Wednesday, April 8, 2009
IPSC 2009 Update
The submissions deadline for the 9th Annual Intellectual Property Scholars Conference at Cardozo School of Law has been extended to April 30th, 2009. Individual submissions should be directed to David Morrison at dmorriso@yu.edu. For more information, visit www.ipscholars.org.
Tuesday, April 7, 2009
Ariad v. Eli Lilly and In Re Kubin: One Federal Circuit Panel Perpetuates the Lilly Written Description Doctrine, While Another Avoids Addressing It
I am one of those that believes the written description requirement should be used only to police against the introduction of new matter into claims, and not as a separate requirement of patentability. In previous posts , I have explained some of the reasoning behind my objection to what I refer to as the “Lilly written description requirement,” named after the 1997 Regents of UC v . Eli Lilly decision, wherein the Federal Circuit relied on written description to invalidate originally filed claims directed towards the insulin gene. Some judges on the Federal Circuit, in particular Judge Rader and Judge Linn, share this distaste for the Lilly written doctrine. Nonetheless, the trend in recent years, both in the courts and Patent and Trademark Office (PTO) has been towards the perpetuation and expansion of Lilly written description as a distinct doctrine of patentability, and this trend continued last week in Ariad v. Eli Lilly.
In Ariad v. Eli Lilly, the Federal Circuit reversed a Massachusetts District Court and invalidated Ariad's claims broadly reciting methods of repressing the activity of NF-kB, an important regulator on gene transcription. The facts of the case are discussed in earlier posts to this blog. Although my interest in the case has primarily been focused on Lilly's argument that the claims are patent ineligible for wholly encompassing a natural phenomenon, the Federal Circuit panel deciding the case avoided the issue of patent eligibility by ruling that all of the asserted claims failed to comply with the written description requirement.
Ariad’s invalidated claims are reminiscent of the University of Rochester's claims, directed towards methods of inhibiting prostaglandin H synthase-2 (PGHS-2, a also referred to as COX-2), which were held invalid for violating the Lilly written description requirement in University of Rochester v. G.D. Searle, 358 F.3d 916 (Fed. Cir. 2004). The University of Rochester's claims broadly recited "a method for selectively inhibiting PGHS-2 activity in a human host, comprising administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product.” The Federal Circuit found that the claims failed written description requirement because the specification did not specifically describe any non-steroidal compound that would perform the claimed function. Rochester is one of the seminal Lilly written description cases, and marked a significant expansion in the reach of the doctrine. This was the first instance in which the Federal Circuit applied the doctrine to invalidate method claims; prior to Rochester, Lilly written description had only been applied to biomolecules claims, i.e. nucleic acids and antibodies.
Similarly, Ariad’s claims purport to broadly cover methods of inhibiting NF-kB activity, while providing little if any disclosure of molecules capable of accomplishing this inhibition. Ariad attempted unsuccessfully to distinguish its claims from those of the University of Rochester’s, pointing out that the University's claims specifically recited the use of a non-steroidal compound, while Ariad's do not explicitly mention any compound. This strikes me as a ridiculous argument. Essentially, Ariad was arguing that because its claims were drafted more broadly than the University’s, implicitly encompassing any compound that would achieve the desired function, its specification was not required to describe any compound. The Federal Circuit saw through this specious argument, and held that “[R]egardless of whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods."
Turning to Ariad’s specification, the Federal Circuit noted that it identified three classes of molecules potentially capable of reducing NF-kB activity: specific inhibitors, dominantly interfering molecules, and decoy molecules. Regarding the first two classes, the Federal Circuit found that, as of the effective filing date in 1989, the specification failed to provide any more than vague functional descriptions of the molecules.
With respect to decoy molecules, the Federal Circuit acknowledged that the specification provides specific examples of decoy molecules, including structures, leaving "little doubt that the specification adequately described the actual molecules to one of ordinary skill in the art." Nonetheless, the court went on to conclude that the specification failed to adequately describe “using those molecules to reduce NF-kB activity.” It noted that the specification taught a method of reducing NF-kB activity using decoy molecules that would bind NF-kB and thereby effect negative regulation of NF-kB activity, and acknowledged that prophetic examples are routinely used to satisfy the written description requirement in the chemical arts, but nevertheless concluded that the “disclosure is not so much an ‘example’ as it is a mere mention of the desired outcome.” The court failed to articulate why Ariad’s disclosure of using specifically described decoy molecules to negatively regulate NF-kB is insufficient to satisfy written description, except for the conclusory statement that "there is no descriptive link between the table of decoy molecules and reducing NF-kB activity” (emphasis added).
