[Federal Register Volume 69, Number 57 (Wednesday, March 24, 2004)]
[Notices]
[Pages 13856-13858]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-6608]


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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, HHS.

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. Foreign patent 
applications are filed on selected inventions to extend market coverage 
for companies and may also be available for licensing.

ADDRESSES: Licensing information and copies of the U.S. patent 
applications listed below may be obtained by writing to the indicated 
licensing contact at the Office of Technology Transfer, National 
Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, 
Maryland 20852-3804; telephone: (301) 496-7057; fax: (301) 402-0220. A 
signed Confidential Disclosure Agreement will be required to receive 
copies of the patent applications.

Cell-Based Assay of I-kappaB Kinase Activity

    Richard Eric Davis et al. (NCI).
    DHHS Reference No. E-109-2004/0--Research Tool.
    Licensing Contact: Mojdeh Bahar; (301) 435-2950; 
[email protected].
    The present invention is directed to a cell-based assay of I-kappaB 
Kinase (IKK) Activity, providing a facile probe for cellular assays of 
activity/activation and drug screening. IKK activation is essential to 
diseases including certain types of cancer and undesired immune 
responsiveness such as autoimmunity and transplant rejection. In the 
assay, cells of interest are engineered to express an easily-measured 
exogenous form of IkB, driven by a promoter that is relatively 
independent of Nuclear factor of Kappa-B (NFkB) activity. Since the 
rate of synthesis of the ``reporter'' from the IkB is stable, its level 
is then principally determined by its rate of degradation, and 
therefore correlates inversely with IKK activity.
    The assay has been used to screen molecules for their IKK inhibitor 
activity, determine whether the toxicity of agents towards NFkB-
dependent lines occurs via the inhibition of IKK, and to determine 
whether genetic manipulations such as overexpression, exogenous 
mutants, or RNA interference affect constitutive or inducible IKK 
activity or activation.
    Available materials include retroviral plasmids encoding the 
reporter or controls, and cell lines stably infected with these 
plasmids and validated in the assay. These reporter cell lines have IKK 
activity that is either constitutively high or easily inducible through 
various pathways (TNF-alpha, CD40L, IL-1beta, etc.).

Specific Antibodies to the Lymphatic Endothelial Cell Specific 
Hyaluronic Acid Receptor, LYVE-1

    Sam T. Hwang, Adela R. Cardones (NCI).
    DHHS Reference No. E-107-2004/0--Research Tool.
    Licensing Contact: Mojdeh Bahar; 301/435-2950; [email protected].
    This invention is drawn to specific anti-sera to human LYVE-1. 
LYVE-1 is a lymphatic endothelial cell-specific transmembrane form of 
CD44 that may have a role in recruitment of immune cells and cancer 
cells to lymphatics. Following skin-immunization of 10 mice with cDNA 
encoding human LYVE-1, the inventors have developed specific anti-sera 
to human LYVE-1. The anti-sera work well for flow cytometry and 
fluorescence microscopy and recognize native LYVE-1 epitopes. The 
antibody would be useful to scientists studying the role of lymphatic 
vessels in immune diseases and cancer. It may also be useful for 
clinical

[[Page 13857]]

pathologists. Commercially available LYVE-1 antibodies have drawbacks 
as they do not work well for flow cytometry analysis or tissue 
staining.

Peptide Inhibitors of HIV-1 Integrase Useful for the Treatment of 
Retroviral Infection and HIV

    Drs. Peter Roller, Christophe Marchand, Krysztof Krajewski, Vinay 
K. Pathak, Yijun Zhang, and Yves Pommier (NCI).
    U.S. Provisional Application No. 60/534,378 filed 06 Jan 2004 (DHHS 
Reference No. E-039-2004/0-US-01).
    Licensing Contact: Sally Hu; 301/435-5606; e-mail: [email protected].
    The invention describes the discovery of short peptides, derived 
from the natural peptide named indolicidin that have an ability to 
inhibit HIV-1 integrase and exhibit antiviral activity. In particular, 
this invention shows that synthesized derivatives of the indolicidin 
peptides named RIN-25 exhibit a significant higher anti-viral and anti-
integrase activity when compared to the parent compound named RIN-42. 
HIV-1 integrase has a good potential of being the next therapeutic 
target since HIV-1 integrase is essential for viral replication and 
there is no cellular equivalent. Thus, subject invention may be used in 
the development of therapeutics for the treatment of retroviral 
infections, such as AIDS, or other retroviral-related diseases (i.e., 
cancer, immune disorders). In addition, these novel peptides described 
in this invention may also have particular value when used in 
combination treatments with other antiviral therapies directed at other 
viral targets, such as protease and reverse transcriptase.

