The present invention relates to particular polypeptides, nucleic acids encoding such polypeptides; to methods for preparing such polypeptides; to host cells expressing or capable of expressing such polypeptides; to compositions and in particular to pharmaceutical compositions that comprise such polypeptides, for prophylactic, therapeutic or diagnostic purposes.

The present invention provides a novel, artificially designed antibody molecule comprising: (i) single-domain antigen-binding sites; (ii) antigen-binding Fab fragments; wherein the single-domain antigen-binding site is located at the N-terminus of a light chain variable domain (VL) of the antigen-binding Fab fragment or the C-terminus of a light chain constant region (CL) of the antigen-binding Fab fragment or the single-domain antigen-binding site is located at the N-terminus of a heavy chain variable domain (VH) or the C-terminus of an immunoglobulin CH1 domain of the antigen-binding Fab fragment, the single-domain antigen-binding site and the antigen-binding Fab fragment bind to the same antigen or different antigens, and the single-domain antigen-binding site and the antigen-binding Fab fragment have or do not have a linker peptide therebetween; and (iii) immunoglobulin Fc domains located at the C-terminus of the single-domain antigen-binding site or the antigen-binding Fab fragment.

The present invention also provides a polynucleotide encoding the antibody molecule, a vector comprising the polynucleotide, a host cell comprising the polynucleotide or the vector, an immunoconjugate and a pharmaceutical composition comprising the antibody molecule, and use of the antibody molecule in the immunotherapy, prevention and/or diagnosis of diseases.

Methods are provided for inhibiting bone resorption and/or osteoclast activity. More specifically, methods are provided wherein polypeptides against RANK-L are administered to a subject less frequently and/or at lower dose, while still maintaining effective inhibition of bone resorption and/or osteoclast activity in the subject at unexpectedly prolonged periods of time, particularly in view of the doses administered.

Disclosed are bispecific molecules, referred to herein as ubiquibodies, that are able to ubiquitinate target cell surface receptors on a target cell. The ubiquibodies can be engineered from fusion polypeptides comprising 1) variable domains of antibodies that specifically bind a target cell surface receptor and 2) variable domains of antibodies that specifically bind a transmembrane E3 ubiquitin ligase (TMUL). Either or both components of the ubiquibodies can also be engineered from non-antibody scaffolds including but not limited to nanobodies, monobodies, cyclic peptides, small molecules, and designed ankyrin repeat proteins (Darpins).

Novel, antibody-based binding agents derived from camelid V.sub.HH and human immunoglobulins are described. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. These binding agents can be used to treat or prevent primary and recurrent CDI. The binding agents include humanized V.sub.HH peptide monomers, linked groups of humanized V.sub.HH peptide monomers, humanized V.sub.HH peptide monomers joined to antibody Fc domains, and humanized V.sub.HH peptide monomers joined to IgG antibodies.

The present invention relates, in part, to chimeric proteins comprising mutant interferon-γ and their use as therapeutic agents.

The present invention provides a novel artificial triple-chain antibody comprising three polypeptide chains, wherein a first polypeptide chain comprises a first heavy-chain variable domain, a second polypeptide chain comprises a first light-chain variable domain that is paired with the first heavy-chain variable domain to form a first antigen-binding site; and a third polypeptide chain comprises a second single-domain antigen-binding site and a third single-domain antigen-binding site. The present invention also provides a polynucleotide encoding the triple-chain antibody, a vector comprising the polynucleotide, a host cell comprising the polynucleotide or vector, an immunoconjugate comprising the triple-chain antibody and a pharmaceutical composition comprising the triple-chain antibody or the immunoconjugate thereof, and use of the triple-chain antibody in immunotherapy, prevention and/or diagnosis of diseases.

T cell recruiting polypeptides are provided that bind the constant domain of TCR on a T cell. The polypeptides can be used in methods for treatment of cancers.

This disclosure describes engineered compounds that engage NK cells and methods of using the compounds. Generally, the compound includes an NK engaging domain, a targeting domain that selectively binds to a target cell, and an NK activating domain operably linking the NK engaging domain and the targeting domain.

The present disclosure provides fusion proteins comprising a nanobody and a glycan modifying enzyme. Also provided herein are methods of glycosylating a protein and methods of removing a sugar from a protein. Further provided in the present disclosure are methods of treating and/or diagnosing diseases. Also provided herein are kits, polynucleotides, vectors, and cells.