Notice (A): Government-Owned Inventions; Availability for Licensing

Federal Register: June 3, 2009 (Volume 74, Number 105)              
                  Page 26704-26707

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.

Novel Method of Treating Cancer Using Ixolaris

    Description of Technology: Aggressive tumors spread between tissues 
in a process known as metastasis. Tumor metastasis, particularly with 
regard to brain cancer (gliomas), has been linked to the aberrant 
expression of membrane-bound tissue factor (TF). TF normally functions 
as a blood coagulation factor and can lead to the production of pro-
angiogenesis factors such as vascular endothelial growth factor (VEGF). 
By doing this in the vicinity of tumors, TF may enhance both tumor 
growth and the ability of tumors to metastasize.
    Ixolaris is a protein that prevents the initiation of blood 
coagulation, specifically by inhibiting TF. NIH inventors have explored 
the possibility that Ixolaris could be effective as an anti-cancer 
therapy. As an inhibitor of TF, Ixolaris could potentially inhibit the 
function of TF, thereby reducing the ability of a tumor to develop and 
to metastasize. Recent data show that Ixolaris has the ability to 
prevent tumor growth in vivo using mouse xenograft models. Importantly, 
the inhibition in vivo occurred without noticeable bleeding. Since 
Ixolaris is not immunogenic, it might be an excellent candidate as an 
anti-cancer therapeutic.
    Application: Treatment and prevention of tumor growth and 
metastasis by inhibiting TF and blood vessel formation.
    Advantages: Provides a novel mechanism for preventing tumor 
metastasis.
    Development Status: Preclinical stage of development.
    Inventors: Ivo Francischetti (NIAID) et al.
    Patent Status: U.S. Provisional Application No. 61/161,223 (HHS 
Reference No. E-148-2009/0-US-01).
    For more information, see:
    1. U.S. Patent 7,078,508 entitled ``Ixodes Scapularis Tissue Factor 
Pathway Inhibitor''.
    2. IM Francischetti et al. Ixolaris, a novel recombinant tissue 
factor pathway inhibitor (TFPI) from the salivary gland of the tick, 
Ixodes scapularis: identification of factor X and factor Xa as 
scaffolds for the inhibition of factor VIIa/tissue factor complex. 
Blood 2002 May 15;99(10):3602-3612.
    3. RA Nazareth et al. Antithrombotic properties of Ixolaris, a 
potent inhibitor of the extrinsic pathway of the coagulation cascade. 
Thromb Haemost. 2006 Jul;96(1):7-13.
    Licensing Status: Available for licensing.
    Licensing Contact: David A. Lambertson, PhD; 301-435-4632; 
lambertsond@mail.nih.gov.
    Collaborative Research Opportunity: The NIAID, OTD, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Ixolaris for cancer treatment. Please contact Dana Hsu at 301-496-2644 
for more information.

Immortalized Virus-Free Human Placental Cell Lines

    Description of Technology: This technology provides immortalized 
virus-free human placental cell lines. To develop these cell lines, 
human placental cells were immortalized with adenovirus-origin-minus 
(ori-)-simian virus-40 (SV40) recombinant viruses containing either 
wild-type or temperature-sensitive (ts) A mutants of SV40. Cells 
transformed with the SV40 tsA chimera (HP-A1 and HP-A2), but not the 
SV40 wild-type chimera (HP-W1), were conditional for

[[Page 26705]]

transformation. All three cell lines expressed trophoblast-specific 
genes, including placental specific genes and the alpha- and beta-
subunits of hCG.
    These immortalized virus-free human placental cell lines expressing 
major proteins of human trophoblasts provide efficient in vitro models 
to study placental functions.
    Inventor: Janice Y. Chou (NICHD).
    Publication: KJ Lei, Y Gluzman, CJ Pan, JY Chou. Immortalization of 
virus-free human placental cells that express tissue-specific 
functions. Mol Endocrinol. 1992 May; 6(5):703-712.
    Patent Status: HHS Reference No. E-052-2009/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing under a Biological 
Materials License Agreement.
    Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-
5020; vepas@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of Child 
Health and Human Development, Section on Cellular Differentiation, is 
seeking statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
Immortalized Virus-Free Human Placental Cell Lines. Please contact 
Joseph Conrad III, PhD at 301-435-3107 or jmconrad@mail.nih.gov for 
more information.

