RU2004135306A - Новые антитела к тканевому фактору в качестве антикоагулянтов - Google Patents
Новые антитела к тканевому фактору в качестве антикоагулянтов Download PDFInfo
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- RU2004135306A RU2004135306A RU2004135306/13A RU2004135306A RU2004135306A RU 2004135306 A RU2004135306 A RU 2004135306A RU 2004135306/13 A RU2004135306/13 A RU 2004135306/13A RU 2004135306 A RU2004135306 A RU 2004135306A RU 2004135306 A RU2004135306 A RU 2004135306A
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- Prior art keywords
- antibody
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- antibody according
- effective amount
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- 108010000499 Thromboplastin Proteins 0.000 title claims 14
- 102000002262 Thromboplastin Human genes 0.000 title claims 14
- 238000000034 method Methods 0.000 claims 8
- 102100023804 Coagulation factor VII Human genes 0.000 claims 4
- 108010023321 Factor VII Proteins 0.000 claims 4
- 108010014173 Factor X Proteins 0.000 claims 4
- 229940012413 factor vii Drugs 0.000 claims 4
- 230000015572 biosynthetic process Effects 0.000 claims 3
- 108091033319 polynucleotide Proteins 0.000 claims 3
- 239000002157 polynucleotide Substances 0.000 claims 3
- 102000040430 polynucleotide Human genes 0.000 claims 3
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 2
- 102000015081 Blood Coagulation Factors Human genes 0.000 claims 2
- 108010039209 Blood Coagulation Factors Proteins 0.000 claims 2
- 102100022641 Coagulation factor IX Human genes 0.000 claims 2
- 206010051055 Deep vein thrombosis Diseases 0.000 claims 2
- 108010076282 Factor IX Proteins 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 206010047249 Venous thrombosis Diseases 0.000 claims 2
- 125000003275 alpha amino acid group Chemical group 0.000 claims 2
- 239000003114 blood coagulation factor Substances 0.000 claims 2
- 229960004222 factor ix Drugs 0.000 claims 2
- 238000001415 gene therapy Methods 0.000 claims 2
- 230000028709 inflammatory response Effects 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- 206010053567 Coagulopathies Diseases 0.000 claims 1
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims 1
- 108010054265 Factor VIIa Proteins 0.000 claims 1
- 208000032382 Ischaemic stroke Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 108010090804 Streptavidin Proteins 0.000 claims 1
- 108090000190 Thrombin Proteins 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 230000002776 aggregation Effects 0.000 claims 1
- 238000004220 aggregation Methods 0.000 claims 1
- 230000002429 anti-coagulating effect Effects 0.000 claims 1
- 239000003146 anticoagulant agent Substances 0.000 claims 1
- 229940127219 anticoagulant drug Drugs 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 208000015294 blood coagulation disease Diseases 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000015271 coagulation Effects 0.000 claims 1
- 238000005345 coagulation Methods 0.000 claims 1
- 239000011248 coating agent Substances 0.000 claims 1
- 238000000576 coating method Methods 0.000 claims 1
- 208000002528 coronary thrombosis Diseases 0.000 claims 1
- 238000002316 cosmetic surgery Methods 0.000 claims 1
- 239000000539 dimer Substances 0.000 claims 1
- 208000009190 disseminated intravascular coagulation Diseases 0.000 claims 1
- 229940012414 factor viia Drugs 0.000 claims 1
- 230000001453 nonthrombogenic effect Effects 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000010118 platelet activation Effects 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 230000001105 regulatory effect Effects 0.000 claims 1
- 238000001356 surgical procedure Methods 0.000 claims 1
- 229960004072 thrombin Drugs 0.000 claims 1
- 230000001732 thrombotic effect Effects 0.000 claims 1
- 210000003462 vein Anatomy 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/36—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against blood coagulation factors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
- C07K14/475—Growth factors; Growth regulators
- C07K14/485—Epidermal growth factor [EGF], i.e. urogastrone
-
- 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
- C07K14/7455—Thrombomodulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- 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
-
- 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
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/32—Immunoglobulins specific features characterized by aspects of specificity or valency specific for a neo-epitope on a complex, e.g. antibody-antigen or ligand-receptor
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Genetics & Genomics (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Gastroenterology & Hepatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Toxicology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Claims (25)
1. Антикоагулирующее антитело, которое связывается с большей аффинностью с комплексом фактор VIIa/тканевый фактор (ТФ), чем со свободным тканевым фактором (ТФ).
2. Антитело по п.1, где антитело обладает по меньшей мере в 2 раза более высокой аффинностью к связыванию с комплексом FVIIa/ТФ, чем со свободным ТФ при измерении с помощью микрокалометрического анализа.
