Today a panel of the Federal Circuit issued a decision in Prometheus v. Mayo, an important case involving the application of the patent eligibility doctrine to biotechnology, and more particularly molecular diagnostic testing and personalized medicine. I have discussed this case in numerous previous blog posts, see for example here.
Background
In a nutshell, the case involves claims directed towards methods for optimizing the amount of drug administered to a specific patient, an example of personalized medicine. The claims are limited to certain categories of thiopurine drugs used to treat immune-mediated gastrointestinal disorders such as Crohn's disease, the use of which is often accompanied by serious adverse side effects, including hepatotoxicity. Because different patients metabolize the drug differently, it had been difficult for doctors to ascertain the proper dosage, and some doctors had reportedly been hesitant to prescribe the drugs at all for fear of toxic side effects.
The challenged claims are directed towards methods that all comprise a step of determining the level of thiopurine drug metabolite in a patient sometime after administering the drug to the patient, and based on the result of that determination recognizing that the dosage of drug administered to the patient should be increased or reduced, i.e.,a determination that the level of drug metabolite exceeds a certain threshold would indicate that the dosage should be decreased, and vice versa. Many of the claims also explicitly recite a step of administering the drug to the patient.
A district court judge, in an opinion clearly influenced by Judge Breyer's provocative dissent in LabCorp, held the claims patent ineligible for allegedly wholly preempting a "natural phenomenon." In its analysis, the judge dismissed the steps of administering drug and determining drug metabolite level as mere "data-gathering steps," irrelevant to the patent eligibility of the claim.
The case was appealed to the Federal Circuit, but before the appeal was decided the Federal Circuit issued its en banc In re Bilski decision (Bilski I) which held the machine or transformation test to be the definitive test for patent eligibility of method claims.
On appeal the Federal Circuit panel reversed and held that the Prometheus claims satisfied applied the newly minted Bilski machine or transformation test. In particular, the panel held that the steps of administering drug to the patient and determining drug metabolite level were both inherently and independently sufficient to satisfy the transformation prong of the machine or transformation test. In contrast with the district court, which dismissed these steps as mere data-gathering, the Federal Circuit characterized the administering and determining steps as central to the purpose of the claim and thus relevant to the question of patent eligibility.
But shortly thereafter, in Bilski v. Kappos (Bilski II), the Supreme Court overturned Bilski I to the extent that it had characterized the machine or transformation test as the definitive test for patent eligibility, and reiterated that the sole and fundamental test for patent eligibility is whether the claim "patents" a fundamental principle, i.e., laws of nature, physical phenomena and abstract ideas. The Supreme Court then vacated the Federal Circuit's decision in Prometheus v. Mayo and remanded the case to the Federal Circuit to decide in a manner consistent with Bilski II.
Today's Post-Bilski II Prometheus Decision
Today's Federal Circuit decision on remand comes to the same conclusion as the first, reversing the district court and holding all of the challenged claims to be patent eligible. The court's analysis is also virtually identical to the original decision, focusing primarily on the transformative nature of the administering and determining steps.
It is important to bear in mind that while Bilski II rejected the notion that the machine or transformation test is the only test for patent eligibility of method claims, it did acknowledge that the machine or transformation test is in many instances highly probative of the fundamental inquiry. Significantly, the Supreme Court did not offer up any other alternative test for determining whether a claim "patents a fundamental principle." As noted by the en banc Federal Circuit in Bilski I, as a practical matter it can be extremely difficult to apply this fundamental test to actual claims, which is why the Federal Circuit tried to institute the use of a definitive machine or transformation test as a more objective and easier to administer proxy for the ultimate inquiry. As a practical matter of expedience, I have predicted that the courts and PTO will continue to rely heavily on the machine or transformation test post-Bilski II.
In today's decision, the Federal Circuit panel pointed out that under Bilski II the scope of patent eligible subject matter remains quite broad, and that while fundamental principles are not patent eligible "particular applications" of fundamental principles are. Applying this standard, the panel held that Prometheus' claims do not preempt the correlations between drug metabolite level and optimal dosage, but rather utilize them in "the treatment of a specific disease by administering specific drugs and measuring specific metabolites."
The panel also emphasized the continuing relevance of the machine or transformation test, pointing out that the Supreme Court had characterize it as a "useful and important clue, an investigative tool" for determining patent eligibility. It then came to the same conclusion as it did in its pre-Bilski II decision, finding that both the administering and determining steps were each inherently and independently sufficient to confer patent eligibility on the claims. In view of this determination, the panel found it unnecessary to address the question of whether the claims satisfy the machine prong of the test.
