Patent Docs: Enablement

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Enablement

March 14, 2023

Patent Law Academics File Amicus Brief in Amgen v. Sanofi

By Kevin E. Noonan --

The Supreme Court's decision to grant certiorari in Amgen v. Sanofi is the first time in almost a hundred years that the Court has deigned to consider sufficiency of disclosure decisions, in this case enablement under 35 U.S.C. § 112(a). While these circumstances themselves might motivate amici to file briefs with the Court to weigh in on the Question Presented, the Federal Circuit's trend in recent years to apply more tightly the strictures of Section 112 to chemical and biotechnology inventions and to pharmaceutical cases has provided its own incentive for such briefing.

Nearly three dozen amicus briefs were filed, with twelve supporting petitioners, seventeen supporting respondents, and five filed in support of neither party (although one of them, filed on behalf of the High Tech Inventors Alliance and the Computer and Communications Industry Association argues that the Federal Circuit's decision below was correct and consistent with settled law); these amici include AbbVie; GlaxoSmithKline; Instil; a combined brief on behalf several pharmaceutical and other companies, and the Association of University Technology Managers; patent law associations, including the NY Patent Law Association, the Intellectual Property Lawyers Association of Chicago, and the National Association of Patent Practitioners; the Intellectual Property Owners association; the American Chemical Society; and more than a dozen intellectual property law professors (with Mark Lemley as Counsel of Record). It is the amicus brief filed by these law professors that is discussed in this post.

The Question Presented in the Supreme Court's certiorari grant frames every brief and states:

Whether enablement is governed by the statutory requirement that the specification teach those skilled in the art to "make and use" the invention, 35 U.S.C. § 112, or whether it must instead enable those skilled in the art "to reach the full scope of claimed embodiments" without undue experimentation ― i.e., to cumulatively identify and make all or nearly all embodiments of the invention without substantial "time and effort," Pet. App. 14a [emphasis in Question].

The professors'* arguments, by lead author Mark Lemley of Stanford University, rely heavily on the late Dmitriy Karshtedt's paper entitled The Death of Genus Claims (Dmitry Karshtedt, Mark A. Lemley & Sean B. Seymore, The Death of the Genus Claim, 35 HARV. J. L. & TECH. 1, 23-35 (2021). "The central feature of patent law in the life sciences industries is the genus claim" is the first assertion in the brief. The basis for the primacy of genus claims the brief explains is that without them, "a competitor could make a minor change to the chemical the patentee invented and avoid liability while capturing the heart of the invention." Prior to the recent spate of Federal Circuit decisions, including this one, the Supreme Court, the Federal Circuit, the C.C.P.A., and the Patent Office had recognized the usefulness and upheld the validity of genus claims in complying with the enablement requirement of 35 U.S.C. § 112(a) under the statutory mandate that the specification teach the skilled worker to make and use a chemical compound (as with every other type of invention) without undue experimentation. Recently however, the professors argue, the Federal Circuit had changed the law ("dramatically") to the extent that "it is no longer possible to have a valid genus claim in the chemical and biotechnology industries." The basis for this change is that "the Federal Circuit now rejects claims as invalid because the genus contains thousands or millions of possible chemicals, unless the patent itself identifies exactly which of those myriad species will work." This burden is impossible to satisfy, in the professors' view, and represents "a categorical shift in thinking away from teaching the PHOSITA and towards a precise delineation of the boundaries of the claim" they argue, citing the Karshtedt article.

Expounding on these arguments, the brief sets forth a brief history of the enablement requirement and how the Court has interpreted it, citing as examples The Telephone Cases, 126 U.S. 1, 539 (1888); Tilghman v. Proctor, 102 U.S. 707, 728-29 (1880); Carnegie Steel Co. v. Cambria Iron Co., 185 U.S. 403, 437 (1902); Cont'l Paper Bag Co. v. E. Paper Bag Co., 210 U.S. 405, 419-20 (1908); and Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 271 (1916). These interpretations, the professors argue, uniformly held that "a patent for such a discovery is not to be confined to the mere means he improvised to prove the reality of his conception" (The Telephone Cases), and that where an invention is "susceptible of being applied in many modes and by the use of many forms of apparatus . . . [t]he inventor is not bound to describe them all in order to secure to himself the exclusive right to the process" (Tilghman). And the law as it was had been sufficient to avoid the issues and uncertainties the Federal Circuit advanced as a rationale for its current jurisprudence, the brief stating that "a genus claim cannot survive if the patentee failed to provide any guidance on how to practice the claimed invention" (emphasis in brief), citing Wood v. Underhill, 46 U.S. (5 How.) 1, 4-5 (1846); Tyler v. Boston, 74 U.S. (7 Wall.) 327, 330 (1868); and Consol. Elec. Light Co. v. McKeesport Light Co., 159 U.S. 465 (1895).

The brief further explicates that the CCPA, Federal Circuit, and PTO had complied with this Supreme Court standard until recently, citing several cases and most prominently In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988), for the principle that a patent satisfies the enablement requirement even when the skilled worker must "engage in a reasonable amount of routine experimentation to figure out compounds that can achieve the claimed result." The need for some experimentation ''does not preclude enablement" the professors argue, citing Atlas Powder Co. v. E.I. du Pont de Nemours & Co., 750 F.2d 1569, 1576-77 (Fed. Cir. 1984). Summarizing, the professors assert that "enablement has not traditionally turned merely on whether there are many compounds within the claimed genus or whether routine screening takes considerable time" under the Wands test.

In contrast, the brief asserts that the current course of Federal Circuit jurisprudence is a "massive shift" in the enablement doctrine as applied by the Federal Circuit. That change is labeled the "full scope" standard, consistent with Amgen and other amici's positions. It differs from the traditional requirement because it "gauges enablement not by whether the experimentation needed to make and test particular species is undue, but by how long it would take the PHOSITA to make and screen every species within the claimed genus—even if that work would be routine" the professors argue, again citing the scholarship in the Karshtedt article. Under this new standard the brief argues that "'[a] chemical genus with any decently large number of species will never be able to satisfy' the Federal Circuit's new enablement standard" and it will become easy for defendants to prevail by arguing the "substantial time and effort" theory regarding satisfaction of the "full scope" test. And the Federal protestations to the contrary in its opinion denying rehearing en banc "ring[] hollow" to these professors because "the Federal Circuit is rejecting essentially every large genus claim challenged on enablement grounds, suggesting that the Federal Circuit's proposed method is illusory." The very basis for the Federal Circuit's distinction (structural differences) "misunderstands the science" because, the professors argue that in biological molecules, "[t]here might sometimes be a structural chemical difference that divides operative from non-operative species, but often there won't be," citing Mark A. Lemley & Jacob S. Sherkow, The Antibody Patent Paradox, Yale L.J.**

In addition, the professors assert that the Federal Circuit's "full scope" standard "misunderstands the point of the enablement requirement." This is because this "new approach . . . focuses on knowing exactly which species of a claimed genus will work instead of knowing how to make and use the invention" as required by the statute (as the CCPA recognized, a "certainty" standard makes any experimentation undue because by definition experimentation involves uncertainty; In re Angstadt, 537 F.2d 498, 503 (C.C.P.A. 1976)). Moreover, the Federal Circuit's emphasis on certainty could, the professors predict, result in "less, not more, disclosure of new ideas to the public" because it "would delay disclosure and frustrate, rather than further, the interests of the public," citing In re Bundy, 642 F.2d 430, 434 (C.C.P.A. 1981). Expanding on this theme, the brief argues that the "full scope" test "threatens patent protection for many inventions in the chemical and life sciences, where large genus claims are ubiquitous," which in turn "frustrates patenting and innovation." The conundrum the test creates is that satisfying the enablement requirement makes inventors "carry out a prohibitive number of actual experiments" and will result in "discourage[ing] inventors from filing patent applications in an unpredictable area since the patent claims would have to be limited to those [working] embodiments which are expressly disclosed," citing In re Angstadt. The reason the test cannot be satisfied for genus claims in the chemical and biotechnological arts is that "[n]o matter how much testing the patentee does, there will always be untested species, so courts cannot know whether they are properly included in the genus," a standard that is "fatal to genus claims." As a consequence:

Patent protection is important in the pharmaceutical and biotechnology industries, perhaps more than anywhere else. Given the importance of strong patent protection in these industries, the unwillingness of courts to permit chemical genus claims seems quite troubling as a policy as well as a doctrinal matter. The new rule makes it unreasonably difficult for a pharmaceutical company that comes up with an innovative new class of drugs to protect that class against imitation. That result threatens innovation.

