Royalty Report: Drugs, Cancer, Therapeutic – Collection: 5158

License Grant

The Company obtained from the Canadaan University the exclusive, worldwide license (the Verotoxin License), with the right to grant sublicenses, to make, use and sell any Verotoxin pharmaceutical composition for the treatment of neoplasia (a tumorous condition) described in the inventions claimed in certain Canadian and United States patent applications and any improvements therein (collectively, the Licensed Verotoxin Technology).

License Property

Verotoxin is a naturally occurring protein produced by certain strains of E. Coli bacteria which binds to specific receptor sites found on the exterior surfaces of certain living cells, including certain types of malignant tumor cells, epithelial intestinal cells of humans, certain dividing endothelial cells and certain lymphocytes. The Verotoxin molecule, after binding itself to a receptive cell, penetrates the cell and kills it.

Field of Use

Preliminary, pre-clinical studies suggest that the receptor to which verotoxin binds itself is found on the exterior surfaces of cells which constitute cancerous ovarian, testicular, cervical, breast and astrocytoma tumors of the brain.  Preliminary, pre-clinical testing of the effects of Verotoxin on astrocytoma tumors implanted in live nude mice has suggested that the molecule may inhibit the growth of such tumors and cause them to regress, in some cases completely, over a short time period and not reoccur.

License Grant

The Licensee exclusively licensed certain patents related to EphA3 from the Licensor, that formed the basis for the KB004 program.

License Property

This gene belongs to the ephrin receptor subfamily of the protein-tyrosine kinase family. EPH and EPH-related receptors have been implicated in mediating developmental events, particularly in the nervous system. Receptors in the EPH subfamily typically have a single kinase domain and an extracellular region containing a Cys-rich domain and 2 fibronectin type III repeats. The ephrin receptors are divided into 2 groups based on the similarity of their extracellular domain sequences and their affinities for binding ephrin-A and ephrin-B ligands. This gene encodes a protein that binds ephrin-A ligands. Two alternatively spliced transcript variants have been described for this gene.  

Anti-EphA3 has shown encouraging preclinical proof-of-concept results in multiple tumor models. The xenograft studies we conducted show that the anti-EphA3 antibody causes growth inhibition in EphA3-positive tumors, as well as in tumors that do not express EphA3 (the latter presumably through the effect on tumor vasculature).

Cancer cells are killed by KB004 binding to EphA3 through apoptosis, or ADCC, at relatively low concentrations. KB004 ex vivo selectively targets and kills leukemic stem cells, but not normal hematopoietic stem cells. In ex vivo assays of these cells, KB004 appears to kill
all cells expressing EphA3.

Field of Use

Under the agreement, the Licensee has rights to develop human antibodies that bind to or modulate EphA3.

License Grant

For the Exclusive Licenses, Licensor grants
–  an exclusive license, including the right to sublicense, under the Licensor Patent Rights, to research, develop, make, have made, use, sell, offer for sale, supply, cause to be supplied and import Compounds and Licensed Products in the Territory;
–  an exclusive license, including the right to sublicense, to use Licensor Technology and Confidential information in connection with the research. development, making, having made, use, sale, oiler for sale, supply, causing to be supplied and importation of Compounds and Licensed Products in the Territory;
–  an exclusive license, including the right to sublicense, under the Licensor Patent Rights to research, develop, make, have made, use, sell, offer for sale, supply, cause to be supplied and import Diagnostic Assays in the Territory; and
–  an exclusive license, including the right to sublicense, to use Licensor Technology and Confidential information in connection with the research, development, making, having made, use, sale, offer for sale, supply, causing to be supplied and importation of Diagnostic Assays in the Territory.

For the Non-Exclusive Research License, Licensor grants a non-exclusive, irrevocable, perpetual license in the Territory, with the right to sublicense to Affiliates, to use for all research purposes the Licensor Technology and Confidential Information disclosed to Licensee during the Term, excluding any Patent Rights relating thereto.

