Monoclonal antibodies against dengue and other viruses with deletion in fc region

Abstract

The present invention relates to a variant of a parent polypeptide comprising an Fc region, which variant binds an Fc gamma receptor (FcγR) with lower affinity than the parent polypeptide and comprises a deletion of at least one amino acid in about position 100 to about position 150 in the Fc region and related nucleic acids, vectors, host cells and methods of producing the variant and methods for preventing or treating a disorder in a mammal.

What is claimed is: 
     
         1 . A composition comprising a peptide of SEQ ID NO: 51 or SEQ ID NO: 52, wherein said peptide comprises a deletion of at least 1 amino acid in about position 100 to about position 150. 
     
     
         2 . The composition of  claim 1 , wherein said peptide comprises a deletion of at least about 4 amino acids. 
     
     
         3 . The composition of  claim 1 , wherein said peptide comprises a deletion of at least about nine amino acids. 
     
     
         4 . The composition of  claim 1 , wherein said peptide binds an Fc gamma receptor (FcγR) with lower affinity than a peptide of SEQ ID NO: 53 or 54. 
     
     
         5 . The composition of any of  claim 1 , wherein said peptide has about 100 fold lower affinity to the Fc gamma receptor (FcγR) than SEQ ID NO: 53 or 54. 
     
     
         6 . The composition of  claim 1 , wherein the deletion is from about position 114 to about position 122. 
     
     
         7 . The composition of  claim 1 , wherein the deletion is APELLGGPS. 
     
     
         8 . The composition of  claim 1 , wherein the peptide is no 5H2. 
     
     
         9 . The composition of  claim 1 , wherein said composition is an antibody or fragment thereof. 
     
     
         10 . A composition comprising a nucleic acid encoding a peptide of SEQ ID NO: 51 or SEQ ID NO: 52, wherein said peptide comprises a deletion of at least 1 amino acid in about position 100 to about position 150. 
     
     
         11 . The composition of  claim 10 , wherein said peeptide comprises a deletion of at least about 4 amino acids. 
     
     
         12 . The composition of  claim 10 , wherein said peptide comprises a deletion of at least about 9 amino acids. 
     
     
         13 . The composition of  claim 1 , wherein said peptide binds an Fc gamma receptor (FcγR) with lower affinity than a peptide of SEQ ID NO: 53 or 54. 
     
     
         14 - 17 . (canceled) 
     
     
         18 . A vector comprising the nucleic acid of  claim 1 . 
     
     
         19 . A host cell comprising the vector of  claim 18 . 
     
     
         20 . A method for preventing or treating dengue virus infection or a symptom thereof in a mammal comprising providing to said mammal a prophylatically or therapeutically effective amount of the composition of  claim 1 . 
     
     
         21 . The method of  claim 20 , further comprising identifying a mammal in need of an agent that prevents or treats dengue virus infection or a symptom thereof. 
     
     
         22 . The method of  claim 21 , wherein said identification is clinical evaluation or evaluation by diagnostic approach. 
     
     
         23 - 24 . (canceled) 
     
     
         25 . A method of reducing antibody-dependent enhancement (ADE) in a mammal comprising providing to said mammal a composition of  claim 1 . 
     
     
         26 . The method of  claim 25 , further comprising identifying a mammal in need of an agent that reduces antibody-dependent enhancement (ADE). 
     
     
         27 - 29 . (canceled) 
     
     
         30 . A method of inducing a complement-mediated neutralization in a mammal comprising providing to said mammal a composition of  claim 1 . 
     
     
         31 . The method of  claim 30 , further comprising identifying a mammal in need of an agent that induces a complement-mediated neutralization. 
     
     
         32 - 34 . (canceled) 
     
     
         35 . A method of inducing antibody-dependent cellular toxicity in a mammal comprising providing to said mammal a composition of  claim 1 . 
     
     
         36 - 39 . (canceled)