Federal Register / Vol. 77, No. 60 / Wednesday, March 28, 2012 / Notices 18831 

FOR FURTHER INFORMATION CONTACT: 

Gerie Voss, Center for Tobacco 

Products, Food and Drug 

Administration, 9200 Corporate Blvd., 

Rockville, MD 20850–3229, 877–287– 

1373, gerie.voss@fda.hhs.gov. 

SUPPLEMENTARY INFORMATION: 

I. Background 

In the Federal Register of February 2, 

2012 (77 FR 5171), FDA issued a final 

rule regarding further amendments to 

the general regulations of the FDA to 

incorporate tobacco products. FDA 

examined the economic implications of 

the final rule as required by the 

Regulatory Flexibility Act (5 U.S.C. 

601–612) and determined that the rule 

would have a significant economic 

impact on a substantial number of small 

entities. In compliance with section 212 

of the Small Business Regulatory 

Enforcement Fairness Act (Pub. L. 104– 

121), FDA is making available this SECG 

stating in plain language the legal 

requirements of the February 2, 2012, 

final rule, set forth in 21 CFR parts 1, 

7, and 16, amending the FDA’s general 

regulations to ensure that tobacco 

products are subject to the same general 

requirements that apply to other FDAregulated products. 

FDA is issuing this SECG as level 2 

guidance consistent with FDA’s good 

guidance practices regulation (21 CFR 

10.115(c)(2)). The SECG represents the 

Agency’s current thinking on this topic. 

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. Comments 

Interested persons may submit to the 

Division of Dockets Management (see 

ADDRESSES) either electronic or written 

comments regarding this document. It is 

only necessary to send one set of 

comments. Identify comments with the 

docket number found in brackets in the 

heading of this document. Received 

comments may be seen in the Division 

of Dockets Management between 9 a.m. 

and 4 p.m., Monday through Friday. 

III. Electronic Access 

Persons with access to the Internet 

may obtain the document at http://www.

fda.gov/TobaccoProducts/ 

GuidanceCompliance

RegulatoryInformation/default.htm or 

http://www.regulation.gov. 

Dated: March 23, 2012. 

Leslie Kux, 

Assistant Commissioner for Policy. 

[FR Doc. 2012–7455 Filed 3–27–12; 8:45 am] 

BILLING CODE 4160–01–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. 

Lenalidomide Analogs for the 

Treatment of Neurodegenerative 

Disorders and Cancer 

Description of Technology: 

Inflammatory processes associated with 

the over-production of tumor necrosisalpha (TNF-a), a potent activator of the 

immune system accompany numerous 

neurodegenerative diseases. TNF-a has 

been validated as a drug target with the 

development of the inhibitors Enbrel 

and Remicade (fusion antibodies) as 

prescription medications. Both, 

however, are large macromolecules that 

require direct injection and have limited 

brain access. The classical drug, 

thalidomide is being increasingly used 

in the clinical management of a wide 

spectrum of immunologically-mediated 

and infectious diseases, and cancers. 

The NIA inventors developed and 

assessed novel thio analogs of 

lenalidomide (Celegene’s Revlimid and 

an analog of thalidomide) as 

immunomodulatory agents, with the 

potential to reduce chronic systemic 

and central nervous system 

inflammation. These compounds were 

synthesized and evaluated for their 

TNF-a inhibitory activity. This 

invention was extended from the 

inventors’ prior work to develop potent 

compounds to reduce 

neuroinflammation as a treatment 

strategy for neurodegenerative 

disorders. The current studies focus the 

compounds activity in classical models 

of neurodegeneration as well as cancer. 

Potential Commercial Applications: 

• Treatment for blood disorders 

(myelodysplastic syndrome), cancer 

(multiple myeloma), inflammatory 

processes and erythema 

• Immunomodulatory agents 

• Reduce chronic systemic and 

central nervous system inflammation 

Competitive Advantages: 

• Effective smaller molecular weight 

compound that can enter brain among 

current agents 

• Experimental therapeutic to reduce 

inflammation systematically and within 

the brain 

• Effective in reducing 

proinflammatory cytokines than existing 

agents 

Development Stage: 

• Prototype 

• Clinical 

• In vitro data available 

• In vivo data available (animal) 

Inventors: Nigel H. Greig, Weiming 

Luo, David Tweedie, Harold W. 

Holloway, Qian-sheng Yu (all of NIA). 

Publication: Luo W, et al. Design, 

synthesis and biological assessment of 

novel N-substituted 3-(phthalimidin-2- 

yl)-2,6-dioxopiperidines and 3- 

substituted 2,6-dioxopiperidines for 

TNF-alpha inhibitory activity. Bioorg 

Med Chem. 2011 Jul 1;19(13):3965– 

3972. [PMID 21658960] 

Intellectual Property: HHS Reference 

No. E–045–2012/0—U.S. Patent 

Application No. 13/310,242 filed 02 Dec 

2011. 

Related Technologies: HHS Reference 

No. E–189–2003/0— 

• U.S. Patent No. 7,973,057 issued 05 

Jul 2011 

• U.S. Application No. 13/153,355 

filed 03 Jun 2011 

• and related international patents/ 

patent applications 

Licensing Contact: Whitney Hastings, 

Ph.D.; 301–451–7337; 

hastingw@mail.nih.gov. 

Use of Englerin A, a Small Molecule 

HSF1 Activator, for the Treatment of 

Diabetes, Obesity, and Other Diseases 

Associated With Insulin Resistance 

Description of Technology: Insulin 

resistance is a causative factor for type 


tkelley on DSK3SPTVN1PROD with NOTICES
18832 Federal Register / Vol. 77, No. 60 / Wednesday, March 28, 2012 / Notices 

2 diabetes, obesity and a number of 

other conditions. This technology 

claims methods for treating diseases or 

conditions associated with insulin 

resistance using the small molecule 

epoxy-guaiane derivative englerin A and 

related compounds. The compounds are 

claimed separately in a related NIH 

technology. 

The inventors have shown that 

englerin A, a compound originally 

isolated from the Phyllanthus plant and 

previously identified as an anti-cancer 

agent, can also be used to treat insulin 

resistance. Insulin resistance is 

associated with reduced gene 

expression and production of heat shock 

protein 70 (HSP70). Using a mouse with 

tumor model, the inventors discovered 

that administration of englerin A 

decreases blood glucose levels by 

activating transcription of HSF1, 

thereby increasing the expression and 

secretion of HSP70. Thus, englerin A 

and related compounds represent 

potential drugs for the treatment of a 

variety of conditions associated with 

insulin resistance. 

Potential Commercial Applications: 

Treatment of diseases or conditions 

associated with insulin resistance, such 

as type 2 diabetes, obesity, 

inflammation, metabolic syndrome, 

polycystic ovary disease, 

arteriosclerosis, non-alcoholic fatty liver 

disease, reproductive abnormality of a 

female, and growth abnormality. 

Competitive Advantages: Use of 

small-molecule compounds targeting 

HSF1 represents a novel approach to the 

treatment of type 2 diabetes and other 

conditions caused by insulin resistance. 

Development Stage: 

• In vitro data available 

• In vivo data available (animal) 

Inventors: Leonard Neckers et al. 

(NCI). 

Publication: Ratnayake R, et al. 

Englerin A, a selective inhibitor of renal 

cancer cell growth, from Phyllanthus 

engleri. Org Lett. 2009 Jan 1;11(1):57– 

60. [PMID 19061394] 

Intellectual Property: HHS Reference 

No. E–042–2012/0—U.S. Application 

No. 61/584,526 filed 09 Jan 2012. 

Related Technologies: HHS Reference 

No. E–064–2008/2—U.S. Application 

No. 12/811,245 filed 29 Jul 2010 and 

related international applications. 

Licensing Contact: Tara Kirby, Ph.D.; 

301–435–4426; tarak@mail.nih.gov. 

Collaborative Research Opportunity: 

The NCI Urologic Oncology Branch is 

seeking statements of capability or 

interest from parties interested in 

collaborative research to further 

develop, evaluate, or commercialize 

epoxyguaianes as anti-type 2 diabetes 

agents. For collaboration opportunities, 

please contact John Hewes, Ph.D. at 

hewesj@mail.nih.gov. 

A Novel, Non-invasive Test for the 

Detection of Chromaffin Cell Tumors 

Associated With SDHB Mutation 

Description of Technology: 

Pheochromocytomas/paragangliomas 

(PHEOs/PGLs) are hormone producing 

tumors of the sympathetic nervous 

system located in the adrenal glands 

(which sit atop the kidneys) or the 

paraganglia, which are distributed 

throughout the upper body. Mutations 

in the gene of a mitochondrial protein, 

succinate dehydrogenase B (SDHB), can 

cause PHEOs/PGLs that have a high rate 

of malignancy. Normally, PHEOs/PGLs 

can be diagnosed by measuring 

increased stress hormone metabolites in 

blood or urine. However, detection of 

SDHB-related PHEOs/PGLs can be 

difficult as up to ten percent do not 

show elevated stress hormone 

metabolites, and thus proper diagnosis 

requires expensive and often notwidely-available imaging. In addition, 

SDHB-PHEO/PGL patients need regular 

imaging to rule out development of 

metastases and family members of 

patients with SDHB-PHEOs/PGLs need 

genetic testing for risk evaluation. A 

significant need remains for additional 

diagnostic methods to prevent 

misdiagnosis of patients with nonsecreting or metastatic SDHB-PHEOs/ 

PGLs and risk evaluation of family 

members. 

