US 12,105,090 B2
Methods of treating a multiple sclerosis patient with anti-VLA-4 therapy
Gary Lewis Bloomgren, Concord, MA (US); Carmen Bozic, Newton, MA (US); Sophia Lee, Waltham, MA (US); Meena Subramanyam, Stoneham, MA (US); and Tatiana Plavina, North Reading, MA (US)
Assigned to Biogen MA Inc., Cambridge, MA (US)
Filed by BIOGEN MA INC., Cambridge, MA (US)
Filed on Dec. 5, 2018, as Appl. No. 16/211,154.
Application 16/211,154 is a continuation of application No. 14/122,754, abandoned, previously published as PCT/US2012/040283, filed on May 31, 2012.
Claims priority of provisional application 61/636,588, filed on Apr. 20, 2012.
Claims priority of provisional application 61/550,257, filed on Oct. 21, 2011.
Claims priority of provisional application 61/508,584, filed on Jul. 15, 2011.
Claims priority of provisional application 61/491,810, filed on May 31, 2011.
Prior Publication US 2019/0227064 A1, Jul. 25, 2019
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/395 (2006.01); A61K 39/00 (2006.01); G01N 33/53 (2006.01); G01N 33/569 (2006.01)
CPC G01N 33/56983 (2013.01) [C12N 2710/22011 (2013.01); G01N 2333/025 (2013.01); G01N 2469/20 (2013.01); G01N 2800/28 (2013.01); G01N 2800/2814 (2013.01); G01N 2800/50 (2013.01); G01N 2800/52 (2013.01)] 10 Claims
 
1. A method of treating a Multiple Sclerosis (MS) patient, the method comprising obtaining a biological sample from the patient, and responsive to a determination that the sample is negative for anti-JCV antibodies, administering to the patient an anti-VLA-4 therapy, said determination comprising:
measuring an anti-JC Virus (JCV) antibody titer reactivity index corresponding to an anti-JCV antibody titer by normalizing an OD value of the biological sample to a cut-off calibrator, said cut-off calibrator comprising a mixture of serum positive for anti-JCV antibodies and serum negative for anti-JCV antibodies and having a reactivity index of 1, wherein the anti-JCV antibody titer reactivity index is determined by an immunoassay to detect anti-JCV antibody in the sample;
classifying said sample as negative when said nOD value is less than 0.2 and positive when said nOD value is greater than 0.4, and responsive to a level of anti-JCV antibody corresponding to a nOD value between 0.2 and 0.4, measuring a percent inhibition by
(i) separating said biological sample into a first aliquot and a second aliquot and pre-incubating the first aliquot in absence of highly purified virus-like particle (HPVLPs) in solution and pre-incubating the second aliquot in presence of HPVLPs in solution under conditions suitable for binding of an anti-JCV antibody in the second aliquot to HPVLPs in solution; and
(ii) detecting a level of unbound anti-JCV antibody in each of the first aliquot and the second aliquot capable of binding to HPVLP disposed on a substrate to measure the percent to which HPVLP in solution inhibits anti-JCV antibody in the second aliquot from binding the HPVLP disposed on the substrate, and classifying said sample as negative when said inhibition is less than 45%.