Provided herein are cleavable linkers, pharmaceutical compositions thereof, as well as nucleic acids, and methods for making and discovering the same. The cleavable linkers described herein have improved efficacy and safety.

Compounds and compositions are disclosed in which a NAMPT Drug Unit is linked to a targeting Ligand Unit through a Unit from which a NAMPT inhibitor compound or derivative thereof is released at the targeted site of action. Methods for treating diseases characterized by the targeted abnormal cells, such as cancer or an autoimmune disease, using the compounds and compositions of the invention are also disclosed.

Provided herein are protein complexes comprising a sensor domain and a therapeutic domain linked by a linker, and methods of use thereof. In aspects of the present disclosure, activity of the therapeutic domain comprises a dependence on sensor domain binding to target markers.

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.

Disclosed is an advancement in provoked chemical cleavage. Thereby the invention provides the use of a diene as a chemically cleavable group attached to a Construct, and the use of a dienophile to provoke the release of the Construct by allowing the diene to react with a dienophile capable of undergoing an inverse electron demand Diels Alder reaction with the diene. The invention includes a kit for releasing a Construct C.sup.A bound to a Trigger T.sup.R, the kit having a tetrazine and a dienophile, wherein the Trigger is the tetrazine. The invention also includes the use of the formation of a pyridazine by reacting a tetrazine having a Construct C.sup.A bound thereto and a dienophile, as a chemical tool for the release, in a chemical, biological or physiological environment, of the Construct.

Phosphonate linkers and their use for delivering compounds with passive cell permeability into a cell wherein the phosphonate group facilitates cellular retention of the compound are described.

Hydrophilic Linkers, Drug-Linker compounds, Drug-Ligand Conjugate compounds and Ligand-Linkers and methods of making and using the same are provided.

The invention provides, inter alia, methods of treating a disorder characterized by pathological activity of CD30+ cells, such as in certain solid, hematological and lymphoid cancers, in a non-adult human subject by administering an effective amount of an anti-CD30 ADC (antibody drug conjugate), such as, brentuximab vedotin, to the subject. The invention also provides corresponding kits and articles of manufacture suitable for performing the methods provided by the invention.

The invention relates to anti-CD98 antibodies and antibody drug conjugates (ADCs), including compositions and methods of using said antibodies and ADCs.

One aspect of the present invention provides a compound in which a functional group capable of binding to a globulin Fc region or a physiologically active polypeptide is introduced at one end of a non-peptidic polymer and a functional group capable of a click reaction is introduced at the other end; a polypeptide conjugate in which a physiologically active polypeptide binds to one end of the compound; a physiologically active polypeptide conjugate in which a physiologically active polypeptide and an immunoglobulin Fc region bind to both ends thereof by using the compound as a linker; and methods for preparing the same compound, polypeptide conjugate, and physiologically active polypeptide conjugate.