The panel emphasized that if the claims had not included a step of administering a drug or determining the level of drug metabolite, but had merely recited recognizing the correlation between drug metabolite level and the desirability of modifying the dosage (i.e., the "wherein" clauses of the claims), then the claims would have been patent ineligible for claiming nothing more than "mental steps." But by including a step of administering a drug and/or determining the level of drug metabolite, transformative steps which are "central to the purpose" of the method, the claim is rendered patent eligible.
In effect, Bilski II had essentially on effect on the outcome of the Prometheus appeal. Fortunately, the Supreme Court decided Bilski II in a manner allows a great deal of discretion for the Federal Circuit and lower courts. This panel of the Federal Circuit clearly sees the importance of permitting the patenting of diagnostic methods and methods of treating patients with drugs, and sought to maintain their patent eligiblity by emphatically establishing that method claims reciting a step of administering a specific class of drugs to a patient, or of performing a molecular diagnostic test of the patient, are patent eligible per se.
However, the panel is also emphatic that claims that could be potentially infringed by merely thinking about or recognizing a physiological correlation cannot be patented, a hypothetical scenario that some critics of gene patents and patents on diagnostic tests often point to.
The one aspect of the decision that I found less than entirely convincing was the panel's attempt to distinguish over the holding in In re Grams, a 1989 Federal Circuit decision. Grams was a case involving the patent eligibility of claims reciting methods that basically involved (1) performing a clinical diagnostic test on an individual patient, and (2) applying an algorithm to the data generated by the test in order to determine whether an abnormality exists, and possible causes of the abnormality. In Grams, the data-gathering steps were disregarded in the court's patent eligibility analysis, and the claims held patent ineligible for "in essence" claiming nothing more than a patent ineligible algorithm.
In a sense, the Grams claims are highly analogous to the Prometheus claims. The determining step in the Prometheus claims involves nothing more than performing a clinical diagnostic tests on individual patient, and the step of using the results to determine whether drug dosage should be altered is nothing more than a simple algorithm. According to the Prometheus panel, the distinction lies in the fact that in Grams the "essence" of the claimed process is the algorithm, and that the Gram patent "focused only on the algorithm rather than a clinical test." I'm not sure how convincing this distinction is, perhaps the panel could have been more straightforward and acknowledged the tension between Grams and Prometheus.
However, I have read the Grams decision and think a plausible distinction is that the Prometheus claims are limited to diagnostic tests for a limited number of specified of drug metabolites, while in Gram the claim appears to broadly encompass any of a host of clinical tests to which the algorithm could be applied. This suggests that if the Prometheus claims had been drafted more broadly to encompass any drug and drug metabolite, rather than being restricted to specific classes of thiopurine drugs, the claims could have been found patent ineligible. In effect, the distinction between the Grams and Prometheus claims is a matter of claim scope, something I think would be better addressed using the enablement requirement rather than patent eligibility, as I argued in the amicus brief I filed with Robert Cook-Deegan in the Myriad gene patent case.
Finally, what are the implications of today's Prometheus decision for the patent eligibility of the genetic diagnostic method claims at issue in the Myriad gene patent case (Association for Pathology v. US Patent and Trademark Office)? Today's decision does not alter my previous prediction, which is that the outcome will depend upon how the Federal Circuit interprets the scope of Myriad's patent claims. If the Federal Circuit adopts the ACLU's broad interpretation the claims (which is the interpretation the district court judge accepted for his analysis), pursuant to which the claims broadly cover the purely mental process of analyzing genetic information, then under Prometheus I believe the claims must be found patent ineligible. Alternatively, if the Federal Circuit adopts Myriad’s interpretation of its claims, under which the claims are limited to methods that involve physically isolating and analyzing DNA molecules, I think under Prometheus the claims should be found patent eligible by virtue of comprising a transformative step (highly analogous to the administering step in the Prometheus claims) central to the purpose of the claimed methods.
Friday, December 17, 2010
Tuesday, December 7, 2010
The American Medical Association et al. File Amici Brief Arguing for Affirmance of AMP v. PTO
An amici brief was filed yesterday by Professors Lori Andrews and Joshua Sarnoff on behalf of the American Medical Association, American Society of Human Genetics, American College of Obstetricians and Gynecologists, American College of Embryology, and the Medical Society of the State of New York, arguing for affirmance of the district court's decision in AMP v. PTO. Professor Andrews has for years been one of the most outspoken critics of gene patents, and was involved with a bill introduced in Congress in 2007 that if enacted would have broadly prohibited the patenting of DNA-based inventions.
