AMP v. PTO Casts Doubt on Patent Eligibility of "Purified" (as Opposed to "Isolated") Biomolecules

On January 5, 2001, the US PTO published Utility Examination Guidelines explaining its long-standing policy of treating "isolated and purified" DNA molecules as patent eligible. Throughout the Guidelines, the PTO consistently refers to these patent-eligible DNA molecules as both isolated and purified, but never explicitly attributes distinct meaning to the two terms. Instead, I think most people have interpreted the terms (as used by the PTO in this context) as essentially redundant, similar to someone referring to a contract provision as "null and void."

If anything, the PTO guidelines might be interpreted as treating "purification" as a more demanding requirement than "isolation." For example, at one point the guidelines state that "an inventor's discovery of a gene can be the basis for a patent on the genetic composition isolated from its natural state and processed through purifying steps that separate the gene from other molecules naturally associated with it,” perhaps implying that mere isolation will not be sufficient unless the DNA molecule is not subsequently purified through processes that separate the gene from other molecules.

In practice, it is my experience that the PTO and most practitioners have interpreted "purification" and "isolation" as essentially redundant. While most "gene patents" recite DNA molecules that are "isolated," "isolated and purified," or "recombinant," there are a substantial number of issued patents that simply recite "purified" DNA molecules. See for example US Patent Nos. 5,780,262, 6,262,247, 6,399,371, 6,448,042 and 6,555,347. The PTO also routinely issues patents on other purified biomolecules, particularly proteins, based no doubt on the assumption that as a general matter purification of a biomolecule from its native environment is sufficient to confer patent eligibility. See for example US Patent Nos. 6,258,556 and 6,284,236.

In the Federal Circuit's recent decision in AMP v. PTO (discussed briefly already on Patently-O and Patent Docs), the two judges in the majority (Lourie and Moore) held that "isolated" DNA molecules are patent eligible, but implied that mere "purification" of a biomolecule is insufficient to render it patent eligible. Writing for the majority, Judge Lourie correctly observes that patent eligibility under 35 USC 101 of purified biomolecules has never been explicitly addressed by the courts. As I pointed out in an earlier blog post:

The cases most commonly cited for the proposition that a purified naturally occurring compound is patent eligible are In re Kratz, 592 F.2d 1169, 1174 (CCPA 1979) (stating that a naturally occurring strawberry constituent compound does not anticipate claims to the substantially pure compound) and In re Bergstrom, 427 F.2d 1394 (CCPA 1970) (stating that a material occurring in nature in less pure form does not anticipate claims to the pure material). The Federal Circuit implicitly seems to support this view, and as recently as 2003 a Federal Circuit panel cited both Kratz and Bergstrom with apparent approval. But it is worth noting that Kratz and Bergstrom dealt specifically with the novelty and nonobviousness of the compounds, not patent eligibility per se. To my knowledge, there is no judicial precedent that has directly addressed the issue of whether isolation of a naturally occurring molecule renders the isolated molecule and eligible under section 101.

Judge Lourie also correctly noted that the Supreme Court's decision in Funk Bros., although often treated as patent eligibility case, was actually decided on the basis of obviousness, a point that Hal Wegner has long made in which I discussed in a previous blog post.


In what might be the most interesting part of the decision, Judge Lourie makes a clear distinction between purification and isolation of DNA. He explicitly states that "isolated DNA is not purified DNA." In his view, “[p]urification makes pure what was the same material, but was previously impure,” while “[i]solated DNA, in contrast, is a free-standing portion of a native DNA molecule, frequently a single gene. Isolated DNA has been cleaved (i.e., had covalent bonds in its backbone chemically severed) or synthesized to consist of just a fraction of a naturally occurring DNA molecule.”

Judge Lourie stresses that unlike a biomolecule that has been merely purified, isolated DNA "has also been manipulated chemically so as to produce a molecule that is markedly different from that which exists in the body." In his view, the test for patent eligibility hinges on whether the claimed molecule is "markedly different" from that which occurs in nature, and differences at the level of chemical structure between synthetic DNA, or genomic DNA that has been excised from the genome, are sufficient to satisfy the test. Implicitly, he seems to suggest that purified DNA molecules that are not structurally distinct from a naturally occurring counterpart would not be patent eligible. This seems to suggest that claims directed towards purified biomolecules, such as proteins, might not be patent eligible.

In its amicus brief, as I recall, the Biotechnology Industry Organization argued that the District Court's decision in AMP v. PTO should be reversed because it implied that a purified natural product, such as Taxol, would be patent ineligible under the logic of the decision. But in fact it seems that even though the Federal Circuit reversed on the patentability of isolated DNA, its decision suggests that a purified natural product is patent ineligible unless it has distinctions in chemical structure sufficient to render it "markedly different" from its naturally occurring counterpart.

Arguably, the Federal Circuit's decision in AMP v. PTO is not inconsistent with the PTO utility examination guidelines. For example, the guidelines provide two examples of patent eligible isolated DNA - DNA that has been chemically synthesized outside of the body, and DNA that has been excised from the chromosome. Judge Lourie explicitly identifies these two forms of DNA as "isolated" and hence patent eligible.

Judge Lourie and Judge Moore get mixed up at times on the nuances of molecular biology, and make some misstatements regarding the nature of genomic DNA and cDNA. However, while a molecular biologist will pick up on these inaccuracies, I don't think they detract from the core of the decision. In a previous blog post, I explained why the amicus brief filed by the DOJ attempting to distinguish between cDNA and genomic DNA missed the mark because it failed to recognize that, in the vast majority of cases, "isolated" DNA refers to DNA that has been synthesized outside of the native context from which it arose in the body. The DOJ brief (which Judge Moore described as being at times “childlike” in its simplicity) assumed wrongly that "isolated" genomic DNA has merely been plucked from the human cell (what Judge Lourie would characterize as purification), when in fact patents on isolated DNA are based on DNA molecules that have been synthesized in the laboratory, either by cloning into a host cell, or by PCR, or something along those lines. I think that at some level Judge Lourie’s decision gets at this distinction between a biomolecule that has merely been purified, and isolated DNA molecules, which are generally the result of human-directed synthesis.

ACLU Responds to Myriad’s Letter Challenging Standing of Dr. Osterer

On Thursday I posted a letter from Myriad's attorneys to the Federal Circuit judges pointing out that the key plaintiff in the case (Dr. Osterer, the only plaintiff found to have standing in yesterday's decision from the Federal Circuit) has moved from NYU to Albert Einstein College of Medicine. Myriad asserts in the letter that Dr. Osterer will not be able to perform clinical genetic testing at Albert Einstein, and thus will not be because it into start conducting clinical BRCA testing if the Myriad gene patents are invalidated.

Yesterday, the ACLU responded with its own letter to the Federal Circuit, stating that Dr. Osterer will continue to offer clinical genetic testing at his new institution. It would seem to be an important point, since the District Court decision would have been vacated if the Federal Circuit had held that all of the plaintiffs lacked standing to bring suit. The only plaintiff that the Federal Circuit found to have standing was Dr. Osterer, and this was based explicitly on the court's understanding that he intended to begin conducting clinical BRCA testing if the patents could be invalidated. One wonders if this information could have altered the outcome if it had come to light sooner.

Myraid Alerts Federal Circuit Judges that Key Plaintiff in AMP v. PTO Apparently Cannot Perform Clinical BRCA Testing

During oral arguments in AMP v. PTO (the ACLU/PubPat attack on Myriad Genetic’s BRCA gene patents, previously discussed here), the panel of Federal Circuit judges hearing the case evinced some skepticism as to whether any of the named plaintiffs have standing to bring the lawsuit. For example, many of the plaintiffs are patients who would not appear to be in any real threat of being sued by Myriad for patent infringement.

The plaintiffs most likely to have standing are probably the clinicians who the ACLU argues would engage in BRCA testing were it not for the Myriad patents. However, the declarations by these plaintiffs do not unambiguously state that the plaintiff would begin doing BRCA testing if the patents are invalidated. Instead, they merely declare that the plaintiff has the "capability and desire" to perform the tests, and that the plaintiff "has all the personnel, expertise, and facilities necessary to do various types of sequencing." These declarations were drafted by lawyers, and I think the language used is meaningful, reflecting the fact that these clinicians have not committed to performing BRCA testing if the patents are invalidated.

During oral arguments the Federal Circuit judges pushed the ACLU attorney to clarify whether this language indicated a commitment to perform the tests, implying that a mere "capability and desire" to perform the test might not be sufficient to generate the degree of controversy necessary for standing. In my opinion, the ACLU attorney never provided a clear answer to the question, which suggests that in fact these clinicians have not committed to performing the tests.

Yesterday, Myriad's attorneys sent a letter to the Federal Circuit judges informing them that one of the key clinician plaintiffs who submitted this sort of declaration, Dr. Harry Osterer, has left his position at the NYU Langone Medical Center, and apparently is no longer in a position to offer clinical BRCA genetic testing. Attached to the letter is a printout from the Albert Einstein College of Medicine, identifying Dr. Osterer as a new professor at Albert Einstein. In the letter, Myriad's attorneys state that Albert Einstein does not offer, and is not qualified offer, clinical genetic testing. If this is correct, this seems to further undercut any pretense that he is committed to offering clinical BRCA testing if the patents are invalidated. A copy of the letter is attached here.

Myriad Genetics Files Amicus Briefs in Joint Infringement Cases Akamai and McKesson

Personalized medicine company Myriad Genetics has filed amicus briefs in Akamai and McKesson, two cases currently pending before the en banc Federal Circuit that address the doctrine of joint infringement (aka divided infringement). These cases have been the subject of much discussion elsewhere, see for example the Patently-O and Patent Docs blogs. In a nutshell, the Federal Circuit seeks to delineate the circumstances under which a party will be held liable for patent infringement when multiple parties perform all steps of the patented method in concert, but no single party performs all of the steps.

