KR880701105A - 신규 응혈촉진 단백질 - Google Patents
신규 응혈촉진 단백질Info
- Publication number
- KR880701105A KR880701105A KR1019880700094A KR880700094A KR880701105A KR 880701105 A KR880701105 A KR 880701105A KR 1019880700094 A KR1019880700094 A KR 1019880700094A KR 880700094 A KR880700094 A KR 880700094A KR 880701105 A KR880701105 A KR 880701105A
- Authority
- KR
- South Korea
- Prior art keywords
- protein
- arg
- sequence
- amino acid
- positions
- Prior art date
Links
- 101000882917 Penaeus paulensis Hemolymph clottable protein Proteins 0.000 title 1
- 235000018102 proteins Nutrition 0.000 claims 15
- 102000004169 proteins and genes Human genes 0.000 claims 15
- 108090000623 proteins and genes Proteins 0.000 claims 15
- 235000001014 amino acid Nutrition 0.000 claims 9
- 150000001413 amino acids Chemical class 0.000 claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 6
- 235000018977 lysine Nutrition 0.000 claims 6
- 108090000765 processed proteins & peptides Proteins 0.000 claims 5
- 239000004472 Lysine Substances 0.000 claims 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 4
- 210000004899 c-terminal region Anatomy 0.000 claims 4
- 239000002299 complementary DNA Substances 0.000 claims 4
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 4
- 229920001184 polypeptide Polymers 0.000 claims 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 4
- 102000004196 processed proteins & peptides Human genes 0.000 claims 4
- 102100026735 Coagulation factor VIII Human genes 0.000 claims 3
- 201000003542 Factor VIII deficiency Diseases 0.000 claims 3
- 208000009292 Hemophilia A Diseases 0.000 claims 3
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 239000003085 diluting agent Substances 0.000 claims 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- 238000011321 prophylaxis Methods 0.000 claims 3
- 238000011282 treatment Methods 0.000 claims 3
- 239000004475 Arginine Substances 0.000 claims 2
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims 2
- 230000015271 coagulation Effects 0.000 claims 2
- 238000005345 coagulation Methods 0.000 claims 2
- 238000012217 deletion Methods 0.000 claims 2
- 230000037430 deletion Effects 0.000 claims 2
- 229940099816 human factor vii Drugs 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 230000001737 promoting effect Effects 0.000 claims 2
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 claims 2
- 102100023804 Coagulation factor VII Human genes 0.000 claims 1
- 108010023321 Factor VII Proteins 0.000 claims 1
- 230000035602 clotting Effects 0.000 claims 1
- 239000000701 coagulant Substances 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 229940012413 factor vii Drugs 0.000 claims 1
- 230000009261 transgenic effect Effects 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/14—Blood; Artificial blood
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S930/00—Peptide or protein sequence
- Y10S930/01—Peptide or protein sequence
- Y10S930/10—Factor VIII, AHF; related peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Zoology (AREA)
- Medicinal Chemistry (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Developmental Biology & Embryology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Cell Biology (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Virology (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (14)
- (ⅰ) 아르기닌-1689가 리신으로 치환되고/되거나, (ⅱ) 하기 (a)~(d)로 이루어진 군에서 선택된 하나 또는 그 이상의 아미노산이 결실되거나 또는 독립적으로 선택된 치환 아미노산에 의해 치환되어 있음을 특징으로 하는, 인체이자 Ⅷ:c- 형 응혈촉진 활성 및 인체인자 Ⅷ:c 또는 Arg-372 와 Ser-1690 사이의 1~1317 아미노산의 결실을 포함하는 그의 유사체와 실질적으로 동일한 아미노산 서열을 갖는 단백질. (a)220, 226, 250, 279, 282, 336, 359, 562, 740, 776, 1313, 1648, 1719 및 1721 위치중 하나 또는 그 이상의 위치의 아르기닌 : (b) 325 및 338 위치중 하나 또는 둘 모두의 리신 : (c) 346,395,407,1364 및 1380 위치중 하나 또는 그 이상의 리신 ; 및 (d)741 위치의 세린.
