公开(公告)号：US20240254199A1

公开(公告)日：2024-08-01

申请号：US18489274

申请日：2023-10-18

Applicant: Genentech, Inc. ,  Hoffmann-La Roche Inc.

Inventor： Amy Shen ,  Inn Huam Yuk ,  Gavin Christian Barnard ,  Shahram Misaghi ,  Simon Auslaender ,  Niels Bauer ,  Benedikt Oswald

IPC: C07K16/00 ,  C12N5/00 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90 ,  C12P21/00

CPC classification number: C07K16/00 ,  C12N5/00 ,  C12N9/22 ,  C12N15/11 ,  C12N15/907 ,  C12P21/00 ,  C12N2310/20 ,  C12N2800/80

Abstract: The present disclosure relates to mammalian cells (e.g., Chinese Hamster Ovary (CHO) cells) that are modified to reduce or eliminate the expression of certain mammalian cell endogenous products (e.g., host cell proteins and virus-like particles), and methods of using such cells in the production of a recombinant product of interest, e.g., a recombinant protein, a recombinant viral particle, or a recombinant viral vector. These modifications were specifically chosen to generate engineered mammalian host cells with desired traits in several key areas, including improved cell culture performance (e.g., higher viability and product titers), improved product quality (e.g., more consistent and favorable glycosylation; more stable drug product), and decreased burden on purification for removing problematic or undesired endogenous host cell products (e.g., hydrolytic host cell proteins and virus-like particles) during biomanufacturing.

公开(公告)号：US20220162295A1

公开(公告)日：2022-05-26

申请号：US17383316

申请日：2021-07-22

Applicant: Hoffmann-La Roche Inc. ,  Genentech, Inc.

Inventor： Styliani Tournaviti ,  Shan-Hua Chung ,  Harald Duerr ,  Claudia Ferrara Koller ,  Amy Shen ,  Shahram Misaghi ,  Shuet Ming Yip

IPC: C07K16/22 ,  C07K16/24

Abstract: Herein is reported a method for producing an antibody-multimer-fusion polypeptide comprising (a) an antibody heavy chain and an antibody light chain, and (b) a first fusion polypeptide comprising in N- to C-terminal direction a first part of a non-antibody multimeric polypeptide, an antibody heavy chain CH1 domain or an antibody light chain constant domain, an antibody hinge region, an antibody heavy chain CH2 domain and an antibody heavy chain CH3 domain, and a second fusion polypeptide comprising in N- to C-terminal direction the second part of the non-antibody multimeric polypeptide and an antibody light chain constant domain if the first polypeptide comprises an antibody heavy chain CH1 domain or an antibody heavy chain CH1 domain if the first polypeptide comprises an antibody light chain constant domain, wherein (i) the antibody heavy chain of (a) and the first fusion polypeptide of (b), (ii) the antibody heavy chain of (a) and the antibody light chain of (a), and (iii) the first fusion polypeptide of (b) and the second fusion polypeptide of (b) are each independently of each other covalently linked to each other by at least one disulfide bond, characterized in that the antibody-multimer-fusion is expressed by a recombinant mammalian cell obtained by transfecting a mammalian cell with the expression cassettes for the antibody heavy chain, the antibody light chain, the first fusion polypeptide and the second fusion polypeptide at a stoichiometric ratio of 1:1:2:1.

公开(公告)号：US20210002669A1

公开(公告)日：2021-01-07

申请号：US16956942

申请日：2018-12-21

Applicant: GENENTECH, INC.

Inventor： Chi Kin Domingos Ng ,  Yongping Guo Crawford ,  Amy Shen ,  Meixia Zhou ,  Bradley R. Snedecor ,  Shahram Misaghi ,  Albert Eric Gao

IPC: C12N15/90 ,  C07K16/00

Abstract: The presently disclosed subject matter relates to targeted integration (TI) host cells suitable for the expression of recombinant proteins, as well as methods of producing and using said TI host cells.

公开(公告)号：US12098365B2

公开(公告)日：2024-09-24

申请号：US17213611

申请日：2021-03-26

Applicant: GENENTECH, INC.

Inventor： Michael Wilson Laird ,  Shahram Misaghi ,  Amy Shen ,  Anthony Tomlinson ,  Inn Huam Yuk

IPC: C12N15/10 ,  C12N5/071

CPC classification number: C12N15/102 ,  C12N5/0682 ,  C12N2510/00

Abstract: The present disclosure relates to methods, cells, and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interest, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have reduced or eliminated activity, e.g., expression, of certain host cell proteins, e.g., enzymes including, but not limited to, certain lipases, esterases, and/or hydrolases.

公开(公告)号：US11802165B2

公开(公告)日：2023-10-31

申请号：US17148456

申请日：2021-01-13

Applicant: Genentech, Inc.

