AMP v. Myriad: A Bad Day At Black Rock

By Daniel Boehnen --

Last week, The Supremes once again stepped into an area of science/law where their limited knowledge of both fields will create more harm than good.  The Supremes' say that the problem with isolated and purified DNA is that it is not chemically distinct from naturally occurring DNA, like cDNA, but persons of skill in the art recognize their reasoning is wrong.  At a minimum, the bonding structure at the ends of the isolated and purified DNA have been inherently and unavoidably changed.  Thus, the distinction between cDNA and purified and isolated DNA is a difference of degree not of kind as reasoned by The Supremes.

The Supremes' deeper mistake is they have, once again, been persuaded by those who conflate the concepts of prior art patentability with the concept of statutory patentability in order to get short term benefit in trade for long term progress.  It is perhaps true that isolating and purifying DNA is no longer patentable today.  But that situation is because the science of molecular biology has progressed to the point where such advancements are now relatively obvious to persons skilled in the art.  That situation certainly was not true in 1983 when an Amgen scientist isolated and purified the DNA for erythropoietin and forever changed the world for patients with kidney failure.  And "but for" that earth changing event by Fu Kwen Lin, who can say whether any of the subsequent discoveries by other Amgen scientists would have occurred.

Therein lays the future mischief that will result from The Supremes' latest decision.  In modern parlance, a core aspect of the patent system is to encourage the capital formation which is needed to tackle the ever-increasingly-difficult challenges that our society faces.  Without the incentive to form the capital pools necessary to tackle increasingly sophisticated and complex problems, technical advances will slow to lower pace.  Perhaps that's a good thing.  Perhaps we have achieved such rapid technical advance over the past 30+ years that we need to slow down for a while, i.e., to give the world a chance to digest all that has been accomplished.

But that slower pace will provide little comfort to patients having a decision whose treatment lies hidden in the leaves of a plant growing in the Amazon forest or inside an insect trapped in an amber rock buried in an African mine.  We have, today, many companies and scientists whose existence is devoted to unlocking such compounds so that they can be used as medicines.  A core mischief of The Supremes' latest decision is that it virtually assures that enormous work of isolating, identifying, and making these compounds available for society will no longer be rewarded with patent protection.  That result won't deter scientists from trying to continue their work; many scientist will still work hard, devoting their energy to unlocking these secrets of nature.  But The Supremes' decision will most definitely deter the money-people, those who provide the money that supports the efforts of those scientists.  The money-people will look elsewhere, and many of them will find other opportunities.  With less monetary support, there will be fewer scientists looking.  And with fewer scientists looking, there will be fewer discoveries.  It's particularly unfortunate that this decision comes at a time when the government, too, is cutting support for science.

Comments

[Dan Feigelson]

Excellent summary of the flaws in Myriad. Clearly, despite Thomas' statements that this decision is limited to isolated DNA, someone will assert that some patented protein or chemical compound was found in nature and that the claim is therefore invalid on the basis of Myriad. We can only hope that when that case reaches the CAFC, Judges Newman and Rader are on the panel to ensure that Myriad is indeed cabined to isolated DNA, so that investment continues to flow to the development of new medicines.

[Skeptical]

To cabin this to isolated DNA as you suggest Dan would be to not understand law.

The law here was the product of nature exception. The fact pattern concerned isolated DNA.

Another case with another fact pattern will apply the law, not the fact pattern.

Plainly speaking (and in reality, plainly speaking is enough), you cannot have a patent on any item that is found in nature.

Period.

One only needs to look at the Chakrabarty case to see other examples that would be not allowed: from simple crystal structures of minerals to complex structures of plants.

And this decision does not stop anyone from obtaining a patent by using the baseline products of nature and changing them into something else. There appears to be too much 'sky is falling' in relation to this decision.

[EG]

"And this decision does not stop anyone from obtaining a patent by using the baseline products of nature and changing them into something else. There appears to be too much 'sky is falling' in relation to this decision."

Agree completely with you, Skeptical

[Edmund Pitcher]

Skeptical states: "Plainly speaking (and in reality, plainly speaking is enough), you cannot have a patent on any item that is found in nature."

