38440 Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 

sale to the consumer. The term ‘‘leafy 

greens’’ as used in this draft guidance 

includes raw agricultural commodities 

and fresh-cut/value-added products. 

Examples of leafy greens include iceberg 

lettuce, romaine lettuce, leaf lettuce, 

butter lettuce, baby leaf lettuce 

(immature lettuce or leafy greens), 

escarole, endive, spring mix, spinach, 

cabbage, kale, arugula, and chard. Leafy 

greens do not include herbs such as 

cilantro and parsley. 

This draft guidance is based primarily 

on leafy greens industry guidelines 

issued in 2006 (Ref. 1), along with 

agency experience and information from 

other recent public and private 

programs. The leafy greens industry has 

since updated and supplemented its 

2006 guidelines with additional 

recommendations on the production 

and harvest of leafy greens that include 

quantitative metrics and measures to 

assist industry in implementing the 

guidelines (Ref. 2). This draft guidance 

does not include these more specific 

and quantitative metrics and measures. 

We are considering the extent to which 

more specific measures, including 

metrics, should be utilized to help 

verify the implementation and efficacy 

of the Federal recommendations and 

industry practices. We are also 

evaluating the extent to which metrics 

can be applied to diverse geographic 

areas within the United States and 

internationally. FDA invites comment 

on whether such information should be 

incorporated into the guidance, when 

finalized. 

FDA is issuing this draft guidance as 

Level 1 draft guidance consistent with 

FDA’s good guidance practices 

regulation (21 CFR 10.115). The draft 

guidance, when finalized, will represent 

the agency’s current thinking on the 

microbiological hazards presented by 

fresh and fresh-cut leafy greens products 

and the recommended control measures 

for such hazards in production and 

harvesting, postharvest operations, 

processing, distribution, and retail and 

food service handling of such produce. 

It does not create or confer any rights for 

or on any person and does not operate 

to bind FDA or the public. An 

alternative approach may be used if 

such approach satisfies the 

requirements of the applicable statutes 

and regulations. 

II. Paperwork Reduction Act of 1995 

Under the Paperwork Reduction Act 

of 1995 (the PRA) (44 U.S.C. 3501– 

3520), Federal agencies must obtain 

approval from the Office of Management 

and Budget (OMB) for each collection of 

information they conduct or sponsor. 

‘‘Collection of information’’ is defined 

in 44 U.S.C. 3502(3) and 5 CFR 

1320.3(c) and includes agency requests 

or requirements that members of the 

public submit reports, keep records, or 

provide information to a third party. 

Section 3506(c)(2)(A) of the PRA (44 

U.S.C. 3506(c)(2)(A)) requires Federal 

agencies to publish notice in the 

Federal Register soliciting public 

comment on each proposed collection of 

information before submitting the 

collection to OMB for approval. To 

comply with this requirement, FDA will 

publish a 60-day notice on the proposed 

collection of information in a future 

issue of the Federal Register. 

III. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) written or electronic 

comments regarding this document. 

Submit a single copy of electronic 

comments or two paper copies of any 

mailed comments, except that 

individuals may submit one paper copy. 

Comments are to be identified with the 

docket number found in brackets in the 

heading of this document. The draft 

guidance and received comments may 

be seen in the Division of Dockets 

Management between 9 a.m. and 4 p.m., 

Monday through Friday. 

IV. Electronic Access 

Persons with access to the Internet 

may obtain the draft guidance at either 

http://www.fda.gov/FoodGuidances or 

http://www.regulations.gov. 

V. References 

The following references have been 

placed on display in the Division of 

Dockets Management, 5630 Fishers 

Lane, rm. 1061, Rockville, MD 20852 

and may be seen by interested persons 

between 9 a.m. and 4 p.m., Monday 

through Friday. 

1. Gorny, J., et al., editors, ‘‘Commodity 

Specific Food Safety Guidelines for the 

Lettuce and Leafy Greens Supply Chain’’ (1st 

ed.); International Fresh-cut Produce 

Association, Produce Marketing Association, 

United Fresh Fruit and Vegetable 

Association, Western Growers Association; 

April 25, 2006. Accessed online at http:// 

www.fda.gov/Food/FoodSafety/ProductSpecificInformation/FruitsVegetablesJuices/ 

GuidanceComplianceRegulatoryInformation/ 

ucm168630.htm. 

2. See ‘‘Commodity Specific Food Safety 

Guidelines for the Production and Harvest of 

Lettuce and Leafy Greens’’; Produce 

Marketing Association, United Fresh Fruit 

and Vegetable Association, and Western 

Growers Association; last revised June 13, 

2008. Accessed online at http:// 

www.caleafygreens.ca.gov/trade/documents/ 

LGMAAcceptedGAPs06.13.08.pdf. (FDA has 

verified the Web site address, but FDA is not 

responsible for any subsequent changes to 

the Web site after this document publishes in 

the Federal Register.) 

