Antibody fc variants

Abstract

The invention relates to engineered polypeptides comprising Fc variants and their uses. More specifically, Fc variants are described exhibiting reduced effector function. These variants cause a benefit for a patient suffering from a disease which could be treated with an antibody for which it is desirable to reduce the effector function elicited by antibodies.

1 - 19 . (canceled) 
     
     
         20 : A polypeptide comprising an Fc variant of a wild-type human IgG1 Fc region, said Fc variant comprising an amino acid substitution at position Pro329 and at least one further amino acid substitution, wherein Pro329 of a wild-type human Fc region is substituted with glycine, and at least one further amino acid substitution, wherein said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region, wherein the residues are numbered according to the EU index of Kabat. 
     
     
         21 : The polypeptide according to  claim 20 , wherein the wild-type human IgG1 polypeptide induces an ADCC and wherein the ADCC induced by the IgG1 Fc variant polypeptide is reduced to 0-20% of the ADCC induced by the polypeptide comprising the wild-type human IgG1 Fc region. 
     
     
         22 : The polypeptide according to  claim 20 , wherein the polypeptide comprising the Fc variant, exhibits a reduced or ablated affinity for an Fc receptor responsible for an effector function compared to a polypeptide comprising the wild-type human IgG1 Fc region. 
     
     
         23 : The polypeptide according to  claim 20 , wherein the polypeptide is an antibody or an Fc fusion protein. 
     
     
         24 : The polypeptide according to  claim 20  wherein the wild-type human IgG1 polypeptide induces thrombocyte aggregation and wherein the thrombocyte aggregation induced by the IgG1 Fc variant polypeptide is reduced compared to the thrombocyte aggregation induced by a polypeptide comprising a wild-type human IgG1 Fc region. 
     
     
         25 : The polypeptide according to  claim 20 , wherein the wild-type human IgG1 polypeptide induces CDC and wherein the CDC induced by IgG1 Fc variant polypeptide is strongly reduced compared to the CDC induced by a polypeptide comprising a wild-type human IgG1 Fc region. 
     
     
         26 : The polypeptide according to  claim 20 , wherein the polypeptide is an anti-CD9 antibody, which is characterized in that the polypeptide comprising the wild-type Fc region comprises as heavy chain variable region SEQ ID NO:9 and as variable light chain region SEQ ID NO:8. 
     
     
         27 : A method for treating a disease in an individual wherein it is favorable that an effector function of the polypeptide is strongly reduced compared to the effector function induced by a polypeptide comprising a wild-type human IgG Fc region, the method comprising administering a therapeutically effective amount of a polypeptide comprising an Fc variant of a wild-type human IgG1 Fc region, said Fc variant comprising an amino acid substitution at position Pro329 and at least one further amino acid substitution, wherein Pro329 of a wild-type human Fc region is substituted with glycine, and at least one further amino acid substitution, wherein said at least one further amino acid substitution is L234A and L235A of the human IgG1 Fc region, wherein the residues are numbered according to the EU index of Kabat. 
     
     
         28 : The method according to  claim 27 , wherein the wild-type human IgG1 polypeptide induces an ADCC and wherein the ADCC induced by the IgG1 Fc variant polypeptide is reduced to 0-20% of the ADCC induced by the polypeptide comprising the wild-type human IgG1 Fc region. 
     
     
         29 : The method according to  claim 27 , wherein the polypeptide comprising the Fc variant, exhibits a reduced or ablated affinity for an Fc receptor responsible for an effector function compared to a polypeptide comprising the wild-type human IgG1 Fc region. 
     
     
         30 : The method according to  claim 27 , wherein the polypeptide is an antibody or an Fc fusion protein. 
     
     
         31 : The method according to  claim 27  wherein the wild-type human IgG1 polypeptide induces thrombocyte aggregation and wherein the thrombocyte aggregation induced by the IgG1 Fc variant polypeptide is reduced compared to the thrombocyte aggregation induced by a polypeptide comprising a wild-type human IgG1 Fc region. 
     
     
         32 : The method according to  claim 27 , wherein the wild-type human IgG1 polypeptide induces CDC and wherein the CDC induced by IgG1 Fc variant polypeptide is strongly reduced compared to the CDC induced by a polypeptide comprising a wild-type human IgG1 Fc region. 
     
     
         33 : The method according to  claim 27 , wherein the polypeptide is an anti-CD9 antibody, which is characterized in that the polypeptide comprising the wild-type Fc region comprises as heavy chain variable region SEQ ID NO:9 and as variable light chain region SEQ ID NO:8.