For these reasons the professors advocate that the Court return enablement law to its "traditional moorings" because this interpretation of the doctrine "serves important purposes, including policing against overbroad and purely functional claims" while the current Federal Circuit standard "to teach or enable every possible species within the genus is unnecessary and unworkable." The law prior to these recent changes was not in need of them according to the professors because "the 'undue experimentation' test articulated in Wands has offered a useful and practical way" to address the question of what constitutes a sufficient enabling disclosure. This is because the focus of the standard was rooted in the understanding of the person of ordinary skill in the art, which provided a basis that was not in the application of "an arbitrary judicial rule." Under this standard the professors maintain that not all genus claims need satisfy the requirement, citing two examples. First, the brief asserts that "a genus claim must be accompanied by disclosure of some operable species within the claim" and "[i]t is doubtful a PHOSITA could 'make and use' a truly new and nonobvious invention without any working examples at all" (emphases in brief). This proscription will avoid the concern understood by the Court regarding "pure functional claiming."*** Second, the brief argues that a genus must share "some identifiable characteristics in common that set it apart from other categories," citing the Court's Consolidated Edison decision. These are instances of "improper generalization" the professors argue, wherein "the patentee defined a genus of things that don't have enough identifiable characteristics in common (something that can happen whether the genus is large or small). These claims are ultimately (according to the professors) dependent on whether "the patentee possess[ed] a true genus or merely a random assemblage of features without identifying a relevant property in common among them"(in the latter case there being no enabled genus claim).

Applying these rubrics the professors argue that Amgen disclosed a sufficient number of species to satisfy the proper test for enablement:

In this case, Amgen disclosed a number of working embodiments of anti-PCSK9 antibodies, it identified the particular epitopes of PCSK9 to which their antibody invention bound, and it provided other detail in its specification about the antibodies constituting its invention, including listing partial amino acid sequences for the business end of twenty-six antibodies. The claims are limited to antibodies that bind at least one of fifteen amino acids on the PCSK9 protein. Amgen's patent therefore does not appear to present either of the concerns identified above –pure functional claiming without workable examples or improper generalization without common identifiable characteristics.

For these reasons the professors argue the Court should reverse the Federal Circuit and specifically reject the full scope enablement standard that was the basis for the decision below.

*Another group of professors have filed an amicus brief in favor of Respondent Sanofi's position.

**This article will be the subject of a future post.

***In a footnote the professors discuss briefly (and somewhat unnecessarily) "prophetic examples" and that applications and patents containing them should be "viewed with special caution."

Posted at 10:58 PM in Enablement, Supreme Court | Permalink | Comments (2)

March 12, 2023

Amgen Files Reply Brief in Amgen v. Sanofi

By Kevin E. Noonan --

Amgen recently filed its Reply brief to the Supreme Court in Amgen v. Sanofi. While a conventional proportion of Amgen's Reply is directed to arguments Respondent Sanofi made in its brief, at trial, and before the Federal Circuit, significant portions of the Reply brief are focused on the Federal Circuit's grounds for its decision, which may be wise for at least two reasons. The first, of course is the seeming anathema the Supreme Court has had for Federal Circuit jurisprudence for over a decade, reversing almost all that circuit court's decisions in whole or part. (It will be understood that the likelihood of reversal of Federal Circuit decisions may be higher than other circuit courts because the court's exclusive jurisdiction over patent matters means the only situations analogous to "circuit splits" arise from disagreements between the Federal Circuit judges, tempered by whatever deference lingers for that court's "special expertise" noted in Warner-Jenkinson Co. v. Hilton Davis Chemical Co.) The other reason is that Amgen's argument in its principal brief is that the Federal Circuit has crafted a new test for enablement, which it termed the "full scope" test, that is contrary to the plain meaning of the statute (as well as Supreme Court precedent) because the new test mandates that each and every species in a claimed genus be set forth rather than that the disclosure merely teach the skilled worker how to make and use the claimed invention.

In its argument, Amgen asserts that the defects of the Federal Circuit's "full scope" enablement test include that it depends on "the cumulative time and effort" needed to determine and disclose the full scope of what is claimed (which for a genus claim would encompass all or substantially all of the species falling within the scope of the genus) (which Amgen asserts that the Solicitor General contends is "a test [that] has no foundation in the text [of § 112] or [the] Court's precedent"). The proper enablement test, Amgen asserts, is the statutory "make and use" test, which "requires a practical inquiry into what skilled artisans can do using the patent's disclosures." And if the disclosure is "sufficiently definite to guide those skilled in the art to" the "successful application" of "the invention," Amgen contends, the patent is enabled, citing Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 271 (1916). Amgen further argues that the number of embodiments (or species in a genus) is irrelevant to this standard (although as a practical matter it seems this argument cannot be an absolute one). "The Federal Circuit's opinion [that Amgen's claims are not enabled] plainly turns on the effort required to identify and make all or nearly all the antibodies within Amgen's patent claims," Amgen asserts, which is a "heightened" enablement standard beyond the statutory requirements. The Federal Circuit's purported new test "consider[s] the quantity of experimentation that would be required to make and use, not only the limited number of embodiments that the patent discloses, but also the full scope of the claim" Amgen contends (emphasis in brief). The amount of experimentation (how many potential species fall within the scope of a genus) needed can by itself amount to undue experimentation under the Federal Circuit's test, Amgen contends. The basis for the Federal Circuit's decision below was the "substantial time and effort" necessary for this identification of all these antibodies (undue experimentation would be required to practice the full scope of these claims) and the consequence of this new interpretation of enablement law, in Amgen's view, is that the Federal Circuit reached its non-enablement conclusion based on the "millions of candidate antibodies" the claims encompass. As a result "'it would be necessary to first generate and then screen each candidate antibody' to determine whether those antibodies fell within the claims" to satisfy the Federal Circuit's test. Illustrating both this meaning of the Federal Circuit's opinion and the potential danger it raises, Amgen cites the decision in Human Power of N Co. v. Heartbeet Ltd., No. PGR2021-00110, 2022 WL 683124, at *9 (P.T.A.B. Feb. 25, 2022), and the district court's decision in Baxalta Inc. v. Genentech, Inc., 579 F. Supp. 3d 595, 616 (D. Del. 2022), and Astra-Zeneca AB v. Mylan Pharms. Inc., No. 1:18CV193, 2022 WL 16857400, at *8 (N.D. W. Va. Nov. 9, 2022), which have applied the Federal Circuit's decision below to impose this increased disclosure requirement in finding claims non-enabled.

The Federal Circuit erred, according to Amgen, because that court "varied the Wands factors by asking whether there would be 'undue experimentation in identifying,' from 'millions of ' potential embodiments, those that 'satisfy' the genus's 'requirement[s],' i.e., the effort to "reach the full scope." Amgen asks the Supreme Court to "restore the statutory standard" of "make and use" which requirement is a clear, practical test, so that "the patentee [is required] to describe his invention so that others may construct and use it after the expiration of the patent," citing Schriber-Schroth Co. v. Cleveland Tr. Co., 305 U.S. 47, 57 (1938). The fact that a claim encompasses numerous embodiments that may be different from one another does not render the claim nonenabled according to Cont'l Paper Bag Co. v. E. Paper Bag Co., 210 U.S. 405, 418-419 (1908), Amgen argues. And rather than the Federal Circuit's new bright line rule what should be used is a flexible inquiry "that takes into account the nature of the claimed invention and the field in which it arises," citing the Solicitor General's amicus brief in this regard.

