Royalty Report: Drugs, Pharmaceuticals, Biotechnology – Collection: 457

License Grant

LICENSOR, an agency of the U.S. federal government responsible for the civilian space program, as well as aeronautics and space research, hereby grants to LICENSEE a terminable, royalty-bearing, exclusive license to practice, i.e., to make, have made, use, offer to sell, sell, transfer, or dispose of, the LICENSED INVENTION as limited to the LICENSED AREA and as limited to a LICENSED FIELD OR EMBODIMENT(S).

Agreement grants a terminable, royalty-bearing, exclusive license to practice, i.e., to make, have made, use, offer to sell, sell, transfer, or dispose of relative to technology for Three-Dimensional Co-Culture Process including culture process for mammalian cells and propagation of in Vitro Human Tissue.

License Property

The process of the present invention relates to a 3-dimensional coculture process. By the process of the present invention a variety of cells may be co-cultured to produce tissue which has 3-dimensionality and has some of the characteristics of in vivo tissue. The process provides enhanced 3-dimensional tissue which creates a multicellular organoid differentiation model.

Three-Dimensional Co-Culture Process U.S. Pat No. 5,153,132 – The process of the present invention relates to a three dimensional co-culture process.  Wherein two distinct types of mammalian cells are co-cultured in a rotating bioreactor which is completely filled with culture media and cell attachment substrates.  As the size of the tissue assemblies formed on the attachment substrates changes the rotation of the bioreactor is adjusted accordingly.

Method for Culturing Mammalian Cells  U.S. Pat No. 5,153,133 – A bio-reactor system where cell growth microcarrier beads are suspended in a zero head space fluid medium by rotation about a horizontal axis and where the fluid is continuously oxygenated from a tubular membrane which rotates on a shaft together with rotation of the culture vessel.  The oxygen is continuously throughput through the membrane and disbursed into the fluid medium along the length of the membrane.

Three-Dimensional Cell to Tissue   U.S. Pat No. 5,155,034 – The present invention relates to a 3-dimensional cell to tissue and maintenance process, more particularly to methods of culturing cells in a culture environment, either in space or in a gravity field, with minimum fluid shear stress, freedom for 3-dimensional spatial orientation of the suspended particles and localization of particles with differing or similar sedimentation properties in a similar spatial region.

Method for Culturing Mammalian Cells  U.S. Pat No. 5,155,035 – A bio-reactor system wherein a tubular housing contains an internal circularly disposed set of blade members and a central tubular filter all mounted for rotation about a common horizontal axis and each having independent rotational support and rotational drive mechanisms. The housing, blade members and filter preferably are driven at a constant slow speed for placing a fluid culture medium with discrete microbeads and cell cultures in a discrete spatial suspension in the housing. Replacement fluid medium is symmetrically input and fluid medium is symmetrically output from the housing where the input and the output are part of a loop providing a constant or intermittent flow of fluid medium in a closed loop.

Multi-Cellular Three-Dimensional   U.S. Pat No. 5,308,764 – The present invention relates to a multicellular, three-dimensional, living mammalian tissue. The tissue is produced by a co-culture process wherein two distinct types of mammalian cells are co-cultured in a rotating bioreactor which is completely filled with culture media and cell attachment substrates. As the size of the tissue assemblies formed on the attachment substrates changes, the rotation of the bioreactor is adjusted accordingly.

Field of Use

Licensed Field or Embodiment(s) shall mean making, using, selling, proliferating, transferring and/or making other disposition of bone marrow cells and tissues, and bone-marrow derived peripheral blood cells and applications thereof, including but not limited to growth and commercialization of bone marrow blood cell cultures, growth and transplantation of blood cells and bone marrow; and the use of blood cells and bone marrow for commercial growth of bone marrow-derived biological products, including but not limited to red blood cells, white blood cells, platelets, cellular growth factors, and intercellular communication factors, and processes for making such products. The sources of testing and commercialization materials shall be derived from sources such as living donor biopsies, harvested from cadaver donors, or from peripheral blood cells. Specifically excluded as a source of bone marrow are human embryonic, fetal or neonatal cells and tissues.

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

License Grant

The Licensor hereby grants to Co-Licensee a terminable, royalty-bearing, exclusive license to practice, to make, have made, use, offer to sell, sell, transfer or dispose of the Licensed Invention in accordance with the Licensed area and Licensed Field of Use.

