Royalty Report: Drugs, Disease, Hormones – Collection: 256257

License Grant

The Licensors and Licensee have entered a Settlement, License and Development Agreement that resolves all outstanding litigation between the companies, including the patent infringement suits brought in the United States and United Kingdom.

With this agreement, Licensee will no longer provide IPLEX to patients with severe Primary IGF-1 Deficiency and other short stature indications and will withdraw its IPLEX marketing authorization application for severe Primary IGF-1 Deficiency in the European Union.

With this agreement, Licensors have waived the damages award by the jury in the U.S. patent infringement litigation.

For the Limited License for Non-Permitted Indications in the United States Licensor grants a non-exclusive, non-sublicenseable license or sublicense, as applicable, under Licensors entire right, title and interest in and to the Licensed Patents to make, have made, use, sell, offer for sale, and import Product for sale in the United States for any Non-Permitted Indication solely for the continuing treatment of any Existing Patient, for a period of twelve months from the Effective Date.

For the License for Named Patient Indications in the European Union on Named Patient Basis;  Licensor grants a limited, non-exclusive, nonsublicenseable license, or sublicense, as applicable, under Licensors entire right, title and interest in and to the Licensed Patents to make, have made, use, sell, offer for sale, and import Product for sale in any country in the European Union solely for the treatment of one or more of the Named Patient Indications, on a Named Patient Basis only.

For the License for Permitted Indications in the Territory, Licensor grants a non-exclusive license, or sublicense, as applicable, with the right to sublicense, under Licensors entire right, title and interest in and to the Licensed Patents to make, have made, use, sell, offer for sale, and import Product for sale in all countries in the Territory, solely for use in the treatment of any of the Permitted Indications.

License Property

Product means any product containing IGF-1 and IGFBP-3, in any dosage, formulation or method of administration, or any co-administration of IGF-1 and IGFBP-3, including without limitation the product known as IPLEX (mecasermin rinfabate) that is sold by Licensee as of the Execution Date. Product does not include any combination product containing IGF-1 and IGFBP-3 and any other active ingredient(s).

Adult Primary IGF-1 Deficiency means abnormally low concentrations of IGF-1 in adults that are not secondary to growth hormone deficiency; and not secondary to specific pathophysiological states outside the GH/IGF-1 system.

ALS means Lou Gehrig’s disease.

IGF-1 means native-sequence insulin-like growth factor-1 from any species with or without an N-terminal methionine, allelic variants thereof, and sequence variants thereof wherein substitutions and/deletions are made in the region from 1 to 5 amino acids from the N-terminus of the mature native-sequence IGF-1 of any species, including des-IGF-1 and variants wherein at least the glutamic acid residue is absent at position 3 from the N-terminus of native-sequence human IGF-1.

IGFBP-3 means native-sequence, insulin-like growth factor binding protein-3 as described in WO 89/09268 published October 5, 1989, that binds IGF-1, including allelic variants of, and animal equivalents to, human BP3 as well as human BP3, for example, the bovine, ovine, porcine and equine species, and may be from any source, whether natural, synthetic, or recombinant, provided that it will bind to the appropriate binding domain of IGF-1.

Trademark means IPLEX(TM)

Licensed Patents means the Licensor controlled patents, that claim the manufacture, use, sale or importation of Product and/or that claim the manufacture, use, sale, or importation of any product or process used in Insmed’s production of Product, including, but not limited to recombinant production of IGF-1 or any IGF-1 binding protein, and purification of IGF-1 or any IGF-1 binding protein.

Field of Use

The field of use Permitted Indications means all indications except the Non-Permitted Indications.   The Non-Permitted Indications are primary IGFD; severe primary IGFD; Noonans syndrome; growth hormone deficiency; adult growth hormone deficiency (as approved by the FDA and consisting of two subgroups: adult and child onset); Adult Primary IGF-1 Deficiency; idiopathic short stature; any other short stature indications; Larons Syndrome; growth hormone insensitivity (OHIS); any diseases or conditions which are approved for sale by Licensors, as of the Effective Date, for the treatment by growth hormone, and all Excluded Indications, which, for the purpose of this Agreement and with respect to Insmed, includes ALS or Lou Gehrig’s disease.

