[Federal Register Volume 69, Number 232 (Friday, December 3, 2004)]
[Notices]
[Pages 70265-70267]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-26596]


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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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[[Page 70266]]

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.

Adoptive Immunotherapy With Enhanced T-Lymphocyte Survival

Richard Morgan (NCI) and Steven Rosenberg (NCI)
U.S. Provisional Patent Application No. 60/617,340 filed 08 Oct 2004 
(DHHS Reference No E-340-2004/0-US-01) and U.S. Provisional Patent 
Application filed 12 Oct 2004 (DHHS Reference No E-340-2004/1-US-01)
Licensing Contact: Jeff Walenta; (301) 435-4633; [email protected].

    Adoptive immunotherapy strategies have existed for several years 
now and many have proven to be highly successful in a limited subset of 
patients. This limited response rate among a diverse patient population 
may not be surprising, given the complexity of the immune system and 
the complicated evolution of a normal cell to a immune evading 
malignancy. A common observation amongst most patients that did not 
respond to adoptive therapy strategies is that the immune response to 
the cancer was not sustained.
    A number of cytokines have been shown to sustain a T-cell response 
when administered systemically with autologous isolated T-cells. 
However, the systemic delivery of many cytokines, such as IL-2, will 
cause significant toxicity before the beneficial immunologic effects of 
the autologous T-cells can occur. This invention describes a method of 
transfecting isolated autologous T-Lymphocytes with endogenous 
cytokines, for example IL-7 and IL-15, to sustain an adoptive T-
lymphocyte response without systemic toxicity. The invention also 
describes a method for improving expression of transfected cytokines 
via a codon optimized IL-15 vector.
    This invention was developed at the NCI Surgery Branch. The Surgery 
Branch plans to initiate clinical studies utilizing this technology and 
collaborative opportunities may be available. Publications which may 
provide background information for this technology include:
    1. Rosenberg, SA and Dudley, ME. Cancer regression in patients with 
metastatic melanoma after the transfer of autologous antitumor 
lymphocytes. Proc Natl Acad Sci U S A. 2004 Oct 5;101 Suppl 2:14639-45. 
Epub 2004 Sep 20.
    2. Klebanoff CA, Finkelstein SE, Surman DR, Lichtman MK, Gattinoni 
L, Theoret MR, Grewal N, Spiess PJ, Antony PA, Palmer DC, Tagaya Y, 
Rosenberg SA, Waldmann TA, Restifo NP. IL-15 enhances the in vivo 
antitumor activity of tumor-reactive CD8+ T cells. Proc Natl Acad Sci U 
S A. 2004 Feb 17;101(7):1969-74. Epub 2004 Feb 04.
    3. Dudley ME, Rosenberg SA. Adoptive-cell-transfer therapy for the 
treatment of patients with cancer. Nat Rev Cancer. 2003 Sep;3(9):666-
75. Review.
    4. Liu K, Rosenberg SA. Interleukin-2-independent proliferation of 
human melanoma-reactive T lymphocytes transduced with an exogenous IL-2 
gene is stimulation dependent. J Immunother. 2003 May-Jun;26(3):190-
201.
    5. Liu K, Rosenberg SA. Transduction of an IL-2 gene into human 
melanoma-reactive lymphocytes results in their continued growth in the 
absence of exogenous IL-2 and maintenance of specific antitumor 
activity. J Immunol. 2001 Dec 1;167(11):6356-65.

A New Approach Toward Macrocyclization of Peptides

Terrence R. Burke, Jr. et al. (NCI)
DHHS Reference No. E-327-2004/0-US-01
Licensing Contact: George Pipia; (301) 435-5560; [email protected]

    The invention relates to cyclic peptides for use as inhibitors of 
oncogenic signal transduction for cancer therapy. The current invention 
discloses novel cyclic peptides resulting from ring closure between the 
alpha and beta positions of C-terminal and N-terminal residues, 
respectively. This allows retention of key functionality needed for 
binding to target proteins, which results in increased affinity.
    Cyclic peptides that retain key chemical functionality may be of 
particular importance in inhibiting oncogenic signaling cascades for 
therapeutic benefit. In many oncogenic signal transduction cascades, 
tyrosine protein kinases phosphorylated target proteins. Propagation of 
the signal is achieved when these phosphorylated tyrosyl residues are 
bound by proteins bearing SH2 domains. Cyclic peptides that disrupt the 
interaction between proteins with SH2 domains and proteins with 
phosphorylated tyrosyl residues could block oncogenic signals and serve 
as powerful cancer therapeutic agents. As several moieties are required 
for optimal recognition by SH2 domains, the cyclic peptides of the 
current invention could be more effective inhibitors of SH2 domain 
proteins, or of other proteins where increased specificity is desired. 
The inventors have determined that the peptides of the current 
invention bind to the Grb2-SH2 domain with high affinity, supporting 
their potential use as therapeutic agents. The current invention is 
related to U.S. Provisional Application No. 60/504,241; DHHS Reference 
No. E-315-2003/0-US-01.

