Claims for Patent: 9,375,485

Summary for Patent: 9,375,485

Title:	Use of telomerase inhibitors for the treatment of myeloproliferative disorders and myeloproliferative neoplasms
Abstract:	Provided herein are methods for reducing neoplastic progenitor cell proliferation and alleviating symptoms associated in individuals diagnosed with or thought to have Essential Thrombocythemia (ET). Also provided herein are methods for using telomerase inhibitors for maintaining blood platelet counts at relatively normal ranges in the blood of individuals diagnosed with or suspected of having ET.
Inventor(s):	Stuart Monic J., Kelsey Stephen
Assignee:	Geron Corporation
Application Number:	US13841711
Patent Claims:	2. The method of claim 1 , wherein the symptom comprises headache claim 1 , dizziness or lightheadedness claim 1 , chest pain claim 1 , weakness claim 1 , fainting claim 1 , vision changes claim 1 , numbness or tingling of extremities claim 1 , redness claim 1 , throbbing or burning pain in extremities (erythromelalgia) claim 1 , enlarged spleen claim 1 , nosebleeds claim 1 , bruising claim 1 , bleeding from mouth or gums claim 1 , bloody stool claim 1 , or stroke.3. The method of wherein the at least one symptom is associated with myelofibrosis (MF).4. The method of wherein the myelodysplastic syndrome is selected from the group consisting of refractory anemia claim 1 , refractory anemia with excess blasts claim 1 , refractory cytopenia with multilineage dysplasia claim 1 , refractory cytopenia with unilineage dysplasia claim 1 , and chronic myelomonocytic leukemia (CMML).5. The method of wherein the myelodysplastic syndrome (MDS) is chronic myelomonocytic leukemia (CMML).7. The method of wherein the individual is diagnosed with or suspected of having myelofibrosis (MF).8. The method of wherein the myelodysplastic syndrome is selected from the group consisting of refractory anemia claim 6 , refractory anemia with excess blasts claim 6 , refractory cytopenia with multilineage dysplasia claim 6 , refractory cytopenia with unilineage dysplasia claim 6 , and chronic myelomonocytic leukemia (CMML).9. The method of claim 6 , wherein the individual is resistant or intolerant to a prior non-telomerase inhibitor-based therapy.11. The method of claim 6 , wherein the telomerase inhibitor comprises an oligonucleotide.12. The method of claim 11 , wherein the oligonucleotide is complementary to the RNA component of telomerase.13. The method of claim 11 , wherein the oligonucleotide is 10-20 bases in length.14. The method of claim 11 , wherein the oligonucleotide comprises the sequence TAGGGTTAGACAA (SEQ ID NO:12).15. The method of claim 11 , wherein the oligonucleotide comprises at least one N3′→P5′ thiophosphoramidate internucleoside linkage.16. The method of claim 15 , wherein the oligonucleotide comprises N3′→P5′ thiophosphoramidate internucleoside linkages.17. The method of claim 11 , wherein the oligonucleotide further comprises a lipid moiety linked to the 5′ and/or 3′ end of the oligonucleotide.18. The method of claim 17 , wherein the lipid moiety is linked to the 5′ and/or 3′ end of the oligonucleotide via a linker.19. The method of claim 18 , wherein the linker is a glycerol or aminoglycerol linker.20. The method of claim 18 , wherein the lipid moiety is a palmitoyl (C16) moiety.21. The method of claim 6 , wherein the telomerase inhibitor is imetelstat.22. The method of claim 6 , wherein the telomerase inhibitor is administered with a pharmaceutically acceptable excipient.23. The method of claim 6 , wherein the telomerase inhibitor is formulated for oral claim 6 , intravenous claim 6 , subcutaneous claim 6 , intramuscular claim 6 , topical claim 6 , intraperitoneal claim 6 , intranasal claim 6 , inhalation claim 6 , or intraocular administration.24. The method of claim 6 , wherein administration of the therapeutically effective amount of the telomerase inhibitor comprises contacting one or more neoplastic progenitor cells with the telomerase inhibitor.25. The method of claim 21 , wherein the effective amount of a telomerase