Anti-CD74 antibody-drug conjugates are disclosed. The anti-CD74 antibody-drug conjugates comprise an Mcl-1 inhibitor drug moiety and an anti-CD74 antibody or antigen-binding fragment thereof that binds an antigen target, e.g., an antigen expressed on a tumor or other cancer cell. The disclosure further relates to methods and compositions for use in the treatment of cancers by administering the antibody-drug conjugates provided herein. Linker-drug conjugates comprising an Mcl-1 inhibitor drug moiety and methods of making same are also disclosed.

An anti-MEFLIN antibody and a pharmaceutical composition comprising the antibody is described. The pharmaceutical composition may comprise an antibody-drug conjugate (ADC) of the anti-MEFLIN antibody and a cytotoxic agent, which may be connected to each other by a linker. The pharmaceutical composition may be used in the treatment of a cancer in a subject.

The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.

The present invention concerns novel and improved antibody-conjugates for targeting HER2. The inventors found that when antibody-conjugates were prepared using a specific mode of conjugation, they exhibit an improved therapeutic index. The mode of conjugation comprises a first step (i) of contacting a glycoprotein comprising 1-4 core N-acetylglucosamine moieties with a compound of the formula S(F.sup.1).sub.x—P in the presence of a catalyst, wherein S(F.sup.1).sub.x is a sugar derivative comprising x functional groups F1 capable of reacting with a functional group Q.sup.1, x is 1 or 2 and P is a nucleoside mono- or diphosphate, and wherein the catalyst is capable of transferring the S(F.sup.1).sub.x moiety to the core-GlcNAc moiety, to obtain a modified antibody; and a second step (ii) of reacting the modified antibody with a linker-conjugate comprising a functional group Q.sup.1 capable of reacting with functional group F.sup.1 and a target molecule D connected to Q.sup.1 via a linker L.sup.2 to obtain the antibody-conjugate wherein linker L comprises S—Z.sup.3-L.sup.2 and wherein Z.sup.3 is a connecting group resulting from the reaction between Q.sup.1 and F.sup.1. The invention also relates to a use for improving the therapeutic index of an antibody-conjugate and to a method for targeting HER2-expressing cells.

Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

Antibody-drug conjugates, compositions thereof, and methods use. The antibody-drug conjugates include a fusion protein comprising an antibody covalently linked to an ADP-ribosyl cyclase protein via a peptide linker moiety at one or more of a C-terminus or N-terminus of a heavy or light chain of the antibody, a NAD or NMN analogue, and a payload such that the NAD or NMN analogue is conjugated to both the payload and the ADP-ribosyl cyclase protein.

As an antitumor drug which is excellent in terms of antitumor effect and safety, there is provided an antibody-drug conjugate in which an antitumor compound represented by the following formula is conjugated to an antibody via a linker having a structure represented by the following formula: -L.sup.1-L.sup.2-L.sup.F-NH—(CH.sub.2)n.sup.1-L.sup.a-L.sup.b-L.sup.c- wherein the antibody is connected to the terminal of L.sup.1, and the antitumor compound is connected to the terminal of L.sup.c with the nitrogen atom of the amino group at position 1 as a connecting position.

The present invention relates to novel prodrugs of primary or secondary amine- or hydroxyl-comprising biologically active moieties and pharmaceutically acceptable salts thereof, prodrug reagents, pharmaceutical compositions comprising these prodrugs and the use of these prodrugs. A disclosed prodrug may include a biologically active moiety reversibly and covalently linked to a specialized protective group; the linker may be reversible (i.e., hydrolytically cleavable in the absence of enzymes under physiological conditions) and, upon cleavage, may release a drug in its unmodified, pharmacologically active form.

The present invention relates to compounds for targeted immunotherapy, as well as compositions comprising the same. Further, the present invention relates to the use of the compounds in the treatment of diseases such as cancer.