RU2006138213A - Гуманизированные анти-тфр-бета-антитела - Google Patents
Гуманизированные анти-тфр-бета-антитела Download PDFInfo
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- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- 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]
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- 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
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
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- 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
- Y10S435/00—Chemistry: molecular biology and microbiology
- Y10S435/81—Packaged device or kit
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
Claims (58)
1. Гуманизированное антитело, которое связывается с TGF-бета, содержащее вариабельный домен тяжелой цепи (VH), который содержит остатки гипервариабельной области, не относящиеся к человеческим, включенные в человеческий домен VH, где указанный вариабельный домен включает замену каркасного участка (FR) в последовательности SEQ ID NO: 6 в положении, выбранном из группы, состоящей из 48, 49, 67, 69, 71, 73 и 78, с использованием системы нумерации, представленной Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD (1991).
2. Гуманизированное антитело по п.1, содержащее замены FR в положениях 49, 67 и 71.
3. Гуманизированное антитело по п.2, в котором в положении 49 аланин заменен на глицин, в положении 67 фенилаланин заменен на аланин и в положении 71 аргинин заменен на аланин.
4. Гуманизированное антитело по п.1, содержащее замены FR в положениях 48, 49 и 71.
5. Гуманизированное антитело по п.4, в котором в положении 48 валин заменен на изолейцин, в положении 49 аланин заменен на глицин и в положении 71 аргинин заменен на аланин.
6. Гуманизированное антитело по п.1, содержащее замены FR в положениях 49, 69 и 71.
7. Гуманизированное антитело по п.6, в котором в положении 49 аланин заменен на глицин, в положении 69 изолейцин заменен на лейцин и в положении 71 аргинин заменен на аланин.
8. Гуманизированное антитело по п.6, в котором дополнительная замена FR находится в положении 73.
9. Гуманизированное антитело по п.8, в котором в положении 73 аспарагин заменен на лизин.
10. Гуманизированное антитело по п.1, содержащее замены FR в положениях 49, 71 и 73.
11. Гуманизированное антитело по п.10, в котором в положении 49 аланин заменен на глицин, в положении 71 аргинин заменен на аланин и в положении 73 аспарагин заменен на лизин.
12. Гуманизированное антитело по п.1, содержащее замены FR в положениях 49, 71 и 78.
13. Гуманизированное антитело по п.12, в котором в положении 49 аланин заменен на глицин, в положении 71 аргинин заменен на аланин и в положении 78 лейцин заменен на аланин.
14. Гуманизированное антитело по любому из пп.1-13, содержащее остатки определяющего комплементарность участка (CDR) вариабельного домена легкой цепи (VL) RASQSVLYSSNQKNYLA (SEQ ID NO: 36) или RASQGISSYLA (SEQ ID NO: 37); WASTRES (SEQ ID NO: 38) или YASSLQS (SEQ ID NO: 39) и HQYLSSDT (SEQ ID NO: 40).
15. Гуманизированное антитело по любому из пп.1-13, содержащее остатки определяющего комплементарность участка (CDR) вариабельного домена легкой цепи (VL) RASQSVLYSSNQKNYLA (SEQ ID NO: 36); WASTRES (SEQ ID NO: 38) и HQYLSSDT (SEQ ID NO: 40).
16. Гуманизированное антитело по любому из пп.1-13, содержащее аминокислотную последовательность домена VL в SEQ ID NO: 3.
17. Гуманизированное антитело по любому из пп.1-13, содержащее остатки определяющего комплементарность участка (CDR) домена VН GYAFTNYLIE (SEQ ID NO: 41); VNNPGSGGSNYNEKFKG (SEQ ID NO: 42) или VINPGSGGSNYNEKFKG (SEQ ID NO: 43) и SGGFYFDY (SEQ ID NO: 44).
18. Гуманизированное антитело по любому из пп.1-13, содержащее остатки определяющего комплементарность участка (CDR) домена VН GYAFTNYLIE (SEQ ID NO: 41); VNNPGSGGSNYNEKFKG (SEQ ID NO: 42) и SGGFYFDY (SEQ ID NO: 44).
19. Гуманизированное антитело по любому из пп.1-13, содержащее остатки определяющего комплементарность участка (CDR) домена VН GYAFTNYLIE (SEQ ID NO: 41); VINPGSGGSNYNEKFKG (SEQ ID NO: 43) и SGGFYFDY (SEQ ID NO: 44).
20. Гуманизированное антитело по любому из пп.1-3, содержащее аминокислотную последовательность домена VН в SEQ ID NO: 4.
21. Гуманизированное антитело по любому из пп.1-13, которое представляет собой интактное IgG1 антитело.
22. Гуманизированное антитело по любому из пп.1-13, которое представляет собой фрагмент антитела.
23. Гуманизированное антитело по п.22, которое представляет собой фрагмент Fab.
24. Гуманизированное антитело по любому из пп.1-13, которое не конъюгировано с цитотоксическим средством.
