RU2011128399A - Антитела к pd-l1 и их применение для усиления функции т-клеток - Google Patents
Антитела к pd-l1 и их применение для усиления функции т-клеток Download PDFInfo
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- RU2011128399A RU2011128399A RU2011128399/10A RU2011128399A RU2011128399A RU 2011128399 A RU2011128399 A RU 2011128399A RU 2011128399/10 A RU2011128399/10 A RU 2011128399/10A RU 2011128399 A RU2011128399 A RU 2011128399A RU 2011128399 A RU2011128399 A RU 2011128399A
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- hvr
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- 102000008096 B7-H1 Antigen Human genes 0.000 title claims 2
- 108010074708 B7-H1 Antigen Proteins 0.000 title claims 2
- 238000005728 strengthening Methods 0.000 title 1
- 229920001184 polypeptide Polymers 0.000 claims abstract 20
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract 20
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract 20
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract 5
- 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 abstract 3
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims 30
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- NFGXHKASABOEEW-UHFFFAOYSA-N 1-methylethyl 11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate Chemical compound COC(C)(C)CCCC(C)CC=CC(C)=CC(=O)OC(C)C NFGXHKASABOEEW-UHFFFAOYSA-N 0.000 claims 6
- 210000001744 T-lymphocyte Anatomy 0.000 claims 6
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- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims 1
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
1. Выделенный полипептид вариабельной области тяжелой цепи, содержащий последовательность HVR-H1, HVR-H2 и HVR-H3, где:(a) последовательность HVR-H1 представляет собой последовательность GFTFSXSWIH (SEQ ID NO:1);(b) последовательность HVR-H2 представляет собой последовательность AWIXPYGGSXYYADSVKG (SEQ ID NO:2);(c) последовательность HVR-H3 представляет собой последовательность RHWPGGFDY (SEQ ID NO:3);и где: Xозначает D или G; Xозначает S или L; Xозначает T или S.2. Полипептид по п.1, в котором Xозначает D; Xозначает S и Xозначает T.3. Полипептид по п.1, дополнительно содержащий каркасные последовательности вариабельной области тяжелой цепи, расположенные между HVR согласно формуле: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4).4. Полипептид по п.3, в котором каркасные последовательности выведены из консенсусных каркасных последовательностей человека.5. Полипептид по п.4, в котором каркасные последовательности представляют собой консенсусный каркас VH подгруппы III.6. Полипептид по п.5, в котором одна или более каркасных последовательностей представляют собой следующие последовательности:HC-FR1 представляет собой EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO:4);HC-FR2 представляет собой WVRQAPGKGLEWV (SEQ ID NO:5);HC-FR3 представляет собой RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR (SEQ ID NO:6);HC-FR4 представляет собой WGQGTLVTVSA (SEQ ID NO:7).7. Выделенный полипептид тяжелой цепи по п.1 в сочетании с вариабельной областью легкой цепи, содержащей HVR-L1, HVR-L2 и HVR-L3, где:(a) последовательность HVR-L1 представляет собой RASQXXXTXXA (SEQ ID NO:8);(b) последовательность HVR-L2 представляет собой SASXLXS (SEQ ID NO:9);(c) последовательность HVR-L3 представляет собой QQXXXXPXT (SEQ ID NO:10);и где: Xозначает D или V; Xозначает V или I; Xозначает S или N; Xозначает A или F; Xозначает V или L; Xозначает F или T; Xозначает Y или A; Xозначает Y, G, F или S; Xозн
Claims (95)
1. Выделенный полипептид вариабельной области тяжелой цепи, содержащий последовательность HVR-H1, HVR-H2 и HVR-H3, где:
(a) последовательность HVR-H1 представляет собой последовательность GFTFSX1SWIH (SEQ ID NO:1);
(b) последовательность HVR-H2 представляет собой последовательность AWIX2PYGGSX3YYADSVKG (SEQ ID NO:2);
(c) последовательность HVR-H3 представляет собой последовательность RHWPGGFDY (SEQ ID NO:3);
и где: X1 означает D или G; X2 означает S или L; X3 означает T или S.
2. Полипептид по п.1, в котором X1 означает D; X2 означает S и X3 означает T.
