Anti-ADDL monoclonal antibody and use thereof
AssigneeMerck & Co., Inc.
InventorsGene Kinney, William R. Strohl, Zhiqiang An
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Abstract
The present invention relates to antibodies that differentially recognize multi-dimensional conformations of Aβ-derived diffusible ligands, also known as ADDLs. The antibodies of the invention can distinguish between Alzheimer's Disease and control human brain extracts and are useful in methods of detecting ADDLs and diagnosing Alzheimer's Disease. The present antibodies also block binding of ADDLs to neurons, assembly of ADDLS, and tau phosphorylation and are there useful in methods for the preventing and treating diseases associated with soluble oligomers of amyloid β 1-42.
Claims12
An isolated antibody, or antigen-binding fragment thereof, capable of differentially recognizing a multi-dimensional conformation of one or more Aβ-derived diffusible ligands, wherein said antibody comprises a complementary determining region (CDR) of Arg-Xaa1-Leu-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Asp-Ala-Met-Asp-Tyr (SEQ ID NO:9), wherein Xaa1 is Gln or Ala;
- Xaa2 is Ser or Gly;
- Xaa3 is Pro, Ala, Lys, Arg, or Thr;
- Xaa4 is Lys or Arg;
- Xaa5 is Gly, Ser, or Lys;
- Xaa6 is Val, Thr, Ile or Arg, wherein the heavy and light chain variable regions of said antibody respectively comprise the amino acid sequence set forth in SEQ ID NO:108 and SEQ ID NO:112.
An isolated antibody, or antigen-binding fragment thereof, capable of differentially recognizing a multi-dimensional conformation of one or more Aβ-derived diffusible ligands, wherein said antibody comprises a complementary determining region (CDR) of Arg-Xaa1-Leu-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Asp-Ala-Met-A5p-Tyr (SEQ ID NO:9), wherein Xaa1 is Gin or Ala;
- Xaa2 is Ser or Gly;
- Xaa3 is Pro, Ala, Lys, Arg, or Thr;
- Xaa4 is Lys or Arg;
- Xaa5 is Gly, Ser, or Lys;
- Xaa6 is Val, Thr, Ile or Arg, wherein the heavy and light chain of said antibody respectively comprise the amino acid sequence set forth in SEQ ID NO:138 and SEQ ID NO:140.
Dependencies are inferred from the claim text.