IP Library › Granted Patent US 12,404,336
Granted Patent B2
US 12,404,336 · App. 18/306,562 · Granted Sep 2, 2025

Bispecific antagonist comprising a LAG-3 binding domain

Inventors: Jackie Sheng (Thousand Oaks, CA); Margaret Karow (Santa Rosa Valley, CA); Wei Zhang (Thousand Oaks, CA)
Assignee: GENSUN BIOPHARMA, INC.
C07K16/2863A61P35/00C07K14/00C07K14/71C07K16/22C07K16/2803C07K16/2818C07K16/2827C07K16/468A61K2039/505C07K2317/31C07K2317/565C07K2317/622C07K2317/64C07K2317/76C07K2317/92C07K2318/10C07K2319/30C07K2319/32
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Quick Facts
Patent No.
US 12,404,336
App. No.
18/306,562
Granted
Sep 2, 2025
Kind
B2
Abstract

Antitumor antagonists that bind specifically to immune checkpoint regulator are disclosed. Also disclosed is a method of treating proliferative disorders with the anti-tumor antagonists.

Claims (29)

1. A polynucleotide encoding a bispecific antagonist, wherein the bispecific antagonist comprises a first targeting domain and a second targeting domain:

wherein the first targeting domain binds specifically to human LAG-3 and comprises:

(1) an immunoglobulin HCVR comprising three HCDRs: HCDR1, HCDR2 and HCDR3, wherein the HCDR 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 163, 166 and 169, wherein the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 164, 167 and 170, and wherein the HCDR3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 165, 168 and 171; and

(2) an immunoglobulin LCVR comprising three LCDRs: LCDR1, LCDR2 and LCDR3, wherein the LCD R 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 172, 175 and 177, wherein the LCDR 2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 173 and 178, and wherein the LCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS; 174, 176 and 179.

2. The polynucleotide of claim 1 , wherein the second targeting domain of the bispecific antagonist binds specifically to human TIGIT.

3. The polynucleotide of claim 2 , wherein the second targeting domain the bispecific antagonist comprises:

(1) an immunoglobulin HCVR comprising three HCDRs: HCDR1, HCDR2 and HCDR3, wherein the HCDR 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 1, 6, 11, 15, 17, 20 and 23, wherein the HCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 2, 4, 7, 9, 12, 13, 16, 18, 21 and 24, and wherein the HCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 3, 5, 8, 10, 14, 19, 22 and 25; and

(2) an immunoglobulin LCVR comprising three LCDRs: LCDR1, LCDR2 and LCDR3, wherein the LCD R 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 26, 29, 31, 33, 35, 39, 42 and 45, wherein the LCDR 2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 27, 30, 36, 37, 40, 43 and 46, and wherein the LCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 28, 32, 34, 38, 41, 44 and 47.

4. The polynucleotide of claim 3 , wherein the second targeting domain the bispecific antagonist comprises an HCDR 1 comprising the amino acid sequence of SEQ ID NO:23, an HCDR2 comprising the amino acid sequence of SEQ ID NO:24, an HCDR 3 comprising the amino acid sequence of SEQ ID NO:25, an LCDR 1 comprising the amino acid sequence of SEQ ID NO:45, an LCDR2 comprising the amino acid sequence of SEQ ID NO:46, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:47.

5. The polynucleotide of claim 4 , wherein the second targeting domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 66 and a light chain variable region comprising the amino acid sequence of SEQ ID NO:67.

6. The polynucleotide of claim 1 , wherein the second targeting domain binds specifically to human PD-1.

7. The polynucleotide of claim 6 , wherein the second targeting domain comprises:

(1) an immunoglobulin HCVR comprising three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3, wherein the HCDR1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 68, 71, 74, 76 and 79, wherein the HCDR 2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 69, 72, 77 and 80, and wherein the HCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 70, 73, 75, 78 and 81; and

(2) an immunoglobulin LCVR comprising three complementarity determining regions (LCDRs): LCDR1, LCDR 2 and LCDR3, wherein the LCDR 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 82, 85, 88, 89, 90 and 93, wherein the LCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 83, 86.91 and 94, and wherein the LCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 84, 87, 92 and 95.

