Compositions and Methods Relating to STOP-1

Abstract

The present invention provides novel polypeptides, antibodies, antagonists, agonists, potentiators, nucleic acid molecules, compositions and methods relating to the STOP-1 polypeptide that are useful for treating and preventing diseases and for medical diagnosis and research. The present invention also provides consensus sequences and specific sequences for antibodies that specifically bind to STOP-1 that are useful in the methods described herein.

1 . A monoclonal antibody that specifically binds to amino acids 94-243 of human STOP-1. 
     
     
         2 . The monoclonal antibody of  claim 1 , wherein the antibody potentiates STOP-1 binding to cells. 
     
     
         3 . The monoclonal antibody of  claim 1 , wherein the monoclonal antibody binds to an oligomeric form of human STOP-1. 
     
     
         4 . The monoclonal antibody of  claim 1  selected from the group consisting of:
 (i) a monoclonal antibody comprising (a) a V H -CDR1 comprising the amino acid sequence TISGSD (SEQ ID NO:8); (b) a V H -CDR2 comprising the amino acid sequence GRISPYGGNTN (SEQ ID NO:9); and (c) a V H -CDR3 comprising the amino acid sequence CARVGGLKLLFDY (SEQ ID NO:10); 
 (ii) a monoclonal antibody comprising (a) a V H -CDR1 comprising the amino acid sequence TITNSD (SEQ ID NO:11); (b) a V H -CDR2 comprising the amino acid sequence ATIYPYGGYTY (SEQ ID NO:12); and (c) a V H -CDR3 comprising the amino acid sequence CARGGGMDGYVMDY (SEQ ID NO:13); 
 (iii) a monoclonal antibody comprising (a) a V H -CDR1 comprising the amino acid sequence TISGSW (SEQ ID NO:17); (b) a V H -CDR2 comprising the amino acid sequence AWIAPYSGATD (SEQ ID NO:18); and (c) a V H -CDR3 comprising the amino acid sequence CAREGGLYWVFDY (SEQ ID NO:19); and 
 (iv) a monoclonal antibody comprising (a) a V H -CDR1 comprising the amino acid sequence TISNYG (SEQ ID NO:20); (b) a V H -CDR2 comprising the amino acid sequence GRISPSNGSTY (SEQ ID NO:21); and (c) a V H -CDR3 comprising the amino acid sequence CAKCSVRFAY (SEQ ID NO:22). 
 
     
     
         5 . The monoclonal antibody of  claim 4  comprising (a) a V H -CDR1 comprising the amino acid sequence TISGSD (SEQ ID NO:8); (b) a V H -CDR2 comprising the amino acid sequence GRISPYGGNTN (SEQ ID NO:9); and (c) a V H -CDR3 comprising the amino acid sequence CARVGGLKLLFDY (SEQ ID NO:10). 
     
     
         6 . The monoclonal antibody of  claim 4  comprising (a) a V H -CDR1 comprising the amino acid sequence TITNSD (SEQ ID NO:11); (b) a V H -CDR2 comprising the amino acid sequence ATIYPYGGYTY (SEQ ID NO:12); and (c) a V H -CDR3 comprising the amino acid sequence CARGGGMDGYVMDY (SEQ ID NO:13). 
     
     
         7 . The monoclonal antibody of  claim 4  comprising (a) a V H -CDR1 comprising the amino acid sequence TISGSW (SEQ ID NO:17); (b) a V H -CDR2 comprising the amino acid sequence AWIAPYSGATD (SEQ ID NO:18); and (c) a V H -CDR3 comprising the amino acid sequence CAREGGLYWVFDY (SEQ ID NO:19). 
     
     
         8 . The monoclonal antibody of  claim 4  comprising (a) a V H -CDR1 comprising the amino acid sequence TISNYG (SEQ ID NO:20); (b) a V H -CDR2 comprising the amino acid sequence GRISPSNGSTY (SEQ ID NO:21); and (c) a V H -CDR3 comprising the amino acid sequence CAKCSVRFAY (SEQ ID NO:22). 
     
     
         9 . The monoclonal antibody of  claim 4  comprising the amino acid sequence of:
 (a) the heavy chain of  FIG. 27  (amino acids 21-250 of SEQ ID NO:93); 
 (b) the heavy chain of  FIG. 28  (amino acids 21-247 of SEQ ID NO:96); 
 (c) the heavy chain of  FIG. 29  (amino acids 21-250 of SEQ ID NO:99); 
 (d) the heavy chain of  FIG. 30  (amino acids 21-251 of SEQ ID NO:102); or 
 (e) the heavy chain of  FIG. 34  (amino acids 17-468 of SEQ ID NO:112). 
 
     
     
         10 . The monoclonal antibody of  claim 9 , further comprising the amino acid sequence of:
 (a) the light chain of  FIG. 27  (amino acids 24-239 of SEQ ID NO:92); or   (b) the light chain of  FIG. 33  (amino acids 20-233 of SEQ ID NO:110).   
     
     
         11 . The monoclonal antibody of  claim 4 , wherein the antibody comprises the light and heavy chain sequences of an antibody selected from the group consisting of S7 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-4-S7, S4 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-2b-S4, S9 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-2b-S9, and S16 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-4-S16. 
     
     
         12 . A monoclonal antibody that potentiates STOP-1 binding to cells. 
     
     
         13 . A monoclonal antibody that specifically binds to STOP-1, wherein the binding of the antibody to STOP-1 can be inhibited by a second monoclonal antibody selected from the group consisting of S7 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-4-S7, S4 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-2b-S4, S9 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-2b-S9, and S16 encoded by the nucleic acid molecule deposited with ATCC as designation V0350-4-S16. 
     
     
         14 . The antibody according to any one of  claims 1 - 8  and  12 - 13 , wherein the antibody is a chimeric antibody, humanized antibody, antibody fragment, or bispecific antibody.