Government-Owned Inventions; Availability for Licensing, 52403-52405 [05-17517]
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Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices
starting pre-clinical studies of the
conjugates using animal cancer models.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Maleiimide Anti-Tumor Phosphatase
Inhibitors
Christopher J. Michejda et al. (NCI).
U.S. Provisional Application No. 60/
546,841 filed 22 Feb 2004 (HHS
Reference No. E–110–2004/0–US–01).
PCT Application No. PCT/US05/05742
filed 22 Feb 2005 (HHS Reference No.
E–110–2004/0–PCT–02).
The present invention describes novel
phosphatase inhibitors that appear to
target the CDC25 family of
phosphatases. The new compounds
have potent activity against human liver
cancer cells in vitro and in vivo against
an orthotopic liver cancer in rats. In
tumor cells, these new inhibitors appear
to target the phosphorylation status of
several cell cycle proteins that are
important for cell survival and thus
could represent a novel class of
chemotherapeutic agents targeting
cancer cells.
2-Amino-O4-Substituted Pteridines and
Their Use as Inactivators of O6Alkylguanine-DNA Alkyltransferase
Robert C. Moschel et al. (NCI).
U.S. Provisional Application No. 60/
534,519 filed 06 Jan 2004 (HHS
Reference No. E–274–2003/0–US–01).
PCT Application No. PCT/US04/41577
filed 10 Dec 2004 (HHS Reference No.
E–274–2003/0–PCT–02).
This invention is directed to 2-aminoO4-benzylpteridine derivatives targeted
for use in cancer treatment in
combination with chemotherapeutic
agents such as 1,3-bis(2-chloroethyl)-1nitrosurea (BCNU) or temozolomide.
The derivatives of the present invention
inactivate the O6-alkylguanine-DNAalkyltransferase repair protein and thus
enhance activity of such
chemotherapeutic agents. Examples of
these derivatives have advantages over
the earlier O6-benzylguanine
compounds from this research group.
Some compounds of the current
invention are more water soluble
compared to O6-benzylguanine and they
exhibit greater specificity for
inactivating O6-alkylguanine-DNAalkyltransferase in certain tumor cells,
compared to normal cells.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
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Beta-Glucuronidase Cleavable Prodrugs
of O6-Alkylguanine-DNA
Alkyltransferase Inactivators
Robert C. Moschel et al. (NCI).
U.S. Provisional Application No. 60/
608,045 filed 08 Sep 2004 (HHS
Reference No. E–307–2004/0–US–01).
The present invention relates to
prodrugs of inactivators of O6alkylguanine-DNA alkyltransferase. The
prodrugs are cleaved by the betaglucuronidase enzyme found in tumor
cells or co-administered to the patient,
and the drugs are targeted for use in
cancer treatment in combination with
antineoplastic alkylating agent such as
1,3-bis(2-cloroethyl)-1-nitrosouria or
temozolomide.
Identification of a Tricyclic Amino
Amide (NSC–644221) Inhibitor of the
Hypoxic Signaling Pathway
Giovanni Melillo (NCI).
U.S. Provisional Application No. 60/
618,279 filed 12 Oct 2004 (HHS
Reference No. E–185–2004/0–US–01).
U.S. Provisional Application No. 60/
570,615 filed 12 May 2004 (HHS
Reference No. E–185–2004/1–US–01).
PCT Application filed 11 May 2005
(HHS Reference No. E–185–2004/2–
PCT–01).
This invention describes the
identification of a tricyclic (1,4-dioxane)
amino amide with confirmed potent
activity in inhibiting HIF–1
transcriptional activity.
HIF–1 is a transcription factor and
plays an important role in adaptation of
cancer cells to an hypoxic environment.
HIF–1 significantly increases the ability
of cancer cells to survive under
strenuous conditions. It contributes to
the ability of cancer cells to migrate and
invade surrounding tissue, and is
important for the formation of new
blood vessels that are essential for
growth and metastasis of cancer cells.
Thus HIF–1 mediates survival and
spreading of cancer cells. Previous
studies have shown that HIF–1 is also
important in human cancers, and
therefore, inhibition of HIF–1 activity is
contemplated in the field as a therapy
for cancer patients.
The inventors, using a cell-based high
throughput screen, identified a new
compound, NSC–644221, with potent
inhibitory activity of the HIF–1
pathway. The compound inhibits
expression of HIF–1 and reduces its
accumulation in the cell. This
compound also inhibits expression of
endogenous genes that are under control
of HIF–1, such as Vascular Endothelial
Growth Factor (VEGF) that is essential
for the formation of new blood vessels.