Dated: July 28, 2009. 

Jeffrey Shuren, 

Associate Commissioner for Policy and 

Planning. 

[FR Doc. E9–18451 Filed 7–31–09; 8:45 am] 

BILLING CODE 4160–01–S 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Government-Owned Inventions; 

Availability for Licensing 

AGENCY: National Institutes of Health, 

Public Health Service, HHS. 

ACTION: Notice. 

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. 

Treatment of Cancer Using Metal 

Coordinating Compounds That Kill 

Multi-Drug Resistant Cancer Cells 

Description of Invention: One of the 

major hindrances to successful cancer 

chemotherapy is the development of 

multi-drug resistance (MDR) in cancer 

cells. MDR is frequently caused by the 

increased expression or activity of ABC 

transporter proteins in response to the 

toxic agents used in chemotherapy. 

Research has generally been directed to 

overcoming MDR by inhibiting the 

activity of ABC transporters. However, 

compounds that inhibit ABC transporter 

activity often elicit strong and 

undesirable side-effects, restricting their 

usefulness as therapeutics. 

In an alternative approach to reducing 

the debilitating effects of MDR during 

cancer therapy, scientists at the NIH 

have identified a family of compounds 


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Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 38441 

whose activities are enhanced, rather 

than decreased, in MDR cancer cells. 

Particular embodiments of these ‘‘MDRselective compounds’’ include certain 

metal coordinating compounds. Recent 

evidence suggests that these MDRselective compounds can be used to kill 

cancer cells that overexpress ABC 

transporters or to re-sensitize multi-drug 

resistant cancer cells to 

chemotherapeutics. Furthermore, the 

effectiveness of these compositions in 

killing MDR cancer cells correlates 

directly with the level of ABC 

transporter expression. Importantly, 

MDR-selective compounds are not 

inhibitors of ABC transporters, thereby 

reducing the likelihood of undesirable 

side-effects during treatment. Thus, 

MDR-selective compounds represent a 

powerful strategy for treating multi-drug 

resistant cancers as a direct 

chemotherapeutic and as agents that can 

re-sensitize MDR cancer cells for 

treatment with additional 

chemotherapeutic agents. 

Applications 

• Treatment of cancers associated 

with multi-drug resistance, either alone 

or in combination with other 

therapeutics. 

• Re-sensitization of multi-drug 

resistant cancer cells to 

chemotherapeutic agents. 

Advantages 

• MDR-selective compounds 

capitalize on one of the most common 

drawbacks to cancer therapies (MDR) by 

using it as an advantage for treating 

cancer. 

• The compositions do not inhibit the 

function of ABC transporters, reducing 

the chance of side-effects during 

treatment. 

• The effects of MDR-selective 

compounds correlate with the level of 

ABC transporter expression, allowing 

healthy cells which do not express high 

levels of ABC transporters to better 

survive treatment. 

Development Status: Preclinical stage 

of development. 

Patent Status: U.S. Provisional 

Application No. 61/182,511 (HHS 

Reference No. E–157–2009/0–US–01). 

Inventors: Gergely Szakacs et al. 

(NCI). 

For More Information, See 

• C Hegedus et al. Interaction of ABC 

multidrug transporters with anticancer 

protein kinase inhibitors: substrates 

and/or inhibitors? Curr Cancer Drug 

Targets. 2009 May;9(3):252–272. 

• MD Hall et al. Synthesis, activity, 

and pharmacophore development for 

isatin-beta-thiosemicarbazones with 

selective activity toward multidrugresistant cells. J Med Chem. 2009 May 

28;52(10):3191–3204. 

• U.S. Patent Application Publication 

20080214606 A1 (U.S. Patent 

Application 11/629,233). 

Licensing Status: Available for 

licensing. 

Licensing Contact: David A. 

Lambertson, Ph.D.; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The Institute of Enzymology is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize MDR-selective 

compounds. Please contact John D. 

Hewes, Ph.D. at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

Non Toxic Peptide Treatment for 

Dyslipidemic and Vascular Disorders 

Description of Invention: 

Dyslipidemia and vascular disorders 

such as hyperlipidemia, 

hypercholesterolemia, HDL deficiency, 

coronary heart disease, atherosclerosis, 

or thrombic stroke, have become major 

health concerns in recent years. Various 

approaches to treating these diseases 

have led to mixed success with some 

undesirable side effects. Long term 

administration of some regimens aimed 

at reducing cholesterol levels in cells 

can lead to persistent 

hypertriglyceridemia; a condition that is 

characterized by chronically high 

triglycerides in the blood. Other 

approaches, such as using peptides to 

stimulate the efflux of lipids from cells, 

are also associated with high toxicity, 

which has limited their use. 

