# US 12,214,008 B2 · Protein interfaces

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- Number: US 12,214,008 B2
- Document ID: US12214008B2
- Status: Granted
- Kind: B2
- Application number: 17/171,841
- Filed: 2021-02-09
- Published: 2021-08-19
- Granted: 2025-02-04
- Earliest claimed: 2016-05-27
- Assignees: SyntheX, Inc.
- Applicants: SyntheX, Inc.
- Inventors: Charly Chahwan; Maria Soloveychik
- Web page: https://patentgrep.com/patent/US12214008B2

## CPC

- A61K 38/02: Peptides of undefined number of amino acids; Derivatives thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 5/1019: {with the first amino acid being basic}
- C07K 7/06: having 5 to 11 amino acids
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- C07K 14/00: Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K 16/30: from tumour cells
- C12N 15/1055: {Protein x Protein interaction, e.g. two hybrid selection}
- C12N 15/81: for yeasts
- G01N 33/5023: {on expression patterns}
- 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)
- A61K 2039/585: {wherein the target is cancer}
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

The present disclosure provides methods to treat conditions, including cancer, using compounds that can target resistant cancer cells. The compounds can be used to sensitize resistant cancer cells or decrease the proliferation of cells. The compounds can target proteins in the DNA damage repair pathway leading to a decrease in DNA damage repair in target cells.

## Claims

### Claim 1

A method for screening for inhibitors of a protein interaction between a first test protein and a second test protein, the method comprising:
expressing, in a plurality of host cells, a first fusion protein comprising a first test protein and a DNA-binding moiety; and
expressing, in each of the plurality of host cells, a second fusion protein comprising the second test protein and a gene-activating moiety,
wherein each of the plurality of host cells comprises a plurality of heterologous polynucleotide sequences that each encode a different cytotoxic agent, wherein expression of each of the heterologous polynucleotide sequences that each encode a different cytotoxic agent is under the control of a promoter that has selective affinity for the DNA-binding moiety, wherein interaction between the first test protein and the second test protein causes the gene-activating moiety to activate expression of each of the different cytotoxic agents encoded by each of the plurality of heterologous polynucleotide sequences;
wherein the DNA-binding moiety is a LexA, cI, Glucocorticoid receptor, TetR, or Ume6 DNA binding moiety;
wherein the gene activating moiety is a GAL4, B42, or Dof1 gene activating moiety;
wherein the plurality of different cytotoxic agents are selected from the group consisting of: a ribosomally-encoded xenobiotic agent, a ribosomally-encoded poison, a ribosomally-encoded recombinase that excises an essential gene for viability, and any combination thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the plurality of different cytotoxic agents are selected from the group consisting of: Cholera toxin, SpvB toxin, CARDS toxin, SpyA Toxin, HopU1, Chelt toxin, Certhrax toxin, EFV toxin, ExoT, CdtB, Diphtheria toxin, ExoU/VipB, HopPtoE, HopPtoF, HopPtoG, VopF, YopJ, AvrPtoB, SdbA, SidG, VpdA, Lpg0969, Lpg1978, YopE, SptP, SopE2, SopB/SigD, SipA, YpkA, YopM, Amatoxin, Phallacidin, Killer toxin KP1, Killer toxin KP6, Killer Toxin K1, Killer Toxin K28 (KHR), Killer Toxin K28 (KHS), Anthrax lethal factor endopeptidase, Shiga Toxin, Ricin Toxin, and any combination thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the plurality of host cells are eukaryotic.

### Claim 4 (depends on 1)

The method of claim 1, wherein the plurality of different cytotoxic agents are prokaryotic toxins.

### Claim 5 (depends on 1)

The method of claim 1, wherein the plurality of host cells are fungal cells.

### Claim 6 (depends on 1)

The method of claim 1, further comprising expressing, in each of the plurality of host cells, a randomized peptide.

### Claim 7 (depends on 6)

The method of claim 6, wherein the randomized polypeptide comprises a polypeptide of 60 or fewer amino acids in length.

### Claim 8 (depends on 6)

The method of claim 6, wherein an N-terminal stabilization sequence is attached to the randomized polypeptide.