Royalty Report: Drugs, Biotechnology, Medical – Collection: 265251

License Grant

Licensor has granted to Licensee a sublicense of certain patents licensed to Licensor by the University of Utah Research Foundation (the “Utah Sublicense”), and has granted to Licensee a direct license of certain patents held by Licensor.  This License will not permit sublicensing and will be non-exclusive for medical products, devices, and services related to human tendon, and will be exclusive for all other licensed fields linked to the HyStem® Technology.

We may only develop, sell, and otherwise commercialize a product under the Utah Sublicense and HyStem License if we spend at least a low seven figure amount on research with respect to the product. Licensor will agree to provide us with a reasonable amount of the hydrogel product for the purpose of our research for we will pay Licensor’s cost of manufacturing and supplying the hydrogel.

License Property

The agreement is related to HyStem® hydrogel technology for use outside of the Licensor Exclusive Field for products that include cells. The intellectual property is connected to PSC-derived clonal embryonic progenitor cell lines (PureStem® technology) and HyStem® delivery matrices.  HyStem® is a patented biomaterial that mimics the extracellular matrix that is the structural network of macromolecules surrounding cells in the body. The extracellular matrix is essential for normal cellular function and survival of transplanted cells. Many tissue engineering and regenerative cell-based therapies are expected to benefit from the delivery of therapeutic cells in a matrix for precise localized delivery and survival. HyStem is a unique hydrogel that has been shown to support cellular attachment in vivo. Current research at medical institutions has shown that HyStem is compatible with a wide variety of cells and tissue types including those of the brain, bone, skin, cartilage, vascular system and heart. The technology underlying HyStem hydrogels was developed at the University of Utah and was been exclusively licensed to Licensor for human therapeutic applications and sublicensed to Licensee for certain fields. The HyStem technology is based on a unique thiol cross-linking chemistry to prepare hyaluronan-based matrices as hydrogels. Since the first published report in 2002, there have been numerous academic scientific publications supporting the biocompatibility of thiol cross-linked hyaluronan-based matrices and their applications as medical devices and in cell culture, tissue engineering, and animal models of cell-based therapies.

Field of Use

This agreement pertains to the medical industry.

License Grant

The License expanded the field of use for which the Licensee is Licensed to produce and market products covered by the core patents underlying HyStem, of hydrogel product technology.

License Property

Our Licensed field of use includes, but is not limited to, all human pharmaceutical and medical device applications, all tissue engineering and regenerative medicine uses, and all research applications.

HyStem kits are for culturing stem cells whose natural environments are rich in hyaluronic acid.

Field of Use

Our Worldwide Licensed field of use includes, but is not limited to, all human pharmaceutical and medical device applications, all tissue engineering and regenerative medicine uses, and all research applications, with the exception of veterinary medicine and animal health.

The Licensor now has a worldwide License for all uses, with the exception of veterinary medicine and animal health.

License Grant

University hereby grants to Licensee a royalty-bearing exclusive license to make, have made, use and sell any Licensed Product and to practice any Licensed Method in the Field of Use under Licensor’s Patent Rights throughout the Territory.

License Property

Proprietary biocompatible hydrogels mimic the extracellular matrix in which cells reside.

Certain inventions, generally characterized as and assigned University identification number U-3405, “In situ Crosslinkable Synthetic Extracellular Matrices”, and U-3656, “Novel Chemical Modifications of Hyaluronan”,

U No.

Matter

Application No.  Date of Filing

Title

Inventor(s)

U-3405

21101.0036U1  Provisional

60/390,504  6/21/2002

Disulfide Crosslinked Hyaluronan Hydrogels

Glenn Preswich, Xiao Shu, Yi Luo, Kelly Kirker

U-3405

21101.0036P1  PCT

PCT/US03/15519  5/15/03

Crosslinked Compounds and Methods of Making and Using Thereof

Glenn Preswich, Xiao Shu, Yi Luo, Kelly Kirker

U-3405

21101.0036U2  Nationalized, United States

10/519,173  12/20/04

Crosslinked Compounds and Methods of Making and Using Thereof

Glenn Preswich, Xiao Shu, Yi Luo, Kelly Kirker

U-3405

21101.0036CA1  Nationalized, Canada

2,489,712  5/15/03

Crosslinked Compounds and Methods of Making and Using Thereof

Glenn Preswich, Xiao Shu, Yi Luo, Kelly Kirker

U-3405

21101.0036EP1  Nationalized, Europe

03799796.2  5/15/03

Crosslinked Compounds and Methods of Making and Using Thereof

Glenn Preswich, Xiao Shu, Yi Luo, Kelly Kirker

U-3656

21101.0051P1  Provisional

60/526,797  12/4/2003

Modified Macromolecules and Methods of Making and Using Thereof

Glenn Prestwich, Xiao Shu

U-3656

21101.0051U1  PCT

PCT/US04/040726  12/6/2004

Modified Macromolecules and Methods of Making and Using Thereof

Glenn Prestwich, Xiao Shu

Field of Use

Licensee intend to initially use the technology in the development of therapeutic products for use in the treatment of osteoarthritis.

