[Federal Register: April 26, 2005 (Volume 70, Number 79)]
[Notices]
[Page 21431-21434]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr26ap05-64]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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.
[[Page 21432]]
Composition and Methods for Diagnosis and Treatment of Metastatic
Disease
Xin Wei Wang and Anuradha Budhu (NCI).
U.S. Provisional Application filed 8 Mar 2005 (DHHS Reference No. E-
127-2005/0-US-01).
Licensing Contact: Michelle A. Booden; 301/451-7337;
boodenm@mail.nih.gov.
Liver cancer, particularly hepatocellular carcinoma (HCC), is a
leading cause of cancer deaths worldwide. In spite of recent progress
in therapeutic strategies, prognosis of patients with advanced HCC
remains very poor. Although routine screening of individuals at risk
for developing HCC may extend the life of some patients, many are still
diagnosed with advanced HCC and have little chance of survival. A small
subset of HCC patients qualifies for surgical intervention, but the
consequent improvement in long-term survival is only modest. The
extremely poor prognosis of HCC is largely the result of a high rate of
recurrence after surgery or of intra-hepatic metastases that develop
through invasion of the portal vein or spread to other parts of the
liver; extra-hepatic metastases are less common.
The present invention describes tools to determine a unique gene
expression profile present in either liver parenchyma through needle
biopsy or blood that can aid diagnosis or prognosis of HCC patients
with or without metastatic potential. This method also provides a
signature-derived polymerase chain reaction or serological screening
method to identify drug candidates to treat metastatic or recurrent
HCC.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Aminoglycosides and Ribosome Inhibitors as Inhibitors of Tyrosyl-DNA-
Phosphodiesterase
Drs. Yves Pommier and Zhi-Yong Liao (NCI).
DHHS Reference No. E-117-2005/0-US-01.
Licensing Contact: John Stansberry; 301/435-5236;
stansbej@mail.nih.gov.
Cancer has long been a leading cause of mortality in the United
States. DNA-damaging therapies, such as radiotherapy and chemotherapy,
are the methods of choice for treating subjects with metastatic cancer
or subjects with diffuse cancers such as leukemias. However,
radiotherapy can cause substantial damage to normal tissue in the
treatment field, resulting in scarring and, in severe cases, loss of
function of the normal tissue. Although chemotherapy can provide a
therapeutic benefit in many cancer subjects, it often fails to treat
the disease because cancer cells may become resistant to the
chemotherapeutic agent. To overcome these limitations additional
antineoplastic strategies, such as enhancing the antineoplastic effect
of existing therapies, are needed.
This invention discloses a method for enhancing an antineoplastic
effect of a DNA-damaging therapy. The method includes administering to
a subject having a neoplasm a therapeutically effective amount of the
DNA-damaging therapy and a ribosome inhibitor that inhibits tyrosyl-DNA
phosphodiesterase 1 (Tdp1) activity, wherein the ribosome inhibitor is
administered in a sufficient amount to enhance the DNA-damaging
therapy.
This disclosure also provides pharmaceutical compositions that
include at least one chemotherapeutic agent and at least one ribosome
inhibitor that inhibits Tdp1 activity, wherein the chemotherapeutic
agent and the ribosome inhibitor are present in a therapeutically
effective amount for the ribosome inhibitor to enhance an
antineoplastic effect of the chemotherapeutic agent.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Inhibition of Proteosome Function to Potentiate the Proapoptotic and
Antitumor Activity of Cytokines
Jon Wigginton et al. (NCI).
U.S. Provisional Patent Application filed 23 Mar 2005 (DHHS Reference
No. E-072-2005/0-US-01).
Licensing Contact: Michelle A. Booden; 301/451-7337;
boodenm@mail.nih.gov.
Protein degradation via the ubiquitin-proteosome pathway is an
important regulator of cell cycle progression and survival. Thus,
inhibitors of this pathway can be directly cytotoxic and can sensitize
several tumor cell types to cytotoxic chemotherapy and radiation.
