Genomics


Biotechnology patents relevant to GEMs Gene targeting technologies Methods applied to a model


The platform technologies used to make a GEM, such as CRISPR/Cas9 gene editing technology


Use of a technique applied to a GEM, such as application of the drug tamoxifen to induce gene deletion in vivo


Specific genetic modifications


Individual genetic alterations can be patented. These patents can sometimes be quite broad and may cover a class of related strains, only some of which may have been made by the patent holder


A single GEM may be covered by multiple patents. The table shows common types of biotechnology patents which may apply to individual GEMs


commercial animal vendor, may rightly be con- cerned about their use of such GEMs. In 2014, Regeneron filed a lawsuit against


Merus and Ablexis alleging infringement of a Regeneron patent covering technology associated with GEMs that produce partly human antibodies. The Ablexis suit was settled when evidence emerged during discovery that Ablexis specifically designed its mouse model to avoid infringing the patent in question. In a surprising twist, the Federal Circuit court held that Regeneron demon- strated misconduct both during patent prosecution and during the Merus trial and rendered the entire Regeneron patent unenforceable. Regeneron was ordered to pay Merus’ litigation costs in the sum of more than $10.5 million. Regeneron has since appealed the decision rendering the patent unen- forceable to the US Supreme Court. Drug companies are increasingly relying on


academia as a critical source of outsourced R&D. Schuhmacher, Gassmann and Hinder studied phar- ma’s changing R&D models and found that “73% of the investigated companies were making process changes in R&D”, for example, “widening the competence field by progressively expanding col- laborations and research partnerships”1. While these partnerships benefit both pharma and academia, the risk to pharma created by poor com- pliance of academic partners with research tool restrictions is non-trivial. As demonstrated above, the cost to defend litigation can be quite large, and revenues of downstream therapeutics developed with problematic IP may be at risk.


Protecting GEM intellectual property The first patented mammal In 1980, the US Supreme Court held in Diamond versus Chakrabarty that “A live, human-made micro-organism is patentable subject matter.” That case involved genetically-modified bacteria. The


Drug Discovery World Fall 2018


first patent on a genetically-modified animal was granted on April 12, 1988 for the so-called ‘Oncomouse’ developed by Philip Leder at Harvard University. This was but the first of many patents on GEMs in the following years.


Technology titans A single GEM may be covered by multiple patents. For example, the technology used to generate the genetic modification may be patented. Patents may cover methods used in the model, such as a reporter system. Finally, the actual genetic modifi- cation can be patented. Note that patent holders often permit non-profit institutions to use patents either under simple terms or without any licence, but that typically applies only to internal non-com- mercial use by the non-profit institution and does not permit the non-profit institution to sell, trans- fer or license any materials covered by the patents or generated using the patented technology.


CRISPR conundrum The hottest new thing in transgenic technology is CRISPR/Cas9 gene editing. Frequently used to make knockout animals and cell lines, its use is being expanded towards generating other types of mutations such as introducing large segments of foreign DNA. Although CRISPR is not yet capable of the sophisticated genetic manipulations which can be accomplished via embryonic stem cell tar- geting, its ease of use, greater speed and applica- tion to a broader range of animal species have made it the technology of choice for a large pro- portion of new GEMs. CRISPR has been rapidly adopted by the scien-


tific community and put to a wide range of uses. As with many high-value technologies, multiple par- ties claim ownership of CRISPR-related intellectu- al property, including The Broad Institute, the University of California at Berkeley and others.


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