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###### Department of Health and Human Services

###### National Institutes of Health 

# AGENCY:

National Institutes of Health, Public Health Service, HHS. 

# 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. 

## New High-Throughput and Bioinformatic Tools To Identify and Use Genomic DNA Sequence Dimorphisms (Indels) 

*Description of Technology:*                     This invention describes new methods to identify genomic DNA sequence dimorphisms called indels and to determine their biological consequences. “Indels” refers to large insertions and deletions, a form of variation in DNA sequences, that can cause genotypic and phenotypic differences between cells, tissues, individuals, populations or species. The technology describes new bioinformatic tools and high-throughput methods to identify such dimorphisms. Additionally, the technology provides new assays to distinguish genomic sequences by genotyping, understand the role of such indels in altering gene expression, for example in disease pathogenesis, develop new models for variation in genomes and in gene expression, and improve methods for the molecular diagnosis and treatment of disease.                 

*Applications:*

1. A new bioinformatics software tool that can easily identify dimorphisms and can help create a searchable database and graphical interface containing sites of dimorphisms and information regarding functional effects of dimorphisms. 

2. Low cost, high-throughput PCR based methods to identify dimorphic repetitive elements from any eukaryotic genome including individual tissue specimens. 

3. Methods to determine functional consequences of dimorphisms (indels). 

*Development Status:*

1. Bioinformatics software tools are ready for use. 

2. High-throughput PCR methods have been validated. 

3. Annotated mouse genes whose expression is altered by dimorphic indels have been identified. 

*Inventors:*                     David E. Symer                     *et al.*                     (NCI).                 

*Relevant Publications:*

1. Manuscripts relating to this invention are under preparation and will be available once accepted for publication. 

                    2. RE Mills                     *et al.*                     An initial map of insertion and deletion (INDEL) variation in the human genome. Genome Res. 2006 Sep;16(9):1182-1190.                 

*Patent Status:*                     U.S. Provisional Application No. 60/841,089 filed 29 Aug 2006 (HHS Reference No. E-301-2006/0-US-01)                 

*Licensing Status:*                     This technology is available for licensing under an                           ( print page 23836)                        exclusive or non-exclusive patent license.                 

*Licensing Contact:*                     Michelle Booden, PhD; 301/451-7337;                     *boodenm@mail.nih.gov*

*Collaborative Research Opportunity:*                     The National Cancer Institute, Center for Cancer Research, Mouse Cancer Genetics Program is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize identification and use of such genomic DNA sequence insertion/deletion dimorphisms (indels). Please contact John D. Hewes, PhD at 301/435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Self-Assembling Nanoparticles Composed of Transmembrane Peptides and Their Application for Specific Intra-Tumor Delivery of Anti-Cancer Drugs 

*Description of Technology:*                     The current invention discloses peptide based nanoparticles as an alternative to liposomes. The nanoparticles have a diameter of 8-10 nm and are much smaller than a liposome thus providing better tumor penetration. Peptides corresponding to transmembrane domains of a number of integral membrane proteins have been discovered that spontaneously self-assemble in aqueous solutions into stable and remarkably uniform nanoparticles. The nanoparticles of the current invention are fully synthetic, and their surfaces can be functionalized with ligands that provide specific binding to cell surface receptors overexpressed on tumor cells. Thus, they are even more specific for tumor targeting.                 

Nanoparticles constructed from transmembrane domains of certain receptors and transporters have biological activity of their own and inhibit metastasis or drug resistance thus sensitizing tumors to therapy. Hydrophobic drugs can be easily entrapped inside the nanoparticles, which not only solve the problem of drug insolubility under physiological conditions, but also generate a form of a drug that concentrates in tumors due to enhanced permeability and retention (EPR) effects. 

*Applications and Modality:*

1. Self-assembling nano-particles as an alternative to liposomes, inorganic, dendrimeric or polymeric nanoparticles. 

2. Nanoparticles have biological activity of their own and can inhibit metastasis (CXCR4 receptor antagonists) or drug resistance (inhibitors of ABCG2 transporter and p-glycoprotein) thus sensitizing tumors to therapy. 

*Advantages:*

1. The nanoparticles are superior in stability, uniformity, ease and reproducibility of preparation compared to conventional liposomes, are much more uniform and less toxic than inorganic, polymeric or dendrimeric nanoparticles. 

2. The nanoparticles are much smaller than a liposome thus providing better tumor penetration. 

3. Synthetic nanoparticles can be easily coated with receptor ligands and loaded with hydrophobic drugs for more specific tumor targeting. 

