Royalty Report: Drugs, Delivery, Pharmaceuticals – Collection: 7297

License Grant

A private Danish pharmaceutical company hereby grants to a Israeli Licensee a worldwide, perpetual license, under its rights in and to the Patents and the Licensed Know-How to develop, manufacture, commercialize, make, use, sell, offer for sale and import Products, in the Field of Use.  The License granted to Licensee is Sublicensable.

License Property

Patent
IP-P03 – Coat (coating with cellulose) – Controlled release composition US 6,787,156
IP-P05 – Polymer release system – Controlled release solid dispersion 10/490,170 /
IP-P08 – Controlled release Carvedilol compositions – Controlled release solid dispersion 10/703,084 /
IP-P09 – Polymer blend – Matrix composition for controlled release 10/550,685

“Product” shall mean Carvedilol – a controlled release pharmaceutical formulation based on a polymeric matrix composition formulated under one or more of the Patents and comprising Carvedilol as an active substance.  The name given to this product by the Licensee is RHB-101.

Field of Use

RHB-101 is for Cardiovascular use.

License Grant

The French Licensor grants to the Licensee in Puerto Rico, an exclusive license, even as to Licensor, with the right to grant sublicenses, under Licensed Technology, to make, have made, use, sell, offer for sale The Parties  have undertaken a feasibility study to develop a Formulation by applying the Licensors Micropump Technology to Carvedilol.

License Property

Licensor has developed certain proprietary technology related to Licensor Micropump Technology.

Carvedilol11 means (l-(9H-carbazol-4-yloxy)-[[2-2(2-methoxyphenoxy)ethyl] amino ]-2-propanol), the compound that is known by the generic name of Carvedilol and including all racemates, chelates, complexes, enantiomers, diastereoisomers, salts, bases, esters, hydrates, solvates, polymorphs, crystal forms, crystal habits, prodrugs, isotopic or radiolabeled equivalents, metabolites, or the like, thereof and all mixtures and any of the foregoing, and compositions comprising Carvedilol.

Licensor Micropump Technology means a multiple-dose system containing a large number of microparticles that may be contained in capsule, tablet, orally dispersible, sachet or suspension formulations. It is expected that the microparticles are released in the stomach and pass into the small intestine, where each microparticle operates as a miniature delivery system, releasing the drug at a controlled rate and over an extended period of time.

Licensor Patent Rights means all patents and patent applications in existence as of the Effective Date or during the Term of this Agreement claiming generically or specifically a product or process using the Licensors Micropump Technology.

Product means any presentation or presentations of Carvedilol that incorporate the Licensed Technology, alone or in combination with other therapeutically active compounds, for the therapeutic or prophylactic treatment of diseases and conditions in humans in any dosage or strength.

Field of Use

The Micropump® technology is a controlled release and taste-masking technology for the oral administration of small molecule drugs.

License Grant

Licensor grants to Israeli Licensee an exclusive worldwide, perpetual license under the Patents and the Licensed Know-How for the sole purpose of developing, manufacturing, commercializing, making, using, selling, offering for sale and importing Products, in the Field of Use (the “License”).

License Property

“Product” shall mean all extended release (including, but not limited to, 24 hour extended release) and all other Ondansetron tablet formulations, that infringe one or more claims of the Patents and Licensed Know How, including CDT® delivery technology.

Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting, often following chemotherapy.

License Grant

Irish Licensor grants, and Licensee accepts, upon the terms set forth in this Agreement, an Exclusive, irrevocable right and license in the Territory, under the Patents and the Know-How, to develop, market, use, distribute, import, export, offer to sell and sell (but not produce or manufacture) the Products and any Improvements thereto.

Licensee desires to acquire from Licensor, and Licensor is willing to grant to Licensee, an Exclusive (as hereinafter defined) license under Licensor’s Patents, Know-How and Trademarks relating to the Products in the Territory.

License Property

Patents means as for Product A as hereinafter defined (a) International Application WO/2000/76478, US App. No. 10/009,532 titled Controlled Release And Taste Masking Oral Pharmaceutical Compositions, US App. No. 11, 268/500 titled Controlled Release And Taste Masking Oral Pharmaceutical Compositions, and related applications thereof, including all other provisional and other patent applications including, but not limited to, US App. No 12/210,969, (c) any and all patents that have issued or in the future issue from the foregoing patent applications, including utility, model and design patents and certificates of invention, including, but not limited to, US Patent No. 7,410,651 titled Controlled release and taste masking oral pharmaceutical compositions, US Patent No. 7.431,943 titled Controlled release and taste masking oral pharmaceutical compositions.

Product A any oral formulation product containing Budesonide or other anti-inflammatory corticosteroids as an active ingredient, formulated with a multi-matrix (MMX) drug releasing technology, for the treatment of patients with Ulcerative Colitis and all other human uses.

Product B any oral formulation product containing Rifamycin SV as an active ingredient, formulated with a multi-matrix (MMX) drug releasing technology, for the treatment of patients with Travelers’ Diarrhea and all other human uses.  

