52400 Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices 

Dated: August 26, 2005. 

Scott Gottlieb, 

Deputy Commissioner for Policy. 

[FR Doc. 05–17470 Filed 9–1–05; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Proposed Collection: Comment 

Request; Extension of OMB No. 0925–

0417/exp. 08/31/05, Responsibility of 

Applicants for Promoting Objectivity in 

Research for Which Public Health 

Service Funding Is Sought and 

Responsible Prospective 

Contractors—42 CFR Part 50, 

Subpart F 

Summary: In compliance with the 

requirement of Section 3507(a)(1)(D) of 

the Paperwork Reduction Act of 1995, 

the Office of the Director (OD), Office of 

Extramural Research (OER), the 

National Institutes of Health (NIH) has 

submitted to the Office of Management 

and Budget (OMB) a request for review 

and approval of the information 

collection listed below. Proposed 

information collection was previously 

published in the Federal Register on 

May 12, 2005, Volume 70, No. 91, page 

25095 and allowed 60 days for public 

comment. No public comments were 

received. The purpose of this notice is 

to allow an additional 30 days for public 

comment. The National Institutes of 

Health may not conduct or sponsor, and 

the respondent is not required to 

respond to, an information collection 

that has been extended, revised, or 

implemented on or after October 1, 

1995, unless it displays a currently valid 

OMB control number. 

Proposed Collection: Title: 

Responsibility of Applicants for 

Promoting Objectivity in Research for 

Which Public Health Service Funding Is 

Sought and Responsible Prospective 

Contractors—42 CFR Part 50, Subpart F; 

Type of Information Collection Request: 

Extension, OMB 0925–0417, Expiration 

Date 8/31/05. Need and Use of 

Information Collection: This is a request 

for OMB approval for the information 

collection and recordkeeping 

requirements contained in the final rule 

42 CFR Part 50 Subpart F and 

Responsible Contractors: 45 CFR Part 

94. Frequency of response: On occasion. 

Affected Public: Individuals or 

households; business or other for-profit; 

not-for-profit institutions; and State, 

Local or Tribal Government. Type of 

Respondents: Any public or private 

entity or organization. The annual 

reporting burden is as follows: 

Estimated Number of Respondents: 

42,800; Estimated Number of Responses 

per Respondent: 1.60; Average Burden 

Hours Per Response: 3.40; and 

Estimated Total Annual Burden Hours 

Request: 232,000. 

Request for Comments: Written 

comments and/or suggestions from the 

public and affected agencies are invited 

on one or more of the following points: 

(1) Whether the proposed collection of 

information is necessary for the proper 

performance of the function of the 

agency, including whether the 

information will have practical utility; 

(2) the accuracy of the agency’s estimate 

of the burden of the proposed collection 

of information, including the validity of 

the methodology and assumptions used; 

(3) ways to enhance the quality, utility, 

and clarity of the information to be 

collected; and (4) ways to minimize the 

burden of the collection of information 

on those who are to respond, including 

the use of appropriate automated, 

electronic, mechanical, or other 

technological collection techniques or 

other forms of information technology. 

Direct Comments to OMB: Written 

comments and/or suggestions regarding 

the item(s) contained in this notice, 

especially regarding the estimated 

public burden and associated response 

time should be directed to the Office of 

Management and Budget, Office of 

Regulatory Affairs, New Executive 

Office Building, Room 10235, 

Washington, DC 20503, Attention: Desk 

Officer for NIR. To request more 

information on the proposed project or 

to obtain a copy of the data collection 

plans and instruments, contact Ms. 

Diane Dean, Division of Grants Policy, 

Office of Policy for Extramural Research 

Administration, NIH, Rockledge 1 

Building, Room 3525, 6705 Rockledge 

Drive, Bethesda, MD 20892–7974, or 

call non-toll-free number 301–435–

0930, or E-mail your request, including 

your address to: hahnm@od.nih.gov. 

