The invention provides anti-HER2 antibodies and immunoconjugates and methods of using the same.

The present invention relates to novel binder-prodrug conjugates (APDCs) where binders are conjugated with inactive precursor compounds of kinesin spindle protein inhibitors, and to antibody-drug conjugates ADCs and to processes for producing these APDCs and ADCs.

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.

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.

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”).

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.

The present invention relates to linkers having a group of propioloyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

This invention describes a method of conjugating a cell binding agent such as an antibody with an effector group (e.g., a cytotoxic agent) or a reporter group (e.g., a radionuclide), whereby the reporter or effector group is first reacted with a bifunctional linker and the mixture is then used without purification for the conjugation reaction with the cell binding agent. The method described in this invention is advantageous for preparation of stably-linked conjugates of cell binding agents, such as antibodies with effector or reporter groups. This conjugation method provides in high yields conjugates of high purity and homogeneity that are without inter-chain cross-linking and inactivated linker residues.

The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.

Provided are compositions and methods for improving tumor penetrability of anti-tumor antibodies or conjugates thereof. The method comprises administering to an individual in need of treatment an anti-idiotypic antibody in addition to the anti-tumor antibody or conjugate. Examples are provided for anti-HER2 antibodies and anti-idiotypic antibodies that are directed to the anti-HER2 antibodies.