Claims for Patent: 7,985,549

Summary for Patent: 7,985,549

Title:	Method for predicting responsiveness to TNF.alpha. blocking agents
Abstract:	The invention provides an in vitro method for predicting whether a patient would be responsive to a treatment with a TNF.alpha. blocking agent, which method comprises determining the expression level of eight genes in a biological sample of said patient, wherein said genes are EPS15, HLA-DPB1, AKAP9, RASGRP3, MTCBP-1, PTNP12, MRPL22 and RPS28. The invention further provides a DNA chip for performing such method.
Inventor(s):	Salier; Jean-Philippe (Les Authieux-Ratieville, FR), Daveau; Maryvonne (Mont-Saint-Aignan, FR), Gauthier-Jauneau; Anne-Christine (Pont de I\'Arche, FR), Vittecoq; Olivier (Saint Ouen de Thouberville, FR), Loet; Xavier Le (Rouen, FR), Daragon; Alain (Rouen, FR), Mejjad; Othmane (Houppeville, FR), Lequerre; Thierry (MontMain, FR)
Assignee:	INSERM (Institut National de la Sante et de la Recherche Medicale) (Paris cedex, FR)
Application Number:	12/300,847
Patent Claims:	1. An in vitro method for predicting whether a patient would be responsive to a treatment with a TNF.alpha. blocking agent, which method comprises determining the expression level of eight genes in a biological sample of said patient, wherein said genes are EPS15, HLA-DPB1, AKAP9, RASGRP3, MTCBP-1, PTNP12, MRPL22 and RPS28. 2. The method of claim 1, wherein the patient is with rheumatoid arthritis. 3. The method of claim 2, wherein the TNF.alpha. blocking agent is an anti-TNF.alpha. antibody. 4. The method of claim 2, wherein the patient is with rheumatoid arthritis that is active. 5. The method of claim 3, wherein the TNF.alpha. blocking agent is an anti-TNF.alpha. antibody. 6. The method of claim 1, wherein the TNF.alpha. blocking agent is an anti-TNF.alpha. antibody. 7. The method of claim 6, wherein the antibody is infliximab. 8. The method of claim 1, further comprising the step of comparing the combined expression level of said genes with reference values obtained from responder and non-responder groups of patients. 9. The method of claim 1, wherein the patient receives a first-line therapy other than TNF.alpha. blocking agent. 10. The method of claim 9, wherein the patient is treated with methotrexate, azathoprine or leflunomide. 11. The method of claim 1, wherein the biological sample is blood. 12. The method of claim 1, wherein the expression level is determined by quantifying the level of mRNA of said genes in the biological sample. 13. The method of claim 12, which comprises the steps of providing total RNAs extracted from PBMCs obtained from a blood sample of the patient, and subjecting the RNAs to amplification and hybridization to specific probes. 14. The method of claim 12, wherein the expression level is determined by real-time quantitative or semi-quantitative RT-PCR. 15. The method of claim 12, wherein the expression level is determined by using a DNA chip. 16. The method of claim 1, further comprising determining the expression level of one or more genes selected from the group consisting of AADAT, COX7AL2, CXCL5, ELMOD2, FBXO5, KNG1, LAMR1, MUCDHL, PFKFB4, PSMB9, RPL35, RPS16, TBL2, THRAP3, 193472 Kininogen 1, 239932, QIL-1, SCAM-1, MUSTN1, WDR39, 114519, 415079, 244313, 295669, 234261, 123983, 82303, and 247176. 17. A DNA chip comprising a solid support which carries nucleic acids that hybridize under a stringent condition to the EPS15, HLA-DPB1, AKAP9, RASGRP3, MTCBP-1, PTNP12, MRPL22, and RPS28 genes. 18. The chip of claim 17, which further carries nucleic acids that hybridize under a stringent condition to any or all of the genes selected from the group consisting of AADAT, COX7AL2, CXCL5, ELMOD2, FBXO5, KNG1, LAMR1, MUCDHL, PFKFB4, PSMB9, RPL35, RPS16, TBL2, THRAP3, 193472 Kininogen 1, 239932, OIL-1, SCAM-1, MUSTN1, WDR39, 114519, 415079, 244313, 295669, 234261, 123983, 82303, and 247176. 19. A method for treating a patient suffering from a TNF.alpha.-related disease, the method comprising: identifying a patient who suffers from a TNF.alpha.-related disease and is classified as a responder to TNF.alpha. blocking agents, wherein classification as a responder is effected by determining expression levels in the patient of the EPS15, HLA-DPB1, AKAP9, RASGRP3, MTCBP-1, PTNP12, MRPL22 and RPS28 genes, and comparing the combined expression level of said genes with pre-determined reference values obtained from responder and non-responder groups; and administering to the patient an effective amount of a TNF.alpha. blocking agent. 20. The method of claim 19, wherein the TNF.alpha. blocking agent is infliximab. 21. The method of claim 19, wherein the disease is rheumatoid arthritis.

Details for Patent 7,985,549

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2026-05-16