RU2015151505A - Антитела, направленные к белку запрограммированной гибели клетки-1 (pd-1) - Google Patents
Антитела, направленные к белку запрограммированной гибели клетки-1 (pd-1) Download PDFInfo
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- RU2015151505A RU2015151505A RU2015151505A RU2015151505A RU2015151505A RU 2015151505 A RU2015151505 A RU 2015151505A RU 2015151505 A RU2015151505 A RU 2015151505A RU 2015151505 A RU2015151505 A RU 2015151505A RU 2015151505 A RU2015151505 A RU 2015151505A
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- 102000004169 proteins and genes Human genes 0.000 title 1
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- 238000000034 method Methods 0.000 claims 11
- 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 9
- 101100519207 Mus musculus Pdcd1 gene Proteins 0.000 claims 9
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- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
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- 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
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
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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
- C07K16/28—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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- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
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- 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
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- A61K2039/507—Comprising a combination of two or more separate antibodies
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- 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
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- C07K2317/33—Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
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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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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Claims (72)
1. Выделенный полипептид тяжелой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 1, аминокислотную последовательность CDR2 из SEQ ID NO: 2 и аминокислотную последовательность CDR3 из SEQ ID NO: 3, где необязательно:
(a) остаток 9 в SEQ ID NO: 1 заменен другим аминокислотным остатком,
(b) один или более остатков 7, 8 и 9 в SEQ ID NO: 2 заменен другим аминокислотным остатком,
(c) один или более остатков 1, 2 и 5 в SEQ ID NO: 3 заменен другим аминокислотным остатком, или
(d) любая комбинация (а)-(с).
2. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 1, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 1, аминокислотную последовательность CDR2 из SEQ ID NO: 2 и аминокислотную последовательность CDR3 из SEQ ID NO: 3, за исключением того, что остаток 9 в SEQ ID NO: 1 заменен другим аминокислотным остатком.
3. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 2, где остаток 9 в SEQ ID NO: 1 заменен остатком метионина (М).
4. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 1, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 1, аминокислотную последовательность CDR2 из SEQ ID NO: 2 и аминокислотную последовательность CDR3 из SEQ ID NO: 3, за исключением того, что один или более остатков 7, 8 и 9 в SEQ ID NO: 2 заменены другим аминокислотным остатком.
5. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 4, где:
(a) остаток 7 в SEQ ID NO: 2 заменен остатком аспарагина (N),
(b) остаток 8 в SEQ ID NO: 2 заменен остатком серина (S),
(c) остаток 9 в SEQ ID NO: 2 заменен остатком треонина (Т), или
(d) любая комбинация (а)-(с).
6. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 1, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 1, аминокислотную последовательность CDR2 из SEQ ID NO: 2 и аминокислотную последовательность CDR3 из SEQ ID NO: 3, за исключением того, что один или больше остатков 1, 2 и 5 в SEQ ID NO: 3 заменены другим аминокислотным остатком.
7. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 6, где:
(a) остаток 1 в SEQ ID NO: 3 заменен остатком глутаминовой кислоты (Е),
(b) остаток 2 в SEQ ID NO: 3 заменен остатком тирозином (Y),
(c) остаток 5 в SEQ ID NO: 3 заменен остатком серина (S), или
(d) любая комбинация (а)-(с).
8. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 1, который включает любую аминокислотную последовательность из SEQ ID NO: 4-11.
9. Выделенный полипептид тяжелой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 12, аминокислотную последовательность CDR2 из SEQ ID NO: 13 и аминокислотную последовательность CDR3 из SEQ ID NO: 14, где необязательно:
(a) остаток 9 в SEQ ID NO: 12 заменен другим аминокислотным остатком,
(b) остаток 8 и/или остаток 9 в SEQ ID NO: 13 заменен другим аминокислотным остатком,
(c) остаток 5 в SEQ ID NO: 14 заменен другим аминокислотным остатком, или
(d) любая комбинация (а)-(с).
10. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 9, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 12, аминокислотную последовательность CDR2 из SEQ ID NO: 13 и аминокислотную последовательность CDR3 из SEQ ID NO: 14, за исключением того, что остаток 9 в SEQ ID NO: 12 заменен другим аминокислотным остатком.
11. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 10, где остаток 9 в SEQ ID NO: 12 заменен остатком лейцина (L).
12. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 9, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 12, аминокислотную последовательность CDR2 из SEQ ID NO: 13 и аминокислотную последовательность CDR3 из SEQ ID NO: 14, за исключением того, что остаток 8 и/или остаток 9 в SEQ ID NO: 13 заменен другим аминоостатком.
13. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 12, где:
(a) остаток 8 в SEQ ID NO: 13 заменен остатком тирозина (Y), и/или
(b) остаток 9 в SEQ ID NO: 13 заменен остатком аланина (А).
14. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 9, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 12, аминокислотную последовательность CDR2 из SEQ ID NO: 13 и аминокислотную последовательность CDR3 из SEQ ID NO: 14, за исключением того, что остаток 5 в SEQ ID NO: 3 заменен другим остатком.
15. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 14, где остаток 5 в SEQ ID NO: 14 заменен остатком треонина (Т).
16. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 9, который включает аминокислотную последовательность SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17 или SEQ ID NO: 18.
17. Выделенный полипептид тяжелой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 19, аминокислотную последовательность CDR2 из SEQ ID NO: 20 и аминокислотную последовательность CDR3 из SEQ ID NO: 21.
18. Выделенный полипептид тяжелой цепи иммуноглобулина по п. 17, который включает аминокислотную последовательность SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24 или SEQ ID NO: 25.
19. Выделенный полипептид тяжелой цепи иммуноглобулина, который включает аминокислотную последовательность, которая по меньшей мере на 90% идентична любой из SEQ ID NO: 4-11, SEQ ID NO: 15-18 и SEQ ID NO: 22-25.
20. Выделенный полипептид легкой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 26 и аминокислотную последовательность CDR2 из SEQ ID NO: 27.
21. Выделенный полипептид легкой цепи иммуноглобулина по п. 20, который включает аминокислотную последовательность SEQ ID NO: 28 или SEQ ID NO: 29.
22. Выделенный полипептид легкой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 30 и аминокислотную последовательность CDR2 из SEQ ID NO: 31, где, необязательно, остаток 12 в SEQ ID NO: 30 заменен другим аминокислотным остатком.
23. Выделенный полипептид легкой цепи иммуноглобулина по п. 22, где остаток 12 в SEQ ID NO: 30 заменен другим аминокислотным остатком.
24. Выделенный полипептид легкой цепи иммуноглобулина по п. 23, где остаток 12 в SEQ ID NO: 30 заменен остатком треонина (Т).
25. Выделенный полипептид легкой цепи иммуноглобулина по п. 22, который включает аминокислотную последовательность SEQ ID NO: 32, SEQ ID NO: 33 или SEQ ID NO: 34.
26. Выделенный полипептид легкой цепи иммуноглобулина, который включает аминокислотную последовательность определяющей комплементарность области 1 (CDR) из SEQ ID NO: 35, аминокислотную последовательность CDR2 из SEQ ID NO: 36 и аминокислотную последовательность CDR3 из SEQ ID NO: 37, где необязательно:
(a) остаток 5 в SEQ ID NO: 36 заменен другим аминокислотным остатком, и/или
(b) остаток 4 в SEQ ID NO: 37 заменен другим аминокислотным остатком.
27. Выделенный полипептид легкой цепи иммуноглобулина по п. 26, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 35, аминокислотную последовательность CDR2 из SEQ ID NO: 36 и аминокислотную последовательность CDR3 из SEQ ID NO: 37, за исключением того, что остаток 5 в SEQ ID NO: 36 заменен другим аминокислотным остатком.
28. Выделенный полипептид легкой цепи иммуноглобулина по п. 27, где остаток 5 в SEQ ID NO: 36 заменен остатком лейцина (L).
29. Выделенный полипептид легкой цепи иммуноглобулина по п. 26, который включает аминокислотную последовательность CDR1 из SEQ ID NO: 35, аминокислотную последовательность CDR2 из SEQ ID NO: 36 и аминокислотную последовательность CDR3 из SEQ ID NO: 37, за исключением того, что остаток 4 в SEQ ID NO: 37 заменен другим аминокислотным остатком.
30. Выделенный полипептид легкой цепи иммуноглобулина по п. 29, где остаток 4 в SEQ ID NO: 37 заменен остатком аспарагина (N).
31. Выделенный полипептид легкой цепи иммуноглобулина по п. 26, который включает аминокислотную последовательность SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40 или SEQ ID NO: 41.
32. Выделенный полипептид легкой цепи иммуноглобулина, который включает аминокислотную последовательность, которая по меньшей мере на 90% идентична SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40 или SEQ ID NO: 41.
