Cohen and Boyer Patented the Tools That Built Biotech

US4237224 was filed on November 4, 1974, and granted on December 2, 1980, after a six-year examination that the Patent Office took its time over because the underlying technology was, in every meaningful sense, brand new. The title is "Process for Producing Biologically Functional Molecular Chimeras." The inventors named on the patent are Stanley N. Cohen of Stanford University and Herbert W. Boyer of the University of California, San Francisco. The patent rights were assigned to the Trustees of Stanford on Cohen's behalf and to the Regents of the University of California on Boyer's.

The mechanism described in the patent is now in every introductory biology textbook. Take a circular piece of bacterial DNA — a plasmid. Cut it open at a specific recognition site using a restriction enzyme. Insert a fragment of DNA from a different organism (a frog, a human, anything) at the cut site. Use a ligase enzyme to seal the plasmid back into a complete loop. Reintroduce the plasmid into a bacterium. The bacterium will now reproduce, and every daughter cell will contain a working copy of the inserted foreign gene. The foreign gene will be expressed. The bacterium will produce the protein the foreign gene codes for.

You have just turned a bacterium into a factory for producing whatever the inserted gene tells it to produce. Insulin. Human growth hormone. Clotting factor. A monoclonal antibody. The active ingredient in a vaccine.

The breakfast

The widely-told version of how the work began involves a delicatessen in Hawaii. Cohen and Boyer met at a conference in November 1972 and continued the discussion afterward at a deli, sketching diagrams on napkins. Each had been working on a piece of the problem — Cohen on plasmid biology at Stanford, Boyer on restriction enzymes at UCSF. Their tools combined obviously and decisively. By March 1973 they had cloned the first recombinant DNA molecule in Cohen's lab. By November 1973 they had used the system to clone a frog gene into a bacterium and shown that the bacterium expressed the frog protein.

The patent application was filed a year later, in November 1974. The decision to file at all was contentious. Cohen and Boyer were academic scientists; the prevailing view at the time was that publicly funded research belonged in the public domain. Stanford's technology-licensing office argued strenuously the other way: that without patent protection, no commercial entity would invest the capital required to translate the technique into pharmaceuticals, and without commercial translation, the discovery would benefit no one. Cohen and Boyer agreed to the filing, with the condition that their personal share of any royalties be donated to research.

$255 million

Stanford's licensing strategy was unusually pragmatic. Rather than litigate to extract maximum royalties from a small number of licensees, Stanford set the per-license fee extremely low — initially around ten thousand dollars per company, with single-digit percentage royalties on resulting products. By the time the patent expired in 1997, roughly 460 companies had licensed it, including every major pharmaceutical company in the world. Stanford and UC together received approximately $255 million over the patent's seventeen-year term. Cohen and Boyer themselves received standard inventor shares; Boyer used some of his to co-found Genentech, the first commercial recombinant- DNA pharmaceutical company, in 1976.

The drugs the patent made possible include essentially every recombinant pharmaceutical on the modern market: human insulin (Humulin, 1982), human growth hormone (1985), tissue plasminogen activator (1987), erythropoietin (1989), and every monoclonal antibody therapy from the late 1980s onward. The current biotech industry, worth something like $1.5 trillion annually, traces — almost in a single direct line — to the 1974 filing and the 1980 grant.

See the original

The full text of US4237224 is on Google Patents.