公开(公告)号：US20180244799A1

公开(公告)日：2018-08-30

申请号：US15908705

申请日：2018-02-28

Applicant: BAYER HEALTHCARE LLC

Inventor： Ye JIN ,  John E. MURPHY ,  Terry HERMISTON ,  Timothy MYLES ,  Frank DITTMER ,  Michael STRERATH ,  Uwe GRITZAN

IPC: C07K16/36 ,  A61K38/48 ,  A61K45/06 ,  C07K16/18 ,  C07K16/38

CPC classification number: C07K16/36 ,  A61K38/4846 ,  A61K45/06 ,  C07K16/18 ,  C07K16/38 ,  C07K2317/21 ,  C07K2317/32 ,  C07K2317/33 ,  C07K2317/55 ,  C07K2317/565

Abstract: This patent document relates to antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human antithrombin β complexed with heparin and/or heparin-like structure (ATβH). These ATβH binding proteins can block the anti-coagulant activity of ATβ to induce coagulation. Therapeutic uses of these antibodies and binders are described herein as are methods of panning and screening specific antibodies.

公开(公告)号：US20170107298A1

公开(公告)日：2017-04-20

申请号：US15221104

申请日：2016-07-27

Applicant: Bayer HealthCare LLC

Inventor： Zhuozhi WANG ,  John E. MURPHY ,  Tobias MARQUARDT ,  Dieter MOOSMAYER

IPC: C07K16/38

Abstract: Isolated monoclonal antibodies that bind to specific epitopes of human tissue factor pathway inhibitor (TFPI) and the isolated nucleic acid molecules encoding them are provided. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided.

公开(公告)号：US20160051633A1

公开(公告)日：2016-02-25

申请号：US14803677

申请日：2015-07-20

Applicant: BAYER HEALTHCARE LLC

Inventor： Clark Q. PAN ,  John E. MURPHY ,  Baisong MEI ,  Jonathan S. STRAUSS ,  Hendri TJANDRA ,  Jianmin CHEN ,  Thomas BARNETT ,  Liang TANG ,  Deqian WANG

IPC: A61K38/37 ,  A61K47/48

Abstract: This invention relates to Factor VIII muteins that are covalently bound, at a predefined site that is not an N-terminal amine, to one or more biocompatible polymers such as polyethylene glycol. The mutein conjugates retain FVIII procoagulant activity and have improved pharmacokinetic properties.

Abstract translation: 本发明涉及在一个或多个生物相容性聚合物例如聚乙二醇上共价结合在不是N-末端胺的预定位点上的因子VIII突变蛋白。 突变蛋白偶联物保留FVIII促凝血活性并具有改善的药代动力学性质。

公开(公告)号：US20160009818A1

公开(公告)日：2016-01-14

申请号：US14772336

申请日：2014-03-14

Applicant: BAYER HEALTHCARE LLC

Inventor： John E. MURPHY ,  George WANG ,  Ruth WINTER

IPC: C07K16/38

CPC classification number: C07K16/38 ,  C07K2317/14 ,  C07K2317/30 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/77 ,  C07K2317/92 ,  C07K2317/94

Abstract: Antibodies are disclosed that bind to and inhibit the anti-coagulant function of TFPI and have a lower affinity for TFPI at pH 6.0 than at pH 7.4. The lower affinity at pH 6 improves circulating half-life (T½) due to reduced target mediated clearance, a process by which an antibody/antigen complex is endocytosed and trafficked to the lysosome where both components are degraded. The lower affinity at pH 6.0 results in disruption of the complex prior to lysosome targeting and allows for re-circulation of the antibody. Specific modifications to antibody binding by histidine residue substitution are disclosed along with methods of use.

Abstract translation: 公开了结合并抑制TFPI的抗凝血功能的抗体，并且在PH6.0下对TFPI的亲和力低于在pH7.4。 由于靶介导的清除率降低，pH6下的较低亲和力改善了循环半衰期（T 1/2），这是抗体/抗原复合物被内吞并被运送到两个成分都被降解的溶酶体的过程。 在pH6.0下的较低亲和力导致在溶酶体靶向之前复合物的破坏并允许抗体的再循环。 公开了通过组氨酸残基取代对抗体结合的具体修饰以及使用方法。

公开(公告)号：US20180334509A1

公开(公告)日：2018-11-22

申请号：US15997481

申请日：2018-06-04

Applicant: Bayer HealthCare LLC

Inventor： Zhuozhi WANG ,  John E. MURPHY ,  Junliang PAN ,  Haiyan Jiang ,  Bing LIU

IPC: C07K16/38 ,  A61K39/395 ,  A61K39/00

CPC classification number: C07K16/38 ,  A61K39/3955 ,  A61K2039/505 ,  C07K2317/21 ,  C07K2317/33 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00 ,  A61K2300/00

Abstract: Isolated monoclonal antibodies that bind human tissue factor pathway inhibitor (TFPI) and the isolated nucleic acid molecules encoding them are provided. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided. Methods of producing the antibodies are also provided.

公开(公告)号：US20170342162A1

公开(公告)日：2017-11-30

申请号：US15644530

申请日：2017-07-07

Applicant: Bayer HealthCare LLC

Inventor： Zhuozhi WANG ,  John E. MURPHY ,  Junliang PAN ,  Haiyan Jiang ,  Bing LIU

IPC: C07K16/38 ,  A61K39/395 ,  A61K39/00

Abstract: Isolated monoclonal antibodies that bind human tissue factor pathway inhibitor (TFPI) and the isolated nucleic acid molecules encoding them are provided. Pharmaceutical compositions comprising the anti-TFPI monoclonal antibodies and methods of treating deficiencies or defects in coagulation by administration of the antibodies are also provided. Methods of producing the antibodies are also provided.

公开(公告)号：US20150307625A1

公开(公告)日：2015-10-29

申请号：US14443710

申请日：2013-11-27

Applicant: BAYER HEALTHCARE LLC

Inventor： Xiao-Yan ZHAO ,  Zhuozhi WANG ,  Jian-Ming GU ,  Ji-Yun KIM ,  Maxine BAUZON ,  John E. MURPHY ,  Kirk MCLEAN ,  Fang JIN ,  Tobias MARQUARDT ,  Xinquan WANG ,  Andreas WILMEN

IPC: C07K16/40 ,  A61K45/06 ,  A61K39/395

CPC classification number: C07K16/40 ,  A61K39/3955 ,  A61K45/06 ,  A61K2039/505 ,  C07K2299/00 ,  C07K2317/21 ,  C07K2317/30 ,  C07K2317/33 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/00

Abstract: Provided herein are antibodies, antigen-binding antibody fragments (Fabs), and other protein scaffolds, directed against human activated Protein C (aPC) with minimal binding to its zymogen Protein C (PC). Moreover, these aPC binding proteins could potentially block the anti-coagulant activity of aPC to induce coagulation. Therapeutic uses of these binders are described herein as are methods of panning and screening specific antibodies.

Abstract translation: 本文提供抗体，抗原结合抗体片段（Fabs）和其他蛋白质支架，其针对人活化蛋白C（aPC），其结合到其酶原蛋白C（PC）。 此外，这些aPC结合蛋白可能潜在地阻断aPC的抗凝血活性以诱导凝血。 这些粘合剂的治疗用途在本文中描述为淘选和筛选特异性抗体的方法。