Preliminary experiments in xenograft
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52403
models have indicated that NSC–644221
reaches the tumor tissue when
administered intraperitoneally and
inhibits HIF–1-dependent luciferase
expression in U251–HRE cells.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Inhibitors of the Protein Kinase Chk2 to
Abrogate Apoptosis and Sensitize
Cancer Cells to DNA Targeted
Therapies
Yves Pommier et al. (NCI).
U.S. Provisional Application filed 29 Jul
2005 (HHS Reference No. E–211–
2005/0–US–01).
Chk2 is a protein kinase activated in
response to DNA double strand breaks.
In normal tissues, Chk2 phosphorylates
and thereby activates substrates that
induce programmed cell death, or
apoptosis, via interactions with p53,
E2F1, PML proteins. In cancer tissues,
where apoptosis is suppressed, Chk2
phosphorylates and inactivates cell
cycle checkpoints (via interactions with
Cdc25, phosphatases and Brca1
proteins), which allows cancer cells to
repair and tolerate DNA damage. Hence,
Chk2 inhibitors would be expected to
protect normal tissues by reducing
apoptosis, and to sensitize cancer cells
to DNA-targeted agents.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Dated: August 25, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–17457 Filed 9–1–05; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Government-Owned Inventions;
Availability for Licensing
National Institutes of Health,
Public Health Service, DHHS.
ACTION: Notice.
AGENCY:
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
E:\FR\FM\02SEN1.SGM
02SEN1
52404
Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices
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.
Method for Inducing T-Cell
Proliferation
Warren J. Leonard et al. (NHLBI).
U.S. Provisional Application No. 60/
555,898 filed 23 Mar 2004 (HHS
Reference No. E–104–2004/0–US–01);
U.S. Utility Application No. 11/
084,408, filed 18 Mar 2005 (HHS
Reference No. E–104–2004/0–US–02).
Licensing Contact: Susan Ano; 301/435–
5515; anos@mail.nih.gov.
This technology relates to the use of
thymic stromal lymphopoietin (TSLP)
or TSLP agonists to induce CD4+ T cell
proliferation as well as the use of TSLP
antagonists to treat IgE-mediated
disorders such as asthma or allergies.
The T cell proliferation application of
this technology could be of particular
relevance for patients in whom this cell
population has been significantly
reduced by e.g., HIV/AIDS infection or
another condition resulting in
immunodeficiency. The patent
application describes methods of
treating individuals afflicted with an
immunodeficiency by administering
CD4+ T cells that have been isolated
and induced to proliferate using TSLP
or by direct administration of TSLP or
a nucleic acid encoding TSLP. The need
for appropriate treatment methods for
conditions such as asthma and allergies
are well recognized. The patent
application describes administration of
a TSLP antagonist to an individual
suffering from an IgE-mediated disorder
to remove or lessen the symptoms.
TSLPR knockout mice are also
described in the patent application and
available for licensing through a
biological materials license agreement.
Vaccines Using Universally Inactivated
Viruses, Parasites, and Tumor Cells
Yossef Raviv et al. (NCI).
U.S. Provisional Application filed 22
Mar 2004 (HHS Reference No. E–303–
2003/0–US–01); PCT Application
filed 22 Mar 2005 (HHS Reference No.
E–303–2003/0–PCT–02).
VerDate Aug<18>2005
18:00 Sep 01, 2005
Jkt 205001
Licensing Contact: Susan Ano; 301/435–
5515; anos@mail.nih.gov.
The current technology describes the
universal inactivation of viruses,
parasites, and tumor cells by
hydrophobic, photoactivatable
compounds. These non-toxic
compounds, such as 1,5iodoanpthylazide (INA), will selectively
accumulate in the innermost regions of
biological membrane bilayers, where the
compounds will bind to proteins and
lipids upon irradiation with light, thus
inactivating deeply embedded proteins
while maintaining integrity and activity
of the proteins on the surface. This
inactivation preserves the structural and
conformational integrity and therefore
immunogenicity of the agent in
question, which overcomes a potential
problem associated with some other
vaccines such as those containing killed
pathogens. As representative examples,
the patent application describes
experimental results obtained using
HIV, SIV, and Ebola viruses. The
inactivation approach presented in this
technology provides for a safe, noninfectious composition for vaccination
against the corresponding agent,
whereas some vaccines, such as those
involving live-attenuated microbial
agents, still have a risk of infectivity
associated with them.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
High Expression Level Vectors
Combining of mRNA Transport
Elements for Use in Mammalian Cells
Barbara K. Felber et al. (NCI).
