Compositions and methods for characterization binding proteins are described that include use of a reporting construct that incorporates a bait region that interacts with the binding protein and a reporter that is susceptible to degradation in the reporter's local environment. Complex formation between the bait region and the binding protein provides protection of the susceptible reporter from degradation. Such a reporting construct can be utilized to identify cells expressing a binding protein when the susceptible reporter is susceptible to degradation in cytosol.

The present specification discloses SNAP-25 compositions, methods of making α-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the P.sub.1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, α-SNAP-25 antibodies that bind an epitope comprising a carboxyl-terminus at the P.sub.1 residue from the BoNT/A cleavage site scissile bond from a SNAP-25 cleavage product, methods of detecting BoNT/A activity, and methods of detecting neutralizing α-BoNT/A antibodies.

It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

A method for determining cleavage of a VAMP by a clostridial neurotoxin in a cell that has been contacted with the clostridial neurotoxin under conditions suitable for clostridial neurotoxin activity, the method comprising contacting the cytoplasmic content of the cell with an antibody that binds to a resulting C-terminal product of such cleavage under suitable conditions in vitro or ex vivo and detecting the binding of the antibody to the C-terminal cleavage product. The antibody may, for example, be capable of binding an antigenic polypeptide consisting of 10 to 65 amino acid residues and comprising an epitope comprising an amino acid sequence that is at least 90% identical to an amino acid sequence of at least 8 amino acid residues that is immediately C-terminal to a clostridial neurotoxin cleavage site in the VAMP.

The present disclosure provides antibodies that specifically bind to botulinum neurotoxins (e.g., BoNT/A, BoNT/B, BoNT/C, BoNT/D, BoNT/E, BoNT/F, BoNT/G, etc.) and the epitopes bound by those antibodies. The antibodies and derivatives thereof that specifically bind to the neutralizing epitopes provided herein can be used to neutralize botulinum neurotoxin and are therefore also useful in the treatment of botulism.

The invention relates to the detection of biomarkers, and methods, compositions and kits for the detection of such biological markers for diagnosing various conditions, such as cancer. In particular, the invention relates to the detection of compounds as diagnostic and prognostic markers for detecting cancer, such as oesophago-gastric cancer.

Antibodies that specifically bind to toxins of C. difficile, antigen binding portions thereof, and methods of making and using the antibodies and antigen binding portions thereof are provided herein.

Vesicles that incorporate reporting constructs for characterizing Botulinum neurotoxin protease activity and suitable for use in an assay are provided. The reporting constructs are a pair of recombinant hybrid proteins that act in concert. The reporting constructs are a pair of recombinant hybrid proteins that act in concert, and that include a Botulinum neurotoxin protease recognition and cleavage sequence positioned to release a fluorophore upon cleavage.

Provided herein is a large immuno-sorbent surface area assay (ALISSA) for the rapid and sensitive detection of botulinum neurotoxins (BoNTs) and anthrax toxin. This assay is designed to capture a low number of toxin molecules and to measure their intrinsic protease activity via conversion of a fluorogenic or luminescent substrate. Also provided herein are novel peptides that can be specifically cleaved by BoNT and novel peptides that are resistant to cleavage by BoNT. The combination of these cleavable and control peptides can be used for implementation of an exemplary ALISSA used to specifically detect BoNT enzymatic activity. Furthermore, the ALISSA as described herein may also be used in a column based format for use in a high-throughput system for testing large quantities of samples.

An human antibody or antigen-binding fragment of a human antibody that specifically binds and inhibits human proprotein convertase subtilisin/kexin type 9 (hPCSK9) characterized by the ability to reduce serum LDL cholesterol by 40-80% over a 24, 60 or 90 day period relative to predose levels, with little or no reduction in serum HDL cholesterol and/or with little or no measurable effect on liver function, as determined by ALT and AST measurements.