Prevention and treatment of amyloidogenic disease

Abstract

The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Such methods entail administering agents that induce a beneficial immunogenic response against the amyloid deposit. The methods are useful for prophylactic and therapeutic treatment of Alzheimer's disease. Preferred agents including N-terminal fragments of Aβ and antibodies binding to the same.

1 - 68 . (Canceled)  
     
     
         69 . A composition comprising one or more antibodies that binds soluble aggregated amyloid β protein.  
     
     
         70 . A composition comprising one or more antibodies that binds soluble, non-fibrillar aggregated amyloid β protein.  
     
     
         71 . A composition comprising one or more antibodies that interacts preferentially with soluble, non-fibrillar oligomeric assemblies of amyloid β protein.  
     
     
         72 . The composition of  claim 69 , wherein the aggregated amyloid β proteins are full length amyloid β.  
     
     
         73 . A composition as in  claim 71 , wherein the assemblies are ADDLs.  
     
     
         74 . A composition comprising one or more antibodies that binds soluble aggregated amyloid β 1-42 .  
     
     
         75 . The composition of  claim 74  wherein the aggregated soluble amyloid β 1-42  is identified as AN1792.  
     
     
         76 . A composition comprising one or more antibodies that binds soluble non-fibrillar aggregated amyloid β 1-42 .  
     
     
         77 . The composition of  claim 76  wherein the soluble non-fibrillar aggregated amyloid β 1-42  is identified as AN1792.  
     
     
         78 . A composition comprising one or more antibodies that specifically binds soluble aggregated amyloid β 1-42 .  
     
     
         79 . The composition of  claim 78  wherein the aggregated soluble amyloid β 1-42  is identified as AN1792.  
     
     
         80 . A composition comprising one or more antibodies that specifically binds soluble non-fibrillar aggregated amyloid β 1-42 .  
     
     
         81 . The composition of  claim 76  wherein the soluble non-fibrillar aggregated amyloid β 1-42  is identified as AN1792.  
     
     
         82 . A composition comprising one or more antibodies that bind preferentially to soluble, globular, non-fibrillar protein assemblies of amyloid β 1-42 .  
     
     
         83 . A composition as in  claim 74 , wherein the assemblies are ADDLs.  
     
     
         84 . A composition as in  claim 82 , wherein the assemblies are ADDLs.  
     
     
         85 . A composition comprising antibodies that binds soluble aggregated amyloid β protein.  
     
     
         86 . The composition of  claim 85  wherein the aggregated soluble amyloid β 1-42  is identified as AN1792.  
     
     
         87 . A composition comprising antibodies that binds soluble non-fibrillar aggregated amyloid β protein.  
     
     
         88 . The composition of  claim 87  wherein the soluble non-fibrillar aggregated amyloid β protein is AN1792.  
     
     
         89 . A composition comprising antibodies that specifically binds soluble aggregated amyloid β protein.  
     
     
         90 . The composition of  claim 89  wherein the aggregated soluble amyloid β 1-42  is identified as AN1792.  
     
     
         91 . A composition comprising antibodies that specifically binds soluble non-fibrillar aggregated amyloid β protein.  
     
     
         92 . The composition of  claim 91  wherein the soluble non-fibrillar aggregated amyloid β protein is AN1792.  
     
     
         93 . A composition comprising antibodies that bind preferentially to amyloid β-derived diffusible ligands (ADDLs).  
     
     
         94 . A composition comprising one or more antibody binding sites that specifically binds soluble amyloid β protein.  
     
     
         95 . A composition comprising one or more antibody binding sites that bind preferentially to ADDLs.  
     
     
         96 . A composition comprising one or more modified antibody binding sites that bind soluble aggregated amyloid β protein.  
     
     
         97 . A composition comprising one or more antibody binding sites that bind soluble amyloid β protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.  
     
     
         98 . A composition comprising one or more modified antibody binding sites that specifically bind soluble aggregated amyloid β protein.  
     
     
         99 . A composition comprising one or more antibody binding sites that specifically bind soluble amyloid β protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.  
     
     
         100 . A composition comprising one or more modified antibody binding sites that bind preferentially to ADDLs.  
     
     
         101 . A composition consisting of one or more binding sites that specifically bind soluble amyloid β protein, wherein said antibody sites are derived from genetically engineered antibodies or fragments thereof.  
     
     
         102 . A composition consisting of one or more binding sites that preferentially bind to ADDLs.  
     
     
         103 . The composition of any of claims  69 ,  70 ,  72 ,  74 - 77 ,  83 ,  85 - 88 ,  96 , or  97 , wherein the aggregated amyloid β protein binding site is incorporated into a human antibody framework.  
     
     
         104 . The composition of any of claims  78 - 81 ,  89 - 92 ,  94 ,  98 ,  99  or  101 , wherein the aggregated amyloid β protein binding site is incorporated into a human antibody framework.  
     
     
         105 . Any composition of any of claims  71 ,  73 ,  82 ,  84 ,  93 ,  95 ,  100  or  102 , wherein the ADDL binding site is incorporated into a human antibody framework.  
     
     
         106 . A method for detecting, in a tissue sample taken from a patient, the presence of soluble aggregated amyloid β protein, the method comprising contacting the sample with the composition of any of claims  69 - 70 ,  72 ,  74 - 81 ,  83 ,  85 - 92 ,  94 ,  96 - 99 ,  101 ,  103 ,  104 ,  106  or  107 .  
     
     
         107 . A method for detecting, in a tissue sample taken from a patient, the presence of soluble non-fibrillar aggregated amyloid β protein, the method comprising contacting the sample with the composition of any of claims  69 - 70 ,  72 ,  74 - 81 ,  83 ,  85 - 92 ,  94 ,  96 - 99 ,  101 ,  103 ,  104 ,  106  or  107 .  
     
     
         108 . A method for detecting, in fluid taken from a patient, the presence of soluble, non-fibrillar assemblies of amyloid β protein, the method comprising contacting the fluid with the composition as in any one of claims  71 ,  73 ,  82 ,  84 ,  93 ,  95 ,  100 ,  102 ,  105  or  108  and determining the presence of the assemblies.  
     
     
         109 . A method for reducing or terminating the progression of amyloidogenic disease in a patient, comprising administering an effective dosage of the composition of any one of claims  69 - 70 ,  72 ,  74 - 81 ,  83 ,  85 - 92 ,  94 ,  96 - 99 ,  101 ,  103 ,  104 ,  106 , or  107  to the patient.  
     
     
         110 . A method for counteracting the effects of soluble, non-fibrillar assemblies of amyloid β protein, the method comprising administering the composition as in any one of claims  71 ,  73 ,  82 ,  84 ,  93 ,  95 ,  100 ,  102 ,  105 , or  108  to a patient in need of such treatment.