Later, the court provides a more convincing justification its decision to invalidate Ariad's claims, holding that regardless of whether the use of decoy molecules was adequately described, the disclosure was insufficient to "bear the weight of the vast scope of these generic claims.” In other words, the court invoked the Lilly written description requirement to invalidate the claims for being overly broad, claiming more subject matter than was justified by the scant disclosure. In closing, the court pointed out that it was the extreme breadth of the claims that had been their undoing, and that "for its own reasons, Ariad maintained the breadth of these claims to claim construction and into trial. . . . The motto, ‘beware of what one asks for,’ might be applicable here."
In a concurring opinion, Judge Linn agreed that the majority's opinion was supported by Federal Circuit precedent, but reiterated his position that the Federal Circuit has been “misguided” in grafting a separate written description requirement onto section 112, paragraph 1. He criticized the panel majority for relying on the Lilly written description requirement and not addressing the important enablement issues in the case. To quote Judge Linn:
As the majority opinion observes, the claims-in-suit broadly claim any method for reducing NF-kB activity in cells, including both known and unknown methods. We have long held that in order to survive the enablement requirement specification "must describe the manner and process of making and using the invention so as to enable a person of skill in the art to making use the full scope of the invention without undue experimentation.” To my knowledge, however, we have not specifically address this requirement in relation to the type of claim at issue here- that is, claims written broadly enough to cover any method for achieving a particular result. It may be, as Lilly argues, that such a claim can never be valid, since the specification cannot enable unknown methods. This is an important issue that we have left unresolved. It is an issue that we would have been compelled to reach had the case been decided on enablement rounds, a basis found in section 112, instead of on written description grounds, a separate basis not justified under that section or any other provision of the Patent Act.
I agree with Judge Linn in this regard. The fundamental problem with Ariad's claims is that they are simply too broad to be justified by the limited disclosure in the patent specification. The enablement requirement is the appropriate tool for policing claim scope, but as observed by Judge Linn, the courts have failed to articulate a workable standard for policing claim scope. Lilly written description doctrine provides nothing in this regard, but to the contrary simply muddies the doctrinal waters. A good example of this can be seen in the majority's opinion in this case, when it struggles to explain why the disclosure of specific structures for decoy molecules in the specification, coupled with a description of using those molecules to inhibit NF-kB, does not constitute adequate description of how to use the molecules to inhibit NF-kB. The majority’s basis for this conclusion, an alleged lack of a “descriptive link” between the disclosed decoy molecules and reducing NF-kB activity, is bizarre. The specification describes the molecules in explicit structural terms, and describes using them to inhibit NF-kB activity. It seems clear that the Federal Circuit's actual concern was that the specification did not enable the use of these molecules to inhibit NF-kB activity, but because the majority chose to rely on written description rather than enablement it had no established doctrinal basis for invalidating the claims, so it coined and apparently novel “descriptive link” requirement for patentability.
The majority's main objection to the claims was based on their broad scope relative to the limited disclosure of the specification; as noted by Judge Linn, traditionally the enablement doctrine has been used to police claim scope. The test for enablement is easy to state: a claim fails to satisfy the enablement requirement if the disclosure is not commensurate in scope with the claims. The actual application of the test to real claims and disclosures is anything but straight forward, as noted by Judge Linn in his concurrence, but at least there is an established standard. In contrast, the Federal Circuit has failed to articulate any meaningful criteria for applying Lilly written description to police claim scope that is distinguishable from enablement. This point was made, for example, by Judge Rader in his dissent from the decision not to hear Lizardtech en banc, and I have discussed in my article “Is Lilly Written Description a Paper Tiger?: A Comprehensive Assessment of the Impact of Eli Lilly and Its Progeny on the Court and PTO.” The emptiness of the Lilly written description requirement is reflected in the Ariad majority’s conclusion that the claims were invalid because the disclosure was insufficient to "bear the weight of the vast scope of these generic claims.”
