[Federal Register Volume 64, Number 31 (Wednesday, February 17, 1999)]
[Notices]
[Pages 7900-7901]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 99-3854]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Government-Owned Inventions; Availability for Licensing

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

ACTION: Notice.

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SUMMARY: 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 U.S.C. 207 to achieve expeditious commercialization of results 
of federally-funded research and development.

ADDRESSES: Licensing information and a copy of the U.S. patent 
applications referenced below may be obtained by contacting J.R. Dixon, 
Ph.D., at the Office of Technology Transfer, National Institutes of 
Health, 6011 Executive Boulevard, Suite 325, Rockville, Maryland 20852-
3804 (telephone: 301/496-7056 ext. 206; fax: 301/402-0220; e-mail: 
[email protected]). A signed Confidential Disclosure Agreement is required 
to receive a copy of any patent application.

Specific Killing of HIV-Infected Lymphocytes by a Recombinant 
Immunotoxin Directed by a Recombinant Immunotoxin Directed Against 
the HIV-1 gp120 Envelope Glycoprotein

Drs. Ira H. Pastan (NCI), Tapan K. Bera (NCI), Paul E. Kennedy (NIAID), 
Edward A. Berger (NIAID), and Carlos F. Barbas III (EM-The Scripps 
Research Institute)
Serial No. 60/088,860--Filed June 11, 1998

    Since the initial isolation of HIV in 1983, and its identification 
as the causative agent of AIDS, tremendous research efforts have been 
expanded to understand the cause and pathogenesis of AIDS, but an 
effective therapy leading to a cure for AIDS has, as of this date, not 
been successful or accomplished. There are several therapeutic drugs 
available to treat infected patients that prolong life and somewhat 
control symptoms.
    The major approaches for the treatment of individuals with AIDS or 
HIV infections are the administration of drugs such as reverse 
transcriptase inhibitors (e.g., AZT (3'-azido-3'-deoxythymidine) or ddi 
(2',3-dideoxyinosine) which act by inhibiting synthesis of proviral 
genome after the virion has entered the host cell and protease 
inhibitors which block the production of infectious virions. Although 
these agents can effectively inhibit HIV spread in vivo and in vitro, 
they do not kill those cells that are already infected with the HIV 
virus. Recently, a highly active antiretroviral therapy (HHAT) shows 
encouraging results in reducing viral load in lymphoid tissue of HIV 
infected patients. In this approach a cocktail consisting of an HIV 
protease inhibitor and two reverse transcriptase inhibitors is 
administered. However, again, while significant progress has been made 
recently in the treatment of HIV-1 infection, we are not yet close to a 
cure for AIDS.
    The technology available from NIH is directed to an immunotoxin 
that specifically binds to and kills cells displaying an HIV gp 120 
coat protein. The immunotoxin comprises an anti-gp 120 antibody 
directed to the conserved CD4 binding site of gp 120 attached to a 
cytotoxin (e.g., a Pseudomonas exotoxin). In one preferred embodiment 
the immunotoxin is a recombinantly expressed fusion protein comprising 
a disultfide linked Fv region attached to a modified Pseudomonas 
exotoxin [i.e., 3B3 (Fv)-PE38]. The technology is directed to a 
pharmaceutical composition, to the composition of the immunotoxin, to 
methods for killing HIV infected cells, and to a kit for killing cells 
that display a gp 120 protein.

Recombinant Anti-Tumor RNases

Drs. Susanna M. Rybak (FCRDC) and Dianne L. Newton (FCRDC)
Serial No. 60/079,751--Filed March 27, 1998

    The above mentioned invention provides for novel recombinant 
ribonuclease proteins which when expressed by bacteria are active 
antitumor agents. Additionally the recombinant ribonucleases of this 
invention can be fused inframe with ligand receptor binding moieties to 
form specifically cytotoxic fusion proteins. Furthermore, these 
proteins are more active than ribonucleases currently available. 
Because these proteins are recombinant proteins, mutations that 
increase cytotoxicity can be engineered. The present invention 
discloses the cloning and the sequence of cDNA from the liver of female 
Rana pipiens that encodes a novel recombinant RNase and describes some 
of the expressed proteins' unique cytotoxic properties. The novel RNase 
is a protent cytotoxic agent to various cancer cell lines (e.g.., 
neoplastic Kaposi's sacrcoma derived endothelial cells) and linked to a 
ligand, such as anti-CD22 antibody, has been found to be efficacious 
against human lymphoma cells.

Targeting Antigens to the MHC Class I Processing Pathway With an 
Anthrax Toxin Fusion Protein

Dr. Kurt R. Klimpel (NIDCR), Theresa J. Goletz (NCI), Naveen Arora 
(NIDCR), Stephen H. Leppla (NIDCR), and Jay A. Berzofsky (NCI)
DHHS Ref. No. E-171-96/0--Filed September 17, 1996; Serial No. 08/
937,276--Filed September 15, 1997

    The mammalian immune system reacts to invading pathogens by 
mounting two broad defenses: the cell-mediated response and the humoral 
response. Viral and other intracellular infections are controlled 
primarily by the cell-mediated immune system. This control is achieved 
through recognition of foreign antigen displayed on the cell surface of 
an infected cell. The objective for a vaccine that stimulates the cell-
mediated immune system is to deliver protein antigens to the cell 
cytosol for processing and subsequent presentation by MHC class I 
molecules. The present

[[Page 7901]]

invention describes a vaccine that stimulates the cell-mediated immune 
system and a method for immunizing mammals. The invention also 
describes a method of inducing antigen-presenting cells to present 
specific antigens using the MHC Class I processing pathway.
    The invention provides a vaccine for inducing an immune response in 
mammals to a specific antigen, where the vaccine comprises a unit dose 
of a binary toxin protective antigen and the antigen, which is bound to 
a binary toxin protective antigen binding protein. In one embodiment 
the vaccine is comprised of an anthrax protective antigen and the 
antigen bound to anthrax protective antigen binding protein. The 
invention also provides a method of immunizing a mammal against an 
antigen using the vaccine, and a method of inducing antigen-presenting 
mammalian cells to present specific antigens via the MHC class I 
processing pathway.
    The advantage of the invention and the anthrax system, unlike other 
bacteria toxin systems which are limited in their capacity to deliver 
large protein antigen to the cell, is the ability to accommodate whole 
protein antigens.
    Some of the major market segments for this technology are: cancer 
vaccine delivery systems; treatment of persistent infectious diseases; 
immunotherapeutics; delivery of DNA vaccines.

    Dated: February 9, 1999.
Jack Spiegel,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer.
[FR Doc. 99-3854 Filed 2-16-99; 8:45 am]
BILLING CODE 4140-01-M