Royalty Report: Drugs, Cancer, Therapeutic – Collection: 26125

License Grant

A  portion of this intellectual property is owned by the Licensor and granted to the Company through an exclusive licensing agreement with Licensor, non-profit academic medical center.

License Property

One of the curaxins from the 9-aminoacridine group is a long-known anti-infective compound known as quinacrine, which we refer to as Curaxin CBLC102. It has  been  used for over 40 years to treat malaria, osteoarthritis and autoimmune disorders. However, we have discovered new mechanisms of action for quinacrine in the area of apoptosis. Through assay testing performed at Dr. Andrei Gudkov's laboratories beginning in 2002, which included testing  in a variety of human tumor-derived cell lines representing cancers of different  tissue origin (including RCC sarcomas, prostate, breast and colon carcinomas),  we have observed that Curaxin CBLC102 behaves as a potent NF-kB suppressor and  activator of p53 in these types of cancer cells. It has favorable  pharmacological and toxicological profiles and demonstrates the anticancer  effect in transplants of human cancer cells into primates. These features make  Curaxin CBLC102 our prime IND drug candidate among other curaxins. The drug  candidate is currently in Phase II clinical trials for treatment of hormone  refractory prostate cancer.  We also intend to conduct additional Phase II  clinical trials with Curaxin CBLC102 for RCC and multiple myeloma.

Field of Use

The rights granted apply to the healthcare industry.  Licensee is engaged in the discovery, development and commercialization of products for cancer treatment and protection of normal tissues from radiation and toxins.

License Grant

The Licensor hereby grants to the Licensee an exclusive license under the Licensed Rights to under the Licensed Property.  The Licensee has a unique opportunity to accelerate our development by utilizing intellectual property, drug leads, new research technologies, technical know-how and original scientific concepts derived from 25 years of research achievements relevant to cancer by licensed patent applications and patents.

License Property

CCF Technology shall mean all CCF’s unpatented inventions, know-how, trade secrets, analysis, discoveries, techniques, methods, clinical and other data, and other intellectual property relating to the research of Doctor or arising out of or in direct connection with work of Doctor in the field of regulating cell death (I) curing cancer treatment side effects by differential modulation cell death / survival mechanisms uniquely deregulated in cancer cells; (ii) selective sensitization of cancer cells to treatment by using the same approach; (iii) using anti-apoptotic proteins secreted by microbial parasites to cure tissue damage associated with cancer treatment, inflammation and other pathologies (stroke, heart attack).

Provisional Patent Application 60/526,538 – Methods of Inhibiting Apoptosis Using Latent TGFβU.S. Provisional Patent Application 60/526,666 – Methods of Identifying of Modulators of Apoptosis From Parasites and Uses Thereof U.S. Provisional Patent Application 60/526,496 – Methods of Inhibiting Apoptosis Using Inducer's of NF-kB U.S. Provisional Patent Application 60/526,667 – Methods of Inhibiting Apoptosis Using Latent TGFβU.S. Provisional Patent Application 60/526,460 – Methods of Protecting Against Radiation Using Inducer's of NF-kB U.S. Provisional Patent Application 60/526,461 – Methods of Protecting Against Radiation Using Flagellin U.S. Provisional Patent Application 60/571,149 – Small Molecules Inhibitors of MRP1 and Other Multi drug Transporters U.S. Provisional Patent Application 60/589,637 – Activation of p53 and Inhibition of NF-kB for cancer treatment.

Field of Use

Licensed Field shall mean shall mean the practice, production, manufacture, sale and use of the Licensed Rights for the discovery, development and commercialization of methods, techniques, devices, systems, animals and therapeutics in the field of regulating cell death

CBLC100 series small molecules that restore the activity of p53 tumor suppressor in cancers, including renal cell carcinomas, sarcomas, prostate cancers and other types of malignancies; curaxines and derivatives thereof are representative examples of this category;
CBLB101 series substances of biological nature (i.e., cytokine, chemokines and other secreted molecules) and their bioactive derivatives produced by tumor cells and capable of modulating cell survival; TGFß2 and derivatives thereof and derivatives thereof are representative examples of this category;
CBLB501 series natural factors produced by extracellular parasites and symbiont of humans and other mammalian species and their bioactive derivatives capable of modulating cell survival mechanisms of host cells; flagellin of Salmonella typhimurium and derivatives thereof are representative examples of this category;
CBLC500 series small molecules modulating tumor and normal cell sensitivity to cytotoxic chemicals by altering activity and substrate specificity of multi drug transporters; inhibitors of MRP1 and derivatives thereof are representative examples of this category.

