公开(公告)号：US20180237524A1

公开(公告)日：2018-08-23

申请号：US15553254

申请日：2016-02-22

申请人： Paul REICHERT ,  Winifred W. PROSISE ,  Giovanna SCAPIN ,  Xiaoyu YANG ,  Ramesh KASHI ,  Corey STRICKLAND ,  Merck Sharp & Dohme Corp.

发明人： Paul Reichert ,  Winifred W. Prosise ,  Giovanna Scapin ,  Xiaoyu Yang ,  Ramesh Kashi ,  Corey Strickland

IPC分类号： C07K16/28 ,  C07K16/00

摘要： Crystals of pembrolizumab and structurally similar anti-PD-1 monoclonal antibodies are provided, as well as methods of producing such crystals, and uses of compositions comprising such antibody crystals, e.g. in treatment of cancers. The present invention satisfies these needs and more by providing pembrolizumab crystals and a method producing pembrolizumab crystals. One embodiment of the method of the invention produces crystals suitable for X-ray diffraction, and the inventors herein used such crystals to solve the three-dimensional structure of pembrolizumab to 2.3 A resolution.

公开(公告)号：US11014986B2

公开(公告)日：2021-05-25

申请号：US15553254

申请日：2016-02-22

申请人： Paul Reichert ,  Winifred W. Prosise ,  Giovanna Scapin ,  Xiaoyu Yang ,  Ramesh Kashi ,  Corey Strickland ,  Merck Sharp & Dohme Corp.

发明人： Paul Reichert ,  Winifred W. Prosise ,  Giovanna Scapin ,  Xiaoyu Yang ,  Ramesh Kashi ,  Corey Strickland

IPC分类号： C07K16/28 ,  C07K16/00

摘要： Crystals of pembrolizumab and structurally similar anti-PD-1 monoclonal antibodies are provided, as well as methods of producing such crystals, and uses of compositions comprising such antibody crystals, e.g. in treatment of cancers. The present invention satisfies these needs and more by providing pembrolizumab crystals and a method producing pembrolizumab crystals. One embodiment of the method of the invention produces crystals suitable for X-ray diffraction, and the inventors herein used such crystals to solve the three-dimensional structure of pembrolizumab to 2.3 A resolution.

公开(公告)号：US20220017612A1

公开(公告)日：2022-01-20

申请号：US17465247

申请日：2021-09-02

申请人： Tilos Therapeutics, Inc. ,  Merck Sharp & Dohme Corp.

发明人： Randall Burton ,  Jessie M. English ,  Barbara S. Fox ,  Stavros Kopsiaftis ,  Yacob Gomez Llorente ,  Renee Moore ,  Patricia Rao ,  Giovanna Scapin ,  Kenneth J. Simon ,  Haihong Zhou

IPC分类号： C07K16/18 ,  A61P35/04 ,  A61P35/00 ,  G01N33/574 ,  G01N33/68

摘要： Provided herein are anti-LAP antibodies (e.g., recombinant humanized, chimeric, and human anti-LAP antibodies) or antigen binding fragments thereof which have therapeutically beneficial properties, such as binding specifically to LAP-TGFβ1 on cells but not to LAP-TGFβ1 in extracellular matrix, as well as compositions including the same. Also provided are uses of these antibodies or antigen binding fragments in therapeutic applications, such as in the treatment of cancer, and diagnostic applications.

公开(公告)号：US20140336222A1

公开(公告)日：2014-11-13

申请号：US14339925

申请日：2014-07-24

申请人： Merck Sharp & Dohme Corp.

