Royalty Report: Drugs, obesity, Disease – Collection: 211839

License Grant

The Australian Licensee desires to collaborate with an Australian University for a Project using the Research Expertise and a license of all Intellectual Property in the result of the Project.

License Property

The University has expertise in one or more areas of the Research Fields, and owns or has an exclusive license of the Pre-existing Intellectual Property.  The Patent has been licensed exclusively to the University and is for the Treatment of Obesity.  Products means the products and results of the Project.

Australian Provisional Patent Application No. PO 1085/96 (annexed hereto) entitled “Treatment of Obesity” filed on 18 July 1996.

Field of Use

The primary aim of this research program is to discover novel genes that will be integral to the development of new therapeutic approaches directed at the treatment and prevention of obesity.

The Project means scientific research using the Research Expertise into the role of potential pharmaceutical agents on food intake, body weight control and parameters of insulin resistance and diabetes as examined in studies into therapeutic regulators of food intake and appetite.

License Grant

Pursuant to this agreement, the Australian Licensor, a non-profit organization, the owner of a Sand Rat colony based at an Australian University, and has agreed to make the Sand Rats available to the University for the purposes of the Project.

The Australian Licensee desires to collaborate with the Australian University for the Project using the Research Expertise and a license of all Intellectual Property in the result of the Project.

License Property

The license is for use of the Sand Rat colony for the project.
The Israeli Sand Rat is the only animal model which develops a broad spectrum of defects in food intake, body fat and diabetes comparable to similar defects measured in humans. For example, it is possible in the Israeli Sand rat to find 2 offspring from the same parents, one will remain lean and free from diabetes, while the other overeats and subsequently develops obesity. Both of these animals have exactly the same environmental influences – Why does one overeat.

By utilising the latest techniques available in molecular biology (gene fingerprinting) we will be able to determine the different genes being expressed in obese animals – isolate these genes and determine their role in obesity development. Novel genes uncovered will be patented and their metabolic potential determined.

Field of Use

The primary aim of this research program is to discover novel genes that will be integral to the development of new therapeutic approaches directed at the treatment and prevention of obesity.

The Project means scientific research using the Research Expertise into the role of potential pharmaceutical agents on food intake, body weight control and parameters of insulin resistance and diabetes as examined in studies into therapeutic regulators of food intake and appetite.

License Grant

The Australian Licensee desires to collaborate with the Australian University for the R&D Program using the Universitys Research Expertise.  The University warrants that it shall make available for the purposes of the Research Proposal and use in the R&D Program, and any commercialization of the results of the R&D Program, all Pre-existing Intellectual Property.

License Property

Products means the products and results of the R&D Program.  One new project relates to depression in psammomys obesus where therapeutic approaches include tricyclic antidepressants and selective serotonin reuptake inhibitors, as well as a number of newer compounds acting on monoamine oxidase, noradrenaline reuptake, the dopaminergic system and various other pathways.

Field of Use

This Agreement involving scientific research using the Research Expertise into the area of gene discovery in depression.
Licensee will utilize the separation model to investigate genes involved in behavioural traits consistent with depression in Psammomys obesus.

Analysis of global gene expression will be conducted using microarray technology. A cDNA library from the hypothalamus of Psammomys obesus will be constructed. 20,000 clones from this library will be spotted onto glass substrates using an automated microarray apparatus. Pooled RNA samples from the hypothalamus of separated animals will be labeled with a fluorescent dye (Cy3), while RNA from control animals will be labeled with Cy5. These two-labeled samples will be competitively hybridized to the glass substrates, and the results analyzed by scanning laser microscopy.

License Grant

The Australian Licensor grants to the French Licensee an exclusive license within the Licensed Field, that is to the exclusion of the Licensor and third parties, in the Territory within that Licensed Field, to use the Licensed Patents and the Licensed Technology and to Exploit the Products utilizing the Licensed Patents and Licensed Technology.

License Property

The Patents are in relation to the AGT 121 Gene Product; A novel gene and uses therefor Beacon, A ligand of the protein beacon, and Novel genes and their use in modulation of obesity, diabetes and energy imbalance.

“AGT 121 Gene Product” means the novel gene the subject of the Autogen Patents, and any novel proteins or novel antigens based on such novel gene, and any product arising from transcription of such gene.

United States patent application 60/330,149 “A gene and uses therefor”

Field of Use

The Licensed Field means the field of human therapeutic applications for the treatment or prevention of Diabetes and as a secondary field, the field of human therapeutic applications for the treatment or prevention of diabetes and its complications.  For clarity it is noted that this does not include diagnostics or veterinary applications.

