Royalty Report: Drugs, Gastrointestinal, Therapeutic – Collection: 253982

License Grant

Licensor grants an exclusive license, under the Licensor Technology to develop, use, sell, offer for sale, import and/or export Licensed Products in the Territory and in the Field, and make and have made Licensed Products in the Territory for such development, use, sale, offering for sale, importation and/or exportation.

Licensor grants to Licensee, a perpetual, non-exclusive license under the Licensor Technology for Licensees research purposes only.

License Property

Licensor owns or possesses certain patent rights and know-how with respect to motilin agonist compounds.

GI Indication means diseases, disorders or impairments of the gastrointestinal tract, including the esophagus, stomach, pancreas, small and large intestines, colon, and gall bladder.

GI Product means a Licensed Product that has been Approved in a GI Indication.

The compound is 9O-(N-methylamidomethyl)-Ndesmethyl-N-isopropyl-(9S)-9-dihydroerythromycin A.

The patents are for Motilide Compounds, Method for Evaluating Therapeutic Efficacy,  ll-Deoxy-6,9-ether Erythromycin Compounds,  N-Desmethyl-N-substituted-11-deoxyerythromycin Compounds, and,  9-Desoxoerythromycin Compounds as Prokinetic Agents.

Motilin, a hormone that is secreted by the small intestine, stimulates gastrointestinal motility (movement). Erythromycin, a polyketide best known for its antibiotic activity, is an agonist of the motilin receptor that enhances esophageal motility in GERD patients and accelerates gastric emptying in patients with diabetic gastroparesis.

Field of Use

The agreement includes Licensor's clinical candidate, KOS-2187 and related compounds. KOS-2187 has demonstrated improved gastric emptying in preclinical studies and may have therapeutic benefit in gastrointestinal diseases such as gastro- esophageal reflux disease (GERD), or diabetic gastroparesis (delayed gastric emptying).

Licensee believes that the mechanism of action of KOS-2187 and its demonstrated activity as a prokinetic agent are significant indications of its potential as a new approach for the treatment of gastrointestinal diseases.

License Grant

South Korean Licensor shall, and hereby does, grant to Licensee an exclusive (even as to Licensor and its Affiliates), royalty-bearing right and license, including the right to sublicense in accordance with this Agreement, under the Licensor Intellectual Property and Licensor’s interest in the Joint Intellectual Property, to Develop, Manufacture, use and Commercialize, including filing for, obtaining and maintaining Regulatory Approval for, Products in the Field in the Territory.

License Property

Product means any pharmaceutical preparation containing one or more Compounds either as its only active ingredient(s) or as part of a Combination Product. For the avoidance of doubt, nothing in this Agreement grants to Licensee or Licensor any right or license under any Patent Rights or Know-How Controlled by Licensor or Licensee, respectively, with respect to any Other API.

Compound means YH12852, which has the chemical structure set forth in this agreement, together with all analogs, derivatives, metabolites, stereoisomers, polymorphs, formulations, mixtures or compositions thereof, and any existing or future improved or modified versions of the foregoing developed by or on behalf of Licensee, its Affiliates or Sublicensees.

Compound (S)-N-(1-(2-((4-amino-3-nitrophenyl)amino)-6-propylpyrimidin-4-yl)pyrrolidin-3-yl)acetamide

Licensor Patent Rights means all Patent Rights in the Territory that are Controlled by Licensor or any of its Affiliates as of the Effective Date or thereafter during the Term (other than Joint Patent Rights) that Cover any Compound or Product. The Licensor Patent Rights existing as of the Effective Date are set forth on Schedule 1.57; provided, however, that, if Licensor is acquired by a Third Party, “Licensor Patent Rights” shall exclude any Patent Rights that (a) are Controlled by such Third Party or the Affiliates of such Third Party (other than Licensor and Licensor Pre-Existing Affiliates) and (b) were not Controlled by Licensor or any of the Licensor Pre-Existing Affiliates immediately prior to the closing of such acquisition transaction; provided further that, if, after the closing of such acquisition, any such Licensor Excluded Affiliate has or acquires Control of any Patent Right that Covers the Development, Manufacture or Commercialization of any Compound or Product and that is used to Develop, Manufacture or Commercialize any such Compound or Product, such additional Patent Right that is Controlled by such Licensor Excluded Affiliate shall be included in Licensor Patent Rights.

