On September 10, 2003 Antisoma, the biopharmaceutical company specialising in novel anti-cancer drugs, reported that it has in-licensed a programme of telomerase inhibitors from Cancer Research Technology Ltd, the technology transfer arm of the charity Cancer Research UK (Press release, Cancer Research Technology, SEP 10, 2003, View Source [SID1234523458]). This programme was developed by Professor Stephen Neidle, working first at the Institute of Cancer Research and more recently at the University of London School of Pharmacy. Under the licensing agreement, Antisoma has obtained rights to a number of existing molecules and an option on further telomerase inhibitors generated by Professor Neidle’s group over the next three years.

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Telomeres are the protective regions found at the ends of chromosomes (the structures into which the genetic material, DNA, is packaged in each cell of the human body). In normal cells, telomeres act as a ‘life clock’, shortening slightly each time the cell divides. Once the telomeres fall below a critical length, the cell undergoes the self-destruct process known as apoptosis or programmed cell death. This is part of the natural process of cellular ageing and removal of old cells to be replaced by new ones. Cancer cells make an enzyme called telomerase that allows them to maintain their telomeres at a length just sufficient to avoid entering the self-destruct pathway. Telomerase thus enables cancer cells to divide continually and indefinitely, a property fundamental to the progression of the disease. By blocking the action of this enzyme, telomerase inhibitors can prevent the maintenance of telomeres and force cancer cells into apoptosis.

Glyn Edwards, CEO of Antisoma, said ‘Telomerase inhibitors have the potential for broad application against both solid and blood cancers because the telomerase enzyme is important to all types of cancer cell. This programme is an excellent addition to our preclinical portfolio.’

On August 6, 2003 Cancer Research Technology Ltd. (CRT), the technology transfer arm of the charity Cancer Research UK, and the technology transfer agent for the Netherlands Cancer Institute (NCI) in Amsterdam, reported that it recently entered into a license agreement granting GlaxoSmithKline exclusive worldwide rights to CRT’s Patent Application WO 00/69390 (the Patent) (Press release, Cancer Research Technology, AUG 6, 2003, View Source [SID1234523460]). The Patent covers technology relating to a novel target that enhances the oral bioavailability of certain cytotoxic oncology drugs, including topotecan. The terms of the Agreement remain confidential.

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The Patent was initially filed by the NCI and is based upon the work of Professor Jan Schellens and Dr Alfred Schinkel. They showed that inhibition of a transporter protein from the family of transporters containing known multi-drug resistance proteins, could also be targeted to enhance the uptake of oncology drugs such as topotecan when orally administered.

Cancer Research Technology stated that it was happy to act as a conduit for the development of this important finding and hopes the Patent’s technology will eventually bring benefit to cancer patients worldwide. CRT initially undertook to cover the costs of the patent prosecution while the technology was being developed and CRT looked for a suitable commercial licensee.

On July 29, 2003 Cancer Research Technology and Alnylam Pharmaceuticals Inc. reported exclusive license to patent application WO 01/36646 ‘Inhibiting gene expression with dsRNA’ for therapeutic applications (Press release, Cancer Research Technology, JUL 29, 2003, View Source [SID1234523462]).

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Cancer Research Technology Limited (CRT) and Alnylam Pharmaceuticals Inc. announce today the execution of an exclusive license in the field of human therapeutics for CRT’s key RNA interference (RNAi) patent application ‘Inhibiting gene expression with dsRNA’ (WO 01/36646). The terms of the license have not been disclosed.

CRT CEO Harpal Kumar stated that ‘Alnylam is well positioned to develop RNAi therapeutics. This license should enable the application of this exciting platform technology to therapeutics, with the long term aim of benefiting patients. This license supplements CRT’s nonexclusive licensing strategy in the field of target validation, and the existing license we have in place for the pSUPER RNAi vector with DNAengine’.

Patent application WO 01/36646 is based on the pioneering research of Dr. Magdalena Zernicka-Goetz and colleagues (Dr. Florence Wianny, Professors David Glover and Martin Evans) at the University of Cambridge (UK), who demonstrated RNAi-mediated inhibition of endogenous genes in mammalian cells.

CRT is the holder of two key patent applications in the field of RNAi. CRT’s RNAi patent applications, together branded the SUPER RNAiTM System, are available for licensing on a nonexclusive basis in the fields of target validation and drug discovery.
The second patent filing from CRT covers pSUPER, a vector for long-term expression of RNAi effectors in mammalian cells, developed at the Netherlands Cancer Institute (Amsterdam) in the group of Professor Rene Bernards.

