aktivt rekombinant menneskefaktor VIII-derivat, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av menneskefaktor VIII-derivat NO308174B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9100799A SE468050C (sv)	1991-03-15	1991-03-15	Rekombinant derivat av human faktor VIII
PCT/SE1992/000150 WO1992016557A1 (en)	1991-03-15	1992-03-11	Recombinant human factor viii derivatives

Publications (3)

Publication Number	Publication Date
NO924395D0 NO924395D0 (no)	1992-11-13
NO924395L NO924395L (no)	1993-01-13
NO308174B1 true NO308174B1 (no)	2000-08-07

Family

ID=20382191

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO924395A NO308174B1 (no)	1991-03-15	1992-11-13	DNA-sekvens som koder for et biologisk aktivt rekombinant menneskefaktor VIII-derivat, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av menneskefaktor VIII-derivat

Country Status (17)

Country	Link
EP (1)	EP0533862B1 (xx)
JP (1)	JP2655752B2 (xx)
AR (1)	AR247590A1 (xx)
AT (1)	ATE186055T1 (xx)
AU (1)	AU650730B2 (xx)
CA (1)	CA2081659C (xx)
DE (1)	DE69230206T2 (xx)
DK (1)	DK0533862T3 (xx)
ES (1)	ES2137182T3 (xx)
FI (1)	FI107539B (xx)
GR (1)	GR3032468T3 (xx)
IE (1)	IE920814A1 (xx)
NO (1)	NO308174B1 (xx)
PT (1)	PT100245B (xx)
SE (1)	SE468050C (xx)
WO (1)	WO1992016557A1 (xx)
ZA (1)	ZA921882B (xx)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5595886A (en) *	1986-01-27	1997-01-21	Chiron Corporation	Protein complexes having Factor VIII:C activity and production thereof
US6060447A (en) *	1987-05-19	2000-05-09	Chiron Corporation	Protein complexes having Factor VIII:C activity and production thereof
US5744446A (en) *	1992-04-07	1998-04-28	Emory University	Hybrid human/animal factor VIII
US5364771A (en) *	1992-04-07	1994-11-15	Emory University	Hybrid human/porcine factor VIII
US5663060A (en) *	1992-04-07	1997-09-02	Emory University	Hybrid human/animal factor VIII
US5888974A (en) *	1992-04-07	1999-03-30	Emory University	Hybrid human/animal factor VIII
AU4719393A (en)	1992-07-31	1994-03-03	Medeva Holdings B.V.	Expression of recombinant fusion proteins in attenuated bacteria
SE9300509D0 (sv) *	1993-02-16	1993-02-16	Kabi Pharmacia Ab	Peg treatment
SE504074C2 (sv) *	1993-07-05	1996-11-04	Pharmacia Ab	Proteinberedning för subkutan, intramuskulär eller intradermal administrering
GB9401787D0 (en) *	1994-01-31	1994-03-23	Medeva Holdings Bv	Vaccine compositions
SE9303601D0 (sv) *	1993-11-01	1993-11-01	Kabi Pharmacia Ab	Improved cell cultivation method and medium
SE9403915D0 (sv) *	1994-11-14	1994-11-14	Annelie Almstedt	Process A
US6200560B1 (en)	1998-10-20	2001-03-13	Avigen, Inc.	Adeno-associated virus vectors for expression of factor VIII by target cells
US6221349B1 (en)	1998-10-20	2001-04-24	Avigen, Inc.	Adeno-associated vectors for expression of factor VIII by target cells
US6197526B1 (en) *	1999-01-04	2001-03-06	Dyax Corp.	Polypeptides for binding human factor VIII and fragments of human factor VIII
US7112438B2 (en)	1999-01-04	2006-09-26	Dyax Corp.	Binding molecules for human factor VIII and factor VIII-like proteins
EP1048726B1 (en) *	1999-04-27	2006-07-26	Négrier, Claude	Modified factor VIII cDNA
EP1038959A1 (en) *	1999-03-17	2000-09-27	Aventis Behring Gesellschaft mit beschränkter Haftung	Factor VIII without B-domain, comprising one or more insertions of a truncated intron I of factor IX
SE9901379D0 (sv)	1999-04-19	1999-04-19	Pharmacia & Upjohn Ab	Receptor structures
EP1233064A1 (en) *	2001-02-09	2002-08-21	Aventis Behring Gesellschaft mit beschränkter Haftung	Modified factor VIII cDNA and its use for the production of factor VIII
EP1284290A1 (en) *	2001-08-08	2003-02-19	Aventis Behring GmbH	Increase of the expression levels of factor VIII by insertion of spliceable nucleotide sequences into factor VIII cDNA
EP1283263A1 (en) *	2001-08-08	2003-02-12	Aventis Behring GmbH	Modified cDNA for high expression levels of factor VIII and its derivatives
PL2292780T3 (pl)	2003-09-30	2018-05-30	The Trustees Of The University Of Pennsylvania	Klady wirusów związanych z adenowirusami (AAV), sekwencje, wektory je zawierające i ich zastosowania
ES2580044T3 (es)	2005-04-07	2016-08-18	The Trustees Of The University Of Pennsylvania	Método de incremento de la función de un vector de AAV
AU2006233638A1 (en) *	2005-04-14	2006-10-19	Csl Behring Gmbh	Modified coagulation Factor VIII with enhanced stability and its derivates
KR20130040844A (ko)	2010-03-29	2013-04-24	더 트러스티스 오브 더 유니버시티 오브 펜실바니아	약학적으로 유발된 전이유전자 제거 시스템
US9315825B2 (en)	2010-03-29	2016-04-19	The Trustees Of The University Of Pennsylvania	Pharmacologically induced transgene ablation system
BRPI1105317A2 (pt)	2011-01-24	2013-04-30	Fundacco Hemoct De Ribeirco Preto	produÇço estÁvel e em larga escala de fviii humano em linhagem celular humana sk-hep-1
TR201908020T4 (tr)	2011-02-17	2019-06-21	Univ Pennsylvania	Doku özgüllüğünü değiştirmek ve aav9-aracılı gen transferini geliştirmek için bileşimler ve yöntemler.
WO2015012924A2 (en)	2013-04-29	2015-01-29	The Trustees Of The University Of Pennsylvania	Tissue preferential codon modified expression cassettes, vectors containing same, and use thereof
CN105017410B (zh) *	2014-04-18	2018-06-08	北京诺思兰德生物技术股份有限公司	一种b区部分缺失型重组人凝血因子ⅷ
WO2016168728A2 (en)	2015-04-16	2016-10-20	Emory University	Recombinant promoters and vectors for protein expression in liver and use thereof
EP3521428A4 (en)	2016-10-03	2020-06-24	Daiichi Sankyo Company, Limited	PROMOTER OF THE HSPA5 GENE
EP4192515A2 (en)	2020-08-07	2023-06-14	Amicus Therapeutics, Inc.	Vesicle targeting proteins and uses of same