Through licensing and development rights granted by Licensors, Licensee will have freedom to operate regarding the manufacture, development and commercialization of IPLEX for certain non short stature indications including severe insulin resistance, myotonic muscular dystrophy and HIV associated adipose redistribution syndrome (HARS), subject to opt-in rights and royalty provisions for Licensors.

License Grant

This Agreement governs the Development and Commercialization of Combination Products for all Indications in the Field in the Territory.

The parties previously entered agreements to develop and commercialize IGF-1 in the United States and in all foreign countries.  The IGF-1 Agreements contain restrictions on each Partys ability to develop a combination product containing both human growth hormone and IGF-1.  This Agreement will collaborate in the development and commercialization of products containing both human growth hormone and IGF-1.

For the Exclusive/Co-Exclusive License, in the event of a Licensee Opt-In,  Licensor grants to a license, under the Licensor Patents and Licensor Know-How and Licensors interest in the Joint Patents and Joint Know-How, in all cases, to use, offer for sale, sell and import Combination Products in the Field in the Territory and otherwise perform its obligations and exercise its rights under this Agreement.

For the Non-Exclusive License,  in the event of a Licensee Manufacturing Opt-In,  Licensor automatically grants a non-exclusive, sublicensable (without any need for consent) license, under the Licensor Patents and Licensor Know-How;  Licensors interest in the Joint Patents and Joint Know-How;  the license granted to Licensee by Licensor under the previous agreements to Manufacture and import Combination Products;  Manufacture and import IGF-1 alone, BP3 alone, ALS alone and/or IGF-1 combined with BP3 and/or ALS, for use in the Manufacture of Combination Products; and perform research and development activities related to the Manufacture of Combination Products or the Manufacture of those compounds, in all cases, for use and sale within the scope of the license granted to Licensee.

For Joint Trademarks, Licensor automatically grants an exclusive license, under Licensors interest in the Joint Trademarks for Combination Products for such Indication, to use such Joint Trademarks for purposes of Developing and Commercializing Combination Products for such Indication in the Field in the Territory.

License Property

The Combination Product means a pharmaceutical formulation or product for use in the Field that contains GH and IGF-1 (including, without limitation, formulations and products containing GH and IGF-1 combined with BP3, IGF-1 combined with ALS or IGF-1 combined with BP3 and ALS) and that, in all cases, except for the purposes of the definitions of Phase I Clinical Trial and Phase II Clinical Trial, is administered either as a Pre-Mixed Formulation or single injection from a pre-filled, dual-chamber container-closure system (e.g., a syringe or vial). Combination Products include Short Stature Products and Non-Short Stature Products.

IGF-1 means native-sequence insulin-like growth factor-1 from any species with or without an N-terminal methionine, allelic variants thereof, and sequence variants thereof wherein substitutions and/or deletions are made in the region from 1 to 5 amino acids from the N-terminus of the mature native-sequence IGF-1 of any species, including des-IGF-1 and variants wherein at least the glutamic acid residue is absent at position 3 from the N-terminus of native-sequence human IGF-1.

There will be at least one Combination Product for Short Stature Indications (a Short Stature Product) and at least one Combination Product for the AGHD Indication and Other Indications (a Non-Short Stature Product).

A short Stature Product means a Combination Product for a Short Stature Indication.

Non-Short Stature Product means a Combination Product developed for an Indication other than a Short Stature Indication (i.e., for the AGHD Indication or an Other Indication) that contains a different concentration of GH and/or IGF-1 relative to the concentration of GH and/or IGF-1, respectively, in any Short Stature Product and/or a different ratio of GH to IGF-1 relative to the ratio of GH to IGF-1 in any Short Stature Product.

AGHD Indication means the Indication in which an adult patient has growth hormone deficiency as measured by a generally accepted growth hormone stimulation test, where such adult patient either has growth hormone deficiency, either alone or associated with multiple hormone deficiencies (hypopituitarism), as a result of pituitary disease, hypothalamic disease, surgery, radiation therapy or trauma; or was growth hormone deficient during childhood as a result of congenital, genetic, acquired or idiopathic causes.

Licensor Patents means the rights granted by a Patent Office under a Patent Controlled by Licensor during the term of this Agreement (excluding Licensors interest in any Joint Patents), which Patent is necessary or used by Licensor for the Development, Manufacture or Commercialization of any Combination Product in the Field.

