[Federal Register Volume 70, Number 177 (Wednesday, September 14, 2005)]
[Notices]
[Pages 54394-54396]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-18168]


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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.

Soluble Fragments of the IGF1R Ectodomain

Dimiter S. Dimitrov et al. (NCI)
HHS Reference No. E-144-2005/0--Research Tool
Licensing Contact: Michelle A. Booden; 301/451-7337; 
<a href="/cdn-cgi/l/email-protection#f79598989392999ab79a969e9bd9999e9fd9909881"><span class="__cf_email__" data-cfemail="21434e4e45444f4c614c40484d0f4f48490f464e57">[email protected]</span></a>.

    The type 1 insulin-like growth factor (IGF) receptor (IGF1R) is 
over-expressed by many tumors and mediates proliferation, motility, and 
protection from apoptosis. Agents that inhibit IGF1R expression or 
function can potentially block tumor growth and metastasis.
    The present invention relates to the identification of soluble 
fragments of the IGF1R ectodomain, where these fragments bind IGF-I, 
IGF-II, or the various other ligands of IFG1R. The identified fragment 
may be useful for identifying agents that block IGF1R and may act as a 
strong dominant negative inhibitor of tumor growth by blocking the 
IGF1R pathway. The invention also encompasses other IGF1R fragments or 
derivatives of the original fragments, methods of identifying IGF1R 
fragments or other similar fragments in the IGF1R ectodomain, methods 
of using said fragments to block binding of ligands, and methods of 
producing antibodies against the IGF1R fragments.
    The technology is available for licensing under a biological 
material license. In addition to licensing, the technology is available 
for further development through collaborative research opportunities 
with the inventors.

Polymer-Linked Pseudomonas Exotoxin Immunotoxin

Ira Pastan (NCI) et al.
U.S. Provisional Application No. 60/636,007 filed 12 Dec 2004 (HHS 
Reference No. E-121-2005/0-US-01)
Licensing Contact: Jesse Kindra; 301/435-5559; <a href="/cdn-cgi/l/email-protection#4b2022252f392a210b262a222765252223652c243d"><span class="__cf_email__" data-cfemail="b5dedcdbd1c7d4dff5d8d4dcd99bdbdcdd9bd2dac3">[email protected]</span></a>.

    Molecules based on monoclonal antibodies hold the promise of highly 
selective therapeutics. However, their efficacy can be limited by poor 
tissue penetration, rapid renal clearance and an immune response to the 
antibody. The present technology provides an immunotoxin that is 
modified to overcome such limitations.
    The technology relates to polymer-conjugated immunotoxins targeted 
to the mesothelin tumor cell antigen. These polymer-immunotoxin 
conjugates possess an enhanced therapeutic index and may provide 
improved methods of treating tumors and cancers expressing the 
mesothelin antigen.

Tumor Suppressor Gene Caliban

Mark A. Mortin et al. (NICHD)
U.S. Provisional Application filed 06 Jun 2005 (DHHS Reference No. E-
118-2005/0-US-01)
Licensing Contact: Jesse S. Kindra; 301/435-5559; <a href="/cdn-cgi/l/email-protection#1c777572786e7d765c717d757032727574327b736a"><span class="__cf_email__" data-cfemail="a3c8cacdc7d1c2c9e3cec2cacf8dcdcacb8dc4ccd5">[email protected]</span></a>.

    This invention relates to the identification of a tumor suppressor 
gene named Caliban from Drosophila melanogaster. The inventors have 
demonstrated that Caliban is very similar to the corresponding human 
gene and they have shown that the human gene is inactive in human lung 
cancer cells but active in normal lung cells. For the first time, it 
has been shown that when full length Caliban is expressed in human lung 
cancer cells they lose many of their tumorigenic properties. Hence, 
using gene therapy to replace the inactive gene with full length 
Caliban may treat cancer. Details of this were published in Bi et al., 
``Drosophila caliban, a nuclear export mediator, can function as a 
tumor suppressor in human lung cancer cells,'' Oncogene advance online 
publication, August 15, 2005; doi:10.1038/sj.onc.1208962.
    This invention also provides a biomarker assay that can be used to 
determine if the fly or human tumor suppressor Caliban gene product is 
functioning in cells. This assay uses a peptide from the fly gene 
Prospero, named HDA, which when fused to a reporter such as green 
fluorescent protein, is exported from the nucleus when Caliban is 
working.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

