Granted Patent
B2
US 12,263,166 · App. 17/811,282 · Granted Apr 1, 2025
Methods of treating cancers having a BRCA1 and/or BRCA2 mutation(s)
Assignee:
DANA-FARBER CANCER INSTITUTE, INC.
A61K31/506A61K31/423A61K31/4439A61K31/454A61K31/713A61K38/1761A61K38/45A61K39/3955A61K45/06A61P35/00C07K16/40C12N15/1137C12Y203/02C07K2317/24C07K2317/54C07K2317/55C12N2310/11C12N2310/14
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Abstract
The disclosure relates to methods for treating cancers (e.g., cancers having a BRCA1 and/or BRCA2 mutation(s)) by administering to the subject an effective amount of a ubiquitin-specific protease 1 (USP1) inhibitor.
Claims (26)
1. A method for treating a human subject having, or at risk of developing, a cancer, the method comprising administering to the human subject an effective amount of a USP1 inhibitor and a PARP inhibitor, wherein the human subject is identified as having a BRCA1 and/or BRCA2 mutation.
2. The method of claim 1 , wherein the USP1 inhibitor is
(a) a small molecule inhibitor;
(b) an inhibitory nucleic acid; or
(c) an anti-USP1 antibody or USP1-binding fragment thereof.
3. The method of claim 2 , wherein the small molecule inhibitor is ML323, C527, SJB019, or SJB2-043.
4. The method of claim 1 , wherein the cancer is resistant to a cross-linking agent.
5. The method of claim 4 , wherein the cross-linking agent is cisplatin, mitomycin, or busulfan.
6. The method of claim 1 , wherein the cancer is:
(a) breast cancer, prostate cancer, pancreatic cancer, fallopian tube cancer, peritoneal cancer, or ovarian cancer;
(b) a basal-like carcinoma or a luminal breast cancer;
(c) a triple-negative breast cancer; or
(d) a high-grade serous ovarian carcinoma.
7. The method of claim 1 , wherein the method comprises identifying the human subject as having
(a) one or more cancer cells that have a BRCA1 mutation,
(b) one or more cancer cells that have a BRCA1 and BRCA2 mutation, or
(c) one or more cancer cells that have a BRCA2, BRCA1 and BRCA2, or Partner And Localizer of BRCA2 (PALB2) mutation.
8. The method of claim 1 , wherein the USP1 inhibitor is an inhibitory nucleic acid or an anti-USP1 antibody or USP1-binding fragment thereof.
9. The method of claim 3 , wherein the small molecule inhibitor is ML323.
10. The method of claim 5 , wherein the cross-linking agent is busulfan.
11. The method of claim 1 , wherein the cancer is:
(a) fallopian tube cancer or peritoneal cancer;
(b) luminal breast cancer;
(c) a triple-negative breast cancer; or
(d) a high-grade serous ovarian carcinoma.
12. The method of claim 1 , wherein the method comprises identifying the human subject as having one or more cancer cells that have a Partner And Localizer of BRCA2 (PALB2) mutation.
Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jul 7, 2022
From: D'ANDREA, ALAN; LIM, KAH SUAN
To: DANA-FARBER CANCER INSTITUTE, INC.
Reel/Frame 060456/0117 →
Continuity (4)
Continuation
16755686
Provisional Application
62719276
· Aug 17, 2018
Provisional Application
62580058
· Nov 1, 2017
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