Antibodies and immunoconjugates and uses therefor

Abstract

Anti-STEAP-1 antibodies and immunoconjugates thereof are provided. Methods of using anti-STEAP-1 antibodies and immunoconjugates thereof are provided.

1 . A method of detecting the presence of STEAP-1 in a biological sample, the method comprising contacting the biological sample with a humanized monoclonal antibody that binds to STEP-1 under conditions permissive for binding of the antibody to STEAP-1, and detecting whether a complex is formed between the antibody and STEAP-1, wherein the antibody comprises
 (a) a heavy chain variable domain comprising:
 (1) an HC-FR1 comprising the amino acid sequence of SEQ ID NO:25; 
 (2) an HVR-H1 comprising the amino acid sequence of SEQ ID NO:14; 
 (3) an HC-FR2 comprising the amino acid sequence of SEQ ID NO:22; 
 (4) an HVR-H2 comprising the amino acid sequence of SEQ ID NO:15; 
 (5) an HC-FR3 comprising the amino acid sequence of SEQ ID NO:138; 
 (6) an HVR-H3 comprising the amino acid sequence of SEQ ID NO:16; and 
 (7) an HC-FR4 comprising the amino acid sequence of SEQ ID NO:24; and 
   (b) a light chain variable domain comprising:
 (1) a LC-FR1 comprising the amino acid sequence of SEQ ID NO:17; 
 (2) an HVR-L1 comprising the amino acid sequence of SEQ ID NO:11; 
 (3) a LC-FR2 comprising the amino acid sequence of SEQ ID NO:18; 
 (4) an HVR-L2 comprising the amino acid sequence of SEQ ID NO:12; 
 (5) a LC-FR3 comprising the amino acid sequence of SEQ ID NO:19; 
 (6) an HVR-L3 comprising the amino acid sequence of SEQ ID NO:13; and 
 (7) a LC-FR4 comprising the amino acid sequence of SEQ ID NO:20. 
   
     
     
         2 . The method of  claim 1 , wherein the antibody is covalently attached to a capture label, a detection label, or a solid support. 
     
     
         3 . The method of  claim 1 , wherein the antibody is covalently attached to a detection label, and the detection label is a radioisotope. 
     
     
         4 . The method of  claim 1 , wherein the biological sample is from a patient suspected of having a prostate, lung, colon, bladder, ovarian cell or Ewing's sarcoma cell proliferative disorder. 
     
     
         5 . The method of  claim 1 , wherein the biological sample is from a patient suspected of having a prostate proliferative disorder. 
     
     
         6 . The method of  claim 1 , wherein the light chain comprises:
 (1) a light chain region comprising the amino acid sequence of SEQ ID NO:90;   (2) a light chain region comprising the amino acid sequence of SEQ ID NO:92;   (3) a light chain region comprising the amino acid sequence of SEQ ID NO:93;   (4) a light chain region comprising the amino acid sequence of SEQ ID NO:94;   (5) a light chain region comprising the amino acid sequence of SEQ ID NO:95;   (6) a light chain region comprising the amino acid sequence of SEQ ID NO:96;   (7) a light chain region comprising the amino acid sequence of SEQ ID NO:97;   (8) a light chain region comprising the amino acid sequence of SEQ ID NO:98;   (9) a light chain region comprising the amino acid sequence of SEQ ID NO:99;   (10) a light chain region comprising the amino acid sequence of SEQ ID NO:100; or   (11) a light chain region comprising the amino acid sequence of SEQ ID NO:101.   
     
     
         7 . The method of  claim 1 , wherein the antibody is an antibody fragment selected from a Fab, Fab′-SH, Fv, scFv, or (Fab′) 2  fragment. 
     
     
         8 . The method of  claim 1 ,wherein the antibody comprises a constant domain selected from the group consisting of a heavy chain constant domain in which one or more amino acid residues naturally occurring in said heavy chain constant domain are replaced with one or more free cysteine amino acids having a thiol reactivity in the range of 0.6 to 1.0; and a light chain constant domain in which one or more amino acid residues naturally occurring in said light chain constant domain are replaced with one or more free cysteine amino acids having a thiol reactivity in the range of 0.6 to 1.0. 
     
     
         9 . The method of  claim 8 , wherein the one or more free cysteine amino acid residues are located in a light chain. 
     
     
         10 . The method of  claim 8 , wherein the one or more free cysteine amino acid residues are located in a heavy chain. 
     
     
         11 . The method of  claim 8 , wherein the antibody comprises a cysteine at one or more positions selected from 110, 144, 168 and 205 of the light chain constant domain according to Kabat numbering convention and 115, 118, 120, 171, 172, 282, 375, and 400 of the heavy chain constant domain according to EU numbering convention. 
     
     
         12 . The method of  claim 11 , wherein a cysteine is at position 205 of the light chain. 
     
     
         13 . The method of  claim 11 , wherein a cysteine is at position 118 of the heavy chain. 
     
     
         14 . The method of  claim 1 , wherein the antibody is a bispecific antibody.