Abstract: Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.
Type:
Application
Filed:
January 5, 2021
Publication date:
September 9, 2021
Applicant:
Ambrx, Inc.
Inventors:
Zhenwei MIAO, Kyle ATKINSON, Sandra BIROC, Timothy BUSS, Melissa NEAL, Vadim KRAYNOV, Robin MARSDEN, Jason PINKSTAFF, Lillian SKIDMORE, Ying SUN, Agnieszka SZYDLIK, Delia Ianina LOPEZ DE VALENTA
Abstract: Disclosed herein are methods, compositions and components for optimizing or increasing expression of a protein, polypeptide or fragment therefrom.
Type:
Application
Filed:
May 1, 2019
Publication date:
April 15, 2021
Applicant:
Ambrx, Inc.
Inventors:
MD Harunur RASHID, Mark SHIMAZU, Feng Tian
Abstract: Disclosed herein are porcine interferon alpha variants (pIFN-?) comprising a synthetic amino acid at select locations in pIFN-? and a one or two amino acid insertion in the N-terminus after removal of the signal peptide. The pIFN-? variants can further be pegylated. Methods of making and administering these compounds to treat virus infections in pigs and formulations comprising the variants are also provided.
Type:
Grant
Filed:
June 16, 2017
Date of Patent:
March 30, 2021
Assignees:
Elanco US Inc., Ambrx, Inc.
Inventors:
Peter Connor Canning, Nickolas Knudsen, Lillian Skidmore
Abstract: Modified FGF-21 polypeptides and uses thereof are provided.
Type:
Grant
Filed:
June 17, 2019
Date of Patent:
March 30, 2021
Assignee:
AMBRX, INC.
Inventors:
Thomas P. Cujec, Roberto Mariani, Anna-Maria A. Hays Putnam, William M. Keefe, Nick Knudsen, Lillian Skidmore, Jason Pinkstaff, Vadim Kraynov
Abstract: Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.
Type:
Grant
Filed:
September 12, 2017
Date of Patent:
March 23, 2021
Assignee:
Ambrx, Inc.
Inventors:
Zhenwei Miao, Kyle Atkinson, Sandra Biroc, Timothy Buss, Melissa Neal, Vadim Kraynov, Robin Marsden, Jason Pinkstaff, Lillian Skidmore, Ying Sun, Agnieszka Szydlik, Delia Ianina Lopez De Valenta
Abstract: The present invention relates to variants of porcine granulocyte colony stimulating factor (pG-CSF). The pG-CSF variants are useful in treating preventing or reducing the incidence of bacterial infections in swine. Methods of treating swine are disclosed.
Type:
Application
Filed:
October 10, 2018
Publication date:
February 25, 2021
Applicants:
Elanco US Inc., Ambrx, Inc.
Inventors:
Peter Connor CANNING, Nickolas KNUDSEN, Md Harunur RASHID
Abstract: Disclosed herein are methods and compositions for generation of cell lines to promote unnatural amino acid-containing protein production using genome engineering technology.
Abstract: The invention relates to prostate specific membrane antigen humanized antibodies (anti-PSMA) and anti-PSMA antibody drug conjugates. The invention also relates to methods and compositions for using anti-PSMA antibody drug conjugates in inhibiting, preventing or treating PSMA related diseases or cancers.
Abstract: Described are antibody peptide conjugates (APCs) comprising an antibody conjugated to a peptide analog of glucagon, which have been modified to be resistant to cleavage and inactivation by dipeptidyl peptidase IV (DPP-IV) and to increase in vivo half-life of the peptide analog while enabling the peptide analog to have agonist activity at the glucagon (GCG) receptor and the glucagon-like peptide 1 (GLP-1) receptor and the use of such APCs for treatment of metabolic disorders such as diabetes, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and obesity.
Type:
Application
Filed:
August 27, 2020
Publication date:
December 17, 2020
Applicants:
Merck Sharp & Dohme Corp., Ambrx, Inc.
Inventors:
Paul E. Carrington, Grigori Ermakov, Robert M. Garbaccio, Wolfgang Seghezzi, Elisabetta Bianchi, Federica Orvieto, Dennis Gately, Nick Knudsen, Anthony Manibusan
Abstract: This invention relates to prostate-specific membrane antigen (PSMA) antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?PSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?PSMA antibodies of the invention are conjugated to one or more toxins. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, dolastatin analogs, and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.
Type:
Grant
Filed:
June 7, 2013
Date of Patent:
October 13, 2020
Assignee:
Ambrx, Inc.
