# US 2013/0157299 A1 · Tyrosine Kinome

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- Number: US 2013/0157299 A1
- Document ID: US20130157299A1
- Status: Published application
- Kind: A1
- Application number: 13/746,376
- Filed: 2013-01-22
- Published: 2013-06-20
- Earliest claimed: 2003-02-21
- Assignees: The Johns Hopkins University
- Inventors: Alberto BARDELLI; D. Williams PARSONS; Victor VELCULESCU; Kenneth W. KINZLER; Bert VOGELSTEIN
- Web page: https://patentgrep.com/patent/US20130157299A1

## CPC

- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- A61K 31/506: not condensed and containing further heterocyclic rings
- C12N 9/1205: {Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases}
- C12Q 1/025: {for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics (antimicrobial activity C12Q1/18)}
- C12Q 1/485: {involving kinase}
- C12Q 1/6809: Methods for determination or identification of nucleic acids involving differential detection
- C12Q 1/6827: for detection of mutation or polymorphism
- G01N 33/575: for cancer
- C12Q 2600/136: Screening for pharmacological compounds
- C12Q 2600/156: Polymorphic or mutational markers
- 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
- 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)
- 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)

## Abstract

Protein kinases are important signaling molecules involved in tumorigenesis. Mutational analysis of the human tyrosine kinase gene family (98 genes) identified somatic alterations in −20% of colorectal cancers, with the majority of mutations occurring in NTRK3, FES, GUCY2F and a previously uncharacterized tyrosine kinase gene called MCCK/MLK4. Most alterations were in conserved residues affecting key regions of the kinase domain. These data represent a paradigm for the unbiased analysis of signal transducing genes in cancer and provide useful targets for therapeutic intervention.

## Claims

### Claim 1

A method of screening test substances for use as anti-cancer agents, comprising:
contacting a test substance with a protein kinase selected from the group consisting of: NTRK3, FES, MCCK, EPHA3, NTRK2, INSRR, JAK1, PDGFRA, EPHA7, EPHA8, KDR, FGFR1, and ERBB4;
testing activity of the protein kinase;
identifying a test substance which inhibits the activity of the protein kinase as a potential anti-cancer agent.

### Claim 2 (depends on 1)

The method of claim 1 wherein the protein kinase is in a cell.

### Claim 3 (depends on 1)

The method of claim 1 wherein the protein kinase is isolated from a cell.

### Claim 4 (depends on 1)

The method of claim 1 wherein the protein kinase is in a cell of a cancer cell line.

### Claim 5 (depends on 1)

The method of claim 1 wherein the protein kinase is in a cell which has been modified to express the protein kinase.

### Claim 6 (depends on 1)

The method of claim 1 wherein the protein kinase is NTRK3.

### Claim 7 (depends on 1)

The method of claim 1 wherein the protein kinase is FES.

### Claim 8 (depends on 1)

The method of claim 1 wherein the protein kinase is MCCK.

### Claim 9 (depends on 1)

The method of claim 1 wherein the protein kinase is EPHA3.

### Claim 10 (depends on 1)

The method of claim 1 wherein the protein kinase is NTRK2.

### Claim 11 (depends on 1)

The method of claim 1 wherein the protein kinase is INSRR.

### Claim 12 (depends on 1)

The method of claim 1 wherein the protein kinase is JAK1.

### Claim 13 (depends on 1)

The method of claim 1 wherein the protein kinase is PDGFRA.

### Claim 14 (depends on 1)

The method of claim 1 wherein the protein kinase is EPHA7.

### Claim 15 (depends on 1)

The method of claim 1 wherein the protein kinase is EPHA8.

### Claim 16 (depends on 1)

The method of claim 1 wherein the protein kinase is ERBB4.

### Claim 17 (depends on 1)

The method of claim 1 wherein the protein kinase is FGFR1.

### Claim 18 (depends on 1)

The method of claim 1 wherein the protein kinase is KDR.

### Claim 19 (depends on 6)

The method of claim 6 wherein the NTRK3 protein kinase has a mutation selected from the group consisting of I695V, G608S, L760I, K732T, and R731Q.

### Claim 20 (depends on 7)

The method of claim 7 wherein the FES protein kinase has a mutation selected from the group consisting of M704V, R706Q, V743M, and S759F.

### Claim 21 (depends on 8)

The method of claim 8 wherein the MCCK protein kinase has a mutation selected from the group consisting of H261Y, H261Q, G291E, A293E, W296STP, R470C, R553Stp, N596I, and K629E.

### Claim 22 (depends on 9)

The method of claim 9 wherein the EPHA3 protein kinase has a mutation selected from the group consisting of S792P and D806N.

### Claim 23 (depends on 10)

The method of claim 10 wherein the NTRK2 protein kinase has a mutation selected from the group consisting of T695I and D751N.

### Claim 24 (depends on 11)

The method of claim 11 wherein the INSRR protein kinase has a mutation T985M.

### Claim 25 (depends on 12)

The method of claim 12 wherein the JAK1 protein kinase has a mutation E886K.

### Claim 26 (depends on 13)

The method of claim 13 wherein the PGDFRA protein kinase is the result of a GA splice site mutation at position 1 of the donor site of exon 15.

### Claim 27 (depends on 14)

The method of claim 14 wherein the EPHA7 protein kinase has a mutation S768I.

### Claim 28 (depends on 15)

The method of claim 15 wherein the EPHA8 protein kinase has a mutation D873N.

### Claim 29 (depends on 16)

The method of claim 16 wherein the ERBB4 protein kinase has a mutation 11030M.

### Claim 30 (depends on 17)

The method of claim 17 wherein the FGFR1 protein kinase has a mutation A429S.

### Claim 31 (depends on 18)

The method of claim 18 wherein the KDR protein kinase has a mutation selected from the group consisting of G800D, R819Stop, and A1073T.