公开(公告)号：US20190248906A1

公开(公告)日：2019-08-15

申请号：US16282834

申请日：2019-02-22

Applicant: Amgen, Inc.

Inventor： Yang LI ,  Jennitte LeAnn STEVENS ,  Chadwick Terence KING ,  Ian Nevin FOLTZ ,  Gunasekaran KANNAN ,  Junming YIE ,  Shaw-Fen Sylvia HU

IPC: C07K16/28 ,  C07K14/71 ,  C07K16/40

CPC classification number: C07K16/2863 ,  A61K2039/505 ,  C07K14/71 ,  C07K16/40 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2319/00 ,  C07K2319/30 ,  C12Y302/01031

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

公开(公告)号：US20210108212A1

公开(公告)日：2021-04-15

申请号：US17080771

申请日：2020-10-26

Applicant: AMGEN INC.

Inventor： Michael OLLMANN ,  Yang LI ,  Jun ZHANG ,  Kaustav BISWAS ,  Oliver HOMANN ,  Leslie P. MIRANDA ,  Justin K. MURRAY ,  Bin WU ,  Oh Kyu YOON ,  John Gordon ALLEN ,  Chawita NETIROJJANAKUL ,  Yuan CHENG

IPC: C12N15/113 ,  A61P9/10 ,  A61P3/06 ,  C07K16/28

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

公开(公告)号：US20190309306A1

公开(公告)日：2019-10-10

申请号：US16328221

申请日：2017-08-25

Applicant: AMGEN INC.

Inventor： Michael OLLMANN ,  Yang LI ,  Jun ZHANG ,  Kaustav BISWAS ,  Oliver HOMANN ,  Leslie P. MIRANDA ,  Justin K. MURRAY ,  Bin WU ,  Oh Kyu YOON ,  John Gordon ALLEN ,  Chawita NETIROJJANAKUL ,  Yuan CHENG

IPC: C12N15/113 ,  A61P3/06 ,  A61P9/10 ,  C07K16/28

Abstract: The present invention relates to RNAi constructs for reducing expression of the ASGR1 gene. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease and myocardial infarction, and to reduce serum non-HDL cholesterol levels are also described.

公开(公告)号：US20170183412A1

公开(公告)日：2017-06-29

申请号：US15400800

申请日：2017-01-06

Applicant: Amgen Inc.

Inventor： Yang LI ,  Jennitte LeAnn STEVENS ,  Chadwick Terence KING ,  Ian Nevin FOLTZ ,  Gunasekaran KANNAN ,  Junming YIE ,  Shaw-Fen Sylvia HU

IPC: C07K16/28 ,  C07K16/40

CPC classification number: C07K16/2863 ,  A61K2039/505 ,  C07K14/71 ,  C07K16/40 ,  C07K2317/21 ,  C07K2317/31 ,  C07K2317/52 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/75 ,  C07K2319/00 ,  C07K2319/30 ,  C12Y302/01031

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins capable of inducing B-Klotho, and or FGF21-like mediated signaling. In embodiments, the antigen binding proteins specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to a complex comprising β-Klotho and at least one of (i) FGFR1c, (ii) FGFR2c and (iii) FGFR3c. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

公开(公告)号：US20230137351A1

公开(公告)日：2023-05-04

申请号：US16349965

申请日：2017-11-14

Applicant: AMGEN INC.

Inventor： Wei YAN ,  Zhi LIU ,  Christopher MURAWSKY ,  Chadwick Terence KING ,  Yang LI ,  Zhonghua HU ,  Desiree LIM

IPC: C07K16/46

Abstract: The present invention relates to bispecific or biparatopic antigen binding proteins, polynucleotides encoding the same, and methods of making bispecific or biparatopic antigen binding proteins. Also described herein is a method to assemble IgG-like biparatopic or bispecific antibodies from VH only antigen binding proteins.

公开(公告)号：US20170015750A1

公开(公告)日：2017-01-19

申请号：US15280662

申请日：2016-09-29

Applicant: AMGEN INC.

Inventor： Shaw-Fen Sylvia HU ,  Ian Nevin FOLTZ ,  Chadwick Terence KING ,  Yang LI ,  Taruna Arora

IPC: C07K16/28

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

Abstract translation: 本发明提供与抗原结合蛋白有关或衍生自抗原结合蛋白的组合物和方法激活FGF21介导的信号传导。 在实施方案中，抗原结合蛋白特异性结合（i）β-Klotho; （ii）FGFR1c，FGFR2c，FGFR3c或FGFR4; 或（iii）包含β-Klotho和FGFR1c，FGFR2c，FGFR3c和FGFR4之一的复合物。 在一些实施方案中，抗原结合蛋白诱导FGF21样信号传导。 在一些实施方案中，抗原结合蛋白是完全人，人源化或嵌合抗体，所述抗体的结合片段和衍生物，以及特异性结合（i）β-Klotho的多肽; （ii）FGFR1c，FGFR2c，FGFR3c或FGFR4; 或（iii）包含β-Klotho和FGFR1c，FGFR2c，FGFR3c和FGFR4之一的复合物。 其它实施方案提供了编码这种抗原结合蛋白的核酸及其片段和衍生物，以及多肽，包含这种多核苷酸的细胞，制备此类抗原结合蛋白的方法及其片段和衍生物以及多肽，以及使用这些抗原结合蛋白的方法 ，其片段及其衍生物和多肽，包括治疗或诊断患有2型糖尿病，肥胖症，NASH，代谢综合征和相关疾病或病症的受试者的方法。

公开(公告)号：US20160008439A1

公开(公告)日：2016-01-14

申请号：US14772910

申请日：2014-03-13

Applicant: AMGEN INC.

