Claims for Patent: 9,726,672

Summary for Patent: 9,726,672

Title:	Anti-VLA-4 related assays
Abstract:	Methods and apparatus for assaying the level of analytes in a sample, related to VLA-4, are disclosed. A method of decreasing the level of an anti-integrin antibody in a subject is described including a) contacting a biological sample from a subject with a detectable capture agent associated with a substrate, wherein the capture agent can bind an anti-integrin antibody in the sample; b) detecting binding of the capture agent with the level of the anti-integrin antibody; and c) treating the subject with plasma exchange until the level of the anti-integrin antibody in the sample reaches a predetermined level.
Inventor(s):	Plavina; Tatiana (North Reading, MA), Hochman; Paula S. (Newton, MA), Lerner; Michaela (West Roxbury, MA)
Assignee:	Biogen MA Inc. (Cambridge, MA)
Application Number:	15/166,514
Patent Claims:	1. A device for assaying the level of a humanized anti-VLA-4 IgG4 antibody in a sample from a subject, the device comprising: a capture agent associated with a substrate, wherein the capture agent can bind a humanized anti-VLA-4 IgG4 antibody in the sample, and wherein the substrate is a portion of a lateral flow immunochromatographic system comprising, in order of flow, a label zone, a sample receiving zone, and a test zone configured such that: the label zone is located upstream of the sample receiving zone and contains one or more secondary agents, the test zone is downstream of the label zone, upon flow through the lateral flow immunochromatographic system the sample reaches the test zone before a secondary agent from the label zone upon flow through the lateral flow immunochromatographic system, and upon flow of the sample through the system, humanized anti-VLA-4 IgG4 antibody from the sample will first bind with a capture agent in the test zone to form a complex, the secondary agent will then reach the test zone, and then the complex will bind with the secondary agent and allow detection of humanized anti-VLA-4 IgG4 antibody; and wherein the capture agent is an antibody or an antigen binding fragment thereof and the secondary agent is an anti-IgG4 antibody or an antigen binding fragment thereof. 2. The device of claim 1, comprising sample. 3. The device of claim 1, comprising sample, and comprising a humanized anti-VLA-4 IgG4 antibody from the sample bound with a capture agent in the test zone to form a complex, wherein the complex does not comprise secondary agent. 4. The device of claim 1, comprising sample, and comprising a complex of a humanized anti-VLA-4 IgG4 antibody from the sample bound with a capture agent in the test zone, and wherein the complex further comprises a secondary agent. 5. The device of claim 1, wherein the binding of the capture agent to the anti-VLA-4 IgG4 antibody produces a detectable signal. 6. The device of claim 1, wherein the device is configured to allow detecting binding of the humanized anti-VLA-4 IgG4 antibody to the capture agent with a secondary agent within the lateral flow immunochromatographic system and determining whether the level of the humanized anti-VLA-4 IgG4 antibody is above or below a predetermined level based on the detecting. 7. The device of claim 6, configured such that the predetermined level is about 1 .mu.g/ml, 2 .mu.g/ml, 3 .mu.g/ml, 4 .mu.g/ml, 5 .mu.g/ml, 6 .mu.g/ml, 7 .mu.g/ml, 8 .mu.g/ml, 9 .mu.g/ml, 10 .mu.g/ml, 15 .mu.g/ml, or 20 .mu.g/ml. 8. The device of claim 1, wherein the sample is blood, plasma, serum, urine, saliva, cerebrospinal fluid, sputum, ocular lens fluid, sweat, milk, ascites fluid, mucous, synovial fluid, peritoneal fluid, transdermal exudates, pharyngeal exudates, bronchoalveolar lavage, tracheal aspirations, semen, cervical mucus, vaginal secretion, urethral secretion, or amniotic fluid. 9. The device of claim 1, wherein the humanized anti-VLA-4 IgG4 antibody is natalizumab. 10. The device of claim 1, wherein the device is configured such that binding of the capture agent to humanized anti-VLA-4 IgG4 antibody is detectable within 30 minutes of the contacting the sample. 11. The device of claim 1, wherein the sample is from a subject that was treated with natalizumab. 12. The device of claim 11, wherein the subject treated with natalizumab has been diagnosed with or is suspected of having a JC virus infection. 13. The device of claim 1, wherein the sample is from a subject that was treated with natalizumab and has been diagnosed with or is suspected of having PML. 14. The device of claim 1, wherein the sample is from a subject that was treated with natalizumab, and wherein the device is configured to allow rapidly monitoring a level of natalizumab in the subject. 15. The device of claim 1, further comprising a control zone downstream from the sample receiving zone. 16. The device of claim 15, wherein the control zone comprises a normalization zone. 17. The device of claim 16, wherein the normalization zone comprises an immobilized antibody against a serum component having similar concentrations across individual samples. 18. The device of claim 16, wherein the normalization zone comprises an immobilized antibody against a protein from an irrelevant species that is not present in blood but which is added at the same concentration to each sample prior to placing the sample in the lateral flow device. 19. The device of claim 18, wherein the protein is added to each sample directly. 20. The device of claim 18, wherein the sample is diluted with a chase buffer comprising the protein. 