Licensor Know-How,, means Know-How (or, with reference to tangible substances, samples of Know-How) Controlled by Licensor during the term of this Agreement (excluding Licensors interest in any Joint Know-How) that is necessary or used by Licensor for the Development, Manufacture or Commercialization of any Combination Product in the Field.

Field of Use

The Field means all prophylactic, diagnostic and therapeutic uses in humans for any Indication. For clarity, Field does not include the Excluded Indications.  'Excluded Indications means any human disease, disorder or condition of the central nervous system (CNS) including, without limitation, CNS diseases and conditions arising out of Closed traumatic injury to head; Open traumatic injury to head; Traumatic or crush injury to spinal cord; Birth asphyxia; Perinatal asphyxia; In utero asphyxia; Toxic injury to brain; Near drowning; Acute meningitis (viral or bacterial); Post cardiac bypass surgery; Post extra corporeal membrane oxygenation; Anaesthetic maladventure; Carbon monoxide poisoning; Status epilepticus; Apparent life threatening event of infancy ( near miss cot death); Asphyxiation; Acute Encephalomyelitis; or, Multiple Sclerosis.

License Grant

The parties previously entered agreements to develop and commercialize IGF-1 in the United States and in all foreign countries.  The IGF-1 Agreements contain restrictions on each Partys ability to develop a combination product containing both human growth hormone and IGF-1.  This Agreement will collaborate in the development and commercialization of products containing both human growth hormone and IGF-1.

For the Exclusive/Co-Exclusive License,  Licensor grants a license, under the Licensor Patents and Licensor Know-How; Licensors interest in the Joint Patents and Joint Know-How; the GNE Patents and GNE Know-how as identified in the previous agreements,  to use, offer for sale, sell and import Combination Products in the Field in the Territory and otherwise perform its obligations and exercise its rights under this Agreement.

For the Non-Exclusive License, Licensor grants a non-exclusive license, under the Licensor Patents and Licensor Know-How; Licensors interest in the Joint Patents and Joint Know-How;  the GNE Patents and GNE Know-how,  as defined in the previous Agreements to Manufacture, but not to have Manufactured,
Combination Products; Manufacture (but not to have Manufactured, and import IGF-l alone, BP3 alone, ALS alone and/or IGF-1 combined with BP3 and/or ALS, for use in the Manufacture of Combination Products; and perform research and development activities related to the Manufacture of Combination Products or the Manufacture of those compounds, for use and sale within the scope of the license granted.

For the Joint Trademarks, Licensor automatically grants exclusive license, under Licensors interest in the Joint Trademarks for Combination Products for such Indication, to use such Joint Trademarks for
purposes of Developing and Commercializing Combination Products for such Indication in the Field in the Territory.

This Agreement governs the Development and Commercialization of Combination Products for all Indications in the Field in the Territory.

License Property

The patents relate to  IGF-1.  IGF-1 means native-sequence insulin-like growth factor-1 from any species with or without an N-terminal methionine, allelic variants thereof, and sequence variants thereof wherein substitutions and/or deletions are made in the region from 1 to 5 amino acids from the N-terminus of the mature native-sequence IGF-1 of any species, including des-IGF-1 and variants wherein at least the glutamic acid residue is absent at position 3 from the N-terminus of native-sequence human IGF-1.

“Joint Trademarks” means any Trademark or pending Trademark application for the identification of a Combination Product that is registered or filed with the United States Patent and Trademark Office or an agency in a foreign country in the Territory, which agency is the foreign equivalent of the United States Patent and Trademark Office.

The Combination Product means a pharmaceutical formulation or product for use in the Field that contains GH and IGF-1 (including, without limitation, formulations and products containing GH and IGF-1 combined with BP3, IGF-1 combined with ALS or IGF-1 combined with BP3 and ALS) and that, in all cases, except for the purposes of the definitions of Phase I Clinical Trial and Phase II Clinical Trial, is administered either as a Pre-Mixed Formulation or single injection from a pre-filled, dual-chamber container-closure system (e.g., a syringe or vial). Combination Products include Short Stature Products and Non-Short Stature Products.

There will be at least one Combination Product for Short Stature Indications (a Short Stature Product) and at least one Combination Product for the AGHD Indication and Other Indications (a Non-Short Stature Product).

