Royalty Report: Drugs, Disease, Therapeutic – Collection: 263948

License Grant

Licensor grants to the Swiss Licensee a worldwide, exclusive, even as to Licensor, license under the Licensor IP to research, develop, make, have made, use, import, have sold, sell and offer to sell Licensed Products.

License Property

The intellectual property is in respect to Recombinant Factor XIII and related preclinical and clinical studies.

Patent Product means a product that contains Recombinant Factor XIII, the making, using, importation, exportation, offer for sale or sale of which product would infringe, in the absence of the licenses granted under this Agreement, any unexpired Patent Claim.

Recombinant Factor VIIa and rFVIIa mean a protein that has an amino acid sequence of human factor VIIa or its subunits and that is produced by recombinant DNA techniques (including without limitation, production in prokaryotic and eukaryotic host cells and transgenic animals), including variants, derivatives, modifications, fragments, hybrids, mutants, conjugates, fusion proteins and analogs of such protein. Recombinant Factor VIIa and rFVIIa shall mean the active Factor VIIa protein in Licensee’s product known as NovoSeven®.

Recombinant Factor XIII and rFXIII mean a protein that has an amino acid sequence of human factor XIII or its subunits, or any combination thereof, and that is produced by recombinant DNA techniques, including, without limitation, production in prokaryotic and eukaryotic host cells and transgenic animals, including variants, derivatives, modifications, fragments, hybrids, mutants, conjugates, fusion proteins and analogs of such protein.

NovoSeven (coagulation factor viia recombinant) is a vitamin K-dependent glycoprotein consisting of 406 amino acid residues (MW 50 K Dalton). NovoSeven (coagulation factor viia recombinant) is structurally similar to human plasma-derived Factor VIIa.

Field of Use

The field of use is Cancer Treatment or Cardiac Surgery.

Cancer Treatment Indication means bleeding in a patient with malignancy that occurs either as a consequence of the malignancy or the treatment of the malignancy and requires medical intervention.

Cardiac Surgery Indication means bleeding or oozing of blood in a patient undergoing cardiac surgery or having undergone cardiac surgery that occurs during or following the surgery and requires medical intervention.

NovoSeven® RT (Coagulation Factor VIIa [Recombinant]) is used for:
– Treatment of bleeding and prevention of bleeding for surgeries and procedures in adults and children with hemophilia A or B with inhibitors, congenital Factor VII (FVII) deficiency, and people with Glanzmann’s thrombasthenia who have a decreased or absent response to platelet transfusions
– Treatment of bleeding and prevention of bleeding for surgeries and procedures in adults with acquired hemophilia

License Grant

The German Licensor hereby grants to Licensee and Licensee hereby accepts from Licensor, upon the terms and conditions herein specified, an exclusive license under the Licensed Patents in the Territory, and in the Field of Use to develop, make, have made, import, have imported, use, offer for sale, sell, have sold and otherwise commercialize Licensed Product(s). For the avoidance of doubt, the exclusive license granted hereby relates solely to Recombinant Factor XIII.

License Property

Licensed Product(s) means any product that contains Recombinant Factor XIII and is covered by a Valid Claim of an issued patent falling within the Licensed Patents or that, but for this Agreement, would infringe a Valid Claim of an issued patent falling within the Licensed Patents.

Recombinant Factor XIII means a protein having the amino acid sequence of naturally occurring factor XIII and that is produced by recombinant DNA techniques, including without limitation production in prokaryotic and eukaryotic host cells and transgenic animals, as well as variants, derivatives, modifications, fragments, hybrids, mutants, conjugates, fusion proteins, analogs, orthologs and homologs thereof.

Licensed Patents means: (a) the patents and the patent applications set forth and made part of this Agreement; (b) all parent, provisional, divisional, continuation (in whole or in part) or substitute applications with respect to any of the patent applications; (c) any other patent applications, both U.S. and foreign, based on the patent applications or; all issued or granted patents resulting from any of the patent applications described above; and (e) all issued or granted reissue, re-examination, renewal or extension patents, supplementary protection certificates, and confirmation or registration patents or patents of addition based on any of the patents described.

