[Federal Register Volume 68, Number 234 (Friday, December 5, 2003)]
[Notices]
[Pages 68088-68090]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-30207]


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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

[[Page 68089]]

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.

Methods of Preparing Lymphocytes That Express Interleukin-2 and Their 
Use in the Treatment of Cancer

Ke Liu and Steven Rosenberg (NCI).
PCT Application No. PCT/US02/33243 filed 15 Oct 2002 (DHHS Reference 
No. E-297-2002/0-PCT-01).
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].

    Adoptive immunotherapy strategies are highly dependent upon a 
sustained immune response to a tumor specific antigen. An effective 
adoptive strategy should ideally recruit and integrate into the 
existing components of a cancer patient's inherent immune system. 
However, most cancer patient's immune systems are unable to sustain the 
expansion of introduced tumor specific T-cells and hence cannot sustain 
a tumor specific response. Interleukin 2 (IL-2) is a natural cytokine 
that will promote the growth and expansion of introduced tumor specific 
T cells. Unfortunately, supplementing a patient's immune system with 
the systemic introduction of IL-2 has severe toxicity effects at a dose 
sufficient to promote T-cell growth, limiting the effectiveness of many 
adoptive strategies.
    This invention relates to methods of preparing autologous T-
lymphocytes and tumor-infiltrating lymphocytes that express IL-2. This 
method comprises the following steps: obtaining peripheral blood 
mononuclear cells (PBMC) or tumor infiltrating lymphocytes (TIL) from a 
patient immunized with an antigen of cancer; stimulating the PBMC's or 
TIL with the antigen of the cancer in vitro; transducing the PBMC's or 
TIL with a retroviral vector encoding IL-2; and reintroducing these 
autologous T-lymphocytes back into the patient. This method overcomes 
the potential toxicity issues from systemic IL-2 delivery and creates 
self-sufficient T-cells for an effective adoptive immunotherapy 
response.

Catalytic Domains of [beta](1,4)-galactosyltransferase I Having Altered 
Donor and Acceptor Specificities, Domains That Promote In Vitro Protein 
Folding, and Methods for Their Use

Pradman Qasba (NCI), Boopathy Ramakrishnan (NCI), Elizabeth Boeggeman 
(NCI).
U.S. Provisional Application No. 60/439,298 filed 10 Jan 2003 (DHHS 
Reference No. E-230-2002/0-US-01); U.S. Provisional Application No. 60/
450,250 filed 23 Feb 2003 (DHHS Reference No. E-230-2002/1-US-01).
Licensing Contact: Peter Soukas; 301/435-4646; [email protected].

    [beta](1,4)-galactosyltransferase I catalyzes the transfer of 
galactose from the donor, UDP-galactose, to an acceptor, N-
acetylglucosamine, to form a galactose-[beta](1,4)-N-acetylglucosamine 
bond. This reaction allows galactose to be linked to an N-
acetylglucosamine that may itself be linked to a variety of other 
molecules. The reaction can be used to make many types of molecules 
having great biological significance. For example, galactose-
[beta](1,4)-N-acetylglucosamine linkages are very important for 
cellular recognition and binding events as well as cellular 
interactions with pathogens, such as viruses. Therefore, methods to 
synthesize these types of bonds have many applications in research and 
medicine to develop pharmaceutical agents and improved vaccines that 
can be used to treat disease.
    The present invention is based on the surprising discovery that the 
enzymatic activity of [beta](1,4)-galactosyltransferase can be altered 
such that the enzyme can make chemical bonds that are very difficult to 
make by other methods. These alterations involve mutating the enzyme 
such that the mutated enzyme can transfer many different types of 
sugars from sugar nucleotide donors to many different types of 
acceptors. Therefore, the mutated [beta](1,4)-galactosyltransferases of 
the invention can be used to synthesize a variety of products that, 
until now, have been very difficult and expensive to produce.
    The invention also provides amino acid segments that promote the 
proper folding of a galactosyltransferase catalytic domain. The amino 
acid segments may be used to properly fold the galactosyltransferase 
catalytic domains of the invention and thereby increase their activity. 
The amino acid segments may also be used to increase the activity of 
galactosyltransferases that are produced recombinantly. Accordingly, 
use of the amino acid segments according to the invention allows for 
production of [beta](1,4)-galactosyltransferases having increased 
enzymatic activity relative to [beta](1,4)-galactosyltransferases 
produced in the absence of the amino acid segments.
    Some of the many uses for this invention are the following: 
synthesis of polysaccharide antigens for conjugate vaccines, 
glycosylation of monoclonal antibodies, and as research tools.

Targeting of the Hepatitis A Cellular Receptor To Treat Renal Cancer

    Gerardo Kaplan (FDA).
U.S. Provisional Patent Application No. 60/442,286 filed 24 Jan 24 2003 
(DHHS Reference No. E-227-2002/0-US-01).
Licensing Contact: Brenda Hefti; (301) 435-4632; [email protected].

    Tumor markers--receptors on the cell surface that are expressed 
preferentially in tumor cells--are extremely useful in the diagnosis 
and treatment of cancers. The inventors have discovered that hHAVcr-1 
is such a tumor marker because it is overexpressed in renal cell 
carcinomas, and its degree of overexpression is correlated to the stage 
of the tumor. In addition, overexpression of this receptor appears to 
affect differentiation.
    The inventors have also demonstrated that they can target this 
receptor specifically in vitro, using monoclonal antibodies tagged with 
toxins and hepatitis A virus vectors. This discovery might be useful as 
a tumor marker or for gene-based therapeutics. Antibodies against the 
receptor encoded by hHAVcr-1 might be useful in an antibody-based 
therapeutic for the treatment of renal cancer.

Novel 2-Alkoxy Estradiols and Derivatives Thereof

    Ravi Varma (NCI).
U.S. Patent Application No. 09/041,212 filed on 12 Mar 1998, which 
issued as U.S. Patent 6,136,992 on 24 October 2000 (DHHS Reference No. 
E-188-1998/1-US-01); U.S. Provisional Application No. 60/040,540 filed 
13 Mar 1997 (DHHS Reference No. E-188-1998/0-US-01).
Licensing Contact: George Pipia; 301/435-5560; [email protected].

    The present invention is directed to novel 2-alkoxy estradiols and 
derivatives of 2-alkoxy estradiols having anticancer activity as 
claimed in the U.S. Patent 6,136,992. The invention is also directed to 
methods of preparing these novel compounds. These compounds have 
improved activity against a wide variety of tumor cell lines, including 
lung, colon, central nervous system, melanoma, ovarian, renal, prostate 
and breast cancers, compared with 2-methoxy estradiols. It is expected 
that these compounds will be very useful in the treatment of a wide 
variety of cancers. In addition, the present compounds have a low 
affinity for the estrogen receptor and are, therefore, expected to have 
fewer side effects than estradiols.


[[Page 68090]]


    Dated: November 25, 2003.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 03-30207 Filed 12-4-03; 8:45 am]
BILLING CODE 4140-01-P