公开(公告)号：US09850242B2

公开(公告)日：2017-12-26

申请号：US15233520

申请日：2016-08-10

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Roch Boivin ,  Eric Carlson ,  Atsushi Endo ,  Hans Hansen ,  Lynn D. Hawkins ,  Sally Ishizaka ,  Matthew Mackey ,  Sridhar Narayan ,  Takashi Satoh ,  Shawn Schiller

IPC: A01N43/90 ,  A61K31/519 ,  C07D471/04 ,  C07D487/04 ,  A61K31/55

CPC classification number: C07D471/04 ,  A61K31/519 ,  A61K31/55 ,  C07D487/04 ,  Y02P20/582

Abstract: Embodiments of the disclosure relate to tetrahydropyrazolopyrimidine compounds that act as antagonists or inhibitors for Toll-like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

公开(公告)号：US20170189487A1

公开(公告)日：2017-07-06

申请号：US15305049

申请日：2015-04-24

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Ryo Ohori ,  Kanta Horie

IPC: A61K38/18 ,  A61K47/02 ,  A61K47/18 ,  A61K9/19 ,  A61K47/26

Abstract: An object of the present invention is to provide a lyophilized formulation having improved storage stability of hepatic growth factor compared to conventional lyophilized formulations.The present invention provides a lyophilized formulation comprising (1) a hepatic growth factor, (2) trehalose and (3) one or more compounds selected from the group consisting of arginine, histidine, lysine, meglumine, glutamic acid, aspartic acid, proline, creatine, creatinine, tris(hydroxymethyl)aminomethane, and pharmaceutically acceptable salts thereof.

公开(公告)号：US20170137436A1

公开(公告)日：2017-05-18

申请号：US15346912

申请日：2016-11-09

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Toshiki Kurokawa ,  Yu Yoshida ,  Kogyoku Shin ,  Yoshihisa Kobayashi ,  Hironori Fukumoto ,  Kunitoshi Takeda ,  Yoshiaki Ohashi ,  Makoto Kotake ,  Tomoyuki Shibuguchi ,  Toru Watanabe ,  Yoichi Kita ,  Shinsuke Hirota ,  Takashi Fukuyama ,  Yasuaki Kamada

IPC: C07D491/147 ,  C07D491/052

CPC classification number: C07D491/147 ,  C07D491/052

Abstract: Compounds represented by formulae (I) to (XXII) or pharmaceutically acceptable salts thereof:

公开(公告)号：US20170100368A1

公开(公告)日：2017-04-13

申请号：US15314200

申请日：2015-05-28

Applicant: David COX ,  Alton KRAMER ,  Sharon MCGONIGLE ,  Jiayi WU ,  Eisai R&D Management Co., Ltd.

Inventor： David COX ,  Alton KREMER ,  Sharon MCGONIGLE ,  Jiayi WU

IPC: A61K31/357 ,  A61K31/555 ,  A61K31/519

CPC classification number: A61K31/357 ,  A61K31/519 ,  A61K31/555 ,  A61K45/06 ,  A61K2300/00

Abstract: The invention features methods for treating cancer in a patient in need thereof by administering eribulin, in combination with one or more PARP inhibitors, and, optionally, a platinum-based antineoplastic drug, and kits therefor. The invention is based in part on the observation that combinations of eribulin mesylate, a PARP inhibitor (e.g., E7449), and, optionally, a platinum-based antineo-plastic drug (e.g., carboplatin), show improved (e.g., synergistic) antitumor effects. Therefore, the present invention features methods of preventing and treating cancer (e.g., homologous recombination (HR)-deficient cancer by the use of combinations of eribulin (e.g., eribulin mesylate) and one or more PARP inhibitors (e.g., E7449 or a pharmaceutically acceptable salt thereof (e.g., the tartrate salt), optionally in combination with a platinum-based antineoplastic drug (e.g., carboplatin).

