HRP20200007T1 - Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba - Google Patents

Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba Download PDF

Info

Publication number
HRP20200007T1
HRP20200007T1 HRP20200007TT HRP20200007T HRP20200007T1 HR P20200007 T1 HRP20200007 T1 HR P20200007T1 HR P20200007T T HRP20200007T T HR P20200007TT HR P20200007 T HRP20200007 T HR P20200007T HR P20200007 T1 HRP20200007 T1 HR P20200007T1
Authority
HR
Croatia
Prior art keywords
fviii
constant region
protein
chimeric protein
xten
Prior art date
Application number
HRP20200007TT
Other languages
English (en)
Inventor
Ekta Seth Chhabra
Tongyao Liu
Pei-Yun Chang
Robert T. Peters
John KULMAN
Original Assignee
Bioverativ Therapeutics Inc.
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
Application filed by Bioverativ Therapeutics Inc. filed Critical Bioverativ Therapeutics Inc.
Publication of HRP20200007T1 publication Critical patent/HRP20200007T1/hr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • 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
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/36—Blood coagulation or fibrinolysis factors
    • A61K38/37—Factors VIII
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/55—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • 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
    • 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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/31—Fusion polypeptide fusions, other than Fc, for prolonged plasma life, e.g. albumin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/35—Fusion polypeptide containing a fusion for enhanced stability/folding during expression, e.g. fusions with chaperones or thioredoxin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/50—Fusion polypeptide containing protease site

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Diabetes (AREA)
  • Mycology (AREA)
  • Peptides Or Proteins (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Claims (15)

1. Kimerni protein koji sadrži (i) ulomak von Willebrandovog faktora (VWF) koji sadrži D' domenu i D3 domenu VWF, (ii) sekvencu polipeptida produljene dužine (XTEN), (iii) protein faktora VIII (FVIII), (iv) prvu Ig konstantnu regiju ili njezin dio, te (v) drugu Ig konstantnu regiju ili njezin dio, pri čemu su VWF ulomak i sekvenca XTEN vezani s proizvoljnom poveznicom, pri čemu sekvenca XTEN ili VWF ulomak su vezani na prvu Ig konstantnu regiju ili njezin dio, pri čemu je protein FVIII vezan na drugu Ig konstantnu regiju ili njezin dio, i pri čemu je prva Ig konstantna regija ili njezin dio povezana sa ili vezana na drugu Ig konstantnu regiju ili njezin dio putem kovalentne veze.
2. Kimerni protein prema patentnom zahtjevu 1, naznačen time što sadrži (i) pojedinačni polipeptidni lanac koji sadrži VWF ulomak, sekvencu XTEN, prvu Ig konstantnu regiju ili njezin dio, drugu Ig konstantnu regiju ili njezin dio i protein FVIII, ili (ii) prvi polipeptidni lanac ili drugi polipeptidni lanac, pri čemu prvi polipeptidni lanac sadrži VWF ulomak, sekvencu XTEN i prvu Ig konstantnu regiju ili njezin dio i drugi polipeptidni lanac sadrži protein FVIII i drugu Ig konstantnu regiju ili njezin dio.
3. Kimerni protein prema patentnom zahtjevu 1, naznačen time što ima formulu: (a) V-L2-X-L1-F1:FVIII-L3-F2; (b) V-L2-X-L1-F1:F2-L3-FVIII; (c) F1-L1-X-L2-V: FVIII-L3-F2; (d) F1-L1-X-L2-V:F2-L3-FVIII; (e) V-L2-X-LI-FI-L4-FVIII-L3-F2; (f) F2-L3-FVIII-L4-F1-L1-X-L2-V; (g) FVIII-L3-F2-L4-V-L2-X-L1-F1; ili (h) F1-L1-X-L2-V-L4-F2-L3-FVIII; pri čemu V je VWF ulomak; svaki od L1, L2, i L3 je proizvoljna poveznica; L4 je proizvoljna poveznica; FVIII je protein FVIII; X je sekvenca XTEN; F1 je prva konstantna regija imunoglobulina (Ig) ili njezin dio; F2 je druga Ig konstantna regija ili njezin dio; (-) je peptidna veza; i (:) je kovalentna veza.
4. Kimerni protein prema patentnom zahtjevu 1, naznačen time što ima formulu: (a) FVIII(X1)-L1-F1:V-L2-X2-L3-F2; (b) FVIII(X1)-L1-F1:F2-L3-X2-L2-V; (c) F1-L1-FVIII(X1):V-L2-X2-L3-F2; (d) F1-L1-FVIII(X1):F2-L3-X2-L2-V; (e) FVIII(X1)-L1-F1-L4-V-L2-X2-L3-F2; (f) FVIII(X1)-L1-F1-L4-F2-L3-X2-L2-V; (g) F1-L1-FVIII(X1)-L4-V-L2-X2-L3-F2; ili (h) F1-L1-FVIII(X1)-L4-F2-L3-X2-L2-V; pri čemu FVIII(X1) sadrži protein FVIII i XTEN sekvencu, pri čemu je sekvenca XTEN vezana na N-terminalni kraj ili C-terminalni kraj proteina FVIII ili se ubacuje neposredno nizvodno od jedne ili više aminokiselina ("jedno ili više mjesta umetanja") u proteinu FVIII; svaki od L1, L2, ili L3 je proizvoljna poveznica; L4 je poveznica; X2 je druga sekvenca XTEN; F1 je prva Ig konstantna regija ili njezin dio; F2 je druga Ig konstantna regija ili njezin dio; V je VWF ulomak; (-) je peptidna veza; i (:) je kovalentna veza.
5. Kimerni protein prema bilo kojem od patentnih zahtjeva 1-4, naznačen time što (a) prva Ig konstantna regija ili njezin dio je prva Fc regija; (b) druga Ig konstantna regija ili njezin dio je druga Fc regija; ili (c) oboje (a) i (b).
6. Kimerni protein prema patentnom zahtjevu 4 ili 5, naznačen time što su jedno ili više mjesta umetanja u protein FVIII odabrana iz skupine koja se sastoji od aminokiselinskih ostataka u Tablici 7, Tablici 8, Tablici 9 i Tablici 10.
7. Kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 6, naznačen time što protein FVIII sadrži B domenu ili njezin dio ili ne sadrži B domenu.
8. Kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 7, naznačen time što kimerni protein sadrži najmanje dva XTEN-a, najmanje tri XTEN-a, najmanje četiri XTEN-a, najmanje pet XTEN-ova, ili najmanje šest XTEN-ova.
9. Kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 8, naznačen time što je protein FVIII jednolančani FVIII.
10. Polinukleotid ili skup polinukleotida naznačen time što kodiraju kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 9.
11. Vektor naznačen time što sadrži polinukleotid ili skup polinukleotida prema zahtjevu 10 i jedan ili više promotora operativno vezan za polinukleotid ili skup polinukleotida.
12. Stanica domaćina naznačena time što sadrži polinukleotid ili skup polinukleotida prema zahtjevu 10 ili vektor prema zahtjevu 11.
13. Farmaceutski pripravak naznačen time što sadrži kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 9, polinukleotid ili skup polinukleotida iz patentnog zahtjeva 10, vektor prema zahtjevu 11, ili stanicu domaćina prema zahtjevu 12, te farmaceutski prihvatljiv nosač.
14. Kimerni protein prema bilo kojem od patentnih zahtjeva 1 do 9, polinukleotid prema zahtjevu 10, vektor prema zahtjevu 11, stanicu domaćina prema zahtjevu 12, ili pripravak prema zahtjevu 13 naznačen time što je za upotrebu u liječenju bolesti krvarenja ili poremećaja krvarenja kod subjekta kojem je potrebno.
15. Postupak za proizvodnju kimernog proteina, naznačen time što obuhvaća transfekciju jedne ili više stanica domaćina s polinukleotidom ili skupom polinukleotida prema zahtjevu 10 ili vektorom prema zahtjevu 11 i eksprimiranje kimernog proteina u stanici domaćinu.
HRP20200007TT 2012-07-11 2020-01-03 Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba HRP20200007T1 (hr)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US201261670401P 2012-07-11 2012-07-11
US201361759819P 2013-02-01 2013-02-01
US201361801544P 2013-03-15 2013-03-15
US201361801504P 2013-03-15 2013-03-15
US201361827158P 2013-05-24 2013-05-24
US201361840811P 2013-06-28 2013-06-28
PCT/US2013/049989 WO2014011819A2 (en) 2012-07-11 2013-07-10 Factor viii complex with xten and von willebrand factor protein, and uses thereof
EP13816031.2A EP2882450B1 (en) 2012-07-11 2013-07-10 Factor viii complex with xten and von willebrand factor protein, and uses thereof

