Abeta antibodies for use in improving cognition
The invention provides improved agents and methods for treatment of diseases associated with beta amyloid (Aβ). Preferred agents include antibodies, e.g., humanized antibodies specific for Aβ.
1 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 1-10 of Aβ and preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ, such that the rapid improvement in cognition is achieved.
2 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 1-10 of Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
3 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 1-10 of Aβ, preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
4 . The method of any one of claims 1 - 3 , wherein the Aβ antibody binds to an epitope within residues 3-7 of Aβ.
5 . The method of any one of claims 1 - 3 , wherein the Aβ antibody is selected from the group consisting of a 3D6 antibody, a 6C6 antibody, a 10D5 antibody, and a 12A11 antibody.
6 . The method of any one of claims 1 - 3 , provided that the Aβ antibody is not a 3D6 antibody.
7 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ and preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ, such that the rapid improvement in cognition is achieved.
8 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
9 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ, preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
10 . The method of any one of claims 7 - 9 , wherein the Aβ antibody binds to an epitope within residues 16-24 of Aβ.
11 . The method of any one of claims 7 - 9 , wherein the Aβ antibody is selected from the group consisting of a 2B1 antibody, a 1C2 antibody, and a 15C11 antibody.
12 . The method of any one of claims 7 - 9 , provided that the Aβ antibody is not a 266 antibody.
13 . The method of any one of the preceding claims, wherein the improvement in cognition in the animal model is an improvement in memory impairment status or a reversal of memory deficit.
14 . The method of any one of the preceding claims, wherein the subject has or is at risk for an Aβ-related disease or disorder.
15 . The method of claim 14 , wherein the Aβ-related disease or disorder is associated with or characterized by soluble Aβ.
16 . The method of claim 15 , wherein the Aβ-related disease or disorder is associated with or characterized by insoluble Aβ.
17 . The method of claim 15 , wherein the Aβ-related disease or disorder is an amyloidogenic disease.
18 . The method of claim 17 , wherein the Aβ-related disease or disorder is Alzheimer's disease.
19 . The method of claim 15 , wherein the Aβ-related disease or disorder is an Aβ-related cognitive disorder.
20 . The method of claim 19 , wherein the Aβ-related cognitive disorder is mild cognitive impairment.
21 . The method of any one of the preceding claims, wherein the subject is substantially free of amyloid deposits.
22 . The method of any one of the preceding claims, wherein the Aβ antibody is administered to the subject prior to substantial plaque deposition in the subject.
23 . The method of any one of the preceding claims, wherein the subject has been diagnosed with Alzheimer's Disease.
24 . The method of any one of claims 1 - 21 , wherein the Aβ antibody is administered to the subject subsequent to substantial plaque deposition in the subject.
25 . The method of any one of the preceding claims, wherein the Aβ antibody is administered to the subject as a single dose.
26 . The method of any one of claims 1 - 24 , wherein the Aβ antibody is administered to the subject in multiple doses.
27 . The method of any one of the preceding claims, wherein the dose of Aβ antibody is from about 100 μg/kg to 100 mg/kg body weight of the patient.
28 . The method of any one of claims 1 - 26 , wherein the dose of Aβ antibody is from about 300 μg/kg to 30 mg/kg body weight of the patient.
29 . The method of any one of claims 1 - 26 , wherein the dose of Aβ antibody is from about 1 mg/kg to 10 mg/kg body weight of the patient.
30 . The method of any one of the preceding claims, wherein the rapid improvement in cognition is achieved within one month after administration of the antibody.
31 . The method of any one of the preceding claims, wherein the rapid improvement in cognition is achieved within one week after administration of the antibody.
32 . The method of any one of claims 1 - 30 , wherein the rapid improvement in cognition is achieved within one day after administration of the antibody.
33 . The method of any one of claims 1 - 30 , wherein the rapid improvement in cognition is achieved within 12 hours after administration of the antibody.
34 . The method of any one of the preceding claims, wherein the subject is a human.
35 . A composition comprising an Aβ antibody in an amount effective to rapidly improve cognition in a subject, wherein the antibody is specific for an epitope within residues 1-10 of Aβ and preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ.
36 . A composition comprising an Aβ antibody in an amount effective to rapidly improve cognition in a subject, wherein the antibody is specific for an epitope within residues 1-10 of Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay.
37 . A composition comprising an Aβ antibody in an amount effective to rapidly improve cognition in a subject, wherein the antibody is specific for an epitope within residues 1-10 of Aβ, preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay.
38 . The composition of any one of claims 35 - 37 , wherein the Aβ antibody binds to an epitope within residues 3-7 of Aβ.
39 . The composition of any one of claims 35 - 37 , wherein the Aβ antibody is selected from the group consisting of a 3D6 antibody, a 6C6 antibody, a 10D5 antibody, and a 12A11 antibody.
40 . The composition of any one of claims 35 - 37 , provided that the Aβ antibody is not a 3D6 antibody.
41 . A composition for effecting rapid improvement in cognition in a subject, comprising an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ and preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ, such that the rapid improvement in cognition is achieved.
42 . A composition for effecting rapid improvement in cognition in a subject, comprising an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
43 . A composition for effecting rapid improvement in cognition in a subject, comprising an effective dose of an Aβ antibody, wherein the antibody is specific for an epitope within residues 13-28 of Aβ, preferentially binds to soluble oligomeric Aβ as compared to monomeric Aβ and effects a rapid improvement in cognition in an animal model of an Aβ-related disorder as determined in a Contextual Fear Conditioning (CFC) assay, such that the rapid improvement in cognition is achieved.
44 . The composition of any one of claims 41 - 43 , wherein the Aβ antibody binds to an epitope within residues 16-24 of Aβ.
45 . The composition of any one of claims 41 - 43 , wherein the Aβ antibody is selected from the group consisting of a 2B1 antibody, a 1C2 antibody, and a 15C11 antibody.
46 . The composition of any one of claims 41 - 43 , provided that the Aβ antibody is not a 266 antibody.
47 . The composition of any one of claims 41 - 46 , wherein the improvement in cognition in the animal model is an improvement in memory impairment status or a reversal of memory deficit.
48 . The composition of any one of claims 41 - 47 , wherein the antibody neutralizes one or more neuroactive Aβ species.
49 . The composition of any one of claims 41 - 48 , wherein the Aβ antibody clears plaques.
50 . The composition of any one of claims 41 - 49 , formulated for single dose administration.
51 . The composition of any one of claims 41 - 49 , formulated for multiple dose administration.
52 . A humanized immunoglobulin comprising complementarity determining regions (CDRs) the 6C6, antibody produced by the cell line having ATCC Accession Number ______.
53 . A humanized version of the monoclonal antibody 6C6 produced by the cell line having ATCC Accession Number ______.
54 . A humanized immunoglobulin comprising complementarity determining regions (CDRs) the 2B1, antibody produced by the cell line having ATCC Accession Number ______.
55 . A humanized version of the monoclonal antibody 2B1 produced by the cell line having ATCC Accession Number ______.
56 . A humanized immunoglobulin comprising complementarity determining regions (CDRs) the 1C2, antibody produced by the cell line having ATCC Accession Number ______.
57 . A humanized version of the monoclonal antibody 1C2 produced by the cell line having ATCC Accession Number ______.
58 . A humanized immunoglobulin comprising complementarity determining regions (CDRs) the 9G8, antibody produced by the cell line having ATCC Accession Number ______.
59 . A humanized version of the monoclonal antibody 9G8 produced by the cell line having ATCC Accession Number ______.
60 . A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of the antibody of any one of claims 52 - 59 , such that the rapid improvement in cognition is achieved.