[Federal Register Volume 69, Number 91 (Tuesday, May 11, 2004)]
[Notices]
[Pages 26171-26173]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-10607]


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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.

Eosinophil-Derived Neurotoxin, an Antimicrobial Protein With 
Ribonuclease Activity, is an Immunostimulant

De Yang et al. (NCI).
U.S. Provisional Patent Application Nos. 60/466,797 and 60/466,796, 
filed 29 Apr 2003 (DHHS Reference Nos. E-175-2003/0-US-01 and E-191-
2003/0-US-01).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    Eosinophil-derived neurotoxin (EDN) has in vitro anti-viral 
activity that is dependent on its ribonuclease activity. This invention 
discloses that EDN is a selective chemoattractant and activator of 
dendritic cells, resulting in dendritic cell migration, maturation, and 
a production of a wide variety of cytokines. Based on these potent 
chemotactic and activating effects on dendritic cells, EDN might be 
useful as a clinical immunoadjuvant for the promotion of immune 
responses to specific antigens of tumors or pathogenic organisms.

Detection of Antigen-Specific T Cells and Novel T Cell Epitopes by 
Acquisition of Peptide/HLA-GFP Complexes

Steven Jacobson, Utano Tomaru, and Yoshihisa Yamano (NINDS).
U.S. Provisional Application No. 60/457,006 filed 24 Mar 2003 (DHHS 
Reference No. E-084-2003/0-US-01); U.S. Provisional Application No. 60/
480,083 filed 20 Jun 2003 (DHHS Reference No. E-084-2003/1-US-01); PCT 
Application filed 24 Mar 2004 (DHHS Reference No. E-084-2003/2-PCT-01).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    This invention relates to a method for identifying specific T cell 
epitopes and antigen-specific T cells through labeling with an HLA-GFP 
complex expressed on an antigen-presenting cell. The T cells acquired 
the peptide-HLA-GFP complex through T cell mediated endocytosis upon 
specific antigen stimulation. This basic method can be used for several 
purposes. First, it can be used to generate a T-cell immune response 
through the attachment of a reporter peptide to the antigen-presenting 
cell. It can also be used as a way to assay a population of cells to 
determine whether any T cells specific for a particular antigen are 
present. This might be useful in applications related to autoimmunity, 
infectious disease, or cancer. Third, it can be used as a therapeutic 
to eliminate antigen-specific T cells associated with disease, if 
coupled to a toxic moiety.

Protein Kinase C Inhibitor, Related Composition, and Method of Use

Shaomeng Wang, Peter Blumberg (NCI), Nancy Lewin (NCI).

[[Page 26172]]

U.S. Provisional Patent Application No. 60/451,214 filed 28 Feb 2003 
(DHHS Reference No. E-073-2003/0-US-01); PCT Application No. PCT/US04/
05855 filed 26 Feb 2004 (DHHS Reference No. E-073-2003/0-PCT-02).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    Protein kinase C is a critical component in cellular signaling, 
involved in cellular growth, differentiation, and apoptosis. It has 
been identified as a promising therapeutic target for cancer, diabetic 
retinopathy, and Alzheimer's disease, among other indications. This 
invention relates to lead compounds that can inhibit protein kinase C 
isoforms through disruption of their C1 domains. The inventors also 
found that these compounds possess isoform selectivity, an important 
feature for therapeutic specificity. Finally, although the disclosed 
compounds are previously known molecules, novel structures are 
described in the invention that have further improved specificity.

Recombinant Immunotoxin and Use in Treating Tumors

Ira Pastan (NCI), Masanori Onda (NCI), Nai-Kong Cheung (EM).
PCT Application No. PCT/US03/38227 filed 01 Dec 2003 (DHHS Reference 
No. E-051-2003/0-PCT-02).
    Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    The current invention relates to the 8H9 monoclonal antibody (MAb), 
which is highly reactive with a cell surface glycoprotein expressed on 
human breast cancers, childhood sarcomas, and neuroblastomas but is not 
reactive with the cell surface of normal human tissues. This specific 
reactivity suggests that this antibody could be useful as a diagnostic, 
or as a therapeutic molecule to treat breast cancer, osteosarcoma, and 
neuroblastoma. The PCT application claims the 8H9 protein, 8H9 
antibodies, 8H9 immunotoxins, pharmaceutical compositions, and methods 
of use.
    More information can be found in a recent publication: M. Onda et 
al., ``In vitro and in vivo cytotoxic activities of recombinant 
immunotoxin 8H9(Fv)-PE38 against breast cancer, osteosarcoma, and 
neuroblastoma,'' Cancer Res. 2004 Feb 15;64(4):1419-1424.

