Patent Eligibility and Biology

By Kevin E. Noonan --

Earlier this month we asked for examples of instances where claims to isolated DNA interfered with basic research (see "The Proper Scope of DNA (or "Gene") Patent Claims").  We posited that the claim would be something like this one:

An isolated (human) nucleic acid (or DNA molecule or gene (specified by name)), encoding an amino acid sequence identified by SEQ ID NO: X,

where the portions of this claim in parentheses are optional, used in some cases but not necessary to properly recite the claimed subject matter.  This type of claim has the following features:

• It must use the term "isolated" in the claim, to distinguish it from naturally occurring molecules in their natural state, so as to evince the "hand of man" in its creation (Diamond v. Chakrabarty) to satisfy 35 U.S.C. § 101;

• It cannot read on the natural molecule (i.e., the claim scope cannot be broad enough to encompass the natural molecule) so that it satisfies the novelty requirement of 35 U.S.C. § 102 (Wood-Paper Patent, 90 U.S. 566 (1874), and Cochrane v. Badische Anilin Soda Fabrik, 111 U.S. 293 (1884));

• Infringement will lie only if the entire amino acid sequence-encoding isolated nucleic acid recited in the claim is made, used, sold, offered to be sold, or imported;

• Portions of the gene can be isolated, sequenced, and characterized and not infringe, and such portions can be changed and then introduced into the gene to produce another gene that does not infringe;

• The gene product (typically, a protein) can be isolated from the cell and studied without infringement, as can antibodies raised against the gene product; and

• The sequence itself can be identified in individuals and compared to wildtype or disease-associated mutations without infringing unless the entire DNA is isolated intact.

Recent posts provide an opportunity to further distinguish what is patent eligible from what is not (see "Dolphin Genes Show Relationships between Large Brains and Energy Metabolism Similar to Humans and Elephants" and "Genetic Marker Map of Sunflower Species Reported").  In the former, researchers have identified a number of genes that have been subjected to positive selection, presumably due to their usefulness in adapting to the aquatic lifestyle.  This information was developed by comparing dolphin genes with their orthologs in related species, including cow, horse, dog, mouse, elephant, opossum, platypus, chicken, and man.  And none of this information is, per se, eligible for patenting, being (like the capacity for certain species of Rhizobium to grow together) to be "part of the storehouse of knowledge of all men [and]  manifestations of laws of nature, free to all men and reserved exclusively to none."  Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127 (1948).

However, the paper does posit that dolphins may be large animal models for type 2 diabetes in humans

During the course of primate evolution, metabolism evolved to provide a constant supply of energy to the increasing demands of a larger brain.  [Leonard et al., 2003, "Metabolic correlates of hominid brain evolution," Comp. Biochem. Physiol. A 136: 5–15].  Humans have evolved several adaptations, including an increase in visceral fat and the evolution of tissue-specific insulin resistance in the brain that protects nervous tissue from energy shortage; however, malfunctions of this system in humans can cause type 2 diabetes (Kuzawa, 2010 Beyond feast-famine: brain evolution, human life history, and the metabolic syndrome. In Human evolutionary biology (ed. Muehlenbein M.), pp. 518–527. Cambridge, UK: Cambridge University Press).  Interestingly, recent research has proposed that dolphins should be seen as a model for type 2 diabetes, as they possess all the hallmarks of the disease [Venn-Watson et al., 2011, "Dolphins as animal models for type 2 diabetes: sustained, post-prandial hyperglycemia and hyperinsulinemia," Gen. Comp. Endocrinol. 170: 193–99)].  Here, we find genomic signatures of adaptive evolution in dolphin genes related to control of food intake such as genes involved in glycerol uptake and/or glucose metabolism (AQP9, OSTN, SOCS6), and a neuropeptide AGRP that is expressed in the hypothalamus and involved in increasing appetite, decreasing metabolism and regulating leptin. In addition, we found several genes under selection related to lipid transport and metabolism [] that may be associated with the large fat reserves found in cetaceans.

Thus, methods for testing compounds as potential drugs for treating human type 2 diabetes using dolphins may be patent eligible, in a claim such as this one:

A method for identifying a compound that is effective in treating type 2 diabetes in the human, comprising the step of administering the compound to a bottlenose dolphin and detecting an antiglycemic effect in the dolphin.

