10378 Federal Register / Vol. 76, No. 37 / Thursday, February 24, 2011 / Notices 

associated with current prostate cancer 

therapies 

Development Status: Preclinical stage 

of development. 

Inventors: Pastan (NCI) et al. 

Patent Status: 

• US Patent 7,816,087 (E–005–2002/ 

0–US–03)—Issued 

• US Patent Application 12/193,604 

(E–005–2002/0–US–05)—Allowed 

• EP Patent Application 02795643.2 

(E–005–2002/0–EP–04)—Pending 

For more information, see: 

• Das et al. ‘‘Topology of NGEP, a 

prostate-specific cell:cell junction 

protein widely expressed in many 

cancers of different grade level.’’ Cancer 

Res. 2008 Aug 1; 68(15):6306–12 

• Das et al. ‘‘NGEP, a prostate-specific 

plasma membrane protein that promotes 

the association of LNCaP cells.’’ Cancer 

Res. 2007 Feb 15; 67(4):1594–601 

• Bera et al. ‘‘NGEP, a gene encoding 

a membrane protein detected only in 

prostate cancer and normal prostate.’’ 

Proc Natl Acad Sci U S A. 2004 Mar 2; 

101(9):3059–64. 

Licensing Status: Available for 

licensing 

Licensing Contact: David A. 

Lambertson, PhD; 301–435–4632; 

lambertsond@mail.nih.gov. 

Stem Cells That Transform To Beating 

Cardiomyocytes 

Description of Technology: Many 

people die each year of congestive heart 

failure occurring from a variety of 

causes including cardiomyopathy, 

myocardial ischemia, congenital heart 

disease and valvular heart disease 

resulting in cardiac cell death and 

myocardial dysfunction. When 

cardiomyocytes are not replaced in 

adult myocardial tissue, physiologic 

demands on existing, healthy 

cardiomyocytes can lead to 

hypertrophy. Heart transplants have 

been the only recourse for patients in 

end-stage heart disease however this is 

complicated by lack of donors, tissue 

incompatibility and high cost. 

An alternative approach to heart 

transplantation is to generate 

cardiomyocytes from stem cells in vitro 

that can be used in the treatment of 

cardiac diseases characterized by 

myocardial cell death or dysfunction. 

This invention discloses a novel 

isolated population of stem cells, called 

spoc cells, isolated from skeletal 

muscle, that can be induced, either in 

vivo or in vitro, to differentiate into 

cardiomyocytes. Spoc cells may be 

differentiated and utilized for screening 

agents that affect cardiomyocytes and as 

therapeutic agents in the treatment of 

cardiac MI. 

Potential Applications and 

Advantages: This invention is an 

alternative approach to heart 

transplantation which is typically 

complicated by lack of donors, tissue 

incompatibility and high cost. 

Inventors: Neal D. Epstein (NHLBI), et 

al. 

Related Publication: SO Winitsky, et 

al. Adult murine skeletal muscle 

contains cells that can differentiate into 

beating cardiomyocytes in vitro. PLoS 

Biol. 2005 Apr;3(4):e87, doi:10.1371/ 

journal.pbio.0030087. [PubMed: 

15757365] 

Patent Status: 

• Issued Australian Patent No. 

2002337949 (HHS Ref. No. E–329–2001/ 

0–AU–03) 

• Issued Japanese Patent No. 4377690 

(HHS Ref. No. E–329–2001/0–JP–04) 

• Allowed Canadian Patent Appl. No. 

2464088 (HHS Ref. No. E–329–2001/0– 

CA–05) 

Licensing Status: Available for 

licensing. 

Licensing Contact: Fatima Sayyid, 

M.H.P.M.; 301–435–4521; 

Fatima.Sayyid@nih.hhs.gov. 

Dated: February 16, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–4170 Filed 2–23–11; 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. 

