8264 Federal Register / Vol. 77, No. 30 / Tuesday, February 14, 2012 / Notices 

using the immunotoxins for the 

treatment of mesothelin-expressing 

cancers (such as mesothelioma, ovarian 

cancer and pancreatic cancer). The 

specific immunotoxin will have an 

antibody targeting domain that contains 

the CDRs of the antibody identified as 

SS1, which was invented at the NIH. 

The specific immunotoxin will also 

have a toxin domain derived from PE 

that is resistant to lysosomal proteases 

due to the deletion of a large portion of 

the exotoxin, and which lacks at least 

one major B-cell epitope due to the 

alteration an amino acid. Ultimately, the 

PE used in the immunotoxin may lack 

multiple B-cell epitopes, as well as 

multiple T-cell epitopes, in an effort to 

minimize immunogenicity. 

Alterations to the toxin that reduce 

immunogenicity improve the 

therapeutic value of the immunotoxin 

while maintaining its ability to trigger 

cell death. Since mesothelin is 

preferentially expressed on certain types 

of cancer cells, the immunotoxins 

selectively bind and kill only those 

cancer cells, allowing healthy, essential 

cells to remain unharmed. This results 

in an effective therapeutic strategy with 

fewer side effects. 

The prospective exclusive license will 

be royalty bearing and will comply with 

the terms and conditions of 35 U.S.C. 

209 and 37 CFR Part 404.7. The 

prospective exclusive license may be 

granted unless the NIH receives written 

evidence and argument that establishes 

that the grant of the license would not 

be consistent with the requirements of 

35 U.S.C. 209 and 37 CFR Part 404.7 

within thirty (30) days from the date of 

this published notice. 

Applications for a license in the field 

of use filed in response to this notice 

will be treated as objections to the grant 

of the contemplated exclusive license. 

Comments and objections submitted to 

this notice will not be made available 

for public inspection and, to the extent 

permitted by law, will not be released 

under the Freedom of Information Act, 

5 U.S.C. 552. 

Dated: February 8, 2012. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

& Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2012–3410 Filed 2–13–12; 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. 

Encapsulated N–Acetylmannosamine or 

N–Acetylneuraminic Acid as a 

Therapeutic Agent for Increasing 

Sialylation in Certain Muscular 

Atrophies, Kidney Disorders, Cancers 

or Poor Immune Function 

Description of Technology: Nacetylmannosamine is a precursor for 

the synthesis of sugar molecules known 

as sialic acids, which play an important 

role in specific biological processes 

such as cellular adhesion, cellular 

communication and signal transduction. 

Lack of sialic acids also plays a crucial 

role in disease processes such as 

inflammation, immune responses, as 

well as certain muscular atrophies 

(including hereditary inclusion body 

myopathy (HIBM) and distal myopathy 

with rimmed vacuoles (DMRV or 

Nonaka myopathy)), certain kidney 

disorders with proteinuria and 

hematuria (including minimal change 

nephrosis and focal segmental 

glomerulosclerosis), and certain cancers 

(including bladder cancer and myeloid 

leukemia). 

This technology relates to methods of 

administering liposome-encapsulated Nacetylmannosamine, Nacetylneuraminic acid, or their 

derivatives to treat human disorders of 

hyposialylation (by increasing sialic 

acid production in patients who are 

deficient in that sugar molecule). 

Liposome-encapsulated delivery of 

these monosaccharides enhances 

successful systemic delivery, including 

to the central nervous system (crossing 

the blood-brain barrier), and liposome 

encapsulation protects against 

gastrointestinal tract degradation. 

Potential Commercial Applications: 

• Treatment of rare diseases such as 

HIBM and Nonaka myopathy (or 

DMRV). 

• Treatment of kidney conditions 

involving sialic acid deficiencies, 

resulting in proteinuria and hematuria. 

• Treatment of other diseases 

involving sialic acid deficiencies. 

• Use as immune stimulant since 

adequate sialic acid is important for 

robust immune function. 

Competitive Advantages: 

• N-acetylmannosamine is the only 

uncharged sugar in the sialic acid 

biosynthesis pathway (thus making it 

easier to deliver than charged sugars) 

and is located after the rate-limiting 

step. 

• N-acetyl mannosamine and Nacetylneuraminic acid have been shown 

to rescue hyposialylation in mouse 

models of HIBM. 

• Encapsulated Nacetylmannosamine or Nacetylneuraminic acid crosses the 

blood-brain barrier and prevents 

gastrointestinal tract degradation more 

efficiently than unencapsulated drug. 

Development Stage: 

• Pre-clinical 

• In vitro data available 

• In vivo data available (animal) 

Inventors: Marjan Huizing et al. 

(NHGRI). 