9,890,138 – Diaminopyrimidine derivatives and processes for the preparation thereof
10,227,330 – Diaminopyrimidine derivatives and processes for the preparation thereof
9,850,227 – Diaminopyrimidine derivatives and processes for the preparation thereof

Licensee is a global pharmaceutical company offering one-stop custom synthesis services of active pharmaceutical products (APIs) and intermediates.

YH12852 is a novel, potent and highly selective 5-hydroxytryptamine 4 (5-HT4) receptor agonist. Other 5-HT receptor agonists with less 5-HT4 selectivity have been shown to successfully treat GI mobility disorders such as chronic constipation, constipation-predominant irritable bowel syndrome, functional dyspepsia and gastroparesis.

Field of Use

YH12852 is a small molecule drug in development for the treatment of functional gastrointestinal (GI) disorders (FGID).

License Grant

Licensor and its Affiliates hereby grant Netherland Licensee (i) an exclusive (even as to Licensor and its Affiliates, royalty-bearing license (with the right to grant sublicenses at one or more tier(s) under the Licensor Technology, (a) to research, have researched, Develop, have Developed, use and have used TZP-101 and Product in the Field in the Licensed Territory and (b) to sell, offer for sale, have sold, import and otherwise Commercialize or have Commercialized Product in the Field in the Licensed Territory; (ii) a nonexclusive, worldwide, royalty-free license (with the right to grant sublicenses at one or more tier(s), under the Licensor Technology, to manufacture and have manufactured TZP-101 and Product worldwide solely for research, Development, use or Commercialization of such Products in the Field in the Licensed Territory under the license granted to Licensee; (iii) an exclusive (even as to Licensor and its Affiliates, royalty free license (with the right to grant sub-licenses at one or more tier(s) under Licensor’s interest in the Joint Inventions to (a) research, have researched, Develop, have Developed and use and have used TZP-101 and Product in the Field in the Licensed Territory and (b) sell, offer for sale, have sold, import and otherwise Commercialize or have Commercialized the Products in the Field in the Licensed Territory; and (iv) a nonexclusive, worldwide, royalty-free license (with the right to grant sublicenses at one or more tier(s), under the Joint Inventions, to manufacture and have manufactured TZP-101 and Product worldwide solely for Development, use or Commercialization of such Product in the Field in the Licensed Territory under the license granted to Licensee. Licensee shall not have the right to conduct or have conducted research and/or Development activities in the Retained Territory for the generation of data in support of Regulatory Filings to the Regulatory Authorities in the Licensed Territory except as expressly permitted under this Agreement or with the prior written consent of Licensor.  For clarity, the licenses granted to Licensee by Licensor and its Affiliates shall not include any rights for Licensee to research, Develop, make, have made, use, sell, offer for sale, distribute, import, export and otherwise commercialize any other proprietary compound of Licensor (including any proprietary compound which Licensor licenses to a Third Party) that is not TZP-101.

License Property

The compound under development, called ghrelin agonist ulimorelin (TZP-101), is entering Phase III clinical trials.
TZP-101 means Licensor’s proprietary ghrelin agonist known as TZP-101 (ulimorelin), having the chemical structure set forth in Agreement, including any salt, ester, solvate, polymorphic form, stereoisomer, metabolite, and pro-drug thereof.

Product means any pharmaceutical product comprising TZP-101 as an active ingredient irrespective of its formulation.

US 7,476,653 – Macrocyclic modulators of the ghrelin receptor

Licensor Product-Specific Patent means (a) the Patents set forth and (b) any other Patent that becomes Controlled by Licensor or its Affiliates at any time after the Effective Date (including Licensor Sole Patents but excluding Licensor’s interest in any Joint Patents) that (i) is necessary for Licensee and/or its Affiliates to have rights under in order to Develop, manufacture, use and/or Commercialize TZP-101 and/or Products in the Field; and (ii) is not a Licensor Other-Product Patent.