Field of Use

The Field means all prophylactic, diagnostic and therapeutic uses in humans for any Indication. For clarity, Field does not include the Excluded Indications.  Excluded Indications means any human disease, disorder or condition of the central nervous system (CNS) including, without limitation, CNS diseases and conditions arising out of Closed traumatic injury to head; Open traumatic injury to head; Traumatic or crush injury to spinal cord; Birth asphyxia; Perinatal asphyxia; In utero asphyxia; Toxic injury to brain; Near drowning; Acute meningitis (viral or bacterial); Post cardiac bypass surgery; Post extra corporeal membrane oxygenation; Anaesthetic maladventure; Carbon monoxide poisoning; Status epilepticus; Apparent life threatening event of infancy ( near miss cot death); Asphyxiation; Acute Encephalomyelitis; or, Multiple Sclerosis.

The collaboration is for the development, manufacture and worldwide commercialization of two products containing Licensor's recombinant human growth hormone Nutropin AQ® [somatropin (rDNA origin)] and Licensee's recombinant insulin-like growth factor-1 Increlex® (mecasermin [rDNA origin] injection) for the treatment of short stature, adult growth hormone deficiency (AGHD), and potentially other metabolic disorders.

License Grant

A jury in the US District Court for the Northern District of California has found that licensee infringed licensor's US Patent No. 5,258,287, willfully infringed US Patent No. 5,187,151 and upheld the validity of US Patent No. 6,331,414. Co-licensor exclusively licensed these patents in April 2002, for use in its manufacture and sale of, among other things, Increlex (mecasermin [rDNA origin] injection). Prior to the trial, the Court had ruled that Licensor's process for making the insulin-like growth factor-1 (IGF-1) in iPlex (me-casermin) literally infringes three claims of the '414 patent.  In March 2007 — The parties reached a settlement that ended the patent-infringement case. Both companies have been selling drugs that treat children who suffer from a rare disorder that makes them abnormally short. Licensee will work with patients who use its drug to identify alternative treatments. Key patents for licensee's drug are held by licensor which licensed the rights to another party in 2002. In December, a California jury said licensee had breached the patents.

Field of Use

The company is free to develop, manufacture and sell its drug, called iPlex, for other diseases – including severe resistance to insulin, a form of muscular dystrophy and an HIV-related condition.

License Grant

Licensee shall have the exclusive option to include the Option Territory.

For the Exclusive License, Licensor grants an exclusive right and license, with the right to grant sublicenses under the Licensor Technology and Licensors interest in and to the Joint Collaboration Technology to make, and have made, use, and import Formulations and Products in the Field in the Licensed Territory and sell and offer for sale Products in the Field in the Licensed Territory.

For the Non-Exclusive License, as applicable prior to the expiration of the Option Period or if Licensee does not exercise the Option, Licensor further grants a non-exclusive right and license, with the right to grant sublicenses, under the Licensor Technology to make, and have made, Formulations and Products in the Field in the Option Territory, and to use, and import, but not sell or offer for sale, Formulations and Products in the Field in the Option Territory; in each case solely for the purpose of developing Formulations and Products and commercializing Products in the Field in the Licensed Territory.

License Property

Licensor is engaged in the development and commercialization of protein therapeutics for patients with chronic gastrointestinal and metabolic diseases and is currently developing a drug product candidate, known as ALTU-238, for the treatment of patients with growth hormone disorders.

ALTU-238 means any pharmaceutical product containing a polyarginine-Complexed crystal formulation,
including the formula designated by the internal Licensor Compound code ALTU-238.

Compound means synthetic, natural or recombinant human growth hormone or any of its active fragments, analogues derivatives or other variants.

Formulation means any composition containing a polycation-Complexed crystallized Compound.

Product means any pharmaceutical product containing a Formulation, and not any other active pharmaceutical ingredient that is not a Compound which active pharmaceutical ingredient is Covered by a Valid Claim within the Licensor Technology or that uses or embodies Licensor Know-How.

ALTU-238 is a long-acting subcutaneous formulation of recombinant human growth hormone, in a ready-to-use liquid suspension formulation, that employs Licensor's proprietary protein crystallization and formulation technology. Altus' technology preserves the structure of the human growth hormone molecule without the need for polymers or encapsulation and enables administration through a fine gauge needle. Recombinant human growth hormone is approved for treating multiple growth disorders in children and adolescents and for growth hormone replacement in adults.

