[Federal Register Volume 69, Number 232 (Friday, December 3, 2004)]
[Notices]
[Pages 70267-70268]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 04-26595]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

National Institutes of Health


Prospective Grant of Exclusive License: Dendrimer Based MRI 
Contrast Agents

AGENCY: National Institutes of Health, Public Health Service, DHHS

ACTION: Notice.

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SUMMARY: This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 
CFR 404.7(a)(1)(i), that the National Institutes of Health (NIH), 
Department of Health and Human Services, is contemplating the grant of 
an exclusive worldwide license to practice the invention embodied in:

    E-151-2002 ``Methods for Functional Kidney Imaging Using 
Dendrimer Conjugate Agents,'' U.S. Patent App. Serial No. 10/229,316 
and International Patent Application No. PCT/US02/27297;
    E-240-2001 ``Macromolecular Imaging Agents for Liver Imaging,'' 
U.S. Patent App. Serial No. 10/481,706, International Patent 
Application No. PCT/US02/20118, European Patent Application 
02752092.3;
    E-338-2003 ``Method for Imaging the Lymphatic Systems Using 
Dendrimer-Based Contrast Agents,'' U.S. Patent App. Serial No. 10/
756,948;
    E-317-2004 ``Synthetic Metal Ion Chelating Amino Acid Suitable 
for Use in Solid Phase Peptide Synthesis.'' Filed October 4, 2004 
(Serial Number to be determined);

to Dendritic NanoTechnologies, Inc., a Delaware corporation having its 
principle place of business in Mount Pleasant, Michigan. The United 
States of America is the assignee to the patent rights of the above 
inventions.
    The contemplated exclusive license may be granted in the field of 
use of MRI imaging contrast agents.

DATES: Only written comments and/or applications for a license received 
by the NIH Office of Technology Transfer on or before February 1, 2005 
will be considered.

ADDRESSES: Requests for a copy of the patent application, inquiries, 
comments and other materials relating to the contemplated license 
should be directed to: Michael A. Shmilovich, Esq., Office of 
Technology Transfer, National Institutes of Health, 6011 Executive 
Boulevard, Suite 325, Rockville, MD 20852-3804; Telephone: (301) 435-
5019; Facsimile: (301) 402-0220; E-mail: [email protected]. A 
signed confidentiality nondisclosure agreement will be required to 
receive copies of the patent applications.

SUPPLEMENTARY INFORMATION: The patent applications intended for 
licensure disclose and/or cover the following:

E-151-2002--Methods for Functional Kidney Imaging Using Dendrimer 
Conjugate Agents

    The invention is a method for functional kidney imaging using small 
dendrimer-based MRI contrast agents that transiently accumulate in 
renal tubules. The accumulation enables visualization of renal 
structure and function, permitting assessment of structural and 
functional damage to the kidneys. Six small dendrimer-based MRI 
contrast agents have been synthesized, and their pharmacokinetics, 
whole body retention and renal MRI images were evaluated in mice. 
Surprisingly, despite having unequal renal clearance properties, all of 
the dendrimer agents clearly visualized the renal anatomy and proximal 
straight tubules of the mice better than Gd-[DTPA]-dimeglumine. 
Dendrimer conjugate contrast agents prepared from PAMAM-G2D, DAB-G3D 
and DAB-G2D dendrimers were excreted rapidly and may be acceptable for 
use in clinical applications.

E-240-2001--Macromolecular Imaging Agents for Liver Imaging

    The invention is a macromolecular imaging agent comprising a 
polyalkylenimine dendrimer conjugated to a metal chelate that has been 
shown to be an excellent agent for imaging liver micrometastases as 
small as about 0.3 mm in a magnetic resonance image of the human liver. 
In a particular embodiment, the imaging agent is a diaminobutane-core 
polypropylenimine dendrimer having surface amino groups conjugated to 
gadolinium metal chelates. The invention makes possible the earlier 
detection of metastatic disease, leading to earlier application of a 
therapeutic regime and an improved prognosis. Accordingly, the method 
of

[[Page 70268]]

using the imaging agent in the detection of metastatic disease in the 
liver is also within the scope of the invention.

E-338-2003--Method for Imaging the Lymphatic Systems Using Dendrimer-
Based Contrast Agents

    The invention is a 4D method of Magnetic Resonance lymphography 
using a 240kD contract agent based on generation-6 polyamidoamine 
dendrimer (G6). The use of the G6 contrast agent greatly enhances 
visualization of lymphatics and node drainage associated with mammary 
tumors and further aids in the diagnosis of metastatic breast cancer. 
After direct injection of the G6 contrast agent into mice, lymphatics 
and nodes were visualized in both spontaneous (HER2 transgenic mouse) 
and xenografted (PT-18) breast tumors to metastatic lymph nodes. The 
conventional clinically approved MRI contract agent, Gd-[DTPA]-
dimeglumine (<1kD) was unable (in murine models) to depict lymphatics 
when used in conjunction with the same imaging system. The invention 
provides a novel method of using a known contrast agent to visualize 
lymphatic drainage that has not been previously reported.

E-317-2004--Synthetic Metal Ion Chelating Amino Acid Suitable for Use 
in Solid Phase Peptide Synthesis

    The invention is metal chelators, metal chelator-targeting moiety 
complexes, metal chelator-targeting moiety-metal conjugates, kits, and 
methods of preparing them. These chelators are useful in diagnosing 
and/or treatment of cancer and thrombosis. The metal chelators may be 
used in conventional synthetic methods to form targeting moieties 
(e.g., peptides, proteins, and Starburst polyamidoamine dendrimers 
(PAMAM), capable of conjugating diagnostic and/or therapeutic metals. 
The formulae for two such chelators is shown below:
[GRAPHIC] [TIFF OMITTED] TN03DE04.000

    The prospective exclusive license will be royalty bearing and will 
comply with the terms and conditions of 35 U.S.C. 209 and 37 CFR 404.7. 
The prospective exclusive license may be granted unless, within sixty 
(60) days from the date of this published notice, NIH receives written 
evidence and argument that establishes that the grant of the license 
would not be consistent with the requirements of 35 U.S.C. 209 and 37 
CFR 404.7.
    Properly filed competing applications for a license filed in 
response to this notice will be treated as objections to the 
contemplated license. Comments and objections submitted in response to 
this notice will not be made available for public inspection, and, to 
the extent permitted by law, will not be released under the Freedom of 
Information Act, 5 U.S.C. 552.

    Dated: November 24, 2004.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of 
Technology Transfer, National Institutes of Health.
[FR Doc. 04-26595 Filed 12-2-04; 8:45 am]
BILLING CODE 4140-01-U