Publications (1)

Publication Number Publication Date
HRP20200007T1 true HRP20200007T1 (hr) 2020-03-20

Family

ID=49916682

Family Applications (1)

Application Number Title Priority Date Filing Date
HRP20200007TT HRP20200007T1 (hr) 2012-07-11 2020-01-03 Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba

Country Status (31)

Country Link
US (3) US10138291B2 (hr)
EP (3) EP2882450B1 (hr)
JP (5) JP6603128B2 (hr)
KR (2) KR102329315B1 (hr)
CN (2) CN110054699A (hr)
AR (1) AR091735A1 (hr)
AU (4) AU2013290173B2 (hr)
BR (1) BR112015000267B1 (hr)
CA (1) CA2878679A1 (hr)
CL (1) CL2015000060A1 (hr)
CO (1) CO7170123A2 (hr)
CY (1) CY1122729T1 (hr)
DK (1) DK2882450T3 (hr)
EA (2) EA201792485A3 (hr)
ES (1) ES2770501T3 (hr)
HK (1) HK1211228A1 (hr)
HR (1) HRP20200007T1 (hr)
HU (1) HUE047088T2 (hr)
IL (1) IL236412B (hr)
LT (1) LT2882450T (hr)
MX (1) MX2015000397A (hr)
NZ (1) NZ703366A (hr)
PH (1) PH12015500039A1 (hr)
PL (1) PL2882450T3 (hr)
PT (1) PT2882450T (hr)
RS (1) RS59876B1 (hr)
SG (3) SG10201701037WA (hr)
SI (1) SI2882450T1 (hr)
TW (1) TWI667258B (hr)
UA (1) UA116632C2 (hr)
WO (1) WO2014011819A2 (hr)

Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8716448B2 (en) 2009-02-03 2014-05-06 Amunix Operating Inc. Coagulation factor VII compositions and methods of making and using same
PT3178835T (pt) * 2009-02-03 2019-06-19 Amunix Pharmaceuticals Inc Polipéptidos recombinantes estendidos e composições que compreendem os mesmos
EA028309B1 (ru) * 2012-01-12 2017-11-30 Байоджен Эмэй Инк. Полипептиды химерного фактора viii и их применение
DK2822577T3 (en) 2012-02-15 2019-04-01 Bioverativ Therapeutics Inc RECOMBINANT FACTOR VIII PROTEINS
ES2935489T3 (es) 2012-02-15 2023-03-07 Bioverativ Therapeutics Inc Composiciones de factor VIII y métodos de preparación y uso de las mismas
WO2014008480A2 (en) 2012-07-06 2014-01-09 Biogen Idec Ma Inc. Cell line expressing single chain factor viii polypeptides and uses thereof
PL2882450T3 (pl) * 2012-07-11 2020-06-29 Bioverativ Therapeutics Inc. Kompleks czynnika viii z xten i białkiem czynnika von willebranda oraz jego zastosowania
EP4223772A3 (en) 2013-02-15 2023-10-18 Bioverativ Therapeutics Inc. Optimized factor viii gene
TWI788044B (zh) 2013-03-15 2022-12-21 美商百歐維拉提夫治療公司 因子ｉｘ多肽調配物
ES2657291T3 (es) * 2013-04-22 2018-03-02 Csl Ltd. Un complejo covalente de factor de von Willebrand y factor VIII asociado por un puente disulfuro
IL297611A (en) * 2013-06-28 2022-12-01 Bioverativ Therapeutics Inc Binding of thrombin that degrades with castane and uses thereof
TW202003554A (zh) 2013-08-14 2020-01-16 美商百歐維拉提夫治療公司 因子ｖｉｉｉ－ｘｔｅｎ融合物及其用途
EP4176894B1 (en) * 2014-01-10 2024-02-28 Bioverativ Therapeutics Inc. Factor viii chimeric proteins and uses thereof
JP6704420B2 (ja) * 2015-03-06 2020-06-03 ツェー・エス・エル・ベーリング・レングナウ・アクチエンゲゼルシャフト フォンヴィレブランド因子の半減期を改善するための化合物
CA2986626A1 (en) * 2015-05-22 2016-12-01 Csl Behring Recombinant Facility Ag Truncated von willebrand factor polypeptides for treating hemophilia
IL257231B (en) 2015-08-03 2022-09-01 Bioverativ Therapeutics Inc Factor ix fusion proteins and methods for their preparation and use
CN107921103A (zh) 2015-08-12 2018-04-17 细胞机械股份有限公司 涉及长半衰期凝血复合物的方法和组合物
EP3341009A4 (en) * 2015-08-28 2019-05-01 Amunix Pharmaceuticals, Inc. CHIMERIC POLYPEPTIDE ASSEMBLY AND METHODS OF PREPARING AND USING THE SAME
US10806774B2 (en) 2016-01-07 2020-10-20 CSL Behring Lengnau AG Mutated truncated von Willebrand Factor
PT3411478T (pt) 2016-02-01 2022-09-13 Bioverativ Therapeutics Inc Genes do fator viii otimizados
EP3458085B1 (en) 2016-05-20 2022-12-07 Octapharma AG Glycosylated vwf fusion proteins with improved pharmacokinetics
WO2017222337A1 (ko) * 2016-06-24 2017-12-28 재단법인 목암생명과학연구소 Fviii 및 vwf 인자를 포함하는 키메라 단백질 및 그 용도
CN106279437B (zh) * 2016-08-19 2017-10-31 安源医药科技（上海）有限公司 高糖基化人凝血因子viii融合蛋白及其制备方法与用途
CN106317226B (zh) 2016-08-19 2017-09-05 安源医药科技（上海）有限公司 用于构建融合蛋白的连接肽
US10738338B2 (en) 2016-10-18 2020-08-11 The Research Foundation for the State University Method and composition for biocatalytic protein-oligonucleotide conjugation and protein-oligonucleotide conjugate
TW201828975A (zh) 2016-11-11 2018-08-16 瑞士商Ｃｓｌ貝林重組技能公司 用於治療血友病之截短型類血友病因子（ｖｏｎ Ｗｉｌｌｅｂｒａｎｄ ｆａｃｔｏｒ）多肽類
CA3043397A1 (en) 2016-11-11 2018-05-17 CSL Behring Lengnau AG Truncated von willebrand factor polypeptides for extravascular administration in the treatment or prophylaxis of a blood coagulation disorder
US20200085915A1 (en) 2016-12-02 2020-03-19 Bioverativ Therapeutics Inc. Methods of inducing immune tolerance to clotting factors
CA3045660A1 (en) 2016-12-02 2018-06-07 Bioverativ Therapeutics Inc. Methods of treating hemophilic arthropathy using chimeric clotting factors
EA201991768A1 (ru) 2017-01-31 2020-01-22 Байоверетив Терапьютикс Инк. Слитые белки на основе фактора ix и способы их получения и пути применения
GB201707139D0 (en) * 2017-05-04 2017-06-21 Imp Innovations Ltd Polypeptides
CA3072334A1 (en) 2017-08-09 2019-02-14 Bioverativ Therapeutics Inc. Nucleic acid molecules and uses thereof
US20200385469A1 (en) * 2017-12-21 2020-12-10 Amunix Pharmaceuticals, Inc. Release segments and binding compositions comprising same
CN112512555A (zh) * 2018-05-18 2021-03-16 比奥维拉迪维治疗股份有限公司 治疗血友病a的方法
MX2021001599A (es) 2018-08-09 2021-07-02 Bioverativ Therapeutics Inc Moleculas de acido nucleico y sus usos para la terapia genica no viral.
US20200219590A1 (en) 2018-11-15 2020-07-09 Quantum-Si Incorporated Methods and compositions for protein sequencing
WO2020118069A2 (en) 2018-12-06 2020-06-11 Bioverativ Therapeutics Inc. Use of lentiviral vectors expressing factor ix
US10654911B1 (en) 2019-04-02 2020-05-19 Beijing Neoletix Biological Technology Co., Ltd. Vector co-expressing truncated von Willebrand factor and factor VIII
CA3144630A1 (en) * 2019-06-19 2020-12-24 Bioverativ Therapeutics Inc. Methods and compositions for treating hemophilia and low bone mineral density
CN112175088B (zh) * 2019-07-02 2023-03-28 江苏晟斯生物制药有限公司 改进的fix融合蛋白、缀合物及其应用
WO2021043127A1 (zh) * 2019-09-02 2021-03-11 甘李药业股份有限公司 嵌合蛋白
US20230287040A1 (en) 2019-11-13 2023-09-14 Amunix Pharmaceuticals, Inc. Barcoded xten polypeptides and compositions thereof, and methods for making and using the same
CN115260313B (zh) 2019-12-31 2023-07-18 北京质肽生物医药科技有限公司 Glp-1和gdf15的融合蛋白以及其缀合物
WO2021139744A1 (en) 2020-01-11 2021-07-15 Beijing Ql Biopharmaceutical Co., Ltd. Conjugates of fusion proteins of glp-1 and fgf21
CN116134046A (zh) * 2020-05-20 2023-05-16 宽腾矽公司 用于蛋白质测序的方法及组合物
CA3193453A1 (en) 2020-09-30 2022-04-07 Beijing Ql Biopharmaceutical Co., Ltd. Polypeptide conjugates and methods of uses
BR112023026782A2 (pt) 2021-06-23 2024-03-12 Bioverativ Therapeutics Inc Formulações de proteínas quiméricas de fator viii e usos das mesmas
CN113862301A (zh) * 2021-08-25 2021-12-31 上海交通大学医学院附属瑞金医院 一种vwf前肽表达载体及其制备方法和应用

