US2003091564A1PendingUtilityA1

Methods of treating an undesired immune response by blocking the binding 0f cd40 ligand to cd40

Priority: Oct 25, 1991Filed: Aug 2, 1999Published: May 15, 2003
Est. expiryOct 25, 2011(expired)· nominal 20-yr term from priority
C07K 2319/32C07K 2319/03C07K 2319/74C07K 2319/73C07K 2319/02C07K 2319/75C07K 2319/00C12N 15/62C07K 14/70575A61K 38/00C07K 2319/30
34
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Claims

Abstract

There is disclosed a polypeptide (CD40-L) and DNA sequences, vectors and transformed host cells useful in providing CD40-L polypeptides. More particularly, this invention provides isolated human and murine CD40-L polypeptides that bind to the extracellular binding region of a CD40 receptor.

Claims

exact text as granted — not AI-modified
What is claimed is:  
     
         1 . A isolated CD40-L polypeptide selected from the group consisting of: 
 (a) a peptide comprising amino acids 1 through 261, 35 through 261, 34 through 225,113 through 261, 113 through 225, 120 through 261, or 120 through 225 of SEQ ID NO:11 and their complementary strands; and    (b) peptides encoded by DNA which hybridizes to a DNA that encodes a peptide of (a), under stringent conditions (hybridization in 6×SSC at 63° C. overnight; washing in 3×SSC at 55° C.), and which bind to CD40.    
     
     
         2 . The isolated CD40-L polypeptide according to  claim 1  which is a soluble CD40-L polypeptide.  
     
     
         3 . The isolated CD40-L polypeptide according to  claim 2  wherein the cysteine at residue 194 of SEQ ID NO:12 is substituted with an amino acid other than cysteine.  
     
     
         4 . The isolated CD40-L polypeptide according to  claim 3  wherein the substituted amino acid is selected from the group consisting of tryptophan, serine, aspartic acid, and lysine.  
     
     
         5 . The isolated CD40-L polypeptide according to  claim 2  which further comprises an oligomerizing zipper peptide.  
     
     
         6 . The isolated CD40-L polypeptide according to  claim 3  which further comprises an oligomerizing zipper peptide.  
     
     
         7 . The isolated CD40-L polypeptide according to  claim 4  which further comprises an oligomerizing zipper peptide.  
     
     
         8 . The isolated DNA according to  claim 5  wherein the oligomerzing zipper peptide is a peptide having an amino acid sequence represented by SEQ ID NO:17.  
     
     
         9 . The isolated CD40-L polypeptide according to  claim 6  wherein the oligomerizing zipper peptide is a peptide having an amino acid sequence represented by SEQ ID NO:17.  
     
     
         10 . The isolated CD40-L polypeptide according to  claim 7  wherein the oligomerizing zipper peptide is a peptide having an amino acid sequence represented by SEQ ID NO:17.  
     
     
         11 . An isolated CD40-L polypeptide which has an amino acid sequence represented by SEQ ID NO:21.  
     
     
         12 . The isolated CD40-L polypeptide according to  claim 11  wherein the cysteine at residue 180 of SEQ ID NO:21 is substituted with an amino acid other than cysteine.  
     
     
         13 . The isolated CD40-L polypeptide according to  claim 12  wherein the substituted amino acid is selected from the group consisting of tryptophan, serine, aspartic acid, and lysine.  
     
     
         14 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 2 , and a suitable diluent or carrier.  
     
     
         15 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 5 , and a suitable diluent or carrier.  
     
     
         16 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 8 , and a suitable diluent or carrier.  
     
     
         17 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 9 , and a suitable diluent or carrier.  
     
     
         18 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 10 , and a suitable diluent or carrier.  
     
     
         19 . A pharmaceutical composition comprising a CD40-L polypeptide according to  claim 11 , and a suitable diluent or carrier.  
     
     
         20 . A method of inhibiting an undesirable immune response comprising administering an effective amount of a CD40 antagonist selected from the group consisting of a soluble CD40 protein, a CD40 fusion protein, a soluble monomeric CD40-L polypeptide, an antagonistic antibody to CD40, an antagonistic antibody to CD40-L, and combinations thereof.  
     
     
         21 . The method according to  claim 20 , wherein the undesirable immune response is selected from the group consisting of allergy, systemic lupus erythematosis, rheumatoid arthritis, insulin dependent diabetes mellitus, and graft versus host disease.  
     
     
         22 . An antibody immunoreactive with CD40-L or a CD40-L immunogen.  
     
     
         23 . An antibody according to  claim 22  which is a monoclonal antibody.

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