Prevention and treatment of amyloidogenic disease

Abstract

The invention provides compositions and methods for treatment of amyloidogenic diseases. Such methods entail administering an agent that induces a beneficial immune response against an amyloid deposit in the patient. The methods are particularly useful for prophylactic and therapeutic treatment of Alzheimer's disease. In such methods, a suitable agent is Aβ peptide, active fragments thereof or an antibody thereto.

1 . A method of preventing or treating a disease characterized by amyloid deposit in a patient comprising administering an effective dosage of an antibody that specifically binds to the amyloid deposit or a component thereof to the patient.  
     
     
         2 - 37 . (Canceled)  
     
     
         38 . A method of preventing or treating Alzheimer's disease, comprising administering an effective dosage of a polypeptide comprising an active fragment of Aβ that induces an immune response to Aβ in the patient.  
     
     
         38 - 53 . (Canceled)  
     
     
         54 . A method of screening an antibody to Aβ or an active fragment of Aβ for use in treatment of Alzheimer's disease, comprising: 
 administering an antibody that specifically binds to Aβ or a fragment of AB to a transgenic animal disposed to develop characteristics of Alzheimers disease;  
 detecting a reduction in the extent or rate of development of the characteristics relative to a control transgenic animal.  
 
     
     
         55 . The method of  claim 54 , further comprising screening a population of antibodies to identify an antibody that binds to an epitope within amino acids 1-28 of Aβ.  
     
     
         56 . A method for effecting rapid improvement of cognition, in a subject having a condition or disease related to Aβ, comprising administering to the subject an effective amount of an anti-Aβ antibody.  
     
     
         57 . The method of  claim 56 , wherein the subject is human.  
     
     
         58 . The method of  claim 57 , wherein the condition or disease is Alzheimer's disease, Down's syndrome, or mild cognitive impairment.  
     
     
         59 . The method of  claim 58 , wherein the disease is Alzheimer's disease.  
     
     
         60 . The method of  claim 58 , wherein the disease or condition is Down's syndrome.  
     
     
         61 . (Canceled)  
     
     
         62 . The method of  claim 58 , wherein the disease or condition is mild cognitive impairment.  
     
     
         63 . The method of any one of claims  56 - 60  and  62 , wherein the antibody has greater affinity for soluble Aβ than 10 −9  M.  
     
     
         64 . The method of any one of claims  56 - 60  and  62 , wherein the antibody has greater affinity for soluble Aβ an humanized antibody 266.  
     
     
         65 . The method of any one of claims  56 - 60  and  62 , wherein the antibody has greater affinity for soluble Aβ than 10 −10  M.  
     
     
         66 . (Canceled)  
     
     
         67 . The method of any one of claims  56 - 60  and  62 , wherein the antibody is a humanized or human antibody.  
     
     
         68 . The method of  claim 67 , wherein the antibody is a humanized 266 antibody, or an analog thereof.  
     
     
         69 . The method of any one of claims  56 - 60  and  62 , wherein the anti-Aβ antibody recognizes the same epitope that antibody 266 recognizes or competes with antibody 266 for binding to soluble. Aβ.  
     
     
         70 . The method of  claim 63 , wherein the affinity is measured with respect to either Aβ1-40 or Aβ1-42.  
     
     
         71 . The method of any one of claims  56 - 60  and  62 , additionally comprising measuring cognition in the subject before administering the antibody.  
     
     
         72 . The method of  claim 71 , additionally comprising measuring cognition in the subject after administering the antibody.  
     
     
         73 . (Canceled)  
     
     
         74 . The method of any one of claims  56 - 60  and  62 , additionally comprising measuring cognition in the subject after administrating the antibody.  
     
     
         75 . The use of an anti-Aβ antibody to prepare a medicament for any one of the methods of claims  56 - 60 ,  62 .  
     
     
         76 . A method for treating cognitive symptoms of a condition or disease associated with Aβ in a subject, comprising administering to the subject an effective amount of an anti-Aβ antibody that has greater affinity for soluble Aβ than 10 −9  M.  
     
     
         77 . A method for reducing disease progression in a subject having a condition or disease associated with Aβ, comprising administering to the subject an effective amount of an anti-Aβ antibody that has greater affinity for soluble Aβ than 10 −9  M.  
     
     
         78 . A method for treating cognitive symptoms of a condition or disease associated with Aβ in a subject, comprising administering to the subject an effective amount of an anti-Aβ antibody that has affinity (KD) for soluble Aβ1-40 or Aβ1-42 higher than 10 −9  M.  
     
     
         79 . A method for reducing disease progression in a subject having a condition or disease associated with Aβ, comprising administering to the subject an effective amount of an anti-Aβ antibody that has affinity (KD) for soluble Aβ1-40 or Aβ1-42 higher than 10 −9  M.  
     
     
         80 . A method for treating cognitive symptoms of a condition or disease associated Aβ in a subject, comprising administering to the subject an effective amount of an anti-Aβ antibody that has greater affinity for soluble Aβ than antibody 266 has.  
     
     
         81 . A method for reducing disease progression in a subject having a condition or disease associated with Aβ, comprising administering to the subject an effective amount of an anti-Aβ antibody that has great affinity for soluble Aβ than antibody 266 has.  
     
     
         82 . The method any one of claims  76 - 81 , wherein the anti-Aβ antibody has greater affinity for soluble Aβ than 10 −10  M.  
     
     
         83 - 84 . (Canceled)  
     
     
         85 . The method of any one of claims  76 - 82 , wherein the affinity of the anti-Aβ antibody is measure with respect to soluble Aβ1-40 or Aβ1-42.  
     
     
         86 . The method of any one of claims  76 - 82 , wherein the subject is human and the anti-Aβ antibody is human or humanized antibody.  
     
     
         87 . The method of any one of claims  76 - 82 , wherein the anti-Aβ antibody recognizes the same epitope that antibody 266 recognizes or competes with antibody 266 for binding to soluble is a human Aβ.  
     
     
         88 . The method of any one of claims  76 - 82 , wherein the condition or disease is Alzheimer's disease.  
     
     
         89 . The method of any one of claims  76 - 82 , wherein the condition or disease is Down's syndrome.  
     
     
         90 . (Canceled)  
     
     
         91 . The method of any one of claims  76 - 82 , wherein the condition or disease is vascular dementia.  
     
     
         92 . The method of any one of claims  76 - 82 , wherein the condition or disease is mild cognitive impairment.  
     
     
         93 . The use of an anti-Aβ antibody having affinity (KD) for soluble Aβ1-40 or Aβ1-42 higher than 10 −9  M to prepare a medicament for treating cognitive symptoms of a condition or disease associated with Aβ.  
     
     
         94 . The use of an anti-Aβ antibody having affinity (KD) for soluble Aβ1-40 or Aβ1-42 higher than 10 −9  M to prepare a medicament for reducing disease progression in a subject having a condition or disease associated with Aβ.  
     
     
         95 . The use of an anti-Aβ antibody having affinity for soluble Aβ than antibody 266 has to prepare a medicament for treating cognitive symptoms in a subject having a condition or disease associated with Aβ.  
     
     
         96 . The use of an anti-Aβ antibody having greater affinity for soluble Aβ than antibody 266 has to prepare a medicament for reducing disease progression in a subject having a condition or disease associated with Aβ.  
     
     
         97 . The use of an anti-Aβ antibody to prepare a medicament for use in a method of any one of claims  76 .  
     
     
         98 - 110 . (Canceled)