公开(公告)号：US10905772B2

公开(公告)日：2021-02-02

申请号：US15872841

申请日：2018-01-16

申请人： AMGEN INC.

发明人： Yuan Cheng ,  Chawita Netirojjanakul ,  Jerry Ryan Holder ,  Bin Wu ,  James R. Falsey ,  Bradley J. Herberich ,  Kelvin Sham ,  Leslie P. Miranda ,  Shu-Chen Lu ,  Murielle M. Veniant-Ellison ,  Shanaka Stanislaus ,  Junming Yie ,  Jing Xu

IPC分类号： A61K47/68 ,  A61K38/26 ,  A61P3/10 ,  C07K16/28 ,  A61K39/395

摘要： Methods of treating metabolic diseases and disorders using a composition comprising an antigen binding protein specific for the GIPR polypeptide conjugated to a GLP-1 receptor agonist are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy. In certain embodiments the composition comprises an antibody or functional fragment thereof comprising a cysteine at one or more conjugation site(s) wherein the GLP-1 receptor agonist is conjugated to the antibody or functional fragment thereof through the side-chain of the cysteine residue.

公开(公告)号：US09777019B2

公开(公告)日：2017-10-03

申请号：US15041835

申请日：2016-02-11

申请人： AMGEN INC.

发明人： Ryan White ,  Yuan Cheng ,  Ana Elena Minatti ,  Bryant Yang ,  Xiao Mei Zheng ,  Patricia Lopez ,  Jason B. Human ,  Oleg Epstein ,  Ted Judd ,  Kelvin Sham ,  Qiufen Xue

IPC分类号： A61K31/537 ,  A61K31/547 ,  C07D498/10 ,  C07D513/10 ,  C07D498/20 ,  C07D513/20

CPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A3, A4, A5, A6, L, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：US09611261B2

公开(公告)日：2017-04-04

申请号：US14932787

申请日：2015-11-04

申请人： AMGEN INC.

发明人： Ana Elena Minatti ,  Jonathan D. Low ,  Jennifer R. Allen ,  Albert Amegadzie ,  James Brown ,  Michael J. Frohn ,  Angel Guzman-Perez ,  Paul E. Harrington ,  Patricia Lopez ,  Vu Van Ma ,  Nobuko Nishimura ,  Wenyuan Qian ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Kelvin Sham ,  Adrian L. Smith ,  Ryan White ,  Qiufen Xue

IPC分类号： C07D471/04 ,  C07D265/12 ,  C07D413/14 ,  C07D413/12 ,  C07D417/14 ,  C07D417/12 ,  C07D413/10 ,  C07D491/048 ,  C07D413/04

CPC分类号： C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

公开(公告)号：US08759532B2

公开(公告)日：2014-06-24

申请号：US13676826

申请日：2012-11-14

申请人： AMGEN Inc.

发明人： Jennifer R. Allen ,  Kaustav Biswas ,  Frank Chavez, Jr. ,  Ning Chen ,  Frenel Fils De Morin ,  James R. Falsey ,  Michael J. Frohn ,  Paul E. Harrington ,  Daniel B. Home ,  Essa Hu Harrington ,  Matthew R. Kaller ,  Roxanne K. Kunz ,  Holger Monenschein ,  Thomas T. Nguyen ,  Alexander J. Pickrell ,  Andreas Reichelt ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Kelvin Sham ,  Guomin Yao

IPC分类号： C07D239/02 ,  A61K31/397

CPC分类号： C07D413/14 ,  C07D401/12 ,  C07D401/14 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00

摘要： Pyridine and pyrimidine compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.

摘要翻译： 吡啶和嘧啶化合物，以及含有它们的组合物，以及制备这些化合物的方法。 本文还提供治疗通过抑制PDE10可治疗的疾病或疾病的方法，例如肥胖症，非胰岛素依赖型糖尿病，精神分裂症，双相情感障碍，强迫症等。

公开(公告)号：US10344060B2

公开(公告)日：2019-07-09

申请号：US14773756

申请日：2014-03-12

申请人： AMGEN INC.