HyStem®-Rx is a biocompatible hydrogel that mimics the extracellular matrix in which cells reside. As an injectable product, HyStem®-Rx may address an immediate need in cosmetic and reconstructive surgery and other procedures by improving the process of transplanting adipose (fat) cells or other adult stem cells. Adult stem cell types such as adipose stem cells obtained from a patient through liposuction can be transplanted back into the same patient in another location in the body, without the risk of rejection associated with the transplant of donor tissues.

The Licensee is developing cellular therapeutics for orthopedic repair diseases and injuries. The lead project is the development of human embryonic progenitor cell (hEPC) lines for cartilage repair. A tissue engineered product is defined as living human tissues or cells on a polymer platform, created at a place other than the point-of-care facility, for transplantation into a human patient.

License Grant

The Company hereby grants a worldwide, non-exclusive, non-transferable, non-assignable, non-sublicensable  terminable license under the Intellectual Property that is the subject of Medtronic’s infringement, to make, have made, use, import, distribute, sell, have sold the Licensed Products incorporating or utilizing such Subject Technology within the Medtronic Area of Interest.

License Property

Medtronic Area of Interest means the areas of cardiovascular (excluding the tissue-engineered vascular grafts), endocrine, neurological, and spinal conditions or diseases.

A. ISSUED U.S. PATENTS
4,721,096   Process for Replicating Bone Marrow In Vitro and Using the Same
4,960,489   Three-Dimensional Cell and Tissue Culture System
5,032,508   Three-Dimensional Cell and Tissue Culture System
5,160,490   Three-Dimensional Cell and Tissue Culture System Apparatus
5,266,480   Three-Dimensional Skin Culture System
5,443,950   Three-Dimensional Cell and Tissue Culture System
5,460,939   Temporary Living Skin Replacement
5,478,739   Three-Dimensional Stromal Cell and Tissue Culture System
5,510,254   Three-Dimensional Cell and Tissue Culture System
5,512,475   Three-Dimensional Skin Cell and Tissue Culture System
5,516,680   Three-Dimensional Kidney Cell and Tissue Culture System
5,516,681   Three-Dimensional Pancreatic Cell and Tissue Culture System
5,518,915   Three-Dimensional Mucosal Cell and Tissue Culture System
5,541,107   Three-Dimensional Bone Marrow Cell and Tissue Culture System
5,559,022   Liver Reserve Cells
5,578,485   Three-Dimensional Blood-Brain Cell and Tissue Culture System
5,580,781   Three-Dimensional Tumor Cell and Tissue Culture System
5,599,788   Method for Accelerating Skin Wound Healing with H3 Protein
5,624,840   Three-Dimensional Liver Cell and Tissue Culture System
5,714,588   Enhancement of Cellular Attachment Using H3 Protein
5,763,267   Apparatus for the Large Scale Growth and Packaging of Cell
            Suspensions and Three-Dimensional Tissue Cultures
5,785,964   Three-Dimensional Genetically Engineered Cell and Tissue Culture
            System
5,792,603   Apparatus and Method for Sterilizing, Seeding, Culturing, Storing,
            Shipping and Testing Tissue, Synthetic or Native, Vascular Grafts
5,827,729   Diffusion Gradient Bioreactor and Extracorporeal Liver Device
            Using a Three-Dimensional Liver Tissue
5,830,708   Methods for Production of a Naturally Secreted Extracellular Matrix
5,842,477   Method for Preparing Cartilage
5,843,766   Apparatus for the Growth and Packaging of Three Dimensional
            Tissue Cultures
5,846,828   Apparatus and Method for Sterilizing, Seeding, Culturing,
            Storing, Shipping and Testing Tissue, Synthetic, or Mechanical
            Heart Valves or Valve Segments
5,849,588   Methods of Use of a Three-Dimensional Liver Cell and Tissue
            Culture System
5,858,721   Three-Dimensional Cell and Tissue Culture System
5,863,531   In Vitro Preparation of Tubular Tissue Structures by Stromal Cell
            Culture on a Three-Dimensional Framework
5,902,741   Three Dimensional Cartilage Cultures
5,919,702   Production of Cartilage Tissue Using Cells Isolated From
            Wharton's Jelly

