Antibodies directed against amyloid-beta peptide and methods using same

Abstract

Antibodies directed to the C-terminal side of β-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described.

The claimed invention is: 
     
         1 . A monoclonal antibody that specifically binds to a β-amyloid peptide or an aggregated form of a β-amyloid peptide, wherein the said antibody binds to an epitope on Aβ 1-40  that includes amino acids 25-34 and 40, wherein said antibody binds to Aβ 1-40  with higher affinity than its binding to Aβ 1-42  and Aβ 1-43 , wherein said antibody binds to Aβ 22-37  with a K D  of less than 1 μM. 
     
     
         2 . The antibody of  claim 1 , wherein the isotype of the antibody is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. 
     
     
         3 . The antibody of  claim 1 , wherein N-glycosylation in the Fc region of the antibody is removed. 
     
     
         4 . The antibody of  claim 1 , wherein the heavy chain constant region of the antibody is a human IgG2a constant region comprising amino acid mutations A330P331 to S330S331, wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence. 
     
     
         5 . A pharmaceutical composition comprising the antibody of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         6 . A method for treating a disease associated with aberrant deposition of β-amyloid in a subject, comprising administering to the subject an effective amount of an antibody that specifically binds to a β-amyloid peptide or an aggregated form of a β-amyloid peptide, wherein the said antibody binds to an epitope on Aβ 1-40  that includes amino acids 25-34 and 40, wherein said antibody binds to Aβ 1-40  with higher affinity than its binding to Aβ 1-42  and Aβ 1-43 , wherein said antibody binds to Aβ 22-37  with a K D  of less than 1 μM. 
     
     
         7 . The method of  claim 6 , wherein the antibody comprises a Fab fragment which binds Aβ 1-40  with an affinity of about 10 nM or less. 
     
     
         8 . The method of  claim 6 , wherein the antibody prevents, treats, inhibits or delays development of a disease associated with altered Aβ or βAPP expression or accumulation of Aβ peptide. 
     
     
         9 . The method of  claim 6 , wherein the disease is Alzheimer's, multi-infarct dementia, mild cognitive impairment, cerebral amyloid angiopathy, Down's syndrome, Parkinson's disease, Creutzfeld-Jakob, dementia with Lewy body, or AIDS. 
     
     
         10 . The method of  claim 6 , wherein the method suppresses formation of or reduction of amyloid plaques in a subject. 
     
     
         11 . The method of  claim 6 , wherein the method improves cognition or reversing cognitive decline associated with amyloid deposit of A□ in a subject. 
     
     
         12 . The method of  claim 6 , wherein the isotype of the antibody is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4. 
     
     
         13 . The method of  claim 6 , wherein N-glycosylation in the Fc region of the antibody is removed. 
     
     
         14 . The method of  claim 6 , wherein the heavy chain constant region of the antibody is a human IgG2a constant region comprising amino acid mutations A330P331 to S330S331, wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence.