Provided herein are antibodies comprising non-natural amino acid residues at site-specific positions, compositions comprising the antibodies, methods of their production and methods of their use. The antibodies are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

Isolated or recombinant EphA5 or GRP78 targeting antibodies are provided. In some cases, antibodies of the embodiments can be used for the detection, diagnosis and/or therapeutic treatment of human diseases, such as cancer. A method of rapidly identifying antibodies or antibody fragments for the treatment of cancer using a combination of in vitro and in vivo methodologies is also provided.

The present invention relates to dimers comprising a first polypeptide and a second polypeptide, wherein each of said first and second polypeptide comprises at least one immunoglobulin single variable domain (1ISVD) and a C-terminal extension comprising a cysteine moiety (preferably at the C-terminus), wherein said first polypeptide and said second polypeptide are covalently linked via a disulfide bond between the cysteine moiety of said first polypeptide and the cysteine moiety of said second polypeptide, in which the dimer outperformed the benchmark constructs, e.g. cognate multivalent and multispecific constructs, in various assays. The present invention provides methods for making the dimers of the invention.

This invention relates to prostate-specific membrane antigen (PSMA) antibodies and antibody drug conjugates comprising at least one non-naturally-encoded amino acid. Disclosed herein are αPSMA antibodies with one or more non-naturally encoded amino acids and further disclosed are antibody drug conjugates wherein the αPSMA antibodies of the invention are conjugated to one or more toxins. Also disclosed herein are non-natural amino acid dolastatin analogs that are further modified post-translationally, methods for effecting such modifications, and methods for purifying such dolastatin analogs. Typically, the modified dolastatin analogs include at least one oxime, carbonyl, dicarbonyl, and/or hydroxylamine group. Further disclosed are methods for using such non-natural amino acid antibody drug conjugates, dolastatin analogs, and modified non-natural amino acid dolastatin analogs, including therapeutic, diagnostic, and other biotechnology uses.

Provided herein are modified Fc proteins comprising non-natural amino acid residues at site-specific positions, conjugates of the modified Fc proteins for therapy or diagnosis, compositions comprising the modified Fc proteins and conjugates thereof, methods of their production and methods of their use. The modified Fc proteins and conjugates are useful for methods of treatment and prevention, methods of detection and methods of diagnosis.

The invention relates to anti-HER3 antigen binding proteins, e.g. anti-HER3 antibodies, that bind to the beta-hairpin of HER3, methods for selecting these antigen binding proteins, their preparation and use as medicament.

The invention relates to binding molecules that bind specifically to prostate specific membrane antigen (PSMA), in particular, single human variable heavy chain domain antibodies and related methods for treatment of cancer.

The invention relates to a lock-release method to be applied to biomolecules, such as antibodies, to improve the purification, production, stability and storage of biomolecules. A biomolecule is covalently bound to a polymer support comprising a diketone group so that the biomolecule can be purified, produced and/or stored before being released from the support. The diketone group of the polymer support is a 1,3-ketoester, 1,3-ketothioester or 1,3-ketoamide is a group of Formula (1): R.sup.1 is an optionally substituted hydrocarbyl, perhalogenated hydrocarbyl, or a heterocyclyl group; Y is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group; X is —O, —NR.sup.2 or —S, wherein the free valence of —O, —NR.sup.2 or —S is bonded to the support optionally via a linker; and R.sup.2 is hydrogen, an optionally substituted hydrocarbyl, or a heterocyclyl group. The invention also relates to a polymer support comprising the diketone group. ##STR00001##

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

The present invention relates to an antibody-linker-drug conjugate in which an antibody and a cytotoxic drug are conjugated through an enzyme cleavable peptide linker capable of directly binding to a lysine residue of an antibody, a preparation method therefor, and an anticancer drug composition containing the same as an active ingredient.