Their brief is more alarmist than the brief submitted by the ACLU/PubPat, arguing that gene patents have cost patient's their lives, and the healthcare system billions of dollars. For example, allege that gene patents are being asserted against physicians across the country, and that physicians have to worry about infringing patents based on nothing more than mere "conscious thoughts." They also contend that gene patents are killing patients. For example, they state that drug companies have used these patents to prevent use of genetic testing to determine whether a drug will help or harm patients, to block the availability of genetic testing (which they allege resulted in the of a 10-year-old patient), and to force patients to use poor quality diagnostic tests rather than improved alternatives (which they allege resulted in a patient undergoing unnecessary removal of ovaries based on erroneous BRC genetic test result).
The AMA et al. adopt a very broad definition of the diagnostic method claims, under which they would be infringed by anyone merely "reading and thinking about the sequence data disclosed in the patent." As discussed in a previous post, this is a much broader interpretation of the claims than Myriad has proffered.
They also argue that patents are not necessary to incentivize the discovery of genetic mutations correlated with disease or the commercialization of diagnostic testing based on these discoveries, citing to the Sec.'s Advisory Committee on Genetics, Health and Society (SACGHS) Report.
In the amici brief submitted by me and Robert Cook-Deegan, we argued that regardless of whether patents are necessary to incentivize the development of genetic diagnostic testing for Mendelian traits, in which mutations in a single gene are highly correlated with a specific disease, they quite likely will be necessary for the optimal development of next-generation genetic diagnostic testing involving much more complex relationships and multiple genes, or if FDA imposes heightened regulation on diagnostic testing. We also argued that a decision broadly rendering gene patents patent ineligible could have serious unintended negative consequences for biotechnology, particularly outside the realm of Mendelian genetic diagnostic testing, and that there are other more focused approaches for dealing with problematic gene patents or gene patent enforcement activities. The AMA brief does not address these points, but rather seems to assume that the only available mechanisms for dealing with problems associated with gene patents is a broad prohibition extending far beyond Myriad and BRCA testing.
Their brief is more alarmist than the brief submitted by the ACLU/PubPat, arguing that gene patents have cost patient's their lives, and the healthcare system billions of dollars. For example, allege that gene patents are being asserted against physicians across the country, and that physicians have to worry about infringing patents based on nothing more than mere "conscious thoughts." They also contend that gene patents are killing patients. For example, they state that drug companies have used these patents to prevent use of genetic testing to determine whether a drug will help or harm patients, to block the availability of genetic testing (which they allege resulted in the of a 10-year-old patient), and to force patients to use poor quality diagnostic tests rather than improved alternatives (which they allege resulted in a patient undergoing unnecessary removal of ovaries based on erroneous BRC genetic test result).
The AMA et al. adopt a very broad definition of the diagnostic method claims, under which they would be infringed by anyone merely "reading and thinking about the sequence data disclosed in the patent." As discussed in a previous post, this is a much broader interpretation of the claims than Myriad has proffered.
They also argue that patents are not necessary to incentivize the discovery of genetic mutations correlated with disease or the commercialization of diagnostic testing based on these discoveries, citing to the Sec.'s Advisory Committee on Genetics, Health and Society (SACGHS) Report.
In the amici brief submitted by me and Robert Cook-Deegan, we argued that regardless of whether patents are necessary to incentivize the development of genetic diagnostic testing for Mendelian traits, in which mutations in a single gene are highly correlated with a specific disease, they quite likely will be necessary for the optimal development of next-generation genetic diagnostic testing involving much more complex relationships and multiple genes, or if FDA imposes heightened regulation on diagnostic testing. We also argued that a decision broadly rendering gene patents patent ineligible could have serious unintended negative consequences for biotechnology, particularly outside the realm of Mendelian genetic diagnostic testing, and that there are other more focused approaches for dealing with problematic gene patents or gene patent enforcement activities. The AMA brief does not address these points, but rather seems to assume that the only available mechanisms for dealing with problems associated with gene patents is a broad prohibition extending far beyond Myriad and BRCA testing.
