IP Library › Granted Patent US 11,230,589
Granted Patent B2
US 11,230,589 · App. 14/440,569 · Granted Jan 25, 2022

Fusion molecules and uses thereof

Inventors: Doron Lipson (Chestnut Hill, MA); Roman Yelensky (Newton, MA); Joel Robert Greenbowe (Cambridge, MA); Jie He (Newton, MA)
Assignee: FOUNDATION MEDICINE, INC.
C07K14/71C07K14/47C07K16/18C07K16/2863C07K16/40C12N9/96C12N15/62
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Quick Facts
Patent No.
US 11,230,589
App. No.
14/440,569
Granted
Jan 25, 2022
Kind
B2
Abstract

Novel fusion molecules and uses are disclosed.

Claims (31)

1. A method of treating a subject having an FGFR3-TACC3 fusion polypeptide associated cancer, comprising:

determining the presence of an FGFR3-TACC3 fusion polypeptide or an mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide in said subject by performing an assay on a sample from the subject, wherein:

(i) the FGFR3-TACC3 fusion polypeptide comprises encoded exons 1-17 of SEQ ID NO: 4 directly fused to encoded exons 8-16 of SEQ ID NO: 6, and a fusion junction between encoded exon 17 of SEQ ID NO: 4 and encoded exon 8 of SEQ ID NO: 6, wherein the cancer is a lung adenocarcinoma or a cervical adenocarcinoma, or

(ii) the FGFR3-TACC3 fusion polypeptide comprises encoded exons 1-18 of SEQ ID NO: 4 directly fused to encoded exons 10-16 of SEQ ID NO: 6, and a fusion junction between encoded exon 18 of SEQ ID NO: 4 and encoded exon 10 of SEQ ID NO: 6, wherein the cancer is a uterus endometrial adenocarcinoma; and

administering to the subject having the FGFR3-TACC3 fusion polypeptide or the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide an effective amount of an anti-cancer agent,

thereby treating the cancer in the subject.

2. The method of claim 1 , wherein said anti-cancer agent is a kinase inhibitor.

3. The method of claim 1 , wherein the determining step comprises determining the presence of the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide by sequencing.

4. The method of claim 1 , wherein the anti-cancer agent is a multi-kinase inhibitor, a kinase-specific inhibitor, TAE-684, PF02341066 (crizotinib), AF-802, LDK-378, ASP-3026, CEP-37440, CEP-28122, CEP-108050, or AP26113.

5. The method of claim 1 , wherein the FGFR3-TACC3 fusion polypeptide comprises encoded exons 1-17 of SEQ ID NO: 4 directly fused to encoded exons 8-16 of SEQ ID NO: 6, wherein the fusion junction is between encoded exon 17 of SEQ ID NO: 4 and encoded exon 8 of SEQ ID NO: 6.

6. The method of claim 1 , wherein the FGFR3-TACC3 fusion polypeptide comprises SEQ ID NO: 2.

7. The method of claim 1 , wherein the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide comprises exons 1-17 of SEQ ID NO: 3 directly fused to exons 8-16 of SEQ ID NO: 5, wherein the fusion junction of the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide is between exon 17 of SEQ ID NO: 3 and exon 8 of SEQ ID NO: 5.

8. The method of claim 1 , wherein the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide comprises SEQ ID NO: 1.

9. The method of claim 1 , wherein the FGFR3-TACC3 fusion polypeptide comprises encoded exons 1-18 of SEQ ID NO: 4 directly fused to encoded exons 10-16 of SEQ ID NO: 6, wherein the fusion junction is between encoded exon 18 of SEQ ID NO: 4 and encoded exon 10 of SEQ ID NO: 6.

10. The method of claim 1 , wherein the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide comprises exons 1-18 of SEQ ID NO: 3 directly fused to exons 10-16 of SEQ ID NO: 5, wherein the fusion junction of the mRNA molecule encoding the FGFR3-TACC3 fusion polypeptide is between exon 18 of SEQ ID NO: 3 and exon 10 of SEQ ID NO: 5.

11. The method of claim 1 , further comprising obtaining the sample from the subject.

12. The method of claim 1 , wherein the sample is a nucleic acid sample.

13. The method of claim 1 , wherein the sample is a blood, serum, or plasma sample.

14. The method of claim 1 , wherein the sample comprises a tumor biopsy or a circulating tumor cell or nucleic acid.

15. The method of claim 1 , wherein the cancer is a lung adenocarcinoma.

16. The method of claim 1 , wherein the cancer is a cervical adenocarcinoma.

17. The method of claim 1 , wherein the cancer is a uterus endometrial adenocarcinoma.

18. The method of claim 6 , wherein said anti-cancer agent is a kinase inhibitor.

19. The method of claim 18 , further comprising obtaining the sample from the subject.

20. The method of claim 18 , wherein the cancer is a lung adenocarcinoma.

21. The method of claim 18 , wherein the cancer is a cervical adenocarcinoma.

22. The method of claim 9 , wherein the cancer is a uterus endometrial adenocarcinoma.

23. The method of claim 18 , wherein the sample is a nucleic acid sample.

24. The method of claim 18 , wherein the sample is a blood, serum, or plasma sample.

25. The method of claim 18 , wherein the sample comprises a tumor biopsy or a circulating tumor cell or nucleic acid.

26. The method of claim 1 , wherein the anti-cancer agent inhibits kinase activity of the FGFR3-TACC3 fusion polypeptide.

Assignments (3)
RELEASE OF SECURITY INTEREST Recorded Jun 30, 2021
From: ROCHE FINANCE LTD
To: FOUNDATION MEDICINE, INC.
Reel/Frame 056715/0711 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 8, 2019
From: LIPSON, DORON; YELENSKY, ROMAN; GREENBOWE, JOEL ROBERT; HE, JIE
To: FOUNDATION MEDICINE, INC.
Reel/Frame 047933/0844 →
PATENT SECURITY AGREEMENT Recorded Sep 27, 2016
From: FOUNDATION MEDICINE, INC.
To: ROCHE FINANCE LTD
Reel/Frame 040165/0615 →