inhibitor is 7.5 mg/kg to 9.3 mg/kg.26. The method of claim 21 , wherein the effective amount of a telomerase inhibitor is 9.5 mg/kg to 11.7 mg/kg.27. The method of claim 6 , wherein administration of the telomerase inhibitor does not inhibit cytokine-dependent megakaryocyte growth.28. The method of claim 6 , wherein the individual carries a V617F gain of function mutation in the Janus kinase 2 (JAK2) gene.29. The method of claim 28 , wherein administration of the telomerase inhibitor decreases the percentage of JAK2 V617F allelic burden in the individual.30. The method of claim 6 , wherein administration of the telomerase inhibitor inhibits cytokine-independent megakaryocyte growth.31. The method of claim 6 , wherein administration of the telomerase inhibitor inhibits CFU-mega.32. The method of claim 31 , wherein inhibition of CFU-Mega is independent of reduction in JAK2 allelic burden.33. The method of claim 1 , wherein the telomerase inhibitor comprises an oligonucleotide with the following characteristics:(a) 10-20 bases in length;(b) complementary to the RNA component of telomerase; and(c) comprises at least one N3′→P5′ thiophosphoramidate internucleoside linkage.34. The method of claim 33 , wherein the telomerase inhibitor further comprises a lipid moiety linked to the 5′ and/or 3′ end of the oligonucleotide.35. The method of claim 34 , wherein the lipid moiety is linked to the 5′ and/or 3′ end of the oligonucleotide via a linker.36. The method of claim 35 , wherein the oligonucleotide comprises a lipid moiety linked to the 5′ end of the oligonucleotide via an aminoglycerol linker.37. The method of claim 36 , wherein the lipid moiety is a palmitoyl (C16) moiety.38. The method of claim 37 , wherein the lipid moiety is linked to the 5′ end of the oligonucleotide via an aminoglycerol linker and a 5′-thiophosphate group.39. The method of claim 33 , wherein the oligonucleotide comprises the sequence TAGGGTTAGACAA (SEQ ID NO:12).40. The method of claim 6 , wherein the telomerase inhibitor comprises an oligonucleotide with the following characteristics:(a) 10-20 bases in length;(b) complementary to the RNA component of telomerase; and(c) comprises at least one N3′→P5′ thiophosphoramidate internucleoside linkage.41. The method of claim 40 , wherein the telomerase inhibitor further comprises a lipid moiety linked to the 5′ and/or 3′ end of the oligonucleotide.42. The method of claim 41 , wherein the lipid moiety is linked to the 5′ and/or 3′ end of the oligonucleotide via a linker.43. The method of claim 42 , wherein the oligonucleotide comprises a lipid moiety linked to the 5′ end of the oligonucleotide via an aminoglycerol linker.44. The method of claim 43 , wherein the lipid moiety is a palmitoyl (C16) moiety.45. The method of claim 44 , wherein the lipid moiety is linked to the 5′ end of the oligonucleotide via an aminoglycerol linker and a 5′-thiophosphate group.46. The method of claim 40 , wherein the oligonucleotide comprises the sequence TAGGGTTAGACAA (SEQ ID NO:12).47. The method of claim 10 , wherein the telomerase inhibitor comprises an oligonucleotide with the following characteristics:(a) 10-20 bases in length;(b) complementary to the RNA component of telomerase; and(c) comprises at least one N3′→P5′ thiophosphoramidate internucleoside linkage.48. The method of claim 47 , wherein the telomerase inhibitor further comprises a lipid moiety linked to the 5′ and/or 3′ end of the oligonucleotide.49. The method of claim 48 , wherein the lipid moiety is linked to the 5′ and/or 3′ end of the oligonucleotide via a linker.50. The method of claim 49 , wherein the oligonucleotide comprises a lipid moiety linked to the 5′ end of the oligonucleotide via an aminoglycerol linker.51. The method of claim 50 , wherein the lipid moiety is a palmitoyl (C16) moiety.52. The method of claim 51 , wherein the lipid moiety is linked to the 5′ end of the oligonucleotide via an aminoglycerol linker and a 5′-thiophosphate group.53. The method of claim 47 , wherein the oligonucleotide comprises the sequence TAGGGTTAGACAA (SEQ ID NO:12).