The present invention relates to therapeutic conjugates with improved ability to target various diseased cells containing a targeting moiety (such as an antibody or antibody fragment), a linker and a therapeutic moiety, and further relates to processes for making and using the conjugates.

The present disclosure is directed to linker-payloads, and salts (including pharmaceutically acceptable salts), solvates, or stereoisomers thereof, comprising a structure of formula I:

##STR00001##

The disclosure is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds, intermediates thereof, and compositions in the prevention or treatment of cancers and/or tumors.

The invention relates to conjugates of biologically active compounds, wherein such a conjugate is comprised of a sequence of amino acids containing a tripeptide that confers selective cleavage by tumor tissue homogenate for release of free drug and/or improves biodistribution into the tumor tissue in comparison to normal tissue homogenate from the same species, wherein the normal tissue is the site of an adverse event associated with administration to a human subject in need thereof of a therapeutically effective amount of a comparator conjugate whose amino acid sequence is a dipeptide known to be selectively cleavable by Cathepsin B.

The present invention provides Polar units, Linker intermediates, Linkers, Drug-Linkers and Conjugates thereof.

The present disclosure provides antibody-drug conjugate structures, where the antibody-drug conjugate includes a cleavable linker containing an ester group that links the antibody to the drug. The disclosure also encompasses compounds and methods for production of such conjugates. In addition, the disclosure also encompasses pharmaceutical compositions and methods of using the conjugates.

The present invention relates to novel anti-NaPi2b antibodies, novel antibody-drug-conjugates (ADCs) based thereon as well as to therapeutic methods and uses thereof, particularly in relation to cancer treatment.

A simpler ADC production method is provided. A method for producing an antibody-drug conjugate including the following step: the step of conjugating a glycan-homogenized antibody and a glycosylated drug. The glycosylated drug consists of a drug bound to a glycan having an oxazolinated reducing end via a linker. The glycan-homogenized antibody and the glycosylated drug can be conjugated with an endo-P-N-acetylglucosaminidase mutant enzyme.

Provided herein are monoclonal antibodies, and antigen-binding fragments thereof, that bind fibroblast growth factor receptor 2 (FGFR2), and methods of use thereof and methods of use thereof. Also included are antibody-drug conjugates (ADCs) comprising the anti-FGFR2 antibodies or antigen-binding fragments thereof linked to a cytotoxic agent, radionuclide, or other moiety, as well as methods of treatment using the same.

The present invention relates to therapeutic ADCs comprising SN-38 attached to an anti-Trop-2 antibody or antigen-binding antibody fragment. The ADC may be administered at a dosage of between 4 mg/kg and 18 mg/kg, preferably 4, 6, 8, 9, 10, 12, 16 or 18 mg/kg, most preferably 8 to 10 mg/kg. When administered at specified dosages and schedules, the ADC can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy. Preferably, the ADC is administered in combination with one or more other therapeutic agents, such as a PARP inhibitor, a microtubule inhibitor, a Bruton kinase inhibitor or a PI3K inhibitor. Most preferably, the ADC is of use for treating a Trop-2 expressing cancer, such as metastatic urothelial cancer.

The present invention relates to an antibody-drug conjugate comprising a monoclonal antibody or an antigen-binding fragment thereof wherein the monoclonal antibody or the antigen-binding fragment thereof binds to Nectin-4 and wherein the drug is an amatoxin, particularly ?-amanitin.