Humanized Aβ antibodies for use in improving cognition
First Claim
1. A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of a 12A11 immunological reagent, such that rapid improvement in cognition is observed within one month of the administering step, wherein the 12A11 immunological reagent is a humanized 12A11 immunoglobulin or antigen binding fragment comprising a humanized heavy chain and a humanized light chain, wherein(a) the humanized light chain comprises three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 12A11 immunoglobulin light chain variable domain designated SEQ ID NO:
- 2, and a variable region framework from a human light chain variable region framework sequence designated SEQ ID NO;
8; and
(b) the humanized heavy chain comprises three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 12A11 immunoglobulin heavy chain variable domain designated SEQ ID NO;
4, and a variable region framework from a human heavy chain variable region framework sequence designated SEQ ID NO;
11 provided that at least one position selected from a group consisting of H24, H28, H29, H37, H48, H67, H71, H73 and H78 (Kabat numbering convention) is occupied by the same amino acid residue present in the equivalent position of the mouse 12A11 immunoglobulin heavy chain variable region framework;
wherein the humanized immunoglobulin specifically binds to beta amyloid peptide (A13) with a binding affinity of at least 107 M−
1, wherein the mouse 12A11 immunoglobulin has the light chain with a variable domain designated SEQ ID NO;
2 and the heavy chain with a variable domain designated SEQ ID NO;
4.
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Accused Products
Abstract
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.
312 Citations
37 Claims
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1. A method for effecting rapid improvement in cognition in a subject, comprising administering to the subject an effective dose of a 12A11 immunological reagent, such that rapid improvement in cognition is observed within one month of the administering step, wherein the 12A11 immunological reagent is a humanized 12A11 immunoglobulin or antigen binding fragment comprising a humanized heavy chain and a humanized light chain, wherein
(a) the humanized light chain comprises three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 12A11 immunoglobulin light chain variable domain designated SEQ ID NO: - 2, and a variable region framework from a human light chain variable region framework sequence designated SEQ ID NO;
8; and(b) the humanized heavy chain comprises three complementarity determining regions (CDR1, CDR2 and CDR3) having amino acid sequences from the corresponding complementarity determining regions of the mouse 12A11 immunoglobulin heavy chain variable domain designated SEQ ID NO;
4, and a variable region framework from a human heavy chain variable region framework sequence designated SEQ ID NO;
11 provided that at least one position selected from a group consisting of H24, H28, H29, H37, H48, H67, H71, H73 and H78 (Kabat numbering convention) is occupied by the same amino acid residue present in the equivalent position of the mouse 12A11 immunoglobulin heavy chain variable region framework;wherein the humanized immunoglobulin specifically binds to beta amyloid peptide (A13) with a binding affinity of at least 107 M−
1, wherein the mouse 12A11 immunoglobulin has the light chain with a variable domain designated SEQ ID NO;
2 and the heavy chain with a variable domain designated SEQ ID NO;
4. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37)
- 2, and a variable region framework from a human light chain variable region framework sequence designated SEQ ID NO;
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17. The method of 1, wherein the humanized heavy chain variable region framework positions H24, H29, H37, and H71 (Kabat numbering convention) are occupied by F, L, I, and K, respectively.
Specification