Heavy chain antibodies binding to psma

Abstract

Anti-PSMA heavy chain antibodies (e.g., UniAbs™) are disclosed, along with methods of making such antibodies, compositions, including pharmaceutical compositions, comprising such antibodies, and their use to treat disorders that are characterized by the expression of PSMA.

1 . A three-chain antibody-like molecule comprising:
 (a) a PSMA-binding heavy chain variable region comprising:   a CDR1 sequence of the formula G G S I S S X 1 X 2 Y X 3  (SEQ ID NO: 67), wherein X 1  is S or N; X 2  is S or N; and X 3  is Y or F; and   a CDR2 sequence of the formula X 4 X 5 X 6 S G X 7 T (SEQ ID NO: 68), wherein X 4  is I or V; X 5  is D or Y; X 6  is Y or D; and X 7  is Y or S; and   a CDR3 sequence of SEQ ID NO: 18; and   (b) a CD3-binding heavy chain variable region that is paired with a light chain variable region, wherein:   the CD3-binding heavy chain variable region comprises a CDR1 sequence of SEQ ID NO: 59, a CDR2 sequence of SEQ ID NO: 60, and a CDR3 sequence of SEQ ID NO: 61; and   the light chain variable region comprises a CDR1 sequence of SEQ ID NO: 62, a CDR2 sequence of SEQ ID NO: 63, and a CDR3 sequence of SEQ ID NO: 64.   
     
     
         2 . The three-chain antibody-like molecule of  claim 1 , wherein the PSMA-binding heavy chain variable region comprises a CDR1 sequence of any one of SEQ ID NOs: 1-3, a CDR2 sequence of any one of SEQ ID NOs: 11-13, and a CDR3 sequence of SEQ ID NO: 18. 
     
     
         3 . The three-chain antibody-like molecule of  claim 1 , wherein the PSMA-binding heavy chain variable region comprises:
 a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18; or   a CDR1 sequence of SEQ ID NO: 1, a CDR2 sequence of SEQ ID NO: 12, and a CDR3 sequence of SEQ ID NO: 18; or   a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18; or   a CDR1 sequence of SEQ ID NO: 3, a CDR2 sequence of SEQ ID NO: 13, and a CDR3 sequence of SEQ ID NO: 18.   
     
     
         4 . The three-chain antibody-like molecule of  claim 1 , wherein the PSMA-binding heavy chain variable region comprises a CDR1 sequence of SEQ ID NO: 2, a CDR2 sequence of SEQ ID NO: 11, and a CDR3 sequence of SEQ ID NO: 18. 
     
     
         5 . The three-chain antibody-like molecule of  claim 1 , wherein the PSMA-binding heavy chain variable region comprises the heavy chain variable region sequence of any one of SEQ ID NOs: 24-28. 
     
     
         6 . The three-chain antibody-like molecule of  claim 1 , wherein the PSMA-binding heavy chain variable region comprises the heavy chain variable region sequence of SEQ ID NO: 25. 
     
     
         7 . The three-chain antibody-like molecule of  claim 1 , wherein the CD3-binding heavy chain variable region comprises the heavy chain variable region sequence of SEQ ID NO: 65, and the light chain variable region comprises the light chain variable region sequence of SEQ ID NO: 66. 
     
     
         8 . The three-chain antibody-like molecule of  claim 1 , wherein:
 the CD3-binding heavy chain variable region comprises the heavy chain variable region sequence of SEQ ID NO: 65;   the light chain variable region comprises the light chain variable region sequence of SEQ ID NO: 66; and   the PSMA-binding heavy chain variable region comprises the heavy chain variable region sequence of any one of SEQ ID NOs: 24-28.   
     
     
         9 . The three-chain antibody-like molecule of  claim 1 , wherein:
 the CD3-binding heavy chain variable region comprises the heavy chain variable region sequence of SEQ ID NO: 65;   the light chain variable region comprises the light chain variable region sequence of SEQ ID NO: 66; and   the PSMA-binding heavy chain variable region comprises the heavy chain variable region sequence of SEQ ID NO: 25.   
     
     
         10 . A three-chain antibody-like molecule that binds to PSMA and CD3, comprising:
 a first polypeptide comprising the sequence of SEQ ID NO: 86;   a second polypeptide comprising the sequence of SEQ ID NO: 87; and   a third polypeptide comprising the sequence of SEQ ID NO: 88.   
     
     
         11 . A three-chain antibody-like molecule that binds to PSMA and CD3, comprising:
 a first polypeptide comprising the sequence of SEQ ID NO: 86;   a second polypeptide comprising the sequence of SEQ ID NO: 87; and   a third polypeptide comprising the sequence of SEQ ID NO: 89.   
     
     
         12 . A pharmaceutical composition comprising the three-chain antibody-like molecule of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         13 . A pharmaceutical composition comprising the three-chain antibody-like molecule of  claim 10  and a pharmaceutically acceptable excipient. 
     
     
         14 . A pharmaceutical composition comprising the three-chain antibody-like molecule of  claim 11  and a pharmaceutically acceptable excipient. 
     
     
         15 . A polynucleotide encoding the three-chain antibody-like molecule of  claim 1 . 
     
     
         16 . A polynucleotide encoding the three-chain antibody-like molecule of  claim 10 . 
     
     
         17 . A polynucleotide encoding the three-chain antibody-like molecule of  claim 11 . 
     
     
         18 . A method of treating prostate cancer in a subject in need thereof, comprising administering the three-chain antibody-like molecule of  claim 1  to the subject. 
     
     
         19 . A method of treating prostate cancer in a subject in need thereof, comprising administering the three-chain antibody-like molecule of  claim 10  to the subject. 
     
     
         20 . A method of treating prostate cancer in a subject in need thereof, comprising administering the three-chain antibody-like molecule of  claim 11  to the subject.