Rspo binding agents and uses thereof

Abstract

The present invention relates to RSPO-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO proteins, such as antibodies that specifically bind RSPO1, RSPO2, and/or RSPO3 and inhibit tumor growth. Also described are methods of treating cancer comprising administering a therapeutically effect amount of an agent or antibody of the present invention to a patient having a tumor or cancer.

1 - 173 . (canceled) 
     
     
         174 . A polynucleotide encoding the heavy chain variable region and/or light chain variable region of an antibody that specifically binds human R-spondin2 (RSPO2), wherein:
 (a) the heavy chain CDR1 comprises SSYAMS (SEQ ID NO:29), the heavy chain CDR2 comprises SISSGGSTYYPDSVKG (SEQ ID NO:30), and the heavy chain CDR3 comprises RGGDPGVYNGDYEDAMDY (SEQ ID NO:31); and   (b) the light chain CDR1 comprises KASQDVSSAVA (SEQ ID NO:32), the light chain CDR2 comprises WASTRHT (SEQ ID NO:33), and the light chain CDR3 comprises QQHYSTP (SEQ ID NO:34).   
     
     
         175 . A polynucleotide encoding the heavy chain variable region and/or light chain variable region of an antibody that specifically binds human RSPO2, wherein:
 (a) the heavy chain variable region has at least 90% sequence identity to SEQ ID NO:27; and   (b) the light chain variable region has at least 90% sequence identity to SEQ ID NO:28.   
     
     
         176 . The polynucleotide of  claim 175 , wherein:
 (a) the heavy chain variable region has at least 95% sequence identity to SEQ ID NO:27; and   (b) the light chain variable region has at least 95% sequence identity to SEQ ID NO:28.   
     
     
         177 . The polynucleotide of  claim 175 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:27; and   (b) the light chain variable region comprises SEQ ID NO:28.   
     
     
         178 . The polynucleotide of  claim 175 , wherein:
 (a) the heavy chain variable region consists essentially of SEQ ID NO:27; and   (b) the light chain variable region consists essentially of SEQ ID NO:28.   
     
     
         179 . A polynucleotide encoding the heavy chain variable region and/or light chain variable region of an antibody that specifically binds human RSPO2, wherein:
 (a) the heavy chain variable region has at least 90% sequence identity to SEQ ID NO:63; and   (b) the light chain variable region has at least 90% sequence identity to SEQ ID NO:67 or SEQ ID NO:76.   
     
     
         180 . The polynucleotide of  claim 179 , wherein:
 (a) the heavy chain variable region has at least 95% sequence identity to SEQ ID NO:63; and   (b) the light chain variable region has at least 95% sequence identity to SEQ ID NO:67 or SEQ ID NO:76.   
     
     
         181 . The polynucleotide of  claim 179 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:63; and   (b) the light chain variable region comprises SEQ ID NO:67 or SEQ ID NO:76.   
     
     
         182 . The polynucleotide of  claim 179 , wherein:
 (a) the heavy chain variable region consists essentially of SEQ ID NO:63; and   (b) the light chain variable region consists essentially of SEQ ID NO:67.   
     
     
         183 . The polynucleotide of  claim 179 , wherein:
 (a) the heavy chain variable region consists essentially of SEQ ID NO:63; and   (b) the light chain variable region consists essentially of SEQ ID NO:76.   
     
     
         184 . The polynucleotide of  claim 174 , wherein the antibody is a recombinant antibody, a monoclonal antibody, a chimeric antibody, or a bispecific antibody. 
     
     
         185 . The polynucleotide of  claim 184 , wherein the antibody is a humanized antibody. 
     
     
         186 . The polynucleotide of  claim 174 , wherein the antibody is an IgG1 or IgG2 antibody. 
     
     
         187 . A polynucleotide encoding the heavy chain and/or the light chain of a monoclonal antibody produced by the hybridoma cell line having ATCC deposit number PTA-12021. 
     
     
         188 . A polynucleotide encoding the heavy chain and/or the light chain of a humanized form of the antibody of  claim 187 . 
     
     
         189 . A vector comprising the polynucleotide of  claim 174 . 
     
     
         190 . A cell comprising the vector of  claim 189 . 
     
     
         191 . A polynucleotide encoding an antibody heavy chain variable region comprising the heavy chain CDRs of 130M23 and/or an antibody light chain variable region comprising the light chain CDRs of the antibody 130M23. 
     
     
         192 . An antibody comprising the heavy and light chain CDRs of the antibody 130M23.