3. Полипептид по п.1, дополнительно содержащий каркасные последовательности вариабельной области тяжелой цепи, расположенные между HVR согласно формуле: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4).
4. Полипептид по п.3, в котором каркасные последовательности выведены из консенсусных каркасных последовательностей человека.
5. Полипептид по п.4, в котором каркасные последовательности представляют собой консенсусный каркас VH подгруппы III.
6. Полипептид по п.5, в котором одна или более каркасных последовательностей представляют собой следующие последовательности:
HC-FR1 представляет собой EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO:4);
HC-FR2 представляет собой WVRQAPGKGLEWV (SEQ ID NO:5);
HC-FR3 представляет собой RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR (SEQ ID NO:6);
HC-FR4 представляет собой WGQGTLVTVSA (SEQ ID NO:7).
7. Выделенный полипептид тяжелой цепи по п.1 в сочетании с вариабельной областью легкой цепи, содержащей HVR-L1, HVR-L2 и HVR-L3, где:
(a) последовательность HVR-L1 представляет собой RASQX4X5X6TX7X8A (SEQ ID NO:8);
(b) последовательность HVR-L2 представляет собой SASX9LX10S (SEQ ID NO:9);
(c) последовательность HVR-L3 представляет собой QQX11X12X13X14PX15T (SEQ ID NO:10);
и где: X4 означает D или V; X5 означает V или I; X6 означает S или N; X7 означает A или F; X8 означает V или L; X9 означает F или T; X10 означает Y или A; X11 означает Y, G, F или S; X12 означает L, Y, F или W; X13 означает Y, N, A, T, G, F или I; X14 означает H, V, P, T или I; X15 означает A, W, R, P или T.
8. Полипептид по п.7, где X4 означает D; X5 означает V; X6 означает S; X7 означает A; X8 означает V; X9 означает F; X10 означает Y; X11 означает Y; X12 означает L; X13 означает Y; X14 означает H; X15 означает A.
9. Полипептид по п.7, дополнительно содержащий каркасные последовательности вариабельной области легкой цепи, расположенные между HVR согласно формуле: (LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4).
10. Полипептид по п.9, где каркасные последовательности выведены из консенсусных каркасных последовательностей человека.
11. Полипептид по п.10, где каркасные последовательности представляют собой консенсусный каркас VL каппа I.
12. Полипептид по п.11, где одна или более каркасных последовательностей представляют собой следующие последовательности:
LC-FR1 представляет собой DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO:11);
LC-FR2 представляет собой WYQQKPGKAPKLLIY (SEQ ID NO:12);
LC-FR3 представляет собой GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:13);
LC-FR4 представляет собой FGQGTKVEIKR (SEQ ID NO:14).
13. Выделенное антитело к PD-L1 или антигенсвязывающий фрагмент, содержащие последовательность вариабельной области тяжелой цепи и легкой цепи, где:
(a) тяжелая цепь содержит HVR-H1, HVR-H2 и HVR-H3, и где:
(i) последовательность HVR-H1 представляет собой GFTFSX1SWIH (SEQ ID NO:1);
(ii) последовательность HVR-H2 представляет собой AWIX2PYGGSX3YYADSVKG (SEQ ID NO:2);
(iii) последовательность HVR-H3 представляет собой RHWPGGFDY (SEQ ID NO:3);
(b) легкая цепь содержит HVR-L1, HVR-L2 и HVR-L3, и где:
(iv) последовательность HVR-L1 представляет собой RASQX4X5X6TX7X8A (SEQ ID NO:8);
(v) последовательность HVR-L2 представляет собой SASX9LX10S (SEQ ID NO:9);
(vi) последовательность HVR-L3 представляет собой QQX11X12X13X14PX15T (SEQ ID NO:10);
где: X1 означает D или G; X2 означает S или L; X3 означает T или S; X4 может означать D или V; X5 может означать V или I; X6 может означать S или N; X7 может означать A или F; X8 может означать V или L; X9 может означать F или T; X10 может означать Y или A; X11 может означать Y, G, F или S; X12 может означать L, Y, F или W; X13 может означать Y, N, A, T, G, F или I; X14 может означать H, V, P, T или I; X15 может означать A, W, R, P или T.