Budesonide MMX is an oral corticosteroid currently being investigated in two multi-center phase III clinical trials and Rifamycin SV MMX is a broad spectrum, semi-synthetic antibiotic that also has targeted release characteristics when taken orally. MMX is a proprietary technology platform designed to produce a controlled release, homogeneous local application of the active pharmaceutical ingredient throughout the colon, thereby limiting systemic absorption and offering an opportunity for reduced side effects. The MMX technology is covered by two issued U.S. patents that expire in mid-2020, and additional patent applications are pending at the U.S. Patent and Trademark Office.

Field of Use

Licensee possesses capabilities in marketing, development and commercialization of pharmaceutical products in the Territory.

License Grant

The English Licensor hereby grants, on behalf of itself and its Affiliates, to the English Licensee, effective on the Effective Date, a royalty-bearing, exclusive (even as to Licensor (except to the extent necessary for Licensor to perform the Licensor Development Activities)) worldwide license, with the right to sublicense, under the Licensor Technology to Manufacture, Develop and Commercialize the Products in the Field in the Territory.

Licensee hereby grants, on behalf of itself and its Affiliates, to Licensor, effective on the Effective Date, a royalty-free, non-exclusive license, with the right to sublicense, (i) under the Licensee Technology to the extent necessary for Licensor to perform the Licensor Development Activities and (ii) under any Licensee Improvement Manufacturing Patent Rights for use other than for the Manufacture, Development and/or Commercialization of the Products in the Field in the Territory.

License Property

Xodol means the product currently marketed under the brand name 'Xodol', which is a combination of 5, 7.5 or 10 milligrams (mg) ofhydrocodone, in each case, combined with 300 mg of acetaminophen (it being understood that (x) Licensors existing sublicensee currently markets such product under a different name and (y) such product, whether marketed under such different name or any other name in the future, shall be deemed to be 'Xodol' for the purposes of this Agreement).

Product means any Hydrocodone Product or Combination Product.

Hydrocodone Product means any pharmaceutical product containing Hydrocodone as its sole Active Ingredient that is in a formulation containing the Licensee Technology and which is Developed, Manufactured and Commercialized pursuant to, and in accordance with, this Agreement.

Combination Product means any pharmaceutical product comprised of Hydrocodone and any non-opioid agonist drug as the Active Ingredients.  For purposes of clarity, S-297995 (also known as Naldemedine) is a non-opioid agonist drug.

S-297995 means (5R, 14S)-17-(Cyclopropylmethyl)-6, 7-didehydro-4,5-epoxy-3 ,6, 14-trihydroxy-N-[1-methyl-l-(3-phenyl-1,2,4-oxadiazol-5-yl)ethyl]morphinan-7-carboxamide Monotosylate including any metabolites, prodrugs, solvates (including hydrates), esters, salts, stereoisomers, racemates, tautomers and polymorphs (including crystal forms), of such compound.

Licensor Technology means the (a) Licensor Know-How and the Licensor Patent Rights, including Licensor Core Technology (b) the Licensor Core Technology Improvements, and (c) all intellectual property rights therein.

Licensor Patent Rights means any Patent Right that Licensor or its Affiliates Controls on the Effective Date or that comes into the Control of Licensor or its Affiliates during the Term (other than any Patent Rights which are Licensee Patent Rights), to the extent that such Patent Right is necessary or useful to Develop, Manufacture, or Commercialize in the Territory, the Products in the Field, including any method of making the Products, any composition or formulations of the Products, or any method of using or administering the Products provided that Licensee Patent Rights excludes any Patent Rights to the extent relating to an Licensee API.  The Licensor Patent Rights existing on the Effective Date are set forth.
8,298,581 – Matrix compositions for controlled delivery of drug substances
8,563,038 – Formulations and methods for the controlled release of active drug substances

Licensor Core Technology means, to the extent covered by any Licensor Patent Rights or Licensor Know-How, in each case, Controlled by Licensor and its Affiliates as of the Effective Date,  (i) any abuse-deterrent drug delivery system, (ii) the formulation of products for which any such abuse-deterrent drug delivery system is used and/or (iii) manufacturing of products containing any such abuse-deterrent drug delivery system.  

Licensor Core Technology includes the Licensor Patent Rights and Licensor Know-How, in each case, Controlled by Licensor and its Affiliates as of the Effective Date to the extent covered by clause (i), (ii) and/or (iii) above.  Notwithstanding anything herein to the contrary, in the event there is a dispute as to whether anything in clause (i), (ii) and/or (iii) above was covered by any such Licensor Know-How as of the Effective Date, Licensor shall have the burden of proof with respect to establishing that it was so covered.

Generic Product means, on a country-by-country basis, any pharmaceutical product that (a) is sold by a Third Party that is not an Affiliate or Sublicensee of Licensee under a marketing authorization granted by a Regulatory Authority to a Third Party and (b) results from (i) an abbreviated new drug application including any amended or successor abbreviated route of approval thereof in the United States (ANDA) or (ii) abbreviated routes of approval in any other countries in the Territory that are comparable to ANDA, which in the case of clause (i) and/or (ii), references the applicable Product, provided that (x) such pharmaceutical product has the same Active Ingredient as the Product and an abuse deterrent system or (y) the Product is the primary basis for the approval of such pharmaceutical product.

