Claims for Patent: 8,574,855

Summary for Patent: 8,574,855

Title:	Assays for the detection of anti-TNF drugs and autoantibodies
Abstract:	The present invention provides assays for detecting and measuring the presence or level of anti-TNF.alpha. drug therapeutics and autoantibodies in a sample. The present invention is useful for optimizing therapy and monitoring patients receiving anti-TNF.alpha. drug therapeutics to detect the presence or level of autoantibodies (e.g., HACA and/or HAHA) against the drug.
Inventor(s):	Singh; Sharat (Rancho Santa Fe, CA), Wang; Shui Long (San Diego, CA), Ohrmund; Linda (San Diego, CA)
Assignee:	Nestec S.A. (Vevey, CH)
Application Number:	13/441,727
Patent Claims:	1. A method for determining the presence or level of an anti-TNF.alpha. drug in a sample, the method comprising: (a) contacting a labeled TNF.alpha. with a sample having an anti-TNF.alpha. drug to form a labeled complex with the anti-TNF.alpha. drug; (b) subjecting the labeled complex to size exclusion chromatography to separate the labeled complex from free labeled TNF.alpha. and to detect an amount of the labeled complex and an amount of the free labeled TNF.alpha.; and (c) comparing the amount of the labeled complex and the amount of the free labeled TNF.alpha. detected in step (b) to a standard curve of known amounts of the anti-TNF.alpha. drug, thereby determining the presence or level of the anti-TNF.alpha. drug. 2. The method of claim 1, wherein the standard curve is generated by incubating the labeled TNF.alpha. with known amounts of the anti-TNF.alpha. drug. 3. The method of claim 1, wherein the sample is serum. 4. The method of claim 1, wherein the anti-TNF.alpha. drug is a member selected from the group consisting of REMICADE.TM. (infliximab), ENBREL.TM. (etanercept), HUMIRA.TM. (adalimumab), CIMZIA.RTM. (certolizumab pegol), and combinations thereof. 5. The method of claim 1, wherein the size exclusion chromatography is size exclusion-high performance liquid chromatography (SE-HPLC). 6. The method of claim 1, wherein the labeled TNF.alpha. is a fluorophore-labeled TNF.alpha.. 7. The method of claim 6, wherein the fluorophore is an Alexa Fluor.RTM. dye. 8. The method of claim 1, wherein the labeled complex is eluted first, followed by the free labeled TNF.alpha.. 9. The method of claim 1, wherein the sample is obtained from a subject receiving therapy with the anti-TNF.alpha. drug. 10. A method for determining the presence or level of an autoantibody to an anti-TNF.alpha. drug in a sample, the method comprising: (a) contacting a labeled anti-TNF.alpha. drug with the sample to form a labeled complex with the autoantibody; (b) subjecting the labeled complex to size exclusion chromatography to separate the labeled complex from free labeled anti-TNF.alpha. drug and to detect an amount of the labeled complex and an amount of the free labeled anti-TNF.alpha. drug; and (c) comparing the amount of the labeled complex and the amount of the free labeled anti-TNF.alpha. drug detected in step (b) to a standard curve of known amounts of the autoantibody, thereby determining the presence or level of the autoantibody. 11. The method of claim 10, wherein the standard curve is generated by incubating the labeled anti-TNF.alpha. drug with serum positive for the autoantibody. 12. The method of claim 10, wherein the sample is serum. 13. The method of claim 10, wherein the anti-TNF.alpha. drug is a member selected from the group consisting of REMICADE.TM. (infliximab), ENBREL.TM. (etanercept), HUMIRA.TM. (adalimumab), CIMZIA.RTM. (certolizumab pegol), and combinations thereof. 14. The method of claim 10, wherein the autoantibody is a member selected from the group consisting of a human anti-mouse antibody (HAMA), a human anti-chimeric antibody (HACA), a human anti-humanized antibody (HAHA), and combinations thereof. 15. The method of claim 10, wherein the size exclusion chromatography is size exclusion-high performance liquid chromatography (SE-HPLC). 16. The method of claim 10, wherein the labeled anti-TNF.alpha. drug is a fluorophore-labeled anti-TNF.alpha. drug. 17. The method of claim 16, wherein the fluorophore is an Alexa Fluor.RTM. dye. 18. The method of claim 10, wherein the labeled complex is eluted first, followed by the free labeled anti-TNF.alpha. drug. 19. The method of claim 10, wherein the sample is obtained from a subject receiving therapy with the anti-TNF.alpha. drug. 20. The method of claim 10, wherein a ratio of the free labeled anti-TNF.alpha. drug to an internal control is determined and used to extrapolate the level of the autoantibody from the standard curve.

Details for Patent 8,574,855

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2029-10-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2029-10-26
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2029-10-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2029-10-26
Immunex Corporation	ENBREL	etanercept	Injection	103795	02/01/2007		2029-10-26
Immunex Corporation	ENBREL MINI	etanercept	Injection	103795	09/14/2017		2029-10-26