发明人： Stephane L. Bogen ,  Yao Ma ,  Yaolin Wang ,  Brian Robert Lahue ,  Latha G. Nair ,  Manami Shizuka ,  Matthew E. Voss ,  Margarita Kirova-Snover ,  Weidong Pan ,  Yuan Tian ,  Bheemashankar A. Kulkarni ,  Craig R. Gibeau ,  Yuan Liu ,  Giovanna Scapin ,  Diane Rindgen ,  Ronald J. Doll ,  Timothy J. Guzi ,  Danny J. Hicklin ,  Amin Nomeir ,  Cynthia Seidel-Dugan ,  Gerald W. Shipps, JR. ,  Malcolm MacCoss

IPC分类号： C07D401/14 ,  C07D409/14

CPC分类号： C07D401/14 ,  C07D409/14

摘要： The present invention provides a compound of Formula 1 as described herein or a pharmaceutically acceptable salt, solvate or ester thereof. The compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same.

摘要翻译： 本发明提供本文所述的式1的化合物或其药学上可接受的盐，溶剂合物或酯。 该化合物可用作HDM2蛋白的抑制剂。 还公开了包含上述化合物的药物组合物和使用其治疗癌症的方法。

公开(公告)号：US20090105210A1

公开(公告)日：2009-04-23

申请号：US11793093

申请日：2006-01-18

申请人： Wallace T. Ashton ,  Charles G. Caldwell ,  Hong Dong ,  Ying-Duo Gao ,  Giovanna Scapin ,  Ann E. Weber

发明人： Wallace T. Ashton ,  Charles G. Caldwell ,  Hong Dong ,  Ying-Duo Gao ,  Giovanna Scapin ,  Ann E. Weber

IPC分类号： A61K31/5377 ,  A61K31/519 ,  C07D487/04

CPC分类号： C07D487/04 ,  C07D495/14

摘要： The present invention is directed to novel substituted bicyclic pyrimidines which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂的新型取代的双环嘧啶，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病， 如糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US20240002534A1

公开(公告)日：2024-01-04

申请号：US18253702

申请日：2021-11-22

申请人： Marc Andre BAILLY ,  Kalyan CHAKRAVARTHY ,  Ghassan Najib FAYAD ,  Laurence FAYAT-DILMAN ,  Esther KOFMAN ,  Masahisa HANDA ,  Jennifer E. O'NEIL ,  Rachel L. PALTE ,  Giovanna SCAPIN ,  Shahriar Shane TAREMI ,  MERCK SHARP & DOHME LLC

发明人： Marc Andre Bailly ,  Kalyan Chakravarthy ,  Ghassan Najib Fayad ,  Laurence Fayadat-Dilman ,  Esther Kofman ,  Masahisa Handa ,  Jennifer E. O'Neil ,  Rachel Lynn Palte ,  Giovanna Scapin ,  Shahriar Shane Taremi

IPC分类号： C07K16/40 ,  C07K16/28 ,  C12N15/85

CPC分类号： C07K16/40 ,  C07K16/2818 ,  C07K16/2827 ,  C12N15/85 ,  C12N2800/107

摘要： Arginase 1 binders that inhibit the activity of human Arginase 1 (hArg1) and comprise human antibodies and antigen-binding fragments thereof comprising human VH and VL are described. These Arginase 1 binders present an alternative mechanism for inhibiting hArg1 activity and highlight the ability to utilize binders as probes in the discovery and development of peptide and small molecule inhibitors for enzymes in general.

公开(公告)号：US08859776B2

公开(公告)日：2014-10-14

申请号：US13501685

申请日：2010-10-05

申请人： Stephane L. Bogen ,  Yao Ma ,  Yaolin Wang ,  Brian Robert Lahue ,  Latha G. Nair ,  Manami Shizuka ,  Matthew Ernst Voss ,  Margarita Kirova-Snover ,  Weidong Pan ,  Yuan Tian ,  Bheemashankar A. Kulkarni ,  Craig R. Gibeau ,  Yuan Liu ,  Giovanna Scapin ,  Diane Rindgen ,  Ronald J. Doll ,  Timothy J. Guzi ,  Danny J. Hicklin ,  Amin Nomeir ,  Gerald W. Shipps, Jr. ,  Malcolm MacCoss