One portion of Amgen's brief illustrates the thorny and contrary considerations the Supreme Court must grapple with:

Amgen agrees patents must reasonably enable the entire scope of the claim. Where an invention has many embodiments, the patent enables the invention's "full scope" if skilled artisans can "reasonabl[y]" make and use "variation[s]," without gaps in subject matter skilled artisans would consider significant with "regard to [the patent's] subject-matter." Minerals Separation, 242 U.S. at 270. If the patent's instructions are "sufficiently definite to guide" skilled artisans to "successful application" across the scope of the "invention," the claims are enabled. Id. at 271. In such cases, the "enabling disclosure" is 'commensurate with the scope of the claims.'" But cataloging every embodiment is a task for "the mechanic, not the inventor." 2 W. Robinson, The Law of Patents for Useful Inventions §485 (1890) (other citations omitted).

Amgen supports this calculus with Supreme Court and other precedent, including Mowry v. Whitney, 81 U.S. (14 Wall.) 620 (1872) (methods for manufacturing railway wheels not required to recite "the specific timing and temperature parameters for every type of wheel skilled artisans might make"); Wood v. Underhill, 46 U.S. (5 How.) 1 (1846) (while exceptions arose in formula for mixing clay and coal dust to make bricks, those exceptions did not amount to non-enablement where "artisans would be able to apply the formula to most types of clay."); and Carver v. Braintree Mfg. Co., 5 F. Cas. 235, 237 (C.C.D. Mass. 1843) (claims enabled where a "skillful mechanic" could use the specification to make a rib for many kinds of cotton).

Addressing the asserted necessity for the "full scope" test, that without it there would be no reasoned way to prevent overbroad genus claiming, Amgen argues that "[t]here are various ways defendants can disprove enablement" including where a skilled artisan cannot make the invention at all, Beidler v. United States, 253 U.S. 447, 453 (1920); where there is a "distinct category of embodiments within the claim's scope that cannot be made following the patent's disclosures, Auto. Techs. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 1285 (Fed. Cir. 2007); or in "needle-in-a-haystack" situations involving "labor-intensive hunt for working embodiments that exceeds what skilled artisans typically do," Consol. Elec. Light Co. v. McKeesport Light Co., 159 U.S. 465, 472-475 (1895); Béné v. Jeantet, 129 U.S. 683, 684-686 (1889); and Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245, 250-251, 257 (1928).

The brief then discusses the impact of inoperative embodiments in a genus claim on enablement, asserting that such emodiments within a genus do not alone invalidate a claim, citing Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984). Amgen illustrates the impact (or lack of it) of inoperative embodiments in Consolidated Electric, wherein the defendant prevailed by presenting clear-and-convincing evidence that months of experimentation, with thousands of materials, was necessary to find one fiber (bamboo) that would function as claimed. 159 U.S. at 472-474. Amgen further states in this regard that the Federal Circuit's decision was based on a factual error: rather than being limited to 26 expressly disclosed antibodies its specification disclosed 384 antibodies (reminiscent of the situation in Wands where the Patent Office considered demonstration of 9 positive antibodies from amongst 143 produced to be nonenabled while the Federal Circuit considered these 9 antibodies in the context of 16 tested). The "millions" of potential candidates forming another (albeit related) basis for the Federal Circuit's decision could be produced by conservative substitution Amgen notes, but counters that the patent teaches these variants. What its specification doesn't do, Amgen concedes, is teach which ones would be functional but according to Amgen there is no "needle in the haystack" problem with their specification because there was no evidence that any conservative substitution produced an inoperative embodiment. Amgen contends that these considerations are only relevant under the full scope test rather than being a reasoned basis for it (and Amgen does not mention that this test bypasses the principle from Wands that even extensive experimentation does not negate enablement if it is routine, well understood in the art, and operative embodiments can be readily and reliably identified).

Another target for Amgen's arguments is the government: Amgen contends that while the Solicitor General's (SG) brief pays lip service to a "reasonableness" standard based on Minerals Separations it then deviates from that standard, "from the record and the rules of procedure and evidence." Amgen cites the government's reliance in its brief on the limited number (26) of expressly exemplified antibodies as a basis for the claims being overbroad, and that the SG asks the Court to infer that accordingly Amgen didn't make additional antibodies because it did not know how to do so (which of course Amgen counters with the 384 antibodies recited in the specification). And with regard to the procedural deficiencies Amgen asserts against the SG's brief, the Reply brief cites the presumption of validity of a granted patent that must be overcome by clear and convincing evidence to the contrary. This quote from Minerals Separations is usefully cited in supporting this argument: "A patent's teachings may "guide" skilled artisans to the "successful application" of a nearly "infinite[ ]" number of embodiments beyond those disclosed in the specification" as well as from Smith v. Snow, 294 U.S. 1, 11 (1935), that "it is "not necessary to . . . describe in the specification[ ] all possible forms in which the claimed principle may be reduced to practice."

One (perhaps novel) government argument identified by Amgen is the requirement that when a patent claims a genus, an enabling disclosure requires "some general quality" described in structural terms that distinguishes the claimed products from others outside the scope of the claimed genus, a rubric derived from Consol. Elec., 159 U.S. at 475 and Holland Furniture, 277 U.S. at 256). The error here, according to Amgen, is that "[w]hile describing a structure may be one way to enable a genus, the Court has never held it is the only way, regardless of the nature of the art," citing examples like Neilson v. Harford (1841) 151 Eng. Rep. 1266, 1273-1274 (Exch.), and more recently Diamond v. Chakrabarty, 447 U.S. 303, 305-306 (1980).

And with regard to Amgen's purported "roadmap" for how to produce functional antibodies having the required specificity, Amgen asserts that "[f]ar from requiring skilled artisans to 'retrace' Amgen's "research steps," the patents allow them to start where Amgen's research ended," which of course is the benefit disclosure in a patent confers on the public, Amgen enumerating eight specific benefits. Amgen refutes the assertion that the roadmap or its other teachings amount to "trial and error" methods, stating rather that these are screening methods understood by the skilled workers.

Most of Amgen's arguments specifically directed to Sanofi's Respondent's brief (besides the rhetorical) are directed to disputes about the record below, whether Sanofi's positions have changed between what was argued before the Federal Circuit and in its Supreme Court briefing and that the level of disclosure in Amgen's competitors' patents (including Sanofi's) are no more enabling under the full scope test than in Amgen's patent-in-suit.

The brief concludes with reference to proper patent policy, where Amgen argues that the Federal Circuit's full-scope test is not consistent with the patent bargain, citing Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 63 (1998). The brief cites the analysis by the late Professor Karshtedt and colleagues, The Death of the Genus Claim, 35 Harv. J.L. & Tech. 1, 1 (2021), regarding the need for genus claiming in biotechnology and antibody inventions and the paucity of protection afforded to antibody claims limited to specific antibody sequences. Amgen further argues that using the roadmap provided by Amgen's patents permits competitions to make their own antibodies based on this disclosure. Amgen also reminds the Court that the doctrine of equivalents is insufficient to protect claims to specifically disclosed antibodies because "[c]ourts . . . have refused to apply 'the equivalence argument' because it is feared that this 'would read the amino acid sequence limitation out of' the claim and 'effectively expand' the claim's scope to encompass any 'antibody that has the [claimed] effect,'" citing Teva Pharms. Int'l GmbH v. Eli Lilly & Co., No. 18-cv-12029, 2022 WL 4824318, at *19 (D. Mass. Oct. 3, 2022). Under these circumstances, Amgen warns that "[n]o company would invest billions in researching and developing new antibodies in hopes that the doctrine of equivalents will prevent competitors from evading an amino-acid-sequence claim."

