US Patent Application 20090285755 – METHODS FOR TUMOR DIAGNOSIS AND THERAPY
The main focus of the patent
The invention selectively delivers anticancer drugs to cancerous tissue at high enough concentrations to be effective without exposing the rest of the body to sustained high levels of the drug.
Limited technical details
The technology consists of two sequential steps that result in localized high concentrations of the drug at the tumor site.
The first step involves either choosing an enzyme that is produced exclusively by the tumor (or at least at concentrations many fold higher than non-tumor tissue). If this is not possible, then an enzyme can be coupled with a monoclonal antibody directed against the tumor to locally concentrate it at that site.
The second step requires creating a water soluble radioactive low molecular weight prodrug molecule that is a substrate for the earlier mentioned enzyme and administering it. Ordinarily this would not enter the cells on account of their water solubility and will be cleared from the body in an expected timeframe. However, due to the high concentration of the enzyme in the immediate environment of the cancer cells in the primary tumor and metastases, the prodrug gets broken down in those sites precipitating the water insoluble drug which gets trapped locally and exerts its action selectively on the tumor.
As a result, the drug is concentrated in the tumor at high enough levels to be effective while simultaneously being present in much lower concentration in the systemic circulation.
Implications/applications and sectors that are addressed by patent/technology
The basic principle of this technology is simple yet extremely versatile. The first step allows a choice of a large number of different enzymes that are known to be over expressed in various tumors. Additionally it also covers a wider scope of artificially creating a local high concentration of any enzyme at the tumor site by targeting via monoclonal antibodies (or modifying gene expression in animals). The second step is determined by the final objective and can involve coupling either a gamma ray emitting radiolabel if one wishes to image the tumor in a diagnostic application or an alpha or beta particle emitting particle if the purpose is to treat the tumor by radiotherapy. As a result, this technology can find wide ranging applications in the field of cancer diagnostics and radiotherapy of solid cancers.
The overall market for cancer treatments is one of the largest and fastest growing areas in the pharmaceutical industry and it is estimated that accrued sales of antineoplastic monoclonal antibodies amass the largest market share of 34.1% (~ $11.3bn in 2007). So a technology that combines monoclonal antibodies with radiotherapeutic or diagnostic agents holds particular promise.
History of the Inventors
Amin I. Kassis is a professor of radiology in the Department of Radiology, Harvard Medical School and the director of the Radiobiology and Experimental Radionuclide Therapy Section of the Laboratory for Experimental Nuclear Medicine. He has published nearly 180 peer-reviewed articles, 30 book chapters/reviews, and holds 34 US and world patents. This particular technology was featured on the cover of a recent issue of the prestigious Cancer Research journal.
Ravi S.Harapanhalli is currently a principal consultant at Parexel Consulting dealing with leads for late stage Product development. He was formerly the chief of the division of premarketing assessment and manufacturing science in the Office of New Drug Quality Assessment at theFDA.
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Patentgo’s opinion:
Cancer remains a top therapeutic area both in terms of overall size as well as growth rate. Worldwide market for cancer treatment is anticipated to exceed US$ 78 Billion by 2012. Due to the high toxicity of existing anti-cancer agents, there is a focused effort to develop therapies that are effective while minimizing the collateral damage to healthy cells. Approaches to specifically target tumor cells include combining drugs with monoclonal antibodies, recombinant adenovirus vectors, hormones whose receptors known to be over expressed in the tumors etc. This technology of this patent has combines two different approaches – tumor cell selectivity achieved by either monoclonal antibodies or a substrate that tumor specific along with a prodrug that gets activated locally. This ensures that the activity is specific to the tumor region, thereby theoretically increasing the specificity of localized tumor site action further.