- 제1항에 있어서, 220, 226, 250, 279, 282, 325, 336, 338, 359, 562, 740, 741, 776, 1313, 1648, 1719 또는 1721 위치중 하나 또는 그 이상을 포함하는 트리펩티드 서열이 Asn-X-Thr 또는 Asn-X-Ser(식중 X는 모든 아미노산이다)을 함유하는 트리펩티드 서열에 의해 치환되어 있음을 특징으로 하는 단백질.
- 제2항에 있어서, X가 Arg이 아님을 특징으로 하는 단백질.
- 제1항 내지 3항의 단백질을 코딩하는 cDNA.
- 형질발현 통제 서열에 기능적으로 연결되어 있는 제4항의 cDNA를 함유하고 cDNA에 의해 코딩된 단백질을 발현시킬 수 있는 숙주 세포.
- 단백질의 생산을 가능하게 하는 조건하에서 제5항의 숙주 세포를 배양함을 특징으로 하는, (ⅰ) 아르기닌-1689가 리신으로 치환되고/되거나, (ⅱ) 하기 (a)~(d)로 이루어진 군에서 선택된 하나 또는 그 이상의 아미노산이 결실되거나 또는 독립적으로 선택된 치환 아미노산에 의해 치환되어 있는, 인체이자 Ⅷ:c- 형 응혈촉진 활성 및 인체인자 Ⅷ:c 또는 Arg-372 와 Ser-1690 사이의 1~1317 아미노산의 결실을 포함하는 그의 유사체와 실질적으로 동일한 아미노산 서열을 갖는 단백질의 제조방법. (a)220, 226, 250, 279, 282, 336, 359, 562, 740, 776, 1313, 1648, 1719 및 1721 위치중 하나 또는 그 이상의 위치의 아르기닌 : (b) 325 및 338 위치중 하나 또는 둘 모두의 리신 : (c) 346,395,407,1364 및 1380 위치중 하나 또는 그 이상의 리신 ; 및 (d)741 위치의 세린.
- 제6항의 방법에 의해 제조된 단백질.
- 비경구적으로 허용되는 담체 또는 희석제와 혼합된 유효량의 제1항의 단백질을 함유함을 특징으로 하는 혈우병 A의 치료 또는 예방을 위한 약학 조성물.
- 비경구적으로 허용되는 담체 또는 희석제와 혼합된 유효량의 제7항의 단백질을 함유함을 특징으로 하는 혈우병 A의 치료 또는 예방을 위한 약학 조성물.
- 하기의 아미노산 서열을 특징으로 하는 인자 Ⅷ:c 형 응혈촉진 활성을 갖는 단백질.A - X - B상기 식중, 영역 A는 표 I 에 나타낸 것과 실질적으로 동일한 Ala-1 ~Arg-372 사이의 폴리펩티드 서열을 나타내고 ; 영역 B 는 표 I에 나타낸 것과 실질적으로 동일한 Ser-1690~ Tyr-2332 사이의 폴리펩티드 서열을 나타내고 ; 영역 X는 표 I 의 서열 Arg-372 ~ Arg-740내의 아미노산 서열과 실질적으로 중복되는 0~367 아미노산을 함유하는 팹티드 서열을 나타내며, X의 아미노 말단은 펩티드 결합을 통하여 A의 카르복시 말단에 공유 결합되어 있고, X의 카르복시 말단은 비슷하게 B의 아미노 말단에 결합되어 있다.
- 제10항의 단백질을 코딩하는 cDNA.
- 형질 발형 통제 서열에 기능적으로 연결되어 있는 제11항의 cDNA를 함유하고 cDNA에 의해 코딩된 단백질을 발현시킬 수 있는 숙주 세포.
