Royalty Report: Drugs, Ophthalmological, Pharmaceuticals – Collection: 2377

Products refers to Vitrase(TM) and Corneaplasty, certain proprietary technology relating to non-surgical therapeutic ophthalmic systems.

We are developing Vitrase, a proprietary formulation of hyaluronidase, for treatment of severe vitreous hemorrhage, a sight threatening condition, and diabetic retinopathy, the leading cause of adult blindness in the United States.  Vitrase is currently in two Phase III clinical trials for treatment of severe vitreous hemorrhage. We are also conducting a pilot Phase IIa clinical trial of Vitrase in Mexico for treatment of diabetic retinopathy.  Vitreous hemorrhage.  A vitreous hemorrhage occurs when retinal blood vessels rupture and bleed into the vitreous humor, the clear, gel-like substance that fills the back of the eye between the lens and the retina.  The blood from the hemorrhage can obscure vision and prevent ophthalmologists from seeing into the eye to diagnose or treat the cause of the hemorrhage.  The only current treatment options are a watchful waiting period, during which no medical treatment is provided in the hope that the hemorrhage will clear on its own, and an invasive surgical procedure to remove the blood filled vitreous humor from the eye.  Vitrase, when injected into the vitreous humor, causes the vitreous humor to liquefy and promotes clearance of vitreous hemorrhage.  Based on market research we commissioned in February 1999, we believe that approximately one million cases of vitreous hemorrhage occur each year in the United States, Europe and Japan and that approximately half of these cases are candidates for treatment using Vitrase.

The macula is the central portion of the retina, a small area rich in cones, the specialized nerve endings that detect color and upon which daytime vision depends.

Silicone oil is indicated for use as a prolonged retinal tamponade in selected cases of complicated retinal detachments when other interventions are not appropriate for patient management. Complicated retinal detachments or recurrent retinal detachments occur most commonly following perforating injuries or in eyes with proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy (PDR), cytomegalovirus (CMV) retinitis, or giant tears.
—Silicone oil is also indicated in the treatment of retinal detachments due to acquired immunodeficiency syndrome (AIDS)-related CMV retinitis and other viral infections.

(a) an exclusive license (even as to Licensor) in the Territory under the Licensor Patent Rights, and Program Patent Rights to research, develop, make, have made, use, offer to sell, sell, have sold, import and export the Products in the Field;
  
(b) an exclusive license (even as to Licensor) in the Territory under the Licensor Know-How, the Licensor Program Know-How, and Licensor’s rights in Joint Program Know-How to research, develop, make, have made, use, offer to sell, sell, have sold, import and export the Products in the Field; and

(c) an exclusive license (even as to Licensor) in the Territory under the Licensor Technology to research, develop, make, have made, use, offer to sell, sell, have sold, import and export the Surgical Instruments solely for use with, or in connection with the sale of, the Products in the Field.

Notwithstanding the license grants set forth above, Licensor shall retain those rights under the Licensor Technology that are necessary to perform Licensor’s obligations under the Research Program and the Feasibility Studies in accordance with Agreement and to manufacture and supply clinical supplies and commercial supply of Product to Licensee and the scale up and transfer of manufacturing capabilities to Licensee in accordance with this Agreement and the Supply Agreement.

Non-Exclusive License Grant. Subject to the terms and conditions of this Agreement, Licensor hereby grants to Licensee a non-exclusive, royalty-free license in the Territory under the Licensor Program Technology, for any and all uses, including without limitation, to research, develop, make, have made, use, offer to sell, sell, have sold, import and export a product other than the Products.

TA Product shall mean the I-vation Platform incorporating a TA Compound as an active ingredient (which shall include without limitation the I-vation TA Product) and, for the purposes of Sections 5.2 through 5.6, that is in final form (i) for sale by prescription, over-the-counter or any other method, or (ii) for administration in a Clinical Trial or post-Marketing Authorization clinical trial.

I-vation Platform shall mean the Intravitreal Implant, together with the polymers applied as a coating thereto, for the purpose of containing and delivering sustained release of one or more active ingredients or therapeutic agents into the vitreous chamber of the eye, and any Improvements thereto,

Target shall mean a distinct, primary molecular target.

Surgical Instruments shall mean the Insertion Tool and/or the Extraction Tool, and any Improvements thereto.

Patent Rights shall mean any and all issued patents and patent applications in the Territory (which for the purposes of this Agreement shall be deemed to include certificates of invention and applications for certificates of invention) and any divisionals, continuations, continuations-in-part, reissues, renewals, substitutions, registrations, re-examinations, revalidations, supplementary protection certificates, pediatric exclusivity periods, any other patent term extensions and exclusivity periods and the like of any such patents and patent applications, and any and all U.S. and foreign equivalents of the foregoing.

Licensor Technology shall mean the Patent Rights, Know-How, Program Technology, rights in Joint Programs and Inventions.and rights in Joint Patent Rights.

The I-vation Intravitreal Implant is a drug delivery system capable of delivering a variety of drugs on a sustained release basis for well over a year, can be implanted in a minimally invasive procedure, and may be removed once the drug has been fully released. Currently, the majority of treatments being developed for AMD and DME require repeated injections into the eye, often with a suboptimal drug dosing profile. Replacing multiple injections with a single implant providing long-term, controlled drug release could represent a significant advance in therapeutic treatment, including improved patient compliance, reduced side effects and greater efficacy.

I-vation TA (a version of the I-vation implant formulated with the steroid triamcinolone acetonide) is being studied in a Phase I human clinical trial called STRIDE (Sustained Triamcinolone Release for Inhibition of Diabetic Macular Edema). The trial is assessing the safety and tolerability of the I-vation(TM) Intravitreal Implant with triamcinolone acetonide (TA) in patients with Diabetic Macular Edema (DME) under an Investigational New Drug application with the U.S. Food and Drug Administration.