Abstract: Antibody constructs engineered to introduce at least one cysteine insertion mutation (“cysteine engineered antibody constructs”) are described. The inserted cysteine residue(s) may be used as a site for conjugation of one or more active agents to the antibody construct to provide conjugates, such as antibody-drug conjugates.

Abstract: Antibody-drug conjugates (ADCs) comprising an antibody construct that specifically binds c-Met conjugated to one or more drugs, such as the auristatin analogue, compound 1, via a linker. Also described are anti-cMet antibody constructs that have been engineered to include one or more cysteine insertion mutations with each inserted cysteine residue providing a conjugation “handle” allowing for conjugation of a drug-linker to provide an ADC. Further described are multivalent drug-linkers comprising a plurality of the auristatin analogues suitable for use in the ADCs described herein.

Abstract: Systems and methods for polymer sequence prediction are provided. Atomic coordinates for at least the main chain atoms of a polypeptide comprising a plurality of residues is obtained and used to encode the residues into residue feature sets. Each residue feature set comprises, for the respective residue and for each neighboring residue within a nearest neighbor cutoff, an indication of secondary structure, a relative solvent accessible surface area of backbone atoms, and cosine and sine values of backbone dihedrals; a C? to C? distance of each neighboring residue; and an orientation and position of each neighboring residue backbone relative to the backbone residue segment of the respective residue. A residue in the plurality of residues is identified, and the corresponding residue feature set is inputted into a neural network comprising at least 500 parameters, thus obtaining a plurality of probabilities, including a probability for each naturally occurring amino acid.

Abstract: Stabilized TCR constructs comprising a TCR alpha chain polypeptide having a variable alpha (V?) domain and a constant alpha (C?) domain and a TCR beta chain polypeptide having a variable beta (V?) domain and a constant beta (C?) domain. The TCR constructs are stabilized by the introduction into the C? domain and/or the C? domain of stabilizing mutations such as non-naturally occurring disulfide bonds between the C? domain and the C? domain (an interchain disulfide bond), non-naturally occurring intrachain disulfide bonds, point mutations, loop truncation mutations, and combinations thereof. TCR fusion proteins comprising one or more of the TCR constructs and a scaffold and/or other biologically active moiety are also described.

Abstract: Stabilized TCR constructs comprising a TCR alpha chain polypeptide having a variable alpha (V?) domain and a constant alpha (C?) domain and a TCR beta chain polypeptide having a variable beta (V?) domain and a constant beta (C?) domain. The TCR constructs are stabilized by the introduction into the C? domain and/or the C? domain of stabilizing mutations such as non-naturally occurring disulfide bonds between the C? domain and the C? domain (an interchain disulfide bond), non-naturally occurring intrachain disulfide bonds, point mutations, loop truncation mutations, and combinations thereof. TCR fusion proteins comprising one or more of the TCR constructs and a scaffold and/or other biologically active moiety are also described.