*Market:*                     Drug delivery remains one of the biggest challenges for the pharmaceutical industry. Nearly all therapeutics currently on the market are delivered in a non-specific manner to the whole body, and this results in unintentional side effects. The Food and Drug Administration (FDA) has created a new class of therapeutic products using nanoparticulate drug delivery system. In 2005, the first nanoparticulate drug delivery product, Abraxane, for the treatment of breast cancer, was launched. The worldwide R&D investment in nanotechnology research and development in 2004 from both public and private sectors was an estimated $US8.4 billion, 15% of which will be focused on nanobiotechnology.                 

*Development Status:*                     The technology is in the pre-clinical stage of development.                 

*Inventors:*                     Nadya I. Tarasova                     *et al.*                     (NCI).                 

*Related Publication:*                     NI Tarasova                     *et al.*                     Transmembrane inhibitors of P-glycoprotein, an ABC transporter. J Med Chem. 2005 Jun 2;48(11):3768-3775.                 

*Patent Status:*                     U.S. Provisional Application No. 60/864,665 filed 07 Nov 2006, entitled “Self-Assembling Nanoparticles Composed of Transmembrane Peptides and Their Application for Specific Intra-Tumor Delivery of Anti-Cancer Drugs” (HHS Reference No. E-256-2006/0-US-01).                 

*Licensing Status:*                     Available for exclusive and non-exclusive licensing.                 

*Licensing Contact:*                     Jennifer Wong; 301/435-4633;                     *wongje@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The NCI Center for Cancer Research is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize self-assembling nanoparticles with intrinsic anti-tumor activity. Please contact John D. Hewes, PhD at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                 

## Sipa-Gene and Sipa-1 Inhibitor for the Diagnosis and Treatment of Metastatic Cancer 

*Market Opportunity:*                     No screening markers are currently available in the market that can diagnose early metastasis, which causes majority of cancer related deaths. Opportunity for new diagnostic and therapeutic technologies exists as personalized medicine is taking a major role in the clinical management of cancer. This invention can provide the much needed new diagnostic marker for predicting early metastasis as well as a new therapy targeting metastasis causing factors.                 

*Description of Technology:*                     This technology relates to methods and compositions of a new gene Sipa-1 that can identify and treat metastatic cancer. The inventors have identified the Sipa-1 gene as a possible metastasis modifying gene. Further analyses revealed that Sipa-1 expression levels correlate with metastasis. Inhibitors that modulate the Sipa-1 expression and reduce metastasis in animal models have been identified. Additionally, single nucleotide polymorphisms (SNPs) present in the mouse Sipa-1 gene have been identified that, if also present in humans, could serve as the basis for diagnosing cancer and metastasis.                 

*Applications and Modality:*                     Method for diagnosing early onset of metastasis with Sipa-1; Sipa-1 as a new therapeutic target for treatment of metastatic cancer.                 

*Advantages:*                     Simple PCR based assay for detecting single nucleotide polymorphisms (SNPs) within the Sipa-1 gene; Inhibitors of Sipa-1 are known in the art, they can be easily screened from existing small molecule libraries.                 

*Current Development Status:*

1. The technology is currently in the pre-clinical stage of development. 

2. Proof of concept results show that inhibition of Sipa-1 reduces metastasis in mouse models. 

3. Laboratory data shows single nucleotide polymorphisms (SNPs) within the Sipa-1 gene linked to metastatic disease. 

*Inventors:*                     Kent Hunter                     *et al.*                     (NCI).                 

*Publications:*

1. PCT Publication No. WO 2006084027, published October 8, 2006. 

                    2. YG Park                     *et al.*                     Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nat Genet. 2005 Oct;37(10):1055-1062. Epub 2005 Sep 4.                 

                    3. NP Crawford                     *et al.*                     Germline polymorphisms in SIPA-1 are associated with metastasis and other indicators of poor prognosis in breast cancer. Breast Cancer Res. 2006;8(2):R16. Epub 2006 Mar 21.                           ( print page 23837)    

*Patent Status:*                     U.S. Provisional Application No. 60/649,365 filed 02 Feb 2005 (HHS Reference No. E-082-2005/0-US-01); PCT Application No. PCT/US2006/003672 filed February 2, 2006 (HHS Reference No. E-082-2005/2-PCT-01).                 

*Related Technology:*                     U.S. Provisional Application No. 60/695,024 filed 29 Jun 2005 (HHS Reference No. E-216-2005/0-US-01).                 

*Licensing Status:*                     Available for exclusive and non-exclusive licensing.                 

*Licensing Contact:*                     Mojdeh Bahar, J.D.; 301/435-2950;                     *baharm@mail.nih.gov.*

 Dated: April 20, 2007. 

Steven M. Ferguson, 

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

 [FR Doc. E7-8288 Filed 4-30-07; 8:45 am] 

BILLING CODE 4140-01-P