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1. 发明申请

US20220354938A1 CELL-TARGETING MOLECULES COMPRISING DE-IMMUNIZED, SHIGA TOXIN A SUBUNIT EFFECTORS AND CD8+ T-CELL EPITOPES 有权
公开(公告)号：US20220354938A1
公开(公告)日：2022-11-10
申请号：US17852669
申请日：2022-06-29
申请人： Molecular Templates, Inc.
发明人： Eric POMA , Erin WILLERT , Sangeetha RAJAGOPALAN , Garrett Lee ROBINSON , Brigitte BRIESCHKE , Jason KIM
IPC分类号： A61K39/00 , A61K47/68 , C07K14/25
摘要： The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of a target cell. The cell-targeting molecules of the invention can be used to deliver virtually any CD8+ T-cell epitope from an extracellular space to the MHC class I pathway of a target cell, which may be a malignant cell and/or non-immune cell. The target cell can then display on a cell-surface the delivered CD8+ T-cell epitope complexed with MHC I molecule. The cell-targeting molecules of the invention have uses which include the targeted labeling and/or killing of specific cell-types within a mixture of cell-types, including within a chordate, as well as the stimulation of beneficial immune responses. The cell-targeting molecules of the invention have uses, e.g., in the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections.

2. 发明申请

US20220267384A1 PROTEINS COMPRISING BINDING REGIONS, SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS, AND CARBOXY-TERMINAL, ENDOPLASMIC RETICULUM LOCALIZATION SIGNAL MOTIFS 有权
公开(公告)号：US20220267384A1
公开(公告)日：2022-08-25
申请号：US17734881
申请日：2022-05-02
申请人： Molecular Templates, Inc.
发明人： Eric POMA , Erin WILLERT , Jason KIM , Jack HIGGINS
IPC分类号： C07K14/245 , C07K16/28 , C07K16/32 , C07K16/30 , A61K49/00
摘要： The present invention provides proteins comprising binding regions for cell-type specific targeting, Shiga toxin effector regions derived from A Subunits of members of the Shiga toxin family for providing Shiga toxin effector functions (e.g. cellular internalization and cytotoxicity), and carboxy-terminal endoplasmic reticulum localization signal motifs. The presently disclosed proteins can comprise additional exogenous materials, such as, e.g., antigens, cytotoxic agents, and detection-promoting agents, and are capable of targeted delivery of these additional exogenous materials into the interiors of target cells. The proteins of the present invention have uses in methods such as, e.g., methods involving targeted killing of target cells, delivering exogenous materials into target cells, labeling subcellular compartments of target cells, and diagnosing and/or treating a variety of conditions including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.

3. 发明申请

US20220195050A1 CLINICAL METHODS FOR USE OF A PD-L1-BINDING MOLECULE COMPRISING A SHIGA TOXIN EFFECTOR 有权
公开(公告)号：US20220195050A1
公开(公告)日：2022-06-23
申请号：US17553333
申请日：2021-12-16
申请人： Molecular Templates, Inc.
发明人： Eric POMA , Erin WILLERT , Hilario RAMOS , Jensing LIU , Roger Waltzman
IPC分类号： C07K16/28 , A61K47/26 , A61K35/74 , A61K31/7036 , A61P35/00 , A61K9/00 , A61K45/06
摘要： The present disclosure relates to PD-L1-binding molecules comprising a Shiga toxin effector region, a PD-L1-binding region, and a T cell epitope, and pharmaceutical compositions thereof. The PD-L1 binding molecules and pharmaceutical compositions thereof have uses for selectively killing specific cells (e.g., PD-L1 positive tumor cells and/or immune cells), for selectively delivering cargos to specific cells (e.g., PD-L1 positive tumor cells or immune cells), and as therapeutics for treating or slowing the progression of cancer (e.g., non-small cell lung cancer or squamous cell carcinoma of the head and neck). The present disclosure also relates to clinical methods for use of the disclosed PD-L1 binding molecules for treating a subject in need thereof.