In re Kubin, decided the same day as Ariad v. Lilly, and described in an earlier post, also involved a written description issue. However, in that case the panel declined to address written description has moot in view of the fact that the claims were invalid based on obviousness. The author of Kubin, Judge Rader, apparently decided that Kubin was not appropriate case to take on the Lilly written description requirement, but perhaps he and other critics of the doctrine will have their chance in another case. The patent office has become much more aggressive in applying Lilly written description as a requirement of patentability requirements separate and distinct from the enablement requirement, as discussed in a previous post, so there should be further opportunities to address the issue in the future.
In Ariad v. Eli Lilly, the Federal Circuit reversed a Massachusetts District Court and invalidated Ariad's claims broadly reciting methods of repressing the activity of NF-kB, an important regulator on gene transcription. The facts of the case are discussed in earlier posts to this blog. Although my interest in the case has primarily been focused on Lilly's argument that the claims are patent ineligible for wholly encompassing a natural phenomenon, the Federal Circuit panel deciding the case avoided the issue of patent eligibility by ruling that all of the asserted claims failed to comply with the written description requirement.
Ariad’s invalidated claims are reminiscent of the University of Rochester's claims, directed towards methods of inhibiting prostaglandin H synthase-2 (PGHS-2, a also referred to as COX-2), which were held invalid for violating the Lilly written description requirement in University of Rochester v. G.D. Searle, 358 F.3d 916 (Fed. Cir. 2004). The University of Rochester's claims broadly recited "a method for selectively inhibiting PGHS-2 activity in a human host, comprising administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product.” The Federal Circuit found that the claims failed written description requirement because the specification did not specifically describe any non-steroidal compound that would perform the claimed function. Rochester is one of the seminal Lilly written description cases, and marked a significant expansion in the reach of the doctrine. This was the first instance in which the Federal Circuit applied the doctrine to invalidate method claims; prior to Rochester, Lilly written description had only been applied to biomolecules claims, i.e. nucleic acids and antibodies.
Similarly, Ariad’s claims purport to broadly cover methods of inhibiting NF-kB activity, while providing little if any disclosure of molecules capable of accomplishing this inhibition. Ariad attempted unsuccessfully to distinguish its claims from those of the University of Rochester’s, pointing out that the University's claims specifically recited the use of a non-steroidal compound, while Ariad's do not explicitly mention any compound. This strikes me as a ridiculous argument. Essentially, Ariad was arguing that because its claims were drafted more broadly than the University’s, implicitly encompassing any compound that would achieve the desired function, its specification was not required to describe any compound. The Federal Circuit saw through this specious argument, and held that “[R]egardless of whether the asserted claims recite a compound, Ariad still must describe some way of performing the claimed methods."
Turning to Ariad’s specification, the Federal Circuit noted that it identified three classes of molecules potentially capable of reducing NF-kB activity: specific inhibitors, dominantly interfering molecules, and decoy molecules. Regarding the first two classes, the Federal Circuit found that, as of the effective filing date in 1989, the specification failed to provide any more than vague functional descriptions of the molecules.
With respect to decoy molecules, the Federal Circuit acknowledged that the specification provides specific examples of decoy molecules, including structures, leaving "little doubt that the specification adequately described the actual molecules to one of ordinary skill in the art." Nonetheless, the court went on to conclude that the specification failed to adequately describe “using those molecules to reduce NF-kB activity.” It noted that the specification taught a method of reducing NF-kB activity using decoy molecules that would bind NF-kB and thereby effect negative regulation of NF-kB activity, and acknowledged that prophetic examples are routinely used to satisfy the written description requirement in the chemical arts, but nevertheless concluded that the “disclosure is not so much an ‘example’ as it is a mere mention of the desired outcome.” The court failed to articulate why Ariad’s disclosure of using specifically described decoy molecules to negatively regulate NF-kB is insufficient to satisfy written description, except for the conclusory statement that "there is no descriptive link between the table of decoy molecules and reducing NF-kB activity” (emphasis added).