Addressing again the weakness (in Amgen's view) of arguments regarding the danger of overbroad genus claims Amgen cites Westinghouse v. Boyden Power Brake Co., 170 U.S. 537, 568 (1898), for the principle that a species (here, an antibody) that "'has so far changed the principle of the' patent claim can be held not to fall within its enabled scope 'even if it "literally" falls within the class [of antibodies])'", and to the argument that broad genus claims harm innovation Amgen argues that improvements (in the form of particular species) incentivizes innovation (i.e., that patents incentivize the search for a "better mousetrap" rather than preclude that search).

Finally, Amgen argues that this case is not the case presented in O'Reilly v. Morse that claimed "'the use of . . . electro-magnetism, however developed, for making or printing intelligible characters . . . at any distances,'" on the basis that there are alternatives (such as siRNA, or antibodies that bind outside the sweet spot and small molecule inhibitors) for the antibodies disclosed in its specification. As a consequence, Amgen argues:

That is the type of innovation the patent system should promote—encouraging companies to develop diverse therapies, not minor variations of antibodies performing the same function in the same way. Upholding genus claims for pioneering inventions accelerates the progress of science as inventors seek their own breakthroughs instead of developing "me too" products . . . ."

The Supreme Court is scheduled to hear oral argument from the parties and the Solicitor General on March 27th; in the meantime posts on the positions of various amici will appear here.

Posted at 10:43 PM in Enablement, Supreme Court | Permalink | Comments (0)

February 19, 2023

Sanofi and Regeneron File Respondents' Brief on Amgen v. Sanofi

By Kevin E. Noonan --

Sanofi and Regeneron filed their brief at the Supreme Court in Amgen v. Sanofi, in which Amgen seeks to have the Court overturn the District Court's grant of JMOL in the issue of whether Amgen's claims were invalid for non-enablement under 35 U.S.C. § 112(a) (see "Amgen Files Its Principal Brief in Amgen v. Sanofi").

To recap, the Question Presented on which the Supreme Court granted certiorari is:

The claims at issue in Amgen's asserted patents, U.S. Patent Nos. 8,829,165 ("'165 patent") and 8,859,741 ("'741 patent"), encompassed antibodies that recognized specific amino acids in the amino acid sequence of the PCSK9 protein, reciting no structural features or limitations of these antibodies but rather the combination of "target" amino acids, as illustrated in Amgen's brief:

The Federal Circuit upheld the District Court's grant of JMOL for non-enablement based on the lack of disclosure regarding the structure of antibodies falling within the scope of the claim in the face of what the District Court understood to be the large number of antibodies (the patents "cover . . . a vast scope of possible antibodies," potentially "millions," or "millions and millions" and implicate "an astronomically large number" of candidates) having the claimed binding properties and the small number (26) of antibodies disclosed in Amgen's specification, as well as the "randomness in how the immune system" produces antibodies means that each immunization creates a "big pool of potential [antibodies]," wherein "you don't know what you're going to get," characterizing such efforts as being "a fishing expedition" (a characterization that may resonate with the Supreme Court).

Sanofi's brief begins with an appropriate amount of advocacy, admirably avoiding purple prose in describing their response to Amgen's assertions in its Opening Brief, stating that Amgen's filing of the patent at issue was strategically aimed at preventing Sanofi from marketing its PCSK9 antibody Praluent® (alirocumab) "in a blatant attempt to corner the market" by claiming a genus of antibodies by function rather than structure (noting that its patent claimed its Praluent antibody by its amino acid structure), and then "asserting a monopoly over an entire genus of functionally defined claims." In so doing, Sanofi argues Amgen created the "high hurdles" Amgen accuses the Federal Circuit of raising by attempting to contravene the "commonsense proposition" that "the more companies claim as their patent monopoly, the more they must enable" which is "the heart of the patent bargain." Regarding the disclosure Amgen relies upon in ts specification, the brief asserts that it merely tells the skilled artisan "to make claimed antibodies by randomly generating and testing candidates via processes well-established in the prior art." The brief illustrates the scope of Amgen's claims with regard to four antibodies made by Amgen's competitors (including Praluent) and how different they were from the antibodies actually disclosed in Amgen's specification:

Regarding the policy consequences attendant upon Amgen's position the brief states that:

The simple reality is that Amgen has claimed a monopoly over far more than it has enabled. Such claims are not just invalid, but dangerous. They can take medicines away from physicians and patients and could allow someone without a clinically valid species to claim an entire genus of medically-vital antibodies they have not yet discovered.

The brief also emphasizes the health risks of LDL-C and attendant importance of Praluent in addressing this risk (which Amgen's patent threatens) and that the matter before the Court does not involve Amgen's patent on Repatha® itself, countering Amgen's arguments in its brief that it had invested "billions of dollars and a decade of research bringing [it] to market" as a reason to overturn the Federal Circuit's decision.

On the law Sanofi argues that the Federal Circuit's straightforward application of the enablement standard applying the Wands factors was entirely consistent with the history of the statute and judicial interpretations thereof, including importantly Supreme Court precedent. This standard "has long been understood to require sufficient disclosure to enable a skilled artisan to make the entire invention claimed, not just a subset, without the need for any significant independent experimentation" under that precedent. The brief characterizes as a "straw man" Amgen's argument in its Opening Brief that the Federal Circuit has established a new, unnecessarily stringent test for enablement.*

The Argument section of the brief assays the precedential history of the Supreme Court's and lower courts' upholding the conventional enablement standard and its relationship to the patent bargain, wherein the scope of enabled claims is determined and cabined by what is disclosed, citing Pennock v. Dialogue, 27 U.S.1, 23 (1829) (Story, J.); J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int'l, Inc., 534 U.S. 124, 142 (2001); Festo Corp. v. Shoketsu Kinzoku Kogyo Kabushiki Co., 535 U.S. 722, 736 (2002), and precedents under English law, King v. Arkwright, (K.B. 1785). The brief draws parallels regarding this understanding of what is required to satisfy enablement under English law to enactment of the first Patent Act in 1790 and the consistency of this standard in subsequent patent law enactments. This interpretation of the enablement statute is supported in the brief by a thorough explication of judicial precedent consistent with Sanofi's argument that scope requiring undue experimentation has historically been deemed inadequate, including Consol. Elec. Light Co. v. McKeesport Light Co. (The Incandescent Lamp Patent), 159 U.S. 465, 474-75 (1895) ("painstaking experimentation"; Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245, 256-57 (1928) ("elaborate experimentation"), and finally the modern "undue experimentation" standard adopted by the CCPA in In re Folkers, 344 F.2d 970, 976 (C.C.P.A. 1965), and adopted by the Federal Circuit in In re Wands, 858 F.2d 731 (Fed. Cir. 1988) (reciting the Wands factors).

The brief then sets forth the recent history of cases illustrating how the Federal Circuit (consistent with this precedent) has held cases to be non-enabled "if a claim encompasses 'thousands' of 'candidate compounds,' and 'testing' or 'screening' of each candidate is necessary 'to determine which . . . meet [the] claim,'" citing Idenix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1156-58, 1162-63 (Fed. Cir. 2019); Enzo Life Scis., Inc. v. Roche Molecular Sys., Inc., 928 F.3d 1340, 1345-49 (Fed. Cir. 2019); Wyeth & Cordis Corp. v. Abbott Labs., 720 F.3d 1380, 1384-86 (Fed. Cir. 2013), characterizing these decisions as "guard[ing] against what Amgen has done here: claim a lot and disclose a little, such that skilled artisans (and even Amgen's own scientists) must engage in undue experimentation because the disclosure leaves them guessing as to how to make and use the full scope of the claimed invention."** This is not a "special rule" for functional genus claims, the brief argues but rather a consequence of "some genus claims assert a monopoly over far more than they enable," contrary to both the statute and precedent.

