6702 Federal Register / Vol. 70, No. 25 / Tuesday, February 8, 2005 / Notices 

Subject name Address Effective date 

WETTEROW, MELANIE .............................................................................. PHOENIX, AZ ........................................... 2/20/2005 

WHITE, SEAN .............................................................................................. GLENDALE, AZ ........................................ 2/20/2005 

WHITTENTON, ANGELA ............................................................................. COATS, NC .............................................. 2/20/2005 

WILD, LISA ................................................................................................... COLUMBIA, CT ........................................ 2/20/2005 

WILLIAMS, PATRICIA .................................................................................. ANNANDALE, VA ..................................... 2/20/2005 

WILLIAMS, WARREN .................................................................................. OAKLAND, CA .......................................... 2/20/2005 

WOOLLEY, TODD ....................................................................................... OLYMPIA, WA .......................................... 2/20/2005 

ZIBA, GRACE ............................................................................................... LOMA LINDA, CA ..................................... 2/20/2005 

FRAUD/KICKBACKS/PROHIBITED ACTS/SETTLEMENT AGREEMENTS

GLANZER, ELROY ...................................................................................... IDAHO FALLS, ID ..................................... 2/18/2004 

OWNED/CONTROLLED BY CONVICTED ENTITIES

MONTECINO’S DRUGS, INC ...................................................................... MARRERO, LA ......................................... 2/20/2005

VALLEY COUNTRY CARE .......................................................................... EDEN VALLEY, MN ................................. 2/20/2005 

DEFAULT ON HEAL LOAN

BUKOWSKI, TODD ...................................................................................... WASHINGTON, DC .................................. 11/19/2004 

MANRIQUEZ, ANTONIO ............................................................................. COACHELLA, CA ..................................... 2/20/2005 

RICHARDS, JOHN ....................................................................................... WASHINGTON, DC .................................. 2/20/2005 

Dated: February 1, 2005. 

Katherine B. Petrowski, 

Director, Exclusions Staff, Office of Inspector 

General.

[FR Doc. 05–2369 Filed 2–7–05; 8:45 am] 

BILLING CODE 4150–04–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 

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. 

Methods for Treating Active Uveitis 

Robert Nussenblatt (NEI) and Thomas 

Waldmann (NCI), Zhuqing Li (NEI), 

Ronald Buggage (NEI). U.S. Provisional Patent Application No. 

60/616,760 filed 06 Oct 2004 (DHHS 

Reference No. E–328–2004/0–US–01). 

Licensing Contact: Susan Carson; 301/

435–5020; carsonsu@mail.nih.gov.

Intraocular inflammatory disease 

(uveitis) is characterized by pain and a 

decrease in vision that can lead to 

blindness if not treated appropriately. 

The incidence and prevalence of the 

disease are approximately 52/100,000 

and 112/100,000, and this translates 

into an incidence of 151,000 per year 

and a prevalence of 322,000. The 

numbers are expected to increase as the 

population ages. Treatment of severe 

uveitis often focuses on the control of 

the inflammatory symptoms using high 

dose corticosteroids, cytotoxic drugs or 

other immunosuppressive agents and 

there is a need for therapies that reduce 

the major side effects associated with 

the prolonged use of systemic steroids 

(e.g. hyperglycemia, osteoporosis and 

loss of immunocompetence). 

Daclizumab is a humanized anti-Tac 

(HAT) antibody that specifically binds 

to the alpha subunit (CD25 or Tac 

subunit) of the human high affinity 

interleukin-2 (IL–2) receptor expressed 

on the surface of activated lymphocytes. 

Dr. Nussenblatt and colleagues at the 

NEI have previously shown that 

daclizumab can be used to successfully 

treat quiescent uveitis. Long term 

daclizumab therapy at a dose of 1mg/kg 

can be used instead of standard 

immunosuppressive agents to treat 

severe uveitis for more than 4 years with 

no adverse effects attributable to the 

medication, and subcutaneously 

administered daclizumab also appeared 

to be clinically effective. However, 

subjects with active uveitis were less 

likely under this regimen to have their 

disease controlled (J. Autoimmunity 

(2003) 21, 283–293). 

The present invention targets patients 

with refractory, active uveitis and 

consists of a high dose intravenous 

induction therapy using daclizumab at 

two different doses and times followed 

by a longer term maintenance therapy. 

Positive therapeutic effects have been 

seen with this protocol in a small group 

of patients within 4–6 weeks after the 

initiation of therapy. As previous work 

indicated that IL–2R receptors have a 

slow turnover rate on CD4 positive 

subpopulation of lymphocytes, a 

possible mechanism of action of this 

new protocol is saturation of CD25 

(TAC) receptors on cells in sequestered 

sites. 

