Method for treating a disease associated with soluble, oligomeric species of amyloid beta 1-42

摘要

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.

主权项

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-Xaa1-Gly-Xaa2-Thr-Tyr-Leu-Glu (SEQ ID NO:1), wherein Xaa1 is Asn, Ser, Thr, Ala, Asp or Glu and Xaa2 is Asn, His, Gln, Ser, Thr, Ala, or Asp,(ii) a CDR2 having the sequence Lys-Ala-Ser-Xaa1-Arg-Phe-Ser (SEQ ID NO:2), wherein Xaa1 is Asn, Gln, Ser, Thr, or Ala, and(iii) a CDR3 having the sequence Phe-Gln-Gly-Ser-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5 (SEQ ID NO:3), wherein Xaa1 is Arg, Lys or Tyr, Xaa2 is Val or Ala, Xaa3 is Pro or His, Xaa4 is Ala, Pro, or Val, and Xaa5 is Ser, Gly, Arg or Phe; anda 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-Xaa1-Gly-Xaa2-Thr-Tyr-Leu-Glu (SEQ ID NO:1), wherein Xaa1 is Ser, Thr, Ala, Asp or Glu and Xaa2 is Asn, His, Gln, Ser, Thr, Ala, or Asp,(ii) a CDR2 having the sequence Lys-Ala-Ser-Xaa1-Arg-Phe-Ser (SEQ ID NO:2), wherein Xaa1 is Asn, Gln, Ser, Thr, or Ala, and(iii) a CDR3 of SEQ ID NO:18; anda 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.