Binding members for sodium channel Nav1.7 and their use in medicine including for treatment of pain or epilepsy. Binding members comprise a fusion protein containing a Nav1.7-binding peptide, e.g., venom toxin peptide or knottin (donor diversity scaffold domain) inserted within an antibody variable domain (recipient diversity scaffold domain), and a partner domain (e.g., antibody variable domain), optionally wherein the partner domain enhances specificity of binding to Nav1.7 over other sodium channels.

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.

Antitumor antagonists that bind specifically to immune checkpoint regulators, angiogenesis pathway regulators and/or TGF pathway regulators are disclosed. Also disclosed are methods for treating proliferative disorders, infections, and immunological disorders with the antitumor antagonists described herein.

This disclosure relates to modified immunoglobulins.

The present disclosure provides antibody cytokine engrafted proteins that bind to and stimulate intracellular signaling through interleukin 10 receptor. Provided antibody cytokine engrafted proteins find use in enhancing anti-inflammatory cell responses, and reducing pro-inflammatory effects in the treatment, amelioration and prophylaxis of immune related disorders. Additionally provided are polynucleotides and vectors that encode antibody cytokine engrafted proteins and host cells capable of producing antibody cytokine engrafted proteins, as well as methods of combining antibody cytokine engrafted proteins with other therapeutics in treating immune related disorder.

The present disclosure provides antigen presenting polypeptide comprising a TGF-? MOD that is reversibly masked and acts as a TGF-? receptor agonist. The antigen presenting polypeptides comprising one or more chemical conjugation sites for incorporation of, for example, epitope containing polypeptides. The present disclosure provides nucleic acids comprising nucleotide sequences encoding antigen-presenting polypeptides comprising one or more chemical conjugation sites, as well as cells genetically modified with the nucleic acids. The antigen-presenting poly peptides and their epitope conjugates are useful for modulating the activity of a T-cell, and accordingly, the present disclosure provides methods of modulating activity of a T-cell in vitro and in vivo as a method of treatment of diseases and disorders including autoimmune diseases, allergies, GVHD, HGVD, and metabolic disorder.

Methods of generating fusion protein variants are provided that comprise introducing sequence diversity at the junction region or regions in the fusion and allows for the generation of variants having a desired activity. Examples include immunoglobulins comprising a domain or polypeptide inserted into, or replacing, a CDR. Also provided are polynucleotides encoding a fusion protein and comprising two or more RSSs, and compositions and host cells comprising same, as well as fusion proteins variants produced by the described methods.

The invention disclosed herein relates to cytotoxic cyclic peptides of Formula (A), methods of inhibiting RNA polymerase with such cyclic peptides, immunoconjugates comprising such cyclic peptides (i.e Antibody Drug Conjugates), pharmaceutical compositions comprising such cyclic peptides immunoconjugates, compositions comprising such cyclic peptides immunoconjugates with a therapeutic co-agent and methods of treatment using such cyclic peptides immunoconjugates:

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The invention relates to a bispecific HER2-targeting agent that includes (a) a first polypeptide ligand that binds to HER2 extracellular domain 1, (b) a second polypeptide ligand that binds to HER2 extracellular domain 4, and (c) a linker covalently attaching said first polypeptide ligand to said second polypeptide ligand.

The invention features isolated mRNAs encoding fusion polypeptides comprising a Stefm A (SteA) scaffold polypeptide and one or more binding polypeptides, such as one or more Bc1-2 homology 3 (BH3) domains, including mRNAs comprising one or more modified nucleobase, and methods of using the same, for example, for inducing apoptosis and/or treating cancer (e.g., liver cancer or colorectal cancer).