Turning to a direct confrontation of Amgen's arguments in its Opening Brief, Sanofi contends that Amgen has provided the Court with no persuasive reasoning for changing the established standard (under which Sanofi contends the District Court and Federal Circuit properly invalidated Amgen's claims on enablement grounds). As characterized by the brief, Amgen itself has not challenged the conventional test (or otherwise would have had to argue contrary to its own arguments below). Rather, the brief argues, Amgen has created, by a "profound mischaracterization" of the decisions below, a chimerical "new" and "different" enablement standard, the "full-scope" requirement, that Sanofi argues is not what the Federal Circuit held, citing language from that Court's decision expressly disclaiming such a standard (the decision "specifically resisted what might be termed a simple 'numerosity' or 'exhaustion' requirement," and that any assertion that the Federal Circuit had "adopted a 'numbers-based standard' to evaluate enablement" that asked "how long it would take to make and screen every species" simply "mischaracterizes our law"). In the Federal Circuit's view (as explained in the brief) "[t]he problem was that the unpredictability of the science combined with a broad functional claim that 'extend[ed] far beyond the examples and guidance provided' left skilled artisans with no ability to generate specific undisclosed embodiments and no option but to engage in trial and error using well-established techniques to generate candidate antibodies that would then still need to be tested to ascertain whether they came within the claimed genus." And Amgen nowhere has identified language in the Federal Circuit's opinion reciting its "new standard" according to the brief. The important distinction made in the brief between what the Federal Circuit held and what Amgen asserts its decision means is:

When a specification enables a skilled artisan to predictably make specific undisclosed embodiments under circumstances where making all of them would take time, the cumulative effort needed to make and use every single embodiment of the claimed invention is unproblematic. But when the specification provides no useful guidance to skilled artisans to make and use specific undisclosed embodiments and consigns them to a trial-and-error process to unpredictably generate antibodies that must then be tested to determine whether they even fall within the broad functionally claimed genus, Federal Circuit precedent along with this Court's precedent and statutory text all indicate that the claimed invention is not enabled.

This does not constitute a new test according to the brief, contrasting the situation with the patents before the Court with Amgen's and Sanofi's patents on their Repatha and Praluent antibodies, respectively, which provide an unchallenged enabling disclosure of the amino acid sequence of these antibodies.

The brief also argues that the Court should reject Amgen's "as-needed" enablement test advocated as an alternative, based on its inconsistency with the "statutory text, settled precedent, or longstanding practice," providing extensive analysis of precedent and the history of enablement law in support of its position.

The brief then sets forth Sanofi's arguments that, contrary to Amgen's assertions it is Amgen's position(s) that threaten to harm innovation, by permitting Amgen (and applicants in Amgen's position in future) to patent protection for claims outside what has been disclosed and thus precluding others from their inventions that have been enabled. Under current Federal Circuit precedent, innovation has not been harmed according to the brief (disregarding the one non-precedential decision by the PTAB cited in Amgen's Opening Brief, which was based on conventional application of the Wands factors). The brief also cites several instances where the Federal Circuit and district courts have upheld satisfaction of the enablement requirement in biotech and pharma cases, specifically Bayer Healthcare LLC v. Baxalta Inc., 989 F.3d 964, 970-71, 980-81 (Fed. Cir. 2021), and Erfindergemeinschaft UroPep GbR v. Eli Lilly & Co., 276 F.Supp.3d 629, 659-663 (E.D. Tex. 2017), and noting that innovation in these areas has proceeded without enablement impediment in these industries (citing paradoxically Prof. Karshtedt's law review article in support of this argument). The brief cites the doctrine of equivalents to counter Amgen's arguments against the threat of mere copyists if genus claims of broad scope are precluded by the enablement requirement, and the countervailing risk to innovation Sanofi asserts is raised by claims having Amgen's scope. The brief argues that this case "perfectly illustrates the risks" wherein Amgen's patents if upheld would ban Sanofi's Praluent from the marketplace and prevent patients needing it from getting it, particularly to the extent that Praluent is available in dosages Amgen cannot provide ("allowing a company that has discovered only particular species to obtain a patent on a broad functionally claimed genus creates a very real risk that important medical treatments will never reach the market"). The brief uses the history of Pfizer's unsuccessful attempts to gain regulatory approval for its anti-PCSK9 antibody as a "cautionary tale," where if Pfizer had adopted the claiming strategy followed by Amgen "it would have stifled innovation, and patients would have had no PCSK9 antibody therapies at all—or, at best, would have had to wait longer for Pfizer to develop a safe and effective antibody through trial and error."

Finally, Sanofi's brief sets forth specifically why Amgen's specification is not enabling for the scope of the functionally defined genus claims at issue before the Court, why Sanofi agrees that the case "does not require a third trip through the Federal Circuit" and that the decisions below should be affirmed.

There are a plethora of amicus briefs on both sides of the issue in this case, and those briefs will be the subject of future posts. The Supreme Court should render its decision by the end of the current term.

* In this regard the brief distinguishes Professor Dmitry Karshtedt's law review article on "The Death of the Genus Claim" by stating even those authorities ultimately concede that innovation has not been harmed by the decision.

** What these cases arguably do is remove the conventional application of the Wands standard that extensive experimentation is not undue if it is routine such that the extensiveness of the experimentation can itself be undue and thus non-enabled (despite the Federal Circuit's assertions to the contrary).

Posted at 11:16 PM in Enablement, Supreme Court | Permalink | Comments (1)

February 05, 2023

Amgen Files Its Principal Brief in Amgen v. Sanofi

By Kevin E. Noonan --

Facing what is likely to be something of an uphill battle in seeking to have the Federal Circuit's decision against it in Amgen v Sanofi overturned before a not always patent-friendly Supreme Court, Amgen in late December filed its opening brief addressing the Question Presented in the granted certiorari petition:

The brief begins by disparaging the decision based on the Federal Circuit "once again" "imposing limitations on the Patent Act that are inconsistent with the Act's text" as the Supreme Court asserted in Bilski v. Kappos, 561 U.S. 593, 612 (2010). Amgen argues that the focus of the Court's consideration of the question before it should be on the statute and its text, which has not changed appreciably since the 1790 Patent Act enacted by the Founders. An important consideration regarding this question is the "patent bargain," recognized by the Court in Universal Oil Prods. Co. v. Globe Oil & Refin. Co., 322 U.S. 471, 484 (1944), and Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 63 (1998), and Amgen's assertion that the Federal Circuit's decision violates all three prongs -- statutory text, precedent, and history -- of enablement law in establishing its full scope" test (illustrating the incorrectness of the test in its view by asserting that patents protecting inventions like Watt's steam engine and the Wright Brothers' airplane would not pass muster under this test). "[T]he law has never required that, for those inventions to be patentable, skilled artisans must be able to cumulatively identify and make every variation without substantial time and effort" (emphasis in brief), Amgen argues and characterizes the standard as "folly" based on treatises from Robinson (1890) to the late Dmitriy Karshtedt's paper entitled The Death of Genus Claims (Dmitry Karshtedt, Mark A. Lemley & Sean B. Seymore, The Death of the Genus Claim, 35 HARV. J. L. & TECH. 1, 23-35 (2021). The basis for the full scope test -- the need to describe a patented invention through its full scope to satisfy enablement -- is contrary to Supreme Court precedent, Amgen argues, citing (amongst many other cases as its argument is developed) Smith v. Snow, 294 U.S. 1, 11 (1935), for the principle that it is "not necessary to . . . describe in the specification[] all possible forms in which the claimed principle may be reduced to practice." Amgen asserts that the proper alternative to the Federal Circuit's test can be found in Consolidated Electric Light Co. v. McKeesport Light Co., 159 U.S. 465 (1895), "which applied the statutory standard to invalidate claims where there was proof that the patent's instructions were not enabling for large classes of claimed subject matter."

