Patents Assigned to Zymeworks Inc.
-
Patent number: 11351251Abstract: The present invention relates to antibodies that are heterodimeric and bind human PD-L1 and human TIM-3, and may be useful for treating cancer alone and in combination with chemotherapy and other cancer therapeutics.Type: GrantFiled: March 12, 2019Date of Patent: June 7, 2022Assignees: Eli Lilly and Company, Zymeworks Inc.Inventors: Yiwen Li, Dale Lincoln Ludwig, Yang Shen, Yi Zhang, Igor Edmondo Paolo D'Angelo
-
Patent number: 11325981Abstract: 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.Type: GrantFiled: June 18, 2018Date of Patent: May 10, 2022Assignee: Zymeworks Inc.Inventors: Nina E. Weisser, Gordon Yiu Kon Ng, Grant Raymond Wickman, Surjit Bhimarao Dixit, Eric Escobar-Cabrera, Mario Sanches
-
Patent number: 11306156Abstract: 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.Type: GrantFiled: May 29, 2015Date of Patent: April 19, 2022Assignee: ZYMEWORKS INC.Inventors: Mario Sanches, Thomas Spreter Von Kreudenstein, Dunja Urosev, Stacey A. L. Tom-Yew, Adam Louis Corper, Igor Edmondo Paolo D'Angelo, Yang-Chieh Chou, Surjit Bhimarao Dixit
-
Patent number: 11286293Abstract: 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.Type: GrantFiled: September 5, 2018Date of Patent: March 29, 2022Assignee: ZYMEWORKS, INC.Inventors: Adam Louis Corper, Dunja Urosev, Stacey A. L. Tom-Yew, Dustin Weyland Blue Bleile, Thomas Spreter Von Kreudenstein, Surjit Dixit, Paula Irene Lario, Mario Sanches
-
Patent number: 11248037Abstract: 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.Type: GrantFiled: May 21, 2019Date of Patent: February 15, 2022Assignee: ZYMEWORKS INC.Inventors: Surjit Bhimarao Dixit, Igor Edmondo Paolo D'Angelo, Mario Sanches, Gordon Yiu Kon Ng
-
Patent number: 11203640Abstract: The present invention relates to antibodies that are heterodimeric and bind human PD-L1 and human PD-1, and may be useful for treating cancer alone and in combination with chemotherapy and other cancer therapeutics.Type: GrantFiled: July 9, 2018Date of Patent: December 21, 2021Assignees: Eli Lilly and Company, Zymeworks Inc.Inventors: Michael Dewain Kalos, Yiwen Li, Dale Lincoln Ludwig, Yang Shen, Igor Edmondo Paolo D'Angelo, Gregory D Plowman
-
Patent number: 11161915Abstract: Provided herein are multispecific antigen-binding polypeptide constructs comprising at least two different heterodimers, each comprising a heavy chain and a light chain. At least one heterodimer comprises a Fab region comprising a lambda light chain and at least one heterodimer comprises a Fab region comprising a kappa light chain. One or more of the immunoglobulin heavy and light chains that form the antigen-binding polypeptide construct comprise amino acid modifications that promote correct pairing between the heavy and light chains to form the desired multispecific antigen-binding polypeptide construct. The amino acid modifications may be in the CH1 and/or CL domains, in the VH and/or VL domains, or a combination thereof.Type: GrantFiled: October 7, 2016Date of Patent: November 2, 2021Assignee: ZYMEWORKS INC.Inventors: Dunja Urosev, Stacey A. L. Tom-Yew, Leonard G. Presta, Mario Sanches
-
Patent number: 11147886Abstract: Bispecific antigen-binding constructs e.g., antibodies conjugated to drugs (ADCs), which bind CD3 and other cell-surface target antigen such as tumor antigens e.g., CD19, CDH3, HER2, HER3 and EGFR antigens and methods of use are disclosed.Type: GrantFiled: July 15, 2016Date of Patent: October 19, 2021Assignee: Zymeworks Inc.Inventors: Gordon Yiu Kon Ng, Leonard G. Presta, Thomas Spreter Von Kreudenstein
-