This technology uses peptide and 

peptide analogues with multiple 

amphipathic alpha helical domains that 

have the dual ability to promote lipid 

efflux from cells and stimulate 

lipoprotein lipase activity, without 

inducing toxicity. It consists of motifs 

that mimick apolipoprotein A–I (apoA– 

I), the most abundant protein 

constituent of high density lipoproteins 

(HDLs) that is capable of inducing 

cellular lipid efflux, and motif 

resembling apolipoprotein C–II (apoC– 

II), a known activator of lipoprotein 

lipase. Peptides constructed with these 

structural domains are capable of 

stimulating lipid efflux and activating 

lipoprotein lipase, leading to a reduced 

incidence of hypertriglyceridemia. 

Unlike previous methods, some 

amphipathic peptides cause transient 

hypertriglyceridema in mice that lasts 

for less than 8 hours. Mice treated with 

these modified peptides have shown 

preserved liver function as they have 

failed to express increased levels of 

biomarkers for liver damage and prevent 

hypertriglyceridemia. Furthermore, 

treated mice show a reduced level of 

pro-atherogenic lipoproteins. This 

technology demonstrates specific 

control of lipid efflux and transport; a 

desirable property that gives it a 

significant advantage for treating or 

preventing a vast range of vascular 

diseases and their dyslipidemic 

precursors. 

This technology also encompasses a 

method for identifying non-cytotoxic 

peptides that promote lipid efflux from 

cells and activates lipoprotein lipase. 

Applications and Advantages 

• Peptide treatment of dyslipidemic 

and vascular disorders. 

• Transient hypertriglyceridemia 

with no reported toxicity. 

• Method of identifying therapeutic 

non-cytotoxic peptides. 

Development Status: Pre-clinical. 

Inventor: Alan T. Remaley and 

Marcelo Amar (NHLBI). 

Publication: AT Remaley, F Thomas, 

JA Stonik, SJ Demosky, SE Bark, EB 

Neufeld, AV Bocharov, TG 

Vishnyakova, AP Patterson, TL 

Eggerman, S Santamarina-Fojo, HB 

Brewer. Synthetic amphipathic helical 

peptides promote lipid efflux from cells 

by an ABCA1-dependent and an 

ABCA1-independent pathway. J Lipid 

Res. 2003 Apr;44(4):828–836. 

Patent Status: U.S. Provisional 

Application No. 60/045,213 filed 15 Apr 

2008 (HHS Reference No. E–138–2008/ 

0–US–01); PCT Application No. PCT/ 

US2009/040560 filed 14 Apr 2009 (HHS 

Reference No. E–138–2008/0–PCT–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

sayyidf@mail.nih.gov. 

Methods for Treating or Ameliorating 

Fibrosis by Inhibiting the Interaction 

Between IL–21 Receptor (IL–21R) and 

IL–21 

Description of Invention: This 

invention includes methods for treating 

or ameliorating fibrosis by inhibiting the 

interaction between IL–21 Receptor (IL– 

21R) and IL–21 using either anti-IL21R 

monoclonal antibodies (or binding 

fragments of anti-IL–21R mAbs), antiIL21 monoclonal antibodies (or binding 

fragments of anti-IL–21 mAbs) or 

soluble IL–21R (or binding fragments of 

IL–21R). It is believed that the TH2 

immune response, induced by IL–21, 

plays a major role in the pathogenesis of 

tissue fibrosis. Antagonism of IL–21R by 

anti-IL–21R monoclonal antibodies or 

the sequestration of IL–21 by soluble IL– 


sroberts on DSKD5P82C1PROD with NOTICES
38442 Federal Register / Vol. 74, No. 147 / Monday, August 3, 2009 / Notices 

21R or anti-IL–21 monoclonal 

antibodies has been demonstrated to 

reduce TH2 immune responses 

associated with fibrosis in animal 

models. 

The causes of chronic tissue fibrosis 

are diverse and the market for a 

therapeutic that targets fibrosis is large. 

Fibrosis is associated with diverse 

causes which include: genetic diseases 

(such as cystic fibrosis); autoimmune 

diseases (such as scleroderma); chronic 

viral infections (such as hepatitis), 

parasitic infections (such as 

schistosomiasis); and occupational 

exposures to causative agents (such as 

asbestosis). Additionally, many cases of 

tissue fibrosis are idiopathic. 

Application: The treatment or 

amelioration of tissue fibrosis. 

Inventors: Thomas A. Wynn (NIAID); 

Deborah A Young; Mary Collins; and 

Michael J. Grusby. 

Relevant Publication: J Pesce et al. 

