IP Library › Granted Patent US 12,617,870
Granted Patent B2
US 12,617,870 · App. 17/278,075 · Granted May 5, 2026

Methods of reversing ticagrelor activity

Inventors: John Lee (Malvern, PA); David James Ballance (Malvern, PA)
Assignee: SFJ Pharmaceutical X, LTD.
C07K16/44A61P7/04A61P39/02A61K2039/505A61K2039/54A61K2039/545C07K2317/55C07K2317/76
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Quick Facts
Patent No.
US 12,617,870
App. No.
17/278,075
Granted
May 5, 2026
Kind
B2
Abstract

The present disclosure provides a method of reversing ticagrelor-associated bleeding in a patient by administering an antibody or fragment thereof that binds to ticagrelor.

Claims (46)

1 . A method of reversing ticagrelor-associated bleeding, or reducing the risk of said bleeding, in a patient who had previously been administered ticagrelor, comprising administering to the patient a pharmaceutical composition comprising a dose of between about 18 g and about 48 g of an antibody or fragment thereof that binds to ticagrelor ((1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol) or a metabolite or derivative thereof,

wherein the antibody or fragment thereof comprises complementarity-determining region (CDR) combinations selected from the group consisting of:

a) SEQ ID NO:53 (VH CDR1), SEQ ID NO:54 (VH CDR2), SEQ ID NO:55 (VH CDR3), SEQ ID NO:58 (VL CDR1), SEQ ID NO:59 (VL CDR2), and SEQ ID NO:60 (VL CDR3);

b) SEQ ID NO:63 (VH CDR1), SEQ ID NO:64 (VH CDR2), SEQ ID NO:65 (VH CDR3), SEQ ID NO:68 (VL CDR1), SEQ ID NO:69 (VL CDR2), and SEQ ID NO:70 (VL CDR3); and

c) SEQ ID NO:73 (VH CDR1), SEQ ID NO:74 (VH CDR2), SEQ ID NO:75 (VH CDR3), SEQ ID NO:78 (VL CDR1), SEQ ID NO:79 (VL CDR2), and SEQ ID NO:80 (VL CDR3).

2 . The method of claim 1 , wherein the antibody or fragment thereof comprises a combination of heavy chain variable region (VH) and light chain variable region (VL) sequences selected from the group consisting of SEQ ID NO:52 and SEQ ID NO:57; SEQ ID NO: 62 and SEQ ID NO:67; and SEQ ID NO:72 and SEQ ID NO:77.

3 . The method of claim 1 , wherein the pharmaceutical composition is administered to the patient intravenously.

4 . The method of claim 3 , wherein the pharmaceutical composition is administered intravenously over about 15 minutes to about 36 hours.

5 . The method of claim 1 , wherein the pharmaceutical composition is administered in the following schedule: 12 g of the antibody or fragment thereof infused over 10 minutes, followed by 12 g of the antibody or fragment thereof over 6 hours, followed by 12 g of the antibody or fragment thereof over 18 hours.

6 . The method of claim 1 , wherein the pharmaceutical composition comprises about 50 mg/mL to about 200 mg/mL of the antibody or fragment thereof, about 5 mM to about 50 mM histidine/histidine hydrochloride buffer, about 100 mM to about 300 mM sucrose, and about 0.01% (w/v) to about 1.0% (w/v) polysorbate 80, at about pH 5.5 to about 6.5.

7 . The method of claim 6 , wherein the pharmaceutical formulation comprises 100 mg/mL of the antibody or fragment thereof, 25 mM histidine/histidine hydrochloride buffer, 290 mM sucrose, and 0.05% (w/v) polysorbate 80, at about pH 6.0.

8 . The method of claim 1 , wherein the ticagrelor-associated bleeding is major bleeding.

9 . The method of claim 1 , wherein the patient requires urgent surgery or intervention.

10 . The method of claim 1 , wherein the patient is at risk of developing, or has been diagnosed with, a disease selected from the group consisting of Acute Coronary Syndrome (ACS), myocardial infarction (MI), unstable angina, stable ischemic heart disease, sickle cell disease, atrial fibrillation, coronary arterial disease, peripheral arterial disease, ischemic stroke requiring one or more coronary stents, carotid artery stents requiring stents following an intracranial aneurysm, and arterio-venous fistulae created for hemodialysis.

11 . The method of claim 1 , wherein administration of the antibody or fragment thereof restores platelet aggregation to at least 80% of baseline within 1 minute to 60 minutes of starting administration.

12 . The method of claim 11 , wherein administration of the antibody or fragment thereof restores platelet aggregation within 5 minutes of starting administration.

13 . The method of claim 11 , wherein the restoration of platelet aggregation is sustained for at least 12 hours after starting administration.

14 . The method of claim 1 , wherein the antibody or a fragment thereof comprises a CDR combination comprising: SEQ ID NO:73 (VH CDR1), SEQ ID NO:74 (VH CDR2), SEQ ID NO:75 (VH CDR3), SEQ ID NO:78 (VL CDR1), SEQ ID NO:79 (VL CDR2), and SEQ ID NO:80 (VL CDR3).

15 . The method of claim 1 , wherein the antibody or fragment thereof comprises a combination of heavy chain variable region (VH) and light chain variable region (VL) sequences comprising SEQ ID NO:72 and SEQ ID NO:77.

16 . The method of claim 1 , wherein the patient has been administered ticagrelor before administration of the anti-ticagrelor antibody or fragment thereof.

