Grant

Heterodimeric protein production

Patent Number ES-2739808-T3

Publication Year 2020

Granted Year: 2020

Application Year 2012

Priority Year 2011

Jurisdiction ES

Status Active

Inventors

GRAMER MICHAEL PARREN PAUL VAN BERKEL PATRICK VOS WERNER L GERRITSEN ARNOUT KUNDU AMITAVA VAN DEN BREMER EWALD T J VAN KAMPEN MURIEL PRIEM PATRICK LABRIJN ARAN FRANK MEESTERS JOYCE NEIJSSEN JOOST J SCHUURMAN JANINE

Applicants

Genmab (Denmark)

[NORA names: Genmab; Private Research; Denmark; Europe, EU; Nordic; OECD]

Abstract

An in vitro method for the production of a full-length bispecific antibody comprising the following steps: a) incubating a first full-length antibody with a second full-length antibody under reducing conditions sufficient to allow reduction of intrachain disulfide bonds in the hinge region, and wherein the CH3 region of said first full length antibody is the first CH3 region and has an Arg at position 409, and the CH3 region of said second full length antibody is a second CH3 region and has : (i) an Asp, Glu, Gly, Asn, Arg, Ser, Thr, Val or Trp at position 368; (ii) a Phe, His, Lys, Arg or Tyr at position 399; (iii) a Gly, Leu, Met or Trp at position 407 and a Lys at position 409, and wherein the first CH3 further has a Tyr at position 407; or (iv) an amino acid other than Phe, Arg or Gly at position 405 and has an Lys at position 409, and wherein the first CH3 further has a Phe at position 405, such that the sequences of said First and second CH3 regions are different and such that the heterodimeric interaction between said first and second CH3 regions is stronger than each of the homodimeric interactions of said first and second CH3 regions, in which the amino acid positions are numbered according with the EU index as described in Kabat, in which said first and second full-length antibodies bind to different epitopes, in which said first and second full-length antibodies: 1) each has an Fc region with an amino acid sequence that is of an IgG1 isotype; 2) each has an Fc region with an amino acid sequence that is of an IgG2 isotype; 3) each has an Fc region with an amino acid sequence that is of an IgG3 isotype; or 4) each has an Fc region with an amino acid sequence that is of an IgG4 isotype; and wherein said first and second antibodies are humanized antibodies or wherein said first and second antibodies each comprise a full length heavy chain of a human antibody; and further wherein step a) comprises incubation for at least 90 minutes at a temperature of at least 20 ° C in the presence of 2-mercaptoethylamine at a concentration of at least 25 mM; b) subjecting at least 10 ml of the composition obtained from step a) under oxidative conditions sufficient to allow the oxidation of the cysteines in the full-length bispecific antibody to intra-chain disulfide bonds and c) obtaining the full-length bispecific antibody.

Patent Family Records (45)

Production of heterodimeric proteins

Jian Mabao GRAMER MICHAEL, P. Palen, P. Van Bouquel, (...more)

2024, CN-110964115-B

Patent Family Records

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Abstract

Patent Family Records (45)

Heterodimeric protein production

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