8. The polynucleotide of claim 7 , wherein the second targeting domain comprises an HCDR 1 comprising the amino acid sequence of SEQ ID NO:76, an HCDR2 comprising the amino acid sequence oaf SEQ ID NO:77, an HCDR 3 comprising the amino acid sequence of SEQ ID NO:78, a LCDR 1 comprising the amino acid sequence of SEQ ID NO: 90, a LCDR 2 comprising the amino acid sequence of SEQ ID NO:91, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:92.

9. The polynucleotide of claim 8 , wherein the second targeting domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 104 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 105.

10. The polynucleotide of claim 7 , wherein the second targeting domain comprises an HCDR 1 comprising the amino acid sequence of SEQ ID NO:79, an HCDR2 comprising the amino acid sequence of SEQ ID NO: 80, an HCDR3 comprising the amino acid sequence of SEQ ID NO:81, a LCDR 1 comprising the amino acid sequence of SEQ ID NO: 93, a LCDR 2 comprising the amino acid sequence of SEQ ID NO;94, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:95.

11. The polynucleotide of claim 10 , wherein the second targeting domain comprises a heavy chain variable region comprising the amino acid sequence f SEQ ID NO: 106 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 107.

12. The polynucleotide of claim 1 , wherein the second targeting domain binds specifically to human PD-L1.

13. The polynucleotide of claim 12 , wherein the second targeting domain comprises:

(1) an immunoglobulin HCVR comprising three complementarity determining regions (HCDRs): HCDR1, HCDR2 and HCDR3, wherein the HCDR 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 108, 111, 117 and 120, wherein the HCDR 2 comprises an amino acid sequence selected from the group consisting SEQ ID NOS: 109, 112, 114, 116, 118, 121 and 125, and wherein the HCDR 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 110, 113, 115, 119 and 122; and

(2) an immunoglobulin LCVR comprising three LCDRs: LCDR1, LCDR2 and LCDR3, wherein the LCD R 1 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 123, 126, 130, 133 and 136, wherein the LCDR2 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 126, 127, 131, 134 and 137, and wherein the LCD R 3 comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 125, 128, 129, 132, 135 and 138.

14. The polynucleotide of claim 13 , wherein the second targeting domain comprises an HCDR 1 comprising the amino acid sequence of SEQ ID NO:111, an HCDR2 comprising the amino acid sequence of SEQ ID NO:114, an HCDR3 comprising the amino acid sequence of SEQ ID NO:115, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 123, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 124, and a LCDR3 comprising the amino acid sequence of SEQ ID NO:125.

15. The polynucleotide of claim 14 , wherein the second targeting domain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 153 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 154.

16. An expression vector, comprising the polynucleotide of claim 1 .

17. The expression vector of claim 16 , wherein the expression vector is a non-viral vector.

18. The expression vector of claim 16 , wherein the expression vector is a viral vector.

19. A method of treating a cell proliferative disorder in a subject, comprising: administering to a subject in need thereof an effective amount of the polynucleotide of claim 1 .

20. A method of treating a cell proliferative disorder in a subject, comprising: administering to a subject in need thereof an effective amount of the expression vector of claim 16 .

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 Jul 2, 2025
From: SHENG, JACKIE; KAROW, MARGARET; ZHANG, WEI
To: GENSUN BIOPHARMA, INC.
Reel/Frame 071588/0373 →
Continuity (5)
Continuation 16795804 · Feb 20, 2020
Continuation 16457421 · Jun 28, 2019
Provisional Application 62823989 · Mar 26, 2019
Provisional Application 62691658 · Jun 29, 2018
Related Publication 20230331857A1 · Oct 19, 2023
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