In its amicus briefs, which are largely redundant, Myriad points out that while the recent joint infringement cases coming out of the Federal Circuit have tended to involve claims directed towards business methods and software, the decisions have created case law with substantial negative implications for patents on diagnostics and personalized medicine. Molecular diagnostics generally involve the discovery of a correlation between a molecular marker (e.g., a genetic variation, or the level of a metabolite) and a clinically relevant indication (e.g., whether an individual has a predisposition to a disease such as cancer, or would be likely to benefit from a particular drug or course of therapeutic treatment). Patent protection for these discoveries is generally achieved by means of a method claim reciting two steps-(1) detecting the molecular marker in a patient, and (2) recognizing the correlation. As noted in the Myriad briefs, product claims on the molecular markers themselves (e.g., isolated DNA molecules or proteins), and methods of testing for them, are generally precluded in the post-Human Genome Project era by prior art (not to mention efforts by the ACLU and others to render such products unpatentable).

The problem from the perspective of a molecular diagnostic innovator company such as Myriad is that the Federal Circuit's recent joint infringement decisions would seem to dictate that such a method claim would not be infringed under circumstances where one party (e.g., a diagnostic testing laboratory) performs the first step and an independent second party (e.g., a doctor) performs the second. Under recent Federal Circuit case law, assuming that the parties are not in an agency relationship, it seems likely that in most instances no party would be found infringing, and the patent owner would be left without a remedy, even in the face of substantial infringement in competition with its business.

In its briefs, Myriad notes that the Federal Circuit has repeatedly admonished patent owners that problems of divided infringement could have been avoided if the claims have been better drafted, i.e., in a manner such that a single party performs all of the steps of a method claim. However, Myriad argues (correctly I think) that the patent eligibility doctrine effectively forecloses this course of action. The Federal Circuit's recent decision in Prometheus (discussed previously on this blogs), in particular, interprets Bilski as rendering patent ineligible a claim reciting nothing more than the mere recognition of a correlation per se (which the court equates with patenting a mental step). In order to be patent eligible, Prometheus seems to require a diagnostic method claim to explicitly recite a transformative step, such as detecting the marker, or treating a patient. This creates a Catch-22 for the diagnostic inventor. The discovery of the correlation is the core of the invention, providing substantial therapeutic benefits to patients, but under Prometheus and Bilksi a claim to the correlation must also include an additional step which will often render the claim highly susceptible to circumvention by two parties separately performing the steps.

To avoid this problem, Myriad proposes the following as an appropriate test for infringement of method claims by multiple parties:

When a first party performing one or more steps of a method claim actively causes another party to perform the other steps of the same method claim, or when two parties act in a concerted manner to perform all steps of a method claim, then the first party and the parties acting in concert should each be deemed a direct infringer.

District Court Rules That Genencor Products Infringe Novozymes Patent

On July 7, a federal district court in the Western District of Wisconsin ruled on a motion for summary judgment that a number of Genencor's thermostable alpha-amylase products (sold under trade names such as Spezyme) infringe Novozyme’s US patent number 7,713,723. I have discussed earlier decisions in this case on this blog, including decisions by the District Court denying a motion to invalidate the claims for failure to satisfy the written description requirement (available here) and denying a motion for preliminary injunction (available here).

Claim 1 is representative of the claims found to be infringed:

1. An isolated variant of a parent alpha-amylase, wherein:
(a) the variant has at least 90% sequence identity to SEQ ID NO: 6,
(b) the variant comprises a substitution of serine at position 239 relative to the parent alpha-amylase, using the amino acid sequence of SEQ ID NO: 8 for determining position numbering, and
(c) the variant has increased thermostability relative to the parent
alpha-amylase, wherein thermostability is determined at pH 4.5, 90° C. and
5 ppm calcium and has alpha-amylase activity.

Prior to deciding the issue of infringement, the court had to construe several terms appearing in the claims.

For example, the court had to define what "thermostability" means in the context of the claims. The defendant Genencor argued that the term is so indefinite that the claims should be invalidated, but the judge disagreed and held that the term was not so ambiguous as to render the claims invalid. The court spent a lot of time discussing the ambiguity of the term, noting that it could be the case that a protein variant would have more activity than wild type at some time points after exposing the proteins to elevated temperature, but less activity at other time points, and it was not entirely clear from the patent whether this would constitute increased thermostability. However, the court held that even under a relatively narrow interpretation of the term, pursuant to which the protein variant would have to be more active at all time points under elevated temperature, the Genencor products still infringed because the retained higher activity than wild type at all times after exposing the proteins to high temperature.