Patent number: 11152081Abstract: 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.Type: GrantFiled: July 27, 2016Date of Patent: October 19, 2021Assignee: ZYMEWORKS INC.Inventors: Paula I. Lario, Johannes Mullegger, Surjit B. Dixit, Tomas Rodinger, Powell Patrick Cheng Tan
-
Patent number: 11098105Abstract: 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.Type: GrantFiled: May 30, 2014Date of Patent: August 24, 2021Assignee: ZYMEWORKS INC.Inventor: Eric Escobar-Cabrera
-
Patent number: 11078296Abstract: Provided are 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 CH1 and/or CL domains, amino acid modifications in the VH and/or VL domains or a combination thereof. The modified amino acid residues are part of the interface between the light chain and heavy chain and are modified in order 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 mammalian 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 preferentially pairs with the second light chain rather than first.Type: GrantFiled: February 14, 2018Date of Patent: August 3, 2021Assignee: ZYMEWORKS INC.Inventors: Adam Louis Corper, Dunja Urosev, Stacey A. L. Tom-Yew, Dustin Weyland Blue Bleile, Thomas Spreter Von Kreudenstein, Surjit Dixit, Paula Irene Lario, Mario Sanches
-
Patent number: 11072658Abstract: Provided herein are anti-PD-1/LAG3 bispecific antibodies and antigen-binding fragments. Also provided here are methods and uses of these antibodies and antigen-binding fragments in the treatment of cancer or infectious disease.Type: GrantFiled: January 31, 2019Date of Patent: July 27, 2021Assignees: MERCK SHARP & DOHME CORP., ZYMEWORKS, INC.Inventors: Laurence Fayadat-Dilman, Veronica Juan, Shireen Khan, Shaopeng Huang, Hua Ying, Eric Escobar Cabrera, Genevieve Desjardins
-
Patent number: 11028182Abstract: Described herein are high affinity antigen binding constructs, e.g., antibodies, directed to the ECD2 domain of HER2. The antigen-binding constructs comprise at least one antigen-binding polypeptide construct that binds to ECD2 of HER2 (HER2 ECD2) with increased affinity compared to a wild-type 2C4 antibody. Such antigen-binding polypeptide constructs comprise one or more amino acid modifications in the framework region and/or CDRs compared to the amino acid sequence of a wild-type 2C4 antibody that increase affinity of the antigen-binding polypeptide construct for ECD2 by 2-fold or greater. The antigen-binding constructs can inhibit the growth of HER2-expressing breast cancer cells and gastric cancer cells. Antigen-binding constructs in biparatopic format are internalized in HER2-expressing cells.Type: GrantFiled: May 13, 2016Date of Patent: June 8, 2021Assignee: Zymeworks Inc.Inventors: Eric Escobar-Cabrera, Leonard G. Presta
-
Patent number: 11031093Abstract: Systems, methods and non-transitory computer readable media identify favored polymer conformations. One or more residues are identified and may be replaced in the polymer, or the original primary sequence of the polymer may be retained. The conformations of residues in a subset of residues in a region of the identified one or more residues are altered. This conformational adjustment is repeated for other subsets of residues in the region of the identified one or more residues, and for other conformations, thereby deriving a plurality of polymer structures. A set of clusters is generated for each residue of the polymer using the conformationally adjusted structures, thereby creating sets of clusters. Structures in the plurality of structures are grouped into subgroups when the structures fall into the same clusters across a threshold number of the sets of clusters.Type: GrantFiled: June 21, 2013Date of Patent: June 8, 2021Assignee: ZYMEWORKS INC.Inventors: Gregory Lakatos, Surjit Bhimarao Dixit
-
