Monsanto v. Bowman: A Unanimous Supreme Court Sides with Monsanto

 

 

Today a unanimous Supreme Court affirmed the Federal Circuit's decision in Monsanto v. Bowman, and held that "patent exhaustion does not permit a farmer to reproduce patented seeds for planting and harvesting without the patent holder's permission." A background on the case can be found in earlier posts to this blog.

The Justices seemed to see through Bowman's arguments and understand what was at stake in this case. Writing for the Court, Justice Kagan noted that it is "well-settled" that the authorized purchaser of a patented product does not acquire any right to make copies of the product, and observed that were the Court to find in favor of Bowman patents would provide "scant benefit" to companies like Monsanto, and little incentive for investment in innovation.

The Court’s decision is explicitly premised on the fact that Monsanto requires farmers to enter into a license agreement which allows them to plant the patented seeds and harvest the resulting crop for use as food or animal feed, but not to replant the seeds or sell them for replanting. In footnote 3, the Court points out that "we do not here confront a case in which Monsanto (or an affiliated seed company) sold Roundup Ready to a farmer without an express license agreement. For reasons we explain below, we think that case unlikely to arise. And in the event it did, the farmer might reasonably claim that the sale came within an implied license to plant and harvest one soybean crop."

Kagan pointed out that a decision in favor of Bowman would be entirely inconsistent with the Court’s 2001 decision in J.E.M Ag Supply v. Pioneer Hi-Bred International, in which the Court held that utility patent protection is available for seeds and plants. In J.E.M., the Court noted that that the requirements for getting a patent are more stringent than those for obtaining a Plant Variety Protection (PVP) certificate, and that the protections afforded by a patent are correspondingly greater.  If the Court had sided with Bowman, it would mean that the owner of a patent would not only not be able to prevent a buyer from saving and replanting harvested seeds, but would be unable to prevent the buyer from selling the seeds, something "even a PVP certificate owner (who, recall, is supposed to have fewer rights) can usually accomplish."

Some supporters of Bowman have argued that farmers have a long-standing tradition of buying commodity grain for planting, but the Court gave short shrift to this contention. In a footnote, the Court observed that grain elevators "purchase grain from farmers and sell it for consumption; under federal and state law, they generally cannot package or market their grain for use as agricultural seed." The Court also noted that the commodity soybeans Bowman purchased were not intended for planting, but for consumption, and that Bowman himself had "conceded in deposition testimony that he knew of no other farmer who employed beans bought from a grain elevator to grow a new crop."

The Court also rejected Bowman's argument that seeds should be treated differently for purposes of exhaustion because they "self-replicate." The Court observed that Bowman was far from a passive observer, and that he had actively "made" (in the infringing sense) the copied seeds by purchasing the seeds knowing that many would be Roundup Ready, applying glyphosate in a way that culled any plants without the patented trait, saving the seeds to plant a later time, planting the beans in his field at the time he thought best, attending and treating them, including by exploiting their patented glyphosate-resistance, and harvesting the seeds, which he either marketed or saved to begin the next cycle. "In all this, the bean surely figure. But it was Bowman, and not the bean, who controlled the reproduction (unto the eighth generation) of Monsanto's patented invention.”

In the final paragraph, Kagan emphasizes that the decision is limited to the facts on hand, and the holding does not extend to hypothetical situations in which an article self-replicates "outside the purchaser’s control," or in which replication might be a necessary or incidental step in using the item for another purpose. She cites to 17 USC  117, a section of the copyright statute that addresses concerns relating to software and copyright that are very analogous to the concerns about inadvertent infringement expressed by supporters of Bowman. This analogy between software copyright and DNA patent was the theme of the Amicus brief I filed in support of Monsanto, in which I particularly pointed out that concerns about unavoidable infringement could be addressed by Congress if necessary, and citing 17 USC 117 as a specific example of that approach.

 

 

Jury finds Cellectis meganuclease claims invalid, but infringed by Precision Biosciences under Doctrine of Equivalents

As reported in an earlier post, on March 1, 2011, Cellectis sued Precision Biosciences in the District Court of Delaware [CIV-No.-11-173] for allegedly infringing US patent number 7,897,372, directed to "I-CreI Meganuclease Variants with Modified Specificity.”   The companies are both attempting to commercialize engineered meganucleases for use in genetic engineering. The litigation between Cellectis and Precision Biosciences has come to include 20 distinct lawsuits filed in Delaware and Eastern North Carolina (Precision licenses its patents from Duke University), and to involve multiple patents owned by both companies, a couple of which were discussed in this earlier post.

On May 3, the jury issued a verdict with respect to asserted claims 37, 40 and 50 from the ‘372 patent, finding all of the claims invalid for obviousness and inadequate written description. The jury also found that none of the claims are literally infringed by Precision’s meganucleases, and that Precision is not liable for inducing or contributory infringement of the claims. The jury did find that Precision meganucleases infringe claims 37 and 50 under the doctrine of equivalents.

Here are the claims:

37. A recombinant monomer of an I-CreI meganuclease variant comprising at least one mutation in the amino acid sequence of SEQ ID NO: 70, wherein said at least one mutation comprises a substitution at one or more of the amino acids residues at positions 44, 68 and 70 and said monomer further comprises at least one additional mutation of an amino acid residue directly contacting a DNA target sequence wherein said amino acid residue directly contacting a DNA target sequence is selected from the group consisting of positions 26, 28, 30, 32, 33 and 38, wherein said monomer when in a dimeric form is able to cleave DNA.

40. The monomer of an I-CreI meganuclease variant of claim 37, wherein said monomer when in a dimeric form has a modified DNA cleavage specificity relative to the I-CreI meganuclease of SEQ ID NO: 70 in at least one nucleotide in the .+-.3 to 5 triplets.

50. A single-chain chimeric meganuclease comprising the fusion of two different monomers according to claim 37.

Earlier, on April 9, 2013, the District Court issued an order denying multiple motions on summary judgment, including one relating to literal infringement of Claim 40. In one interesting aspect of the decision, the District Court judge held that the term "variant of the wild-type monomer from 1-Crel"  (which appears in the preamble of claim 37, from which claim 40 depends) is an indefinite “limitation,” essentially because the court found that one of skill in the art would not be able to discern the breath of the term "variant." The court pointed out that the claim does not limit the number of mutations that could be present in the amino acid sequence of the claimed “variant,” and it is unclear at what point the number of mutations would cause the sequence to diverge so substantially from wild- type as to no longer constitute a "variant" of the wild type protein, but rather a distinct protein.  The use of this sort of open-ended "variant" language is not uncommon in patent claims of this type.

It will be interesting to follow this case if it is appealed to the Federal Circuit, particularly with respect to the issue of infringement under the doctrine of equivalents. The most important Federal Circuit precedent in this area of which I am aware comes from Genentech v. Wellcome, a 1994 decision in which the Federal Circuit reversed a jury's verdict which found a claim reciting tissue plasminogen activator (t-PA) infringed under the doctrine of equivalents by a substantially re-engineered, synthetic version of t-PA (marketed as a pharmaceutical). The allegedly infringing product differed substantially in structure from the claimed protein, with 15% fewer amino acids and 10-fold greater half-life. In a concurrence, Judge Lourie pointed out that while the traditional "function-way-result" test for infringement under the doctrine of equivalents might work well for some inventions, such as in the mechanical arts, it seems a poor fit for inventions like recombinant proteins.

 

 

 

Federal Circuit Affirms Decision Finding Biogen’s Patent Not Infringed by Arzerra

 Today in Biogen Idec v. GlaxoSmithKline a divided panel of the Federal Circuit affirmed a district court’s decision that GSK's monoclonal antibody product Arzerra does not infringe Biogen's patent number 7,682,612. I discussed the district court's decision in an October 2011 blog post. Arzerra is a fully human antibody that specifically binds to a small loop on the CD20 antigen. Biogen markets a competing product, Rituxan, which is a chimeric antibody that targets a different, larger loop on the CD20 antigen.

Representative claim 1 of Biogen's patent recites:

1.       A method of treating chronic lymphocytic leukemia in a human patient, comprising administering an anti-CD20 antibody to the patient in an amount effective to treat the chronic lymphocytic leukemia, wherein the method does not include treatment with a radiolabeled anti-CD20 antibody.

The dispute centered on the interpretation of the claim term "anti-CD20 antibody."  The District Court construed the term as limited to antibodies that bind to the same epitope of the CD20 antigen as Rituxan, i.e., the large loop. Under this interpretation, Biogen stipulated to noninfringement, since it is undisputed that Arzerra binds to a different epitope, i.e., the small loop.

On appeal, the Federal Circuit majority affirmed the district court's claim interpretation, based on the doctrine of "prosecution history disclaimer." The majority noted that while claim terms are generally given their ordinary and customary meaning, a "clear and unmistakable" disavowal of subject matter during prosecution overcomes the "heavy presumption" that claim terms carry their full ordinary and customary meaning. In this case, although the ordinary meaning of anti-CD20 antibody would presumably encompass any antibody that specifically recognizes any epitope on the CD20 antigen, the majority found that statements made during prosecution limited the claim to antibodies that bind at the same epitope as Rituxan. The majority pointed out that when representations are made by the time the during prosecution, "competitors are entitled to rely on those representations when determining a course of lawful conduct, such as launching a new product or designing-around a patented invention."

To summarize, during prosecution the examiner rejected Biogen’s claims for lack of enablement, finding that while the specification was enabling for Rituxan, but that it was "silent concerning what sort of specificity and affinity would be necessary" for other anti-CD20 antibodies. In response, Biogen pointed to its disclosure of Rituxan and argued that:

even though antibodies directed to the same antigen might have different affinities and functional characteristics, one of skill in the art could readily identify an antibody that binds to CD20 with similar affinity and specificity as does Rituxan using techniques that are well known in the art . . . With that knowledge in hand, the skilled artisan could readily produce anti-CD20 antibodies using similar techniques, and screen such antibodies for those having an affinity and functional activity similar to Rituxan.

After considering this argument, the examiner withdrew the enablement rejection. Even though the claims were not amended, the majority found that by arguing that the specification was enabling for antibodies with similar affinity and specificity as Rituxan, instead of challenging the examiner's understanding of the crucial terms, Biogen had effectively limited its claims to antibodies similar to Rituxan, i.e., antibodies binding the same epitope.

A dissenting opinion was filed by Judge Plager, who found that Biogen's arguments during prosecution were sufficiently ambiguous that they did not meet the "clear and unmistakable" disclaimer standard necessary to overcome the presumption that claim terms should be attributed their plain meaning. He voiced the opinion that Biogen's argument represented nothing more than "the give-and-take that is often part of the process of negotiation between it and examiner and an applicant [which] may result in less-than-clear understandings,” and that the majority had made "too much of such ambiguous statements."

A Critique of a Recent Article Which Found That Sequence Patents Cover the Entire Human Genome

 

I recently fielded a phone call from a reporter with a leading international scientific journal, asking for my opinion of an article entitled "Pervasive Sequence Patents Cover the Entire Human Genome,”recently published in a publication called Genome Medicine. I have published several articles debunking the myth that 20% of human genes are patented, and the reporter thought that the article in Genome Medicine, authored by a researcher affiliated with Yale Law School’s The Information Society Project, contradicted the results of my study. I took a look at the "Pervasive Sequence Patents" article and found it to be a fundamentally flawed empirical study that will sadly be used to further support the widespread misperception that access to a large percentage of the human genome is precluded by a thicket of gene patents.

The "Pervasive Sequence Patents" article does cite to my 2012 Nature Biotechnology article Debunking the Myth That Whole GenomeSequencing Infringes Thousands of Gene Patents, but the authors apparently missed the main point I was trying to make. The myth that 20% of human genes are patented was born out of a 2005 article published in Science by Jensen and Murray that found that the sequence of 20% of human genes (or in some cases the protein encoded by human gene) is mentioned in a US patent claim. The problem arose when people assumed that the mention of a gene’s DNA sequence in a patent claim is equivalent to the patenting of the gene, which led to an assumption that any use of or research on any of these genes would result in patent infringement. In my article, I explained that in patent law "the name of the game is the claim "(to quote Judge Rich), and that when one actually reads the patent claims in the patents identified by Jensen and Murray it is clear that few if any of the patents would be infringed by many forms of research or genetic testing, including diagnostic testing and whole genome sequencing.

Unfortunately, the authors of "Pervasive Sequence Patents" have apparently fallen into the same trap, assuming that mention of a gene’s DNA sequence in a patent claim results in the patenting of the gene in a manner that totally blocks access to the gene. Even more problematically, the authors seem to assume that every patent with a claim mentioning a gene sequence also claims every 15mer present in the sequence, i.e., every contiguous 15 nucleotide sequence appearing in the gene. Presumably they made this assumption because the Myriad gene patent litigation includes a patent claim directed to 15mers of the BRCA1 encoding sequence, including Claim 5 from US patent number 5,747,282:

An isolated DNA having at least 15 nucleotides of the DNA of claim 1.

There are two fundamental problems with this empirical approach. One is that it does not necessarily follow that the mention of a gene's DNA sequence in a claim equates with the patenting of the gene - that was the main point of my Nature Biotechnology article. The other is to assume that all of these patents include claims analogous to Claim 5 of the ‘282 patent.

In my experience, claims of this type are extremely rare. I looked at hundred patents identified as gene patents in the Jensen Murray study and found that most only claim the full-length gene sequence, and if fragments were claimed the fragments are much larger than 15 nucleotides. In fact, I looked through hundreds of gene patents trying to find another 15mer claim analogous to those in the Myriad patents and could not find one. The patent claims at issue in the Myriad case will be expiring within the next few years I believe, and I doubt that this sort of broad 15mer claim has been issued by the patent office in recent years, or if it has it seems to be extremely rare.

In any event, in 2010 Keppler et al. published an article entitled “Metastasizing Patent Claims in BRCA1” which showed that if the BRCA 15mer claims are interpreted so broadly as to cover any DNA sequence comprising any 15mer appearing in a BRCA gene, there appears to be a wealth of prior art that would invalidate the claim regardless of the claims patent eligibility.

The flawed methodology used in the "Pervasive Sequence Patents" article is readily apparent from the results of their empirical study. Here is what they reported as the result of their study:

[W]hen we took existing gene patents and matched their 15mers to known genes, we found that 100% of known genes have at least one 15mer claimed in a known patent. Current gene patents were observed to match each gene many times, with 1,295 matches to other genes on average (standard deviation 1,208). When we examined the amount of total sequence space in human genes that is covered by 15mers in claims from current patents (Additional file 2), we found 58 patents whose claims covered at least 10% of the bases of all human genes. The top patent was US7795422, whose claims' sequences matched 91.5% of human genes. Interestingly, we also observed a patent for improving bovine traits (US7468248) with explicit claims for 15mers that matched 84% of human genes. This patent was not even aimed at any human sequence, yet covered a majority of human genes once we examined the claim's matches at the 15mer scale.

First off, let's look at the "top patent" they found, US7795422, “whose claims sequences matched 91.5% of human genes.”  The ‘422 patent has only one independent claim:

1.       A chemically modified short interfering nucleic acid (siNA) molecule, wherein: (a) the siNA molecule comprises a sense strand and an antisense strand, each strand having one or more pyrimidine nucleotides and one or more purine nucleotides; (b) each strand is independently 18 to 27 nucleotides in length, and together comprise a duplex having between 17 and 23 base pairs; (c) the antisense strand is complementary to a human Hypoxia Inducible Factor 1 (HIF1) RNA sequence comprising SEQ ID NO:567; (d) a plurality of pyrimidine nucleotides present in the sense strand are 2'-deoxy-2-fluoro pyrimidine nucleotides and a plurality of purine nucleotide present in the sense strand are 2'-deoxy purine nucleotides; and (e) a plurality of pyrimidine nucleotides present in the antisense strand are 2'-deoxy-2'-fluoro pyrimidine nucleotides and a plurality of purine nucleotides present in the antisense strand are 2'-O-methyl-puine nucleotides.

When one reads the claim, it is apparent on the face that the claim is limited to "chemically modified" molecules comprising 2'-deoxy-2-fluoro pyrimidine nucleotides and 2'-deoxy purine nucleotides.  DNA does not contain 2'-deoxy-2-fluoro pyrimidine nucleotides and 2'-deoxy purine nucleotides, these are synthetic analogues to the nucleotides that appear in DNA. This patent that the authors found to match 91.5% of human genes does not cover any gene or any DNA molecule, only chemically modified synthetic molecules for use in RNA interference.

Next the authors reported that US7468248 contains "explicit claims for 15mers that matched 84% of human genes.” In fact, the ‘248 patent has only two independent claims, both of them method claims:

1.       A method for inferring a trait of a bovine subject from a nucleic acid sample of the bovine subject, comprising identifying in the nucleic acid sample, a nucleotide occurrence of a single nucleotide polymorphism (SNP) at position 300 of SEQ ID NO:21645, thereby inferring the trait, wherein the trait is marbling, tenderness, fat thickness, red meat yield, or average daily weight gain.

22. A method for determining a nucleotide occurrence of a polymorphism in a bovine sample, comprising: a) contacting a bovine polynucleotide in the sample with an oligonucleotide that binds to a target region, wherein the target region comprises a position at position 300 of SEQ ID NO:21645 or wherein the target region is within 3000 nucleotides of a nucleotide at position 300 of SEQ ID NO:21645, and b) determining the nucleotide occurrence of a single nucleotide polymorphism (SNP) at position 300 of SEQ ID NO:21645, wherein the determination comprises analyzing binding of the oligonucleotide or detecting an amplification product generated using the oligonucleotide, thereby determining the nucleotide occurrence of the polymorphism.

Both of these claims would only be infringed by someone performing a specific genetic test on a bovine subject (colloquially a cow). The patent does not include any claim covering any DNA sequence, and the authors’ assumption that the patent “explicitly claims 15mers that matched 84% of human genes” implies that they either did not read the claims or do not understand the basics of claim interpretation.

The problems with this article are pretty apparent once one reads the claims of the patents that were identified as "matching" human genes. Unfortunately, it is just the latest installment of a prolific stream of fundamentally flawed academic articles that are being cited in support of the notion that human gene patents are a pervasive problem.  I don't doubt that the authors meant well, but it's dangerous to conduct empirical patent studies without appreciating and understanding the critical role of the patent claim. And the publication of the article highlights the limitations of peer review (assuming Genome Medicine engages in peer review).

Myriad's BRCA Claims Held Patent Eligible in Australia

Today the Federal Court of Australia issued a decision in Cancer Voices Australia v. Myriad Genetics upholding the patent eligibility of three of Myriad's patent claims that recite isolated BRCA-encoding nucleic acids. Based on my understanding of the Australian court system (gleaned from Wikipedia) the decision seems to be analogous to a federal district court decision in the United States, i.e., the case was decided by a single judge, it can be appealed to the Full Court (a panel of 3 to 5 judges), and ultimately to the Australian High Court (the analog of the US Supreme Court). As in the case of the US challenge to Myriad’s BRCA patents, only patent eligibility is at issue, no other grounds of invalidity (including lack of novelty, lack of inventive step, lack of utility or lack of fair basis) were raised.

Looking to Australian precedent, the court held the claimed nucleic acids to be patent eligible “manner[s] of manufacture” within the meaning the Australian Statute of Monopolies, because the claimed nucleic acids constitute “an artificially created state of affairs which has economic significance.”

Although the Australian court came to the same conclusion as the Federal Circuit with respect to the patent eligibility of the claims, it declined to follow the reasoning of the Federal Circuit's Judge Lourie. In particular, the court rejected Judge Lourie’s conclusion that the isolated DNA claims are limited to DNA molecules that have been excised from the human chromosome in a way that requires covalent bonds to be broken. The Australian judge found that the claims are silent with respect to the length of the claimed nucleic acids, and that "there is nothing to suggest either in the claims themselves or in the body of the specification that the complete molecule of DNA as originally found on chromosome 17 that has been isolated . . . would be outside the scope of the disputed claims. . . . To interpret the disputed claims [so as to require that every isolated DNA sequence within the scope of the claims must have had at least some covalent bonds broken as a result the isolation process] would require me to impose an impermissible gloss upon the words of the claim.”  I entirely agree with the Australian court, and think that Judge Lourie was incorrect on this point.

In reaching its decision, the Australian court found it to be significant that:

(1) The Australian High Court had previously interpreted the scope of patent eligible subject matter expansively, and "made clear that metaphorical analysis may not be helpful in determining whether or not something constitutes patentable subject matter” [our US Supreme Court might benefit from this approach];

(2) “[I]n the absence of human intervention, naturally occurring nucleic acid does not exist outside the cell, and ‘isolated’ nucleic acid does not exist inside the cell;” and

(3)  "It would lead to very odd results if a person whose skill and effort culminated in the isolation of a micro-organism (a fortiori, an isolated DNA sequence) could not be independently rewarded by the grant of a patent because the isolated micro-organism, no matter how practically useful or economically significant, was held to be inherently non-patentable.”

 The court noted that it is “trite law that you cannot patent a discovery, but if on the basis of that discovery you can tell people how it can be usefully employed, then a patentable invention may result.”

The court made a number of other important observations:

(1) “The disputed claims are not to genetic information per se. They claim tangible materials. Much emphasis was placed by the [patent challengers] upon the informational character of DNA as a storehouse of genetic information. But the disputed claims are not to information as such. They could never be infringed by someone who merely reproduced a DNA sequence in written or digitised form.

(2) “Because each of the claims is to an isolated chemical composition, naturally occurring DNA and RNA as they exist in cell are not within the scope of any of the disputed claims and could never, at least not until they had been isolated, result in the infringement of any such claim."

(3) “ [Australian precedent] does not require the Court to ask whether a composition of matter is a “product of nature” for the purpose of deciding whether or not it constitutes patentable subject matter. [Precedent] recognises that it may be unhelpful to approach the problem in this way. I think this is especially so in the field of biotechnology in which micro-organisms play a critical role in the development, manufacture and use of diagnostic and therapeutic products and techniques.”

(4) “[Australian precedent] does not require the Court to ask whether a micro-organism is “markedly different” to something that already exists in nature for the purpose of deciding whether it constitutes patentable subject matter (cf. Chakrabarty at 310).”

(5) “In the context of biological material, an artificial state of affairs may manifest itself in different ways. The physical properties of the naturally occurring material may have changed as a result of it having been isolated. But even if the physical properties of the material have not changed, the removal of the material from its natural environment and its separation from other cellular components may still give rise to what might reasonably be described as an artificial state of affairs. “

(6) “In my opinion the patentability of the isolated nucleic acids referred to in the disputed claims does not turn upon what changes have been made to the chemical composition of such substances as a result of them having been isolated. In particular, the question of whether these substances constitute patentable subject matter does not depend upon the type of chemical bond that may have been broken in the process of isolating them.”

The court also found significant, although not determinative, the fact that the Australian Parliament had considered and rejected proposals to limit the patenting of isolated nucleic acids, as well as the long-standing practice of the Australian patent office to grant claims to isolated nucleic acids.

In short, the decision of the Australian court broadly supports the patent eligibility of not only isolated DNA, but more generally isolated naturally occurring molecules.  It is entirely consistent with the long-standing interpretation of the US patent office, and the general understanding in the US prior to the Myriad case, that isolation of a naturally occurring molecule can constitute sufficient human intervention to satisfy the requirement of patent eligibility. It rejects many of the arguments being raised in the US by ACLU/PubPat and their supporters.

SCOTUSblog Hosts Online Gene Patenting Symposium

 

Prompted no doubt by the Supreme Court’s grant of certiorari in the Myriad gene patent case, widely read Supreme Court blog SCOTUSblog is hosting an online Gene Patenting Symposium, which features guest articles authored by a number of invited contributors, including myself. 

 

Prolume Sues Companies for Infringement of GFP and Luciferase Gene Patents

With the Supreme Court about to weigh in on the controversial subject of gene patents, it bears noting that humans are not the only ones whose genes are patented. A company called  Prolume, located in Pinetop, Arizona, apparently owns a couple of gene patents claiming the DNA encoding green fluorescent proteins (GFPs) and luciferases from a variety of sea creatures of the genera Renilla, Gaussia and Pleuromamma (6,232,107 and 7,109,315).

Recently, Prolume filed a lawsuit in the Southern District of California against a multiple companies, including Gentarget, alleging infringement of the patents.  Prolume appears to have targeted these companies based on the description of products provided on the company websites. For example, the complaint states that "a search of the word ‘gaussia’ at www.gentarget.com reveals 14 products that incorporate Gaussia Luciferase.” 

The complaint notes that Prolume cannot determine from the Gentarget website which claims are being infringed without an analysis of the DNA sequence used in their products. However, Prolume infers infringement based upon the frequency of light that excites the protein, and that is emitted, as described in the company's product literature. Presumably Prolume will seek discovery to ascertain the DNA sequences used by the defendants in the production of their products.