The other paper, on the sunflower genome identified more than 10,000 genetic loci (by virtue of small nucleotide polymorphisms or SNPs) to provide a genetic map of the sunflower genome.  That genome was represented graphically as follows:

Like the dolphin genome, this map is also not patent eligible.  However, sunflowers are of great economic importance, being the fourth largest source of cultivated vegetable oils worldwide (www.fas.usda.gov).  In addition to these maps, the "sunflower genome project" is under active pursuit (Kane et al. 2011, "Progress towards a reference genome for sunflower," Botany-Botanique 89: 429–37), wherein genes that may increase yield or resistance to insect predation or aridity may be mapped to portions of the sunflower genome close to one of these SNPs.  In such a case, methods for identifying sunflowers having a desirable trait associated with one of these polymorphisms may be patentable:

A method for producing sunflowers having [a desirable trait], wherein the trait is genetically linked to [a particular SNP], the method comprising the step of identifying the SNP in said sunflower and cultivating said sunflower.

These examples are not meant to be exhaustive.  But they are intended to illustrate the difference between patent eligible and ineligible subject matter, and to show that the mere intersection of patents and biology should not be the occasion to disqualify patent eligible subject matter.

This is illustrated by the drawing below, which discloses relationships between gene expression in mammalian development.  If you squint a little looking at the drawing (or click on the image), these inter-relationships look somewhat like a circuit drawing, and in some ways they are.  These interrelationships are not, per se, eligible for patenting.  But components thereof, and methods taking advantage of the elucidation of these interrelationships should be, and their provenance in the natural world should not be enough to categorically exclude them from patent eligibility.

Figure from Ellis, "Animal Evolution: A View from the Genome," Engineering & Science 3/4: 42-51 (2001).

Comments

[Skeptical]

Dr. Noonan,

Your example of dolphin testing would not be patent eligible according to Prometheus.

In "comprising the step of administering the compound to a bottlenose dolphin and detecting an antiglycemic effect in the dolphin." you are doing nothing above a law of nature. Just as in Prometheus, the administering step only sets the table for the claim and would be parsed out. The antiglycemic effect is only nature doing its thing. Here, you are not even saying "just apply it;" but you are saying "just observe it."

You have to do more to illustrate patent eligibility.

On the other hand, the sunflower iem would be patent eligible as it evinces the application of the hand of man to actually achieve something.

[Bob Hodges]

If it was not conventional to administer the compound to dophins, then wouldn't the claim involve other than routine or conventional steps and thus be patent-eligible? Also, if the combiniation of a step of adminitering a compound to a dolphin and then detecting an antiglycemic effect had not previously been combined, this new combination would be applying the natural process in a new and limited context.

[EG]

Skeptical,

I would be careful about saying the dolphin testing isn't patent-eligible, even in view of Prometheus/Mayo. First, the method in Prometheus/Mayo was about determining a level of the metabolite that would indicate too high or too low a dosage. Second, the claimed method might have been written differently (and was written differently in other patents owned by Prometheus) to reach the patent-eligibility zone.

By contrast, what Kevin's proposed "dolphin testing" method is essentially is an animal model for screening potential diabetes treatment drugs for humans. I might also suggest rewriting Kevin's proposed method this way:

A method which comprises the following steps:

(a) administering a compound having a potential for treating type 2 diabetes in the human; and (b)

(b) measuring the degree of antiglycemic effect in the dolphin to thereby determine whether the compound is or is not effective for treating type 2 diabetes.

What I think is important is to move the preamble from Kevin's proposed method claim into the body of the claim. In my opiinion, relying on the preamble language for anything is fraught with danger. (Prometheus' claimed method had this issue too.)

You might also add to step (b) that the "measuring" is carried out with an analytical instrument of some type to avoid a potential "mental steps" issue. The problem is that if animal drug screens like this one are patent-ineligible, you are really putting a crimp on the ability to protect such drug screens except in a very rare circumstance.

[Skeptical]

Bob,

I suggest you read (again) the Prometheus decision and then see if you can apply your comments (please note that I NOT saying that your logic is flawed).

EG,

Respectfully, I stand by my post and maintain that the claim as provided would be found NOT patent eligible in view of Prometheus (the difference in subject matter is immaterial, and "re-writing" the claim may or may not help - but is not part of the discussion).

I am not sure what you are talking about as to a preamble, as the inset claim has no preamble.

Further, I doubt that the addition of a step of 'measuring carried out with analytical instruments' would even help, as I am sure that you recall, Prometheus had that very type of step (which Breyer parsed out) in its claim that was ruled patent ineligible (again, I am not saying that the Supreme Court logic was correct).