[[Page 54395]]

SIPA-1 Gene and SIPA-1 Inhibitor for the Treatment, Prevention and 
Diagnosis of Cancer

Kent Hunter et al. (NCI)
U.S. Provisional Application No. 60/649,365 filed 02 Feb 2005 (HHS 
Reference No. E-082-2005/0-US-01); U.S. Provisional Application No. 60/
657,943 filed 02 Mar 2005 (HHS Reference No. E-082-2005/1-US-01); U.S. 
Provisional Application No. 60/695,024 filed 29 Jun 2005 (HHS Reference 
No. E-216-2005/0-US-01)
Licensing Contact: Mojdeh Bahar; 301/435-2950; <a href="/cdn-cgi/l/email-protection#9af8fbf2fbe8f7daf7fbf3f6b4f4f3f2b4fdf5ec"><span class="__cf_email__" data-cfemail="e98b8881889b84a984888085c7878081c78e869f">[email protected]</span></a>.

    The technology relates to methods and compositions of matter used 
to identify and treat metastatic cancer. Using genetics, the inventors 
identified the mouse Sipa-1 gene as a possible metastasis modifying 
gene. Further analyses revealed that Sipa-1 expression levels correlate 
with metastasis. The inventors developed compounds that modulate Sipa-1 
expression and reduce metastasis in animal models. The inventors also 
identified single nucleotide polymorphisms (SNPs) present in the mouse 
Sipa-1 gene that, if also present in humans, could serve as the basis 
for diagnosing cancer and metastasis.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Diagnostic Tool for Diagnosing Benign Versus Malignant Thyroid Lesions

Steven K. Libutti et al. (NCI)
PCT Patent Application No. PCT/US05/12289 filed 11 Apr 2005 (HHS 
Reference No. E-124-2004/2-PCT-01)
Licensing Contact: Mojdeh Bahar; 301/435-2950; <a href="/cdn-cgi/l/email-protection#4123202920332c012c20282d6f2f28296f262e37"><span class="__cf_email__" data-cfemail="8be9eae3eaf9e6cbe6eae2e7a5e5e2e3a5ece4fd">[email protected]</span></a>.

    The present invention relates to methods for the diagnosis and 
staging of thyroid cancer. The invention employs analysis of gene 
expression using microarrays or quantitative RT-PCR to distinguish 
between malignant and benign tumors. Primer and probe sequences are 
described that represent a six gene or ten gene model for diagnosing 
benign and malignant thyroid cancer. Analysis of the expression of 
these genes in thyroid lesions taken from patients could be used for 
molecular classification of the lesions. As analysis of thyroid lesions 
by traditional means, such as fine needle biopsy with cytologic 
examination, can result in indeterminate results, the current invention 
may provide a superior method for molecular diagnoses of thyroid 
cancer.
    This research is described, in part, in Mazzanti et al., ``Using 
gene expression profiling to differentiate benign versus malignant 
thyroid tumors,'' Cancer Res. 2004 Apr 15 64(8):2898-2903.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Recombinant Vaccinia Viruses Expressing IL-15 and Methods of Using the 
Same

Liyanage Perera et al. (NCI)
U.S. Provisional Application No. 60/433,703 filed 16 Dec 2002 (HHS 
Reference No. E-243-2002/0-US-01); PCT Application No. PCT/US03/39967 
filed 15 Dec 2003, which published as WO 2004/058278A1 on 15 Jul 2004 
(HHS Reference No. E-243-2002/1-PCT-01); U.S. Patent Application filed 
14 Jun 2005 (HHS Reference No. E-243-2002/1-US-02)
Licensing Contact: John Stansberry; 301/435-5236; 
<a href="/cdn-cgi/l/email-protection#9ae9eefbf4e9f8fff0daf7fbf3f6b4f4f3f2b4fdf5ec"><span class="__cf_email__" data-cfemail="c1b2b5a0afb2a3a4ab81aca0a8adefafa8a9efa6aeb7">[email protected]</span></a>.

