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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：US20230099074A1
公开(公告)日：2023-03-30
申请号：US18049711
申请日：2022-10-26
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：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：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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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：US20220033518A1
公开(公告)日：2022-02-03
申请号：US17003952
申请日：2020-08-26
申请人： Ambrx,Inc.
发明人： Richard Barnett , Feng Tian , Anna-Maria A. Hays Putnam , Marco Gymnopoulos , Nickolas 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：US20150152190A1
公开(公告)日：2015-06-04
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.
摘要翻译： 本发明涉及包含至少一种非天然编码氨基酸的前列腺特异性膜抗原（PSMA）抗体和抗体药物偶联物。 本文公开了具有一种或多种非天然编码氨基酸的αPSMA抗体，并且还公开了抗体药物偶联物，其中本发明的αPSMA抗体与一种或多种毒素缀合。 本文还公开了在翻译后进一步修饰的非天然氨基酸多拉司他汀类似物，用于实现这种修饰的方法，以及纯化这种多拉司他汀类似物的方法。 通常，修饰的多拉司他汀类似物包括至少一个肟，羰基，二羰基和/或羟胺基团。 进一步披露的是使用这种非天然氨基酸抗体药物偶联物，多拉司他汀类似物和经修饰的非天然氨基酸多拉司他汀类似物的方法，包括治疗，诊断和其他生物技术用途。
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9.发明申请公开(公告)号：US20150152187A1
公开(公告)日：2015-06-04
申请号：US14407792
申请日：2013-06-14
申请人： Ambrx, Inc.
发明人： Ying Sun , Ning Zou , Amha Hewet , Jason K. Pinkstaff , Shailaja Srinagesh , Richard S. Barnett , Feng Tian , Anna-Maria A. Hays Putnam , Marco Gymnopoulos , Nick Knudsen , Andrew Beck
CPC分类号： C07K16/3076 , A61K47/6869 , C07K16/3069
摘要： This invention relates to anti-prostate-specific membrane antigen antibodies (αPSMA) and αPSMA antibody—nuclear receptor ligand (NRL) conjugates comprising at least one non-naturally-encoded amino acid.
摘要翻译： 本发明涉及包含至少一种非天然编码氨基酸的抗前列腺特异性膜抗原抗体（αPSMA）和αPSMA抗体 - 核受体配体（NRL）缀合物。
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