Researchers at the Eunice Kennedy 

Shriver National Institute of Child 

Health and Human Development 

(NICHD) have developed methods to 

identify SDHB mutation based on the 

presence/absence of just four urinary 

peptides. Further data from the 

researchers suggests that metastatic 

PGLs can also be identified in patients 

based on their urinary peptide pattern. 

Potential Commercial Applications: 

Diagnostic kits for non-secreting or 

metastatic PHEOs/PGLs in patients, or 

for risk assessment of their family 

members. 

Competitive Advantages: 

• Cost-effective 

• Non-invasive 

• Sample collection could occur at 

home or doctor’s office 

Inventors: Karel Pacak (NICHD) et al. 

Intellectual Property: HHS Reference 

No. E–201–2011/0 — U.S. Provisional 

Application No. 61/498,428 filed 17 Jun 

2011. 

Licensing Contact: Patrick P. McCue, 

Ph.D.; 301–435–5560; 

mccuepat@mail.nih.gov. 

Collaborative Research Opportunity: 

The Eunice Kennedy Shriver National 

Institute of Child Health and Human 

Development is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate or 

commercialize a urine-based diagnostic 

to detect proteins associated with 

pheochromocytoma/paraganglioma 

(PHEO/PGL). For collaboration 

opportunities, please contact Joseph M. 

Conrad III, Ph.D., J.D. at 

jmconrad@mail.nih.gov. 

T Lymphocyte (T Cell) Clones That 

Recognize the Tumor Associated 

Antigens gp100 and MART–1 

Description of Technology: Scientists 

at the National Institutes of Health (NIH) 

have developed cytotoxic, CD8+ T 

lymphocyte (T cell) clones, designated 

R6C12 and JKF6, derived from tumor 

infiltrating lymphocytes (TIL) of cancer 

patients. The R6C12 clone recognizes 

the tumor associated antigen (TAA) 

gp100 and has been shown to be 

specific for amino acids 209–217 of the 

gp100 protein, known as the 210M or 

g209–2M peptide. The JKF6 clone 

recognizes the TAA MART–1, 

specifically the peptide represented by 

amino acids 27–35 of the MART–1 

protein. TIL are a subset of T cells found 

within tumors that have high specificity 

for the antigen(s) expressed by that 

tumor. 

MART–1 (also known as Melan-A) 

and gp100 are TAAs expressed 

primarily by melanomas and at low 

levels in normal melanocytes. MART–1 

is a melanocyte differentiation antigen 

found on the surface of these cells and 

gp100 is a transmembrane glycoprotein. 

Both proteins are located in the 

melanosomes of normal melanocytes, 

the melanin producing organelle of 

these cells. In cancer patients with 

gp100+ and or MART–1+ tumors, T 

cells, such as TIL, have been identified 

that recognize particular epitopes of 

these TAAs to mediate tumor cell 

killing. Cancer vaccines and adoptive T 

cell immunotherapies have been 

developed to generate immune 

responses to target one or both of these 

antigens for cancer regression. 

Potential Commercial Applications: 

• Characterize and develop T cell 

receptors for use in adoptive 

immunotherapy of MART–1+ and 

gp100+ cancers 

• Develop molecular screens to 

characterize tumor antigen expression of 

patient samples and/or laboratory cell 

lines 

• Develop research materials to better 

understand T cell functions, including 

antigen recognition, cell signaling, and 

immune responses 

• Positive controls for T cells with 

high reactivity to gp100 and MART–1 


tkelley on DSK3SPTVN1PROD with NOTICES
Federal Register / Vol. 77, No. 60 / Wednesday, March 28, 2012 / Notices 18833 

Competitive Advantages: 

• These T cell clones were isolated 

and selected from the bulk TIL cultures 

of the respective patients from which 

they were derived due to their superior 

reactivity to their TAA antigen. 

• Significant data has been collected 

on their characteristics, including 

identification of the tumor associated 

antigen and specific cancer peptide 

recognized by the T cell receptor of each 

clone. 

Development Stage: 

• Pre-clinical 

• Clinical 

• In vitro data available 

• In vivo data available (human) 

Inventors: Mark E. Dudley and Steven 

A. Rosenberg (both of NCI). 

Publications: 

1. Dudley M, et al. Cancer regression 

and autoimmunity in patients after 

clonal repopulation with antitumor 

lymphocytes. Science. 2002 Oct 

25;298(5594):850–854. [PMID 12242449] 

2. Dudley M, et al. Adoptive transfer 

of cloned melanoma-reactive T 

lymphocytes for the treatment of 

patients with metastatic melanoma. J 

Immunother. 2001 Jul–Aug;24(4):363– 

373. [PMID 11565838] 

Intellectual Property: HHS Reference 

No. E–267–2010/0—Research Tool. 

