WO2016015685A1 - 抗pd-1抗体及其应用 - Google Patents
抗pd-1抗体及其应用 Download PDFInfo
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- WO2016015685A1 WO2016015685A1 PCT/CN2015/088384 CN2015088384W WO2016015685A1 WO 2016015685 A1 WO2016015685 A1 WO 2016015685A1 CN 2015088384 W CN2015088384 W CN 2015088384W WO 2016015685 A1 WO2016015685 A1 WO 2016015685A1
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Definitions
- Immune activation can also be achieved by blocking the co-suppression signaling pathway with antagonists such as programmed cell death protein 1 (PD-1), B7 homolog 1 (B7-H1, also known as PDL1) pathway, and cytotoxic T lymphocytes.
- antagonists such as programmed cell death protein 1 (PD-1), B7 homolog 1 (B7-H1, also known as PDL1) pathway, and cytotoxic T lymphocytes.
- Pathways such as antigen 4 (CTLA4) and B/T lymphocyte attenuator (BTLA).
- the recombinant DNA vector is an expression vector, and a person skilled in the art clones the DNA molecule of the antibody into an expression vector, transforms the host cell, and obtains an antibody by inducing expression.
- the expression vector of the present invention contains the DNA sequence of the heavy chain variable region, the light chain variable region and/or the constant region of the encoded anti-PD-1 antibody.
- two expression vectors separately. One contains a heavy chain variable region and a constant region, and the other contains a light chain variable region and a constant region, and is transfected together with a mammal.
- the expression vector further comprises a promoter and a DNA sequence encoding a secretion signal peptide, and at least one drug resistance gene for screening.
- L-CDR2 SEQ ID No: 13 SEQ ID No: 13 L-CDR3 SEQ ID No: 14 SEQ ID No: 14
- Anti-PD-1BA08-1 and BA08-2 antibodies significantly abolished the inhibitory effect of PD-L1 on IL-2 and IFN- ⁇ production by CD3-stimulated T cells (**p ⁇ 0.01), and their immunopotentiating effect was significantly higher. At MK-3475analog (*p ⁇ 0.05).
Abstract
Description
10F8 | 15H6 | |
H-CDR1 | SEQ ID No:7 | SEQ ID No:9 |
H-CDR2 | SEQ ID No:8 | SEQ ID No:10 |
H-CDR3 | SEQ ID No:11 | SEQ ID No:11 |
10F8 | 15H6 | |
L-CDR1 | SEQ ID No:12 | SEQ ID No:12 |
L-CDR2 | SEQ ID No:13 | SEQ ID No:13 |
L-CDR3 | SEQ ID No:14 | SEQ ID No:14 |
抗体 | ka | kd | KD |
BA08-1 | 1.22E+6 | 3.9E-6 | 4.8E-12 |
BA08-2 | 1.15E+6 | 7.91E-6 | 9.1E-12 |
Claims (13)
- 能够特异性结合PD-1的抗体,其中所述抗体包含重链和轻链,其中(i)所述重链包含分别具有如SEQ ID NO:7、8和11或者9、10和11所示的氨基酸序列的H-CDR1、H-CDR2和H-CDR3;和(ii)所述轻链包含分别具有如SEQ ID NO:12、13和14所示的氨基酸序列的L-CDR1、L-CDR2和L-CDR3。
- 根据权利要求1所述的抗体,其中(i)所述重链包含具有如SEQ ID NO:1、2、4或5所示氨基酸序列的重链可变区;并且(ii)所述轻链包含具有如SEQ ID NO:3或6所示氨基酸序列的轻链可变区。
