Method for treating a disease associated with soluble, oligomeric species of amyloid beta 1-42
This invention is a method and kit for treating a disease associated with, or resulting from, the accumulation of soluble oligomer amyloid beta 1-42 using an antibody, or antibody fragment thereof, that has a higher affinity for amyloid beta 1-42 oligomers than for amyloid beta 1-42 monomer, amyloid beta 1-40 monomer, plaques and amyloid beta fibrils and, optionally, a tau therapeutic or an inhibitor of amyloid beta production or aggregation.
1. A method for treating a disease associated with or resulting from the accumulation of soluble oligomer amyloid beta 1-42 comprising administering to a subject in need thereof a dose of less than 10 mg/kg body weight of
(a) an antibody, or antibody fragment thereof, which has an affinity for amyloid beta 1-42 oligomers compared to amyloid beta 1-40 monomers in a competitive binding assay of at least 500:1 and has:
a light chain variable region comprising,
(i) a CDR1 having the sequence Arg-Ser-Ser-Gln-Ser-Ile-Val-His-Ser-Xaa 1 -Gly-Xaa 2 -Thr-Tyr-Leu-Glu (SEQ ID NO:1), wherein Xaa 1 is Asn, Ser, Thr, Ala, Asp or Glu and Xaa 2 is Asn, His, Gln, Ser, Thr, Ala, or Asp,
(ii) a CDR2 having the sequence Lys-Ala-Ser-Xaa 1 -Arg-Phe-Ser (SEQ ID NO:2), wherein Xaa 1 is Asn, Gln, Ser, Thr, or Ala, and
(iii) a CDR3 having the sequence Phe-Gln-Gly-Ser-Xaa 1 -Xaa 2 -Xaa 3 -Xaa 4 -Xaa 5 (SEQ ID NO:3), wherein Xaa 1 is Arg, Lys or Tyr, Xaa 2 is Val or Ala, Xaa 3 is Pro or His, Xaa 4 is Ala, Pro, or Val, and Xaa 5 is Ser, Gly, Arg or Phe; and
a heavy chain variable region comprising,
(i) a CDR1 of SEQ ID NO:4,
(ii) a CDR2 of SEQ ID NO:5, and
(iii) a CDR3 of SEQ ID NO:6; or
(b) an antibody, or antibody fragment thereof, which has an affinity for amyloid beta 1-42 oligomers compared to amyloid beta 1-40 monomers in a competitive binding assay of at least 500:1 and has:
a light chain variable region comprising,
(i) a CDR1 having the sequence Arg-Ser-Ser-Gln-Ser-Ile-Val-His-Ser-Xaa 1 -Gly-Xaa 2 -Thr-Tyr-Leu-Glu (SEQ ID NO:1), wherein Xaa 1 is Ser, Thr, Ala, Asp or Glu and Xaa 2 is Asn, His, Gln, Ser, Thr, Ala, or Asp,
(ii) a CDR2 having the sequence Lys-Ala-Ser-Xaa 1 -Arg-Phe-Ser (SEQ ID NO:2), wherein Xaa 1 is Asn, Gln, Ser, Thr, or Ala, and
(iii) a CDR3 of SEQ ID NO:18; and
a heavy chain variable region comprising,
(i) a CDR1 of SEQ ID NO:4,
(ii) a CDR2 of SEQ ID NO:5, and
(iii) a CDR3 of SEQ ID NO:6,
so that the disease associated with or resulting from the accumulation of soluble oligomer amyloid beta 1-42 is treated.