3. Антитело по п.2, где антитело обладает по меньшей мере в 5 раза более высокой аффинностью к связыванию с комплексом FVIIa/ТФ, чем со свободным ТФ.
4. Антитело по п.3, где антитело обладает по меньшей мере в 10 раза более высокой аффинностью к связыванию с комплексом FVIIa/ТФ, чем со свободным ТФ.
5. Антитело по п.1, где антитело представляет собой моноклональное антитело.
6. Антитело по п.5, где антитело представляет собой одноцепочечное антитело, Fab-димерное антитело или антитело в виде IgG.
7. Антитело по п.6, где антитело представляет собой одноцепочечное антитело.
8. Антитело по п.7, где антитело не конкурирует за связывание с ТФ с одним или несколькими факторами свертывания, выбранными из ряда, включающего фактор VII (FVII), фактор IX (FIX) и фактор Х (FX).
9. Антитело по п.8, где факторы свертывания представляют собой FVII и FX.
10. Антитело по п.1, где антитело является гликозилированным.
11. Антитело по п.1, где антитело модифицируют путем добавлением полиэтиленгликоля.
12. Антитело по п.1, где антитело биотинилируют для связывания со стрептавидином.
13. Фармацевтическая композиция, содержащая антитело по п.1, где композиция включает фармацевтически приемлемый эксципиент и терапевтически эффективное количество антитела.
14. Способ предупреждения образования тромба, заключающийся в том, что вводят терапевтически эффективное количество антитела по п.1, где антитело ингибирует образование тромбина, не оказывая непосредственного воздействия на другие параметры свертывания, такие как активация и агрегация тромбоцитов.
15. Способ по п.14, где способ предназначен для защиты от образования тромба при ишемическом ударе, тромботических осложнениях после пластической операции на сосудах или микрососудистой хирургии.
16. Способ снижения и лечения тромбоза глубоких вен (ТГВ), диссеминированного внутрисосудистого свертывания крови (ДВС), острого коронарного тромбоза или рака с признаками коагулопатии у пациента, заключающийся в том, что пациенту вводят терапевтически эффективное количество антитела по п.1.
17. Способ регуляции воспалительного ответа у пациента, заключающийся в том, что пациенту вводят терапевтически эффективное количество антитела по п.1.
18. Способ по п.17, где воспалительный ответ выбирают из ряда, включающего сепсис, трансплантаты кожи и вен и трансплантаты органов.
19. Антитело по п.1, где антитело можно применять для формирования нетромбогенного покрытия на поверхности медицинского устройства, где медицинское устройство приходит в контакт с кровью.
20. Набор, содержащий антитело по п.1.
21. Набор, содержащий последовательности ДНК, которые кодируют антитело по п.1.
22. Композиция для генной терапии, содержащая полинуклеотидную последовательность SEQ ID NO:2 или SEQ ID NO:4, которая кодирует антитело, аминокислотная последовательность которого представлена в SEQ ID NO:1 или SEQ ID NO:3, в сочетании с терапевтически эффективным количеством вектора, применяемого в генной терапии.
23. Антикоагулирующее антитело, где антитело представляет собой одноцепочечное антитело, которое связывается с большей аффинностью с комплексом FVIIa/ТФ, чем со свободным ТФ, и где антитело не конкурирует за связывание с ТФ с FVII и FX.
24. Антитело по п.23, где антитело содержит аминокислотную последовательность SEQ ID NO:1 или SEQ ID NO:3.
