Claims for Patent: 7,919,251
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Summary for Patent: 7,919,251
Title: | Non-thiopurine methyltransferase related effects in 6-mercaptopurine therapy |
Abstract: | The present invention provides methods for predicting tolerance associated with 6-mercaptopurine drug treatment of an immune-mediated gastrointestinal disorder such as inflammatory bowel disease. In particular, the present invention provides methods for predicting a patient\'s risk of an adverse drug reaction (or tolerance) to a 6-mercaptopurine drug by genotyping a patient at a polymorphic site in at least one gene selected from the group consisting of a xanthine dehydrogenase (XDH) gene, molybdenum cofactor sulfurase (MOCOS) gene, and aldehyde oxidase (AOX) gene. The present invention further provides methods for optimizing therapeutic efficacy in a patient receiving a 6-mercaptopurine drug by determining whether the patient should be given an alternative drug based on the presence or absence of a polymorphism in at least one of the XDH, MOCOS, and AOX genes. |
Inventor(s): | Sanderson; Jeremy D. (London, GB), Marinaki; Anthony M. (London, GB), Smith; Melissa A. (Hampshire, GB) |
Assignee: | Guy\'s and St. Thomas\' NHS Foundation Trust (London, GB) |
Application Number: | 12/248,866 |
Patent Claims: | 1. A method for identifying a human subject who is likely to lack response to azathioprine (AZA) or 6-mercaptopurine (6-MP), said method comprising: (a) genotyping nucleic
acid in a sample from said subject for the presence of the 3404 A to G mutation in the Aldehyde oxidase (AOX) coding sequence; (b) detecting a G at position 3404 in the AOX coding sequence; and (c) identifying the subject as likely to lack response to
AZA or 6-MP when a G at position 3404 in the AOX coding sequence is detected.
2. The method of claim 1, wherein said individual has a disease or disorder selected from the group consisting of an immune-mediated gastrointestinal disorder, an autoimmune disease, and graft versus host disease. 3. The method of claim 2, wherein said immune-mediated gastrointestinal disorder is inflammatory bowel disease. 4. The method of claim 1, wherein the method further comprises genotyping thiopurine methyltransferase (TPMT). 5. A method for treating a human subject having inflammatory bowel disease (IBD), said method comprising: (a) genotyping nucleic acid in a sample from said subject for the presence of the 3404 A to G mutation in the Aldehyde oxidase (AOX) coding sequence; (b) detecting a G at position 3404 in the AOX coding sequence; and (c) treating the human subject having the presence of a G at position 3404 in the AOX coding sequence with a drug other than AZA or 6-MP. 6. The method of claim 5, wherein said drug other than AZA or 6-MP is an anti-inflammatory agent. 7. The method of claim 6, wherein said anti-inflammatory agent is infliximab. 8. The method of claim 5, wherein said drug other than AZA or 6-MP is an immunosuppressive agent. 9. The method of claim 5, wherein the human subject having IBD has Crohn's disease. 10. The method of claim 1 or 5, wherein the method further comprises genotyping the xanthine dehydrogenase (XDH) gene for a variant allele selected from the group consisting of 2211C>T (exon 21), 3030T>C (exon 27), 837 C>T (exon 10), 37170>A (exon 34), 2107A>G (exon 20), 1936 A>G (exon 18) and a combination thereof. 11. The method of claim 1 or 5, wherein the method further comprises genotyping the molybdenum cofactor sulfurase (MOCOS) gene for a variant allele selected from the group consisting of 2107C>A (exon 11), 509 C>T (exon 4), 1072 G>A (exon 6), 2600T>C (exon 15), 3590>A (exon 4) and a combination thereof. |
Details for Patent 7,919,251
Applicant | Tradename | Biologic Ingredient | Dosage Form | BLA | Approval Date | Patent No. | Expiredate |
---|---|---|---|---|---|---|---|
Janssen Biotech, Inc. | REMICADE | infliximab | For Injection | 103772 | 08/24/1998 | ⤷ Try a Trial | 2027-10-12 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
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