Broadly Applicable Modules for Improved Expression and Detection of 
Membrane Proteins

    Description of Technology: NIH investigators have designed and 
tested a set of expression modules that are applicable to a wide 
variety of membrane proteins. Prior to this invention, cloned membrane 
proteins have sometimes been difficult to detect due to the lack of 
effective antibodies. Moreover, currently available expression vectors 
lack the signal sequences, tags, and multiple cloning sites to clone 
membrane proteins and express them on the cell surface. This invention 
is the first of its kind to contain all of these elements to facilitate 
biochemical studies on membrane proteins.
    This technology is a set of nucleic acid modules designed for the 
expression and tagging of membrane proteins in mammalian cells. The 
module includes a signal peptide, an exchangeable tag, and a multiple 
cloning site. The gene of a membrane protein may be conveniently 
inserted into the multiple cloning site, and the signal peptide will 
target the cloned membrane protein to the cell surface. The tag, in 
frame with the signal peptide, is either a fluorescent protein or an 
epitope for a known antibody, both of which enable detection of the 
protein by several standard biochemical methodologies.
    Applications: This technology can provide improved expression and 
detection of membrane proteins in common laboratory cell lines.
    Development Status: Each module contains either one of two 
different epitope tag, and the expression vector contains either 
zeocin- or neomycin-resistant markers. There are two sets of module 
(four vectors) available.
    Inventors: Li Lin et al. (NIA).
    Publication: J Pang, X Zeng, R-P Xiao, EG Lakatta, L Lin. Design, 
generation, and testing of mammalian expression modules that tag 
membrane proteins. Protein Science, in press (2009).
    Patent Status: U.S. Provisional Application No. 61/142,531 filed 05 
Jan 2009 (HHS Reference No. E-016-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, MHPM; 301-435-4521; 
Fatima.Sayyid@nih.hhs.gov.
    Collaborative Research Opportunity: The National Institute on 
Aging, Laboratory of Cardiovascular Sciences, is seeking statements of 
capability or interest from parties interested in collaborative 
research to further develop, evaluate, or commercialize the technology 
of mammalian membrane protein expression and detection. Please contact 
Vio Conley at 301-496-0477 or conleyv@mail.nih.gov for more 
information.

Inhibitors of CD25 To Treat Autoimmune Diseases and Tumors

    Description of Technology: This invention discloses therapeutics 
for the treatment of Multiple Sclerosis, uveitis, and certain cancers 
by providing methods and compositions for selectively blocking CD25 on 
T cells or dendritic cells. The therapeutics developed using the 
current technologies have the potential to exhibit superior specificity 
and minimal side-effects. In this invention, NIH investigators, for the 
first time, demonstrate that mature dendritic cells (mDC) use CD25 for 
trans-presentation of IL-2, and the blockade of CD25 on the surface of 
mDCs abrogates T cell proliferation. Further, CD25 expression on T 
cells is not only dispensable for their proliferation, but it also 
limits effector T cell survival. These observations form the basis for 
the development of novel therapies for certain cancers and autoimmune 
disorders.
    Applications: Therapeutics for autoimmune diseases; Therapeutics 
for tumors.
    Development Status: Early stage.
    Inventors: Bibiana Bielekova et al. (NINDS).
    Publication: Manuscript submitted for publication.
    Patent Status: U.S. Provisional Application No. 61/201,589 filed 12 
Dec 2008 (HHS Reference No. E-007-2009/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Suryanarayana (Sury) Vepa, PhD, J.D.; 301-435-
5020; vepas@mail.nih.gov.
    Collaborative Research Opportunity: The National Institute of 
Neurological Disorders and Stoke is seeking statements of capability or 
interest from parties interested in collaborative research to further 
develop, evaluate, or commercialize methods of treating multiple 
sclerosis by administering agents that block the interaction of 
dendritic cells and T cells via CD25. Please contact Dr. Martha Lubet 
at 301-435-3120, e-mail: lubetm@mail.nih.gov for more information.

