Anti-PD-1 antibodies
AssigneeShanghai Henlius Biotech, Inc.
InventorsWeidong Jiang, Pei-Hua Lin, Chi-Ling Tseng
Life of this patent
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Abstract
Provided are anti-PD-1 antibodies, and antigen binding fragments thereof. Also provided are isolated nucleic acid molecules that encode the anti-PD-1 antibodies or antigen binding fragments thereof, related expression vectors, and host cells. Provided are methods of making anti-PD-1 antibodies, and antigen binding fragments thereof. Also provided are related pharmaceutical compositions and methods of their use to treat subjects. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.
Claims18
An anti-PD-1 antibody comprising an amino acid sequence selected from the group consisting of:
- (a) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTTAVA (SEQ ID NO:9);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising:
- (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDF (SEQ ID NO:14);
- (b) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASTDVTTAVA (SEQ ID NO:15);
- (2) a CDR-L2 comprising the amino acid sequence WASLRHT (SEQ ID NO:16);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYGIPWT (SEQ ID NO:17), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FRFSNYGMS (SEQ ID NO:18);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNAY (SEQ ID NO:19);
- and (3) a CDR-H3 comprising the amino acid sequence TSYYYGIDF (SEQ ID NO:20);
- (c) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KAKQDVTTAVA (SEQ ID NO:21);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYWIPWT (SEQ ID NO:22), and a heavy chain variable (VH) domain sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDL (SEQ ID NO:23);
- and
- (d) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTNAVA (SEQ ID NO:24);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence SSYYYGIDL (SEQ ID NO:25).
A composition comprising an anti-PD-1 antibody and a pharmaceutically acceptable carrier, wherein the anti-PD-1 antibody comprises:
- (a) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTTAVA (SEQ ID NO:9);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising:
- (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDF (SEQ ID NO:14);
- (b) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASTDVTTAVA (SEQ ID NO:15);
- (2) a CDR-L2 comprising the amino acid sequence WASLRHT (SEQ ID NO:16);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYGIPWT (SEQ ID NO:17), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FRFSNYGMS (SEQ ID NO:18);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNAY (SEQ ID NO:19);
- and (3) a CDR-H3 comprising the amino acid sequence TSYYYGIDF (SEQ ID NO:20);
- (c) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KAKQDVTTAVA (SEQ ID NO:21);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYWIPWT (SEQ ID NO:22), and a heavy chain variable (VH) domain sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDL (SEQ ID NO:23);
- or
- (d) a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTNAVA (SEQ ID NO:24);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence SSYYYGIDL (SEQ ID NO:25).
A method of treating cancer in a subject expressing PD-1, comprising administering to the subject an effective amount of a composition comprising an anti-PD-1 antibody and a pharmaceutically acceptable carrier, wherein the anti-PD-1 antibody comprises:
- a. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTTAVA (SEQ ID NO:9);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising:
- (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDF (SEQ ID NO:14);
- b. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASTDVTTAVA (SEQ ID NO:15);
- (2) a CDR-L2 comprising the amino acid sequence WASLRHT (SEQ ID NO:16);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYGIPWT (SEQ ID NO:17), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FRFSNYGMS (SEQ ID NO:18);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNAY (SEQ ID NO:19);
- and (3) a CDR-H3 comprising the amino acid sequence TSYYYGIDF (SEQ ID NO:20);
- c. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KAKQDVTTAVA (SEQ ID NO:21);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYWIPWT (SEQ ID NO:22), and a heavy chain variable (VH) domain sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDL (SEQ ID NO:23);
- or
- d. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTNAVA (SEQ ID NO:24);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence SSYYYGIDL (SEQ ID NO:25).
A method of detecting a PD-1 protein in a sample from a patient comprising contacting an anti-PD-1 antibody to the sample and detecting the anti-PD-1 antibody bound to the PD-1 protein, wherein the anti-PD-1 antibody comprises:
- a. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTTAVA (SEQ ID NO:9);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising:
- (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDF (SEQ ID NO:14);
- b. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASTDVTTAVA (SEQ ID NO:15);
- (2) a CDR-L2 comprising the amino acid sequence WASLRHT (SEQ ID NO:16);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYGIPWT (SEQ ID NO:17), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FRFSNYGMS (SEQ ID NO:18);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNAY (SEQ ID NO:19);
- and (3) a CDR-H3 comprising the amino acid sequence TSYYYGIDF (SEQ ID NO:20);
- c. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KAKQDVTTAVA (SEQ ID NO:21);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYWIPWT (SEQ ID NO:22), and a heavy chain variable (VH) domain sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence VSYYYGIDL (SEQ ID NO:23);
- or
- d. a light chain variable domain (VL) sequence comprising (1) a CDR-L1 comprising the amino acid sequence KASQDVTNAVA (SEQ ID NO:24);
- (2) a CDR-L2 comprising the amino acid sequence WASTRHT (SEQ ID NO:10);
- and (3) a CDR-L3 comprising the amino acid sequence QQHYTIPWT (SEQ ID NO:11), and a heavy chain variable domain (VH) sequence comprising (1) a CDR-H1 comprising the amino acid sequence FTFSNYGMS (SEQ ID NO:12);
- (2) a CDR-H2 comprising the amino acid sequence TISGGGSNIY (SEQ ID NO:13);
- and (3) a CDR-H3 comprising the amino acid sequence SSYYYGIDL (SEQ ID NO:25).
Dependencies are inferred from the claim text.