Available for licensing are methods 

directed to this treatment of active 

uveitis using a high dose pulsatile 

induction protocol of an interleukin-2 

(Il–2) receptor antagonist. Methods are 

also provided for the treatment of 

corneal transplant rejection, limbal stem 

cell rejection following transplantation, 

optic neuritis and dry eye. 

Novel Thermostable Y-Family DNA 

Polymerases 

Roger Woodgate (NICHD), John P. 

McDonald (NICHD), and Wei Yang 

(NIDDK). 

U.S. Provisional Patent Application No. 

60/573,684 filed 20 May 2004 (DHHS 

Ref No. E–166–2004/0–US–01); U.S. 

Provisional Patent Application No. 

60/623, 490 filed 29 Oct 2004 (DHHS 

Ref No. E–166–2004/1–US–01).

Federal Register / Vol. 70, No. 25 / Tuesday, February 8, 2005 / Notices 6703

Licensing Contact: Susan Carson; 301/

435–5020; carsonsu@mail.nih.gov.

Y-family polymerases are able to 

bypass lesions in DNA that would 

otherwise block replication by high 

fidelity DNA polymerases and are key to 

the effective study of ancient DNA and 

for use in forensic medicine. These 

enzymes are ubiquitous and are found 

in all kingdoms of life: bacteria, archaea 

and eukaryotes. The number of proteins 

related to the Y-family polymerases is 

well over 200 orthologs and despite 

being closely related at the phylogenetic 

level, the few polymerases now 

characterized, each show a unique set of 

properties including processivity, 

fidelity, and the ability to bypass certain 

types of DNA. Y-family polymerases 

from thermostable organisms are of 

particular interest because the enzymes 

isolated from such species tend to be 

more stable, easy to work with and may 

have more utility in assays at higher 

temperatures, such as Polymerase Chain 

Reaction (PCR). For example, the 

thermostable archeal Sulfolobus 

solfataricus DinB-like polymerase Dpo4 

can bypass lesions by generally 

inserting the correct complementary 

nucleotide opposite a variety of 

damaged bases and can, under 

appropriate conditions substitute for 

Taq polymerase in PCR applications 

[NAR (2001) 29, 4607–4616; DHHS Ref. 

No. E–232–2001/0]. Additionally, 

functional and structural organization of 

this family of polymerases permits 

domain swapping designed to optimize 

specific properties of use in novel 

applications [J. Biol. Chem. (2004) 279, 

32932–32940]. 

Dr. Woodgate’s group at the National 

Institute of Child Health and 

Development have expanded their 

earlier work and have now discovered 

several additional thermostable dpo4 

homologs from other strains found in 

the Sulfolobaceae family, some of which 

have optimal growth temperatures 

higher than 80°C. These novel DinB-like 

proteins have thermostable DNA 

polymerase activity and are capable of: 

(1) PCR amplifications over 1kb in 

length, (2) replication past DNA lesions 

such as abasic sites and CPD (cis-syn 

cyclobutane pyrimidine dimer) lesions 

and (3) incorporation of several different 

labeled DNA nucleotides into DNA 

during replication. These enzymes may 

therefore be a good substitute for Taq 

polymerase in applications utilizing 

fluorescent nucleoside triphosphate 

derivatives. These lesion-bypassing 

Dpo4-like polymerases could also be 

included along with a conventional 

thermostable polymerase in a PCR 

protocol designed to amplify old or 

damaged DNA samples which could 

greatly increase recoverability, accuracy 

and length of products. Other 

applications could include labelling or 

tagging DNA, real-time PCR, detection 

of SNPs, mismatches or DNA lesions, 

mutagenic PCR, directed-evolution 

methods and expanding the ‘‘DNA 

alphabet’’ utilizing non-natural 

nucleotides. 

Available for licensing are seven 

novel Y-family polymerases. Claims are 

directed to these sequences and 

chimeras, as well as to methods of 

identifying other Y-family polymerases 

and generating other chimeric Y-family 

polymerases and methods of use. These 

enzymes and methods of identifying 

and generating novel Y-family 

polymerases should be of interest to 

forensic DNA service companies as well 

as to research reagent companies 

pursuing novel thermophlic enzymes 

for use in ancient and damaged DNA 

analysis and for novel applications with 

modified nucleotides. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research with the inventors via a 

Cooperative Research and Development 

Agreement (CRADA).

Related technologies available for 

licensing as research tools include: 

DHHS Ref. No. E–232–2001/0 (dpo4 Yfamily polymerase) and DHHS E–229–

2001/0 (pol iota Y-family polymerase). 

