Royalty Report: Medical, Device, cardiac – Collection: 356974

License Grant

Licensor, two individuals from Italy, grants an exclusive, perpetual and irrevocable license to make, use, have made, sell, offer to sell, import, manufacture, market and distribute the Licensed Technology within the Territory. Licensee shall appoint an exclusive distributor of the Licensed Technology in Italy at the conditions to be separately agreed between the parties.

License Property

Licensor is the inventor of certain processes and devices that allow for the migration of organic cells into tissue samples while being incubated in a specialized bioreactor, the Technology.

lmprovements mean any Intellectual Property developed after the Effective Date by the Inventor/Licensor or any third party affiliated with Licensor that constitutes an improvement or enhancement of the functions of the Technology, that is associated to the Technology and that relates to a bioreactor device able to feed and repopulate a rotating tubular structure, with the exclusion of different or new functions relating to generation of electrical fields, pressure fields and fluid dynamic fields.

Field of Use

The intellectual property rights relates to our InBreath Bioreactor.

This bioreactor is the first in a series of products that Licensee is developing to address what we believe is a long-term growth opportunity in the emerging field of regenerative medicine. Regenerative medicine is a new field that uses stem cells to repair damaged organs (e.g., spinal cord and heart) and also to grow tissue (e.g., bladder and bronchus) and organs (e.g., heart and lung) outside the body for transplant.

InBreath hollow organ bioreactor is a device that can be used by a surgeon to seed cells onto a scaffold. The InBreath bioreactor enables the surgeon to
•
secure the scaffold to the bioreactor;
•
seed the patient’s cells on the scaffold under sterile conditions;
•
automatically rotate the scaffold to allow good cell distribution into the pores of the scaffold; and
•
remotely monitor the scaffold during the course of the two to three days incubation period before the transplant.
The InBreath bioreactor has several novel features such as allowing for separate cell seeding conditions on the inside and outside of the scaffold and for pumping cell culture media through the inside of the scaffold without the need for an external pump and tubes. The Licensee believe the InBreath hollow organ bioreactor is the world’s first bioreactor that has been used to perform a human transplant of a regenerated organ.

The Technology has proven beneficial medical uses in organ transplant as well as the potential for use in other areas.

License Grant

Sub-licensor grants to sub-licensee, a not-for-profit cardiology and heart surgery center, an exclusive, even as to sub-licensor, non-transferrable, non-sub-licensable, worldwide license under the sub-licensor Patents for performance of research in the Product Area and the development of Products in accordance with the terms and conditions hereinafter set forth. The Parties agree that the foregoing license to sub-licensee includes the right to research and develop parts of the heart, including, but not limited to, heart valves, cardiac patches, blood vessels, AV node, and the like, provided sub-licensee is conducting such research and development of parts of the heart solely in furtherance of  sub-licensees research and development of Products; provided, that this shall not be construed as a license to conduct clinical trials of, or sell, offer to sell, have sold, supply or import or otherwise commercialize or have commercialized, parts of the heart (including, without limitation, heart valves, cardiac patches, blood vessels, AV node and the like). The foregoing license shall be retroactive to the first publication date of a patent application falling within the sub-licensor Patents. Sub-licensor represents and warrants that it possesses all rights to bring demands, claims, and causes of action against the sub-licensee, and sub-licensees representatives, officers, shareholders, directors, employees, subsidiaries, affiliates, divisions, successors and assigns (collectively the “Released Parties”) for infringement of the sub-licensor Patents, and that such demands, claims, and causes of action are within the scope of the license set forth in this agreement.

License Property

Intellectual property related to the transplantation of the heart organ in human beings, whereby perfusion decellularization and/or perfusion recellularization has been utilized in any portion of the creation or manufacture of such whole heart organ.

Sub-licensor is engaged in the research, development, manufacture and marketing of perfusion decellularization and recellularization technology and the products that are created utilizing such technology.

Decellularization. The anatomical structure of organs is highly complex and enormously challenging to reproduce synthetically. We utilize porcine organs as the scaffold for creating human organs because significant anatomical and vascular similarities exist between the two species’ scaffolding. Using our proprietary perfusion decellularization process we remove the porcine cells from harvested porcine organs leaving behind a scaffold of extracellular matrix (“ECM”) that retains the architecture, mechanical properties, and vascular network of the original organ structure. Porcine ECM is estimated to be over 93% homologous to human ECM which significantly reduces potential for antibody formation and adverse reaction. In addition, we have generated human clinical data demonstrating the safety of our decellularized porcine liver scaffold in clinical trials of two products we previously developed, commercialized and spun out, Miromesh® and Miroderm®.

Recellularization. Recellularization is the process of growing new functional organs starting with the ECM that remains after the decellularization process is completed. We currently use living human cells harvested from organ donors to re-seed the ECM, and in the future intend to develop new techniques using patient-derived stem cells. Living human cells are adaptive, and when introduced into the decellularized ECM display unique regenerative, plasticity, and adhesion properties. The process of recellularization occurs in a bioreactor where media and living human cells are perfused into the ECM in the appropriate sequence in order to facilitate cellular regeneration and organ functionality.