Monday, December 6, 2010
Myriad and the ACLU Disagree over Claim Scope, But Apparently Not over Patent Eligibility of Genetic Diagnostic Methods
After reading the briefs submitted by Myriad and the ACLU/PubPat in AMP v. PTO (the challenge to Myriad’s gene patents, described in previous posts to this blog), one thing that struck me was that the parties do not appear to disagree over the patent eligibility of genetic diagnostic methods. In fact, with respect to these method claims, the only dispute is with respect to the proper interpretation of the claims.
The challenged diagnostic method claims recite processes of either "analyzing" or "comparing" nucleotide sequences. For example, claim 1 of US patent number 6,033,857 claims:
Myriad argues for a relatively narrow interpretation of the claims, under which the claims are limited to methods which require actual physical analysis of DNA molecules. Under their interpretation, the term "nucleotide sequence," as used in the claims, refers to actual polynucleotides, i.e., DNA or RNA molecules, and the step of comparing these molecules necessarily requires physically isolating polynucleotides from a patient's tissue sample, and then processing and analyzing the molecules. Myriad argues that these processes are all clearly transformative of physical molecules, and because the transformations are “central to the purpose of the claims,” the claims satisfy the machine or transformation test. They cite to Prometheus for the proposition that transformative steps that are central to the purpose of the claims cannot be disregarded in the analysis as mere "data-gathering steps,” and argue these transformative steps render the claim patent eligible.
The ACLU, on the other hand, argues for a much broader interpretation of the method claims. They argue that the term "nucleotide sequence" in the claims refers to sequence information, not to molecules, and that the claims cover the purely mental process of "comparing" or "analyzing" DNA sequence information. Under this broad interpretation, the claims clearly do not require any sort of physical transformation, and on this basis the ACLU argues they fail the machine or transformation test, which they correctly note remains "a useful and important clue" to patent eligibility (using the language of the Supreme Court).
Interestingly, the ACLU never suggests in their brief that the diagnostic method claims would be patent ineligible if limited to methods involving actual isolation and processing of DNA molecules, i.e., the only processes covered by the claims under Myriad's interpretation of the claims. Conversely, Myriad never argues that a method claim that encompasses purely mental processes for comparing DNA sequence information would be patent eligible. Thus, both parties seem implicitly to agree on a consensus approach under which a claim directed toward a genetic diagnostic method is patent eligible if limited to diagnostic methods that involve actual isolation and manipulation of DNA molecules, but patent ineligible if the claim would also cover merely comparing DNA sequence information.
Notably, the district court adopted the ACLU's broad interpretation of the claims, and held that the claims cover a process of comparing or analyzing DNA sequence information. However, in dicta the district court went even further, stating that "[e]ven if the challenged claims were read to include the transformations associated with isolating and sequencing human DNA, these transformations would constitute no more than ‘data-gathering step[s]’ that are not central to the purpose of the claimed process.. . . . Consequently, even if the method claims-in-suit were construed to include the physical transformations associated with isolating and sequencing DNA, they would still fail the ‘machine or transformation’ test under Section 101 for subject matter patentability."
In my analysis of the district court decision, I pointed out that this dicta seems clearly wrong, and is inconsistent with the Federal Circuit's decision in Prometheus. Clearly, these data-gathering steps are central to the purpose of the claim and should be included in the machine or transformation analysis. I suspect that the ACLU agrees with my assessment, and is not even trying to argue for more extreme position taken by the district court.
It seems to me that the implicit consensus between Myriad and the ACLU is correct, i.e., method of genetic diagnostic claims are patent eligible if they include steps involving the actual physical manipulation of DNA molecules, but patent ineligible if they would cover the wholly mental process of analyzing DNA sequence information.
As a side note, another point of contention regarding claim interpretation exists with respect to whether some of the claims are limited to cDNA molecules. In its amicus brief, the United States government has argued that claims to isolated genomic DNA are patent ineligible, but claims limited to cDNA molecules are patent eligible (as reported in an earlier post to this blog). For some reason, in its brief the ACLU argues that the United States is mistaken, and that none of the challenged claims is limited to cDNA. ACLU seems to be clearly mistaken on this point--for example, Claim 2 of US patent 5,747,282 (one of the challenged claims) recites "DNA [having] the nucleotide sequence set forth in SEQ ID NO:1.” The Sequence Listing section of the patent specification explicitly identifies SEQ ID NO:1 as a cDNA.
