Methods of producing two chain proteins in prokaryotic host cells

    公开(公告)号:US12291712B2

    公开(公告)日:2025-05-06

    申请号:US17307877

    申请日:2021-05-04

    Abstract: Provided herein are methods and host cells for producing a polypeptide containing two chains, such as an antibody, half-antibody, antibody fragment, or one-armed antibody. The methods and host cells allow for two-chain polypeptide production using expression of polynucleotides encoding the polypeptide chains from extra-chromosomal polynucleotide(s), and expression of one or more chaperone protein(s) (e.g., peptidyl-prolyl isomerases and/or protein disulfide oxidoreductases) from the host cell chromosome using non-native combination(s) of promoters and translational units encoding a chaperone protein.

    Subcutaneous anti-HER2 Antibody Formulations and Uses Thereof

    公开(公告)号:US20250121059A1

    公开(公告)日:2025-04-17

    申请号:US18991315

    申请日:2024-12-20

    Abstract: The present invention relates to a highly concentrated, stable pharmaceutical formulation of a pharmaceutically active anti-HER2 antibody, such as e.g. Trastuzumab (HERCEPTIN™), Pertuzumab or T-DM1, or a mixture of such antibody molecules for subcutaneous injection. In particular, the present invention relates to formulations comprising, in addition to a suitable amount of the anti-HER2 antibody, an effective amount of at least one hyaluronidase enzyme as a combined formulation or for use in form of a co-formulation. The formulations comprise additionally at least one buffering agent, such as e.g. a histidine buffer, a stabilizer or a mixture of two or more stabilizers (e.g. a saccharide, such as e.g. α,α-trehalose dihydrate or sucrose, and optionally methionine as a second stabilizer), a nonionic surfactant and an effective amount of at least one hyaluronidase enzyme. Methods for preparing such formulations and their uses thereof are also provided.

    DUAL SPECIFIC ANTIBODIES
    6.
    发明申请

    公开(公告)号:US20250109195A1

    公开(公告)日:2025-04-03

    申请号:US18980433

    申请日:2024-12-13

    Abstract: The invention provides dual specific antibodies and methods of making and using such antibodies. In general, the dual specific antibodies are generated by identification of a monospecific antibody having light chain variable region VL residues that are electrostatic or hydrophobic and altering the nucleic acid sequence encoding one or more solvent accessible residues in the VH of the antibody either alone or in combination with alteration of the nucleic acid sequence encoding the VL of the antibody. The altered VH and the VL are expressed and dual specific antibodies, or antigen-binding fragments thereof, are selected. Exemplary dual specific antibodies are also provided as well as methods of using the antibodies.

    IDENTIFICATION OF BINDING SITES IN A PROTEIN STRUCTURE

    公开(公告)号:US20250087299A1

    公开(公告)日:2025-03-13

    申请号:US18960282

    申请日:2024-11-26

    Abstract: In one aspect, a method for identifying residues in a particular conformation of a protein molecule capable of forming a stable binding between a compound and the protein molecule is provided. The method can include identifying, for inclusion in a perturbation set, one or more residues from the conformation of the protein molecule that exhibit a protection factor satisfying one or more thresholds. One or more residues may be excluded from the perturbation set based at least on a spatial arrangement and/or an orientation of the one or more residues. One or more rounds of molecular dynamics simulations whose result is indicative of an interaction between the compound and the residues in the perturbation set may be performed. The residues in the perturbation set may be identified as forming a stable binding between the compound and the protein molecule based at least on the result of the molecular dynamics simulation

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