Family Cites Families (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
US4215051A (en) 1979-08-29 1980-07-29 Standard Oil Company (Indiana) Formation, purification and recovery of phthalic anhydride
US4713339A (en) 1983-01-19 1987-12-15 Genentech, Inc. Polycistronic expression vector construction
US4757006A (en) 1983-10-28 1988-07-12 Genetics Institute, Inc. Human factor VIII:C gene and recombinant methods for production
US4965199A (en) 1984-04-20 1990-10-23 Genentech, Inc. Preparation of functional human factor VIII in mammalian cells using methotrexate based selection
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4965188A (en) 1986-08-22 1990-10-23 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences using a thermostable enzyme
US4683195A (en) 1986-01-30 1987-07-28 Cetus Corporation Process for amplifying, detecting, and/or-cloning nucleic acid sequences
US5981216A (en) 1985-04-01 1999-11-09 Alusuisse Holdings A.G. Transformed myeloma cell-line and a process for the expression of a gene coding for a eukaryotic polypeptide employing same
ES8801674A1 (es) 1985-04-12 1988-02-16 Genetics Inst Un procedimiento para la preparacion de una proteina que presenta actividad procoagulante.
KR910006424B1 (ko) 1985-08-21 1991-08-24 인코텍스 비.브이 편성브리프(brief) 제조방법
JP2525022B2 (ja) 1986-01-03 1996-08-14 ジェネティックス・インスチチュ−ト・インコ−ポレ−テッド ▲ＶＩＩＩ▼：ｃ因子型タンパク質の改良生産方法
US5595886A (en) 1986-01-27 1997-01-21 Chiron Corporation Protein complexes having Factor VIII:C activity and production thereof
US4800159A (en) 1986-02-07 1989-01-24 Cetus Corporation Process for amplifying, detecting, and/or cloning nucleic acid sequences
US5610278A (en) 1986-06-24 1997-03-11 Novo Nordisk A/S Process for producing a coagulation active complex of factor VIII fragments
US4912040A (en) 1986-11-14 1990-03-27 Genetics Institute, Inc. Eucaryotic expression system
JP3101690B2 (ja) 1987-03-18 2000-10-23 エス・ビィ・２・インコーポレイテッド 変性抗体の、または変性抗体に関する改良
CA1331157C (en) 1987-04-06 1994-08-02 Randal J. Kaufman Method for producing factor viii:c-type proteins
US6060447A (en) 1987-05-19 2000-05-09 Chiron Corporation Protein complexes having Factor VIII:C activity and production thereof
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
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
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
US4994371A (en) 1987-08-28 1991-02-19 Davie Earl W DNA preparation of Christmas factor and use of DNA sequences
US6780613B1 (en) 1988-10-28 2004-08-24 Genentech, Inc. Growth hormone variants
US5004803A (en) 1988-11-14 1991-04-02 Genetics Institute, Inc. Production of procoagulant proteins
SE465222C5 (sv) 1989-12-15 1998-02-10 Pharmacia & Upjohn Ab Ett rekombinant, humant faktor VIII-derivat och förfarande för dess framställning
US5846951A (en) 1991-06-06 1998-12-08 The School Of Pharmacy, University Of London Pharmaceutical compositions
MX9204374A (es) 1991-07-25 1993-03-01 Idec Pharma Corp Anticuerpo recombinante y metodo para su produccion.
US5859204A (en) 1992-04-07 1999-01-12 Emory University Modified factor VIII
US6376463B1 (en) 1992-04-07 2002-04-23 Emory University Modified factor VIII
US5364771A (en) 1992-04-07 1994-11-15 Emory University Hybrid human/porcine factor VIII
US6037452A (en) 1992-04-10 2000-03-14 Alpha Therapeutic Corporation Poly(alkylene oxide)-Factor VIII or Factor IX conjugate
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
US5643575A (en) 1993-10-27 1997-07-01 Enzon, Inc. Non-antigenic branched polymer conjugates
GB9422383D0 (en) 1994-11-05 1995-01-04 Wellcome Found Antibodies
US6818439B1 (en) 1994-12-30 2004-11-16 Chiron Corporation Methods for administration of recombinant gene delivery vehicles for treatment of hemophilia and other disorders
US6086875A (en) 1995-01-17 2000-07-11 The Brigham And Women's Hospital, Inc. Receptor specific transepithelial transport of immunogens
US6485726B1 (en) 1995-01-17 2002-11-26 The Brigham And Women's Hospital, Inc. Receptor specific transepithelial transport of therapeutics
