Royalty Report: Drugs, Cancer, Disease – Collection: 158673

License Grant

Licensor hereby grants to Licensee of Switzerland the exclusive right to utilize such rights as are held by Licensor to develop, use, promote, market and sell, directly or indirectly, each Product in the Territory pursuant to the Know-How, Patents and Improvements.

License Property

The Patent Rights are for Chystalline amifostine compositions and methids for the preparation and use of same.  The Trademark means the trademark Ethyol(R) or the trademark NeuTrexin(R).

Licensor has rights relating to a pharmaceutical product known as Ethyol(R) (amifostine) which is being developed by Licensor for use in reducing toxicities of chemotherapeutic cancer treatments and as a radioprotective agent and Licensor has rights relating to a pharmaceutical product known as NeuTrexin(R) (trimetrexate glucuronate for injection).

Amifostine is a cytoprotective adjuvant used in cancer chemotherapy and radiotherapy involving DNA-binding chemotherapeutic agents.

Field of Use

The product are of use in treating Pneumocystis carinii pneumonia ('PCP') and as an anti-cancer agent.

License Grant

Licensor hereby grants to Licensee of Switzerland the exclusive right to utilize such rights as are held by Licensor to develop, use, promote, market and sell, directly or indirectly, each Product in the Territory pursuant to the Know-How, Patents and Improvements.

License Property

The product is any product containing as its sole active ingredient Ethyol(R) (amifostine) or NeuTrexin(R) (trimetrexate glucuronate for injection) and any Improvements thereto, as further described in the Product Specifications.  The term Product also shall include any pharmaceutical product containing Ethyol(R) (amifostine) or NeuTrexin(R) (trimetrexate glucuronate for injection) in combination with another active ingredient, including combination packages containing separate active ingredients.

The Trademark means the trademark Ethyol(R) or the trademark NeuTrexin(R).

Field of Use

The products are of use in treating Pneumocystis carinii pneumonia ('PCP') and as an anti-cancer agent.

License Grant

The Licensee acquired the exclusive rights to commercialize Ethyol in the United States from the English Licensor.

License Property

Ethyol is a patented, prescription brand indicated to reduce xerostomia (dry mouth) as a side-effect in patients undergoing post-operative radiation treatment for head and neck cancer.

Field of Use

Ethyol is a FDA approved cytoprotective drug indicated as an adjuvant therapy to reduce the incidence of xerostomia (dry mouth) as a side-effect in patients undergoing post-operative radiation treatment for head and neck cancer. It also reduces the cumulative renal toxicity associated with the repeated administration of cisplatin in patients with advanced ovarian cancer.

License Grant

This Letter Agreement is a binding agreement setting forth the terms upon which the Parties will research, develop, finance the research and development of, manufacture and market the technology and compounds owned by a consortium of Universities and currently licensed or optioned to Licensor B and described hereto (the Current Compounds) and all technology and compounds developed by the Consortium after the date hereof through use of Licensee sponsored research funding or National Cooperative Drug Development grant funding made available to the Consortium (the Future Compounds and, collectively with the Current Compounds, the Compounds).

License of the Compounds.

(a) From the date of this Letter Agreement until the completion of the IPO or an Alternative Financing, Licensee may request Universitys written consent for Licensee to use one or more of the Compounds to conduct clinical studies.   Licensee will also have the right to describe, and to provide information regarding, the Compounds to facilitate the completion of the IPO or an Alternative Financing.

(b) Upon the completion of the IPO or an Alternative Financing, Licensor B will grant or assign to Licensee, and University will take any action necessary to consent to the grant or assignment by Licensor B to Licensee of, an exclusive worldwide license to use, manufacture, have manufactured, promote, sell, distribute or otherwise dispose of any and all products based directly or indirectly on the Current Compounds (the Current Products).

(c) Licensee will have the right to grant sublicenses to any third party who agrees to be bound by the terms of this Letter Agreement in accordance with the terms of its License Agreement with University.

(d) Upon completion of the IPO or an Alternative Financing, University will grant to Licensee, and Licensor B will take any action necessary to consent to the grant by University to Licensee of, an exclusive worldwide license to use, manufacture, have manufactured, promote, sell, distribute or otherwise dispose of any and all products based directly or indirectly on the Future Compounds (the Future Products and, collectively with the Current Products, the Products).

