The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.

Herein is reported a method for the humanization of non-human antibodies using a structure-based scoring matrix. With the scoring matrix it is possible to determine (the requirement for and) the suitability of specific (back)mutations of amino acid residues at defined positions of a selected human germline sequence. The scoring matrix takes into account the topology, the three-dimensional structure and the interactions of the respective residue and change. Thereby the influence on antigen binding of a specific amino acid residue change can be determined.

The present invention relates to peptides that bind with high specificity and which functionally interact with the transferrin receptor (“TfR”) and which may be used in making molecular vehicles that carry biomolecules across membranes, including, e.g., across the blood brain barrier or the gastrointestinal tract. TfR specific binding moieties may also be used alone or as components in specific molecules that target the transferrin/transferrin receptor transport system. The invention relates more specifically to VNAR single chain antibodies derived from nurse shark that bind to TfR, compounds and compositions comprising a TfR specific VNAR binding moiety, methods for preparing them, diagnostic and therapeutic methods of use in vitro or in vivo, e.g., to diagnose, treat and/or prevent a pathological condition, disorder or disease in which it is beneficial to deliver a heterologous biomolecule across the blood brain barrier by association with a TfR specific VNAR binding moiety. Other uses for TfR specific VNAR binding moieties of the invention include, e.g., regulating the interaction of iron-charged transferrin with TfR (receptor cycling or cell surface presentation), such as may be therapeutic in treatment of certain cancer cells and tumors of various tissue types.

The present invention discloses a mouse-human chimeric antibody preferably recognizes the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and the encoding sequences, wherein the monoclonal antibody having a light chain and a heavy chain. Moreover, the present invention provides humanized light and heavy chains, and the encoding sequences. The results of paired expression show that humanized antibodies also recognize the MUC1 glycopeptide epitope RPAPGS(GalNAc)TAPPAHG (SEQ ID NO.: 34) on the surface of cancer cells, and show the same specificity as the parental antibody.

The present invention relates to amino acid sequences that are directed against proteins from the group of the Angiopoietin/Tie family such as Tie1, Tie2, Ang1, Ang2, Ang3, Ang4, Angptl1, Angptl2, Angptl3, Angptl4, Angptl5, Angptl6, as well as to compounds or constructs, and in particular proteins and polypeptides, that comprise or essentially consist of one or more of such amino acid sequences.

Isolated binding proteins, e.g., antibodies or antigen binding portions thereof, which bind to tumor necrosis factor-alpha (TNF-α), e.g., human TNF-α, and related antibody-based compositions and molecules are disclosed. Also disclosed are pharmaceutical compositions comprising the antibodies, as well as therapeutic and diagnostic methods for using the antibodies.

Cytotoxic conjugates comprising a cell binding agent and a cytotoxic agent, therapeutic compositions comprising the conjugate, methods for using the conjugates in the inhibition of cell growth and the treatment of disease, and a kit comprising the cytotoxic conjugate are disclosed are all embodiments of the invention. In particular, the cell binding agent is a monoclonal antibody, and epitope-binding fragments thereof, that recognizes and binds the CA6 glycotope. The present invention is also directed to humanized or resurfaced versions of DS6, an anti-CA6 murine monoclonal antibody, and epitope-binding fragments thereof.

The invention relates to an antibody molecule having specificity for antigenic determinants of IL-17, therapeutic uses of the antibody molecule and methods for producing said antibody molecule.

Provided herein are antibodies and antigen-binding fragments thereof with low or no immunogenicity in humans and optionally with desirable manufacturing properties. Also provided are compositions comprising such antibodies or antigen-binding fragments, methods of using such antibodies, and methods for making such antibodies.

The application relates to a dual cytokine fusion protein composition, pharmaceutical composition, and/or formulation thereof comprising IL-10 or IL-10 variant molecules fused to a single chain variable fragment scaffolding system and a second cytokine, where the second cytokine is linked in the hinge region of the scFv. The application also relates to methods of using the dual cytokine fusion protein composition for treating cancer, inflammatory diseases or disorders, and immune and immune mediated diseases or disorders.