Licensed Patents:
6,084,074 – Stabilized aqueous liquid preparations of blood coagulation factor XIII
6,204,036 – Stable transglutaminase preparations and processes for their production
5,688,919 – Process for the purification of factor XIII, monoclonal antibodies against factor XIIIA, the preparation and use thereof

Field of Use

These include rFactor XIII for the treatment of congenital and acquired Factor XIII deficiencies, recombinant human Thrombin (rhThrombin) as a topical hemostat to control surgical bleeding and TACI-Ig for the treatment of autoimmune diseases including Systemic Lupus Erythematosus.

License Grant

The parties amend and replace the Original Agreement to separate the next generation recombinant coagulation Factor VIII into its own Agreement.  Licensor hereby grants, and agrees to grant, to Danish Licensee, as of the Original Date , the following rights and licenses:

Exclusive License.  As of the Original Date, Licensor hereby grants, and agrees to grant, to Licensee an exclusive (even as to Licensor), royalty-bearing license in the Field of Use under the Licensor Intellectual Property used or required to be used in the Field of Use during the Term, (i) to conduct research, sample, develop (including clinical development), manufacture, make, use, market, promote, sell, offer for sale, have sold, distribute, import and export New Products in the Territory, and (ii) to use the Reagents in the Territory solely for the purpose of making New Products.

Limited Sublicense Rights: Licensee shall be entitled to grant full sublicenses to its Affiliates and limited sublicenses to its distribution, marketing and/or sales partners, in each case, in compliance with this Agreement.

License Property

Licensor Patents means (a) all Patent Rights relating to methods and processes for glycosylation design and remodeling of proteins, peptides and antibodies that are  Controlled by Licensor, including, but not limited to the Patent Rights listed.
6,800,468 – UDP-galactose: .beta.-N-acetyl-glucosamine .beta.1,3galactosyltransferases, .beta.3Gal-T5
6,995,004 – UDP-N-ACETYLGLUCOSAMINE: GALACTOSE-.beta. 1,3-N-ACETYLGALACTOSAMINE-.alpha.-R / N-ACETYLGLUCOSAMINE-.beta. 1,3,-N-ACETYLGALACTOSAMINE-.alpha.-R (GLCNAC TO GALNAC) .beta.1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE, C2/4GNT
6,635,461 – UDP-N-acetylglucosamine: galactose-.beta.1, 3-N-acetylgalactosamine-.alpha.-R/(GlcNAc to GalNAc) .beta.1,6-N-acetylglucosaminyltransferase, C2GnT3

New Product shall mean the following: (a) any of the Licensee Materials modified using either (i) the Licensor Technology, (ii) any Licensor Improvements, or (iii) any combination of all or some of (i) and (ii) above, and (b) any Licensee Materials covered by any Carved Factor VIII Claims (except to the extent such claims constitute Licensee Improvements).

M1 Profile for the New Factor VIII Product means the parameters for candidate selection required for PEG-F8.

Reagents means the enzymes and sugar nucleotides required to use the Licensor Technology in the manufacture of New Products.

Carved Factor VIII Claims shall mean any Potential Carved Factor VIII Claim with respect to which the parties have filed a separate patent application.

Potential Carved Factor VIII Claims shall mean any composition-of-matter claims and any method of treatment claims that are supported by Patent Rights Controlled by Licensor that (i) do or could explicitly and solely recite and claim Licensee Materials, or (ii) any Licensee Improvements made or reduced to practice by Licensor.

Product-Candidate means any new hemostasis product-candidate Controlled by Licensor during the Term.

Licensor Intellectual Property means Licensor Technology and the Licensor Improvements.

Licensor Technology means the Licensor Patents and any Know-How Controlled by Licensor relating to methods and processes for the glycosylation design and remodeling of proteins, peptides and antibodies, including, without limitation, its GlycoAdvance®, GlycoPEGylation™ and GlycoConjugation™ technologies, and other carbohydrate synthesis processes, and all Know-How resulting from work conducted by Licensor during the Term.

Licensor Improvements means any and all Improvements relating to the Licensor Technology made, conceived, or reduced to practice by (i) either Licensor or Licensee or both in the conduct of the Original Work Plan under the Original Agreement or the Work Plan under this Agreement, (ii) either Licensor or Licensee or both under this Agreement.

GlycoPEG-FVIIa is a long-acting form of recombinant Factor VIIa that is being developed by our partner, Novo Nordisk A/S, utilizing our GlycoPEGylation technology. Factor VIIa is used in the treatment of bleeding episodes and for the prevention of bleeding during surgery or invasive procedures in patients with congenital hemophilia with inhibitors to coagulation Factors VIII or IX.

