E8-4187. 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: [phone]; fax: [phone]. A signed Confidential Disclosure Agreement will be required to receive copies of the patent applications.

PSM Peptides as Vaccine Targets Against Methicillin-Resistant

Staphylococcus aureus

Description of Technology: Available for licensing and commercial development are compositions and methods for the treatment and inhibition of Methicillin-resistant Staphylococcus aureus (MRSA), a dangerous human pathogen. The invention concerns immunogenic peptides that can be used to induce protective immunity against MRSA, including phenol-soluble modulin (PSM) peptides.

In addition to the MRSA infections that occur in immunocompromised patients in hospitals, new MRSA strains have recently emerged that can cause severe infections (such as necrotizing fasciitis) or death in otherwise healthy adults. These strains are increasingly involved in community-associated (CA)-MRSA infections, and can be contracted outside of the health care settings. The incidence of CA-MRSA infections is increasing and the majority of infections in patients reporting to emergency departments in the U.S. is now due to CA-MRSA.

The invention describes a class of secreted staphylococcal peptides with an extraordinary ability to recruit, activate, and subsequently lyse human neutrophils, thus eliminating the main cellular defense against S. aureus infection. The peptides are encoded by the PSM gene cluster and include PSMα1, PSMα2, PSMα3, and PSMα4, all of which activate and subsequently lyse neutrophils. These peptides are produced at especially high levels in CA-MRSA and to a large extent determine their aggressive behavior and ability to cause disease in animal models of infection. Thus, the peptides represent a set of virulence factors of S. aureus that account for the enhanced virulence of CA-MRSA. The identification of these peptides enables the production of vaccines and other preventative and/or therapeutic agents for use in subjects infected with MRSA.

Applications: Development of new classes of antibiotics and vaccines against Methicillin-resistant Staphylococcus aureus infections.

Inventors: Michael Otto and Rong Wang (NIAID).

Publication: R Wang et al. Identification of novel cytolytic peptides as key virulence determinants for community-associated MRSA. Nat Med. 2007. Dec;13(12):1510-1514.

Patent Status: U.S. Provisional Application No. 60/933,573 filed 06 Jun 2007 (HHS Reference No. E-239-2007/0-US-01); U.S. Provisional Application No. 60/983,141 filed 26 Oct 2007 (HHS Reference No. E-239-2007/1-US-01).

Development Status: Early stage.

Licensing Status: Available for non-exclusive or exclusive licensing.

Licensing Contact: Cristina Thalhammer-Reyero, PhD., M.B.A.; 301-435-4507; [e-mail].

Collaborative Research Opportunity: The NIAID Laboratory of Human Bacterial Pathogenesis is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact William Ronnenberg at 301-451-3522 or [e-mail] for more information.

Active MRI Compatible and Visible iMRI Catheter

Description of Technology: MRI is a promising imaging modality that provides superior soft tissue contrast and multi planar real-time imaging without harmful ionizing radiation for therapeutic procedures. Interventional magnetic resonance imaging (iMRI) has gained important popularity in many fields such as interventional cardiology and radiology, owing to the development of minimally invasive techniques and visible catheters under MRI for conducting MRI-guided procedures and therapies. This invention relates to a novel MRI compatible and active visible catheter for conducting interventional and intraoperative procedures under the guidance of MRI. The catheter features a non conductive transmission line and the use of ultrasonic transducers that transform RF signals to ultrasonic signals for transmitting RF signal to the MRI scanner. The unique design of this catheter overcomes the concern of patient/sample heating (due to the coupling between RF transmission energy and long conductors within catheter) associated with the design of conventional active MRI catheters.

Inventor: Ozgur Kocaturk (NHLBI).

Patent Status: U.S. Provisional Application No. 60/716,503 filed 14 Sep 2005 (HHS Reference No. E-298-2005/0-US-01); PCT Application No. PCT/US2006/035636 filed 13 Sep 2006, which published as WO 2007/033240 on 22 Mar 2007 (HHS Reference No. E-298-2005/0-PCT-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Michael Shmilovich, Esq.; 301/435-5019; [e-mail].

Collaborative Research Opportunity: The National Heart, Lung, and Blood Institute, Cardiac Catheterization Lab is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the alternative Active MRI compatible and visible catheters using ultrasonic technology. Please contact Peg Koelble at [e-mail] for more information.