4. 发明授权

US11365223B2 De-immunized, Shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same 有权
公开(公告)号：US11365223B2
公开(公告)日：2022-06-21
申请号：US17233911
申请日：2021-04-19
申请人： Molecular Templates, Inc.
发明人： Eric Poma , Erin Willert , Garrett Lee Robinson , Sangeetha Rajagopalan , Brigitte Brieschke
IPC分类号： C07K14/25 , C07K19/00
摘要： The present invention relates to Shiga toxin A Subunit derived polypeptides and cell-targeting molecules comprising amino acid substitutions which equip the polypeptides with 1) de-immunization; 2) reduced, protease-cleavage sensitivity; and/or 3) a heterologous epitope cargo(s) while retaining Shiga toxin function(s), such as, e.g., potent cytotoxicity. Certain polypeptides of the invention exhibit reduced immunogenic potential in mammals and/or are capable of delivering an epitope to an MHC class molecule of a cell in which the polypeptide is present. Certain molecules comprising a polypeptide of the invention are well-tolerated by mammals while retaining one or more of the features mentioned above. The Shiga toxin polypeptides of the invention have uses as components of cell-targeting molecules for selectively killing specific cells; for selectively delivering cargos to specific cells, and as therapeutic and/or diagnostic molecules for treating and diagnosing a variety of conditions, including cancers, immune disorders, and microbial infections.

5. 发明申请

US20220152213A1 SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES, SHIGA TOXIN EFFECTOR SCAFFOLDS, AND CELL-TARGETING MOLECULES FOR SITE-SPECIFIC CONJUGATION 有权
公开(公告)号：US20220152213A1
公开(公告)日：2022-05-19
申请号：US17533552
申请日：2021-11-23
申请人： Molecular Templates, Inc.
发明人： Eric Poma , Erin Willert
IPC分类号： A61K47/68 , A61K38/16 , C07K14/195 , C07K14/25 , A61K8/99
摘要： The present invention provides Shiga toxin A Subunit derived polypeptides, scaffolds, and cell-targeting molecules comprising amino acid substitutions which equip the molecules with site-specific positions (and often unique amino acid residues in the molecule) for linking other molecules while retaining Shiga toxin function(s), such as, e.g., efficient intracellular routing and/or potent cytotoxicity. The present invention also provides cell-targeting molecules, and/or components thereof, which comprise site-specific positions for linking other molecules, such as, e.g., agents that alters a property of the cell-targeting molecule or a cargo for delivery. Certain molecules comprising a polypeptide of the present invention exhibit reduced immunogenicity and/or are well-tolerated by mammals. The cell-targeting molecules of the present invention, and compositions thereof, have uses, e.g., for the selective delivery of cargos to target-expressing cells and as diagnostic and/or therapeutic molecules for the treatment of a variety of diseases, disorders, and conditions, which include genetic disorders, genetic predispositions, infections, cancers, tumors, growth abnormalities, and/or immune disorders.

6. 发明申请

US20210040160A1 HER2-TARGETING MOLECULES COMPRISING DE-IMMUNIZED, SHIGA TOXIN A SUBUNIT SCAFFOLDS 有权
公开(公告)号：US20210040160A1
公开(公告)日：2021-02-11
申请号：US17072562
申请日：2020-10-16
申请人： Molecular Templates, Inc.
发明人： Eric POMA , Erin WILLERT
IPC分类号： C07K14/25 , A61K47/02 , A61K47/26 , A61P35/00 , C07K16/32
摘要： Provided herein are HER2-targeting molecules comprising Shiga toxin A Subunit derived polypeptides having 1) de-immunization and 2) reduced, protease-cleavage sensitivity while retaining Shiga toxin function(s), such as, e.g., potent cytotoxicity via ribosome inhibition. Certain HER2-targeting molecules of the present invention exhibit reduced immunogenic potential in mammals and are well-tolerated by mammals while retaining aforementioned features. The HER2-targeting molecules of the present invention have uses for selectively killing specific cells (e.g., HER positive tumor cells); for selectively delivering cargos to specific cells (e.g., HER positive tumor cells), and as therapeutic and/or diagnostic molecules for treating and diagnosing a variety of conditions, including cancers and tumors involving the expression or over-expression of cell-surface HER2.

