# US 12,006,503 B2 · Fusion proteins and methods thereof

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- Number: US 12,006,503 B2
- Document ID: US12006503B2
- Status: Granted
- Kind: B2
- Application number: 16/899,312
- Filed: 2020-06-11
- Published: 2020-09-24
- Granted: 2024-06-11
- Earliest claimed: 2012-07-24
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University in the City of New York
- Inventors: Antonio Iavarone; Anna Lasorella
- Web page: https://patentgrep.com/patent/US12006503B2

## CPC

- C12N 15/62: DNA sequences coding for fusion proteins
- C07K 14/47: from mammals
- C07K 14/71: for growth factors; for growth regulators
- C07K 14/82: Translation products from oncogenes
- C07K 16/18: against material from animals or humans
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C12N 9/12: transferring phosphorus containing groups, e.g. kinases (2.7)
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- C07K 2319/00: Fusion polypeptide
- C07K 2319/73: containing coiled-coiled motif (leucine zippers)
- C12Q 2600/158: Expression markers
- G01N 2333/91205: Phosphotransferases in general
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- 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)
- 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
- 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

The invention discloses oncogenic fusion proteins. The invention provides methods for treating gene-fusion based cancers.

## Claims

### Claim 1

A method for treating a FGFR3-TACC3 fusion associated cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of JNJ-42756493, wherein the subject has a FGFR3-TACC3 fusion associated cancer, wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 fused to the TACC domain of transforming acidic coiled-coil-containing (TACC)3.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has FGFR3-TACC3 fusion associated epithelial cancer, glioma, glioblastoma multiforme, breast cancer, lung cancer, prostate cancer, bladder carcinoma, squamous lung carcinoma, head and neck carcinoma or colorectal carcinoma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the subject has FGFR3-TACC3 fusion associated epithelial cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein the subject has FGFR3-TACC3 fusion associated glioblastoma multiforme.

### Claim 5 (depends on 1)

The method of claim 1, wherein the subject has FGFR3-TACC3 fusion associated glioma.

### Claim 6 (depends on 5)

The method of claim 5, wherein the glioma is a grade II or III glioma.

### Claim 7 (depends on 4)

The method of claim 4, wherein the subject does not have mutations in IDH1 or IDH2 genes.

### Claim 8 (depends on 4)

The method of claim 4, wherein the subject does not have a gene amplification in EGFR.

### Claim 9 (depends on 4)

The method of claim 4, wherein the subject does not express EGFRγIII transcript variant.

### Claim 10 (depends on 4)

The method of claim 4, wherein the subject has a gene amplification of CDK4, MDM2, or both.

### Claim 11 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 85, 86, 87, or 89.

### Claim 12 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 85.

### Claim 13 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 87.

### Claim 14 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 158, 159, 160, or 161.

### Claim 15 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises SEQ ID NO: 542, 543, 544, 545, 546, or 547.

### Claim 16 (depends on 1)

The method of claim 1, wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 transcript variant 1 fused to the TACC domain of TACC3.

### Claim 17 (depends on 1)

The method of claim 1, wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 1-77, 80-82, or 84.

### Claim 18 (depends on 1)

The method of claim 1, wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 519-527, or 530-538.

### Claim 19 (depends on 1)

The method of claim 1, wherein a nucleotide sequence encoding the FGFR3-TACC3 fusion comprises SEQ ID NO: 533-538.

### Claim 20

A method for diagnosing and treating a FGFR3-TACC3 fusion associated cancer in a subject in need thereof, the method comprising:
a. obtaining a biological sample from the subject;
b. detecting whether the subject has a FGFR3-TACC3 fusion is present in the biological sample, wherein the FGFR3-TACC3 fusion comprises a tyrosine kinase domain of FGFR3 fused to the TACC domain of transforming acidic coiled-coil-containing (TACC) 3; and
c. diagnosing the subject with a FGFR3-TACC3 fusion associated cancer when the presence of the FGFR3-TACC3 fusion in the biological sample is detected; then
d. administering to the subject an effective amount of JNJ-42756493.

### Claim 21 (depends on 6)

The method of claim 6, wherein the subject does not have mutations in IDH1 or IDH2 genes.

### Claim 22 (depends on 6)

The method of claim 6, wherein the subject does not have a gene amplification in EGFR.

### Claim 23 (depends on 6)

The method of claim 6, wherein the subject does not express EGFRγIII transcript variant.

### Claim 24 (depends on 6)

The method of claim 6, wherein the subject has a gene amplification of CDK4, MDM2, or both.