- 단백질의 생산을 가능하게 하는 조건하에서 제12항의 숙주 세포를 배양함을 특징으로 하는, 하기 아미노산 서열을 포함하는 Ⅷ:c형 응혈 촉진 활성을 갖는 단백질.A - X - B상기 식중, 영역 A는 표 I 에 나타낸 것과 실질적으로 동일한 Ala-1 ~Arg-372 사이의 폴리펩티드 서열을 나타내고 ; 영역 B 는 표 I에 나타낸 것과 실질적으로 동일한 Ser-1690~ Tyr-2332 사이의 폴리펩티드 서열을 나타내고 ; 영역 X는 표 I 의 서열 Arg-372 ~ Arg-740내의 아미노산 서열과 실질적으로 중복되는 0~367 아미노산을 함유하는 펩티드 서열을 나타내며, X의 아미노 말단은 펩티드 결합을 통하여 A의 카르복시 말단에 공유 결합되어 있고, X의 카르복시 말단은 비슷하게 B의 아미노 말단에 결합되어 있다.
- 비경구적으로 허용되는 담체 또는 희석제와 혼합된 유효량이 제10항의 단백질을 함유함을 특징으로 하는 혈우병 A의 치료 또는 예방을 위한 약학 조성물.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86841086A | 1986-05-29 | 1986-05-29 | |
US93276786A | 1986-11-18 | 1986-11-18 | |
US932767 | 1986-11-18 | ||
US06/939,658 US5451521A (en) | 1986-05-29 | 1986-12-09 | Procoagulant proteins |
PCT/US1987/001299 WO1987007144A1 (en) | 1986-05-29 | 1987-05-29 | Novel procoagulant proteins |
US868410 | 1992-04-14 | ||
US939658 | 2010-11-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
KR880701105A true KR880701105A (ko) | 1988-07-25 |
Family
ID=27420451
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1019880700094A KR880701105A (ko) | 1986-05-29 | 1987-05-29 | 신규 응혈촉진 단백질 |
Country Status (8)
Country | Link |
---|---|
US (1) | US5451521A (ko) |
EP (1) | EP0270618A4 (ko) |
JP (1) | JPS63503357A (ko) |
KR (1) | KR880701105A (ko) |
AU (1) | AU609043B2 (ko) |
CA (1) | CA1341229C (ko) |
DK (1) | DK42588A (ko) |
WO (1) | WO1987007144A1 (ko) |
Families Citing this family (57)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR910006424B1 (ko) * | 1985-08-21 | 1991-08-24 | 인코텍스 비.브이 | 편성브리프(brief) 제조방법 |
US5198349A (en) * | 1986-01-03 | 1993-03-30 | Genetics Institute, Inc. | Method for producing factor VIII:C and analogs |
US5595886A (en) | 1986-01-27 | 1997-01-21 | Chiron Corporation | Protein complexes having Factor VIII:C activity and production thereof |
US5422260A (en) * | 1986-05-29 | 1995-06-06 | Genetics Institute, Inc. -Legal Affairs | Human factor VIII:c muteins |
US6060447A (en) * | 1987-05-19 | 2000-05-09 | Chiron Corporation | Protein complexes having Factor VIII:C activity and production thereof |
IE69026B1 (en) * | 1987-06-12 | 1996-08-07 | Immuno Ag | Novel proteins with factor VIII activity process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them |
EP0690126B1 (en) * | 1987-06-12 | 2001-11-28 | Baxter Aktiengesellschaft | Novel proteins with factor VIII activitiy: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them |
US6346513B1 (en) | 1987-06-12 | 2002-02-12 | Baxter Trading Gmbh | Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them |
DE3720246A1 (de) * | 1987-06-19 | 1988-12-29 | Behringwerke Ag | Faktor viii:c-aehnliches molekuel mit koagulationsaktivitaet |
FR2619314B1 (fr) * | 1987-08-11 | 1990-06-15 | Transgene Sa | Analogue du facteur viii, procede de preparation et composition pharmaceutique le contenant |
SE459586B (sv) * | 1987-09-14 | 1989-07-17 | Mta Szegedi Biolog Koezponti | Strukturgen som kodar foer autentiskt humant serum albumin och foerfarande foer dess framstaellning |
US5879907A (en) * | 1987-09-14 | 1999-03-09 | Skandigen Ab | Artificial gene coding for authentic human serum albumin, use thereof and method |
