Royalty Report: cardiac, Drugs, Disease – Collection: 2719

License Grant

Seller shall sell, transfer, assign, convey, deliver, license or sublicense, as specified below, to Buyer, or shall cause to be sold, transferred, assigned, conveyed, delivered, licensed or sublicensed, as specified below, to Buyer, and Buyer shall acquire all of Seller’s right, title and interest in and to the properties and assets of Seller.

Field of Use

The Licensee would acquire all rights to the cardiovascular products, including related trademarks, patents, intellectual property, product inventory and other related assets consisting of Cardene® I.V. (nicardipine hydrochloride), Cardene SR® and new formulations of Cardene in development, as well as Retavase® (reteplase) and the development product ularitide.  Cardene®  is for the short-term treatment of hypertension when oral therapy is not feasible or desirable. Cardene I.V. is the only intravenous calcium channel blocker (calcium ion influx inhibitor) for this indication.  Cardene I.V. offers rapid, precise blood pressure control and has been proven to be as effective as sodium nitroprusside with fewer dose adjustments (1).  Cardene I.V. prevents calcium ions from entering cardiac and vascular smooth muscle cells (the cells that line the arteries) through specific ion channels in the cell membrane. When these channels are blocked, calcium cannot enter the cell, thereby preventing the vascular smooth muscle from contracting.  Retavase® (reteplase) is a fibrinolytic agent for the management of acute myocardial infarction (AMI) or heart attack in adults for the improvement of ventricular function following AMI, the reduction of the incidence of congestive heart failure and the reduction of mortality associated with AMI. Treatment. Retavase, a recombinant plasminogen activator, works by generating plasmin, an enzyme produced naturally by the body’s blood plasma. Plasmin breaks down fibrin, a major constituent of blood clots, thereby helping to dissolve the clots.

License Grant

The University, with permissions as applicable, grant an exclusive, sublicensable license for the field of Use in the Territory to
—  practice under the Patent Rights
—  make, have made, use, lease, import, export and/or sell Licensed Products,
—  sell, use and/or practice Licensed Services.

The University grants a non-exclusive license to use Know-how for the Field of Use in the territory to
—  make, have made, use, lease and/or sell Licensed Products
—  sell, use and/or practice Licensed Services.

License Property

The University has rights to patents titles Reactive Oxygen Generating Enzyme and Inhibitor with Nitric Oxide Bioactivity and Uses Thereof, and, Composition for the Treatment and Prevention of Heart Disease and Methods of Using the Same.

The Phase II candidate and all other drugs in the portfolio are designed to correct nitric oxide and redox disequilibrium in the failing heart and cardiovascular system. All have a dual mechanism of action of inhibiting the creation of reactive oxygen radicals and concurrently providing nitric oxide in the failing heart. The therapeutic target is the ryanodine receptor, the ion channel in the heart that provides the calcium necessary for the heart to beat. The investigational drugs are believed to improve calcium cycling in the heart by acting on the ryanodine receptor to significantly improve the efficiency of heart contractility.

Field of Use

The field of use means all therapeutic uses for allopurinol, oxypurinol, ptcein-6-aldehyde and mixtures thereof, that are provided with a nitrate group thereon, as well as therapeutic uses for any combinations of these agents with nitrates or other NO donors.

The drug portfolio is to develop and commercialize certain of Licensee's proprietary cardiovascular drugs to treat heart failure.

License Grant

The Israel Licensors hereby grants to the Licensee the exclusive, royalty-bearing right and license in the Territory under the Licensee's Intellectual Property (including, for clarity, a sublicense under the Sublicensed IP) to Develop, Manufacture and Commercialize Products for use in the Field.

License Property

The Licensor owns or controls certain intellectual property rights covering a liquid polymer composed of Sodium Alginate and Ca-D-Gluconate (designated by BioLineRx as “BL-1040”).  The Licensor is currently developing the Product (as defined below) as a medical device for the direct treatment of cardiac tissue following acute myocardial infarction.

Bioabsorbable cardiac matrix, or BCM, is currently in a placebo-controlled clinical trial designed to support CE mark registration in the European Union.

BCM is a medical device intended to prevent congestive heart failure following a STEMI, which is a type of severe heart attack.

BCM is delivered during a minimally invasive, commonly performed cardiac procedure called a percutaneous coronary intervention procedure. BCM is a formulated sterile solution of sodium alginate and calcium gluconate designed to be administered as a liquid through the coronary artery. When administered following a STEMI, BCM flows into damaged heart muscle where, in the presence of abnormally high extracellular calcium released by the damaged cells, it forms a protective hydrogel meshwork within the wall of the heart’s left ventricle. Based on pre-clinical animal studies, we believe that BCM has the potential to act as a flexible scaffold to provide physical support to the ventricle wall in the early stages of recovery following a STEMI and prevent further structural damage while the heart muscle heals. In addition, in our pre-clinical animal studies, as calcium levels in the damaged area returned to normal, BCM dissolved and was excreted through normal kidney function.

Field of Use

The Licensee is developing BCM for the prevention of cardiac remodeling, which often leads to congestive heart failure following an ST-segment elevated myocardial infarction, or STEMI.

License Grant

Under the terms of collaborative agreement in 1988, the Licensee bores all of the costs of research and development according to a budget agreed by the Company and Licensee.  In return, the Company granted Licensee an exclusive license to market Dilacor XR throughout the world.

License Property

Dilacor XR is a once per day Zero Order Geomatrix formulation of diltiazem hydrochloride, a calcium channel blocking agent indicated for hypertension and for the management of chronic stable angina.  Geomatrix technologies can improve the efficacy of orally administered drugs and enhance compliance by patients with prescribed medical treatments by permitting the drug to be taken less frequently, by reducing side effects and by causing the drug to be released at more specific locations within the body.  The Geomatrix technologies use hydrophillicmethylcellulose, or HPMC, matrices which govern the release profile of a drug depending on the viscosity of HPMC used and the rate of surface area exposure.  The 'release profile' refers to the rates at which a drug tablet releases the active drug component over the period of time after the drug is taken.

Field of Use

Dilacor XR (diltiazem hydrochloride) is a calcium channel blocker used to treat hypertension (high blood pressure), angina (chest pain), and certain heart rhythm disorders.

License Grant

University grants to Licensee a license under Universitys interest in Patent Rights to make, use, sell, offer for sale, and import Licensed Products and to practice Licensed Methods in the Field, within the Territory and during the Term.  The amendment adds the patent information.

The licenses granted in this paragraph is exclusive with respect to the Field only.

License Property

The patent is for the therapy treatment or prevention of cardiovascular disease.

Field of Use

The Field means gene therapy for the treatment or prevention of cardiovascular diseases by the delivery of a gene or a synthetic equivalent (DNA, deoxyribonucleic acid or polydeoxyribonucleotide sequence), in whole or in part or in combination, including those encoding one or more phospholamban genes and/or SERCA-2 (sacroplasmic reticulum calcium ATPase) genes, or their mutants, excepting the involvement of anti-sense RNA (ribonucleic acid or polyribonucleotide sequence) of the phospholamban gene.