Publications: 

1. Galeano B, et al. Mutation in the 

key enzyme of sialic acid biosynthesis 

causes severe glomerular proteinuria 

and is rescued by Nacetylmannosamine. J Clin Invest. 2007 

Jun;117(6):1585–1594. [PMID 17549255] 

2. Nemunaitis G, et al. Hereditary 

inclusion body myopathy: single patient 

response to intravenous dosing of GNE 

gene lipoplex. Hum Gene Ther. 2011 

Nov;22(11):1331–1341. [PMID 

21517694] 

3. Kakani S, et al. The Gne M712T 

mouse as a model for human 

glomerulopathy. Am J Pathol., in press 

(Dec 2011) (available online in Feb 

2012) 

Intellectual Property: HHS Reference 

No. E–270–2011/0 — U.S. Application 

No. 61/531,934 filed 07 Sep 2011. 

Licensing Contact: Tara L. Kirby, 

Ph.D.; 301–435–4426; 

tarak@mail.nih.gov. 

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Federal Register / Vol. 77, No. 30 / Tuesday, February 14, 2012 / Notices 8265 

Chimeric Antigen Receptors to CD22 for 

Treating Hematological Cancers 

Description of Technology: Chimeric 

antigen receptors (CARs) are hybrid 

proteins consisting of an antibody 

binding fragment fused to protein 

signaling domains that cause some Tcells to become cytotoxic. Once 

activated, these cytotoxic T-cells can 

selectively eliminate the cells which 

they recognize. Thus, by engineering a 

T-cell to express a CAR that is specific 

for a certain cell surface protein, it is 

possible to selectively target cells for 

destruction. This is a promising new 

therapeutic approach known as 

adoptive cell therapy. 

CD22 is a cell surface protein that is 

expressed on a large number of B-cell 

lineage hematological cancers. Several 

promising therapies are being developed 

which target CD22, including 

therapeutic antibodies and 

immunotoxins. This technology 

concerns the use of a high affinity 

antibody binding fragment to CD22 as 

the targeting moiety of a CAR, adding 

adoptive cell therapy as a new 

prospective treatment for certain 

leukemias and lymphomas. 

Potential Commercial Applications: 

• Treatment of diseases associated with 

increased or preferential expression of 

CD22 

• Specific diseases include 

hematological cancers such as chronic 

lymphocytic leukemia, hairy cell 

leukemia and pediatric acute 

lymphoblastic leukemia 

Competitive Advantages: 

• Targeted therapy decreases nonspecific killing of healthy, essential 

cells, resulting in fewer non-specific 

side-effects and healthier patients 

• Hematological cancers are susceptible 

to cytotoxic T-cells for treating 

because they are present in the 

bloodstream 

• Expression of CD22 only on mature 

cells allows the avoidance of stem cell 

elimination during treatment 

• High affinity of the antibody binding 

fragment for CD22 increases the 

likelihood of successful targeting 

Development Stage: 

• Pre-clinical 

• In vitro data available 

• In vivo data available (animal) 

Inventors: Rimas J. Orentas et al. 

(NCI). 

Intellectual Property: HHS Reference 

No. E–265–2011/0–US–01—US 

provisional application 61/549,516. 

Related Technology: HHS Reference 

No. E–129–2001/0–US–03—US Patent 

7,355,012. 

Licensing Contact: David A. 

Lambertson, Ph.D.; 301–435–4632; 

lambertsond@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Cancer Institute is seeking 

statements of capability or interest from 

parties interested in collaborative 

research to further develop, evaluate or 

commercialize Chimeric Antigen 

Receptor for CD22, High Affinity. A 

gene vector to target T cells to B cell 

leukemia and lymphoma. For 

collaboration opportunities, please 

contact John Hewes, Ph.D. at 

hewesj@mail.nih.gov. 

Increased Therapeutic Effectiveness of 

Immunotoxins That Use Toxin Domains 

Lacking Both T-Cell and B-Cell 

Epitopes 

Description of Technology: 

Immunotoxins can kill cancer cells 

while allowing healthy, essential cells 

to survive. As a result, patients 

receiving an immunotoxin are less 

likely to experience the deleterious sideeffects associated with non-discriminate 

therapies such as chemotherapy or 

radiation therapy. Unfortunately, the 

continued administration of 

immunotoxins often leads to a reduced 

patient response due to the formation of 

neutralizing antibodies against 

immunogenic B-cell and T-cell epitopes 

contained within PE. To improve the 

therapeutic effectiveness of PEcontaining immunotoxins through 

multiple rounds of drug administration, 

NIH inventors have sought to remove 

the B-cell and T-cell epitopes within PE. 

Previous work demonstrated that the 

removal of the major B-cell epitopes 

from PE reduced the immunogenicity of 

PE. This technology involves the 

identification of major T-cell epitopes 

on PE, and the removal of the primary 

T-cell epitope by mutation or deletion. 

By combining the T-cell epitope 

mutations with modifications that 

remove B-cell epitopes, it is possible to 

create PE-based immunotoxins that have 

even greater resistance to the formation 

of neutralizing antibodies. 

Immunotoxins containing these new PEvariants are expected to have improved 

therapeutic efficacy. 

Potential Commercial Applications: 

• Essential component of 

immunotoxins 

• Treatment of any disease associated 

with increased or preferential 

expression a specific cell surface 

receptor 

• Specific diseases include 

hematological cancers, lung cancer, 

ovarian cancer, breast cancer, and 

head and neck cancers 

Competitive Advantages: 

• PE variants now include the 

removal of both B-cell and T-cell 

epitopes, further reducing the formation 

of neutralizing antibodies against 

immunotoxins which contain the PE 

variants. 

• Less immunogenic immunotoxins 

result in improved therapeutic efficacy 

by permitting multiple rounds of 

administration. 

• Targeted therapy decreases nonspecific killing of healthy, essential 

cells, resulting in fewer non-specific 

side-effects and healthier patients. 

Development Stage: Pre-clinical. 

Inventors: Ira H. Pastan et al. (NCI). 

Patent Status: 

• HHS Reference No. E–174–2011/0– 

US–01 — U.S. Provisional 

Application 61/495,085. 

Related Technologies: 

• HHS Reference No. E–269–2009/0– 

PCT–02 — PCT Patent Publication 

WO 2011/032022 

• HHS Reference No. E–292–2007/0– 

US–06 — US Patent Publication US 

20100215656 A1 

• HHS Reference No. E–262–2005/0– 

US–06 — US Patent Publication US 

20090142341 A1 

• HHS Reference No. E–139–1999/0– 

US–07 — US Patent 7,081,518 

• Multiple additional patent families 

Licensing Contact: David A. 

Lambertson, Ph.D.; 301–435–4632; 

lambertsond@mail.nih.gov. 

Ketamine Metabolites for the Treatment 

of Depression and Pain 

Description of Technology: The 

market continues to have a need for 

therapeutics for treating pain and 

depression that have efficacy in a high 

percentage of patients but have reduced 

anaesthetic properties and reduced 

abuse liability. Ketamine, a drug 

currently used in human anesthesia and 

veterinary medicine, has been shown in 

clinical studies to be effective in the 

treatment of several conditions, 

including the of treatment-resistant 

bipolar depression, major depressive 

disorder, neuropathic pain, and chronic 

pain, including complex regional pain 

syndrome (CRPS). However the routine 

use of the drug is hindered by unwanted 

central nervous system (CNS) effects 

and a patient response rate of ∼70%. 

New data suggests that ketamine 

metabolites can be used with similar 

results but with an increase in patient 

response rates and a decrease in 

undesirable side effects. 

Potential Commercial Applications: 

Treatment of pain and depression. 

Competitive Advantages: 

• Increased number of patients able to 

respond to the treatment because it 

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8266 Federal Register / Vol. 77, No. 30 / Tuesday, February 14, 2012 / Notices 

bypasses the human metabolic 

machinery needed to convert the drug 

into its active metabolite(s). 

• Decreased CNS side effects. 

Development Stage: In vivo data 

available (animal). 

Inventors: Irving W. Wainer, Ph.D. 

(NIA), Carlos A. Zarate, M.D. (NIMH), 

Ruin Moaddel, Ph.D. (NIA), Michel 

Bernier (NIA), Michael E. Goldberg, 

M.D., Marc C. Toriman, Ph.D. 

Publications: 

1. Moaddel R, et al. A parallel chiralachiral liquid chromatographic 

method for the determination of the 

stereoisomers of ketamine and 

ketamine metabolites in the plasma 

and urine of patients with complex 

regional pain syndrome. Talanta. 

2010 Oct. 15;82(5):1892–1904. 

[PMID 20875593] 

2. Zarate CA Jr., et al. Relationship of 

Ketamine’s Plasma Metabolites with 

Response and Diagnosis, and Side 

Effects in Major Depression. 

Manuscript in preparation. 

3. Ibrahim L, et al. Course of 

Improvement in Depressive 

Symptoms to a Single Intravenous 

Infusion of Ketamine vs. Add-on 

Riluzole: Results from a Four-Week, 

Double-Blind, Placebo-Controlled 

Study. Neuropsychopharmacology, 

in press. 

4. Zhao X, et al. Population 

Pharmacokinetic Modeling of 

Ketamine and Three Major 

Metabolites in Patients with 

Treatment-Resistant Bipolar 

Depression. Br. J. Clin. Phamaco., in 

press. 

Intellectual Property: HHS Reference 

No. E–092–2011/0—U.S. Provisional 

Application No. 61/547,336 filed 14 

Oct. 2011. 

