IP Library › Granted Patent US 12,275,800
Granted Patent B2
US 12,275,800 · App. 18/302,033 · Granted Apr 15, 2025

Anti-coagulation factor XI antibodies

Inventors: Zhu Chen (Warren, NJ); Kenneth Ellsworth (Cranbury, NJ); James Milligan (Sevierville, TN); Elizabeth Oldham (Santa Clara, CA); Dietmar Seiffert (Lawrence Township, NJ); Bianka Prinz (Lebanon, NH); Vaishnavi Ganti (Foster City, CA); Mohammad Tabrizifard (Moranga, CA)
Assignees: Merck Sharp & Dohme LLC; Adimab, LLC
C07K16/36A61K39/3955A61K2039/505A61K2039/58C07K2317/75C07K2317/76C07K2317/90C07K2317/92
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Quick Facts
Patent No.
US 12,275,800
App. No.
18/302,033
Granted
Apr 15, 2025
Kind
B2
Abstract

Antibodies that bind the apple 3 domain of human coagulation Factor XI and inhibit activation of FXI by coagulation factor XIIa as well as activation of FIX by FXIa are described.

Claims (25)

1. A method for therapeutic or prophylactic treatment of a thromboembolic disorder or disease in a subject comprising:

administering to the subject an effective amount of an antibody or antigen binding fragment comprising:

(i) six complimentary determining regions (CDRs) of an anti-FXI antibody of the αFXI-18611 family,

wherein the six CDRs comprise

(a) CDR1, CDR2, and CDR3 of the heavy chain (HC) having the amino acid sequence shown in SEQ ID NO: 37 or 39; and

(b) CDR1, CDR2, and CDR3 of the light chain (LC) having the amino acid sequence shown in SEQ ID NO: 26.

2. The method of claim 1 , wherein the antibody or antigen binding fragment comprises (a) a heavy chain complementarity determining region (HC-CDR) 1 having the amino acid sequence shown in SEQ ID NO: 1, an HC-CDR 2 having the amino acid sequence shown in SEQ ID NO: 2, and an HC-CDR 3 having the amino acid sequence shown in SEQ ID NO: 4 and (b) a light chain complementarity determining region (LC-CDR) 1 having the amino acid sequence shown in SEQ ID NO: 5, an LC-CDR 2 having the amino acid sequence shown in SEQ ID NO: 6, and an LC-CDR 3 comprises having the amino acid sequence shown in SEQ ID NO: 7.

3. The method of claim 2 , wherein the antibody or antigen binding fragment comprises an HC variable domain having the amino acid sequence shown in SEQ ID NO: 23 or 24 and an LC variable domain having the amino acid sequence shown in SEQ ID NO: 25.

4. The method of claim 1 , wherein the antibody comprises a HC constant domain comprising the amino acid sequence shown in SEQ ID NO:16, 17, 18, or 19.

5. The method of claim 1 , wherein the antibody comprises a LC constant domain comprising the amino acid sequence shown in SEQ ID NO:20.

6. The method of claim 1 , wherein the antibody or antigen binding fragment binds the apple 3 domain of coagulation factor XI (FXI) and inhibits activation of FXI and/or Factor XIa-mediated activation of Factor IX.

7. The method of claim 1 , wherein the antibody comprises:

(a) an HC having a constant domain and a variable domain wherein the variable domain comprises a heavy chain-complementary determining region (HC-CDR) 1 having the amino acid sequence shown in SEQ ID NO: 1, a HC-CDR 2 having the amino acid sequence shown in SEQ ID NO: 2, and a HC-CDR 3 having the amino acid sequence shown in SEQ ID NO: 4; and

(b) an LC having a constant domain and a variable domain wherein the variable domain comprises a light chain-complementary determining region (LC-CDR) 1 having the amino acid sequence shown in SEQ ID NO: 5, a LC-CDR 2 having the amino acid sequence shown in SEQ ID NO: 6, and a LC-CDR 3 having the amino acid sequence shown in SEQ ID NO: 7.

8. The method of claim 7 , wherein the antibody comprises an HC constant domain comprising the amino acid sequence shown in SEQ ID NO: 16, 17, 18, or 19.

9. The method of claim 7 , wherein the antibody comprises an LC constant domain comprising the amino acid sequence shown in SEQ ID NO: 20.

10. The method of claim 1 , wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 37 and a light chain having the amino acid sequence shown in SEQ ID NO: 26.

11. The method of claim 1 , wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 39 and a light chain having the amino acid sequence shown in SEQ ID NO: 26.

12. The method of claim 1 , wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 61 and a light chain having the amino acid sequence shown in SEQ ID NO: 26.

13. The method of claim 1 , wherein the antibody comprises a heavy chain having the amino acid sequence shown in SEQ ID NO: 63 and a light chain having the amino acid sequence shown in SEQ ID NO: 26.

14. The method of claim 1 , wherein the subject has end-stage renal disease (ESRD).

15. The method of claim 1 , wherein the thromboembolic disorder or disease is venous thromboembolism (VTE).

16. The method of claim 1 , wherein the therapeutic or prophylactic treatment of a thromboembolic disorder or disease in a subject is for Stroke Prevention in Atrial Fibrillation (SPAF).

17. The method of claim 1 , wherein the thromboembolic disorder or disease is medical device-related.

18. The method of claim 17 , wherein the medical device is a stent, endovascular stent graft, cardiac or venous catheter, continuous flow ventricular assist device (CF-LVAD), hemodialysis device, cardiopulmonary bypass device, Extracorporeal Membrane Oxygenation (ECMO) device, or ventricular assist device (VAD).

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2023
From: PRINZ, BLANKA
To: ADIMAB, LLC
Reel/Frame 063354/0115 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 18, 2023
From: CHEN, ZHU; ELLSWORTH, KENNETH P.; MILLIGAN, JAMES; OLDHAM, ELIZABETH; SEIFFERT, DIETMAR; GANTI, VAISHNAVI; TABRIZIFARD, MOHAMMAD
To: MERCK SHARP & DOHME CORP.
Reel/Frame 063354/0229 →
MERGER Recorded Apr 18, 2023
From: MERCK SHARP & DOHME CORP.
To: MERCK SHARP & DOHME LLC
Reel/Frame 063354/0322 →
Continuity (4)
Continuation 16864559 · May 1, 2020
Division 15619620 · Jun 12, 2017
Provisional Application 62349888 · Jun 14, 2016
Related Publication 20230287141A1 · Sep 14, 2023
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