[Federal Register Volume 68, Number 122 (Wednesday, June 25, 2003)]
[Notices]
[Pages 37850-37852]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 03-15971]


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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, HHS.

ACTION: Notice.

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SUMMARY: The inventions listed below are owned by agencies 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

[[Page 37851]]

be required to receive copies of the patent applications.

Transgenic Mouse Model of Human B-cell Neoplasia Based on Myc Insertion 
into IgH (IgH-Myc)

Siegfried Janz, M.D. (NCI)
DHHS Reference No. E-160-2003/0
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Some types of cancers are caused by the translocation of genes 
between two different chromosomes. When a translocation occurs near a 
highly active promoter, uncontrolled cell growth can be the result if 
the translocated chromosome piece contains an oncogene. For example, in 
some types of B cell neoplasias the Myc oncogene from chromosome 8 is 
translocated into the highly transcribed region of the IgH locus in 
chromosome 14.
    This invention is a transgenic mouse model that mimics the 
t(8;14)(q24;q32) translocation commonly found in human sporadic 
Burkitt's Lymphoma. Specifically, this model has the Myc gene inserted 
into the IgH locus just upstream of the constant region Cm.
    Since the Myc translocation can occur at various regions within the 
IgH locus, several mouse models of Myc-IgH translocations have been 
developed. Two of these, the IgH-MycEIgH-
MycC, have been made available previously. The 
present specific translocation (IgH-MycC) animal 
model will deepen the understanding of the pathogenesis of B-cell 
neoplasia, uncover new targets for treatment, and serve as a pre-
clinical model for innovative intervention approaches.

Inducing a T-Cell Response With Recombinant Pestivirus Replicons or 
Recombinant Pestivirus Replicon-Transfected Dendritic Cells

Barbara Rehermann et al. (NIDDK) Serial No. 60/462,165 filed 11 Apr 
2003 (DHHS Reference No. E-098-2003); Serial No. 60/463,097 filed 14 
Apr 2003 (DHHS Reference No. E-230-2003),
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Cancer and diseases such as Hepatitis C Virus (HCV), Human 
Immunodeficiency Virus (HIV), Respiratory Syncytial Virus (RSV), 
Mycobacterium tuberculosis, Plasmodium falciparum infection, are not 
effectively prevented by the humoral immune response initiated by 
standard antigen vaccinations. The neutralizing antibody response 
created by these types of vaccinations is not effective enough to 
prevent the progression of the disease. In these cases, a cellular, T-
Cell mediated immune response is a much more effective vaccination 
strategy.
    This invention describes the use of recombinant pestivirus 
replicons or recombinant pestivirus replicon transfected dendritic 
cells to induce and/or enhance a T-cell mediated immune response by 
exploiting the cross-priming ability of endogenous antigen-presenting 
cells (APCs). These recombinant pestivirus replicons contain an antigen 
specific to a disease requiring a T-cell response. This antigen is 
presented to APCs in the lymphatic system by the apoptotic transfected 
dendritic cells that initiate cross-priming.
    This invention generates a stronger immune response than current 
dendritic cell/APC methods. Because dendritic cells transfected with 
the recombinant pestivirus replicons survive longer than dendritic 
cells transfected with other viral replicons, more transfected 
dendritic cells enter the lymphatic system and undergo apoptosis there. 
This results in a greater amount of cross-priming and a stronger T-Cell 
response.

Inhibition of Ubiquitin-Mediated Process by UBA Domain Peptides

Stan Lipkowitz et al. (NCI)
Serial No. 60/464,658 filed 23 Apr 2003 (DHHS Reference No. E-324-2002/
0)
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Ubiquitin is a protein tag that targets cellular proteins for 
degradation by the multicatalytic protease, the proteasome. A three-
component system of ubiquitin activating enzyme (E1), ubiquitin 
conjugating enzyme (E2), and ubiquitin protein ligase (E3) promotes the 
covalent attachment of ubiquitin to a protein to be degraded. Of the 
three components, the E3 component confers the specificity to the 
ubiquitination.
    This invention describes isolated peptides comprising an ubiquitin-
associated (UBA) domain that inhibits ubiquitin-mediated protein 
degradation by binding ubiquitin and polyubiquitin. The series of UBA 
domain peptides contain a structurally conserved core and a 
characteristic set of three alpha helices. Specifically, these studies 
centered on the UBA domain of the proto-oncogene, cbl-b. Expression of 
the cbl-b UBA-domain peptide in a cell inhibits the degradation of 
epithelial growth factor (EGFR), murine double minute 2 (Mdm2), and 
seven in absentia homologue-1 (Siah-1).
    UBA domain peptides will be useful in treating conditions 
associated with an unusually high level of an ubiquitin-mediated 
process. Defects in the functioning of the ubiquitin/proteasome system 
can have severe consequences on biological homeostasis, causing a 
multitude of pathological conditions. The most obvious treatment 
options using the UBA-domain peptides could be for cancer, 
developmental disorders, and inflammatory conditions. In addition, UBA 
domain peptides can be used to inhibit ubiquitin mediated processes to 
further the understanding of the cell biological and development roles 
of these processes.

