Claims for Patent: 8,815,508

Summary for Patent: 8,815,508

Title:	Method of identifying disease risk factors
Abstract:	Provided herein is a method for identifying a genetic variant that is associated with development of a condition of interest (e.g., Alzheimer\'s disease), and genetic variants so identified. Methods of treatment with an active agent (e.g., with a particular active agent and/or at an earlier age) is also provided, upon detecting a genetic variant described herein. In some embodiments, the genetic variant is a deletion/insertion polymorphism (DIP) of the TOMM40 gene. Kits for determining if a subject is at increased risk of developing late onset Alzheimer\'s disease is also provided. Kits for determining if a subject is responsive to treatment for a condition of interest with an active agent are further provided.
Inventor(s):	Roses; Allen D. (Chapel Hill, NC)
Assignee:	Zinfandel Pharmaceuticals, Inc. (Durham, NC)
Application Number:	13/058,724
Patent Claims:	1. A method of determining increased risk for development of Alzheimer's disease in a human subject, comprising: (a) detecting the length of a poly-T deletion/insertion polymorphism (DIP) at rs10524523 in intron 6 of the TOMM40 gene from a biological sample containing DNA taken from said subject, wherein said poly-T DIP has a length of 21, 22, 23, 26, 27, 28, 29, or 30; (b) correlating the detected poly-T length of 21, 22, 23, 26, 27, 28, 29, or 30 at rs10524523 with an increased risk of development of Alzheimer's disease; and (c) administering an anti-Alzheimer's disease active agent to said subject in an amount effective for treating said subject. 2. The method of claim 1, further comprising detecting an ApoE genotype of E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4 in said subject. 3. The method of claim 2, comprising detecting the Apo E3/E3 or E3/E4 genotype in said subject. 4. The method of claim 1, wherein said administering is carried out in said subject at an earlier age compared to a subject that does not have an rs10524523 allele with a poly-T length of 21, 22, 23, 26, 27, 28, 29, or 30. 5. The method of claim 1 wherein said active agent is selected from the group consisting of acetylcholinesterase inhibitors, NMDA receptor antagonists, peroxisome proliferator-activated receptor agonists or modulators, antibodies, fusion proteins, therapeutic RNA molecules, and combinations thereof. 6. A method of treating a non-symptomatic human subject at increased risk of developing Alzheimer's disease comprising: (a) detecting the length of a poly-T deletion/insertion polymorphism (DIP) at rs10524523 in intron 6 of the TOMM40 gene from a biological sample containing DNA taken from said subject, wherein said poly-T DIP has a length of 21, 22, 23, 26, 27, 28, 29, or 30; and (b) administering an anti-Alzheimer's disease active agent to said subject in an amount effective for treating said subject. 7. The method of claim 6, further comprising detecting an ApoE genotype of E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4 in said subject. 8. The method of claim 7, comprising detecting the Apo E3/E3 or E3/E4 genotype in said subject. 9. The method of claim 6 wherein said active agent is selected from the group consisting of acetylcholinesterase inhibitors, NMDA receptor antagonists, peroxisome proliferator-activated receptor agonists or modulators, antibodies, fusion proteins, therapeutic RNA molecules, and combinations thereof. 10. A method of determining the risk for developing Alzheimer's disease in a patient comprising: (i) obtaining a patient profile, comprising: detecting the presence or absence of at least one ApoE 2, ApoE 3, or ApoE 4 allele in a biological sample of said patient, and detecting the length of a poly-T deletion/insertion polymorphism (DIP) at rs10524523 in intron 6 of the TOMM40 gene from a biological sample containing DNA taken from said patient, wherein said poly-T DIP has a length of 21, 22, 23, 26, 27, 28, 29, or 30; (ii) determining that said patient is at an increased risk for developing Alzheimer's disease; and (iii) administering an anti-Alzheimer's disease active agent to said patient in an amount effective for treating said patient. 11. The method claim 10, further comprising detecting an ApoE genotype of E2/E2, E2/E3, E2/E4, E3/E3, E3/E4, or E4/E4 in said patient. 12. The method of claim 1, wherein said active agent is a thiazolidinedione. 13. The method of claim 12, wherein said thiazolidinedione is formulated in a pharmaceutical carrier. 14. The method of claim 6, wherein said active agent is a thiazolidinedione. 15. The method of claim 14, wherein said thiazolidinedione is formulated in a pharmaceutical carrier. 16. The method of claim 1, wherein said treating comprises delaying the onset of Alzheimer's disease. 17. The method of claim 6, wherein said treating comprises delaying the onset of Alzheimer's disease. 18. A method of delaying the onset of Alzheimer's disease in a non-symptomatic human subject, comprising: a) detecting the length of a poly-T deletion/insertion polymorphism (DIP) at rs10524523 in intron 6 of the TOMM40 gene from a biological sample containing DNA taken from said subject, wherein said poly-T DIP has a length of 21, 22, 23, 26, 27, 28, 29, or 30; and b) administering an active agent to said subject in an amount effective to delay the onset of Alzheimer's disease. 19. The method of claim 1, wherein said detecting the poly-T deletion/insertion polymorphism (DIP) at rs10524523 comprises PCR amplification and/or DNA sequencing. 20. The method of claim 10, wherein said detecting the poly-T deletion/insertion polymorphism (DIP) at rs10524523 comprises PCR amplification and/or DNA sequencing. 21. The method of claim 1, wherein said active agent is a peroxisome proliferator-activated receptor agonist or modulator. 22. The method of claim 6, wherein said active agent is a peroxisome proliferator-activated receptor agonist or modulator.

Details for Patent 8,815,508

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132	06/04/1986		2028-08-12
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2028-08-12
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2028-08-12