The more I look at this, the more I think AntiCancer is foolish to raise this issue at all. From Yang et. al. #6,649,159 (AntiCancer):
>>U.S. Pat. No. 5,650,135 discloses a noninvasive method for detecting the localization of an entity under study from within a mammalian subject, which method comprises: (a) administering to the subject a conjugate of the entity and a light-generating moiety or a transformed cell expressing the light-generating moiety; (b) after a period of time in which the conjugate or transformed cell can achieve localization in the subject, immobilizing the subject within the detection field of a photodetector device; (c) maintaining the subject in an immobilized condition, (d) during said maintaining, measuring photon emission from the light-generating moiety, localized in the subject, with the photodetector device until an image of photon emission can be constructed; and (e) detecting said image through an opaque tissue of said mammal. U.S. Pat. No. 5,650,135 also discloses a noninvasive method for detecting the level of an entity under study in a mammalian subject over time, which method comprises: (a) administering to the subject a conjugate of the entity and a light-generating moiety or a transformed cell expressing the light-generating moiety; (b) placing the subject within the detection field of a photodetector device; (c) maintaining the subject in the detection field of the device; (d) during said maintaining, measuring photon emission from the light-generating moiety, in the subject, with the photodetector device; and (e) repeating steps (b) through (d) at selected intervals, wherein said repeating is effective to detect changes in the level of the entity in the subject over time.
Recently, Yang et al. conducted whole-body optical imaging of green fluorescent protein-expressing tumors and metastases (Yang et al., Proc. Natl. Acad. Sci. (USA), 97(3): 1206-11 (2000)). Yang et al. have imaged, in real time, fluorescent tumors growing and metastasizing in live mice. The whole-body optical imaging system is external and noninvasive. It affords unprecedented continuous visual monitoring of malignant growth and spread within intact animals. Yang et al. have established new human and rodent tumors that stably express very high levels of the Aequorea victoria green fluorescent protein (GFP) and transplanted these to appropriate animals. B16F0-GFP mouse melanoma cells were injected into the tail vein or portal vein of 6-week-old C57BL/6 and nude mice. Whole-body optical images showed metastatic lesions in the brain, liver, and bone of B 16F0-GFP that were used for real time, quantitative measurement of tumor growth in each of these organs. The AC3488-GFP human colon cancer was surgically implanted orthotopically into nude mice. Whole-body optical images showed, in real time, growth of the primary colon tumor and its metastatic lesions in the liver and skeleton. Imaging was with either a trans-illuminated epifluorescence microscope or a fluorescence light box and thermoelectrically cooled color charge-coupled device camera. The depth to which metastasis and micrometastasis could be imaged depended on their size. A 60-micrometer diameter tumor was detectable at a depth of 0.5 mm whereas a 1, 800-micrometer tumor could be visualized at 2.2-mm depth. The simple, noninvasive, and highly selective imaging of growing tumors, made possible by strong GFP fluorescence, enables the detailed imaging of tumor growth and metastasis formation. This should facilitate studies of modulators of cancer growth including inhibition by potential chemotherapeutic agents.
Methods for monitoring gene expression are known in the art (see generally, Ausubel et al. (Ed.), Current Protocols in Molecular Biology, John Wiley & Sons, Inc.). However, whole-body external optical imaging of gene expression, which offers simple, noninvasive, highly selective, and real-time recording and analysis of gene expression in an intact multi-cellular organisms, e.g., animals, is not available currently. The present invention addresses this and other related needs in the art. <<
Emphasis mine. If one looks at the '135 patent, which is the Contag/Stanford/Xenogen patent, it sure looks to me as though everything in the bolded section of this one is either claimed in '135 or really obvious. Gene expression is used to express the moiety in '135, so obviously it can be monitored in real time. Tumors are specifically mentioned as an embodiment there. AntiCancer might be able to defend their special tumor line/animal models, but Xenogen says they will pursue invalidation of AntiCancer's patents, and I now think Xenogen has a very good chance of doing that.
The reason bioluminescence (Xenogen) beats fluorescence (AntiCancer) is that fluorescence requires excitation by an external radiation source. Some tissue not tagged by GFP is going to fluoresce at that wavelength, which introduces noise. If, as I suspect, all AntiCancer has going for it here is their proprietary tumor lines/animal models, they would be well advised to license that and hope Xenogen doesn't invalidate most of the rest of their system. IMHO. My guess is that this is what they are really trying for. In which case, a closer look at Xenogen's IP in the animal model area might be worth looking at.
Cheers, Tuck |
