Royalty Report: Drugs, Cancer, Therapeutic – Collection: 368508

License Grant

Licensor hereby grants to Japanese Licensee with respect to Licensor’s rights in and to the Licensed Technology, an exclusive sublicense, to the extent that such Licensed Technology is Controlled by Licensor with Licensor having obtained such Control, directly or indirectly, from a Third Party, and an exclusive license, to the extent that such Licensed Technology is Controlled by Licensor without Licensor having obtained such Control, directly or indirectly, from a Third Party, in each case within the Field of Use, and solely within the Territory, to research, develop, use, sell, offer for sale, promote and/or import IL13 and/or Products during the Term and the Additional Term. Such sublicense and license shall include rights to Licensee to designate its employees and the employees of its Affiliates to promote Products and to use Third Parties to inspect Products for receipt of shipment of Products.  Licensee acknowledges that the exclusive sublicense granted herein is subject to certain retained rights of the Licensors in some of the Licensed Patent Rights.

License Property

Intellectual property relating to IL13-PE38QQR, generically know as cintredekin besudotox.  Cintredekin besudotox is made from a human protein, Interleukin 13 (IL13), linked to a bacterial toxin, Pseudomonas exotoxin (PE). The IL13 portion binds to receptors on the tumor.

Licensor has determined that the key to making a useful tumor-targeting drug is the targeting mechanism that selects tumor cells while ignoring healthy ones. Cintredekin besudotox is a recombinant protein consisting of a single molecule composed of two parts a tumor-targeting molecule (interleukin-13) and a cytotoxic agent (Pseudomonas Exotoxin, or PE). IL13 receptors are found on malignant glioma cells, but not on healthy brain cells. The IL13 portion binds to receptors on the tumor like a key fits into a lock. The cancer cell latches onto and absorbs the IL13 and the attached PE, causing destruction of the cancer cell. Healthy brain cells appear to be unharmed because they do not have the IL13 receptors, and thus do not ingest the PE. IL13-PE38QQR has received orphan drug designation in Europe and the U.S., and fast track drug development program status from the U.S. Food and Drug Administration (FDA).

App. No. PCT/US00/31044 – Use of the Product in gene therapy applications to treat human cancers.
App. No. PCT/US01/25663 – Use of the Product in gene therapy applications to treat human cancers.

IL13 shall mean hIL13-PE38QQR and/or cphIL13-PE38QQR.

Product(s) shall mean any pharmaceutical product containing IL13 as the active component, in any formulation or dosage.

Licensed Technology shall mean any technology, know-how and other intellectual property (other than Trademarks) directed to IL13 and/or Products, formulations and/or methods Controlled on the Effective Date or to be Controlled during the Term and the Additional Term by Licensor or its Affiliates which are necessary or useful to research, Develop, use or Commercialize IL13 and/or the Product in the Territory in the Field of Use and shall include the Licensed Patent Rights and any Licensor Data.

Field of Use

IL13-PE38QQR generically knowns as cintredekin besudotox (sin' tre dek' in be soo' doe tox), which is a lead drug candidate for the treatment of glioblastoma multiforme (GBM).
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive type of cancer that begins within the brain.

Field of Use shall mean, for each patent or application included in the Licensed Patent Rights listed hereto, the field of use designated below for such patent estate, and for any other Licensed Technology, the Field of Use shall mean the field of use for treating human cancer.

Licensed Fields of Use Use of the Licensed Product(s) and/or the Licensed Process(es) in gene therapy applications to treat human cancers. Specifically, transfection of cancer cells with the IL-13 Receptor-alpha-2 (IL-13Ra2) claim in order to sensitize such cells to the therapeutic effects of the IL-13 Receptor targeted immunoconjugates, hIL-13-PE38QQR or cphIL-13-PE38QQR, which were exclusively licensed to Licensee under DHHS exclusive patent license L-226-96/0.

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 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, non-profit hospital, grants to Licensee the exclusive, worldwide License, with the right to grant subLicenses, to conduct research, develop Products, modify existing and/or future Products, and market such Products in the Field of Use using the Patent Rights and/or the Technical Information and to develop, use, make, have made, practice, import, carry out, manufacture, have manufactured, offer for sale, sell and/or have sold Products in the Field of Use in the territory using the Patent Rights and/or the Technical Information.

License Property

The Licensor owns and is entitled to grant License rights with respect to certain Patent Rights and Technical Information invented or developed in the course of the Licensor’s Molecular Oncology Research Program in the field of human therapeutic products, including new pharmaceutical products and/or non-prescriptive products based on, or utilizing the Patent Rights and/or Technical Information developed in the course of the Program.

Product or Products shall mean any human therapeutics, diagnostics (including algorithms or any components thereof), bioinformatics and any other human health care products and/or services in the Field of Use utilizing or derived in any manner whatsoever from any of the Patent Rights, Technical Information or Licensee Improvements, which Product(s), except for the license granted hereunder, would infringe a Valid Claim, the Patent Rights or those Future Patent Rights licensed to Licensee.