Multipotent Postnatal Stem Cells From Human Periodontal Ligament and 
Uses Thereof

    Dr. Songtao Shi et al. (NIDCR).
    U.S. Provisional Application filed 20 Nov 2003 (DHHS Reference No. 
E-033-2004/0-US-01).
    Licensing Contact: Marlene Shinn-Astor; (301) 435-4426; 
[email protected].
    It is estimated that over 40 percent of the adult population in the 
United States has periodontal disease in one form or another. 
Periodontal Disease is a chronic infection of the periodontal ligament 
(PDL) and the adjacent bone and cementum. The effects of Periodontal 
Disease range from simple gum inflammation to, in extreme cases, tooth 
loss.
    The NIH announces a new technology wherein stem cells from the PDL 
have been isolated from adult human PDL. These cells are capable of 
forming cementum and PDL in immunocompromised mice. In cell culture, 
PDL stem cells differentiate into collagen fiber forming cells 
(fibroblasts), cementoblasts, and adipocytes. It is anticipated that 
these PDL stem cells will be useful for periodontal tissue regeneration 
to treat periodontal disease.

A Novel Interferon-Gamma-Inducible Secretoglobin

    Anil B. Mukherjee et al. (NICHD).
    U.S. Provisional Application No. 60/534,381 filed 06 Jan 2004 (DHHS 
Reference No. E-028-2004/0-US-01).
    Licensing Contact: Michael Ambrose; (301) 594-6565; 
[email protected].
    Interferons (IFNs) are a family of cytokines that are paramount in 
protecting the host from viral infections. The effects of the IFNs is 
mediated through interactions with specific cellular receptors, 
activation of second messenger systems effecting the expression of 
several antiviral and immunomodulatory proteins.
    This invention describes a novel gene that is induced by IFN-gamma 
treatment of lymphoblast cells. This gene, termed IIS (IFN-inducible 
Secretoglobin), is a member of the uteroglobin (UG) superfamily and 
shares 30% amino acid identity with uteroglobin (UG), the founding 
member of the secretoglobin family of proteins. Data shows that IIS is 
expressed in virtually all tissues with highest levels found in lymph 
nodes, tonsils, lymphoblasts and ovary. IIS levels are also highly 
elevated in CD8+ and CD19+ cells. In further 
experiments, antisense-s-oligonucleotides to IIS are shown to prevent 
chemotactic migration and invasion of immune cells. Taken together, 
these data give insight into the immunological function of this novel 
IIS gene.

Method Evolved for Recognition of Thrombophilia (MERT)

    Cigdem F. Dogulu et al. (NICHD).
    DHHS Reference No. E-282-2003/0-US-01 filed 15 Jan 2004.
    Licensing Contact: Fatima Sayyid; 301/435-4521; 
[email protected].
    Venous thrombosis affects 1 per 1000 individuals annually and is 
one of the leading causes of mortality and morbidity resulting in 
approximately 300,000 hospitalizations and 50,000 fatalities per year 
in the United States alone.
    Although venous thrombosis is one of the leading causes of 
morbidity and mortality in developed countries, it is an avoidable 
disease by the use of prophylactic treatment that is currently 
available. To avoid the development of venous thromboembolism, it is 
beneficial to estimate the individual thrombotic risk to develop 
stratification protocols for an individual risk-adapted prophylaxis.
    This invention proposes methods to predict an individual's genetic 
susceptibility to venous thrombosis, as well as arrays and kits that 
can be used to practice such methods. The method includes screening for 
combinations of mutations and polymorphisms in venous thrombosis-
related molecules such as factor V, prothrombin (factor II), 
fibrinogen, protein C, protein S, antithrombin III, angiotensin I-
converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR) 
that allow one to predict the genetic susceptibility of an individual 
to developing venous thrombosis with high accuracy in several ethnic 
populations.

Stimulation or Inhibition of Gamma Delta T-Cells To Promote or Inhibit 
Bone Growth

    Dr. Nona T. Colburn (NIAMS).
    U.S. Provisional Application filed 07 Nov 2003 (DHHS Reference No. 
E-277-2003/0-US-01).
    Licensing Contact: Marlene Shinn-Astor; (301) 435-4426; 
[email protected].
    Bone injury is a common occurrence that disables people from 
working and otherwise carrying on their daily lives and is an important 
health concern. When fracture healing does not go as intended, the 
ability of a bone to heal without a scar is lost. This can result in 
disfigurement, pain, and loss or impairment of bodily function. It has 
been shown that within the segment of the clinical population afflicted 
with non-healing fractures, a large number of these non-unions are a 
direct result of the patient's immune system status. Bone repair 
involves a series of phases, the first of which is the initial 
inflammatory phase controlled by the body's innate immune response. Of 
those first responder cells are the gamma delta T-cells that are 
capable of recognizing products of cell damage. This technology relates 
to the stimulation or inhibition of the gamma delta T-cells to modulate 
bone growth. It is anticipated that the manipulation of the gamma delta 
T-cell population will reduce the need to perform operations such as 
bone grafting which are currently used to treat non-unions.