License Grant

The Canadian Licensor grants to the Israeli Licensee an exclusive, even as to Licensor, right and license throughout the Territory, with the right to grant sublicenses, under the Licensor Intellectual Property
– to Develop, have Developed, make, have made, and use the Licensed Compound and Licensed Product in the Field, and
– to sell, offer for sale, register, Commercialize and otherwise exploit the Licensed Product in the Field; provided that notwithstanding the exclusive rights granted to Licensee in the foregoing grant, Licensor shall retain the limited right to use the Licensor Intellectual Property to the extent necessary to perform its express obligations under this Agreement, including the Clinical Development Plan,  to conduct the Licensor Clinical Studies,  subject to the approval of the Joint Steering Committee, and as otherwise agreed to in writing by the Parties.

The exclusivity of the sublicense granted under such Licensor Intellectual Property is subject to the applicable non-exclusivity terms in the another Agreement.

Included with this agreement is also a non-exclusive, non-sublicensable, except to subcontractors as permitted under this Agreement, solely to permit such subcontractors to perform Licensors assigned responsibilities under the Clinical Development Plan, royalty-free, fully-paid right and license, by Licensee to Licensor under the Licensee Know-How and Licensee Patent Rights, solely to the extent necessary to conduct the activities assigned to Licensor by the Joint Steering Committee under the Clinical Development Plan.

License Property

The licensed property includes
TRPM-2 Antisense Therapy;
TRPM-2 Antisense Therapy and Combination composition;
TRPM-2 Antisense Therapy Using ai Oligonucleotide Having 2-0-(2- Methoxy)Ethyl Modifications Compound;
Chemo-and radiation-sensitization or cancer by antisense TRPM-2 oligodcoxynucleotides;
Treatment of Melanoma by Reduction in Clusterin Levels;
Clusterin antisense therapy for treatment of cancer;
Treatment of Cancer By Perturbation of Clusterin Levels;
Human Type 2 RNASE H;
Gapped Oligonucleotides, Directed to Gapmer and Hemimer Compounds with 2-O-ALKYL modifications;
2-O-Modified Nucleosides and Phosphoramidites; and others.

The collaboration agreement is for developing and commercializing OGX-011. OGX-011 is a Phase III cancer therapy designed to inhibit cancer treatment resistance. OGX-011 is expected to be used as adjunct therapy to enhance the effectiveness of chemotherapy and has shown promising results when added to currently available chemotherapies in several tumor types addressing a significant unmet medical need.

Field of Use

The Field means the prevention, diagnosis or treatment of any disease or medical condition in humans.  Specific fields addressed in the patents include prostate cancer cells, human renal cell cancer (RCC) cells and some breast cancer cells.

License Grant

Licensor hereby grants to Licensee an exclusive license under the Licensed Patents in the Territory to make, have made, develop, use, practice, import, export, distribute, market, promote, offer for sale, and sell Licensed Products in the Licensed Field.

Licensor hereby grants to Licensee a non-exclusive license in the Territory under Licensor’s rights in the Know-How to use and practice any method, process, or procedure within the Know-How and otherwise use and exploit the Know-How; all in the Licensed Field; provided however, that with respect to Project Information, such non-exclusive license shall be limited to the Project Information Licensed Field.

License Property

The technology relates to drugs used in the treatment of various cancers.

Licensed Patents means
Patent Applications 61/249,596; 61/423,842; 61/423,825; 61/392,296; 61/423,832; 61/254,395; 61/423,838

1.
REVERCOM

·
Drug summary Liposome-packaged combination of proprietary molecule, inhibitor of multidrug resistance transporter, and conventional chemotherapeutic agent.

·
Potential use adjuvant applied as part of chemotherapy of cancer patients.

2.
MOBILAN

·
Drug summary Adenovirus-based treatment inducing immune response. Ready for final stage of preclinical development.

·
Potential use Universal anti-cancer vaccine.

3.
ARKIL

·
Drug summary Androgen receptor inhibitor, prepared for Hit-2-Lead optimization studies.

·
Potential use Nanodrugs for treatment of prostate cancer (both hormone (androgen)-dependent and –independent/refractory forms).

4.
ANTIMYCON

·
Drug summary MYC inhibitor.

·
Potential use Drugs for treatment of a broad range of solid tumors (breast, prostate, colon, non-small cell lung carcinoma, etc.) and hematological malignancies.