21. The device of claim 1, wherein the sample comprises a specificity control for assessing specificity of the lateral flow immunochromatographic system. 22. The device of claim 21, wherein the specificity control comprises an agent to which the capture agent and/or secondary agent cross-reacts. 23. The device of claim 22, wherein the agent is an anti-VLA-1 antibody. 24. The device of claim 1, wherein the sample is diluted in buffer. 25. The device of claim 24, wherein the buffer comprises a blocking agent. 26. The device of claim 1, further comprising a chase buffer port for applying chase buffer to the lateral flow immunochromatographic system. 27. A device for assaying the level of a humanized anti-VLA-4 IgG4 antibody in a sample from a subject, the device comprising: a capture agent associated with a substrate, wherein the capture agent can bind a humanized anti-VLA-4 IgG4 antibody in the sample, and wherein the substrate is a portion of a lateral flow immunochromatographic system comprising, in order of flow, a label zone, a sample receiving zone, and a test zone configured such that: the label zone is located upstream of the sample receiving zone and contains one or more secondary agents, the test zone is downstream of the label zone, upon flow through the lateral flow immunochromatographic system the sample reaches the test zone before a secondary agent from the label zone upon flow through the lateral flow immunochromatographic system, and upon flow of the sample through the system, humanized anti-VLA-4 IgG4 antibody from the sample will first bind with a capture agent in the test zone to form a complex, the secondary agent will then reach the test zone, and then the complex will bind with the secondary agent and allow detection of humanized anti-VLA-4 IgG4 antibody; and wherein the capture agent is an antibody or an antigen binding fragment thereof and the secondary agent is an anti-anti-VLA-4 antibody or an antigen binding fragment thereof. 28. The device of claim 27, comprising sample. 29. The device of claim 27, comprising sample, and comprising a humanized anti-VLA-4 IgG4 antibody from the sample bound with a capture agent in the test zone to form a complex, wherein the complex does not comprise secondary agent. 30. The device of claim 27, comprising sample, and comprising a complex of a humanized anti-VLA-4 IgG4 antibody from the sample bound with a capture agent in the test zone, and wherein the complex further comprises a secondary agent. 31. The device of claim 27, wherein the binding of the capture agent to the anti-VLA-4 IgG4 antibody produces a detectable signal. 32. The device of claim 27, wherein the device is configured to allow detecting binding of the humanized anti-VLA-4 IgG4 antibody to the capture agent with a secondary agent within the lateral flow immunochromatographic system and determining whether the level of the humanized anti-VLA-4 IgG4 antibody is above or below a predetermined level based on the detecting. 33. The device of claim 32, wherein the device is configured such that the predetermined level is about 1 .mu.g/ml, 2 .mu.g/ml, 3 .mu.g/ml, 4 .mu.g/ml, 5 .mu.g/ml, 6 .mu.g/ml, 7 .mu.g/ml, 8 .mu.g/ml, 9 .mu.g/ml, 10 .mu.g/ml, 15 .mu.g/ml, or 20 .mu.g/ml. 34. The device of claim 27, wherein the sample is blood, plasma, serum, urine, saliva, cerebrospinal fluid, sputum, ocular lens fluid, sweat, milk, ascites fluid, mucous, synovial fluid, peritoneal fluid, transdermal exudates, pharyngeal exudates, bronchoalveolar lavage, tracheal aspirations, semen, cervical mucus, vaginal secretion, urethral secretion, or amniotic fluid. 35. The device of claim 27, wherein the humanized anti-VLA-4 IgG4 antibody is natalizumab. 36. The device of claim 27, wherein the device is configured such that binding of the capture agent to humanized anti-VLA-4 IgG4 antibody is detectable within 30 minutes of the contacting the sample. 37. The device of claim 27, wherein the sample is from a subject that was treated with natalizumab. 38. The device of claim 37, wherein the subject treated with natalizumab has been diagnosed with or is suspected of having a JC virus infection. 39. The device of claim 27, wherein the sample is from a subject that was treated with natalizumab and has been diagnosed with or is suspected of having PML. 40. The device of claim 27, wherein the sample is from a subject that was treated with natalizumab, and wherein the device is configured to allow rapidly monitoring a level of natalizumab in the subject. 41. The device of claim 27, further comprising, a control zone downstream from the sample receiving zone. 42. The device of claim 41, wherein the control zone comprises a normalization zone. 43. The device of claim 42, wherein the normalization zone comprises an immobilized antibody against a serum component having similar concentrations across individual samples. 44. The device of claim 42, wherein the normalization zone comprises an immobilized antibody against a protein from an irrelevant species that is not present in blood but which is added at the same concentration to each sample prior to placing the sample in the lateral flow device. 45. The device of claim 44, wherein the protein is added to each sample directly. 46. The device of claim 44, wherein the sample is diluted with a chase buffer comprising the protein.

Details for Patent 9,726,672

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Biogen Inc.	TYSABRI	natalizumab	Injection	125104	11/23/2004		2029-10-11