公开(公告)号：US10908165B2

公开(公告)日：2021-02-02

申请号：US16002749

申请日：2018-06-07

Applicant: Purdue Research Foundation ,  AMGEN INC.

Inventor： Stephen T. Ayrton ,  Robert Graham Cooks ,  Tawnya Flick ,  Da Ren

IPC: G01N33/68 ,  H01J49/10 ,  H01J49/00

Abstract: The invention generally relates to methods for determining whether a peptide includes aspartate or isoaspartate. In certain aspects, methods of the invention involve binding an aspartate/isoaspartate residue in a peptide with a label to produce a labeled peptide. The labeled peptide is then ionized. The ionizing process causes the label to undergo rearrangement in a gas phase at a higher rate if the label is bound to the aspartate residue as compared to if the label is bound to the isoaspartate residue. The methods of the invention then involve performing a mass spectrometry analysis to detect the rearrangement of the label, thereby determining whether the peptide includes aspartate or isoaspartate.

公开(公告)号：US11385238B2

公开(公告)日：2022-07-12

申请号：US16022850

申请日：2018-06-29

Applicant: AMGEN INC.

Inventor： Da Ren ,  Izydor Apostol ,  Alexander Julian Veach

IPC: G01N33/68 ,  B01D15/34

Abstract: The disclosed methods are directed to detecting polypeptide fragments (“clips”) of parental polypeptides. Parental polypeptides and clips are optionally denatured and then fractionated using a matrix. After a first elution (high molecular weight fraction), an additional elution step retrieves a low molecular weight fraction containing clips. If the clips are an appropriate size for the targeted detection method, such as mass spectrometry, then analysis of this fraction proceeds separately from the high molecular weight fraction, or the clips fraction is mixed with the proteolyzed high molecular weight fraction before analysis. However, if the clips are too large for the intended analytical method(s), then the clips are also proteolyzed. The digested high molecular weight and low molecular weight fractions can be analyzed separately or combined. Analysis of combined samples favors clip quantitation because the clips are analyzed together with the remaining counterpart of the parental polypeptide.

公开(公告)号：US11427627B2

公开(公告)日：2022-08-30

申请号：US14916993

申请日：2014-09-05

Applicant: AMGEN INC.

Inventor： Zhimei Du ,  Pranhitha Reddy ,  Randal B. Bass ,  Feng He ,  William C. Fanslow, III ,  Yuling Zhang ,  Da Ren ,  Randal R. Ketchem

IPC: C07K1/00 ,  C07K16/00 ,  A61K39/395 ,  A61K39/40

Abstract: The present invention relates to variant Fc-containing molecules, such as antibodies and Fc-fusion molecules, having glycosylation characteristics favorable to largescale production of therapeutic molecules containing such variant Fc. Described herein are compositions and methods to improve glycosylation maturation of and to minimize the culture process-dependent effects of Fc-containing molecules, e.g., Fc-fusion molecules and antibodies. Creating single and multiple amino acid substitutions within the Fc domain with the aim to improve high mannose processing and glycosylation maturation.

公开(公告)号：US11059908B2

公开(公告)日：2021-07-13

申请号：US16338292

申请日：2017-09-28

Applicant: AMGEN INC.

Inventor： Joon Hoi Huh ,  Riki Stevenson ,  Pavel Bondarenko ,  Andrew Nichols ,  Da Ren ,  Neeraj Jagdish Agrawal

IPC: C07K16/40 ,  C07K16/28 ,  G01N11/14

Abstract: The present invention concerns a method for preparing antigen binding proteins with reduced viscosity. The method proceeds by replacing residues in high viscosity variable domain subfamilies with residues in correlating low viscosity subfamilies. The method further comprises substituting residues in the Fc domain with residues associated with low viscosity and adding charged residues to the C-terminus of the Fc domain. The present invention further concerns antigen binding proteins produced by this method.

公开(公告)号：US11993663B2

公开(公告)日：2024-05-28

申请号：US17346156

申请日：2021-06-11

Applicant: AMGEN INC.

Inventor： Joon Hoi Huh ,  Riki Stevenson ,  Pavel Bondarenko ,  Andrew Nichols ,  Da Ren ,  Neeraj Jagdish Agrawal ,  Richard Smith

IPC: C07K16/40 ,  C07K16/28 ,  G01N11/14

CPC classification number: C07K16/40 ,  C07K16/2869 ,  C07K2317/21 ,  C07K2317/24 ,  C07K2317/52 ,  C07K2317/55 ,  C07K2317/90 ,  C07K2317/92 ,  C07K2317/94 ,  G01N11/14

Abstract: The present invention concerns a method for preparing antigen binding proteins specific for PCSK9 with reduced viscosity. The method proceeds by replacing residues in high viscosity variable domain subfamilies with residues in correlating low viscosity subfamilies. The method further comprises substituting residues in the Fc domain with residues associated with low viscosity and adding charged residues to the C-terminus of the Fc domain. The present invention further concerns antigen binding proteins produced by this method.

公开(公告)号：US20210223260A1

公开(公告)日：2021-07-22

申请号：US17158369

申请日：2021-01-26

Applicant: Purdue Research Foundation ,  AMGEN INC.

Inventor： Stephen T. Ayrton ,  Robert Graham Cooks ,  Tawnya Flick ,  Da Ren

IPC: G01N33/68 ,  H01J49/10 ,  H01J49/00

Abstract: The invention generally relates to methods for determining whether a peptide includes aspartate or isoaspartate. In certain aspects, methods of the invention involve binding an aspartate/isoaspartate residue in a peptide with a label to produce a labeled peptide. The labeled peptide is then ionized. The ionizing process causes the label to undergo rearrangement in a gas phase at a higher rate if the label is bound to the aspartate residue as compared to if the label is bound to the isoaspartate residue. The methods of the invention then involve performing a mass spectrometry analysis to detect the rearrangement of the label, thereby determining whether the peptide includes aspartate or isoaspartate.