Neuroblastoma is the most common extracranial solid tumor in
children, and the development of clinical resistance to cytotoxic
therapies is a major therapeutic obstacle in these patients. Several
apoptosis abnormalities, which result from decreased expression of pro-
apoptotic proteins, are associated with increased resistance to
standard therapeutic interventions. In addition, neuroblastoma cells
also show increased expression of several pro-survival proteins such as
Bcl-2, FLIP, and AKT. Preclinical models suggest that IFN-gamma/TNF-
alpha cytokines including IL-2, IL-12 and IL-18 among others may have
potent antitumor efficacy in several preclinical models, and that these
regimens may act by inducing an adaptive cell-mediated immune response.
Although some single agent cytokine regimens have achieved modest
efficacy in the clinical setting, the utility of some approaches has
been limited overall by side effects that can be associated with high-
dose cytokine therapy.
The present invention describes a method for combining ubiquitin-
proteosome inhibitors with various cytokines to overcome mechanisms of
tumor self-defense and sensitize both tumor and/or endothelial cell
populations to apoptosis. These combination approaches may not only
offer the prospect for improved therapeutic efficacy, but achieve these
effects at lower, more clinically tolerable doses than can be achieved
utilizing either respective agent alone. It is anticipated that this
therapeutic intervention could be directed towards multiple human
carcinomas, and potentiate the efficacy of multiple different cytokines
both in the setting of oncology and infectious disease applications.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Methods for Inhibiting or Treating Cancer
Ernest Hamel (NCI), et al.
U.S. Provisional Application No. 60/616,347 filed 05 Oct 2004 (DHHS
Ref. No. E-323-2004/0-US-01).
Licensing Contact: Thomas P. Clouse; 301/435-4076;
clouset@mail.nih.gov.
This invention describes novel arylthioindole derivatives having
enhanced interaction with tubulin and increased effectiveness in growth
inhibition of MCF-7 breast cancer cells as well as other cell types.
Antitubulin drugs have an established role in the treatment of cancer,
parasitic diseases and inflammatory disorders. These new chemical
compounds have the potential to result in more effective therapeutics
for the treatment of neoplastic, inflammatory and parasitic diseases.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
[[Page 21433]]
Regulation of ATG7 Beclin 1 Program of Autophagic Cell Death by
Caspase-8
Michael Lenardo and Yu Li (NIAID), et al.
U.S. Provisional Application No. 60/556,857 filed 30 May 2004 (DHHS
Reference No. E-318-2004/0-US-01).
Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.
The invention discloses the role of autophagy in regulation cell
death. Further it teaches a method of inducing autophagic cell death by
administering a caspase inhibitor. The invention also discloses that
autophagic cell death can be induced by caspase-8 inhibition and
requires the genes ATG7 and Beclin 1.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Cancer Specific SPANX-N Markers
Natalay Kouprina et al. (NCI).
DHHS Reference No. E-212-2004/0-US-01.
Licensing Contact: Mojdeh Bahar; 301/435-2950; baharm@mail.nih.gov.
The invention provides SPANX-N polypeptides, nucleic acids and
antibodies that could be useful for detecting and treating prostate or
other cancers. The SPANX-N genes are a family of related genes that are
expressed in normal testis and in tumor cells in humans including
melanoma, bladder carcinomas and myelomas. The SPANX cancer/testis
antigens thus represent good candidates for diagnosis or treatment of
several cancers.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Methods for Inhibiting or Treating Cancer
Srividya Swaminathan, Shyam Sharan (NCI).
U.S. Provisional Application No. 60/588,918 filed 16 Jul 2004 (DHHS
Reference No. E-160-2004/0-US-01).
Licensing Contact: Thomas P. Clouse; 301/435-4076;
clouset@mail.nih.gov.
