Claims for Patent: 7,972,780

Summary for Patent: 7,972,780

Title:	ITPase gene polymorphisms associated with adverse drug reactions to azathioprine therapy
Abstract:	The present invention provides methods for predicting a patient\'s risk of an adverse drug reaction to a thiopurine drug such as AZA or 6-MP by genotyping the patient for a polymorphism in the gene encoding ITPase (ITPA). The present invention also provides methods for predicting a patient\'s risk of an adverse drug reaction to a thiopurine drug by determining a level of ITPase activity or ITP in a sample from the patient. The present invention further provides methods for optimizing therapeutic efficacy in a patient receiving a thiopurine drug by determining whether the patient should be given an alternative drug based on the presence or absence of a polymorphism in the ITPA gene.
Inventor(s):	Duley; John A. (Brisbane, AU), Sanderson; Jeremy D. (London, GB), Marinaki; Anthony M. (London, GB)
Assignee:	Guy\'s and St. Thomas\' NHS Foundation Trust (London, GB)
Application Number:	11/060,972
Patent Claims:	1. A method for predicting tolerance to azathioprine (AZA) or 6-mercaptopurine (6-MP) in a human subject having Crohn's disease or ulcerative colitis, said method comprising: (a) genotyping nucleic acid in a sample from said subject for the presence of a 94 C to A mutation in the inosine triphosphate pyrophosphatase (ITPA) coding region; (b) indicating that the presence of said mutation is predictive of decreased tolerance to AZA or 6-MP; and (c) predicting the subject with said mutation has increased risk of flu-like symptoms relative to a subject without said mutation and predicting the subject with said mutation does not have increased risk of myelosuppression relative to a subject without said mutation. 2. The method of claim 1, wherein said subject is heterozygous for said 94 C to A mutation. 3. The method of claim 1, wherein said subject is homozygous for said 94 C to A mutation. 4. The method of claim 1, wherein said subject is compound heterozygous for said 94 C to A mutation and a 21 A to C mutation in intron 2 of the ITPA gene. 5. The method of claim 1, said method further comprising: correlating the genotype of said subject with a level of inosine triphosphate pyrophosphatase (ITPase) activity. 6. A method for optimizing therapeutic efficacy in a human subject having Crohn's disease or ulcerative colitis and receiving azathioprine (AZA) or 6-mercaptopurine (6-MP), said method comprising: (a) genotyping nucleic acid in a sample from said subject for the presence of a 94 C to A mutation in the inosine triphosphate pyrophosphatase (ITPA) coding region; (b) predicting the presence of said mutation indicates an increased risk of flu-like symptoms relative to a subject without said mutation and predicting the presence of said mutation does not indicate an increased risk of myelosuppression relative to a subject without said mutation; and (c) optimizing therapeutic efficacy by administering an alternative therapeutic agent to a subject to avoid flu-like symptoms. 7. The method of claim 6, wherein said alternative therapeutic agent is selected from the group consisting of an anti-inflammatory agent, an immunosuppressive agent, and combinations thereof. 8. The method of claim 6, wherein said alternative therapeutic agent is 6-thioguanine or a derivative thereof. 9. The method of claim 6, wherein said alternative therapeutic agent is a lower dose of AZA or 6-MP. 10. The method of claim 6, said method further comprising: correlating the genotype of said subject with a level of inosine triphosphate pyrophosphatase (ITPase) activity. 11. The method of claim 1, wherein said nucleic acid comprises genomic DNA. 12. The method of claim 1, wherein said nucleic acid is genotyped using the polymerase chain reaction. 13. The method of claim 1, wherein said sample is selected from the group consisting of whole blood, plasma, and serum. 14. The method of claim 6, wherein said nucleic acid comprises genomic DNA. 15. The method of claim 6, wherein said nucleic acid is genotyped using the polymerase chain reaction. 16. The method of claim 6, wherein said sample is selected from the group consisting of whole blood, plasma, and serum. 17. The method of claim 6, wherein said subject is heterozygous for said 94 C to A mutation. 18. The method of claim 6, wherein said subject is homozygous for said 94 C to A mutation. 19. The method of claim 6, wherein said subject is compound heterozygous for said 94 C to A mutation and a 21 A to C mutation in intron 2 of the ITPA gene.

Details for Patent 7,972,780

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		2024-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	For Injection	103132			2024-02-18
Merck Sharp & Dohme Corp.	INTRON A	interferon alfa-2b	Injection	103132			2024-02-18