Claims for Patent: 8,865,417
✉ Email this page to a colleague
Summary for Patent: 8,865,417
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: | 14/046,863 |
Patent Claims: | 1. A method for detecting 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 and labeled TNF.alpha. with the sample to form a first labeled complex between the labeled anti-TNF.alpha. drug, the labeled TNF.alpha., and the autoantibody and a second labeled complex between the labeled anti-TNF.alpha. drug and the
autoantibody, wherein the labeled anti-TNF.alpha. drug and the labeled TNF.alpha. comprise different labels; (b) subjecting the first labeled complex and the second labeled complex to size exclusion chromatography to separate the first labeled complex
and the second labeled complex; and (c) detecting the first labeled complex and the second labeled complex, thereby detecting the presence or level of a non-neutralizing form of the autoantibody when both the first labeled complex and the second labeled
complex are present, and detecting the presence or level of a neutralizing form of the autoantibody when only the second labeled complex is present.
2. The method of claim 1, wherein the sample is serum. 3. The method of claim 1, wherein the anti-TNF.alpha. drug is a member selected from the group consisting of infliximab, etanercept, adalimumab, certolizumab pegol, and combinations thereof. 4. The method of claim 1, 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. 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 anti-TNF.alpha. drug is a fluorophore-labeled anti-TNF.alpha. drug. 7. The method of claim 6, wherein the fluorophore is selected from the group consisting of a polymethine dye, a pthalocyanine dye, a cyanine dye, a xanthene dye, a fluorene dye, a rhodamine dye, a coumarin dye, and a fluorescein dye. 8. The method of claim 1, wherein the labeled TNF.alpha. is a fluorophore-labeled TNF.alpha.. 9. The method of claim 8, wherein the fluorophore is selected from the group consisting of a polymethine dye, a pthalocyanine dye, a cyanine dye, a xanthene dye, a fluorene dye, a rhodamine dye, a coumarin dye, and a fluorescein dye. 10. The method of claim 1, wherein the sample is obtained from a subject receiving therapy with the anti-TNF.alpha. drug. 11. A method for detecting 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 firm a first labeled complex between the labeled anti-TNF.alpha. drug and the autoantibody; (b) subjecting the first labeled complex to a first size exclusion chromatography to separate the first labeled complex from free labeled anti-TNF.alpha. drug; (c) detecting the first labeled complex, thereby detecting the presence or level of the autoantibody; (d) contacting labeled TNF.alpha. with the first labeled complex from step (c) to form a second labeled complex between the labeled anti-TNF.alpha. drug and the labeled TNF.alpha., wherein the labeled anti-TNF.alpha. drug and the labeled TNF.alpha. comprise different labels, and wherein the second labeled complex does not include the autoantibody; (e) subjecting the second labeled complex to a second size exclusion chromatography to separate the second labeled complex from free labeled TNF.alpha.; and (f) detecting the second labeled complex, thereby detecting the presence or level of a neutralizing form of the autoantibody. 12. The method of claim 11, wherein the sample is serum. 13. The method of claim 11, wherein the anti-TNF.alpha. drug is a member selected from the group consisting of infliximab, etanercept, adalimunab, certolizumab pegol, and combinations thereof. 14. The method of claim 11, 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 11, wherein the first and/or the second size exclusion chromatography is size exclusion-high performance liquid chromatography (SE-HPLC). 16. The method of claim 11, 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 selected from the group consisting of a polymethine dye, a pthalocyanine dye, a cyanine dye, a xanthene dye, a fluorene dye, a rhodamine dye, a coumarin dye, and a fluorescein dye. 18. The method of claim 11, wherein the labeled TNF.alpha. is a fluorophore-labeled TNF.alpha.. 19. The method of claim 18, wherein the fluorophore is selected from the group consisting of a polymethine dye, a pthalocyanine dye, a cyanine dye, a xanthene dye, a fluorene dye, a rhodamine dye, a coumarin dye, and a fluorescein dye. 20. The method of claim 11, wherein the sample is obtained from a subject receiving therapy with the anti-TNF.alpha. drug. |
Details for Patent 8,865,417
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 | 2029-10-26 |
Immunex Corporation | ENBREL | etanercept | For Injection | 103795 | 11/02/1998 | ⤷ Try a Trial | 2029-10-26 |
Immunex Corporation | ENBREL | etanercept | For Injection | 103795 | 05/27/1999 | ⤷ Try a Trial | 2029-10-26 |
Immunex Corporation | ENBREL | etanercept | Injection | 103795 | 09/27/2004 | ⤷ Try a Trial | 2029-10-26 |
Immunex Corporation | ENBREL | etanercept | Injection | 103795 | 02/01/2007 | ⤷ Try a Trial | 2029-10-26 |
>Applicant | >Tradename | >Biologic Ingredient | >Dosage Form | >BLA | >Approval Date | >Patent No. | >Expiredate |
Make Better Decisions: Try a trial or see plans & pricing
Drugs may be covered by multiple patents or regulatory protections. All trademarks and applicant names are the property of their respective owners or licensors. Although great care is taken in the proper and correct provision of this service, thinkBiotech LLC does not accept any responsibility for possible consequences of errors or omissions in the provided data. The data presented herein is for information purposes only. There is no warranty that the data contained herein is error free. thinkBiotech performs no independent verification of facts as provided by public sources nor are attempts made to provide legal or investing advice. Any reliance on data provided herein is done solely at the discretion of the user. Users of this service are advised to seek professional advice and independent confirmation before considering acting on any of the provided information. thinkBiotech LLC reserves the right to amend, extend or withdraw any part or all of the offered service without notice.