U.S. Provisional Application No. 60/
471,988 filed 19 May 2003 (HHS
Reference No. E–223–2003/0-US–01);
U.S. Provisional Application No. 60/
472,223, filed 20 May 2003 (HHS
Reference No. E–258–2003/0–US–01);
PCT Application No. PCT/US04/
15776 filed 19 May 2004, which
published as WO2004/113547 on 29
Dec 2004 (HHS Reference No. E–223–
2003/1–PCT–01).
Licensing Contact: Susan Ano; 301/435–
5515; anos@mail.nih.gov.
This technology relates to improving
levels of gene expression using a
combination of a constitutive RNA
transport element (CTE) with a mutant
form of another RNA transport element
(RTE). The combination of these
elements results in a synergistic effect
on stability of mRNA transcripts, which
in turn leads to increased expression
levels. Using HIV–1 gag as reporter
mRNA, one mutated RTE in
PO 00000
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Fmt 4703
Sfmt 4703
combination with a CTE was found to
improve expression of unstable mRNA
by about 500-fold. Similarly this
combination of elements lead to
synergistically elevated levels of HIV–1
Env expression. The function of CTEs
and RTEs is conserved in mammalian
cells, so this technology is a simple and
useful way of obtaining high levels of
expression of otherwise poorly
expressed genes and can be used in a
number of applications such as but not
limited to improvements of gene
therapy vectors, expression vectors for
mammalian cells.
In addition to licensing, the
technology is available for further
development through collaborative
research opportunities with the
inventors.
Recombinant Plasmids Containing HIV
Reverse Transcriptase
Stephen H. Hughes and Paul L. Boyer
(NCI).
HHS Reference Nos. E–034–1991/0, /1,
/2, /3, and /4—Research Tools.
Licensing Contact: Sally Hu; 301/435–
5606; hus@mail.nih.gov.
NIH offers below HIV–1 Reverse
Transcriptase (RT) Expression plasmids
that are available for licensing via
biological material licenses (BML). In an
appropriate strain of E. coli, these
plasmids cause the expression of an
HIV–1 RT heterodimer (p66/p51). In the
expression plasmid, the RT coding
region is flanked by synthetic initiation
and termination codons. The amino
terminus of the RT made in E. coli has
two additional amino acids relative to
the viral enzyme (MV); these have no
obvious effect on enzymatic activity.
The carboxy terminus of p66 carries a 6histidine tag that facilitates purification.
The plasmid also causes the expression
of a low level of HIV–1 protease; this
leads to the conversion of the
approximately half of the p66
synthesized in E. coli to p51. The p66/
p51 heterodimer can be easily extracted
from the E. coli host and purified by
metal-chelate chromatography.
Expression constructs for many of the
common drug-resistant versions of HIV–
1 RT (a partial list is given below) and
for a number of other mutants are
available. Alternate RT expression
plasmids that encode versions of HIV–
1 RT that do not have his tags and
plasmids that separately encode p51
and p66 (allowing subunit selective
mutagenesis) are also available. The
HIV–1 RT expression plasmids can be
used to generate wild-type and drug
resistant RTs that can be used in both
biological and medical research. The
RTs are particularly useful in the
screening and development of RT
E:\FR\FM\02SEN1.SGM
02SEN1
52405
Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices
inhibitors in vitro and can be used to
test drug candidates for their
effectiveness against common drug
resistant mutants of HIV–1 RT. Please
contact Dr. Hughes directly
(hughes@ncifcrf.gov) if you want
additional information about RT
expression plasmids that are not listed
below.
Vector
Description
Reference No.
Wild-type HIV–1 RT .................................................................
L100I ........................................................................................
K103N ......................................................................................
V106A ......................................................................................
V108I ........................................................................................
E138K ......................................................................................
Y181I ........................................................................................
Y181C ......................................................................................
Y188L .......................................................................................
Y188H ......................................................................................
G190A ......................................................................................
G190S ......................................................................................
P236L .......................................................................................
full length, wild type .................................................................
NNRTI resistant .......................................................................
