Human Monoclonal Antibody To Treat P. aeruginosa Infections in Cystic Fibrosis

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$543,629.00
Award Year:
2007
Program:
STTR
Phase:
Phase I
Contract:
1R41AI072866-01A1
Award Id:
85291
Agency Tracking Number:
AI072866
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
ARIDIS PHARMACEUTICALS, LLC, 5941 Optical Court, SAN JOSE, CA, 95138
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
141088463
Principal Investigator:
ERIC PATZER
(408) 385-1742
PATZERE@ARIDISPHARMA.COM
Business Contact:
PATXER
() -
patzere@aridispharma.com
Research Institution:
BRIGHAM AND WOMEN'S HOSPITAL

BRIGHAM AND WOMEN'S HOSPITAL
RESEARCH ADMINISTRATION
BOSTON, MA, 2115

Domestic nonprofit research organization
Abstract
DESCRIPTION (provided by applicant): Cystic Fibrosis (CF) is an autosomal recessive disorder, which leads to the abnormal composition and physical properties of airway secretions in CF patients. Additionally, the lungs of CF patients are particularly susce ptible to chronic bacterial infections with gt80% of CF patients becoming chronically infected by 18 years of life with mucoid forms of Pseudomonas aeruginosa that over-produce the surface polysaccharide alginate. The long term goal of this project (which is outside the scope of this application) is to investigate the use of alginate specific monoclonal antibodies (mAb) as an immunotherapeutic to treat chronic P. aeruginosa lung infections in CF patients. The major hypothesis to be tested is whether alginat e specific mAbs can be used to reduce P. aeruginosa lung infections and result in improvement in lung function. One key observation of P. aeruginosa infections in CF is that the infection fails to elicit opsonic/protective antibodies in patients. This inef fective immune response allows the organism to escape elimination by acquired host immune defenses and underlies the progressive decline in lung function. The alginate-specific human mAbs are both opsonic and protective against both mucoid strains of P. ae ruginosa as well as classical non- mucoid strains isolated from patients with nosocomial infections. Preliminary data indicate that these human mAbs recognize an epitope on alginate that is defined by the highly charged carboxylic acid component of the uro nic acid monomers that make up alginate, and represent a broadly reactive epitope that may be an effective target for immunotherapeutic intervention. In this application, we propose further preclinical development of alginate-based immunotherapeutics by pr eparing and testing the protective activities of a human mAb against acute P. aeruginosa pulmonary infection in wild-type (WT) mice and chronic P. aeruginosa oropharyngeal colonization and lung disease in transgenic CF mice. We will first develop cell cult ure processes to provide sufficient quantities of a mAb to perform preclinical testing in animal models and to determine whether the existing cell lines expressing mAb will be adequate to provide sufficient quantities for clinical testing. We will also inv estigate whether a mAb can be formulated and delivered optimally as a liquid in a mouse inhalation model. The studies proposed in this application are designed to further development of a human monoclonal antibody to treat chronic Pseudomonas aerug inosa lung infections of CF patients. At present, 80-95% of CF patients ultimately succumb to respiratory failure due to chronic P. aeruginosa infection and airway inflammation.

* information listed above is at the time of submission.

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