Claims for Patent: 9,856,480

Summary for Patent: 9,856,480

Title:	Dnazyme for silencing the expression of EGFR
Abstract:	The invention provides DNAzymes which are capable to silence the expression of EGFR at allele-specific level. These allele-specific DNAzymes against EGFR T790M mutation will knockdown the expression of EGFR T790M mRNA while keeping EGFR wild-type mRNA intact. Hence, these allele-specific DNAzymes against EGFR T790M mutation may overcome T790M-derived TKI resistance accompanied with lower unwanted side effects on normal cells in lung cancer patients.
Inventor(s):	Yang; Pan-Chyr (Taipei, TW), Lai; Wei-Yun (Taipei, TW), Peck; Konan (Taipei, TW), Chang; Cheng-Ju (Taipei, TW), Chen; Chi-Yuan (Taipei, TW), Yang; Shuenn-Chen (Taipei, TW)
Assignee:	National Taiwan University (Taipei, TW) ACADEMIA SINICA (Taipei, TW)
Application Number:	14/760,904
Patent Claims:	1. An oligonucleotide or a modified sequence thereof, which specifically hybridizes to EGFR mutation mRNA so as to inhibit the translation thereof in a cell, wherein the oligonucleotide comprises consecutive nucleotides having a sequence selected from the group consisting of SEQ ID NOs:1 to 7. 2. The oligonucleotide or a modified sequence thereof of claim 1, which has the sequence of SEQ ID NO:1 or SEQ ID NO:2. 3. The oligonucleotide or a modified sequence thereof of claim 1, which has the sequence of SEQ ID NO:1. 4. The oligonucleotide or a modified sequence thereof of claim 1, wherein the modified sequence comprises a modified base on nucleotide structure, a modified linkage bond between nucleotides, or a functional group at the 5'- or 3'-end of the oligonucleotide. 5. The oligonucleotide or a modified sequence thereof of claim 4, wherein the modified base is amine-modified dA, phenol-modified dU, imidazole-modified dU, or pyridine-modified U. 6. The oligonucleotide or a modified sequence thereof of claim 1, wherein the modified sequence comprises a phosphorothioate bond between 3 bases at both ends and a cholesterol-TEG group at the 3'-end. 7. A vector which comprises a sequence encoding the oligonucleotide or a modified sequence thereof of any of claims 1 and 2-6. 8. A host which comprises the vector of claim 7. 9. A pharmaceutical composition comprising the oligonucleotide or a modified sequence thereof of any of claim 1 and a pharmaceutically acceptable carrier. 10. The pharmaceutical composition of claim 9, which further comprises an EGFR TK inhibitor or an EGFR-specific antibody. 11. The pharmaceutical composition of claim 10, wherein the EGFR TK inhibitor is afatinib (BIBW2992), XL647 (N-(3,4-dichloro-2-fluorophenyl)-6-methoxy-7-(((3aR,6aS)-2-methyloctahydr- ocyclopenta[c]pyrrol-5-yl)methoxy)quinazolin-4-amine), Neratinib (HKI-272), dacomitinib (PF-00299804), BMS-6690514 ((3R,4R)-4-Amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triaz- in-5-yl]methyl]piperidin-3-ol), gefitinib or erlotinib. 12. The pharmaceutical composition of claim 10, wherein the EGFR-specific antibody is cetuximab or panitumumab. 13. A method of specifically inhibiting the expression of EGFR mutation mRNA in a cell that would otherwise express EGFR mutation protein, comprising contacting the cell with either of the oligonucleotides of any of claims 1 and 2-6 so as to specifically inhibit the expression of EGFR mutation protein in the cell. 14. A method of specifically inhibiting the expression of EGFR T790M mutation mRNA in a cell that would otherwise express EGFR T790M Protein, comprising contacting the cell with either of the oligonucleotides or a modified sequence thereof of any of claims 1 and 2-6 so as to specifically inhibit the expression of EGFR T790M protein in the cell. 15. A method of treating an EGFR-dependent cancer in a subject, comprising administering an effective amount of an oligonucleotide or a modified sequence thereof of any of claims 1 and 2-6 to the subject. 16. The method of claim 15, which can be used as an adjuvant therapy given after surgery, radiation or chemotherapy. 17. A method of treating EGFR-dependent cancer in a subject, comprising administering a TKI inhibitor or an EGFR-specific antibody and an oligonucleotide or a modified sequence thereof of any of claims 1 and 2-6 to the subject. 18. The method of claim 17, wherein the TKI inhibitor or a EGFR-specific antibody and an oligonucleotide or a modified sequence thereof of any of claims 1 and 2-6 can be administered concurrently, sequentially or separately. 19. The method of claim 17, wherein the EGFR TK inhibitor is afatinib (BIBW2992), XL647 (N-(3,4-dichloro-2-fluorophenyl)-6-methoxy-7-(((3aR,6aS)-2-methyloctahydr- ocyclopenta[c]pyrrol-5-yl)methoxy)quinazolin-4-amine), Neratinib (HKI-272), dacomitinib (PF-00299804), BMS-6690514 ((3R,4R)-4-Amino-1-[[4-[(3-methoxyphenyl)amino]pyrrolo[2,1-f][1,2,4]triaz- in-5-yl]methyl]piperidin-3-ol), gefitinib or erlotinib. 20. The method of claim 17, wherein the EGFR-specific antibody is cetuximab or panitumumab. 21. The method of claim 15, wherein the EGFR-dependent cancer is a lung cancer. 22. The method of claim 21, wherein the lung cancer is NSCLC. 23. The method of claim 17, wherein the EGFR-dependent cancer is a lung cancer. 24. The method of claim 23, wherein the lung cancer is NSCLC.

Details for Patent 9,856,480

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2039-02-26
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2039-02-26
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2039-02-26