US6030613A (en) 1995-01-17 2000-02-29 The Brigham And Women's Hospital, Inc. Receptor specific transepithelial transport of therapeutics
US5739277A (en) 1995-04-14 1998-04-14 Genentech Inc. Altered polypeptides with increased half-life
US6096871A (en) 1995-04-14 2000-08-01 Genentech, Inc. Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life
US6121022A (en) 1995-04-14 2000-09-19 Genentech, Inc. Altered polypeptides with increased half-life
US5869046A (en) 1995-04-14 1999-02-09 Genentech, Inc. Altered polypeptides with increased half-life
SE9503380D0 (sv) 1995-09-29 1995-09-29 Pharmacia Ab Protein derivatives
US6458563B1 (en) 1996-06-26 2002-10-01 Emory University Modified factor VIII
JP2001506967A (ja) 1996-08-02 2001-05-29 ブリストル―マイヤーズ・スクイブ・カンパニー 治療およびインビボ診断における免疫グロブリンの使用の結果としての免疫グロブリン誘発毒性の抑制方法
WO1998023289A1 (en) 1996-11-27 1998-06-04 The General Hospital Corporation MODULATION OF IgG BINDING TO FcRn
US6277375B1 (en) 1997-03-03 2001-08-21 Board Of Regents, The University Of Texas System Immunoglobulin-like domains with increased half-lives
CA2225189C (en) 1997-03-06 2010-05-25 Queen's University At Kingston Canine factor viii gene, protein and methods of use
GB9722131D0 (en) 1997-10-20 1997-12-17 Medical Res Council Method
US6194551B1 (en) 1998-04-02 2001-02-27 Genentech, Inc. Polypeptide variants
EP1068241B1 (en) 1998-04-02 2007-10-10 Genentech, Inc. Antibody variants and fragments thereof
US6242195B1 (en) 1998-04-02 2001-06-05 Genentech, Inc. Methods for determining binding of an analyte to a receptor
US6528624B1 (en) 1998-04-02 2003-03-04 Genentech, Inc. Polypeptide variants
GB9809951D0 (en) 1998-05-08 1998-07-08 Univ Cambridge Tech Binding molecules
EP1105427A2 (en) 1998-08-17 2001-06-13 Abgenix, Inc. Generation of modified molecules with increased serum half-lives
EP1006183A1 (en) 1998-12-03 2000-06-07 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Recombinant soluble Fc receptors
US6737056B1 (en) 1999-01-15 2004-05-18 Genentech, Inc. Polypeptide variants with altered effector function
PL209786B1 (pl) 1999-01-15 2011-10-31 Genentech Inc Przeciwciało zawierające wariant regionu Fc ludzkiej IgG1, przeciwciało wiążące czynnik wzrostu śródbłonka naczyń oraz immunoadhezyna
US7829085B2 (en) 1999-07-14 2010-11-09 Life Sciences Research Partners Vzw Methods of treating hemostasis disorders using antibodies binding the C1 domain of factor VIII
CA2405563A1 (en) 2000-04-12 2001-10-25 Human Genome Sciences, Inc. Albumin fusion proteins
WO2001087922A2 (en) 2000-05-16 2001-11-22 Lipoxen Technologies Limited Derivatisation of proteins in aqueous solution
GB0029407D0 (en) 2000-12-01 2001-01-17 Affitech As Product
EP2357187A1 (en) 2000-12-12 2011-08-17 MedImmune, LLC Molecules with extended half-lives, compositions and uses thereof
EP1377306A1 (en) 2001-03-09 2004-01-07 Dyax Corp. Serum albumin binding moieties
US20080194481A1 (en) 2001-12-21 2008-08-14 Human Genome Sciences, Inc. Albumin Fusion Proteins
KR101271635B1 (ko) 2001-12-21 2013-06-12 휴먼 게놈 사이언시즈, 인코포레이티드 알부민 융합 단백질
ES2500918T3 (es) 2001-12-21 2014-10-01 Human Genome Sciences, Inc. Proteínas de fusión de albúmina e interferón beta
US20040002587A1 (en) 2002-02-20 2004-01-01 Watkins Jeffry D. Fc region variants
US7317091B2 (en) 2002-03-01 2008-01-08 Xencor, Inc. Optimized Fc variants
US20040018557A1 (en) 2002-03-01 2004-01-29 Immunomedics, Inc. Bispecific antibody point mutations for enhancing rate of clearance
US20040132101A1 (en) 2002-09-27 2004-07-08 Xencor Optimized Fc variants and methods for their generation
AU2002316574B2 (en) 2002-03-15 2008-05-01 Brandeis University Central airway administration for systemic delivery of therapeutics
EP1534335B9 (en) 2002-08-14 2016-01-13 Macrogenics, Inc. Fcgammariib-specific antibodies and methods of use thereof
AU2003275103A1 (en) 2002-09-17 2004-04-08 Diffusion Science, Inc. Electrochemical generation, storage and reaction of hydrogen and oxygen using gas permeable catalyst-coated hollow microspheres
