RU2009126766A - Антитела человека к дельта-подобному лиганду-4 человека - Google Patents
Антитела человека к дельта-подобному лиганду-4 человека Download PDFInfo
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- 108700041286 delta Proteins 0.000 title claims abstract 3
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims abstract 33
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims abstract 33
- 101100112922 Candida albicans CDR3 gene Proteins 0.000 claims abstract 12
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims abstract 4
- 238000002198 surface plasmon resonance spectroscopy Methods 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 11
- 201000010099 disease Diseases 0.000 claims 6
- 239000012634 fragment Substances 0.000 claims 6
- 208000035475 disorder Diseases 0.000 claims 5
- 239000000427 antigen Substances 0.000 claims 4
- 102000036639 antigens Human genes 0.000 claims 4
- 108091007433 antigens Proteins 0.000 claims 4
- 230000005764 inhibitory process Effects 0.000 claims 4
- 230000001404 mediated effect Effects 0.000 claims 4
- 206010028980 Neoplasm Diseases 0.000 claims 3
- 208000034038 Pathologic Neovascularization Diseases 0.000 claims 3
- 206010052779 Transplant rejections Diseases 0.000 claims 3
- 201000011510 cancer Diseases 0.000 claims 3
- 210000004027 cell Anatomy 0.000 claims 3
- 230000007812 deficiency Effects 0.000 claims 3
- 230000004054 inflammatory process Effects 0.000 claims 3
- 238000004519 manufacturing process Methods 0.000 claims 3
- 241000588724 Escherichia coli Species 0.000 claims 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 210000003527 eukaryotic cell Anatomy 0.000 claims 1
- 210000000987 immune system Anatomy 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 150000007523 nucleic acids Chemical class 0.000 claims 1
- 102000039446 nucleic acids Human genes 0.000 claims 1
- 108020004707 nucleic acids Proteins 0.000 claims 1
- 239000002773 nucleotide Substances 0.000 claims 1
- 125000003729 nucleotide group Chemical group 0.000 claims 1
- 210000001236 prokaryotic cell Anatomy 0.000 claims 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 abstract 1
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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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- 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
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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
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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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
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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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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- 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
-
- 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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- 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
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
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- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
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- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
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- 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
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- 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
- C07K2317/732—Antibody-dependent cellular cytotoxicity [ADCC]
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- 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
- C07K2317/734—Complement-dependent cytotoxicity [CDC]
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- 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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- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
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- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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Abstract
1. Антитело человека или фрагмент антитела, которые специфическим образом связывают дельта-подобный лиганд-4 человека (hDII4), указанное антитело человека или фрагмент антитела содержит вариабельную область тяжелой цепи (HCVR), содержащую три определяющих комплементарность области (CDR) тяжелой цепи, и вариабельную область легкой цепи (LCVR), содержащую три CDR легкой цепи, где указанные три CDR тяжелой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NО:429 или SEQ ID NО:901, а указанные три CDR легкой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NО:437 или SEQ ID NО:903, и где указанное антитело или фрагмент антитела связывается с эпитопом в пределах N-концевого-DSL домена hDII4. ! 2. Антитело человека или фрагмент антитела по п.1, которые связывают hDII4 с константой аффинности (KD), измеренной с помощью поверхностного плазмонного резонанса, менее чем примерно 500 пМ или менее примерно 300 пМ. ! 3. Антитело человека или фрагмент антитела по п.2, где KD для димерного hDII4 меньше 50 пМ. ! 4. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 тяжелой цепи, содержащие SEQ ID NO:431, 433 и 435, соответственно. ! 5. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 легкой цепи, содержащие SEQ ID NO:439, 441 и 443, соответственно. ! 6. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 тяжелой цепи, содержащие SEQ ID NO:431, 433 и 435 соответственно; и последовательности CDR1, CDR2 и CDR3 легкой цепи, содержащие SEQ ID NO:439, 441 и 443, соответственно. ! 7. Антитело человека или фрагмент антитела по п.6, соде
Claims (22)
1. Антитело человека или фрагмент антитела, которые специфическим образом связывают дельта-подобный лиганд-4 человека (hDII4), указанное антитело человека или фрагмент антитела содержит вариабельную область тяжелой цепи (HCVR), содержащую три определяющих комплементарность области (CDR) тяжелой цепи, и вариабельную область легкой цепи (LCVR), содержащую три CDR легкой цепи, где указанные три CDR тяжелой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NО:429 или SEQ ID NО:901, а указанные три CDR легкой цепи содержат CDR1, CDR2 и CDR3 последовательности SEQ ID NО:437 или SEQ ID NО:903, и где указанное антитело или фрагмент антитела связывается с эпитопом в пределах N-концевого-DSL домена hDII4.
2. Антитело человека или фрагмент антитела по п.1, которые связывают hDII4 с константой аффинности (KD), измеренной с помощью поверхностного плазмонного резонанса, менее чем примерно 500 пМ или менее примерно 300 пМ.
3. Антитело человека или фрагмент антитела по п.2, где KD для димерного hDII4 меньше 50 пМ.
4. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 тяжелой цепи, содержащие SEQ ID NO:431, 433 и 435, соответственно.
5. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 легкой цепи, содержащие SEQ ID NO:439, 441 и 443, соответственно.
6. Антитело человека или фрагмент антитела по п.1, где антитело или фрагмент антитела содержит последовательности CDR1, CDR2 и CDR3 тяжелой цепи, содержащие SEQ ID NO:431, 433 и 435 соответственно; и последовательности CDR1, CDR2 и CDR3 легкой цепи, содержащие SEQ ID NO:439, 441 и 443, соответственно.
