ANTIGEN BINDING MOLECULES THAT BIND LIGHT
The present invention relates antigen binding molecules, particularly antibodies, fragments and variants thereof, that bind to the TNF-related cytokine LIGHT (TNFSF14), competing with LIGHT binding to cellular receptors Herpes virus entry mediator (HVEM) and lymphotoxin beta receptor, and the use of said antigen binding molecules in treating and/or preventing inflammatory disorders and immune disorders.
1 .- 32 . (canceled)
33 . An anti-LIGHT antigen binding molecule, wherein the antigen binding molecule has a higher affinity for membrane-bound LIGHT compared to soluble LIGHT, and wherein the anti-LIGHT antigen binding molecule comprises:
(a) a heavy chain variable region (VH) comprising a heavy chain complementarity determining region 1 (HCDR1) comprising the amino acid sequence DYYMY (SEQ ID NO: 110), a heavy chain complementarity determining region 2 (HCDR2) comprising the amino acid sequence AIGDGGIYTYYADTVKG (SEQ ID NO: 111), and a heavy chain complementarity determining region 3 (HCDR3) comprising the amino acid sequence GTGDGFAY (SEQ ID NO: 112); and
(b) a light chain variable region (VL) comprising a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence RASESVDSYGNSFMH (SEQ ID NO: 106), a light chain complementarity determining region 2 (LCDR2) comprising the amino acid sequence LASNLES (SEQ ID NO: 107), and a light chain complementarity determining region 3 (LCDR3) comprising the amino acid sequence QQNNEDPYT (SEQ ID NO: 108).
34 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the VH comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 109.
35 . The anti-LIGHT antigen binding molecule of claim 34 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 109.
36 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the VL comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 105.
37 . The anti-LIGHT antigen binding molecule of claim 36 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 105.
38 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the VH comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 109 and wherein the VL comprises an amino acid sequence having at least 80% sequence identity to SEQ ID NO: 105.
39 . The anti-LIGHT antigen binding molecule of claim 38 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 109 and wherein the VL comprises the amino acid sequence of SEQ ID NO: 105.
40 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the antigen binding molecule has from about 10 times to about 100 times higher affinity for membrane bound human LIGHT compared to soluble human LIGHT.
41 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the antigen binding molecule is an antibody, antigen-binding fragment, or derivative thereof.
42 . The anti-LIGHT antigen binding molecule of claim 41 , wherein the antigen-binding fragment, or derivative is Fab, F(ab′)2, Fv, scFv dAb, Fd, or a diabody.
43 . The anti-LIGHT antigen binding molecule of claim 41 , wherein the antibody or antigen-binding fragment is an IgA, IgD, IgE, IgG, IgM or IgY antibody or antigen-binding fragment.
44 . The anti-LIGHT antigen binding molecule of claim 43 , wherein the antibody or antigen-binding fragment is an IgG4 antibody or antigen-binding fragment.
45 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the antigen binding molecule inhibits the binding of membrane LIGHT to HVEM and LTpR or the binding of LIGHT expressing cells to HVEM and LTpR.
46 . The anti-LIGHT antigen binding molecule of claim 33 , wherein the antigen binding molecule partially inhibits the binding of membrane LIGHT to decoy receptor 3 or cells expressing membrane LIGHT to decoy receptor 3.
47 . A nucleic acid encoding the anti-LIGHT antigen binding molecule of claim 33 .
48 . A plasmid comprising the nucleic acid of claim 47 .
49 . A pharmaceutical composition comprising the anti-LIGHT antigen binding molecule of claim 33 and a pharmaceutically acceptable excipient.
50 . A method of treating a LIGHT-mediated disease or disorder in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the anti-LIGHT antigen binding molecule of claim 33 .
51 . A method of treating an inflammatory disorder or disease or an autoimmune disorder or disease in a subject in need thereof comprising administering to the subject a therapeutically effective amount of the anti-LIGHT antigen binding molecule of claim 33 .
52 . A method of inhibiting interferon-gamma (IFN-γ) release by administering to a subject in need thereof a therapeutically effective amount of the anti-LIGHT antigen binding molecule of claim 33 .