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AssigneeBiogen Idec MA Inc.
InventorsJeffrey L. Browning, Christopher D. Benjamin, Paula S. Hochman
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This invention relates to compositions and methods comprising “lymphotoxin-β receptor blocking agents”, which block lymphotoxin-β receptor signalling. Lymphotoxin-β receptor blocking agents are useful for treating lymphocyte-mediated immunological diseases, and more particularly, for inhibiting Th1 cell-mediated immune responses. This invention relates to soluble forms of the lymphotoxin-β receptor extracellular domain that act as lymphotoxin-β receptor blocking agents. This invention also relates to the use of antibodies directed against either the lymphotoxin-β receptor or its ligand, surface lymphotoxin, that act as lymphotoxin-β receptor blocking agents. A novel screening method for selecting soluble receptors, antibodies and other agents that block LT-β receptor signalling is provided.
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a subject having a Th1 cell-mediated autoimmune disorder comprising administering to the subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent, and a pharmaceutically acceptable carrier, wherein the LT-β-R blocking agent comprises a soluble LT-β-R.
A method for inhibiting lymphotoxin-β receptor (LT-β-R) signaling in a subject having a Th1 cell-mediated autoimmune disorder comprising administering to the subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent comprising a soluble LT-β-R fused to one or more heterologous protein domains, and a pharmaceutically acceptable carrier, wherein the soluble LT-β-R has a ligand binding domain that can selectively bind to a surface LT ligand.
A method for inhibiting lymphotoxin-β receptor (LT-β-R) signaling in a subject having a Th1 cell-mediated autoimmune disorder comprising administering to the subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent comprising a soluble LT-β-R fused to a heterologous domain comprising a human immunoglobulin Fc domain, and a pharmaceutically acceptable caffier, wherein the soluble LT-β-R comprises a functional sequence of amino acids selected from the amino acids of SEQ ID NO:
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a subject having a Th1 cell-mediated chronic inflammatory disease comprising administering to the subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent, and a pharmaceutically acceptable carrier, wherein the LT-β-R blocking agent comprises a soluble LT-β-R.
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a subject having a Th1 cell-mediated autoimmune disorder or a Th1 cell-mediated chronic inflammatory disease comprising administering to the subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent, and a pharmaceutically acceptable carrier, wherein the LT-β-R blocking agent comprises an antibody directed against LT-β-R.
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a human subject having rheumatoid arthritis comprising administering to the human subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent comprising a soluble LT-β-R fused to a heterologous domain comprising a human immunoglobulin Fc domain, and a pharmaceutically acceptable carrier, wherein the soluble LT-β-R comprises a functional sequence of amino acids selected from the amino acids of SEQ ID NO:
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a human subject having ulcerative colitis comprising administering to the human subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent comprising a soluble LT-β-R fused to a heterologous domain comprising a human immunoglobulin Fc domain, and a pharmaceutically acceptable carrier, wherein the soluble LT-β-R comprises a functional sequence of amino acids selected from the amino acids of SEQ ID NO:
A method for inhibiting lymphotoxin-β-receptor (LT-β-R) signaling in a human subject having Crohn's disease comprising administering to the human subject a pharmaceutical composition comprising an effective amount of an LT-β-R blocking agent comprising a soluble LT-β-R fused to a heterologous domain comprising a human immunoglobulin Fc domain, and a pharmaceutically acceptable carrier, wherein the soluble LT-β-R comprises a functional sequence of amino acids selected from the amino acids of SEQ ID NO:
Dependencies are inferred from the claim text.