公开(公告)号：US20200276280A1

公开(公告)日：2020-09-03

申请号：US16869117

申请日：2020-05-07

Applicant: Portola Pharmaceuticals, Inc.

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

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

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.

公开(公告)号：US20190127720A1

公开(公告)日：2019-05-02

申请号：US16127864

申请日：2018-09-11

Applicant: Portola Pharmaceuticals, Inc.

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

IPC: C12N9/64 ,  C12N9/50

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：US10190111B2

公开(公告)日：2019-01-29

申请号：US15435086

申请日：2017-02-16

Applicant: Portola Pharmaceuticals, Inc.

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

IPC: C07K14/745 ,  C12N9/64 ,  A61K38/48 ,  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：US09587233B2

公开(公告)日：2017-03-07

申请号：US14790305

申请日：2015-07-02

Applicant: PORTOLA PHARMACEUTICALS, INC.

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

IPC: C07K14/755 ,  C12N9/64 ,  A61K38/48 ,  A61K47/48 ,  C07K14/745 ,  A61K39/00

CPC classification number: C12N9/6432 ,  A61K38/482 ,  A61K38/4826 ,  A61K38/4833 ,  A61K38/4846 ,  A61K38/4853 ,  A61K39/00 ,  A61K47/60 ,  C12Y304/21006

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.

Abstract translation: 本发明涉及靶向因子Xa的抗凝剂的解毒剂。 解毒剂是与因子Xa抑制剂结合的因子X和因子Xa蛋白衍生物，从而基本上中和它们，但不组装到凝血酶原酶复合物中。 本文所述的衍生物缺乏或具有降低的内在凝结剂活性。 本文公开的是使用因子Xa抑制剂正在进行抗凝治疗的患者中的抗凝，停止或预防出血的方法。

公开(公告)号：US20150352194A1

公开(公告)日：2015-12-10

申请号：US14762098

申请日：2013-03-13

Applicant: PORTOLA PHARMACEUTICALS, INC.

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

IPC: A61K38/48 ,  A61K47/48 ,  A61K45/06

CPC classification number: A61K38/37 ,  A61K38/4846 ,  A61K45/06 ,  A61K47/50 ,  C12N9/6432 ,  C12Y304/21006 ,  A61K2300/00

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.

Abstract translation: 本公开涉及通过降低组织因子途径抑制剂（TFPI）的循环浓度来治疗出血性疾病如血友病A，血友病B，血管性血友病（vWF）疾病和因子XII缺乏症的组合物和方法， 一个因子Xa导数。

公开(公告)号：US20150239929A1

公开(公告)日：2015-08-27

申请号：US14406645

申请日：2013-06-12

Applicant: Portola Pharmaceuticals, Inc.

Inventor： Genmin Lu ,  Uma Sinha

IPC: C07K1/22 ,  C12N9/64

CPC classification number: C07K1/22 ,  C12N9/6424 ,  C12N9/6432

Abstract: Disclosed herein are methods and kits for purifying a serine protease. The methods entail loading the serine protease to a soybean trypsin inhibitor (STI) based affinity chromatograph, and eluting the serine protease with an elution buffer comprising an agent that disrupts interaction between the STI and the serine protease.

Abstract translation: 本文公开了用于纯化丝氨酸蛋白酶的方法和试剂盒。 所述方法需要将丝氨酸蛋白酶加载到基于大豆胰蛋白酶抑制剂（STI）的亲和层析仪中，并用包含破坏STI和丝氨酸蛋白酶之间的相互作用的试剂的洗脱缓冲液洗脱丝氨酸蛋白酶。

公开(公告)号：US09062298B2

公开(公告)日：2015-06-23

申请号：US13889014

申请日：2013-05-07

Applicant: Portola Pharmaceuticals, Inc.

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

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

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

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.

Abstract translation: 本发明涉及靶向因子Xa的抗凝剂的解毒剂。 解毒剂是与因子Xa抑制剂结合的因子Xa蛋白衍生物，从而基本上中和它们，但不组装到凝血酶原酶复合物中。 本文所述的衍生物缺乏或具有降低的内在凝结剂活性。 本文公开了在目前正在进行使用因子Xa抑制剂进行抗凝治疗的患者中停止或预防出血的方法。

公开(公告)号：US09023796B2

公开(公告)日：2015-05-05

申请号：US13889014

申请日：2013-05-07

Applicant: Portola Pharmaceuticals, Inc.

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

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

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.

公开(公告)号：US20130230901A1

公开(公告)日：2013-09-05

申请号：US13766652

申请日：2013-02-13

Applicant: PORTOLA PHARMACEUTICALS, INC.

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

IPC: C12N9/50

CPC classification number: C12N9/6432 ,  C12N9/50 ,  C12N9/6454 ,  C12N2510/02 ,  C12Y304/21006

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：US20210085762A1

公开(公告)日：2021-03-25

申请号：US16943933

申请日：2020-07-30

Applicant: Portola Pharmaceuticals, Inc.

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

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

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.