7. 发明申请

US20180291359A1 CELL-TARGETING MOLECULES COMPRISING AMINO-TERMINUS PROXIMAL OR AMINO-TERMINAL, SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS 审中-公开
公开(公告)号：US20180291359A1
公开(公告)日：2018-10-11
申请号：US16013600
申请日：2018-06-20
申请人： Molecular Templates, Inc.
发明人： Eric Poma , Erin Willert , Jack Higgins , Jason Kim
IPC分类号： C12N9/24 , C07K16/28 , A61K38/00
摘要： The present invention provides cell-targeting molecules comprising binding regions for cell-type specific targeting and Shiga toxin A Subunit effector regions for Shiga toxin effector functions, wherein the Shiga toxin effector regions are at and/or proximal to an amino-terminus of a polypeptide component of the cell targeted molecule, and optionally comprising a disrupted, furin-cleavage motif between the Shiga toxin effector region and the binding region. The cell-targeting molecules of the invention exhibit a more optimized cytotoxicity and/or improved, in vivo tolerability as compared to related molecules comprising less amino-terminus proximal, Shiga toxin effector regions and/or furin-cleavage sensitive, wild-type, Shiga toxin effector regions. The cell targeting molecules of the invention have uses, such as, e.g., in methods involving targeted killing of cells, delivering exogenous materials into cells, labeling subcellular compartments of cells, and diagnosing and/or treating a variety of conditions, including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.

8. 发明申请

US20170143814A1 IMMUNOTHERAPY USING CELL-TARGETING MOLECULES COMPRISING SHIGA TOXIN A SUBUNIT EFFECTORS AND CD8+ T-CELL EPITOPES 审中-公开
公开(公告)号：US20170143814A1
公开(公告)日：2017-05-25
申请号：US15421758
申请日：2017-02-01
申请人： MOLECULAR TEMPLATES, INC.
发明人： Eric Poma , Erin Willert , Jason Kim
IPC分类号： A61K39/00
CPC分类号： A61K39/0011 , A61K47/6851 , A61K2039/55516 , A61K2039/572 , C07K16/2863 , C07K16/2866 , C07K16/2896 , C07K16/30 , C07K16/3007 , C07K16/32 , C07K2317/622 , C07K2319/33 , C07K2319/55
摘要： The present invention provides cell-targeting molecules which can deliver a CD8+ T-cell epitope cargo to the MHC class I presentation pathway of the cell. The cell-targeting molecules of the invention can be used to deliver virtually any CD8+ T-cell epitope from an extracellular space to the MHC class I pathway of a target cell, which may be a malignant cell and/or non-immune cell. The target cell can then display on a cell-surface the delivered CD8+ T-cell epitope complexed with MHC I molecule. The cell-targeting molecules of the invention have uses which include the targeted labeling and/or killing of specific cell-types within a mixture of cell-types, including within a chordate, as well as the stimulation of beneficial immune responses. The cell-targeting molecules of the invention have uses, e.g., in the treatment of a variety of diseases, disorders, and conditions, including cancers, tumors, growth abnormalities, immune disorders, and microbial infections.