33. Выделенная или очищенная последовательность нуклеиновой кислоты, кодирующая выделенный полипептид тяжелой цепи иммуноглобулина по любому из пп. 1-19.
34. Выделенная или очищенная последовательность нуклеиновой кислоты, кодирующая выделенный полипептид легкой цепи иммуноглобулина по любому из пп. 20-32.
35. Вектор, включающий выделенную или очищенную молекулу нуклеиновой кислоты по п. 33 или по п. 34.
36. Выделенное белок programmed death-1 (PD-1)-связывающее средство, включающее (а) полипептид тяжелой цепи иммуноглобулина по любому из пп. 1-19 и (b) полипептид легкой цепи иммуноглобулина по любому из пп. 20-32.
37. Выделенное PD-1-связывающее средство по п. 36, которое является антителом, конъюгатом антитела или его антигенсвязывающим фрагментом.
38. Выделенное PD-1-связывающее средство по п. 36, которое является фрагментом антитела, выбранным из F(ab')2, Fab', Fab, Fv, scFv, dsFv, dAb и одноцепочечного связывающего полипептида.
39. Выделенная или очищенная последовательность нуклеиновой кислоты, кодирующая PD-1-связывающее средство по п. 36.
40. Вектор, включающий выделенную или очищенную последовательность нуклеиновой кислоты по п. 39.
41. Выделенная клетка, включающая вектор по п. 40.
42. Композиция, включающая выделенное PD-1-связывающее средство по п. 36, причем связывающее средство может в случае необходимости представлять собой антитело или фрагмент антитела, или кодирующий его вектор, и фармацевтически приемлемый носитель.
43. Способ лечения рака или инфекционного заболевания у млекопитающего, где способ включает введение эффективного количества композиции по п. 42 млекопитающему, имеющему рак или инфекционное заболевание, посредством чего осуществляется лечение рака или инфекционного заболевания у млекопитающего.
44. Способ по п. 43, где композицию вводят млекопитающему, имеющему рак.
45. Способ по п. 44, где рак является меланомой, почечно-клеточным раком, раком легкого, раком мочевого пузыря, раком молочной железы, раком шейки матки, раком толстой кишки, раком желчного пузыря, раком гортани, раком печени, раком щитовидной железы, раком желудка, раком слюнной железы, раком предстательной железы, раком поджелудочной железы или карциномой Меркеля.
46. Способ по п. 43, где композицию вводят млекопитающему, имеющему инфекционное заболевание.
47. Способ по п. 46, где инфекционное заболевание вызвано вирусом или бактерией.
48. Способ по п. 47, где вирусом является вирус иммунодефицита человека (ВИЧ), респираторно-синцитиальный вирус (RSV), вирус гриппа, вирус лихорадки Денге или вирус гепатита В (HBV).
49. Способ по п. 43, где продолжительность полупериода существования PD-1-связывающего средства у млекопитающего составляет от 30 минут до 45 дней.
50. Способ по п. 43, где PD-1-связывающее средство связывает PD-1 с KD от приблизительно 1 пикомоль (пМ) до приблизительно 100 микромоль (мкМ).
51. Способ по п. 43, дополнительно включающий введение млекопитающему композиции, включающей (i) антитело, которое связывается с белком TIM-3, и (ii) фармацевтически приемлемый носитель.
52. Способ по п. 43, дополнительно включающий введение млекопитающему композиции, включающей (i) антитело, которое связывается с белком LAG-3, и (ii) фармацевтически приемлемый носитель.
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| CN107530419B (zh) | 2014-10-31 | 2021-05-18 | 昂考梅德药品有限公司 | 治疗疾病的组合疗法 |
| MA41217A (fr) | 2014-12-19 | 2017-10-24 | Advaxis Inc | Polythérapies ayant des souches de listeria recombinées |
| WO2016100882A1 (en) | 2014-12-19 | 2016-06-23 | Novartis Ag | Combination therapies |
| CA2971734C (en) | 2014-12-22 | 2025-11-18 | Enumeral Biomedical Holdings Inc | Anti-pd-1 antibodies |
| EP3240801B1 (en) | 2014-12-31 | 2021-01-20 | Checkmate Pharmaceuticals, Inc. | Combination tumor immunotherapy |
| CA2968141C (en) | 2015-01-16 | 2020-08-04 | Hsing-Mao CHU | Molecular constructs with targeting and effector elements |
| MA46724A (fr) * | 2016-11-01 | 2021-04-21 | Anaptysbio Inc | Anticorps dirigés contre la mort programmée 1 (pd -1) |
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