7. Антитело человека или фрагмент антитела по п.6, содержащие вариабельную область тяжелой цепи (HCVR), выбранную из SEQ ID NO:429 и SEQ ID NO:901.
8. Антитело человека или фрагмент антитела по п.6, содержащие вариабельную область легкой цепи (LCVR), выбранную из SEQ ID NO:437 и SEQ ID NO:903.
9. Антитело человека или фрагмент антитела по п.6, где HCVR/LCVR выбраны из SEQ ID NO:429/437 и 901/903.
10. Антитело человека или фрагмент антитела по п.9, дополнительно содержащие константную область, выбранную из группы, состоящей из SEQ ID NO:950, 951 и 952.
11. Выделенная молекула нуклеиновой кислоты, кодирующая антитело или антигенсвязывающий фрагмент по любому из предшествующих пунктов.
12. Вектор, содержащий нуклеотидную последовательность по п.11.
13. Система «хозяин-вектор» для получения антитела или антигенсвязывающего фрагмента антитела, который специфически связывает DII4 человека, содержащая вектор по п.12, в подходящей клетке-хозяине.
14. Система «хозяин-вектор» по п.13, где клетка-хозяин является прокариотической или эукариотической клеткой, выбранной из E.coli или клетки СНО.
15. Способ получения антитела против DII4 человека или его антигенсвязывающего фрагмента, включающий выращивание клеток системы «хозяин-вектор» по п.13 в условиях, допускающих получение антитела или его фрагмента, и выделение антитела или фрагмента, полученных таким образом.
16. Применение антитела или антигенсвязывающего фрагмента антитела по любому из пп.1-10 для получения лекарственного средства, используемого для облегчения течения или ингибирования заболевания или расстройства человека, опосредованного DII4.
17. Применение по п.16, где связанное с DII4 заболевание или расстройство представляет собой патологический ангиогенез, рак, недостаточность иммунной системы, реакцию отторжения трансплантата или воспалительный процесс.
18. Антитело или фрагмент антитела по п.1-10, используемые для облегчения течения или ингибирования заболевания или расстройства человека, опосредованного DII4.
19. Антитело или фрагмент антитела по п.18, используемые для облегчения течения или ингибирования заболевания, выбранного из патологического ангиогенеза, рака, иммунной недостаточности, реакции отторжения трансплантата или воспалительного процесса.
20. Композиция, содержащая антитело или фрагмент антитела по любому из пп.1-10 и приемлемый носитель.
21. Антитело или фрагмент антитела по любому из пп.1-10, используемые в способе лечения заболевания или расстройства, опосредованного DII4, благодаря облегчению течения или ингибированию активности DII4, который включает введение человеку указанного антитела или фрагмента антитела.
22. Антитело или фрагмент антитела по п.21, где заболевание или расстройство, опосредованное DII4, представляет собой патологический ангиогенез, рак, иммунную недостаточность, реакцию отторжения трансплантата или воспалительный процесс.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US87492206P | 2006-12-14 | 2006-12-14 | |
| US60/874,922 | 2006-12-14 | ||
| US91641507P | 2007-05-07 | 2007-05-07 | |
| US60/916,415 | 2007-05-07 | ||
| US98532307P | 2007-11-05 | 2007-11-05 | |
| US60/985,323 | 2007-11-05 | ||
| PCT/US2007/025653 WO2008076379A2 (en) | 2006-12-14 | 2007-12-14 | Human antibodies to human delta like ligand 4 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2009126766A true RU2009126766A (ru) | 2011-01-20 |
| RU2448979C2 RU2448979C2 (ru) | 2012-04-27 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2009126766/10A RU2448979C2 (ru) | 2006-12-14 | 2007-12-13 | Антитела человека к дельта-подобному лиганду-4 человека |
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| US (9) | US7919593B2 (ru) |
| EP (2) | EP2423227A1 (ru) |
| JP (2) | JP5677744B2 (ru) |
| KR (1) | KR101516569B1 (ru) |
| CN (1) | CN101611055B (ru) |
| AU (1) | AU2007334366B2 (ru) |
| BR (1) | BRPI0720021A2 (ru) |
| CA (1) | CA2672622C (ru) |
| CR (1) | CR10863A (ru) |
| CY (1) | CY1113087T1 (ru) |
| DK (1) | DK2115003T3 (ru) |
| DO (1) | DOP2009000140A (ru) |
| EC (1) | ECSP099404A (ru) |
| ES (1) | ES2386480T3 (ru) |
| GT (1) | GT200900167A (ru) |
| HK (1) | HK1138019A1 (ru) |
| HR (1) | HRP20120536T1 (ru) |
| IL (1) | IL198612A (ru) |
| MA (1) | MA31092B1 (ru) |
| ME (1) | ME00812B (ru) |
| MX (2) | MX2009005963A (ru) |
| MY (1) | MY164461A (ru) |
| NI (1) | NI200900115A (ru) |
| NO (1) | NO347649B1 (ru) |
| NZ (1) | NZ577616A (ru) |
| PL (1) | PL2115003T3 (ru) |
| PT (1) | PT2115003E (ru) |
| RS (1) | RS52439B (ru) |
| RU (1) | RU2448979C2 (ru) |
| SG (2) | SG177193A1 (ru) |
| SI (1) | SI2115003T1 (ru) |
| SV (1) | SV2009003296A (ru) |
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| WO (1) | WO2008076379A2 (ru) |
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