25. Полинуклеотидная последовательность, кодирующая антитело по п.23, где полинуклеотидная последовательность содержит нуклеотидную последовательность SEQ ID NO:2 или SEQ ID NO:4.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US37656602P | 2002-05-01 | 2002-05-01 | |
| US60/376,566 | 2002-05-01 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2004135306A true RU2004135306A (ru) | 2005-07-10 |
| RU2345789C2 RU2345789C2 (ru) | 2009-02-10 |
Family
ID=29401364
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2004135306/13A RU2345789C2 (ru) | 2002-05-01 | 2003-04-30 | Новые антитела к тканевому фактору в качестве антикоагулянтов |
| RU2004135308/15A RU2320366C2 (ru) | 2002-05-01 | 2003-04-30 | Новые слитые белки тромбомодулина, обеспечивающие направленный перенос к тканевому фактору, в качестве антикоагулянтов |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2004135308/15A RU2320366C2 (ru) | 2002-05-01 | 2003-04-30 | Новые слитые белки тромбомодулина, обеспечивающие направленный перенос к тканевому фактору, в качестве антикоагулянтов |
Country Status (29)
| Country | Link |
|---|---|
| US (3) | US7250168B2 (ru) |
| EP (2) | EP1549341B1 (ru) |
| JP (2) | JP4460443B2 (ru) |
| KR (2) | KR101080587B1 (ru) |
| CN (2) | CN100563709C (ru) |
| AR (1) | AR039515A1 (ru) |
| AT (2) | ATE484524T1 (ru) |
| AU (2) | AU2003225256B2 (ru) |
| BR (2) | BR0304660A (ru) |
| CA (2) | CA2483909A1 (ru) |
| CR (1) | CR7584A (ru) |
| DE (2) | DE60334538D1 (ru) |
| DK (2) | DK1549341T3 (ru) |
| EC (2) | ECSP045467A (ru) |
| ES (2) | ES2354419T3 (ru) |
| HK (1) | HK1080372A1 (ru) |
| IL (3) | IL164733A0 (ru) |
| MX (2) | MXPA04010851A (ru) |
| NO (2) | NO20035848L (ru) |
| NZ (2) | NZ536242A (ru) |
| PE (1) | PE20040597A1 (ru) |
| PL (2) | PL210582B1 (ru) |
| PT (2) | PT1503785E (ru) |
| RS (2) | RS102404A (ru) |
| RU (2) | RU2345789C2 (ru) |
| TW (1) | TWI343388B (ru) |
| UA (2) | UA81114C2 (ru) |
| WO (2) | WO2003092602A2 (ru) |
| ZA (2) | ZA200409694B (ru) |
Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE60043728D1 (de) * | 1999-06-02 | 2010-03-11 | Chugai Pharmaceutical Co Ltd | Neues hämopoietin rezeptorprotein nr10 |
| AU7445900A (en) * | 1999-09-27 | 2001-04-30 | Chugai Seiyaku Kabushiki Kaisha | Novel hemopoietin receptor protein, nr12 |
| AU2001296305B2 (en) | 2000-09-26 | 2007-12-06 | Duke University | RNA aptamers and methods for identifying the same |
| US7579000B2 (en) | 2002-05-01 | 2009-08-25 | Bayer Schering Pharma Ag | Tissue factor targeted antibodies as anticoagulants |
| PE20040597A1 (es) * | 2002-05-01 | 2004-10-06 | Schering Ag | Proteinas de fusion de trombomodulina dirigidas al factor tisular como anticoagulantes |
| EP1539235A2 (en) * | 2002-07-01 | 2005-06-15 | Human Genome Sciences, Inc. | Antibodies that specifically bind to reg iv |
| US7425328B2 (en) | 2003-04-22 | 2008-09-16 | Purdue Pharma L.P. | Tissue factor antibodies and uses thereof |
| US7833978B2 (en) * | 2004-02-20 | 2010-11-16 | Emory University | Thrombomodulin derivatives and conjugates |
| PL1745062T3 (pl) | 2004-04-22 | 2014-10-31 | Regado Biosciences Inc | Ulepszone modulatory czynników krzepnięcia |
| EP1889908A4 (en) | 2005-06-03 | 2012-04-25 | Mochida Pharm Co Ltd | PROTEIN FUSED WITH ANTI-CD14 ANTIBODY |
| WO2008039206A2 (en) * | 2005-10-05 | 2008-04-03 | The Trustees Of The University Of Pennsylvania | Fusion proteins for inhibition and dissolution of coagulation |
| WO2007115953A1 (en) * | 2006-04-07 | 2007-10-18 | Novo Nordisk Health Care Ag | Covalent factor vii-tissue factor complex |
| CN101500608A (zh) | 2006-06-08 | 2009-08-05 | 中外制药株式会社 | 炎性疾病的预防或治疗药 |
| RU2433829C2 (ru) * | 2006-10-06 | 2011-11-20 | Асахи Касеи Фарма Корпорейшн | Средство для лечения и/или улучшения состояния при диссеминированном внутрисосудистом свертывании |
| WO2008121814A1 (en) | 2007-03-28 | 2008-10-09 | Ats Medical, Inc. | Method for inhibiting platelet interaction with biomaterial surfaces |
| WO2009037297A2 (en) * | 2007-09-20 | 2009-03-26 | Bracco Imaging Spa | Method for the preparation of new oligoclonal antibodies |
| MY185647A (en) | 2007-12-05 | 2021-05-27 | Chugai Pharmaceutical Co Ltd | Therapeutic agent for pruritus |
| US8333973B2 (en) * | 2008-01-02 | 2012-12-18 | The Trustees Of The University Of Pennsylvania | Targeting recombinant therapeutics to circulating red blood cells |
| UA112050C2 (uk) * | 2008-08-04 | 2016-07-25 | БАЄР ХЕЛСКЕР ЛЛСі | Терапевтична композиція, що містить моноклональне антитіло проти інгібітора шляху тканинного фактора (tfpi) |
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