Recombinant BoCPB: An Enzymatic 

Reagent for Removing Disordered, 

Positively Charged C-terminal Residues 

From Recombinant Proteins 

Description of Technology: Affinity 

tags are commonly used to facilitate the 

purification of recombinant proteins, 

but concerns about the potential impact 

of the tags on the biological activity of 

the target proteins makes it necessary to 

remove them in most cases. Proteases 

with high sequence specificity, such as 

tobacco etch virus (TEV) protease, are 

typically used for this purpose. Affinity 

tags on the amino-terminus (N-terminal 

tag) can be cleaved by TEV protease to 

yield a recombinant protein product 

with only one nonnative residues on its 

C-terminus (usually G or S). In contrast, 

removal by TEV protease of tags added 

to the carboxy-terminus (C-terminal tag) 

of proteins has proven to be somewhat 

problematic, yielding a recombinant 

protein product with six nonnative 

residues on its C-terminus (ENLYFQ). 

Since C-terminal affinity tags are 

potentially very useful, particularly 

when used in combination with Nterminal tags in an ‘‘affinity sandwich’’ 

format, it would be very desirable to 

have a reagent to remove the C-terminal 

affinity tags without leaving extra 

nonnative residues behind. 

Previously, the NIH inventors created 

a tagged version of a fungal 

carboxypeptidase from Metarhizium 

anisopliae (MeCPA) that is capable of 

removing histidine residues and many 

other types of amino acids from the Ctermini of recombinant proteins. The 

only limitation of the MeCPA enzyme is 

that it does not remove positively 

charged residues (arginine and lysine). 

To overcome this drawback of MeCPA, 

the NIH inventors have now cloned, 

expressed and purified bovine 

carboxypeptidase B (BoCPB), which is 

specific for the removal of these 

positively charged residues. Like the 

genetically engineered MeCPA, the 

recombinant BoCPB has a C-terminal 

polyhistidine tag. This feature facilitates 

the purification of the enzyme, and, 

because this His-tag as been engineered 

to be immune to the action of MeCPA 

and BoCPB, it can be used to separate 

the enzymes from the products of a 

carboxypeptidase digest. By using a 

mixture of MeCPA and BoCPB, it should 

be possible to remove any short affinity 

tag along with disordered C-terminal 

residues of a recombinant protein with 

the exception of proline, which can be 

used as a ‘‘stop sign’’ to facilitate the 


emcdonald on DSK2BSOYB1PROD with NOTICES
Federal Register / Vol. 76, No. 37 / Thursday, February 24, 2011 / Notices 10379 

production of a digestion product with 

a homogeneous C-terminus. 

Applications 

• Removal short C-terminal affinity 

tags from recombinant proteins without 

leaving any nonnative residues behind 

when used in combination with 

MeCPA. 

• Identification and removal of 

disordered residues from the C-termini 

of native (untagged) proteins, thereby 

increasing their propensity to 

crystallize. 

Inventors: David Waugh et al. (NCI) 

Related Publications: None. 

Patent Status: HHS Reference No. E– 

027–2011/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute, Protein 

Engineering Section, is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate, or 

commercialize recombinant BoCPB and/ 

or similar enzymes. Please contact John 

Hewes, PhD at 301–435–3121 or 

hewesj@mail.nih.gov for more 

information. 

A DsbC Expression Vector for the 

Production of Proteins With Disulfide 

Bonds in the Cytosol of E. coli 

Description of Technology: Many 

proteins of biomedical importance 

contain disulfide bonds and such 

proteins are notoriously difficult to 

produce in Escherichia coli. Current 

methods to address this problem either 

export the protein to the periplasmic 

space, which is a more favorable redox 

environment for disulfide bond 

formation, or utilize genetically 

modified strains of E. coli to alter the 

redox potential of the cytosol (such as 

‘‘Origami’’ or ‘‘Shuffle’’ cells). 

Unfortunately, these methods generally 

result in very low yields of the desired 

product, thus emphasizing the need for 

a novel method. 

The NIH inventors have designed a 

DsbC expression vector that can be used 

to improve the yield of correctly 

oxidized recombinant proteins in the 

cytosol of E. coli. By overproducing 

DsbC on a separate plasmid and 

coexpressing it with carboxypeptidases 

in the cytosol of E. coli, the inventors 

were able to increase the amount of 

properly oxidized, active 

carboxypeptidases that could be 

recovered from the cytosol by at least 4- 

fold. Further, they believe that coexpression of DsbC from a multicopy 

plasmid vector will also improve the 

yield of other disulfide bond-containing 

proteins in E. coli. 

Applications: Improving the yield of 

correctly oxidized recombinant proteins 

in the cytosol of E. coli. 

