Abstract: Provided herein are isolated CD3×PSMA-bispecific antigen-binding molecules or bispecific antigen-binding fragment thereof wherein a FN3 domain specifically binds human prostate specific membrane antigen (PSMA) and a second antigen-binding site immunospecifically binds CD3. Also described are fusion proteins and related polynucleotides capable of encoding the provided fusion proteins and, cells expressing the provided fusion proteins. In addition, methods of using the provided isolated CD3×PSMA-bispecific antigen-binding molecules or bispecific antigen-binding fragment thereof are described.

Abstract: Macrocyclic chelators for chelation of alpha-emitting radiometal ions, such as actinium-225 are provided. Also provided are radiometal complexes containing an alpha-emitting radiometal ion bound to the macrocyclic chelator via coordinate bonding, and radioimmunoconjugates containing the radiometal complexes covalently linked to a targeting ligand, such as an antibody or antigen binding fragment thereof. The radioimmunoconjugates can be produced by click chemistry reactions. Methods of using the radiocomplexes and radioimmunoconjugates for selectively targeting neoplastic cells for radiotherapy and for treating neoplastic diseases and disorders are also described.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: A fibronectin type III (FN3) domain-nanoparticle or direct conjugate complex containing a polynucleotide molecule, a toxin, polynucleotide molecule or other pharmaceutically active payload is obtained by panning an FN3 domain library with a protein or nucleotide of interest, recovering the FN3 domain and conjugating the FN3 domain with a toxin or nanoparticle containing an active polynucleotide, such as an ASO or siRNA molecule. A fibronectin type III (FN3) domain-nucleic acid conjugate is obtained by panning an FN3 domain library with a protein or nucleotide of interest, recovering the FN3 domain and conjugating the FN3 domain to a nucleic acid (e.g., ASO or siRNA). The nanoparticle complex, nucleic acid conjugate or FN3 domain toxin conjugate may be used in the treatment of diseases and conditions, for example, oncology or auto-immune indications.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.

Abstract: Provided herein are isolated CD3×PSMA-bispecific antigen-binding molecules or bispecific antigen-binding fragment thereof wherein a FN3 domain specifically binds human prostate specific membrane antigen (PSMA) and a second antigen-binding site immunospecifically binds CD3. Also described are fusion proteins and related polynucleotides capable of encoding the provided fusion proteins and, cells expressing the provided fusion proteins. In addition, methods of using the provided isolated CD3×PSMA-bispecific antigen-binding molecules or bispecific antigen-binding fragment thereof are described.

Abstract: PSMA binding FN3 domains, their conjugates, isolated nucleotides encoding the molecules, vectors, host cells, and methods of making thereof are useful in the generation of therapeutic molecules and treatment and diagnosis of diseases and disorders.

Abstract: Cysteine engineered monospecific and bispecific EGFR and/or c-Met FN3 domain containing molecules comprising one or more free cysteine amino acids are prepared by mutagenizing a nucleic acid sequence of a parent molecule and replacing one or more amino acid residues by cysteine to encode the cysteine engineered FN3 domain containing monospecific or bispecific molecules; expressing the cysteine engineered FN3 domain containing molecules; and recovering the cysteine engineered FN3 domain containing molecule. Isolated cysteine engineered monospecific or bispecific FN3 domain containing molecules may be covalently attached to a detection label or a drug moiety and used therapeutically.