License Property

The License agreement refers to the use of U.S. Patent No. 6,730,498 B1, an invention entitled Production of Functional Proteins Balance of Shear Stress and Gravity, which was issued on May 4, 2004.

The Licensee currently uses the Patent process to develop anti-aging skin creams and shampoos.

Field of Use

Licensed Field of Use shall mean the production of biomolecules and growth factors for use in topical applications for cosmetics and topical treatment for burns, scars, stretch marks, acne and joint pain.

License Grant

This exclusive License Agreement is for the use of two (2) patents.  The License Agreement requires that the Company achieve a practical application of the Patent within eighteen (18) months from the commencement date of the License Agreement.

License Property

U.S. Patent No.’s 6,485,963 B1, an invention entitled “Growth Stimulation Of Biological Cells and Tissue By Electromagnetic Fields and Uses Thereof” which was filed on June 2, 2000, and U.S. Patent No. 6,673,597 B2, for an invention entitled “Growth Stimulation of Biological Cells and Tissue By Electromagnetic Fields and Uses Thereof which was filed on February 28, 2001.

Field of Use

We currently use the Patents process to develop our anti-aging skin creams and shampoos.  The License Agreement permits the Company to use the Patents as well as the Licensor's name with its products.

License Grant

Licensor, non-profit health care organization, grants the worldwide right and exclusive license, with the right to grant sublicenses, under the Patent Rights to make, have made, use, lease, sell, offer for sale and import for use or resale the Licensed Products, and to practice the Licensed Processes, in the Territory for the Field.

Licensor also grants a non-exclusive license to Know-how, and a non-exclusive license to use Biological Materials in connection with licensees research and development of Licensed Products.

License Property

The patents include Reconstruction of Urological Structures with Polymeric Matrices;  Achievement of Excretory Renal Function Using a Neo-Morphogenic System In Vivo; Penile Reconstruction; Ex vivo Engineered Stents for Urethral Structures; Creation of Tissue Engineered Female Productive Organs (Vagina); Augmentation of Organ Function;  and, Tissue Engineered Uterus and Fallopian Tubes.

Biological Materials shall mean the specific proprietary biological materials, including Progeny and Unmodified Derivatives of those materials.  Progeny shall mean an unmodified descendant from the material, such as a virus from virus, cell from a cell, or organism from an organism; Unmodified Derivatives shall mean substances created by the Licensee which constitute an unmodified functional subunit or product expressed by the original material, such as subclones of unmodified cell lines, purified or fractionated subsets of the original material, proteins expressed by DNA/RNA, or monoclonal antibodies secreted by a hybridoma cell line; and Modifications shall mean substances created by the Licensee which contain or incorporate the material.

Field of Use

Field of Use shall mean the development and commercialization of tissue engineered products for human and animal therapeutics in the subfields of genitourinary, vascular tissue, nervous tissue, trachea and other subfields when and if mutually agreed upon by the parties in writing.

License Grant

Licensor grants a sole and exclusive worldwide license or sublicense, as applicable, to the Licensor Technology for the CPS in the Field.

License Property

The patents include  Apparatus and Method for Maintaining  and Growing Biological Cells;  Methods of Increasing Rates of !n!ection by Directing Motion of Vectors;  Methods, Compositions and Apparatus for Cell Transfection; and, Methods, Compositions and Devices for Maintaining and Growing Human Stem and/or Hematopoietic Cells.

CPS means any system or device for substantially increasing, the number of cells, ex vivo, for human therapeutic uses, that may be configured in different component structures (such as described for the Automated CPS or the Manual CPS).

Licensed Product means the Automated CPS (both the Durables and the Disposables) as used for one or more specific Lymphoid Cell Applications.

Licensor is developing proprietary process technologies and devices for a range of cell therapy applications, including stem cell therapies and gene therapy. The lead product under development, the Licensors Cell Production System (the CPS) consists of a clinical cell culture system with disposable cassettes and reagents for use in the rapidly growing stem cell therapy market.

