IP Library › Granted Patent US 11,421,040

Granted Patent B2

US 11,421,040 · App. 15/993,874 · Granted Aug 23, 2022

Antibodies specific for FLT3 and their uses

Inventors: Danielle Elizabeth Dettling (San Francisco, CA); Yik Andy Yeung (South San Francisco, CA); Kristian Todd Poulsen (San Francisco, CA); Veena Krishnamoorthy (Burlingame, CA); Cesar Adolfo Sommer (San Mateo, CA)

Assignee: Pfizer Inc.

C07K16/461 A61P35/00 A61P35/02 C07K16/2809 C07K16/2863 A61K2039/505 C07K2317/21 C07K2317/31 C07K2317/33 C07K2317/52 C07K2317/62 C07K2317/71 C07K2317/73 C07K2317/92

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Quick Facts

Patent No.: US 11,421,040
App. No.: 15/993,874
Granted: Aug 23, 2022
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention provides antibodies that specifically bind to FLT3 (Fms-Like Tyrosine Kinase 3). The invention further provides bispecific antibodies that bind to FLT3 and another antigen (e.g., CD3). The invention further relates to antibody encoding nucleic acids, and methods of obtaining such antibodies (monospecific and bispecific). The invention further relates to therapeutic methods for use of these antibodies for the treatment of FLT3-mediated pathologies, including cancer such as Acute Myeloid Leukemia (AML).

Claims (307)

1. An isolated antibody, which specifically binds to Fms-like tyrosine kinase 3 (FLT3), wherein the antibody comprises:

(a) a heavy chain variable (VH) region comprising:

a VH complementarity determining region one (CDR1) comprising the sequence shown in SEQ ID NO: 90, 91, or 92;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 93 or 94; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 95;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 171;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 172; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 173;

(b) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 49, 44, 50;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 51 or 52; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 53;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 150;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 151; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 152;

a VH CDR1 comprising the sequence shown in SEQ ID NO: 37, 38 or 39;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 40 or 41; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 42;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 144;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 145; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 146;

(d) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 43, 44, or 45;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 46 or 47; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 48;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 147;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 148; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 149;

(e) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 54, 55 or 56;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 57 or 58; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 59;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 153;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 154; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 155;

(f) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 60, 61 or 62;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 63 or 64; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 65;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 156;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 157; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 158;

(g) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 66, 67 or 68;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 69 or 70; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 71;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 159;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 160; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 161;

(h) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 72, 73 or 74;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 75 or 76; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 77;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 162;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 163; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 164;

(i) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 78, 79 or 80;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 81 or 82; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 83;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 165;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 166; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 167;

(j) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 84, 85 or 86;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 87 or 88; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 89;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 168;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 169; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 170;

(k) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 96, 97 or 98;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 99 or 100; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 101;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 174;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 175; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 176;

(l) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 177;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 178; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 179;

(m) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 108, 109 or 110;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 111 or 112; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 113;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 180;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 181; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 182;

(n) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 114, 115 or 116;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 117 or 118; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 119;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 183;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 184; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 185;

(o) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 120, 121 or 122;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 123 or 124; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 125;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 186;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 187; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 188;

(p) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 126, 127 or 128;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 129 or 130; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 131;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 189;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 190; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 191;

(q) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 132, 133 or 134;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 135 or 136; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 137;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 192;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 193; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 194;

(r) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 138, 139 or 140;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 141 or 142; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 143;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 195;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 196; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 197;

(s) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 126, 127 or 128;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 129 or 130; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 245;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 189;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 190; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 256;

(t) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 247, 127 or 246;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 248 or 249; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 250;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 257;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 190; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 258;

(u) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 72, 73 or 74;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 100 or 251; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 77;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 174;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 175; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 176;

(v) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 49, 44 or 50;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 253 or 252; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 254;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 177;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 259; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 260;

(w) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 177;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 178; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 179;

(x) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 255 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 177;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 178; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 179;

(y) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 138, 139 or 140;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 255 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 275;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 259; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 264;

(z) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 261;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 259; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 262;

(aa) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 263;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 259; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 264;

(bb) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 265;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 266; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 267;

(cc) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 268;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 266; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 269;

(dd) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 270;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 271; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 272;

(ee) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 105 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 273;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 266; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 274; or

(ff) a heavy chain variable (VH) region comprising:

a VH CDR1 comprising the sequence shown in SEQ ID NO: 102, 103 or 104;

a VH CDR2 comprising the sequence shown in SEQ ID NO: 255 or 106; and

a VH CDR3 comprising the sequence shown in SEQ ID NO: 107;

and a light chain variable (VL) region comprising

a VL CDR1 comprising the sequence shown in SEQ ID NO: 275;

a VL CDR2 comprising the sequence shown in SEQ ID NO: 259; and

a VL CDR3 comprising the sequence shown in SEQ ID NO: 264.