Later, the court provides a more convincing justification its decision to invalidate Ariad's claims, holding that regardless of whether the use of decoy molecules was adequately described, the disclosure was insufficient to "bear the weight of the vast scope of these generic claims.” In other words, the court invoked the Lilly written description requirement to invalidate the claims for being overly broad, claiming more subject matter than was justified by the scant disclosure. In closing, the court pointed out that it was the extreme breadth of the claims that had been their undoing, and that "for its own reasons, Ariad maintained the breadth of these claims to claim construction and into trial. . . . The motto, ‘beware of what one asks for,’ might be applicable here."
In a concurring opinion, Judge Linn agreed that the majority's opinion was supported by Federal Circuit precedent, but reiterated his position that the Federal Circuit has been “misguided” in grafting a separate written description requirement onto section 112, paragraph 1. He criticized the panel majority for relying on the Lilly written description requirement and not addressing the important enablement issues in the case. To quote Judge Linn:
As the majority opinion observes, the claims-in-suit broadly claim any method for reducing NF-kB activity in cells, including both known and unknown methods. We have long held that in order to survive the enablement requirement specification "must describe the manner and process of making and using the invention so as to enable a person of skill in the art to making use the full scope of the invention without undue experimentation.” To my knowledge, however, we have not specifically address this requirement in relation to the type of claim at issue here- that is, claims written broadly enough to cover any method for achieving a particular result. It may be, as Lilly argues, that such a claim can never be valid, since the specification cannot enable unknown methods. This is an important issue that we have left unresolved. It is an issue that we would have been compelled to reach had the case been decided on enablement rounds, a basis found in section 112, instead of on written description grounds, a separate basis not justified under that section or any other provision of the Patent Act.
I agree with Judge Linn in this regard. The fundamental problem with Ariad's claims is that they are simply too broad to be justified by the limited disclosure in the patent specification. The enablement requirement is the appropriate tool for policing claim scope, but as observed by Judge Linn, the courts have failed to articulate a workable standard for policing claim scope. Lilly written description doctrine provides nothing in this regard, but to the contrary simply muddies the doctrinal waters. A good example of this can be seen in the majority's opinion in this case, when it struggles to explain why the disclosure of specific structures for decoy molecules in the specification, coupled with a description of using those molecules to inhibit NF-kB, does not constitute adequate description of how to use the molecules to inhibit NF-kB. The majority’s basis for this conclusion, an alleged lack of a “descriptive link” between the disclosed decoy molecules and reducing NF-kB activity, is bizarre. The specification describes the molecules in explicit structural terms, and describes using them to inhibit NF-kB activity. It seems clear that the Federal Circuit's actual concern was that the specification did not enable the use of these molecules to inhibit NF-kB activity, but because the majority chose to rely on written description rather than enablement it had no established doctrinal basis for invalidating the claims, so it coined and apparently novel “descriptive link” requirement for patentability.
The majority's main objection to the claims was based on their broad scope relative to the limited disclosure of the specification; as noted by Judge Linn, traditionally the enablement doctrine has been used to police claim scope. The test for enablement is easy to state: a claim fails to satisfy the enablement requirement if the disclosure is not commensurate in scope with the claims. The actual application of the test to real claims and disclosures is anything but straight forward, as noted by Judge Linn in his concurrence, but at least there is an established standard. In contrast, the Federal Circuit has failed to articulate any meaningful criteria for applying Lilly written description to police claim scope that is distinguishable from enablement. This point was made, for example, by Judge Rader in his dissent from the decision not to hear Lizardtech en banc, and I have discussed in my article “Is Lilly Written Description a Paper Tiger?: A Comprehensive Assessment of the Impact of Eli Lilly and Its Progeny on the Court and PTO.” The emptiness of the Lilly written description requirement is reflected in the Ariad majority’s conclusion that the claims were invalid because the disclosure was insufficient to "bear the weight of the vast scope of these generic claims.”
In re Kubin, decided the same day as Ariad v. Lilly, and described in an earlier post, also involved a written description issue. However, in that case the panel declined to address written description has moot in view of the fact that the claims were invalid based on obviousness. The author of Kubin, Judge Rader, apparently decided that Kubin was not appropriate case to take on the Lilly written description requirement, but perhaps he and other critics of the doctrine will have their chance in another case. The patent office has become much more aggressive in applying Lilly written description as a requirement of patentability requirements separate and distinct from the enablement requirement, as discussed in a previous post, so there should be further opportunities to address the issue in the future.