And such an analysis is not needed in this case, according to the brief, because there is no evidence that the disclosure is actually deficient in any way regarding Amgen's "breakthrough" invention of monoclonal antibodies with real world benefits (reducing cholesterol). While setting forth an explication of the technology is unnecessary here, the brief emphasizes the limited area of the PCSK9 protein involved in the antibody interaction that provides the therapeutic benefit and constrains the antibodies that can interact with it, shown in this drawing as the purple-colored section of the molecule:

The brief emphasizes the extent of disclosure in the patent specifications instructing the skilled worker on how to make antibodies that recognize these limited portions of the protein, and the "roadmap" that teaches the skilled artisan how to make antibodies having the relevant therapeutic properties (many steps of which are "high throughput"), as well as the capacity to make "conservative" substitutions to provide alternative embodiments of antibodies having the requisite therapeutic function. The disclosure satisfies the Wands test, the brief asserts, and that should be enough.

In the face of this evidence from the specification (and the two juries' fact-finding supporting their verdict that the claims were not shown to be non-enabled), Amgen argues that the Federal Circuit's basis for invalidating for non-enablement was mere speculation, citing portions of the decision in support of these assertions stating that "there might be 'millions of candidates' that fall within the claims, each of which would have to be 'generate[d] and then screen[ed]' to determine whether it met the claims' requirements"; "'you could be immunizing mice for a hundred years,'" but "'[t]here might be kind of an antibody that you didn't come up with in that time period'"; and that those same conservative substitutions could produce (unpredictably) a non-functional antibody. Amgen emphasizes the contrariness of the Federal Circuit's imposition of its invalidation on enablement grounds to the two juries' decisions that the claims were enabled as well as the clear and convincing evidence standard of proof Amgen contends the juries' decisions establish Respondent did not satisfy juxtaposed to what Amgen deems speculation by the Federal Circuit panel rendering the decision.

With regard to the statute, Amgen argues that its purpose is "to require the patentee to describe his invention so that others may construct and use it after the expiration of the patent," citing Schriber-Schroth Co. v. Cleveland Tr. Co., 305 U.S. 47, 57 (1938), and that the full scope test has no basis in the statutory language. The statutory standard is straightforward, Amgen maintains, and evidence of this straightforwardness is that the Court has applied it without necessary interpretation ("directly"), citing Wood v. Underhill, 46 U.S. (5 How.) 1, 5 (1846) (permitting unspecified variations in types of clay used to make bricks and tiles); Mowry v. Whitney, 81 U.S. (14 Wall.) 620, 644 (1872) (method for manufacturing railway wheels that avoided "strain" due to different wheel parts cooling at different rates without requiring all types of wheels and all temperatures to be expressly exemplified); Loom Co. v. Higgins, 105 U.S. 580, 586 (1882); The Telephone Cases, 126 U.S. 1, 536 (1888); Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 271 (1916) (wherein a method for concentrating mineral ores using mixture and hearing with oil was permitted a scope that encompasses unexemplified ores and variations on the method to adapt it to different ores); and Universal Oil Prods. Co. v. Globe Oil & Refin. Co., 322 U.S. 471, 484 (1944). Amgen argues that the application of the standard in these cases is consistent with the plain meaning of the statute. On the contrary, the Federal Circuit's "full scope" requirement deviates from the statutory text by requiring more than the statute does, by "focus[ing] on the "number of possible candidates within the scope of the claims"—the number of theoretical embodiments that might meet the claims' requirements" (emphasis in brief). And this heightened requirement has not been applied to other genus claims Amgen argues, citing McRo inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 1100, as an example. What the Federal Circuit has done with its heightened "full scope" requirement is to have turned enablement into a "numbers game" with regard to the 26 exemplified disclosed antibodies and the theoretical "millions of candidat[e]" antibodies which would then need to be generate[d] and screen[ed]" to satisfy the full scope test. And this is an impossibility, Amgen states, as the Supreme Court has recognized in holding this was not the proper test, citing Mowry.

Amgen's arguments harken back to the Framer's adoption of English patent law (citing several English cases in which Amgen argues the full scope standard would have "flunked"), codified in the 1790 Patent Act that has remained essentially unchanged to the present 1952 statute. The consistency in the statute and its interpretation "tends to negate the existence of" the Federal Circuit's new "full scope" standard Amgen argues, citing Printz v. United States, 521 U.S. 898, 918 (1997). 19th and early 20th Century U.S. case law is consistent with Amgen's interpretation, the brief citing Carver v. Braintree Manufacturing Co., 5 F. Cas. 235 (C.C.D. Mass. 1843) (Justice Story) (cotton gins), as well as treatises (W. Phillips, The Law of Patents for Inventions 237 (1837); G. Curtis, A Treatise on the Law of Patents for Useful Inventions §124 (1849)) and regional Circuit Courts of Appeal decisions (Toledo Rex Spray Co. v. Cal. Spray Chem. Co., 268 F. 201, 204 (6th Cir. 1920); Donner v. Am. Sheet & Tin Plate Co., 165 F. 199, 206 (3d Cir. 1908); Philip A. Hunt Co. v. Mallinckrodt Chem. Works, 177 F.2d 583, 585 (2d Cir. 1949); Ill. Tool Works, Inc. v. Foster Grant Co., 547 F.2d 1300, 1309 (7th Cir. 1976)). Amgen also cites several pre-Federal Circuit cases that would have invalidated the patents at issue under the full scope test, including Franc-Strohmenger & Cowan, Inc. v. Arthur Siegman, Inc., 27 F.2d 785, 785-786 (2d Cir. 1928) (neckties made with "resilient" linings); and Ansul Co. v. Uniroyal, Inc., 448 F.2d 872, 877878 (2d Cir. 1971) (methods to grow plants encompassing "the entire plant kingdom"). Finally, the brief cites decisions from the Federal Circuit's predecessor Court, the Court of Custom and Patent Appeals that (Amgen argues) support its "plain meaning" interpretation of the enablement requirements of Section 112, including In re Gay, 309 F.2d 769, 772 (C.C.P.A. 1962); In re Halleck, 422 F.2d 911, 912, 914 (C.C.P.A. 1970); and In re Angstadt, 537 F.2d 498 (C.C.P.A. 1976) (citing Minerals Separation).

Amgen further argues that the statute provides a "reasonableness" standard dependent on the patented subject matter that can balance the scope of the claims and whether the "specific instructions" are "sufficiently robust to permit skilled artisans to reasonably make and use individual embodiments as needed" rather than requiring a skilled artisan to be able to make "all embodiments, seriatim with minimal time and effort." Amgen asserts that the Federal Circuit's "full scope" standard "serves no valid patent-law policy and harms innovation[,] fundamentally alters the basic patent bargain[, and] discourages breakthrough innovations by cutting off patent protection for the most significant inventions simply because they have too many useful applications," which "threatens devastating consequences." The brief argues that the Federal Circuit's full scope test is contrary to the constitutional mandate that the patent laws "promote progress" because "[o]nce an invention has been described sufficiently for skilled artisans to make and use it, disclosing thousands more examples of variations that achieve the same result contributes little to the store of human knowledge." And worse, the brief argues, application of the test "destroys incentives for breakthrough inventions" like the case at bar, positing a correlation between "the more pioneering the innovation, the more likely it is to have a broad range of applications." Perversely in Amgen's view, the Federal Circuit test creates a situation where "[i]t makes no sense to deny groundbreaking innovations patent protection because they somehow have too many useful implementations" (emphasis in brief).

