Vancouver, Canada
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.


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The invention provides methods and systems of determining biopolymer profiles and correlations between structural units (residues) of a biopolymer based on sampling of the conformational space available to the molecule. The correlations between these structural units can further be used to find networks within a biopolymer such as the coupled residue networks in a protein. The invention also provides for designing and engineering biopolymers including polypeptides, nucleic acids and carbohydrates using the information derived from the conformation clustering and subsequent methods described herein.


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 CH1 and/or CL domains, one or more amino acid modifications in the VH and/or VL 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.


Patent
Zymeworks | Date: 2016-02-17

Rationally designed antibodies and polypeptides that comprise multiple Fc region amino acid substitutions that synergistically provide enhanced selectivity and binding affinity to a target Fc receptor are provided. The polypeptides are mutated at multiple positions to make them more effective when incorporated in antibody therapeutics than those having wild-type Fc components.


Patent
Zymeworks | Date: 2015-01-15

Antigen-binding constructs, e.g., antibodies, which bind CD3 and CD 19 and methods of use are disclosed.


Patent
Zymeworks | Date: 2014-07-11

Bispecific antigen binding constructs are described that bind to CD3 and CD19 or CD20 antigens.


The present disclosure provides light chain polypeptides that include a C-terminal extension, as well as antibodies and antibody conjugates containing such modified light chain polypeptides, where the C-terminal extension includes one or more cysteine residues. Conjugates that include an antibody of the present disclosure conjugated to an agent via the cysteine residue of the C-terminal amino acid extension are also provided. The present disclosure further provides nucleic acids encoding an antibody light chain polypeptide that includes a C-terminal amino acid extension including a cysteine residue. Pharmaceutical compositions including the antibodies or conjugates of the present disclosure are also provided, as are methods of making and use of the modified anti-bodies and conjugates of the present disclosure.


Provided herein are isolated heteromultimers comprising: at least one single domain antigen-binding construct attached to at least one monomer of a heterodimer Fc region; wherein the heterodimer Fc region comprises a variant CH3 domain comprising amino acid mutations that promote the formation of said heterodimer with stability comparable to that of a native Fc homodimer; and wherein said isolated heteromultimer is devoid of immunoglobulin light chains and optionally devoid of immunoglobulin CH1 region. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.


Patent
Zymeworks | Date: 2016-01-19

Provided herein are multifunctional heteromultimer proteins. In specific embodiments is a heteromultimer comprising: at least two polypeptide constructs, each polypeptide construct comprising at least one cargo polypeptide attached to a transporter polypeptide, said transporter polypeptides derived from a monomeric native protein such that said monomeric constructs associate to form the heteromultimer and said transporter polypeptides associate to form a quasi-native structure of the monomeric native protein or analog thereof. These therapeutically novel molecules encompass heteromultimers comprising constructs that function as scaffolds for the conjugation or fusion of therapeutic molecular entities (cargo polypeptides) resulting in the creation of bispecific or multivalent molecular species. Provided herein is a method for creation of bispecific or multivalent molecular species.


Provided herein are monovalent antigen-binding constructs targeting EGFR and/or HER2. The monovalent antigen-binding constructs can include at least one antigen-binding polypeptide comprising a heavy chain variable domain, wherein the antigen-bind polypeptide specifically binds EGFR and/or HER2; and a heterodimeric Fc domain, the Fc domain comprising at least two CH3 domains, wherein the Fc domain is coupled, with or without a linker, to the antigen-binding polypeptide. Also provided are methods of making the constructs and methods of using the constructs.


Patent
Zymeworks | Date: 2014-11-27

Provided herein are biparatopic antigen-binding constructs that specifically bind HER2. The biparatopic antigen-binding constructs comprise one antigen-binding moiety that binds to ECD2 of HER2, a second antigen-binding moiety that binds to ECD4 of HER2, and an Fc. At least one of the antigen-binding moieties is an scFv. The biparatopic antigen-binding constructs can be used in the treatment of cancer.

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