Royalty Report: Drugs, Cancer, Disease – Collection: 372535

License Grant

Licensor grants an exclusive, world-wide license under the Licensed Patents to import, make, have made, use, sell, offer for sale and have sold Licensed Products for the Field of Use.

License Property

Licensor has certain intellectual property rights related to nucleoside analog pharmaceuticals including Nicotinamide Adenine Dinucleotide and prodrugs of Cordycepin.

The patents relate to Nucleoslde Prodrugs Resistant to Metabolic Deactivatlon.

Field of Use

Cordycepin has been studied in a National Cancer Institute-sponsored Phase I clinical trial for treating TdT-positive ALL leukemia patients. The therapy depends upon the presence of TdT for its activity. TdT is a polymerase expressed in immature, pre-B, pre-T lymphoid cells, and acute lymphoblastic leukemia/lymphoma cells. TdT, and similar enzymes found in fungi and parasites, recognize Cordycepin and its analogues and add them onto growing nucleic acid chains thereby terminating synthesis of the nucleic acid and replication of the cell. Importantly, TdT expression in normal human tissue is limited to primitive lymphoid cells in the bone marrow and thymus, so most normal cells in the body are unaffected by the drug. In addition to effectively treating TdT-positive ALL and CML, Cordycepin can also be used to treat diffuse high-grade lymphoblastic lymphoma, which also expresses TdT.

License Grant

This agreement is for development and commercialization of the clinical compound forodesine hydrochloride in markets across Europe, Asia and Australasia.

Licensor grants the Licensee of Bermuda an exclusive right and license in the Territory, with the right to sublicense, to Develop, make, have made, package and have packaged, use, promote, market, offer for sale, sell and import Licensed Products in the Field, under the Licensor Patents, Licensor Know-How and the Trademark.

Licensor grants during the Term of this Agreement a limited non-exclusive right to use the Licensor Logo on Promotional Literature in the Field in the Territory.

License Property

Licensor owns or controls patents and know-how related to a series of proprietary compounds which act as PNP Inhibitors, including the compound known as __X-1777.

Licensed Products means all pharmaceutical preparations in all dosage strengths, formulations and methods of administration that contain the Compound as its active ingredient, alone or in combination with another active ingredient.

Trademark means the trademark Fodosine or such other trademark approved by the JDC for use in connection with the Licensed Products, but excluding the Secondary Marks.

B-cell Acute Lymphoblastic Leukemia/lymphoma or B-ALL means a disease in which certain cells of the B lymphocytes or B-cells are malignant, and have populated the bone marrow.

B-CLL means B-type chronic lymphocytic leukemia.

B-NHL means a Non-Hodgkin’s lymphoma in which the malignant cells have characteristics predominantly of the B lineage.

Field of Use

Field means the treatment of all Cancerous and/or Pre-Cancerous States in humans, specifically for the treatment of certain T-cell and B-cell mediated diseases in the area of oncology.
Fodosineâ„¢ is a transition-state analog inhibitor of the target enzyme purine nucleoside phosphorylase (PNP). The drug is currently being studied in a number of clinical trials including a Phase IIa clinical trial in patients with T-cell leukemia.

License Grant

Licensee received an exclusive worldwide license from the University.  This includes the rights to sublicense and the intellectual property associated with SDX-101 and SDX-102, as well as issued patents and patent applications for several pre-clinical-stage projects, including the SDX-103 program.

License Property

SDX-101 is an oral compound which does not suppress the body’s immune system for the treatment of CLL. SDX-101 is an isomer, or component, of Lodine®, a marketed anti-inflammatory drug. The U.S. Food and Drug Administration, or FDA, has granted orphan drug status, a designation for drugs intended to treat a rare disease or condition affecting no more than 200,000 individuals in the U.S., for SDX-101 for the treatment of CLL.

SDX-102 is an intravenously administered small molecule which laboratory studies have shown kills tumors which cannot produce an important metabolic enzyme. Safety and tolerability data on SDX-102 were collected in clinical trials conducted at academic centers sponsored by the National Cancer Institute, or the NCI. These clinical trials tested the drug across a variety of cancers which are now known to produce this enzyme with a high frequency. The Licensee developed a proprietary, practical laboratory assay, or test, to identify patients whose cancers cannot produce this metabolic enzyme. In 2004, the Licensee was conducting Phase II trials of SDX-102 and are using their assay to select patients for these trials in difficult-to-treat cancers, including non-small cell lung cancer, or NSCLC, pancreatic and mesothelioma, none of which was previously studied by the NCI. The SDX-103 program involves analogs of the compound indanocine. Indanocine and indanocine analogs were synthesized and characterized at the University by the Licensee's founders. Indanocine displayed potent anti-proliferative activity when tested against a multitude of cancer cell lines at the NCI. These compounds differ from many clinically used drugs that block cell division in that they are active against multi-drug resistant cells and selectively kill non-dividing malignant cells. Anti-tumor activity of SDX-103 analogs has been observed in preliminary animal studies.