Rapid, Efficient In Vivo Site-Directed 

Mutagenesis Using Oligonucleotides 

Francesca Storici, Michael A. Resnick, 

Lysle Kevin Lewis (NIEHS). 

PCT Application No. PCT/US02/23634 

filed 26 July 2002, which published as 

International Publication No. WO03/

012036 on 13 Feb 2003 (DHHS 

Reference No. E–204–2001/0–PCT–

02). 

National Stage Entry: EPC, CA, AU, US, 

JP. 

U.S. Patent Application No. 10/484,989 

filed 26 Jan 2004 (DHHS Reference 

No. E–204–2001/0–US–07). 

Licensing Contact: Susan Carson; 301/

435–5020; carsonsu@mail.nih.gov.

The rapid modification of genes 

provides opportunities to study gene 

function and evaluate drug 

responsiveness. Scientists at the 

National Institute for Environmental 

and Health Sciences have developed a 

new system in yeast, delitto perfetto,

which provides for rapid, efficient and 

accurate in vivo genomic mutagenesis 

using oligonucleotides (IROs) and 

involves the complete removal of the 

heterologous sequence previously 

integrated at the target locus (Nature 

Biotechnol. (2001) 19, 773–776). They 

have demonstrated that synthetic 

oligonucleotides can target a desired 

mutation to almost any chromosomal 

locus where a marker cassette has been 

previously integrated. The 

oligonucleotides, which are designed 

with short sequence homology to sites 

up- and down-stream of the marker 

cassette, replace the marker cassette 

with the chosen mutation without 

leaving any heterologous sequence in 

the targeted locus. Since the system 

always provides selection for the clones 

containing the desired mutation, it can 

be used to generate any kind of 

modification: i.e., it is not constrained 

by the generation of mutations that 

provide a detectable phenotype. 

Additionally, induction of doublestrand breaks (delitto perfetto-DSB) in 

vivo before standard transformation 

procedures provides 1,000 to 10,000 

fold stimulation of oligonucleotide 

targeting, resulting in 5–20% of all cells 

in the population being efficiently 

targeted by small oligonucleotides 

(PNAS (2003), 100, 14994–14999). With 

such a high stimulation of targeting 

even gross rearrangements, like large 

DNA deletions, chromosome fusions, 

circularizations, reciprocal or non 

reciprocal translocations are obtained 

with high frequency and direct 

selection. 

The core invention is a novel selfcloning system for simple and highthroughput in vivo site-directed 

mutagenesis applicable to all organisms 

capable of homologous recombination 

and developed in the non-pathogenic 

yeast Saccharomyces cerevisiae. Since 

changes are created through a selfcloning process, this system could 

represent a highly versatile tool to 

generate modifications of genes in 

yeasts for commercial application in the 

food and beverage industries (such as, 

baking, brewing, wine and sake) without 

the resulting organisms being classified 

as GMO (genetically modified 

organisms). This approach could also be 

well positioned within drug discovery 

protocols where the need to mutagenize 

particular target sequences forms an 

integral part of the drug development 

process. 

Delitto perfetto-DSB is efficient for 

targeting homologous sequences that are 

close or distant to the DSB and in the 

presence of a competing homologous 

chromosome in diploid cells, and can 

strongly stimulate recombination with 

single-stranded DNA, without strand 

bias. The mechanism of DSB repair with 

oligonucleotides follows primarily a 

single-strand annealing pathway of 

recombinational repair. This novel 

system is also independent of restriction 

sites, requires minimal sequence 

6704 Federal Register / Vol. 70, No. 25 / Tuesday, February 8, 2005 / Notices 

analysis. This method has been used in 

S. cerevisiae for many yeast 

chromosomal genes and the human gene 

p53 and has obvious potential for use 

with YAC and TAR clones. Claims are 

directed to several methods for 

generating DNA nucleic acid mutations 

in vivo and are applicable to any 

organism that has a homologous 

recombination system, as well as to kits. 

This methodology is available for 

licensing and is a highly versatile tool 

of direct use to drug discovery, pharma 

and research reagent companies as well 

as to companies working with industrial 

yeast strains. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research with the inventors via a 

Cooperative Research and Development 

Agreement (CRADA). 

Related technologies also available for 

licensing include: DHHS Ref. No. E–

121–1996/0–US–06, TransformationAssociated Recombination Cloning (U.S. 

Patent No. 6,391,642 issued 21 May 

2002); and DHHS Ref. No. E–262–1984/

0–US–03, Process for Site Specific 

Mutagenesis Without Phenotypic 

Selection (U.S. Patent No. 4,873,192 

issued 10 Oct 1989). 

