TREATMENT OF ALZHEIMER'S DISEASE SUBPOPULATIONS WITH POOLED IMMUNOGLOBULIN G
The present invention provides, among other aspects, methods for the treatment of Alzheimer's disease in a subject in need thereof, the method including administration of a therapeutically effective amount of a pooled human immunoglobulin G (IgG) composition to a subject with moderately severe Alzheimer's disease, a subject carrying an ApoE4 allele, or both, where the amount of pooled human IgG is from 300 mg/kg to 800 mg/kg body weight of the subject per two week period, and where the amount is administered in one or more doses during the two week period after initiation of a therapeutic regimen. Also provided, are methods for selecting a treatment regimen for a subject with Alzheimer's disease, including diagnosing the severity of the Alzheimer's disease, determining if the subject carries an APOE4 allele, or both, and assigning a treatment regimen including administration of pooled human immunoglobulin G and/or an anti-beta amyloid monoclonal antibody.
1 - 78 . (canceled)
79 . A method for treating Alzheimer's disease in a subject in need thereof, the method comprising: administering a therapeutically effective amount of a composition comprising pooled human immunoglobulin G (IgG) to a subject with moderately severe Alzheimer's disease who is carrier of at least one APOE4 allele, wherein the amount of pooled human IgG is from 300 mg/kg to 800 mg/kg body weight of the subject per two week period, and wherein the amount is administered in one or more doses during the two week period after initiation of a therapeutic regimen.
80 . The method of claim 79 , further comprising the step of diagnosing the subject with moderately severe Alzheimer's disease prior to initiating the therapeutic regimen.
81 . The method of claim 79 , wherein the APOE4 status of the subject is determined prior to starting the therapeutic regimen.
82 . The method of claim 81 , wherein the subject is homozygous for the APOE4 allele.
83 . The method of claim 81 , wherein the subject is heterozygous for the APOE4 allele.
84 - 104 . (canceled)
105 . The method of claim 79 , wherein the amount of pooled human IgG is administered by intravenous administration, subcutaneous administration, intramuscular administration, or intraperitoneal administration.
106 . The method of claim 105 , wherein the amount of pooled human IgG is administered subcutaneously.
107 . The method of claim 106 , wherein the amount of pooled human IgG is co-administered with a tissue permeation agent.
108 . The method of claim 107 , wherein the permeation agent is a hyaluronidase.
109 . The method of claim 108 , wherein the hyaluronidase is PH20, or a truncated form thereof.
110 . The method of claim 79 , wherein the amount of pooled human IgG is administered by intranasal administration, intrathecal administration, intracerebral administration, intracerebroventricular administration, epidural administration, or spinal administration.
111 . The method of claim 79 , further comprising administering a therapeutically effective amount of a second composition for treatment of Alzheimer's disease.
112 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 14 to 23.
113 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 14 to 22.
114 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 14 to 21.
115 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 14 to 20.
116 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 15 to 23.
117 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 15 to 22.
118 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 15 to 21.
119 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 15 to 20.
120 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 16 to 23.
121 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 16 to 22.
122 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 16 to 21.
123 . The method of claim 79 , wherein the subject has a Mini-Mental Status Examination (MMSE) score of from 16 to 20.
124 - 138 . (canceled)
139 . A method of selecting a treatment regimen for a subject with Alzheimer's disease, the method comprising the steps of:
(a) diagnosing the severity of the Alzheimer's disease as mildly severe, moderately severe or severe;
(b) determining if the subject carries the APOE4 allele; and
(c) assigning a treatment regimen comprising administration of pooled human immunoglobulin (IgG) if the subject has moderately severe Alzheimer's disease and is a carrier of an APOE4 allele or assigning a treatment regimen comprising administration of an anti-beta amyloid monoclonal antibody if the subject has mildly severe Alzheimer's disease and is not a carrier of an APOE4 allele.
140 - 157 . (canceled)
158 . A method for treating Alzheimer's disease in a subject in need thereof, the method comprising: administering directly to the CNS a therapeutically effective amount of a composition comprising pooled human immunoglobulin G (IgG) to a subject with moderately severe Alzheimer's disease who is carrier of at least one APOE4 allele, wherein the amount of pooled human IgG is from 50 mg/kg to 400 mg/kg body weight of the subject per two week period, and wherein the amount is administered in one or more doses during the two week period after initiation of a therapeutic regimen.
159 - 187 . (canceled)
188 . A method for treating Alzheimer's disease in a subject in need thereof, the method comprising: administering directly to the CNS a therapeutically effective amount of a composition comprising pooled human immunoglobulin G (IgG) to a subject with moderately severe Alzheimer's disease who is carrier of at least one APOE4 allele, wherein the amount of pooled human IgG is from 375 mg/kg to 1,000 mg/kg body weight of the subject per two week period, and wherein the amount is administered in one or more doses during the two week period after initiation of a therapeutic regimen.
189 - 239 . (canceled)