# US 10,765,726 B2 · Unit dose formulation of antidotes for factor Xa inhibitors and methods of using the same > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,765,726 B2 - Document ID: US10765726B2 - Status: Granted - Kind: B2 - Application number: 15/833,520 - Filed: 2017-12-06 - Published: 2018-08-23 - Granted: 2020-09-08 - Earliest claimed: 2009-07-15 - Assignees: Portola Pharmaceuticals, Inc. - Applicants: Portola Pharmaceuticals, Inc. - Inventors: Uma Sinha; Genmin Lu; Athiwat Hutchaleelaha; Stanley J. Hollenbach - Web page: https://patentgrep.com/patent/US10765726B2 ## CPC - A61K 38/4846: {Factor VII (3.4.21.21); Factor IX (3.4.21.22); Factor Xa (3.4.21.6); Factor XI (3.4.21.27); Factor XII (3.4.21.38)} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61P 7/00: Drugs for disorders of the blood or the extracellular fluid - A61P 7/04: Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents - A61P 39/00: General protective or antinoxious agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - C12N 9/6432: {Coagulation factor Xa (3.4.21.6)} - C12Y 304/21006: Coagulation factor Xa (3.4.21.6) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) - C12Y: ENZYMES ## Abstract The present invention relates unit dose formulations of antidotes to anticoagulants targeting factor Xa. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor. ## Claims ### Claim 1 A method for reversing anticoagulation in a subject undergoing an anticoagulant therapy with a factor Xa inhibitor, comprising administering to the subject from about 10 mg to about 2 grams of a two-chain polypeptide comprising a first chain comprising the amino acid sequence of SEQ ID NO:14 or a first polypeptide having at least 90% sequence identity to SEQ ID NO:14, and a second chain comprising the amino acid sequence of SEQ ID NO:15 or a second polypeptide having at least 95% sequence identity to SEQ ID NO:15, wherein the two-chain polypeptide has reduced catalytic activity as compared to the wild-type factor Xa protein, and is capable to bind to the factor Xa inhibitor. ### Claim 2 (depends on 1) The method of claim 1, wherein about 100 mg to about 900 mg of the two-chain polypeptide is administered intravenously by bolus. ### Claim 3 (depends on 1) The method of claim 1, wherein the two-chain polypeptide is administered as a combination of bolus plus infusion. ### Claim 4 (depends on 3) The method of claim 3, wherein about 100 mg to about 900 mg of the two-chain polypeptide is administered as a bolus and the remaining is infused over a period until bleeding has substantially ceased. ### Claim 5 (depends on 3) The method of claim 3, wherein the administration lasts up to about 6 hours. ### Claim 6 (depends on 1) The method of claim 1, which comprises administering to the subject from about 100 mg to about 1.5 grams of the two-chain polypeptide. ### Claim 7 (depends on 1) The method of claim 1, which comprises administering to the subject from about 200 mg to about 1 gram of the two-chain polypeptide. ### Claim 8 (depends on 1) The method of claim 1, which comprises administering to the subject from about 400 mg to about 900 mg of the two-chain polypeptide. ### Claim 9 (depends on 1) The method of claim 1, wherein the first chain comprises the amino acid sequence of SEQ ID NO:14 or a first polypeptide having at least 95% sequence identity to SEQ ID NO:14, and the second chain comprises the amino acid sequence of SEQ ID NO:15 or a second polypeptide having at least 95% sequence identity to SEQ ID NO:15. ### Claim 10 (depends on 9) The method of claim 9, which comprises administering to the subject from about 100 mg to about 1.5 grams of the two-chain polypeptide. ### Claim 11 (depends on 9) The method of claim 9, which comprises administering to the subject from about 200 mg to about 1 gram of the two-chain polypeptide. ### Claim 12 (depends on 9) The method of claim 9, which comprises a bolus administration of about 200 mg to about 1 gram of the two-chain polypeptide. ### Claim 13 (depends on 1) The method of claim 1, wherein the first chain comprises the amino acid sequence of SEQ ID NO:14, and the second chain comprises the amino acid sequence of SEQ ID NO:15. ### Claim 14 (depends on 13) The method of claim 13, which comprises administering to the subject from about 100 mg to about 1.5 grams of the two-chain polypeptide. ### Claim 15 (depends on 13) The method of claim 13, which comprises administering to the subject from about 200 mg to about 1 gram of the two-chain polypeptide. ### Claim 16 (depends on 1) The method of claim 1, wherein the factor Xa inhibitor is selected from the group consisting of fondaparinux, idraparinux, biotinylated idraparinux, enoxaparin, fragmin, NAP-5, rNAPc2, tissue factor pathway inhibitor, DX-9065a, YM-60828, YM-150, apixaban, rivaroxaban, TAK-442, PD-348292, otamixaban, edoxaban, LY517717, GSK913893, razaxaban, low molecular weight heparin, betrixaban or a pharmaceutically acceptable salt thereof, and combinations thereof. ### Claim 17 (depends on 1) The method of claim 1, wherein the factor Xa inhibitor is apixaban. ### Claim 18 (depends on 1) The method of claim 1, wherein the factor Xa inhibitor is rivaroxaban. ### Claim 19 (depends on 1) The method of claim 1, wherein the factor Xa inhibitor is edoxaban. ### Claim 20 (depends on 1) The method of claim 1, wherein the factor Xa inhibitor is betrixaban.