The IL–21 receptor augments Th2 

effector function and alternative 

macrophage activation. J Clin Invest 

2006 Jul;116(7):2044–2055. 

Patent Status: U.S. patent application 

no. 11/402,885 (priority date April 14, 

2005) and international patent 

applications including European patent 

application No. EP06/0750009 (HHS 

Reference No. E–250–2005). 

Licensing Status: Available for nonexclusive licensing. 

Licensing Contact: Surekha Vathyam, 

Ph.D.; 301–435–4076; 

vathyams@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute of Allergy and 

Infectious Diseases is seeking statements 

of capability or interest from parties 

interested in collaborative research to 

further develop, evaluate, or 

commercialize this invention. Please 

contact Nicole Mahoney at 301–435– 

9017 or mahoneyn@niaid.nih.gov for 

more information. 

Use of Discoidin Domain Receptor 1 

(DDR1) and Agents That Affect the 

DDR1/Collagen Pathway 

Description of Invention: Dendritic 

cells (DCs) are pivotal antigenpresenting cells for initiation of an 

immune response. Indeed, dendritic 

cells provide the basis for the 

production of an effective immune 

response to a vaccine, particularly for 

antigens wherein conventional 

vaccination is inadequate. DCs are also 

important in the production on an 

immune response to tumor antigens. 

The present invention discloses 

methods of using the receptor tyrosine 

kinase discoidin domain receptor 1 

(DDR1) to facilitate the maturation/ 

differentiation of DCs or macrophages. 

Activating agents of DDR1 may be 

useful in the induction of highly potent, 

mature DCs or highly differentiated 

macrophages from DC precursors, such 

as monocytes. Use of this method may 

enhance the antigen presenting 

capabilities of the immune system, 

leading to a more effective overall 

immune response. 

Inventor: Teizo Yoshimura (NCI). 

Relevant Publications 

1. H Kamohara et al. Discoidin 

domain receptor 1 isoform-a (DDR1a) 

promotes migration of leukocytes in 

three-dimensional collagen lattices. 

FASEB J. 2001 Dec;15(14):2724–2726. 

2. W Matsuyama et al. Interaction of 

discoidin domain receptor 1 isoform b 

(DDR1b) with collagen activates p38 

mitogen-activated protein kinase and 

promotes differentiation of 

macrophages. FASEB J. 2003 

Jul;17(10):1286–1288. 

Patent Status: U.S. Application No. 

10/507,385 filed 09 Sep 2004 (HHS 

Reference No. E–083–2002/2–US–02). 

Licensing Status: Available for 

licensing. 

Licensing Contact: Betty B. Tong, 

Ph.D.; 301–594–6565; 

tongb@mail.nih.gov. 

Dated: July 28, 2009. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. E9–18504 Filed 7–31–09; 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, 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 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. 

A Tumorigenic MEF/3T3 Tet-Off Mouse 

Fibroblast Cell Line Stably Transfected 

With a T7–Tagged Srp20 Expression 

Construct (pJR17) 

Description of Technology: 

Alternative RNA splicing is a means by 

which the human genome can produce 

many more proteins from the genes 

available. It is emerging that aberrations 

in alternative RNA splicing contributes 

to the development of cancers. SRp20 is 

a cellular splicing factor that is involved 

in the process of alternative splicing of 

RNA. Investigators at the National 

Cancer Institute (NCI), National 

Institutes of Health (NIH) have 

discovered that SRp20 is overexpressed 

in many types of cancer and 

furthermore promotes the induction and 

maintenance of tumor cell growth. This 

was demonstrated in part by 

engineering a non-tumorigenic cell to 

become tumorigenic in mice by 

overexpressing SRp20. 

Research Material available for 

licensing is a tumorigenic MEF/3T3 tetoff mouse fibroblast cell line stably 

transfected with a T7-tagged SRp20 

expression construct (pJR17) that is 

under the transcriptional control of 

tetracycline. 

Applications: Use in pre-clinical 

development of therapeutic approaches 

to cancer that target aberrant alternative 

RNA splicing. 

Advantages: Transcriptional control 

of expression using Tet-off system; 

Availability of stably transfected cell 

line saves time and effort for other 

investigators. 

Market: Research Tool. 

Development Status: Ready to use. 

Inventors: Zhi-Ming Zheng and Rong 

Jia (NCI). 

Publications: Manuscript in 

preparation. 

Patent Status: HHS Reference No. E– 

229–2009/0—Research Material. Patent 

protection is not being sought for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Sabarni Chatterjee, 

Ph.D.; 301–435–5587; 

chatterjeesa@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Center for 

Cancer Research, HIV and AIDS 

Malignancy Branch, is seeking 

statements of capability or interest from 


sroberts on DSKD5P82C1PROD with NOTICES