License Property

Licensor owns or otherwise controls certain patents, patent applications, technology, know-how and scientific and technical information relating to an EGFRvIII mutant peptide comprising the amino acid sequence LYS-LYS-GLY-ASN-TYR.

CDX-110 means the EGFRvlll mutant peptide consisting of the amino acid sequence LEU-GLU-GLU-LYS-LYS-GLY-ASN-TYR-V AL-V AL-THR-ASP-HIS covalently linked to a Cysteine and conjugated to keyhole limpet hemocyanin (KLH).  CDX-110 is a therapeutic cancer vaccine candidate.

Compound means a peptide that comprises at least a portion of an EGFRvIII comprising the amino acid sequence LYS-LYS-GLY-ASN-TYR. as an antigen. alone or as a component of a larger peptide. protein or molecule.

EGFRvIII means EGFR variant III peptide, a variant of EGFR. previously referred to as a type II variation of EGFR, consisting of the amino acid sequence of EGFR as set forth in GenBank Accession No, CAA2524Q. except amino acids number 1 through 24 have been deleted and where amino acids number 30 through 297 have been replaced by a Glycine. and naturally occurring variants thereof.

Additional Component means a therapeutically active (alone or in combination) adjuvant. immunomodulator. immunoregulator or hapten.

APC Product means an antibody or fragment thereof. that is targeted to an antigen-presenting cell (APC) and that comprises or is connected to a Compound or Licensed Product.

Patents are for the EGFRvlll Patent Family 1, 2, and 3.

Field of Use

The field of use for CDX-110 includes the treatment of glioblastoma multiforme or GBM.

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of cancer that begins within the brain.

Rindopepimut is an experimental therapeutic cancer vaccine that targets the tumor-specific molecule epidermal growth factor receptor variant III (EGFRvIII) in patients with Glioblastoma Multiforme (GBM)

License Grant

The University grants to Licensee
– the exclusive worldwide license in the Field of Use to use the Patent to manufacture and sell the Product; and,
– the right to grant sublicenses to any Patent licensed exclusively hereunder, provided that any Sublicensee agrees to be bound by the terms and conditions of this Agreement applicable to Sublicensees.

The agreement is exclusive except for the non-exclusive license granted to the U.S. government

License Property

The patents are for Method and Composition for Angiogenesis Inhibition, Generation And Use Of Mab FM155 To Inhibit Angiogenesis and Tumor Growth, and, Generation And Use Of MABXL313 To Inhibit
Angiogenesis And Tumor Growth In Vivo.

2805 60/114,878 January 6, 1999 Method and Composition for Angiogenesis Inhibition

2806 60/114,877 January 6, 1999 Method and Composition for Angiogenesis Inhibition

2908 60/143,581 July 13, 1999 Generation And Use Of Mab FM155 To Inhibit Angiogenesis and Tumor Growth

2909 60/143,534 July 13, 1999 'Generation And Use Of MAB XL313 To Inhibit Angiogenesis And Tumor Growth In Vivo

Anti-Angiogenesis for the Treatment of Cancer

In a process known as angiogenesis, cancer cells stimulate the formation of new blood vessels in order to bring oxygen and nutrients to rapidly-growing tumor tissue. The onset of angiogenesis is caused mainly by tumor cell production of growth factors that activate the cells that line the blood vessels. These activated cells begin to divide and lead to the remodeling of the extracellular matrix, which is a dense protein network that provides support and growth signals for blood vessels and tumors.

Field of Use

Field of Use shall mean any field of use.

License Grant

The Licensor granted an exclusive license to the patent, Tumor Radiosensitization Using Gene Therapy, for the prevention and treatment of all cancers except colon cancer, brain tumors and melanoma.

Field of Use

'Field' shall mean the prevention and treatment of all cancers except colon cancer, brain tumors and melanoma.

