Methods of treating amyloidosis comprising the use of anti-amyloid beta antibodies

Abstract

The present invention is related to methods and compositions for the therapeutic and diagnostic use in the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of disorders and abnormalities associated with amyloid protein such as Alzheimer's disease. The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies having the ability to specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies enabled by the teaching of the present invention are particularly useful for the treatment of diseases and disorders which are caused by or associated with amyloid or amyloid-like proteins including amyloidosis, a group of diseases and disorders associated with amyloid plaque formation including secondary amyloidosis and age-related amyloidosis including, but not limited to, neurological disorders such as Alzheimer's Disease (AD).

1 . A method for treating or alleviating the effects of an amyloidosis in a mammal comprising administering to the mammal an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid, and wherein the antibody or antigen-binding fragment comprises:
 a. a light chain variable region (LCVR) comprising a LCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a LCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 25; or   b. a heavy chain variable region (HCVR) comprising a HCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a HCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a HCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 28;   
       whereby at least one effect of amyloidosis is treated or alleviated. 
     
     
         2 . The method of  claim 1  wherein the antibody or antigen-binding fragment comprises:
 a. a LCVR comprising a LCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a LCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and 
 b. a HCVR comprising a HCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a HCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a HCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 28. 
 
     
     
         3 . The method of  claim 1 , wherein the amyloidosis is Alzheimer's Disease. 
     
     
         4 . The method of  claim 2 , wherein the amyloidosis is Alzheimer's Disease. 
     
     
         5 . A method for retaining or increasing cognitive memory capacity in a mammal comprising administering to the mammal an effective amount of an antibody or antigen-binding fragment thereof, wherein the monoclonal antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid, and wherein the antibody or antigen-binding fragment comprises:
 a. a LCVR comprising a LCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a LCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 25; or   b. a HCVR comprising a HCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a HCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a HCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 28.   
     
     
         6 . The method of  claim 5  wherein the antibody or antigen-binding fragment comprises:
 a. a LCVR comprising a LCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 23, a LCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 24, and a LCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 25; and 
 b. a HCVR comprising a HCVR CDR1 comprising the amino acid sequence of SEQ ID NO: 26, a HCVR CDR2 comprising the amino acid sequence of SEQ ID NO: 27, and a HCVR CDR3 comprising the amino acid sequence of SEQ ID NO: 28. 
 
     
     
         7 . The method of  claim 5 , wherein the mammal has Alzheimer's Disease, mild cognitive impairment (MCI), Lewy body dementia, Down's syndrome, or hereditary cerebral hemorrhage with amyloidosis (Dutch type). 
     
     
         8 . The method of  claim 6 , wherein the mammal has Alzheimer's Disease, mild cognitive impairment (MCI), Lewy body dementia, Down's syndrome, or hereditary cerebral hemorrhage with amyloidosis (Dutch type). 
     
     
         9 . A method for treating or alleviating the effects of an amyloidosis in a mammal comprising administering to the mammal a therapeutically effective amount of an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid, and wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of:
 (i) antibody or antigen-binding fragment thereof comprising six CDRs of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (ii) antibody or antigen-binding fragment thereof comprising epitope-binding fragments of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (iii) antibody or antigen-binding fragment thereof comprising a LCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (iv) antibody or antigen-binding fragment thereof comprising a HCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750; and   (v) antibody or antigen-binding fragment thereof comprising a LCVR and a HCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750.   
     
     
         10 . A method for retaining or increasing cognitive memory capacity in a mammal comprising administering to the mammal a therapeutically effective amount of an antibody or antigen-binding fragment thereof, wherein the antibody or antigen-binding fragment thereof is capable of specifically binding beta-amyloid, and wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of:
 (i) antibody or antigen-binding fragment thereof comprising six CDRs of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (ii) antibody or antigen-binding fragment thereof comprising epitope-binding fragments of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (iii) antibody or antigen-binding fragment thereof comprising a LCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750;   (iv) antibody or antigen-binding fragment thereof comprising a HCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750; and   (v) antibody or antigen-binding fragment thereof comprising a LCVR and a HCVR of the monoclonal antibody produced by the hybridoma cell line FP 12H3-C2, deposited as DSM ACC2750.   
     
     
         11 . The method of  claim 2 , wherein the mammal is a human. 
     
     
         12 . The method of  claim 2 , wherein the antibody or antigen-binding fragment is administered with a pharmaceutically acceptable carrier. 
     
     
         13 . The method of  claim 6 , wherein the mammal is a human. 
     
     
         14 . The method of  claim 9 , wherein the mammal is a human. 
     
     
         15 . The method of  claim 10 , wherein the mammal is a human. 
     
     
         16 . The method of  claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a LCVR comprising the amino acid sequence of SEQ ID NO: 7. 
     
     
         17 . The method of  claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 8. 
     
     
         18 . The method of  claim 2 , wherein the antibody or antigen-binding fragment thereof comprises a LCVR comprising the amino acid sequence of SEQ ID NO: 7 and a HCVR comprising the amino acid sequence of SEQ ID NO: 8. 
     
     
         19 . The method of  claim 6 , wherein the antibody or antigen-binding fragment thereof comprises a LCVR comprising the amino acid sequence of SEQ ID NO: 7. 
     
     
         20 . The method of  claim 6 , wherein the antibody or antigen-binding fragment thereof comprises a HCVR comprising the amino acid sequence of SEQ ID NO: 8. 
     
     
         21 . The method of  claim 6 , wherein the antibody or antigen-binding fragment thereof comprises a LCVR comprising the amino acid sequence of SEQ ID NO: 7 and a HCVR having the amino acid sequence of SEQ ID NO: 8. 
     
     
         22 . The method of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         23 . The method of  claim 2 , wherein the antibody is a monoclonal antibody. 
     
     
         24 . The method of  claim 5 , wherein the antibody is a monoclonal antibody. 
     
     
         25 . The method of  claim 6 , wherein the antibody is a monoclonal antibody. 
     
     
         26 . The method of  claim 9 , wherein the antibody is a monoclonal antibody. 
     
     
         27 . The method of  claim 10 , wherein the antibody is a monoclonal antibody. 
     
     
         28 . The method of  claim 9 , wherein the amyloidosis is Alzheimer's Disease. 
     
     
         29 . The method of  claim 10 , wherein the mammal has Alzheimer's Disease, mild cognitive impairment (MCI), Lewy body dementia, Down's syndrome, or hereditary cerebral hemorrhage with amyloidosis (Dutch type). 
     
     
         30 . The method of  claim 2 , wherein the amyloidosis is mild cognitive impairment (MCI), Lewy body dementia, Down's syndrome, or hereditary cerebral hemorrhage with amyloidosis (Dutch type).