RU2012119788A - Связывающие il-1 белки - Google Patents
Связывающие il-1 белки Download PDFInfo
- Publication number
- RU2012119788A RU2012119788A RU2012119788/10A RU2012119788A RU2012119788A RU 2012119788 A RU2012119788 A RU 2012119788A RU 2012119788/10 A RU2012119788/10 A RU 2012119788/10A RU 2012119788 A RU2012119788 A RU 2012119788A RU 2012119788 A RU2012119788 A RU 2012119788A
- Authority
- RU
- Russia
- Prior art keywords
- seq
- binding protein
- cdr
- group
- amino acid
- Prior art date
Links
- 108010002352 Interleukin-1 Proteins 0.000 title 1
- 102000014914 Carrier Proteins Human genes 0.000 claims abstract 42
- 108091008324 binding proteins Proteins 0.000 claims abstract 42
- 125000003275 alpha amino acid group Chemical group 0.000 claims abstract 14
- 229920001184 polypeptide Polymers 0.000 claims abstract 8
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 8
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 8
- 108010047041 Complementarity Determining Regions Proteins 0.000 claims abstract 5
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract 2
- 102000018358 immunoglobulin Human genes 0.000 claims abstract 2
- 230000000694 effects Effects 0.000 claims 7
- 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 claims 6
- 238000000034 method Methods 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003937 drug carrier Substances 0.000 claims 2
- 102000039446 nucleic acids Human genes 0.000 claims 2
- 108020004707 nucleic acids Proteins 0.000 claims 2
- 150000007523 nucleic acids Chemical class 0.000 claims 2
- 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 1
- 108010003272 Hyaluronate lyase Proteins 0.000 claims 1
- 102000001974 Hyaluronidases Human genes 0.000 claims 1
- 108010003723 Single-Domain Antibodies Proteins 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 230000008827 biological function Effects 0.000 claims 1
- 238000012258 culturing Methods 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 239000002254 cytotoxic agent Substances 0.000 claims 1
- 231100000599 cytotoxic agent Toxicity 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 239000006185 dispersion Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 230000009977 dual effect Effects 0.000 claims 1
- 230000002708 enhancing effect Effects 0.000 claims 1
- 230000006870 function Effects 0.000 claims 1
- 230000013595 glycosylation Effects 0.000 claims 1
- 238000006206 glycosylation reaction Methods 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 229960002773 hyaluronidase Drugs 0.000 claims 1
- 239000012216 imaging agent Substances 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 102000004169 proteins and genes Human genes 0.000 claims 1
- 108090000623 proteins and genes Proteins 0.000 claims 1
Classifications
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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
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
- C07K16/245—IL-1
-
- 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
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
-
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
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- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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Abstract
