Anti-tau antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-2016376351-A1
Application number	US-201615171143-A
Country	US
Kind code	A1
Filing date	Jun 2, 2016
Priority date	Jun 5, 2015
Publication date	Dec 29, 2016
Grant date	—

Abstract

The invention provides anti-Tau antibodies and methods of using the same.

First claim

1 . An isolated antibody that binds to human Tau, wherein the antibody binds to monomeric Tau, oligomeric Tau, non-phosphorylated Tau, and phosphorylated Tau.

2 . The isolated antibody of claim 1 , wherein the antibody binds an epitope within amino acids 2 to 24 of mature human Tau.

3 . The isolated antibody of claim 2 , which is a monoclonal antibody.

4 . The isolated antibody of claim 3 , which is a human, humanized, or chimeric antibody.

5 . The isolated antibody of claim 2 , which is an antibody fragment that binds human Tau.

6 . The isolated antibody of claim 2 , wherein the epitope within amino acids 2 to 24 of mature human Tau has the sequence of SEQ ID NO: 2.

7 . (canceled)

8 . (canceled)

9 . The isolated antibody of claim 2 , wherein the antibody comprises:
a) HVR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 342, 12, 22, 282, and 292; HVR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 343, 13, 23, 283, and 293; HVR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 344, 14, 24, 284, and 294; HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs: 345, 15, 25, 285, 295, and 468 to 556; HVR-L2 comprising an amino acid sequence selected from SEQ ID NOs: 346, 16, 26, 286, and 296; and HVR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 347, 17, 27, 287, and 297; b) HVR-H1 comprising an amino acid sequence selected from SEQ ID NOs: 72 and 302; HVR-H2 comprising an amino acid sequence selected from SEQ ID NOs: 73 and 303; HVR-H3 comprising an amino acid sequence selected from SEQ ID NOs: 74 and 304; HVR-L1 comprising an amino acid sequence selected from SEQ ID NOs: 75 and 305; HVR-L2 comprising an amino acid sequence selected from SEQ ID NOs: 76 and 306; and HVR-L3 comprising an amino acid sequence selected from SEQ ID NOs: 77 and 307; c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 42; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 43; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 44; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 45; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 46; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 47; d) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 62; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 63; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 64; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 65; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 66; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 67; e) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 212; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 213; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 214; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 215; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 216; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 217; f) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 32; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 33; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 34; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 35; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 36; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 37; or g) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 52; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 53; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 54; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 55; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 56; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 57.

10 . The antibody of claim 9 , wherein the antibody comprises:
a) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to a sequence selected from SEQ ID NOs: 340, 10, 20, 280, 290, 560, 570, and 580; b) a light chain variable region (VL) comprising a sequence that is at least 95% identical to a sequence selected from SEQ ID NOs: 341, 11, 21, 281, 291, 561, 571, and 581; c) a VH as in (a) and a VL as in (b); d) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to a sequence selected from SEQ ID NOs: 70, 300, and 452 to 459; e) a light chain variable region (VL) comprising a sequence that is at least 95% identical to a sequence selected from SEQ ID NOs: 71, 301, and 460 to 467; f) a VH as in (d) and a VL as in (e); g) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 40; h) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 41; i) a VH as in (g) and a VL as in (h); j) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 60; k) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 61; l) a VH as in (j) and a VL as in (k); m) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 210; n) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 211; o) a VH as in (m) and a VL as in (n); p) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 30; q) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 31; r) a VH as in (p) and a VL as in (q); s) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 50; t) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 51; or u) a VH as in (s) and a VL as in (t).

11 . The antibody of claim 10 , wherein the antibody comprises:
a) a heavy chain variable region (VH) comprising a sequence selected from SEQ ID NOs: 340, 10, 20, 280, 290, 560, 570, and 580; b) a light chain variable region (VL) comprising a sequence selected from SEQ ID NOs: 341, 11, 21, 281, 291, 561, 571, and 581; c) a VH as in (a) and a VL as in (b); d) a heavy chain variable region (VH) comprising a sequence selected from SEQ ID NOs: 70, 300, and 452 to 459; e) a light chain variable region (VL) comprising a sequence selected from SEQ ID NOs: 71, 301, and 460 to 467; f) a VH as in (d) and a VL as in (e); g) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 40; h) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 41; i) a VH as in (g) and a VL as in (h); j) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 60; k) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 61; l) a VH as in (j) and a VL as in (k); m) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 210; n) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 211; o) a VH as in (m) and a VL as in (n); p) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 30; q) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 31; r) a VH as in (p) and a VL as in (q); s) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 50; t) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 51; or u) a VH as in (s) and a VL as in (t).

12 . The isolated antibody of claim 2 , wherein the antibody comprises HVR-H1 comprising the amino acid sequence of SEQ ID NO: 342; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 343; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 344; HVR-L1 compris

Assignees

• Genentech Inc
• Ac Immune Sa

Inventors

• Adolfsson Oskar
• Ayalon Gai
• Hotzel Isidro
• Di Cara Danielle Marie

Classifications

• A61K39/3955 Primary

  against proteinaceous materials, e.g. enzymes, hormones, lymphokines · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P21/02

  Muscle relaxants, e.g. for tetanus or cramps · CPC title

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title