发明人： Justin K. Murray ,  Jerry Ryan Holder ,  Malgorzata Wanska ,  Christopher M. Tegley ,  James R. Falsey ,  Elizabeth M. Doherty ,  Leslie P. Miranda ,  Kaustav Biswas ,  Bin Wu ,  Kelvin Sham ,  Jason C. Long

IPC分类号： C07K14/00 ,  C07K14/435 ,  C07K16/00 ,  C07K19/00 ,  C07K14/46 ,  C07K14/47 ,  A61K38/00 ,  A61K38/16 ,  A61K38/17 ,  A61K47/64 ,  A61K47/68

摘要： Disclosed is a composition of matter comprising an isolated polypeptide, which is a peripherally-restricted NaV1.7 inhibitor. In some disclosed embodiments, the isolated polypeptide is an inhibitor of NaV1.7. Other embodiments are conjugated embodiments of the inventive composition of matter and pharmaceutical compositions containing the inventive composition of matter. Isolated nucleic acids encoding some embodiments of inventive polypeptides and expression vectors, and recombinant host cells containing them are disclosed. A method of treating or preventing pain is also disclosed.

公开(公告)号：US09725469B2

公开(公告)日：2017-08-08

申请号：US14435516

申请日：2013-11-12

申请人： Amgen Inc.

发明人： Ryan White ,  Oleg Epstein ,  Jason B. Human ,  Xiao Mei Zheng ,  Yuan Cheng ,  Kelvin Sham ,  Qingyian Liu ,  Ning Chen

IPC分类号： C07D491/052 ,  C07D513/10 ,  C07D519/00 ,  C07D498/10 ,  C07D498/20 ,  C07D311/80 ,  C07D513/20

CPC分类号： C07D519/00 ,  C07D311/80 ,  C07D491/052 ,  C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, L, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

公开(公告)号：US09296759B2

公开(公告)日：2016-03-29

申请号：US14346252

申请日：2012-09-21

申请人： AMGEN INC.

发明人： Ryan White ,  Yuan Cheng ,  Ana Elena Minatti ,  Bryant Yang ,  Xiao Mei Zheng ,  Patricia Lopez ,  Jason B. Human ,  Oleg Epstein ,  Ted Judd ,  Kelvin Sham ,  Qiufen Xue

IPC分类号： C07D498/20 ,  C07D513/20 ,  A61K31/537 ,  A61K31/547 ,  C07D513/10 ,  C07D498/10

CPC分类号： C07D498/10 ,  C07D498/20 ,  C07D513/10 ,  C07D513/20

摘要： The present invention comprises a new class of compounds useful for the modulation of Beta-secretase enzyme activity and for the treatment of Beta-secretase mediated diseases, including Alzheimer's disease (AD) and related conditions. In one embodiment, the compounds have a general Formula I wherein A1, A2, A3, A4, A5, A6, L, R2, R7, X, Y and Z of Formula I are defined herein. The invention also includes use of these compounds in pharmaceutical compositions for treatment, prophylactic or therapeutic, of disorders and conditions related to the activity of beta-secretase protein. Such disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairment, schizophrenia and other central nervous system conditions related to and/or caused by the formation and/or deposition of plaque on the brain. The invention also comprises further embodiments of Formula I, intermediates and processes useful for the preparation of compounds of Formula I.

摘要翻译： 本发明包括可用于调节β-分泌酶酶活性和用于治疗β-分泌酶介导的疾病（包括阿尔茨海默病（AD））和相关病症的新一类化合物。 在一个实施方案中，化合物具有通式I，其中式I中的A1，A2，A3，A4，A5，A6，L，R2，R7，X，Y和Z如本文所定义。 本发明还包括在药物组合物中用于治疗，预防或治疗与β-分泌酶蛋白活性相关的病症和病症的用途。 这种病症包括例如阿尔茨海默氏病，认知缺陷，认知障碍，精神分裂症和与脑上形成和/或沉积斑块相关和/或引起的其他中枢神经系统病症。 本发明还包括式I的其它实施方案，可用于制备式I化合物的中间体和方法。

公开(公告)号：US20150031668A1

公开(公告)日：2015-01-29

申请号：US14331426

申请日：2014-07-15

申请人： AMGEN INC.

