Immunomedics, Inc.

Christopher A D'Souza

David M Goldenberg

William John McBride

Chien-Hsing Chang

The present invention relates to methods and compositions for pretargeting delivery of therapeutic agents. In preferred embodiments, the pretargeting method comprises: a) administering a bispecific antibody with a first binding site for a disease-associated antigen and a hapten on a targetable construct; b) administering a targetable construct comprising at least one therapeutic agent. In preferred embodiments, the bispecific antibody is made by the dock-and-lock (DNL) technique. In a more preferred embodiment, the targetable construct comprises one or more SN-38 moieties.

Delivery system for cytotoxic drugs by bispecific antibody pretargeting

The present application discloses compositions and methods of synthesis and use ofF- orF-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, theF orF is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may then be directly or indirectly attached to the targeting molecule. In other embodiments, theF orF labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the bifunctional chelating agent bound toF- orF-metal complex may be conjugated to the molecule to be labeled at a reduced temperature, e.g. room temperature.

Methods and compositions for improved F-18 labeling of proteins, peptides and other molecules

The present application discloses compositions and methods of synthesis and use ofF orF-labeled molecules of use in PET, SPECT and/or MR imaging. Preferably, theF orF is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a bifunctional chelating agent, which may be directly or indirectly attached to the targeting molecule. In other embodiments, theF orF labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. The disclosed methods and compositions allow the simple and reproducible labeling of molecules at very high efficiency and specific activity in 30 minutes or less. In preferred embodiments, the labeled molecule may be used for imaging in a subject without purification after labeling.

The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use forF imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitrone or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited toF labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

In vivo copper-free click chemistry for delivery of therapeutic and/or diagnostic agents

The present application discloses compositions and methods of synthesis and use involving click chemistry reactions for in vivo or in vitro formation of therapeutic and/or diagnostic complexes. Preferably, the diagnostic complex is of use forF imaging, while the therapeutic complex is of use for targeted delivery of chemotherapeutic drugs or toxins. More preferably, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment, using a click chemistry reaction involving cyclooctyne, nitron or azide reactive moieties. In most preferred embodiments, the click chemistry reaction occurs in vivo. In vivo click chemistry is not limited toF labeling but can be used for delivering a variety of therapeutic and/or diagnostic agents.

The present application discloses compositions and methods of synthesis and use ofGa,F orF labeled molecules of use in PET or MRI imaging. Preferably, theF orF is conjugated to a targeting molecule by formation of a complex with a group IIIA metal and binding of the complex to a chelating moiety, which may be directly or indirectly attached to the targeting molecule. In other embodiments, theGa,F orF labeled moiety may comprise a targetable construct used in combination with a bispecific antibody to target a disease-associated antigen. In more preferred embodiments, a chelating moiety or targetable construct may be conjugated to a targeting molecule, such as an antibody or antibody fragment.

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Pomona, NY, United States of America

Christopher A D'Souza