Claims for Patent: 9,377,458

Summary for Patent: 9,377,458

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:	13/501,111
Patent Claims:	1. A method of assaying the level of a humanized anti-VLA-4 IgG4 antibody in a subject, the method comprising: a) contacting a biological sample from a subject with 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 b) 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; 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 method of claim 1, wherein the binding of the capture agent to the anti-VLA-4 IgG4 antibody produces a detectable signal. 3. The method of claim 1, wherein 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. 4. The method of claim 1, wherein the biological 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. 5. The method of claim 1, wherein the humanized anti-VLA-4 IgG4 antibody is natalizumab. 6. The method of claim 1, wherein the binding of the capture agent to humanized anti-VLA-4 IgG4 antibody is detectable within 30 minutes of the contacting. 7. The method of claim 1, wherein the subject was treated with natalizumab. 8. The method of claim 7, wherein the subject treated with natalizumab has been diagnosed with or is suspected of having a JC virus infection. 9. The method of claim 1, wherein the subject was treated with natalizumab and has been diagnosed with or is suspected of having PML. 10. The method of claim 1, wherein the subject was treated with natalizumab, and wherein the detecting comprises rapidly monitoring a level of natalizumab in the subject. 11. The method of claim 1, further comprising treating the subject based on the detecting. 12. The method of claim 11, wherein treating the subject comprises blood apheresis selected from therapeutic plasma exchange, cytoreduction, photopheresis, and selective absorption. 13. The method of claim 12, wherein treating comprises plasma exchange to decrease the level of humanized anti-VLA-4 IgG4 antibody. 14. The method of claim 13, wherein the detecting occurs one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, or four weeks after a plasma exchange treatment. 15. The method of claim 13, wherein the plasma exchange treatment is repeated once a day, or once every two days, three days, four days, five days, six days, one week, two weeks, three weeks, or four weeks. 16. The method of claim 1, comprising evaluating a treatment. 17. The method of claim 16, wherein the treatment comprises blood apheresis selected from therapeutic plasma exchange, cytoreduction, photopheresis, and selective absorption. 18. The method of claim 1, wherein the lateral flow device further comprises, a control zone downstream from the sample receiving zone. 19. The method of claim 18, wherein the control zone comprises a normalization zone. 20. The method of claim 19, wherein the normalization zone comprises an immobilized antibody against a serum component having similar concentrations across individual samples. 21. The method of claim 19, 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. 22. The method of claim 21, wherein the protein is added to each sample directly. 23. The method of claim 21, wherein the sample is diluted with a chase buffer comprising the protein. 24. The method of claim 1, wherein the sample comprises a specificity control for assessing specificity of the lateral flow immunochromatographic system. 25. The method of claim 24, wherein the specificity control comprises an agent to which the capture agent and/or secondary agent cross-reacts. 26. The method of claim 25, wherein the agent is an anti-VLA-1 antibody. 27. The method of claim 1, wherein the sample is diluted in buffer prior to the contacting. 28. The method of claim 1, wherein the buffer comprises a blocking agent. 29. The method of claim 1, further comprising applying chase buffer to the lateral flow immunochromatographic system. 30. The method of claim 1, wherein the lateral flow immunochromatographic system further comprises a chase buffer port for applying chase buffer to the lateral flow immunochromatographic system. 31. A method of assaying the level of a humanized anti-VLA-4 IgG4 antibody in a subject, the method comprising: a) contacting a biological sample from a subject with 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 b) 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; 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. 32. The method of claim 31, further comprising treating the subject based on the detecting. 33. The method of claim 32, wherein treating the subject comprises blood apheresis selected from therapeutic plasma exchange, cytoreduction, photopheresis, and selective absorption. 34. The method of claim 33, wherein treating comprises plasma exchange to decrease the level of humanized anti-VLA-4 IgG4 antibody. 35. The method of claim 34, wherein the detecting occurs one day, two days, three days, four days, five days, six days, one week, two weeks, three weeks, or four weeks after a plasma exchange treatment. 36. The method of claim 34, wherein the plasma exchange treatment is repeated once a day, or once every two days, three days, four days, five days, six days, one week, two weeks, three weeks, or four weeks. 37. The method of claim 31, wherein the binding of the capture agent to the anti-VLA-4 IgG4 antibody produces a detectable signal. 38. The method of claim 31, wherein 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. 39. The method of claim 31, wherein the biological 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. 40. The method of claim 31, wherein the humanized anti-VLA-4 IgG4 antibody is natalizumab. 41. The method of claim 31, wherein the binding of the capture agent to humanized anti-VLA-4 IgG4 antibody is detectable within 30 minutes of the contacting. 42. The method of claim 31, wherein the subject was treated with natalizumab. 43. The method of claim 42, wherein the subject treated with natalizumab has been diagnosed with or is suspected of having a JC virus infection. 44. The method of claim 31, comprising evaluating a treatment. 45. The method of claim 44, wherein the treatment comprises blood apheresis selected from therapeutic plasma exchange, cytoreduction, photopheresis, and selective absorption. 46. The method of claim 31, wherein the subject was treated with natalizumab and has been diagnosed with or is suspected of having PML. 47. The method of claim 31, wherein the subject was treated with natalizumab, and wherein the detecting comprises rapidly monitoring a level of natalizumab in the subject. 48. The method of claim 31, wherein the lateral flow device further comprises, a control zone downstream from the sample receiving zone. 49. The method of claim 48, wherein the control zone comprises a normalization zone. 50. The method of claim 49, wherein the normalization zone comprises an immobilized antibody against a serum component having similar concentrations across individual samples. 51. The method of claim 49, 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. 52. The method of claim 51, wherein the protein is added to each sample directly. 53. The method of claim 51, wherein the sample is diluted with a chase buffer comprising the protein.

Details for Patent 9,377,458

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