IP Library › Granted Patent US 12,433,952
Granted Patent B2
US 12,433,952 · App. 18/677,564 · Granted Oct 7, 2025

Antibody-drug conjugates targeting folate receptor alpha and methods of use

Inventors: James R. Rich (Vancouver, CA); Stuart Daniel Barnscher (Vancouver, CA); Mark Edmund Petersen (Vancouver, CA); Raffaele Colombo (Vancouver, CA); Michael G. Brant (Vancouver, CA); Manuel Michel Auguste Lasalle (Vancouver, CA); Rupert H. Davies (Seattle, WA); Dunja Urosev (Vancouver, CA); Sukhbir Singh Kang (Vancouver, CA); Peter Wing Yiu Chan (Vancouver, CA); Samir Das (Vancouver, CA); Andrea Hernandez Rojas (Vancouver, CA); Robert William Gene (Vancouver, CA); Ada G. H. Young (Vancouver, CA); Samuel Oliver Lawn (Vancouver, CA); Danny Chui (Vancouver, CA); Duncan Browman (Vancouver, CA); Brandon Clavette (Vancouver, CA)
Assignee: Zymeworks BC Inc.
A61K47/68037A61K47/6849A61K47/6889A61P35/00C07K16/28
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Quick Facts
Patent No.
US 12,433,952
App. No.
18/677,564
Granted
Oct 7, 2025
Kind
B2
Abstract

Antibody-drug conjugates (ADCs) comprising an antibody construct that binds specifically binds human folate receptor alpha (FRα) (an anti-FRα antibody construct) conjugated to a camptothecin analogue of Formula (I). The ADCs are useful as therapeutics, in particular in the treatment of cancer.

Claims (51)

1. An antibody-drug conjugate having a structure:

wherein:

T is an anti-folate receptor alpha (anti-FRα) antibody construct comprising an antigen-binding domain operably linked to an IgG Fc region, the antigen-binding domain comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3) and three light chain CDRs (LCDR1, LCDR2, and LCDR3), wherein:

(i) the HCDR1 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 20, 23, 26, 28 or 31; the HCDR2 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 21, 24, 29, 32 or 51, and the HCDR3 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 22, 25 or 30, and

(ii) the LCDR1 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 40, 45 or 65; the LCDR2 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 41, 44 or 46, and the LCDR3 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 42 or 47,

and wherein n is between about 4 and about 8.

2. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises:

(i) the HCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 20; the HCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 21, and the HCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NOs: 22, and

(ii) the LCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 40; the LCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 41, and the LCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 42.

3. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises:

(i) the HCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 26; the HCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 51, and the HCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NOs: 25, and

(ii) the LCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 65; the LCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 44, and the LCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 42.

4. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises:

(i) the HCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 23; the HCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 24, and the HCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NOs: 25, and

(ii) the LCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 65; the LCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 44, and the LCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 42.

5. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises:

(i) the HCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 31; the HCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 32, and the HCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NOs: 25, and

(ii) the LCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 65; the LCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 44, and the LCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 42.

6. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises:

(i) the HCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 28; the HCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 29, and the HCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NOs: 30, and

(ii) the LCDR1 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 45; the LCDR2 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 46, and the LCDR3 amino acid sequence comprising a sequence as set forth in SEQ ID NO: 47.

7. The antibody-drug conjugate according to claim 1 , wherein n is about 8.

8. The antibody-drug conjugate according to claim 2 , wherein n is about 8.

9. The antibody-drug conjugate according to claim 3 , wherein n is about 8.

10. The antibody-drug conjugate according to claim 4 , wherein n is about 8.

11. The antibody-drug conjugate according to claim 5 , wherein n is about 8.

12. The antibody-drug conjugate according to claim 6 , wherein n is about 8.

13. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises a light chain variable domain (VL) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain (VH) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 50.

14. The antibody-drug conjugate according to claim 1 , wherein the antigen-binding domain comprises a light chain variable domain (VL) amino acid sequence consisting of a sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain (VH) amino acid sequence consisting of a sequence as set forth in SEQ ID NO: 50.

15. The antibody-drug conjugate according to claim 1 , wherein the IgG Fc region is an IgG1 Fc region or a human IgG1 Fc region.

16. The antibody-drug conjugate according to claim 13 , wherein the IgG Fc region is an IgG1 Fc region or a human IgG1 Fc region.

17. The antibody-drug conjugate according to claim 1 , wherein the anti-FRαantibody construct comprises two heavy chains and two light chains, wherein each heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 142 or 157 and each light chain comprises an amino acid sequence as set forth in SEQ ID NO: 62.