17 . The method of claim 1 , wherein the antibody or fragment thereof is an antibody fragment.

18 . The method of claim 17 , wherein the antibody fragment is a Fab.

19 . The method of claim 1 , wherein the pharmaceutical composition is administered in three or more segments, and wherein the first segment is a bolus.

20 . The method of claim 1 , wherein the patient is at risk of developing, or has been diagnosed with Acute Coronary Syndrome (ACS).

21 . The method of claim 1 , wherein the patient is at risk of developing, or has been diagnosed with myocardial infarction (MI).

22 . The method of claim 1 , wherein the patient is at risk of developing, or has been diagnosed with ischemic stroke.

23 . The method of claim 1 , wherein the patient has been administered aspirin (acetylsalicylic acid).

24 . The method of claim 1 , wherein the method reverses ticagrelor-associated bleeding in the patient.

25 . The method of claim 1 , wherein the method reduces the risk of ticagrelor-associated bleeding in the patient.

26 . The method of claim 1 , wherein the dose is 18 g.

27 . The method of claim 1 , wherein the dose is 24 g.

28 . The method of claim 1 , wherein the dose is 36 g.

29 . The method of claim 1 , wherein the antibody or fragment thereof binds to ticagrelor active metabolite (TAM).

30 . The method of claim 1 , wherein the patient has been administered ticagrelor and one or more additional drugs that inhibit the activity of cytochrome P450 isoform 3A (CYP3A).

31 . The method of claim 1 , wherein the patient is receiving concomitant oral or intravenous therapy with a strong CYP3A inhibitor.

32 . The method of claim 18 , wherein the Fab is a human IgG1 monoclonal Fab.

33 . The method of claim 1 , wherein the pharmaceutical composition comprises about 100 mg/mL of the antibody or fragment thereof.

34 . A method of reversing ticagrelor-associated bleeding, or reducing the risk of said bleeding, in a patient who had previously been administered ticagrelor, comprising administering to the patient a pharmaceutical composition comprising a dose of about 36 g of an antibody Fab fragment that binds to ticagrelor ((1S,2S,3R,5S)-3-[7-{[(1R,2S)-2-(3,4-difluorophenyl)cyclopropyl]amino}-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-5-(2-hydroxyethoxy)cyclopentane-1,2-diol) or ticagrelor active metabolite (TAM),

wherein the Fab thereof comprises complementarity-determining region (CDR) combination: SEQ ID NO:73 (VH CDR1), SEQ ID NO:74 (VH CDR2), SEQ ID NO:75 (VH CDR3), SEQ ID NO:78 (VL CDR1), SEQ ID NO:79 (VL CDR2), and SEQ ID NO:80 (VL CDR3);

wherein the pharmaceutical composition is administered in the following schedule: 12 g of the antibody or fragment thereof infused over 10 minutes, followed by 12 g of the antibody or fragment thereof over 6 hours, followed by 12 g of the antibody or fragment thereof over 18 hours.

35 . The method of claim 34 , wherein the Fab comprises a combination of heavy chain variable region (VH) and light chain variable region (VL) sequences comprising SEQ ID NO:72 and SEQ ID NO:77.

36 . The method of claim 35 , wherein the patient requires urgent surgery or intervention.

37 . The method of claim 35 , wherein the patient is at risk of developing, or has been diagnosed with, a disease selected from the group consisting of Acute Coronary Syndrome (ACS), myocardial infarction (MI), unstable angina, stable ischemic heart disease, sickle cell disease, atrial fibrillation, coronary arterial disease, peripheral arterial disease, ischemic stroke requiring one or more coronary stents, carotid artery stents requiring stents following an intracranial aneurysm, and arterio-venous fistulae created for hemodialysis.

38 . The method of claim 35 , wherein the patient is receiving concomitant oral or intravenous therapy with a strong CYP3A inhibitor.

39 . The method of claim 35 , wherein the Fab is a human IgG1 monoclonal Fab.

40 . The method of claim 35 , wherein the pharmaceutical composition comprises about 100 mg/mL of the antibody or fragment thereof.

Assignments (5)
RELEASE OF SECURITY INTEREST Recorded Jan 13, 2023
From: JMB CAPITAL PARTNERS LENDING, LLC
To: PHASEBIO PHARMACEUTICALS, INC.
Reel/Frame 062376/0850 →
SECURITY INTEREST Recorded Oct 31, 2022
From: PHASEBIO PHARMACEUTICALS, INC.
To: JMB CAPITAL PARTNERS LENDING, LLC
Reel/Frame 061601/0001 →
ASSIGNMENT OF INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Oct 4, 2022
From: SILICON VALLEY BANK
To: JMB CAPITAL PARTNERS LENDING, LLC
Reel/Frame 061606/0035 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 10, 2021
From: LEE, JOHN; BALLANCE, DAVID JAMES
To: PHASEBIO PHARMACEUTICALS, INC.
Reel/Frame 057130/0283 →
SECURITY INTEREST Recorded Jun 1, 2021
From: PHASEBIO PHARMACEUTICALS, INC.
To: SILICON VALLEY BANK
Reel/Frame 056405/0575 →
Continuity (4)
Provisional Application 62836373 · Apr 19, 2019
Provisional Application 62806225 · Feb 15, 2019
Provisional Application 62733892 · Sep 20, 2018
Related Publication 20210347915A1 · Nov 11, 2021
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