The challenged diagnostic method claims recite processes of either "analyzing" or "comparing" nucleotide sequences. For example, claim 1 of US patent number 6,033,857 claims:
A method for identifying a mutant BRCA2 nucleotide sequence in a suspected mutant BRCA2 allele which comprises comparing the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence, wherein a difference between the suspected mutant and the wild-type sequence identifies a mutant BRCA2 nucleotide sequence.
Myriad argues for a relatively narrow interpretation of the claims, under which the claims are limited to methods which require actual physical analysis of DNA molecules. Under their interpretation, the term "nucleotide sequence," as used in the claims, refers to actual polynucleotides, i.e., DNA or RNA molecules, and the step of comparing these molecules necessarily requires physically isolating polynucleotides from a patient's tissue sample, and then processing and analyzing the molecules. Myriad argues that these processes are all clearly transformative of physical molecules, and because the transformations are “central to the purpose of the claims,” the claims satisfy the machine or transformation test. They cite to Prometheus for the proposition that transformative steps that are central to the purpose of the claims cannot be disregarded in the analysis as mere "data-gathering steps,” and argue these transformative steps render the claim patent eligible.
The ACLU, on the other hand, argues for a much broader interpretation of the method claims. They argue that the term "nucleotide sequence" in the claims refers to sequence information, not to molecules, and that the claims cover the purely mental process of "comparing" or "analyzing" DNA sequence information. Under this broad interpretation, the claims clearly do not require any sort of physical transformation, and on this basis the ACLU argues they fail the machine or transformation test, which they correctly note remains "a useful and important clue" to patent eligibility (using the language of the Supreme Court).
Interestingly, the ACLU never suggests in their brief that the diagnostic method claims would be patent ineligible if limited to methods involving actual isolation and processing of DNA molecules, i.e., the only processes covered by the claims under Myriad's interpretation of the claims. Conversely, Myriad never argues that a method claim that encompasses purely mental processes for comparing DNA sequence information would be patent eligible. Thus, both parties seem implicitly to agree on a consensus approach under which a claim directed toward a genetic diagnostic method is patent eligible if limited to diagnostic methods that involve actual isolation and manipulation of DNA molecules, but patent ineligible if the claim would also cover merely comparing DNA sequence information.
Notably, the district court adopted the ACLU's broad interpretation of the claims, and held that the claims cover a process of comparing or analyzing DNA sequence information. However, in dicta the district court went even further, stating that "[e]ven if the challenged claims were read to include the transformations associated with isolating and sequencing human DNA, these transformations would constitute no more than ‘data-gathering step[s]’ that are not central to the purpose of the claimed process.. . . . Consequently, even if the method claims-in-suit were construed to include the physical transformations associated with isolating and sequencing DNA, they would still fail the ‘machine or transformation’ test under Section 101 for subject matter patentability."
In my analysis of the district court decision, I pointed out that this dicta seems clearly wrong, and is inconsistent with the Federal Circuit's decision in Prometheus. Clearly, these data-gathering steps are central to the purpose of the claim and should be included in the machine or transformation analysis. I suspect that the ACLU agrees with my assessment, and is not even trying to argue for more extreme position taken by the district court.
It seems to me that the implicit consensus between Myriad and the ACLU is correct, i.e., method of genetic diagnostic claims are patent eligible if they include steps involving the actual physical manipulation of DNA molecules, but patent ineligible if they would cover the wholly mental process of analyzing DNA sequence information.
As a side note, another point of contention regarding claim interpretation exists with respect to whether some of the claims are limited to cDNA molecules. In its amicus brief, the United States government has argued that claims to isolated genomic DNA are patent ineligible, but claims limited to cDNA molecules are patent eligible (as reported in an earlier post to this blog). For some reason, in its brief the ACLU argues that the United States is mistaken, and that none of the challenged claims is limited to cDNA. ACLU seems to be clearly mistaken on this point--for example, Claim 2 of US patent 5,747,282 (one of the challenged claims) recites "DNA [having] the nucleotide sequence set forth in SEQ ID NO:1.” The Sequence Listing section of the patent specification explicitly identifies SEQ ID NO:1 as a cDNA.
Tuesday, November 23, 2010
Boston Globe Editorial Acknowledges Importance of Gene Patents, and Suggests Issue Should Be Decided by Congress, Not the Courts
In an apparent shift of position, the Boston Globe has parted company with much of the mainstream media by acknowledging the importance of gene patents to biotechnology, the potential deleterious impact if Judge Sweet's decision finding gene patents ineligible were to be upheld on appeal. The editorial points out that:
It is good to see that at least some in the mainstream media are waking up to the reality of what is at stake in the ACLU's challenge to gene patents.
