Companion diagnostic tool for peptidomimetic macrocycles

Patent metadata

Field	Value
Publication number	US-2017349638-A1
Application number	US-201715463826-A
Country	US
Kind code	A1
Filing date	Mar 20, 2017
Priority date	Mar 21, 2016
Publication date	Dec 7, 2017
Grant date	—

Abstract

The present invention provides diagnostic tools, systems, and methods for detecting wild type p53 and p53-associated mutations for the treatment of disease with peptidomimetic macrocycles.

First claim

What is claimed is:

1 . A method for treating a condition in a subject in need thereof, the method comprising:
a) performing an assay to determine a mutational status of a gene that modulates the p53 pathway in the subject; and b) administering to the subject a therapeutically-effective amount of a peptidomimetic macrocycle or a pharmaceutically-acceptable salt thereof.

2 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises a sequence that is at least 60% identical to a subsequence of p53.

3 . The method of claim 1 , wherein the peptidomimetic macrocycle binds to MDM2, HDM2, MDMX, or HDMX.

4 . The method of claim 1 , wherein the gene is TP53.

5 . The method of claim 1 , wherein the mutational status relates to a mutation that is a frameshift.

6 . The method of claim 1 , wherein the mutational status relates to a mutation that is a splice site mutation.

7 . The method of claim 1 , wherein the mutational status relates to a mutation that is an insertion.

8 . The method of claim 1 , wherein the mutational status relates to a mutation that is a deletion.

9 . The method of claim 1 , wherein the mutational status relates to a mutation that is a substitution.

10 . The method of claim 1 , wherein the mutational status relates to a mutation that is a copy number loss.

11 . The method of claim 1 , wherein the mutational status relates to a mutation that is a single nucleotide polymorphism.

12 . The method of claim 1 , wherein the assay is next-generation sequencing.

13 . The method of claim 1 , wherein the assay is DNA sequencing.

14 . The method of claim 1 , wherein the assay is RNA sequencing.

15 . The method of claim 1 , wherein the condition is a cancer.

16 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises an amino acid sequence that is at least about 60% identical to an amino acid sequence of the amino acid sequences in Tables 9-24.

17 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises an amino acid sequence that is at least about 80% identical to an amino acid sequence of the amino acid sequences in Tables 9-24.

18 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises an amino acid sequence that is at least about 90% identical to an amino acid sequence of the amino acid sequences in Tables 9-24.

19 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises an amino acid sequence that is at least about 95% identical to an amino acid sequence of the amino acid sequences in Tables 9-24.

20 . The method of claim 1 , wherein the peptidomimetic macrocycle comprises an amino acid sequence that is an amino acid sequence of the amino acid sequences in Tables 9-24.

21 . The method of claim 1 , wherein the peptidomimetic macrocycle is an amino acid sequence of the amino acid sequences in Tables 9-24.

Assignees

• Aileron Therapeutics Inc

Inventors

• Aivado Manuel

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12Q2600/156

  Polymorphic or mutational markers · CPC title

• C12Q2600/158

  Expression markers · CPC title

• C12Q1/6886 Primary

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61K38/12 Primary

  Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)} · CPC title