Immunoglobulins With Potent and Broad Antiviral (HIV) Activity Based on scFv Joined by Flexible Linker to Fc

Description of Technology: This invention describes methods of inhibiting viral infection (e.g., HIV-1 infection). The method comprises administering a fusion protein comprising a small size, single chain Fv (scFv) antibody binding domain joined to an Fc region by a long flexible linker. In particular, scFv m6 or m9, the single chain variable fragments that were previously identified from a phage display library for binding to gp140_89.6, gp120_JRFL, gp140_IIIB, and their complex with two-domain soluble CD4 is joined to Fc by a long flexible linker to provide a new agent for the inhibition of HIV infection or immunotherapy of HIV-infected individuals. The Fc region provides stability, long half-life, and biological effector functions. The scFv-Fc fragment provides antigen recognition and neutralizing activity. The small size of the scFv-Fc fusion molecule provides easy access to conserved viral epitopes exposed before or during viral entry. In addition, these fusion molecules exhibit neutralization activity that is higher than that of whole IgGs. Thus, this invention may offer a novel approach to treat and prevent HIV-1 infection and/or AIDS.

Inventors: Dimiter Dimitrov (NCI) and Mei-Yun Zhang (NCI/SAIC).

Patent Status: U.S. Patent Application No. 10/573,962 filed 29 Mar 2006, claiming priority to 29 Sep 2003 (HHS Reference No. E-316-2003/0-US-03).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Sally Hu; 301/435-5606; [e-mail].

Modulators of Nuclear Hormone Receptor Activity: Novel Compounds, Diverse Applications for Infectious Diseases, Including Anthrax (B. anthracis)

Description of Technology: Nuclear hormones such as glucocorticoids dampen inflammatory responses, and thus provide protection to mammals against inflammatory disease and septic shock. The Anthrax lethal factor represses nuclear hormone receptor activity, and thus may contribute to the infectious agent causing even more damage to the host. This observation can be exploited to find new means of studying and interfering with the normal function of nuclear hormone receptors. Scientists at NIH have shown that under the appropriate conditions, these molecules can be used to modulate the activity of various nuclear hormone receptors. Identifying useful agents that modify these important receptors can provide relief in several human disorders such as inflammation, autoimmune disorders, arthritis, malignancies, shock and hypertension.

Applications: This invention provides novel agents that can interfere with the action of nuclear hormone receptors. It is well known that malfunction or overdrive of these receptors can lead to a number of diseases such as enhanced inflammation; worse sequelae of infection including shock; diabetes; hypertension and steroid resistance. Hence a means of controlling or fine-tuning the activity of these receptors can be of great benefit. Current means of affecting steroid receptor activity are accompanied by undesirable side-effects. Since the conditions for which these treatments are sought tend to be chronic, there is a critical need for safer drugs that will have manageable side-effects.

Advantages: The observation that the lethal factor from Anthrax has a striking effect on the activity of nuclear hormone receptors opens up new routes to controlling their activity. The means of action of this repressor is sufficiently different from known modulators of hormone receptors (i.e., the classical antagonists). For instance, the repression of receptor activity is non-competitive, and does not affect hormone binding or DNA binding. Also, the efficacy of nuclear hormone receptor repression by Anthrax lethal factor is sufficiently high that the pharmacological effect of this molecule is seen at vanishingly small concentrations. Taken together, these attributes may satisfy some of the golden rules of drug development such as the uniqueness or novelty of the agent's structure, a low threshold for activity, high level of sophistication and knowledge in the field of enquiry, and the leeway to further refine the molecule by rational means.

Development Status: In vitro studies have been completed, and a limited number of animal studies have been carried out.

Inventors: Esther M. Sternberg (NIMH), Jeanette Webster (NIMH), Leonardo H. Tonelli (NIMH), Stephen H. Leppla (NIAID), Mahtab Moayeri (NIAID).

Patent Status: U.S. Patent Application No. 10/530,254 filed 04 Apr 2005, claiming priority to 04 Oct 2002 (HHS Reference No. E-247-2002/1-US-02).

Licensing Status: Available for exclusive or non-exclusive licensing.

Licensing Contact: Peter Soukas; 301/435-4646; [e-mail].

Dated: February 27, 2008.

Bonny Harbinger,

Deputy Director, Office of Technology Transfer, National Institutes of Health.