Bottom line is that drug screen methods (written as provided) are not patent eligible methods because they do not even approach the "just apply it" threshold.

Wouldn't you be skeptical to accept "just observe it," if "just apply it" is "not enough"? A research plan is not an invention. Research results are not an invention.

[EG]

Skeptical,

You could well be correct in view of the "fuzzy" flawed reasoning in Prometheus/Mayo. See my comment below about reconciling Prometheus/Mayo with Diamond v. Diehr.

What is the "preamble" in Kevin's proposed claim is everything before "comprising the following steps"; everything afterwards is the "body" of the claim. Federal Circuit case law on the impact of the "preamble" on the validity of the claim is all over the place.

Actually, Breyer didn't parse out in Prometheus/Mayo a claim which required any mechanical device. All Breyer said was: "For present purposes we may assume that the other claims in the patents do not differ significantly from claim 1." What may have bothered Breyer (especially given all I heard about this claimed method patenting "thought", possibly based on an ill-advised infringement assertion by Prometheus) is that the claimed method might potentially cover "mental steps." (There is a reference in Prometheus that "mental processes" are not patentable.)

In effect, the dolphin is being used in this method just like a mechanical instrument to evaluate whether a compound is or is not a potential drug for treating diabetes. How is this different from a mechanical instrument doing the same thing? How is this different from "measuring the temperature inside the mold and feeding the temperature measurements into a computer that repeatedly recalculates the cure time" as in the Diamond v. Diehr case? (And you don't need to tell me that the reasoning in Prometheus/Mayo can't be squared with Diehr, no matter what Breyer says.)

All I'm saying is that until something like this dolphin drug screen method is evaluated in the "crucible of litigation," any judgment we make now as to what will fly is about as good as using a Ouija board (my favorite metaphor now on determing patent-eligibility under 35 USC 101).

[Keep It Real]

A method which comprises the following steps:

(a) administering at least two compounds having a potential for treating type 2 diabetes in the human;

(b) measuring the degree of antiglycemic effect of the at least two compounds in the dolphin; and

(c) recording the results in a manner that allows identification of one or more compounds with greatest antiglycemic effect.
---------------------

If (a) or (b) are not in the prior art the case is immediately distinguished from Prometheus. The claim might still be ineligible under some other 101 theory but the facts here (i.e., the elements in the claim and their relationship to excepted subject matter and the prior art) are completely different from the facts in Prometheus. This true even if step (c) is omitted.

[Keep It Real]

"any judgment we make now as to what will fly is about as good as using a Ouija board (my favorite metaphor now on determing patent-eligibility under 35 USC 101)."

Actually there are an infinite number of claims that are very very easy to swat down as ineligible under 101, especially after the clear guidance in Prometheus.

[Skeptical]

EG,

A dolphin is not a mechanical device and any biological interaction will fall according to the Law of Nature doctrine as explained in Prometheus (along the lines of a human may introduce a substance, but the reaction of the substance, and the metabolites, thus created, merely follow natural law).

Malcolm,

I see that you are still trying to sneak a 102/103 analysis into the 101 analysis. Your (b) will not distinguish for a 101 analysis even if the measurement of effect is not in the prior art. It is not "some other" 101 theory. It is the same 101 theory used in Prometheus.

[EG]

Skeptical,

You're still missing my point: the dolphin model is still be used like it was a mechanical/analytical device. Also, how is this different from using Chakrabarty's microorganism which contained 4 plasmid vectors from other microorganisms to degrade oil spills? SCOTUS in Chakrabarty has already ruled that the fact the claimed subject matter involves life forms doesn't make it automatically patent-ineligible under 35 USC 101.

Dolphins, in nature, don't ingest the potential anti-diabetic drugs; that requires human intervention. This is one of the great fallacies of Prometheus/Mayo being based on a "law of nature" exception as the drugs administered there don't exist in "nature." I can rationalize the result in Prometheus/Mayo on "abstract idea" grounds, but not on "law of nature" grounds.

Again, your view could be adopted by the courts, but it still needs to be tested in the courts. What Prometheus/Mayo says is so nebulous and in conflict with the reasoning in Diehr that it will take potentially many subsequent cases to sort out what is and is not within the patent-eligibility zone. I, for one, am not going to assume what the boundaries are based Prometheus/Mayo.

[Skeptical]

With all respect EG, no I am not missing the point.

I understand full well what you are saying.

I disagree that that line of thought works.