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1200773A (en) *	1980-02-29	1986-02-18	William J. Rutter	Expression linkers
JPS62181786A (ja) *	1985-08-12	1987-08-10	シンテツクス（ユ−・エス・エイ）インコ−ポレイテツド	融合蛋白質の製造法
US4935233A (en) *	1985-12-02	1990-06-19	G. D. Searle And Company	Covalently linked polypeptide cell modulators
US5451521A (en) *	1986-05-29	1995-09-19	Genetics Institute, Inc.	Procoagulant proteins
IL83192A (en) *	1986-07-18	1992-11-15	Gist Brocades Nv	Method for the preparation of proteins with factor viii activity by microbial host cells;expression vectors,host cells,antibodies
NZ219516A (en) *	1987-02-10	1991-02-26	Wellcome Found	Fusion proteins of hbcag (hepatitis b virus core antigen)
DE3720246A1 (de) *	1987-06-19	1988-12-29	Behringwerke Ag	Faktor viii:c-aehnliches molekuel mit koagulationsaktivitaet
HUT70457A (en) *	1989-11-17	1995-10-30	Chiron Corp	Protein complexes having factor viii:c activity and production thereof
SE465222C5 (sv) *	1989-12-15	1998-02-10	Pharmacia & Upjohn Ab	Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning
CA2078721A1 (en) *	1991-09-24	1993-03-25	Hiroshi Yonemura	Process for preparing human coagulation factor viii protein complex

