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：US20230406929A1

公开(公告)日：2023-12-21

申请号：US18251120

申请日：2021-11-08

Applicant: AMGEN INC. ,  AMGEN RESEARCH (MUNICH)

Inventor： Doris Rau ,  Tobias Raum ,  Partrick Hoffmann ,  Markus Muenz ,  Matthias Klinger ,  Virginie Naegele ,  Lisa Winkel ,  Pavan Ghattyvenkatakrishna ,  Joon Hoi Huh ,  Arnold McAuley ,  Sekhar Kanapuram

IPC: C07K16/28

CPC classification number: C07K16/2809 ,  C07K16/2875 ,  C07K2317/31 ,  C07K2317/622 ,  C07K2317/73 ,  C07K2317/94 ,  C07K2317/92

Abstract: The invention relates to a polypeptide or polypeptide construct comprising: a binding domain binding to an extracellular epitope of the human CD3s chain comprising or consisting of a VH region and a VL region, wherein i) the VH region comprises: a CDR-H1 sequence of X1YAX2N, where X1 is K, V, S, G, R, T, or I; and X2 is M or I; a CDR-H2 sequence of RIRSKYNNYATYYADX1VKX2, where X1 is S or Q; and X2 is D, G, K, S, or E; and a CDR-H3 sequence of HX1NFGNSYX2SX3X4AY, where X1 is G, R, or A; X2 is I, L, V, or T; X3 is Y, W or F; and X4 is W, F or Y; and ii) wherein the VL region comprises: a CDR-L1 sequence of X1 SSTGAVTX2X3X4YX5N, where X1 is G, R, or A; X2 is S or T; X3 is G or S; X4 is N or Y and X5 is P or A; a CDR-L2 sequence of X1TX2X3X4X5X6; where X1 is G or A; X2 is K, D, or N; X3 is F, M or K; X4 is L or R; X5 is A, P, or V; and X6 is P or S; and a CDR-L3 sequence of X1LWYSNX2VW, where X1 is V, A, or T; and X2 is R or L; and iii) wherein one or more of CDR sequences of the VH region of i) and/or of the VL region of ii) comprise one amino acid substitution or a combination thereof selected from X24V and X24F in CDR-H1; D15, and X116A in CDR-H2; H1, X12E, F4, and N6 in CDR-H3; and X11L and W3 in CDR-L3. The invention also relates to a polynucleotide encoding the polypeptide or polypeptide construct of the invention, a vector comprising said polynucleotide and a host cell transformed or transfected with said polynucleotide or with said vector. Moreover, the invention also provides for a process for the production of said polypeptide or polypeptide construct and a pharmaceutical composition comprising said polypeptide or polypeptide construct of the invention. Furthermore, the invention relates to medical uses of said polypeptide or polypeptide construct and kits comprising said polypeptide or polypeptide construct.