This is a truly misguided and absurd statement. Almost all drugs in the pharmacopia are found in nature, from aspirin to digitalis to lithium to taxol to erethropoietin. It has always been legal and proper, and hopefully still is, for one to obtain patent claims to an isolated naturally ocurring molecule, perhaps in a pharmaceutically acceptable vehicle, that has a valuable medical property. The problem here is an activist supreme court making what is fundamentally a political decision based on naive concepts of science and impelled by organizations that want medical technology to be "free."

[Skeptical]

Edmund,

I find your own statement to be "a truly misguided and absurd statement."

You have expressed an opinion with no backing whatsoever. I have expressed the nutshell of the law.

Thank you, but I will trust my statement far more than yours.

You can try to augment your opinion with legal backing. Will you find any such backing? Well, I remain...

[Shrivan]

Skeptical "And this decision does not stop anyone from obtaining a patent by using the baseline products of nature and changing them into something else."

Why not? Myriad changed a "product of nature" into something else, yet they were denied a patent.

[6]

"The Supremes' say that the problem with isolated and purified DNA is that it is not chemically distinct from naturally occurring DNA, like cDNA, but persons of skill in the art recognize their reasoning is wrong. "

Actually that's not what they said, you need to read the decision again. They said, and you will note that they said it quite plainly, that Myriad's invention was in the discovery of two things. Precisely where Myriad said it was at oral args.

[6]

"There appears to be too much 'sky is falling' in relation to this decision."

I haven't noticed much sky falling talk of late. Where is the sky falling talking going on? Even MM's sky is still firmly upheld.

[6]

"and impelled by organizations that want medical technology to be "free."

On the contrary, all they want is for the science underlying the medical tech to be "free" of being entirely caught up in patents. I.e. the discovery made by, and effectively patented, by Myriad.

They could care less about the whole of medical tech being free.

[Shrivan]

6: "all they want is for the science underlying the medical tech to be "free" of being entirely caught up in patents"

I think this is probably an accurate reflection of the Supreme Court's feelings. But they did a pretty good job of burying that concern underneath a lot of verbiage that is tangential at best and will likely cause confusion moving forward. They also avoided making a clear case for why the breadth of their holding is appropriate, given their concerns. As you know, the holding applies to more than just "medical tech."

I also realize that there is nothing at all unusual about a Supreme Court decision with such flaws. It's the way things are. That's why we have the checks and balances in our system. If the public is unhappy with the results of the Supreme Court's decision, it's easy enough for that decision to be "corrected" with legislation.

[EG]

"Almost all drugs in the pharmacopia are found in nature, from aspirin to digitalis to lithium to taxol to erethropoietin."

Edmund,

Actually, at least taxol is an instance where isolation from its native environment to make it into a drug will/should make it past the "product of nature" doctrine which Myriad's claimed isolated DNA sequence didn't in terms of a "difference in kind rather than degree." You could chew on bark from the Pacific Yew all you wanted, and get no meaningful pharmacologically benefit from the taxol contained therein; instead that taxol has to be isolated from the bark (or now synthesized) to make it useful as a drug.

[Donald Zuhn]

EG: You would have a difficult time getting a PCR reaction to work if the source of your primers was a lysed cell.

[Dan D]

What I also find disturbing - and this reflects the scientific subtleties - is that the distinction between cDNA versus purified and isolated DNA is irrelevant for important categories of genes that are not spliced. And the biggest category of such genes are almost all those encoding G protein-coupled receptors (GPCRs) - by far the most cruical drug target in Pharma. Indeed, these targets account for at least one-third of approved drugs, and hundreds of drugs currently in trials.

And what about intronless genes isolated from non-human animals?

Is the fact that the mRNA looks just like the native DNA enough to render it ineligible as patentable subject matter?

And what if I simply optimize codon usage for a lower eukaryotic gene product? This is a routine step for most lower eukaryotic genes, such as those encoding fluorescent proteins, and the Supreme Code expressly declined to rule on such altered nucleic acid sequences.

[Skeptical]

In essence, Shrivan, Myriad was found to have NOT changed a product of nature.

Why are you using quotation marks with product of nature?

Dan D,

Why do you think the human/non-human animal distinction is legally important? Does the case discuss this as an important factor or limitation to the universal judicial exception?

[Shrivan]

EG: "Actually, at least taxol is an instance where isolation from its native environment to make it into a drug will/should make it past the "product of nature" doctrine which Myriad's claimed isolated DNA sequence didn't in terms of a "difference in kind rather than degree."

As Dr. Zuhn suggests, the test you seem to be "applying" is one where you (meaning, the Supreme Court) decide what the result should be and then you re-state the test accordingly. One man's "kind" is another man's "degree".

Imagine my client engineers a novel protein from scratch with incredibly useful properties. I claim a purified polynucleotide encoding the protein: 83 nucleotides long, each nucleotide recited. The sequence of my molecule is later shown to be part of a longer, untranslated pseudogene in the mitochondrial genome of an incredibly toxic organism that is essentially banned in the US. And even within that pseudogene, the sequence is out-of-frame and would encode nonsense if the gene were translated.

How is the difference between my composition (ineligible under Myriad) and the "natural" composition a mere "difference in degree"? And why is it the case that a recombinant organism with a single conservative nucleotide change (or one missing intron) in its 5 billion base genome is deemed to be so "different in kind" from the natural organism that it's now eligible for patenting?

Here's another brainteaser, inspired by a comment I read elsewhere: what about a mixture of two short DNA sequences, where both sequences individually would be ineligible for patenting according to the Myriad case? What about a claim to "A synthetic container or synthetic surface, wherein said container or surface contains or comprises Polynucleotide A," where Polynucleotide A is itself ineligible? Is that a "difference in kind" or a "difference in degree"?

[GD]

Given an apparently flawed generalist, metaphysical supreme court dealing with technical specialist questions, it seems to be up to an arguably more flawed generalist congress to fix this. Hm. Who is going to lead that fun-filled charge? Patent bar? Big pharma?

Scalia gave a very strange and damning concurrence/admission. He admitted he was in over his head and didn't understand. Why didn't he just recuse himself (or resign). How many other times has that happened without the same refreshing candor? This can't be the first. Where were the court's expert, neutral advisers/teachers? How did the court arrive at earlier decisions that dealt with nucleic acids and similar subject matter? Maybe the court needs a bigger budget for expert advice to deal with complicated technologies and areas of law that are beyond its comprehension. Maybe there needs to be a separate court of technologists for complex technical areas. It is time for a change.

[EG]

"Imagine my client engineers a novel protein from scratch with incredibly useful properties. I claim a purified polynucleotide encoding the protein: 83 nucleotides long, each nucleotide recited. The sequence of my molecule is later shown to be part of a longer, untranslated pseudogene in the mitochondrial genome of an incredibly toxic organism that is essentially banned in the US. And even within that pseudogene, the sequence is out-of-frame and would encode nonsense if the gene were translated."

Shrivan,

Actually, the purified polynucleotide you propose would be a "difference in kind" and thus outside the "product of nature" doctrine. Consider the fact situation you presented: in its native environment, this polynucleotide would only encode nonsense, not the novel protein. Contrast that with Myriad's claimed isolated DNA sequence that encoded outside it's native environment the same as it encoded in it, i.e., no "difference in kind," only in "degree," and therefore a "product of nature."

And I'm not simply "deciding the result" and then "applying" the test, i.e., the "product of nature" doctrine. Read page 1 of the slip opinion of the Supreme Court opinion which says squarely that Myriad's claimed "isolated" DNA was a "product of nature" and for that reason, patent-ineligible. You or I may not like how the Supreme Court got there, but that's how they did.

[Shrivan]

EG: "Actually, the purified polynucleotide you propose would be a "difference in kind" and thus outside the "product of nature" doctrine."

I wish I could believe you, EG! But I don't.

"Read page 1 of the slip opinion of the Supreme Court opinion which says squarely that Myriad's claimed "isolated" DNA was a "product of nature" and for that reason, patent-ineligible. "

That statement does not appear on page 1 or page 2 of the Slip Opinion. Page 2 states that "A naturally occurring DNA segment is a product of nature". It certainly does not say that an "isolated DNA segment is a product of nature" (they plainly state the opposite, in fact, on page 14). All they are doing on page 2 is stating the holding: a man-made, non-natural polynucleotide is ineligible for patenting if it is merely "isolated" with respect to a longer sequence that occurs "naturally". Period.

The Court also makes it clear on page 14 that it doesn't matter how much effort went into obtaining the claimed composition or what methods were used. Nor does it matter that the sequence is, in fact, complementary to an mRNA (i.e., a "cDNA"). All that matters for determining eligiblity is whether the sequence of the claimed polynucleotide is identical to a sequence found somewhere in nature.

Happy to be wrong. I'd love to know that the holding applies only to genes that encode and express proteins in their "natural" environment. Of course, if that's the case then the Myriad opinion is even more poorly reasoned and written than it would appear to be at first glance.

[Matt D. Paul]

"But that situation is because the science of molecular biology has progressed to the point where such advancements are now relatively obvious to persons skilled in the art. That situation certainly was not true in 1983 when an Amgen scientist isolated and purified the DNA for erythropoietin and forever changed the world for patients with kidney failure."

Yes, the methods and means for isolating and purifying DNA have indeed advanced. Therefore, these advancements were ruled patentable by the Court. DNA, however, is the natural building block of life. Moreover, the author's argument that "Without the incentive to form the capital pools necessary to tackle increasingly sophisticated and complex problems, technical advances will slow to lower pace," is without merit in my opinion. Marie Curie did not patent her discovered techniques for isolating radioactive isotopes, and one can easily argue that technical advances in the field of nuclear physics and radioactivity were in no way slowed. On the contrary, her process of isolating radium led to some of the most substantial advances in human civilization, notwithstanding the lack of patent protection. The Court got this one correct.

[Dan D]

Skeptical:

Actually I was not trying to draw a substantive distinction between humans and non-humans. My point is that the Supreme Court does not seem to recognize that many genes do not have introns. And for that reason, I also doubt that they appreciated that their decision would likely render patent ineligible ANY gene in any bacteria, because the cDNA coding for that bacterial gene would be identical to the natural DNA sequence. So operationally, the decision has drawn a distinction between (at least) eukaryotes and prokaryotes - even if not intended. And BTW: it seems bizarre that I would be looking at a Supreme Court decision at this level.

[EG]

"Page 2 states that 'A naturally occurring DNA segment is a product of nature.'"

Shrivan,

I was referring to page 1 of the actual opinion, not the headnotes, so we're on the same page there..

"It certainly does not say that an 'isolated DNA segment is a product of nature."

Shrivan,

It does, in SCOTUS speak. What the Myriad opinion says at page 14, at most, is that Myriad's claimed isolated DNA sequence is nonnaturally occurring. But that's not the same as saying it isn't a "product of nature." Again, you've got to read this Myriad opinion in the context of the "product of nature" doctrine which requires considering whether the difference is one of "kind" (i.e., chemically and especially functionally different in the case of your purified polynucleotide and thus not a "product of nature") rather than simply "degree" (e.g., no functional difference as in the case Myriad's isolated DNA sequence which was held to be a "product of nature").

I wrote a law review article 30 years ago that discusses the "product of nature" doctrine, including when it applies and even it exists. See Guttag, “The Patentability of Microorganisms: Statutory Subject Matter and Other Living Things,” University of Richmond Law Review, Vol. 13, page 247 (1979). If you don't put this holding in Myriad in the context of the "product of nature" doctrine, this decision will truly make no sense to you or anyone else, including me.

[Shrivan]

EG: "If you don't put this holding in Myriad in the context of the "product of nature" doctrine, this decision will truly make no sense to you or anyone else, including me."

The Supreme Court said nothing about "difference in kind" or "difference in degree" and I think that's because it realized that those "tests" are not helpful to anyone.