Field of Use

Licensee is also developing long-acting forms of recombinant Factor VIII and recombinant Factor IX utilizing our GlycoPEGylation technology. Factor VIII products are used in the treatment of Hemophilia A, and Factor IX products are used in the treatment of Hemophilia B.

License Grant

The parties amend and replace the Original Agreement to separate the next generation recombinant coagulation Factor IX into its own Agreement.  Licensor hereby grants, and agrees to grant, to Danish Licensee, as of the Original Date , the following rights and licenses:
Exclusive License.  As of the Original Date, Licensor hereby grants, and agrees to grant, to Licensee an exclusive (even as to Licensor), royalty-bearing license in the Field of Use under the Licensor Intellectual Property used or required to be used in the Field of Use during the Term, (i) to conduct research, sample, develop (including clinical development), manufacture, make, use, market, promote, sell, offer for sale, have sold, distribute, import and export New Products in the Territory, and (ii) to use the Reagents in the Territory solely for the purpose of making New Products.  
Limited Sublicense Rights.  Licensee shall be entitled to grant full sublicenses to its Affiliates and limited sublicenses to its distribution, marketing and/or sales partners.

License Property

Licensor Patents means (a) all Patent Rights relating to methods and processes for glycosylation design and remodeling of proteins, peptides and antibodies that are   Controlled by Licensor, including, but not limited to, (i) the Patent Rights listed.

6,800,468 – UDP-galactose: .beta.-N-acetyl-glucosamine .beta.1,3galactosyltransferases, .beta.3Gal-T5
6,995,004 – UDP-N-ACETYLGLUCOSAMINE: GALACTOSE-.beta. 1,3-N-ACETYLGALACTOSAMINE-.alpha.-R / N-ACETYLGLUCOSAMINE-.beta. 1,3,-N-ACETYLGALACTOSAMINE-.alpha.-R (GLCNAC TO GALNAC) .beta.1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE, C2/4GNT
6,635,461 – UDP-N-acetylglucosamine: galactose-.beta.1, 3-N-acetylgalactosamine-.alpha.-R/(GlcNAc to GalNAc) .beta.1,6-N-acetylglucosaminyltransferase, C2GnT3

Carved Factor IX Claims shall mean any Potential Carved Factor IX Claim with respect to which the parties have filed a separate patent application.

Potential Carved Factor IX Claims shall mean any composition-of-matter claims and any method of treatment claims that are supported by Patent Rights Controlled by Licensor that (i) do or could explicitly and solely recite and claim Licensee Materials, or (ii any Licensee Improvements made or reduced to practice by Licensor.

Reagents means the enzymes and sugar nucleotides required to use the Licensor Technology in the manufacture of New Products.

New Product shall mean the following: (a) any of the Licensee Materials modified using either (i) the Licensor Technology, (ii) any Licensor Improvements, or (iii) any combination of all or some of (i) and (ii) above, and (b) any Licensee Materials covered by any Carved Factor IX Claims (except to the extent such claims constitute Licensee Improvements).

Licensor Exclusive Compounds shall mean any and all forms of erythropoietin and granulocyte colony stimulating factor including, but not limited to, with respect to either of the foregoing: full length proteins, truncated proteins, fusion proteins, analogs, mutants, splice variants, and conjugates with other molecular entities such as proteins, peptides, organic or inorganic substances.

M1 Profile for the New Factor IX Product means the parameters for candidate selection required for PEG-F9, as amended from time to time.

Licensor Intellectual Property means Licensor Technology and the Licensor Improvements.

Licensor Technology means the Licensor Patents and any Know-How Controlled by Licensor relating to methods and processes for the  glycosylation design and remodeling of proteins, peptides and antibodies, including, without limitation, its GlycoAdvance®, GlycoPEGylationâ„¢ and GlycoConjugationâ„¢ technologies, and other carbohydrate synthesis processes, and all Know-How resulting from work conducted by Licensor during the Term.

Licensor Improvements means any and all Improvements relating to the Licensor Technology made, conceived, or reduced to practice by (i) either Licensor or Licensee or both in the conduct of the Original Work Plan under the Original Agreement or the Work Plan under this Agreement, (ii) either Licensor or Licensee or both under this Agreement.

