SOUTH SAN FRANCISCO, CA, United States
SOUTH SAN FRANCISCO, CA, United States

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Patent
Avidbiotics Corporation | Date: 2011-05-27

This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous human pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous producer cells that, unlike C. difficile, do not die in the presence of oxygen. Disclosed also is the specific gene of the isolated gene cluster that determines the killing spectrum of the R-type bacteriocin and the demonstration that the killing spectra of diffocins can be altered by engineering orf1374 of the diffocin genetic locus. This invention offers a potent bactericidal agent and a means to make it in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.


Patent
Avidbiotics Corporation | Date: 2014-12-05

This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their 1-2 platform domain, to the intended target cell specifically. The 1-2 domain is contiguous with a heterologous 3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the 3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified 3 domain of a MIC protein.


This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified 1-2 domains of NKG2D ligands.


Patent
Avidbiotics Corporation | Date: 2013-03-14

This disclosure relates to the discovery and isolation of the entire cluster of genes encoding R-type high molecular weight bacteriocins that specifically kill Clostridium difficile bacteria, dangerous pathogens. Also disclosed are methods of producing the R-type bacteriocins in innocuous aerobic producer cells. Disclosed also are small, non-ORF1374 receptor binding domains (RBDs), which are incorporated into diffocins to form engineered or variant diffocins having altered killing spectra. Variant diffocins provided herein may include a heterologous RBD and its cognate base plate attachment region (BPAR), or a fused BPAR. This invention offers a potent bactericidal agent with increased thermal and pH stability, and methods for producing it, in order to kill selectively C. difficile bacteria in the environment of the gastrointestinal tract where they can cause great harm and even death of the infected patient or farm animal.


Patent
Avidbiotics Corporation | Date: 2013-03-12

Recombinant P4 bacteriophage containing modified tail fibers having a base plate attachment region (BPAR) from a P2 bacteriophage gene H product and a heterologous receptor binding domain (RBD) are disclosed. Methods for the use of the recombinant P4 bacteriophage, such as to detect the presence of a target bacterium in a sample, are also described.


Patent
Avidbiotics Corporation | Date: 2015-11-06

The disclosure relates to the identification, cloning, and expression of a genetic locus within a Listeria monocytogenes genome that encodes a phage tail-like bacteriocin (PTLB), termed a monocin. Also provided are non-natural monocins, which have been engineered to have altered bactericidal specificity. Nucleic acid molecules encoding natural or non-natural monocins, vector constructs containing such nucleic acids operably linked to a heterologous promoter, producer cells containing such vectors, the encoded monocins, as well as methods of making and using such monocins are described.


This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified 1-2 domains of NKG2D ligands. This application further relates to modified 1-2 domains of NKG2D ligands attached to polypeptides, in some embodiments antibodies or fragments of antibodies. This application further relates to antigen-binding peptides derived from light and heavy chain antibody variable domains, which contain two linker regions and a split variable domain.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 600.00K | Year: 2012

DESCRIPTION (provided by applicant): The ultimate goal of this proposal and any subsequent phase II proposal is to develop a unique protein agent to prevent Clostridium difficile associated diseases in those patients at high risk rather than wait to treattheir dangerous and costly infections. We aim in this SBIR phase I project to determine the feasibility of oral delivery of a lead, specifically targeted bactericidal protein to eliminate C. difficile cariage without untended collateral damage to the intestinal microbiota. The lead candidate, termed a diffocin , kills 27 of a collection of 28 BI/NAP1/027 strains; and Lawley et al (2010) have described a mouse model of C. difficile carriage. We have recently shown that another engineered R-type bacteriocin administered orally to rabbits can transit the GI tract to act as a specific bactericidal agent killing another bacterial pathogen in the terminal ileum and colon. Thus, after improving the lab scale production of this lead recombinant protein in B. subtilis and conducting preliminary pharmacology and pharmacodynamic studies to guide dosing, we shall evaluate the efficacy of diffocins in C57Bl/6 mice that are asymptomatic carriers and shedders of a sensitive strain of C. difficile. If diffocins eliminateC. difficile from carrier mice, the efect of oral diffocins on the mouse intestinal microbiota will be determined by ribotyping the fecal microbiome of normal and C. difficile carrier mice after diffocin administration. PUBLIC HEALTH RELEVANCE: Clostridium difficile is a bacterium that can reside in human intestines and not cause disease until the healthy bacteria sharing the intestinal space are damaged by antibiotics. Because Clostridium difficile bacteria are usually resistant to antibiotics they can then proliferate, make potent toxins, and cause severe diarrhea and potentially lethal inflammation of the colon. Such infections are now more common in hospitals than MRSA. We have discovered, cloned and made a protein that specifically kills the most toxic form of Clostridium difficile bacteria. We intend to determine whether this agent, a diffocin , when administered orally is capable of eliminating Clostridium difficile bacteria residing innocuously i the intestine of a mouse model of the humaninfection. If so, we plan to develop this bacteria-killing protein as an agent to kill Clostridium difficile present in patients before they receive antibiotics and thereby prevent the severe, recurring infections without damaging the healthy bacteria ofthe gut.


Patent
Avidbiotics Corporation | Date: 2014-06-20

This invention describes soluble, monovalent, non-natural protein molecules that can activate NK cells and certain T-cells to attack specific cellular target cells by attaching the NKG2D-binding portions of monovalent MICA or MICB protein, i.e. their 1-2 platform domain, to the intended target cell specifically. The 1-2 domain is contiguous with a heterologous 3 domain that has been genetically modified to bind directly or indirectly to the extracellular aspect of the target cell, thereby serving as the targeting domain. The genetic modification to create a non-natural and non-terminal targeting motif within the 3 domain can include a portion of an antibody, another protein molecule or portion thereof, a peptide, or a non-natural, modified 3 domain of a MIC protein.


Patent
Avidbiotics Corporation | Date: 2011-10-05

Modified forms of naturally occurring bacteriocins, such as the R-type pyocins of Pseudomonas aeruginosa, are disclosed. The bacteriocins are modified at the ends of their tail fibers in a region responsible for binding specificity and affinity to their cognate binding partners, or receptors, such as those on the surface of bacteria. Methods for the use of the modified bacteriocins, such as to bind receptors, including virulence or fitness factors, on the surfaces of bacteria, are also described.

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