Dolly The Sheep: A Cautionary Tale

Roughly twenty years ago, newspaper headlines were packed with stories about Dolly the sheep — the first cloned mammal. More recently, in 2014, In re Roslin[iii] finally laid the patent claims related to Dolly to rest.  Although Roslin speaks specifically to cloning technologies, the saga highlights an essential problem in the current judicial approach to patenting life science inventions.  We will look first at the history of Roslin and then at its implications for patent law.

Dolly the Sheep

To create Dolly, inventors removed the nucleus of a sheep egg that had not matured. From another sheep, they took the nucleus of an adult cell containing genetic blueprint material and fused that into the egg cell to develop an embryo. The embryo was then implanted into a surrogate animal. Voilà, Dolly was born.

Of course, this was not an easy process. At the time, it was the stuff of science fiction. That was 1996 — yet the legal battle over the patents for Dolly continued to rage on for eighteen years after her birth in a case known as In re Roslin. (“Roslin” refers to the Roslin Institute, the Scottish institute at the University of Edinburgh where Dolly was created.) The patents at issue in Roslin are for the cloned sheep — not for the process of creating the sheep, but for the cloned mammals themselves.

Recent Decisions on Life-Science Patents

When the patents were filed in 1999, the notion of patenting living organisms was not unheard of. Patents for bacterial clones were at issue in the 1980s Supreme Court case Diamond v. Chakrabarty, [iv] and the United States Patent and Trademark Office (USPTO) had previously granted patents to higher-order life forms, such as for “triploid” oysters with extra chromosomes.[v] But times have changed, and the climate for patents at the Supreme Court is decidedly chillier now. In particular, in the 2013 case Association for Molecular Pathology v. Myriad Genetics,[vi] the Supreme Court rejected patents on isolated genetic sequences if those sequences already exist in nature. The Myriad inventor attempted to patent isolated DNA containing particular gene mutations that are associated with certain forms of breast and ovarian cancer. The Justices in Myriad held that the isolated sequences are not patentable because they occur naturally. In contrast, the Justices upheld patents for complimentary DNA—essentially the mirror image of naturally occurring DNA sequences, with the noncoding regions spliced out. Myriad was one of a quartet of cases in which the Court has severely cut back on the types of subject matter that may be patented.[vii]

The direction taken by the Justices in Myriad could not have been worse for the Dolly inventors. The inventors were entirely focused on projecting to the outside world that the sheep clones were identical to the donor sheep. The inventors’ scientific literature was written in the service of demonstrating the identical nature of the creature. In order to generate the significant publicity that resulted, the inventors claimed absolute identity, both in the media and in the patent language itself.[viii]

The inventors may have been concerned that, in order for the technology to be commercially viable, it was critical to demonstrate that the clones were identical. They also may have worried about environmental backlash, with doomsday heralds arguing that mad scientists modifying nature would result in disaster. In fact, our cloned animals do have serious deficiencies.[ix] They do not live as long, they are susceptible to strange diseases, and some have led quite miserable lives. Nature really does work better when it comes to reproduction—at least for now—but it is nowhere near as sexy to make this qualified claim.

It was the eventual over-claiming that got the inventors into hot water from a patent perspective. We are not just speaking from the benefit of 20/20 hindsight after the Myriad decision. Granted, Myriad was a dramatic departure from decades of USPTO and lower court decision-making, although one that might have been predictable.[x] But long before Myriad, lawyers were asking their clients to look at gene expression data in order to make more fully fleshed out and appropriately detailed claims to their new inventions. The Roslin inventors ran into trouble when their business and public relations goals clashed with the demands of the patent system. And in the end, years of legal wrangling in the courts could not save them.

The In Re Roslin Decision

In the Roslin case, finally decided in May 2014, the Federal Circuit denied patentability for Dolly and her ilk. The judges held that the sheep couldn’t be patentable because the cloned sheep was “an exact replica of another sheep” and therefore “does not possess ‘markedly different characteristics than any [farm animals] found in nature.’”[xi]

In reaching its ruling, the Federal Circuit rejected a variety of arguments advanced by the patent holders that claimed Dolly was not actually identical to her predecessors. For example, the inventors tried to argue that Dolly was phenotypically different from her natural forebears, as a result of environmental factors that create variations in characteristics over time, including shape, size, color and behavior. The judges, however, ruled that such variations are due to the environment—not to any intervention by the inventor.[xii] And, more importantly, the patent holder did not mention such variations as part of its patent application. [xiii]

The judges also were entirely unimpressed by the argument that the cloned mammals were distinct because they are “time-delayed” versions of the original. The court responded by stating the obvious: all copies are time-delayed versions of the original.[xiv]

Finally, the judges rejected arguments based on variations in the parts of the egg cells used. Recall that Dolly was made by removing the nucleus of an egg cell that had not matured. But there are non-nucleic portions of the egg cell that remained that contained DNA—specifically in the mitochondria of the egg—and thus, Dolly’s cells would differ from the donor’s cells as they replicated in Dolly’s system.

Again, the judges noted that the inventors hadn’t claimed any of these differences. And, in a significant part of the case, they noted that the inventors still weren’t claiming that these distinctions mattered in any way.[xv] That notion—that differences alone are not enough for patentability—is likely to play a role in case law going forward. The question is what the courts will do when someone claims that there are differences, but the differences have only disadvantages. We’re not referring to “silver lining” or individual disadvantages that may have societal benefits, like mice bred to rapidly develop cancer so that we can test cancer treatments more quickly, but to differences with truly no benefits—for the animal or for society. Then what? Is a simple difference enough? As for Dolly, would it have been enough to claim the creation of animals inferior to what exists in nature, and should this be the type of line we are looking for in creating criteria for patentability? This, of course, is the broader implication of Roslin: in determining patentability, patent law inevitably stumbles when it relies only on differences between natural organisms and ones in the lab.

A New Approach to Patentable Subject Matter

In this manner, the lingering question from Roslin goes to the heart of the problem with the current judicial approach to patentable subject matter for life science inventions. The question should not be whether something is the same as nature. If we look closely enough, nothing we do in the lab will ever be precisely the same as nature.[xvi] The question should be whether what we have created in the lab allows us to do something beneficial that nature does not. In other words, can we now do something we want to do in a way that we could not with what nature provided?  That is the heart of a life science invention. It is also the core concept of a 1911 case by Judge Learned Hand, Parke-Davis & Co. v. H.K. Mulford Co.,[xvii] which was penned long before anyone dreamed of isolating and replicating genetic sequences, let alone cloning mammals. The case concerned a therapeutic product extracted from the adrenal glands of animals.[xviii] The extracted substance could be used to treat patients without the unwanted elements found in nature. In finding patentability, Judge Hand noted that there was a minor difference between the substance in the lab and the substance in nature—specifically, the new substance was not in the form of a salt—but the judge declined to rest the decision on that distinction.[xix] Rather, Judge Hand explained the following:

[the substance] became for every practical purpose a new thing commercially and therapeutically… . The line between different substances and degrees of the same substance is to be drawn rather from the common usages of men than from nice considerations of dialectic.[xx]

In other words, the question was not just whether the invention differed but whether it was new in a way that opened new avenues for people to do what could not be done before.[xxi]

The modern Supreme Court Justices carefully avoided the Parke-Davis decision in their quartet of patentable subject matter cases, but perhaps it is time to return to Learned Hand’s wisdom. Otherwise, the courts may find themselves continually deciding whether to allow patenting of life science inventions based on distinctions that make no earthly difference.