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###### Department of Health and Human Services

###### National Institutes of Health

# 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.

## Erythroid Progenitor Cell Line for Hematological Disease Applications

*Description of Invention: Plasmodium vivax*                     (malaria) is a significant health concern in many parts of Asia, Latin America, North Africa, and the Middle East. There is a lack of continuous culture systems for this pathogen. The subject technology is an erythroid progenitor continuous cell line (termed CD36E) identified by erythroid markers CD36, CD33, CD44, CD71, CD235, and globoside. These CD36E cells are heterozygous for Fya and Fyb (Duffy antigen). Due to recent evidence that                     *Plasmodium vivax*                     (                    *P. vivax*) can infect erythroid progenitor cells (reference: YX Ru                     *et al.*                     and T Panichakul                     *et al.*), these cells can be potentially used for culturing                     *P. vivax*                     and other species of malaria. This in turn could aid development of malaria related treatments and/or products. In addition, the cell line can also be used for other hematological disease applications that involve red blood cells or red blood cell precursors. The CD36E cells also produce alpha, beta, and chi hemoglobin and therefore may be used for research involving hemoglobin.                

*Applications:*
      - Culture system for Plasmodium                      species (malaria)                
      - Hematological diseases

*Advantages:*                     Immortalized erythroid progenitor cell line.                

*Development Status: In vitro*                     data can be provided upon request.                

Market:
      - Malaria
      - Anti-malaria drug screening
      - Hematological diseases
      - Hemoglobin

*Inventors:*                     Susan Wong, Neal S. Young, Ning Zhi (NHLBI).                

*Relevant Publications:*

                    1. YX Ru                     *et al.*                     Invasion of erythroblasts by Pasmodium vivax: A new mechanism contributing to malarial anemia. Ultrastruct Pathol. 2009 Oct;33(5):236–242. [PubMed: 19895296].                

                    2. T Panichakul                     *et al.*                     Production of erythropoietic cells in vitro for continuous culture of Plasmodium vivax. Int J Parasitol. 2007 Dec;37(14):1551–1557. [PubMed: 17610880].                

*Patent Status:*                     HHS Reference No. E–151–2010/0—Research Tool. Patent protection is not being pursued for this technology.                

*Licensing Status:*                     Available for biological materials licensing.                

*Licensing Contact:*                     Kevin W. Chang, Ph.D.; 301–435–5018;                     *changke@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Heart Lung and Blood Institute, Hematology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the CD36E cell line. Please contact Cecilia Pazman, Ph.D., at                     *pazmance@mail.nih.gov*                     for more information.                

## Parvovirus B19 Codon Optimized Structural Proteins for Vaccine and Diagnostic Applications

*Description of Invention:*                     Parvovirus B19 (B19V) is the only known pathogenic human parvovirus. Infection by this viral pathogen can cause transient aplastic crisis in individuals with high red cell turnover, pure red cell aplasia in immunosuppressed patients, and hydrops fetalis during                           ( print page 26259)                        pregnancy. In children, B19V most commonly causes erythema infectiosum, or fifth's disease. Infection can also cause arthropathy and arthralgia. The virus is very erythrotropic, targeting human erythroid (red blood) progenitors found in the blood, bone marrow, and fetal liver. Currently, there are no approved vaccines or antiviral drugs for the treatment or prevention of B19V infection.                

The subject technology is a series of plasmid constructs with codon optimized B19 viral capsid genes (VP1 and VP2) that can be expressed in mammalian cells. Transfection of vectors encoding these optimized VP1 and VP2 genes into different mammalian cell lines, including 293, Cos7, and Hela cells produce virus-like particles (VLPs). The vectors include bicistronic plasmids expressing the VP1 and VP2 proteins at different ratios to produce B19V VLPs with optimal antigenicity for vaccine applications. This technology can also be used for diagnostic applications and development of a viral packaging system for producing infectious B19V virus.

*Applications:*
      - VLPs based vaccines for the prevention and/or treatment of B19V infection
      - DNA based vaccines for the prevention and/or treatment of B19V infection
      - B19V diagnostics
      - Viral packaging system

Advantages:
      - Codon optimized VP1 and VP2 genes for better expression in mammalian cell lines
      - Expression of B19V VLPs from “nonpermissive” cell lines

*Development Status: In vitro*                     data can be provided upon request.                

Market:
      - B19V vaccines (VLPs and DNA)
      - B19V diagnostics

*Inventors:*                     Ning Zhi, Sachiko Kajigaya, and Neal S. Young (NHLBI).                

*Patent Status:*                     U.S. Provisional Application No. 61/337,983 filed 12 Feb 2010 (HHS Reference No. E–011–2010/0–US–01).                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Kevin W. Chang, Ph.D.; 301–435–5018;                     *changke@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The National Heart Lung and Blood Institute, Hematology Branch, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the subject technology. Please contact Cecilia Pazman, Ph.D., at                     *pazmance@mail.nih.gov*                     for more information.                