Field of Use

ALTU-238 is a subcutaneously administered, once-per-week formulation of human growth hormone, which employs Licensor's proprietary protein crystallization and formulation technology, for patients with growth hormone deficiencies.

License Grant

For the Conduct of Development Plan, Licensor grants a non-exclusive, non-transferable, non-sublicenseable right and license under the Licensor Technology, Licensor Collaboration Technology, Licensee Technology and Joint Collaboration Technology; in each case to make and use, but not sell, offer for sale or import, Products in the Field in the North American Territory solely to the extent necessary for Licensee to perform those development activities with respect to a Formulation or Product to be performed by Licensee, and, to conduct certain other activities approved in advance by Licensor.

For the Co-Promotion, Licensor grants a non-exclusive, non-transferable, non-sublicenseable, right and license under the Licensor Technology, Licensor Collaboration Technology, Licensee Technology and Joint Collaboration Technology; in each case solely to the extent necessary, to Co-Promote Products in the Co-Promote Territory in the Field.

For the Polycation Collaboration Technology, Licensor grants a non-exclusive, non-transferable right and license under the Polycation Collaboration Technology to make, use, sell, offer for sale or import any product that is not a Formulation or Product in the Licensed Territory, and any product outside of the Licensed Territory.

For the Licensor Housemarks, Licensor grants a non-exclusive, non-transferable, non-sublicenseable, right and license to use the Licensor Housemarks and Product Trademarks solely in connection with Licensees Co-Promotion of Products in the Co-Promote Territory in the Field.

This agreement also includes exclusive grants back to Licensor from Licensee.

License Property

Licensor has significant experience in the development and commercialization of drug products, particularly growth hormone products,

Compound means synthetic, natural or recombinant human growth hormone or any of its active fragments, analogues derivatives or other variants.

Formulation means any composition containing a polycation-Complexed crystallized Compound.

Product means any pharmaceutical product containing a Formulation, and not any other active pharmaceutical ingredient that is not a Compound which active pharmaceutical ingredient is Covered by a Valid Claim within the Licensor Technology or that uses or embodies Licensor Know-How.

Field of Use

This agreement pertains to the drug industry.  Field means the prevention, treatment or control of any disease or condition in humans.

License Grant

The European Commission granted marketing authorization for Increlex® in the European Union for the long-term treatment of growth failure in children and adolescents with severe primary insulin-like growth factor deficiency. Under the Increlex License, the Licensee paid the Licensor a milestone payment for receiving marketing authorization of Increlex® in the European Union for the targeted product label set forth in the Increlex License. Increlex® was launched in the Licensee's territory in November 2007.

License Property

Increlex is used to treat growth failure in children whose bodies do not make enough IGF-1 or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH.

License Grant

The Licensee became the exclusive subLicensee of US Patent No. 5,288,703 for the U.S. market.

This Sublicense includes the rights to distribute the L-glutamine treatment for the treatment of Short Bowel Syndrome under the trademark NutreStore® in the U.S., and commercially launched NutreStore® in June 2008.

License Property

The subLicense is subject to a subLicense that the Licensor holds from Ares Trading, S.A., and if the Ares License is terminated for any reason, then our subLicense will also terminate.

Field of Use

The rights granted apply to the mammal industry relating to gut absorption.

License Grant

Irish Party A sold the United States and Canadian rights to Macrilenâ„¢ (macimorelin) under the License and Assignment Agreement to Party B for a payment plus tiered royalties on net sales and Party B will fund Party As Macrilenâ„¢(macimorelin) field organization as a contract field force to promote the product in the United States for up to three years.  Party A had a License and Assignment Agreement with Party C to to carry out development, manufacturing, registration, regulatory and supply chain services for the commercialization of Macrilenâ„¢ (macimorelin) in the U.S. and Canada. This agreement provides (i) for the 'right to use' license relating to the Adult Indication.

License Property

The Adult Indication is Macrilenâ„¢ (macimorelin), a ghrelin receptor agonist, is a novel orally-active small molecule that stimulates the secretion of growth hormone. The FDA has granted marketing approval for Macrilenâ„¢ (macimorelin) to be used in the diagnosis of adult growth hormone deficiency (AGHD).

Field of Use

This agreement pertains to the drug industry.