发明人： Stephane L. Bogen ,  Yao Ma ,  Yaolin Wang ,  Brian Robert Lahue ,  Latha G. Nair ,  Manami Shizuka ,  Matthew Ernst Voss ,  Margarita Kirova-Snover ,  Weidong Pan ,  Yuan Tian ,  Bheemashankar A. Kulkarni ,  Craig R. Gibeau ,  Yuan Liu ,  Giovanna Scapin ,  Diane Rindgen ,  Ronald J. Doll ,  Timothy J. Guzi ,  Danny J. Hicklin ,  Amin Nomeir ,  Gerald W. Shipps, Jr. ,  Malcolm MacCoss

IPC分类号： C07D401/00 ,  A01N43/40 ,  C07D401/14 ,  C07D409/14

CPC分类号： C07D401/14 ,  C07D409/14

摘要： The present invention provides a compound of Formula 1 as described herein or a pharmaceutically acceptable salt, solvate or ester thereof. The compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same.

摘要翻译： 本发明提供本文所述的式1的化合物或其药学上可接受的盐，溶剂合物或酯。 该化合物可用作HDM2蛋白的抑制剂。 还公开了包含上述化合物的药物组合物和使用其治疗癌症的方法。

公开(公告)号：US20120208844A1

公开(公告)日：2012-08-16

申请号：US13501685

申请日：2010-10-05

申请人： Stephane L. Bogen ,  Yao Ma ,  Yaolin Wang ,  Brian Robert Lahue ,  Latha G. Nair ,  Manami Shizuka ,  Matthew Ernst Voss ,  Margarita Kirova-Snover ,  Weidong Pan ,  Yuan Tian ,  Bheemashankar A. Kulkarni ,  Craig R. Gibeau ,  Yuan Liu ,  Giovanna Scapin ,  Diane Rindgen ,  Ronald J. Doll ,  Timothy J. Guzi ,  Danny J. Hicklin ,  Amin Nomeir ,  Cynthia Seidel-Dugan ,  Gerald W. Shipps, JR. ,  Malcolm MacCoss

发明人： Stephane L. Bogen ,  Yao Ma ,  Yaolin Wang ,  Brian Robert Lahue ,  Latha G. Nair ,  Manami Shizuka ,  Matthew Ernst Voss ,  Margarita Kirova-Snover ,  Weidong Pan ,  Yuan Tian ,  Bheemashankar A. Kulkarni ,  Craig R. Gibeau ,  Yuan Liu ,  Giovanna Scapin ,  Diane Rindgen ,  Ronald J. Doll ,  Timothy J. Guzi ,  Danny J. Hicklin ,  Amin Nomeir ,  Cynthia Seidel-Dugan ,  Gerald W. Shipps, JR. ,  Malcolm MacCoss

IPC分类号： A61K31/4545 ,  A61P35/02 ,  A61P35/00 ,  C07D409/14 ,  C07D401/14

CPC分类号： C07D401/14 ,  C07D409/14

摘要： The present invention provides a compound of Formula (1) as described herein or a pharmaceutically acceptable salt, solvate or ester thereof. The compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions comprising the above compounds and methods of treating cancer using the same.

摘要翻译： 本发明提供本文所述的式（1）化合物或其药学上可接受的盐，溶剂合物或酯。 该化合物可用作HDM2蛋白的抑制剂。 还公开了包含上述化合物的药物组合物和使用其治疗癌症的方法。

公开(公告)号：US07956061B2

公开(公告)日：2011-06-07

申请号：US11793093

申请日：2006-01-18

申请人： Wallace T. Ashton ,  Charles G. Caldwell ,  Hong Dong ,  Ying-Duo Gao ,  Giovanna Scapin ,  Ann E. Weber

发明人： Wallace T. Ashton ,  Charles G. Caldwell ,  Hong Dong ,  Ying-Duo Gao ,  Giovanna Scapin ,  Ann E. Weber

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P3/10

CPC分类号： C07D487/04 ,  C07D495/14

摘要： The present invention is directed to novel substituted bicyclic pyrimidines which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及作为二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂的新型取代的双环嘧啶，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病， 如糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。