25. Гуманизированное антитело по любому из пп.1-13, которое конъюгировано с цитотоксическим средством.
26. Композиция, содержащая гуманизированное антитело по любому из пп.1-25 и носитель.
27. Выделенная нуклеиновая кислота, кодирующая гуманизированное антитело по любому из пп.1-25.
28. Вектор, содержащий нуклеиновую кислоту по п.27.
29. Клетка-хозяин, содержащая нуклеиновую кислоту по п.27.
30. Способ получения гуманизированного антитела, предусматривающий культивирование клетки-хозяина по п.29 таким образом, что экспрессируется нуклеиновая кислота и продуцируется антитело.
31. Способ по п.30, дополнительно предусматривающий выделение антитела из культуры клетки-хозяина.
32. Способ по п.31, в котором антитело выделяют из культуральной среды клетки-хозяина.
33. Способ по любому из пп.30-32, в котором перед культивированием клетку-хозяина котрансфицируют с вектором, содержащим нуклеиновую кислоту, кодирующую вариабельный домен тяжелой цепи и с вектором, содержащим нуклеиновую кислоту, кодирующую вариабельный домен легкой цепи.
34. Способ лечения нарушения, опосредованного TGF-бета, у млекопитающего, предусматривающий введение млекопитающему эффективного количества гуманизированного антитела по любому из пп.1-25.
35. Способ по п.34, в котором млекопитающее является приматом.
36. Способ по п.34 или 35, в котором млекопитающее является человеком.
37. Способ по любому из пп.34-35, в котором нарушение представляет фиброз, повреждение артерий, инфекцию, ревматоидный артрит или злокачественную опухоль.
38. Способ по п.37, в котором злокачественная опухоль представляет злокачественную опухоль ободочной кишки, злокачественную опухоль ободочной и прямой кишки, злокачественную опухоль прямой кишки, злокачественную опухоль легких, злокачественную опухоль молочной железы, злокачественную опухоль яичников или злокачественную меланому.
39. Способ по любому из пп.34-35, дополнительно предусматривающий введение млекопитающему эффективного количества терапевтического средства иного чем гуманизированное антитело.
40. Способ по п.39, в котором терапевтическое средство представляет химиотерапевтическое средство, цитотоксический препарат, цитокин, средство, ингибирующее рост, антиангиогенный препарат или антитело.
41. Способ по п.40, в котором терапевтическое средство представляет антиангиогенный препарат.
42. Способ по п.39, в котором терапевтическое средство представляет антитело.
43. Способ по п.42, в котором антитело связывается с васкулярным эндотелиальным фактором роста.
44. Способ по п.42, в котором антитело связывается с антигеном Her-2.
45. Способ по любому из пп.42-44, в котором антитело представляет собой интактное антитело.
46. Способ по любому из пп.42-44, в котором антитело представляет собой фрагмент антитела.
47. Способ по п.46, в котором фрагмент антитела представляет собой фрагмент Fab.
48. Способ по любому из пп.42-44, в котором антитело конъюгировано с цитотоксическим средством.
49. Способ по любому из пп.42-44, в котором антитело не конъюгировано с цитотоксическим средством.
50. Способ детектирования TGF-бета в пробе из организма, который предусматривает контактирование гуманизированного антитела по любому из пп.1-25 с пробой из организма и определение того, происходит ли связывание антитела с TGF-бета.
51. Изделие, содержащее контейнер, включающий гуманизированное антитело по любому из пп.1-25 и инструкции для потребителя с указанием для лечения опосредованного TGF-бета нарушения у млекопитающего антителом в эффективном количестве.
52. Изделие по п.51, дополнительно содержащее контейнер, включающий терапевтическое средство иное, чем гуманизированное антитело, где инструкции указывают потребителю, как лечить нарушение антителом в комбинации со средством в эффективных количествах.
53. Изделие по пп.51 или 52, где млекопитающее является человеком.
54. Способ лечения злокачественной опухоли у млекопитающего, предусматривающий введение млекопитающему эффективного количества антитела против TGF-бета и антитела, которое связывается с васкулярным эндотелиальным фактором роста.
55. Способ по п.54, в котором млекопитающее является человеком.
56. Способ по пп.54 или 55, в котором антитело против TGF-бета связывается с любым одним или несколькими из следующих: TGF-бета1, TGF-бета2 и TGF-бета3.
57. Способ по любому из пп.54-55, в котором антитело связывается с TGF-бета1.
