[Federal Register Volume 63, Number 235 (Tuesday, December 8, 1998)]
[Pages 67696-67697]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-32491]



National Institutes of Health

National Institute of Diabetes and Digestive and Kidney Diseases; 
Licensing Opportunity and/or Cooperative Research and Development 
Agreement (CRADA) Opportunity to Develop a Hepatitis C virus (HCV) 
Vaccine Based Upon the Synthesis and Purification of Non-infectious 
HCV-like Particles Containing HCV Structural Proteins

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

ACTION: Notice.


SUMMARY: The National Institute of Diabetes and Digestive and Kidney 
Diseases (NIDDK) of the National Institutes of Health (NIH) is seeking 
licensees and/or capability statements from parties interested in 
entering into a Cooperative Research and Development Agreement (CRADA) 
to develop a hepatitis C virus (HCV) vaccine based on in the synthesis, 
large scale production and purification of non-infectious HCV-like 
particles containing HCV structural proteins (Baumert, TF et al. 1998, 
J. Virol. 72:3827-3836).
    The invention claimed in DHHS Reference No. E-009-97/0, ``Synthesis 
and Purification of Hepatitis C Virus-Like Particles In Vitro'' (TJ 
Liang, TF Baumert), field 08 Nov 96, is available for licensing (in 
accordance with 35 U.S.C. 207 and 37 CFR Part 404) and/or further 
development under one or more CRADAs in the clinically important 
applications described below in the Supplementary Information section.

DATES: Only written CRADA capability statements received by the NIDDK 
on or before March 1, 1999 will be considered. There is no deadline by 
which license applications must be received.

ADDRESSES: Capability statements should be submitted to Dr. Michael W. 
Edwards, Office or Technology Development, National Institute Diabetes 
and Digestive and Kidney Diseases, National Institutes of Health, BSA 
Building, Suite 350 MSC 2690, 9190 Rockville Pike, Bethesda, MD 20814-
3800; Tel: 301/496-7778, Fax: 301/402-0535; Electronic mail: 
[email protected].
    Questions about the licensing opportunity, copies of the patent 
application, or requests for license applications should be addressed 
to Carol Salata, Ph.D., Technology Licensing Specialist, Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Rockville, MD 20852-3804; Tel: 301/496-7057 ext. 232; Fax: 
301/402-0220; Electronic mail: [email protected].

SUPPLEMENTARY INFORMATION: HCV is a major causative agent of post-
transfusion and community-acquired non-A, non-B hepatitis world-wide. 
About 4 million people in the U.S. and probably more than 100 million 
worldwide are infected with HCV. The majority of HCV infected 
individuals become persistently infected and many develop chronic 
hepatitis which progresses eventually to liver cirrhosis and 
hepatocellular carcinoma.
    HCV is a member of the flavivirus family. The HCV viron contains a 
positive-strand RNA genome of 9.5 kilobases including a highly 
conserved 5' non-coding region followed by a long open reading frame of 
9030 to 9099 nucleotides that is translated into a single polyprotein 
about 3,010 to 3030 amino acids long. Although the viral genomic 
organization has been characterized in detail, morphologic analysis of 
hepatitis C virus has been hampered by low levels of HCV particles in 
infected patients and the inability to propagate efficiently the virus 
in cultured cells. The levels of the viral particles present in 
infected patient plasma and/or liver tissues are very low, making it 
difficult to visualize the virus. Studies of HCV infection in 
chimpanzees, a reliable animal model for hepatitis C, have provided 
evidence that HCV is inactivated by chloroform, indicating that it 
contains lipids and therefore is probably enveloped. Filtration studies 
have estimated the viron particle size to be about 30-60 nm in 
    Under the CRADA the synthesis, large scale production, and 
purification of HCV virus-like particles 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 humans.
    NIDDK's principal investigator has extensive experience with 
recombinant technology as applied to the synthesis, purification and 
testing of HCV-like particles. The Collaborator in this endeavor is 
expected to assist NIDDK in evaluating its current system for producing 
HCV vaccine formulation and to develop and optimize adjuvants, if 
necessary, to manufacture sufficient quantities of the product for 
preclimical testing in animals and initial safety studies in humans. 
The Collaborator must have experience in the manufacture of vaccine 
formulations 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 NIDDK PI'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 vaccine formulation and development, 
(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, efficacy and 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.
    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 applications for licensing was first 
published in the Federal Register on January 28, 1998 (63 FR 4274). 
Information about the patent applications and pertinent information not 
yet publicly described may be obtained under a Confidential Disclosure 
Agreement. Respondees interested in licensing the invention(s) will be 
required to submit an Application for License to Public Health Service 
Inventions. Respondees interested in submitting a CRADA proposal should 
be aware that it may be necessary to secure a license to the above 
patent rights in order to

[[Page 67697]]

commercialize products arising from a CRADA.

    Dated: December 1, 1998.
Jack Spiegel,
Director, Division of Technology, Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 98-32491 Filed 12-7-98; 8:45 am]