# US 11,897,925 B2 · Treatment of homologous recombination deficient cancers

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- Number: US 11,897,925 B2
- Document ID: US11897925B2
- Status: Granted
- Kind: B2
- Application number: 17/520,638
- Filed: 2021-11-06
- Published: 2022-05-19
- Granted: 2024-02-13
- Earliest claimed: 2020-11-17
- Assignees: Sinai Health System
- Applicants: Sinai Health System
- Inventors: Daniel Durocher; Salomé Adam; Silvia Emma Rossi; Yibo Xue
- Web page: https://patentgrep.com/patent/US11897925B2

## CPC

- C07K 14/4703: {Inhibitors; Suppressors}
- A61P 35/00: Antineoplastic agents
- A61K 38/00: 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)
- C07K 2319/02: containing a signal sequence
- C07K 2319/50: containing protease site
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Disclosed are compounds, compositions, uses and methods using inhibitors of the CIP2A-TOPBP1 complex or agents that inhibit phosphopeptide recognition of TOPBP1 BRCT7/8, for treatment of a cancer associated with or characterized by a homologous recombination (HR) deficiency or treatment of cancer cells having HR deficiency.

## Claims

### Claim 1

A method for inhibiting, reducing or suppressing the growth or survival of cancer cells with homologous recombination (HR) deficiencies comprising
i) contacting the cancer cells with an effective amount of a compound or agent that reduces or inhibits phosphopeptide recognition of TOPBP1 BRCT7/8 domains, wherein the compound or agent comprises a peptide of TOPBP1 comprising residues 756 to 1000, 756 to 891, 776-851, or 830 to 851 of SEQ ID NO: 11, or a sequence having 95% identity thereto, and binds CIP2A or a fragment thereof; wherein binding of the peptide to CIP2A reduces the ability of TOPBP1 to interact with CIP2A or destabilizes or inhibits an existing CIP2A-TOPBP1 interaction, either directly or indirectly.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer cells have a defect or mutation associated with HR deficiency in one or more of BRCA1, BRCA2, dual BRCA1/BRCA2, PALB2, BARD1, BRIP1, RAD51C and RAD51D.

### Claim 3 (depends on 2)

The method of claim 2, wherein the cancer cells have a defect or mutation in BRCA1, BRCA2, or both.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer cells are ovarian cancer cells.

### Claim 5

A method of treating a cancer associated with or characterized by a homologous recombination deficiency comprising administering to an individual in need thereof an effective amount of a CIP2A-TOPBP1 inhibitor comprising a peptide of TOPBP1 comprising residues 756 to 1000, 756 to 891, 776 to 851, or 830 to 851 of SEQ ID NO: 11, or a sequence having 95% identity thereto, and binds CIP2A or a fragment thereof; wherein binding of the peptide to CIP2A reduces the ability of TOPBP1 to interact with CIP2A or destabilizes or inhibits an existing CIP2A-TOPBP1 interaction, either directly or indirectly.