Licensee has developed a new anti-cancer agent as well as a new methodology specific for the treatment of invasive tumors such as glioblastoma multiforme, the most aggressive form of brain cancer, as well as both Her2-positive and Her2-negative breast cancers.

Licensee believes this approach is effective against brain and breast cancer in rodents, significantly extending their longevity and decrease the tumor size. Licensee proposes to expand this proprietary technology to other forms of cancer treatments together with common eye diseases such as age-related macular degeneration and diabetic retinopathy.

The technology is a family of related nano-biopolymers collectively referred to as Polycefin™ that are capable of acting as a drug delivery and targeting platform for cancer therapy and diagnostics. The new nanoscale drug, Polycefin, based on Licensee’s delivery system, was developed and patented by Licensee’s scientists. It is non-toxic, non-immunogenic, and biodegradable. It is based on a naturally derived polymer, i.e., polymalic acid. A significant feature of this novel agent is its ability to target multimeric tumor-associated proteins with one drug, a capability that other existing agents do not have. Licensee has proven that the significant anti-tumor and anti­angiogenic activity of this new drug is effective against both brain and breast cancers.

Polycefin are designed to target cancer cells and deliver a variety of bound therapeutics to them. In vivo pre-clinical studies have shown evidence that existing cancer drugs could have increased efficacy and reduced side effects when attached to the Polycefin  platform. Polycefin’s have the ability to harbor various drugs at the same time making it a master delivery vehicle that can be customized for a particular tumor and potentially for an individual patient.  Additionally, in vivo testing has shown efficacy against more than one type of cancer (breast and  brain) suggesting that Polycefin may have application to a wide range of cancer types, therapeutics and diagnostics.

Patent Rights
Title
Antisense Inhibition of Laminin-8 expression to Inhibit Human Gliomas
U.S. Patent & Trademark Office
Application No.
10/570,747
Filing Date
January 30, 2007
Patent No.
7,547,511
Issue Date
June 16, 2009

U.S. Patent & Trademark Office
Application No.
12/473,992
Filing Date
May 28, 2009

Japanese Patent Office
Application No.
2006-526391
Filing Date
September 13, 2004

Title
Polymalic Acid-Based Multifunctional Drug
Delivery System
U.S. Patent & Trademark Office
Application No.
10/580,999
Filing Date
March 12, 2007

European Patent Office
Application No.
04813049.6
Filing Date
December 3, 2004

Japanese Patent Office
Application No.
2006-542822
Filing Date
December 3, 2004

Title
Poly(Beta Malic Acid) with Pendant Leu-Leu-Leu
Tripeptide for effective Cytoplasmic Drug deliver

U.S. Patent & Trademark Office
Application No.
PCT/US2009/40252
Filing Date
April 10, 2009

Title
Drug delivery of Temozolomide for Systemic based treatment of Cancer
U.S. Patent & Trademark Office
Application No.
61/285,495
Filing Date
December 10, 2009

Field of Use

Field of Use shall mean human therapeutic products, including new pharmaceutical products and/or non-prescriptive products based on, or utilizing the Patent Rights and/or Technical Information developed in the course of the Program.

License Grant

Licensee grants to German Licensor an exclusive license to make, have made, use, import, export, distribute for sale and to offer to sell the Licensed Products in all territories of the world (the Territory) the Technology within the Field (collectively referred to as the License).

License Property

Technology shall mean that technical information owned by or licensed to Licensee related to the combination of a Pseudomonas exotoxin, or a derivative thereof (hereinafter referred to as PE), with erbB2 ligand or portion(s) thereof capable of targeting the erbB2 antigen.

Licensed Product(s) shall mean compounds and methods of therapy utilizing the Technology within the Field.

Specialties means finished pharmaceutical preparations in dosage form which contain a Licensed Product as an active ingredient.

Patents
License L-318-91, Oncologix, Inc./Medical Oncology, Inc. erbB-2 License

U.S. Patent Number 5,458,878 (USSN 07/522,562 (CIP of 07/459,635)), filed May 14, 1990, issued October 17, 1995, entitled  'Target-Specific, Cytotoxic, Recombinant Pseudomonas Exotoxin,' Pastan et al.

Background Licensed Patent Rights

U.S. Patent Number 4,892,827 (USSN 06/911,227), filed September 24, 1986, entitled  'Recombinant Pseudomonas Exotoxins Construction of an Active Immunotoxin with Low Side Effects'

U.S. Patent Application Number 06/836,414, filed March 5, 1986, entitled 'Human Gene Related to but Distinct From EGF Receptor Gene,' Richter et al.

L-211-84/0, Oncologix, Inc./Medical Oncology, Inc. EGF License

Field of Use

This agreement pertains to the drug industry relating to cancer therapy.