License Property

Dicationic compounds have two positively charged ends held together by a neutrally charged chemical linker group. The unique structures of the compounds with positive charges on the ends (shaped like molecular barbells) allow them to bind to the negatively charged surface in the minor groove of an organism's DNA (like a band-aid), preventing necessary life-sustaining enzymes from attaching to the DNA's active sites. Once a site is occupied by one of the compounds, the necessary enzyme cannot bind to the DNA, preventing the organism from dividing and stopping the spread of the related disease by inhibiting or killing the growth of the organism.

Current Compounds
Invention                                                                        Filed In                                         Issued-App. or Patent #

Dications – Treatment of Pneumocystis carinii        US                                                 US – June 12, 1990 4,933,347
Pneumonia (0RS88-4)

Dications – Treatment of Leishmaniasis                    US                                                 US – April 13, 1993 5,202,320
             (0RS88-4)
ions – Treatment of Malaria                                         US, EPO, Argentina,                   US – April 27, 1993 5,206,236
             (0RS88-4)                                                            Brazil, Australia, Canada          EPO – March 1, 1995 0,366,066
                                                                                         China, Denmark, Israel,            Argentina – May 31, 1995 248,011
                                                                                         Japan, Mexico, Pakistan,          Australia – Jan 25, 1993 626,033
                                                                                         Philippines, Korea,                    Mexico – August 30, 1995 179,371
                                                                                         Switzerland, Venezuela,           Pakistan – Oct. 19, 1989 131,965
                                                                                         Finland, India, Norway,            Switzerland – Apr 30, 1996
                                                                                         Taiwan                                         Venezuela – Jan 5, 1996

Dications – Treatment of Fungal Infections               US                                               DIV-08/641,510
             (0TD95-51)                                                                                                             USSN-08/472,996

HIV – Inhibition of the Integrase Enzyme                  US, PCT, Australia, Brazil,        US- 08,185,079 NZ-279619
             (0RS94-34)                                                         Canada, Japan, New                PCT- PCT/US95/01599
                                                                                         Zealand, EPO, Venezuela        AU- 16798/95 VZ-503-96
                                                                                                                                            EPO- 95908504.4
Dications – Detection of nucleic acids and                US, PCT
  cytoskeleton elements (0RS94-43)

Inhibition of Pneumocystis carinii Pneumonia         US, PCT, Argentina, Israel,    US – May 28, 1996 5,521,189
             (0RS94-81)                                                          South Africa, Taiwan              DIV-08/564,879

Inhibition of Giardia Lamblia                                        US, PCT, Argentina, Israel,
             (0RS94-81)                                                           South Africa, Taiwan

Inhibition of Cryptosporidium parvum                       US, PCT, Argentina, Israel,
             (0RS94-81)                                                           South Africa, Taiwan

Inhibition of Pneumocystis carinii Pneumonia         US, Canada, PCT, Japan,        US – June 27, 1995 5,428,051
             (0RS93-17)                                                          Brazil, Australia, New
                                                                                          Zealand, EPO, Venezuela

Prodrugs for PCP Infection                                           US                                             USSN-08/558,716
             (0RS95-50)
Methods of Treating Microbial Infections                   US                                            USSN-08/474,440
             (0TD95-48)                                                                                                            USSN-08/477,876
                                                                                    
TIDWELL                                                                                                                             PCT/US96/08972

Field of Use

The objective of the Licensee's pharmaceutical program is the development of effective, safe drugs against a variety of micro-organisms, including fungal, protozoan, parasitic, bacterial, and viral micro-organisms.

The Licensee has two dicationic compounds ready to begin human clinical trials. The first compound, DAP-092, is for the treatment of Cryptosporidium parvum, a parasite that causes severe diarrhea and wasting. The second compound, DB-289, is for the treatment of Pneumocystis carinii pneumonia. These two orally administered drugs are ideally suited to demonstrate the power of the dicationic technology platform. DAP-092 was developed to treat a parasite that is found only in the gastro-intestinal tract ('gut'). DAP-092, because of its positive charges, cannot cross the digestive membranes, and stays in the digestive tract.