This agreement is in the Field of Diabetes and Obesity.

License Grant

University grants to Company an exclusive, worldwide license in the Patent Rights to make, have made, use, offer to sell, sell, have sold and imported Licensed Products in the Field, including research for development of Licensed Products.

License Property

University owns intellectual property rights which relate to therapeutic applications of RNAi, as described in University’s invention Methods of Efficient siRNA Delivery in Human Cells — New Approaches for the Development of siRNA Therapeutics; and,  Design, Synthesis, and Formulation of Nanotransporters for Efficient Nucleic Acids and other Pharmaceutics Delivery in Cells and Animals; and, Therapeutic Silencing of Genes Involved in Cholesterol Biosynthesis and Other Metabolic Disorders by Chemically Modified siRNA and New Delivery Agents.

Field of Use

The Field means Primary Field and Secondary Field collectively. Any commercial sale of research reagents covered by the Patent Rights is specifically excluded from the Field.

Primary Field means therapeutic, prophylactic, or diagnostic health care applications for amyotrophic lateral sclerosis (ALS), diabetes, and obesity, in humans.

Secondary Field means therapeutic, prophylactic, or diagnostic health care applications in humans that are not included in the Primary Field.

License Grant

University grants to Company an exclusive, worldwide license in the Patent Rights to make, have made, use, offer to sell, sell, have sold and imported Licensed Products in the Field, including research for development of Licensed Products.

License Property

University owns intellectual property rights which relate to therapeutic applications of RNAi, as described in Universitys invention entitled Methods and Synthesis of Reagents to Treat ALS.

Field of Use

The Field means Primary Field and Secondary Field collectively. Any commercial sale of research reagents covered by the Patent Rights is specifically excluded from the Field.

Primary Field means therapeutic, prophylactic, or diagnostic health care applications for amyotrophic lateral sclerosis (ALS), diabetes, and obesity, in humans.

Secondary Field means therapeutic, prophylactic, or diagnostic health care applications in humans that are not included in the Primary Field.

License Grant

Licensor grants to the Licensee, of Sweden, a perpetual, exclusive, subject to a retained right thereto for the sole purpose of Licensor carrying out its obligations under the Research Collaboration, right and license in the Territory, with the right to grant sublicenses, under Licensors right, title and interest in and to the Compounds, the Licensed Products, the Licensed Patents, the Licensed Know-How and the
Licensed Improvements to use and otherwise Exploit the Compounds, the Licensed Products, the Licensed Patents, the Licensed Know-How and the Licensed Improvements for use within the Licensed Field.

License Property

The collaboration is based on Licensors melanocortin receptor Obesity program and includes access to compound libraries, core technologies and expertise in melanocortin receptor drug discovery and development.

Licensor is engaged in research regarding modulation of the activity of the MC4 receptor, including regulation of appetite for treatment of obesity, diabetes and related metabolic syndrome.

The licensed know-how is for Information relating to Compounds, including without limitation cell binding, functional and efficacy Information, including both in vitro and in vivo data, to the extent not disclosed in the Licensed Patents;  Information relating to development plans and proposed activities. including but not limited to proposed work and activities with respect to chemotypes, modification of existing chemotypes, synthetic methods, formulations and routes of administration; and,  Information relating to other signal transduction pathways, such as activation of MAPkinase and regulation of levels of intracellular calcium, linked to activation of MC4 receptors, including exploration of correlations to the mechanism of action of Compounds.

60/712.283 Compounds and Methods for Treating Obesity

60/712.282 Methods for Selection of Melanocortin Receptor-Specific Agents for Treatment of Obesity

Field of Use

The Licensed Field means the palliative, prophylactic or therapeutic treatment of mammalian, including human, obesity, diabetes and related metabolic syndrome by use of a Compound, other than such Compound mentioned under, which binds to the melanocortin-4 receptor or the melanocortin-3 receptor; or a Compound which binds to the melanocortin-4 receptor and is effective for palliative, prophylactic or therapeutic treatment of any mammalian, including human, disease, syndrome or condition as a result of such binding to the melanocortin-4 receptor, but specifically excluding from either of the compounds which are functionally antagonists at either or both the melanocortin-4 receptor and the melanocortin-3 receptor as determined by an adenylyl cyclase assay system and which at clinical relevant doses, in either animal models or humans, result over a clinically relevant period in an increase in body weight such that the specifically excluded compounds may be useful for treatment of cachexia and related indications, provided. however, that any such compound otherwise excluded shall if useful for treatment of obesity, diabetes or related metabolic syndrome be included in the Licensed Field; and Compounds used or useful solely for the SD Field.

