[Federal Register Volume 70, Number 106 (Friday, June 3, 2005)]
[Notices]
[Pages 32632-32634]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 05-11096]


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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 32633]]

Method of Diagnosing Cancer Using beta-Catenin Splice Variants

    Mark J. Roth and Konrad Huppi (NCI); U.S. Provisional Application 
No. 60/652,154 filed 10 Feb 2005 (DHHS Reference No. E-018-2005/0-US-
01); Licensing Contact: Susan S. Rucker; (301) 435-4478; 
[email protected].
    This application relates to methods for early detection, diagnosis, 
and prognosis of cancers and their associated preneoplastic lesions. 
The methods are useful in evaluating the status of preneoplastic 
lesions as well as tumor tissue. Because of this, the methods can be 
used to track the progression and therapeutic response of disease in 
cell and tissue samples of normal, dysplasia or cancerous epithelium 
procured by routine cytology, i.e., exfoliated/brush or fine needle 
aspiration, or surgical methods.
    The methods are particularly useful with respect to adenocarcinomas 
and squamous cell carcinomas. In particular, the methods described and 
claimed in the application are useful with respect to preneoplasias and 
carcinomas involving the upper aerodigestive tract.
    The methods involve the measurement of levels of one or more pairs 
of transcripts or the protein products of these pairs of transcripts or 
the cellular localization of the transcripts or proteins. The primary 
transcripts or protein products useful in this method are those of the 
beta-Catenin gene (CTNNB1). In particular, the levels of the 16A and 
16B CTNNB1 transcripts or protein products are of importance in 
carrying out the methods of this patent application. Other gene 
transcripts or protein products that may be used in conjunction with 
CTNNB1 16A and 16B to provide additional information are WAF1 (p21) and 
cMYC.
    The methods can be practiced using fresh or frozen cell and/or 
tissue specimens and techniques such as laser capture microdissection 
(LCM) RT-PCR.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Method of Diagnosing and Treating Cancer Using beta-Catenin Splice 
Variants

    Mark J. Roth and Konrad Huppi (NCI); U.S. Provisional Application 
No. 60/667,084 filed 30 Mar 2005 (DHHS Reference No. E-018-2005/1-US-
01); Licensing Contact: Susan S. Rucker; (301) 435-4478; 
[email protected].
    This application relates to methods for treatment of cancers and 
preneoplastic lesions. The treatment methods may also be used in 
conjunction with the diagnostic/prognostic methods disclosed in related 
provisional patent application 60/652,154 (NIH Ref: E-018-2005/0-US-
01).
    The methods are particularly useful with respect to adenocarcinomas 
and squamous cell carcinomas. In particular, the methods described and 
claimed in the application are useful with respect to preneoplasias and 
carcinomas involving the upper aerodigestive tract.
    The methods employ small interfering RNA molecules (siRNAs) as a 
means to alter the expression of one or more particular CTNNB1 
transcripts. In particular, preferred siRNA molecules alter the 
expression of the CTNNB1 transcripts 16A and/or 16B. The siRNA 
molecules may be single-stranded (ss) or double-stranded (ds). The 
siRNA molecules may be delivered using a construct, which is capable of 
expressing the siRNA molecule upon delivery to the target cell.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Framework Residue Substituted Humanized COL-1 Antibodies and Their Use

    Syed Kashmiri (NCI), Eduardo Padlan (NIDDK), and Jeffrey Schlom 
(NCI); U.S. Provisional Application No. 60/640,672 filed 30 Dec 2004 
(DHHS Reference No. E-339-2004/0-US-01); Licensing Contact: Michelle A. 
Booden; (301) 451-7337; [email protected].
    Carcinoembryonic antigen (CEA) has been found to be an important 
marker of colorectal cancer. CEA is expressed in 85 percent of all 
gastric cancers and may function as a metastatic potentiator of such 
cancers. In addition, it has been shown that CEA is up regulated when 
certain cancers are treated with standard chemotherapy drugs. A 
treatment modality that focuses specifically on CEA could be an 
effective way of treating many carcinomas, including colorectal, 
gastric, pancreatic, lung and breast cancers.
    The present invention relates to humanized monoclonal antibodies 
that bind to CEA. Specifically, these antibody variants have amino acid 
substitutions in the heavy chain framework that reduces the likelihood 
of human anti-mouse antibodies (HAMA).
    The original murine COL-1 antibody has been shown to be reactive to 
CEA without cross reactivity with other potential antigens of the CEA 
family: specifically Antigens NCA-1 and normal fecal antigen Ag1. The 
increased specificity to CEA and reduced human immunogenicity of these 
COL-1 humanized variants makes these antibodies attractive therapeutic 
and/or diagnostic compounds.
    The COL-1 antibody is described in the following background 
publications:
    (i) Gonzales NR, Padlan EA, De Pascalis R, Schuck P, Schlom J, and 
Kashmiri SV. SDR grafting of a murine antibody using multiple human 
germline templates to minmize its immunogenicity. Mol. Immunol. 41(9): 
863-872, 2004.
    (ii) De Pascalis R, Iwahashi M, Tamura M, Padlan EA, Gonzales NR, 
Santos AD, Giuliano M, Schuck P, Schlom J, and Kashmiri SV. Grafting of 
``abbreviated'' complementarity-determining regions containing 
specificity-determining residues essential for ligand contact to 
engineer a less immunogenic humanized monoclonal antibody. J. Immunol. 
169: 3076-3084, 2002.
    (iii) Gonzales NR, Padlan EA, De Pascalis R, Schuck P, Schlom J, 
Kashmiri SV. Minimizing immunogenicity of the SDR-grafted humanized 
antibody CC49 by genetic manipulation of the framework residues. Mol. 
Immunol. 40:337-349, 2003.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Inhibiting IL-13 Receptor-Expressing Cancer Cells With Anti-IL-13 
Receptor Immunotoxin and Alkylating Agents

