Prostate specific membrane antigen binding protein

Abstract

Disclosed are PSMA binding proteins with improved binding affinities, and robust aggregation profiles. Also described are multispecific binding proteins comprising a PSMA binding protein according to the instant disclosure. Pharmaceutical compositions comprising the binding proteins disclosed and methods of using such formulations are further provided.

1 - 23 . (canceled) 
     
     
         24 . A method for the treatment or amelioration of prostate cancer, the method comprising administration of a pharmaceutical composition comprising a single domain antibody that specifically binds to a PSMA polypeptide, wherein the single domain antibody comprises complementarity determining regions CDR1, CDR2, and CDR3, wherein
 (a) the amino acid sequence of CDR1 comprises SEQ ID NO: 5;   (b) the amino acid sequence of CDR2 comprises SEQ ID NO: 17; and   (c) the amino acid sequence of CDR3 comprises SEQ ID NO: 15, to a subject in need thereof.   
     
     
         25 - 30 . (canceled) 
     
     
         31 . The method of  claim 24 , wherein the single domain antibody has a higher affinity towards a human PSMA antigen than that of a binding protein comprises the amino acid sequence set forth in SEQ ID NO: 4. 
     
     
         32 . The method of  claim 24 , wherein the single domain antibody has a higher affinity towards a cynomolgus PSMA antigen than that of a binding protein comprises the amino acid sequence set forth in SEQ ID NO: 4. 
     
     
         33 . The method of  claim 24 , wherein the single domain antibody comprises the following formula:
   f1-r-f2-r2-f3-r3-f4   
       wherein, r1 is CDR1; r2 is CDR2; and r3 is CDR3; and wherein f 1 , f 2 , f 3  and f 4  are framework residues selected so the amino acid sequence of the single domain antibody is at least eighty percent identical to the amino acid sequence set forth in SEQ ID No: 4. 
     
     
         34 . The method of  claim 24 , wherein the amino acid sequence of the single domain antibody comprises SEQ ID NO: 32. 
     
     
         35 . The method of  claim 24 , wherein the single domain antibody is part of a trispecific protein. 
     
     
         36 . The method of  claim 35 , wherein the amino acid sequence of the trispecific protein comprises SEQ ID NO: 153. 
     
     
         37 . The method of  claim 24 , wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier. 
     
     
         38 . The method of  claim 24 , wherein the subject is human. 
     
     
         39 . The method of  claim 24 , wherein pharmaceutical composition further comprises an agent in combination with the single domain antibody. 
     
     
         40 . The method of  claim 24 , wherein the prostate cancer is an advanced stage prostate cancer. 
     
     
         41 . The method of  claim 24 , wherein the prostate cancer is drug resistant. 
     
     
         42 . The method of  claim 24 , wherein the prostate cancer is anti-androgen drug resistant. 
     
     
         43 . The method of  claim 24 , wherein the prostate cancer is metastatic. 
     
     
         44 . The method of  claim 24 , wherein the prostate cancer is metastatic and drug resistant. 
     
     
         45 . The method of  claim 24 , wherein the prostate cancer is castration resistant. 
     
     
         46 . The method of  claim 24 , wherein the prostate cancer is metastatic and castration resistant. 
     
     
         47 . The method of  claim 24 , wherein the prostate cancer is enzalutamide resistant. 
     
     
         48 . The method of  claim 24 , wherein the prostate cancer is enzalutamide and arbiraterone resistant. 
     
     
         49 . The method of  claim 24 , wherein the prostate cancer is enzalutamide, arbiraterone, and bicalutamide resistant. 
     
     
         50 . The method of  claim 24 , wherein the prostate cancer is docetaxel resistant. 
     
     
         51 . The method of  claim 24 , wherein the prostate cancer is enzalutamide, arbiraterone, bicalutamide, and docetaxel resistant.