Whatever the principle at stake, one practical effect of Judge Sweet’s ruling, if it isn’t reversed, will be to eliminate part of the legal structure upon which the biotechnology industry was founded. The US might leave the company of Japan, Canada, Australia, and the European Union to become the biggest industrialized nation to consider a gene that’s been discovered, characterized, and isolated through scientific inquiry as categorically non-patentable.
. . .
There is still, of course, the very legitimate, and clearly urgent, question of whether gene patents serve the larger goal of advancing medical research and promoting the creation of therapies. But the best answer to this question is unlikely to arrive through a patent challenge. Determining the benefit to society of gene patents involves much more than just the narrow legal consideration of whether DNA isolated through the process of scientific discovery fits the definition of an invention under the US Patent Act.
. . .
Perhaps the best policy would be to simply do away with these patents. But the issue is of such magnitude that it would be best addressed outside the court system, by an act of Congress.
It is good to see that at least some in the mainstream media are waking up to the reality of what is at stake in the ACLU's challenge to gene patents.
Regeneron Sues for Declaratory Judgment That VEGF Trap Does Not Infringe Genentech Patents
On November 19, Regeneron sued Genentech in the US District Court for the Southern District of New York seeking a declaration that no activities relating to the Regeneron VEGF Trap infringe any claim of US patent numbers 5,952,199; 6,100,071; 6,383,486; 6,897,294; and 7,771,721 (all assigned to Genentech according to the complaint). The complaint is available here, compliments of PriorSmart.com.
Vascular Endothelial Growth Factor, or VEGF, is a protein growth factor which is required for formation of blood vessels, a process known as angiogenesis. According to Wikipedia:
Genentech has developed an antibody called Avastin that binds VEGF. Avastin is already approved for the treatment of colon cancer. The five Genentech patents which are the subject of the declaratory judgment action are directed toward chimeric VEGF receptor proteins capable of binding VEGF.
Vascular Endothelial Growth Factor, or VEGF, is a protein growth factor which is required for formation of blood vessels, a process known as angiogenesis. According to Wikipedia:
In the adult human, angiogenesis is only consistently active in the gut - however in pathological cases such as cancer, where a solid tumor grows rapidly and therefore requires a blood supply, there is also active angiogenesis. Therefore, the blockade of VEGF is a potentially viable strategy for treating solid tumors.Regeneron has developed a chimeric (i.e., fusion) protein, which it refers to as VEGF Trap (aflibercept), that comprises the extra-cellular domain of VEGF Receptor (the growth factor's natural receptor). The extra-cellular domain of the receptor is used to bind, or "trap" VEGF, and thereby keep it from binding receptors on the surface of blood vessels. Regeneron is working towards FDA approval to market VEGF Trap for a number of ophthalmologic and oncology indications. According to the complaint, the company intends to submit a Biologic License Application before the end of the second quarter of 2011 to market the product for a wet age-related macular degeneration. Yesterday, Regeneron stock rose 19.7% after the company announced positive Phase 3 clinical trial results for the drug (see here).
Genentech has developed an antibody called Avastin that binds VEGF. Avastin is already approved for the treatment of colon cancer. The five Genentech patents which are the subject of the declaratory judgment action are directed toward chimeric VEGF receptor proteins capable of binding VEGF.
Wednesday, November 10, 2010
Amicus Brief Filed By Alnylam Pharmaceuticals Argues That Funk Bros. Is About Obviousness, Not Patent Eligibility
Alnylam Pharmaceuticals is a biopharmaceutical company based in Cambridge, Massachusetts focused on developing synthetic "small interfering RNAs" (SiRNAs) as therapeutic agents. It has filed an amicus curiae brief in the Myriad gene patent case (AMP v. US PTO) that makes a number of insightful points, particularly in attempting to "debunk myths of Funk Brothers Seed Co. v. Kalo Inoculant Co."
Funk Brothers is generally assumed to be a case about patent eligibility. However, Alnylam points out that Funk Brothers was decided by the Supreme Court in 1948, prior to the enactment of the 1952 patent statute and thus prior to 35 USC 101, which is the statutory basis for the patent eligibility doctrine. Prior to 1952, the Court used the term “invention” to refer to "inventiveness," a concept that subsequent to 1952 and the enactment of 35 USC 103 we refer to as "nonobviousness." The Court in Funk Brothers found the claimed subject matter was not the “product of invention,” but Alnylam argues that post-1952 this statement should be interpreted a finding of obviousness, not patent ineligibility.