The brief also juxtaposes the practical application of the enablement test under well-established precedent under the statute with the "theoretical inquiry into hypothetical applications" engendered by the Federal Circuit's full scope test. Defendants are not without means to challenge enablement under the conventional standard, Amgen asserts, as exemplified by instances where the skilled worker cannot practice a claimed invention at all, citing Beidler v. United States, 253 U.S. 447, 453 (1920), or that practicing the invention requires the public to achieve invention "in their own right" to obtain an operative embodiment, citing Consol. Elec. Light Co. v. McKeesport Light Co., 159 U.S. 465, 472-474 (1895), or reciting alternative embodiments in the claims where there is no teaching regarding one of them, citing Auto. Techs. Int'l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 1285 (Fed. Cir. 2007). There are also the "needle in a haystack" forms of non-enablement according to Amgen, such as in Idenix Pharms. LLC v. Gilead Scis. Inc., 941 F.3d 1149, 1162 (Fed. Cir. 2019), cert. denied, 141 S. Ct. 1234 (2021); and Wyeth & Cordis Corp. v. Abbott Labs., 720 F.3d 1380, 1384-1385 (Fed. Cir. 2013), or circumstances where the number of inoperative embodiments is so large that the effort required to produce an operative embodiment "becomes significant" as in Atlas Powder Co. v. E.I. du Pont De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984); in all these instances the claims are not enabled under the conventional enablement test without need for recourse to the Federal Circuit's full scope test. These cases also illustrate that there is no overbroad claiming "problem" in need of the full scope test to remedy, Amgen states, because "[i]f the claim truly exceeds what the patent enables, challengers will always be able to show, through evidence, that skilled artisans cannot reasonably 'make and use' large areas of the claimed invention by following the patent's teaching" (emphasis in brief), as illustrated by the Court's decision in Consolidated Electric, and several other cases, including Béné v. Jeantet, 129 U.S. 683 (1889); and Holland Furniture Co. v. Perkins Glue Co., 277 U.S. 245 (1928). Thus Amgen asserts the Federal Circuit's full scope test is unnecessary in attempting to solve a problem that does not exist, and in doing so in this case "allow[ed] clearly enabled claims to be invalidated based on speculation rather than proof" as evidenced by Respondents' failure "to identify even one actual antibody that could not be made following the patent's disclosures" (emphasis in brief).

The brief takes the time (as it almost must) to set forth the deleterious consequences that are likely to arise if the full scope enablement test is affirmed. These include harm to genus claims not limited to chemical, biotechnological, and pharmaceutical arts, exemplified by a recent Patent Trial and Appeals Board decision holding unpatentable genus claims to glass-making method based on this Federal Circuit precedent. But the bulk of this portion of the argument is focused on the expected effects on claims in the biotechnology and pharmaceutical fields, based on the nature of these inventions, the complexities of the claimed subject matter, and the triviality of changes that can be made. These vulnerabilities are exacerbated by the costs of bringing a patented product to market, the brief citing as an average almost $3 billion, where the possibilities of "free-rider" issues that are enhanced under the full scope enablement test undermine incentives to invest. In addition to these negative effects on progress, Amgen argues the situation under the full scope test also delays effective disclosure if undue efforts must be undertaken for "rote identification of permutations within an invention"; the time and effort to do so will delay disclosure in patent applications until "sufficient" species within a genus have been identified to satisfy the full scope test.

Finally, the brief applies the rubrics to the case at bar, which the brief argues establishes that the specification enabled preparation of the 26 exemplified antibodies as well as providing a roadmap to making other embodiments using routine methods known in the art, and that Respondents could not show any failure to make any antibody falling within the scope of the invalidated claims. Amgen directly addresses Respondents' argument that their claims "preempt the future" (likely one of the more compelling arguments for Respondents' position) by ignoring the availability of further, later-arising improvements on the invention by others, citing Seymour v. Osborne, 78 U.S. (11 Wall.) 516, 548 (1871). The two juries' verdicts that Amgen's claims had not been shown not to be enabled was supported by "[m]ountains of evidence" they argue, and this evidence was not countered by any evidence that the disclosed methods ever failed. The brief enumerates the disclosures in the patents' specifications regarding the 26 exemplified antibodies, the "roadmap" teaching how to produce additional antibodies and reliance on well-established prior art methods for making monoclonal antibodies generally, and the ability to identify conservative amino acid substitutions to produce antibodies having variations in structure but retaining the functional properties of the claimed antibodies that gave them their therapeutic effectiveness. While emphasizing the lack of factual evidence contrary to the juries' verdicts, the brief concludes by emphasizing the error of law Amgen asserts against the Federal Circuit's decision in its use of the full scope test in the face of a jury verdict supported by substantial evidence, in urging the Supreme Court to reverse the adverse decision below.

Posted at 11:37 PM in Enablement, Supreme Court | Permalink | Comments (1)

January 18, 2023

November 27, 2022

Pharmacyclics LLC v. Alvogen, Inc. (Fed. Cir. 2022)

By Kevin E. Noonan --

On November 15th, the Federal Circuit handed down its opinion affirming all aspects of the District Court's decision in Pharmacyclics LLC v. Alvogen, Inc. The case illustrates once more the importance of the clear error standard in support of factual aspects of a district court's decision, even regarding ultimate questions of law, such as enablement and obviousness that are based on factual considerations.

The case arose as ANDA litigation between Pharmacyclics LLC and Janssen Biotech, Inc., whose patents for the compound ibrutinib (an inhibitor of Burton's tyrosine kinase (BTK) and the basis for their Imbruvica Product) was challenged by Alvogen and Natco Pharma Ltd. The drug is used for treatment of immune system cancer, specifically relapsed/refractory mantle cell lymphoma (RR/MCL). At trial, Pharmacyclics asserted five claims:

Claim 10, U.S. Patent No. 8,008,309 ("the '309 patent"):

10. The compound of claim 1 [which claims a genus of BTK inhibitor compounds] having the formula 1-((R)-3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one.

Claim 2, U.S. Patent No. 8,754,090 ("the '090 patent"):

1. A method for treating mantle cell lymphoma in an individual who has already received at least one prior therapy for mantle cell lymphoma comprising administering to the individual once per day be- tween about 420 mg to about 840 mg of an oral dose of an inhibitor of Bruton's tyrosine kinase (Btk) having the structure:

2. The method of claim 1, wherein the once per day oral dose is about 560 mg.

Claim 5, U.S. Patent No. 9,725,455 ("the '455 patent") :

1. A crystalline form A of [ibrutinib] that has an X-ray powder diffraction (XRPD) pattern comprising 2-Theta peaks at 5.7±0.1^o, 18.9±0.1^o, and 21.3±0.1^o.

5. The crystalline form of claim 1, wherein the X- ray powder diffraction (XRPD) pattern further comprises 2-Theta peaks at 13.6±0.1^o, 16.1±0.1^o, and 21.6±0.1^o.

Claim 30, U.S. Patent No. 9,655,857 ("the '857 patent"):

30. The high-load solid tablet formulation of claim 1 [which recites a genus tablet formulation for ibrutinib], consisting essentially of:
    a) about 70% w/w of ibrutinib,
    b) about 14% w/w of lactose monohydrate,
    c) about 5% w/w of microcrystalline cellulose,
    d) about 2% w/w of polyvinylpyrrolidone,
    e) about 7% w/w of croscarmellose sodium,
    f) about 1% w/w of sodium lauryl sulfate,
    g) about 0.5% w/w of colloidal silicon dioxide, and
    h) about 0.5% w/w of magnesium stearate.

Claim 37, the '857 patent:

37. The solid tablet formation of claim 27 [which recites a genus tablet formulation for ibrutinib in an amount of about 70 mg to about 840 mg] consisting essentially of
    a) about 69% w/w to about 71% w/w of ibrutinib,
    b) about 13% w/w to about 15% w/w of lactose monohydrate,
    c) about 2% w/w to about 5% w/w of microcrystalline cellulose,
    d) about 1% w/w to about 3% w/w of polyvinylpyrrolidone,
    e) about 6% w/w to about 8% w/w of croscarmellose sodium,
    f) about 1% w/w to about 4% w/w of sodium lauryl sulfate,
    g) about 0.4% w/w to about 0.6% w/w of colloidal silicon dioxide, and
    h) about 0.4% w/w to about 0.6% w/w of magnesium stearate.

The parties stipulated to infringement of the asserted '309, '090, and '455 patent claims and the District Court found Alvogen's proposed generic ibrutinib would infringe the asserted claims of the '857 patent. The District Court found against Alvogen on all arguments of invalidity (only some of which were the subject of this appeal, and none of these other arguments raised any additional significant issues). Alvogen and Natco appealed.

