Claims for Patent: 12,037,644

Summary for Patent: 12,037,644

Title:	Use of FGFR mutant gene panels in identifying cancer patients that will be responsive to treatment with an FGFR inhibitor
Abstract:	Disclosed herein are methods of identifying a cancer patient that will be responsive to treatment with a fibroblast growth factor receptor (FGFR) inhibitor and methods of treating cancer patients. The methods involve evaluating a biological sample from the patient for the presence of one or more FGFR mutants from a FGFR mutant gene panel. Kits and primers for identifying the presence of one or more FGFR mutant genes in a biological sample are also disclosed herein.
Inventor(s):	Suso Jesus PLATERO, Jayaprakash Karkera
Assignee:	Janssen Pharmaceutica NV
Application Number:	US16/136,201
Patent Claims:	1. A method of treating bladder cancer in a patient, the method comprising: determining that a fibroblast growth factor receptor (FGFR) single nucleotide polymorphism FGFR3 Y373C is present in a biological sample from the patient, and administering a FGFR inhibitor to the patient, wherein the FGFR inhibitor comprises a compound having Structural Formula I: or a pharmaceutically acceptable salt thereof, thereby treating said bladder cancer. 2. The method of claim 1, wherein the FGFR inhibitor is a compound having Structural Formula I: 3. The method of claim 1, wherein the patient has been diagnosed with metastatic bladder cancer. 4. The method of claim 1, further comprising determining that one or more additional FGFR mutants from a FGFR mutant gene panel are present in the biological sample, wherein the one or more additional FGFR mutants comprise a) a FGFR fusion gene comprising FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:TACC3 Intron, FGFR3:BAIAP2L1, FGFR2:BICC1, FGFR2:AFF3, FGFR2:CASP7, FGFR2:CCDC6, or FGFR2:OFD1, or any combination thereof, b) a FGFR single nucleotide polymorphism comprising FGFR3 R248C, FGFR3 S249C or FGFR3 G370C, or any combination thereof, or c) any combination of a) and b). 5. The method of claim 4, wherein the one or more additional FGFR mutants comprise one or more of: FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, FGFR3:TACC3 v1, FGFR3:TACC3 v3, FGFR3:BAIAP2L1, FGFR2:CASP7 and FGFR2:BICC1. 6. The method of claim 4, wherein the one or more additional FGFR mutants comprise one or more of: FGFR3 R248C, FGFR3 S249C, FGFR3 G370C, FGFR3:TACC3 v1 and FGFR3:TACC3 v3. 7. The method of claim 1, wherein the patient has been diagnosed with urothelial carcinoma. 8. The method of claim 1, wherein the patient has been diagnosed with advanced bladder cancer. 9. The method of claim 1 comprising administering the FGFR inhibitor to the patient according to a dosing regimen comprising a once daily dose of about 9 mg. 10. The method of claim 1 comprising administering the FGFR inhibitor to the patient according to a dosing regimen comprising a once daily dose of from about 0.5 mg to about 9 mg. 11. The method of claim 1 comprising administering the FGFR inhibitor to the patient according to a dosing regimen comprising a once daily dose of from about 4 mg to about 9 mg. 12. A method of treating bladder cancer in a patient, the method comprising: determining that a fibroblast growth factor receptor (FGFR) single nucleotide polymorphism FGFR3 Y373C is present in a biological sample from the patient, and administering a FGFR inhibitor to the patient, wherein the FGFR inhibitor comprises a compound having Structural Formula I: or a pharmaceutically acceptable salt thereof, wherein the method comprises administering the FGFR inhibitor to the patient according to a dosing regimen comprising a once daily dose of from about 6 mg to about 9 mg, thereby treating said bladder cancer. 