公开(公告)号：US09527921B2

公开(公告)日：2016-12-27

申请号：US15098869

申请日：2016-04-14

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Yoshimasa Sakamoto ,  Yusuke Adachi ,  Junji Matsui ,  Yu Kato ,  Yoichi Ozawa ,  Takanori Abe ,  Ken Ito ,  Yuya Nakazawa ,  Sho Tachino ,  Katsuhisa Suzuki ,  Kishan Agarwala ,  Kana Hoshino ,  Masahiko Katayama

IPC: A61K39/395 ,  C07K16/32 ,  A61K33/24 ,  A61K31/47 ,  A61K31/337 ,  C07K16/28 ,  C07K16/30 ,  C07K14/705 ,  C07K14/71 ,  A61K39/00

CPC classification number: C07K16/32 ,  A61K31/337 ,  A61K31/47 ,  A61K33/24 ,  A61K39/395 ,  A61K39/3955 ,  A61K39/39558 ,  A61K2039/505 ,  C07K14/705 ,  C07K14/71 ,  C07K16/28 ,  C07K16/2863 ,  C07K16/3023 ,  C07K16/303 ,  C07K2317/20 ,  C07K2317/24 ,  C07K2317/34 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/76 ,  C07K2317/92 ,  C07K2319/21 ,  C07K2319/42 ,  C12N9/14 ,  C12Y301/03001 ,  A61K2300/00

Abstract: The present invention provides an anti-human Notch4 antibody or a Notch4 binding fragment thereof that may have neutralizing activity against human Notch4, as well as a pharmaceutical composition comprising the same as the active ingredient. The present inventors obtained a mouse anti-human Notch4 antibody that has high neutralizing activity and binding affinity towards human Notch4 and determined the complementarity determining region (CDR) sequence of the mouse anti-human Notch4 antibody. This enabled the production of a humanized antibody comprising the variable region of heavy and light chains as well as the CDR sequence of the mouse anti-human Notch4 antibody.

Abstract translation: 本发明提供了可能对人Notch4具有中和活性的抗人Notch4抗体或Notch4结合片段，以及包含与活性成分相同的药物组合物。 本发明人获得了对人Notch4具有高中和活性和结合亲和力的小鼠抗人Notch4抗体，并确定了小鼠抗人Notch4抗体的互补决定区（CDR）序列。 这使得能够生产包含重链和轻链的可变区以及小鼠抗人Notch4抗体的CDR序列的人源化抗体。

公开(公告)号：US20160339032A1

公开(公告)日：2016-11-24

申请号：US15233520

申请日：2016-08-10

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Roch Boivin ,  Eric Carlson ,  Atsushi Endo ,  Hans Hansen ,  Lynn D. Hawkins ,  Sally Ishizaka ,  Matthew Mackey ,  Sridhar Narayan ,  Takashi Satoh ,  Shawn Schiller

IPC: A61K31/519 ,  A61K31/55

CPC classification number: C07D471/04 ,  A61K31/519 ,  A61K31/55 ,  C07D487/04 ,  Y02P20/582

Abstract: Embodiments of the disclosure relate to tetrahydropyrazolopyrimidine compounds that act as antagonists or inhibitors for Toll-like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis

公开(公告)号：US09481669B2

公开(公告)日：2016-11-01

申请号：US14710687

申请日：2015-05-13

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Gregg F. Keaney ,  John Wang ,  Baudouin Gerard ,  Kenzo Arai ,  Xiang Liu ,  Guo Zhu Zheng ,  Kazunobu Kira ,  Parcharee Tivitmahaisoon ,  Sudeep Prajapati ,  Nicholas C. Gearhart ,  Yoshihiko Kotake ,  Satoshi Nagao ,  Regina Mikie Kanada Sonobe ,  Masayuki Miyano ,  Norio Murai ,  Silvia Buonamici ,  Lihua Yu ,  Eunice Sun Park ,  Betty Chan ,  Peter G. Smith ,  Michael P. Thomas ,  Ermira Pazolli ,  Kian Huat Lim

IPC: C07D405/06 ,  C07D405/14 ,  A61K31/496

CPC classification number: C07D405/14 ,  C07D405/06

Abstract: The present invention provides novel pladienolide pyridine compounds, pharmaceutical compositions containing such compounds, and methods for using the compounds as therapeutic agents. These compounds may be useful in the treatment of cancer, particularly cancers in which agents that target the spliceosome and mutations therein are known to be useful.