Advantages: Substantial increase in 

the amount of active carboxypeptidases 

recovered from the cytosol and 

improved yield of disulfide bondcontaining proteins in E. coli. 

Inventors: David Waugh et al. (NCI) 

Related Publications 

1. Prinz WA, Aslund F, Holmgren A, 

Beckwith J. The role of the thioredoxin 

and glutaredoxin pathways in reducing 

protein disulfide bonds in the 

Escherichia coli cytoplasm. J Biol Chem. 

1997 Jun 20;272(25):15661–15667. 

[PubMed: 9188456] 

2. Levy R, Weiss R, Chen G, Iverson 

BL, Georgiou G. Production of correctly 

folded Fab antibody fragment in the 

cytoplasm of Escherichia coli trxB gor 

mutants via the coexpression of 

molecular chaperones. Protein Expr 

Purif. 2001 Nov;23(2):338–347. 

[PubMed: 11676610] 

Patent Status: HHS Reference No. E– 

028–2011/0—Research Tool. Patent 

protection is not being pursued for this 

technology. 

Licensing Status: Available for 

licensing. 

Licensing Contact: Whitney Hastings; 

301–451–7337; hastingw@mail.nih.gov. 

Dated: February 16, 2011. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2011–4168 Filed 2–23–11; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Laboratory Animal Welfare: Proposed 

Adoption and Implementation of the 

Eighth Edition of the Guide for the 

Care and Use of Laboratory Animals 

AGENCY: National Institutes of Health, 

HHS. 

ACTION: Notice. 

SUMMARY: The National Institutes of 

Health (NIH) requests public comments 

on (1) NIH’s adoption of the eighth 

edition of the Guide for the Care and 

Use of Laboratory Animals (Guide) as a 

basis for evaluation of institutional 

programs receiving or proposing to 

receive Public Health Service (PHS) 

support for activities involving animals; 

and (2) if NIH decides to adopt the 

eighth edition of the Guide, NIH’s 

proposed implementation plan, which 

would require that institutions complete 

at least one semiannual program and 

facility evaluation using the eighth 

edition of the Guide as the basis for 

evaluation by March 31, 2012. NIH will 

consider comments on (1) the adoption 

of the Guide and (2) the implementation 

plan. 

DATES: Written comments on the 

adoption and implementation of the 

eighth edition of the Guide must be 

received by NIH within 30 days of the 

date of publication of this notice in 

order to be considered. 

ADDRESSES: Public comments may be 

entered at 

http://grants.nih.gov/grants/olaw/ 

2011guidecomments/add.htm. 

Comments will be made publicly 

available. Personally identifiable 

information (except organizational 

affiliations) will be removed prior to 

making comments publicly available. 

FOR FURTHER INFORMATION CONTACT: 

Office of Laboratory Animal Welfare, 

Office of Extramural Research, National 

Institutes of Health, RKL1, Suite 360, 

6705 Rockledge Drive, Bethesda, MD 

20892–7982; telephone 301–496–7163. 

SUPPLEMENTARY INFORMATION: 

I. Background 

The Guide, first published in 1963, is 

a widely accepted primary reference on 

animal care and use. Recommendations 

in the Guide are based on published 

data, scientific principles, expert 

opinion, and experience with methods 

and practices that are determined to be 

consistent with high quality, humane 

animal care and use. The eighth edition 

of the Guide was published in January 

2011 following a study by the Institute 

for Laboratory Animal Research of the 

National Academy of Sciences (NAS). 

The NAS study process began in 2008 

and followed the requirements of 

Section 15 of the Federal Advisory 

Committee Act. The NAS study process 

is described at the NAS Web site: http:// 

www.nationalacademies.org/ 

studyprocess/index.html. 

Since 1985, the PHS Policy on 

Humane Care and Use of Laboratory 

Animals, authorized by Public Law 99– 

158, 42 U.S.C. 289d, and incorporated 

by reference at 42 CFR 52.8 and 42 CFR 

52a.8, has required that institutions 

receiving PHS support for animal 

activities base their animal care and use 

programs on the current edition of the 

Guide and comply, as applicable, with 

the Animal Welfare Act and other 

Federal statutes and regulations relating 


emcdonald on DSK2BSOYB1PROD with NOTICES