E7-1378. Prospective Grant of Exclusive License: Use of Inhaled Nitrite Therapy for the Treatment of Pulmonary Conditions

AGENCY:

National Institutes of Health, Public Health Service, HHS.

ACTION:

Notice.

SUMMARY:

This is notice, in accordance with 35 U.S.C. 209(c)(1) and 37 CFR 404.7(a)(1)(i), that the National Institutes of Health (NIH), Department of Health and Human Services (HHS), is contemplating the grant of an exclusive license to practice the invention embodied in: PCT patent applications PCT/US2004/21985 and PCT/US2004/22232, filed July 9, 2004, both entitled “Use of Nitrite Salts for the Treatment of Cardiovascular Conditions” [HHS Reference Number: E-254-2003/2-3-PCT-01], to Aires Pharmaceuticals, Inc., a portfolio company of ProQuest Investments LLC, Princeton, N.J. The field of use of inhaled administration of nitrite salts for this exclusive license may be limited to the use of inhaled formulations of nitrite salts for the treatment of Pulmonary Hypertension and pulmonary and/or cardiopulmonary conditions. The United States of America is an assignee of the patent rights in these inventions.

DATES:

Only written comments and/or application for a license, which are received by the NIH Office of Technology Transfer on or before April 2, 2007 will be considered.

ADDRESSES:

Requests for a copy of the patent application, inquiries, comments and other materials relating to the contemplated license should be directed to: Susan Carson, D.Phil., Office of Technology Transfer, National Institutes of Health, 6011 Executive Boulevard, Suite 325, Rockville, MD 20852-3804; E-mail: [e-mail]; Telephone: [phone]; Facsimile: [phone].

SUPPLEMENTARY INFORMATION:

The core invention is the unexpected finding that low, physiological and non-toxic concentrations of sodium nitrite are able to increase blood flow and produce vasodilation by infused and nebulized routes of administration. Pulmonary Hypertension (PH) occurs as a primary or idiopathic disease as well as secondary to a number of pulmonary and systemic diseases, such as neonatal PH and sickle cell disease. There is no cure for pulmonary hypertension, a nitric-oxide deficient state characterized by pulmonary vasoconstriction and systemic hypoxemia and therapies vary in efficacy and cost. Recent studies by NIH researchers and their collaborators provided evidence that the blood anion nitrite contributes to hypoxic vasodilation through a heme-based, nitric oxide (NO)-generating reaction with deoxyhemoglobin and potentially other heme proteins [Nature Medicine 2003 9: 1498-1505]. These initial results indicate that sodium nitrite can be used as a potential cost-effective platform therapy for a wide variety of disease indications characterized broadly by constricted blood flow or hypoxia.

These results have been further corroborated by work in the neonatal lamb model for PH. Inhaled sodium nitrite delivered by aerosol to newborn lambs with hypoxic pulmonary hypertension elicited a rapid and sustained reduction (65%) in hypoxia-induced pulmonary hypertension. Pulmonary vasodilation elicited by aerosolized nitrite was deoxyhemoglobin- and pH-dependent and was associated with increased blood levels of iron-nitrosyl-hemoglobin. Notably, short term delivery of nitrite dissolved in saline through nebulization produced selective, sustained pulmonary vasodilation with no clinically significant increase in blood methemoglobin levels. [Nature Medicine 2004 10: 1122-1127]. Method of use claims for nitrite salt formulations are directed to conditions associated with high blood pressure, decreased blood flow and for the treatment of specific conditions such as pulmonary hypertension and other indications.

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 404.7. The prospective exclusive license may be granted unless, within 60 days from the date of this published Notice, 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 404.7.

Properly filed competing applications for a license filed in response to this notice will be treated as objections to the contemplated license. Comments and objections submitted in response 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: January 22, 2007.

Steven M. Ferguson,

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