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公开(公告)号：US10800826B2
公开(公告)日：2020-10-13
申请号：US15765505
申请日：2016-10-04
发明人： Paul Carrington , Grigori Ermakov , Robert M. Garbaccio , Wolfgang Seghezzi , Elisabetta Bianchi , Federica Orvieto , Dennis Gately , Nick Knudsen , Anthony Manibusan
摘要： 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.
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公开(公告)号：US10550190B2
公开(公告)日：2020-02-04
申请号：US15301564
申请日：2015-03-30
发明人： Robert M. Garbaccio , Jeffrey Kern , Philip E. Brandish , Sanjiv Shah , Linda Liang , Ying Sun , Jianing Wang , Nick Knudsen , Andrew Beck , Anthony Manibusan , Dennis Gately
摘要： 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).
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公开(公告)号：US11510993B2
公开(公告)日：2022-11-29
申请号：US15765515
申请日：2016-09-30
发明人： Philip E. Brandish , Robert M. Garbaccio , Jeffrey Kern , Linda Liang , Sanjiv Shah , Dennis Zaller , Andrew Beck , Dennis Gately , Nick Knudsen , Anthony Manibusan , Jianing Wang , Ying Sun
摘要： Antibody drug conjugates (ADCs) comprising an antibody conjugated to an anti-inflammatory therapeutic agent via a phosphate-based linker with tunable extracellular and intracellular stability are described.
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公开(公告)号：US20200164085A1
公开(公告)日：2020-05-28
申请号：US15765515
申请日：2016-09-30
发明人： Philip E. Brandish , Robert M Garbaccio , Jeffrey Kern , Linda Liang , Sanjiv Shah , Dennis Zaller , Andrew Beck , Dennis Gately , Nick Knudsen , Anthony Manibusan , Jianing Wang , Ying Sun
摘要： Antibody drug conjugates (ADCs) comprising an antibody conjugated to an anti-inflammatory therapeutic agent via a phosphate-based linker with tunable extracellular and intracellular stability are described.
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公开(公告)号：US20170182181A1
公开(公告)日：2017-06-29
申请号：US15301564
申请日：2015-03-30
发明人： Robert M. Garbaccio , Jeffrey Kern , Philip E. Brandish , Sanjiv Shah , Linda Liang , Ying Sun , Jianing Wang , Nick Knudsen , Andrew Beck , Anthony Manibusan , Dennis Gately
CPC分类号： C07K16/2866 , A61K47/6803 , A61K47/6817 , A61K47/6849 , A61K47/6889 , A61K51/1045 , C07F9/091 , C07F9/098 , C07F9/12 , C07F9/2458 , C07F9/572 , C07F9/65517 , C07F9/65583 , C07F9/65586 , C07F9/6561 , C07H19/10
摘要： 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).
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6.发明申请公开(公告)号：US20190071483A1
公开(公告)日：2019-03-07
申请号：US15765505
申请日：2016-10-04
发明人： Paul Carrington , Grigori Ermakov , Robert M. Garbaccio , Wolfgang Seghezzi , Elisabetta Bianchi , Federica Orvieto , Dennis Gately , Nick Knudsen , Anthony Manibusan
IPC分类号： C07K14/605 , A61K47/68 , C07K16/26 , C07K16/28 , A61P3/10
CPC分类号： C07K14/605 , A61K47/6811 , A61K47/6843 , A61K2039/505 , A61P3/10 , C07K16/26 , C07K16/2869 , C07K2317/75 , C07K2319/00
摘要： 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.
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公开(公告)号：US11993637B2
公开(公告)日：2024-05-28
申请号：US17165351
申请日：2021-02-02
申请人： AMBRX, INC.
发明人： Thomas P. Cujec , Roberto Mariani , Anna-Maria A. Hays Putnam , William M. Keefe , Nick Knudsen , Lillian Skidmore , Jason Pinkstaff , Vadim Kraynov
摘要： Modified FGF-21 polypeptides and uses thereof are provided.
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公开(公告)号：US10800856B2
公开(公告)日：2020-10-13
申请号：US14406190
申请日：2013-06-07
申请人： Ambrx, Inc.
发明人： Richard S. Barnett , Feng Tian , Anna-Maria A. Hays Putnam , Marco Gymnopoulos , Nick Knudsen , Andrew Beck , Ying Sun
摘要： 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 αPSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the αPSMA 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.
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公开(公告)号：US10751391B2
公开(公告)日：2020-08-25
申请号：US16285986
申请日：2019-02-26
申请人： AMBRX, INC.
发明人： Vadim Kraynov , Nick Knudsen , Amha Hewet , Kristine De Dios , Jason Pinkstaff , Lorraine Sullivan
摘要： 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.
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公开(公告)号：US20170096463A1
公开(公告)日：2017-04-06
申请号：US15292700
申请日：2016-10-13
申请人： AMBRX, INC.
发明人： Thomas P. CUJEC , Roberto Mariani , Anna-Maria A. Hays Putnam , Wiliam M. Keefe , Nick Knudsen , Lillian Skidmore , Jason Pinkstaff , Vadim Kraynov
CPC分类号： C07K14/50 , A61K38/00 , A61K38/1825 , A61K45/06 , A61K47/60 , C12N15/70 , Y02A50/473
摘要： Modified FGF-21 polypeptides and uses thereof are provided.
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