Related Technologies: HHS Reference 

No. E–174–2006/0— 

• U.S. Patent Application No. 11/ 

688,603 filed 20 Mar. 2007 

• Related international applications 

Licensing Contact: Jaime M. Greene, 

M.S.; 301–435–5559; 

greenejaime@mail.nih.gov. 

Collaborative Research Opportunity: 

The National Institute on Aging, 

Laboratory of Clinical Investigation, 

Bioanalytical Chemistry and Drug 

Discovery Section, 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 Nicole Guyton, Ph.D. at 

darackn@mail.nih.gov. 

Improved DNA-Protein Vaccination 

Protocols 

Description of Technology: Nucleic 

acid based vaccines are attractive 

alternatives to conventional vaccines for 

a number of reasons. One of the issues 

with nucleic acid based vaccines is the 

poor immunogenicity in humans. The 

subject technology is a method for 

eliciting improved immune responses 

with DNA based vaccines. The method 

involves co-administration of a nucleic 

acid vaccine with a protein vaccine for 

the same antigen of interest that is 

encoded by the DNA vaccine in a primeboost protocol. This methodology 

increased the immune responses in a 

SIV macaque model to examine DNA 

based vaccines of HIV and vaccine 

protocols. The methodology can 

potentially be applied to other disease 

indications to elicit greater immune 

responses. 

Potential Commercial Applications: 

Improve immunogenicity of nucleic 

acid based vaccines. 

Competitive Advantages: The 

methodology increases the immune 

response of DNA based vaccines. 

Development Stage: 

• Early-stage 

• Pre-clinical 

• In vitro data available 

• In vivo data available (animal) 

Intellectual Property: HHS Reference 

No. E–239–2009/0—International PCT 

Application No. PCT/US2011/026325 

filed 25 Feb. 2011. 

Licensing Contact: Kevin W. Chang, 

Ph.D.; 301–435–5018; 

changke@mail.nih.gov. 

Dated: February 8, 2012. 

Richard U. Rodriguez, 

Director, Division of Technology Development 

and Transfer, Office of Technology Transfer, 

National Institutes of Health. 

[FR Doc. 2012–3412 Filed 2–13–12; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

National Eye Institute; Notice of Closed 

Meeting 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App), notice is 

hereby given of the following meeting. 

The meeting will be closed to the 

public in accordance with the 

provisions set forth in section 

552b(c)(6), Title 5 U.S.C., as amended, 

for the review, discussion, and 

evaluation of individual intramural 

programs and projects conducted by the 

National Eye Institute, including 

consideration of personnel 

qualifications and performances, and 

the competence of individual 

investigators, the disclosure of which 

would constitute a clearly unwarranted 

invasion of personal privacy. 

Name of Committee: Board of Scientific 

Counselors, National Eye Institute. 

Date: March 4–5, 2012. 

Time: 7:00 PM to 5:00 PM. 

Agenda: To review and evaluate personal 

qualifications and performance, and 

competence of individual investigators. 

Place: National Institutes of Health, 

Building 31, 31 Center Drive, Bethesda, MD 

20892. 

Contact Person: Sheldon S. Miller, Ph.D., 

Scientific Director, National Institutes of 

Health, National Eye Institute, Bethesda, MD 

20892, (301) 451–6763. 

In the interest of security, NIH has 

instituted stringent procedures for entrance 

onto the NIH campus. All visitor vehicles, 

including taxicabs, hotel, and airport shuttles 

will be inspected before being allowed on 

campus. Visitors will be asked to show one 

form of identification (for example, a 

government-issued photo ID, driver’s license, 

or passport) and to state the purpose of their 

visit. 

Information is also available on the 

Institute’s/Center’s home page: 

www.nei.nih.gov, where an agenda and any 

additional information will be posted when 

available. 

(Catalogue of Federal Domestic Assistance 

Program Nos. 93.867, Vision Research, 

National Institutes of Health, HHS) 

Dated: February 8, 2012. 

Jennifer S. Spaeth, 

Director, Office of Federal Advisory 

Committee Policy. 

[FR Doc. 2012–3432 Filed 2–13–12; 8:45 am] 

BILLING CODE 4140–01–P 

DEPARTMENT OF HEALTH AND 

HUMAN SERVICES 

National Institutes of Health 

Center for Scientific Review; Notice of 

Closed Meetings 

Pursuant to section 10(d) of the 

Federal Advisory Committee Act, as 

amended (5 U.S.C. App.), notice is 

hereby given of the following meetings. 

The meetings will be closed to the 

public in accordance with the 

provisions set forth in sections 

552b(c)(4) and 552b(c)(6), Title 5 U.S.C., 

as amended. The grant applications and 

the discussions could disclose 

confidential trade secrets or commercial 

property such as patentable material, 

and personal information concerning 

individuals associated with the grant 

applications, the disclosure of which 

mstockstill on DSK4VPTVN1PROD with NOTICES