Claims for Patent: 9,784,748

Summary for Patent: 9,784,748

Title:	Methods for determining anti-drug antibody isotypes
Abstract:	The present invention provides assay methods for the determination of one or more anti-drug antibody (ADA) isotypes in a sample. As a non-limiting example, the assays of the present invention are particularly useful for determining different ADA isotypes in samples from ADA-positive patients receiving an anti-TNF.alpha. drug such as REMICADE.TM. (infliximab) or HUMIRA.TM. (adalimumab). The present invention also provides methods for optimizing therapy and/or reducing toxicity in subjects receiving TNF.alpha. inhibitors for the treatment of TNF.alpha.-mediated disease or disorders.
Inventor(s):	Wang; Shui Long (San Diego, CA), Ohrmund; Linda (San Diego, CA), Hauenstein; Scott (San Diego, CA), Singh; Sharat (Rancho Santa Fe, CA)
Assignee:	NESTEC S.A. (Vevey, CH)
Application Number:	13/865,139
Patent Claims:	1. A method for detecting the presence or level of an IgA isotype and an IgG isotype of an autoantibody to an anti-TNF.alpha. drug in a sample, the method comprising: (a) contacting a labeled anti-TNF.alpha. drug, a labeled anti-Ig antibody specific for the IgA isotype, and a labeled anti-Ig antibody specific for the IgG isotype with a sample having or suspected of having the IgA isotype and the IgG isotype to form (i) a first labeled complex between the labeled anti-TNF.alpha. drug, the labeled anti-Ig antibody specific for the IgA isotype, and the IgA isotype, and (ii) a second labeled complex between the labeled anti-TNF.alpha. drug, the labeled anti-Ig antibody specific for the IgG isotype, and the IgG isotype, wherein the labeled anti-TNF.alpha. drug and the labeled anti-Ig antibodies comprise different labels; (b) subjecting the first and second labeled complexes to size exclusion chromatography to separate the first and second labeled complexes from each other, from free labeled anti-TNF.alpha. drug, and/or from free labeled anti-Ig antibodies; and (c) detecting the first and second labeled complexes, thereby detecting the presence or level of an IgA isotype and an IgG isotype of the autoantibody to the anti- TNF.alpha. drug; wherein the method uses anti-Ig antibodies specific for the IgA and IgG isotypes only and wherein only the IgA and IgG isotypes are detected. 2. The method of claim 1, wherein the anti-TNF.alpha. drug is selected from the group consisting of infliximab, adalimumab, etanercept, certolizumab pegol, and combinations thereof. 3. The method of claim 1, wherein the autoantibody to the anti-TNF.alpha. drug is selected from the group consisting of a human anti-chimeric antibody (HACA), a human anti-humanized antibody (HAHA), a human anti-mouse antibody (HAMA), and combinations thereof. 4. The method of claim 1, wherein the labeled anti-TNF.alpha. drug and the labeled anti-Ig antibodies bind to different epitopes. 5. The method of claim 1, wherein the sample is whole blood, serum, or plasma. 6. The method of claim 1, wherein the autoantibody to the anti-TNF.alpha. drug is a HACA and the sample is obtained from a subject receiving infliximab therapy. 7. The method of claim 1, wherein the autoantibody to the anti-TNF.alpha. drug is a HAHA and the sample is obtained from a subject receiving adalimumab therapy. 8. The method of claim 1, wherein the labeled anti-TNF.alpha. drug is a fluorophore-labeled anti-TNF.alpha. drug. 9. The method of claim 1, wherein the labeled anti-Ig antibodies are fluorophore-labeled anti-Ig antibodies. 10. The method of claim 1, wherein the labeled anti-Ig antibodies each comprise the same label or different labels. 11. The method of claim 1, wherein the first and second labeled complexes are detected using fluorescence label detection. 12. The method of claim 1, wherein the first labeled complex is detected by detecting a signal that is generated by proximity binding of both the labeled anti-TNF.alpha. drug and the labeled anti-Ig antibody specific for the IgA isotype to the IgA isotype of the autoantibody; and wherein the second labeled complex is detected by detecting a signal that is generated by proximity binding of both the labeled anti-TNF.alpha. drug and the labeled anti-Ig antibody specific for the IgG isotype to the IgG isotype of the autoantibody. 13. The method of claim 12, wherein the signal is a fluorescent signal that is detected by fluorescence resonance energy transfer (FRET). 14. The method of claim 1, wherein the size exclusion chromatography is size exclusion-high performance liquid chromatography (SE-HPLC). 15. The method of claim 1, wherein the method comprises detecting the presence or level of subclasses of the IgA isotype and the IgG isotype.

Details for Patent 9,784,748

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2030-10-18
Immunex Corporation	ENBREL	etanercept	For Injection	103795	11/02/1998		2030-10-18
Immunex Corporation	ENBREL	etanercept	For Injection	103795	05/27/1999		2030-10-18
Immunex Corporation	ENBREL	etanercept	Injection	103795	09/27/2004		2030-10-18