    Vaccinia-based vaccines have a proven record of being effective 
vaccines in humans as well as in animals. However, accumulating 
evidence reveals the need for technology to improve the immune 
responses such vaccines generate.
    The present invention discloses recombinant vaccinia viruses 
capable of expressing interleukin 15 (IL-15), and methods for 
modulating immune responses using such viruses. This invention shows 
that by inserting the human IL-15 gene into the vaccinia genome, more 
effective vaccines can be generated against infectious agents and 
cancer. Currently, IL-2 has been approved by the FDA for use in the 
treatment of patients with metastatic renal cell carcinoma or with 
metastatic melanoma. It has been used as a component of cancer vaccines 
and in various approaches for the treatment of AIDS. However, 
administration of IL-2 is associated with activation-induced cell death 
(AICD), and may lead to death of T-cells that recognize the antigens 
expressed in the tumor cells. Thus, IL-15 may be a superior agent in 
the treatment of cancer, or as a component of a vaccine directed 
towards cancer or infectious agents. Co-expression of IL-15 with 
antigens during the immunization process, according to the current 
invention, leads to induction of CD8+ memory T cells with higher 
avidity that proliferate more effectively in vivo and persist much 
longer in the immunized individual in addition to enhancing the levels 
and persistence of antigen specific antibodies thus providing 
substantially longer lasting cellular and humoral immunity.
    This invention has the potential to be used in a variety of ways, 
including: (i) an improved, more efficacious vaccine candidate for 
smallpox, (ii) for incorporation into existing vaccinia based vaccines 
to enhance and confer superior long lasting immune response to viral 
and cancer antigens, or (iii) as a valuable source material for IL-15 
production, especially should IL-15 be proven as an alternate of more 
efficacious cytokine than IL-2.
    This research has been described, in part, in SK Oh et al., 
``Coadministration of HIV vaccine vectors with vaccinia viruses 
expressing IL-15 but not IL-2 induces long-lasting cellular immunity,'' 
Proc. Natl. Acad. Sci USA 2003 Mar 18;100(6):3392-3397, online 
publication 10.1073/pnas.0630592100.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Amelioration of Inflammatory Arthritis Targeting the Pre-ligand 
Assembly Domain (PLAD) of Tumor Necrosis Factor Receptors

Michael J. Lenardo et al. (NIAID)
U.S. Provisional Application No. 60/694,015 filed 24 Jun 2005 (HHS 
Reference No. E-095-2000/2-US-01)
Licensing Contact: Mojdeh Bahar; 301/435-2950; <a href="/cdn-cgi/l/email-protection#4f2d2e272e3d220f222e26236121262761282039"><span class="__cf_email__" data-cfemail="e785868f86958aa78a868e8bc9898e8fc9808891">[email protected]</span></a>.

    The invention relates to compositions of matter and methods for 
treating arthritis by modulating Tumor Necrosis Factor Alpha (TNFalpha) 
signaling. TNFalpha plays a key role in the pathogenesis of numerous 
diseases including rheumatoid and septic arthritis, and other 
autoimmune and inflammatory diseases. TNFalpha mediates its effects 
through receptors that contain a Pre-ligand Assembly Domain (PLAD). The 
inventors have discovered compounds that interfere with PLAD can block 
the effects of TNFalpha in vitro. Treatment of mice with these 
compounds in vivo ameliorated disease in several models of arthritis. 
Therefore, the compositions and methods of the current invention may 
lead to novel arthritis treatments.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

[[Page 54396]]

Disubstituted Levendustin A Analogs (Including Adaphostin) and 
Pharmaceutical Compositions Comprising the Analogs

Venkatacha L. Narayanan et al. (NCI)
U.S. Patent Application No. 09/623,000 filed 25 Aug 2000 (DHHS 
Reference No. E-013-1998/0-US-07)
Licensing Contact: John Stansberry; (301) 435-5236; 
<a href="/cdn-cgi/l/email-protection#8bf8ffeae5f8e9eee1cbe6eae2e7a5e5e2e3a5ece4fd"><span class="__cf_email__" data-cfemail="730007121d00111619331e121a1f5d1d1a1b5d141c05">[email protected]</span></a>.