Methods of Diagnosing Potential for Developing Hepatocellular Carcinoma 
or Metastasis and of Identifying Therapeutic Agents

Xin Wei Wang et al. (NCI).
U.S. Provisional Application No. 60/370,895 filed 05 Apr 2002 (DHHS 
Reference No. E-125-2002/0-US-01); PCT Application No. PCT/US03/10783 
filed 04 Apr 2003 (DHHS Reference No. E-125-2002/0-PCT-02).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    Expression of nearly 10,000 genes was analyzed in hepatocellular 
carcinoma (HCC) tumors, and a molecular signature was identified that 
targets genes that are most likely relevant to the prediction outcome 
of metastases, including patient survival. A specific therapeutic 
target protein was also identified, and antibodies against this protein 
prevent invasion of metastatic HCC cells in vitro. These data identify 
this target protein both as a diagnostic marker and a therapeutic 
target for metastatic HCC. In addition, by analyzing premalignant 
cirrhotic liver tissues from high risk liver disease patients, a 
molecular signature were identified that may be useful in diagnosing 
early onset of HCC. Some of the biomarkers have been validated with 
serum samples to have potentially predictive values.
    This invention may be useful in diagnosing early onset of HCC and 
HCC metastatic tumors, evaluating risk for development of HCC and HCC 
metastatic tumors, and identifying HCC therapeutic targets. This 
invention also identifies a specific therapeutic target protein, and 
identifies methods of identifying antagonists to this protein, which 
might be useful in developing a variety of HCC therapeutics.

p-Toluemesulfonhydrazide Derivatization for Separation and Measurement 
of Endogenous Estrogen Metabolites by High-Pressure Liquid 
Chromatography-Electrospray-Mass Spectrometry

Xia Xu, David Waterhouse, Joseph Saavedra, Larry Keefer, Regina Ziegler 
(NCI).
U.S. Provisional Patent Application 60/372,848 filed 15 Apr 2002 (DHHS 
Reference No. E-103-2002/0-US-01); PCT Application No. PCT/US03/11562 
filed 15 Apr 2003, which published as WO 03/089921 on 30 Oct 2003 (DHHS 
Reference No. E-103-2002/0-PCT-02).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    The current invention relates to a method for measuring endogenous 
estrogen levels, and this technology may be generalizable to all 
endogenous ketolic steroids, including estrogens, androgens, and 
phytoestrogens.
    Specifically, the current invention is a derivatization technique 
that forms estrogen-p-toluenesulfonhydrazones, which can be separated 
and then measured using high-pressure liquid chromatography-
electrospray-mass spectrometry (HPLC-ESI-MS). This method offers a 
number of improvements over current methods. It is more sensitive, it 
is faster, it is more accurate, and it requires a smaller sample size.

Cloning and Mutational Analysis of the Hyperparathyroidism-Jaw Tumor 
Syndrome (HPT-JT) Gene

John D. Carpten et al. (NHGRI).
U.S. Provisional Application No. 60/378,022 filed 13 May 2002 (DHHS 
Reference No. E-004-2002/0-US-01); PCT Application No. PCT/US03/15081 
filed 13 May 2003, which published as WO 03/094860 on 20 Nov 2003 (DHHS 
Reference No. E-004-2002/0-PCT-02).
Licensing Contact: Brenda Hefti; 301/435-4632; [email protected].

    Hyperparathyroidism is a key feature of some hereditary endocrine 
neoplasias and the autosomal dominant disorder HPJT, all of which are 
characterized by the presence of tumors in endocrine tissues. The 
current invention identifies a series of mutations in chromosome 1 open 
reading frame 28 (C10RF28)--the HPT-JT gene. Linkage analysis and 
physical mapping studies of clinical samples from multiple families 
with HPT-JT syndrome were used to identify these mutations. These 
genomic changes are predicted to result in truncated gene products.
    This new technology might be useful for: (1) Diagnosis of HPT-JT 
and/or a predisposition to HPT-JT; (2) development of a treatment for 
HPT-JT; and (3) determination of the effectiveness of various potential 
HPT-JT therapies.
    Additional information may be found in: J.D. Carpten et al., 
``HRPT2, encoding parafibromin, is mutated in hyperparathyroidism-jaw 
tumor syndrome,'' Nat. Genet. (2002 Dec) 32(4):676-80, Epub 2002 Nov 
18.; J.D. Chen et al., ``Hyperparathyroidism-jaw tumour syndrome,'' J. 
Int. Med. (2003 Jun) 253(6):634-642, doi: 10.1046/j.1365-
2796.2003.01168.x; T.M. Shattuck et al., ``Somatic and germ-line 
mutations of the HRPT2 gene in sporadic parathyroid carcinoma,'' N. 
Engl. J. Med. (2003 Oct) 349(18):1722-1729; W.F. Simonds et al., 
``Familial isolated hyperparathyroidism is rarely caused by germline 
mutation in HRPT2, the gene for the hyperparathyroidism-jaw tumor 
syndrome,'' J. Clin. Endocrinol. Metab. (2004 Jan) 89(1):96-102, doi: 
10.1210/jc.2003-030675; A. Villablanaca et al., ``Germline and de

[[Page 26173]]

novo mutations in the HRPT2 tumour suppressor gene in familial isolated 
hyperparathyroidism (FIHP),'' J. Med. Genet. (2004 Mar) 41(3):e32, doi: 
10.1136/jmg.2003.012369.

    Dated: May 4, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-10607 Filed 5-10-04; 8:45 am]
BILLING CODE 4140-01-P