2. An isolated antibody which specifically binds to Fms-like tyrosine kinase 3 (FLT3), wherein the antibody comprises:

(a) a VH region comprising of the VH sequence shown in SEQ ID NO: 20, and a VL region comprising the VL sequence shown in SEQ ID NO: 19; or

(b) a VH region comprising the VH sequence shown in SEQ ID NO: 6, and a VL region comprising the VL sequence shown in SEQ ID NO: 5; or

(c) a VH region comprising the VH sequence shown in SEQ ID NO: 4, and a VL region comprising the VL sequence shown in SEQ ID NO: 3; or

(d) a VH region comprising the VH sequence shown in SEQ ID NO: 8, and a VL region comprising the VL sequence shown in SEQ ID NO: 7; or

(e) a VH region comprising the VH sequence shown in SEQ ID NO: 10, and a VL region comprising the VL sequence shown in SEQ ID NO: 9; or

(f) a VH region comprising the VH sequence shown in SEQ ID NO: 12, and a VL region comprising the VL sequence shown in SEQ ID NO: 11; or

(g) a VH region comprising the VH sequence shown in SEQ ID NO: 14, and a VL region comprising the VL sequence shown in SEQ ID NO: 13; or

(h) a VH region comprising the VH sequence shown in SEQ ID NO: 16, and a VL region comprising the VL sequence shown in SEQ ID NO: 15; or

(i) a VH region comprising the VH sequence shown in SEQ ID NO: 18, and a VL region comprising the VL sequence shown in SEQ ID NO: 17; or

(j) a VH region comprising the VH sequence shown in SEQ ID NO: 2, and a VL region comprising the VL sequence shown in SEQ ID NO: 1; or

(k) a VH region comprising the VH sequence shown in SEQ ID NO: 22, and a VL region comprising the VL sequence shown in SEQ ID NO: 21; or

(l) a VH region comprising the VH sequence shown in SEQ ID NO: 24, and a VL region comprising the VL sequence shown in SEQ ID NO: 23; or

(m) a VH region comprising the VH sequence shown in SEQ ID NO: 26, and a VL region comprising the VL sequence shown in SEQ ID NO: 25; or

(n) a VH region comprising the VH sequence shown in SEQ ID NO: 28, and a VL region comprising the VL sequence shown in SEQ ID NO: 27; or

(o) a VH region comprising the VH sequence shown in SEQ ID NO: 30, and a VL region comprising the VL sequence shown in SEQ ID NO: 29; or

(p) a VH region comprising the VH sequence shown in SEQ ID NO: 32, and a VL region comprising the VL sequence shown in SEQ ID NO: 31; or

(q) a VH region comprising the VH sequence shown in SEQ ID NO: 34, and a VL region comprising the VL sequence shown in SEQ ID NO: 33; or

(r) a VH region comprising the VH sequence shown in SEQ ID NO: 36, and a VL region comprising the VL sequence shown in SEQ ID NO: 35; or

(s) a VH region comprising the VH sequence shown in SEQ ID NO: 205, and a VL region comprising the VL sequence shown in SEQ ID NO: 204; or

(t) a VH region comprising the VH sequence shown in SEQ ID NO: 207, and a VL region comprising the VL sequence shown in SEQ ID NO: 206; or

(u) a VH region comprising the VH sequence shown in SEQ ID NO: 209, and a VL region comprising the VL sequence shown in SEQ ID NO: 208; or

(v) a VH region comprising the VH sequence shown in SEQ ID NO: 211, and a VL region comprising the VL sequence shown in SEQ ID NO: 210; or

(w) a VH region comprising the VH sequence shown in SEQ ID NO: 213, and a VL region comprising the VL sequence shown in SEQ ID NO: 212; or

(x) a VH region comprising the VH sequence shown in SEQ ID NO: 215, and a VL region comprising the VL sequence shown in SEQ ID NO: 214; or

(y) a VH region comprising the VH sequence shown in SEQ ID NO: 217, and a VL region comprising the VL sequence shown in SEQ ID NO: 216; or

(z) a VH region comprising the VH sequence shown in SEQ ID NO: 219, and a VL region comprising the VL sequence shown in SEQ ID NO: 218; or

(aa) a VH region comprising the VH sequence shown in SEQ ID NO: 221, and a VL region comprising the VL sequence shown in SEQ ID NO: 220; or