US 7,452,862 – Conformationally-controlled biologically active macrocyclic small molecules as motilin antagonists or ghrelin agonists

Licensor Other-Product Patent means (a) the Patents set forth and (b) any other Patent that becomes Controlled by Licensor or its Affiliates after the Effective Date (including Licensor Sole Patents but excluding Licensor’s interest in any Joint Patents) that (i) is necessary for Licensee and/or its Affiliates to have rights under in order to Develop, manufacture, use and/or Commercialize TZP-101 and/or Products in the Field; and (ii) covers any of Licensor’s proprietary technology (A) that is generally applicable or can be applied to Licensor’s discovery or development program in addition to the development program relating to TZP-101 and Product, or (B) that is applicable or can be applied to one or more compounds or products in addition to TZP-101 or Product, or (C) that covers the composition of matter of, or the method of discovering, making or using, any compounds or products (or any design, component, formulation or part thereof) in addition to TZP-101 or Product.

US 7,491,695 – Methods of using macrocyclic modulators of the ghrelin receptor

Field of Use

TZP-101 is for the acceleration of gastrointestinal (GI) recovery in patients undergoing abdominal surgery.

The deal is for development of a treatment targeting diseases of the muscles of the gastrointestinal track – called gastrointestinal dysmotility –

License Grant

Japanese Licensor hereby grants to Licensee, during the Term, an exclusive, royalty-bearing license, with the right to sublicense, under the Licensor Technology (other than Licensor Improvements) to develop, use, distribute, import and export Compounds and to develop, register, use, distribute, promote, market, offer for sale, sell, have sold, import and export Products, in each case only in the Field and in the Licensed Territory. Licensor further grants Licensee an exclusive license, with the right to sublicense, to use Licensor Technology (other than Licensor Improvements) to the extent necessary to formulate or have Compounds formulated into bulk Product and package bulk Product into finished Product, solely for sale of Products in the Field and in the Licensed Territory. Without limiting the foregoing, under the license granted under this agreement, Licensor hereby grants to Licensee, during the Term, an exclusive right to access, use and reference all clinical data and regulatory filings, correspondence and approvals of Licensor in order to develop, use, distribute, import and export Compounds and to develop, register, use, distribute, promote, market, offer for sale, sell, have sold, import and export Products, in each case only for the Field and for the Licensed Territory.

License Property

Compound shall mean (a) the drug substance which is known as Kremezin (AST-120), which shall be the spherical adsorptive carbon described in DMF Number 16077 as of the Effective Date, (b) any other carbon-based adsorbent product(activated carbon) consisting of more than 90% carbon, Controlled by Licensor or its Affiliates, which is equivalent or alternative to Kremezin (AST-120), as such terms are defined in the FDA’s “Orange Book” or comparable regulatory standards of the EMEA, or (c) any composition covered under Licensor Technology, which is equivalent or alternative to Kremezin (AST-120), as such terms are defined in the FDA’s “Orange Book” or regulatory standards of the EMEA.

Licensor Patents shall mean
U.S. Patent # 6,830,753 – Adsorbent for oral administration
U.S. Patent # 5,686,081 – Divided package of adsorbent for internal use
U.S. Patent # 5,554,370 – Method for the treatment of inflammatory bowel diseases

Field of Use

Field shall mean any human therapeutic indications in the areas of Gastro-Intestinal Disease and Liver Disease.

This pivotal, double-blind, placebo controlled study, FHAST1 (Fistula Healing with AST-120), has been designed to determine the efficacy and safety of oral AST-120 in 240 patients with Crohn's disease suffering from perianal fistulas.  AST-120 is an oral agent known to adsorb bile acids, toxins and mediators of inflammation from the gastrointestinal tract with the potential to address multiple gastrointestinal diseases.

Licensee also recently announced the initiation of Phase 2 trials with AST-120 in Irritable Bowel Syndrome and Hepatic Encephalopathy.
Irritable bowel syndrome (IBS), referred to previously as spastic or nervous colon, and spastic bowel, is a functional gastrointestinal disorder characterized by a group of symptoms accompanied together that include abdominal pain and changes in the consistency of bowel movements.  Irritable bowel syndrome (IBS) is a common disorder that affects the large intestine. Signs and symptoms include cramping, abdominal pain, bloating, gas, and diarrhea or constipation, or both. IBS is a chronic condition that you'll need to manage long term.