58. Способ по любому из пп.54-55, в котором антитело связывается с TGF-бета1 и TGF-бета2.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55829004P | 2004-03-31 | 2004-03-31 | |
| US60/558,290 | 2004-03-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2006138213A true RU2006138213A (ru) | 2008-05-10 |
| RU2386638C2 RU2386638C2 (ru) | 2010-04-20 |
Family
ID=34965114
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2006138213/13A RU2386638C2 (ru) | 2004-03-31 | 2005-03-31 | Гуманизированные анти-тфр-бета-антитела |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US7527791B2 (ru) |
| EP (1) | EP1740615B1 (ru) |
| JP (1) | JP5128935B2 (ru) |
| KR (1) | KR101245983B1 (ru) |
| CN (1) | CN1961003B (ru) |
| AU (1) | AU2005230848B9 (ru) |
| BR (1) | BRPI0508761A (ru) |
| CA (1) | CA2561686C (ru) |
| ES (1) | ES2527292T3 (ru) |
| IL (1) | IL178409A (ru) |
| MX (1) | MXPA06011199A (ru) |
| NZ (1) | NZ550217A (ru) |
| RU (1) | RU2386638C2 (ru) |
| WO (1) | WO2005097832A2 (ru) |
| ZA (1) | ZA200608130B (ru) |
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| US7211644B1 (en) * | 1996-08-27 | 2007-05-01 | University Of South Florida | Diagnostic markers of human female infertility |
| US6683156B1 (en) | 1996-08-27 | 2004-01-27 | University Of South Florida | Method for diagnosing selected adenocarcinomas |
| BRPI0607639B1 (pt) * | 2005-02-08 | 2022-04-05 | Genzyme Corporation | Moléculas de anticorpo humano ou fragmento de ligação a antígeno das mesmas que se ligam e neutralizam tgf-beta1, 2 e 3, uso das mesmas e composição farmacêutica |
| US20080267946A1 (en) * | 2005-03-08 | 2008-10-30 | Medigenes Co., Ltd | Pharmaceutical Composition for Treating Avellino Cornea Dystrophy Comprising an Antibody Against Tgf-Beta |
| ATE505489T1 (de) | 2005-04-22 | 2011-04-15 | Lilly Co Eli | Tgf-beta-1-spezifische antikörper |
| US7741448B2 (en) * | 2005-06-21 | 2010-06-22 | Medical & Biological Laboratories Co., Ltd. | Antibody having inhibitory effect on amyloid fibril formation |
| WO2007076391A1 (en) * | 2005-12-23 | 2007-07-05 | Eli Lilly And Company | Tgf-beta binding compositions |
| KR20080100353A (ko) * | 2006-02-01 | 2008-11-17 | 더 존스 홉킨스 유니버시티 | 신생물성 또는 감염성 질환의 면역예방 또는 면역요법용 폴리펩티드-핵산 접합체 |
| WO2007108992A2 (en) * | 2006-03-13 | 2007-09-27 | The Johns Hopkins University | Augmentation of endothelial thromboresistance |
| ES2647472T3 (es) | 2006-10-03 | 2017-12-21 | Genzyme Corporation | Anticuerpos contra TGF-BETA para uso en el tratamiento de lactantes con riesgo de desarrollar displasia broncopulmonar |
| MX2009003774A (es) | 2006-10-12 | 2009-04-22 | Genentech Inc | Anticuerpos para linfotoxina-alfa. |
| US7884184B2 (en) * | 2007-01-30 | 2011-02-08 | Epivax, Inc. | Regulatory T cell epitopes, compositions and uses thereof |
| JP4936379B2 (ja) * | 2007-03-27 | 2012-05-23 | 独立行政法人産業技術総合研究所 | 乳癌の肺及びまたは肝臓転移解析用動物モデル |
| US20100291024A1 (en) * | 2007-03-30 | 2010-11-18 | Xuebin Qin | Methods and compositions for the treatment of proliferative and pathogenic diseases |
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Also Published As
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|---|---|
| CN1961003A (zh) | 2007-05-09 |
| NZ550217A (en) | 2009-11-27 |
| IL178409A (en) | 2015-02-26 |
| US20050276802A1 (en) | 2005-12-15 |
| CN1961003B (zh) | 2013-03-27 |
| RU2386638C2 (ru) | 2010-04-20 |
| ES2527292T3 (es) | 2015-01-22 |
| KR20060133604A (ko) | 2006-12-26 |
| EP1740615B1 (en) | 2014-11-05 |
| AU2005230848B9 (en) | 2011-06-02 |
| JP2008505610A (ja) | 2008-02-28 |
| BRPI0508761A (pt) | 2007-08-14 |
| US7527791B2 (en) | 2009-05-05 |
| MXPA06011199A (es) | 2007-04-16 |
| IL178409A0 (en) | 2007-02-11 |
| JP5128935B2 (ja) | 2013-01-23 |
| WO2005097832A2 (en) | 2005-10-20 |
| AU2005230848A1 (en) | 2005-10-20 |
| US8012482B2 (en) | 2011-09-06 |
| CA2561686C (en) | 2014-12-02 |
| ZA200608130B (en) | 2008-12-31 |
| EP1740615A2 (en) | 2007-01-10 |
| AU2005230848B2 (en) | 2010-09-09 |
| KR101245983B1 (ko) | 2013-06-28 |
| WO2005097832A3 (en) | 2005-12-01 |
| CA2561686A1 (en) | 2005-10-20 |
| US20090285810A1 (en) | 2009-11-19 |
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