Patent Rights shall mean individually and collectively any and all patents and/or patent applications and provisional applications, all inventions disclosed therein, and any and all continuations, continuations-in-part, continued prosecution applications, divisions, renewals, patents of addition, reissues, confirmations, registrations, revalidations, revisions and re-examinations thereof, utility models, petty patents, design registrations and any and all patents issuing therefrom and any and all foreign counterparts thereof and extensions of any of the foregoing including without limitation extensions under the U.S. Patent Term Restoration Act, extensions under the Japanese Patent Law, and Supplementary Protection Certificates (SPCs) according to Counsel Regulation (EEC) No. 1768/92 and similar extensions for other patents under any applicable law in any country of the world.

Field of Use

Factor VIIa is used in the treatment of bleeding episodes and for the prevention of bleeding during surgery or invasive procedures in patients with congenital hemophilia with inhibitors to coagulation Factors VIII or IX.

License Grant

The parties collaborated to develop a long-acting Factor VII compound and amended the Original Agreement to incorporate all of the Amendments into one document.

Licensor hereby grants, and agrees to grant, to Swiss Licensee an exclusive (even as to Licensor), royalty-bearing license under the Licensor Intellectual Property in the Field of Use during the Term, (i) to conduct research, sample, develop (including clinical development), manufacture, make, use, market, promote, sell, offer for sale, have sold, distribute, import and export New Products in the Territory, and (ii) to use the Reagents in the Territory solely for the purpose of making New Products. Such license does not permit Licensee (x) to practice or use the Licensor Intellectual Property outside the Field of Use or (y) to sublicense any of its rights without the prior written approval of Licensor.

Licensor hereby grants, and agrees to grant, to Licensee a worldwide, exclusive (even as to Licensor), perpetual, irrevocable, and royalty-bearing (subject only to the payment of royalties in accordance with this agreement) license, with the right to sublicense, to any Carved Factor VII Claims that do not constitute Licensee Improvements for any and all purposes. In addition to the foregoing, Licensor hereby grants, and agrees to grant, to Licensee a worldwide, exclusive (even as to Licensor), perpetual, irrevocable, and royalty-free license, with the right to sublicense, to any Carved Factor VII Claims that constitute Licensee Improvements for any and all purposes.

License Property

New Product shall mean the following: (a) any of the Licensee Materials modified using either (i) the Licensor Technology, (ii) any Licensor Improvements, or (iii) any combination of all or some of (i) and (ii) above, and (b) any Licensee Materials covered by any Carved Factor VII Claims (except to the extent such claims constitute Licensee Improvements) .

Potential Carved Factor VII Claims shall mean any composition-of-matter claims and any method of treatment claims that are supported by Patent Rights Controlled by Licensor that (i) do or could explicitly and solely recite and claim Licensee Materials, or (ii) any Licensee Improvements made or reduced to practice by Licensor.

Licensor Technology means the Licensor Patents and any Know-How Controlled by Licensor relating to methods and processes for the glycosylation design and remodeling of proteins, peptides and antibodies, including, without limitation, its GlycoAdvance®, GlycoPEGylation™ and GlycoConjugation™ technologies, and other carbohydrate dynthesis processes, and all Know-How resulting from work conducted by Licensor during the Term.

Licensor Patents means (a) all Patent Rights relating to methods and processes for glycosylation design and remodeling of proteins, peptides and antibodies that are Controlled by Licensor, including, but not limited to: (i) the Patent Rights listed, (ii) the Patent Rights developed by Licensor in the conduct of the Work Plan during the Term of this Agreement, and (iii) any later acquired Patent Rights Controlled by Licensor and used to develop any New Product, and (b) all Patent Rights Controlled by Licensor that would be infringed by the research, development (including clinical development), manufacture, making, use, marketing, promotion, sale, offer for sale, distribution, import and export of New Products in the Territory.
US Patent #6,800,468 – UDP-galactose: .beta.-N-acetyl-glucosamine .beta.1,3galactosyltransferases, .beta.3Gal-T5
US Patent #6,995,004 – UDP-N-ACETYLGLUCOSAMINE: GALACTOSE-.beta. 1,3-N-ACETYLGALACTOSAMINE-.alpha.-R / N-ACETYLGLUCOSAMINE-.beta. 1,3,-N-ACETYLGALACTOSAMINE-.alpha.-R (GLCNAC TO GALNAC) .beta.1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE, C2/4GNT
US Patent #6,635,461 – UDP-N-acetylglucosamine: galactose-.beta.1, 3-N-acetylgalactosamine-.alpha.-R/(GlcNAc to GalNAc) .beta.1,6-N-acetylglucosaminyltransferase, C2GnT3