Another claim term, which the court spent a lot of time was "isolated." Novozymes argued that "isolated" was not a limitation on the claim scope because it is part of the claims’ preamble. The district court spent some time considering this argument, but ultimately sided with Genencor and held that "isolated" does limit the scope of the claim. In part, it reached this decision because "isolated" did not appear in the claim originally but was introduced during prosecution of the patent application, which the court found implied that the term "isolated" was significant.

The parties disputed the meaning of the term “isolated,” with Novozymes arguing for a broad interpretation that would cover protein existing at a higher concentration in a cell or cell extract than it would naturally, while Genencor argued for a narrower interpretation in which the protein must to some extent be separated from other cellular components. The court adopted the narrower interpretation, but nonetheless found that most Genencor products infringed because they included isolated protein. However, the court did find that some Genencor products are not infringing in which the thermostable alpha-amylase is not separated from other cellular components, which the court referred to as "whole broth" products, because the protein is not isolated.

The proper interpretation of "isolated" in claims such as this has important implications for biotechnology patenting outside the confines of this particular case. For example, the patent office will not issue patents claiming naturally occurring gene sequences unless the claims specifically recite that the DNA molecule is isolated, purified, and/or recombinant, in order to exclude genes as they occur naturally (for example in the human genome). The assumption is that inclusion of the term "isolated" in the claim limits the scope of the claim. I don't think it is even accurate to consider the use of the term "isolated" in claims of this format as preamble, but in any event it should generally be treated as limiting the scope of the claim.

Furthermore, the scope of the term isolated is important in the context of gene patent. As I have discussed elsewhere, the question of whether genetic diagnostic testing or whole genome sequencing infringes gene patents could in many cases dependent on how broadly a court interprets the term isolated in these claims (I have always assumed that "isolated" is a meaningful limitation on claim scope in this context).

In this case, the prosecution history was apparently silent as to why Novozymes amended the claim to include the "isolated" language. It would not seem to be necessarily required in this case if the claim only covers non-naturally occurring variants, because then there would be no danger of the claim reading on a naturally occurring biomolecule. But perhaps Novozymes intended for the claim to cover naturally occurring thermostable variants, in which case limiting the claim to isolated variants would be necessary in order for the claim to be valid.

In any event, the fact that "isolated" was introduced by amendment was significant, because it led the court to rule that under Festo the term could not be expanded beyond its literal scope under the doctrine of equivalents.

Thanks to Docket Navigator for bringing this decision to my attention.

PTO Agrees to Reexamine Broad Codon-Optimization Patents

Many important applications of biotechnology involve the expression of recombinant genes in heterologous systems. Since the genetic code is degenerate (ie each amino acid can be coded by on average three different codons), the DNA sequence can be modified by synonymous nucleotide substitutions without altering the amino acid sequence of the encoded protein. A biotechnologist might find it useful to make a synonymous substitution for any of a variety of reasons, e.g., to introduce or remove restriction sites, or to remove repeats.

Today genes are also often altered for the specific purpose of optimizing expression, i.e., the entire coding region of the gene is recoded to fit one of a variety of codon optimization schemes. Examples of popular codon optimization schemes used in designing a gene for recombinant expression include:

A) Replace a degenerate codon with the most common codon present in the host chromosome; the rationale being that the most common codon correspond to the most common tRNA results in most protein yield.

B) Reengineer the gene so that it uses the same frequency of codons that are present in the host chromosome; the rationale being that the recombinant gene should have the same codon bias as the host chromosome to fit the translational machinery.

C) Re-code the pattern of rare and common codons found in the wild type by replacing it with the corresponding rare/common codons in the heterologous host; the rationale being that protein folding and expression requires rare (slow) and common (fast) codons distributed according to the folding domains in the protein.

D) Empirically identify codons and other variables that correlate with high protein expression in a systematically varied recombinant gene.

Codon optimization has become standard practice in the recombinant expression of heterologous proteins such as biologic drugs. Gene synthesis companies such as DNA2.0 and Blue Heron assist their customers by providing codon optimization as a part of their services.

Two U.S. patents (both assigned to the Massachusetts General Hospital) include claims directed towards codon optimization, both the method and the resulting codon-optimized gene (US Patent Numbers 5,786,464 and 6,114,148). These patents are very broad, purporting to cover any "synthetic gene encoding a protein normally expressed in an eukaryotic cell wherein at least one non-preferred or less preferred codon . . . has been replaced by a preferred codon encoding the same amino acid, [and wherein the replacement results in at least 10% increase in the level of protein expressed] in an in vitro mammalian cell culture system under identical conditions”

These patents appear to not only cover any successfully codon-optimized recombinant gene, but also many genes that have been reengineered for purposes other than codon optimization. For example, a silent mutation introduced for the purpose of removing a restriction site could easily constitute infringement if it results in the introduction of any of the 17 codons identified in the patent as “preferred,” if it turns out that the substitution results in a modest 10% increase in expression in any in vitro mammalian cell culture system. Rarely would an experimenter test for such an increase in expression at that level of accuracy, and a practical matter it would be virtually impossible to rule out the possibility of a 10% increase in expression in some mammalian cell culture system.