Monday, April 6, 2009
In Re Kubin: Federal Circuit Clarifies Obviousness Standard in Context of cDNA Cloning Invention
In In re Kubin, an important decision for biotechnology, the Federal Circuit affirmed the Patent and Trademark Office’ (PTO’s) rejection of Amgen’s claims directed to the cDNA encoding the human NAIL protein.
The facts of the case are discussed in detail in a previous post, where I pointed out that Kubin provided the Federal Circuit with a good opportunity to address the current significance of In re Deuel, a 1995 Federal Circuit decision. In particular, does Deuel broadly establish that a nucleic acid is only rendered obvious by the disclosure of a structurally similar nucleic acid in the prior art, the position argued by Amgen and others? Many have interpreted Deuel as imposing an extremely low bar to the patentability of cloned cDNA molecules, and indeed biotechnology in general, and have accepted the conventional wisdom that the disclosure of a protein in the prior art does not render the successful cloning and sequencing of the gene encoding the protein obvious. On the other hand, I have felt that Deuel should be read much more narrowly, particularly in view of subsequent developments in the technology of cloning and the law, particularly the Supreme Court's decision in KSR v. Teleflex. I think that in Kubin the Federal Circuit has answered that question pretty emphatically: while not expressly overruling Deuel, it appears to have effectively limited Deuel to the facts of that case.
While many view Kubin as a substantial change in the law of obviousness, I disagree. Kubin basically says that the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. There is nothing remarkable about this standard - it is entirely consistent with the law of obviousness as it is applied outside the context of gene cloning, and it surprises me that people have believed that a very different standard applies to gene cloning. As I pointed out in my previous post, the BPAI has previously seemed to interpret the holding in Deuel as effectively limited to the specific facts of that case. For example, in Ex parte Goldgaber, decided shortly after Deuel, the BPAI affirmed an obviousness rejection of claims directed to newly isolated cDNA sequences based on prior art teaching the encoded protein and general methodologies for cloning and sequencing cDNA, i.e., facts very analogous to both Deuel and Kubin.
Legal presumptions, burdens of proof and the standard of appellate review were critical in the outcome of this case. First off, the Federal Circuit has held that there is a presumption that anything described in issued US patent is enabled, including prophetic examples, i.e., examples that were never actually carried out. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003). The PTO relied on this presumption, and Amgen never really argued against it. During oral arguments, the judges on the panel treated this presumption as established law, as it apparently it.
In my view, this presumption that anything asserted in addition patent is enabled makes very little sense. Anybody familiar with actual patents knows that patent specifications are full of wild assertions that are clearly not enabled, and in most cases the patent examiner is in no position to assess the enablement of these assertions. If a prophetic example, or other prophetic assertion in a patent, is not critical to the patentability of the patent claims, there is no reason for the examiner ever to delve into whether the prophetic example could actually be accomplished by one of skill in the art without undue experimentation. Nonetheless, the PTO and courts presume that anything described in a patent application is enabled, and this can be a difficult presumption to overcome in arguing for the patentability of a claim apparently rendered anticipated or obvious by a prophetic disclosure in an issued patent. I have faced this conundrum often in arguing for the patentability of claims with a patent examiner. In my view, a disclosure in a peer-reviewed scientific article is much more likely to be enabled than a prophetic example in a patent, but that is not how the law currently sees things.
In the case of Kubin, the prior art included a patent (Valiante) with a prophetic example essentially describing the cloning of the NAIL cDNA claimed by Kubin. Amgen argued that there was no reasonable expectation that one of skill in the art would have been successful in carrying out Valiante’s prophetic cloning protocol, and they may very well have been correct. Amgen argued that in reality it was much more difficult and complicated then suggested in the prophetic example, and Kubin’s success required a “specific mixture of resting cells, resting NK cells and NK cells stimulated with a very specific cocktail of activators.” But these are technical questions, which Federal Circuit judges are ill-suited to decide de novo. The Federal Circuit was correct to note that the process successfully employed by Kubin to clone the claimed cDNA is irrelevant: the standard is whether one of skill in the art would have had a reasonable expectation of cloning the claimed polynucleotides by any method. In KSR, the Supreme Court correctly chastised the Federal Circuit for considering how difficult the invention was for the alleged inventor (a subjective test), when they should have been considering how difficult the invention would have been for the person having ordinary skill in the art (the correct, objective test). The problem for Amgen was that regardless of the actual difficulties experienced by Kubin, the invention is obvious if one of skill in the art could have cloned a nucleic acid falling within the scope of a claim, by any method. Valiante, a prior art patents, provided a prophetic example purporting to teach just such a method, and because there is a presumption that the example is enabled, the PTO and court presumed that the prior art provided an enabling method for arriving at the claimed nucleic acids with a reasonable expectation of success. Because of the presumption of enablement, the burden was on Amgen to provide evidence that the prophetic example was not actually enabled, and they failed to convince the PTO or the court on this issue.