SD Field means the palliative, prophylactic or therapeutic treatment of mammalian, including human, sexual dysfunction, including erectile dysfunction and all related subindications, such as organic, psychogenic or iatrogenic inability to achieve or maintain an erection, ejaculatory failure, premature ejaculation, retrograde ejaculation. inability to achieve an orgasm. and the like. and female sexual dysfunction and all related subindications, such as organic, psychogenic or iatrogenic persistent or recurrent failure to attain or maintain the lubrication-swelling response of sexual excitement until completion of sexual activitv, including inhibited orgasm, dvspareunia, hypoactive sexual desire disorder, sexual anhedonia, sexual arousal disorder, vagjnismus, and the like.

License Grant

Licensor, a non-profit biomedical research institution, grants to the Australian Licensee an exclusive, permanent, worldwide license to use the Project Intellectual Property for the purpose of developing and commercially exploiting the results of the Project and Licensee shall have the right to sub-license its rights and to decide in its absolute discretion as to how the Intellectual Property and the Products are to be commercially exploited.

License Property

The licensed property relates to Gene Discovery for Diabetes/Obesity in Human Families.

1) Establishment of Autogen Center for Statistical Genomics including dedicated computing resources.
In order to meet the needs of Autogen’s Human Genomics program, a computer cluster comprising 300 processors (described in the Budget in Item 2 of Schedule 1) will be added to the extant processor cluster at SFBR. While it will be completely integrated into the larger computer system (and thus benefit from an existing administrative structure), these processors will be available as required for Autogen statistical genomics research. These computers will be placed in the new SBC Genomics Computing Center building (projected opening date: February 14, 2003).

2) Analysis of 4 ISR Candidate Genes for Diabetes/Obesity in Human Populations.
In order to conclusively test for the effects of variation in Autogen proprietary genes on diabetes/obesity related phenotypes in humans, we will perform an exhaustive series of statistical genomic analyses on human samples. The possible sample sources (to be negotiated independently of this document) for these studies include (but are not limited to) the Wisconsin families from the MRCOB study, Mexican American families from the San Antonio Family Heart Study, and Autogen’s extant samples from Pacific Island populations.
Tasks:
a) Genotype cleaning: Mendelian error checking, elimination of double recombinants. This task is limited to family-based samples.
b) Haplotype inference and genotype imputation.
c) Quantitative trait nucleotide analysis using the Bayesian model selection/model averaging approach.
d) Conditional linkage analysis to test whether best SNP Gene Action model accounts for linkage. This task is limited to family-based samples.
These analyses will allow us to determine whether or not variants in a given gene appear to have functional effects on relevant human phenotypes and whether or not the gene completely identifies the underlying human QTL. Final analyses will include estimates of the posterior probability that a given variant has functional effects for each DNA variant examined.

3) Gene Discovery for Diabetes/Obesity in Human Families
This aim launches a gene discovery research program based around samples from human families. We plan to take existing well defined and localized QTLs and attempt identification of novel genes in the original family material. It is anticipated (although not mandatory) that these analyses will be performed on samples from current Autogen collaborations (including the MRCOB Wisconsin family study or the San Antonio Family Heart Study).
Tasks:
a) Additional STR genotype cleaning and map integration. It is anticipated that approximately 5 additional markers will be analyzed per QTL region.
b) Identity-by-descent probability calculation for region including new STRs.
c) Quantitative trait linkage analysis using the additional STRs to refine localization interval.
d) Strategy 1: Focal positional candidate gene approach. For SNPs within positional candidate genes chosen via bioinformatic methods, a similar set of tasks to those described in Aim 2 will be performed. These will include genotype cleaning, haplotype inference and genotype imputation, quantitative trait nucleotide analysis, and conditional linkage analysis to verify QTL dissection. The total time per QTL (assuming 3 genes will be analyzed exhaustively) is 48 weeks.
e) Strategy 2: Positional candidate region approach without obvious candidate genes. For QTL regions, which lack obvious positional candidate genes, a general SNP coverage strategy will be pursued. : Specific analytical tasks to be performed include: analysis of linkage disequilibrium followed by optimal choice of independent SNPs; preliminary association analysis of 200 individuals for 5 SNPs per gene for 30 genes; SNP analyses within families including genotype cleaning, haplotype inference and genotype imputation, QTN analysis and conditional linkage analysis per gene = 2 weeks. The total time per QTL (assuming 2 genes ultimately will be analyzed exhaustively) is 48 weeks.