14. Антитело или фрагмент антитела по п.13, в которых X1 означает D, X2 означает S и X3 означает T.
15. Антитело или фрагмент антитела по п.13, в которых X4=D, X5=V, X6=S, X7=A и X8=V, X9=F и X10=Y, X11=Y, X12=L, X13=Y, X14=H и X15=A.
16. Антитело или фрагмент антитела по п.13, в которых X1=D, X2=S и X3=T, X4=D, X5=V, X6=S, X7=A и X8=V, X9=F и X10=Y, X11=Y, X12=L, X13=Y, X14=H и X15=A.
17. Антитело или фрагмент антитела по любому из пп.13-16, дополнительно содержащие:
(a) каркасные последовательности вариабельной области тяжелой цепи, расположенные между HVR согласно формуле: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4), и
(b) каркасные последовательности вариабельной области легкой цепи, расположенные между HVR согласно формуле: (LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4).
18. Антитело или фрагмент антитела по п.17, в которых каркасные последовательности выведены из консенсусных каркасных последовательностей человека.
19. Антитело или фрагмент антитела по п.18, в которых каркасные последовательности вариабельной области тяжелой цепи представляют собой консенсусный каркас VH подгруппы III.
20. Антитело или фрагмент антитела по п.19, в которых одна или более каркасных последовательностей представляют собой следующие последовательности:
HC-FR1 представляет собой EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO:4);
HC-FR2 представляет собой WVRQAPGKGLEWV (SEQ ID NO:5);
HC-FR3 представляет собой RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR (SEQ ID NO:6);
HC-FR4 представляет собой WGQGTLVTVSA (SEQ ID NO:7).
21. Антитело или фрагмент антитела по п.18, в которых каркасные последовательности вариабельной области легкой цепи представляют собой консенсусный каркас VL каппа I.
22. Антитело или фрагмент антитела по п.21, в которых одна или более каркасных последовательностей представляют собой следующие последовательности:
LC-FR1 представляет собой DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO:11);
LC-FR2 представляет собой WYQQKPGKAPKLLIY (SEQ ID NO:12);
LC-FR3 представляет собой GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:13);
LC-FR4 представляет собой FGQGTKVEIKR (SEQ ID NO:14).
23. Антитело или фрагмент антитела по п.18, в которых:
(a) каркасные последовательности вариабельной области тяжелой цепи представляют собой следующие последовательности:
(i) HC-FR1 представляет собой EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO:4);
(ii) HC-FR2 представляет собой WVRQAPGKGLEWV (SEQ ID NO:5);
(iii) HC-FR3 представляет собой RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR (SEQ ID NO:6);
(iv) HC-FR4 представляет собой WGQGTLVTVSA (SEQ ID NO:7);
(b) каркасные последовательности вариабельной области легкой цепи представляют собой следующие последовательности:
(i) LC-FR1 представляет собой DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO:11);
(ii) LC-FR2 представляет собой WYQQKPGKAPKLLIY (SEQ ID NO:12);
(iii) LC-FR3 представляет собой GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:13);
(iv) LC-FR4 представляет собой FGQGTKVEIKR (SEQ ID NO:14).
24. Антитело или фрагмент антитела по п.23, дополнительно содержащие константную область человека.
25. Антитело или фрагмент антитела по п.24, в которых константная область выбрана из группы, состоящей из IgG1, IgG2, IgG3 и IgG4.
26. Антитело или фрагмент антитела по п.25, в которых константная область получена из IgG1.
27. Антитело или фрагмент антитела по п.23, дополнительно содержащие константную область мыши.
28. Антитело или фрагмент антитела по п.27, в которых константная область выбрана из группы, состоящей из IgG1, IgG2A, IgG2B и IgG3.
29. Антитело или фрагмент антитела по п.28, в которых константная область получена из IgG2A.
30. Антитело или фрагмент антитела по п.25 или 28, обладающие пониженной или минимальной эффекторной функцией.
31. Антитело или фрагмент антитела по п.30, в которых минимальная эффекторная функция является результатом Fc-мутации с утратой эффекторной функции.
32. Антитело или фрагмент антитела по п.31, в которых Fc-мутацией с утратой эффекторной функции является мутация N297A.
