# US 10,768,179 B2 · Method for predicting responsiveness to cancer treatment using p300-inhibiting compound

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- Number: US 10,768,179 B2
- Document ID: US10768179B2
- Status: Granted
- Kind: B2
- Application number: 15/121,001
- Filed: 2015-02-23
- Published: 2017-03-09
- Granted: 2020-09-08
- Earliest claimed: 2014-02-24
- Assignees: National Cancer Center; Daiichi Sankyo Company, Limited
- Applicants: National Cancer Center; Daiichi Sankyo Company, Limited
- Inventors: Takashi Kohno; Hideaki Ogiwara; Yuichi Tominaga; Saito Higuchi
- Web page: https://patentgrep.com/patent/US10768179B2

## CPC

- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61K 31/4155: non condensed and containing further heterocyclic rings
- A61P 35/00: Antineoplastic agents
- C12N 15/09: Recombinant DNA-technology
- C12Q 1/68: involving nucleic acids
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/50: Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing (measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q)
- G01N 33/575: for cancer
- C12Q 2600/106: Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/158: Expression markers
- G01N 2333/47: Assays involving proteins of known structure or function as defined in the subgroups
- G01N 2333/91057: with definite EC number (2.3.1.-)
- G01N 2500/10: involving cells
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES

## Abstract

It has been found that CBP and p300 are in the relationship of synthetic lethality, and treatment inhibiting p300 is a promising approach for the treatment of CBP-mutated cancer. It has also been revealed that this therapeutic strategy achieves efficient treatment based on companion diagnostics because a p300 inhibitor can be administered to a cancer patient selected with functional suppression of CBP as an index.

## Claims

### Claim 1

A method for improving the response rate of the treatment of cancer, comprising using a biological sample derived from a cancer patient, detecting the presence of a CBP mutation contained in the biological sample, determining the patient is responsive to the treatment of cancer with a compound inhibiting p300, and treating the patient by a method consisting of administrating to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly.

### Claim 2

A method for improving the response rate of the treatment of cancer, comprising using a biological sample derived from a cancer patient, detecting the presence of a CBP mutation in the biological sample, selecting the patient as the candidate for the treatment of cancer with a compound inhibiting p300, and treating the patient by a method consisting of administrating to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly.

### Claim 3

A method for treating cancer having functional suppression of CBP, comprising using a biological sample derived from a cancer patient, detecting the presence of functional suppression of CBP contained in the biological sample, and treating the patient by a method consisting of administering to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, and suppressing the growth of the cancer cells to the patient.

### Claim 4 (depends on 1)

The method of claim 1, wherein detecting the presence of a CBP mutation contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
(a) an oligonucleotide primer specifically binding to the CBP gene,
(b) an oligonucleotide probe specifically binding to the CBP gene, and
(c) an antibody specifically binding to the CBP protein.

### Claim 5 (depends on 2)

The method of claim 2, wherein detecting the presence of a CBP mutation contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
(a) an oligonucleotide primer specifically binding to the CBP gene,
(b) an oligonucleotide probe specifically binding to the CBP gene, and
(c) an antibody specifically binding to the CBP protein.

### Claim 6 (depends on 3)

The method of claim 3, wherein detecting the presence of functional suppression of CBP contained in the biological sample comprises contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
(a) an oligonucleotide primer specifically binding to the CBP gene,
(b) an oligonucleotide probe specifically binding to the CBP gene, and
(c) an antibody specifically binding to the CBP protein.

### Claim 7 (depends on 3)

The method of claim 3, wherein detecting the presence of functional suppression of CBP contained in the biological sample comprises detecting the presence of a CBP mutation contained in the biological sample, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly.

### Claim 8 (depends on 3)

The method of claim 3, wherein the cancer having functional suppression of CBP is lung cancer, bladder cancer, lymphoma, or adenoid cystic cancer.

### Claim 9

A method for treating a cancer patient, wherein the patient has been determined to have functional suppression of CBP, comprising treating the patient by a method consisting of administering to the patient an amount of a compound inhibiting p300 and a pharmaceutically acceptable carrier effective to suppress the growth of cancer cells, and suppressing the growth of the cancer cells.

### Claim 10 (depends on 9)

The method of claim 9, wherein the presence of functional suppression of CBP is determined by using a biological sample derived from the patient, contacting the biological sample with a reagent comprising any of the following molecules (a) to (c) as an active ingredient:
(a) an oligonucleotide primer specifically binding to the CBP gene,
(b) an oligonucleotide probe specifically binding to the CBP gene, and
(c) an antibody specifically binding to the CBP, and
detecting the presence of functional suppression of CBP in the biological sample.

### Claim 11 (depends on 9)

The method of claim 9, wherein the presence of functional suppression of CBP is determined by detecting the presence of a CBP mutation contained in a biological sample derived from the patient, wherein the mutation is a homozygous CBP deletion, a nonsense mutation, or one of the mutations Asn83Thr, Ser893Leu, Arg1446Cys, Trp1472Cys, Asn2175Ser, Glu1835Stop, Asn2111 Ser, Leu551Ile, Gly1411Glu, or Ala2044Gly.

### Claim 12 (depends on 9)

The method of claim 9, wherein the patient is affected by lung cancer, bladder cancer, lymphoma, or adenoid cystic cancer.
