We are working through the history of nicotine patches, to learn what we can from UC’s claim to have invented the nicotine patch, and AUTM’s claim that this is a success story, and the Bayh-Dole Coalition’s claim that this success was due to the Bayh-Dole Act.
In Sweden, in an efficient version of technology change, scientist Ove Fernö at Aktiebolaget Leo, a Swedish pharmaceutical firm that would end up owned by Pharmacia, was prompted to create a nicotine gum–Nicorette–by a suggestion from professor friends at Lund University, who noted that sailors assigned to submarines switched from smoking to chewing tobacco. Fernö filed for a patent in the UK in 1970 and in the US in 1974, including his two Lund University colleagues as co-inventors. The US patent issued in 1975. By the mid-1970s, then, it was established that nicotine could be absorbed through the mucosa–the skin of the mouth, as it were, and doing so provided a way to stop smoking, at least for a while–even if one still remained attached to a regular hit of nicotine.
Nicorette (Swedish, combining “nicotine” + “right”) gum was approved in various countries, including Canada, by 1980, and in the U.S. in 1984. In a way, this was the most effective, collaborative form of “technology transfer” from a university. Faculty with an idea wrote to their colleague in industry and whatever patenting there was came after, not before, the “transfer” of the idea. The idea transferred, saving everyone the hassle of attempting to “develop” “technology” in a university and in isolation from industry, and then trying to “transfer” it later, when it’s a bunch of patent claims, experimental setups that have been dismantled, and with students and staff with essential working knowledge often scattered to the winds.
In August 1981, when Alza came out with its patch for motion sickness and two months later with a patch to treat angina by delivering nitroglycerine, the idea that other agents could be delivered via a skin patch was, as it were, “in the air.” One might even say any other agent that didn’t take more than ordinary effort to put in a patch was by that time “obvious.” For instance, in 1975, Michaels et al. published an article looking at ten substances that might be delivered transdermally. One might think, then, that most of the patch patenting to follow would have to do with non-obvious construction of new patches or special handling to get a balky agent to move into the skin at the right dosing level for the right amount of time without damaging the skin and the like. You would be right, but it won’t be clear for a bit, so hold that thought.
That’s a snapshot of where things were in April 1985. Next we look at the work of Frank Etscorn, who claims to be “first patent holder for the nicotine patch for use in tobacco cessation.” That appears to be correct, though UC lawyers had a good time beating him up for it. He gave a talk in October 2018, reported here. And there’s a write up about his work here. His work on a patch started in 1979, when he spilled nicotine on his arm and felt nauseated. Voilà! Maybe nicotine on the skin would replace nicotine in cigarette smoke and help people avoid lung cancer, even if they still wanted nicotine. Later, Etscorn put nicotine on a circular bandage for his brother, a heavy smoker, who said “it felt like he had just smoked a cigarette.” That sounds a lot like actual reduction to practice.
Etscorn filed a patent application for a nicotine patch six years later, on January 23, 1985–a few months before UC–and the patent issued July 1, 1986 (4,597,961; “Transcutaneous application of nicotine”). Etscorn claimed a method of administrating nicotine “via an occlusive pad adhered to the skin . . . comprising a nicotine-impermeable backing and nicotine-permeable, porous, inert membrane . . .” with a cavity in between, “said cavity containing liquid nicotine therein.” Sure looks like a nicotine patch–or at least a method of using a patch, involving liquid nicotine, for nicotine replacement therapy. Now, if you want to get around a patent like this, one way to do it is to use nicotine in some form other than liquid, or use more than one cavity, or make the backing not quite impermeable to nicotine, or don’t have an inner membrane, or make the inner membrane not inert (such as infused with an accelerator for nicotine uptake). You see how things go when there’s an incentive to work around an invention rather than use it.
Etscorn’s patch implementation differs from a Japanese approach to transdermal patches invented at Teijin Limited (4,292,299, Suzuki et al. issued 1981) by having a porous membrane between the nicotine and the skin. Suzuki’s patent is for a general patch and doesn’t mention nicotine–but it would appear that the Suzuki patent could be used to deliver most anything that had an easy time moving through the skin to the bloodstream. Etscorn’s patch implementation also differs from Zaffoni’s system by omitting the pressure-sensitive adhesive (which might contain microcapsules of therapeutic agent) in favor of a pad with a cavity behind to hold liquid nicotine.