33. Антитело или фрагмент антитела по п.31, в которых Fc-мутацией с утратой эффекторной функции является мутация D265A/N297A.
34. Антитело или фрагмент антитела по п.30, в которых минимальная эффекторная функция является результатом отсутствия гликозилирования.
35. Антитело или антигенсвязывающий фрагмент, содержащие последовательность вариабельной области тяжелой цепи и легкой цепи, где:
(a) тяжелая цепь содержит HVR-H1, HVR-H2 и HVR-H3, имеющие, по меньшей мере, 85% суммарную идентичность последовательности с последовательностями GFTFSDSWIH (SEQ ID NO:15), AWISPYGGSTYYADSVKG (SEQ ID NO:16) и RHWPGGFDY (SEQ ID NO:3) соответственно, и
(b) легкая цепь содержит HVR-L1, HVR-L2 и HVR-L3, имеющие, по меньшей мере, 85% суммарную идентичность последовательности с последовательностями RASQDVSTAVA (SEQ ID NO:17), SASFLYS (SEQ ID NO:18) и QQYLYHPAT (SEQ ID NO:19) соответственно.
36. Антитело или фрагмент антитела по п.35, в которых идентичность последовательностей составляет, по меньшей мере, 90%.
37. Антитело или фрагмент антитела по п.36, дополнительно содержащие:
(a) каркасные последовательности вариабельной области тяжелой цепи (VH), расположенные между HVR согласно формуле: (HC-FR1)-(HVR-H1)-(HC-FR2)-(HVR-H2)-(HC-FR3)-(HVR-H3)-(HC-FR4), и
(b) каркасные последовательности вариабельной области легкой цепи (VL), расположенные между HVR согласно формуле: (LC-FR1)-(HVR-L1)-(LC-FR2)-(HVR-L2)-(LC-FR3)-(HVR-L3)-(LC-FR4).
38. Антитело или фрагмент антитела по п.37, дополнительно содержащие каркасную область VH и VL, полученную из консенсусной последовательности человека.
39. Антитело или фрагмент антитела по п.38, в которых каркасная последовательность VH получена из последовательности подгруппы I, II или III согласно Кабату.
40. Антитело или фрагмент антитела по п.39, в которых каркасная последовательность VH представляет собой консенсусную каркасную последовательность подгруппы III согласно Кабату.
41. Антитело или фрагмент антитела по п.40, в которых каркасные последовательности VH представляют собой следующие последовательности:
HC-FR1 представляет собой EVQLVESGGGLVQPGGSLRLSCAAS (SEQ ID NO:4);
HC-FR2 представляет собой WVRQAPGKGLEWV (SEQ ID NO:5);
HC-FR3 представляет собой RFTISADTSKNTAYLQMNSLRAEDTAVYYCAR (SEQ ID NO:6);
HC-FR4 представляет собой WGQGTLVTVSA (SEQ ID NO:7).
42. Антитело или фрагмент антитела по п.38, в которых каркасная последовательность VL получена из последовательности подгруппы каппа I, II, III или IV согласно Кабату.
43. Антитело или фрагмент антитела по п.42, в которых каркасная последовательность VL представляет собой консенсусную каркасную последовательность каппа I согласно Кабату.
44. Антитело или фрагмент антитела по п.43, в которых каркасные последовательности VL представляют собой следующие последовательности:
LC-FR1 представляет собой DIQMTQSPSSLSASVGDRVTITC (SEQ ID NO:11);
LC-FR2 представляет собой WYQQKPGKAPKLLIY (SEQ ID NO:12);
LC-FR3 представляет собой GVPSRFSGSGSGTDFTLTISSLQPEDFATYYC (SEQ ID NO:13);
LC-FR4 представляет собой FGQGTKVEIKR (SEQ ID NO:14).
45. Выделенное антитело к PD-L1 или антигенсвязывающий фрагмент, содержащие последовательность вариабельной области тяжелой цепи и легкой цепи, где:
(a) последовательность тяжелой цепи имеет, по меньшей мере, 85% идентичность последовательности с последовательностью тяжелой цепи:
и
(b) последовательность легкой цепи имеет, по меньшей мере, 85% идентичность последовательности с последовательностью легкой цепи:
46. Антитело или антигенсвязывающий фрагмент по п.45, где идентичность последовательностей составляет, по меньшей мере, 90%.