Field of Use

Field of use is for the prevention and treatment of cardiovascular disease.

License Grant

Licensor, an university division of public health sciences, hereby grants to Licensee and Licensee accepts from Licensor, an exclusive, worldwide right and license, including the right to sublicense, to make, use and sell the Improvement Products under Licensors rights in the Improvement Patents in the Licensed Field only.

Licensor hereby grants to Licensee and Licensee accepts from Licensor, a non-exclusive, worldwide, right and license, including the right to sublicense, to the Know-How.

Licensor hereby grants to Licensee and Licensee accepts from Licensor for the Option Period (in each case) a non-transferable (except as specifically stated in Agreement), exclusive option to negotiate in good faith for a royalty-bearing, worldwide, exclusive license, including the right to sublicense, to practice all the rights under the New Development Patents in the Licensed Field only (the Option).

License Property

Patent Rights
6,673,339 – Prosthetic kidney and its use for treating kidney disease
6,576,019 – Bladder reconstruction
6,514,292 – Corporal tissue penile reconstruction

Field of Use

The agreement is in the field of regenerative medicine that will advance the development of organs and tissues to treat human diseases and disabilities.

The primary focus of the research will be on creating “neo-organs” and tissues. Neo-organs and tissues are derived from a patient’s own cells that are grown on a scaffold or model that is bioresorbable, or can be absorbed by the body. These neo-organs become functional replacements after being implanted in the patient’s body. Since they come from a patient’s own cells (autologous cells) there is virtually no risk of rejection from the body’s immune system.
In tissue engineering, neo-organ is a final structure of procedure based on transplantation of constructs consisting of endogenous stem/progenitor cells grown ex vivo within predesigned matrix scaffolds. The scaffold eventually is resorbed, leaving transplanted cells and the stroma that they produce in the body.

Licensed Field means human and animal organs, tissues and tissue-engineered and regenerative medicine products directed to their functions in the following areas (i) Genitourinary Tissue, (ii) Kidney Tissue, (iii) Cardiovascular Tissue, (iv) Nervous Tissue, and (v) Trachea Tissue. Each of Genitourinary Tissue, Kidney Tissue, Cardiovascular Tissue and Nervous Tissue is a Subfield.

Genitourinary Tissue means the reproductive system and the urinary system, including the male and female internal and external genitalia as well as all organs concerned in the formation and voidance of urine, but excluding Kidney Tissue. For the removal of doubt, Genitourinary Tissue is not to be considered Cardiovascular Tissue merely because it contains components of Cardiovascular Tissue.

Kidney Tissue means the kidney.

Cardiovascular Tissue means arteries, arterial tissue, veins and venous tissue. Cardiovascular Tissue does not include cardiac muscle tissue or heart valves.

Nervous Tissue means the (i) central nervous system, (ii) peripheral nervous system, and (iii) functional subcomponents and subunits of (i) and (ii) above. For the removal of doubt, a tissue or organ is not considered Nervous Tissue merely because it contains components of Nervous Tissue.

Trachea Tissue means the trachea and functional subcomponents and subunits thereof. Trachea Tissue does not include the bronchus and larynx.

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

According to the agreement, the Licensees U.S. Subsidiary was granted a worldwide, royalty bearing, exclusive license from the Israeli Licensor, an affiliate of university,  to develop and commercialize technology directed to RAFT modification of polysaccharides and use of a bioreactor for supporting cell constructs.

License Property

Bioreactors and polysaccharides are part of the Cell & Gene Therapy Platform.

Bioreactors is for cell culture.

Polysaccharides is part of the Scaffold group. Scaffolds, including alginate and sulfated alginate scaffolds, polysaccharides thereof, and scaffolds for use for cell propagation, trans-differentiation, and transplantation in the treatment of autoimmune diseases.

Field of Use

The field of use is for the treatment of autoimmune diseases and to identify the most promising new autologous therapies and provide a pathway for them to reach patients more quickly, more efficiently and in a scalable way, thereby unlocking the power of cell and gene therapy for all patients. A wide range of therapies and supporting technologies include, but not limited to, Tumor Infiltrating Lymphocytes (“TILs”), CAR-T and CAR-NK, dendritic cell technologies, exosomes and bioxomes and viral vectors.

RUXIENCE is approved in the US for treating chronic Lymphotic leukemia, non-Hodgkin’s lymphoma, Microscopic Polyangiitis with glucocorticoids, and Granulomatosis with Polyangiitis.

Microscopic polyangiitis (MPA) is a condition that causes small blood vessels to be inflamed. It's a rare type of vasculitis. The disease can damage the blood vessels and cause problems in organs around the body. MPA most often affects people in their 50s and 60s, but it can happen in people of any age.

Granulomatosis with polyangiitis is an uncommon disorder that causes inflammation of the blood vessels in your nose, sinuses, throat, lungs and kidneys. Formerly called Wegener's granulomatosis, this condition is one of a group of blood vessel disorders called vasculitis. It slows blood flow to some of your organs.