Aria Diagnostics v. Sequenom: Genetic Diagnostic Claims Patent Ineligible

 

A recent decision out of the ND of California portends poorly for the patent eligibility of genetic diagnostic testing methods.

Sequenom is the exclusive licensee of US patent 6,258,540, which Sequenom licensed from Isis
Innovation Limited.  The patent relates to prenatal detection methods performed on a maternal serum or plasma sample from a pregnant female, which methods comprise detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample, and is based on the discovery that cell-free fetal DNA (sometimes referred to as “cffDNA”) is detectable in maternal serum or plasma samples. The “invention enables non-invasive prenatal diagnosis, including for example sex determination, blood typing and other genotyping, and detection of pre-eclampsia in the mother.”

Ariosa, formerly known as Aria Diagnostics, sued Sequonom in the Northern District of California seeking a declaratory judgment that it does not infringe the ‘540 patent. On October 30, the court granted summary judgment in favor of Arioso, declaring a number of claims of the ‘540 patent invalid for being directed towards patent ineligible subject matter under 35 USC 101. The decision is available here.

Claim 1 is representative of the invalidated claims. It recites:

 

1. A method for detecting a paternally inherited nucleic acid of fetal origin performed on a maternal serum or plasma sample from a pregnant female, which method comprises:

amplifying a paternally inherited nucleic acid from the serum or plasma sample and

detecting the presence of a paternally inherited nucleic acid of fetal origin in the sample.

 

Recent Supreme Court decisions addressing patent eligibility, particularly Mayo v. Prometheus, have emphasized two criteria for assessing patent eligibility of method claims directed towards a practical application of the discovery of a “natural phenomenon.” First, does the claimed method add something to the natural phenomenon beyond what is already “well-understood, routine, or conventional.” Second, does the claimed method “preempt” the natural phenomenon.

 

With regard to the first criterion, the District Court interpreted the requirement of something more than well understood, routine and conventional activity as imposing a requirement that the claimed method must constitute an “inventive” application of the natural phenomenon. The court held that “use of a newly discovered natural phenomenon [] will not render a claim patentable if the use of that natural phenomenon, [] is the only innovation contained in the patent.”  The court found that the only inventive aspect of the method was the discovery of the presence of cffDNA in maternal plasma, and that the detection of cffDNA using conventional techniques for DNA detection was not sufficiently inventive to render the claim patent eligible.

 

One way of looking at it is that the court essentially conducted a nonobviousness analysis, usually the province of Section 103, under the guise of Section 101 patent eligibility, treating the newly discovered natural phenomenon which formed the basis for the claim method as something akin to prior art, and concluding that it was not inventive (i.e., it was obvious) to combine the natural phenomenon with prior art methods for DNA detection. It will be interesting to see how the Federal Circuit responds to this interpretation of the “well understood, routine and conventional” language the Supreme Court used in Mayo.  Unfortunately, it seems to comport with a literal reading of Mayo. However, in the Federal Circuit’s recent fractured en banc decision in CLS Bank Int’l v. Alice Chief Judge Rader authored an opinion explicitly stating that, in his view, the Supreme Court’s use of the language “well-understood, routine and conventional” does not inject a requirement of inventiveness into the section 101 patent eligibility analysis.  Other Federal Circuit judges offered different interpretations, and there appear to be some that are much more receptive to that the Supreme Court has injected an “inventiveness” criterion in the test for patent eligibility.

 

Regarding the second criterion, the District Court found that the claim would cover all “commercially viable” means of testing for paternal cffDNA and thus preempted use of the natural phenomenon.  Sequenom presented evidence that there are alternate methods available for detecting cffDNA  that are not covered by the claim, but the court characterized these methods as not “commercially viable,” and hence not relevant to its preemption analysis, which focused on the practical impact of the patent claims.  The decision suggests that a method claim such as this is patent ineligible unless, “at the time of the invention or at the time of issuance of the patent,” there are available commercially viable alternatives for applying the claimed natural phenomenon.

 

If the approach used by this court is upheld by the Federal Circuit and applied generally to diagnostic claims, it would seem to severely limit the availability of patent protection for diagnostics.   One well-known patent that immediately comes to mind is Genetic Technology Ltd’s so-called “junk DNA” diagnostic patent, US Patent No. 5,612,179, which involves diagnostic analysis of non-coding DNA and has been asserted against numerous alleged infringers. But even if this approach is adopted, there remains some reason to be optimistic with respect to personalized medicine claims, particularly if the claim includes a step actually applying diagnostic information, for example by administering a drug to a patient. I think the Federal Circuit’s recent decision in Classen Immunotherapies, Inc. v. Biogen IDEC would support that position.