The standard of review was also important. The Federal Circuit reviews the factual findings of the PTO's Board of Patent Appeals and Interferences for “lack of substantial evidence” to support the findings. In this case, the PTO and Board made a factual determination that the Valiante prophetic example, when combined with other prior art, provided both the motivation to clone the NAIL cDNA and a reasonable expectation of success. As a consequence of the standard of review, the Federal Circuit is required to show a great deal of deference to this factual determination. In effect, if the PTO’s finding of a reasonable expectation of success is at least plausible, based on some substantial evidence, the court will defer to that determination, even if there is also substantial evidence pointing the other direction.
Because the question of whether there was a reasonable expectation of success is a factual finding, Amgen faced a very tough burden to prove that there was no substantial evidence supporting the PTO's decision. When compounded with the presumption that prophetic examples appearing in a patent are enabled, it becomes apparent that Amgen could only prevail by providing compelling evidence that, in fact, the cloning of this particular gene was much more difficult and unpredictable than suggested by the cited prior art, and they appear to have failed to meet this heavy burden.
What about the impact of this case on biotechnology? To quote Patent Docs, “the sky is not falling.” For one thing, Kubin does not mean that any patent claiming a cDNA is necessarily obvious if the encoded protein was known in the prior art. It simply means that we can no longer continue to interpret Deuel as establishing that the cDNA is never rendered obvious under those circumstances. Rather, the inquiry should shift to whether or not there was any kind of suggestion or motivation to clone the cDNA, and if there was, whether there was a reasonable expectation of success. In cases where the patent applicant can bring forth sufficient evidence to show that the cloning of a particular cDNA was more technically challenging, creating a sufficient level of unpredictability with regard to success, the invention should still be patentable under Kubin. After KSR, it should be clear that in many cases it will be necessary for a patent applicant to provide evidence of technical challenges and lack of predictable success to overcome an effective presumption that an invention is obvious, and Kubin simply applies that principle to a cDNA cloning invention.
Of course, the Kubin patent application was prosecuted prior to KSR, and it is unclear whether Amgen could have provided more compelling factual evidence that the cloning of this particular gene was actually more technically challenging and unpredictable than normal. The lesson for biotechnology patent prosecutors might be that this factual support of technical unpredictability of success is more important today than it was pre-KSR.
Also, as noted by Patent Docs, while this sort of invention, based on the successful cloning of a cDNA encoding a protein of known significance, was very important in the early days of biotechnology, it is becoming much less relevant with the passage of time. Today, in the age of high-throughput genomics, it is much more likely that a gene will be discovered prior to the isolation and characterization of the encoded protein. For most known proteins of clinical significance, the corresponding cDNA has already been cloned, in which case it is too late to patent the cDNA. If there are cases where the cDNA as yet to be cloned, that suggests that either there was no motivation or suggestion to do it, or that the cloning has proven unusually difficult technically, in which case it is likely nonobvious under Kubin.
In the early days of biotechnology, the main products were biologic drugs which basically were recombinant versions of naturally occurring human proteins. Patents claiming cloned human cDNA were important in protecting these inventions. But the trend in biotechnology is towards monoclonal antibodies and engineered second-generation proteins bearing less and less structural similarity to naturally occurring proteins. As a result, patents on cloned human genes should be less relevant. This might explain my finding, reported in a recent law review article and Science article, that litigation involving human gene patents has dropped off dramatically in recent years, particularly in the area of biologic drugs. Gene patent filings have also reportedly dropped off in recent years.
In sum will, many in biotechnology will view Kubin as a negative development. I am not so sure it will be that significant, unless investors perceive that it does have serious negative implications for biotechnology. I think we should try to counter that - a perception among investors that biotechnology has been harmed by Kubin could cause more damage to biotechnology than the decision itself.