Field of Use

Field means Lymphoid Cell Applications.  Application means (a) the expansion of any Lymphoid Cell for one or more therapeutic uses, or (b) the transfection of a specific Lymphoid Cell type modified with a naturally occurring gene or a synthetic modification thereof for a specific therapeutic use. One Application is tumor infiltrating lymphocytes (TIL), such that TIL therapy for renal cell carcinoma and TIL therapy for breast cancer are part of the same Application.

Licensee, a competitor, along with others, are in advanced stages of development of technologies and products for use in stem cell therapy and other market applications currently being pursued by the Licensor.

License Grant

The University hereby grants to Licensee an exclusive world-wide license, without the right to grant sublicenses,  under Licensed Patents and to use Know-How to make, use, and sell Product(s), except that University hereby retains the right to use Licensed Patents and Know-How solely for research purposes, and except that to the extent funding from federal agencies results in Licensed Technology or Licensed Patents in addition to Project funding, the federal government may have its standard license rights with respect to such Licensed Technology or Licensed Patents.

License Property

'Licensed Technology' means all patentable inventions and Know-how for the production of red blood cells, white blood cells, platelets and bone marrow cells, which are either described in University Project proposal, or conceived or reduced to practice as part of Project, or conceived or reduced to practice, whether or not pursuant to or as part of the Project.

'Product(s)' means any red blood cells, white blood cells, platelets and bone marrow cells as well as any components, by-products, progeny or derivatives thereof and any factor, composition, substance, equipment, mechanism, device or other property and combinations thereof, the manufacture, use or sale of which would, but for this License, comprise an infringement of one or more Valid Claims.

Field of Use

A.  U.S. APPLICATION, SER. #07/366,639, OSMMN REF. #2363-022-55

        Methods, Compositions and Devices for Growing Cells.

        Filed  6/15/89

    B.  U.S. APPLICATION, SER. #07/628,343, OSMMN REF. #2363-023-55 CIP

        Methods and Compositions for the Ex Vivo Replication of Stem Cells

        and for the Optimization of Hematopoietic Progenitor Cell Cultures.

        Filed  12/17/90

    E.  U.S. APPLICATION, SER. #07/737,024, OSMMN REF. #2363-034-55

        Methods and Compositions for the Ex Vivo Replication of Stem Cells,

        for the Optimization of Hematopoietic Progenitor Cell Cultures,

        and for Increasing the Metabolism, GM-CSF Secretion and/or IL-6

        Secretion of Human Stromal Cells.

        Filed 7/29/91

    F.  U.S. APPLICATION, SER. #07/740,590, OSMN REF. #2363-035-55

        Methods for Human Gene Therapy, Including Methods and Compositions

        for the Ex Vivo Replication and Stable Genetic Transformation of Human

        Stem Cells, for the Optimization of Human Hematopoietic Progenitor Cell

        Cultures and Stable Genetic and/or IL-6 Secretion of Human Stromal

        Cells.

        Filed 8/5/91

    H.  U.S. APPLICATION, SER. #07,815,513, OSMMN REF. #2363-036-55

        Methods for Regulating the Specific Lineages of Cells Produced in

        a Human Hematopoietic Cell Culture, Methods for Assaying the Effect

        of Substances on Lineage-Specific Cell Production, and Cell Compositions

        Produced by these Cultures.

        Filed  1/2/92

    I.  U.S. APPLICATION, SER. #07/822,136, OSMMN REF. #2363-055-55

        Targeted Virus.

        Filed  1/17/92

    J.  PENDING U.S. APPLICATION, OSMMN REF. #2363-043-55

        Methods, Compositions and Devices for Maintaining and Growing Human

        Stem and/or Hematopoietic Cells.

        Filed  3/4/92

License Grant

The Israeli Licensor hereby grants to the Licensee, an exclusive license to exploit in any manner and for any and all purposes the Patent, including the right to grant sublicenses, make, have made, use, market and sell the Products.

License Property

The Company entered into a License Agreement to acquire a License of stem cell expansion technology related to bone marrow transplants. The Company received an exclusive, worldwide License to use the technology over the life of the related patent. The License grants exclusivity over all products, uses and related intellectual property, and grants the Company the right to enter into sub-Licenses. This technology, if fully developed, will offer novel solutions to make procedures like bone marrow transplants and other methods of cell therapy more accessible to patients suffering from leukemia, lymphoma, myeloma and a broad range of complicated diseases and disorders.