Humanized antibodies that recognize beta amyloid peptide
First Claim
Patent Images
1. A purified humanized antibody which specifically binds beta amyloid peptide (Aβ
- ), or antigen-binding fragment of said humanized antibody, the humanized antibody or antigen-binding fragment comprising a humanized light chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) from the monoclonal antibody 12A11 light chain variable region sequence set forth as SEQ ID NO;
2, and wherein L2 is occupied by V, L4 is occupied by M, L36 is occupied by Y, L38 is occupied by Q, L40 is occupied by P, L44 is occupied by P, L46 is occupied by L, L47 is occupied by L, L48 is occupied by I, L49 is occupied by Y, L64 is occupied by G, L66 is occupied by G, L68 is occupied by G, L69 is occupied by T, L71 is occupied by F, L87 is occupied by Y, and L98 is occupied by F (Kabat numbering convention) and a humanized heavy chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) from the monoclonal antibody 12A11 heavy chain variable region sequence and wherein at least three variable region framework residues and amino acids occupying them are selected from the group consisting of H24 occupied by F, H28 occupied by S, H29 occupied by L, H37 occupied by I, H48 occupied by L, H67 occupied by L, H71 occupied by K, H73 occupied by T, and H78 occupied by V (Kabat numbering convention).
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Abstract
The invention provides improved agents and methods for treatment of diseases associated with amyloid deposits of Aβ in the brain of a patient. Preferred agents include antibodies, e.g., humanized antibodies.
293 Citations
32 Claims
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1. A purified humanized antibody which specifically binds beta amyloid peptide (Aβ
- ), or antigen-binding fragment of said humanized antibody, the humanized antibody or antigen-binding fragment comprising a humanized light chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) from the monoclonal antibody 12A11 light chain variable region sequence set forth as SEQ ID NO;
2, and wherein L2 is occupied by V, L4 is occupied by M, L36 is occupied by Y, L38 is occupied by Q, L40 is occupied by P, L44 is occupied by P, L46 is occupied by L, L47 is occupied by L, L48 is occupied by I, L49 is occupied by Y, L64 is occupied by G, L66 is occupied by G, L68 is occupied by G, L69 is occupied by T, L71 is occupied by F, L87 is occupied by Y, and L98 is occupied by F (Kabat numbering convention) and a humanized heavy chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) from the monoclonal antibody 12A11 heavy chain variable region sequence and wherein at least three variable region framework residues and amino acids occupying them are selected from the group consisting of H24 occupied by F, H28 occupied by S, H29 occupied by L, H37 occupied by I, H48 occupied by L, H67 occupied by L, H71 occupied by K, H73 occupied by T, and H78 occupied by V (Kabat numbering convention). - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 32)
- ), or antigen-binding fragment of said humanized antibody, the humanized antibody or antigen-binding fragment comprising a humanized light chain comprising three complementarity determining regions (CDR1, CDR2 and CDR3) from the monoclonal antibody 12A11 light chain variable region sequence set forth as SEQ ID NO;
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10. A purified immunoglobulin which specifically binds to beta amyloid peptide (Aβ
- ), or antigen-binding fragment of said immunoglobulin, comprising a heavy chain variable region sequence as set forth in SEQ ID NO;
10 and a light chain variable region sequence as set forth in SEQ ID NO;
7, and constant regions from IgG1.
- ), or antigen-binding fragment of said immunoglobulin, comprising a heavy chain variable region sequence as set forth in SEQ ID NO;
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11. A purified immunoglobulin which specifically binds to beta amyloid peptide (Aβ
- ), or antigen-binding fragment of said immunoglobulin, comprising a light chain variable region sequence set as forth in SEQ ID NO;
7 and a heavy chain variable region sequence selected from the group consisting of;
SEQ ID NO;
10, SEQ ID NO;
13, SEQ ID NO;
14, SEQ ID NO;
15, SEQ ID NO;
16, SEQ ID NO;
17, SEQ ID NO;
18, SEQ ID NO;
19, SEQ ID NO;
20, SEQ ID NO;
21, SEQ ID NO;
22, SEQ ID NO;
23, SEQ ID NO;
24, SEQ ID NO;
25, SEQ ID NO;
26, SEQ ID NO;
27, SEQ ID NO;
28, SEQ ID NO;
29, SEQ ID NO;
30, and SEQ ID NO;
31. - View Dependent Claims (12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30)
- ), or antigen-binding fragment of said immunoglobulin, comprising a light chain variable region sequence set as forth in SEQ ID NO;
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31. A purified immunoglobulin which specifically binds to beta amyloid peptide (Aβ
- ), or antigen-binding fragment of said immunoglobulin, comprising a heavy chain variable region sequence as set forth in SEQ ID NO;
10 and a light chain variable region sequence as set forth in SEQ ID NO;
7.
- ), or antigen-binding fragment of said immunoglobulin, comprising a heavy chain variable region sequence as set forth in SEQ ID NO;
Specification