Neutralizing Monoclonal Antibodies to Respiratory Syncytial Virus


Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis and pneumonia among infants and children under 1 year of age. Illness begins most frequently with fever, runny nose, cough, and sometimes wheezing. During their first RSV infection, between 25% and 40% of infants and young children have signs or symptoms of bronchiolitis or pneumonia, and 0.5% to 2% require hospitalization. Most children recover from illness in 8 to 15 days. The majority of children hospitalized for RSV infection are under 6 months of age. RSV also causes repeated infections throughout life, usually associated with moderate-to-severe cold-like symptoms; however, severe lower respiratory tract disease may occur at any age, especially among the elderly or among those with compromised cardiac, pulmonary, or immune systems.

This invention is a human monoclonal antibody fragment (Fab) discovered utilizing phage display technology. The neutralizing monoclonal antibody was isolated and its binding site was identified. Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant Fab generated by antigen selection from a random combinatorial library displayed on the surface of filamentous phage. In an in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a variety of field isolates representing viruses of both RSV subgroups A and B. The Fab recognized an antigenic determinant that differed from the only other human anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic regimen for RSV infection in humans.

Potential Commercial Applications: Competitive Advantages:
Respiratory Syncytial Virus prophylaxis/therapeutic. 


Development Stage:
The antibodies have been synthesized and preclinical studies have been performed.

Inventors:

James Crowe (NIAID)  ➽ more inventions...

Brian Murphy (NIAID)  ➽ more inventions...

Robert Chanock (NIAID)  ➽ more inventions...


Intellectual Property:
U.S. Pat: 7,488,477 issued 2009-02-10
US Application No. 10/425,855
PCT Application No. PCT/US96/14937
US Application No. 60/003,931
US Application No. 12/082,000
US Application No. 13/250,357
Foreign rights are also available.

Publications:
JE Crowe et al. Isolation of a second recombinant human respiratory syncytial virus monoclonal antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo. J Infect Dis. 1998 Apr;177(4):1073-1076. PubMed abs

Licensing Contact:
Peter Soukas, J.D.
Email: peter.soukas@nih.gov
Phone: 301-496-2644

OTT Reference No: E-001-1996/0
Updated: Sep 1, 2008