The present disclosure provides for dosing regimens for the treatment of patients with cancer, particularly a HER2-expressing cancer, with an anti-HER2 antibody-drug conjugate (ADC). The present disclosure further provides for methods for the treatment of patients with cancer in which an anti-HER2 ADC is administered. In one embodiment, the anti-HER2 ADC is T(kK183C+K290C)-vc0101 (PF-06804103), in which the antibody T(kK183C+K290C) is linked to the auristatin drug 2-methylalanyl-N-[(3R,4S,5S)-3-methoxy-1-{(2S)-2-[(1R,2R)-1-methoxy-2-methyl-3-oxo-3-{[(1S)-2 -phenyl-1-(1,3-thiazol-2-yl) ethyl]amino}propyl]pyrrolidin-1-yl}-5-methyl-1-oxoheptan-4-yl]-N-methyl-L-valinamide (also known as “0101”) via the cleavable linker maleimidocaproyl-valine-citmlline-p-aminobenzyloxycarbonyl (also known as “vc”).

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.

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.

A therapeutic agent capable of binding to the receptor CLPTM1 at the surface of an immune cell and modulating its activity for use in modulating the activity of the immune system to treat cancer, wherein the therapeutic agent is capable of inhibiting the growth and/or viability of an anti-inflammatory and/or immunosuppressive cell to relieve unwanted or deleterious immunosuppression by eliminating anti-inflammatory and/or immunosuppressive immune cells; and/or the therapeutic agent is capable of stimulating an antigen-presenting immune cell and acts to stimulate antigen-presenting immune cells to activate an anti-cancer immune response.

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].

The use of ionic liquids as a solvent for chemoselective bioconjugation reactions is described. For example, methods of preparing bioconjugates in ionic liquids via a phosphine-mediated azide-amine reaction to form a urea linkage between a biomolecule substrate and a second molecule are described. Methods of preparing bioconjugates with amide or enamine linkages in ionic liquids are also described. The methods can be used to prepare tagged biomolecules, such as dye-tagged proteins, peptides, nucleic acids, or saccharides (e.g., aminosaccharides), for use in various applications; to form biomolecule-polymer conjugates; or to form biomolecule-therapeutic agent conjugates, such as antibody-drug conjugates.

The invention relates to novel binder-drug conjugates (ADCs) having improved properties, to active metabolites of these ADCs and to processes for their preparation. The present invention furthermore relates to the use of these conjugates for the treatment and/or prevention of diseases and to the use of these conjugates for preparing medicaments for treatment and/or prevention of diseases, in particular hyperproliferative and/or angiogenic disorders such as, for example, cancer diseases.

The present invention relates to technology capable of labeling a certain site of an antibody with a certain number of chemical functional groups or cargo moieties. The present invention may provide an antibody product having high uniformity. The present invention may provide an antibody product whose antibody functions are not degraded. That is, the present invention may provide an antibody product whose antibody binding affinity and half-life are not degraded. The present invention is of great significance as being the first technology allowing site-specific labeling of an antibody without any complicated processes.