Projects and Licensed Patents
1. Projects

Drug
Definition

Mobilan = Research, development and support of an immunotherapeutic drug candidate based on recombinant adenovirus vector, stimulating immune response in humans as a vaccine-like treatment for cancer or other indications.

Revercom = Research, development, formulation and support of a drug candidate based on proprietary Reversan compound as an adjuvant for chemotherapy.

Antimycon = Research, development, lead optimization, formulation and support of a drug candidate regulating cMyc transcription factor for cancer indications.

Arkil = Research, development, lead optimization, formulation and support of a drug candidate regulating androgen receptor for prostate cancer.

Xenomycin = Research, development, lead optimization, formulation and support of a drug candidates based on proprietary Curaxin family of compounds for anti-infective/anti-biotic/anti-fungal applications.

2. Licensed Patents

Product
Title
Inventors
Country
Application No.
Patent No.

MOBILAN = Use of Toll-Like Receptor and Agonist for Treating Cancer
Andrei Gudkov (RPCI, CBLI)
U.S.
61/249,596
n/a

MOBILAN = Toll-like receptor 5 agonist produced and secreted by mammalian cells
Andrei Gudkov (RPCI), Venkatesh Natarajan (RPCI)
U.S.
61/423,842
n/a

MOBILAN = Functional bacreriophage-based nanoparticles coated by Toll-like receptor 5 agonist
Andrei Gudkov (RPCI, CBLI), Venkatesh Natarajan (RPCI)
U.S.
61/423,825
n/a

ANTIMYCON = Small molecules inhibiting oncoprotein MYC
Andrei Gudkov (RPCI), Catherine Burkhart (CBLI), Mikhail Nikiforov (RPCI), Michelle Haber (CCIA), Murray Norris (CCIA)
U.S.
61/392,296
n/a

ANTIMYCON = Small Molecules Inhibiting Oncoprotein MYC
Andrei Gudkov (RPCI), Catherine Burkhart (CBLI), Mikhail Nikiforov (RPCI), Michelle Haber (CCIA), Murray Norris (CCIA)
U.S.
61/423,832
n/a

ARKIL = Method for treating androgen receptor positive cancers
Katerina Gurova (RPCI), Natalia Narizhneva (CBL)
U.S.
61/254,395
n/a

REVERCOM = Dual cargo nanoparticles combining MRP1 inhibitors with chemotherapeutic drugs
Andrei Gudkov (RPCI, CBLI), Aridam Sen (RPCI), Catherine Burkhart (CBLI), Padmaja Kunapuli (RPCI)
U.S.
61/423,838
n/a

Field of Use

“Application” means the intended use for a Licensed Product, including the diagnosing, treating, curing, mitigating, and/or preventing a disease or other condition in a human or other animal, such as small cell lung cancer, large cell lung cancer, or other specific disease state.

License Grant

This agreement grants the Company an exclusive world-wide license to patents, patent applications, and other intellectual property related to GCS-100 Material.

License Property

The Company's lead drug candidate GCS-100 (formerly known as GBC-590), a potential treatment for multiple forms of cancer, recently completed Phase II(a) clinical trials for pancreatic cancer and completed Phase II(a) clinical trials for colorectal cancer in 2001.

Field of Use

The rights granted apply to the medical industry.

License Grant

The Parties, one U.S. and the other Japanese, desire and intend to collaborate with respect to the Development and Commercialization of Products in the Field in the Territory.

License Property

Two pharmaceutical companies entered into a global agreement to develop and commercialize MDV3100, a investigational drug for the treatment of prostate cancer.  MDV3100 is currently being evaluated in the Phase 3 AFFIRM clinical trial in men with castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy.

MDV3100 is currently being evaluated in the Phase 3 AFFIRM clinical trial in men with castration-resistant prostate cancer who were previously treated with docetaxel-based chemotherapy.

MDV3100, a new generation of oral anti-androgen, which shows different pharmacological profiles from current anti-androgens, has been shown in preclinical studies to provide more complete suppression of the androgen receptor pathway than bicalutamide, the most commonly used anti-androgen. MDV3100 slows growth and induces cell death in bicalutamide-resistant cancers via three complementary actions – MDV3100 blocks testosterone binding to the androgen receptor, impedes movement of the androgen receptor to the nucleus of prostate cancer cells (nuclear translocation), and inhibits binding to DNA. Preclinical data published in Science earlier this year demonstrated that MDV3100 is superior to bicalutamide in each of these three actions.

Field of Use

The rights granted apply to the healthcare industry.