公开(公告)号：US20240197922A1

公开(公告)日：2024-06-20

申请号：US18333607

申请日：2023-06-13

Applicant: AMGEN INC.

Inventor： Nathan JOH ,  Marisa JOUBERT ,  Gerd Richard KLEEMAN ,  Linda Owers NARHI ,  Noel J. RIEDER ,  Joshua TOKUDA ,  Zhongqi ZHANG ,  Yunlong ZHANG

IPC: A61K49/00

CPC classification number: A61K49/0004

Abstract: Methods of manufacturing a biological therapy are described. The methods can comprise detecting a level of a molecular attribute of the biological therapy in a formulation, determining a rate of change of the molecular attribute under the storage conditions, and estimating a level of molecular attribute exposure received by the subjects at the time of said administration. Production lots of the biological therapy comprising the molecular attribute can be manufactured comprising the molecular attribute at or below a specified specification for permissible levels of the molecular attribute based on the estimated level of molecule attribute exposure. Methods of developing a manufacturing process for a biological therapy are described. Methods of assessing the clinical impact of a molecular attribute of a biological therapy are described.

公开(公告)号：US20230035363A1

公开(公告)日：2023-02-02

申请号：US17436218

申请日：2020-03-04

Applicant: AMGEN INC.

Inventor： Dong XIANG ,  Qingchun ZHANG ,  Marisa JOUBERT ,  Trent MUNRO ,  Ronandro DE GUZMAN

IPC: G01N33/68 ,  G01N30/14 ,  G01N21/64

Abstract: Provided herein are in vitro methods of assaying an in vivo level of high molecular weight (HMW) species of a therapeutic protein. In exemplary embodiments, the method comprises (a) incubating a mixture comprising (i) a sample comprising the therapeutic protein and (ii) serum, or a depleted fraction thereof; and (b) assaying the level of HMW species of the therapeutic protein present in the mixture at one or more time points after step (a). Also methods of determining the in vivo reversibility of HMW species of a therapeutic protein are provided herein. In exemplary instances, the method comprises (A) assaying the in vivo level of high molecular weight (HMW) species of a therapeutic protein according to a presently disclosed in vitro method, and (B) comparing the level(s) of HMW species present in the mixture to the level of HMW species present in the sample prior to the incubating step.