IP Library › Granted Patent US 12,350,333
Granted Patent B2
US 12,350,333 · App. 18/053,878 · Granted Jul 8, 2025

Checkpoint regulator antagonists

Inventors: Jackie Z. Sheng (Thousand Oaks, CA); Bo Liu (Thousand Oaks, CA)
Assignee: Gensun Biopharma Inc.
A61K39/39558A61K38/1774A61K39/0011A61P35/00C07K16/2803C07K16/2818A61K2039/507C07K2317/31C07K2317/33C07K2317/74C07K2317/76C07K2317/92
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Quick Facts
Patent No.
US 12,350,333
App. No.
18/053,878
Granted
Jul 8, 2025
Kind
B2
Abstract

Checkpoint regulator antagonists that bind specifically to TIGIT, PD-1 and/or PD-L1 are disclosed. Also disclosed are methods of making and using the checkpoint regulator inhibitors, including monospecific, bispecific and trispecific checkpoint regulator antagonists thereof.

Claims (92)

1. An antibody, or an antigen-binding portion thereof, comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 76, 79, 85 and 88,

wherein HCDR2 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 77, 80, 82, 84, 86 and 89, and

wherein HCDR3 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 78, 81, 83, 87 and 90; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 91, 94, 98, 101 and 104,

wherein LCDR2 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 92, 95, 99, 102 and 105, and

wherein LCDR3 has an amino acid sequence selected from the group consisting of SEQ ID NOS: 93, 96, 97, 100, 103 and 106, and

wherein the antibody, or the antigen-binding portion thereof, binds specifically to human PD-L1.

2. A bispecific checkpoint regulator antagonist, comprising an antigen binding domain comprising the antigen-binding portion of the antibody of claim 1 .

3. A nucleic acid encoding the bispecific checkpoint regulator antagonist of claim 2 .

4. An expression vector comprising the nucleic acid of claim 3 .

5. A nucleic acid encoding the antibody, or an antigen-binding portion thereof, of claim 1 .

6. An expression vector comprising the nucleic acid of claim 5 .

7. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:76,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:77, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:78; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:91,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:92, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:93.

8. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:79,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:80, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:81; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:94,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:95, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:96.

9. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:78,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:79, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:84; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:92,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:94, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:96.

10. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:78,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:79, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:84; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:92,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:94, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:97.

11. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:85,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:86, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:87; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:98,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:99, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:100.

12. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:88,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:89, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:90; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:101,

wherein LCDR2 has the amino acid sequence of SEQ ID NO: 102, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:103.

13. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:88,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:89, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:90; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:104,

wherein LCDR2 has the amino acid sequence of SEQ ID NO: 105, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:106.

14. The antibody, or an antigen-binding portion thereof, of claim 1 , comprising:

(1) a heavy chain variable region, wherein the heavy chain variable region comprises three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3,

wherein HCDR1 has the amino acid sequence of SEQ ID NO:79,

wherein HCDR2 has the amino acid sequence of SEQ ID NO:82, and

wherein HCDR3 has the amino acid sequence of SEQ ID NO:83; and

(2) a light chain variable region, wherein the light chain variable region comprises three complementarity determining regions (LCDRs): LCDR1, LCDR2 and LCDR3,

wherein LCDR1 has the amino acid sequence of SEQ ID NO:91,

wherein LCDR2 has the amino acid sequence of SEQ ID NO:92, and

wherein LCDR3 has the amino acid sequence of SEQ ID NO:93.

15. An antibody, or an antigen-binding portion thereof, comprising:

(1) a heavy chain variable region having an amino acid sequence selected from the group consisting of SEQ ID NOS: 139, 141, 143, 145, 147, 149, 151 and 153; and

(2) a light chain variable region having an amino acid sequence sequence selected from the group consisting of SEQ ID NOS: 140, 142, 144, 146, 148, 150, 152 and 154,

wherein the antibody, or the antigen-binding portion thereof, binds specifically to human PD-L1.

16. A bispecific checkpoint regulator antagonist, comprising an antigen binding domain comprising the antigen-binding portion of the antibody of claim 15 .

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2025
From: GENSUN BIOPHARMA INC.
To: ZELGEN HOLDINGS LIMITED
Reel/Frame 073225/0789 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 16, 2025
From: ZELGEN HOLDINGS LIMITED
To: SUZHOU ZELGEN BIOPHARMACEUTICALS CO. LTD.
Reel/Frame 073226/0963 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2025
From: SHENG, JACKIE Z.; LIU, BO; LOUCKS, EMILY
To: GENSUN BIOPHARMA INC
Reel/Frame 071280/0921 →
Continuity (4)
Continuation 16696253 · Nov 26, 2019
Continuation 15858963 · Dec 29, 2017
Provisional Application 62442642 · Jan 5, 2017
Related Publication 20230293684A1 · Sep 21, 2023
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