Methods of treating cancers

Patent metadata

Field	Value
Publication number	US-11413288-B2
Application number	US-201816755686-A
Country	US
Kind code	B2
Filing date	Oct 15, 2018
Priority date	Nov 1, 2017
Publication date	Aug 16, 2022
Grant date	Aug 16, 2022

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.

First claim

What is claimed is:

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 ubiquitin-specific protease 1 (USP1) inhibitor, wherein the human subject is identified as having a breast cancer gene 1 (BRCA1) and/or breast cancer gene 2 (BRCA2) mutation, and the USP1 inhibitor is administered as a monotherapy.

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 1 , wherein the cancer is resistant to a PARP inhibitor.

4. The method of claim 3 , wherein the cancer has intrinsic PARP inhibitor resistance, or acquired PARP inhibitor resistance.

5. The method of claim 2 , wherein the small molecule inhibitor is ML323, C527, pimozide, SJB019, or SJB2-043.

6. The method of claim 1 , wherein the cancer is resistant to a cross-linking agent.

7. The method of claim 6 , wherein the cross-linking agent is cisplatin, mitomycin, or busulfan.

8. 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.

9. 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 mutation and are PARP inhibitor-resistant; or
(c) one or more cancer cells that have a BRCA2, BRCA1 and BRCA2, or Partner And Localizer of BRCA2 (PALB2) mutation.

Assignees

• Dana Farber Cancer Inst Inc

Inventors

• D'Andrea Alan
• Lim Kah Suan

Classifications

• G01N33/57595

  involving intracellular compounds · CPC title

• A61K31/423

  condensed with carbocyclic rings · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• G01N2800/52

  Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis · CPC title

• C07K2317/24

  containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered · CPC title