Humanized antibodies that recognize beta amyloid peptide
First Claim
Patent Images
1. A humanized immunoglobulin which specifically binds beta amyloid peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain comprising(i) the variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin light chain variable region sequence set forth as SEQ ID NO;
2, and(ii) a variable framework region from a human acceptor immunoglobulin light chain, provided that at least three framework residues selected from the group consisting of L1, L2, L36 and L46 (Kabat numbering convention) are substituted with the corresponding amino acid residues from the mouse 3D6 light chain variable region sequence.
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Abstract
The invention provides improves agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Preferred agents include humanized antibodies.
278 Citations
63 Claims
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1. A humanized immunoglobulin which specifically binds beta amyloid peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain comprising
(i) the variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin light chain variable region sequence set forth as SEQ ID NO;
2, and(ii) a variable framework region from a human acceptor immunoglobulin light chain, provided that at least three framework residues selected from the group consisting of L1, L2, L36 and L46 (Kabat numbering convention) are substituted with the corresponding amino acid residues from the mouse 3D6 light chain variable region sequence. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9)
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain comprising
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10. A humanized immunoglobulin which specifically binds amyloid beta peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a heavy chain comprising
(i) the variable region complementarity determining regions (CDRs) from the 3D6 heavy chain variable region sequence set forth as SEQ ID NO;
4, and(ii) a variable framework region from a human acceptor immunoglobulin heavy chain, provided that at least the framework residues H49, H93 and H94 (Kabat numbering convention) are substituted with the corresponding amino acid residues from the mouse 3D6 heavy chain variable region sequence. - View Dependent Claims (11, 12, 13, 14, 15, 16, 17, 18, 19)
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a heavy chain comprising
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20. A humanized immunoglobulin which specifically binds beta amyloid peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain comprising the complementarity determining regions (CDRs) and variable region framework residues L1, L2, L36 and L46 (Kabat numbering convention) from the monoclonal antibody 3D6 light chain, wherein the remainder of the light chain is from a human immunoglobulin.
- View Dependent Claims (21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
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31. A humanized immunoglobulin which specifically binds beta amyloid peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a heavy chain comprising the complementarity determining regions (CDRs) and variable region framework residues H49, H93 and H94 (Kabat numbering convention) from the monoclonal antibody 3D6 heavy chain, wherein the remainder of the heavy chain is from a human immunoglobulin.
- View Dependent Claims (32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42)
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43. A humanized immunoglobulin which specifically binds beta amyloid peptide, or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain selected from the group consisting of:
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(a) a light chain comprising the variable region complementarity determining regions (CDRs) from the 3D6 immunoglobulin light chain variable region sequence set forth as SEQ ID NO;
2, and a variable framework region from a human acceptor immunoglobulin light chain, provided that at least three framework residues selected from the group consisting of L1, L2, L36 and L46 (Kabat numbering convention) are substituted with the corresponding amino acid residues from the mouse 3D6 light chain variable region sequence;(b) a light chain comprising the complementarity determining regions (CDRs) and variable region framework residues L1, L2, L36 and L46 (Kabat numbering convention) from the monoclonal antibody 3D6 light chain, wherein the remainder of the light chain is from a human immunoglobulin; and (c) a light chain comprising the complementarity determining regions (CDRs) and variable region framework residues L2, L36 and L46 (Kabat numbering convention) from the monoclonal antibody 3D6 light chain, wherein the remainder of the light chain is from a human immunoglobulin, and a heavy chain selected from the group consisting of; (a) a heavy chain comprising the variable region complementarity determining regions (CDRs) from the 3D6 heavy chain variable region sequence set forth as SEQ ID NO;
4, and a variable framework region from a human acceptor immunoglobulin heavy chain, provided that at least the framework residues H49, H93 and H94 (Kabat numbering convention) are substituted with the corresponding amino acid residues from the mouse 3D6 heavy chain variable region sequence; and(b) a heavy chain comprising the complementarity determining regions (CDRs) and variable framework residues H49, H93 and H94 (Kabat numbering convention) from the monoclonal antibody 3D6 heavy chain, wherein the remainder of the heavy chain is from a human immunoglobulin. - View Dependent Claims (44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54)
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55. A humanized immunoglobulin which specifically binds to beta amyloid peptide (Aβ
- ), or antigen binding fragment thereof, the humanized immunoglobulin or antigen binding fragment comprising a light chain comprising the complementarity determining regions (CDRs) and variable region framework residues L2, L36 and L46 (Kabat numbering convention) from the monoclonal antibody 3D6 light chain, wherein the remainder of the light chain is from a human immunoglobulin.
- View Dependent Claims (56, 57, 58, 59, 60, 61, 62, 63)
Specification