US2017267776A1PendingUtilityA1

RSPO3 Binding Agents and Uses Thereof

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Assignee: ONCOMED PHARM INCPriority: Jul 13, 2012Filed: Feb 22, 2017Published: Sep 21, 2017
Est. expiryJul 13, 2032(~6 yrs left)· nominal 20-yr term from priority
Inventors:Austin GurneyChristopher J. Bond
A61P 35/00A61P 43/00A61P 11/00C07K 2319/30C07K 2317/24A61K 45/06C07K 2317/92C12Q 2600/158C07K 2319/32A61K 2039/505C07K 2319/60A61K 2039/507A61K 39/39533C07K 16/24C07K 16/18C07K 2317/73C07K 16/30A61K 39/39558C07K 2317/34C07K 2317/76C12Q 1/6886C12Q 2600/106C07K 2319/03
53
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Claims

Abstract

The present invention relates to RSPO-binding agents, particularly RSPO3-binding agents and methods of using the agents for treating diseases such as cancer. The present invention provides antibodies that specifically bind human RSPO3 proteins and modulate β-catenin activity. The present invention further provides methods of using agents that modulate the activity of RSPO3 proteins 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.

Claims

exact text as granted — not AI-modified
1 - 113 . (canceled) 
     
     
         114 . A polynucleotide encoding the heavy chain variable region and/or light chain variable region of an antibody that specifically binds human R-spondin 3 (RSPO3), wherein:
 (a) the heavy chain CDR1 comprises KASGYTFTDYS (SEQ ID NO:9), KASGYTFTSYTF (SEQ ID NO:34), or DYSIH (SEQ ID NO:78), the heavy chain CDR2 comprises IYPSNGDS (SEQ ID NO:10) or YIYPSNGDSGYNQKFK (SEQ ID NO:79), and the heavy chain CDR3 comprises ATYFANYFDY (SEQ ID NO:11), ATYFANNFDY (SEQ ID NO:35), or TYFANNFD (SEQ ID NO:80); and   (b) the light chain CDR1 comprises QSVDYDGDSYM (SEQ ID NO:12) or KASQSVDYDGDSYMN (SEQ ID NO:81), the light chain CDR2 comprises AAS (SEQ ID NO:13) or AASNLES (SEQ ID NO:82), and the light chain CDR3 comprises QQSNEDPLT (SEQ ID NO:14) or QQSNEDPLTF (SEQ ID NO:83).   
     
     
         115 . The polynucleotide of  claim 114 , wherein:
 (a) the heavy chain CDR1 comprises KASGYTFTDYS (SEQ ID NO:9) or KASGYTFTSYTF (SEQ ID NO:34), the heavy chain CDR2 comprises IYPSNGDS (SEQ ID NO:10), and the heavy chain CDR3 comprises ATYFANYFDY (SEQ ID NO:11) or ATYFANNFDY (SEQ ID NO:35), and   (b) the light chain CDR1 comprises QSVDYDGDSYM (SEQ ID NO:12), the light chain CDR2 comprises AAS (SEQ ID NO:13), and the light chain CDR3 comprises QQSNEDPLT (SEQ ID NO:14).   
     
     
         116 . The polynucleotide of  claim 114 , wherein:
 (a) the heavy chain CDR1 comprises KASGYTFTDYS (SEQ ID NO:9) or DYSIH (SEQ ID NO:78), the heavy chain CDR2 comprises YIYPSNGDSGYNQKFK (SEQ ID NO:79), and the heavy chain CDR3 comprises TYFANNFD (SEQ ID NO:80); and   (b) the light chain CDR1 comprises KASQSVDYDGDSYMN (SEQ ID NO:81), the light chain CDR2 comprises AASNLES (SEQ ID NO:82), and the light chain CDR3 comprises QQSNEDPLTF (SEQ ID NO:83).   
     
     
         117 . The polynucleotide of  claim 114 , wherein:
 (a) the heavy chain CDR1 comprises DYSIH (SEQ ID NO:78), the heavy chain CDR2 comprises YIYPSNGDSGYNQKFK (SEQ ID NO:79), and the heavy chain CDR3 comprises TYFANNFD (SEQ ID NO:80); and   (b) the light chain CDR1 comprises KASQSVDYDGDSYMN (SEQ ID NO:81), the light chain CDR2 comprises AASNLES (SEQ ID NO:82), and the light chain CDR3 comprises QQSNEDPLTF (SEQ ID NO:83).   
     
     
         118 . The polynucleotide of  claim 114 , wherein:
 (a) the heavy chain CDR1 comprises KASGYTFTDYS (SEQ ID NO:9) or DYSIH (SEQ ID NO:78), the heavy chain CDR2 comprises IYPSNGDS (SEQ ID NO:10), and the heavy chain CDR3 comprises TYFANNFD (SEQ ID NO:80); and   (b) the light chain CDR1 comprises QSVDYDGDSYM (SEQ ID NO:12), the light chain CDR2 comprises AAS (SEQ ID NO:13), and the light chain CDR3 comprises QQSNEDPLT (SEQ ID NO:14).   
     
