US 11,702,467 B2
High affinity antibodies targeting tau phosphorylated at serine 413
Jeanne E. Baker, Redwood City, CA (US); Sophie Parmentier Batteur, Haverford, PA (US); Ming-Tang Chen, Dover, MA (US); Alan C. Cheng, San Francisco, CA (US); Chung-Ming Hsieh, Newton, MA (US); Carl Mieczkowski, Hercules, CA (US); and Sokreine Suon, King of Prussia, PA (US)
Assigned to Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed by Merck Sharp & Dohme LLC, Rahway, NJ (US)
Filed on Jun. 23, 2021, as Appl. No. 17/355,529.
Claims priority of provisional application 63/044,921, filed on Jun. 25, 2020.
Prior Publication US 2021/0403541 A1, Dec. 30, 2021
Prior Publication US 2023/0167168 A9, Jun. 1, 2023
Int. Cl. C07K 16/28 (2006.01); C07K 16/18 (2006.01); A61P 25/28 (2006.01); C07K 16/06 (2006.01); C07K 16/40 (2006.01); C07K 16/44 (2006.01); A61P 25/00 (2006.01); A61K 45/06 (2006.01); A61K 39/00 (2006.01)
CPC C07K 16/18 (2013.01) [A61K 45/06 (2013.01); A61P 25/00 (2018.01); A61K 2039/505 (2013.01)] 33 Claims
OG exemplary drawing
 
1. An antibody or antigen binding fragment thereof that binds to tau-pS413, comprising:
(a) a heavy chain variable region complementarity determining region 1 (VH-CDR1) comprising the amino acid sequence of SEQ ID NO:41; a heavy chain variable region complementarity determining region 2 (VH-CDR2) comprising the amino acid sequence of SEQ ID NO:42; and a heavy chain variable region complementarity determining region 3 (VH-CDR3) comprising the amino acid sequence of SEQ ID NO:43; and
a light chain variable region complementarity determining region 1 (VL-CDR1) comprising the amino acid sequence of SEQ ID NO:29; a light chain variable region complementarity determining region 2 (VL-CDR2) comprising the amino acid sequence of SEQ ID NO:30; and a light chain variable region complementarity determining region 3 (VL-CDR3) comprising the amino acid sequence of SEQ ID NO:31;
(b) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:43; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:33; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:34; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:35;
(c) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:43; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:37; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:38; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:39;
(d) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:43; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:25; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:26; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:27;
(e) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:41; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:42; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:43; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:17; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:18; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:19;
(f) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:45; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:47; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:29; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:30; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:31;
(g) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:45; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:47; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:33; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:34; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:35;
(h) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:45; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:47; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:37; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:38; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:39;
(i) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:45; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:47; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:25; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:26; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:27;
(j) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:45; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:46; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:47; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:17; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:18; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:19;
(k) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:49; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:51; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:29; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:30; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:31;
(l) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:49; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:51; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:33; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:34; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:35;
(m) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:49; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:51; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:37; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:38; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:39;
(n) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:49; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:51; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:25; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:26; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:27;
(o) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:49; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:50; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:51; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:17; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:18; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:19;
(p) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:53; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:55; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:29; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:30; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:31;
(q) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:53; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:55; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:33; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:34; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:35;
(r) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:53; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:55; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:37; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:38; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:39;
(s) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:53; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:55; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:25; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:26; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:27;
(t) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:53; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:54; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:55; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:17; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:18; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:19;
(u) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:21; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:22; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:23; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:29; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:30; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:31;
(v) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:21; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:22; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:23; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:33; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:34; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:35;
(w) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:21; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:22; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:23; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:37; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:38; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:39;
(x) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:86; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:87; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:88; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:83; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:84; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:85;
(y) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:92; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:93; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:94; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:89; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:90; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:91;
(z) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:98; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:99; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:100; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:95; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:96; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:97;
(aa) a VH-CDR1 comprising the amino acid sequence of SEQ ID NO:104; a VH-CDR2 comprising the amino acid sequence of SEQ ID NO:105; and a VH-CDR3 comprising the amino acid sequence of SEQ ID NO:106; and
a VL-CDR1 comprising the amino acid sequence of SEQ ID NO:101; a VL-CDR2 comprising the amino acid sequence of SEQ ID NO:102; and a VL-CDR3 comprising the amino acid sequence of SEQ ID NO:103;
(bb) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO:44; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO:32;
(cc) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:44; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:36;
(dd) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:44; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:40;
(ee) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:44; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:28;
(ff) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:44; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:20;
(gg) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:48; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:32;
(hh) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:48; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:36;
(ii) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:48; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:40;
(jj) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:48; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:28;
(kk) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:48; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:20;
(ll) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:52; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:32;
(mm) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:52; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:36;
(nn) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:52; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:40;
(oo) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:52; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:28;
(pp) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:52; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:20;
(qq) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:56; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:32;
(rr) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:56; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:36;
(ss) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:56; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:40;
(tt) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:56; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:28;
(uu) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:56; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:20;
(vv) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:24; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:32;
(ww) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:24; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:36; or
(xx) a VH-CDR1, a VH-CDR2, and a VH-CDR3 of a VH comprising the amino acid sequence of SEQ ID NO:24; and
a VL-CDR1, a VL-CDR2, and a VL-CDR3 of a VL comprising the amino acid sequence of SEQ ID NO:40.