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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.

## Rapid Diagnostic Applications of Phage

*Description of Technology:*                     The NIH has available for licensing two techniques for rapid detection of a particular bacteria strain. Similar detection using currently available technologies take 1-2 days; this technology reduces the time to less than one hour. These technologies utilize phage, which has no pathogenic effect on higher plants and animals and are part of approved food-preparation formulations, indicating their known safety profile and an existing regulatory pathway. The first technique involves a phage that incorporates a reporter gene (                    *e.g.,*                     luciferase) that will be expressed only when the phage successfully infects a bacterium. This technique is particularly useful where only bacteria-killing (“lytic”) phages are known because the method also deactivates the lytic genes, enabling infection and subsequent detection. The second technique involves an engineered phage that will bind with quantum dots upon infection of bacteria; if a sample is treated first with this phage and then with quantum dots, the sample will only respond if the bacteria are present. Both techniques can be used to diagnose a clinical sample (tissue, blood, etc.) or an environmental isolate.                

### Applications

      - Bacterial detection and diagnostics, including clinical or environment samples.
      - Food safety and biodefense.

### Advantages

      - Detection methods are novel, rapid, and potentially applicable in many contexts ( e.g.,                      clinic, food preparation, bioterror response).                
      - Phage is easy and inexpensive to cultivate.
      - Phage is on sale in the US for food-preparation formulations and thus has a known regulatory pathway.

*Development Status:*                     A range of phages have been synthesized, many of which have been tested proof-of-principle using major standardized testing systems.                

*Inventors:*                     Dr. Carl Merrill (NIMH), Dr. Sankar Adhya (NCI),                     *et al.*

### Publications

                    1. R Edgar                     *et al.*                     High-sensitivity bacterial detection using biotin-tagged phage and quantum-dot nanocomplexes. Proc Natl Acad Sci. USA 2006 Mar 28;103(13):4841-4845.                

                    2. C Merril                     *et al.*                     The prospect for bacteriophage therapy in Western medicine. Nat Rev Drug Discov. 2003 Jun;2(6):489-497.                

### Patent Status

*HHS Reference No. E-169-2004*                    —U.S. Patent Application No. 11/547,587 filed 05 Oct 2006.                

*HHS Reference No. E-281-2005*                    —U.S. Patent Application No. 11/884,604 filed 17 Aug 2007.                

*HHS Reference No. E-318-2000*                    —Research Materials (patent protection is not being pursued for this technology): “Method for Determining Sensitivity to a Bacteriophage.”                

*Licensing Status:*                     Technologies are available for licensing, either individually or as a package.                

*Licensing Contact:*                     Bruce Goldstein, J.D., M.S.; 301-435-5470;                     *goldsteb@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, PhD at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

### Therapeutic Antibacterial Applications of Phage

*Description of Technology:*                     The NIH, in collaboration with others, has developed three groups of inventions related to the use of bacteriophages in therapeutic situations. The first group is a method of adapting phages to survive in the body substantially longer than wild-type phages, using serial passaging and/or genetic engineering. The second group involves phages designed to bind the toxins and cytokines that killed bacteria release into the bloodstream, reducing the pathogenic properties of the bacteria. The third group is a method of engineering a phage to have multiple binding sites, such that a single phage can target multiple types of bacteria.                

*Application:*                     Therapeutic applications of phage to treat bacterial infection.                

### Advantages

      - Improved efficacy through longer circulation.
      - Additional antibacterial functions.
      - Can be used independently or as an adjuvant to another antibacterial therapy.

*Development Status:*                     A range of phages have been synthesized and tested                     *in vivo.*                     A Phase 1 study of a phage targeting vancomycin-resistant                     *Enterococcus faecium*                     was completed by Exponential Biotherapies, Inc., with no adverse effects reported.                

*Inventors:*                     Dr. Carl Merrill (NIMH), Dr. Sankar Adhya (NCI),                     *et al.*

### Publications

                    1. C Merril                     *et al.*                     The prospect for bacteriophage therapy in Western medicine. Nat Rev Drug Discov. 2003 Jun;2(6):489-497.                

                    2. B Biswas                     *et al.*                     Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium. Infect Immun. 2002 Jan;70(1):204-210.                

                    3. C Merrill                     *et al.*                     Long-circulating bacteriophage as antibacterial agents. Proc Natl Acad Sci. USA 1996 Apr 16;93(8):3188-3192.                

### Patent Status

*HHS Reference No. E-110-1993*                    —U.S. Patent No. 5,688,601 issued 19 Jun 1997; U.S. Patent No. 7,332,307 issued 19 Feb 2008.                

*HHS Reference No. E-257-2000*                    —U.S. Patent No. 7,163,818 issued 16 Jan 2007.                

*HHS Reference No. E-178-1996*                    —Research Materials (patent protection is                           ( print page 46607)                        not being pursued for this technology): “Deletion of Lysogeny Genes and Toxin Genes from Bacteriophage Used in the Epidemiologic Control of Bacterial Illness.”                

*HHS Reference No. E-179-1996*                    —Research Materials (patent protection is not being pursued for this technology): “Therapeutics Use of Phage Expressing Toxin-Binding and/or Cytokine-Binding Proteins and Elimination of Genes Associate with Lysogeny.”                

*HHS Reference No. E-196-1997*                    —Research Materials (patent protection is not being pursued for this technology): “Antibacterial Therapy with Bacteriophage Genotypically Modified to Delay Inactivation by the Host Defense System.”                

*HHS Reference Nos. E-089-1998 and E-257-2003*                    —Research Materials (patent protection is not being pursued for this technology): “Two Enterocin-Producing Strains of Bacteria and Their Enterocins, Both of Which Are Lethal to Vancomycin-Resistant                     *Enterococcus faecium.”*

*HHS Reference No. E-012-1999*                    —Research Materials (patent protection is not being pursued for this technology): “Long Circulating Phage Vectors.”                

*Licensing Status:*                     Technologies are available for licensing, either individually or as a package.                

*Licensing Contact:*                     Bruce Goldstein, J.D., M.S.; 301-435-5470;                     *goldsteb@mail.nih.gov.*

*Collaborative Research Opportunity:*                     The NCI Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, PhD at 301-435-3121 or                     *hewesj@mail.nih.gov*                     for more information.                

Dated: September 1, 2009.

Richard U. Rodriguez,

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

[FR Doc. E9-21787 Filed 9-9-09; 8:45 am]

BILLING CODE 4140-01-P