[Federal Register: December 1, 1998 (Volume 63, Number 230)]
[Notices]               
[Page 66190-66191]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr01de98-107]

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health

 
National Institute of Allergy and Infectious Diseases; 
Opportunity for a Cooperative Research and Development Agreement 
(CRADA) to Develop Eosinophil-Derived Neutralizing Agent (EDNA) to 
Treat Infections in Children and the Elderly Caused by Respiratory 
Syncytical Virus and Parainfluenza Virus

AGENCY: National Institutes of Health, Public Health Service, DHHS.

ACTION: Notice.

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SUMMARY: The National Institute of Allergy and Infectious Diseases 
(NIAID) of the National Institutes of Health (NIH) is seeking 
capability statements from parties interested in entering into a 
Cooperative Research and Development Agreement (CRADA) to develop 
eosinophil-derived neutralizing agent (EDNA) for the treatment of 
infections in children and/or the elderly caused by respiratory 
syncytical virus (RSV) and parainfluenza virus (PIV). RSV and PIV are 
medically the most important single-stranded enveloped RNA viruses; 
infections caused by these viruses hospitalize over 100,000 infants per 
year in the U.S.
    EDNA is the major eosinophil ribonuclease. Recombinant human EDNA 
is envisioned as an agent for direct inhalation therapy in patients 
with established RSV or PIV bronchiolitis, in those with a high index 
of suspicion, and as prophylactic therapy in children with predisposing 
conditions (prematurity, bronchopulmonary, dysplasia, congenital heart 
disease, and immunodeficiency).
    Recombinant human EDNA has been produced in bacterial and 
baculovirus expression systems and is not toxic to respiratory 
epithelial cells. ENDA is a soluble and thermostable low molecular 
weight protein not requiring demanding conditions for storage or 
administration. In vitro experiments have shown it to have potent 
antiviral activity against RSV (Domachowske, JB et al. 1998. J. Infect. 
Dis. 177:1458-1464). Initial studies in the Balb/C mouse model of RSV 
infection support its effectiveness against this virus. This project is 
part of the study of ribonucleases and host defense in the Laboratory 
of Host Defenses (LHD), Division of Intramural Research, NIAID.

DATES: Only written capability statements received by the NIAID on or 
before March 1, 1999 will be considered.

ADDRESSES: Capability statements should be submitted to Dr. Michael R. 
Mowatt, Office of Technology Development, National Institute of Allergy 
and Infectious Diseases, National Institutes of Health, 31 Center Drive 
MSC 2137, Building 31, Room 3B62, Bethesda, MD 20892-2137; Tel: 301/
496-2644, Fax: 301/402-7132; Electronic mail: mmowattanih.gov.

SUPPLEMENTARY INFORMATION:
Under the CRADA the production of biologically active recombinant human 
EDNA will be optimized and the agent evaluated in a series of 
preclinical studies in animals as well as initial safety testing in 
humans. Positive outcomes of these studies will indicate continued 
clinical development aimed at supporting regulatory approval of a 
product to be labeled for use in children and/or the elderly. The 
Public Health Service (PHS) has filed patent applications both in the 
U.S. and internationally related to this technology. Notice of the 
availability of the patent application for licensing was first 
published in the Federal Register (Vol. 62, No. 219, page 60909) on 
November 13, 1997.
    NIAID's principal investigator has extensive experience with 
recombinant technology as applied to ribonucleases, their purification 
and testing. The Collaborator in this endeavor is expected to assist 
NIAID in evaluating its current system for producing recombinant EDNA 
and to develop and optimize an alternative expression system, if 
necessary, to manufacture sufficient quantities of the product for 
preclinical testing in animals and initial safety studies in humans. 
The Collaborator must have experience in the manufacture of recombinant 
protein products according to applicable FDA guidelines and Points to 
Consider documents to include Good Manufacturing Procedures (GMP). In 
addition, it is expected that the Collaborator would provide funds to 
supplement the LHD's research budget for the project and to support the 
preclinical and initial human testing.
    The capability statement should include detailed descriptions of: 
(1) Collaborator's expertise in the expression of recombinant proteins, 
(2) Collaborator's ability to manufacture sufficient quantities of the 
product according to FDA guidelines and Points to Consider documents, 
(3) the technical expertise of the Collaborator's principal 
investigator and laboratory group in preclinical safety testing (e.g., 
expertise in in vitro and in vivo toxicity and

[[Page 66191]]

pharmacology studies) and initial human safety studies, and (4) 
Collaborator's ability to provide adequate funding to support 
preclinical and initial human safety studies required for marketing 
approval.

    Dated: November 17, 1998.
Mark Rohrbaugh,
Director, Office of Technology Development, NIAID.
[FR Doc. 98-31920 Filed 11-30-98; 8:45 am]
BILLING CODE 4140-01-M