Several pharmaceutical and biotechnology companies are working with CRT towards generating RNAi-based systems to meet the current demands of the industry for higher throughput analysis of mammalian gene function and rapid production of disease models to aid drug discovery. In addition, in association with CRT, Cancer Research UK is cofunding development of a library of pSUPER vectors expressing short interfering RNA targeted against cancer genes, which is under development at the Netherlands Cancer Institute.

On May 21, 2003 Cancer Research Technology Ltd. (CRT), the technology transfer arm of the charity Cancer Research UK, and the University of Newcastle, both based in the UK, reported to recently disclose that a new alliance with the US and UK-based biotechnology company OSI Pharmaceuticals (UK) had recently commenced and was expected to accelerate the validation of certain new targets for cancer therapeutic intervention (Press release, Cancer Research Technology, MAY 21, 2003, View Source [SID1234523463]).

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This exciting collaboration will enable the development of selective and potent modulators of protein acetylation and evaluate their potential as inhibitors of tumour cell growth. Furthermore, the co-funded research programme may also enable the discovery and validation of other targets against which new drugs can be screened in the fight against cancer.

The research funding that had enabled developments in this field at the University of Newcastle to progress to this stage predominantly stemmed from Cancer Research UK who are continuing to support the programme. CRT was happy to act on Cancer Research UK’s behalf to secure the fast track development of this exciting work regarding the potential discovery of new compounds with a partner who has a proven track record of taking such compounds that act on new cancer-specific signal transduction pathways in to the clinic.

Such a collaboration may help scientists to understand why certain cancer patients become resistant to currently available therapies.

On November 18, 2002 Researchers from the internationally renowned Netherlands Cancer Institute (NKI) in Amsterdam, reported to have recently published a paper in the leading journal Cancer Cell [Cancer Cell 2, 243-247 (2002)] showing that specific inhibition of cancer-causing genes (oncogenes) results in inhibition of the growth of human pancreatic cancer cells in experimental mice (Press release, Cancer Research Technology, NOV 18, 2002, View Source [SID1234523464]). This is the first evidence in living animals that cancer can be controlled by blocking the expression of a single mutant protein using the technique of RNA interference (RNAi).

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The paper, entitled "Stable suppression of tumorigenicity by virus-mediated RNA interference", is the second from the group led by Dr. Reuven Agami and Professor René Bernards describing their pSUPER vector system for performing RNAi. Together with the lead author, Thijn Brummelkamp, they were the inventors of the pSUPER vector system, which allows researchers to perform long-term experiments to study the effect of blocking the production of specific proteins within cells and whole organisms, and may lead to the development of RNAi as a major new therapeutic weapon against many diseases including HIV, cancer and other genetic disorders. The pSUPER vector was first described in a paper published in the prestigious journal Science in April. Such was its impact that the NKI received an unprecedented 1500 requests from other scientists asking for access to the vector for their own studies. As a result the pSUPER vector is becoming a standard workhorse in laboratories worldwide, providing insight into the essential proteins involved in a wide range of diseases from neurodegenerative diseases such as Alzheimer’s and Parkinsons, through infectious diseases such as HIV and hepatitis, to cancer and other genetically based diseases.

Summary of the Cancer Cell paper

Most human tumors harbor multiple genetic alterations, including dominant mutant oncogenes. It is often not clear which of these oncogenes are continuously required and which, when inactivated, may inhibit tumourigenesis. One oncogene that is frequently mutated in human cancer is named K-RAS. A activated mutant of this gene, known as K-RASV12, carries a single mutation in the gene encoding the protein. The normal form of K-RAS appears to be essential for cell viability and therapies which do not differentially target the normal K-RAS protein and the oncogenic K-RASV12 protein are likely to be toxic.

Using a retroviral version of the pSUPER vector the NKI group were able to specifically and stably inhibit expression of only the oncogenic K-RASV12 allele in human pancreatic cancer cells, without affecting the normal K-Ras protein.
Importantly, the researchers found that loss of K-RASV12 protein in the pancreatic carcinoma cells leads to loss of anchorage-independent growth and tumourigenicity. These results indicate that viral delivery of small interfering RNA’s can be used for tumor-specific gene therapy to reverse the oncogenic phenotype of cancer cells, and is the first study to demonstrate the power of vector mediated RNAi to treat cancer in vivo.