Antidotes for factor Xa inhibitors and methods of using the same

Patent metadata

Field	Value
Publication number	US-10675335-B2
Application number	US-201615176461-A
Country	US
Kind code	B2
Filing date	Jun 8, 2016
Priority date	Sep 28, 2007
Publication date	Jun 9, 2020
Grant date	Jun 9, 2020

Abstract

The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

First claim

The invention claimed is:

1. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a polypeptide comprising:
a first chain comprising amino acid residues 95-105 of SEQ ID NO: 14 or a first amino acid sequence having at least 95% sequence identity to amino acid residues 95-105 of SEQ ID NO: 14 and
a second chain comprising SEQ ID NO: 15 or a second amino acid sequence having at least 95% sequence identity to SEQ ID NO: 15,
wherein the polypeptide (a) has reduced catalytic activity as compared to the corresponding wild-type factor Xa protein, (b) is capable of binding to a factor Xa inhibitor and (c) cannot assemble into a prothrombinase complex.

2. The pharmaceutical composition of claim 1 , wherein the polypeptide comprises an amino acid residue that is modified to be different from natural amino acids.

3. The pharmaceutical composition of claim 1 , wherein the first chain comprises the amino acid sequence of SEQ ID NO: 14.

Assignees

• Portola Pharm Inc

Inventors

• Lu Genmin
• Phillips David R
• Andre Patrick
• Sinha Uma

Classifications

• C12N9/6432

  Coagulation factor Xa (3.4.21.6) · CPC title

• C07K14/435

  from animals; from humans · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title

• A61K38/4846 Primary

  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) · CPC title

• C12Y304/21006

  Coagulation factor Xa (3.4.21.6) · CPC title