Amyloid-beta binding proteins

Abstract

The present invention relates to amyloid-beta (Aβ) binding proteins. Antibodies of the invention have high affinity to Aβ(20-42) globulomer or any Aβ form that comprises the globulomer epitope. Method of making and method of using the antibodies of the invention are also provided.

1 - 17 . (canceled) 
     
     
         18 . A method for treating a subject for a disease or a disorder selected from the group consisting of Systemic AL amyloidosis, Nodular AL amyloidosis, Systemic AA amyloidosis, Prostatic amyloidosis, Hemodialysis amyloidosis, Familial visceral amyloidosis, Senile systemic amyloidosis, Familial cardiac amyloidosis and Down syndrome by administering to the subject an effective amount of an anti-Aβ(20-42) globulomer antibody comprising:
 a first amino acid sequence which is at least 90% identical to SEQ ID NO:2 or SEQ ID NO:3; and a second amino acid sequence which is at least 90% identical to SEQ ID NO: 1, 
 wherein the first amino acid sequence comprises three complementary determining regions consisting of amino acids 31-35, 50-65 and 98-101, respectively, of SEQ ID NO:2 or SEQ ID NO:3; and the second amino acid sequence comprises three complementary determining regions consisting of amino acids 24-39, 55-61 and 94-102, respectively, of SEQ ID NO: 1. 
 
     
     
         19 . The method of  claim 18 , wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11. 
     
     
         20 . The method of  claim 18 , wherein the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16. 
     
     
         21 . The method of  claim 18 , wherein the first amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO: 11; and the second amino acid sequence is at least 90% identical to an amino acid sequence selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16. 
     
     
         22 . The method of  claim 18 , wherein the first amino acid sequence is selected from the group consisting of SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, and SEQ ID NO:11; and the second amino acid sequence is selected from the group consisting of SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, and SEQ ID NO:16. 
     
     
         23 . The method of  claim 18 , wherein the binding protein is selected from the group consisting of: a monoclonal antibody, a multispecific antibody, a dual specific antibody, a DVD, and a bispecific antibody. 
     
     
         24 . The method of  claim 18 , wherein the binding protein further comprises an immunoglobulin light chain constant region having an amino acid sequence selected from the group consisting of SEQ ID NO:27 and SEQ ID NO:28. 
     
     
         25 . The method of  claim 18 , wherein the binding protein further comprises an agent selected from the group consisting of: an immunoadhesion molecule, an imaging agent, and a therapeutic agent. 
     
     
         26 . The method of  claim 18 , wherein the binding protein possesses a human glycosylation pattern. 
     
     
         27 . A method for treating a subject for a disease or a disorder selected from the group consisting of Systemic AL amyloidosis, Nodular AL amyloidosis, Systemic AA amyloidosis, Prostatic amyloidosis, Hemodialysis amyloidosis, Familial visceral amyloidosis, Senile systemic amyloidosis, Familial cardiac amyloidosis and Down syndrome by administering to the subject an effective amount of a pharmaceutical composition, the pharmaceutical composition comprising:
 an anti-Aβ(20-42) globulomer antibody comprising:   a first amino acid sequence which is at least 90% identical to SEQ ID NO:2 or SEQ ID NO:3; and a second amino acid sequence which is at least 90% identical to SEQ ID NO: 1,   wherein the first amino acid sequence comprises three complementary determining regions consisting of amino acids 31-35, 50-65 and 98-101, respectively, of SEQ ID NO:2 or SEQ ID NO:3; and the second amino acid sequence comprises three complementary determining regions consisting of amino acids 24-39, 55-61 and 94-102, respectively, of SEQ ID NO: 1; and   a pharmaceutically acceptable carrier.   
     
     
         28 . The method of  claim 27 , wherein the pharmaceutical composition further comprises at least one additional therapeutic agent.