发明人： Kaustav Biswas ,  Jian J. Chen ,  Vijay Keshav Gore ,  Scott Harried ,  Daniel B. Horne ,  Matthew R. Kaller ,  Vu Van Ma ,  Kelvin Sham ,  James Brown ,  Wenge Zhong ,  Thomas T. Nguyen

IPC分类号： C07D491/052 ,  C07D498/04 ,  C07D471/04

CPC分类号： C07D491/052 ,  C07D471/04 ,  C07D498/04

摘要： Chroman compounds and derivatives of Formula I are useful inhibitors of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

摘要翻译： 色甘酸化合物和式I的衍生物是TRPM8的有用抑制剂。 这些化合物可用于治疗多种TRPM8介导的病症和病症，并且可用于制备用于治疗这种病症和病症的药物和药物组合物。 这些疾病的实例包括但不限于偏头痛和神经性疼痛。 式I的化合物具有以下结构：其中本文提供变量的定义。

公开(公告)号：US09085576B2

公开(公告)日：2015-07-21

申请号：US14199844

申请日：2014-03-06

申请人： AMGEN INC.

发明人： Ana Elena Minatti ,  Jonathan D. Low ,  Jennifer R. Allen ,  Albert Amegadzie ,  James Brown ,  Michael J. Frohn ,  Angel Guzman-Perez ,  Paul E. Harrington ,  Patricia Lopez ,  Vu Van Ma ,  Nobuko Nishimura ,  Wenyuan Qian ,  Shannon Rumfelt ,  Robert M. Rzasa ,  Kelvin Sham ,  Adrian L. Smith ,  Ryan White ,  Qiufen Xue

IPC分类号： C07D471/04 ,  C07D265/12 ,  C07D417/12 ,  C07D417/14 ,  C07D413/12 ,  C07D413/14 ,  A61K31/537 ,  C07D413/10 ,  C07D491/048

CPC分类号： C07D413/12 ,  C07D265/12 ,  C07D413/04 ,  C07D413/10 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048

摘要： The present invention provides a new class of compounds useful for the modulation of beta-secretase enzyme (BACE) activity. The compounds have a general Formula I: wherein variables A4, A5, A6, A8, each of Ra, Rb, R1, R2, R3 and R7 of Formula I, independently, are defined herein. The invention also provides pharmaceutical compositions comprising the compounds, and uses of the compounds and compositions for treatment of disorders and/or conditions related to A-beta plaque formation and deposition, resulting from the biological activity of BACE. Such BACE mediated disorders include, for example, Alzheimer's Disease, cognitive deficits, cognitive impairments, schizophrenia and other central nervous system conditions. The invention further provides compounds of Formulas II and III, and sub-formula embodiments thereof, intermediates and methods for preparing compounds of the invention.

摘要翻译： 本发明提供了一类可用于调节β-分泌酶（BACE）活性的化合物。 化合物具有通式I：其中式I中的每个R a，R b，R 1，R 2，R 3和R 7各自独立地定义的变量A4，A5，A6，A8在本文中定义。 本发明还提供包含该化合物的药物组合物，以及该化合物和组合物用于治疗由BACE的生物学活性产生的与A-β斑块形成和沉积有关的病症和/或病症的用途。 这种BACE介导的疾病包括例如阿尔茨海默病，认知缺陷，认知障碍，精神分裂症和其他中枢神经系统疾病。 本发明还提供式II和III的化合物及其分子式实施方案，用于制备本发明化合物的中间体和方法。

公开(公告)号：US08952009B2

公开(公告)日：2015-02-10

申请号：US13958478

申请日：2013-08-02

申请人： Amgen Inc.

发明人： Kaustav Biswas ,  Jian J. Chen ,  Vijay Keshav Gore ,  Scott Harried ,  Daniel B. Horne ,  Matthew R. Kaller ,  Vu Van Ma ,  Kelvin Sham ,  Wenge Zhong

IPC分类号： C07D491/052 ,  C07D401/12 ,  C07D311/68 ,  C07D215/40 ,  C07D471/04 ,  C07D491/04

CPC分类号： C07D491/052 ,  C07D215/40 ,  C07D311/68 ,  C07D401/12 ,  C07D471/04 ,  C07D491/04

摘要： Chroman compounds and derivatives of Formula I are useful inhibitors of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

摘要翻译： 色甘酸化合物和式I的衍生物是TRPM8的有用抑制剂。 这些化合物可用于治疗多种TRPM8介导的病症和病症，并且可用于制备用于治疗这种病症和病症的药物和药物组合物。 这些疾病的实例包括但不限于偏头痛和神经性疼痛。 式I的化合物具有以下结构：其中本文提供变量的定义。