Hepatic encephalopathy (HE) is a common neuropsychiatric complication of liver disease.

License Grant

This agreement is between the Licensor, the Licensee and the Institute Licensee which is a division of the Licensee.

For the Research Program, Licensor agrees to conduct the Research Program in collaboration with the Licensee Institute partner with a goal of discovering, identifying and synthesizing Licensed Compounds for Development by Institute Licensee into one or more Products for commercialization by Licensee, an Affiliate or Sublicensee.

During the Exclusive Screening Period, the Institute Licensee shall have the exclusive right to screen Macrolides provided by Licensor for Antibiotic Activity.

During the Non-exclusive screening period, the Institute Licensee and its Affiliates shall have the non-exclusive right to screen the Macrolides, for any biological activity, in any biological test system for any therapeutic indication.

During the Non-exclusive screening period, the Institute Licensee shall have a non-exclusive right to screen the Aromatic Polyketides for any biological activity in any biological test system for any therapeutic indication.

For the Research Licenses to the Institute Licensee, Licensor grants the Institute Licensee a non-exclusive license, with no right to grant sublicenses, under Licensor Patent Rights  and Know-how to make and use methods and materials to carry, out the Research Program during the Research Term.

For the Screening Licenses, Licensor grants to the Institute Licensee the non-transferable licenses, with the right to grant sublicenses to the Institute Licensee Affiliates, under the Licensor Patent Rights and Know-how to conduct screening, an exclusive, worldwide license during the exclusive screening period to use the Macrolides, to conduct screening for Antibiotic Activity;

– a non-exclusive, worldwide license during the non-exclusive screening period (a) to use the Macrolides to conduct screening for Antibiotic Activity; (b) to use the Aromatic Polyketides to conduct screening for any activity; and

– a non-exclusive, worldwide license during the Exclusive Screening Period and Non-exclusive screening period to use the Macrolides to conduct screening for activities other than Antibiotic Activity, excluding any right to screen the Macrolides for Motilide or Anti-inflammatory Activity.

For the Development and Commercialization License Grant, Licensor grants to Licensee a worldwide, exclusive license, with the right to grant sublicenses, under the Licensor patent rights and know-how, to make, use and develop Licensed Compounds, and, to make, have made, use, import, offer for sale, sell and have Sold Products.

License Property

The Licensed Compound shall mean a particular Macrolide or Aromatic Polyketide, as the case may be, with respect to which the Institute Licensee has provided a Designated Notice and acquired an exclusive license. For purposes of this Agreement, each Close Structure Analog of any such Licensed Compound shall also be deemed to be a Licensed Compound.

Macrolides shall mean 14-membered macrolactones, such as erythromycin, their 3-ketolide congeners, 12-membered macrolactones, 15-membered and 16-membered macrolactones, and other macrolactones or ketolide congeners agreed by the Joint Committee, in each case, obtained by expression of genes from, polyketide, synthase gone clusters including, but not limited to, the erythromycin, rapamycin, tylosin, candicidin, picromycin, or oleandomycin] polyketide, synthase gene clusters, in each case, which are actually utilized in connection with the Research Program that exist in Licensors proprietary compound library as of the effective date; or are synthesized or acquired by or on behalf of Licensor or Licensee in connection with the Research Program.

Motilide Activity shall mean motilin receptor agonist or antagonist activity.

Product shall mean any pharmaceutical product containing a Licensed Compound or a Derivative thereof which is selected for Development and/or marketing by Licensee or its Affiliates or Subllicensees.

Field of Use

Field shall mean the treatment of bacterial infections for all human and animal pharmaceutical applications.

License Grant

The parties agreed to collaborate in the execution of a two-part Phase 2 program to test the efficacy, safety and tolerability of velusetrag.  Licensee has an exclusive option to develop and commercialize velusetrag in the EU, Russia, China, Mexico and certain other countries, while the Licensee from Cayman Islands retain full rights to velusetrag in the United States, Canada, Japan and certain other countries.

License Property

Velusetrag is used in the treatment of patients with gastroparesis (a medical condition consisting of a paresis (partial paralysis) of the stomach, resulting in food remaining in the stomach for a longer time than normal).

Field of Use

This agreement pertains to the drug industry.