公开(公告)号：US20240189401A1

公开(公告)日：2024-06-13

申请号：US18352637

申请日：2023-07-14

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Uma Sinha ,  Genmin Lu ,  Athiwat Hutchaleelaha ,  Stanley J. Hollenbach

IPC: A61K38/48 ,  A61K9/00 ,  C12N9/64

CPC classification number: A61K38/4846 ,  A61K9/0019 ,  C12N9/6432 ,  C12Y304/21006

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.

公开(公告)号：US10954503B2

公开(公告)日：2021-03-23

申请号：US16250870

申请日：2019-01-17

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Uma Sinha ,  Genmin Lu ,  Pamela B. Conley

IPC: A61K38/48 ,  C12N9/64 ,  A61K47/60 ,  A61K39/00

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and 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 reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

公开(公告)号：US20220251534A1

公开(公告)日：2022-08-11

申请号：US17629999

申请日：2020-08-05

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Genmin Lu

IPC: C12N9/64

Abstract: The present disclosure relates to protein sequences which can be used to generate factor Xa proteins and derivatives thereof. The protein sequences include a factor Xa light chain portion, a heavy chain catalytic domain portion, and an activation peptide C-terminal to the heavy chain catalytic domain portion. It is discovered that when an activation peptide (AP) is fused to the C-terminal end of the heavy chain of the factor Xa protein or derivative, the resulting protein can be more efficiently expressed, and the attachment of the activation peptide (AP) to the heavy chain does not affect the activity of the protein.

公开(公告)号：US20210340515A1

公开(公告)日：2021-11-04

申请号：US17196197

申请日：2021-03-09

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Uma Sinha ,  Genmin Lu ,  Pamela B. Conley

IPC: C12N9/64 ,  A61K38/48 ,  A61K47/60

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor X and 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 reversing anticoagulation, stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

公开(公告)号：US10954504B2

公开(公告)日：2021-03-23

申请号：US16740001

申请日：2020-01-10

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Mark Karbarz ,  Pamela B. Conley ,  Genmin Lu

IPC: A61K38/36 ,  C12N9/64 ,  C07K1/18 ,  C07K1/20 ,  C07K1/22

Abstract: The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.

公开(公告)号：US20230265483A1

公开(公告)日：2023-08-24

申请号：US18010076

申请日：2021-06-10

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Joel Freeberg ,  Genmin Lu ,  Pamela Conley

IPC: C12Q1/56 ,  G01N33/52 ,  G01N33/86

CPC classification number: C12Q1/56 ,  G01N33/52 ,  G01N33/86

Abstract: The present disclosure relates kits and methods for measuring the potency of an andexanet sample in neutralizing a factor Xa inhibitor and restoring the activity of a wild-type factor Xa.

公开(公告)号：US20220098565A1

公开(公告)日：2022-03-31

申请号：US17387806

申请日：2021-07-28

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Genmin Lu ,  Pamela B. Conley ,  Uma Sinha

IPC: C12N9/64

Abstract: Disclosed are methods and isolated cells useful for the improved production of function fXa derivative protein that acts as a fXa inhibitor antidote. One aspect relates to an isolated cell comprising the r-Antidote polynucleotide and Furin polynucleotide. Another aspect relates to a method for preparing the cleaved two-chain r-Antidote by expressing, in a cell, the pre-processed r-Antidote polypeptide and a Furin polypeptide.

公开(公告)号：US20210379163A1

公开(公告)日：2021-12-09

申请号：US17176939

申请日：2021-02-16

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Genmin Lu ,  Uma Sinha ,  Mark Karbarz ,  Anjali Pandey ,  Pamela B. Conley

IPC: A61K38/37 ,  A61K45/06 ,  A61K47/50 ,  A61K38/48 ,  C12N9/64

Abstract: The present disclosure relates to compositions and methods for the treatment of bleeding disorders, such as hemophilia A, hemophilia B, von Willebrand (vWF) disease, and factor XII deficiency, by reducing the circulating concentration of tissue factor pathway inhibitor (TFPI), with a factor Xa derivative.

公开(公告)号：US20240082367A1

公开(公告)日：2024-03-14

申请号：US18500675

申请日：2023-11-02

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Genmin Lu ,  David R. Phillips ,  Patrick Andre ,  Uma Sinha

IPC: A61K38/48 ,  A61K47/60 ,  C07K14/435 ,  C12N9/64

CPC classification number: A61K38/4846 ,  A61K38/4826 ,  A61K38/4833 ,  A61K38/4853 ,  A61K47/60 ,  C07K14/435 ,  C12N9/6432 ,  C12Y304/21006 ,  A61K39/00

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidoes 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.

公开(公告)号：US20240076642A1

公开(公告)日：2024-03-07

申请号：US18505022

申请日：2023-11-08

Applicant: Alexion Pharmaceuticals, Inc.

Inventor： Mark Karbarz ,  Pamela B. Conley ,  Genmin Lu

IPC: C12N9/64 ,  C07K1/18 ,  C07K1/20 ,  C07K1/22

CPC classification number: C12N9/6432 ,  C07K1/18 ,  C07K1/20 ,  C07K1/22

Abstract: The present disclosure provides methods for manufacturing a fXa derivative protein at large scale leading to high yield of highly pure protein product. The method may include adding a detergent to a sample that contains a polynucleotide construct encoding the protein and purifying the protein through a soybean trypsin inhibitor (STI)-based affinity chromatograph, an ion exchange and mixed mode chromatograph and a hydrophobic interaction.