Use of Discoidin Domain Receptor 1 (DDR1) and Agents That Affect the 
DDR1/Collagen Pathway

Teizo Yoshimura (NCI)
PCT/US02/39793 filed 11 Dec 2002 (DHHS Reference No. E-083-2002/2-PCT-
01),
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Dendritic cells (DCs) are pivotal antigen-presenting cells for 
initiation of an immune response. Indeed, dendritic cells provide the 
basis for the production of an effective immune response to a vaccine, 
particularly for antigens wherein conventional vaccination is 
inadequate. DCs are also important in the production on an immune 
response to tumor antigens.
    The present invention discloses methods of using the receptor 
tyrosine kinase discoidin domain receptor 1 (DDR1) to facilitate the 
maturation/differentiation of DCs or macrophages. Activating agents of 
DDR1 may be useful in the induction of a highly potent, mature DCs or 
highly differentiated macrophages from DC precursors, such as 
monocytes. Use of this method may enhance the antigen presenting 
capabilities of the immune system, leading to a more effective overall 
immune response.
    This research is further described in Kamohara et al., FASEB J. 
10.1096/fj.01-0359fje (published online October 15, 2001) and Matsuyama 
et al., FASEB J. 10.1096/fj.02-0320fje (published online May 8, 2003).

Production of Adeno-Associated Viruses in Insect Cells

    Robert Kotin et al. (NHLBI)
Serial No. 09/986,618 filed 09 Nov 2001 (DHHS Reference No. E-325-2001/
0); Serial No. 10/216,870 filed 13 Aug 2002 (DHHS Reference No. E-325-
2001/1); PCT/US02/35829 filed 08 Nov 2002 (DHHS Reference No. E-325-
2001/2),
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Currently, adeno-associated virus (AAV) is being developed for gene 
therapy applications. This virus type presents several advantages over 
alternate vectors for therapeutic gene

[[Page 37852]]

delivery. AAV is not considered pathogenic and transduces stably 
dividing and non-dividing cells; and shows good serotype specificity to 
various cell types for targeted gene delivery.
    This invention is a highly scalable AAV vector production method in 
insect cells. This production method produces virus particles much more 
efficiently than the standard mammalian cell culture system. For 
example, to produce 1015 rAAV particles may require 5,000 
175cm2 flasks. With this new production method, 10 to 50 
liters of Sf9 insect cells are required to produce the same quantity of 
AAV particles. This is a striking improvement in production efficiency. 
In addition, all serotypes of AAV can be produced, with the respective 
AAV serotype vectors available for the immediate scale up of AAV 
production.
    This invention coupled with NIH invention E-308-2001, titled 
``Scalable Purification of AAV2, AAV4 or AAV5 Using Ion-Exchange 
Chromatography,'' gives a licensee a highly scalable production and 
purification system for efficient clinical trial development and 
commercialization of AAV.

Scalable Purification of AAV2, AAV4 or AAV5 Using Ion-Exchange 
Chromatography

Nikola Kaludov (NIDCR)
John Chiorini (NIDCR)
Serial No. 60/381,180 filed 17 May 2002; Serial No. 10/166,347 filed 17 
May 2003 (DHHS Reference No. E-308-2001/0),
Licensing Contact: Jeffrey Walenta; 301/435-4633; 
[email protected].
    Adeno-associated viruses (AAVs) constitute, as a group, the vehicle 
of choice for gene therapy because of several attractive features. 
Among others, AAVs are less pathogenic than other viruses, and they can 
be used for the long-term expression of therapeutic genes.
    This invention describes a simple ion-exchange (HPLC) methodology 
to purify different AAV serotypes. The protocol, which can be readily 
scaled up, details the efficient concentration of fully infective AAV 
particles, and is applicable to a number of promising serotypes for 
which efficient purification methodologies are currently lacking. 
Significantly, the method consistently produces higher infectivity per 
particle ratios than standard methods.
    This invention, coupled with NIH invention E-325-2001, entitled 
``Highly Scalable Production of AAV in Insect Cells,'' would give a 
licensee a purification system that can be readily scaled-up to 
efficiently produce recombinant adeno-associated viruses for clinical 
trial development.
    This work is further described in Kaludov et al., Hum. Gene Ther. 
(2002) 13:1235-43.

    Dated: June 16, 2003.
Steven M. Ferguson,
Acting Director, Division of Technology Development and Transfer, 
Office of Technology Transfer, National Institutes of Health.
[FR Doc. 03-15971 Filed 6-24-03; 8:45 am]
BILLING CODE 4140-01-P