The facts of the case are discussed in detail in a previous post, where I pointed out that Kubin provided the Federal Circuit with a good opportunity to address the current significance of In re Deuel, a 1995 Federal Circuit decision. In particular, does Deuel broadly establish that a nucleic acid is only rendered obvious by the disclosure of a structurally similar nucleic acid in the prior art, the position argued by Amgen and others? Many have interpreted Deuel as imposing an extremely low bar to the patentability of cloned cDNA molecules, and indeed biotechnology in general, and have accepted the conventional wisdom that the disclosure of a protein in the prior art does not render the successful cloning and sequencing of the gene encoding the protein obvious. On the other hand, I have felt that Deuel should be read much more narrowly, particularly in view of subsequent developments in the technology of cloning and the law, particularly the Supreme Court's decision in KSR v. Teleflex. I think that in Kubin the Federal Circuit has answered that question pretty emphatically: while not expressly overruling Deuel, it appears to have effectively limited Deuel to the facts of that case.
While many view Kubin as a substantial change in the law of obviousness, I disagree. Kubin basically says that the successful cloning and sequencing of the cDNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. There is nothing remarkable about this standard - it is entirely consistent with the law of obviousness as it is applied outside the context of gene cloning, and it surprises me that people have believed that a very different standard applies to gene cloning. As I pointed out in my previous post, the BPAI has previously seemed to interpret the holding in Deuel as effectively limited to the specific facts of that case. For example, in Ex parte Goldgaber, decided shortly after Deuel, the BPAI affirmed an obviousness rejection of claims directed to newly isolated cDNA sequences based on prior art teaching the encoded protein and general methodologies for cloning and sequencing cDNA, i.e., facts very analogous to both Deuel and Kubin.
Legal presumptions, burdens of proof and the standard of appellate review were critical in the outcome of this case. First off, the Federal Circuit has held that there is a presumption that anything described in issued US patent is enabled, including prophetic examples, i.e., examples that were never actually carried out. See Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1355 (Fed. Cir. 2003). The PTO relied on this presumption, and Amgen never really argued against it. During oral arguments, the judges on the panel treated this presumption as established law, as it apparently it.
In my view, this presumption that anything asserted in addition patent is enabled makes very little sense. Anybody familiar with actual patents knows that patent specifications are full of wild assertions that are clearly not enabled, and in most cases the patent examiner is in no position to assess the enablement of these assertions. If a prophetic example, or other prophetic assertion in a patent, is not critical to the patentability of the patent claims, there is no reason for the examiner ever to delve into whether the prophetic example could actually be accomplished by one of skill in the art without undue experimentation. Nonetheless, the PTO and courts presume that anything described in a patent application is enabled, and this can be a difficult presumption to overcome in arguing for the patentability of a claim apparently rendered anticipated or obvious by a prophetic disclosure in an issued patent. I have faced this conundrum often in arguing for the patentability of claims with a patent examiner. In my view, a disclosure in a peer-reviewed scientific article is much more likely to be enabled than a prophetic example in a patent, but that is not how the law currently sees things.
In the case of Kubin, the prior art included a patent (Valiante) with a prophetic example essentially describing the cloning of the NAIL cDNA claimed by Kubin. Amgen argued that there was no reasonable expectation that one of skill in the art would have been successful in carrying out Valiante’s prophetic cloning protocol, and they may very well have been correct. Amgen argued that in reality it was much more difficult and complicated then suggested in the prophetic example, and Kubin’s success required a “specific mixture of resting cells, resting NK cells and NK cells stimulated with a very specific cocktail of activators.” But these are technical questions, which Federal Circuit judges are ill-suited to decide de novo. The Federal Circuit was correct to note that the process successfully employed by Kubin to clone the claimed cDNA is irrelevant: the standard is whether one of skill in the art would have had a reasonable expectation of cloning the claimed polynucleotides by any method. In KSR, the Supreme Court correctly chastised the Federal Circuit for considering how difficult the invention was for the alleged inventor (a subjective test), when they should have been considering how difficult the invention would have been for the person having ordinary skill in the art (the correct, objective test). The problem for Amgen was that regardless of the actual difficulties experienced by Kubin, the invention is obvious if one of skill in the art could have cloned a nucleic acid falling within the scope of a claim, by any method. Valiante, a prior art patents, provided a prophetic example purporting to teach just such a method, and because there is a presumption that the example is enabled, the PTO and court presumed that the prior art provided an enabling method for arriving at the claimed nucleic acids with a reasonable expectation of success. Because of the presumption of enablement, the burden was on Amgen to provide evidence that the prophetic example was not actually enabled, and they failed to convince the PTO or the court on this issue.