I have always found it extremely difficult, if not impossible, to find a principled distinction between the inventions claimed in Funk Brothers and Diamond V. Chakrabarty that would justify finding only Dr. Chakrabarty's invention patent eligible. In Funk Brothers, the alleged invention was a novel and useful combination, in a single inoculant, of naturally occurring microorganisms in a combination that did not exist naturally. Chakrabarty’s invention was a novel and useful combination, in a single microorganism, of naturally occurring plasmids in a combination that did not exist naturally. It is important to bear in mind that Chakrabarty's invention did not involve any genetic engineering at the molecular level.
In Funk Brothers, it has been pointed out that while the combination of bacteria in a single inoculant was novel, the bacteria function in the same manner and have the same characteristics as they would have in nature. But the same can be said regarding the plasmids Dr. Chakrabarty introduced into a single microorganism. These were naturally occurring plasmids, and in the claimed microorganism they encoded the exact same proteins, and performed the exact same function as they did in their natural state.
In a nutshell, Funk Brothers was a novel combination of naturally occurring bacteria capable of achieving novel and useful function, with the bacteria functioning in the same manner as they do in nature. Chakrabarty was a novel combination of naturally occurring plasmid DNA capable of achieving novel and useful function, with the plasmid DNA functioning in the same manner as they do in nature. I don't see how one invention can be patent eligible and the other not. However, if Funk Brothers was really decided based on obviousness rather than patent eligibility, as argued by Alnylam, the two decisions are easily reconciled.
Funk Brothers is generally assumed to be a case about patent eligibility. However, Alnylam points out that Funk Brothers was decided by the Supreme Court in 1948, prior to the enactment of the 1952 patent statute and thus prior to 35 USC 101, which is the statutory basis for the patent eligibility doctrine. Prior to 1952, the Court used the term “invention” to refer to "inventiveness," a concept that subsequent to 1952 and the enactment of 35 USC 103 we refer to as "nonobviousness." The Court in Funk Brothers found the claimed subject matter was not the “product of invention,” but Alnylam argues that post-1952 this statement should be interpreted a finding of obviousness, not patent ineligibility.
I have always found it extremely difficult, if not impossible, to find a principled distinction between the inventions claimed in Funk Brothers and Diamond V. Chakrabarty that would justify finding only Dr. Chakrabarty's invention patent eligible. In Funk Brothers, the alleged invention was a novel and useful combination, in a single inoculant, of naturally occurring microorganisms in a combination that did not exist naturally. Chakrabarty’s invention was a novel and useful combination, in a single microorganism, of naturally occurring plasmids in a combination that did not exist naturally. It is important to bear in mind that Chakrabarty's invention did not involve any genetic engineering at the molecular level.
In Funk Brothers, it has been pointed out that while the combination of bacteria in a single inoculant was novel, the bacteria function in the same manner and have the same characteristics as they would have in nature. But the same can be said regarding the plasmids Dr. Chakrabarty introduced into a single microorganism. These were naturally occurring plasmids, and in the claimed microorganism they encoded the exact same proteins, and performed the exact same function as they did in their natural state.
In a nutshell, Funk Brothers was a novel combination of naturally occurring bacteria capable of achieving novel and useful function, with the bacteria functioning in the same manner as they do in nature. Chakrabarty was a novel combination of naturally occurring plasmid DNA capable of achieving novel and useful function, with the plasmid DNA functioning in the same manner as they do in nature. I don't see how one invention can be patent eligible and the other not. However, if Funk Brothers was really decided based on obviousness rather than patent eligibility, as argued by Alnylam, the two decisions are easily reconciled.
Friday, November 5, 2010
Superficial Appeal of DOJ Brief Proves Illusory
I can understand why many people find the position advanced by the US government in AMP v. PTO (the DOJ amicus brief, discussed in an earlier post) quite appealing. On its face, it seems to offer a reasonable compromise: patent eligibility for "engineered" cDNA, but not for genomic DNA merely "excised" from a human chromosome. However, the distinction is superfical, and does not in my view withstand closer scrutiny.