SE468050C (sv) * | 1991-03-15 | 1998-04-27 | Pharmacia & Upjohn Ab | Rekombinant derivat av human faktor VIII |
US5661008A (en) * | 1991-03-15 | 1997-08-26 | Kabi Pharmacia Ab | Recombinant human factor VIII derivatives |
US6376463B1 (en) * | 1992-04-07 | 2002-04-23 | Emory University | Modified factor VIII |
DK53792D0 (da) * | 1992-04-24 | 1992-04-24 | Novo Nordisk As | Fremgangsmaade til fremstilling af proteiner |
DK0615451T3 (da) | 1992-05-26 | 2006-04-24 | Immunex Corp | Hidtil ukendt cytokin der binder til CD30 |
US5563045A (en) | 1992-11-13 | 1996-10-08 | Genetics Institute, Inc. | Chimeric procoagulant proteins |
SE504074C2 (sv) * | 1993-07-05 | 1996-11-04 | Pharmacia Ab | Proteinberedning för subkutan, intramuskulär eller intradermal administrering |
DK128093D0 (da) * | 1993-11-12 | 1993-11-12 | Novo Nordisk As | Hidtil ukendte forbindelser |
ES2157326T3 (es) * | 1994-04-22 | 2001-08-16 | Sanquin Bloedvoorziening | Sistema para el tratamiento de anomalias en la cascada de coagulacion sanguinea. |
WO1997003195A1 (en) * | 1995-07-11 | 1997-01-30 | Chiron Corporation | Novel factor viii:c polypeptide analogs with altered protease sites |
AU6456096A (en) * | 1995-07-11 | 1997-02-10 | Chiron Corporation | Lysine 1689 factor viii:c polypeptide analogs |
EP1754718B1 (en) * | 1996-04-24 | 2011-03-23 | The Regents Of The University Of Michigan | Inactivation resistant factor VIII |
US20040092442A1 (en) * | 1996-04-24 | 2004-05-13 | University Of Michigan | Inactivation resistant factor VIII |
US8183344B2 (en) * | 1996-04-24 | 2012-05-22 | University Of Michigan | Inactivation resistant factor VIII |
ATE222925T1 (de) | 1998-03-12 | 2002-09-15 | Inst Genetics Llc | Verbessertes verfahren zur herstellung von faktor viii |
US7820796B2 (en) | 1998-03-12 | 2010-10-26 | Genetics Institute, Llc. | Methods for producing Factor VIII proteins |
US6221349B1 (en) | 1998-10-20 | 2001-04-24 | Avigen, Inc. | Adeno-associated vectors for expression of factor VIII by target cells |
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CA2349468C (en) | 1998-11-10 | 2013-07-09 | Baxter Aktiengesellschaft | Factor viii polypeptide having factor viii:c activity |
CA2404163C (en) * | 2000-03-22 | 2009-09-29 | Octagene Gmbh | Production of recombinant blood clotting factors in human cell lines |
IL156843A0 (en) * | 2001-02-05 | 2004-02-08 | Novo Nordisk Healthcare Ag | Combined use of factor vii polypeptides and factor viii polypeptides |
US7041635B2 (en) | 2003-01-28 | 2006-05-09 | In2Gen Co., Ltd. | Factor VIII polypeptide |
DK2345731T3 (en) | 2003-09-30 | 2016-01-25 | Univ Pennsylvania | Adeno-associated virus (AAV) groupings, sequences, vectors containing the same and uses thereof |
WO2006027111A1 (en) * | 2004-09-06 | 2006-03-16 | Zlb Behring Gmbh | Modified coagulation factor viii with enhanced stability |
CN107082806A (zh) | 2004-11-12 | 2017-08-22 | 拜尔健康护理有限责任公司 | Fviii的位点定向修饰 |
EP1707634A1 (en) | 2005-03-29 | 2006-10-04 | Octapharma AG | Method for isolation of recombinantly produced proteins |
WO2006103298A2 (en) * | 2005-04-01 | 2006-10-05 | Novo Nordisk Health Care Ag | Blood coagulation fviii analogues |
EP2359867B1 (en) | 2005-04-07 | 2014-10-08 | The Trustees of The University of Pennsylvania | Method of increasing the function of an AAV vector |