## Optimized Expression of IL–12 Cytokine Family

*Description of Invention:*                     The IL–12 family of cytokines (IL–12, IL–23, and IL–27) has an important role in inflammation and autoimmune diseases. IL–12 is produced by macrophages and dendritic cells in response to certain bacterial and parasitic infections and is a powerful inducer of IFN-gamma production. IL–23 is proposed to stimulate a subset of T cells to produce IL–17, which in turn induce the production of proinflammatory cytokines that lead to a protective response during infection. IL–27 appears to have duel functions as an initiator of TH1-type (cellular immunity) immune responses and as an attenuator of immune/inflammatory responses.                

The present inventions provide methods for improved expression of multimeric proteins by engineering different ratios of the subunit expression units in a cell or upon expression from a multi-promoter plasmid having different strength promoters. The inventors have improved the levels and efficiency of expression of the IL–12 family of cytokines, which includes IL–12, IL–23, and IL–27, by adjusting the transcription and translation of the alpha and beta subunits that comprise the heterodimeric proteins. Optimal ratios of expression for the two (2) subunits were determined for IL–12, IL–23, and IL–27.

*Applications:*
      - Tumor treatment
      - Anti-viral therapy
      - Anti-inflammatory therapy

*Advantages:*                     Increased expression and stability of in vitro expressed IL–12, IL–23 and IL–27 cytokines                

*Development Status: In vitro*                     data and data in animal models can be provided upon request                

*Market:*
      - Infectious Diseases
      - Cancer
      - Inflammatory Diseases

*Inventors:*                     George N. Pavlakis and Barbara K. Felber (NCI)                

*Patent Status:*                     International PCT Patent Application No. PCT/US09/043481 filed 11 May 2009, which published as WO 2009/140206 on 19 Nov 2009 (HHS Reference No. E–192–2008/1–PCT–02)                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Kevin W. Chang, Ph.D.; 301–435–5018;                     *changke@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The Center for Cancer Research, Human Retrovirus Section, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize delivery of cytokines of the IL–12 family in cancer and other indications. Please contact John D. Hewes, Ph.D. at 301–435–3121 or                     *hewesj@mail.nih.gov*                     for more information.                

##                     Radiotracers for Imaging Cannabinoid Sub-Type 1 (CB1) Receptor                

*Description of Invention:*                     The present invention relates to novel radiolabeled compounds for imaging cannabinoid sub-type 1 (CB1) receptors in brains of mammals, particularly humans, using positron emission tomography (PET) or single photon emission computed tomography (SPECT). These radioligands can be used in clinical research, diagnostics, or drug discovery and development, in that, they permit understanding of the role of CB1                     receptors in neuropsychiatric disorders such as Parkinson's disease, Huntington's disease, Alzheimer's disease, multiple sclerosis, depression, mood disorder, anxiety, schizophrenia, drug addiction, alcohol disorder, obesity and anorexia.                

*Applications:*
      -  In vivo                      imaging of CB 1                      receptor in mammals, particularly humans                
      - Diagnostic imaging of CB 1                      receptors in subjects having a neurological, neuropsychiatric, neurodegenerative or other condition and treatment                
      - Pharmaceutical composition
      - Diagnostic kits

*Advantages:*                     The principal radioligand under the claim is effective for imaging CB1                     receptors                     *in vivo*                     with PET.                

*Development Status:*                     Primary radioligand has been evaluated in non-human primates with PET.                

*Market:*                     Radioligands may be useful for performing drug occupancy studies of CB1                     receptors, and for neuropsychiatric studies and investigations with imaging techniques (                    *e.g.,*                     PET or SPECT).                

*Inventors:*                     Victor W. Pike (NIMH), Sean R. Donohue (NIMH),                     *et al.*

*Relevant Publications:*

                    1. SR Donohue, C Halldin, VW Pike. Synthesis and structure–activity relationships (SARs) of 1,5-diarylpyrazole cannabinoid type-1 (CB1) receptor ligands for potential use in molecular imaging. Bioorg Med Chem. 2006 Jun 1;14(11):3712–3720. [PubMed: 16466922].                

                    2. SR Donohue, VW Pike, SJ Finnema, P Truong, J Andersson, B Gulyás, C Halldin. Discovery and labeling of high affinity 3,4-diarylpyrazolines as                           ( print page 26260)                        candidate radioligands for                     *in vivo*                     imaging of cannabinoid subtype-1 (CB1) receptors. J Med Chem. 2008 Sep 25;51(18):5608–5616. [PubMed: 18754613].                

*Licensing Status:*                     Available for licensing.                

*Licensing Contact:*                     Susan Ano, PhD; 301–435–5515;                     *anos@mail.nih.gov.*

Dated: May 5, 2010.

Richard U. Rodriguez,

Director, Division of Technology Development and Transfer, Office of Technology Transfer, National Institutes of Health.

[FR Doc. 2010–11173 Filed 5–10–10; 8:45 am]

BILLING CODE 4140–01–P