Monoclonal antibodies to growth and differentiation factor 15 (gdf-15)

Abstract

The present invention relates to novel monoclonal anti-human-GDF-15 antibodies, pharmaceutical compositions, kits, methods and uses and the cell lines capable of producing the monoclonal antibodies described herein. The present invention further relates to novel antibodies to human GDF-15 capable of inhibiting cancer growth.

1 . A monoclonal antibody capable of binding to human GDF-15, or an antigen-binding portion thereof, wherein the heavy chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 5 or an amino acid sequence at least 90% identical thereto, and wherein the light chain variable domain comprises a CDR3 region comprising the amino acid sequence of SEQ ID NO: 7 or an amino acid sequence at least 85% identical thereto. 
     
     
         2 . The monoclonal antibody or antigen-binding portion thereof according to  claim 1 , wherein the antibody is the antibody to human GDF-15 obtainable from the cell line B1-23 deposited with the Deutsche Sammlung für Mikroorganismen und Zellkulturen GmbH (DMSZ) under the accession No. DSM ACC3142 or an antigen-binding portion thereof. 
     
     
         3 . The monoclonal antibody or antigen-binding portion thereof of any one of  claims 1 - 2 , wherein the antibody is capable of inhibiting cancer growth in a mammal, preferably a human patient. 
     
     
         4 . The monoclonal antibody or antigen-binding portion thereof of any one of  claims 1 - 3 , wherein the human GDF-15 is recombinant human GDF-15 having the amino acid sequence represented by SEQ ID No: 8. 
     
     
         5 . The monoclonal antibody or antigen-binding portion thereof of any one of  claims 1 - 4 , wherein the binding is binding to a conformational or discontinuous epitope on human GDF-15. 
     
     
         6 . The monoclonal antibody or antigen-binding portion thereof of  claim 5 , wherein the binding to a conformational or discontinuous epitope on human GDF-15 is binding to a conformational or discontinuous epitope comprised by the amino acid sequences of SEQ ID No: 25 and SEQ ID No: 26. 
     
     
         7 . A monoclonal antibody capable of binding to human GDF-15, or an antigen-binding portion thereof, wherein the binding is binding to a conformational or discontinuous epitope on human GDF-15 comprised by the amino acid sequences of SEQ ID No: 25 and SEQ ID No: 26. 
     
     
         8 . The monoclonal antibody or antigen-binding portion thereof of  claim 7 , wherein the antibody or antigen-binding portion thereof is an antibody or antigen-binding portion thereof as defined in any one of  claims 1 - 4 . 
     
     
         9 . A pharmaceutical composition comprising the antibody or antigen-binding portion thereof according to any one of  claims 1  to  8 . 
     
     
         10 . An antibody or antigen-binding portion thereof according to any one of  claims 1  to  8  or a pharmaceutical composition according to  claim 9  for use in a method for treating cancer in a mammal, the method comprising administering the antibody or antigen-binding portion thereof or the pharmaceutical composition to said mammal. 
     
     
         11 . The antibody or antigen-binding portion thereof or the pharmaceutical composition according to  claim 10  for the use according to  claim 10 , wherein the mammal is human patient. 
     
     
         12 . The antibody or antigen-binding portion thereof or the pharmaceutical composition according to any one of  claims 10  to  11  for the use according to any one of  claims 10  to  11 , wherein the method comprises inhibiting cancer growth. 
     
     
         13 . The antibody or antigen-binding portion thereof or the pharmaceutical composition according to any one of  claims 11  to  12  for the use according to any one of  claims 11  to  12 , wherein the method comprises the induction of killing of cancer cells by NK cells and CD8+ T cells in the human patient. 
     
     
         14 . A kit comprising the pharmaceutical composition of  claim 9 . 
     
     
         15 . The kit of  claim 14  for a use according to any one of  claims 10  to  13 . 
     
     
         16 . An expression vector comprising a nucleotide sequence encoding the antibody or antigen-binding portion thereof according to any of  claims 1 - 8 . 
     
     
         17 . A cell line capable of producing an antibody or antigen-binding portion thereof according to any one of  claims 1  to  8 . 
     
     
         18 . The cell line according to  claim 17 , wherein the cell line is the cell line B1-23 deposited with the Deutsche Sammlung für Mikroorganismen und Zellkulturen GmbH (DMSZ) under the accession No. DSM ACC3142.