Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

Disclosed herein are compositions and methods of use comprising hexavalent DNL complexes. Preferably, the complexes comprise anti-CD20 and/or anti-CD22 antibodies or fragments thereof. More preferably, the anti-CD20 antibody is veltuzumab and the anti-CD22 antibody is epratuzumab. Administration of the subject hexavalent DNL complexes induces apoptosis and cell death of target cells in diseases such as B-cell lymphomas or leukemias, autoimmune disease or immune dysfunction disease. In most preferred embodiments, the DNL complexes increase levels of phosphorylated p38 and PTEN, decrease levels of phosphorylated Lyn, Akt, ERK, IKKα/β and IκBα, increase expression of RKIP and Bax and decrease expression of Mcl-1, Bcl-xL, Bcl-2, and phospho-BAD in target cells. The subject DNL complexes show EC.sub.50 values for inhibiting tumor cell growth in the low nanomolar or even sub-nanomolar concentration range.

The present invention relates to protein drug conjugates, methods of manufacturing the same and their use in therapy. In particular, the present invention relates to protein drug conjugates comprising a globular protein, an improved linker and a drug for use in targeted drug delivery applications.

Novel antibodies, such as single domain antibodies (sdAbs), or antigen-binding fragments thereof that specifically bind a transferrin are described. Compositions, methods and systems for increasing the half-life of a target protein in a serum using an antibody or fragment thereof against a transferrin are also described.

The present application provides for IL-2 muteins, compositions comprising the same, and methods of using the same.

A method for increasing a lymphocyte count in a subject in need thereof including administering to the subject (i) a modified interleukin-7 of the following formula (I): A−IL-7 wherein A is an oligopeptide consisting of 1 to 10 amino acid residues, and the IL-7 is a polypeptide which is capable of binding to IL-7 receptor; or (ii) an interleukin-7 fusion protein comprising (a) the modified interleukin-7, (b) a second domain containing an oligopeptide having 1 to 10 amino acid residues consisting of methionine, glycine, or a combination thereof; and (c) a third domain which prolongs the half-life of the interleukin-7 fusion protein.

The present invention provides method for promoting the maturation and export of T cells from thymic tissue by contacting the thymic tissue with supraphysiological levels of interleukin (IL)-15. The present invention also provides methods for preventing, alleviating, reducing, and/or inhibiting lymphopenia or peripheral depletion of lymphocytes in a patient in need thereof by administering to the patient IL-15.

The invention relates to a novel antibody capable of binding specifically to the human c-Met receptor and/or capable of specifically inhibiting the tyrosine kinase activity of said receptor, with an improved antagonistic activity, said antibody comprising a modified hinge region.

The invention also relates to a composition comprising such an antibody antagonist to c-Met and its use as a medicament for treating cancer.

Antibodies and meditopes that bind to the antibodies are provided, as well as complexes, compositions and combinations containing the meditopes and antibodies, and methods of producing, using, testing, and screening the same, including therapeutic and diagnostic methods and uses.

The present invention relates, in part, to targeted chimeric proteins with beneficial therapeutic effects, including, for example, effects mediated by chimeric proteins which comprise modified signaling agents two or more targeting moieties. Methods of treatment and pharmaceutical compositions comprising the chimeric proteins are also provided. The present invention finds use in the treatment of various disease and disorders.