Licensor Improvements means any and all Improvements relating to the Licensor Technology made, conceived, or reduced to practice by (i) either Licensor or Licensee or both in the conduct of the Work Plan under this Agreement, (ii) either Licensor or Licensee or both under this Agreement, (iii) Licensee in the practice of any Licensor Technology under the licenses granted to Licensee in this agreement, or (iv) Licensee in the conduct of any activity using any Ownership Rights assigned to Licensee pursuant to this Agreement, in each case of (i), (ii), (iii) or (iv), other than the Licensee Materials, the Licensee Materials modified using the Licensor Technology and New Product. Specifically excluded from Licensor Improvements are (1) formulations, combinations and methods of treatment to the extent relating to Licensee Materials, the Licensee Materials modified using the Licensor Technology and New Products and (2) analytical techniques and purification methods invented, developed or reduced to practice solely by Licensee that did not originate from or are not derived from Licensor (collectively, the Techniques).

Licensor Intellectual Property means Licensor Technology and the Licensor Improvements.

Patent Rights shall mean individually and collectively any and all patents and/or patent applications and provisional applications, all inventions disclosed therein, and any and all continuations, continuations-in-part, continued prosecution applications, divisions, renewals, patents of addition, reissues, confirmations, registrations, revalidations, revisions and re-examinations thereof, utility models, petty patents, design registrations and any and all patents issuing therefrom and any and all foreign counterparts thereof and extensions of any of the foregoing including without limitation extensions under the U.S. Patent Term Restoration Act, extensions under the Japanese Patent Law, and Supplementary Protection Certificates (SPCs) according to Counsel Regulation (EEC) No. 1768/92 and similar extensions for other patents under any applicable law in any country of the world. Licensee hereby grants to Licensor, for the term of the Work Plan, a non-exclusive, royalty free, license under the Licensee Technology to use such Licensee Technology for the sole purpose of carrying out its obligations under the Work Plan. Licensee shall retain at all times all of its rights, title and interest to the Licensee Technology.

Licensor Exclusive Compounds shall mean any and all forms of erythropoietin and granulocyte colony stimulating factor including, but not limited to, with respect to either of the foregoing: full length proteins, truncated proteins, fusion proteins, analogs, mutants, splice variants, and conjugates with other molecular entities such as proteins, peptides, organic or inorganic substances.

Field of Use

Licensor's technology is to develop and commercialize next-generation versions of Factors VIIa, VIII and IX.

Factor VIIa is used in the treatment of bleeding episodes and for the prevention of bleeding during surgery or invasive procedures in patients with congenital hemophilia with inhibitors to coagulation factors VIII or IX.

License Grant

The development and commercialization agreement is to develop and commercialize ELOCTATE and ALPROLIX globally.  Each party have specific territories.

License Property

ELOCTATE [Antihemophilic Factor (Recombinant), Fc Fusion Protein] and ALPROLIX [Coagulation Factor IX (Recombinant), Fc Fusion Protein], are extended half-life clotting-factor therapies for the treatment of hemophilia A and hemophilia B, respectively. ELOCTATE and ALPROLIX use a process known as Fc fusion to link recombinant factor VIII and factor IX, respectively, to a protein fragment in the body known as Fc. The fusion of the factor with the Fc protein fragment uses a naturally occurring pathway and is designed to extend the half-life of the factor, thereby making the product last longer in a persons blood than traditional factor therapies.

Field of Use

The agreement is for the drug industry, specifically for clotting-factor therapies.

License Grant

Licensor, an university grants:
—  an exclusive license under the Licensed Patent Rights to manufacture, have manufactured, import, have imported, use, sell, offer for sale, lease or otherwise dispose of Products in the Territory in the Field of Use; and

—  a Co-Exclusive license under the Licensed Patent Rights to manufacture, have manufactured, import, have imported, use, sell, offer for sale, lease or otherwise dispose of Products in the Territory in the Field of Use.