Field of Use

The Research Fields means the fields of diabetes, obesity, osteoporosis, depression, allergy, asthma and autoimmunity and such other fields as may be included by mutual written agreement.

License Grant

In fiscal 2006, the Licensee issued 414,492  common shares to the Canadian Licensor in exchange for patents related to the use of GLP-1 in type I diabetes patients.

License Property

Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion.

Field of Use

The Licensee product is TT401, a dual agonist of the GLP-1 (Glucagon-Like Peptide-1) and glucagon receptors. These receptors play an integral role in regulating appetite, food intake, satiety and energy utilization in the body. Stimulating both these receptors, TT401 has the potential to regulate blood glucose levels with important additional outcomes, such as weight loss.

License Grant

University grants to Company a nonexclusive, worldwide license, without the right to sublicense, in the Patent Rights to make, have made, use, offer to sell, sell, have sold and imported Licensed Products in the Field, including research for development of Licensed Products.

License Property

The University intellectual property rights relate to therapeutic applications of RNAi, entitled Methods of Synthesis and Formulation of New Reagents for Efficient Nucleic Acids Delivery in Cells and Animals, and,  Microwave Assisted Method of Synthesis of New Cationic Reagents for Efficient Drug Delivery in Cells and Animals.

Field of Use

The Field means Primary Field and Secondary Field collectively. Any commercial sale of research reagents covered by the Patent Rights is specifically excluded from the Field.

Primary Field means therapeutic, prophylactic, or diagnostic health care applications for amyotrophic lateral sclerosis (ALS), diabetes, and obesity, in humans.

Secondary Field means therapeutic, prophylactic, or diagnostic health care applications in humans that are not included in the Primary Field.

License Grant

Licensor shall and hereby does grant to Licensee an exclusive worldwide license, with rights to sublicense, under the Licensor Patent Rights and the Licensor Research Tool Patents to develop, make, use, have made and sell Development Candidates in the Licensee Development Field, except that the rights granted under the Licensor Research Tool Patents shall not include rights relating to targets other than ACE2.  

Licensor hereby agrees to grant and does grant Licensee a non-exclusive worldwide license, with rights to sublicense, under any Licensor Consulting IP, to develop, make, use, have made, and sell Development Candidates in the Licensee Development Field.

Licensor will and hereby does grant to Licensee a non-exclusive worldwide license, with the right to sublicense, under Licensor’s interest in such invention, patent or patent application, to develop, make, use, have made and sell Development Candidates in the Licensee Development Field.

License Property

Licensor Patent Rights means U.S. Patent 6,632,830 and U.S. Patent 7,045,532 and any related foreign patents and patent applications related thereto, including (a) any continuation, continuation-in-part, divisional, resissue, reexamination or extension thereof, (b) any patent issued from any such applications, and (c) all inventions claimed in any of the foregoing.

Licensor Research Tool Patents means the U.S. Patents listed and any related foreign patents and patent applications related thereto, including (a) any continuation, continuation-in-part, divisional, resissue, reexamination or extension thereof, (b) any patent issued from any such applications, and (c) all inventions claimed in any of the foregoing.

U.S. Patent No 6,632,830 – ACE-2 inhibiting compounds and methods of use thereof
U.S. Patent No 7,045,532 – ACE-2 modulating compounds and methods of use thereof
US Patent No 6,194,556 – The present invention relates to the discovery of novel genes encoding an angiotensin converting enzyme, Angiotensin Converting Enzyme-2 (ACE-2). Therapeutics, diagnostics and screening assays based on these molecules are also disclosed.
US Patent No 6,989,363 – Angiotensin converting enzyme homolog and therapeutic and diagnostic uses therefor
US Patent No 6,610,497 – Angiotensin converting enzyme homolog and therapeutic and diagnostic uses therefor
US Patent No 6,884,771 – Angiotensin converting enzyme homolog and uses therefor
US Patent Application No. 11/059218
US Patent Application No. 10/659000

Development Candidate means any Compound or Biotherapeutic Compound that is developed by Licensee alone or by a third party (with or without the participation of Licensee) under a Development Arrangement.

Compound means (a) MLN 4760; (b) any other compound covered by a Valid Claim under Licensor Patent Rights; (c) any compound made under Licensee’s development hereunder; (d) any metabolite, ester, salt, hydrate, solvate, polymorph, stereoisomer, prodrug, or formulation of the foregoing described in (a), (b), or (c); and (e) any product that has as an active ingredient (a), (b), (c), or (d).

