Anti-amyloid beta antibodies and their use

Abstract

The present invention relates to antibody molecules capable of specifically recognizing two regions of the β-A4 peptide, wherein the first region comprises the amino acid sequence AEFRHDSGY as shown in SEQ ID NO: 1 or a fragment thereof and wherein the second region comprises the amino acid sequence VHHQKLVFFAEDVG as shown in SEQ ID NO: 2 or a fragment thereof. Furthermore, nucleic acid molecules encoding the inventive antibody molecules and vectors and hosts comprising said nucleic acid molecules are disclosed. In addition, the present invention provides for compositions, preferably pharmaceutical or diagnostic compositions, comprising the compounds of the invention as well as for specific uses of the antibody molecules, nucleic acid molecules, vectors or hosts of the invention.

1 - 16 . (canceled) 
     
     
         17 . A method for treating a disease associated with amyloidogenesis and/or amyloid-plaque formation in a subject in need thereof comprising administering to the subject an antibody comprising:
 (a) a variable V L -Region comprising complementary determining regions, L-CDR1, L-CDR2, L-CDR3, wherein:
 (1) L-CDR1 comprises SEQ ID NO: 143; 
 (2) L-CDR2 comprises SEQ ID NO: 144; and 
 (3) L-CDR3 comprises SEQ ID NO: 95; and 
   (b) a variable V H -Region comprising complementary determining regions, H-CDR1, H-CDR2, H-CDR3, wherein:
 (1) H-CDR1 comprises SEQ ID NO: 146; 
 (2) H-CDR2 comprises SEQ ID NOs: 192; and 
 (3) H-CDR3 comprises SEQ ID NOs: 93 in an amount effective to treat the disease. 
   
     
     
         18 . A method for detecting a disease associated with amyloidogenesis and/or amyloid-plaque formation in a subject comprising:
 (i) providing a brain tissue from the subject;   (ii) contacting the brain tissue with a composition comprising an antibody comprising:   (a) a variable V L -Region comprising complementary determining regions, L-CDR1, L-CDR2, L-CDR3, wherein:
 (1) L-CDR1 comprises SEQ ID NO: 143; 
 (2) L-CDR2 comprises SEQ ID NO: 144; and 
 (3) L-CDR3 comprises SEQ ID NO: 95; and 
   (b) a variable V H -Region comprising complementary determining regions, H-CDR1, H-CDR2, H-CDR3, wherein:
 (1) H-CDR1 comprises SEQ ID NO: 146; 
 (2) H-CDR2 comprises SEQ ID NOs: 192; and 
 (3) H-CDR3 comprises SEQ ID NOs: 93; and 
   (iii) detecting the binding of antibody to the brain tissue.   
     
     
         19 . A method for disintegrating β-amyloid plaques comprising contacting said β-amyloid plaque with an antibody comprising:
 (a) a variable V L -Region comprising complementary determining regions, L-CDR1, L-CDR2, L-CDR3, wherein:
 (1) L-CDR1 comprises SEQ ID NO: 143; 
 (2) L-CDR2 comprises SEQ ID NO: 144; and 
 (3) L-CDR3 comprises SEQ ID NO: 95; and 
 
 (b) variable V H -Region comprising complementary determining regions, H-CDR1, H-CDR2, H-CDR3, wherein:
 (1) H-CDR1 comprises SEQ ID NO: 146; 
 (2) H-CDR2 comprises SEQ ID NOs: 192; and 
 (3) H-CDR3 comprises SEQ ID NOs: 93. 
 
 
     
     
         20 . A method for passively immunizing a subject in need thereof against β-amyloid plaque formation comprising administering to the subject an effective amount of an antibody comprising:
 (a) a variable V L -Region comprising complementary determining regions, L-CDR1, L-CDR2, L-CDR3, wherein:
 (1) L-CDR1 comprises SEQ ID NO: 143; 
 (2) L-CDR2 comprises SEQ ID NO: 144; and 
 (3) L-CDR3 comprises SEQ ID NO: 95; and 
 
 (b) a variable V H -Region comprising complementary determining regions, H-CDR1, H-CDR2, H-CDR3, wherein:
 (1) H-CDR1 comprises SEQ ID NO: 146; 
 (2) H-CDR2 comprises SEQ ID NOs: 192; and 
 (3) H-CDR3 comprises SEQ ID NOs: 93. 
 