NNRTI resistant .......................................................................
NNRTI resistant .......................................................................
..................................................................................................
NNRTI resistant .......................................................................
..................................................................................................
NNRTI resistant .......................................................................
..................................................................................................
NNRTI resistant .......................................................................
..................................................................................................
..................................................................................................
NNRTI resistant .......................................................................
E–034–1991/0
E–034–1991/1
E–034–1991/1
E–034–1991/1
..............................
E–034–1991/1
..............................
E–034–1991/1
..............................
E–034–1991/1
..............................
..............................
E–034–1991/1
RTs that carry some combinations of NNRTI mutations, e.g., K103N+Y181I, are also available.
K65R ........................................................................................
T69G ........................................................................................
L74V .........................................................................................
M184I .......................................................................................
M184V ......................................................................................
AZT–R (5 mutations) ...............................................................
D67 complex ............................................................................
Q151M .....................................................................................
Q151M Complex ......................................................................
SSGR/T215Y ...........................................................................
SSSR/T215Y ............................................................................
Dated: August 20, 2005.
Steven M. Ferguson,
Director, Division of Technology Development
and Transfer, Office of Technology Transfer,
National Institutes of Health.
[FR Doc. 05–17517 Filed 9–1–05; 8:45 am]
BILLING CODE 4140–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Center on Minority Health and
Health Disparities; Notice of Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given by the National
Advisory Council on Minority Health
and Health Disparities.
The meeting will be open to the
public as indicated below, with
attendance limited to space available.
Individuals who plan to attend and
need special assistance, such as sign
language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
as amended. The grant applications and
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Jkt 205001
NRTI resistant .........................................................................
..................................................................................................
NRTI resistant .........................................................................
Lamivudine (3TC) resistant .....................................................
Lamivudine (3TC) resistant .....................................................
AZT resistant ...........................................................................
Multi-NRTI resistant .................................................................
Multi-NRTI resistant .................................................................
Multi-NRTI resistant .................................................................
Multi-NRTI resistant .................................................................
Multi-NRTI resistant .................................................................
the discussions could disclose
confidential trade secrets or commercial
property such as patentable material,
and personal information concerning
individuals associated with the grant
applications, the disclosure of which
would constitute a clearly unwarranted
invasion of personal privacy.
Name of Committee: National Advisory
Council on Minority Health and Health
Disparities.
Date: September 20, 2005.
Closed: 8:30 a.m. to 10 a.m.
Agenda: To review and evaluate grant
applications and/or proposals.
Place: National Institutes of Health, Two
Democracy Plaza, 6707 Democracy
Boulevard, Suite 800, Bethesda, MD 20892.
Open: 10:30 a.m. to 5:30 p.m.
Agenda: The agenda will include Opening
Remarks, Administrative Matters, Director’s
Report, NCMHD, IC Health Disparities
Research Report, NCMHD Program
Highlights, and other business of the Council.
Place: National Institutes of Health, Two
Democracy Plaza, 6707 Democracy
Boulevard, Suite 800, Bethesda, MD 20892.
Contact Person: Donna Brooks, Asst.
Director for Administration, National Center
on Minority Health and Health Disparities,
National Institutes of Health, 6707
Democracy Blvd., Suite 800, Bethesda, MD
20892, 301–435–2135,
brooksd@ncmhd.nih.gov.
Any interested person may file written
comments with the committee by forwarding
the statement to the Contact Person listed on
this notice. The statement should include the
name, address, telephone number and when
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E–034–1991/2
..............................
E–034–1991/1
..............................
E–034–1991/1
E–034–1991/1
E–034–1991/4
E–034–1991/4
E–034–1991/4
E–034–1991/4
E–034–1991/4
applicable, the business or professional
affiliation of the interested person.
Dated: August 25, 2005.
Anthony M. Coelho, Jr.,
Acting Director, Office of Federal Advisory
Committee Policy.
[FR Doc. 05–17514 Filed 9–1–05; 8:45 am]
BILLING CODE 4140–01–M
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
National Eye Institute; Notice of
Meeting
Pursuant to section 10(d) of the
Federal Advisory Committee Act, as
amended (5 U.S.C. Appendix 2), notice
is hereby given of a meeting of the
National Advisory Eye Council.
The meeting will be open to the
public as indicated below, with
attendance limited to space available.
Individuals who plan to attend and
need special assistance, such as sign
language interpretation or other
reasonable accommodations, should
notify the Contact Person listed below
in advance of the meeting.