18. The antibody-drug conjugate according to claim 1 , wherein the anti-FRαantibody construct comprises two heavy chains and two light chains, wherein each heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 142 and each light chain comprises an amino acid sequence as set forth in SEQ ID NO: 62.

19. The antibody-drug conjugate according to claim 18 , wherein n is about 8.

20. An antibody-drug conjugate having a structure:

wherein:

T is an anti-folate receptor alpha (anti-FRα) antibody construct comprising two antigen-binding domains operably linked to an IgG Fc region, each of the antigen-binding domains comprising a light chain variable domain (VL) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain (VH) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 50,

wherein the IgG Fc region is a human IgG1 Fc region,

and wherein n is about 8.

21. The antibody-drug conjugate according to claim 20 , wherein the anti-FRαantibody construct comprises two heavy chains and two light chains, wherein each heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 142 or 157 and each light chain comprises an amino acid sequence as set forth in SEQ ID NO: 62.

22. The antibody-drug conjugate according to claim 20 , wherein the anti-FRα antibody construct comprises two heavy chains and two light chains, wherein each heavy chain comprises an amino acid sequence as set forth in SEQ ID NO: 142 and each light chain comprises an amino acid sequence as set forth in SEQ ID NO: 62.

23. A pharmaceutical composition comprising an antibody-drug conjugate according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

24. A pharmaceutical composition comprising an antibody-drug conjugate according to claim 20 , and a pharmaceutically acceptable carrier or diluent.

25. A pharmaceutical composition comprising an antibody-drug conjugate according to claim 22 , and a pharmaceutically acceptable carrier or diluent.

26. The antibody-drug conjugate according to claim 1 , wherein the anti-FRαantibody construct comprises a second antigen-binding domain operably linked to the IgG Fc region, the second antigen-binding domain comprising three heavy chain complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3) and three light chain CDRs (LCDR1, LCDR2, and LCDR3), wherein:

(i) the HCDR1 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 20, 23, 26, 28 or 31; the HCDR2 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 21, 24, 29, 32 or 51, and the HCDR3 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 22, 25 or 30, and

(ii) the LCDR1 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 40, 45 or 65; the LCDR2 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 41, 44 or 46, and the LCDR3 amino acid sequence comprises a sequence as set forth in any one of SEQ ID NOs: 42 or 47.

27. The antibody-drug conjugate according to claim 26 , wherein the second antigen-binding domain comprises a light chain variable domain (VL) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain (VH) amino acid sequence comprising a sequence as set forth in SEQ ID NO: 50.

28. The antibody-drug conjugate according to claim 26 , wherein the second antigen-binding domain comprises a light chain variable domain (VL) amino acid sequence consisting of a sequence as set forth in SEQ ID NO: 64 and a heavy chain variable domain (VH) amino acid sequence consisting of a sequence as set forth in SEQ ID NO: 50.

29. The antibody-drug conjugate according to claim 26 , wherein the IgG Fc is a human IgG1 Fc.

30. The antibody-drug conjugate according to claim 26 , wherein n is about 8.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: DAVIES, RUPERT H.
To: ZYMEWORKS BIOPHARMACEUTICALS INC.
Reel/Frame 068140/0240 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: ZYMEWORKS BIOPHARMACEUTICALS INC.
To: ZYMEWORKS BC INC.
Reel/Frame 068140/0392 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 31, 2024
From: RICH, JAMES R.; BARNSCHER, STUART DANIEL; PETERSEN, MARK EDMUND; COLOMBO, RAFFAELE; BRANT, MICHAEL G.; LASALLE, MANUEL MICHEL AUGUSTE; UROSEV, DUNJA; KANG, SUKHBIR SINGH; CHAN, PETER WING YIU; DAS, SAMIR; HERNANDEZ ROJAS, ANDREA; GENE, ROBERT WILLIAM; YOUNG, ADA G. H.; LAWN, SAMUEL OLIVER; CHUI, DANNY; BROWMAN, DUNCAN; CLAVETTE, BRANDON
To: ZYMEWORKS BC INC.
Reel/Frame 068223/0923 →
Continuity (5)
Continuation PCTCA2023050406 · Mar 24, 2023
Provisional Application 63450607 · Mar 7, 2023
Provisional Application 63417250 · Oct 18, 2022
Provisional Application 63324003 · Mar 25, 2022
Related Publication 20240424125A1 · Dec 26, 2024
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