[Federal Register Volume 65, Number 125 (Wednesday, June 28, 2000)]
[Notices]
[Page 39917]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 00-16327]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing: Novel 
Multiple Peptide Conjugate System

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

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies of the U.S. 
Government and are available for licensing in the U.S. in accordance 
with 35 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.
    This novel multiple peptide conjugate system is described in DHHS 
Reference Nos. E-208-99/0, E-280-99/0, and E-114-00/0--all now 
incorporated under a PCT application, DHHS Reference No. E-208-99/1.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by Carol Salata, Ph.D., at 
the Office of Technology Transfer, National Institutes of Health, 6011 
Executive Boulevard, Suite 325, Rockville, Maryland 20852-3804; 
telephone: 301/496-7735 ext. 232; fax: 301/402-0220; e-mail: 
[email protected]. A signed Confidential Disclosure Agreement will be 
required to receive copies of the patent applications.

Novel Multiple Peptide Conjugate System

I. Pathogenic TAT Peptides

Subhash Dhawan, Robert A. Boykins, Kenneth M. Yamada (FDA)

    Infection with HIV, the causative agent of Acquired Immune 
Deficiency Syndrome (AIDS), is responsible for a large number of deaths 
annually and represents a significant threat to human health. 
Accordingly, an extensive effort has been mounted to characterize the 
HIV virus and to identify potential targets for therapeutics. The 
present invention relates to the identification of functional domains 
within the HIV Tat protein which are capable of mediating many of the 
effects of the full length Tat protein. In particular, this invention 
describes the use of peptides comprising functional domains to induce 
an immune response against the HIV Tat protein and the identification 
of dominant-negative mutants and chimeras of these functional domains 
which may be used as therapeutics. Another aspect of the present 
invention relates to the use of these functional domains as reagents 
for elucidating the biochemical mechanisms of HIV gene expression. This 
invention is described further in Boykins et al. July 1999, J. Immunol. 
163:15-20.

II. Multiple Peptide Conjugates

Robert A. Boykins, Manju B. Joshi, Chiang Syin, Subhash Dhawan, Hira 
Nakhasi (FDA)

    This invention describes the design and synthesis of a multi-
peptide conjugate (MPC) system containing antigens from the human 
malaria parasite (Plasmodium falciparium) and the Tat protein of HIV 
type-1 (HIV-1-Tat) for use as a subunit vaccine. Prior multiple antigen 
peptides (MAPs) prepared by the classical solid phase synthesis led to 
heterogeneity, due in part to the aggregation and steric hindrance of 
the growing peptide chains during synthesis. Aggregation of the peptide 
chain may be a factor in the formation of intra-chain hydrogen bonding 
by the peptide backbone, causing the formation of beta sheets or other 
secondary structures. The current multiple peptide conjugates (MPCs) 
have distinct advantages over prior MAPs because only two adjacent 
peptide branches are elongated on the solid phase at either the alpha 
or epsilon amino groups thereby allowing maximum spacing between the 
resin bound peptide chains. Cysteine is inserted at the respective 
position in the sequence thus permitting the thiol groups to be used in 
the formation of stable thioether bonds with haloacetyl peptides 
coupled through solution chemistry. A modification to the coupling 
solvent and key amino acid derivatives are used in the sequence to 
minimize peptide chain aggregation. Furthermore, the elongation of only 
two peptide chains at the alpha or epilson groups of opposite lysine 
residues yields a dimeric or base peptide. These modifications of the 
solid phase methodology for the traditional MAP plus a coupling solvent 
modification, and the addition of key amino acid derivatives for amide 
bond protection allow the synthesis of base peptides on the solid phase 
greater than 7500kDa. These peptides are then reacted with high 
performance liquid chromatography purified haloacetyl peptides to 
generate multiple peptide conjugates with molecular masses of 10 to 13 
kDa. This invention is described further in Boykins et al., Peptides 
Jan 2000;21(1):9-17.

III. HIV-1-Tat-Multiple Peptide Conjugate: A Potential Synthetic AIDS 
Vaccine Candidate

Subhash Dhawan and Robert A. Boykins (FDA)

    The present invention is directed to a novel highly immunogenic 
synthetic multiple peptide conjugate constituting three Tat functional 
domains. Vaccination of mice with this HIV-1-Tat multiple peptide 
conjugate induces an effective immune response to three Tat functional 
domains. Anti-HIV-1-Tat multiple peptide conjugate antibodies 
efficiently inhibit Tat-induced viral activation in monocytes infected 
with HIVBa-L as well as with various clinical HIV-1 isolates, and 
reduce Tat-mediated cytopathicity in infected cells by greater than 
75%. The results indicate that anti-HIV-1-Tat multiple peptide 
conjugate antibodies inhibit viral pathogenesis, possibly by blocking 
functional determinants of Tat and disrupting autocrine and paracrine 
actions of secreted Tat protein. This epitope-specific synthetic Tat 
construct provides a subunit AIDS vaccine for inducing and effective 
immunoprophylaxis response to reduce progression of HIV infection.

    Dated: June 15, 2000.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 00-16327 Filed 6-27-00; 8:45 am]
BILLING CODE 4140-01-P