This invention describes a novel role for BRCA2 in the repair of
O6-alkylguanine adducts and provides evidence that after
treatment with O6-benzylguanine, tumor cells with intact
BRCA2, are susceptible to ionizing radiations. In this invention the
essential and novel function of BRCA2 in the repair of O6-
methylguanine is described and demonstrated. BRCA2 physically interacts
with alkylated-AGT and undergoes repair-associated degradation.
Treatment with O6-benzylguanine renders cell radiation
hypersensitive due to degradation of BRCA2. Radio-sensitization of
tumors by O6-benzylguanine should have a significant impact
on cancer therapeutics. The elucidation of the mechanism of action for
the chemotherapeutic agent O6-benzylguanine relative to
BRCA2 may potentially improve the success rate of treating BRCA2
expressing tumors.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Chinese Hamster Ovary Cells Resistant to Colcemid With Altered beta-
Tubulin
Michael M. Gottesman and Fernando R. Cabral (NCI).
DHHS Reference No. E-156-2004/0--Research Tool.
Licensing Contact: Thomas P. Clouse; 301/435-4076;
clouset@mail.nih.gov.
The invention is Chinese hamster ovary cells (CHO) resistant to
colcemid with altered beta-tubulin. These mutants establish the
essential role of tubulin in forming mitotic spindles and identify
beta-tubulin as the target for colcemid toxicity.
Cloning and Characterization of an Avian Adeno-Associated Virus and
Uses Thereof
Ioannis Bossis (NIDCR).
U.S. Provisional Application No. 60/472,066 filed 19 May 2003 (DHHS
Reference No. E-105-2003/0-US-01); PCT Application No. PCT/US04/15534
filed 18 May 2004, which published as WO 2005/017101 A2 on 24 Feb 2005
(DHHS Reference No. E-105-2003/0-PCT-02).
Licensing Contact: Jesse S. Kindra; 301/435-5559; kindraj@mail.nih.gov.
Currently, adeno-associated virus (AAV) represents the gene therapy
vehicle of choice because it has many advantages over current
strategies for therapeutic gene insertion. AAV is less pathogenic than
other virus types; stably integrates into dividing and non-dividing
cells; integrates at a consistent site in the host genome; and shows
good specificity towards various cell types for targeted gene delivery.
To date, eight AAV isolates have been isolated and characterized,
but new serotypes derived from other animal species may add to the
specificity and repertoire of current AAV gene therapy techniques.
This invention describes vectors derived from an avian AAV. These
vectors have innate properties related to their origin that may confer
them with a unique cellular specificity in targeted human gene therapy.
Therefore, vectors derived from this avian AAV are likely to find novel
applications for gene therapy in humans and fowl.
This research has been described, in part, in Bossis and Chiorini
(2003) J. Virol. (77)12:6799-6810.
Identification of Novel Birt-Hogg-Dub[eacute] (BHD) Gene
Laura S. Schmidt (NCI).
U.S. Patent Application No. 10/514,744 filed 16 Nov 2004 (DHHS
Reference No. E-190-2002/2-US-02).
Licensing Contact: John Stansberry; 301/435-5236;
stansbej@mail.nih.gov.
Birt-Hogg-Dub[eacute] (BHD) syndrome is an inherited autosomal
dominant neoplasia syndrome characterized by benign hair follicle
tumors and is associated with a higher risk for developing renal
cancer, spontaneous pneumothorax and /or lung cysts.
The present invention describes identification of the BHD syndrome
associated germline mutations in a novel human gene, herein called BHD
gene. This gene encodes for the protein, folliculin, functions of which
remain currently unknown.
This discovery makes possible the development of a diagnostic
method for BHD syndrome using a simple blood test. The test is
particularly useful in detecting BHD mutations in asymptomatic carriers
within BHD families.
Patients with kidney tumors can be evaluated for BHD gene mutations
using a similar genetic diagnostic test, which will allow for a more
accurate diagnosis of a kidney cancer and improved patient prognosis.