Comments Due Date: Comments 

regarding this information collection are 

best assured of having their full effect if 

received within 30 days of the date of 

this publication. 

Dated: August 25, 2005. 

Charles Mackay, 

Chief, Project Clearance Branch, OPERA, 

OER, National Institutes of Health. 

[FR Doc. 05–17458 Filed 9–1–05; 8:45 am] 

BILLING CODE 4140–01–M 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Government-Owned Inventions; 

Availability for Licensing: Selected 

Technologies From the NIH Cancer 

Therapeutics Portfolio 

AGENCY: National Institutes of Health, 

Public Health Service, HHS. 

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 

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 

contacting George G. Pipia, Ph.D., 

Technology Licensing Specialist, Office 

of Technology Transfer, National 

Institutes of Health, 6011 Executive 

Boulevard, Suite 325, Rockville, 

Maryland 20852; telephone: 301/435–

5560; fax: 301/402–0220; e-mail: 

pipiag@mail.nih.gov. A signed 

Confidential Disclosure Agreement will 

be required to receive copies of the 

patent applications. 

Antitumor Macrocyclic Lactones 

Michael R. Boyd (NCI). 

U.S. Patent No. 6,353,019 issued 05 Mar 

2002 (HHS Reference No. E–244–

1997/0–US–07) and related foreign 

patent applications. 

Vacuolar-Type (H+)-ATPase-Inhibiting 

Compounds and Uses Thereof 

Michael R. Boyd (NCI). 

U.S. Patent Application No. 09/914,708 

filed 31 Aug 2001 (HHS Reference No. 

E–244–1997/3–US–06) and related 

foreign patent applications. 

This technology covers a broad 

composition of matter which includes 

the salicylihalamides, lobatamides, and 

numerous other structurally related 

small molecules which have been 

shown to inhibit mammalian vacuolar 

ATPase at low nanomolar 

concentrations. The compounds are also 

potent inhibitors of cancer cell growth, 

with particular specificity for 

melanoma, osteosarcoma and selected 

lung, colon and CNS tumor cell lines. 

Experimental tumor and 

pharmacokinetic studies are underway 

Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices 52401 

to select the most effective analogs for 

further development. The potential of 

these compounds to inhibit invasion 

and metastasis to bone sites is also 

under investigation. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research opportunities with the 

inventors. 

Novel 2-Alkoxy Estradiols and 

Derivatives Thereof 

Ravi Varma (NCI), et al. 

U.S. Patent No. 6,136,992 issued 24 Oct 

2000 (HHS Reference No. E–188–

1998/1–US–01). 

The present invention is directed to 

novel 2-alkoxy estradiols and 

derivatives of 2-alkoxy estradiols having 

anticancer activity as claimed in the 

U.S. Patent 6,136,992. The invention is 

also directed to methods of preparing 

these novel compounds. These 

compounds have improved activity 

against a wide variety of tumor cell 

lines, including lung, colon, central 

nervous system, melanoma, ovarian, 

renal, prostate and breast cancers, 

compared with 2-methoxy estradiols. It 

is expected that these compounds will 

be very useful in the treatment of a wide 

variety of cancers. In addition, the 

present compounds have a low affinity 

for the estrogen receptor and are, 

therefore, expected to have fewer side 

effects than estradiols. 

In addition to licensing, the 

technology is available for further 

development through clinical 

collaborative research opportunities 

with the inventors under a clinical 

CRADA. 

A Combined Growth Factor-Deleted 

and Thymidine Kinase-Deleted 

Vaccinia Virus Vector for Cancer 

Therapy 

J. Andrea McCart (NCI), David L. 

Bartlett (NCI), and Bernard Moss 

(NIAID). 

U.S. Patent Application No. 09/991,721 

filed 13 Nov 2001, claiming priority to 

28 May 1999 (HHS Reference No. E–

181–1999/0–US–05). 