You are engaging in what can only be called a combiantion of wishful thinking/buyer's remorse. You cannot undo what the 9-0 Supreme Court said in Prometheus.

You are confusing yourself by thinking the question is concerning a life form or not - it is not.

The question is what is being done with that life form.

In the dolphin example, there is nothing inventive - just observation. In Chakrabarty, a manufacture (even though of living things) was undertaken.

You are also missing the point made in Prometheus that the introduction of the drug - even by human action - is MEANINGLESS to the patent eligibility of the claim. All that is, per Breyer, is setting the stage - pre-solution activity that does not count. Yes, we both may agree that this may be considered a "great fallacy," but you would be incorrect to say that the courts COULD adopt the view. Courts are BOUND to adopt the view because the Supreme Court said so. There is no "to be tested."

To suggest otherwise is to fly in the face of the direct words the court has used, removing the logical pinning that the decision iteslef requires and making a dead letter of the decision. Do you think that such would survive judicial scrutiny? Me, I'm skeptical.

[Jaded]

With all due respect to all of "Bob", "EG" and "Skeptical", in addition to the Prometheus decision, we now have the CAFC (admittedly a lower court) decision in Myriad after GVR to the effect that a claim to a method for screening drugs by observing their effect on a model system is patent eligible.

Notwithstanding all of the controversy surrounding both decisions, I think that the Supreme Court decision in Prometheus was driven mostly by an understanding (right or wrong) that patents on diagnostic methods drive up their cost to the public, and such costs are to be minimized now.

So, to the degree that model systems make development of drugs less expensive, and that savings is passed on to consumers ultimately (or maybe to the insurance companies and Medicare/Medicaid, who are the entities actually buying), I think it is probable that the CAFC's decision on the question of patent eligibility of drug screening methods will stand if reviewed by the Supreme Court.

[Keep It Real]

Skeptical: "You are also missing the point made in Prometheus that the introduction of the drug - even by human action - is MEANINGLESS to the patent eligibility of the claim. "

That's because the step of administering the drug was old in the art and the only additional step was a step of thinking about an unpatentable correlation. The claim was therefore effectively a patent on the correlation itself and was declared ineligible for that reason. You really have not idea what Prometheus was about, Skeptical. We've established that already.

"Do you think that such would survive judicial scrutiny? Me, I'm skeptical."

You're also wrong pretty much 100% of the time.

[Keep It Real]

EG "This is one of the great fallacies of Prometheus/Mayo being based on a "law of nature" exception as the drugs administered there don't exist in "nature.""

Not a great fallacy, but certainly an unnecessary distraction that has caused great confusion amongst those who are inclined to be confused whenever the Supreme Court finds a patent invalid.

If you read the decision with an intent to understand what the Court is talking about, you'll see that they make no distinction between "natural correlations" and "laws of nature." A key point of the case (or "holding" if you will) is that you can't practice the prior art, discover something new that "naturally" results from that practice, and then obtain a patent that turns practitioners of the prior art into infringers when they THINK about your discovery. There has to be more in the claim.

[Keep It Real]

Jaded: "we now have the CAFC (admittedly a lower court) decision in Myriad after GVR to the effect that a claim to a method for screening drugs by observing their effect on a model system is patent eligible."

Except that's not the correct holding of the case. The correct holding is that "a claim to a method for screening drugs by observing their effect on a NOVEL, NON-OBVIOUS model system is patent eligible."

This is, in fact, an example of the permitted and correct application of the machine-or-transformation test (in this case, it's a biological machine).

Note that if all limitations in the claim are old, the mere recitation of a step of "observing [something new]" will not rescue the claim from ineligiblity under 101 (although it will rescue the claim from being anticipated). That is because such a recitation lands us right back in the Prometheus problem: people practicing the prior art will become infringers merely because they look at something in a new way.

[Keep It Real]

Skeptical: "I see that you are still trying to sneak a 102/103 analysis into the 101 analysis. "

I'm not trying to "sneak" in any analysis. I don't need to "sneak" in any analysis. The Supreme Court didn't "sneak" in a "102/103 analysis" into their 101 analysis. They performed the 102/103 analysis expressly, and even explained why they did so.

You've already been asked to explain WHY the Supreme Court chose to use the language "old" and "conventional" when they explained the failure of the transforming steps at converting the ineligible recited mental step (thinking about a "natural correlation") in Prometheus' claim into eligible subject matter.

You failed to provide an answer, Skeptical. And you won't be able to provide one now. That much is absolutely certain.