48. Композиция, содержащая антитело к PD-L1 или антигенсвязывающий фрагмент по любому из пп.13-47 и, по меньшей мере, один фармацевтически приемлемый носитель.
49. Выделенная нуклеиновая кислота, кодирующая полипептид по любому из пп.1-11.
50. Выделенная нуклеиновая кислота, кодирующая последовательность вариабельной области легкой цепи или тяжелой цепи антитела к PD-L1 или антигенсвязывающего фрагмента, где:
(a) тяжелая цепь дополнительно содержит последовательности HVR-H1, HVR-H2 и HVR-H3, имеющие, по меньшей мере, 85% идентичность последовательности с последовательностями GFTFSDSWIH (SEQ ID NO:15), AWISPYGGSTYYADSVKG (SEQ ID NO:16) и RHWPGGFDY (SEQ ID NO:3) соответственно, или
(b) легкая цепь дополнительно содержит последовательности HVR-L1, HVR-L2 и HVR-L3, имеющие, по меньшей мере, 85% идентичность последовательности с последовательностями RASQDVSTAVA (SEQ ID NO:17), SASFLYS (SEQ ID NO:18) и QQYLYHPAT (SEQ ID NO:19) соответственно.
51. Нуклеиновая кислота по п.50, где идентичность последовательностей составляет 90%.
52. Нуклеиновая кислота по п.50, где антитело к PD-L1 дополнительно содержит каркасные области VL и VH, выведенные из консенсусной последовательности человека.
53. Нуклеиновая кислота по п.52, где последовательность VH выведена из последовательности подгруппы I, II или III согласно Кабату.
54. Нуклеиновая кислота по п.52, где последовательность VL выведена из последовательности подгруппы каппа I, II, III или IV согласно Кабату.
55. Нуклеиновая кислота по п.50, где антитело к PD-L1 содержит константную область, выведенную из мышиного антитела.
56. Нуклеиновая кислота по п.50, где антитело к PD-L1 содержит константную область, выведенную из антитела человека.
57. Нуклеиновая кислота по п.56, где константная область получена из IgG1.
58. Нуклеиновая кислота по п.57, имеющая пониженную или минимальную эффекторную функцию.
59. Нуклеиновая кислота по п.58, где минимальная эффекторная функция является результатом Fc-мутации с утратой эффекторной функции.
60. Нуклеиновая кислота по п.59, где Fc-мутацией с утратой эффекторной функции является мутация N297A.
61. Вектор, содержащий нуклеиновую кислоту по любому из пп.49-60.
62. Клетка-хозяин, содержащая вектор по п.61.
63. Клетка-хозяин по п.62, которая является эукариотической клеткой.
64. Клетка-хозяин по п.63, которая является клеткой млекопитающего.
65. Клетка-хозяин по п.64, которая является клеткой яичника китайского хомячка (CHO).
66. Клетка-хозяин по п.62, которая является прокариотической клеткой.
67. Клетка-хозяин по п.66, которая является клеткой E. coli.
68. Способ получения антитела к PD-L1, включающий культивирование клетки-хозяина по любому из пп.62-67 в условиях, подходящих для экспрессии вектора, кодирующего антитело к PD-L1 или антигенсвязывающий фрагмент, и извлечение антитела или фрагмента.
69. Изделие производства, содержащее композицию по п.48 и, по меньшей мере, одну молекулу BNCA.
70. Изделие производства, содержащее композицию по п.48 и, по меньшей мере, одно химиотерапевтическое средство.
71. Изделие производства по п.70, в котором химиотерапевтическим средством является гемцитабин.
72. Изделие производства, содержащее композицию по п.48 и, по меньшей мере, один агонист позитивной костимулирующей молекулы.
73. Изделие производства по п.72, дополнительно содержащее антагонист BNCA.
74. Изделие производства, содержащее композицию по п.48 и, по меньшей мере, один антибиотик.
75. Изделие производства по п.74, в котором антибиотик является противовирусным средством.
76. Изделие производства по п.75, в котором противовирусным средством является ингибитор обратной транскриптазы.