I'm pretty sure your "exception" to the rule set forth in Myriad regarding sequence identity (where an indentical sequence is eligible if the "natural" sequence can be shown to have a different function? is that your test?) will never be adopted unless the Myriad decision is blotted out by Congress. We'll find out soon enough, perhaps.

And your "difference in kind" test does not explain why a recombinant organism with a single conservative nucleotide change (or one missing intron) in its 5 billion base genome would be deemed eligible under Myriad.

You might consider that the Myriad decision just doesn't make much legal sense, EG. It's happened before. The Supreme Court does make mistakes, sometimes very big mistakes (I wouldn't put this case in that category; I'd just say it's poorly reasoned and unmoored from reality).

[Skeptical]

Perhaps it is because I have read your article, but I really do not see why people are being so 'confused.'

Perhaps it is not on purpose, and that people really do not understand the policy driver of the 101 exclusion at work.

But to that, I am...

[Shrivan]

Dan D: " I also doubt that they appreciated that their decision would likely render patent ineligible ANY gene in any bacteria, because the cDNA coding for that bacterial gene would be identical to the natural DNA sequence. So operationally, the decision has drawn a distinction between (at least) eukaryotes and prokaryotes - even if not intended."

This is just one of many elementary facts about biology that seems to have been ignored about the Court. I'm also convinced that at least some of the Justices do not understand (1) that A, T, G, C are terms for chemical structures in exactly the same way that "water" is a term for H20; (2) that cDNA and DNA are the same chemical, unlike mRNA and DNA; (3) that the vast majority of life on earth is microbial and less than 0.001% of those have been cultured or studied; (4) that the genetic code is redundant; and (5) that the nucleotides coding for a given protein are instantly ascertainable if the sequence of the protein is known.

[Skeptical]

'Shrivan,'

Perhaps you are aware that the product of nature judicial exclusion is not limited to biology.

Perhaps you are not just another troll of the infamous Malcolm Mooney, but your argumentative tone and willful ignoring of points raise make me...

[Shrivan]

Skeptical: "Perhaps you are aware that the product of nature judicial exclusion is not limited to biology."

I was aware of that.

In order to write a coherent, meaningful decision about claims that surely are biological, a court needs to recognize basic facts about biology and explain how their holding incorporates those basic facts. That's not a particularly controversial point. I was just expanding on Dan's point. Do you want to argue with both of us about this issue?

"Perhaps you are not just another troll"

Seems to me that a "troll" is the type of person who posts a comment exactly like the one you just posted.

[Skeptical]

While you say "seems to me," it is apparent that is exactly what the Troll Malcolm Mooney would do. You have turned around and accused somebody else of the thing that you are doing. Thank you for removing any doubt as to who you really are.

Now that it is clear that you are THAT Malcolm Mooney, let's look at your statement and see which point you think that you are expanding of Dan's.

Squint as I may, I cannot see it.

Is it the point that there are quite a few things that will fall due to the product of nature judicial exception? How is this a meaningful expansion, given as my comment already captured that thought?

Rather, it appears that you want to 'argue' the perceived wrong you have with this decision based on the Justices' summary of the science.

That is a rather pedantic way of looking at the decision. What is 'coherent and meaningful' is the rule of law that you take away from the decision - not your pedantic scrutiny of the claims because you do not like how the decision came out.

That you have a firm grasp of the law and the legal process, I am very

[Shrivan]

Skeptical: "Now that it is clear that you are THAT Malcolm Mooney"

I don't know who are you referring to. You seem to have a personal issue with somebody. Maybe you should get over it? See a specialist?

My point is that the Myriad decision is nonsensical from the viewpoint of one skilled in the art, for the reasons I explained. If you don't think so, that's fine. You're entitled to your opinion. I'm entitled to disagree with you and, to the extent I explain why, my views may persuade others or reinforce the views of others. This is how the comments sections of blogs work, the last time I checked.

As for my "scrutiny of the claims", that's just a patent attorney doing what a patent attorney does. If you want an excellent example of "pedantry", I suggest reading your own comment. Have a nice day.

[Igor Faynshteyn, Esq.]

Dear everyone,

Please disregard Skeptical. He is a troll. See his commentaries in other posts.