Claims for Patent: 9,518,098

Summary for Patent: 9,518,098

Title:	Uses of NANOG inhibitors and related methods
Abstract:	The present invention relates to substances and compositions thereof useful in the control of cancer stem cell persistence and concomitant tumor recurrence and/or control of tumor growth. In particular, the invention relates to substances and compositions useful in the treatment of cancers and/or tumors linked to cancer stem cells, preferably brain cancers and/or tumors, in a subject.
Inventor(s):	Ruiz Altaba; Ariel (Geneva, CH)
Assignee:	UNIVERSITE DE GENEVE (Geneva, CH)
Application Number:	14/128,882
Patent Claims:	1. A NANOG antagonist that is a NANOG dominant-negative polypeptide comprising a NANOG homeodomain fused to the repressor domain of a heterologous protein. 2. The NANOG antagonist according to claim 1, wherein the NANOG homeodomain has the amino acid sequence of SEQ ID NO:5, or the NANOG homeodomain is a NANOG homeodomain of a mammalian NANOG protein that binds to the DNA consensus sequence of SEQ ID NO:34. 3. The NANOG antagonist according to claim 1, wherein the repressor domain comprises the repressor domain of Pit-1beta (SEQ ID NO: 37), or the repressor domain of an Engrailed protein selected from SEQ ID NO: 36 or 38, the repressor domain of IRF1 (SEQ ID NO: 39), or the WRPW motif of the hairy-related protein (SEQ ID NO: 44). 4. The NANOG antagonist according to claim 1, wherein the NANOG dominant-negative polypeptide further comprises a cell penetrating peptide for translocating the polypeptide across the cell membrane and/or a brain tumor targeting peptide and/or a tag selected from SEQ ID NO: 42 or SEQ ID NO: 43 at the N-terminus or the C-terminus of the NANOG antagonist polypeptide. 5. The NANOG antagonist according to claim 4, wherein the cell penetrating peptide comprises penetratin from Antennapedia of SEQ ID NO: 40 and the brain tumor targeting peptide comprises a transferrin-like peptide of SEQ ID NO: 41. 6. The NANOG antagonist according to claim 1, wherein the NANOG dominant-negative polypeptide further comprises the dimerization domain of SEQ ID NO: 35. 7. A pharmaceutical formulation comprising a NANOG antagonist according to claim 1 and at least one pharmaceutically acceptable carrier. 8. The pharmaceutical formulation according to claim 7 further comprising a co-agent selected from bevacizumab, temazolomide, procarbazine, carmustine, or cilengitide. 9. A method of repressing or treating cancers linked to cancer stem cells in a subject, said method comprising administering to a subject in need thereof a therapeutically effective amount of a NANOG antagonist selected from: a) a NANOG dominant-negative polypeptide comprising a NANOG homeodomain fused to the repressor domain of a heterologous protein; b) a vector driving the expression of said NANOG antagonist; or c) a pharmaceutical formulation comprising a) or b). 10. The method of claim 9 wherein said cancers are brain cancers. 11. The method according to claim 9, wherein the NANOG homeodomain has the amino acid sequence of SEQ ID NO:5, or the NANOG homeodomain is a NANOG homeodomain of a mammalian NANOG protein that binds to the DNA consensus sequence of SEQ ID NO:34. 12. The method of claim 9, wherein the NANOG dominant-negative polypeptide further comprises a cell penetrating peptide for translocating the polypeptide across the cell membrane and/or a brain tumor targeting peptide and/or a Tag selected from FLAG of SEQ ID NO:42 and HA of SEQ ID NO:43 at the N-terminus or the C-terminus part of the NANOG antagonist. 13. The method according to claim 9, wherein the NANOG dominant-negative polypeptide is administered systemically. 14. A method of controlling cancer stem cell persistence and concomitant tumor recurrence in a subject comprising administering to a subject in need thereof an amount of a NANOG antagonist selected from: a) a NANOG dominant-negative polypeptide comprising a NANOG homeodomain fused to the repressor domain of a heterologous protein; b) a vector driving the expression of said NANOG antagonist; or c) a pharmaceutical formulation comprising a) or b). 15. A method of repressing or treating cancers linked to cancer stem cells in a subject, said method comprising administering to a subject in need thereof a therapeutically effective amount of a NANOG antagonist, wherein said NANOG antagonist is a) a short hairpin RNA selected from: i) shNANOG1 of nucleotide sequence SEQ ID NO:11, ii) shNANOG2 of nucleotide sequence SEQ ID NO:12 or iii) shNANOGP8 consisting of SEQ ID NO:13; b) a vector driving the expression of said NANOG antagonist; or c) a pharmaceutical formulation comprising a) or b). 16. The method of claim 15 wherein said cancers are brain cancers. 17. A method of controlling cancer stem cell persistence and concomitant tumor recurrence in a subject comprising administering to a subject in need thereof an amount of a NANOG antagonist, wherein said NANOG antagonist is a) a short hairpin RNA selected from: i) shNANOG1 of nucleotide sequence SEQ ID NO:11, ii) shNANOG2 of nucleotide sequence SEQ ID NO:12 or iii) shNANOGP8 consisting of SEQ ID NO:13; b) a vector driving the expression of said NANOG antagonist; or c) a pharmaceutical formulation comprising a) or b).

Details for Patent 9,518,098

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2032-06-25