Tumor-selective, replicating viruses 

may infect and kill cancer cells and 

efficiently express therapeutic genes in 

cancer cells. The current invention 

embodies mutant vaccinia virus 

expression vectors. These vectors, 

which are vaccinia virus growth factordeleted and thymidine-kinase deleted, 

are substantially incapable of replicating 

in non-dividing cells, and as such have 

specificity for cancer cells. It is therefore 

believed that the vectors will be of value 

for cancer therapy either by directly 

killing cancer cells or by expressing 

therapeutic agents in cancer cells while 

sparing normal, non-dividing cells. 

This research is described, in part, in: 

E. Chang et al., ‘‘Targeting vaccinia to 

solid tumors with local hyperthermia,’’

Hum Gene Ther. 2005 Apr, 16(4):435–

44; J.A. McCart, ‘‘Oncolytic vaccinia 

virus expressing the human 

somatostatin receptor SSTR2: molecular 

imaging after systemic delivery using 

111In-pentetreotide,’’ Mol Ther. 2004 

Sep, 10(3):553–61; H.J. Zeh, 

‘‘Development of a replication-selective, 

oncolytic poxvirus for the treatment of 

human cancers,’’ Cancer Gene Ther. 

2002 Dec, 9(12):1001–12; J.A. McCart, 

‘‘Systemic cancer therapy with a tumorselective vaccinia virus mutant lacking 

thymidine kinase and vaccinia growth 

factor genes,’’ Cancer Res. 2001 Dec 15, 

61(24):8751–7. 

SH2 Domain Binding Inhibitors 

Terrence R. Burke, Jr., et al. (NCI). 

U.S. Patent Application No. 10/362,231 

filed 22 Aug 2001, claiming priority to 

22 Aug 2000 (HHS Reference No. E–

262–2000/0–US–03). 

U.S. Patent Application No. 10/517,717 

filed 17 Mar 2005, claiming priority to 

28 Jun 2002 (HHS Reference No. E–

262–2000/1–US–03). 

Signal transduction processes 

underlie the transfer of extracellular 

information to the interior of the cell 

and ultimately to the nucleus. A variety 

of signal transduction processes are 

critical for normal cellular homeostasis, 

with protein-tyrosine kinases (PTKs) 

playing central roles in many of these 

pathways. Examples of such PTKs 

include the PDGF receptor, the FGF 

receptor, the HGF receptor, members of 

the EGF receptor family, such as the 

EGF receptor, erb-B2, erb-B3 and erb-B4, 

the src kinase family, Fak kinase and the 

Jak kinase family. Protein-tyrosine 

phosphorylation that results from the 

action of PTKs can modulate the activity 

of certain target enzymes as well as 

facilitate the formation of specific multiprotein signaling complexes through the 

actions of homologous protein modules 

termed Src homology 2 (SH2) domains, 

which recognize specific 

phosphotyrosyl containing sequences. A 

malfunction in this system through 

tyrosine kinase overexpression and/or 

deregulation can be manifested by 

various oncogenic and 

hyperproliferative disorders, including 

cancers, inflammation, autoimmune 

disease, hyperproliferative skin 

disorders, psoriasis and allergy/asthma, 

etc. The disclosed compounds, e.g. 

peptides, preferably, macrocyclic 

peptides, are Grb2 SH2 domain 

signaling antagonists with enhanced 

binding affinity. The claims of the 

current application are directed to 

compositions of matter and methods of 

use which provide for the diagnosis, 

testing and treatment of the 

aforementioned disease states. 

SH2 Domain Binding Inhibitors 

Terrence R. Burke, Jr., et al. (NCI). 

U.S. Provisional Application No. 60/ 

504,241 filed 18 Sep 2003 (HHS 

Reference No. E–315–2003/0–US–01). 

U.S. Patent Application No. 10/944,699 

filed 17 Sep 2004 (HHS Reference No. 

