Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices 52403 

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 O6- 

Alkylguanine-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)-1- 

nitrosurea (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. 

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 O6- 

alkylguanine-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 

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 

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 

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). 

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, 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 

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 

Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices 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 type ................................................................. E–034–1991/0 

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) resistant ..................................................... E–034–1991/1 

AZT–R (5 mutations) ............................................................... AZT resistant ........................................................................... E–034–1991/1 

D67 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 

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 

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 

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.,