13. The method of claim 12, wherein the FGFR inhibitor is a compound having Structural Formula I: 14. The method of claim 1, wherein the determining comprises amplifying a cDNA with a pair of primers that amplify FGFR3 Y373. 15. The method of claim 14, wherein the pair of primers have the sequences of SEQ ID NO: 29 and SEQ ID NO: 30or SEQ ID NO: 37 and SEQ ID NO: 38. 16. The method of claim 14, wherein the determining comprises: isolating an RNA from the biological sample and synthesizing the cDNA from the isolated RNA. 17. The method of claim 16, further comprising pre-amplifying the cDNA prior to the amplifying. 18. The method of claim 14, wherein the cDNA is preamplified. 19. The method of claim 14, wherein the amplifying comprises performing a real-time PCR. 20. The method of claim 19, wherein the real-time PCR is performed with one or more probes comprising SEQ ID NO:55. 21. The method of claim 20, wherein the real-time PCR is further performed with one or more 3′comprising SEQ ID NO:42. 22. The method of claim 14, comprising sequencing the amplified cDNA. 23. The method of claim 4, wherein the determining comprises amplifying a cDNA with a pair of primers that amplify the one or more additional FGFR mutants from the FGFR mutant gene panel. 24. The method of claim 23, wherein one or more additional FGFR mutants and the pair of primers comprise: FGFR3:TACC3 v1 and primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6; FGFR3:TACC3 v3 and primers having the sequences of SEQ ID NO:7 and SEQ ID NO:8; FGFR3:TACC3 Intron and primers having the sequences of SEQ ID NO:9 and SEQ ID NO:10; FGFR3:BAIAP2L1 and primers having the sequences of SEQ ID NO:11 and SEQ ID NO:12; FGFR2:BICC1 and primers having the sequences of SEQ ID NO:13 and SEQ ID NO:14; FGFR2:AFF3 and primers having the sequences of SEQ ID NO:15 and SEQ ID NO:16; FGFR2:CASP7 and primers having sequences of SEQ ID NO:17 and SEQ ID NO:18; FGFR2:CCDC6 and primers having the sequences of SEQ ID NO:19 and SEQ ID NO:20; FGFR2:OFD1 and primers having the sequences of SEQ ID NO:21 and SEQ ID NO:22; FGFR3 SC249C and primers having sequences of SEQ ID NO:25 and SEQ ID NO:26 or SEQ ID NO:33 and SEQ ID NO:34; FGFR3 G370C and primers having the sequences of SEQ ID NO:27 and SEQ ID NO:28 or SEQ ID NO:35 and SEQ ID NO:36; FGFR3 R248C and primers having the sequences of SEQ ID NO:23 and SEQ ID NO:24 or SEQ ID NO:31 and SEQ ID NO:32; or any combination thereof. 25. The method of claim 23, wherein one or more additional FGFR mutants and the pair of primers comprise: FGFR3:TACC3 v1 and primers having the sequences of SEQ ID NO:5 and SEQ ID NO:6; FGFR3:TACC3 v3 and primers having the sequences of SEQ ID NO:7 and SEQ ID NO:8; FGFR3:TACC3 Intron and primers having the sequences of SEQ ID NO:9 and SEQ ID NO:10; FGFR3:BAIAP2L1 and primers having the sequences of SEQ ID NO:11 and SEQ ID NO:12; FGFR2:BICC1 and primers having the sequences of SEQ ID NO:13 and SEQ ID NO:14; FGFR2:CASP7 and primers having sequences of SEQ ID NO:17 and SEQ ID NO:18; FGFR3 SC249C and primers having sequences of SEQ ID NO:25 and SEQ ID NO:26 or SEQ ID NO:33 and SEQ ID NO:34; FGFR3 G370C and primers having the sequences of SEQ ID NO:27 and SEQ ID NO:28 or SEQ ID NO:35 and SEQ ID NO:36; FGFR3 R248C and primers having the sequences of SEQ ID NO:23 and SEQ ID NO:24 or SEQ ID NO:31 and SEQ ID NO:32; or any combination thereof.