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    CELL-TARGETING MOLECULES COMPRISING DE-IMMUNIZED, SHIGA TOXIN A SUBUNIT EFFECTORS AND CD8+ T-CELL EPITOPES
    3.
    发明申请
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT ,  Sangeetha RAJAGOPALAN ,  Garrett Lee ROBINSON ,  Brigitte BRIESCHKE ,  Jason KIM

    IPC: A61K39/00 ,  A61K47/68 ,  C07K14/25

    Abstract: 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.

    PROTEINS COMPRISING BINDING REGIONS, SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS, AND CARBOXY-TERMINAL, ENDOPLASMIC RETICULUM LOCALIZATION SIGNAL MOTIFS
    4.
    发明申请
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT ,  Jason KIM ,  Jack HIGGINS

    IPC: C07K14/245 ,  C07K16/28 ,  C07K16/32 ,  C07K16/30 ,  A61K49/00

    Abstract: 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.

    De-immunized, Shiga toxin a subunit scaffolds and cell-targeting molecules comprising the same
    6.
    发明授权
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric Poma ,  Erin Willert ,  Garrett Lee Robinson ,  Sangeetha Rajagopalan ,  Brigitte Brieschke

    IPC: C07K14/25 ,  C07K19/00

    Abstract: 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.

    SHIGA TOXIN A SUBUNIT EFFECTOR POLYPEPTIDES, SHIGA TOXIN EFFECTOR SCAFFOLDS, AND CELL-TARGETING MOLECULES FOR SITE-SPECIFIC CONJUGATION
    7.
    发明申请
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric Poma ,  Erin Willert

    IPC: A61K47/68 ,  A61K38/16 ,  C07K14/195 ,  C07K14/25 ,  A61K8/99

    Abstract: 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.

    HER2-TARGETING MOLECULES COMPRISING DE-IMMUNIZED, SHIGA TOXIN A SUBUNIT SCAFFOLDS
    8.
    发明申请
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT

    IPC: C07K14/25 ,  A61K47/02 ,  A61K47/26 ,  A61P35/00 ,  C07K16/32

    Abstract: 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.

    CELL-TARGETING MOLECULES COMPRISING AMINO-TERMINUS PROXIMAL OR AMINO-TERMINAL, SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS
    9.
    发明申请
    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

    Applicant: Molecular Templates, Inc.

    Inventor： Eric Poma ,  Erin Willert ,  Jack Higgins ,  Jason Kim

    IPC: C12N9/24 ,  C07K16/28 ,  A61K38/00

    Abstract: 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.

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