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Therapeutic Antibodies for Biofilm Infections

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41AI120425-01
Agency Tracking Number: R41AI120425
Amount: $224,946.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NIAID
Solicitation Number: PA14-072
Timeline
Solicitation Year: 2015
Award Year: 2015
Award Start Date (Proposal Award Date): 2015-07-01
Award End Date (Contract End Date): 2016-06-30
Small Business Information
1505-B O'BRIEN DR
Menlo Park, CA 94025-1435
United States
DUNS: 962700048
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 LAWRENCE KAUVAR
 (415) 567-6815
 kauvarlm@earthlink.net
Business Contact
 STEFAN RYSER
Phone: (650) 616-1100
Email: miltinno@gmail.com
Research Institution
 LA BIOMED RES INST/ HARBOR UCLA MED CTR
 
1124 WEST CARSON ST
TORRANCE, CA 90502-2006
United States

 Domestic Nonprofit Research Organization
Abstract

DESCRIPTION provided by applicant About of serious bacterial infections are biofilm mediated Not only do biofilms provide an anchor and physical protection for bacterial cells but the physiology and genetic programming of bacteria also shifts between the planktonic free floating and sessile stationary states Most notably antibiotic sensitivity differs betwen the two states with bacteria being less sensitive to antibiotics in the sessile state Biofilms ar known to include a variety of polymers and proteins One of these proteins has previously been shown to anchor the three dimensional scaffolding of the polymers Trellis has used its proprietary antibody discovery technology to clone a high affinity antibody from human B lymphocytes TRL that binds the homologs of this protein from both gram positive and gram negative bacteria Extraction of the protein from the biofilm by this antibody leads to the biofilm dissolving in a few hours in vitro as shown for both Staphylococcus aureus and Pseudomonas aeruginosa The proposed work will extend the in vitro characterization to include additional bacterial species more detailed time course and dose response studies Based on those results the antibody will then be tested in a rat model for infective endocarditis using an innovative non invasive monitoring system that detects bacteria engineered to express a luminescent protein If successful this work will provide a compelling rationale to advance TRL into IND enabling manufacturing and toxicity studies for which we plan to seek Phase II funding This antibody offers potential clinical benefit against a wide range of infections that
are currently very difficult to treat Infective endocarditis in particular is a well defined indiction for which current therapy often fails leading to expensive heart valve replacement surgery that has a significant relapse rate re establishment of the biofilm protected infection leading to death

PUBLIC HEALTH RELEVANCE This project will extend to an animal model studies on a native human monoclonal antibody with specificity for a key protein component of bacterial biofilms Antibody mediated extraction of the protein leads to dissolution of the biofilm within a few hours thereby increasing antibiotic efficacy This antibody offers potential clinical benefit against a wide range of infections that are currently very difficult to treat

* Information listed above is at the time of submission. *

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