     
         119 . The polynucleotide of  claim 114 , wherein the antibody is a chimeric antibody or a bispecific antibody. 
     
     
         120 . The polynucleotide of  claim 114 , wherein the antibody is a humanized antibody. 
     
     
         121 . The polynucleotide of  claim 114 , wherein the antibody is an antibody fragment comprising an antigen binding site. 
     
     
         122 . A polynucleotide encoding the heavy chain variable region and/or light chain variable region of an antibody that specifically binds human RSPO3, wherein:
 (a) the heavy chain variable region has at least 90% sequence identity to SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:44, SEQ ID NO:45, OR SEQ ID NO:62; and   (b) the light chain variable region has at least 90% sequence identity to SEQ ID NO:17, SEQ ID NO:72, or SEQ ID NO:86.   
     
     
         123 . The polynucleotide of  claim 114 , wherein:
 (a) the heavy chain variable region has at least 95% sequence identity to SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:44, SEQ ID NO:45, or SEQ ID NO:62; and   (b) the light chain variable region has at least 95% sequence identity to SEQ ID NO:17, SEQ ID NO:72, or SEQ ID NO:86.   
     
     
         124 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:15; and   (b) the light chain variable region comprises SEQ ID NO:17 or SEQ ID NO:72.   
     
     
         125 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:16; and   (b) the light chain variable region comprises SEQ ID NO:17 or SEQ ID NO:72.   
     
     
         126 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:36; and   (b) the light chain variable region comprises SEQ ID NO:17 or SEQ ID NO:72.   
     
     
         127 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:37 and   (b) the light chain variable region comprises SEQ ID NO:17 or SEQ ID NO:72.   
     
     
         128 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:44; and   (b) the light chain variable region comprises SEQ ID NO:17, SEQ ID NO:72, or SEQ ID NO:86.   
     
     
         129 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:44; and   (b) the light chain variable region comprises SEQ ID NO:86.   
     
     
         130 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:45; and   (b) the light chain variable region comprises SEQ ID NO:17, SEQ ID NO:72, or SEQ ID NO:86.   
     
     
         131 . The polynucleotide of  claim 123 , wherein:
 (a) the heavy chain variable region comprises SEQ ID NO:62; and   (b) the light chain variable region comprises SEQ ID NO:17, SEQ ID NO:72, or SEQ ID NO:86.   
     
     
         132 . The polynucleotide of  claim 123 , which is an IgG1 antibody. 
     
     
         133 . The polynucleotide of  claim 123 , which is an IgG2 antibody. 
     
     
         134 . A polynucleotide encoding:
 (a) an antibody heavy chain sequence comprising SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:39, SEQ ID NO:42, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:64, or SEQ ID NO:69; and/or   (b) an antibody light chain sequence comprising SEQ ID NO:29, SEQ ID NO:74, or SEQ ID NO:88.   
     
     
         135 . The polynucleotide of  claim 134 , wherein the heavy chain sequence comprises SEQ ID NO:48 and the light chain sequence comprises SEQ ID NO:74 or SEQ ID NO:88. 
     
     
         136 . The polynucleotide of  claim 134 , wherein the heavy chain sequence comprises SEQ ID NO:64 and the light chain sequence comprises SEQ ID NO:74 or SEQ ID NO:88. 
     
     
         137 . The polynucleotide of  claim 134 , wherein the heavy chain sequence comprises SEQ ID NO:69 and the light chain sequence comprises SEQ ID NO:74 or SEQ ID NO:88. 
     
     
         138 . The polynucleotide of  claim 137 , wherein the heavy chain sequence comprises SEQ ID NO:69 and the light chain sequence comprises SEQ ID NO:88. 
     
     
         139 . A vector containing the polynucleotide of  claim 138 . 
     
     
         140 . A cell containing the vector of  claim 139 . 
     
     
         141 . A polynucleotide encoding the antibody heavy chain variable region that is encoded by the plasmid deposited with ATCC as PTA-120420. 
     
     
         142 . A polynucleotide encoding the antibody light chain variable region that is encoded by the plasmid deposited with ATCC as PTA-120421. 
     
     
         143 . A polynucleotide encoding the antibody heavy chain variable region that is encoded by the plasmid deposited with ATCC as PTA-120420 and the antibody light chain variable region that is encoded by the plasmid deposited with ATCC as PTA-120421. 
     
     
         144 . A vector containing the polynucleotide of  claim 143 . 
     
     
         145 . A cell containing the vector of  claim 144 . 
     
     
         146 . A polynucleotide encoding (a) an antibody heavy chain variable region comprising the heavy chain CDRs of h131R010 and/or an antibody light chain variable region comprising the light chain CDRs of h131R010. 
     
     
         147 . An antibody comprising the heavy chain CDRs of h131R010 and the light chain CDRs of h131R010.

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