 
     
     
         21 . The method according to  claim 17 , wherein said disease is selected from the group consisting of dementia, Alzheimer's disease, motor neuropathy, Down's syndrome, Creutzfeld Jacob disease, hereditary cerebral hemorrhage with amyloidosis Dutch type, Parkinson's disease, HIV-related dementia, amyotropic lateral sclerosis (ALS), and neuronal disorders related to aging. 
     
     
         22 - 28 . (canceled) 
     
     
         29 . The method according to  claim 17 , wherein the antibody is of the IgG1 subtype. 
     
     
         30 . The method according to  claim 17 , wherein the variable V H -region comprises SEQ ID NO: 89; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         31 . The method according to  claim 30 , wherein the antibody is of the IgG1 subtype. 
     
     
         32 . The method according to  claim 17 , wherein the variable V H -region comprises SEQ ID NO: 425; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         33 . The method according to  claim 32 , wherein the antibody is of the IgG1 subtype. 
     
     
         34 . The method according to  claim 17 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent. 
     
     
         35 . The method according to  claim 31 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent. 
     
     
         36 . The method according to  claim 33 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent. 
     
     
         37 . The method according to  claim 18 , wherein said disease is selected from the group consisting of dementia, Alzheimer's disease, motor neuropathy, Down's syndrome, Creutzfeld Jacob disease, hereditary cerebral hemorrhage with amyloidosis Dutch type, Parkinson's disease, HIV-related dementia, amyotropic lateral sclerosis (ALS), and neuronal disorders related to aging. 
     
     
         38 . The method according to  claim 18 , wherein the brain tissue is a brain section. 
     
     
         39 . The method according to  claim 18 , wherein the antibody is of the IgG1 subtype. 
     
     
         40 . The method according to  claim 18 , wherein the variable V H -region comprises SEQ ID NO: 89; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         41 . The method according to  claim 40 , wherein the antibody is of the IgG1 subtype. 
     
     
         42 . The method according to  claim 18 , wherein the variable V H -region comprises SEQ ID NO: 425; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         43 . The method according to  claim 42 , wherein the antibody is of the IgG1 subtype. 
     
     
         44 . The method according to  claim 19 , wherein disintegrating of the β-amyloid plaque occurs in vivo. 
     
     
         45 . The method according to  claim 19 , wherein the antibody is of the IgG1 subtype. 
     
     
         46 . The method according to  claim 19 , wherein the variable V H -region comprises SEQ ID NO: 89; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         47 . The method according to  claim 46 , wherein the antibody is of the IgG1 subtype. 
     
     
         48 . The method according to  claim 19 , wherein the variable V H -region comprises SEQ ID NO: 425; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         49 . The method according to  claim 48 , wherein the antibody is of the IgG1 subtype. 
     
     
         50 . The method according to  claim 20 , wherein the antibody is of the IgG1 subtype. 
     
     
         51 . The method according to  claim 20 , wherein the variable V H -region comprises SEQ ID NO: 89; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         52 . The method according to  claim 51 , wherein the antibody is of the IgG1 subtype. 
     
     
         53 . The method according to  claim 20 , wherein the variable V H -region comprises SEQ ID NO: 425; and the variable V L -region comprises SEQ ID NO: 91. 
     
     
         54 . The method according to  claim 53 , wherein the antibody is of the IgG1 subtype. 
     
     
         55 . The method according to  claim 20 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent. 
     
     
         56 . The method according to  claim 53 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent. 
     
     
         57 . The method according to  claim 55 , wherein the antibody is administered as a part of a pharmaceutical composition comprising the antibody and a pharmaceutically acceptable diluent.