Humanized antibodies that recognize beta amyloid peptide
View Patent ↗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 humanized antibodies.
1. A humanized antibody, or fragment thereof, comprising a humanized light chain comprising three light chain complementarily determining regions (CDRs) from the mouse monoclonal antibody 10D5 and a light chain variable region framework sequence from a human immunoglobulin light chain; and a humanized heavy chain comprising three heavy chain CDRs from the mouse monoclonal antibody 10D5 and a heavy chain variable region framework sequence from a human immunoglobulin heavy chain; wherein the light chain CDRs have the following amino acid sequences:
light chain CDR1:
Arg Ser Ser Gln Asn Ile Ile His Ser Asn Gly Asn
Thr Tyr Leu Glu
(residues 24-39 of SEQ ID NO: 14)
light chain CDR2:
Lys Val Ser Asn Arg Phe Ser
(residues 55-61 of SEQ ID NO: 14)
light chain CDR3:
Phe Gln Gly Ser His Val Pro Leu Thr
(residues 94-102 of SEQ ID NO: 14)
and the heavy chain CDRS have the following amino
acid sequences:
heavy chain CDR1:
Thr Ser Gly Met Gly Val Ser
(residues 31-37 of SEQ ID NO: 16)
heavy chain CDR2:
His Ile Tyr Trp Asp Asp Asp Lys Arg Tyr Asn Pro
Ser Leu Lys Ser
(residues 52-67 of SEQ ID NO: 16)
and,
heavy chain CDR3:
Arg Pro Ile Thr Pro Val Leu Val Asp Ala Met Asp
Tyr
(residues 100-112 of SEQ ID NO: 16).
2. An antibody fragment obtainable by enzymatic cleavage of the humanized antibody of claim 1 .
3. An Fab or F(ab′) 2 fragment of the humanized antibody of claim 1 .
4. The F(ab′) 2 fragment of claim 3 .
5. The Fab fragment of claim 3 .
6. The humanized antibody or fragment of any one of claims 1 - 5 , which is a single chain antibody.
7. The humanized antibody or fragment of any one of claims 1 - 5 that is an IgG1 immunoglobulin isotype.
8. The humanized antibody or fragment of any one of claims 1 - 5 , wherein the antibody or fragment thereof is produced in a host cell selected from the group consisting of a myeloma cell and a chinese hamster ovary (CHO) cell.
9. A chimeric antibody or antigen binding fragment thereof, comprising a light chain comprising a variable region sequence of residues 1-112 of SEQ ID NO: 14 and a human constant region, and a heavy chain comprising a heavy chain variable region of residues 1-123 of SEQ ID NO: 16 and a human constant region.