Anti-abeta antibodies
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Abstract
This invention provides variant 266 antibodies that are engineered to lack an N-glycosylation site within the CDR2 of the heavy chain, pharmaceutical compositions thereof, and polynucleotide sequences, vectors, and transformed cells useful to express the variant antibodies. The variants sequester soluble Aβ peptide from human biological fluids and specifically bind an epitope contained within position 13-28 of the amyloid beta peptide Aβ with significantly greater affinity than either mouse antibody 266 or humanized 266 antibodies retaining N-glycosylation sites. The variant antibodies are useful for treatment or prevention of conditions and diseases associated with Aβ, including Alzheimer'"'"'s disease, Down'"'"'s syndrome, cerebral amyloid angiopathy, mild cognitive impairment, and the like.
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Citations
53 Claims
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1-28. -28. (cancelled)
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29. an antibody, or fragment thereof, comprising a light chain and a heavy chain, wherein the light chain comprises the three light chain complementarity determining regions (CDRs) from mouse monoclonal antibody 266 (SEQ ID NO:
- 1-3), and wherein the heavy chain comprises heavy chain CDR1 and CDR3 from mouse monoclonal antibody 266 (SEQ ID NO;
4 and 6, respectively), and a heavy chain CDR2 having the sequence given by SEQ ID NO;
5;
Gln Iie Asn Ser Val Gly Xaa Xaa Xaa Tyr Tyr Pro Asp Thr Val Lys Gly (SEQ ID NO;
5)wherein, Xaa at position 7 of SEQ ID NO;
5 is any amino acid, provided that if Xaa at position 8 is neither Asp nor Pro and Xaa at position 9 is Ser or Thr, then Xaa at position 7 is not Asn;
Xaa at position 8 of SEQ ID NO;
5 is any amino acid, provided that if Xaa at position 7 is Asn and Xaa at position 9 is Ser or Thr, then Xaa at position 8 is Asp or Pro; and
Xaa at position 9 of SEQ ID NO;
5 is any amino acid, provided that if Xaa at position 7 is Asn and Xaa at position 8 is neither Asp nor Pro, then Xaa at position 9 is neither Ser nor Thr. - View Dependent Claims (30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53)
- 1-3), and wherein the heavy chain comprises heavy chain CDR1 and CDR3 from mouse monoclonal antibody 266 (SEQ ID NO;
Specification