    Raj Puri and Syed Husain (FDA); U.S. Provisional Application No. 
60/621,035 filed 20 Oct 2004 (DHHS Reference No. E-302-2003/0-US-01); 
Licensing Contact: Brenda Hefti; (301) 435-4632; [email protected].
    The present invention relates to methods of inhibiting the growth 
of cancer cells expressing the IL-13 receptor. Most generally, the 
patent application claims immunotoxins consisting of anti-IL-13 
antibodies bound to toxins such as pseudomonas exotoxin or diphtheria 
toxin, or a cytotoxic fragment thereof, used in combination with 
alkylating agents. This combination appears to have significant 
advantages over use of either agent alone in the treatment of malignant 
gliomas, head and neck cancers, adenocarcinomas of the colon, stomach 
of skin, and Hodgkin's disease.

Regulation of RNA Stability

    Wi Lai et al. (NIEHS); U.S. Provisional Application No. 60/451,976 
filed 06 Mar

[[Page 32634]]

2003 (DHHS Reference No. E-314-2002/0-US-01); PCT Application No. PCT/
US04/06703 filed 05 Mar 2004, which published as WO 2004/081179 A2 on 
10 Feb 2005 (DHHS Reference No. E-314-2002/0-PCT-02); Licensing 
Contact: Jesse S. Kindra; (301) 435-5559; [email protected].
    This invention relates to the discovery that tristetraprolin (TTP) 
can promote the poly(A)RNase (PARN) mediated deadenylation of 
polyadenylated substrates containing AU-rich elements (AREs). As one 
aspect of the invention, the inventors have developed a cell free 
system that may be used for the purposes of assessing the effects of 
the various system components or their derivatives (i.e. AREs, PARN, or 
TTP) on the deadenylation process or the effects of various test agents 
on the deadenylation process. Aspects of this work have been published 
as follows: Lai et al., 2003, Tristetraprolin and Its Family Members 
Can Promote the Cell-Free Deadenylation of AU-Rich Element-Containing 
mRNAs by Poly(A) Ribonuclease, MCB 23(11):3798-3812.
    This technology is available for licensing on an exclusive or a 
non-exclusive basis.
    In addition to licensing, the technology is available for further 
development through collaborative research opportunities with the 
inventors.

Tristetraprolin (TTP) Knockout Mice

Perry Blackshear et al (NIEHS).
DHHS Reference No. B-015-1999/0--Research Material.
Licensing Contact: Michelle A. Booden; 301/451-7337; 
[email protected].

    National Institutes of Health researchers have developed knockout 
mice that do not express Tristetraprolin (TTP). TTP is an AU-rich 
element (ARE) binding protein and the prototype of a family of CCCH 
zinc finger proteins. AREs were identified as conserved sequences found 
in the 3' untranslated region (3' UTR) of a variety of transiently 
expressed genes including early respsonse genes, proto-oncogenes, and 
other growth regulatory genes. AREs function as instability sequences 
that target ARE-containing transcripts for rapid mRNA decay. TTP 
functions by binding directly to the ARE sequence contained in the TNF-
alpha mRNA, which destabilizes and mediates rapid decay of the TNF-
alpha mRNA. More recent studies demonstrate TTP's ability to 
downregulate IL-2 gene expression.
    TTP knockout mice appear normal at birth but soon develop 
inflammatory arthritis, dermatitis, cachexia, autoimmunity, and myeloid 
hyperplasia. Almost all aspects of these phenotypes can be prevented 
with repeated injections of antibodies to TNF. Moreover, macrophages 
isolated from these mice exhibit increased production of TNF-alpha and 
increased amounts of TNF-alpha mRNA.
    This transgenic mouse model will be valuable in advancing our 
understanding of the mechanisms controlling mRNA turnover in immune 
homeostasis as well as autoimmune diseases. This model will also permit 
the development of screening assays to elucidate the functions and 
binding partners for other members of the CCCH zinc finger family as 
well as compounds capable of inhibiting aberrant TNF-alpha and IL-2 
biosynthesis. Lastly, this model will advance understanding of the 
pathogenetic role for IL-2 and/or TNF in various autoimmune and 
inflammatory diseases. The mice will be made available on a non-
exclusive basis under a Biological Materials License Agreement.
    Background scientific detail may be found in Immunol. 2005 Jan 15; 
174(2):953-61; Arthritis Res Ther. 2004; 6(6):248-64; and Science. 1998 
Aug 14; 281(5379):1001-5.

    Dated: May 23, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 05-11096 Filed 6-2-05; 8:45 am]
BILLING CODE 4140-01-P