Patent number: 11000598Abstract: Anti-HER2 biparatopic antibody-drug conjugates (ADCs) in which the drug is an auristatin analogue and is conjugated to the antibody at a low average drug-to-antibody ratio (DAR), and methods of using the ADCs in the treatment of a HER2-expressing cancer. The low average DAR (<3.9) ADCs as described herein have improved tolerability and decreased toxicity as compared to a corresponding ADC having a DAR?3.9 when administered at the same toxin dose.Type: GrantFiled: October 7, 2019Date of Patent: May 11, 2021Assignee: Zymeworks Inc.Inventors: Kevin Hamblett, Rupert H. Davies, James R. Rich, Gerald J. Rowse, Vincent K. C. Fung, Stuart D. Barnscher
-
Patent number: 10947319Abstract: 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.Type: GrantFiled: November 27, 2014Date of Patent: March 16, 2021Assignee: Zymeworks Inc.Inventors: Nina E. Weisser, Gordon Yiu Kon Ng, Grant Raymond Wickman, Surjit Bhimarao Dixit, Eric Escobar-Cabrera, Mario Sanches
-
Patent number: 10875931Abstract: The provided scaffolds have heavy chains that are asymmetric in the various domains (e.g. CH2 and CH3) to accomplish selectivity between the various Fc receptors involved in modulating effector function, beyond those achievable with a natural homodimeric (symmetric) Fc molecule, and increased stability and purity of the resulting variant Fc heterodimers. These novel molecules comprise complexes of heterogeneous components designed to alter the natural way antibodies behave and that find use in therapeutics.Type: GrantFiled: January 18, 2017Date of Patent: December 29, 2020Assignee: ZYMEWORKS, INC.Inventors: Thomas Spreter Von Kreudenstein, Eric Escobar-Cabrera, Surjit Bhimarao Dixit, Paula Irene Lario, David Kai Yuen Poon
-
Patent number: 10832794Abstract: The invention provides a computer implemented method of quantifying the quality of packing for a residue comprising one or more residue atoms in a first protein in a first conformation, the method comprising: (a) calculating one or more close contact potentials based on a distance between the one or more residue atoms and one or more environment atoms, (b) calculating a contact area of the one or more residue atoms that is exposed to the one or more environment atoms and (c) calculating a close contact surface density (CCSD) by dividing the sum of the one or more close contact potentials by the contact area.Type: GrantFiled: September 22, 2011Date of Patent: November 10, 2020Assignee: ZYMEWORKS INC.Inventor: Anders Ohrn
-
Patent number: 10711051Abstract: Provided herein are multifunctional heteromer proteins. In specific embodiments is a heteromultimer that comprises: at least two monomeric proteins, wherein each monomeric protein comprises at least one cargo polypeptide, attached to a transporter polypeptide, such that said monomeric proteins associate to form the heteromultimer. These therapeutically novel molecules comprise monomers that function as scaffolds for the conjugation or fusion of therapeutic molecular entities resulting in the creation of bispecific or multivalent molecular species.Type: GrantFiled: November 5, 2018Date of Patent: July 14, 2020Assignee: ZYMEWORKS INC.Inventors: Surjit Bhimarao Dixit, Igor Edmondo Paolo D'Angelo, David Kai Yuen Poon
-
Patent number: 10675355Abstract: VAR2CSA-drug conjugates having biological activity are disclosed. Methods associated with preparation and use of such conjugates, as well as pharmaceutical compositions comprising such conjugates, are also disclosed.Type: GrantFiled: December 29, 2014Date of Patent: June 9, 2020Assignees: VAR2 PHARMACEUTICALS APS, ZYMEWORKS INC.Inventors: James R. Rich, John Babcook, Ali El-Salanti, Mads Daugaard, Madeleine Dahlback, Bradley J. Hedberg, Geoffrey C. Winters, Alexander L. Mandel, Elyse Marie Josée Bourque, Tom Han Hsiao Hsieh