Methods for Identifying Breast Cancer Patients for Therapy With mTOR 
Inhibitors

    Description of Technology: This technology relates to methods of 
identifying individuals with invasive breast cancer who may benefit 
from treatment with an inhibitor of mammalian Target of Rapamycin 
(mTOR), particularly those having a gene amplification including 
chromosome 8p11-12 or a portion thereof. Chromosome 8p11-12 is the 
second most commonly amplified region in breast cancer cases, after 
HER2 amplification at chromosome 17. Similar to HER2 amplification, the 
amplification of 8p11-12 is associated with decreased survival. 
However, whereas patients diagnosed with HER2 amplifications can be 
more effectively treated with adjuvant therapy using HER2 inhibitors 
such as trastuzumab, no specific therapy has been identified for breast 
cancer patients having an amplification of chromosome 8p11-12.
    Investigators at NIH have shown that amplification of chromosome 
8p11-12 leads to increased copy number of the gene for eukaryotic 
translation initiation factor 4E binding protein 1, or EIF4EBP1 and 
elevated expression of the protein in these breast cancer cell lines. 
EIF4E is a rate limiting component of a multi-subunit complex that 
recruits 40S ribosomal subunits to the 5' end of

[[Page 26706]]

mRNAs. EIF4EBP1 interacts and inhibits EIF4E complex assembly and thus, 
represses translation. In breast cancer cell lines with EIF4EBP1 
amplification, the elevated EIF4EBP1 is largely inactivated via 
hyperphosphorylation. As the phosphorylation of EIF4EBP1 is controlled 
by mTOR, its hyperphosphorylation can be reversed with rapamycin. 
Indeed, rapamycin is much more effective in inhibiting the formation of 
active translational complex and the growth of breast cancer cells with 
chromosome 8p11-12/EIF4EBP1 amplification. Thus, detection of 
chromosome 8p11-12 amplification, and/or over-expression or increased 
phosphorylation of EIF4EBP1 can be used to identify breast cancer 
patients for treatment with inhibitors of mTOR, such as rapamycin or 
its derivatives or analogs.

Applications

     Diagnostic kit for measuring DNA amplification of 
chromosome 8p11-12 and/or EIF4EBP1 to identify breast cancer patients 
that could benefit from mTOR inhibitor drugs.
     Diagnostic kit for measuring EIF4EBP1 mRNA or protein 
levels to help identify breast cancer patients that could benefit from 
mTOR inhibitor drugs.

Advantages

     This molecular diagnostics may optimize the therapeutic 
use of mTOR inhibitors in the treatment of breast cancer.
     This molecular diagnostics may stratify breast cancer 
patients for clinical trials with mTOR targeted agents for increased 
responses.
    Development Status: Early stage; Pre-clinical data available.
    Market: Breast cancer is the most common cancer among women in the 
United States, other than skin cancer. It is the second leading cause 
of cancer death in women, after lung cancer. An estimated 182,460 new 
cases of invasive breast cancer were expected to occur among women in 
the U.S. during 2008. Amplification of chromosome 8p11-12 occurs in 
about 10-15% of the invasive breast cancer cases.
    Inventors: Liang Cao and Paul S. Meltzer (NCI).
    Publications: None related to this technology.
    Patent Status: U.S. Provisional Application No. 61/152,920 filed 16 
Feb 2009 (HHS Reference No. E-340-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Surekha Vathyam, PhD; 301-435-4076; 
vathyams@mail.nih.gov.
    Collaborative Research Opportunity: The Genetics Branch at National 
Cancer Institute is seeking statements of capability or interest from 
parties interested in collaborative research to further develop, 
evaluate, or commercialize. Please contact John D. Hewes, PhD at 301-
435-3121 or hewesj@mail.nih.gov for more information.