BRPI0314814C1 (pt) 2002-09-27 2021-07-27 Xencor Inc anticorpo compreendendo uma variante de fc
PT1562972E (pt) 2002-10-15 2010-11-10 Facet Biotech Corp Alteração de afinidades de ligação ao fcrn ou semi-vidas séricas de anticorpos por mutagénese
GB2395337B (en) 2002-11-14 2005-12-28 Gary Michael Wilson Warning Unit
US7355008B2 (en) 2003-01-09 2008-04-08 Macrogenics, Inc. Identification and engineering of antibodies with variant Fc regions and methods of using same
US7041635B2 (en) 2003-01-28 2006-05-09 In2Gen Co., Ltd. Factor VIII polypeptide
CN1767857A (zh) 2003-02-26 2006-05-03 尼克塔治疗亚拉巴马公司 聚合物－因子ⅷ部分共轭物
KR100851263B1 (ko) 2003-02-28 2008-08-08 가부시키가이샤 구라레 경화성 수지 조성물
US8388955B2 (en) 2003-03-03 2013-03-05 Xencor, Inc. Fc variants
US20090010920A1 (en) 2003-03-03 2009-01-08 Xencor, Inc. Fc Variants Having Decreased Affinity for FcyRIIb
EP2298347B1 (en) 2003-05-06 2015-09-30 Biogen Hemophilia Inc. Clotting factor chimeric proteins for treatment of a hemostatic disorder
US7348004B2 (en) 2003-05-06 2008-03-25 Syntonix Pharmaceuticals, Inc. Immunoglobulin chimeric monomer-dimer hybrids
TWI353991B (en) 2003-05-06 2011-12-11 Syntonix Pharmaceuticals Inc Immunoglobulin chimeric monomer-dimer hybrids
WO2005016949A2 (en) 2003-08-12 2005-02-24 Lipoxen Technologies Limited Sialic acid derivatives
GB0324368D0 (en) 2003-10-17 2003-11-19 Univ Cambridge Tech Polypeptides including modified constant regions
US7211559B2 (en) 2003-10-31 2007-05-01 University Of Maryland, Baltimore Factor VIII compositions and methods
WO2005047327A2 (en) 2003-11-12 2005-05-26 Biogen Idec Ma Inc. NEONATAL Fc RECEPTOR (FcRn)-BINDING POLYPEPTIDE VARIANTS, DIMERIC Fc BINDING PROTEINS AND METHODS RELATED THERETO
WO2005077981A2 (en) 2003-12-22 2005-08-25 Xencor, Inc. Fc POLYPEPTIDES WITH NOVEL Fc LIGAND BINDING SITES
EP2154157A3 (en) 2004-01-12 2010-04-28 Applied Molecular Evolution Inc. FC region variants
EP2053062A1 (en) 2004-03-24 2009-04-29 Xencor, Inc. Immunoglobin variants outside the Fc region
WO2005123780A2 (en) 2004-04-09 2005-12-29 Protein Design Labs, Inc. Alteration of fcrn binding affinities or serum half-lives of antibodies by mutagenesis
WO2006085967A2 (en) 2004-07-09 2006-08-17 Xencor, Inc. OPTIMIZED ANTI-CD20 MONOCONAL ANTIBODIES HAVING Fc VARIANTS
KR100863776B1 (ko) 2004-07-15 2008-10-16 젠코어 인코포레이티드 최적화된 Ｆｃ 변이체
US7566701B2 (en) 2004-09-07 2009-07-28 Archemix Corp. Aptamers to von Willebrand Factor and their use as thrombotic disease therapeutics
WO2006047350A2 (en) 2004-10-21 2006-05-04 Xencor, Inc. IgG IMMUNOGLOBULIN VARIANTS WITH OPTIMIZED EFFECTOR FUNCTION
US7884075B2 (en) * 2004-12-27 2011-02-08 Baxter International Inc. Polymer-factor VIII-von Willebrand factor-conjugates
KR20080071119A (ko) 2005-08-12 2008-08-01 휴먼 게놈 사이언시즈, 인코포레이티드 알부민 융합 단백질
US7846445B2 (en) * 2005-09-27 2010-12-07 Amunix Operating, Inc. Methods for production of unstructured recombinant polymers and uses thereof
WO2007103515A2 (en) 2006-03-06 2007-09-13 Amunix, Inc. Unstructured recombinant polymers and uses thereof
ES2889920T3 (es) 2006-06-14 2022-01-14 Csl Behring Gmbh Proteínas de fusión escindibles proteolíticamente con alta actividad específica molar
US20080280818A1 (en) 2006-07-21 2008-11-13 Neose Technologies, Inc. Glycosylation of peptides via o-linked glycosylation sequences
EP2068905A4 (en) 2006-09-14 2009-12-30 Human Genome Sciences Inc ALBUM INFUSION PROTEINS
US8969532B2 (en) 2006-10-03 2015-03-03 Novo Nordisk A/S Methods for the purification of polypeptide conjugates comprising polyalkylene oxide using hydrophobic interaction chromatography
EP2068907B1 (en) 2006-10-04 2017-11-29 Novo Nordisk A/S Glycerol linked pegylated sugars and glycopeptides
EP1935430A1 (en) 2006-12-22 2008-06-25 CSL Behring GmbH Modified coagulation factors with prolonged in vivo half-life
KR101542752B1 (ko) * 2006-12-22 2015-08-10 체에스엘 베링 게엠베하 연장된 생체내 반감기를 갖는 변형된 응고 인자