Abstract translation: 本发明提供新颖的扁桃苷内酰吡啶化合物，含有这些化合物的药物组合物，以及使用该化合物作为治疗剂的方法。 这些化合物可用于治疗癌症，特别是癌症，其中靶向剪接体的试剂和其中的突变已知是有用的。

公开(公告)号：US09458176B2

公开(公告)日：2016-10-04

申请号：US14190356

申请日：2014-02-26

Applicant: Eisai R&D Management Co., Ltd.

Inventor： Mamoru Takaishi ,  Nobuhiro Sato ,  Tomoyuki Shibuguchi ,  Takafumi Motoki ,  Yoshinori Takahashi ,  Takeo Sasaki ,  Alan Braunton

IPC: A61K31/553 ,  C07D498/04

CPC classification number: C07D498/04

Abstract: A compound represented by the following formula (I) or a pharmaceutically acceptable salt thereof works as an mGluR2 antagonist, and is applicable as a therapeutic agent for neurological disorders related to glutamate dysfunction and diseases involving the mGluR2, such as Alzheimer's disease: wherein R is a hydrogen atom, a C1-6 alkyl group or the like, R1 is a C1-6 alkyl group, a C1-6 alkoxy group or the like, R2 is a halogen atom, a C1-6 alkyl group, a C1-6 alkoxy group or the like, R3 is a hydrogen atom, a C1-6 alkyl group or the like, and R4 is a C1-6 alkyl group or the like.

公开(公告)号：US09446046B2

公开(公告)日：2016-09-20

申请号：US14806174

申请日：2015-07-22

Applicant: EISAI R&D MANAGEMENT CO., LTD.

Inventor： Roch Boivin ,  Eric Carlson ,  Atsushi Endo ,  Hans Hansen ,  Lynn D. Hawkins ,  Sally Ishizaka ,  Matthew Mackey ,  Sridhar Narayan ,  Takashi Satoh ,  Shawn Schiller

IPC: A01N43/90 ,  A61K31/519 ,  C07D471/04 ,  C07D487/04

CPC classification number: C07D471/04 ,  A61K31/519 ,  A61K31/55 ,  C07D487/04 ,  Y02P20/582

Abstract: Embodiments of the disclosure relate to tetrahydropyrazolopyrimidine compounds that act as antagonists or inhibitors for Toll-like receptors 7 and/or 8, and their use in pharmaceutical compositions effective for treatment of systemic lupus erythematosus (SLE) and lupus nephritis.

公开(公告)号：US20160264594A1

公开(公告)日：2016-09-15

申请号：US15033970

申请日：2014-11-04

Applicant: Francis G. FANG ,  Eisai R&D Management Co., Ltd.

Inventor： Francis G. FANG ,  Dae-Shik KIM ,  Hyeong-Wook CHOI ,  Charles E. CHASE ,  Jaemoon LEE

IPC: C07D493/22 ,  C07D307/28 ,  C07D493/14 ,  C07F7/18 ,  C07D407/06

CPC classification number: C07D493/22 ,  C07D307/28 ,  C07D407/06 ,  C07D407/14 ,  C07D493/14 ,  C07F7/1804

Abstract: The invention provides methods for the synthesis of eribulin or a pharmaceutically acceptable salt thereof (e.g., eribulin mesylate) through a macrocyclization strategy. The macrocyclization strategy of the present invention involves subjecting a non-macrocyclic intermediate to a carbon-carbon bond-forming reaction (e.g., an olefination reaction (e.g., Homer-Wadsworth-Emmons olefination), Dieckmann reaction, catalytic Ring-Closing Olefin Metathesis, or Nozaki-Hiyama-Kishi reaction) to afford a macrocyclic intermediate. The invention also provides compounds useful as intermediates in the synthesis of eribulin or a pharmaceutically acceptable salt thereof and methods for preparing the same.

Abstract translation: 本发明提供了通过大环化策略合成干燥蛋白或其药学上可接受的盐（例如甲磺酸艾美林）的方法。 本发明的大环化策略涉及使非大环中间体进行碳 - 碳键形成反应（例如，烯化反应（例如，Homer-Wadsworth-Emmons烯化），Dieckmann反应，催化闭环烯烃复分解， 或Nozaki-Hiyama-Kishi反应），得到大环中间体。 本发明还提供了用作合成干扰素或其药学上可接受的盐的中间体的化合物及其制备方法。