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US 12,716,899 B2Granted
Methods for determining differences in alpha-4 integrin activity by correlating differences in sVCAM and/or sMAdCAM levels
AssigneeBiogen MA Inc.
InventorAlissa A. Chackerian
Life of this patent
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Abstract
Provided herein is a method of monitoring the change of the alpha-4 integrin activities in an individual by correlating with the soluble vascular cell adhesion molecule (sVCAM) and/or soluble mucosal addressin cell adhesion molecule (sMAdCAM) levels. Particularly, this method can be used, for example, to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) of an alpha-4 integrin inhibitor used to treat a disease associated with pathological or chronic inflammation.
Claims18
A method of adjusting the treatment of an individual with an alpha-4 integrin inhibitor, comprising:
- a) measuring a soluble molecule in a first biological sample obtained from the individual immediately before administration of a first dose of an alpha-4 integrin inhibitor, wherein the soluble molecule is soluble Vascular Cell Adhesion Molecule (sVCAM) and/or Mucosal addressin cell adhesion molecule 1 (sMAdCAM) and the alpha-4 integrin inhibitor is an anti-alpha-4 integrin antibody;
- b) measuring the soluble molecule in a second biological sample, wherein the second biological sample has been obtained from the individual within 1, 2, 3 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days after administration of the first dose of the alpha-4 integrin inhibitor;
- c) determining whether there is a decrease in the levels of the soluble molecule between the first and second biological samples, wherein the decrease correlates with a decrease in alpha-4 integrin activity in the individual, and thereby determining whether there is a difference in alpha-4 integrin activity in the individual after administration of the alpha-4 integrin inhibitor compared with before administration of the alpha-4 integrin inhibitor;
- and
- d) administering either an increased second dose of the same alpha-4 integrin inhibitor to the individual, or a dose of a different alpha-4 integrin inhibitor, when there is no decrease or a statistically insignificant decrease (p>0.05) in the levels of the soluble molecule between the first and second biological samples indicating an ineffective response to the alpha-4 integrin inhibitor, or administering the same dose of the same alpha-4 integrin inhibitor to the individual when there is a statistically significant decrease (p<0.05) in the levels of sVCAM and/or sMAdCAM between the first and second biological samples.
2 more elements
A method of treating an individual having an autoimmune disease, comprising:
- a) measuring a soluble molecule in a first biological sample obtained from the individual immediately before administration of a first dose of an alpha-4 integrin inhibitor;
- b) administering the first dose of the alpha-4 integrin inhibitor to the individual;
- c) measuring the soluble molecule in a second biological sample, wherein the second biological sample is obtained from the individual within 1, 2, 3 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days after administration of the first dose of the alpha-4 integrin inhibitor;
- d) determining whether there is a decrease in the levels of the soluble molecule between the first and the second biological samples;
- and
- e) administering a second dose of the alpha-4 integrin inhibitor to the individual, wherein the second dose of the alpha-4 integrin inhibitor is based on whether there is a decrease in the levels of the soluble molecule between the first and the second biological samples, wherein the decrease correlates with a decrease in alpha-4 integrin activity in the individual, and thereby determining whether there is a difference in alpha-4 integrin activity in the individual after administration of the alpha-4 integrin inhibitor compared with before administration of the alpha-4 integrin inhibitor;
- wherein the soluble molecule is sVCAM and/or sMAdCAM, and wherein the alpha-4 integrin inhibitor is an anti-alpha-4 integrin antibody.
4 more elements
Dependencies are inferred from the claim text.