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Vancouver, Canada

Zymeworks Inc. is a privately held biotechnology company based in Vancouver, British Columbia that develops protein therapeutics for the treatment of cancer as well as for autoimmune and inflammatory diseases. The products are based upon the company's molecular modeling software for optimizing protein structure. In 2014, Zymeworks raised $44 million across various funding rounds according to PitchBook, placing it among the top 10 HealthTech businesses in the world to raise the most capital that year. Wikipedia.


The present invention provides heterodimer pairs comprising a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain. At least one of the heterodimers comprises amino acid modifications in the C


Systems and methods for evaluating thermodynamics of atomic changes in a polymer include using a first portion of a refined derived set of three-dimensional coordinates for a derivation of the polymer, which incorporates the atomic change under study, to compute a first effective atomistic Hessian. A second effective atomistic Hessian is computed using a second portion of a refined native set of three-dimensional coordinates for the native polymer. Atoms in the first and second portions are identical. A thermodynamic property of the first portion is determined using the refined derived set of three-dimensional coordinates and the first effective atomistic Hessian. A thermodynamic property of the second portion of the native polymer is determined using the refined native set of three-dimensional coordinates and the second effective atomistic Hessian. The effect of the atomic changes is quantified by taking the difference between the calculated thermodynamic properties of the first and second portions.


The present invention provides a process and methods for producing asymmetric antibodies in a mammalian expression system. The asymmetric antibodies are transiently or stably expressed and in cells that stably express the asymmetric antibody, following a rapid 2-step process of stable pool to clone, a highly pure asymmetric antibody expressing clone can be identified at a success frequency that permits for screening of tens of clones rather than thousands. The asymmetric antibodies are produced at a high titre and with a high level of purity with no contaminating homodimer antibodies following protein A purification with a step yield of near 100%. Typical downstream purification processes employ standard hydrophobic interaction chromatography (HIC) and/or cation exchange (CEX) resins and the antibody is stable within a wide dynamic range of buffer pH (4-8) and within the requirements for manufacturing antibodies for pre-clinical and clinical applications.


The present invention provides heterodimer pairs that can comprise a first heterodimer and a second heterodimer wherein each heterodimer comprises an immunoglobulin heavy chain or fragment thereof and an immunoglobulin light chain or fragment thereof. At least one of the heterodimers can comprise one or more amino acid modifications in the C H and/or C L domains, one or more amino acid modifications in the V H and/or V L domains, or a combination thereof. The modified amino acid(s) can be part of the interface between the light chain and heavy chain and are typically modified to create preferential pairing between each heavy chain and a desired light chain such that when the two heavy chains and two light chains of the heterodimer pair are co-expressed in a cell, the heavy chain of the first heterodimer preferentially pairs with one of the light chains rather than the other. Likewise, the heavy chain of the second heterodimer typically preferentially pairs with the second light chain rather than first.


Provided herein are heteromultimer constructs with reduced or silenced effector function. In an embodiment is provided a heteromultimer construct comprising an IgG Fc construct having a first and a second Fc polypeptide, each Fc polypeptide comprising a modified lower hinge region wherein: the modified lower hinge region of said first Fc polypeptide comprises at least one amino acid modification, the modified lower hinge region of said second Fc polypeptide comprises at least one amino acid modification which is different from at least one amino acid modification of said first Fc polypeptide, and the IgG Fc construct displays reduced binding to all Fc receptors and to C1q protein as compared to a corresponding parent IgG Fc construct. Also provided are methods of producing such heteromultimer constructs, and methods of reducing ADCC for an antibody construct by reducing effector function.

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