Judge Calls Anticancer Inc.’s Attempts to Enforce GFP Patents “Misguided,” Warns that Future Enforcement Activity Could Warrant an Award of Attorney’s Fees

On June 26, in the case of Anticancer, Inc. v. Leica Microsystems, Inc., a federal judge in the Southern District of California granted a motion for summary judgment against Anticancer Inc., finding that Anticancer had failed to raise a genuine issue of material fact with respect to the allegation that Leica Microsystems had induced the infringement of US patent numbers 6,649,159; 6,759,038; and 6,251,384.  (see the Court’s Order) The patents generally relate to the use of green fluorescent protein (GFP) as an indicator of promoter activity in research animals. The judge denied the defendants’ motion for attorneys fees, but just barely, characterizing Anticancer’s efforts to enforce its patent rights as “misguided.” Although the court did not find the level of “bad faith” necessary to award attorney’s fees, it suggested that if Anticancer continues to bring meritless lawsuits an award of attorney’s fees could be justified.

The defendant, Leica Microsystems, sells imaging equipment that presumably can be used in a manner thatAnticancer believes would infringe  its patents, but the mere act of selling an item that can be used to infringe a patent does not in and of itself constitute patent infringement. Under 35 USC 271(b) a party can be held liable for inducing its customers to infringe a patent, but in order to prevail under an inducement theory the patent owner must prove that the customers have directly infringed the patent, and that the customer's were induced to infringe by the defendant . In this case, the court found that Anticancer had failed to produce sufficient evidence to withstand summary judgment with respect to both elements, i.e., direct infringement by Leica's customers and inducement by Leica.

Anticancer’s purported evidence of direct infringement comprised numerous articles published by scientists at various universities and research institutes that reported the use of an instrument purchased from Leica. Anticancer attempted to establish infringement by means of an expert declaration, but the court found that the declaration did not raise a genuine issue of material fact with respect to direct infringement by the third-party researchers. The court pointed out that the expert declaration did not identify which of Anticancer's patent claims in particular were infringed by the methodologies described in the publications. Furthermore, the court noted that all of the allegedly infringe claims are method claims, and that the expert had not explained “how the papers cited reflect the performance of each step of the methods claimed, much less that they were performed in the required order.”

Anticancer’s purported evidence of inducement consisted largely of Leica promotional materials, such as press releases, articles and brochures used by the company to promote its products. The court found two critical problems with this evidence. First, and most importantly, Anticancer had failed to present any evidence that the third-parties who had allegedly infringe the patents had ever seen any of the promotional materials. Second, some of the evidence actually showed that the products could be put to noninfringing use.

The court denied Leica’s request for an award of attorney’s fees, essentially concluding that a determination of “bad faith” is required for an award of attorney’s fees, and finding insufficient evidence that Anticancer’s actions were sufficiently egregious to constitute bad faith. However, the court went on to note that this is the third case in which Anticancer’s claims of patent infringement have been resolved in the defendant’s favor on summary judgment, and that although “Plaintiff’s efforts to enforce its patent rights may, at this point, be misguided, a finding of bad faith may be warranted if Plaintiff continues to press claims that ultimately have no merit, especially if courts continue to rule against it on summary judgment based on failures similar to those in this case."

The judge’s comments regarding the potential for a finding of bad faith if Anticancer continues to attempt to enforce its patents in this manner brings to mind a recent New York Times op-ed authored by Chief Judge of the Federal Circuit Rader and law profs Colleen Chien and David Hricik.  These authors suggested that a way to deal with the problem of frivolous patent lawsuits (i.e., patent trolls) would be for the courts to make more use 35 USC 285 and Rule 11 of the Federal Rules of Civil Procedure to shift the cost of litigation from defendants to patent owners filing frivolous lawsuits. They reported that, according to their count, attorneys fees were shifted under Section 285 in only 20 out of nearly 3000 patent cases filed in 2011, a statistic they found to be “remarkable.” The district court judge in the Anticancer case seemed close to awarding attorneys fees to Leica, and perhaps with the encouragement of Chief Judge Rader the next district court judge considering an award of sanctions against Anticancer might actually pull the trigger.

 

 

 

In Myriad the Supreme Court Has, Once Again, Increased the Uncertainty of U.S. Patent Law

On June 13 the U.S. Supreme Court issued a unanimous decision in Association for Molecular Pathology v. Myriad Genetics (Myriad) which essentially upheld the patent eligibility of claims reciting cDNA molecules encoding BRCA proteins, but struck down as patent ineligible claims encompassing isolated fragments of BRCA-encoding genomic DNA. Unfortunately, as a consequence of the manner in which the case was decided Myriad will in all likelihood only serve to increase the ambiguity and uncertainty plaguing the U. S. patent system. Clearly, the mere isolation of a naturally occurring biomolecule is no longer sufficient to confer patent eligibility on the isolated product, regardless of how useful, nonobvious or inventive the isolated product is relative to the prior art. What is less clear is the patent eligibility status of a synthetic molecule that shares a common, or highly similar, structure with a naturally occurring biomolecule.

 I have written an article that addresses some of the ambiguities created by the Myriad decision, and the practical implications for patenting in the life sciences arena.  The article, which appears in Biotechnology Law Report, is available here for the interested reader.

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.

My Amicus Brief in Bowman v. Monsanto

Over the last several days, I have posted a number of briefs that have been filed by various parties in Bowman v. Monsanto. Today I filed my own Amicus brief in the case, in support of affirmance, available here.

Here is my "Summary of Argument":

Intellectual property plays a critical role in the development of self-replicating technologies such as Monsanto's genetically modified soybeans. Without some mechanism to constrain the use and dissemination of replica products, free riders would quickly flood the market with copies and impair the innovator’s ability to secure an adequate return on investment. Because of the ease with which genetically modified soybeans can be replicated by any user who comes into possession of even a single seed, whatever the source, enforceable patent protection is essential to maintain an adequate incentive for innovation.

The potential impact of this case goes well beyond Monsanto and soybeans. A decision that results in the exhaustion of patent rights in copies of self-replicating products could dramatically undermine investment in a host of promising green technologies for sustainably feeding, fueling and healing the world. It might also discourage commercialization of synthetic biology, the much heralded next iteration of the biotechnology revolution.  Such a dramatic and far-reaching shift in the patent landscape is certainly not warranted, particularly on the facts of this case.

It is important to recognize that it is petitioner, not the Federal Circuit, who is seeking to create an exception to the doctrine of patent exhaustion.  In essence, petitioner is arguing for an expansion of the doctrine to encompass not only patented products that have been the subject of an authorized sale, but also copies of the product - copies that were never the subject of an authorized sale. Petitioner alleges that this drastic measure is warranted because the use of Monsanto’s product inherently and unavoidably results in the production of copies, citing numerous hypothetical policy concerns. But these potential concerns are not presented in this case, involving a farmer who intentionally used and benefitted from Monsanto’s patented technology without paying for it.  To the extent any of these concerns actually become an issue in the real world, they can and should be addressed in a manner that does not effectively deprive innovators of the ability to enforce their patents with respect to self-replicating technologies.

It is informative to consider how analogous concerns have been addressed with respect to another important self-replicating technology, computer software. Even though the use of many software programs inherently and unavoidably results in the production of a copy on the user's computer, which would technically constitute copyright infringement, it makes little sense for software companies to sue their customers for this sort of infringement. It is simply not a problem.  If the potential for an infringement lawsuit became a concern, the software company could address it by explicitly authorizing purchasers to make a copy of the software, at least to the extent that such copying is an essential step in using the software. In any event, to resolve any lingering concern, Congress took the step of amending the copyright statute to explicitly exempt authorized users of computer software from liability for producing a copy that is used solely as a necessary element of running the software.

Significantly, it has not been deemed necessary to expand copyright's first sale doctrine (copyright’s analog to the doctrine of patent exhaustion) in a manner that exhausts patent rights in copies of copyrighted software that are inherently created when the software is used. To do so would effectively strip software developers of meaningful copyright protection once a first round of copies has been sold and replicated. In the same way, and for much the same reasons, it is unnecessary to expand the doctrine of patent exhaustion with respect to self-replicating patented technologies like Monsanto's seeds. To the contrary, to do so would effectively deny enforceable patent protection to many self-replicating technologies.

Congress is in the position to weigh competing interests, and if necessary enact legislation to address any unique policy concerns presented by the interplay of intellectual property rights and self-replicating technologies.  It has done so with respect to computer software, and in a manner that does not deprive software producers of the ability to enforce their copyrights against free riders. It can do so with respect to patented self-replicating technologies as well. In fact, a bill is currently pending in Congress that would effectively create a compulsory license in patented seeds. Leaving aside the question of whether this would be the best approach, it illustrates that Congress is fully capable of addressing concerns expressed by petitioner and its amici without entirely stripping innovators like Monsanto of their patent rights.

 

Three Briefs Filed in Support of Affirmance in Bowman

Here are links to three Amicus briefs that have been filed in support of affirmance in Monsanto v. Bowman (other briefs filed in the case are provided in earlier posts to this blog)

The Intellectual Property Owners Association argues that "while patent exhaustion would have prevented Monsanto from restricting the distribution or use of [the original seeds that were the subject of an authorized sale by Monsanto], those original seeds were completely consumed (as intended) in the growing of the first crop. The commodity seeds that resulted from the first crop . . . constitute an entirely new manufacturer and, as such, are not subject to the doctrinal patent exhaustion." Their brief also points out that seeds are not the only technologies that would be negatively impacted if "making" is considered an exhausted "use," citing examples such as recombinant host cells used in the production of biological drugs, computer programs, and potentially "self-replicating" nanotechnology.

The New York Intellectual Property Law Association brief provides some background on conditional sales and contributory infringement, and argues that the exhaustion doctrine should not be extended beyond Quanta. The Association goes on to argue that Bowman violated valid and enforceable field of use restraints, and that each successive generation of a patented self-replicating biological material is a separate actionable "making" under 35 U.S.C. § 271(a) .

 
BayhDole25, Inc. describes itself as a nonprofit, nongovernmental organization with a mission of "educating for the powerful social and economic benefits that have continued to flow from technology transfer relating to agricultural biotechnology advances, both in the United States and in developing and developed countries around the world." BayhDole25 argues that that Bowman's activities "represent transactions intended to essentially 'launder' Respondents' Roundup Ready technology through the grain elevator,” and that there are substantial differences between the instant case and Quanta and other president supporting application of the exhaustion doctrine. The brief discusses "the historical social contract for technology transfer that has fueled growth in agricultural productivity and global development." BayhDole25 notes that Monsanto must be compensated for the use of this technology in order to support "long-term investment in new technologies for the continued vibrancy of US agricultural for biotechnology, where the private sector now provides the lion's share of R&D critical to continuing agricultural activity gains.”  They point out the importance of this technology as a means for meeting global challenges associated with population growth and climate change.

 

 

 

 

Briefs Filed by Monsanto and the Solicitor General in Bowman v. Monsanto

 

Last week, I posted briefs filed by petitioner Vernon Bowman and his amici in Bowman v. Monsanto. Today, I'm posting respondent Monsanto's brief, along with a brief filed by the US Solicitor General in support of affirmance (i.e., in support of Monsanto).

Monsanto argues that the first sale doctrine (i.e., patent exhaustion) is inapplicable to the soybeans grown by Bowman because they are second-generation seeds, and were not the subject of an authorized sale.  Monsanto further argues that if the Court were to accept petitioner's argument, it would result in utility patent owners receiving less protection than is provided under the Plant Patent Act and the Plant Variety Protection Act, which would be contrary to Congress's intent and Supreme Court precedent holding that utility patent owners receive greater protection than is provided under the PPA or PVPA. The brief concludes by explaining that contractual remedies alone are inadequate to encourage innovation in "readily replicable technologies," (a more accurate label than the one used by Bowman, i.e., "self-replicating technology").

The US Solicitor General argues that the authorized sale of one article embodying a patented invention (i.e., a patented seed) does not exhaust the patentees right to control the creation of other articles embodying the same invention (i.e., subsequent generations of that seed). The Solicitor General characterizes the Federal Circuit's Mallinkrodt line of cases applying a "conditional sale" doctrine as erroneous, but that this “do[es] not cast doubt on the correctness of the decision below.”

Briefs Filed by Petitioner and His Amici in Bowman v. Monsanto

In Bowman v. Monsanto, the Supreme Court will have the opportunity to address the extent to which the doctrine of patent exhaustion applies to progeny of patented recombinant seeds. For background on the case, see this previous post.

Here are links to briefs recently filed by petitioner Bowman and his amici, with some brief commentary:

Petitioner (Vernon Bowman) argues that an authorized sale of recombinant seeds exhausts patent rights in progeny seeds that were not themselves the subject of an authorized sale. He bases this argument on a theory that subsequent generations of seeds are "embodied” in the first-generation authorized seeds.  Bowman is apparently attempting to leverage the Supreme Court's questionable use of the term "embodies" with respect to method patents in Quanta.  He also argues that production of progeny seeds does not constitute "making" the seeds because the use of genetically modified seeds inherently results in the production of progeny seeds. Bowman contends that contract law provides adequate remedies to owners of patents on self-replicating technologies.

Center for Food Safety argues that extending patent exhaustion to progeny seeds will benefit farmers by curtailing Monsanto's patent enforcement actions targeting farmers. The Center also claims that extending the patent exhaustion doctrine in this way will benefit scientific research and innovation in agriculture, and lower the cost of farming. The Center further contends the Federal Circuit's decision is contrary to Quanta, and reiterates petitioner's argument that producing progeny seed constitutes use of the patented seed, not making it, and hence falls within the scope of patent exhaustion. The amici voice is concerned that farmers whose fields have been "contaminated” by Monsanto's patented seeds could be subject to infringement lawsuits.

The American Antitrust Institute argue that the Federal Circuit's decision is contrary to Supreme Court precedent, particularly Quanta, and departs from long-standing Congressional patent policy.  They warn that the Federal Circuit's decision "portends dangerous unintended consequences" for other industries, particularly the computer software industry. They suggest that Monsanto should learn from the software industry, and engage in "effective product differentiation and efficient third-degree price discrimination" in order to counter the threat posed by the ease with which their products can be replicated. They contend that Monsanto could have avoided its need to rely on patents by not working with soybean seeds and other inbred seed lines, and confining their activities to hybrid seeds (i.e., corn) that do not produce true copies of themselves. Somewhat surprisingly, the Institute suggests that Monsanto "could have developed its ‘terminator’ gene, which would have rendered progeny seeds sterile." “Terminator” is a pejorative term for Genetic Use Restriction Technology (GURT), highly controversial technology that Monsanto pledged not to use in 1999.

The Automotive Aftermarket Industry Association et al. are concerned that affirmance of the Federal Circuit's decision weakens the patent exhaustion doctrine. This brief was filed on behalf of companies that market automotive replacement parts and refurbished inkjet cartridges.

Knowledge Ecology International essentially argues that effective patent protection is not necessary for self-replicating genetically engineered crops, because "a plethora of alternative mechanisms to patent regimes exist to reward research and development."  For example, they argue that an inventor "can still protect his investment through contractual agreements governing post-sale uses” (while at the same time acknowledging that contract law would not have helped in this case, due to a lack of privity between Bowman and Monsanto).  The plethora of alternative mechanisms includes "sui generis systems of rewards or cash innovation inducement prizes," which KEI characterizes as "viable alternatives to the patent system."  They voice concern that "even plants exhibiting the genetically modified trait found in the wild as a result of cross-pollination, would fall under the patent rights the patent holder.)

The Public Patent Foundation expresses concern that under the Federal Circuit's ruling, "contaminated farmers are infringers," and "Monsanto's customers routinely make and sell new infringing articles." In a previous post, I discussed a lawsuit that the Public Patent Foundation has filed against Monsanto on behalf of a variety of groups including associations of organic farmers.

 

 

 

MIT Sues Shire Alleging that Dermagraft Infringes Cell-Scaffold Patents

On January 4, 2013, MIT sued Shire Pharmaceuticals in the District of Massachusetts for infringing US Patent Numbers 5,759,830; 5,770,417; and 5,770,193. The patents all issued in 1998, and are generally directed towards “three-dimensional fibrous scaffolds containing attached cells for producing vascularized tissue in vivo.”  For example, claim 1 of the ‘830 patent recites:

1. A cell-scaffold composition prepared in vitro for growing cells to produce functional vascularized organ tissue in vivo, comprising:

a fibrous three-dimensional scaffold composed of fibers of a biocompatible, biodegradable, synthetic polymer; and
cells derived from a vascularized tissue attached in vitro to the surface of the fibers of the scaffold uniformly throughout the scaffold;
wherein the fibers of the scaffold provide sufficient surface area to permit attachment in vitro of an amount of the cells effective to produce the functional vascularized organ tissue in vivo;
wherein the fibers of the scaffold are spaced apart such that the maximum distance over which diffusion of nutrients and gases must occur through a mass of cells attached to the fibers is between 100 and 300 microns; and
wherein the diffusion provides free exchange of nutrients, gases and waste to and from the cells uniformly attached to the fibers of the scaffold and proliferating throughout the scaffold in an amount effective to maintain cell viability throughout the scaffold in the absence of vascularization.

The allegedly infringing product is Dermagraft, a human fibroblast-derived dermal substitute approved by FDA in 2001 for use in treatment of full thickness diabetic foot ulcers. According to the complaint, Dermagraft is manufactured from human fibroblast cells derived from newborn foreskin tissue, which are seeded onto a bioabsorbable polyglactin three-dimensional mesh scaffold. MIT alleges that the fibroblasts proliferate to fill the interstices of this scaffold and secrete human dermal collagen, matrixproteins, growth factors,  and cytokines to create a three-dimensional human dermal substitute containing metabolically active,  living cells.