License Grant

Licensor, Chief Scientific Officer of Licensee, hereby grants to Licensee and its Affiliates during the Term an exclusive, worldwide, royalty bearing license, with the right to grant sublicenses through multiple tiers of sublicenses, in and to, the Technology, Licensed Products, Licensed Improvements, and Patents; and to develop, distribute, market, make, have made, use, have used, sell, have sold, offer for sale, and import Licensed Products.

License Property

Licensed Technology Primary human cells that secrete factors inhibiting tumor cell proliferation.

Recent experiments have led to the identification of a novel source of primary human cells that secrete a factor capable of inhibiting tumor cell growth. Co culture of tumor cell lines with these human cells results in inhibition of proliferation of the tumor cells and ultimate death. Further media conditioned by the primary human cells also inhibits proliferation of the tumor cells lines and death of the cells. The technology consists of methods for isolation and propagation of the primary human cells, gene profiles obtained from the cells identifying candidate micro RNAs and growth factor genes, and methods for generating media conditioned by these cells for isolation of the inhibitory factor(s).

This technology offers the potential to identify molecules that can kill tumor cells and further provides insight into the potential use of cells for delivery of these inhibitory factors in vivio.

Field of Use

The Licensee is a biotechnology company engaged in the discovery and development of cell therapeutic products and is developing pre-clinical-stage therapeutic agents and treatments for cancer, diabetes, heart, lung, and kidney diseases as well as for bone marrow and organ transplants. The Licensee's discoveries involve cell treatments.

License Grant

The Licensor, government public health organization, hereby grants and Licensee accepts, subject to the terms and conditions of this Agreement, an exclusive license under the Licensed Patent Rights in the Licensed Territory to make and have made, to use and have used, and to sell and have sold any Licensed Products in the Licensed Fields of Use and to practice and have practiced any Licensed Processes in the Licensed Fields of Use.  Upon written approval by PHS which will be given within thirty (30) days of a written request by Licensee, said approval not to be unreasonably withheld, Licensee may enter into sublicensing agreements under the Licensed Patent Rights.

License Property

Patent(s) or Patent Application(s) that are Licensed Patent Rights
– U.S. Patent 5,614,191 issued March 25, 1997
– USSN 08/821,840 (div of 08/404,685) filed March 21, 1997
Patent(s) or Patent Application(s) that are Background Patent Rights
– U.S. Patent 4,892,827 issued January 9, 1990

The Company entered into an exclusive worldwide licensing agreement with the National Institutes of Health and the FDA to develop and commercialize an IL-13 chimeric protein therapy.

The IL-13 chimeric protein is the fusion of the receptor-binding ligand IL-13 with a derivative of Pseudomonas exotoxin (PE38QQR).  Research has demonstrated that some solid tumors express high numbers of IL-13 receptors on their cell surfaces.  These receptor sites become a specific target for the IL-13 chimeric protein for inducing cytotoxicity at nanogram concentrations.  IL-13 Chimeric Protein Exotoxin is a genetically engineered compound incorporating a highly toxic material that destroys cells once linked to the target receptor on its surface.  Pre-clinical trials ongoing, initiate Phase I in the 2nd Quarter, 1999.

Cancer Indication Renal Cell, Brain, Kaposi's Sarcoma, Breast.

Field of Use

Licensed Fields of Use To use of the chimeric molecule hIL-13-PE38QQR or cphIL-13-PE38QQR to treat cancer.

License Grant

The Licensor, an University, granted a worldwide, exclusive license to the Licensee for patents and technology in the field.

License Property

License Patents European Patent No. 0636171 issued 6/7/00,  Patent No.6,403,326 issued 6/11/02 and its continuation, U.S. Patent number 6,339,143 issued January 15, 2002 and certain Antibodies and Cell Lines.

Field of Use

Therapeutic Subfield of cancer therapy (active and passive immunotherapy) in humans and non-humans and fertility control in non-humans.

The Animal Subfield shall include all therapeutic treatment in non-humans.

The Diagnostic Subfield shall include all diagnostics in humans and non-humans.