Method of treatment of neurodementing diseases using isolated, monoclonal, human, anti-B-amyloid antibody
First Claim
Patent Images
1. A method of treating a neurodementing disease in a patient comprising administering to said patient a therapeutically acceptable amount of an antibody, wherein the antibody comprises:
- a full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
15, 23 and
29) and three from the variable light chain region (VL) (SEQ ID NOs;
33, 41 and
45);
ora full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
13, 21 and
28) and three from the variable light chain region (VL) (SEQ ID NOs;
34, 38 and
44);
ora full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
14, 27 and
30) and three from the variable light chain region (VL) (SEQ ID NOs;
33, 42 and
44);
orthe three CDRs from the VL and the three CDRs from the VH amino acid sequence pairs of SEQ ID NO;
53 and SEQ ID NO;
60, SEQ ID NO;
47 and SEQ ID NO;
56, SEQ ID NO;
48 and SEQ ID NO;
57, SEQ ID NO;
145 and SEQ ID NO;
60, SEQ ID NO;
51 and SEQ ID NO;
60, SEQ ID NO;
52 and SEQ ID NO;
60, SEQ ID NO;
146 and SEQ ID NO;
60, SEQ ID NO;
53 and SEQ ID NO;
148, SEQ ID NO;
55 and SEQ ID NO;
61, SEQ ID NO;
145 and SEQ ID NO;
62, SEQ ID NO;
54 and SEQ ID NO;
60, SEQ ID NO;
54 and SEQ ID NO;
61, SEQ ID NO;
54 and SEQ ID NO;
148, SEQ ID NO;
145 and SEQ ID NO;
148, or SEQ ID NO;
146 and SEQ ID NO;
61;
wherein said antibody binds to dimeric forms of Aβ
with higher affinity than to monomeric forms of Aβ
;
and wherein the neurodementing disease is selected from the group consisting of Alzheimer'"'"'s disease, Down'"'"'s syndrome, dementia with Lewy bodies, fronto-temporal dementia and cerebral amyloid angiopathy.
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Accused Products
Abstract
Isolated, monoclonal, human, anti-β-amyloid antibodies are provided which bind to dimeric forms of Ab with higher affinity than to monomeric forms of Ab and when bound to an Aβ polypeptide comprising Aβ(21-37) shield Aβ(21-37) from proteolytic digestion. The antibodies were shown to inhibit fibril formulation and reduce plaque size in vivo and to not bind brain vessel walls. Accordingly, the antibodies are useful in human and veterinary medicine for the treatment and prophylaxis of Alzheimer'"'"'s disease and other neurodementing diseases. Methods of detecting or measuring the progression of a neurodementing disease also are provided.
22 Citations
7 Claims
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1. A method of treating a neurodementing disease in a patient comprising administering to said patient a therapeutically acceptable amount of an antibody, wherein the antibody comprises:
-
a full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
15, 23 and
29) and three from the variable light chain region (VL) (SEQ ID NOs;
33, 41 and
45);
ora full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
13, 21 and
28) and three from the variable light chain region (VL) (SEQ ID NOs;
34, 38 and
44);
ora full set of six CDRs, three from the variable heavy chain region (VH) (SEQ ID NOs;
14, 27 and
30) and three from the variable light chain region (VL) (SEQ ID NOs;
33, 42 and
44);
orthe three CDRs from the VL and the three CDRs from the VH amino acid sequence pairs of SEQ ID NO;
53 and SEQ ID NO;
60, SEQ ID NO;
47 and SEQ ID NO;
56, SEQ ID NO;
48 and SEQ ID NO;
57, SEQ ID NO;
145 and SEQ ID NO;
60, SEQ ID NO;
51 and SEQ ID NO;
60, SEQ ID NO;
52 and SEQ ID NO;
60, SEQ ID NO;
146 and SEQ ID NO;
60, SEQ ID NO;
53 and SEQ ID NO;
148, SEQ ID NO;
55 and SEQ ID NO;
61, SEQ ID NO;
145 and SEQ ID NO;
62, SEQ ID NO;
54 and SEQ ID NO;
60, SEQ ID NO;
54 and SEQ ID NO;
61, SEQ ID NO;
54 and SEQ ID NO;
148, SEQ ID NO;
145 and SEQ ID NO;
148, or SEQ ID NO;
146 and SEQ ID NO;
61;wherein said antibody binds to dimeric forms of Aβ
with higher affinity than to monomeric forms of Aβ
;and wherein the neurodementing disease is selected from the group consisting of Alzheimer'"'"'s disease, Down'"'"'s syndrome, dementia with Lewy bodies, fronto-temporal dementia and cerebral amyloid angiopathy. - View Dependent Claims (2, 3, 4, 5, 6, 7)
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Specification
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Current AssigneeMichael Bacher, Richard Dodel
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Original AssigneePhilipps-Universitã¤T
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InventorsDodel, Richard, Bacher, Michael, Przybylski, Michael, Stefanescu, Raluca, Manea, Marilena
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Primary Examiner(s)Kemmerer, Elizabeth C
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Assistant Examiner(s)BALLARD, KIMBERLY
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Application NumberUS13/079,852Publication NumberTime in Patent Office840 DaysField of SearchNoneUS Class Current424/142.1CPC Class CodesA61K 2039/505 comprising antibodiesA61P 25/00 Drugs for disorders of the ...A61P 25/28 for treating neurodegenerat...A61P 9/00 Drugs for disorders of the ...C07K 16/18 against material from anima...C07K 2317/21 from primates, e.g. manC07K 2317/56 variable (Fv) region, i.e. ...C07K 2317/565 Complementarity determining...