(bb) a VH region comprising the VH sequence shown in SEQ ID NO: 223, and a VL region comprising the VL sequence shown in SEQ ID NO: 222; or

(cc) a VH region comprising the VH sequence shown in SEQ ID NO: 225, and a VL region comprising the VL sequence shown in SEQ ID NO: 224; or

(dd) a VH region comprising the VH sequence shown in SEQ ID NO: 227, and a VL region comprising the VL sequence shown in SEQ ID NO: 226; or

(ee) a VH region comprising the VH sequence shown in SEQ ID NO: 229, and a VL region comprising the VL sequence shown in SEQ ID NO: 228; or

(ff) a VH region comprising the VH sequence shown in SEQ ID NO: 231, and a VL region comprising the VL sequence shown in SEQ ID NO: 230; or

(gg) a VH region comprising the VH sequence shown in SEQ ID NO: 233, and a VL region comprising the VL sequence shown in SEQ ID NO: 232.

3. The isolated antibody of claim 1 , wherein (a) the VH CDR1 comprises the sequence shown in SEQ ID NO: 90, the VH CDR2 comprising the sequence shown in SEQ ID NO: 93 and the VH CDR3 comprising the sequence shown in SEQ ID NO: 95; and

(b) the VL CDR1 comprises the sequence shown in SEQ ID NO: 171, the VL CDR2 comprises the sequence shown in SEQ ID NO: 172 and the VL CDR3 comprises the sequence shown in SEQ ID NO: 173.

4. The isolated antibody of claim 1 , wherein (a) the VH CDR1 comprises the sequence shown in SEQ ID NO: 91, the VH CDR2 comprises the sequence shown in SEQ ID NO: 94 and the VH CDR3 comprises the sequence shown in SEQ ID NO: 95; and

(b) the VL CDR1 comprises the sequence shown in SEQ ID NO: 171, the VL CDR2 comprises the sequence shown in SEQ ID NO: 172 and the VL CDR3 comprises the sequence shown in SEQ ID NO: 173.

5. The isolated antibody of claim 1 , wherein (a) the VH CDR1 comprises the sequence shown in SEQ ID NO: 92, the VH CDR2 comprises the sequence shown in SEQ ID NO: 93 and the VH CDR3 comprises the sequence shown in SEQ ID NO: 95; and

(b) the VL CDR1 comprises the sequence shown in SEQ ID NO: 171, the VL CDR2 comprises the sequence shown in SEQ ID NO: 172 and the VL CDR3 comprises the sequence shown in SEQ ID NO: 173.

6. The isolated antibody of claim 1 , wherein the VH CDR1 comprises the sequence shown in SEQ ID NO: 92, the VH CDR2 comprises the sequence shown in SEQ ID NO: 94 and the VH CDR3 comprises the sequence shown in SEQ ID NO: 95; and

(b) the VL CDR1 comprises the sequence shown in SEQ ID NO: 171, the VL CDR2 comprises the sequence shown in SEQ ID NO: 172 and the VL CDR3 comprises the sequence shown in SEQ ID NO: 173.

7. The isolated antibody of claim 2 , wherein the antibody comprises a VH region comprising the sequence shown in SEQ ID NO: 20 and a VL region comprising the sequence shown in SEQ ID NO: 19.

8. A pharmaceutical composition comprising the antibody of claim 1 .

9. A pharmaceutical composition comprising the antibody of claim 2 .

10. A pharmaceutical composition comprising the antibody of claim 3 .

11. A pharmaceutical composition comprising the antibody of claim 4 .

12. A pharmaceutical composition comprising the antibody of claim 5 .

13. A pharmaceutical composition comprising the antibody of claim 6 .

14. A pharmaceutical composition comprising the antibody of claim 7 .

Assignments (4)

CORRECTIVE ASSIGNMENT TO CORRECT THE THE 4TH INVNEORS NAME PREVIOUSLY RECORDED AT REEL: 057808 FRAME: 0779. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Dec 10, 2021

From: DETTLING, DANIELLE ELIZABETH; YEUNG, YIK ANDY; POULSEN, KRISTIAN TODD; KRISHNAMOORTHY, VEENA; SOMMER, CESAR ADOLFO

To: PFIZER INC.

Reel/Frame 058478/0895 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2021

From: DETTLING, DANIELLE ELIZABETH; YEUNG, YIK ANDY; POULSEN, KRISTIAN TODD

To: RINAT NEUROSCIENCE CORP.

Reel/Frame 057808/0632 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2021

From: RINAT NEUROSCIENCE CORP.

To: PFIZER INC.

Reel/Frame 057808/0733 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 15, 2021