E–315–2003/0–US–02). 

The present invention provides for 

ultra-potent Grb2 SH2 domain-binding 

compounds, or a pharmaceutically 

acceptable salt thereof. The compounds 

of the present invention represent 

tetrapeptide mimetics whose 

conformation is constrained through 

macrocyclization. Low picomolar 

binding affinity is achieved in in vitro 

Grb2 SH2 domain binding assays. 

Addition of the covered agent to the 

extracellular media of erbB–2 overexpressing breast cancer cells at low 

nanomolar concentrations results in 

effective intracellular blockade of Grb2 

association with activated cytoplasmic 

erbB–2 tyrosine kinase. Antimitogenic 

effects are observed in erbB–2- 

dependent breast cancer cells in culture 

at sub-micromolar concentrations. The 

present invention further provides a 

pharmaceutical composition comprising 

a pharmaceutically or 

pharmacologically acceptable carrier 

and a compound of the present 

invention. The present invention also 

provides a method for inhibiting an SH2 

domain from binding with a 

phosphoproteins comprising contacting 

an SH2 domain with a compound of the 

present invention. The present 

invention also provides a method of 

preventing or treating a disease, state, or 

condition by the use of the compound. 

While the invention has been described 

and disclosed below in connection with 

certain embodiments and procedures, it 

is not intended to limit the invention to 

those specific embodiments. Rather it is 

intended to cover all such alternative 

embodiments and modifications as fall 

within the spirit and scope of the 

invention. 

This research is described, in part, in: 

Z. Shi et al., ‘‘A novel macrocyclic 

tetrapeptide mimetic that exhibits lowpicomolar Grb2 SH2 domain-binding 

affinity,’’ Biochem. Biophys. Res. 

Commun. (2003 Oct 17) 310(2):378–383, 

doi:10.1016/j.bbrc.2003.09.029; Z. Shi et 

al., ‘‘Synthesis of a 5-methylindolylcontaining macrocycle that displays 

ultrapotent Grb2 SH2 domain-binding 

52402 Federal Register / Vol. 70, No. 170 / Friday, September 2, 2005 / Notices 

affinity,’’ J. Med. Chem. (2004 Feb 12) 

47(4):788–791, doi:10.1021/jm030440b. 

A New Approach Toward 

Macrocyclization of Peptides 

Terrence R. Burke, Jr., et al. (NCI). 

U.S. Provisional Application No. 60/ 

614,800 filed 30 Sep 2004 (HHS 

Reference No. E–327–2004/0–US–01). 

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 

(HHS Reference No. E–315–2003/0–US–

01). 

Conjugates of Ligand, Linker, and 

Cytotoxic Agent and Related 

Compositions and Methods of Use 

Nadya Tarasova, Christopher J. 

Michejda, Marcin Dyba, Carolyn 

Cohran (NCI). 

U.S. Patent Application No. 10/505,239 

filed 19 Aug 2004, claiming priority to 

27 Feb 2002 (HHS Reference No. E–

057–2002/2–US–02). 

Systemic toxicity of drugs is one of 

the most serious problems in cancer 

chemotherapy and frequently is dose 

limiting. Specific delivery of cytotoxic 

drugs to cancer cells remains among the 

most intractable problems of cancer 

therapy. Targeted delivery of antiproliferation drugs through the cell 

surface receptors that are over expressed 

on cancer cells can reduce systemic 

toxicity and increase effectiveness of a 

treatment. 