Inventors:
Richard S. Barnett, Feng Tian, Anna-Maria A. Hays Putnam, Marco Gymnopoulos, Nick Knudsen, Andrew Beck, Ying Sun
Abstract: Modified relaxin polypeptides and their uses thereof are provided. Exemplary embodiments provide relaxin polypeptides which include one or more amino acid substitutions with natural or non-naturally encoded amino acids, and/or linkage to a water-soluble polymer, such as polyethylene glycol. Additionally, use of said relaxin polypeptides for treatment of disease, such as heart failure, is also provided.
Type:
Grant
Filed:
February 26, 2019
Date of Patent:
August 25, 2020
Assignee:
AMBRX, INC.
Inventors:
Vadim Kraynov, Nick Knudsen, Amha Hewet, Kristine De Dios, Jason Pinkstaff, Lorraine Sullivan
Abstract: Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).
Type:
Grant
Filed:
March 30, 2015
Date of Patent:
February 4, 2020
Assignees:
Merck Sharp & Dohme Corp., Ambrx, Inc.
Inventors:
Robert M. Garbaccio, Jeffrey Kern, Philip E. Brandish, Sanjiv Shah, Linda Liang, Ying Sun, Jianing Wang, Nick Knudsen, Andrew Beck, Anthony Manibusan, Dennis Gately
Abstract: This invention relates to anti-CD70 antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?CD70 antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?CD70 antibodies of the invention are conjugated to one or more toxins. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, including therapeutic, diagnostic, and other biotechnology uses.
Type:
Application
Filed:
December 18, 2018
Publication date:
November 7, 2019
Applicant:
Ambrx, Inc.
Inventors:
Richard S. Barnett, Nick Knudsen, Ying Sun, Sandra Biroc, Timothy Buss, Tsotne Javahishvili, Damien Bresson, Shailaja Srinagesh, Amha Hewet, Jason Pinkstaff
Abstract: Compositions and methods of producing vaccines, including methods wherein whole organism vaccines are provided with limited replication abilities, thereby increasing vaccine safety and efficacy, through the use of non-natural, unnatural, or non-naturally encoded amino acids.
Abstract: Modified FGF-21 polypeptides and uses thereof are provided.
Type:
Grant
Filed:
April 13, 2018
Date of Patent:
August 13, 2019
Assignee:
AMBRX, INC.
Inventors:
Thomas P. Cujec, Roberto Mariani, Anna-Maria A. Hays Putnam, William M. Keefe, Nick Knudsen, Lillian Skidmore, Jason Pinkstaff, Vadim Kraynov
Abstract: The present application discloses PEG modified variants of a bFGF-21 polypeptide, compositions containing a bFGF-21 polypeptide variant, and methods useful in treating and/or preventing ketosis that administer the variant or a composition containing said bFGF-21 variant.
Type:
Application
Filed:
August 18, 2017
Publication date:
July 4, 2019
Applicants:
Elanco US Inc., Ambrx, Inc.
Inventors:
Peter Connor CANNING, Shailaja SRINAGESH, Anthony MANIBUSAN, Jason PINKSTAFF, Nickolas KNUDSEN
Abstract: Therapeutic uses of modified relaxin polypeptides for the treatment of cardiovascular disease, treatment of heart failure, and decreasing fibrotic disorders are provided. Exemplary embodiments provide for the use of relaxin polypeptides which include one or more amino acid substitutions with natural or non-naturally encoded amino acids, and/or linkage to a water-soluble polymer, such as polyethylene glycol.
Type:
Grant
Filed:
December 21, 2016
Date of Patent:
April 9, 2019
Assignee:
AMBRX, INC.
Inventors:
Vadim Kraynov, Nick Knudsen, Amha Hewet, Kristine De Dios, Jason Pinkstaff, Lorraine Sullivan
Abstract: This invention relates to anti-CD70 antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are ?CD70 antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the ?CD70 antibodies of the invention are conjugated to one or more toxins. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, including therapeutic, diagnostic, and other biotechnology uses.
Type:
Grant
Filed:
June 19, 2013
Date of Patent:
February 19, 2019
Assignee:
Ambrx, Inc.
Inventors:
Richard S. Barnett, Nick Knudsen, Ying Sun, Sandra Biroc, Timothy Buss, Tsotne Javahishvili, Damien Bresson, Shailaja Srinagesh, Amha Hewet, Jason K. Pinkstaff