Method for the Diagnosis and Prognosis of Age-Related Cardiovascular 
Disorders

    Description of Technology: NIH investigators have discovered a 
method for the diagnosis and prognosis of cardiovascular aging. Current 
methodologies include the measurement of patient lipid profiles or 
expression of up to two proteins. In contrast, this technology utilizes 
the expression levels of a panel of proteins not previously known to be 
related to cardiovascular aging and may prove to be a more accurate 
diagnostic or prognostic of cardiovascular aging than currently 
available tests or it may improve the accuracy of currently available 
tests when used in concert.
    The technology relates to methods for determining susceptibility to 
having an extremely common age-associated vascular disorder. It also 
describes the subsequent use of these proteins as markers for disease. 
While the underlying cellular and molecular mechanisms of age-related 
vascular disease remain largely undefined, the expression levels of the 
genes described in this technology have been empirically determined to 
differ between healthy and age-inflamed arterial tissue. Further, this 
technology includes a companion mass spectroscopic-based methodology 
for reproducible quantification of specific expression levels of 
interest.
    Application: Diagnosis of age-related vascular disorder.
    Development Status: Early stage.
    Inventors: Mingyi Wang et al. (NIA).
    Patent Status: U.S. Provisional Application No. 61/154,329 filed 20 
Feb 2009 (HHS Reference No. E-219-2008/0-US-01).
    Licensing Status: Available for licensing.
    Licensing Contact: Fatima Sayyid, MHPM; 301-435-4521; 
Fatima.Sayyid@nih.hhs.gov.
    Collaborative Research Opportunity: The National Institute on 
Aging, Cardiovascular Biology Unit-Vascular Group, is seeking 
statements of capability or interest from parties interested in 
collaborative research to further develop, evaluate, or commercialize 
idea of how to assess and retard accelerated arterial aging and its 
attendant risks for atherosclerosis and hypertension. Please contact 
Vio Conley at 301-496-0477 or conleyv@mail.nih.gov for more 
information.

CCR5-Specific Human Monoclonal Antibodies

    Description of Technology: The subject invention describes the 
anti-CCR5 monoclonal antibodies, their fusion protein, conjugates, 
derivatives, or fragments, DNA sequences encoding such antibodies, host 
cells containing such DNA sequences, as well as the methods to produce 
them recombinantly and their pharmacological composition.
    It has been demonstrated that the HIV co-receptor CCR5 plays an 
important role in virus entry. The subject antibodies exhibited 
neutralization activity against HIV-1 infection by binding to cell 
associated CCR5 in vitro. Therefore, subject anti-CCR5 antibodies can 
be useful research materials for the research in HIV/AIDS fields.
    Applications: Research tools.
    Development Status: In vitro data is available at this time.
    Inventors: Dimiter S. Dimitrov and Mei-Yun Zhang (NCI).

Related Publications

    1. C Pastori et al. Long-lasting CCR5 internalization by antibodies 
in a subset of long-term nonprogressors: a possible protective effect 
against disease progression. Blood. 2006 Jun 15;107(12):4825-4833.
    2. MY Zhang, B Vu, CC Huang, I Sidirov, V Choudhly, PD Kwong, DS 
Dimitrov. Identification of human monoclonal antibodies specific for 
CCR5 from an antibody library derived from HIV-infected long-term non-
progressors. Retrovirology. 2006 Dec 21;3 Suppl 1:S61.
    3. DS Dimitrov. Virus entry: molecular mechanisms and biomedical 
applications. Nat Rev Microbiol. 2004 Feb;2(2):109-122.
    Patent Status: HHS Reference No. E-297-2006/0--Research Tool. 
Patent protection is not being pursued for this technology.
    Licensing Status: Available for licensing.
    Licensing Contact: Sally Hu, PhD; 301-435-5606; HuS@mail.nih.gov.


[[Page 26707]]


    Dated: May 27, 2009.
Richard U. Rodriguez,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. E9-12873 Filed 6-2-09; 8:45 am]

BILLING CODE 4140-01-P