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    CD38-BINDING PROTEINS COMPRISING DE-IMMUNIZED SHIGA TOXIN A SUBUNIT EFFECTORS
    1.
    发明公开
    CD38-BINDING PROTEINS COMPRISING DE-IMMUNIZED SHIGA TOXIN A SUBUNIT EFFECTORS 审中-公开

    公开(公告)号：US20240092860A1

    公开(公告)日：2024-03-21

    申请号：US18332366

    申请日：2023-06-09

    Applicant: Millennium Pharmaceuticals, Inc. ,  Molecular Templates, Inc.

    Inventor： Nibedita CHATTOPADHYAY ,  Eric POMA ,  Erin WILLERT

    IPC: C07K14/705 ,  A61P35/00 ,  C12N15/63

    CPC classification number: C07K14/70521 ,  A61P35/00 ,  C12N15/63 ,  A61K38/00

    Abstract: The instant invention provides binding proteins (“CD38-binding proteins”) which each comprise (1) a CD38-binding region for cell-targeting and (2) a Shiga toxin A Subunit effector polypeptide (“Shiga toxin effector polypeptide”). The Shiga toxin effector polypeptide components of the CD38-binding proteins may comprise a combination of mutations relative to a wild-type Shiga toxin sequence providing (1) de-immunization and/or (2) a reduction in protease sensitivity; wherein each Shiga toxin effector polypeptide retains one or more Shiga toxin function, such as, e.g., stimulating cellular internalization, directing intracellular routing, catalytic activity, and/or potent cytotoxicity. The CD38-binding proteins may have one or multiple uses, e.g., the selective killing of a specific CD38-expressing cell-type; and more generally, for the diagnosis and treatment of cancers and disorders involving CD38-expressing cells, e.g., in CD38-positive hematopoietic cancers such as multiple myeloma.

    MHC CLASS I EPITOPE DELIVERING POLYPEPTIDES
    2.
    发明申请
    MHC CLASS I EPITOPE DELIVERING POLYPEPTIDES 有权

    公开(公告)号：US20220306701A1

    公开(公告)日：2022-09-29

    申请号：US17705619

    申请日：2022-03-28

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT

    IPC: C07K14/25 ,  C07K14/245 ,  C12N9/10 ,  C12N9/24 ,  C12N15/62 ,  C07K16/00 ,  C07K16/08 ,  C07K16/10 ,  C07K16/28 ,  C07K16/32

    Abstract: The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

    MULTIVALENT CD20-BINDING MOLECULES COMPRISING SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS AND ENRICHED COMPOSITIONS THEREOF
    4.
    发明申请
    MULTIVALENT CD20-BINDING MOLECULES COMPRISING SHIGA TOXIN A SUBUNIT EFFECTOR REGIONS AND ENRICHED COMPOSITIONS THEREOF 审中-公开

    公开(公告)号：US20180057544A1

    公开(公告)日：2018-03-01

    申请号：US15549099

    申请日：2016-02-04

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT ,  Jason KIM ,  Jack HIGGINS ,  Jensing LIU ,  Rodney FLORES-LEFRANC

    IPC: C07K14/25 ,  C07K16/28

    CPC classification number: C07K14/25 ,  C07K16/2887 ,  C07K2317/35 ,  C07K2317/622 ,  C07K2319/55

    Abstract: The present invention provides multivalent CD20-binding molecules, and compositions thereof, such as enriched compositions comprising large proportions of multivalent CD20-binding molecule relative to monovalent CD20-binding molecule. Certain multivalent CD20-binding molecules of the present invention comprise 1) two or more CD20 binding regions and 2) one or more Shiga toxin effector polypeptide regions derived from an A Subunit of a member of the Shiga toxin family. Certain multivalent CD20-binding molecules of the present invention, and compositions thereof, have uses for selective killing specific cell types and as therapeutics for the treatment of a variety of diseases, including cancers, tumors, and immune disorders. Certain multivalent CD20-binding molecules of the present invention, and compositions thereof, have uses for delivering agents into CD20-expressing cells, including for the intracellular labeling of CD20-expressing cells, collecting diagnostic information, and monitoring the treatment of variety diseases, such as cancers, tumors, and immune disorders which involve CD20-expressing cells.

    MHC CLASS I EPITOPE DELIVERING POLYPEPTIDES
    6.
    发明申请
    MHC CLASS I EPITOPE DELIVERING POLYPEPTIDES 有权

    公开(公告)号：US20210253648A1

    公开(公告)日：2021-08-19

    申请号：US17231526

    申请日：2021-04-15

    Applicant: Molecular Templates, Inc.

    Inventor： Eric POMA ,  Erin WILLERT

    IPC: C07K14/25 ,  C07K14/245 ,  C12N9/10 ,  C12N9/24 ,  C12N15/62 ,  C07K16/00 ,  C07K16/08 ,  C07K16/10 ,  C07K16/28 ,  C07K16/32

    Abstract: The present invention is directed to T-cell epitope delivering polypeptides which deliver one or more CD8+ T-cell epitopes to the MHC class I presentation pathway of a cell, including toxin-derived polypeptides which comprise embedded T-cell epitopes and are de-immunized. The present invention provides cell-targeted, CD8+ T-cell epitope delivering molecules for the targeted delivery of cytotoxicity to certain cells, e.g., infected or malignant cells, for the targeted killing of specific cell types, and the treatment of a variety of diseases, disorders, and conditions, including cancers, immune disorders, and microbial infections. The present invention also provides methods of generating polypeptides capable of delivering one or more heterologous T-cell epitopes to the MHC class I presentation pathway, including polypeptides which are 1) B-cell and/or CD4+ T-cell de-immunized, 2) comprise embedded T-cell epitopes, and/or 3) comprises toxin effectors which retain toxin functions.

    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：US20210008208A1

    公开(公告)日：2021-01-14

    申请号：US16467737

    申请日：2017-12-07

    Applicant: MOLECULAR TEMPLATES, INC.

    Inventor： Eric POMA ,  Erin WILLERT

    IPC: A61K45/06 ,  A61K38/00 ,  C07K14/195

    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.

    CD20-BINDING IMMUNOTOXINS FOR INDUCING CELLULAR INTERNALIZATION AND METHODS USING SAME
    8.
    发明申请
    CD20-BINDING IMMUNOTOXINS FOR INDUCING CELLULAR INTERNALIZATION AND METHODS USING SAME 审中-公开

    公开(公告)号：US20200002387A1

    公开(公告)日：2020-01-02

    申请号：US16568638

    申请日：2019-09-12

    Applicant: Molecular Templates, Inc.

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

    IPC: C07K14/25 ,  C07K16/08 ,  C07K16/20 ,  C07K16/28 ,  C07K16/30 ,  C07K16/32 ,  C07K14/245 ,  C07K16/40

    Abstract: 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.

    CELL-TARGETING MOLECULES COMPRISING DE-IMMUNIZED, SHIGA TOXIN A SUBUNIT EFFECTORS AND CD8+ T-CELL EPITOPES
    10.
    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.

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