cDNA for Murine PEDF

IR Rodriguez, GJ Chader, VK Singh (NEI)
DHHS Reference No. E-112-2004/0--Research Tool
Licensing Contact: Susan Rucker; (301) 435-4478; [email protected].

    This technology is a cDNA, obtained from mouse liver, which encodes 
the open reading frame of the murine homolog of pigment epithelium-
derived factor (mPEDF). PEDF is a serpin protein that has not been 
demonstrated to have serine protease activity in a physiological 
setting but which exhibits diverse biologic properties including 
neurotrophic activity and anti-angiogenic activity. The mPEDF cDNA may 
be used to study PEDF function and may be particularly useful in 
research applications comparing mPEDF to hPEDF. The cDNA, provided as a 
plasmid designated pMOU12A, can be readily inserted into an expression 
vector. The cDNA is further described in Singh, VK et al. Mol Vision 4: 
7 (April 20, 1998). No patent application has been or will be filed by 
the NIH for this technology. The cDNA is available through a biological 
materials license agreement.

Novel Compounds That Release Both Nitric Oxide (NO) and Nitroxyl (HNO) 
as Pharmacological Agents

Larry Keefer et al. (NCI)
U.S. Provisional Application No. 60/540,368 filed 30 Jan 2004 (DHHS 
Reference No. E-095-2004/0-US-01)

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Licensing Contact: Norbert Pontzer; (301) 435-5502; 
[email protected]

    The simple diatomic molecule nitric oxide (NO) is known to play a 
diverse and complex role in cellular physiology. NCI scientists have 
previously produced a number of nucleophile/nitric oxide adducts 
(diazeniumdiolates) that spontaneously dissociate at physiological pH 
to release nitric oxide by stable first order kinetics. These compounds 
are finding diverse therapeutic uses as pharmacological agents. Growing 
evidence suggests that redox related forms of NO such as nitroxyl (HNO) 
also have a rich pharmacological potential and may complement that of 
NO. The present invention provides compounds that release both NO and 
HNO under physiological conditions, compositions comprising those 
compounds and methods of using the compounds alone and in conjunction 
with medical devices such as stents to treat disease. Included among 
the compositions claimed is a glycosylated prodrug derivative that can 
be cleaved to active form by [beta]-D-glucosidase (J. Am. Chem. Soc. 
2004, 126, 12880-12887).

A Method With Increased Yield for Production of Polysaccharide-Protein 
Conjugate Vaccines Using Hydrazide Chemistry

Che-Hung Robert Lee and Carl Frasch (FDA), U.S. Provisional Application 
No. 60/493,389 filed 06 Aug 2003 (DHHS Reference No. E-301-2003/0-US-
01)

Licensing Contact: Peter Soukas; (301) 435-4646; [email protected].

    Current methods for synthesis and manufacturing of polysaccharide-
protein conjugate vaccines employ conjugation reactions with low 
efficiency (about twenty percent). This means that up to eighty percent 
of the added activated polysaccharide (PS) is lost. In addition, 
inclusion of a chromatographic process for purification of the 
conjugates from unconjugated PS is required.
    The present invention utilizes the characteristic chemical property 
of hydrazide groups on one reactant to react with aldehyde groups or 
cyanate esters on the other reactant with an improved conjugate yield 
of at least sixty percent. With this conjugation efficiency the 
leftover unconjugated protein and polysaccharide would not need to be 
removed and thus the purification process of the conjugate product can 
be limited to diafiltration to remove the by-products of small 
molecules. The new conjugation reaction can be carried out within one 
or two days with reactant concentrations between 1 and 25 mg/mL at PS/
protein ratios from 1:2 to 3:1, at temperatures between 4 and 40 
degrees Centigrade, and in a pH range of 5.5 to 7.4, optimal conditions 
varying from PS to PS.
    Therefore, this invention can reduce the cost of conjugate vaccine 
manufacture.

    Dated: November 24, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-26596 Filed 12-2-04; 8:45 am]
BILLING CODE 4140-01-P