The meeting will be closed to the
public in accordance with the
provisions set forth in sections
552b(c)(4) and 552b(c)(6), Title 5 U.S.C.,
E:\FR\FM\02SEN1.SGM
02SEN1
]]>Agencies
[Federal Register Volume 70, Number 170 (Friday, September 2, 2005)]
[Notices]
[Pages 52403-52405]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-17517]
-----------------------------------------------------------------------
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.
-----------------------------------------------------------------------
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
[[Page 52404]]
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.
Method for Inducing T-Cell Proliferation
Warren J. Leonard et al. (NHLBI).
U.S. Provisional Application No. 60/555,898 filed 23 Mar 2004 (HHS
Reference No. E-104-2004/0-US-01); U.S. Utility Application No. 11/
084,408, filed 18 Mar 2005 (HHS Reference No. E-104-2004/0-US-02).
Licensing Contact: Susan Ano; 301/435-5515; anos@mail.nih.gov.
This technology relates to the use of thymic stromal lymphopoietin
(TSLP) or TSLP agonists to induce CD4+ T cell proliferation as well as
the use of TSLP antagonists to treat IgE-mediated disorders such as
asthma or allergies. The T cell proliferation application of this
technology could be of particular relevance for patients in whom this
cell population has been significantly reduced by e.g., HIV/AIDS
infection or another condition resulting in immunodeficiency. The
patent application describes methods of treating individuals afflicted
with an immunodeficiency by administering CD4+ T cells that have been
isolated and induced to proliferate using TSLP or by direct
administration of TSLP or a nucleic acid encoding TSLP. The need for
appropriate treatment methods for conditions such as asthma and
allergies are well recognized. The patent application describes
administration of a TSLP antagonist to an individual suffering from an
IgE-mediated disorder to remove or lessen the symptoms. TSLPR knockout
mice are also described in the patent application and available for
licensing through a biological materials license agreement.
Vaccines Using Universally Inactivated Viruses, Parasites, and Tumor
Cells
Yossef Raviv et al. (NCI).
U.S. Provisional Application filed 22 Mar 2004 (HHS Reference No. E-
303-2003/0-US-01); PCT Application filed 22 Mar 2005 (HHS Reference No.
E-303-2003/0-PCT-02).
Licensing Contact: Susan Ano; 301/435-5515; anos@mail.nih.gov.
The current technology describes the universal inactivation of
viruses, parasites, and tumor cells by hydrophobic, photoactivatable
compounds. These non-toxic compounds, such as 1,5-iodoanpthylazide
(INA), will selectively accumulate in the innermost regions of
biological membrane bilayers, where the compounds will bind to proteins
and lipids upon irradiation with light, thus inactivating deeply
embedded proteins while maintaining integrity and activity of the
proteins on the surface. This inactivation preserves the structural and
conformational integrity and therefore immunogenicity of the agent in
question, which overcomes a potential problem associated with some
other vaccines such as those containing killed pathogens. As
representative examples, the patent application describes experimental
results obtained using HIV, SIV, and Ebola viruses. The inactivation
approach presented in this technology provides for a safe, non-
infectious composition for vaccination against the corresponding agent,
whereas some vaccines, such as those involving live-attenuated
microbial agents, still have a risk of infectivity associated with
them.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
High Expression Level Vectors Combining of mRNA Transport Elements for
Use in Mammalian Cells
Barbara K. Felber et al. (NCI).
U.S. Provisional Application No. 60/471,988 filed 19 May 2003 (HHS
Reference No. E-223-2003/0-US-01); U.S. Provisional Application No. 60/
472,223, filed 20 May 2003 (HHS Reference No. E-258-2003/0-US-01); PCT
Application No. PCT/US04/15776 filed 19 May 2004, which published as
WO2004/113547 on 29 Dec 2004 (HHS Reference No. E-223-2003/1-PCT-01).
Licensing Contact: Susan Ano; 301/435-5515; anos@mail.nih.gov.
This technology relates to improving levels of gene expression
using a combination of a constitutive RNA transport element (CTE) with
a mutant form of another RNA transport element (RTE). The combination
of these elements results in a synergistic effect on stability of mRNA
transcripts, which in turn leads to increased expression levels. Using
HIV-1 gag as reporter mRNA, one mutated RTE in combination with a CTE
was found to improve expression of unstable mRNA by about 500-fold.