The standard of review was also important. The Federal Circuit reviews the factual findings of the PTO's Board of Patent Appeals and Interferences for “lack of substantial evidence” to support the findings. In this case, the PTO and Board made a factual determination that the Valiante prophetic example, when combined with other prior art, provided both the motivation to clone the NAIL cDNA and a reasonable expectation of success. As a consequence of the standard of review, the Federal Circuit is required to show a great deal of deference to this factual determination. In effect, if the PTO’s finding of a reasonable expectation of success is at least plausible, based on some substantial evidence, the court will defer to that determination, even if there is also substantial evidence pointing the other direction.
Because the question of whether there was a reasonable expectation of success is a factual finding, Amgen faced a very tough burden to prove that there was no substantial evidence supporting the PTO's decision. When compounded with the presumption that prophetic examples appearing in a patent are enabled, it becomes apparent that Amgen could only prevail by providing compelling evidence that, in fact, the cloning of this particular gene was much more difficult and unpredictable than suggested by the cited prior art, and they appear to have failed to meet this heavy burden.
What about the impact of this case on biotechnology? To quote Patent Docs, “the sky is not falling.” For one thing, Kubin does not mean that any patent claiming a cDNA is necessarily obvious if the encoded protein was known in the prior art. It simply means that we can no longer continue to interpret Deuel as establishing that the cDNA is never rendered obvious under those circumstances. Rather, the inquiry should shift to whether or not there was any kind of suggestion or motivation to clone the cDNA, and if there was, whether there was a reasonable expectation of success. In cases where the patent applicant can bring forth sufficient evidence to show that the cloning of a particular cDNA was more technically challenging, creating a sufficient level of unpredictability with regard to success, the invention should still be patentable under Kubin. After KSR, it should be clear that in many cases it will be necessary for a patent applicant to provide evidence of technical challenges and lack of predictable success to overcome an effective presumption that an invention is obvious, and Kubin simply applies that principle to a cDNA cloning invention.
Of course, the Kubin patent application was prosecuted prior to KSR, and it is unclear whether Amgen could have provided more compelling factual evidence that the cloning of this particular gene was actually more technically challenging and unpredictable than normal. The lesson for biotechnology patent prosecutors might be that this factual support of technical unpredictability of success is more important today than it was pre-KSR.
Also, as noted by Patent Docs, while this sort of invention, based on the successful cloning of a cDNA encoding a protein of known significance, was very important in the early days of biotechnology, it is becoming much less relevant with the passage of time. Today, in the age of high-throughput genomics, it is much more likely that a gene will be discovered prior to the isolation and characterization of the encoded protein. For most known proteins of clinical significance, the corresponding cDNA has already been cloned, in which case it is too late to patent the cDNA. If there are cases where the cDNA as yet to be cloned, that suggests that either there was no motivation or suggestion to do it, or that the cloning has proven unusually difficult technically, in which case it is likely nonobvious under Kubin.
In the early days of biotechnology, the main products were biologic drugs which basically were recombinant versions of naturally occurring human proteins. Patents claiming cloned human cDNA were important in protecting these inventions. But the trend in biotechnology is towards monoclonal antibodies and engineered second-generation proteins bearing less and less structural similarity to naturally occurring proteins. As a result, patents on cloned human genes should be less relevant. This might explain my finding, reported in a recent law review article and Science article, that litigation involving human gene patents has dropped off dramatically in recent years, particularly in the area of biologic drugs. Gene patent filings have also reportedly dropped off in recent years.
In sum will, many in biotechnology will view Kubin as a negative development. I am not so sure it will be that significant, unless investors perceive that it does have serious negative implications for biotechnology. I think we should try to counter that - a perception among investors that biotechnology has been harmed by Kubin could cause more damage to biotechnology than the decision itself.
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