The Whey Acidic Protein (WAP) 

Promoter and Its Use to Express 

Therapeutic Proteins in the Milk of 

Transgenic Mammals 

Lothar Hennighausen (NIDDK), Heiner 

Westphal (NICHD), et al. U.S. Patent 

No. 6,727,405 issued 27 Apr 2004 

(DHHS Reference No. E–411–1987/0–

US–03). 

Licensing Contact: Susan Carson; 301/

435–5020; carsonsu@mail.nih.gov.

Transgenic animals can be engineered 

to express complex human proteins at 

high concentrations in milk. Protein 

replacement therapy is often the only 

treatment available for congenital 

diseases such as hemophilia or 

lysosomal storage disease, and the cost 

of treatment can be high with the 

therapeutic protein market estimated to 

reach more than $50 billion by 2010. 

U.S. Patent No. 6,727,405 has recently 

been issued (expiry date 2021) to NIH 

scientists and their collaborators. This 

patent provides for a non-human 

mammal such as mouse, sheep, pig, goat 

and cow whose genome contains a DNA 

sequence comprising a milk serum 

protein (whey acidic protein) promoter 

linked to a heterologous gene sequence 

and secretory peptide, as well as 

methods for producing a secreted 

protein into the transgenic animal’s 

milk and claims directed to the DNA 

construct. The invention permits the 

production of any desired protein in an 

easily maintained, stable, mammalian 

bioreactor, which is capable not only of 

producing the desired protein in milk, 

but can also pass the ability to do so to 

its female offspring. Although other 

methods of obtaining recombinant 

protein products are available, these 

require inefficient, expensive 

purification of the protein from the 

blood or from cell culture media and 

there remains a need for an efficient and 

cost effective method for producing 

therapeutic proteins. 

This WAP promoter platform 

technology provides a viable alternative 

to other milk protein promoters and is 

available for non-exclusive licensing.

Dated: January 31, 2005. 

Steven M. Ferguson, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health.

[FR Doc. 05–2364 Filed 2–7–05; 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 

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. 

A3 Adenosine Receptor Agonists 

Kenneth A. Jacobson et al. (NIDDK). 

U.S. Provisional Patent Application No. 

60/608,823 filed 09 Sep 2004 (DHHS 

Reference No. E–248–2004/0–US–01). 

Licensing Contact: Marlene Shinn-Astor; 

(301) 435–4426; 

shinnm@mail.nih.gov.

Researchers have been pursuing 

compounds that activate or inhibit 

adenosine A3 receptors because these 

cell membrane proteins have a wide 

range of physiological and diseaserelated effects and are thus considered 

to be promising drug targets. The 

adenosine A3 receptors are G-proteincoupled receptors and are found mostly 

in brain, lung, liver, heart, kidney, and 

testis. When this receptor is activated 

moderately, a cytoprotective effect is 

observed, such as reducing damage to 

heart cells from lack of oxygen. 

However, at high levels of stimulation 

they can cause cell death. Both agonists 

and antagonists are being tested for 

therapeutic potential, for example, 

treatment of cancer, heart conditions, 

neurological conditions, pain, asthma, 

inflammation and other immune 

implications. 

Adenosine receptors have provided 

fertile leads for pharmaceutical 

development, and there are currently a 

variety of adenosinergic compounds 

advancing toward clinical trials. 

Therapeutics which target the adenosine 

A3 receptors is now an emerging focus 

that the major pharmaceutical 

companies are developing. Smaller 

companies are also developing drugs 

that stem from proprietary technology 

targeting adenosine A3 receptors. These 

companies have products in clinical 

trials for colorectal cancer and 

rheumatoid arthritis. 

This invention pertains to highly 

potent A3 adenosine receptor agonists, 

pharmaceutical compositions 

comprising such nucleosides, and a 

method of use of these nucleosides. 

This research has been published, in 

part, in S. Tchilibon, B.V. Joshi, S.-K. 

Kim, H.T. Duong, Z.-G. Gao, and K.A. 

Jacobson, ‘‘N-methano adenosine 

derivatives as A3 receptor agonists,’’ J. 

Med. Chem., ASAP web release date 23 

Sep 2004, doi: 10.1021/jm049580r. 

In addition to licensing, the 

technology is available for further 

development through collaborative 

research with the inventors via a 

Cooperative Research and Development 

Agreement (CRADA). 

Apparatus for Multifocal Deposition 

and Analysis 

Bradford Wood, Alexander Gorbach, Ziv 

Neeman, Julia Hvisda (all of NIHCC), 

et al. U.S. Provisional Patent 

Application No. 60/403,875 filed 16 

Aug 2002 (DHHS Reference No. E–

248–2001/0–US–01); International 

Application Number PCT/US03/

25575 filed 14 Aug 2003, which