Inventor： Daniel C.H. LIN ,  Jinghong WANG ,  Yang LI

IPC: A61K38/46 ,  A61B5/145 ,  C12N9/20

CPC classification number: A61K38/465 ,  A61B5/14532 ,  C12N9/20 ,  C12Y301/01004

Abstract: Methods of treating or ameliorating metabolic diseases using a PLA2G12A polypeptide or PLA2G12A mutant polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes mellitus, obesity, dyslipidemia elevated glucose levels, elevated insulin levels and diabetic nephropathy.

Abstract translation: 提供了使用PLA2G12A多肽或PLA2G12A突变体多肽治疗或改善代谢疾病的方法。 在各种实施方案中，代谢疾病或病症是2型糖尿病，肥胖症，血脂异常升高的葡萄糖水平，升高的胰岛素水平和糖尿病性肾病。

公开(公告)号：US20200325200A1

公开(公告)日：2020-10-15

申请号：US16918088

申请日：2020-07-01

Applicant: AMGEN INC.

Inventor： Yumei XIONG ,  Yang LI ,  Wen-Chen YEH ,  Bei SHAN ,  Jackie Zeqi SHENG

IPC: C07K14/495 ,  A61K38/18

Abstract: Methods of treating metabolic diseases and disorders using a GDF15 polypeptide are provided. In various embodiments the metabolic disease or disorder is type 2 diabetes mellitus, obesity, dyslipidemia, elevated glucose levels, elevated insulin levels and diabetic nephropathy.

公开(公告)号：US20200216546A1

公开(公告)日：2020-07-09

申请号：US16744734

申请日：2020-01-16

Applicant: Amgen, Inc.

Inventor： Shaw-Fen Sylvia HU ,  Ian Nevin FOLTZ ,  Chadwick Terence KING ,  Yang LI ,  Taruna ARORA

IPC: C07K16/28 ,  C07K16/18 ,  C07K14/71 ,  C07K16/40

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

公开(公告)号：US20160145351A1

公开(公告)日：2016-05-26

申请号：US15012939

申请日：2016-02-02

Applicant: Amgen Inc.

Inventor： Shaw-Fen Sylvia HU ,  Ian Nevin FOLTZ ,  Chadwick Terence KING ,  Yang LI ,  Taruna Arora

IPC: C07K16/40 ,  C07K16/28

CPC classification number: C07K16/2863 ,  A61K2039/505 ,  C07K14/71 ,  C07K16/18 ,  C07K16/28 ,  C07K16/40 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/32 ,  C07K2317/34 ,  C07K2317/53 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/56 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/626 ,  C07K2317/75 ,  C07K2317/92 ,  C07K2319/30

Abstract: The present invention provides compositions and methods relating to or derived from antigen binding proteins activate FGF21-mediated signaling. In embodiments, the antigen binding proteins specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. In some embodiments the antigen binding proteins induce FGF21-like signaling. In some embodiments, an antigen binding protein is a fully human, humanized, or chimeric antibodies, binding fragments and derivatives of such antibodies, and polypeptides that specifically bind to (i) β-Klotho; (ii) FGFR1c, FGFR2c, FGFR3c or FGFR4; or (iii) a complex comprising β-Klotho and one of FGFR1c, FGFR2c, FGFR3c, and FGFR4. Other embodiments provide nucleic acids encoding such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, cells comprising such polynucleotides, methods of making such antigen binding proteins, and fragments and derivatives thereof, and polypeptides, and methods of using such antigen binding proteins, fragments and derivatives thereof, and polypeptides, including methods of treating or diagnosing subjects suffering from type 2 diabetes, obesity, NASH, metabolic syndrome and related disorders or conditions.

Abstract translation: 本发明提供与抗原结合蛋白有关或衍生自抗原结合蛋白的组合物和方法激活FGF21介导的信号传导。 在实施方案中，抗原结合蛋白特异性结合（i）＆amp; bgr; -Klotho; （ii）FGFR1c，FGFR2c，FGFR3c或FGFR4; 或（iii）包含α-Klotho和FGFR1c，FGFR2c，FGFR3c和FGFR4之一的复合物。 在一些实施方案中，抗原结合蛋白诱导FGF21样信号传导。 在一些实施方案中，抗原结合蛋白是完全人，人源化或嵌合抗体，所述抗体的结合片段和衍生物，以及特异性结合（i）和/或Klotho的多肽; （ii）FGFR1c，FGFR2c，FGFR3c或FGFR4; 或（iii）包含α-Klotho和FGFR1c，FGFR2c，FGFR3c和FGFR4之一的复合物。 其它实施方案提供了编码这种抗原结合蛋白的核酸及其片段和衍生物，以及多肽，包含这种多核苷酸的细胞，制备此类抗原结合蛋白的方法及其片段和衍生物以及多肽，以及使用这些抗原结合蛋白的方法 ，其片段及其衍生物和多肽，包括治疗或诊断患有2型糖尿病，肥胖症，NASH，代谢综合征和相关疾病或病症的受试者的方法。