Fusion proteins and methods thereof
AssigneeThe Trustees of Columbia University in the City of New York
InventorsAntonio IAVARONE, Anna LASORELLA, Raul RABADAN
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Abstract
The invention discloses oncogenic fusion proteins. The invention provides methods for treating gene-fusion based cancers.
Claims44
A cDNA encoding a fusion protein comprising the tyrosine kinase domain of EGFR fused to:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
A purified fusion protein comprising the tyrosine kinase domain of EGFR fused to:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
An antibody or antigen-binding fragment thereof, that specifically binds to a purified fusion protein comprising a tyrosine kinase domain of an EGFR protein fused to a polypeptide comprising:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
A composition for decreasing the expression level or activity of a fusion protein in a subject comprising the tyrosine kinase domain of an EGFR protein fused to a polypeptide comprising:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein;
- the composition in an admixture of a pharmaceutically acceptable carrier comprising an inhibitor of the fusion protein.
A method of decreasing growth of a solid tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of an EGFR fusion molecule inhibitor, wherein the inhibitor decreases the size of the solid tumor, and wherein the EGFR fusion comprises the tyrosine kinase domain of EGFR fused to:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
A diagnostic kit for determining whether a sample from a subject exhibits a presence of an EGFR fusion, the kit comprising at least one oligonucleotide that specifically hybridizes to an EGFR fusion, or a portion thereof, wherein the EGFR fusion comprises the tyrosine kinase domain of EGFR fused to:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
A diagnostic kit for determining whether a sample from a subject exhibits a presence of an EGFR fusion protein, the kit comprising an antibody that specifically binds to an EGFR fusion protein comprising SEQ ID NO:
- 1, 3, 5, 7, 9, 11, 13, 16, or 8495, wherein the antibody will recognize the protein only when an EGFR fusion protein is present.
A method for detecting the presence of an EGFR fusion in a human subject, the method comprising:
- (a) obtaining a biological sample from the human subject;
- and
- (b) detecting whether or not there is an EGFR fusion present in the subject;
- wherein the EGFR fusion comprises the tyrosine kinase domain of EGFR fused to:
- (i) the coiled-coil domain of a Septin protein;
- (ii) a phosphoserine phosphatase (PSPH) protein;
- or
- (iii) a Cullin-associated and neddylation-dissociated (CAND) protein.
Dependencies are inferred from the claim text.