77. Изделие производства по п.76, в котором ингибитор обратной транскриптазы является ингибитором полимеразы.
78. Изделие производства по п.75, в котором противовирусным средством является ингибитор протеаз.
79. Изделие производства, содержащее композицию по п.48 и, по меньшей мере, одну вакцину.
80. Способ усиления функции T-клеток, включающий введение эффективного количества композиции по п.48 к дисфункциональным T-клеткам.
81. Способ лечения T-клеточного дисфункционального расстройства, включающий введение терапевтически эффективного количества композиции по п.48 пациенту, страдающему T-клеточным дисфункциональным расстройством.
82. Способ по п.81, где T-клеточным дисфункциональным расстройством является инфекция.
83. Способ по п.82, где инфекция является хронической.
84. Способ по п.81, где T-клеточным дисфункциональным расстройством является опухолевый иммунитет.
85. Способ по п.83, где хроническая инфекция является персистирующей.
86. Способ по п.83, где хроническая инфекция является латентной.
87. Способ по п.83, где хроническая инфекция является медленной.
88. Способ по п.82, где инфекция вызвана патогеном, выбранным из группы, состоящей из бактерий, вирусов, грибов и простейших.
89. Способ по п.88, где патогеном является бактерия, и способ дополнительно включает введение антибактериального средства.
90. Способ по п.88, где патогеном является вирус, и способ дополнительно включает введение противовирусного средства.
91. Способ по п.88, где патогеном является гриб, и способ дополнительно включает введение противогрибкового средства.
92. Способ по п.88, где патогеном является простейшее, и способ дополнительно включает введение противопротозойного средства.
93. Способ по п.88, дополнительно включающий введение вакцины.
94. Способ по п.84, где способ дополнительно включает применение схемы лечения, выбранной из группы, состоящей из: лучевой терапии, химиотерапии, целенаправленной терапии, иммунотерапии, гормональной терапии, ингибирования ангиогенеза и паллиативного лечения.
95. Способ по п.84, где опухолевый иммунитет возникает в результате наличия злокачественной опухоли, выбранной из группы, состоящей из: рака молочной железы, легкого, ободочной кишки, яичника, меланомы, рака мочевого пузыря, почки, печени, слюнных желез, желудка, глиом, рака щитовидной железы, вилочковой железы, эпителиального рака, рака головы и шеи, рака желудка и поджелудочной железы.
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RU2715038C2 (ru) * | 2014-07-11 | 2020-02-21 | Дженентек, Инк. | Антитела анти-pd-l1 и способы их диагностического применения |
RU2742373C2 (ru) * | 2015-03-13 | 2021-02-05 | Эктив Байотек Аб | Комбинация тасквинимода или его фармацевтически приемлемой соли и ингибитора pd-1 и/или pd-l1 для применения в качестве лекарственного средства |
RU2715595C2 (ru) * | 2015-07-31 | 2020-03-02 | 3Д Медисинес (Бейджинг) Ко., Лтд. | Однодоменное антитело и его производные белки к лиганду-1 белка программируемой смерти клеток (pdli) |
RU2736151C2 (ru) * | 2015-08-06 | 2020-11-12 | Уси Байолоджикс (Шанхай) Ко. Лтд. | Новые антитела против pd-l1 |
US10981995B2 (en) | 2015-08-06 | 2021-04-20 | Wuxi Biologies Ireland Limited | Anti-PD-L1 antibodies |
RU2665790C1 (ru) * | 2017-04-17 | 2018-09-04 | Закрытое Акционерное Общество "Биокад" | Моноклональное антитело к pd-l1 |
WO2018194496A3 (ru) * | 2017-04-17 | 2019-01-10 | Закрытое Акционерное Общество "Биокад" | Моноклональное антитело к pd-l1 |
US11236167B2 (en) | 2017-04-17 | 2022-02-01 | Joint Stock Company “Biocad” | Monoclonal antibody to PD-L1 |
RU2779652C2 (ru) * | 2017-10-03 | 2022-09-12 | Акционерное общество "БИОКАД" | АНТИТЕЛА, СПЕЦИФИЧНЫЕ К CD47 и PD-L1 |
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