Patent protection is not being pursued 

for this technology. 

Related Technologies: 

• HHS Reference No. E–057–1994— 

elanoma Antigens and Their Use in 

Diagnostic and Therapeutic Methods 

• HHS Reference No. E–086–2001— 

Peptides of a Melanoma Antigen and 

Their Use in Diagnostic, Prophylactic, 

and Therapeutic Methods 

• HHS Reference No. E–106–2004— 

Compositions Comprising T cell 

Receptors and Methods of Use Thereof 

• HHS Reference No. E–304–2006— 

Modified T cell Receptors and Related 

Materials and Methods 

• HHS Reference No. E–059–2007— 

gp100-specific T cell Receptors and 

Related Materials and Methods 

• HHS Reference No. E–312–2007— 

Modified T cell Receptors and Related 

Materials and Methods 

• HHS Reference No. E–257–2008— 

Melanoma Associated Peptide 

Analogues and Vaccines Against 

Melanoma 

• HHS Reference No. E–261–2008— 

Melanoma Associated Antigenic 

Polypeptide, Epitopes Thereof and 

Vaccines Against Melanoma 

Licensing Contact: Samuel E. Bish, 

Ph.D.; 301–435–5282; 

bishse@mail.nih.gov. 

Dated: March 22, 2012. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2012–7420 Filed 3–27–12; 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. 

Personalized Body Weight Management 

System Using Monitoring Devices and 

Mathematical Models of Metabolism 

Description of Technology: Attempts 

to manage body weight are often 

unsuccessful or only temporary. This is, 

in part, due to antiquated dieting 

methods that attempt to address calorie 

consumption while ignoring metabolic 

and physical changes. It is becoming 

clear that personalized methods to 

manage body weight must be developed. 

Scientists at the NIH have developed 

new methods for prescribing and 

monitoring personalized weight 

management interventions. The system 

uses validated mathematical models of 

human metabolism to set weight 

management goals and predict 

individual body weight outcomes in the 

context of changing metabolic needs 

and calorie consumption. The system 

uses repeated monitoring of a patient’s 

body weight to assess progress and 

provide specific feedback to the patient 

and health care professional. Projected 

outcomes and body weight goals can be 

revised over time along with required 

prescription modifications to meet the 

body weight goals. The system is 

integrated into a network of one or more 

devices that may additionally monitor 

various physiological parameters, 

physical activities, food intake, or other 

behaviors. Such an enhanced 

personalized weight management 

program has great promise in the 

management of obesity. 

Potential Commercial Applications: 

• Devices—Weight management 

diagnostic. 

• Software for the integration of 

multiple devices. 

Competitive Advantages: Integrated 

system provides feedback to health care 

professional and patient with more 

accurate predictors of weight loss 

outcomes. Combined with other 

devices, patient receives encouragement 

to stay on track. 

Inventor: Kevin D. Hall (NIDDK). 

Publications: 

1. Hall KD, Sacks G, Chandramohan 

D, Chow CC, Wang YC, Gortmaker SL, 

Swinburn BA. Quantification of the 

effect of energy imbalance on 

bodyweight. Lancet. 2011 378 

(9793):826–837. [PMID 21872751] 

2. Hall KD and Chow CC. Estimating 

changes in free-living energy intake and 

its confidence interval. Am J Clin Nutr. 

2011 Jul;94(1):66–74. [PMID 21562087] 

3. Hall KD. Predicting metabolic 

adaptation, body weight change, and 

energy intake in humans. Am J Physiol 

Endocrinol Metab. 2010 

Mar;298(3):E449–466. [PMID 19934407] 

Intellectual Property: HHS Reference 

No. E–063–2012/0—U.S. Provisional 

Application No. 61/592,325 filed 30 Jan 

2012. 

Licensing Contact: Michael A. 

Shmilovich, Esq., CLP; 301–435–5019; 

shmilovm@mail.nih.gov. 

Collaborative Research Opportunity: 

The NIDDK Laboratory of Biological 

Modeling is seeking statements of 

capability or interest from parties 

interested in collaborative research to 

further develop, evaluate or 

commercialize this technology. For 

collaboration opportunities, please 

contact Marguerite J. Miller at 301–496– 

9003 or millermarg@niddk.nih.gov. 

Direct Impact Spark Ionization (DISI) 

Mass Spectrometry (MS) for 

Identification of Microbes 

Description of Technology: Generating 

reproducible mass spectra from bacterial 

samples in a timely fashion at 

atmospheric pressure remained 

problematic for many years. FDA/NCTR 


tkelley on DSK3SPTVN1PROD with NOTICES