Anti-B7-H4 Antibodies And Methods

Abstract

Compositions, methods, and uses of recombinant B7-H4 protein or binding motifs to B7-H4 protein that can reduce the immune suppression effect of B7-H4 in relation to T cell activation, proliferation, and conversion. Preferably, the recombinant B7-H4 protein has a plurality of mutations in N-glycosylation residue to reduce its inhibitory effect to T cell activation and proliferation. The recombinant protein having binding motifs to B7-H4 protein preferably includes a binding motif to IgC domain and another binding motif to IgV domain such that the immune-suppressive effects by two Ig-like domains are concurrently reduced.

What is claimed is: 
     
         1 - 53 . (canceled) 
     
     
         54 . A pharmaceutical composition comprising an extracellular portion of a hypo-glycosylated mutant form of B7-H4. 
     
     
         55 . The pharmaceutical composition of  claim 54 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least one mutation of the amino acid arginine, wherein the arginine is selected from the group consisting of N112, N160, N190, N196, N205, N216, and N220 with reference to the wild type B7-H4 amino acid sequence. 
     
     
         56 . The pharmaceutical composition of  claim 55 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least three arginine mutations. 
     
     
         57 . The pharmaceutical composition of  claim 55 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least five arginine mutations. 
     
     
         58 . The pharmaceutical composition of  claim 55 , wherein the hypo-glycosylated mutant form of B7-H4 comprises mutations at positions N160, N190, N196, N205, N216, and N220. 
     
     
         59 . The pharmaceutical composition of  claim 58 , wherein the hypo-glycosylated mutant form of B7-H4 comprises N160G, N190G, N196G, N205G, N216G, and N220G mutations. 
     
     
         60 . The pharmaceutical composition of  claim 54 , wherein the hypo-glycosylated mutant form of B7-H4 is coupled to a pharmaceutically acceptable carrier. 
     
     
         61 . A chimeric protein comprising the pharmaceutical composition of  claim 54 . 
     
     
         62 . The chimeric protein of  claim 61 , further comprising a IgG Fc portion, and optionally further comprising at least one of an Interleukin 15 receptor alpha (IL-15Ra) portion, an IL-15 portion, and an IL-15 superagonist portion. 
     
     
         63 . The pharmaceutical composition of  claim 54 , wherein the hypo-glycosylated mutant form of B7-H4 competitively inhibits endogenous B7-H4 from binding to its receptor on a T cell. 
     
     
         64 . The pharmaceutical composition of  claim 54 , wherein the hypo-glycosylated mutant form of B7-H4 inhibits T cell proliferation. 
     
     
         65 . A recombinant expression vector comprising a nucleic acid sequence that encodes a hypoglycosylated mutant form of B7-H4. 
     
     
         66 . The recombinant expression vector of  claim 65 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least one mutation of the amino acid arginine, wherein the arginine is selected from the group consisting of N112, N160, N190, N196, N205, N216, and N220 with reference to the wild type B7-H4 amino acid sequence. 
     
     
         67 . The recombinant expression vector of  claim 66 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least three arginine mutations. 
     
     
         68 . The recombinant expression vector of  claim 66 , wherein the hypo-glycosylated mutant form of B7-H4 comprises at least five arginine mutations. 
     
     
         69 . The recombinant expression vector of  claim 66 , wherein the hypo-glycosylated mutant form of B7-H4 comprises mutations at positions N160, N190, N196, N205, N216, and N220. 
     
     
         70 . The recombinant expression vector of  claim 66 , wherein the hypo-glycosylated mutant form of B7-H4 comprises N160G, N190G, N196G, N205G, N216G, and N220G mutations. 
     
     
         71 . The recombinant expression vector of  claim 66 , wherein the the expression vector is selected from a group consisting of a viral expression vector, a bacteria expression vector, and a yeast expression vector. 
     
     
         72 . The recombinant expression vector of  claim 66 , wherein the vector is formulated for administration by subcutaneous, subdermal, intravenous, or intratumoral injection.