[[Page 13858]]

Methods for Inhibiting HIV and Other Viral Infections by Modulating 
Ceramide Metabolism

    Robert Blumenthal, Catherine M. Finnegan (NCI).
    U.S. Provisional Application No. 60/528,411 filed 09 Dec 2003 (DHHS 
Reference No. E-265-2003/0-US-01).
    Licensing Contact: Sally Hu; (301) 435-5606; [email protected].
    This invention provides methods of inhibiting or preventing HIV-1 
infections by inducing either the de novo biosynthesis of ceramide, or 
by activating enzymes (e.g., sphingomyelinase) involved in the 
generation of ceramide at the plasma membrane, or by direct 
incorporation of exogenous ceramide into target cell membranes. The 
invention describes methods for administration of a retinamide 
compound, particularly an N-(aryl) retinamide compound such as N-(4-
hydroxyphenyl) retinamide (4-HPR) resulting in increased plasma 
membrane ceramide levels, which results in the inhibition of HIV-1 
infection in monocyte/macrophages by perturbing membrane organization. 
In addition, because of its low toxicity in non-tumor cells, 4-HPR and 
related compounds are particularly suitable for long-term preventative 
or therapeutic administration to subjects suffering from an HIV 
infection or who are at risk of contracting an HIV infection. Thus, 
this invention provides a novel means of treating or inhibiting HIV and 
other viral infections by administering a retinamide compound to a 
patient suffering from or susceptible to such a viral infection.

ELISA Assay of Serum Soluble CD22 To Assess Tumor Burden/Relapse in 
Subjects With Leukemia and Lymphoma

    Robert Kreitman et al. (NCI).
    PCT Application No. PCT/US03/16298 filed 20 May 2003 (DHHS 
Reference No. E-065-2002/0-PCT-02), with priority to 20 May 2002.
    Licensing Contact: Jesse Kindra; (301) 435-5559; 
[email protected].
    Disclosed are methods of using previously unknown soluble forms of 
CD22 (sCD22) present in the serum of subjects with B-cell leukemias and 
lymphomas to assess tumor burden in the subjects. Also disclosed are 
methods of diagnosing or prognosing development or progression of a B-
cell lymphoma or leukemia in a subject, including detecting sCD22 in a 
body fluid sample taken or derived from the subject, for instance, 
serum. In some embodiments, soluble CD22 levels are quantified. By way 
of example, the B-cell lymphoma or leukemia can be hairy cell leukemia, 
chronic lymphocytic leukemia, or non-Hodgkin's lymphoma. Soluble CD22 
in some embodiments is detected by a specific binding agent, and 
optionally, the specific binding agent can be detectably labeled.
    Also disclosed are methods of selecting a B-cell lymphoma or 
leukemia therapy that include detecting an increase or decrease in 
sCD22 levels in a subject compared to a control, and, if such increase 
or decrease is identified, selecting a treatment to prevent or reduce 
B-cell lymphoma or leukemia or to delay the onset of B-cell lymphoma or 
leukemia.
    Other embodiments are kits for measuring a soluble CD22 level, 
which kits include a specific binding molecule that selectively binds 
to the CD22, e.g. an antibody or antibody fragment that selectively 
binds CD22.
    Further disclosed methods are methods for screening for a compound 
useful in treating, reducing, or preventing B-cell lymphomas or 
leukemias, or development or progression of B-cell lymphomas or 
leukemias, which methods include determining if application of a test 
compound lowers soluble CD22 levels in a subject, and selecting a 
compound that so lowers sCD22 levels.

C-C Chemokines That Inhibit Retrovirus Infection

    Paolo Lusso, Robert C. Gallo, Fiorenza Cocchi, Anthony L. De Vico, 
Alfredo Garzino-Demo (NCI).
    PCT Application No. PCT/US96/18993 filed 27 Nov 1996 (DHHS 
Reference No. E-008-1996/0-PCT-02); U.S. Patent Application No. 09/
077,614 filed 29 May 1998 (DHHS Reference No. E-008-1996/0-US-04) (with 
priority to 30 Nov 1995).
    Licensing Contact: Sally Hu; (301) 435-5606; [email protected].
    This invention concerns three members of the human C-C chemokine 
family, RANTES, macrophage inflammatory protein 1alpha (MIP-1alpha) and 
macrophage inflammatory protein 1beta (MIP-1beta), which are produced 
and secreted by several cell types, including CD8-positive T 
lymphocytes, and which act in vitro as HIV suppressive factors. These 
factors and their respective genes may be used in the diagnosis, 
prognosis, treatment and prevention of AIDS and other retrovirus-
induced diseases. The invention provides a therapeutic preparation, 
methods for therapeutic and prophylactic treatment of retroviral 
infection, and a method of prognosis for retroviral infection. The 
technology was reported in Science 270(8):1560-1561 (December 8, 1995).

    Dated: March 18, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-6608 Filed 3-23-04; 8:45 am]
BILLING CODE 4140-01-P