5,928,945   Application of Shear Flow Stress to Chondrocytes or Chondrocytre
            Stem Cells to Produce Cartilage
5,962,325   Three-Dimensional Stromal Tissue Cultures
6,008,049   Diffusion Gradient Bioreactor and Extra-Corporeal Liver Device
6,022,743   Three-Dimensional Culture of Pancreatic Parenchymal Cells
            Cultured Living Stromal Tissue Prepared In Vitro
6,027,935   Gene Up-Regulated in Regenerating Liver
6,060,306   Apparatus and Method for Sterilizing, Seeding, Culturing, Storing,
            Shipping and Testing Replacement Cartilage Tissue Constructs
6,121,042   Apparatus and Method for Simulating In Vivo Conditions While
            Seeding And Culturing Three-Dimensional Tissue Constructs
6,140,039   Three-Dimensional Filamentous Tissue Having Tendon or Ligament
            Function
6,218,182   Method For Culturing Three-Dimensional Tissue in Diffusion
            Gradient Bioreactor and Use Thereof
6,284,284   Compositions and Methods for Production and Use of an Injectable
            Naturally Secreted Extracellular Matrix
6,291,240   Cells or Tissues With Increased Protein Factors and Method of
            Making Same

B. PENDING U.S. PATENT APPLICATIONS
08/488,165  Three-Dimensional Human Cell Cultures on Cardiac Valve Frameworks
            and Their Uses – on appeal
08/660,787  Compositions and Methods for Production and Use of an Injectable,
            Naturally Secreted Extracellular Matrix
09/256,649  Living Chimeric Skin Replacement
09/313,538  Conditioned Cell Culture Medium Compostions and Methods of Use
09/362,948  Genetically Engineered Cells Responsive to Environmental Cues
09/350,386  Human Naturally Secreted Extracellular Matrix-Coated Device and
            Methods for the Production and Uses Thereof
09/401,445  Three Dimensional Human Cell Cultures on Cardiac Valve Frameworks
            and Their Uses
09/411,585  Methods of Using a Three-Dimensional Stromal Tissue to Promote
            Angiogenesis
09/457,519  Application of Shear Flow Stress to Smooth Muscle Cells for the
            Production of Implantable Structures
09/482,203  Apparatus and Method for Sterilizing, Seeding, Cultiring, Storing,
            Shipping and Testing Tissue Synthetic or Native Vascular Grafts
09/603,642  Monitorable Three Dimensional Scaffolds and Tissue Culture
09/724,410  Cells or Tissues with Increased Protein Factors and Methods for
            Making Same
09/847,902  Container for Shipping Tissue
60/297,177  Compositions Comprising Conditioned Cell Culture Media and Uses
            Thereof

II. UNITED STATES PATENTS LICENSED TO ADVANCED TISSUE SCIENCES, INC.

A. LICENSED FROM THE MASSACHUSETTS INSTITUTE OF TECHNOLOGY
4,418,691   Method of Promoting the Regeneration of Tissue at a Wound
4,458,678   Cell-Seeding Procedures Involving Fibrous Lattices
4,505,266   Method of Using a Fibrous Lattice
4,638,045   Non-Peptide Polyamino Acid Bioerodible Polymers
4,806,621   Biocompatible, Bioerodible, Hydrophobic, Implantable Polyamino
            Carbonate Article
4,947,840   Biodegradable Templates for the Regeneration of Tissues
5,041,138   Neomorphogenesis of Cartilage In Vivo From Cell Culture
5,128,420   Method of Making Hydroxamic Acid Polymers From Primary Amide
            Polymers
5,399,665   Biodegradable Polymers For Cell Transplantation
5,514,378   Biocompatible Polymer Membranes and Methods of Preparation of Three
            Dimensional Membrane Structures
5,516,532   Injectable Non-Immunogenic Cartilage and Bone Preparation
5,654,381   Functionalized Polyester Graft Copolymers
5,736,372   Biodegradable Synthetic Polymeric Fibrous Matrix Containing
            Chondrocyte For In Vivo Production of a Cartilaginous Structure
5,759,830   Three-Dimensional Fibrous Scaffold Containing Attached Cells for
            Producing Vascularized Tissue In Vivo
5,770,193   Preparation of Three-Dimensional Fibrous Scaffold For Attaching
            Cells to Produce Vascularized Tissue In Vivo
5,770,417   Three-Dimensional Fibrous Scaffold Containing Attached Cells for
            Producing vascularized Tissue In Vivo
5,804,178   Implantation of Cell-Matrix Structure Adjacent Mesentery, Omentum or
            Peritoneum Tissue
6,123,727   Tissue Engineered Tendons and Ligaments
6,095,148   Neuronal Stimulation Using Electrically Conducting Polymers
6,224,893   Semi-Interpenetrating or Interpenetrating Polymer Network for Drug
            Delivery and Tissue Engineering

B. LICENSED FROM THE UNIVERSITY OF FLORIDA
5,650,299   Cells Producing Stem Cell Proliferation Factor
5,981,708   Stem Cell Proliferation Factor