Selective integrin inhibitors
AssigneeElan Pharmaceuticals, Inc.
InventorsAnthony Pepio, Gordon Francis, Theodore A. Yednock, Alissa Chackerian, Brian Todd Wipke
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Abstract
This invention provides methods for selectively antagonizing the α4β1 integrin heterodimer in a subject in need thereof, and preferably in a human subject. The methods of the invention utilize conjugates comprising two or more α4β1 small molecule antagonists covalently attached to a biocompatible polymer. These methods of selectively inhibiting α4β1 may be used modulate both normal and pathological biological processes mediated at least in part through α4β1 activity.
Claims44
A method of treating a disease mediated by α4β1-mediated leukocyte trafficking into the CNS while substantially preserving α4β7-mediated trafficking, comprising administering a compound of Formula (I) to a subject in need of such treatment at a therapeutically effective dose and interval.
A method of selectively inhibiting α4β1 activity in a subject, comprising administering to the subject a therapeutically effective amount of a conjugate comprising two or more α4β1 small molecule antagonists covalently attached to a biocompatible polymer, wherein the conjugate has a 20 to 100 fold greater potency towards α4β1 than α4β7.
A method of treating multiple sclerosis in a subject in need thereof, comprising administering to the subject a compound having a 30 to 80 fold greater potency towards α4β1 than α4β7 in a dose from about 0.01 mg/kg to about 5 mg/kg.
A method of treating an autoimmune disease in a subject in need thereof, comprising administering to the subject a compound having a 30 to 80 fold greater potency towards α4β1 than α4β7 in a dose from about 0.01 mg/kg to about 5 mg/kg.
A method of treating an inflammatory disease in a subject in need thereof, comprising administering to the subject a compound having a 30 to 80 fold greater potency towards α4β1 than α4β7 in a dose from about 0.01 mg/kg to about 5 mg/kg.
A method of treating a cell proliferative disorder in a subject in need thereof, comprising administering to the subject a compound having a 30 to 80 fold greater potency towards α4β1 than α4β7 in a dose from about 0.01 mg/kg to about 10 mg/kg.
A method of treating an autoimmune disease that is mediated in part by α4β1 integrin receptors while sparing α4β7 mediated immune cell interactions in a patient comprising administering to the patient a weekly, bi-weekly or monthly dose of a compound of Formula (I) of from about 0.2 mg/kg to about 1.0 mg/kg.
A method of treating an autoimmune disease that is mediated in part by α4β1 integrin receptors while sparing α4β7 mediated immune cell surveillance in a patient comprising administering to the patient a weekly, bi-weekly or monthly dose of a compound of Formula (I) of from about 0.2 mg/kg to about 1.0 mg/kg.
Dependencies are inferred from the claim text.