1. Связывающий белок, способный связывать IL-1β, где указанный связывающий белок содержит по меньшей мере одну область, определяющую комплементарность (CDR), содержащую аминокислотную последовательность, выбранную из группы, состоящей из остатков 31-35 SEQ ID NO: 26 (CDR-H1); остатков 50-65 SEQ ID NO: 26 (CDR-H2); остатков 98-111 SEQ ID NO: 26 (CDR-H3); остатков 24-34 SEQ ID NO: 27 (CDR-L1); остатков 50-56 SEQ ID NO: 27 (CDR-L2); и остатков 89-97 SEQ ID NO: 27 (CDR-L3).2. Связывающий белок по п.1, дополнительно содержащий акцепторную каркасную область человека.3. Связывающий белок по п.2, где акцепторная каркасная область человека содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 10-17 и SEQ ID NO: 18-25.4. Связывающий белок по п.1, содержащий полипептид вариабельной области тяжелой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, и SEQ ID NO: 33, и полипептид вариабельной области легкой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39 и SEQ ID NO: 40.5. Связывающий белок по п.4, где указанный связывающий белок содержит полипептид вариабельной области тяжелой цепи и полипептид вариабельной области легкой цепи, содержащий соответствующие аминокислотные последовательности, выбранные из группы, состоящей из: SEQ ID NO: 30 и SEQ ID NO: 36; SEQ ID NO: 30 и SEQ ID NO: 37, SEQ ID NO: 30 и SEQ ID NO: 39; SEQ ID NO: 30 и SEQ ID NO: 40; SEQ ID NO: 33 и SEQ ID NO: 36; и SEQ ID NO: 33 и SEQ ID NO: 37, SEQ ID NO: 33 и SEQ ID NO: 39, SEQ ID NO: 33 и SEQ ID NO: 40.6. Связывающий белок по п.1, где указанный связывающий белок выбран из группы, состоящей из: молекулы иммуноглобулина, связанного дисульфидной связью Fv, моноклонального антител�
Claims (26)
1. Связывающий белок, способный связывать IL-1β, где указанный связывающий белок содержит по меньшей мере одну область, определяющую комплементарность (CDR), содержащую аминокислотную последовательность, выбранную из группы, состоящей из остатков 31-35 SEQ ID NO: 26 (CDR-H1); остатков 50-65 SEQ ID NO: 26 (CDR-H2); остатков 98-111 SEQ ID NO: 26 (CDR-H3); остатков 24-34 SEQ ID NO: 27 (CDR-L1); остатков 50-56 SEQ ID NO: 27 (CDR-L2); и остатков 89-97 SEQ ID NO: 27 (CDR-L3).
2. Связывающий белок по п.1, дополнительно содержащий акцепторную каркасную область человека.
3. Связывающий белок по п.2, где акцепторная каркасная область человека содержит аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 10-17 и SEQ ID NO: 18-25.
4. Связывающий белок по п.1, содержащий полипептид вариабельной области тяжелой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, и SEQ ID NO: 33, и полипептид вариабельной области легкой цепи, содержащий аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39 и SEQ ID NO: 40.
5. Связывающий белок по п.4, где указанный связывающий белок содержит полипептид вариабельной области тяжелой цепи и полипептид вариабельной области легкой цепи, содержащий соответствующие аминокислотные последовательности, выбранные из группы, состоящей из: SEQ ID NO: 30 и SEQ ID NO: 36; SEQ ID NO: 30 и SEQ ID NO: 37, SEQ ID NO: 30 и SEQ ID NO: 39; SEQ ID NO: 30 и SEQ ID NO: 40; SEQ ID NO: 33 и SEQ ID NO: 36; и SEQ ID NO: 33 и SEQ ID NO: 37, SEQ ID NO: 33 и SEQ ID NO: 39, SEQ ID NO: 33 и SEQ ID NO: 40.
6. Связывающий белок по п.1, где указанный связывающий белок выбран из группы, состоящей из: молекулы иммуноглобулина, связанного дисульфидной связью Fv, моноклонального антитела, scFv, химерного антитела, однодоменного антитела, антитела с пересаженными CDR, диантитела, гуманизированного антитела, полиспецифического антитела, Fab, антитела с двойной специфичностью, белка DVD-Ig, Fab', биспецифического антитела, F(ab')2 и a Fv.
7. Связывающий белок по п.1, дополнительно содержащий константную область тяжелой цепи, имеющую аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 2 и SEQ ID NO: 3.
8. Связывающий белок по п.1, дополнительно содержащий константную область легкой цепи, имеющую аминокислотную последовательность, выбранную из группы, состоящей из SEQ ID NO: 4 и SEQ ID NO: 5.
9. Связывающий белок по п.1, где указанный связывающий белок способен модулировать биологическую функцию IL-1β человека.
10. Связывающий белок по п.1, где указанный связывающий белок способен нейтрализовать IL-1β человека.
11. Связывающий белок по п.1, где указанный связывающий белок дополнительно содержит средство, выбранное из группы, состоящей из молекулы иммуноадгезии, визуализирующего средства, лекарственного средства и цитотоксического средства.
