The present invention relates to the fields of molecular medicine and targeted delivery of therapeutic or diagnostic agents to cells outside the vascular system and into the parenchymal tissue of organs within the body. More specifically, the present invention relates to improved TfR-binding moieties based on shark VNARs capable of crossing the blood brain barrier (BBB) and capable of carrying and releasing cargo specifically targeted to the parenchymal tissue of the brain.

The present invention relates to binding molecules comprising two polypeptide chains, wherein the peptide chains comprise modified EHD2 domains allowing heterodimerization only, thereby preventing homodimers, nucleic acids encoding such binding molecules and uses of such binding molecules or nucleic acids encoding such binding molecules in therapy.

This disclosure provides a multimeric binding molecule, e.g., an IgM, IgM-like, IgA, or IgA-like binding molecule, e.g., an antibody with enhanced selectivity for cells expressing a target antigen at high density, e.g., tumor cells. Enhanced selectivity can be achieved, e.g., through modulation of binding affinity for the target antigen and/or through adjusting avidity via multimeric antigen binding.

The invention features polypeptides that include variants of plasminogen activator inhibitor 1 (PAI-1) having a reduced ability to bind with vitronectin, having a reduced ability to interact with the PAI-1 clearance receptor LDL receptor-related protein 1 (LRP1), and having the ability to efficiently inhibit neutrophil elastase in the presence of neutrophil extracellular traps (NETS). In some embodiments, a polypeptide of the invention includes PAI-1 variants optionally fused to an Fc domain monomer or moiety. The invention also features pharmaceutical compositions and methods of using the polypeptides to treat diseases and conditions characterized with aberrant neutrophil elastase activity (e.g., Idiopathic Pulmonary Fibrosis).

The present disclosure provides, inter alia, bivalent small molecules and methods for treating or ameliorating the effects of a disease, such as long QT syndrome, or cystic fibrosis, in a subject, using the bivalent small molecules disclosed herein. Also provided are methods of identifying and preparing small molecule binders that target proteins of interest.

DNA-targeted nanocarriers for encapsulating an active agent and delivering it to extracellular DNA are provided. The nanocarriers, for example, polymeric particles, liposomes, and multilamellar vesicles have targeting moiety that targets DNA conjugated thereto. The targeting moiety that targets DNA is typically an antibody, or variant, fragment, or fusion protein derived therefrom that binds to DNA or nucleosomes. The targeting moiety can be a circulating autoantibody that binds DNA such as those commonly found in patients with SLE. In some embodiments, the targeting moiety is antibody 3E10 or a variant, fragment, or fusion protein derived therefrom. Pharmaceutical compositions, methods of use, and dosage regimens are also provided.

The invention relates to PD-1 binding agents that block the interaction of PD-1 with its ligands, and the use of such binding agents in the treatment, prevention and detection of disease.

The present invention relates to multispecific procoagulant antibodies capable of binding to coagulation Factor IX (FIX) and/or the activated form thereof Factor IXa (FIXa), and Factor X (FX) and/or the activated form thereof Factor Xa (FXa) and promoting FX activation by FIXa, antibodies binding their epitopes or parts thereof and methods and composition for treating subjects suffering from a coagulopathy such as haemophilia A as well as kits, methods of manufacture and methods of use.

This disclosure provides multimeric binding molecules that bind to a human coronavirus, e.g., MERS-CoV, SARS-CoV or SARS-CoV-2. This disclosure also provides compositions comprising the multimeric binding molecules, polynucleotides that encode the multimeric binding molecules, and host cells that can produce the binding molecules. Further this disclosure provides methods of using the multimeric binding molecules, including methods for treating and preventing human coronavirus disease, e.g., coronavirus disease 2019 (COVID-19).

An objective is to provide an Fc-modified antibody or the like having a long serum half-life according to a CCAP method, more specifically, an antibody or the like where IgBP is bound to only one site, based on findings of the inventors. Provided is an objective antibody or the like by purification and production of an Fc-modified antibody or the like with a column bound to an Fc region of an antibody. Specifically, an antibody where only one of two binding sites of Fc is selectively modified is provided by allowing an IgBP-bound antibody produced by a CCAP method to adsorb to a carrier of an IgBP-immobilized column, or forming a state where only one Fc of an antibody is bound to an IgBP binding column and then adding a peptide reagent for CCAP to the column to perform a reaction of a CCAP method in the column.