Rutgers, The State University of New Jersey

Georgetown University

Zoltan Szekely

Patrick J Sinko

Xiaoping Zhang

Joseph R Bertino

Chen-Yong Lin

Siang-Yo Lin

The present invention relates to anti-matriptase antibodies and immunoconjugates of anti-matriptase antibodies with cytotoxic agents and the use thereof for killing or inhibiting the growth of matriptase-expressing cancer cells, such as those of multiple myeloma and breast cancers. In particular, immunoconjugates comprising an anti-matriptase monoclonal antibody and anticancer agents such as auristatin, including monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) are introduced, which have potent antitumor activity in vivo. Moreover, importantly; there was no weight loss or other evidence of toxicity in the animals, indicating that no significant free drug was released into the circulation from the conjugate. The present invention also provides compositions comprising these new immunoconjugates and use of them for treatment of malignancies comprising cells that express matriptase. In addition, administration of an anti-matriptase antibody or immunoconjugates of an anti-matriptase antibody and a cytotoxic agent in combination with administration of an immunomodulatory agent, such as thalidomide or an analog thereof, provides a more effective treatment of these cancers.

Targeting tumor cells with chemotherapeutic agents conjugated to anti-matriptase antibodies by in vivo cleavable linking moieties

Peptide ligands for transporting therapeutic agents across the intestinal epithelial barrier that ordinarily are inadequately absorbed and must be delivered by alternative means, which contain an isolated amino acid sequence wherein at least one pair of amino acids are of an opposite charge and the pair members are separated by a spacer of 1-12 amino acid residues including at least one hydrophobic amino acid, and wherein the length of the amino acid sequence is greater than 5 and less than 20 amino acids. Pharmaceutical compositions for gastro-intestinal delivery and methods for the gastrointestinal delivery of poorly absorbed therapeutic agents are also disclosed.

Intestinal peptide targeting ligands

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New Brunswick, NJ, United States of America

Zoltan Szekely