1991
- 1991-03-15 SE SE9100799A patent/SE468050C/sv not_active IP Right Cessation
1992
- 1992-03-11 JP JP4505642A patent/JP2655752B2/ja not_active Expired - Lifetime
- 1992-03-11 DE DE69230206T patent/DE69230206T2/de not_active Expired - Lifetime
- 1992-03-11 DK DK92905708T patent/DK0533862T3/da active
- 1992-03-11 AU AU13513/92A patent/AU650730B2/en not_active Expired
- 1992-03-11 CA CA002081659A patent/CA2081659C/en not_active Expired - Lifetime
- 1992-03-11 AT AT92905708T patent/ATE186055T1/de active
- 1992-03-11 WO PCT/SE1992/000150 patent/WO1992016557A1/en active IP Right Grant
- 1992-03-11 ES ES92905708T patent/ES2137182T3/es not_active Expired - Lifetime
- 1992-03-11 EP EP92905708A patent/EP0533862B1/en not_active Expired - Lifetime
- 1992-03-13 AR AR92321933A patent/AR247590A1/es active
- 1992-03-13 IE IE081492A patent/IE920814A1/en not_active IP Right Cessation
- 1992-03-13 ZA ZA921882A patent/ZA921882B/xx unknown
- 1992-03-13 PT PT100245A patent/PT100245B/pt not_active IP Right Cessation
- 1992-11-11 FI FI925131A patent/FI107539B/fi not_active IP Right Cessation
- 1992-11-13 NO NO924395A patent/NO308174B1/no not_active IP Right Cessation
2000
- 2000-01-25 GR GR20000400162T patent/GR3032468T3/el unknown

Also Published As

Publication number	Publication date
GR3032468T3 (en)	2000-05-31
JPH05507420A (ja)	1993-10-28
CA2081659A1 (en)	1992-09-16
FI925131A (fi)	1992-11-11
JP2655752B2 (ja)	1997-09-24
FI107539B (fi)	2001-08-31
WO1992016557A1 (en)	1992-10-01
PT100245B (pt)	1999-08-31
PT100245A (pt)	1993-07-30
AU650730B2 (en)	1994-06-30
AR247590A1 (es)	1995-01-31
ZA921882B (en)	1992-11-25
EP0533862B1 (en)	1999-10-27
SE468050C (sv)	1998-04-27
ATE186055T1 (de)	1999-11-15
DE69230206D1 (de)	1999-12-02
NO924395D0 (no)	1992-11-13
SE468050B (sv)	1992-10-26
DE69230206T2 (de)	2000-05-18
SE9100799L (sv)	1992-09-16
ES2137182T3 (es)	1999-12-16
FI925131A0 (fi)	1992-11-11
CA2081659C (en)	2002-06-25
IE920814A1 (en)	1992-09-23
EP0533862A1 (en)	1993-03-31
AU1351392A (en)	1992-10-21
NO924395L (no)	1993-01-13
DK0533862T3 (da)	2000-01-17
SE9100799D0 (sv)	1991-03-15

Legal Events

Date	Code	Title	Description
2012-04-10	MK1K	Patent expired

Publication	Publication Date	Title
NO308174B1 (no)	2000-08-07	DNA-sekvens som koder for et biologisk aktivt rekombinant menneskefaktor VIII-derivat, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av menneskefaktor VIII-derivat
US5661008A (en)	1997-08-26	Recombinant human factor VIII derivatives
NO309041B1 (no)	2000-12-04	DNA-sekvens, rekombinant ekspresjonsvektor og vertscelle omfattende DNA-sekvensen, samt fremgangsmÕte for fremstilling av human faktor VIII-derivat
US6060447A (en)	2000-05-09	Protein complexes having Factor VIII:C activity and production thereof
US6228620B1 (en)	2001-05-08	Protein complexes having factor VIII:C activity and production thereof
JP2513993B2 (ja)	1996-07-10	ヒト第ｖｉｉｉ：ｃ因子活性を有する組換えタンパク複合体
CA2068728A1 (en)	1991-05-18	Protein complexes having factor viii:c activity and production thereof
CA2130900C (en)	2009-04-14	Therapeutic domains of von willebrand factor
AU606925B2 (en)	1991-02-21	A method for producing factor viii in high yield
JP4804356B2 (ja)	2011-11-02	第ＶＩＩＩ因子及びその誘導体の高発現レベルのための改変されたｃＤＮＡ