    Chronic myelogenous leukemia (CML) is almost universally associated 
with a translocation that juxtaposes the Bcr and Abl genes. Because the 
resulting kinase, p210 <SUP>Brc/Abl</SUP>, is found exclusively in 
malignant hematopoietic cells there has been considerable interest in 
identifying inhibitors of this enzyme. Adaphostin induces cytotoxicity 
in human leukemia cells by down-regulating p210 <SUP>Bcr/Abl</SUP>, 
inducing DNA damage and initiating apoptosis. Adaphostin exhibits 
selectivity for CML myeloid progenitors in vitro and retained its 
catholicity when cytotoxicity mesylate-resistant K562 cells were 
examined. Adaphostin may kill a wide range of human leukemia cells and 
may be effective against other cancer types. The present invention 
provides pharmaceutical compositions comprising effective amounts of 
adaphostin. The compound and composition of the present invention may 
be used for treating human leukemia and other proliferative diseases.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Heterologous Boosting Immunizations

Ronald S. Chamberlain et al. (NCI)
U.S. Patent Application No. 09/171,086 filed 22 Jan 1999 (HHS Reference 
No. E-087-1996/0-US-04); U.S. Patent Application No. 09/838,987 filed 
20 Apr 2001 (HHS Reference No. E-087-1996/0-US-05); U.S. Patent 
Application No. 11/007,115 filed 08 Dec 2004 (HHS Reference No. E-087-
1996/0-US-06); PCT Application No. PCT/US97/06632 filed 21 Apr 1997, 
which published as WO 97/39771 on 30 Oct 1997 (HHS Reference No. E-087-
1996/0-PCT-02); and Canadian Patent Application Serial No. 2,252,406 
(HHS Reference No. E-087-1996/0-CA-03)
Licensing Contact: Michelle A. Booden; 301/451-7337; 
<a href="/cdn-cgi/l/email-protection#50323f3f34353e3d103d31393c7e3e39387e373f26"><span class="__cf_email__" data-cfemail="97f5f8f8f3f2f9fad7faf6fefbb9f9feffb9f0f8e1">[email protected]</span></a>.

    The identification of tumor-associated antigens and the cloning of 
DNA sequences encoding them have enabled the development of anticancer 
vaccines. Such vaccines target tumors by stimulating an immune response 
against the antigens. One method of vaccination involves the delivery 
of antigen-encoding DNA sequences, and a number of recombinant vectors 
have been used for this purpose. To optimize the efficacy of 
recombinant vaccines, Dr. Steve Rosenberg and colleagues at the NCI 
have developed treatment regimens that use two different vectors (i.e., 
heterologous boosting).
    The present invention describes the method of heterologous boosting 
immunizations, which in essence is the use of a priming vaccination and 
a boosting vaccination using two different recombinant vectors that 
contain a similar or different tumor associated antigen (TAA). The use 
of different recombinant vectors unexpectedly increases and maintains 
the immune response to most tumor-associated antigens included in the 
vectors. The claims are directed, but not limited to, various 
recombinant viral vectors: poxvirus, vaccine, adenovirus, etc. 
Additional embodiments and claims are directed, but not limited to, 
melanoma tumor antigens such as Mart1, gp100, or Hep B surface antigen. 
These tumor antigen expressing recombinant vectors are coupled with 
distinctly different recombinant vectors, which express various 
cytokines and co-stimulatory and accessory molecules such as B7-1, B7-
2, ICAM-1, etc. This therapeutic intervention could be directed toward 
multiple human carcinomas but, with respect to this technology, has 
been customized as a therapeutic intervention for melanoma.
    This technology is available under an exclusive or non-exclusive 
license. In addition to licensing, the technology is available for 
further development through collaborative research opportunities with 
the inventors.

    Dated: September 2, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-18168 Filed 9-13-05; 8:45 am]
BILLING CODE 4140-01-P


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