[Federal Register Volume 70, Number 79 (Tuesday, April 26, 2005)]
[Notices]
[Pages 21431-21434]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-8287]


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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. 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; 
[email protected].

    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; 
[email protected].

    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; 
[email protected].

    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; 
[email protected].

    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; [email protected].

    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; [email protected].

    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; 
[email protected].

    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; 
[email protected].

    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; [email protected].

    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; 
[email protected].

    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; [email protected].

    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