In particular, the DOJ conveniently ignores the fact that in almost all cases isolation of genomic DNA involves amplification, either through laboratory techniques such as PCR, or by replication in recombinant cells. This distinguishes DNA and RNA from other biomolecules. Prior to the development of recombinant molecular biology in the 1970s, isolation of a naturally occurring biomolecule, such as a protein, involved removing the biomolecule produced in a naturally occurring from other biological constituents. Importantly, all of the purified biomolecule originated in the natural source, and was purified by separating it from other cellular constituents.
In contrast, because DNA can serve as a template for its own replication, DNA is normally isolated by amplifying it many times ("million-fold" is the term used in the amici brief filed by BIO and AUTM). As a result, a typical preparation of "isolated genomic DNA" actually consists primarily of synthetic copies of the genomic DNA molecule.
The DOJ makes much of the fact that a cDNA molecule does not contain the introns, which exist in most human genes, and implies that molecular biologists have "engineered" the introns out. In fact, the introns are naturally removed in the body when genomic DNA is transcribed into mRNA. There is no human engineering involved; production of a cDNA molecule simply entails making a DNA copy of a naturally occurring mRNA and then amplifying it.
In most instances a preparation of isolated genomic DNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring genomic DNA. A preparation of cDNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring mRNA. Considered in this light, I think that the distinction DOJ makes between "excised" genomic DNA versus "engineered" cDNA proves largely illusory.
True, a cDNA molecule has a slightly different chemical structure than the mRNA on which it is based, but the differences are small. The sugar group (ribose) in DNA is lacking an oxygen atom (hence the “deoxy”), and one of the four base groups in RNA (uracil) is slightly different than the corresponding base in DNA (thymine), due to replacement of a methyl group with a hydrogen atom. But mRNA and its corresponding cDNA both encode the same information, and both hybridize to the same complementary strand.
In many instances, a synthetic copy of a genomic DNA molecule is also chemically different from the original. Most naturally occurring genomic DNA is methylated, a form of epigenetic modification, while synthetic copies are often not methylated.
In short, the minor structural difference between cDNA and mRNA is not so qualitatively different than the difference between amplified genomic DNA and genomic DNA of natural origin to warrant using this distinction as the basis for drawing a line between patent eligible and patent ineligible subject matter.
In particular, the DOJ conveniently ignores the fact that in almost all cases isolation of genomic DNA involves amplification, either through laboratory techniques such as PCR, or by replication in recombinant cells. This distinguishes DNA and RNA from other biomolecules. Prior to the development of recombinant molecular biology in the 1970s, isolation of a naturally occurring biomolecule, such as a protein, involved removing the biomolecule produced in a naturally occurring from other biological constituents. Importantly, all of the purified biomolecule originated in the natural source, and was purified by separating it from other cellular constituents.
In contrast, because DNA can serve as a template for its own replication, DNA is normally isolated by amplifying it many times ("million-fold" is the term used in the amici brief filed by BIO and AUTM). As a result, a typical preparation of "isolated genomic DNA" actually consists primarily of synthetic copies of the genomic DNA molecule.
The DOJ makes much of the fact that a cDNA molecule does not contain the introns, which exist in most human genes, and implies that molecular biologists have "engineered" the introns out. In fact, the introns are naturally removed in the body when genomic DNA is transcribed into mRNA. There is no human engineering involved; production of a cDNA molecule simply entails making a DNA copy of a naturally occurring mRNA and then amplifying it.
In most instances a preparation of isolated genomic DNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring genomic DNA. A preparation of cDNA comprises synthetic DNA molecules, produced in the laboratory by amplification, that correspond in sequence to a naturally occurring mRNA. Considered in this light, I think that the distinction DOJ makes between "excised" genomic DNA versus "engineered" cDNA proves largely illusory.
True, a cDNA molecule has a slightly different chemical structure than the mRNA on which it is based, but the differences are small. The sugar group (ribose) in DNA is lacking an oxygen atom (hence the “deoxy”), and one of the four base groups in RNA (uracil) is slightly different than the corresponding base in DNA (thymine), due to replacement of a methyl group with a hydrogen atom. But mRNA and its corresponding cDNA both encode the same information, and both hybridize to the same complementary strand.
In many instances, a synthetic copy of a genomic DNA molecule is also chemically different from the original. Most naturally occurring genomic DNA is methylated, a form of epigenetic modification, while synthetic copies are often not methylated.
In short, the minor structural difference between cDNA and mRNA is not so qualitatively different than the difference between amplified genomic DNA and genomic DNA of natural origin to warrant using this distinction as the basis for drawing a line between patent eligible and patent ineligible subject matter.
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