License Property

The patents are for Modified vitamin K-dependent polypeptides.

Vitamin K serves as an essential cofactor for a carboxylase that catalyzes carboxylation of glutamic acid residues on vitamin K-dependent proteins. The key vitamin K-dependent proteins include: Coagulation proteins: factors II (prothrombin), VII, IX and X. Anticoagulation proteins: proteins C, S and Z.

Field of Use

The Fields of Use are:
—  Use of Factor VII and/or Factor VIIa, optionally linked to one or more PEG polymers, alone or in combination with other active ingredients for treating or preventing human or animal diseases, with the proviso that any such Factor VII and/or Factor VII a includes at least one mutation in the GLA domain; and,
—  Use of Factor VH and/or Factor VIIa, linked to one or more PEG polymers, alone or in combination with other active ingredients for treating or preventing human or animal diseases, with the proviso that any such Factor VII and/or Factor VIIa includes at least one mutation outside the GLA domain and no mutations in the GLA domain.

License Grant

The development and commercialization agreement is to develop and commercialize ELOCTATE and ALPROLIX globally.  Each party has specific territories.

License Property

ELOCTATE [Antihemophilic Factor (Recombinant), Fc Fusion Protein] and ALPROLIX [Coagulation Factor IX (Recombinant), Fc Fusion Protein], are extended half-life clotting-factor therapies for the treatment of hemophilia A and hemophilia B, respectively. ELOCTATE and ALPROLIX use a process known as Fc fusion to link recombinant factor VIII and factor IX, respectively, to a protein fragment in the body known as Fc. The fusion of the factor with the Fc protein fragment uses a naturally occurring pathway and is designed to extend the half-life of the factor, thereby making the product last longer in a persons blood than traditional factor therapies.

Field of Use

The agreement is for the drug industry, specifically for clotting-factor therapies.

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

The License is granted for the purpose of developing, making, using, selling and otherwise disposing of Product.

The Licensor of England grants to the Licensee the following License:
(i)  a non-exclusive sub-license under United States Patent 4,994,371 to manufacture or have made for it Products and to use, sell or otherwise dispose of, anywhere in the world, Products made in the United States; and,
(ii)  a non-exclusive license under the other Patents to manufacture or have made for it Products and to use, sell or otherwise dispose of, anywhere in the world, Products made in the countries covered by the aforesaid other Patents.

License Property

The patents are for Factor IX Gene Clone.

Field of Use

The field of use is human recombinant Factor IX protein produced from cell culture.  The Field shall exclude any product, therapy, treatment or procedure in which living material is administered or howsoever brought into contact with the recipient of the therapy, treatment or procedure, or any product made for such purpose.  The Field shall also exclude gene therapy or transgenics, or the production by gene therapy, or transgenic animals or transgenic plants, of recombinant Factor IX protein.

License Grant

For the Co-Development license,  Licensor grants to the Licensee of Bermuda, an exclusive, except as to Licensor and its Affiliates and sublicensees, sublicensable license under the Licensor Collaboration Technology to Develop Collaboration Products for Commercialization in the Territory in the Field.

For the Commercialization license, Licensor grants an exclusive, except in the United States as to Licensor and its Affiliates and sublicensees in accordance with the terms of this Agreement, sublicensable license under the Licensor Collaboration Technology to make, have made, use, have used, sell, have sold, offer for sale, import, have imported and otherwise Commercialize Collaboration Products in the Territory in the Field.

Licensor grants an exclusive license under the Manufacturing Technology and under any Patent Rights and other intellectual property rights which may arise that are directed thereto, to develop, have developed, use, make, have made, have used, sell, have sold, offer for sale, import, have imported and otherwise Commercialize the Collaboration Products in the Territory in the Field.

License Property

Albuferon is a novel, long-acting form of interferon alpha. It is a Human Genome Sciences drug created using the Licensor's proprietary albumin fusion technology. This technology enables scientists to improve the pharmacological properties of therapeutic proteins by fusing the gene that expresses human albumin to the gene that expresses the active protein. Albuferon results from the genetic fusion of human albumin and interferon alpha 2b. Recombinant interferon alpha is approved for the treatment of hepatitis C, hepatitis B and a broad range of cancers

Licensors product Albuferon means a polypeptide having an interferon-alpha molecule, or any variants, analogs, homologs, derivatives, modifications, mutants or fragments thereof, including species-specific modifications thereof, genetically fused to recombinant human albumin, or any variants, analogs, homologs, derivatives, modifications, mutants or fragments thereof, including species-specific modifications thereof, as a single polypeptide chain. For the sake of clarity, Albuferon shall include, but not be limited to, interferon alpha 2a and 2b, but shall not include other non-interferon-alpha molecules, such as interferon-beta or interferon-gamma.

