Abstract: Modified canine leptin polypeptides and formulations and uses thereof, are provided including polyethylene glycol (PEG) modified canine leptin polypeptides, wherein the PEG moiety is covalently attached to a para-acetyl-phenylalanine (pAF) residue of the polypeptide, and related compositions and methods useful in treating companion animal obesity and other leptin-related disorders.
Type:
Grant
Filed:
March 12, 2014
Date of Patent:
October 23, 2018
Assignees:
ELANCO US INC., AMBRX, INC.
Inventors:
Michael Bledsoe, Peter Connor Canning, Michael Deguzman, Nick Knudsen, Ianina Valenta
Abstract: Modified FGF-21 polypeptides and uses thereof are provided.
Type:
Grant
Filed:
October 13, 2016
Date of Patent:
May 22, 2018
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: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in vertebrate cells. The components include orthogonal tRNA's, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNA's/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in vertebrate cells are also provided. The present invention provides vertebrate cells with translation components, e.g., pairs of orthogonal aminoacyl-tRNA synthetases (O-RSs) and orthogonal tRNA's (O-tRNA's) and individual components thereof, that are used in vertebrate protein biosynthetic machinery to incorporate an unnatural amino acid in a growing polypeptide chain, in a vertebrate cell.
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.
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:
May 24, 2012
Date of Patent:
October 24, 2017
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: 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:
Application
Filed:
March 30, 2015
Publication date:
June 29, 2017
Applicants:
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: Modified animal erythropoietin polypeptides and uses thereof are provided.
Type:
Grant
Filed:
September 15, 2015
Date of Patent:
May 9, 2017
Assignees:
Ambrx, Inc., Eli Lilly and Company
Inventors:
Feng Tian, Anna-Maria A. Hays Putnam, Frank Song, Stephanie Chu, Joseph Sheffer, Richard S. Barnett, Marc Siladi, Kyle Atkinson, Darin Lee, Peter C. Canning
Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid of Formula (I), and methods for making such non-natural amino acids and polypeptides.
Type:
Grant
Filed:
May 29, 2014
Date of Patent:
May 2, 2017
Assignee:
AMBRX, INC.
Inventors:
Zhenwei Miao, Junjie Liu, Thea Norman, Russell Driver
Abstract: This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in vertebrate cells. The components include orthogonal tRNA's, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNA's/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in vertebrate cells are also provided. The present invention provides vertebrate cells with translation components, e.g., pairs of orthogonal aminoacyl-tRNA synthetases (O-RSs) and orthogonal tRNA's (O-tRNA's) and individual components thereof, that are used in vertebrate protein biosynthetic machinery to incorporate an unnatural amino acid in a growing polypeptide chain, in a vertebrate cell.
Abstract: Disclosed herein are non-natural amino acids and polypeptides that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of possible functionalities, but typical have at least one aromatic amine group. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such polypeptides. Typically, the modified non-natural amino acid polypeptides include at least one alkylated amine group. Further disclosed are methods for using such non-natural amino acid polypeptides and modified non-natural amino acid polypeptides, including therapeutic, diagnostic, and other biotechnology uses.
Abstract: The invention provides water-soluble compounds that include a polymer and at least one terminal azide or acetylene moiety. Also provided are highly efficient methods for the selective modification of proteins with PEG derivatives, which involves the selective incorporation of non-genetically encoded amino acids, e.g., those amino acids containing an azide or acetylene moiety, into proteins in response to a selector codon and the subsequent modification of those amino acids with a suitably reactive PEG derivative.
Abstract: Modified relaxin polypeptides and their uses, including therapeutic uses thereof for the treatment of a fibrotic disorder or heart failure 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:
February 22, 2013
Date of Patent:
February 14, 2017
Assignee:
AMBRX, INC.
Inventors:
Vadim Kraynov, Nick Knudsen, Amha Hewet, Kristine de Dios, Jason Pinkstaff, Lorraine Sullivan
Abstract: Modified FGF-21 polypeptides and uses thereof are provided.
Type:
Grant
Filed:
April 7, 2015
Date of Patent:
December 13, 2016
Assignee:
AMBRX, INC.
Inventors:
Thomas P. Cujec, Roberto Mariani, Anna-Maria A. Hays Putnam, Wiliam M. Keefe, Nick Knudsen, Lillian Skidmore, Jason Pinkstaff, Vadim Kraynov
Abstract: Disclosed herein are methods of detecting non-natural amino acids and polypeptides that include at least one non-natural amino acid. The non-natural amino acids, by themselves or as a part of a polypeptide, can include a wide range of functionalities, including but not limited to oxime, carbonyl, and/or hydroxylamine groups. Also disclosed herein are non-natural amino acid polypeptides that are further modified post-translationally, and methods for detecting such polypeptides.
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:
May 24, 2012
Publication date:
February 25, 2016
Applicant:
AMBRX, INC.
Inventors:
Zhenwei Miao, Kyle Atkinson, Sandra Biroc, Timothy Buss, Melissa Neal, Vadim Kraynov, Robin Marsden, Jason Pinkstaff, Lillian Skidmore, Ying Sun