9. 发明申请

US20160177284A1 CELL-TARGETED MOLECULES COMPRISING AMINO-TERMINUS PROXIMAL OR AMINO-TERMINAL SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS 审中-公开
标题翻译：包含氨基端基或氨基末端毒素亚细胞效应区的细胞靶向分子
公开(公告)号：US20160177284A1
公开(公告)日：2016-06-23
申请号：US14965882
申请日：2015-12-10
申请人： MOLECULAR TEMPLATES, INC.
发明人： Eric POMA , Erin WILLERT , Jack HIGGINS , Jason KIM
IPC分类号： C12N9/24 , C07K16/28 , C07K16/14 , C07K16/20 , C07K16/10 , C07K16/18 , C07K16/40 , C07K16/08
CPC分类号： C12N9/2497 , A61K38/00 , C07K16/2803 , C07K16/2896 , C07K2317/622 , C07K2317/76 , C07K2317/77 , C07K2319/33 , C07K2319/55 , C12Y302/02022
摘要： The present invention provides cell-targeted molecules comprising binding regions for cell-type specific targeting and Shiga toxin A Subunit effector regions for Shiga toxin effector functions, wherein the Shiga toxin effector regions are at and/or proximal to an amino-terminus of a polypeptide component of the cell-targeted molecule, and optionally comprising a disrupted, furin-cleavage motif between the Shiga toxin effector region and the binding region. The cell-targeted molecules of the invention exhibit a more optimized cytotoxicity and/or improved, in vivo tolerability as compared to related molecules comprising less amino-terminus proximal, Shiga toxin effector regions and/or furin-cleavage sensitive, wild-type, Shiga toxin effector regions. The cell-targeted molecules of the invention have uses, such as, e.g., in methods involving targeted killing of cells, delivering exogenous materials into cells, labeling subcellular compartments of cells, and diagnosing and/or treating a variety of conditions, including cancers, tumors, other growth abnormalities, immune disorders, and microbial infections.
摘要翻译：本发明提供了包含用于细胞型特异性靶向的结合区域和用于志贺毒素效应子功能的志贺毒素A亚基效应区的细胞靶向分子，其中志贺毒素效应区位于多肽的氨基末端和/或近端细胞靶向分子的组分，并且任选地在志贺毒素效应子区域和结合区域之间包含破坏的弗林蛋白酶裂解基序。本发明的细胞靶向分子与包含较少氨基末端近端，志贺毒素效应子区和/或弗林蛋白酶切割敏感野生型滋贺的相关分子相比，表现出更优化的细胞毒性和/或改善的体内耐受性毒素效应区。本发明的细胞靶向分子具有例如用于靶向杀死细胞的方法，将外源性材料递送至细胞，标记细胞的亚细胞区室以及诊断和/或治疗多种病症（包括癌症）的用途，肿瘤，其他生长异常，免疫疾病和微生物感染。

10. 发明申请

US20160017047A1 CD20-BINDING IMMUNOTOXINS FOR INDUCING CELLULAR INTERNALIZATION AND METHODS USING SAME 审中-公开
标题翻译：用于诱导细胞内含物的CD20结合免疫原和使用其的方法
公开(公告)号：US20160017047A1
公开(公告)日：2016-01-21
申请号：US14774609
申请日：2014-03-11
申请人： MOLECULAR TEMPLATES, INC.
发明人： Eric Poma , Erin Willert , Jason Kim , Jack Higgins , Sangeetha Rajagopalan
IPC分类号： C07K16/28 , C07K14/245
CPC分类号： C07K14/25 , A61K38/00 , A61K2039/505 , C07K14/245 , C07K16/085 , C07K16/20 , C07K16/2863 , C07K16/2866 , C07K16/2887 , C07K16/2896 , C07K16/30 , C07K16/32 , C07K16/40 , C07K2317/56 , C07K2317/569 , C07K2317/622 , C07K2317/73 , C07K2317/77 , C07K2317/92 , C07K2319/00 , C07K2319/33 , C07K2319/55
摘要： The present invention provides CD20-binding proteins that bind to and rapidly internalize CD20 antigens from a cell surface location to the interior of a cell. CD20-binding proteins of the invention comprise a CD20 binding region and a Shiga toxin effector region. Certain of the disclosed CD20-binding proteins kill cells that express CD20 on their surface. Further, the presently disclosed CD20-binding proteins can comprise additional exogenous materials and are capable of targeted delivery of these additional exogenous materials into the interior of CD20 expressing cells. Such additional materials may include peptides, antigens, enzymes, and polynucleotides. These CD20-binding proteins have uses in methods of internalizing themselves, targeted killing of CD20 expressing cells, delivering exogenous materials into CD20 expressing cells, and treating a variety of diseases involving CD20 expressing cells, such as cancers and immune disorders.
摘要翻译：本发明提供结合并快速将CD20抗原从细胞表面位置内部化到细胞内部的CD20结合蛋白。本发明的CD20结合蛋白包含CD20结合区和志贺毒素效应区。某些所公开的CD20结合蛋白杀死表达CD20的细胞。此外，目前公开的CD20结合蛋白可以包含额外的外源性材料，并且能够将这些额外的外源材料靶向递送到表达CD20的细胞的内部。这样的另外的材料可以包括肽，抗原，酶和多核苷酸。这些CD20结合蛋白在自身内化的方法中有用途，靶向杀死表达CD20的细胞，将外源物质递送到CD20表达细胞中，以及治疗涉及表达CD20的细胞例如癌症和免疫疾病的各种疾病。

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