Patent Right means any and all (a) patent applications filed in any jurisdiction, including all provisional applications, substitutions, continuations, continuations-in-part, divisions, renewals, and all patents granted thereon; (b) all patents, reissues, reexaminations and extensions or restorations by existing or future extension or restoration mechanisms, including supplementary protection certificates or the equivalent thereof; and (c) any other form of government-issued right substantially similar to any of the foregoing, including certificates of invention and applications for certificates of invention.

Field of Use

The collaboration is for the development and commercialization of abuse-deterrent hydrocodone-based product candidates.  Abuse-deterrent is for the treatment of pain and in other indications.

License Grant

The Company has previously agreed to pay royalties to CONSULTANT, a member of the Company's Board of Directors, in recognition of the patents developed by CONSULTANT for TIMERx.

License Property

The Company has developed the TIMERx delivery system, a novel drug delivery technology, to address the limitations of currently available oral controlled release delivery systems. The Company believes that the TIMERx system is a major advancement in oral drug delivery that represents the first easily-manufactured oral controlled release drug delivery system that is applicable to a wide variety of drug classes, including soluble drugs, insoluble drugs and drugs with a narrow therapeutic index. The Company is utilizing the TIMERx system to formulate generic versions of branded controlled release drugs, controlled release formulations of currently-marketed.

The TIMERx drug delivery system is a hydrophilic matrix combining primarily a heterodispersed mixture, usually polysaccharides xanthan and locust bean gums, in the presence of dextrose. The physical interaction between these components works to form a strong, binding gel in the presence of water. Drug release is controlled by the rate of water penetration from the gastrointestinal tract into the TIMERx gum matrix, which expands to form a gel and subsequently releases the active drug substance. The TIMERx system can precisely control the release of the active drug substance in a tablet by varying the proportion of the gums, together with the third component, the tablet coating and the tablet manufacturing process. Drugs using TIMERx technology are formulated by combining the active drug substance, the TIMERx drug delivery system and additional excipients and compressing such materials into a tablet.

1)  Directly compressible sustained release excipient.

2)  Sustained release excipient and tablet formulation.

3)  Compressible sustained release solid dosage forms.

4)  EPO Application No. 89309518.2; filed September 19, 1989.

5)  Australian Patent Application No. 43057/89

6)  Japanese Patent Application No. 1-510135

7)  Irish Patent Application No. 2968/89

8)  Canadian Patent Application No. 611,700

9)  Verapamil Tablet Application, Serial No. 736,031 & EPO PCT Applications.

10)  2 U.S. Applications on Bi-modal release.

License Grant

Swiss Licensor hereby grants to English Licensee an exclusive license, with the right to grant sublicenses under the patents, SPCs and Licensor-Know-How to make, have made, use and sell product in the territory, subject to the terms and conditions of this agreement. The rights to make, have made, use and sell shall include all activities concerning the subject matter of patents, SPCs and Licensor-Know-How with respect to the making, use and sale of product only, which activities would, but for the license herein granted, infringe Patents, SPCs and/or Licensor-Know-How. In addition, Licensor hereby grants to Licensee an exclusive license, with the right to grant sublicenses subject to this agreement, to make, have made, use and sell any invention or know-how related to Product which arose under the Letter, whether patented and/or patentable or not, for any purpose directly related to any selective serotonin reuptake inhibitor, provided that Licensor shall be allowed to use any such invention or know-how and the patents covering same, if any, for any other purpose not directly related to any selective serotonin reuptake inhibitor.

License Property

Paroxetine shall mean the chemical compound known as paroxetine, the more specific chemical name of which is [(-)-trans-4-(4- fluorophenyl)-3-[3,4-methylene-dioxyphenoxy) methyl] piperidine] and all pharmaceutically active derivatives thereof such as, but not limited to esters, salts (such as, but not limited to, the hydrochloride salt), hydrates, solvates, polymorphs, prodrugs and isomers thereof.

Geomatrix® Technology shall mean Licensors proprietary oral, modified release (i.e., controlled-release, sustained-release, or delayed release) drug delivery and related technology which utilizes a hydrophilic drug-containing matrix tablet which controls the release of the drug through the use of one or more barrier layers, together with all improvements thereon or thereto.

Product shall mean shall mean an oral delivery system for Paroxetine based on or using the Geomatrix® Technology.

Patents shall mean
4,839,177 – System for the controlled-rate release of active substances
5,422,123 – Tablets with controlled-rate release of active substances
5,476,654 – Process for preparing pharmaceutical compositions having an increased active substance dissolution rate, and the compositions obtained

SPC shall mean a right based upon a patent to exclude others from making, using or selling product, such as a Supplementary Protection Certificate.

Field of Use

Licensee will utilize such technology to develop drugs taken orally in tablet form formulated so as to control the amount, timing and location of the release of the drug in the body for pharmaceutical use in human prescriptions.