The present invention provides antibody compounds that contain a substitution of arginine for the reactive lysine residue (Lys99) in the hydrophobic cleft (38C2_Arg). The invention also provides antibody drug conjugate compounds (ADCs) that contain cargo moieties that are site-specifically conjugated to the engineered arginine residue in the 38C2_Arg variant antibody. Further provided in the invention are therapeutic applications of the compounds.

This invention provides a binding modulator (BMOD) system. The BMOD can bind to targeting and/or therapeutic molecule(s) (TO AT) to make a BMOD-TOAT (BMODT) complex. When the BMOD is bound to the TO AT, the BMOD can affect M various properties of the TO AT and/or BMODT complex. A first BMOD can bind to a TO AT to create a BMODT complex to affect properties of the TO AT, and one or more additional BMODs can bind to that BMODT to further modify the properties of the BMODT. This can be used to generate BMODT complex(es) with higher efficacy and functionality than the TOAT that was used to create the BMODT complexes. This higher efficacy could be a result of increased engagement with effector cells caused by the BMOD(s). Antibody biobetters can be made as well by attaching a BMOD to an antibody.

The present disclosure provides compositions and methods for efficient and effective protein delivery in vitro and in vivo. In some aspects, proteins are reversibly crosslinked to each other and/or modified with functional groups and protected from protease degradation by a polymer-based or silica-based nanoshell.

Provided are a compound including a cleavable linker, a use thereof, and an intermediate compound for preparing the same, and more particularly, the compound including a cleavable linker of the present invention may include an active agent (for example, a drug, a toxin, a ligand, a probe for detection, etc.) having a specific function or activity, a SO.sub.2 functional group which is capable of selectively releasing the active agent, and a functional group which triggers a chemical reaction, a physicochemical reaction and/or a biological reaction by external stimulation, and may further include a ligand (for example, oligopeptide, polypeptide, antibody, etc.) having binding specificity for a desired target receptor.

Provided herein are compounds, trifunctional antibody products thereof, and methods and pharmaceutical compositions for use in treatment of inflammatory and/or proliferative diseases.

This application relates to nanoparticles, including nanoparticles derived from a plasma, and their use in the formation of conjugates. The nanoparticles can be stably conjugated to a wide variety of second species, forming conjugates which can be used, for example, in therapeutic, diagnostic and experimental methods.

The invention relates to a chimeric monomer-dimer hybrid protein wherein the protein comprises a first and a second polypeptide chain, the first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and the second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.

A compound for the sequestration of undesirable antibodies associated with hemophilia A, in particular when treated by factor VIII replacement therapy. The compound includes a biopolymer scaffold and at least two peptides derived from factor VIII with a sequence length of 6-13 amino acid, wherein each of the peptides independently includes a 6-amino-acid fragment of the amino-acid sequence of factor VIII, optionally wherein at most three, preferably at most two, more preferably at most one amino acid is independently substituted by any other amino acid. Also provided are pharmaceutical compositions including the compound, as well as methods for treating hemophilia A.

A compound for the sequestration of undesirable neutralizing antibodies against viral vectors in a patient. The compound includes an inert biopolymer scaffold and at least a first peptide n-mer of the general formula P ( - S - P ) .sub.(n-1) and a second peptide n-mer of the general formula P ( - S - P ) .sub.(n-1); wherein, P is a peptide with a sequence length of 2-13 amino acids and S is a non-peptide spacer, independently for each of the peptide n-mers, n is an integer of at least 1, each of the peptide n-mers is bound to the biopolymer scaffold. Independently for each occurrence, P has an amino-acid sequence including a sequence fragment with a length of at least six amino acids of a capsid protein sequence of a viral vector. Compositions including the compound and sequestering and inhibiting methods are also provided.

A compound for the sequestration of undesirable antibodies associated with an autoantibody-mediated condition, such as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), Autoimmune Autonomic Ganglionopathy (AAG), Idiopathic Dilated Cardiomyopathy (IDC), Chronic Chagas heart disease (cChHD) and other neurological, neuromuscular and neuropsychiatric disorders, in particular, autoimmune channelopathies is provided. The compound includes a biopolymer scaffold and at least two peptides with a sequence length of 6-13 amino acid, wherein each of the peptides independently comprises a 6-amino-acid fragment of an amino-acid sequence of a human neuroreceptor, optionally wherein at most three amino acids are independently substituted by any other amino acid. Also provided are pharmaceutical compositions including the compound, as well as methods of ameliorating or treating the conditions mentioned above.