Antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau
The disclosure relates to antibodies and antigen-binding fragments that specifically bind to microtubule-associated protein tau. The disclosure also relates to diagnostic, prophylactic and therapeutic methods using anti-tau antibodies.
1. A monoclonal antibody that binds tau deposits in human Alzheimer's disease (“AD”) brain tissue and does not bind tau deposits in Progressive Supranuclear Palsy (“PSP”) brain tissue, wherein the antibody comprises
a heavy chain CDR1 region comprising SEQ ID NO:163, a heavy chain CDR2 region comprising SEQ ID NO:164, and a heavy chain CDR3 region comprising SEQ ID NO:165, a light chain CDR1 region comprising SEQ ID NO:166, a light chain CDR2 region comprising SEQ ID NO:167 and a light chain CDR3 region comprising SEQ ID NO:168.
2. An antigen-binding fragment that binds tau deposits in human Alzheimer's disease (“AD”) brain tissue,
wherein the antigen-binding fragment binds tau deposits in human AD brain tissue, but does not bind tau in normal human brain tissue and does not bind tau deposits in Progressive Supranuclear Palsy (“PSP”) brain tissue; and
wherein the antigen-binding fragment comprises an antigen-binding site of a VH of SEQ ID NO:87 and an antigen-binding site of a VL of SEQ ID NO:88.
3. The antigen-binding fragment of claim 2 , wherein the antigen-binding fragment is phosphospecific.
4. The antigen-binding fragment of claim 2 , wherein the antigen-binding fragment binds to a peptide comprising SEQ ID NO: 315 or SEQ ID NO: 353 and does not bind to a peptide comprising SEQ ID NO: 316 or SEQ ID NO: 356.
5. An immunoconjugate comprising the antigen-binding fragment of claim 2 , and
at least one therapeutic agent and/or detectable agent.
6. A pharmaceutical composition comprising:
the antigen binding fragment of claim 2 , and at least one pharmaceutically acceptable excipient.
7. A kit comprising the antigen-binding fragment of claim 2 .
8. An isolated nucleic acid molecule encoding an antigen binding fragment of claim 2 .
9. A vector comprising a nucleic acid molecule according to claim 8 .
10. A host cell comprising the vector according to claim 9 .
11. A method of producing an antibody or an antigen-binding fragment thereof, the method comprising:
culturing the host cell of claim 10 ; and recovering the antibody or fragment thereof produced by the host cell.