ES2362386T3 (es) 2007-06-21 2011-07-04 Technische Universität München Proteínas activas biológicas que tienen estabilidad aumentada in vivo y/o in vitro.
EP2185701A4 (en) 2007-08-15 2011-03-02 Amunix Operating Inc COMPOSITIONS AND METHODS FOR ENHANCING THE PRODUCTION OF RECOMBINANT POLYPEPTIDES
AU2008319183B2 (en) 2007-11-01 2014-09-04 University Of Rochester Recombinant factor VIII having increased stability
US8173597B2 (en) 2007-11-09 2012-05-08 Baxter International Inc. Modified recombinant factor VIII and von Willebrand factor and methods of use
SG187410A1 (en) 2007-12-28 2013-02-28 Baxter Int Recombinant vwf formulations
RU2528855C2 (ru) 2008-06-24 2014-09-20 Цсл Беринг Гмбх Модифицированный фактор виллебранда с удлиненным полупериодом существования in vivo, его применения и способы получения
JP2012510060A (ja) 2008-11-24 2012-04-26 バイエル・ヘルスケア・エルエルシー シリカをベースとする活性化部分トロンボプラスチン時間アッセイにおけるｐｅｇ化血液凝固因子の活性の測定方法
PT3178835T (pt) 2009-02-03 2019-06-19 Amunix Pharmaceuticals Inc Polipéptidos recombinantes estendidos e composições que compreendem os mesmos
US8680050B2 (en) 2009-02-03 2014-03-25 Amunix Operating Inc. Growth hormone polypeptides fused to extended recombinant polypeptides and methods of making and using same
US8703717B2 (en) 2009-02-03 2014-04-22 Amunix Operating Inc. Growth hormone polypeptides and methods of making and using same
US8716448B2 (en) 2009-02-03 2014-05-06 Amunix Operating Inc. Coagulation factor VII compositions and methods of making and using same
EP2416799B1 (en) 2009-04-10 2017-11-01 Tufts Medical Center, Inc. Par-1 activation by metalloproteinase-1 (mmp-1)
WO2010144508A1 (en) 2009-06-08 2010-12-16 Amunix Operating Inc. Glucose-regulating polypeptides and methods of making and using same
NO2440241T3 (hr) 2009-06-08 2018-01-06
EP2467166A2 (en) 2009-08-20 2012-06-27 CSL Behring GmbH Albumin fused coagulation factors for non-intravenous administration in the therapy and prophylactic treatment of bleeding disorders
WO2011028344A2 (en) 2009-08-25 2011-03-10 Amunix Operating Inc. Interleukin-1 receptor antagonist compositions and methods of making and using same
US8759293B2 (en) * 2009-11-13 2014-06-24 Grifols Therapeutics Inc. von Willebrand factor (vWF)-containing preparations, and methods, kits, and uses related thereto
CA3121739A1 (en) * 2009-12-06 2011-06-09 Bioverativ Therapeutics Inc. Factor viii-fc chimeric and hybrid polypeptides, and methods of use thereof
US20130040888A1 (en) 2010-02-16 2013-02-14 Novo Nordisk A/S Factor VIII Molecules With Reduced VWF Binding
EP2536754A1 (en) 2010-02-16 2012-12-26 Novo Nordisk A/S Factor viii fusion protein
ES2600463T3 (es) 2010-05-20 2017-02-09 Allergan, Inc. Toxinas clostridiales degradables
TW201217526A (en) 2010-07-09 2012-05-01 Biogen Idec Hemophilia Inc Chimeric clotting factors
US9611310B2 (en) 2010-07-09 2017-04-04 Bioverativ Therapeutics Inc. Systems for factor VIII processing and methods thereof
US20130017997A1 (en) 2010-08-19 2013-01-17 Amunix Operating Inc. Factor VIII Compositions and Methods of Making and Using Same
EA028309B1 (ru) 2012-01-12 2017-11-30 Байоджен Эмэй Инк. Полипептиды химерного фактора viii и их применение
ES2935489T3 (es) 2012-02-15 2023-03-07 Bioverativ Therapeutics Inc Composiciones de factor VIII y métodos de preparación y uso de las mismas
DK2822577T3 (en) 2012-02-15 2019-04-01 Bioverativ Therapeutics Inc RECOMBINANT FACTOR VIII PROTEINS
PL2882450T3 (pl) 2012-07-11 2020-06-29 Bioverativ Therapeutics Inc. Kompleks czynnika viii z xten i białkiem czynnika von willebranda oraz jego zastosowania
WO2014210547A1 (en) 2013-06-28 2014-12-31 Biogen Idec Ma Inc. Thrombin cleavable linker
IL297611A (en) 2013-06-28 2022-12-01 Bioverativ Therapeutics Inc Binding of thrombin that degrades with castane and uses thereof
EP4176894B1 (en) 2014-01-10 2024-02-28 Bioverativ Therapeutics Inc. Factor viii chimeric proteins and uses thereof
CN112512555A (zh) * 2018-05-18 2021-03-16 比奥维拉迪维治疗股份有限公司 治疗血友病a的方法