Licensors Collaboration Technology shall mean Licensors Patent Rights and Know-How, but shall not include Manufacturing Technology.  Licensors Patent Rights and Know-how shall mean Albumin Fusion Patent Rights, Albuferon Patent Rights, and Licensors Arising Patent Rights, and, Albumin Fusion Know-How and Arising Know-How.

Field of Use

The Field shall mean all therapeutic, diagnostic and prophylactic indications in humans and animals, with specific First Indication meaning the Hepatitis C indication and general disease.

Clinical studies to date indicate that Albuferon could offer improved dosing in the treatment of chronic hepatitis C, with efficacy and safety at least comparable to the current standard of care, pegylated interferons. These results demonstrate that Albuferon is well tolerated, remains in the blood substantially longer than is reported for recombinant interferon alpha and pegylated interferon alpha, and exhibits robust antiviral activity.

License Grant

The agreement is to develop products with an extended half-life of certain proteins and molecules using the Licensor’s patent protected PolyXen® technology whereby polysialyic acid (“PSA” – a chain of polysialic acids) is chemically conjugated with the Licensee’s proprietary molecule(s) to create a new generation of drugs to treat the failure of blood to coagulate in the therapeutic treatment of blood and bleeding disorders, such as hemophilia. The lead candidate in this collaboration is a longer-acting form of a full length recombinant Factor VIII protein.  Under the terms of the Agreement, the Licensor is entitled to research and development funding and is responsible for providing Licensee with a transfer of the Licensor's proprietary technology and supplying its requirements for PSA.

License Grant

The University grants the non-exclusive right and license to make, have made, use, lease and sell the Licensed Products, and to practice the Licensed Processes in the Territory for the Fields of Use to the end of the term for which the Patent Rights are granted unless sooner terminated according to the terms hereof.

License Property

The patent is for AAV Transduction Vectors.

A Licensed Process is any process which is covered in whole or in part by an issued, unexpired claim or a pending claim contained in the Patent Rights; or, Patent Rights; or, is derived from Patent Rights or know-how, and related to or described in is sold, manufactured or used in any country under this Agreement.

A Licensed Product shall mean any product or part thereof which is covered in whole or in part by an issued, unexpired claim or a pending claim contained in the Patent Rights in the country in which any Licensed Products are made, used or sold; or,  is manufactured by using a process which is covered in whole or in part by an issued, unexpired claim or a pending claim contained in the Patent Rights in the country in which any Licensed Process is used or in which such product or part thereof is used or sold; or,
is derived from Patent Rights or know-how, and related to or described in Patent Rights.

Field of Use

The Fields of Use shall mean:
(a) Human [blood] disorders, [metabolic and congenital]. This field includes human [hematological] diseases that arise due to the absence, over-expression or altered expression of proteins normally (present in blood]. The primary site and location of these proteins is [blood]. Specifically included are human [hemoglobinopathies (i. e. Sickle Cell Anemia and Thalassemia)] and human disorders of the [coagulation metabolism (i.e., Hemophilia A (factor VIII), Von Willebrands Disease (factor VIII) and Hemophilia B (factor IX))]. Specifically excluded are human [neoplasias of the lymphoreticular system (lymphomas, reticuloendothelioses, or plasma cell dyscrasias)].

(b) Human [malignant neoplastic] diseases. This field includes all forms of human (cancer, including but not limited to skin cancers and all solid tumors]. This field also includes all forms of human [cancers of the hematopoietic tissues (the leukemias), Hodgkins Disease and Non-Hodgkins Lymphoma].

c) relating to a syndrome (AIDS) characterized by opportunistic infections occuring as a result of profound
deficiency of the helper – T4 lymphocytes (CD4 lymphocytes). At any time during the life of this Agreement the definition of AIDs shall be that definition currently in use by the Centers for Disease Control, Atlanta, Georgia].

