ANTI-PD-L1 ANTIBODIES AND THEIR USE TO ENHANCE T-CELL FUNCTION
First Claim
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1. An isolated heavy chain variable region polypeptide comprising an HVR-H1, HVR-H2 and HVR-H3 sequence, wherein:
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Abstract
The present application relates to anti-PD-L1 antibodies, nucleic acid encoding the same, therapeutic compositions thereof, and their use enhance T-cell function to upregulate cell-mediated immune responses and for the treatment of T cell dysfunctional disorders, including infection (e.g., acute and chronic) and tumor immunity.
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Citations
95 Claims
- 1. An isolated heavy chain variable region polypeptide comprising an HVR-H1, HVR-H2 and HVR-H3 sequence, wherein:
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13. An isolated anti-PD-L1 antibody or antigen binding fragment comprising a heavy chain and a light chain variable region sequence, wherein:
(a) the heavy chain comprises an HVR-H1, HVR-H2 and HVR-H3, wherein further; - View Dependent Claims (14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 48, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95)
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35. An antibody or antigen binding fragment comprising a heavy chain and a light chain variable region sequence, wherein:
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(a) the heavy chain comprises an HVR-H1, HVR-H2 and an HVR-H3, having at least 85% overall sequence identity to GFTFSDSWIH (SEQ ID NO;
15), AWISPYGGSTYYADSVKG (SEQ ID NO;
16) and RHWPGGFDY (SEQ ID NO;
3), respectively, and(b) the light chain comprises an HVR-L1, HVR-L2 and an HVR-L3, having at least 85% overall sequence identity to RASQDVSTAVA (SEQ ID NO;
17), SASFLYS (SEQ ID NO;
18) and QQYLYHPAT (SEQ ID NO;
19), respectively. - View Dependent Claims (36, 37, 38, 39, 40, 41, 42, 43, 44)
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45. An isolated anti-PD-L1 antibody or antigen binding fragment comprising a heavy chain and a light chain variable region sequence, wherein:
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(a) the heavy chain sequence has at least 85% sequence identity to the heavy chain sequence;
EVQLVESGGGLVQPGGSLRLSCAASGFTFSDSWIHWVRQAPG KGLEWVAWISPYGGSTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDT AVYYCARRHWPGGFDYWGQGTLVTVSA (SEQ ID NO;
20), and(b) the light chain sequence has at least 85% sequence identity to the light chain sequence;
DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGK APKWYSASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQYLYH PATFGQGTKVEIKR (SEQ ID NO;
21). - View Dependent Claims (46)
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47. An isolated anti-PD-L1 antibody or antigen binding fragment comprising a heavy chain and light chain variable region sequence, wherein:
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(a) the heavy chain comprises the sequence;
EVQLVESGGGLVQPGGSLRLS CAASGFTFSDSWIHWVRQAPGKGLEWVAWISPYGGSTYYADSVKGRFTI SADTSKNTAYLQMNSLRAEDTAVYYCARRHWPGGFDYWGQGTLVTVS A (SEQ ID NO;
20), and(b) the light chain comprises the sequence;
DIQMTQSPSSLSASVGDRVTITC RASQDVSTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSGSGTDFTL TISSLQPEDFATYYCQQYLYHPATFGQGTKVEIKR (SEQ ID NO;
21).
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50. An isolated nucleic acid encoding a light chain or a heavy chain variable sequence of an anti-PD-L1 antibody or antigen binding fragment, wherein:
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(a) the heavy chain further comprises and HVR-H1, HVR-H2 and an HVR-H3 sequence having at least 85% sequence identity to GFTFSDSWIH (SEQ ID NO;
15), AWISPYGGSTYYADSVKG (SEQ ID NO;
16) and RHWPGGFDY (SEQ ID NO;
3), respectively, or(b) the light chain further comprises an HVR-L1, HVR-L2 and an HVR-L3 sequence having at least 85% sequence identity to RASQDVSTAVA (SEQ ID NO;
17), SASFLYS (SEQ ID NO;
18) and QQYLYHPAT (SEQ ID NO;
19), respectively. - View Dependent Claims (51, 52, 53, 54, 55, 56, 57, 58, 59, 60)
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Specification