Immunotherapy regimes dependent on apoe status

Abstract

The invention provides methods of immunotherapy of Alzheimer's and similar diseases in which the regime administered to a patient depends on the ApoE genotype of the patient.

What is claimed is: 
     
         1 - 27 . (canceled) 
     
     
         28 . A method of treating Alzheimer's disease, comprising subcutaneously administering to a patient having the disease and one or two copies of an ApoE4 allele an effective regime of an antibody that binds to an N-terminal epitope of Aβ. 
     
     
         29 - 33 . (canceled) 
     
     
         34 . A method of treating Alzheimer's disease, comprising
 administering to a patient having the disease and one or two ApoE4 alleles an effective regime of an antibody that binds to an N-terminal epitope of Aβ;   administering a corticosteroid to the patient to treat vasogenic edema arising from the administration of the antibody.   
     
     
         35 - 37 . (canceled) 
     
     
         38 . A method of treating or effecting prophylaxis in a population of patients of an amyloidogenic disease characterized by amyloid deposits of Aβ in the brain, comprising:
 administering different regimes to different patients in the population depending on which allelic forms of ApoE are present in the patients; wherein at least one of the regimes comprises administering an antibody to Aβ to a patient. 
 
     
     
         39 - 74 . (canceled) 
     
     
         75 . A method of monitoring a population of patients undergoing treatment or prophylaxis for a disease characterized by amyloid deposits of Aβ in the brain with an antibody to Aβ, the method comprising:
 performing different monitoring regimes in different patients in the population for vasogenic edema, wherein the frequency of monitoring is greater for: 
 (a) patients having two copies of ApoE4 relative to patients having zero copies of ApoE4; 
 (b) patients having one copy of an ApoE4 allele relative to patients having zero copies of an ApoE4 allele; and/or 
 (c) patients having two copies of an ApoE4 allele relative to patients having one copy of an ApoE4 allele. 
 
     
     
         76 - 83 . (canceled) 
     
     
         84 . A method of monitoring a population of patients undergoing treatment or prophylaxis for a disease characterized by amyloid deposits of Aβ in the brain with an agent that induces an antibody to Aβ, the method comprising:
 performing different monitoring regimes in different patients in the population for vasogenic edema, wherein the frequency of monitoring is greater for: 
 (a) patients having two copies of ApoE4 relative to patients having zero copies of ApoE4; 
 (b) patients having one copy of an ApoE4 allele relative to patients having zero copies of an ApoE4 allele; and/or 
 (c) patients having two copies of an ApoE4 allele relative to patients having one copy of an ApoE4 allele. 
 
     
     
         85 . A method of treating or effecting prophylaxis of a patient for a disease characterized by amyloid deposits of Aβ in the brain, comprising
 administering to a patient with at least one ApoE4 allele an antibody to an epitope within residue 1-11 of Aβ or an agent that induces such an antibody to Aβ, and 
 monitoring the patient for vasogenic edema by MRI. 
 
     
     
         86 - 88 . (canceled) 
     
     
         89 . A method of treating or effecting prophylaxis of a disease characterized by amyloid deposits of Aβ in the brain in a patient having at least one ApoE4 allele, comprising
 administering a first regime to the patient before vasogenic edema appears, and a second regime after vasogenic edema has resolved; 
 wherein the first and second regimes each comprise administering an antibody to Aβ; wherein the first regime differs relative to the second regime in at least of (i)-(iii) below: 
 (i) the dose of the antibody is reduced; 
 (ii) the frequency of administration of the antibody is reduced; 
 (iii) the capacity of the antibody to clear amyloid deposits is reduced. 
 
     
     
         90 . A method of treating or effecting prophylaxis of a disease characterized by amyloid deposits of Aβ in the brain in a patient having at least one ApoE4 allele, comprising
 administering a first regime to the patient before vasogenic edema appears, and a second regime after vasogenic edema has resolved; 
 wherein the first and second regimes each comprise administering an agent that induces an antibody to Aβ on administration to a patient; wherein the first regime differs relative to the second regime in at least of (i)-(iii) below: 
 (i) the dose of the agent is reduced; 
 (ii) the frequency of administration of the agent is reduced; 
 (iii) the capacity of the agent to clear amyloid deposits is reduced. 
 
