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Tuesday, April 23, 2013

Impact of the “Lander Brief” in the Myriad (Gene Patent) Case – and an answer to Justice Alito’s Question

The Supreme Court heard oral arguments on April 15 in Association of Molecular Pathology et al. v Myriad, concerning whether human genes are patent-eligible subject matter. The case focused on Myriad’s patents on two genes, BRCA1 and BRCA2, involved in early-onset breast cancer

Surprisingly, many of the Court’s questions for Myriad’s counsel focused on what Justice Breyer dubbed the “Lander Brief” – an amicus filed on behalf of neither party by one of the country’s leading scientists, Dr. Eric Lander. (Lander was one of the leaders of the Human Genome Project and co-chair’s the Presidents Council of Advisors on Science and Technology.) [Full Disclosure: I am one of the authors of this brief] Justices Breyer, Ginsburg and Alito referred to the brief by name, and several other Justices were clearly influenced by the information in the brief.

I believe that the “Lander brief” was a hot topic of conversation because the Justices realized that it was central to applying the Court’s product-of-nature doctrine to DNA. Importantly, the brief demolished the scientific foundation of the Federal Circuit decision on appeal. The Federal Circuit panel held that human chromosomes are not patent-eligible because they are products of nature, but a majority found that “isolated DNA” fragments of human chromosomes (such as pieces of the breast cancer genes) are patent-eligible. The Federal Circuit’s distinction rested on its assumption that (unlike whole chromosomes) isolated DNA fragments do not themselves occur in nature, but instead only exist by virtue of the hand of man.

The Federal Circuit cited no scientific support for its crucial assumption – neither in the record below, nor in any scientific literature. 

Embarrassingly, the Federal Circuit’s assumption turned out to be flat-out wrong. The Lander brief summarized 30 years of scientific literature showing that natural processes in the human body routinely cleave into isolated DNA fragments. Isolated DNA fragments turn out to be abundant outside of cells – including in cell-free blood, urine and stool. They are so common that they can be used for genetic diagnostics of inherited diseases and cancers. In fact, they are so prevalent that several scientific groups have shown that it is possible to determine the entire genome sequence of a fetus based on analyzing the isolated DNA fragments found in a teaspoons-worth of its mother’s blood. 

Justice Breyer relentlessly pushed Myriad’s counsel to declare whether he agreed or disagreed with the Lander Brief. When the counsel finally declared that he disagreed, Justice Breyer demanded:

JUSTICE BREYER: Okay. Very well. If you are saying it is wrong, as a matter of science, since neither of us are scientists, I would like you to tell me what I should read that will, from a scientist, tell me that it's wrong.

The only reply that Myriad’s counsel could muster was to point to a declaration that had been filed (by Dr. Mark Kay) in the District Court case in 2009. (In fact, Dr. Kay’s declaration said nothing whatsoever about whether isolated DNA fragments occur in Nature. It concerned how to construe terms in Myriad’s patent.)

A few minutes later, Justice Ginsburg returned to the point:

JUSTICE GINSBURG: Do you concede at least that the decision in the Federal Circuit, that Judge Lourie did make an incorrect assumption, or is the Lander brief inaccurate with respect to that, too? That is, Judge Lourie thought that isolated DNA fragments did not exist in the human body and Dr. Lander says that --

MR. CASTANIAS: No, what -- I think Justice -- Judge Lourie was exactly correct to say that there is nothing in this record that says that isolated DNA fragments of BRCA1 exist in the body. Neither does Dr. Lander's brief, for that matter. And for that matter, those isolated fragments that are discussed in Dr. Lander's brief again are -- are what are known not -- not in any way as isolated DNA, but as pseudogenes. They're typically things that have been killed off or mutated by a virus, but they do not –

Here, Myriad’s counsel proved to be confused. Contrary to Mr. Castanias’s statement, the Lander brief (on page 16) explicitly stated that isolated DNA fragments were found covering the entire BRCA1 and BRCA2 genes. Also, “pseudogenes” had nothing to do with Lander’s brief; they arose in the ACLU’s brief for Petitioners and in Myriad’s reply. (“Pseudogenes” are sequences in the human genome that occur when RNA is rarely reverse transcribed into DNA; they are relevant to the patentability of cDNA but are unrelated to the patentability of genomic DNA.)

Justice Alito then jumped in, offering the only glimmer of hope for Myriad’s counsel:

JUSTICE ALITO: But isn't this just a question of probability? To get back to your baseball bat example, which at least I -- I can understand better than perhaps some of this biochemistry, I suppose that in, you know, I don't know how many millions of years trees have been around, but in all of that time possibly someplace a branch has fallen off a tree and it's fallen into the ocean and it's been manipulated by the waves, and then something's been washed up on the shore, and what do you know, it's a baseball bat.

In other words, Justice Alito asked whether isolated DNA fragments of the BRCA genes might be freakishly rare. Neither opposing counsel nor the Solicitor General had an opportunity to address Justice Alito’s question, because they had already spoken.

The answer to Justice Alito’s questions turns out to be: VERY common. A typical person contains roughly one billion isolated DNA fragments of the BRCA genes circulating in his or her blood.

The Lander Brief (in footnote 23) cites several papers showing that, in 1 milliliter of blood (1/4000th of total circulation), each nucleotide in the human genome was covered by about 250 fragments on average. In total circulation, this corresponds to about 1 million fragments (= 4000 x 250) covering each individual base. Across the length of the BRCA genes, this translates to about 1 billion fragments.

 More explicitly, footnote 25 points to a web site published by Stanford Professor Stephen Quake (the author of one of the studies), in which he specifically reported the coverage of the BRCA genes in the blood stream. Dr. Quake’s data directly showed that a typical person carries roughly 945 million fragments of isolated DNA from the BRCA1 and BRCA2 genes.

I was very happy the Lander brief has got this much attention, since I think that once the Court understands the fundamental mistake made by the Federal Circuit (and apparently Myriad’s counsel), as several of the Justices questions suggested they did at oral argument, the outcome of the case becomes clear. The Court actually can sidestep a number of more difficult questions in patent law (about the precise meaning of the standard under Diamond v. Chakrabarty for when a molecule is “markedly different” than a product of nature), because isolated DNA fragments of the human genome are precisely products of nature themselves.

Posted by Ivan Cohen on April 23, 2013 at 02:28 PM in Intellectual Property, Web/Tech | Permalink

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