JP2008537680A (ja) * | 2005-04-14 | 2008-09-25 | ツェー・エス・エル・ベーリング・ゲー・エム・ベー・ハー | 安定性の増大された改変型凝固第viii因子およびその誘導体 |
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US20090203077A1 (en) * | 2006-06-30 | 2009-08-13 | The Regents Of The University Of Michigan | Method of producing factor viii proteins by recombinant methods |
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US9315825B2 (en) | 2010-03-29 | 2016-04-19 | The Trustees Of The University Of Pennsylvania | Pharmacologically induced transgene ablation system |
BR112012024934A2 (pt) | 2010-03-29 | 2016-12-06 | Univ Pennsylvania | sistemas de ablação de transgene induzida farmacologicamente |
DK2675902T3 (da) | 2011-02-17 | 2019-06-03 | Univ Pennsylvania | Sammensætninger og fremgangsmåder til at ændre vævsspecificitet og forbedre aav9-medieret genoverførsel |
CA2850579A1 (en) | 2011-10-18 | 2013-04-25 | Carsten Horn | Method for improving the stability of purified factor viii after reconstitution |
US10023628B2 (en) | 2012-07-06 | 2018-07-17 | Bioverativ Therapeutics Inc. | Cell line expressing single chain factor VIII polypeptides and uses thereof |
ES2680942T3 (es) * | 2013-03-15 | 2018-09-11 | Bayer Healthcare Llc | Variante de polipéptidos del factor VIII y procedimientos para su producción y utilización |
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 |
CN108093639B (zh) | 2015-04-16 | 2022-07-19 | 埃默里大学 | 用于肝脏中蛋白质表达的重组启动子和载体及其用途 |
US20170205149A1 (en) * | 2016-01-15 | 2017-07-20 | Hamilton Sundstrand Corporation | Heat exchanger channels |
CA3188420A1 (en) | 2020-08-07 | 2022-02-10 | Joseph Bauman | Vesicle targeting proteins and uses of same |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4518584A (en) * | 1983-04-15 | 1985-05-21 | Cetus Corporation | Human recombinant interleukin-2 muteins |
EP0218712B1 (en) * | 1985-04-12 | 1992-02-26 | Genetics Institute, Inc. | Novel procoagulant proteins |
KR910006424B1 (ko) * | 1985-08-21 | 1991-08-24 | 인코텍스 비.브이 | 편성브리프(brief) 제조방법 |
EP0253870B1 (en) * | 1986-01-03 | 1993-03-31 | Genetics Institute, Inc. | Method for producing factor viii:c-type proteins |
-
1986
- 1986-12-09 US US06/939,658 patent/US5451521A/en not_active Expired - Lifetime
-
1987
- 1987-05-28 CA CA000538233A patent/CA1341229C/en not_active Expired - Lifetime
- 1987-05-29 KR KR1019880700094A patent/KR880701105A/ko not_active Application Discontinuation
- 1987-05-29 AU AU74868/87A patent/AU609043B2/en not_active Expired - Fee Related
- 1987-05-29 EP EP19870903819 patent/EP0270618A4/en not_active Ceased
- 1987-05-29 WO PCT/US1987/001299 patent/WO1987007144A1/en not_active Application Discontinuation
- 1987-05-29 JP JP62503481A patent/JPS63503357A/ja active Pending
-
1988
- 1988-01-28 DK DK042588A patent/DK42588A/da not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
US5451521A (en) | 1995-09-19 |
EP0270618A4 (en) | 1989-02-16 |
EP0270618A1 (en) | 1988-06-15 |
AU609043B2 (en) | 1991-04-26 |
AU7486887A (en) | 1987-12-22 |
DK42588D0 (da) | 1988-01-28 |
CA1341229C (en) | 2001-05-15 |
WO1987007144A1 (en) | 1987-12-03 |
JPS63503357A (ja) | 1988-12-08 |
DK42588A (da) | 1988-01-28 |
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