     
     
         91 - 96 . (canceled) 
     
     
         97 . A method of treating or effecting prophylaxis of Alzheimer's disease in a patient, comprising
 administering to the patient an antibody that specifically binds to an epitope within residues 1-11 of Aβ to a patient having one or two ApoE4 alleles, wherein the antibody is administered in a regime in which 0.15-1 mg/kg of antibody is administered quarterly by intravenous administration, or at a dose frequency and route of administration that generates an equivalent average serum concentration or area under the curve.   
     
     
         98 - 105 . (canceled) 
     
     
         106 . A method of treating or effecting prophylaxis of Alzheimer's disease in a population of patients, comprising
 administering an antibody that specifically binds to an epitope within residues 1-11 of Aβ to the patients, wherein the antibody is administered at a dose of 0.15-1 mg/kg in patients of the population having one or two ApoE4 alleles and a dose of 0.5-2.5 mg/kg in patients of the population having zero ApoE4 alleles, and the mean dose is higher in the patients having zero ApoE4 alleles.   
     
     
         107 - 110 . (canceled) 
     
     
         111 . A method of effecting prophylaxis of a disease characterized by deposits of Aβ deposits in the brain of a patient comprising
 administering an effective regime of an agent that is an antibody to AB or an agent that induces an antibody to Aβ on administration to a patient, wherein the patient has at least one ApoE4 allele. 
 
     
     
         112 - 120 . (canceled) 
     
     
         121 . A method of treating or effecting prophylaxis of Alzheimer's disease in a patient population, comprising
 administering an antibody that specifically binds to an epitope within residues 1-11 of Aβ and has mutations in the constant region that reduce binding to an Fcγ receptor and/or C1q to the patient, wherein the antibody is administered at the same dose and/or frequency to each patient regardless of the number of ApoE4 alleles in the patient.   
     
     
         122 - 123 . (canceled) 
     
     
         124 . A method of treating or effecting prophylaxis of Alzheimer's disease in a patient population, comprising
 administering an antibody to Aβ to some of the patients in the population, wherein patients in the population having zero ApoE4 alleles receive the antibody and patients in the population having two ApoE4 alleles do not receive the antibody.   
     
     
         125 . (canceled) 
     
     
         126 . A method of treating or effecting prophylaxis of Alzheimer's disease in a patient population, comprising
 administering an agent that induces an antibody to Aβ on administration to some of the patients in the population, wherein patients in the population having zero ApoE4 alleles receive the agent and patients in the population having two ApoE4 alleles do not receive the agent.   
     
     
         127 - 160 . (canceled) 
     
     
         161 . A method of determining a regime for bapineuzumab administration comprising providing instructions to a healthcare professional that assists the healthcare professional determine a regime of bapineuzumab to administer to a patient having zero copies of an ApoE4 allele. 
     
     
         162 - 165 . (canceled) 
     
     
         166 . A method of determining a regime for bapineuzumab administration comprising providing instructions to a healthcare professional that assists the healthcare professional determine a regime of bapineuzumab to administer to a patient having one or two copies of an ApoE4 allele. 
     
     
         167 - 193 . (canceled) 
     
     
         194 . A method for improving the safety of bapineuzumab in patients having one or two ApoE4 alleles, comprising advising the physician to administer a lower dose of bapineuzumab to a patient having one or two ApoE alleles relative to that of a patient having zero ApoE alleles. 
     
     
         195 . A method for improving the safety of bapineuzumab in patients having one or two ApoE4 alleles, comprising advising the physician to monitor the patient by MRI more frequently than a patient having one or two ApoE alleles relative to that of a patient having zero ApoE alleles.