IP Library › Granted Patent US 10,836,817

Granted Patent B2

US 10,836,817 · App. 16/420,678 · Granted Nov 17, 2020

Anti-Tau antibodies and methods of use

Inventors: Oskar Adolfsson (Bercher, CH); Kristin Ruth Wildsmith (Half Moon Bay, CA); Marcel Van Der Brug (Daly City, CA); Andreas Muhs (Cugy, CH)

Assignees: AC Immune SA; Genentech, Inc.

C07K16/18 A61K45/06 C07K2317/24 C07K2317/31 C07K2317/56 C07K2317/92

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Quick Facts

Patent No.: US 10,836,817
App. No.: 16/420,678
Granted: Nov 17, 2020
Kind: B2

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USPTO Patent Center↗ Full Patent PDF↗

Abstract

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

Claims (129)

1. An isolated antibody that binds to human Tau, wherein the antibody comprises:

a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 605; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 606; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 607; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 608; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 609; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 610;

b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 613; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 614; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 615; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 616; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 617; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 618;

c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 621; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 622; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 623; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 624; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 625; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 626;

d) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 629; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 630; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 631; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 632; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 633; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 634;

e) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 637; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 638; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 639; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 640; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 641; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 642;

f) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 645; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 646; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 647; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 648; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 649; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 650;

g) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 653; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 654; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 655; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 656; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 657; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 658;

h) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 661; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 662; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 663; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 664; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 665; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 666;

i) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 669; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 670; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 671; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 672; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 673; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 674;

j) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 677; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 678; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 679; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 680; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 681; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 682;

k) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 685; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 686; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 687; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 688; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 689; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 690; or

l) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 693; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 694; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 695; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 696; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 697; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 698.

2. The antibody of claim 1 , wherein the antibody comprises:

a) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 603;

b) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 604;

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 SEQ ID NO: 611;

e) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 612;

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: 619;

h) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 620;

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: 627;

k) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 628;

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: 635;

n) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 636;

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: 643;

q) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 644;

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: 651;

t) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 652;

u) a VH as in (s) and a VL as in (t);

v) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 659;

w) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 660;

x) a VH as in (v) and a VL as in (w);

y) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 667;

z) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 668;

aa) a VH as in (y) and a VL as in (z);

bb) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 675;

cc) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 676;

dd) a VH as in (bb) and a VL as in (cc);

ee) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 683;

ff) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 684;

gg) a VH as in (ee) and a VL as in (ff);

hh) a heavy chain variable region (VH) comprising a sequence that is at least 95% identical to SEQ ID NO: 691;

ii) a light chain variable region (VL) comprising a sequence that is at least 95% identical to SEQ ID NO: 692; or

jj) a VH as in (hh) and a VL as in (ii).

3. The antibody of claim 1 , wherein the antibody comprises:

a) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 603;

b) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 604;

c) a VH as in (a) and a VL as in (b);

d) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 611;

e) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 612;

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: 619;

h) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 620;

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: 627;

k) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 628;

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: 635;

n) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 636;

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: 643;

q) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 644;

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: 651;

t) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 652;

u) a VH as in (s) and a VL as in (t);

v) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 659;

w) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 660;

x) a VH as in (v) and a VL as in (w);

y) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 667;

z) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 668;

aa) a VH as in (y) and a VL as in (z);

bb) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 675;

cc) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 676;

dd) a VH as in (bb) and a VL as in (cc);

ee) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 683;

ff) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 684;

gg) a VH as in (ee) and a VL as in (ff);

hh) a heavy chain variable region (VH) comprising the sequence of SEQ ID NO: 691;

ii) a light chain variable region (VL) comprising the sequence of SEQ ID NO: 692; or

jj) a VH as in (hh) and a VL as in (ii).

4. The isolated antibody of claim 1 , wherein the antibody binds each of monomeric Tau, phosphorylated Tau, non-phosphorylated Tau, and oligomeric Tau with a K D of less than 400 nM, less than 100 nM, less than 75 nM, or less than 50 nM.

5. The isolated antibody of claim 1 , which binds cynomolgus monkey Tau.

6. An isolated nucleic acid that encodes the antibody of claim 1 .

7. An isolated host cell comprising the nucleic acid of claim 6 .

8. A method of producing an antibody comprising culturing the host cell of claim 7 under conditions suitable for producing the antibody.

9. An immunoconjugate comprising the isolated antibody of claim 1 and a second therapeutic agent.

10. A labeled antibody comprising the antibody of claim 1 and a detectable label.

11. A method of detecting Tau, neurofibrillary tangles, neuropil threads, and/or dystrophic neurites in a sample, comprising contacting the sample with the antibody of claim 1 .

12. The isolated antibody of claim 1 , wherein the antibody binds to monomeric Tau, oligomeric Tau, non-phosphorylated Tau, and phosphorylated Tau.

13. The isolated antibody of claim 1 , which is a monoclonal antibody.

14. The isolated antibody of claim 13 , wherein the antibody is an IgG1 or an IgG4 antibody.

15. The isolated antibody of claim 1 , which is a mouse, humanized, or chimeric antibody.

16. The isolated antibody of claim 1 , which is an antibody fragment that binds human Tau.

17. The isolated antibody of claim 1 , wherein the human Tau comprises the sequence of SEQ ID NO: 2.

18. A method of selecting a patient for treatment with a therapeutic anti-Tau antibody, comprising detecting Tau in a sample from the subject with a detection anti-Tau antibody, wherein the detection anti-Tau antibody is an antibody comprising:

b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 653; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 654; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 655; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 656; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 657; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 658;

c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 661; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 662; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 663; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 664; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 665; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 666; or

d) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 669; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 670; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 671; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 672; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 673; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 674.

19. A method of monitoring treatment with a therapeutic anti-Tau antibody, comprising detecting Tau in a sample from a subject undergoing treatment with a detection anti-Tau antibody, wherein the detection anti-Tau antibody is an antibody comprising:

20. A method of selecting a patient for treatment with a therapeutic anti-Tau antibody, comprising detecting Tau in a sample from the patient with a detection anti-Tau antibody, wherein the detection anti-Tau antibody is an antibody comprising:

a) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 613; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 614; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 615; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 616; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 617; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 618;

b) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 621; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 622; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 623; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 624; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 625; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 626;

c) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 629; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 630; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 631; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 632; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 633; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 634;

d) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 637; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 638; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 639; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 640; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 641; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 642; or

e) HVR-H1 comprising the amino acid sequence of SEQ ID NO: 677; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 678; HVR-H3 comprising the amino acid sequence of SEQ ID NO: 679; HVR-L1 comprising the amino acid sequence of SEQ ID NO: 680; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 681; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 682.

21. A method of monitoring the progression of cognitive impairment in a subject with a tauopathy, comprising detecting Tau in a sample from the subject with a detection anti-Tau antibody, wherein the detection anti-Tau antibody is an antibody comprising:

22. A method of monitoring treatment with a therapeutic anti-Tau antibody, comprising detecting Tau in a sample from a subject undergoing treatment with a detection anti-Tau antibody, wherein the detection anti-Tau antibody is an antibody comprising:

Continuity (3)

Continuation PCTUS2017064855 · Dec 6, 2017

Provisional Application 62431183 · Dec 7, 2016

Related Publication 20190367592A1 · Dec 5, 2019

Cited By (4)

US 12,195,525 US 12,234,280 US 12,479,910 US 12,735,507