In view of their scope, and the pervasive use of codon replacement in the expression of high-value heterologous proteins (such as biologic drugs), these patents could potentially have sweeping implications for biotechnology. However, although the patents issued in 1998 and 2000, they have never been asserted in court and until recently appear to have received little attention.

However, the patents have recently become a thorny issue for those involved in the business of expressing heterologous proteins, particularly gene synthesis companies providing codon optimized genes for their customers. Last year Geneart (a German gene synthesis company owned by Life Technologies) began sending letters to companies engaged in the expression of heterologous proteins announcing that "we are very pleased to inform you that Geneart has acquired a license under [the Massachusetts General Hospital (MGH) Patents].” The letter goes on to state that under the license “Geneart is in the excellent position to offer a broad range of sublicensing opportunities." The licensing “opportunities” include a royalty-free sublicense to use synthetic genes purchased from Geneart in internal R&D, and a royalty-bearing commercial sublicense for synthetic genes used for purposes other than internal research and development. According to the letter, Geneart has executed a non-prosecution agreement with respect to synthetic genes delivered by Geneart to customers prior to May 30, 2010, so these customers are apparently free to use the genes in any manner without liability for infringement.

The letter goes on to imply that customers who choose to purchase synthetic genes from competing gene synthesis companies could be sued for infringing the MGH Patents, stating that "to Geneart’s knowledge, no other Gene Synthesis Service Provider has obtained a respective license under the MGH Patents."

This poses a problem for any biotechnologist wishing to use a synthetic or partially modified gene. Even slight variations to the wild-type sequence, such as restriction site removal or addition, could infringe.
It certainly poses a problem to other synthetic gene companies, whose customers might switch to Geneart in order to avoid a perceived threat of patent infringement liability for using synthetic genes not purchased from Geneart.


DNA2.0, a leading provider of synthetic genes headquartered in Menlo Park California, has responded to this perceived threat by successfully petitioning for reexamination of both patents, arguing that the broad claims are anticipated and/or rendered obvious by prior art not previously considered by the PTO. The orders granting the ex parte reexamination of the ‘148 and ‘464 patents were issued on December 14, 2010 and January 26, 2011, respectively.

The orders granting reexamination state that a number of references cited by DNA2.0 in the request for reexamination raise substantial new questions of patentability with respect to most of the claims in the patents, particularly the broadest claims. For example, an article published in the Journal of Virology in 1992 by Schwartz et al. describes the characterization of inhibitory RNA elements in the gag region of human immunodeficiency virus type I (HIV-1). This involved replacing many of the codons in the wild type gene with synonymous codons defined as "preferred" in the MGH Patents, resulting in at least a five-fold increase in expression. As another example, the PTO found an article disclosing a computer program for optimizing DNA sequences for protein expression, in combination with another article disclosing the most frequent human codon usage together with preferred codon choice patterns, also raise substantial new questions of patentability for many of the claims.

It is interesting to note that the corresponding codon optimization patent issued to MGH in Europe (EP 0 781 329 B2) is much narrower in scope, claiming a method for preparing a synthetic gene wherein at least 50% of the non-preferred codons and less preferred codons are replaced by preferred codons and resulting in a 10% increase in expression. In contrast, the US patents purport to claim any method that involves replacing even one codon with a preferred codon, and any gene made by such a process.

It is my understanding that, as a practical matter, the European patent only poses a substantial impediment to the “A” form of codon optimization described above, i.e., replacement of all degenerate codons with the most common codon present in the host chromosome. Most other codon optimizations do not require the substitution of 50% of non- or less preferred codons. In contrast, the U.S. patents would appear to cover the majority of recombinant protein expression that has been done in recent years. The patents should expire 2015, but the pending reexamination could be important if it results in cancellation or narrowing of the claims in the US patents, thereby providing assurance that companies will not be sued for expressing recombinant proteins prior to patent expiration.

Organic Seed Growers and Trade Association Et al. v. Monsanto: The Public Patent Foundation Takes on Agricultural Biotechnology

The Public Patent Foundation (PubPat), housed at the Cardozo School of Law in New York, is probably best known to readers of this blog for its role in the challenge to Myriad gene patents in AMP v. PTO (PubPat is co-counsel, along with the ACLU). PubPat has brought a number of other "public interest" actions against other patents, including reexamination of some of the key University of Wisconsin embryonic stem cell patents.

On March 29 PubPat took on agricultural biotechnology, filing a declaratory judgment action in the Southern District of New York against Monsanto, on behalf of a large contingent of plaintiffs, including agricultural member organizations, farms and farmers, and seed companies. The plaintiffs are primarily, but not entirely, organic, and all have purportedly have disavowed the use of genetically modified seed.

The primary contention of the plaintiffs is that they "are increasingly being threatened by transgenic seed contamination despite using their best efforts to avoid it." The allege that Monsanto "has aggressively asserted [its patents] against literally hundreds of farmers, including those farmers who became contaminated by Monsanto's transgenic seed through no fault of their own." They have asked the court to declare a long list of Monsanto patents invalid, unenforceable, and not infringed, and that Monsanto would not be entitled to any remedies against the plaintiffs even if found to infringe a valid and enforceable patent.

Interestingly, I was talking with someone who works for Monsanto recently and he mentioned that to his knowledge the complaint had never been served upon Monsanto. I checked PACER on June 1, and the docket indicates that PubPat has yet to file notice that the complaint was served on Monsanto, even though the complaint was filed more than two months ago (March 29). For comparison, in the Myriad case notice of service on the plaintiffs was filed within one month after the complaint was filed.

Do the Plaintiffs Have Standing?

Perhaps the biggest stumbling block for PubPat will be establishing that any of the plaintiffs have standing to bring suit (a big issue in the Myriad lawsuit). The standing of the plaintiffs seems even more problematic in this case, since the plaintiffs all avow that they are doing everything they can to avoid infringing Monsanto's patent, and there appears to be no evidence that Monsanto has ever filed suit against an involuntary/inadvertent infringer. The complaint filed by PubPat makes this allegation, but does not document a single example of a case where a party was sued for infringement that was involuntary. The closest it comes is a reference to a 2008 segment of the CBS Evening News, which the complaint alleges described an incident in which farmers (Mr. and Mrs. Runyon), "who never intended to use transgenic seeds," were threatened with a patent infringement suit (but apparently never sued).

The complaint also alleges that Monsanto has litigated patent infringement claims against other farmers who did not want to be contaminated by transgenic seeds, including notably Percy Schmeiser. Schmeiser has become something of a folk hero, a Canadian farmer who was sued by Monsanto for patent infringement in a case that was eventually decided by the Canadian Supreme Court. Critics of Monsanto in the popular media routinely point to Schmeiser as an example of a honest Canadian farmer sued by corporate villain Monsanto for patent infringement that was completely involuntary and inadvertent, while failing to note that the Canadian courts found unambiguously that Schmeiser’s infringement was in fact voluntary, and that he went out of his way to collect and plant transgenic seed incorporating the patented Monsanto trait. Here are some excerpts from the Canadian Supreme Court decision [Monsanto Canada Inc. v. Schmeiser, 2004 SCC 34, [2004] 1 S.C.R. 902]:

The remaining question was how such a pure concentration of Roundup Ready Canola came to grow on the appellants’ land in 1998. The trial judge rejected the suggestion that it was the product of seed blown or inadvertently carried onto the appellants’ land . . .

Invoking the concepts of implied licence and waiver, the appellants argue that this Court should grant an exemption from infringement to “innocent bystanders”. The simple answer to this contention is that on the facts found by the trial judge, Mr. Schmeiser was not an innocent bystander; rather, he actively cultivated Roundup Ready Canola.

Given the issues of standing, one has to wonder why PubPat has chosen the declaratory judgment route to challenge Monsanto's patents. After all, PubPat asserts that Monsanto has aggressively asserted its patents against "literally hundreds of farmers," including farmers whose only offense was to have their crops contaminated by Monsanto's seed. In the Myriad case, the ACLU and PubPat were forced to assemble a group of plaintiffs and file a declaratory judgment action, because for years Myriad has disappointed its critics by never suing anyone for infringing its gene patents. But that is not the case with Monsanto, which I believe has filed patent infringement suits against farms numbering in the hundreds.

Why isn't PubPat defending one of these farmers that has already been sued? This would give PubPat the opportunity to challenge the Monsanto's patents, without any issue of standing. Perhaps they find it is preferable to conduct "public interest litigation" on behalf of recruited plaintiffs rather than actual defendants potentially liable for damages.

In fact, at least one farmer is currently before the Federal Circuit arguing one of the legal theories raised in the PubPat complaint, i.e., that "Monsanto's patent rights in transgenic seed exhaust upon the authorized distribution by Monsanto to its customers." In 2009, a district court in the Southern District of Indiana rejected this very argument in Monsanto v. Bowman, citing earlier Federal Circuit decisions in Monsanto v. Scruggs and Monsanto v. McFarling. Mr. Bowman argued unsuccessfully that he should not be held liable for infringement based on the use of "commodity" soybean seed he had purchased and that inadvertently included seed containing the patented Roundup Ready trait. The district court decision indicates that Mr. Bowman argued the case as a pro se defendant, but the appeal briefs being filed with the Federal Circuit this year indicate that he is currently being represented by Frommer Lawrence & Haug LLP.

Below, I briefly address some of the arguments raised in the PubPat complaint, including moral utility, exhaustion and inadvertent infringement.

Moral Utility

Historically, US law had a doctrine of moral utility, under which a patent could be found invalid if the claimed invention lacks sufficient social or moral use. The doctrine traces its origin to a statement by Justice Story in the 1817 Lowell v. Lewis decision to the effect that inventions that are "injurious to the well-being, good policy, or sound morals of society" are unpatentable. Examples provided by Justice Story included "a new invention to poison people, or to promote debauchery, or to facilitate private assassination."

Although technically still on the books, the doctrine of moral utility has generally been considered moribund in the US since the 1999 Federal Circuit decision in Juicy Whip v. Orange Bang, which essentially held that patent law is not the appropriate legal vehicle for addressing questions of morality. I think this is the proper approach. For example, I would rather not have the patent office deciding whether or not a gambling invention is patentable based on the morality or social utility of gambling. A patent does not confer any positive right to practice in invention, only the right to exclude others from practicing it, so the patent would in no way shields the patent owner from anti-gambling laws, which is the more appropriate way to address morality or social concerns associated with gambling.

European patent law, on the other hand, explicitly provides that inventions that are "immoral and against the public order" are patent ineligible. The European High Court is currently considering a case challenging the patent eligibility of embryonic stem cells based on allegations that the use of viable human embryos in the industrial process of producing cultured embryonic stem cells is immoral. The Court's advocate general has in fact put forth such a position, as discussed recently on the Patent Docs blog.

I cannot imagine PubPat prevailing on this theory. The doctrine of moral utility has generally been considered pretty much irrelevant after Juicy Whip, but even if the doctrine still has some teeth, there is a wealth of data supporting the benefits of transgenic crops, which explains why they have been so widely adopted in the US, and increasingly throughout the world. The PubPat complaint goes to great lengths reciting a host of alleged evils of agricultural biotechnology, and asserts that transgenic crops have failed to provide any benefits, citing authorities such as England's Prince Charles, but I think this flies in the face of a wealth of evidence going the other direction.

Patent Exhaustion

As mentioned above, PubPat alleges that Monsanto's patent rights in transgenic seeds are exhausted by their first authorized sale, presumably relying on the Supreme Court's 2009 Quanta decision. This was one of the main concerns that I raised regarding Quanta, i.e., the potential for the decision to preclude the ability of biotechnology companies to adequately enforce patents covering products capable of self-replication.

Prior to the Supreme Court deciding Quanta, the Federal Circuit held in Monsanto v. Scruggs (2006) that patent exhaustion did not shield from infringement liability a farmer who saved and replanted patented seeds without Monsanto's authorization because (1) the initial sale from Monsanto was not an “unrestricted sale” and (2) the second generation of seeds were never “sold.” Scruggs filed a petition for certiorari with the Supreme Court, which was denied. The case was remanded to the district court, where Scruggs moved for reconsideration in light of the Supreme Court's decision in Quanta. The district court denied the motion, but certified the issue for interlocutory appeal to the Federal Circuit, to resolve the question of whether the Federal Circuit's decision regarding patent exhaustion in Monsanto v. Scruggs was still good law in view of Quanta. But in 2009 the Federal Circuit exercised its discretion and declined to decide the interlocutory appeal, advising Scruggs to appeal the issue after the district court issues a final decision or injunction.

Thus, the question of whether the Federal Circuit decision in Monsanto v. Scruggs regarding patent exhaustion of transgenic seeds survives Quanta has yet to be resolved. The Federal Circuit could address the issue in Monsanto v. Bowman, or perhaps in the PubPat lawsuit if it goes forward.

Inadvertent Infringement

At a doctrinal level, for me perhaps the most interesting argument raised by PubPat is that the plaintiffs are not liable for infringement because any infringement would be involuntary and inadvertent, the result of contamination by transgenic seed used by other farmers. To my knowledge, this issue has never been directly addressed by the courts, and as a practical matter I doubt that Monsanto has sued farmers for legitimate good-faith but inadvertent infringement. As noted above, the PubPat complaint does not appear to identify any specific occurrence of this, and the widely propagated story that Schmeiser was a good-faith inadvertent infringer is contrary to the findings of the Canadian courts.

But how would a court deal with involuntary and inadvertent infringement if the issue ever did arise? It is well-established that, as a general matter, patent infringement is a matter of strict liability, i.e., intent is not an element of patent infringement. However, I am convinced that a court faced with a true case of inadvertent infringement would find some doctrinal loophole to shield the alleged infringer from liability. However, there is to my knowledge no specific doctrinal defense addressing the issue.

For example, in Monsanto v. Schmeiser, the Canadian Supreme Court indicated that if Schmeiser’s infringement had been inadvertent he would not have been liable for infringement, because under such circumstances his mere possession of patented seeds would not lead to a presumption that he had "used" the seeds in an infringing manner.

In the US, the issue of inadvertent infringement was addressed in the fascinating case of SmithKline Beecham v. Apotex, 403 F.3d 1331 (2005), which involved allegations that a generic drug manufacturer would not be able to produce a non-infringing generic drug without inadvertently producing an infringing polymorph of the drug, thus involuntarily infringing the patent. At the district court level, the decision was written by Judge Posner, a famous judge on the Seventh Circuit Court of Appeals, sitting by designation for this case as a district court judge. Judge Posner noted the policy concern attendant to holding an inadvertent infringer liable for patent infringement, and spent a great deal of time grappling with the question of how existing patent doctrine could be interpreted in a manner to arrive at the outcome, i.e. no liability for inadvertent infringement.

Here is an excerpt from Judge Posner's opinion in SmithKline Beecham v. Apotex, 247 F.Supp.2d 1011 (2003):

The reason for excusing the alleged infringement in this case is not that Apotex stole only a little hemihydrate from SmithKline. It stole nothing from SmithKline. It doesn't want hemihydrate, and it derives no value from the hemihydrate that it unavoidably creates and “sells.” If it made hemihydrate deliberately, or if it took advantage of 100 percent conversion to obtain a product that had hemihydrate's superior handling characteristics, that would be theft and it would be nonsense to point out that paroxetine is only 10 percent of the pill by weight. But if the person sitting next to me at dinner spills his soup on my sleeve, I am not a thief even though I cannot remove the stain.

On appeal, the Federal Circuit rendered the question of inadvertent infringement moot by invalidating the SmithKline patent for inherent anticipation. However, in a concurring opinion Judge Gajarsa addressed the issue of inadvertent infringement, in a manner that would probably resonate with PubPat and other opponents of patents on transgenic seeds. Judge Gajarsa essentially advocated a position that the issue of inadvertent infringement could be dealt with in situations such as this by recognizing that any product capable of being "spread and reproduced by natural processes" is patent ineligible under 35 USC 101. I think this assertion is incorrect, and would be inconsistent with the Supreme Court's decision in Diamond v. Chakrabarty, which explicitly found genetically modified living organisms to be patent eligible.

Nevertheless, here are some excerpts from Judge Gajarsa’s concurrence:

The asserted breadth of Claim 1 makes sense only under the erroneous belief that patents may protect products spread and reproduced by natural processes, directly contradicting our well established understanding of the limits imposed by section 101. Given current scientific trends, such a belief could easily lead to misdirected research investments, to inappropriately issued patents, and to a widespread in terrorem effect crippling entire industries whose artisans learn that even their best efforts to respect patent rights may not save them from liability as inadvertent, inevitable infringers. As the district court recognized, the notice function of patents is meaningless in such an environment, SK II, 247 F.Supp.2d at 1028. The lack of suitable notice could easily chill innovation, inquiry, experimentation, and commercial development. The patent law does not sanction the concept of inevitable infringement.
. . .

Consider, for example, what might happen if the wind blew fertile, genetically modified blue corn protected by a patent, from the field of a single farmer into neighboring cornfields. The harvest from those fields would soon contain at least some patented blue corn mixed in with the traditional public domain yellow corn-thereby infringing the patent. The wind would continue to blow, and the patented crops would spread throughout the continent, thereby turning most (if not all) North American corn farmers into unintentional, yet inevitable, infringers.FN7 The implication-that the patent owner would be entitled to collect royalties from every farmer whose cornfields contained even a few patented blue stalks-cannot possibly be correct. The underlying question that engaged the district court, and that led it to develop numerous alternative holdings, is why this implication is incorrect.

FN7. Although intent is not a factor in determining infringement, public notice is required as a predicate to the validity of a patent. Jurgens v. CBK, Ltd., 80 F.3d 1566, 1570 n. 2 (Fed.Cir.1996). The hypothetical causes unavoidable infringement even in situations where the public would, in good faith, want to avoid infringing.

At oral argument, when faced with this hypothetical, SKB expressed its belief that such a blue-corn patent would be “very strong.” Such a belief is misplaced. The implicit concept of “inevitable infringement” stems from the inevitable failure of the patent to provide public notice-which, in turn, stems from the inherently unpatentable nature of the claimed subject matter.

This section 101 problem therefore brings us full circle, back to the impossibility of public notice. Under normal circumstances, inventors other than the patentee will understand how to avoid infringing a patent by avoiding the claimed product. Because products, such as our hypothetical blue corn or SKB's paroxetine hemihydrate, that can be “made” through a natural process of spontaneous conversion imply inevitable infringement, no combination of claim language and written description could possibly teach even one skilled in the art how to avoid infringement. It is unsurprising that a requirement considered so trivial for most patentable products that we are content to let it remain implicit, namely a lesson in infringement avoidance, is effectively impossible for subject matter unpatentable under section 101. In short, patent claims drawn broadly enough to encompass products that spread, appear, and “reproduce” through natural processes cover subject matter unpatentable under section 101-and are therefore invalid.

It will be interesting to see how the PubPat challenge to Monsanto, and the patenting of Arab cultural biotechnology in general, plays out.