Federal Register, Volume 64 Issue 3 (Wednesday, January 6, 1999)

[Federal Register Volume 64, Number 3 (Wednesday, January 6, 1999)]
[Notices]
[Pages 903-904]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-240]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing: 
Therapeutic Respiratory Syncytial Virus Monoclonal Antibodies

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

ACTION: Notice.

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SUMMARY: Respiratory Syncytial Virus (RSV) is the major cause of 
serious viral lower respiratory tract illness in infants and children 
worldwide. Research at the National Institutes of Health (NIH) has 
resulted in the discovery of several different anti-RSV monoclonal 
antibody (MAb) technologies important for the treatment of this 
disease. Used separately or in combination, these technologies could 
provide the basis for the commercial development of a new anti-RSV 
therapeutic. The therapeutic technologies available for licensing 
consist of a patented human MAb against RSV, a unpatented panel of 
murine MAbs against RSV and patent applications relating to methods of 
treating RSV infection utilizing more than one antibody. The human and 
murine MAbs bind the F glycoprotein of RSV at different nonoverlapping 
epitopes. A product combining the human MAb with a humanized version of 
a least one of the murine antibodies may provide an improvement to 
current single MAb therapies by reducing the likelihood of the 
formation of RSB escape mutants.

ADDRESSES: Questions about these licensing opportunities, copies of the 
patent and/or patent applications should be addressed to Peter Soukas, 
J.D., Technology Licensing Specialist, Office of Technology Transfer, 
National Institutes of Health, 6011 Executive Boulevard, Suite 325, 
Rockville, Maryland 20852-3804; Telephone: 301/496-7735 ext. 268; Fax: 
301/402-0220; E-mail: [email protected]. A signed Confidential Disclosure 
Agreement will be required to receive copies of the patent application.

SUPPLEMENTARY INFORMATION: The inventions listed below are owned by an 
agency of the U.S. Government and are available for licensing in the 
U.S. in accordance with 35 USC 207 and 37 CFR Part 404 to achieve 
expeditious commercialization of results of federally-funded research 
and development. Foreign patented applications are filed on selected 
inventions to extend market coverage for companies and may also be 
available for licensing.

[[Page 904]]

Human Neutralizing Monoclonal Antibodies to Respiratory Syncytial 
Virus and Human Neutralizing Antibodies to Respiratory Syncytial 
Virus

    Inventors: Robert Chanock, Dennis Burton, Carlos Barbas III, Brian 
Murphy, and James Crowe Jr.
    Serial Number 08/162,102 filed 10 Dec 93 (with priority to 16 Sep 
92) which issued as U.S. Patent Number 5,762,905 on 09 Jun 98 and 
Serial Number 08/920,100 filed 26 Aug 97 (divisional of 08/162,102)
    This invention is a human monoclonal antibody fragment (Fab) 
discovered utilizing phage display technology. It is described in Crowe 
et al., P.N.A.S. 91:1386-1390 (1994) and Barbas et al., P.N.A.S. 
89:10164-10168 (1992). This MAb binds an epitope on the RSV F 
glycoprotein at amino acid 266 with an affinity of approximately 
10⁹ M^-1. This MAb neutralized each of 10 subgroup 
A and 9 subgroup B RSV strains with high efficiency. It was effective 
in reducing the amount of RSV in lungs of RSV-infected cotton rats 24 
hours after treatment, and successive treatments caused an even greater 
reduction in the amount of RSV detected. The invention has been foreign 
filed as PCT/US93/08786.

Murine Monoclonal Antibodies Effective To Treat Respiratory 
Syncytial Virus

    Inventors: Robert Chanock, Brian Murphy, Judy Beeler, and Kathleen 
van Wyke Coelingh
    Available for licensing through a Biological Materials License 
Agreement are the murine MAbs described in Beeler, J. A. et al. 
``Neutralization Epitopes of the F Glycoprotein of Respiratory 
Syncytial Virus: Effect of Mutation Upon Fusion function,'' J. Virology 
63:2941-2950 (1989). The MAbs that are available for licensing are the 
following: 1129, 1153, 1142, 1200, 1214, 1237, 1121, 1112, 1269, and 
1243. One of these MAbs, 1129, is the basis for a humanized murine MAb 
(see U.S. Patent Number 5,824,307 to humanized 1129 owned by MedImmune, 
Inc.), recently approved for marketing in the United States. MAbs in 
the panel reported by Beeler, et al. have been shown to be effective 
therapeutically when administered into the lungs of cotton rats by 
small-particle aerosol. Among these MAbs several exhibited a high 
affinity (approximately 10 \9\M^- \1\) for the RSV F 
glycoprotein and are directed at epitopes encompassing amino acid 262, 
272, 275, 276 or 389. These epitopes are separate, nonoverlapping and 
distinct from the epitope recognized by the human Fab of patent 
5,762,905 (see above for description).

Immunotherapeutic Method of Preventing or Treating Viral 
Respiratory Tract Disease

    Inventors: Robert Chanock, Gregory Prince, James Young, Brian 
Murphy, Val Hemming, Judy Beeler, Kathleen Coelingh Serial Number 08/
479,797 filed 97 Jun 95 (CIP of combined applications 07/555,091 and 
07/937,909)
    Rather than the use of a single monoclonal antibody to treat lower 
respiratory infections, this invention contemplates the use of a 
mixture of neutralizing, prophylactic and therapeutic monoclonal 
antibodies each directed to a specific epitope on the surface of a 
major viral protein (for example, the F glycoprotein of RSV) to treat 
infections. Utilizing a mixture of antibodies significantly lessens the 
possibility of escape mutants. This invention discloses an improved 
method of treating or preventing lower respiratory tract viral diseases 
through the administration of multiple neutralizing and therapeutic 
antibodies in a small particle aerosol. Prior to this invention, there 
has not been a convenient method of administration. Previously, small 
children and infants have only been able to use this therapy when 
incubated and attached to a ventilator. An aerosol nebulizer is 
utilized in this invention. Furthermore, a prophylactic, neutralizing, 
and therapeutic combination of various antiviral agents is also 
described.

    Dated: December 28, 1998.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-240 Filed 1-5-99; 8:45 am]
BILLING CODE 4140-01-M