Field of Use

SDX-101 is covered by two use patents in the U.S. that prohibit third parties from using etodolac and etodolac analogs to treat CLL and NHL and R-etodolac and R-etodolac analogs to treat leukemias. These use patents expire in 2019. In the U.S. and selected foreign countries, the Licensee is pursuing additional use patents for etodolac, R-etodolac and etodolac analogs as well as composition of matter patents for etodolac analogs in the U.S. and in selected foreign countries.  SDX-102 and assay methods were covered by two use patents in the U.S. that prohibit third parties from using an assay to measure MTAP status in a patient and then treating with an adenyl succinate synthetase inhibitor such as alanosine. These patents expired in 2013. SDX-102 is also covered by a patent in the U.S. that prohibits third parties from treating multiple drug resistance in MTAP-deleted tumors using an adenine synthesis inhibitor, such as l-alanosine. A patent application covering an assay method and monoclonal antibody for determining the presence or absence of MTAP is currently pending. Similar applications are being pursued or have issued in selected foreign countries.

License Grant

University hereby grants a worldwide exclusive license under the Licensed Technology, to develop, manufacture, have manufactured, use, market, import, have imported, offer for sale and sell Licensed Products.

License Property

“Licensed Products” shall mean all products derived from a combination of LYM-1 antibody or LYM-2 antibody plus the radioactive Iodine 131 combination.

United States Patent 4,724,213 issued February 9, 1988; Epstein, “Murine Hybridoma LYM-1 and Diagnostic Antibody Produced Thereby.”  United States Patent 4,724,212 issued February 9, 1988; Epstein, “Murine Hybridoma LYM-2 and Diagnostic Antibody Produced Thereby.”

“Hybridoma 173-9, Lym-1” (NU 8314-A)    A hybridoma clone, designated Lym-1, was produced from the fusion of primed mouse splenocytes and mouse myeloma NS-a cells. Hybridoma Lym-1 produced a murine IgG2a monoclonal antibody which recognizes a 31, 32, 33 and 35 kilodalton cell surface protein expressed in normal and malignant B lymphocytes.  Immunoperoxidase staining of a panel of normal human tissues shows that Lym-1 reacts with germinal center and mantle zone B lymphocytes and interdigitating histiocytes of the lymph node, medullary dendritic cells of the thymus, and weakly with surface epithlium of the colon. A subset of peripheral blood B cells are positive and no reactivity has been observed in human bone marrow by flow cytometric analysis. The antigen recognized by Lym-1 is not shed from the surface of lymphoma cells either in cell culture or in patients and is not modulated after Lym-1 binding. Lym-1 itself has been shown to have high avidity to human lymphoma cells IN VIVO as demonstrated by radionuclide binding studies in lymphoma patients using I-123 conjugates. Binding to normal tissues such as the bone marrow, spleen, lymph node, liver, kidney, lung or central nervous system has not been demonstrated in over 30 patients studied. Lym-1 has further been found to be highly stable to radionuclide conjugation methods and may be prepared as F(ab1)2 or F(ab) fragments without significant loss of antibody activity. Collectively, these data suggest that Lym-1 will be an appropriate reagent for IN VIVO diagnosis and therapy of the human B-cell lymphomas and leukemias.

'Hybridoma Clone 1010-9, Lym-2” (NU 8314-B) A hybridoma clone, designated Lym-2, was produced from the fusion of primed mouse splenocytes and mouse myeloma NS-1 cells. Hybridoma Lym-2 produced a murine IgG1 monoclonal antibody which recognizes a cell surface protein expressed in normal and malignant B lymphocytes. Immunoperoxidase staining of a panel of normal human tissues show that Pym-2 reacts with germinal center and mantle zone B lymphocytes and interdigitating histiocytes of the lymph node. A subset of peripheral blood B cells are positive and no reactivity has been observed in human bone marrow by flow cytometric analysis. Because of the remarkable specificity of Lym-2 for human B-cells and derived malignancies, these data suggest that Lym-2 will be appropriate for reagent for in vivo diagnostic and therapy of the human B-cell lymphomas and leukemias.

“Hybridoma Clone 818-18, BM-1” (NU 8216-C)  A hybridoma clone, designated 818-18, was produced from the fusion of primed mouse splenocytes and mouse myeloma NS-1 cells. Clone 818-18 produces a murine IgG1 monoclonal antibody which recognizes a nuclear antigen expressed in human granulocytes and myeloid precursors and acute and chronic myeloid leukemia. Immunoperoxidase staining with 818-18 on B5 fixed, paraffin embedded clot preparations of bone marrow aspirates shows positive nuclear staining of myeloid cells with normal non-specific background staining. The remarkable specificity of this reagent and its ability to stain B5 fixed, paraffin embedded tissues makes it a unique reagent for the diagnosis of myeloid derived leukemias.

Field of Use

Oncolym(R) was in a Phase II/III clinical trial for the treatment of non-Hodgkin's B-cell Lymphoma.