The present application is directed to compounds of Formula (I)-(VIII): ##STR00001## compositions comprising these compounds and their uses, for example as medicaments and/or diagnostics.

Bispecific antibodies which comprise one antigen-binding region binding to an epitope of human epidermal growth factor receptor 2 (HER2) and one antigen-binding region binding to human CD3, and related antibody-based compositions and molecules, are disclosed. Pharmaceutical compositions comprising the antibodies and methods for preparing and using the antibodies are also disclosed.

The present disclosure relates to benzoselenophene-based compounds, method of preparing the benzoselenophene-based compounds, pharmaceutical compositions and antibody-drug conjugates including the benzoselenophene-based compounds.

A conjugate is disclosed. The conjugate may be represented by Formula I: [D-G-L].sub.n-T Formula I wherein D is a payload molecule; O is an oxygen atom of said payload molecule; T is a targeting unit capable of binding a target molecule, cell and/or tissue; and n is at least 1.

The present invention provides modified catalytic antibody 38C2 with arylation of the reactive lysine residue (Lys99). The Lys99 residue is arylated with a heteroaryl methyl sulfonyl compound such as methylsulfone phenyl oxadiazole (MS-PODA). The invention also provides antibody conjugated agents (e.g., antibody drug conjugates) that contain an agent moiety that is site-specifically conjugated to 38C2 via a methyl sulfonyl compound. Further provided in the invention are methods of making the antibody conjugated agents and therapeutic applications of the antibody conjugated agents.

The invention provides an immunoconjugate comprising an antibody construct which includes an antigen binding domain and an Fc domain, an adjuvant moiety, and a linker, wherein each adjuvant moiety is covalently bonded to the antibody via the linker. Methods for treating cancer with the immunoconjugates of the invention are also described.

Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.

Disclosed herein are non-natural amino acids and dolastatin analogs that include at least one non-natural amino acid, and methods for making such non-natural amino acids and polypeptides. The dolastatin analogs can include a wide range of possible functionalities, but typically have at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid dolastatin analogs and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology use.

A pharmaceutical product for administration of an anti HER2 antibody-drug conjugate in combination with a CDK9 inhibitor is provided. The anti-HER2 antibody-drug conjugate is an antibody-drug conjugate in which a drug linker represented by the following formula (wherein A represents the connecting position to an antibody) is conjugated to an anti-HER2 antibody via a thioether bond. Also provided is a therapeutic use and method wherein the antibody-drug conjugate and the CDK9 inhibitor are administered in combination to a subject: Formula (I):

##STR00001##

This invention concerns the treatment of HER-2 positive breast cancer cells by mediating the signal of GRB7 using an anti-HER-1 antibody, such as panitumumab.