IP Library › Granted Patent US 12679893

Granted Patent B2

US 12679893 · App. 18/018,863 · Granted Jul 14, 2026

PD-L1 binding agents and uses thereof

Inventors: Bryan Glaser (Madison, WI); Bonnie Hammer (Madison, WI); Seema Kantak (Pacifica, CA)

Assignee: EXELIXIS, INC.

C07K16/2827 C07K2317/24 C07K2317/35 C07K2317/565 C07K2317/567 C07K2317/92

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Quick Facts

Patent No.: US 12679893
App. No.: 18/018,863
Granted: Jul 14, 2026
Kind: B2

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Abstract

The present disclosure provides PD-L1 binding agents (e.g., antibodies, including multispecific antibodies, such as bispecific antibodies) and uses thereof.

Claims (169)

1 . An antibody or fragment thereof that binds to PD-L1 comprising all three heavy chain complementarity determining regions (CDRs) and/er all three light chain CDRs from:

the antibody designated P22 that comprises a VH sequence that is SEQ ID NO:25 and a VL sequence that is SEQ ID NO:26;

the antibody designated P24 that comprises a VH sequence that is SEQ ID NO:51 and a VL sequence that is SEQ ID NO:52; or

the antibody designated P31.2 that comprises a VH sequence that is SEQ ID NO:77 and a VL sequence that is SEQ ID NO:78;

wherein the heavy chain CDRs and the light chain CDRs are determined according to Kabat numbering system, Chothia numbering system, AbM numbering system, Contact numbering system, IMGT numbering system, or Exemplary numbering system.

2 . The antibody or fragment thereof of claim 1 , wherein the antibody comprises:

(i) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:1;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:2; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:3; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:4;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:5; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:6;

(ii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:7;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:8; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:9; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:10;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:6;

(iii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:12;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:2; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:3; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:4;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:5; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:6;

(iv) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:13;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:14; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:15; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:16;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:17;

(v) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:18;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO: 19; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:20; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:21;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:22; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:23; or

(vi) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:1;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:24; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:3; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:4;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:5; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:6.

3 . The antibody or fragment thereof of claim 1 , wherein the antibody comprises:

(i) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:27;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:28; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:29; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:30;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:31; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:32;

(ii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:33;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:34; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:35; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:36;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:32;

(iii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:38;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:28; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:29; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:30;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:31; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:32;

(iv) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:39;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:40; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:41; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:42;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:43;

(v) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:44;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:45; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:46; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:47;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:48; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:49; or

(vi) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:27;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:50; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:29; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:30;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:31; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:32.

4 . The antibody or fragment thereof of claim 1 , wherein the antibody comprises:

(i) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:53;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:54; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:55; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:56;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:57; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:58;

(ii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:59;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:60; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:61; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:62;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:58;

(iii) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:64;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:54; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:55; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:56;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:57; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:58;

(iv) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:65;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:66; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:67; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:68;

(2) a V L CDR2 having the amino acid sequence of SAS; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:69;

(v) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:70;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:71; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:72; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:73;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:74; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:75; or

(vi) (a) a heavy chain variable (V H ) region comprising:

(1) a V H CDR1 having the amino acid sequence of SEQ ID NO:53;

(2) a V H CDR2 having the amino acid sequence of SEQ ID NO:76; and

(3) a V H CDR3 having the amino acid sequence of SEQ ID NO:55; and

(b) a light chain variable (V L ) region comprising:

(1) a V L CDR1 having the amino acid sequence of SEQ ID NO:56;

(2) a V L CDR2 having the amino acid sequence of SEQ ID NO:57; and

(3) a V L CDR3 having the amino acid sequence of SEQ ID NO:58.

5 . The antibody or fragment thereof of claim 1 , wherein the V H region and/or V L region further comprises (i) human framework sequences; and/or (ii) a framework 1 (FR1), a framework 2 (FR2), a framework 3 (FR3) and/or a framework 4 (FR4) sequence.

6 . The antibody or fragment thereof of claim 1 , wherein

(i) the antibody is a monoclonal antibody;

(ii) the antibody is a humanized, human or chimeric antibody;

(iii) the antibody or fragment thereof is a Fab, Fab′, F(ab′) 2 , Fv, scFv, (scFv) 2 , single chain antibody molecule, dual variable region antibody, single variable region antibody, linear antibody, V region, or a multispecific antibody formed from antibody fragments; and/or

(iv) the antibody or fragment thereof is conjugated or recombinantly fused to a diagnostic agent, detectable agent or therapeutic agent.

7 . One or more vectors comprising one or more polynucleotides encoding the antibody or fragment thereof of claim 1 .

8 . A pharmaceutical composition that comprises the antibody or fragment thereof of claim 1 , and a pharmaceutically acceptable carrier.

9 . A method for treating a cancer or a tumor in a subject, for alleviating one or more symptoms associated with a cancer or a tumor in a subject, for decreasing tumor size in a subject with a tumor, for enhancing tumor cell removal in a subject with a tumor, for treating a T cell dysfunctional disease, disorder or condition in a subject, or for enhancing T cell function in a subject, comprising administering to the subject the antibody or fragment thereof of claim 1 .

10 . The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises

a V H comprising the amino acid sequence of SEQ ID NO.25 and a V L comprising the amino acid sequence of SEQ ID NO.26.

11 . One or more polynucleotides encoding the antibody or fragment thereof of claim 1 .

12 . A cell comprising the one or more vectors of claim 7 .

13 . The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:51 and a VL comprising the amino acid sequence of SEQ ID NO:52.

14 . The antibody or fragment thereof of claim 1 , wherein the antibody or fragment thereof comprises a VH comprising the amino acid sequence of SEQ ID NO:77 and a VL comprising the amino acid sequence of SEQ ID NO:78.

15 . The antibody or fragment thereof of claim 6 , wherein the antibody or fragment thereof is conjugated or recombinantly fused to a therapeutic agent, wherein the therapeutic agent is a chemotherapeutic agent or cytotoxin.

16 . The method of claim 9 , wherein the subject is administered one or more therapeutic agents in combination with the antibody or fragment thereof.