- 根据权利要求1所述的抗体,其中(i)所述重链包含具有如SEQ ID NO:4或5所示氨基酸序列的重链可变区;并且(ii)所述轻链包含具有如SEQ ID NO:6所示氨基酸序列的轻链可变区。
- 根据权利要求1所述的抗体,其中所述抗体选自10F8、15H6、BA08-1和BA08-2。
- 分离的多核苷酸,其编码根据前述权利要求任一项所述的抗体。
- 分离的多核苷酸的组合,其包括:编码根据权利要求1-4中任一项所述抗体之轻链的多核苷酸和编码根据权利要求1-4中任一项所述抗体之重链的多核苷酸。
- 表达载体,其包含根据权利要求5的多核苷酸或者根据权利要求6的多核苷酸的组合,所述多核苷酸与允许其所编码的多肽在宿主细胞或无细胞表达***中表达的调节序列有效连接。
- 药物组合物,其包含权利要求1至4中任一项的抗体,以及可药用载体。
- 用于在有需要的对象中治疗或预防癌症或感染性疾病的方法,其包括将权利要求1至4中任一项的抗体、权利要求5的多核苷酸、权利要求6的多核苷酸组合、权利要求7的表达载体和/或权利要求8的药物组合物施用给所述对象。
- 根据权利要求9的方法,其中所述癌症为肺癌或黑素瘤,所述感染性疾病为HIV感染或乙型肝炎病毒感染。
- 用于在有需要的对象中增强T细胞免疫应答的方法,其包括将权利要求1至4中任一项的抗体、权利要求5的多核苷酸、权利要求6的多核苷酸组合、权利要求7的表达载体和/或权利要求8的药物组合物施用给所述对象。
- 根据权利要求11的方法,其中增强T细胞免疫应答包括增强T细胞的细胞因子产生,优选地所述细胞因子包括IL-2和/或IFN-γ。
- 根据权利要求11的方法,其中所述方法还包括将抗CD3抗体施用给所述对象。
Priority Applications (8)
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AU2015295946A AU2015295946B2 (en) | 2014-07-30 | 2015-08-28 | Anti-PD-1 antibody and use thereof |
US15/328,462 US10414821B2 (en) | 2014-07-30 | 2015-08-28 | Anti-PD-1 antibody and use thereof |
EP15826387.1A EP3176180B1 (en) | 2014-07-30 | 2015-08-28 | Anti-pd-1 antibody and use thereof |
BR112017000664A BR112017000664A2 (pt) | 2014-07-30 | 2015-08-28 | anticorpo anti-pd-1 e seu uso |
KR1020177002113A KR102540601B1 (ko) | 2014-07-30 | 2015-08-28 | 항-pd-1 항체 및 이의 용도 |
CA2955541A CA2955541C (en) | 2014-07-30 | 2015-08-28 | Anti-pd-1 antibody and use thereof |
RU2017102399A RU2661678C1 (ru) | 2014-07-30 | 2015-08-28 | Антитело против белка запрограммированной смерти клетки 1 (pd-1) и его применение |
JP2017505240A JP6654186B2 (ja) | 2014-07-30 | 2015-08-28 | 抗pd−1抗体およびその用途 |
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CN201410369300.7A CN105330740B (zh) | 2014-07-30 | 2014-07-30 | 抗pd-1抗体及其应用 |
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US (1) | US10414821B2 (zh) |
EP (1) | EP3176180B1 (zh) |
JP (1) | JP6654186B2 (zh) |
KR (1) | KR102540601B1 (zh) |
CN (1) | CN105330740B (zh) |
AU (1) | AU2015295946B2 (zh) |
BR (1) | BR112017000664A2 (zh) |
CA (1) | CA2955541C (zh) |
RU (1) | RU2661678C1 (zh) |
WO (1) | WO2016015685A1 (zh) |
Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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US10414821B2 (en) | 2019-09-17 |
EP3176180A1 (en) | 2017-06-07 |
CN105330740B (zh) | 2018-08-17 |
JP6654186B2 (ja) | 2020-02-26 |
CA2955541C (en) | 2023-06-27 |
AU2015295946B2 (en) | 2020-06-25 |
CA2955541A1 (en) | 2016-02-04 |
KR20180035728A (ko) | 2018-04-06 |
US20170210806A1 (en) | 2017-07-27 |
KR102540601B1 (ko) | 2023-06-07 |
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CN105330740A (zh) | 2016-02-17 |
RU2661678C1 (ru) | 2018-07-18 |
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