Granted Patent
B2
US 12,303,544 · App. 18/112,402 · Granted May 20, 2025
Cytotoxic and anti-mitotic compounds, and methods of using the same
Inventors:
Geoffrey C. Winters (Vancouver, CA); Alexander Laurence Mandel (Vancouver, CA); James R. Rich (Vancouver, CA); Bradley John Hedberg (Vancouver, CA); Tom Han Hsiao Hsieh (Vancouver, CA); Elyse Marie Josée Bourque (L'Etang-du-Nord, CA); John Babcook (Vancouver, CA)
Assignee:
ZYMEWORKS BC INC.
A61K38/05A61K31/445A61K38/06A61K39/3955A61K47/54A61K47/64A61K47/6415A61K47/6803A61P35/00C07C311/51C07C323/12C07C323/67C07C327/06C07C381/08C07D207/08C07D207/452C07D211/34C07D211/60C07D213/56C07D213/71C07D333/34C07K5/0205C07K5/06078C07C317/28C07C317/32C07C317/50C07C2601/02C07C2601/08C07C2601/14C07K16/2863C07K16/32Y02A50/30
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Abstract
Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.
Claims (32)
1. An antibody-drug conjugate comprising a targeting moiety (T), a linker (L) and a drug moiety (D), wherein the targeting moiety (T) is an antibody or antigen-binding antibody fragment and the drug moiety (D) is a compound of Formula (Ib):
wherein:
R 16 is selected from the group consisting of H and C 1-6 alkyl;
R 17 is selected from the group consisting of H and C 1-6 alkyl;
R 18 is C 1-6 alkyl;
R 26 is selected from the group consisting of optionally substituted alkyl and optionally substituted aryl, and
R 27 is
and
wherein a C-terminus of the drug moiety (D) forms the point of attachment to the targeting moiety (T) via the linker (L).
2. The antibody-drug conjugate according to claim 1 , wherein R 16 is H or methyl.
3. The antibody-drug conjugate according to claim 1 , wherein R 17 is H or methyl.
4. The antibody-drug conjugate according to claim 1 , wherein R 18 is methyl.
5. The antibody-drug conjugate according to claim 1 , wherein R 16 is H, R 17 is methyl and R 18 is methyl.
6. The antibody-drug conjugate according to claim 1 , wherein R 26 is optionally substituted alkyl or optionally substituted phenyl.
7. The antibody-drug conjugate according to claim 1 , wherein drug moiety (D) is selected from:
8. The antibody-drug conjugate according to claim 1 , wherein drug moiety (D) is:
9. The antibody-drug conjugate according to claim 1 , wherein linker (L) is a cleavable linker.
10. The antibody-drug conjugate according to claim 1 , wherein linker (L) is joined to targeting moiety (T) by reaction of an electrophilic group on linker (L) with a nucleophilic group on targeting moiety (T).
11. The antibody-drug conjugate according to claim 10 , wherein the electrophilic group is a maleimide and the nucleophilic group is a sulfhydryl group.
12. The antibody-drug conjugate according to claim 1 , wherein targeting moiety (T) is a bispecific antibody or antigen-binding antibody fragment.
13. The antibody-drug conjugate according to claim 1 , wherein the antibody or antigen-binding antibody fragment binds a cancer antigen.
14. The antibody-drug conjugate according to claim 8 , wherein linker (L) is a cleavable linker.
15. The antibody-drug conjugate according to claim 8 , wherein linker (L) is joined to targeting moiety (T) by reaction of an electrophilic group on linker (L) with a nucleophilic group on targeting moiety (T).
16. The antibody-drug conjugate according to claim 15 , wherein the electrophilic group is a maleimide and the nucleophilic group is a sulfhydryl group.
17. The antibody-drug conjugate according to claim 8 , wherein targeting moiety (T) is a bispecific antibody or antigen-binding antibody fragment.
18. The antibody-drug conjugate according to claim 8 , wherein the antibody or antigen-binding antibody fragment binds a cancer antigen.
19. A pharmaceutical composition comprising the antibody-drug conjugate according to claim 1 , and a pharmaceutically acceptable carrier, diluent or excipient.
20. A pharmaceutical composition comprising the antibody-drug conjugate according to claim 8 , and a pharmaceutically acceptable carrier, diluent or excipient.
21. A method of inhibiting tumor growth in a subject, the method comprising administering to a subject in need thereof an effective amount of the antibody-drug conjugate according to claim 1 .
22. The method according to claim 21 , wherein the subject is a human.
23. A method of inhibiting tumor growth in a subject, the method comprising administering to a subject in need thereof an effective amount of the antibody-drug conjugate according to claim 8 .
24. The method according to claim 23 , wherein the subject is a human.
Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 13, 2024
From: WINTERS, GEOFFREY C.; MANDEL, ALEXANDER L.; RICH, JAMES R.; HEDBERG, BRADLEY J.; HSIEH, TOM HAN HSIAO; BOURQUE, ELYSE MARIE JOSEE; BABCOOK, JOHN
To: CENTRE FOR DRUG RESEARCH AND DEVELOPMENT
Reel/Frame 066760/0722 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 13, 2024
From: CENTRE FOR DRUG RESEARCH AND DEVELOPMENT
To: CDRD VENTURES INC.
Reel/Frame 066760/0734 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Mar 13, 2024
From: CDRD VENTURES INC.
To: ZYMEWORKS INC.
Reel/Frame 066760/0739 →
CHANGE OF NAME
Recorded Mar 13, 2024
From: ZYMEWORKS INC.
To: ZYMEWORKS BC INC.
Reel/Frame 066760/0745 →
Continuity (5)
Continuation
14776654
Provisional Application
61792020
· Mar 15, 2013
Provisional Application
61792066
· Mar 15, 2013
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