12. Связывающий белок по п.1, где указанный связывающий белок обладает паттерном гликозилирования человека.
13. Связывающий белок по п.1, где указанный связывающий белок представляет собой кристаллизованный связывающий белок.
14. Выделенная нуклеиновая кислота, кодирующая аминокислотную последовательность связывающего белка по п.1.
15. Вектор, содержащий выделенную нуклеиновую кислоту, кодирующую аминокислотную последовательность связывающего белка по п.14.
16. Клетка-хозяин, содержащая вектор по п.15.
17. Способ продуцирования связывающего белка, способного связывать IL-1β, причем способ включает стадии культивирования клетки-хозяина по п.16 в культуральной среде в условиях, достаточных для продуцирования связывающего белка, способного связывать IL-1β.
18. Композиция для высвобождения связывающего белка, причем указанная композиция содержит:
(a) состав, где указанный состав содержит кристаллизованный связывающий белок по п.13 и ингредиент; и
(b) по меньшей мере один полимерный носитель.
19. Способ лечения млекопитающего, включающий стадию введения млекопитающему эффективного количества композиции по п.18.
20. Фармацевтическая композиция, содержащая связывающий белок по п.1 и фармацевтически приемлемый носитель.
21. Фармацевтическая композиция по п.20, где указанный фармацевтически приемлемый носитель функционирует как адъювант, пригодный для увеличения всасывания или диспергирования указанного связывающего белка.
22. Фармацевтическая композиция по п.21, где указанный адъювант представляет собой гиалуронидазу.
23. Фармацевтическая композиция по п.20, дополнительно содержащая по меньшей мере одно дополнительное средство для лечения нарушения, при котором активность IL-1β является вредоносной.
24. Способ снижения активности IL-1β человека, включающий контактирование IL-1β со связывающим белком по п.1, так чтобы активность IL-1β человека снижалась.
25. Способ снижения активности IL-1β человека у человека, страдающего от нарушения, при котором активность IL-1β является вредоносной, включающий введение человеку связывающего белка по п.1, так чтобы активность IL-1β человека у человека снижалась.
26. Способ лечения индивидуума от заболевания или нарушения, при котором активность IL-1β является вредоносной, путем введения индивидууму связывающего белка по п.1, так чтобы достигалось лечение.
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- 2010-10-15 MX MX2012004412A patent/MX2012004412A/es not_active Application Discontinuation
- 2010-10-15 CA CA2775402A patent/CA2775402A1/en not_active Abandoned
- 2010-10-15 EP EP10824167.0A patent/EP2488201A4/en not_active Withdrawn
- 2010-10-15 IN IN2634DEN2012 patent/IN2012DN02634A/en unknown
- 2010-10-15 UY UY0001032949A patent/UY32949A/es not_active Application Discontinuation
- 2010-10-15 TW TW099135501A patent/TW201124427A/zh unknown
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- 2010-10-15 JP JP2012534395A patent/JP2013507929A/ja not_active Withdrawn
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| CA2775402A1 (en) | 2011-04-21 |
| EP2488201A1 (en) | 2012-08-22 |
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| ZA201202610B (en) | 2012-12-27 |
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| US20130295004A1 (en) | 2013-11-07 |
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| UY32949A (es) | 2011-02-28 |
| AU2010306681A1 (en) | 2012-04-19 |
| EP2488201A4 (en) | 2013-12-25 |
| JP2013507929A (ja) | 2013-03-07 |
| US8398966B2 (en) | 2013-03-19 |
| AR078650A1 (es) | 2011-11-23 |
| IN2012DN02634A (ru) | 2015-09-04 |
| IL219202A0 (en) | 2012-06-28 |
| BR112012007365A2 (pt) | 2016-11-22 |
| MX2012004412A (es) | 2012-05-08 |
| TW201124427A (en) | 2011-07-16 |
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