In the design space for patches, there has been plenty of room for variations on the theme. It’s striking that any of it is inventive, once the general idea of a patch to deliver a therapeutic agent is out there, unless the variation involves something that no one would think of. Otherwise, the “prior art” won’t include “what’s obvious” because no one would think to spend the effort to document all the many variations that one might pursue. If Zaffoni pursues one approach, then Suzuki pursues another, and Etscorn a third, and so on. It’s less that all of these approaches are inventive than that they are clever.
In a sense, if the USPTO issues a patent for the first bit of cleverness, then it ends up allowing potentially scores of patents for other bits of cleverness, rather than sorting out what has been documented because it is clever or inventive and what hasn’t been documented because it is either so obvious to those skilled in the art that they don’t bother documenting it or it has not been thought of before and won’t be without a spark of inventive insight. But as these things go, the USPTO doesn’t distinguish between obvious clevernesses and sparks of inventive insight, and thus creates space for a mess of patenting of what appears to be clever–and mostly clever workarounds to past clevernesses for which patents have issued.
Etscorn assigned his patent to the New Mexico Tech Research Foundation and they filed multiple foreign patent applications in addition to his U.S. application. NMTRF then licensed the patent to Ciba-Geigy (between 1990 and 1993), and the patch was sold under the name Habitrol. The name even sounds liquidy. In a sense, Etscorn took another classic faculty approach to technology transfer, the way Frederick Cottrell envisioned–file a patent application, and then work with a university-affiliated research foundation to manage the rights and licensing.
A third line of development of nicotine patches involves a Bay Area startup called Pharmetrix and a company called Membrane Technology & Research. In October 1987, Richard Baker, Frank Kochinke, and Carl Huang filed for a patent on “Novel transdermal nicotine patch”–two and half years after UC–which issued in 1989 (4,839,174). The inventors obtain a second patent, “Prolonged activity nicotine patch” (4,943,435) on July 24, 1990. These patents have had a convoluted life. The inventors assigned to a small company, Pharmetrix, but then about the same time a second company, Membrane Technology & Research, granted to the government a nonexclusive license to the same patents, citing a federal grant (R43 DA 04249), which appears to be a Phase 2 SBIR grant to develop an entirely different technology–an antibiotic cream that would stick in the teeth and gums. Perhaps the nicotine patch was developed at the same time, but on the face of it, the nicotine patch wasn’t a subject invention and the government should not have gotten any rights. Pharmetrix then assigned the patent to Elan Corporation in 1991 (we will see why soon), and then Elan reassigned the patent to Pharmetrix in 1994. The next year Pharmetrix assigned the patent to a “PP Holdings,” which a few days later assigned to Pharmacia. In 2004, Pharmacia assigned to Pfizer, and in 2007 (at the end of the patent’s life) Pfizer assigned to McNeil (a unit of Johnson & Johnson). It seems like a hot patent to move around this much. The movement of the patent tracks the right to exclude, not necessarily any “technology transfer,” other than what is taught in the patent’s specification (for which one doesn’t need a license to read and figure out how to design around).
Meanwhile, Elie S. Nuwayser, the owner of Biotek, a company started in 1980 in Massachusetts, obtained multiple patents for a “method of transdermal drug delivery.” In his first application, filed October 1, 1984 (six months before UC), Nuwayser states
Transdermal delivery of medication is not a new concept, as a variety of medications that are readily available for delivery through the skin have been available in ointment form for over thirty years. With ointments, however, it is difficult to achieve precise drug dosage. In a transdermal patch system, this problem is eliminated by controlling the rate of drug release over a prescribed period of time. ‘
Nuwayser then cites the Alza patch systems for motion sickness and angina. What we learn from all this activity is that by 1984, transdermal patch technology was well established, as was nicotine replacement therapy with nicotine moving across mucosa, at least, to enter the bloodstream (delivered by gum). Transdermal patches were being used for the delivery of a number of compounds to treat a number of disorders. It would seem that adding nicotine would be, if not obvious, then at least less than inventive, unless there was something that prevented nicotine from being added to existing patch technology. Otherwise, patents don’t mark invention so much as they mark getting to something clever first, before anyone bothers to document by publication some particular rather mundane variation on the theme.