The present disclosure relates to antibody conjugates with binding specificity for BCMA (BCMA) and its isoforms and homologs, and compositions comprising the antibody conjugates, including pharmaceutical compositions. Also provided are methods of producing the antibody conjugates and compositions as well as methods of using the antibody conjugates and compositions, such as in therapeutic and diagnostic methods.

Methods for using anti-B7-H4 antibodies and antibody-drug conjugates, including anti-B7-H4 antibody-drug conjugates, to inhibit proliferation of a cell, such as a B7-H4-expressing cell, as well as for the treatment of cancers, such as, e.g., B7-H4-associated solid tumors and breast cancer (e.g., locally advanced or metastatic breast cancer), are provided.

Provided herein are compounds, compositions, and methods for the treatment of diseases and disorders associated with cancer, including tubulysins and protein (e.g., antibody) drug conjugates thereof.

Immunoconjugates of the Formula (I) include a linking group for linking an antibody targeting ligand (Ab) to a drug (D). Embodiments of such immunoconjugates are useful for delivering the drug to selected cells or tissues, e.g., for the treatment of cancer.

Ab-[S-L.sup.1-L.sup.2-L.sup.3-L.sup.4-L.sup.5-L.sup.6-L.sup.7-D].sub.n   (I)

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Provided herein are compounds, compounds including traceless linkers, protein conjugates thereof, and compositions thereof. Also provided herein are methods for the treatment of diseases, disorders, and conditions, and/or the management of the symptoms thereof, associated with inflammatory diseases and autoimmune disorders further associated with the glucocorticoid receptor, glucocorticoid binding, and/or glucocorticoid receptor signalling, including administration of the compounds or payloads via traceless linker-payloads, and protein conjugates thereof.

An antibody-drug conjugate (ADC) has a structure represented by Formula (I): a pharmaceutically acceptable salt thereof wherein Ab is an antibody without glycans (i.e., the protein portion an antibody); G.sub.1 and G.sub.2 are glycan moieties, which may be the same or different; C.sub.n1 and C.sub.n2 are conjugation moieties, which may be the same or different; L.sub.1 and L.sub.2 are linker moieties, which may be the same or different; D.sub.1 and D.sub.2; are drug units which may be the same or different; and x and y are independently an integer from 0 to 8, provided that x+y≠0.

In one aspect, the present disclosure provides compounds of the formula (I): wherein the variables are as defined herein. In another aspect, the present disclosure provides compounds of the formula (V): wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein. In another aspect, the present disclosure provides antibody drug conjugates comprising compounds of the present disclosure. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds and anti-body drug conjugates disclosed herein. ##STR00001##

A novel antibody-pyrrolodiazepine derivative and a novel antibody-pyrrolodiazepine derivative conjugate using the same, comprising substituted benzo[e]pyrrolo[1,2-a][1,4]diazepines represented by the [Formula 24], [Formula 25], [Formula 26], and/or [Formula 27].

This disclosure provides compositions and methods for the targeted and localized in vivo delivery of oligonucleotides. Compositions containing targeted oligonucleotide-HES conjugates are provided as are methods of making and using the conjugates in therapeutic, diagnostic, and other applications. The oligonucleotide-HES complexes contained in the targeted oligonucleotide-HES conjugates can cross membranes in a receptor-independent manner and can deliver oligonucleotides to complementary sequences in the cytosol of live cells in vivo. The targeted oligonucleotide-HES conjugates have uses that include the targeted and/or localized delivery of antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNA, and other nucleic acid sequence in a living organism.