(d) All human [infectious diseases other than HIV]. This Field includes: [human viral diseases (besides HIVs, human bacterial, yeast and other microorganism based diseases, and all other human infectious diseases.

License Grant

University hereby grants to Licensee and the Covered Affiliates for the term of this Agreement the worldwide right and license, with the right to grant sublicenses, to develop, have developed, make, have made, use, have used, import, have imported, sell, offer for sale and have sold University Licensed Products under the Group 1 Patents in all fields of use. Such right and license shall be non-exclusive to Licensee.

Group 2 License Grant. University hereby grants to Licensee and the Covered Affiliates for the term of this Agreement the worldwide right and license, with the right to grant sublicenses, to develop, have developed, make, have made, use, have used, import, have imported, sell, offer for sale and have sold University Licensed Products under the Group 2 Patents in all fields of use. Such right and license shall be non-exclusive to Licensee in the LSD Field.  Subject to this Agreement, such right and license shall be exclusive to Licensee outside the LSD Field.

University hereby grants to Licensee and the Covered Affiliates for the term of this Agreement the worldwide right and license, with the right to grant sublicenses, to develop, have developed, make, have made, use, have used, import, have imported, sell, offer for sale and have sold University Licensed Products under the Group 3 Patents in in all fields of use.   Subject to this Agreement, such rights and license shall be exclusive to Licensee.

License Property

Group 1 Patents means the following patents:
US 6,475,769 – Methods and cell line useful for production of recombinant adeno-associated viruses
US 7,238,526 – Methods and cell line useful for production of recombinant adeno-associated viruses

Group 2 Patents means the following patents:
US 6,759,237 – Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same
US 7,186,552 – Adeno-associated virus serotype 1 nucleic acid sequences, vectors and host cells containing same

Group 3 Patents means
US 7,056,502 – Recombinant aav vectors with AAV5 capsids and AAV5 vectors pseudotyped in heterologous capsids

University Licensed Product(s) means products that in the absence of this Agreement would, where and when made, used, sold, or imported, infringe at least one issued claim or pending claim of University Patent Rights; and products that are made using a process or machine that in the absence of this Agreement would, where and when used, infringe at least one issued claim or pending claim of University Patent Rights. All University Licensed Products intended to deliver the same Gene shall be considered a single University Licensed Product for purposes of this Agreement.

University Patent Rights means those patents and patent applications listed in this Agreement and all foreign counterparts thereof, as well as continuation, continuation-in-part, provided that such continuation-in-part relates directly to existing patents or patent applications and not to any new matter, divisional and re-issue applications
thereof, together with any and all patents issuing thereupon or upon any foreign counterparts thereof; provided, however, that Licensee acknowledge that the invention relating to non-invasive delivery of transgenes into the bloodstream, which is disclosed in Example 6 of International Patent Application No. PCT/USO1/13000 (M2304PCT), and in a US CIP application No. 09/955,444 (N2605), was made at University following termination of the research under the Sponsored Research Agreement.  Licensee hereby acknowledge that they have no rights in this invention relating to non-invasive delivery of transgenes into the bloodstream, as defined in these applications and divisionals, continuations, re-examinations, re-issues, and any foreign counterparts thereof, and any patents issuing therefrom. Licensee agree that they will not make or pursue any claims that this invention as so defined is or should have been part of the University Patent Rights.

Gene means any nucleotide sequence that is capable of encoding, or of causing or modulating the expression of, a proteiin, protein fragment, or other genetic element.  For the purposes hereof, a Gene having 90% homology to that of another Gene, and which expresses essentially the same protein for at least one biological function, shall be considered the same Gene as such other Gene.

LSD Field means the prevention, treatment, or cure of lysosomal storage diseases whether by in vivo or ex vivo means (together with preparation, research, development, and attempts to do the foregoing).

Cancer Field means the prevention, treatment or cure of malignancies whether by in vivo or ex vivo means together with preparation, research, development, and attempts to do the foregoing).

TNFr/Inflammatory Field means the prevention, treatment, or cure of any disease or diseases in whole or in part through use or delivery of the TNFr Gene or any other Gene acting in the Inflammatory Pathway, whether by in vivo or ex vivo means (together with preparation, research, development, and attempts to do the foregoing).

Field of Use

This agreement pertains to the drug industry relating to Gene Therapy.