Similarly this combination of elements lead to synergistically elevated
levels of HIV-1 Env expression. The function of CTEs and RTEs is
conserved in mammalian cells, so this technology is a simple and useful
way of obtaining high levels of expression of otherwise poorly
expressed genes and can be used in a number of applications such as but
not limited to improvements of gene therapy vectors, expression vectors
for mammalian cells.
In addition to licensing, the technology is available for further
development through collaborative research opportunities with the
inventors.
Recombinant Plasmids Containing HIV Reverse Transcriptase
Stephen H. Hughes and Paul L. Boyer (NCI).
HHS Reference Nos. E-034-1991/0, /1, /2, /3, and /4--Research Tools.
Licensing Contact: Sally Hu; 301/435-5606; hus@mail.nih.gov.
NIH offers below HIV-1 Reverse Transcriptase (RT) Expression
plasmids that are available for licensing via biological material
licenses (BML). In an appropriate strain of E. coli, these plasmids
cause the expression of an HIV-1 RT heterodimer (p66/p51). In the
expression plasmid, the RT coding region is flanked by synthetic
initiation and termination codons. The amino terminus of the RT made in
E. coli has two additional amino acids relative to the viral enzyme
(MV); these have no obvious effect on enzymatic activity. The carboxy
terminus of p66 carries a 6-histidine tag that facilitates
purification. The plasmid also causes the expression of a low level of
HIV-1 protease; this leads to the conversion of the approximately half
of the p66 synthesized in E. coli to p51. The p66/p51 heterodimer can
be easily extracted from the E. coli host and purified by metal-chelate
chromatography. Expression constructs for many of the common drug-
resistant versions of HIV-1 RT (a partial list is given below) and for
a number of other mutants are available. Alternate RT expression
plasmids that encode versions of HIV-1 RT that do not have his tags and
plasmids that separately encode p51 and p66 (allowing subunit selective
mutagenesis) are also available. The HIV-1 RT expression plasmids can
be used to generate wild-type and drug resistant RTs that can be used
in both biological and medical research. The RTs are particularly
useful in the screening and development of RT
[[Page 52405]]
inhibitors in vitro and can be used to test drug candidates for their
effectiveness against common drug resistant mutants of HIV-1 RT. Please
contact Dr. Hughes directly (hughes@ncifcrf.gov) if you want additional
information about RT expression plasmids that are not listed below.
------------------------------------------------------------------------
Vector Description Reference No.
------------------------------------------------------------------------
Wild-type HIV-1 RT............ full length, wild E-034-1991/0
type.
L100I......................... NNRTI resistant...... E-034-1991/1
K103N......................... NNRTI resistant...... E-034-1991/1
V106A......................... NNRTI resistant...... E-034-1991/1
V108I......................... ..................... .................
E138K......................... NNRTI resistant...... E-034-1991/1
Y181I......................... ..................... .................
Y181C......................... NNRTI resistant...... E-034-1991/1
Y188L......................... ..................... .................
Y188H......................... NNRTI resistant...... E-034-1991/1
G190A......................... ..................... .................
G190S......................... ..................... .................
P236L......................... NNRTI resistant...... E-034-1991/1
-------------------------------
RTs that carry some combinations of NNRTI mutations, e.g., K103N+Y181I,
are also available.
------------------------------------------------------------------------
K65R.......................... NRTI resistant....... E-034-1991/2
T69G.......................... ..................... .................
L74V.......................... NRTI resistant....... E-034-1991/1
M184I......................... Lamivudine (3TC) .................
resistant.
M184V......................... Lamivudine (3TC) E-034-1991/1
resistant.
AZT-R (5 mutations)........... AZT resistant........ E-034-1991/1
[Delta]67 complex............. Multi-NRTI resistant. E-034-1991/4
Q151M......................... Multi-NRTI resistant. E-034-1991/4
Q151M Complex................. Multi-NRTI resistant. E-034-1991/4
SSGR/T215Y.................... Multi-NRTI resistant. E-034-1991/4
SSSR/T215Y.................... Multi-NRTI resistant. E-034-1991/4
------------------------------------------------------------------------
Dated: August 20, 2005.
Steven M. Ferguson,
Director, Division of Technology Development and Transfer, Office of
Technology Transfer, National Institutes of Health.
[FR Doc. 05-17517 Filed 9-1-05; 8:45 am]
BILLING CODE 4140-01-P