MLN 4760 means the chemical compound known as MLN 4760 and more fully described as (S,S)-2-[1-carboxy-2-[3-(3,5-dichlorobenzyl)-3H-imidazol-4-yl]-ethylamino]-4-methylpentanoic acid.

Biotherapeutic Compound means any molecule that has a molecular weight in excess of 1500 Daltons and that is covered by, or is developed through activities covered by, Licensor Research Tool Patents.

Field of Use

Licensee Development Field means the prevention, diagnosis, and treatment of any human disease other than Oncology Diseases (as that term is defined below).  Notwithstanding the previous sentence, it is understood that Licensee will be restricted from developing a Development Candidate for the treatment of Type 1 Diabetes, Type 2 Diabetes and Obesity as specified in the existing Separation Agreement between Licensor and Abbott Laboratories, dated August 8, 2003, which restriction shall expire and be inapplicable and unenforceable hereunder as of September 29, 2008.

Type 1 Diabetes means insulin-dependent diabetes mellitus as diagnosed according to criteria published in the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (Diabetes Care, Vol. 24, Supp. 1, January 2001) whereby fasting plasma glucose level is greater than or equal to 126 milligrams per deciliter and for which the primary cause is beta-cell destruction.

Type 2 Diabetes non-insulin-dependent diabetes mellitus as diagnosed according to criteria published in the Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (Diabetes Care, Vol. 24, Supp. 1, January 2001) whereby fasting plasma glucose level is greater than or equal to 126 milligrams per deciliter.

Obesity means the condition of excess body fat (adipose tissue), in accordance with the National Institutes of Health Federal Obesity Clinical Guidelines for adults, whereby body mass index calculated by dividing body mass in kilograms by height in meters squared is equal to or greater than twenty-five (25) (for purposes of this definition, Obesity shall include an overweight condition in accordance with the above guidelines and comparable obesity and overweight condition in children).

Oncology Diseases means the prevention, diagnosis, and treatment of oncological diseases (including modulation of tumor angiogenesis).

License Grant

The Australian Licensor grants to the French Licensee with effect on and from the Commencement Date until expiry of the Term an exclusive licence within the Licensed Field, that is to the exclusion of Autogen and third parties, in the Territory within that Licensed Field, to use the Licensed Patents and the Licensed Technology and to Exploit the Products utilising the Licensed Patents and Licensed Technology.

License Property

The patents relate to inventions for Novel genes and their use in modulation of obesity, diabetes and energy imbalance.

The Licensed Patents and the Licensed Technology relates to develop new anti-obesity therapies using the Company's U.S. patent relative to the Beacon gene for use in treating or diagnosing obesity, diabetes and energy imbalance.

“Tanis Gene Product” means the novel gene the subject of the Autogen Patents, and any novel proteins or novel antigens based on such novel gene, and any product arising from transcription of such gene.

Invention entitled “A novel gene and uses therefor” Beacon (claiming priority from Australian Patent Application Nos. PP0117/97 and PP0323/97).

Field of Use

“Licensed Field” means the field of human therapeutic applications for the treatment or prevention of Diabetes and its complication and as a secondary field, the field of human therapeutic applications for the treatment or prevention of obesity. For clarity it is noted that this does not include diagnostics or veterinary applications.

License Grant

With the Agreement, the Licensor granted to the Licensee of Sweden a license to the Licensed Patents and the Parties agreed to collaborate to generate Collaboration Compounds to be owned by Licensee.

The Parties are amending the Agreement to inter alia provide for a reduction of royalties and certain milestone payments otherwise due, permit Licensee to use certain data relating to bremelanotide, and, have Licensor conduct one or more additional clinical trials using bremelanotide.

Licensor grants the right, at Licensees expense, to inspect and copy, or otherwise obtain from Licensor, Safety Data relating to bremelanotide, and Licensee agrees to use such Safety Data.

As amended,  Licensor shall,  send to Licensee the originals of all Research Records including laboratory notebooks in respect of all work done and results achieved by Licensor under the Research Collaboration.

License Property

Bremelanotide is a compound, developed by Licensor outside and independent of the Agreement, on food intake, obesity or other metabolic parameters in healthy volunteers or patients.

Field of Use

The field of use is in further evaluating the potential of melanocortin-4 receptor compounds as effective treatments of obesity or other metabolic disorders.