The BHD encoding sequence is the third gene found to be responsible for
inherited kidney cancer, and mutation testing allows for a correct
diagnosis and initiation of the proper treatment, which is different
for each of the types of kidney cancer caused by the three genes. Since
BHD is the first gene found to be associated with chromophobe renal
cancer or renal oncocytoma, this invention will enable the development
of specific treatments or therapies for these particular histologic
types of kidney cancer.
Methods of using BHD encoding sequence also allows for a
differential genetic diagnosis of spontaneous pneumothorax, or
collapsed lung. Since collapsed lung can be caused by several factors,
a BHD diagnostic test allows a physician to determine predisposition to
and possible recurrence of additional spontaneous pneumothoraces due to
mutation(s) in the BHD gene.
[[Page 21434]]
The discovery should also lead to the development of novel
pharmaceutical products and methods for treating BHD skin lesions using
creams containing the BHD gene product, folliculin. Such products and
methods of treatment are expected to reduce the size and appearance of
the benign hair follicle tumors.
The disclosed technology will provide new and exciting
methodologies to correctly diagnose BHD syndrome and should lead to the
development of novel pharmaceutical reagents for treatment of BHD skin
lesions as well as other skin diseases.
This research is also described in: MB Warren et al., Mod Pathol.
(2004 Aug) 17(8):998-1011; ML Nickerson et al., Cancer Cell (2002 Aug)
2(2):157-164; B Zbar et al., Cancer Epidem. Bio. Prev. (2002 Apr)
11(4):393-400; LS Schmidt et al., Am. J. Hum. Genet. (2001 Oct)
69(4):876-882; Toro et al., Arch. Dermatol. (1999 Oct) 135(10): 1195-
1202.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Compositions Of Transforming Growth Factor Beta (TGF-beta) Which
Promotes Wound Healing and Methods for Their Use
Michael Sporn et al. (NCI).
U.S. Patent No. 5,104,977, granted April 14, 1992, entitled ``Purified
Transforming Growth Factor Beta'' (DHHS Ref. No. E-070-1982/2-US-05);
U.S. Patent No. 5,656,587, granted August 12, 1997, entitled
``Promotion Of Cell Proliferation By Use Of Transforming Growth Factor
Beta (TGF-Beta)'' (DHHS Ref. No. E-070-1982/2-US-07); and
U.S. Patent No. 5,705,477, granted January 6, 1998, entitled
``Compositions Of Transforming Growth Factor Beta (TGF-Beta) Which
Promotes Wound Healing And Methods For Their Use'' (DHHS Ref. No. E-
070-1982/2-US-08).
Licensing Contact: Jesse S. Kindra; 301/435-5559; kindraj@mail.nih.gov.
There is a continuing need for the promotion of rapid cell
proliferation at the site of wounds, burns, diabetic and decubitus
ulcers, and other traumata. Prior to this invention, a number of
``growth factors'' were known to promote the rapid growth of cells.
None of these growth factors, however, had been found to be
pharmaceutically acceptable agents for the acceleration of wound
healing.
This invention relates to compositions of Transforming Growth
Factor beta (TGF-beta) which promote repair of tissue, particularly
fibroblast cells, in animals and human beings. This invention also
relates to a method of treating wounds by the topical or systemic
administration of the compositions. The discovery of this invention
initiated a worldwide field of research aimed at the characterization
and development of TGF-beta in wound healing and disease. It is now
known that TGF-beta's role in wound healing is complex. Its diverse
effects on the many individual participating cell types in a wound are
integrated into a specific temporal sequence of events within a defined
tissue architecture. In addition to its many roles in wound healing,
TGF-beta is also implicated in the pathogenesis of diseases such as
autoimmune disease, fibrosis, and cancer.
Current research in TGF-beta biology is leading to the development
of novel wound healing and disease therapies related to the growth
factor and its signaling pathways.
Dated: April 18, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-8287 Filed 4-25-05; 8:45 am]
BILLING CODE 4140-01-P