University System of Maryland

Tufts University

The University of Texas System

The Hospital for Sick Children

Fzata, Inc.

Hanping Feng

Charles Bix Shoemaker

Yongrong Zhang

James Eugene Galen

Kevin Chen

Zhiyong Yang

Yixuan Zhu

Hua Yu

Saul Tzipori

Roman Alexander Melnyk

Yongjun Guan

Zhilei Chen

Rudo Simeon

Zeyu Peng

Therwa Hamza

Guilin Yang

Ana M Chamoun-Emanuelli

Lianfa Shi

Yifan Zhang

Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventinginfections using the engineered strains of yeast. These binding agents recognize and bind with specificity totoxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VH peptide monomers, linked groups of VH peptide monomers, VH peptide monomers joined to antibody Fc domains, and VH peptide monomers joined to IgG antibodies.

Yeast-based immunotherapy againstinfection

In an embodiment, the present disclosure pertains to a method of treating or preventinginfections. In some embodiments, the method includes administering an antitoxin to a subject in need thereof. In some embodiments, the antitoxin includes a designed ankyrin repeat protein (DARPin). In an additional embodiments, the present disclosure pertains to a composition including an antitoxin for treating or preventinginfections. In some embodiments, the anti-toxin includes a DARPin. In some embodiments, the anti-toxin is a monomeric or dimeric DARPin for the neutralization oftoxin B (TcdB).

Protein inhibitors of clostridium difficile toxin b

Methods, compositions and kits are provided for treating a subject exposed to or at risk for exposure to a disease agent using a pharmaceutical composition including at least one recombinant heteromultimeric neutralizing binding protein including two or multiple binding regions, such that the binding regions are not identical, and each binding region specifically binds a non-overlapping portion of the disease agent, thereby treating the subject for exposure to the disease agent. In a related embodiment, the heteromultimeric neutralizing binding protein includes two or multiple binding regions that neutralize a plurality of disease agents. In certain embodiments, the disease agent includes a bacterium, a bacterial protein, a virus, a viral protein, a cancer cell, and a protein or molecule produced therefrom. In certain embodiments, the disease agent is a plurality of different disease agents.

Methods, compositions and kits for treating a subject using a recombinant heteromultimeric neutralizing binding protein

Novel, antibody-based binding agents derived from camelid VH and human immunoglobulins are described. These binding agents recognize and bind with specificity totoxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. These binding agents can be used to treat or prevent primary and recurrent CDI. The binding agents include humanized VH peptide monomers, linked groups of humanized VH peptide monomers, humanized VH peptide monomers joined to antibody Fc domains, and humanized VH peptide monomers joined to IgG antibodies.

Humanized tetra-specific octavalent antibody against clostridium difficile toxin A and B

Yeast-based immunotherapy against clostridium difficile infection

A method of protecting a host from an enteric toxigenic pathogen comprises administering a salicylanilide to the host. A method of reducing virulence of an enteric toxigenic pathogen comprises administering a salicylanilide to a host infected with or at risk of infection with pathogen. A method of reducing recurrence of an infection caused by an enteric toxigenic pathogen, comprises administering a salicylanilide to a host previously infected with the pathogen.

Compositions and methods for protecting a host from enteric toxigenic pathogens

Novel, antibody-based binding agents derived from human and camelid immunoglobulins are described. These binding agents recognize and bind with specificity totoxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. These binding agents can be used to treat or prevent primary and recurrent CDI. The binding agents include camelid VH peptide monomers, linked groups of VH peptide monomers, VH peptide monomers joined to antibody Fc domains, and VH peptide monomers joined to IgG antibodies.

Tetra-specific, octameric binding agents and antibodies againsttoxin A and toxin B for treatment ofinfection

Cell-based methods for rapid real time assay of a presence oftoxin and/or cells are provided, using an assay having a toxin-enhancing antibody and a sensitive cell line carrying FcyR receptors, and kits for this assay. An ultrasensitive cell based immunocytotoxicity assay for detecting less then 1 pg/ml oftoxins in clinical samples. A TcdA-specific monoclonal antibody, AIH3, was found to significantly enhance the cytotoxicity of TcdA to macrophages and monocytes. The AIH3-dependent enhancement of glucosyltransferase activity, cytoskeleton disruption, and TNF-a production induced by TcdA was demonstrated also in RAW 264.7 cells. Methods for high level recombinant expression oftoxins incells, and vectors for expression, strains ofcarrying the vectors are provided.

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Growing community of inventors

Ellicott City, MD, United States of America

Hanping Feng