Also Published As

Publication number Publication date
US10138291B2 (en) 2018-11-27
LT2882450T (lt) 2020-03-25
SG10201913893XA (en) 2020-03-30
US20150266943A1 (en) 2015-09-24
AU2018203206B2 (en) 2020-08-06
BR112015000267A2 (pt) 2018-03-06
AU2018203206A1 (en) 2018-05-24
UA116632C2 (uk) 2018-04-25
MX2015000397A (es) 2015-11-23
CN110054699A (zh) 2019-07-26
CA2878679A1 (en) 2014-01-16
JP2022000471A (ja) 2022-01-04
TW201414749A (zh) 2014-04-16
JP2015527882A (ja) 2015-09-24
HK1211228A1 (en) 2016-05-20
IL236412B (en) 2020-10-29
PH12015500039A1 (en) 2015-03-16
AU2022252703A1 (en) 2022-11-10
DK2882450T3 (da) 2020-02-24
AU2013290173B2 (en) 2018-02-15
PL2882450T3 (pl) 2020-06-29
RS59876B1 (sr) 2020-03-31
EP2882450B1 (en) 2019-11-27
EP2882450A4 (en) 2016-06-22
SI2882450T1 (sl) 2020-02-28
US20190169267A1 (en) 2019-06-06
AU2020264355A1 (en) 2020-12-03
KR20210143931A (ko) 2021-11-29
EA201590198A1 (ru) 2015-06-30
JP2020078352A (ja) 2020-05-28
US20220056108A1 (en) 2022-02-24
SG10201701037WA (en) 2017-03-30
ES2770501T3 (es) 2020-07-01
KR102403545B1 (ko) 2022-05-30
IL236412A0 (en) 2015-02-26
AU2013290173A1 (en) 2015-01-22
WO2014011819A2 (en) 2014-01-16
CY1122729T1 (el) 2021-03-12
EP3674410A1 (en) 2020-07-01
KR102329315B1 (ko) 2021-11-19
KR20150036510A (ko) 2015-04-07
JP2023166024A (ja) 2023-11-17
US11091534B2 (en) 2021-08-17
EP4269431A1 (en) 2023-11-01
BR112015000267B1 (pt) 2023-01-24
TWI667258B (zh) 2019-08-01
CL2015000060A1 (es) 2015-08-28
JP7022165B2 (ja) 2022-02-17
NZ703366A (en) 2018-03-23
EP2882450A2 (en) 2015-06-17
HUE047088T2 (hu) 2020-04-28
JP6603128B2 (ja) 2019-11-06
AR091735A1 (es) 2015-02-25
EA029685B1 (ru) 2018-04-30
EA201792485A2 (ru) 2018-08-31
CO7170123A2 (es) 2015-01-28
WO2014011819A3 (en) 2014-03-06
SG11201500045RA (en) 2015-02-27
JP2018102323A (ja) 2018-07-05
CN104661674A (zh) 2015-05-27
PT2882450T (pt) 2020-02-19
EA201792485A3 (ru) 2019-03-29

Similar Documents

Publication Publication Date Title
HRP20200007T1 (hr) Kompleks proteina faktora viii s xten i von willebrandovim faktorom, te njegova uporaba
HRP20192314T1 (hr) Pripravci faktora viii i postupci pripreme i njihove uporabe
HRP20191920T1 (hr) Kimerni polipeptidi faktora viii i njihova uporaba
HRP20220960T1 (hr) Kimerni proteini faktora viii i njihova upotreba
HRP20190799T1 (hr) Imunocitokini na bazi il-15 i sushi domene il-15r alfa
HRP20150664T1 (hr) Antikancerogeni fuzijski protein
HRP20171608T1 (hr) Protutijela koja vežu albumin i njihovi vezujući fragmenti
HRP20210411T1 (hr) Jednoručni receptori fuzijskih proteina tipa i i tipa ii i njihove uporabe
HRP20161608T1 (hr) Modificirani tuberkulozni antigeni
UY31123A1 (es) Proteinas de fusion natriureticas
HRP20200871T1 (hr) Izmjenjeni rsv f proteini i postupci njihove uporabe
HRP20190472T4 (hr) Klaudin-6 specifični imunoreceptori i t-stanični epitopi
CA2863944A1 (en) Fusion proteins comprising immunoglobulin constant domain-derived scaffolds
HRP20221139T1 (hr) Stabilizirane formulacije koje sadrže antitijela protiv interleukin-6 receptora (il-6r)
PE20190920A1 (es) Anticuerpos modificados de union a fcrn humano y metodos de utilizacion
HRP20220147T1 (hr) Pripravci i postupci povezani s multimodalnim terapijskim staničnim sustavima za indikacije raka
HRP20200085T1 (hr) Topljivi cd33 za liječenje mijelodisplastičnih sindroma (mds)
JP2013527765A5 (hr)
NZ630848A (en) Fusion polypeptides comprising an active protein linked to a mucin-domain polypeptide
CL2013003634A1 (es) Complejo que comprende una proteina de fusion que comprende, un peptido viral, peptido conector, microglobulina beta 2 , peptido conector, dominios extracelulares alfa 1, 2 y 3 de mhc de clase i y un tercer peptido conector; metodo de produccion; formulacion farmaceutica que lo comprende; y su uso
JP2013172734A5 (hr)
HRP20220214T1 (hr) Imunomodulacijska sredstva
IL278014B1 (en) Anti-myostatin antibodies, polypeptides containing variable fc regions and methods of use
JP2012025766A5 (hr)
JP2017527272A5 (hr)