The present invention describes 

cytotoxic compounds with an 

intracellular target that can selectively 

enter tumor cells through specific 

receptors on the cell surface. The 

invention also describes a conjugate 

comprising a cytotoxic agent, a linker 

arm and a ligand capable of delivering 

a cytotoxic agent in a cell specific 

manner. Such conjugates of a cytotoxic 

agent and a ligand (delivery moiety) 

have increased selectivity for tumor 

cells. The toxic moiety and the ligand 

are joined by a linker arm that is stable 

in circulation, but is easily cleaved in 

lysosomes upon internalization of the 

conjugate. A panel of compounds 

comprised of a variety of cytotoxic 

warheads, against various intracellular 

targets linked to an assortment of 

ligands, has been developed and tested 

in a model system. Ligand moieties of 

these conjugates are capable of specific 

delivery of cytotoxic agents to receptors 

that are frequently over expressed in 

gastric, colon, lung, breast, ovarian and 

pancreatic tumors. These compounds 

have the potential to be highly effective 

anti-tumor agents with considerably 

little negative effect. This disclosed 

technology could provide new and 

exciting methodologies to treat cancer. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research opportunities with the 

inventors. 

DNA-Binding Polyamide Drug 

Conjugates 

Zoltan Szekely, Humcha K. 

Hariprakasha, Marek W. Cholody, 

Christopher J. Michejda (NCI). 

U.S. Patent Application No. 10/506,085 

filed 01 Oct 2004, claiming priority to 

27 Feb 2002 (HHS Reference No. E–

060–2002/2–US–02). 

Many current anti-cancer drugs have 

the DNA of cancer cells as their 

principal target. However, in most 

instances, the drugs are not selective 

and are plagued by toxicities, which are 

frequently dose limiting. The present 

invention seeks to enhance anti-tumor 

selectivity and decrease unspecific 

toxicity. It has been known that various 

polyamides can target the minor groove 

of DNA, and rules have been devised to 

ascertain the sequence-reading 

properties of the component residues of 

the polyamide chain. The present 

invention utilizes sequence-selective 

polyamide technology together with 

groups that modify DNA, either by 

sequence-selective alkylation or strand 

cleavage. The DNA-modifying moieties 

that are used for this purpose are novel 

derivatives based on the 

cyclopropylbenzindole (CBI) core 

structure. These compounds alkylate the 

DNA only when bound into the minor 

groove, and they provide some DNAsequence recognizing capability of their 

own. The DNA-modifying agents are 

either embedded in the polyamide chain 

as components of the chain or are 

located at the termini. These 

compounds are highly toxic to cancer 

cells that over-express a targeted DNA 

sequence (e.g. the c-Myc oncogene 

promoter sequence) and are much less 

toxic to non-cancerous tissue. The 

compounds of the present invention 

represent a novel method for targeting 

DNA of cancer cells. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research opportunities with the 

inventors. 

New Building Blocks for DNA Binding 

Agents 

Zoltan Szekely et al. (NCI). 

U.S. Provisional Application No. 60/ 

508,543 filed 03 Oct 2003 (HHS 

Reference No. E–291–2003/0–US–01). 

PCT Application No. PCT/US04/32617 

filed 01 Oct 2004, which published as 

WO 2005/032594 on 14 Apr 2005 

(HHS Reference No. E–291–2003/0–

PCT–02). 

There remains a need for therapeutic 

conjugates that have improved 

antitumor selectivity and nucleic acid 

sequence-binding specificity. Ideally 

such conjugates will have fewer side 

effects and lower cytotoxicity to healthy 

cells and tissues. The knowledge of the 

geometry of conjugates allows for a 

rational design of therapeutic 

conjugates, ones that have increased 

specificity of binding to a minor groove 

of the DNA, while maintaining 

maximum activity of the alkylating 

subgroup of the conjugates. The present 

invention provides such conjugates. The 

conjugates of the present invention bind 

to the minor grove of DNA in a 

sequence-specific manner and deliver 

an alkylating moiety to a specific site on 

the DNA. The present invention 

provides a pharmaceutical composition 

comprising a pharmaceutically or 

pharmacologically acceptable carrier 

and compounds of the present 

invention. The present invention also 

provides a method of preventing or 

treating a disease or condition by the 

use of the compound. The NIH 

inventors currently are testing the 

conjugates in in-vitro assay and are 

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