Inventor： Shahram Misaghi ,  John B. Lowe ,  Bradley Richard Snedecor

IPC: C07K16/44 ,  C07K14/435 ,  G01N33/68

CPC classification number: C07K16/44 ,  C07K14/435 ,  G01N33/6854 ,  C07K2317/41 ,  C07K2317/52 ,  C07K2317/732 ,  C07K2319/00

Abstract: The present application relates to methods of producing a protein in fucosylated and afucosylated forms at a predetermined ratio.

公开(公告)号：US10975168B2

公开(公告)日：2021-04-13

申请号：US15968214

申请日：2018-05-01

Applicant: Genentech, Inc.

Inventor： Shahram Misaghi ,  John B. Lowe ,  Bradley Richard Snedecor

IPC: C07K16/44 ,  C07K14/435 ,  G01N33/68

Abstract: The present application relates to methods of producing a protein in fucosylated and afucosylated forms at a predetermined ratio.

公开(公告)号：US20240011066A1

公开(公告)日：2024-01-11

申请号：US18303451

申请日：2023-04-19

Applicant: Genentech, Inc. ,  Hoffmann-La Roche Inc.

Inventor： Shahram Misaghi ,  Amy Shen ,  Inn Huam Yuk ,  Gavin Christian Barnard ,  Simon Auslaender ,  Niels Bauer ,  Benedikt Oswald

IPC: C12P21/02 ,  C12N15/90 ,  C12N15/11 ,  C12N9/00 ,  C12N9/22 ,  C12N9/10 ,  C12N9/86

CPC classification number: C12P21/02 ,  C12N15/907 ,  C12N15/11 ,  C12N9/93 ,  C12N9/22 ,  C12N9/1029 ,  C12Y203/01 ,  C12N9/86 ,  C12Y305/02006 ,  C12N2310/20 ,  C12N2800/80

Abstract: Herein are reported modified mammalian cells wherein the expression of the MYC gene and one or more of the BAK, BAX, SIRT-1 and ICAM-1 genes has been reduced or eliminated as well as methods for the recombinant production of a heterologous polypeptide using a modified mammalian cell according to the current invention. Further reported are use of the reduction of the expression of the genes for increasing volumetric productivity, increasing cell volume, increasing viability and increasing the possible cultivation time without cell split.

公开(公告)号：US20230279583A1

公开(公告)日：2023-09-07

申请号：US18129976

申请日：2023-04-03

Applicant: GENENTECH, INC.

Inventor： Shahram Misaghi ,  Bradley R. Snedecor

IPC: C40B30/06 ,  C07K16/00 ,  C12N15/85 ,  C12N15/90 ,  C40B40/02

CPC classification number: C40B30/06 ,  C07K16/005 ,  C12N15/85 ,  C12N15/907 ,  C40B40/02 ,  C07K2317/14 ,  C07K2317/31

Abstract: The presently disclosed subject matter relates to “Randomized Configuration Targeted Integration” (also referred to herein as “Randomized Chain Targeted Integration”) (RCTI) strategies for the generation and identification of host cells capable of expressing recombinant proteins, e.g., monoclonal antibodies, as well as compositions derived from the same, e.g., bispecific antibodies, and other complex format proteins, e.g., membrane protein complexes and other difficult to express molecules.

公开(公告)号：US20210009988A1

公开(公告)日：2021-01-14

申请号：US17036075

申请日：2020-09-29

Applicant: GENENTECH, INC.

Inventor： Shahram Misaghi ,  Masaru Ken Shiratori ,  Bradley Richard Snedecor ,  Michael W. Laird

IPC: C12N15/10 ,  C12N5/071 ,  C12N15/113 ,  C12N9/22

Abstract: The present disclosure relates to methods, cells and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interests, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have modulated lactogenic activity. The present disclosure also relates to methods and compositions for modulating pyruvate kinase muscle (PKM) expression (e.g., PKM-1 expression) in a mammalian cell to thereby reduce or eliminate the lactogenic activity of the cell, as well compositions comprising a cell having reduced or eliminated lactogenic activity and methods of using the same.

公开(公告)号：US12286619B2

公开(公告)日：2025-04-29

申请号：US17036075

申请日：2020-09-29

Applicant: GENENTECH, INC.

Inventor： Shahram Misaghi ,  Masaru Ken Shiratori ,  Bradley Richard Snedecor ,  Michael W. Laird

IPC: C12N15/10 ,  C12N5/071 ,  C12N9/22 ,  C12N15/113

Abstract: The present disclosure relates to methods, cells and compositions for producing a product of interest, e.g., a recombinant protein. In particular, the present disclosure provides improved mammalian cells expressing the product of interests, where the cells (e.g., Chinese Hamster Ovary (CHO) cells) have modulated lactogenic activity. The present disclosure also relates to methods and compositions for modulating pyruvate kinase muscle (PKM) expression (e.g., PKM-1 expression) in a mammalian cell to thereby reduce or eliminate the lactogenic activity of the cell, as well compositions comprising a cell having reduced or eliminated lactogenic activity and methods of using the same.