Use of Unnatural D-amino Acids to Recruit Endogenous Antibodies as a Novel Antibacterial Therapy

SUMMARY

Lehigh University has developed an unnatural synthetic amino acid (D-dinitrophenyllysine) as a novel single-agent anti-bacterial (gram positive) agent. It has been recently discovered (2009) that almost every straing of bacteria tested (both gram positive and negative), including many that are pathogenic, will incorporate D-amino acids (unnatural and natural amino acids) from their surroundings in their peptidoglycan. Peptidoglycans are structures that serve to reinforce the structural integrity of the cell wall. Here, we propose to use the unnatural D-nitrophenyllysine to induce bacteria to decorate their cell well with this unnatural amino acid. The display of dinitrophenyl on the surface of bacteria is expected to recruit the endogenous anti-dinitro antibodies that exist in human serum. The activation of the endogenous immune system specifically to the bacteria is expected to lead to a selective clearance of the bacteria with little to no side effects to healthy human cells. Human cells do not metabolize/utilize D-amino acids, and therefore, are not expected to recruit dinitrophenyl antibodies.

 

Lehigh Tech ID#032613-01

 

THE MARKET

Antibacterial sales in the seven largest markets—the US, Japan, France, Italy, Germany, Spain and the UK--totaled $19.6 billion in 2009 with the global market being around $30 billion. [1]  As the effects of biofilms in clinical settings can be devastating, pharmaceutical companies are looking for new alternatives to existing antibiotics. In the US alone, an estimated 300 million catheters are used annually [2] and about 3% of all patients receiving catheters develop a biofilm related infection, which can have high mortality rates. The European Centre for Disease Prevention and Control (ECDC) has suggested that some 3 million people per year are infected with multidrug-resistant bacteria with mortality at about 25,000. [3]

 

The antibacterial market is increasingly moving towards the hospital sector where bacterial resistance is of concern due to limited ability to treat serious infections, increased mortality rates, prolonged hospital stays and ultimately higher health costs. There is a growing need to develop a compound that is effective against multiple kinds of bacteria that are now resistant to the antibacterials currently used. [4]

 

[1] “Forecast Insight: Antibacterials.” Report Linker web site. http://www.reportlinker.com/p0487121-summary/Forecast-Insight-Antibacterials.html (accessed April 30, 2012).

[2] Diego Romero and Roberto Kolter, “Will biofilm disassembly agents make it to market?” Cell Press web site. http://download.cell.com/trends/microbiology/pdf/PIIS0966842X11000497.pdf?intermediate=true (accessed May 1, 2012).

[3] http://www.european-hospital.com/en/article/8818-Killing_copper.html , accessed May 3, 2012.

[4] “Analysis of antibacterial market in the hospital sector.” News Medical web site. http://www.news-medical.net/news/20100130/Analysis-of-antibacterial-market-in-the-hospital-sector.aspx (accessed April 30, 2012).

 

THE OPPORTUNITY

Lehigh University is initially interested in identifying industry partners to co-develop the material, ultimately leading to licensing.

App Type Country Serial No. Patent No. File Date Issued Date Expire Date
Provisional [PR] United States 61/815,943 4/25/2013   4/25/2014
Provisional [PR] United States 61/980,334 4/16/2014   4/16/2015
Category(s):
Biology
Chemistry
For Information, Contact:
Thomas Meischeid
Interim Director
Lehigh University
tjm5@lehigh.edu
Inventors:
Marcos Pires
Keywords: