Thursday, October 20, 2011

Claim Construction Ruling in Arzerra Infringement Case

On October 17, a judge in the Southern District of California issued a significant claim construction ruling in the case of Biogen Idec and Genentech v. GlaxoSmithKline. The plaintiffs allege that defendants anti-CD20 monoclonal antibody Ofatumumab (trade name Arzerra) infringes US patent number 7,682,612. Plaintiffs market a competing anti-CD20 antibody, Rituximab (trade name Rituxan).

Based on my understanding of the case, the ruling appears to be a substantial victory for GlaxoSmithKline.

The disputed claim terms are found in claim 1 of the patent, which 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 court construed the terms "anti-CD20 antibody” and “CD20 binding fragment” as “rituximab and antibodies that bind to the same epitope of the CD20 antigen with similar affinity and specificity as rituximab” and "the portion of the anti-CD20 antibody that binds to the same epitope of the CD20 antigen with similar affinity and specificity as rituximab.” This is significant, because Arzerra does not bind to the same epitope as rituximab, which appears to rule out infringement if this construction of the terms is affirmed on appeal.

The plaintiffs argued for a broader construction, such that the disputed terms would cover any antibody that binds to CD20, even antibodies that bind to different epitopes, such as Arzerra. However, the court found that the prosecution history of the patent established that during prosecution plaintiffs represented that the claims were limited to antibodies binding to the same epitope as rituximab, and the court held them to this more limited construction of the term.

The court also construed the terms "does not include treatment with a radiolabeled anti-CD20 antibody" and "radiation is not used" as "excludes the use of a radiolabeled anti-CD20 antibody or the administration of a separate radiolabeled anti-CD20 antibody," and "no form of radiation (including radiolabeled antibodies) is used," respectively. This construction is significant, because it appears to rule out infringement when Arzerra is used in conjunction with Bexxar or Zevalin, which are both radiolabeled anti-CD20 antibodies.

Thanks to Docket Navigator for making me aware of the ruling.

Wednesday, October 19, 2011

Pioneer-DuPont Sues Monsanto for Infringing "Low Tech" Agricultural Biotechnology Patents

Yesterday Pioneer Hi-Bred (a subsidiary of DuPont) sued Monsanto, its rival in the agricultural biotechnology sector, for allegedly infringing its patents directed towards a method of increasing "seed vigor" in maize that entails defoliating maize plants during a specific period after pollination. The lawsuit was filed in the Southern District of Iowa, Pioneer's home territory.

The two companies have been involved in a high-profile patent litigation ever since Pioneer announced its plans to release genetically modified maize comprising Pioneers Optimum GAT trait stacked with Monsanto's Roundup Ready trait. Both traits confer resistance to glyphosate (i.e. Roundup), albeit by different mechanisms - Roundup Ready essentially works by rendering the plant resistant to glyphosate, while Optimum GAT causes the plant to express a protein that breaks down the glyphosate molecule.

Pioneer responded by suing Monsanto for antitrust violations, based on the company’s licensing and enforcement practices with respect to its patents covering the Roundup Ready trait. The patent infringement case is scheduled to go to trial next June, while the antitrust counterclaims are scheduled to go to trial April 2013.

The two patents being asserted by Pioneer in the most recent lawsuit are US patent numbers 5,518,989 and 6,162,974. The ‘989 patent claims a method of increasing seed vigor in maize by defoliating plants during a specific time window after pollination, based upon how long the growing plant has been exposed to warm days. The ‘974 patent claims an "assemblage" of maize seeds produced using the method. Here are a couple of representative claims.

Claim 1 from the ‘989 patent:

1. A method for treating a stand of maize plants, comprising the steps of

(A) reducing functional leaf area in substantially all of said plants, wherein said reducing is effected at between about 600 and about 850 GDDs after pollination of said plants, and then

(B) harvesting said stand, such that a seed assemblage is obtained from said stand that is characterized by a level of seed vigor that is enhanced relative to the level of seed vigor in a seed assemblage harvested from a comparison stand of maize plants not subjected to said reducing of functional leaf area.
Claim 1 from the ‘974 patent:

1. A maize seed assemblage having enhanced seed vigor, wherein said seed assemblage is obtained by the method comprising the steps of:

(a) reducing functional leaf area in substantially all of a stand of maize plants, wherein said reducing is effected at between about 600 and about 850 GDDs after pollination of said plants, and

(b) harvesting said stand to obtain an assemblage of seeds,

wherein said seed assemblage is characterized by a level of seed vigor that is enhanced relative to the level of seed vigor in a seed assemblage harvested from a comparison stand of maize plants not subjected to said reducing of functional leaf area.

According to Wikipedia, “GDD [,which stands for Growing Degree Day, is] a measure of heat accumulation used by horticulturists, gardeners, and farmers to predict plant and pest development rates such as the date that a flower will bloom or a crop reach maturity.” Wikipedia states that "plants grow in a cumulative stepwise manner which is strongly influenced by the ambient temperature. Growing degree days take aspects of local weather into account and allow gardeners to predict (or, in greenhouses, even to control) the plants’ pace toward maturity."

The patents state that "functional leaf area can be reduced" (i.e., the plant can be defoliated) using mechanical or chemical means. "Chemical means" would include treatment with an herbicide such as Roundup (the dependent claims explicitly identify Roundup as an herbicide to be used in the method.

The patents remind me of the patents at issue in In re Cruciferous Sprouts litigation that occurred several years ago. In that case, as I recall, researchers at Johns Hopkins University discovered that cruciferous sprouts (e.g., broccoli sprouts) harvested at a particular point in time after germination (in particular, prior to the "two-leaf stage") contain high levels of certain compounds believed to be useful in preventing cancer.

A representative claim at issue in that case recited " “A method of preparing a food product rich in glucosinolates, comprising germinated cruciferous seeds, with the exception of cabbage, cress, mustard and radish seeds, and harvesting sprouts prior to the 2-leaf stage, to form a food product comprising a plurality of sprouts.”

The Federal Circuit held that the claims were invalid based on inherent anticipation. Although the Johns Hopkins researchers might have been the first to recognize the health benefits of eating cruciferous sprouts harvested prior to the two-leaf stage, in fact people had been eating sprouts harvested at this stage for many years. This was surely the correct result - if the claims were held valid, that would mean that Johns Hopkins would have the right to exclude others from doing something that had long been part of the prior art, i.e., eating broccoli sprouts and the like.

The same sort of issue of inherent anticipation could potentially be raised with respect to Pioneer's patents on methods of defoliating maize plants at a certain time after pollination. It would seem to me that if Monsanto can show that, prior to Pioneers invention, maize plants had been defoliated during this stage of growth (perhaps by treatment with Roundup), a court might come to the conclusion that the claims are inherently anticipated.

The claims also might raise issues of patent eligibility, at least in the minds of people like Justice Breyer. Recall that in his LabCorp dissent Justice Breyer expressed a view that a patent claim that preempts substantially all practical use of a newly discovered natural phenomenon is patent ineligible. Some might characterize Pioneer’s discovery that defoliation of maize at a certain time results in increased seed vigor as the discovery of a "natural phenomenon," and conclude that Pioneer’s claims effectively preempt all substantial practical application of this discovery.

Pioneer's claims directed towards a "maize seed assemblage" might also raise patent eligibility issues. The claimed maize seeds are arguably not genetically modified, in which case they might be considered "products of nature" and not patent eligible under Chakrabarty. In order to be patent eligible, it would seem that a court would have to determine that either the defoliation resulted in a "man-made" seed, or that grouping seeds in an "assemblage" is sufficient human intervention to establish patent eligibility.

Wednesday, October 5, 2011

Patent Battle over Modified Meganucleases Heats Up

Meganucleases are endodeoxyribonucleases characterized by a large recognition site (double-stranded DNA sequences of 12 to 40 base pairs); as a result this site generally occurs only once in any given genome. For example, the 18-base pair sequence recognized by the I-SceI meganuclease would on average require a genome twenty times the size of the human genome to be found once by chance. Meganucleases are therefore considered to be the most specific naturally occurring restriction enzymes.

The high specificity of meganucleases gives them a high degree of precision and much lower cell toxicity than other naturally occurring restriction enzymes; they were identified in the 1990s as particularly promising tools for genome engineering.

However, the meganuclease-induced genetic recombinations that could be performed were limited by the repertoire of meganucleases available. Despite the existence of hundreds of meganucleases in nature, and the fact that each one is able to tolerate minor variations in its recognition site, the probability of finding a meganuclease able to cut a given gene at the desired location is extremely slim. Several research laboratories therefore soon began trying to engineer new meganucleases targeting the desired recognition sites.

Cellectis and Precision Biosciences are two competing biotechnology companies, both seeking to commercialize engineered meganucleases for use in genetic engineering.

On March 1, 2011, Cellectis sued Precision Biosciences in the District Court of Delaware for allegedly infringing US patent number 7,897,372, directed to "I-CreI Meganuclease Variants with Modified Specificity.” That case is presently proceeding with discovery, and trial is set for February 2013.

On September 20, 2011, the US patent office issued US patent number 8,021,867, which is directed towards "Rationally-Designed Meganucleases with Altered Sequence Specificity and DNA-Binding Affinity." The named assignee on the patent is Duke University, but according to Celectis the patent is actually owned by Precision.

On September 30, 2011, Cellectis filed another lawsuit against Precision Biosciences, again in the District Court of Delaware, and this time it is a declaratory judgment action seeking a declaration that the Duke/Precision patent is invalid and not infringed by Cellectis.

In the complaint, Cellectis does not allege that it has explicitly been threatened with a lawsuit by Precision. Instead, it argues that declaratory judgment is appropriate because: both patents-in-suit concern the same field of technology, i.e., "modified" or "altered" I-CreI meganucleases; the Cellectis patent is prior art to the precision patent, the parties in both cases are the same, and the discovery in both cases likely would substantially overlap.

Tuesday, September 13, 2011

Mirus Bio Files Lawsuit Alleging that Roche’s FuGENE 6 Transfection Reagent Infringes Patent

On September 12, 2011, Mirus Bio sued Fugent, LLC for allegedly infringing its patent entitled "Process of Transfecting a Cell with a Polynucleotide Mixed with an Amphipathic Compound and a DNA-Binding Protein" (U.S. Patent No. 5,744,335). The patent issued in 1998. Claim 1 of the patent recites:

A process of transfecting a polynucleotide into a cell comprising: associating a selected cell with an amphipathic compound, an effective amount of a polynucleotide-binding protein, the polynucleotide-binding protein is selected from the group consisting of histone and histone with a nuclear localizing signal, and a selected polynucleotide, in solution, wherein encapsulation of the polynucleotide by the amphipathic compound is not required for transfection.

Both companies are located in Madison Wisconsin.

The complaint alleges that Fugent infringes the patent, both directly and indirectly (i.e., by inducing its customers to infringe the patent, and/or by contributing to the infringing actions of its customers) by making, using, selling and offering to sell the transfection reagent known as FuGene 6.

FuGene 6 is a Roche product, and appears in the Roche Applied Science catalog. I'm not sure what the relationship is between Fugent and Roche, nor why Roche was not named in the lawsuit.

If you go to Mirus Bio website homepage, this is what you will see:

FuGENE® 6 Supply Problems?
Transfect with TransIT®-LT1
Achieve Comparable Performance
"TransIT-LT1 (MirusBio) has the same performance as FuGENE® 6 (Roche) in our comparison tests."
-The RNAi Consortium (TRC), Broad Institute of MIT and Harvard

Perhaps they are referring to the lawsuit when they suggest people will be having supply problems with FuGENE 6, and might need to switch to the Mirus Bio product TransIT-LT1.

Thanks to Docket Report from Docket Navigator for making me aware of the complaint.

Friday, September 9, 2011

University Sues Makers of Heart-Healthy Cookies

In a complaint filed September 7 in the Western District of Wisconsin, Brandeis University joins its exclusive licensee (GFA Brands) in suing a number of cookie companies, including Keebler, Famous Amos, Nestlé's and Pillsbury for infringing its patents directed towards methods of "Increasing the HDL Level in the HDL/LDL Ratio in Human Serum by Balancing Saturated and Polyunsaturated Dietary Fatty Acids." As an example, one of the asserted claims is claim 7 of US patent 5,843,497, which recites:

7. A prepared food product, comprising a cholesterol-free fat composition suitable for human or animal ingestion for increasing the HDL concentration and the HDL/LDL concentration ratio in the blood serum, comprising one part by weight polyunsaturated fat and at least one part by weight cholesterol-free saturated fat, where said fat composition comprises linoleic acid and at least one saturated fatty acid selected from the group including lauric acid, myristic acid, and palmitic acid, said linoleic acid constituting between 15% by weight and 40% by weight of the fat in said fat composition and said saturated fatty acid constituting between 20% and 40% by weight of the fat in said fat composition.

Thanks to Docket Report (a service of Docket Navigator) for making me aware of the complaint, which is available here.

One might question the University's decision to patent and exclusively license this discovery, and then proceed to join in a lawsuit against cookie manufacturers apparently employing the fruits of university research in an attempt to make healthier cookies. In an article I published a few years ago with Josh Sarnoff entitled Recent Developments Affecting the Enforcement, Procurement and Licensing of Research Tool Patents (available here), we discussed the policy behind the Bayh-Dole Act, which was primarily intended to increase access to, and the dissemination of, federally-funded University research.

Prior to buy Bayh-Dole, there was a sense that much of the fruits of University research was essentially left sitting on the shelf, due to insufficient incentives for the investment necessary to translate basic University research into useful commercial products. In order to increase the social benefit to be derived from federally funded University research, Bayh-Dole facilitated the ability of universities to patent and license discoveries coming out of such research. But, at least to my understanding, the primary policy justification was not to simply create profit centers for Universities, but rather to permit universities to license patented technologies to companies in the private sector who might only be willing to invest in the commercialization of these technologies if there was some patent protection in place. A good example would be a potentially useful pharmaceutical compound - without a patent in place, few companies would be willing to make the substantial investment the would be required to develop and bring to market a drug based on the compound.

In recent years, there has been much criticism of the manner in which some University technology transfer offices operate, and allegations that university patenting and licensing practices at times impede rather than promote dissemination of the fruits of federally funded University research. For example, in congressional hearings held to address the alleged problem of "gene patents," much of the testimony seemed to suggest that it was University patenting and licensing processes that were more problematic than gene patents per se. In an article I published on human gene patent litigation a few years ago (available here) I found that every gene patent litigation involving genetic diagnostic testing (which is the most controversial use of gene patents) involved gene patents arising out of University research.

In 2007, the trustees of the Association of University Technology Managers (AUTM) published a white paper entitled In the Public Interest: Nine Points to Consider and Licensing University Technology. Point 2 states in part that:

When significant investment of time and resources in a technology are needed in order to achieve its broad implementation, an exclusive license often is necessary and appropriate. However, it is important that technology transfer offices be aware of the potential impact that the exclusive license might have on further research, unanticipated uses, future commercialization efforts and markets. Universities need to be mindful of the impact of granting overly broad exclusive rights and should strive to grant just those rights necessary to encourage development of the technology.
In other words, University technology transfer offices are encouraged to only grant exclusive licenses in technology when a "significant investment of time and resources in a technology are needed in order to achieve its broad implementation." To the extent the patents are licensed exclusively, the University "should strive to grant just those rights necessary to encourage development of the technology."

In this case, the patented technology does not seem to be the type that required a significant investment of time or resources in order to be implemented, as evidenced by the large number of nonlicensed cookie manufacturers who are allegedly employing the suggested "balance of saturated and polyunsaturated dietary fatty acids" in their cookies, presumably in an effort to provide safer products for consumers.

One might question whether the decision of Brandeis University to exclusively license a patent covering these healthy products was the proper decision, or even whether this might be the sort of technology that would be better left unpatented, particularly if one views the University's primary mission as generating and disseminating useful discoveries such as this.

What Does Classen v. Biogen Mean for the Patent Eligibility of Diagnostics and Personalized Medicine?

In previous posts to this blog, I have discussed three important cases that pertain to the patent eligibility of inventions based on the discovery of medically useful correlations involving patient clinical data - Prometheus v. Mayo, Association for Molecular Pathology v. PTO (AMP) and Classen v. Biogen. Correlations of this type lie at the heart of diagnostics and personalized medicine, so the outcomes of these cases has important ramifications for the patent eligibility of these increasingly important technologies.

Classen v. Biogen was decided on August 31, 2012, so now we have Federal Circuit decisions on all three cases. None of the three cases is necessarily “over” - the Supreme Court has granted certiorari in Prometheus, the parties are petitioning the Federal Circuit for a rehearing of AMP, and the parties in Classen will have the opportunity to do the same. Still, it seems like an appropriate time to step back and assess where we are in light of these three important post-Bilski patent eligibility decisions.

In all three cases, the heart of the underlying invention was a clinically significant correlation between clinical data obtained from patients and a predicted medical outcome. In Prometheus, the inventor discovered a correlation between the level of drug metabolite in an individual patient's body and the optimal drug dosing regimen. In AMP, the inventor isolated the BRCA genes, thus providing a means for testing for the presence of variations in the gene correlated with the likelihood the patient will develop cancer. In Classen, the inventor discovered a correlation between immunization schedule (i.e., the timing at which vaccinations are given to a child) and the likelihood that the immunized patient will develop an autoimmune disorder.

The discoveries forming the basis of these three patents would all appear to be of substantial (and potentially life-saving) clinical significance, but the challenge for the inventor was how to draft a patent claim that would not only be valid, but would also be valuable, in the sense that it would provide meaningful protection from a competitor seeking to commercially exploit the discovery. Clearly, the inventors could have obtained very narrow claims that would be patent eligible, but such claims might be essentially worthless if competitors could easily design around them. Understandably, the inventors chose to claim their inventions in broad terms, which ultimately resulted in allegations that the claims are patent ineligible under 35 USC 101. Note that all three of the patents were drafted years ago, prior to Bilski and the recent tightening of the patent eligibility standard.

Now that all three cases have been decided by the Federal Circuit, we have learned that some of the claims have passed muster, while others have been invalidated for lack of patent eligibility. In Prometheus, the method claims were ruled patent eligible and upheld. In AMP, the diagnostic method claims were ruled patent ineligible and invalidated. And now in Classen, some of the method claims have been upheld, while others have been ruled patent ineligible. Is it possible to reconcile these decisions? I think the Classen majority does a poor job of explaining its decision, but that there are meaningful distinctions between the claims that have been deemed patent ineligible and those that have been deemed patent eligible, and in this article I will discuss those distinctions and attempt, to the extent possible, to reconcile the outcomes in three cases.

The Classen Majority Opinion Rests upon a Gross Misinterpretation of the Claim Language

The Classen claims held to be patent ineligible are essentially directed towards methods of evaluating immunization schedules (i.e., the timing of when immunizations are given to the patient, typically a child) in order to develop an immunization schedule that minimizes the risk of and autoimmunity disorder. Not surprisingly, many people do not like the patent claims, including the district court judge who heard the case at all the Federal Circuit judges who heard the case on appeal. The problem is, the claims explicitly recite a step of "immunizing mammals," which is inherently transformative, and under Prometheus would seem to require a strong presumption of patent eligibility.

The first time the Federal Circuit decided Classen (prior to the Supreme Court's Bilski decision's clarification of the role of the machine or transformation test in the analysis for patent eligibility), it completely ignored the explicit immunization step in the claims, and simply concluded that the claim is patent ineligible because it fails the machine or transformation test. The decision provided absolutely no explanation as to the rationale for ignoring a clearly transformative step, as discussed in a previous post to this blog.

The Supreme Court ordered the Federal Circuit to vacate its earlier decision and re-decide Classen in light of the Supreme Court's Bilski decision, which resulted in the August 31 decision. In this more recent decision, the majority does not ignore the immunization step, but instead grossly misinterprets it in a manner that seems to me entirely inconsistent with the express language of the claims.

The exemplary claim of the ‘283 patent, which was the focus of the court's patent eligibility analysis, recites in full:

1. A method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals, which comprises immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens, according to said immunization schedule, and comparing the incidence, prevalence, frequency or severity of said chronic immune-mediated disorder or the level of a marker of such a disorder, in the treatment group, with that in the control group.

In attempting to distinguish between this claim and other claims found to be patent eligible, the majority opinion states that "the immunizing in the ‘283 patent refers to the gathering of published data." But the court provides no explanation for how it arrived at its conclusiong that a relatively straightforward word like "immunize" actrually means "gathering published data” (a point raised by Judge Moore in their dissent).

The majority opinion goes on to state that Claim 1 of the '283 patent "is directed to the single step of reviewing the effects of known immunization schedules, as shown in the relevant literature." It also asserts that claim 1 "claims the idea of comparing known immunization results that are . . . found in the scientific literature." By reading the express "immunization" limitation of the claims, the court is able to simply conclude that the claims are directed towards methods of reviewing published data, which woif it were true clearly render the claims ineligible under Prometheus and AMP (i.e., if there actually was no immunization step).

In Prometheus, the Federal Circuit clearly stated that methods of treatment involving administration of drug to patient are inherently transformative because the body is transformed by the drug (and the drug itself is also typically transformed as it is metabolized), and this is clearly the case with respect to immunization of patients. In order to provide a meaningful and principled decision, it was incumbent upon the Federal Circuit to explain why it was that this clearly transformative step was nonetheless insufficient to render the claim patent ineligible. Unfortunately, the majority skirted this important point by reading the immunization step out of the claim. But in fact I think there is a plausible distinction between Classen's patent ineligible claim and the claims held to be patent eligible in Prometheus and Classen, and in the remainder of this article I attempt to articulate that distinction.

The Classen Claims Are Not Directed to Diagnostics or Personalized Medicine

Although the Classen decision is relevant to the patent eligibility of diagnostics and personalized medicine, it is important to point out that the purported inventions claimed by Dr. Classen do not fall into either category. Diagnostics and personalized medicine involve the use of physiological information pertaining to a particular individual patient to diagnose that patient for some clinically significant trait (such as a heightened likelihood of cancer), or discern the optimal therapeutic treatment for that patient (such as whether a particular drug is appropriate for that patient, or the optimal dosage for the patient). Significantly, true personalized medicine and diagnostic claims are directed towards methods of obtaining physiological information from a specific patient and applying that information to the medical treatment of that individual patient.

In contrast, the Classen claims are not directed towards methods of using individual patient data to diagnose or treat that patient. Instead, they are directed towards methods of comparing data derived from two groups of patients, i.e., a control group and a treatment group. This is not personalized medicine - in the words of Judge Moore, Classen is attempting to "claim a monopoly over the scientific method itself.” Classen's method does not involve using information relating to a specific patient to tailor the medical treatment of the patient, but instead involves using information relating to two cohorts of patients (a control group and a treatment group) to arrive at a generally applicable vaccination schedule.

Although none of Classen's claims are directed towards diagnostics or personalized medicine, some of the claims are directed towards methods of treating specific patient, and those claims were deemed patent eligible. This distinction between Classen's patent eligible and patent ineligible claims is clearly reflected in the preambles of the two exemplary claims analyzed by the court. Patent ineligible Claim 1 of the ‘237 patent is directed towards a "method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals." In contrast, the preamble of patent eligible Claim 1 of the ‘739 patent recites a "method of immunizing a mammalian subject."

In essence, the ’237 patent claims a method of assessing the safety of an immunization schedule applicable to "a treatment group of mammals." Even though the claim explicitly recites immunizing mammals, in the context of the claim the role of the immunization step is to provide data for evaluating an immunization schedule. In contrast, again in the context of the claim, the immunization step of Claim 1 of the ‘739 patent is directed towards the immunization of the specific mammalian subject (e.g., child) recited in the claims preempt all as the intended beneficiary of the claim. Although I don't believe this distinction was never raised by the Federal Circuit judges in their decisions, I think it is a significant distinction that might justify the disparate treatment of the two claims.

In Prometheus, the Federal Circuit basically voiced a policy of treating method of treatment claims as presumptively patent eligible. Fundamentally, the claims held to be patent eligible in Classen are directed towards methods of treating individual patients, while Classen's patent ineligible claims are directed towards methods of analyzing data derived from a group of patients to evaluate and optimize an immunization schedule. Significantly, the immunization schedule being evaluated is a general immunization schedule applicable to a population of patients, such as children, and hence is not diagnostic in nature. I think that if patient data from a specific patient was used to design an optimized immunization schedule for the individual patient, which would I think constitute a form of personalized medicine, the outcome might very well have been different.

When Can a Treatment Step Be Ignored?

In Prometheus, the Federal Circuit stated emphatically that a method of treating a patient with a drug is always transformative, since it transforms the patient's body, and in many cases the drug itself is transformed during the process, and seems to stand for the proposition that any method claim including a step of treating a patient with a drug should be deemed patent eligible. In particular, many of the claims in Prometheus include a step of administering a drug to patient, and the court held that this treatment step was independently sufficient to render the claims patent eligible.

As discussed above, the claims held to be patent ineligible in Classen explicitly recite a step of "immunizing a mammal," which is clearly a form of treatment that results in transformation of the patient's body. Judge Moore in dissent pointed out that this raises an apparent inconsistency; why is the clearly transformative treatment step in these claims insufficient to confer patent eligibility, while in Prometheus it was sufficient (and it was also sufficient in the case of the other Classen claims held to be patent eligible).

The majority dismisses the distinction by reading the "immunizing a mammal" step out of the claims, interpreting "immunized" to mean "gathering data," a clear misinterpretation of the claims as described above. However, there are meaningful distinctions between the treatment step in the patent eligible claims as compared to the patent ineligible claims, which I think arguably justifies the disparate outcomes.

In the patent eligible Classen claims, the immunization step is performed on the individual patient who benefits from the claimed method. Remember, the patent eligible claims are directed to methods of treating patients, and the claims explicitly recite the treatment step, i.e., immunization of the patient. I think that in general, under Prometheus and Classen, a claim directed towards a method of treating a specific patient with a drug will be deemed patent eligible, even if the inventive aspect of the claim is the use of a newly discovered correlation (or other relative information) that informs treatment decision.

Prometheus is a little closer to the edge, because, in the context of the claims, the purpose of the treatment step is to generate data which can be used to infer an optimal dosing regimen for the drug. In particular, the patient is treated with the drug, then the patient is tested for the level of drug metabolites in the body, and the level of drug metabolites is used to determine whether the dosage of the drug should be modified, either up or down. Significantly, the Prometheus claims do not recite a step of treating the patient once the correlation has been used to determine optimal drug dosage, which distinguishes the Prometheus claims from the patent eligible Classen claims, which do explicitly recite immunizing patients according to an improved immunization schedule

Still, I think the critical distinction between the patent ineligible Classen claims and the Prometheus claims is that in Prometheus the individual patient who is the subject of the claim, and the beneficiary of the information, is the same patient that was initially treated with the drug. The Prometheus decision stresses the significance of the fact that the method of treatment is tightly bound up with the overall purpose of the claim, and treats the claim as essentially directed towards a method of optimizing the treatment of an individual patient.

In contrast, the treatment (i.e. immunization) step in the patent ineligible Classen claims is applied to populations of patients (control group and subject group), and then the outcomes of those multiple treatments are used to evaluate a generally applicable immunization schedule, for the benefit of other patients. In the context of these claims, the patient's that are being treated are not the subject or beneficiary the claims, and treatment of individual patients is not the object of the claim. The objective the claim is merely to evaluate a general immunization schedule, and the immunization step is used to generate the data for this evaluation, not to use the improved immunization schedule in the treatment of patient.

In short, in the claims deemed patent eligible the method of treatment step is an integral part of a method claim whose overall goal is to optimize the treatment of the individual receiving the treatment step. In the patent ineligible claims, the treatment step is solely for the purpose of generating data to be used for the more abstract purpose of evaluating a generally applicable immunization schedule. I think the distinction between claims aimed at treating individual patients versus claims directed towards methods of analyzing data for the purpose of identifying medically significant correlations is crucial, and perhaps explains the outcomes in these cases.

When Can a Data Acquisition Step Be Ignored?

In Prometheus, some of the claims did not include a treatment step (i.e., these claims did not explicitly recited administering a drug to a patient), but the Federal Circuit held that even the claims lacking a treatment step were patent eligible because they included a step of "determining" the amount of drug metabolite in the patient's body, and the court held that the determining step inherently involves a physical transformation, and thus constitutes an independent and sufficient basis for patent eligibility under Bilski. The court emphasized that determining drug metabolite levels in a patient's body inherently requires substantial transformative steps, such as physically removing and isolating a sample from the body, and using analytical devices and physically manipulative laboratory processes to make the determination.

Under this rationale, I think it is clear that a method of genetic diagnosis claim that actually requires the analysis of DNA molecules (as opposed to DNA sequence information) inherently involves physically transformative analytical techniques that would necessarily render the claim patent eligible. In AMP, the court explicitly found that the patent ineligible method claims did not require the analysis of DNA molecules, but could be infringed by the mere analysis of genetic information, which explains why the claims were found patent ineligible. If the claims had inherently included a step of physically analyzing DNA molecules (which Myriad argued unsuccessfully was the correct interpretation of the claims), I think the claims should have been, and would have been found patent eligible by the Federal Circuit.

In the Classen claims found to be patent ineligible, the data acquisition step in the claim can be satisfied by merely "comparing the incidence, prevalence, frequency or severity of [a] chronic immune-mediated disorder” in groups of patients that had already been immunized. This determination step does not inherently require the use of transformative analytical processes; one does not necessarily need to use transformative analytical techniques in order to determine whether a patient has developed a chronic immune-mediated disorder. This is I think what the Classen majority was getting at when it complained that the ‘283 patent "claims the idea of comparing known immunization results that are . . . found in the scientific literature. "While the Prometheus claims require the use of transformative analytical methodology to determine the level of drug metabolites, the comparison step in the Classen claim can be satisfied by simply reviewing the incidence of immune-mediated disorders in patients who have been immunized.

How Integral Is a Transformative Step to the Purpose of the Claim?

All of the claims found to be patent eligible in Prometheus and Classen include a transformative step that is central to the purpose of the claim. In Prometheus, all of the claims include a step of determining the level of drug metabolite in a patient's body. Not only is the step transformative, but the purpose behind the step is in furtherance of the claimed method. In other words, the reason a diagnostic test is being performed to determine drug metabolite level is for the purpose of applying the correlation embodied in the claim to determine the optimal drug dosage. Similarly, in the patent eligible Classen claims, the transformative treatment step (immunizing the patient) is integral to the purpose of the claim, which is to immunize the patient according to a safer immunization schedule.

In contrast, in the patent ineligible Classen claim, the "comparing" step is not necessarily transformative, and the "immunizing" step, while clearly transformative of the patient, is not integral to the purpose of the claim. In practice, the patients who are being immunized are doing so for the purpose of obtaining immunity to disease, not for the purpose of generating data for evaluating and immunization schedule. The immunization of these patients is an event that occurs independently of the purpose of the method claim, and would occur regardless of whether or not someone was going to come around later and determine the incidence of autoimmune-mediated disorders that arise in the patients. This is what the majority is getting at I think when it repeatedly asserts that the claims are infringed by someone merely reviewing published data.

As a practical matter, people are immunized for the purpose of obtaining immunity against some disease, and then some level of autoimmune-mediated disorder occurs. This all happens independently of Classen's claimed method. What Classen's claimed method does is analyze this data in order to evaluate the efficacy of immunization schedule used. I think this disconnect between the transformative step and the practical objective of the claimed method likely contributed to the finding of patent eligibility.

The Importance of Specificity

Another attribute of the ‘283 claim that might have contributed to the finding of patent eligibility is a relative lack of specificity. In a previous blog post, I pointed to specificity (or lack thereof) as the most plausible distinction between the claims found patent eligible in Prometheus, compared to the claims found to be patent ineligible in In re Grams (an older case cited with approval in Prometheus). In Prometheus, the Federal Circuit emphasized that the claims at issue recite methods in which correlations between drug metabolite level and optimal dosage are used in "the treatment of a specific disease by administering specific drugs and measuring specific metabolites." In contrast, in Grams the claim found to be patent ineligible was not limited to any particular clinical test, nor to any particular drug.

In Classen, the claims deemed patent eligible are directed towards methods of immunizing a particular "mammalian subject," and specifically recite a step of immunizing the patient. In contrast, the patent ineligible claims recite a "method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals." No particular patient is treated, and the data that is analyzed for determining the immunization schedule is collected from two distinct groups of patients, not an individual patient. Moreover, as complained of by Judge Moore, the claim is not limited to any specific immunogen or any specific immune-mediated disorder.

Patent Eligibility as a Wildcard

In my view, patent eligibility is essentially a doctrinal wildcard that a court can use to dispose of a patent claim deemed unworthy of patent protection; Judge Rader has made the same statement with respect to the Lilly written description requirement. Classen appears to be an example of a court using patent eligibility to dispose of some claims that many people would deem inappropriate, without having to resort to the more established and principled doctrines of patentability.

Because there is no coherent standard for what constitutes patent eligibility, a court faced with claims it doesn't like can pretty easily dispose of them by simply concluding that they are patent ineligible. This is particularly the case where, as was done here, the court misinterprets the claims and ignores explicit claim limitations. Unfortunately, in taking this route court denies the public a rational explanation as to exactly why the claims were deemed patent ineligible, which harms the predictability and coherency of the law.

Where Do We Stand Now?

Now that Classen, Prometheus, and AMP have all been decided by the Federal Circuit, where do we stand with respect to the patent eligibility of personalized medicine diagnostics? I think that with respect to a method claim that recites a physically transformative data acquisition step targeting a specific patient, such as measuring the level of drug metabolite in the patient's body, or analyzing the patient's DNA molecules (as opposed to mere DNA sequence information) for genetic variations, and the data acquired is used in the diagnosis or treatment of that patient, the claim will be deemed patent eligible.

Furthermore, if a method claim recites a physically transformative treatment step directed towards a specific patient, such as administering a specific drug to a patient, or immunizing a patient with a specific vaccine, and the specific patient being treated is the intended beneficiary of the claim process, the claim will likewise be patent eligible. For example, if a claim dictates that a patient be given a particular drug based on the outcome of a genetic test of that patient, the claim should be patent eligible.

However, if the claim lacks any physically transformative step, as was the case with respect to the method of diagnosis claims found to be patent ineligible in AMP, the claim will be found patent ineligible for claiming nothing more than mental processes. Even a claim with a physically transformative step might be found patent ineligible if the claim is not sufficiently specific, such as was the case in In re Grams. Or if the physically transformative step is not integral to the purpose of the claim, as was the case in the patent ineligible Classen claims, they also will be in danger of being ruled patent ineligible.

Overall, inventors of diagnostics and personalized medicine should still be able to claim their inventions, as long as they include an integral physically transformative step. It remains an open question, however, if inclusion of such a step will render the claims too easy to avoid, as Myriad argues in its recent amicus filings in the divided infringement cases to be heard shortly by the Federal Circuit, as discussed on a previous post to this blog.

Monday, August 15, 2011

AMP v. PTO Does Not Appear to Invalidate Very Many Gene Patent Method Claims

In this post, I explain why my recent analysis of 533 patents identified by Jensen and Murray as "gene patents" (described in a previous post) suggests the Federal Circuit’s recent decision in AMP v. PTO implicates the validity of very few gene patent method claims.


As I pointed out in a blog post last December, the patent eligibility of Myriad's claims to methods of detecting mutations in the BRCA gene by "analyzing" or "comparing" DNA sequences hinged entirely on the court's interpretation of the word "sequence" as it appears in the claims. In the field of molecular biology, the term "sequence" is routinely used not only to refer to the description of the chemical structure of a DNA molecule, but also to the actual DNA molecule as well.

For example, a scientist might say that "I determined the sequence of the BRCA gene." In this context, she is using the word sequence in reference to the abstract description of the order of nucleotides appearing in the gene. But the same scientist might also say that "I cloned the BRCA sequence into an expression vector," in which case she is using the term "sequence" to refer to the DNA molecule itself.

In the first example, "sequence" refers to abstract information describing a chemical structure, while in the second "sequence" is used to refer to a physical object, i.e., a specific DNA molecule. Molecular biologists are usually not bothered by the dual meaning of "sequence," because in practice the meaning of the term is understood based on the context in which it is used. However, it can lead to ambiguity, as seen in AMP v. PTO.

In AMP v. PTO, Myriad argued that as used in its claims the term "sequence" refers to an actual DNA molecule, and thus that analyzing or comparing "sequences of the BRCA gene" would involve physically manipulating and processing molecules in a manner that would render the claims patent eligible under Prometheus. I think it is clear that if the court had adopted this interpretation of "sequence" it would have upheld the validity of the claims. The ACLU plaintiffs never argued that a method claim that requires the analysis of physical DNA molecules would be patent ineligible.

Instead, as explained in a previous post, the ACLU's case was based on its argument that the term "sequence" in the claims refers to information, not to a physical molecule, and hence would cover the mental activity of analyzing or comparing genetic information. The court adopted the ACLU's interpretation of "sequence,” and ruled the claims patent ineligible for claiming nothing more than a mental step. This outcome was specifically dictated by the Federal Circuit’s earlier Prometheus decision, where it stated that a claim directed only to mental analysis of information is patent ineligible.

The Federal Circuit based its interpretation of “sequence” on its finding that Myriad's patent specifications implicitly defined “sequence” broadly to cover pure information, as set forth in this excerpt from the case:

The patent specifications make clear that “sequence” does not exclusively specify a DNA molecule, but refers more broadly to the linear sequence of nucleotide bases of a DNA molecule. For example, Figure 10A–10H is described as showing the “genomic sequence of BRCA1.” ′473 patent col.5 l.66. Figure 10 does not show a physical DNA molecule; the figure lists a series of letters (Gs, As, Ts, and Cs) corresponding to the nucleotides guanine, adenine, thymine, and cytosine of a DNA molecule. Similarly, the patent specifications state that “[t]he nucleotide sequence for BRCA1 exon 4 is shown in SEQ ID NO: 11.” Id. col.53 ll.50–53. SEQ ID NO: 11 again lists a series of Gs, As, Ts, and Cs corresponding to the nucleotide sequence of BRCA1 exon 4.

Thus, Myriad’s claims might very well have been found patent eligible if the specification had defined the term "sequence" to refer only the DNA molecule itself. Alternatively, the claim probably would have been found patent eligible if it recited analyzing "DNA molecules" instead of analyzing sequences. If the claims could only be infringed by someone who physically analyzes the DNA molecule, it would certainly be patent eligible under the Federal Circuit's interpretation of Bilski as set forth in Prometheus.

Claims that could be infringed by merely analyzing genetic data appear to be rare in Jensen and Murray dataset

In essence, Myriad’s method claims were patent ineligible because, as interpreted by the court, they could be infringed by analysis of genetic information. However, my research suggests that few if any of the gene patents identified by Jensen and Murray fall into this category. To the contrary, the vast majority of the claims in these patents would appear to be patent eligible.

Of the 533 patents I analyzed in my study, I only found 12 that included a claim reciting a method of analyzing a DNA sequence for a mutation or variation, and most if not all of those claims appear to require a physical manipulation of a patient's DNA in order for there to be infringement.

In 8 of the 12 patents (6,395,482; 6,087,107; 6,458,541; 6,743,579; 5,830,649; 5,840,486; 5,955,265; and 6,410,226) the broadest claims specifically require obtaining a sample from a patient's body, or analyzing for the genetic variation directly in a patient's body.

For example, Claim 1 of US patent number 6,395,482 recites:

1. A method for determining susceptibility in a human subject to schizophrenia wherein the method comprises the steps of:

(a) removing a bodily sample from the subject, wherein the sample comprises a polynucleotide sequence of a PRODH gene;

(b) determining whether the PRODH gene of the bodily sample comprises a DNA sequence comprising a variation in SEQ ID NO:1 consisting of a T to C transition in the first position of codon 497, such that the presence of said variation in said PRODH gene is indicative of said subject's susceptibility to schizophrenia.
These eight claims would all appear to be patent eligible under AMP and Prometheus because they all involve physically manipulating a human sample obtained from patient.

The remaining four of the 12 patents (5,916,748; 6,630,304; 5,989,815; 6,432,644) are a little more ambiguous, and do not explicitly recite obtaining or analyzing a bodily sample. But arguably all of these claims do require physical manipulation of a sample, depending upon how a court interprets the claim, which will depend in part on how the claim terms were used in the patent specification

For example, Claim 1 of 6,432,644 recites:

1. A method for diagnosing the presence of a polymorphism in human KCNE1 (the coding region of which is bases 193-579 of SEQ ID NO:3) which causes long QT syndrome wherein said method is performed by means which identify the presence of said polymorphism, wherein said polymorphism is one which results in the presence of a KCNE1 polypeptide of SEQ ID NO:4 with an altered amino acid, said altered amino acid being selected from the group consisting of: a) a Leu at residue 74.
Note that this claim uses "means plus function" language, and would probably be interpreted to only cover means for identifying polymorphisms (a polymorphism is a genetic variation) that are described in the specification. If the only means for identifying polymorphisms described in the specification rely on physically analyzing DNA molecules, the claim would appear to be so-limited and thus patent eligible.

Similarly, Claim 1 of 6,630,304 recites:

1. A method of diagnosing a susceptibility to osteoporosis in an individual, comprising detecting a polymorphism in a human BMP2 gene of SEQ ID NO: 1, wherein the presence of a "T" at nucleotide position 11980 is indicative of a susceptibility to osteoporosis, compared with an individual having an "A" at nucleotide position 11980.
This claim refers to detecting a genetic variation in a "gene," as opposed to a "sequence" (the language used by Myriad). If a court were to interpret the claim limitation "detecting a polymorphism in the gene" as requiring actual analysis of a DNA molecule (which could depend upon how the term "gene" is using the specification), the claim would appear to be patent eligible. However, if the claim is interpreted to encompass detecting a polymorphism by analyzing genetic sequence data, it would appear to be patent ineligible.

Monday, August 8, 2011

Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing the Myth That 20% of the Human Genome Is Patented

I am in the process of finalizing an article entitled “Will Gene Patents Impede Whole Genome Sequencing?: Deconstructing the Myth That 20% of the Human Genome Is Patented,” which I think many readers of this blog will find of interest, particularly in light of the recent decision in the Myriad a gene patent case (AMP v. PTO). I will be presenting my work this Thursday at the Intellectual Property Scholars Conference at Depaul Law school in Chicago, and have posted a working draft on SSRN.

In my article, I point out that there is a widely held perception that 20% of human genes are "patented," and that these patents preclude researchers and clinicians from using, studying or even "looking at" the patented genes without obtaining a license or risk being sued for patent infringement. In recent years the basis for this belief has increasingly become obscured.

For example, in AMP v. PTO Judge Lourie states that it “is estimated that . . . By 2005, [the PTO] had granted 40,000 DNA-related patents covering, in non-native form, twenty percent of the genes in the human genome.” In support of this assertion he cites to a law review article: J. Rogers, Can You Patent Genes? Yes and No, 93 J. Pat. & Trademark Off. Soc’y 19, 40 (2010). If you read the article by Rogers, you see that he cites to other secondary sources for the proposition that 20% of human genes are patented. Ultimately, if you trace the string of references back to their primary source, one arrives at the seminal article by Kyle Jensen & Fiona Murray: Intellectual Property Landscape of the Human Genome, 310 Science 239 (2005).

It is no surprise that Judge Lourie believes that 20% of human genes are “patented” - over the years the figure has been quoted so often in so many venues that it has become something of an urban legend. Oftentimes the statement that 20% of human genes are patented is made without any supporting reference (for example, this occurred in a recent article published in Science entitled: The Human Genome (Patent) Project). Other authors, such as Judge Lourie, cite to various secondary sources that parrot the conventional wisdom. But if you trace back through the citations, invariably you will find that the sole basis for the myth that 20% of human genes are patented is the 2005 Science article by Jensen and Murray.

Believing that 20% of human genes are patented, and that a patented gene is effectively off-limits, many have become concerned that whole genome sequencing will result in the infringement of hundreds or even thousands of patents. This specific point was made by Judge Bryson in his dissent to AMP v. PTO. During oral arguments, he asked Myriad's attorney whether Myriad's isolated DNA sequence claims would be infringed by personal whole genome sequencing, to which the attorney essentially responded "no" (the ACLU attorney later voiced his opinion that the patents would cover genome sequencing).

Later during oral arguments, Judge Bryson expressed his concern that whole genome sequencing could result in infringement of thousands of gene patents. His perception that isolated DNA claims create a thicket of patents that will impede personal whole genome sequencing might have contributed to his view that these claims should be declared patent ineligible.

In fact, a careful reading of the supporting online material for the Jensen and Murray article reveals that their study has been grossly misinterpreted by those who claim the 20% of human genes are patented. In fact, those authors only purported to show that, with respect to 20% of human genes known at the time they conducted their study, either (1) the DNA sequence of the gene, or (2) the amino acid sequence encoded by the gene, was mentioned in a US patent claim. The myth that 20% of human genes are “patented” has taken root because too many have incorrectly inferred that the mere “mention” of a gene in a patent claim precludes all uses of the gene.

To better understand the actual implications of Jensen and Murray’s findings, I analyzed the claims from a random sampling of 533 of the 4270 patents identified in their article as “gene patents.” (Jensen and Murray graciously provided me with the entire data set of patents identified in their study). Significantly, I found that, under any reasonable interpretation, 140 of the 533 patents would not be infringed by any form of genetic testing. In fact, many of these patents only claim proteins, or recombinant cells, or methods for using DNA that have nothing to do with DNA sequencing. The implicit assumption that the “gene patents” identified by Jensen and Murray cover all uses of the gene (or in some cases corresponding protein) mentioned in the patent claims is clearly false.

The remaining 393 patents include claims with respect to which I cannot entirely rule out the possibility that at least some form of genetic testing would be found infringing. These claims fall into two categories - products claims directed to polynucleotides (e.g., DNA molecules), and method claims that might cover at least some forms of genetic testing. The language used in these claims is extremely heterogeneous, and it is impossible to predict with any certainty exactly how broadly a court would interpret their scope if they were ever asserted in litigation, but to varying degrees a majority of these patents would appear not to be infringed by at least some, perhaps all, forms of genetic testing.

Perhaps most significantly, few (if any) of these patents would appear likely to be infringed by next-generation whole genome sequencing technologies, particularly those that do not require DNA amplification.

In short, there is absolutely no basis to infer from the Jensen & Murray article that 20% of human genes are off-limits to the patents, nor that whole genome sequencing, and other multiplex genetic diagnostic testing technologies, would result in the infringement of a large number of human gene patents. To the contrary, it appears that a vast majority of these patents were drafted in a manner that would not encompass whole genome sequencing.

Monday, August 1, 2011

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.

Saturday, July 30, 2011

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.

Thursday, July 28, 2011

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.

Sunday, July 24, 2011

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.

Thursday, July 14, 2011

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.

Monday, July 11, 2011

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.

Wednesday, June 1, 2011

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.