The Federal Circuit affirmed, in an opinion by Judge Bryson joined by Judges Hughes and Chen. The opinion addressed each ground of appeal raised against each asserted claim seriatim, noting initially that in an appeal from a bench trial the Court reviews factual determinations for clear error, citing UCB, Inc. v. Watson Lab'ys Inc., 927 F.3d 1272, 1286 (Fed. Cir. 2019), for the principle and Biogen Int'l GmbH v. Mylan Pharms. Inc., 18 F.4th 1333, 1341 (Fed. Cir. 2021), for the standard (i.e., that the Court finds clear error only when it has a "definite and firm conviction that a mistake has been made").

Regarding claim 2 of the '090 patent, the opinion addresses the District Court's finding that this claim was supported by an adequate written description, with an enabling specification, and was not obvious. The basis for the Court's affirmance of an adequate written description was that the '090 specification disclosed two related clinical trial protocols for using a BTK inhibitor to treat R/R MCL. The first of these taught using a variety of such inhibitors at dosages based on patient weight, and the other used a broader range of such inhibitors as a specific dosage ("about 560 mg/day). In addition, the Summary of the Invention section of the patent expressly disclosed ibrutinib for treating R/R MCL. Applying its "blazemarks" analysis (see Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1346 (Fed. Cir. 2013) (quoting In re Ruschig, 379 F.2d 990, 994–95 (C.C.P.A. 1967)), the Court held it was not clearly erroneous for the District Court to find an adequate written description where ibrutinib was "'the only BTK inhibitor identified by name in the Summary of the Invention and is the only BTK [inhibitor] identified for the treatment of R/R MCL' in the '090 patent." The Court expressly distinguished the circumstances here from its decision in Biogen (a failure to satisfy the written description requirement) because there the only disclosure of the claimed dosage was as one end of a broader disclosed range (in the context of "a long series of ranges") whereas here the claimed dosage was "expressly recited by itself" both in the claim and the specification as filed. (Undiscussed were the decidedly different circumstances arising during prosecution of the patent-in-suit in Biogen supporting the Court's opinion.) Regarding Alvogen's similar arguments on enablement, that the specification disclosed exactly 560 mg/d and claimed "about" 560 mg/d, the Federal Circuit found no clear error in the District Court's determination that there was sufficient disclosure in the specification for the skilled artisan to follow the disclosed protocol and practice the claimed method.

As for obviousness, the Federal Circuit rejected Alvogen's argument that the District Court incorrectly determined that the skilled worker would not have been motivated to treat R/R MCL with ibrutinib from prior art references teaching treatment of MCL with the drug, in light of the District Court's finding of fact that disclosure of treating MCL would not be interpreted by the skilled worker as evidence of effective treatment of RR/ MCL. The panel also refused to find error in the District Court's finding that disclosure of two R/R MCL patients having experienced a "partial response" to ibrutinib in a press release, in view of the small sample size and the propensity for oncology drugs to have a low frequency of receiving FDA approval ("less than five percent of oncology drugs that enter a Phase I trial ultimately receive FDA approval"). Another asserted and rejected obviousness argument was that the skilled worker was capable of finding the recited dose (560 mg/d) as a therapeutically effective amount by routine experimentation, based on evidence that "typical" dose escalation studies would have involved dosages greater than 560 mg/d and would require "a study using pharmacodynamic endpoints" that was not disclosed in Alvogen's combination of references. With regard to the motivation to combine, the panel recognized that Alvogen's expert testified to safety concerns in 2006 rather than 2010 (when the application was filed) and Pharmacyclics asserted contrary expert testimony that the District Court found persuasive. The panel also affirmed the District Court's decision regard a "presumption of obviousness" from the cited prior art teachings, on two grounds. The first was that such a presumption is proper "when the only difference from the prior art is a difference in the range or value of a particular variable," citing In re Kumar, 418 F.3d 1361, 1366 (Fed. Cir. 2005), which was not the case here, and second that Pharmacyclics "would have rebutted any [such] presumption." Finally, the Court did not reach the question of secondary considerations because the District Court's non-obviousness determination made this argument unnecessary.

Turning to claim 5 of the '455 patent, the Federal Circuit affirmed the District Court's determination that the claim was neither inherently anticipated nor obvious over the cited art. Alvogen's inherent anticipation argument was grounded in an assertion that the Form A polymorph of ibrutinib (recited in claim 5) was the only polymorph used in clinical trials disclosed in the art, wherein Alvogen relied upon Abbott Laboratories v. Geneva Pharmaceuticals, Inc., 182 F.3d 1315 (Fed. Cir. 1999) (an on-sale bar case). The Federal Circuit distinguished the circumstances here from those in the Abbott case, and cited Schering Corp. v. Geneva Pharms., 339 F.3d 1373, 1377 (Fed. Cir. 2003), as the more apt precedent. According to the opinion, the circumstances before the District Court in this case were more analogous to those in Endo Pharms. Sols., Inc. v. Custopharm Inc., 894 F.3d 1374, 1382 (Fed. Cir. 2018), upon which the District Court relied, there being no evidence in this case that the only therapeutically effective polymorph of ibrutinib was Form A, and that the District Court's factual determinations in this regard were not clearly erroneous. As for Alvogen's obviousness arguments, the Federal Circuit affirmed the District Court based on, inter alia, there being no clear error in that court's reliance on Pharmacyclics' expert over one of Alvogen's experts (another one agreeing with Pharmacyclics), based on the District Court's appreciation that production of polymorphs and their physical properties was unpredictable. The panel held as not clearly erroneous the District Court's finding that "given the lack of teaching in the art regarding crystalline forms of ibrutinib and the expert testimony that polymorph screening can produce unpredictable results, a skilled artisan would not have reasonably expected success in producing Form A of ibrutinib," citing Grunenthal GmbH v. Alkem Lab'ys Ltd., 919 F.3d 1333, 1344 (Fed. Cir. 2019).

Next, the Federal Circuit held as not clearly erroneous the District Court's finding that claims 30 and 37 of the '875 patent were adequately supported by the written description. Alvogen's argument was that the specification of the '875 patent disclosed one species in a range of species recited in these claims. Alvogen's "problem," according to the Federal Circuit, was that "the precise ranges recited in the claims are found in formulations disclosed in the specification," and on this basis the Federal Circuit affirmed the District Court's determination that these claims were adequately described.

Finally, the Federal Circuit affirmed the District Court's decision that claim 10 of the '309 patent was not anticipated by the cited art, Alvogen arguing that a skilled worker could not have synthesized a needed intermediate without undue experimentation and accordingly the '309 patent was not entitled to its earliest priority date. Alvogen's assertion of error in this regard was that the District Court should not have relied upon Pharmacyclics' testimony that his undergraduate students could have produced the intermediate without undue experimentation based on the disclosure in the priority documents. The District Court also relied upon the intermediate having been known in a prior art reference upon which the skilled artisan could have relied, and Alvogen argued that the District Court did not apply the proper legal standard for incorporating this document by reference. The panel found this argument not dispositive because "a skilled artisan could have synthesized Intermediate 2 and thus ibrutinib" without reference to the reference. Moreover, the opinion states that "formal incorporation by reference is not necessary if the material being incorporated is background art," citing Falko-Gunter Falkner v. Inglis, 448 F.3d 1357, 1365 (Fed. Cir. 2006). On these grounds, the Federal Circuit held that the District Court committed no clear error in rejecting Alvogen's argument.

To the extent there is any question about the importance of the standard of review in the Federal Circuit's opinion, mere casual perusal thereof finds 15 instances of some version of "clear error" and "clearly erroneous" recited by the Court. A cautionary tale indeed.

Pharmacyclics LLC v. Alvogen, Inc. (Fed. Cir. 2022)
Panel: Circuit Judges Chen, Bryson, and Hughes
Opinion by Circuit Judge Bryson

Posted at 10:41 PM in Enablement, Federal Circuit, Novelty, Obviousness, Written Description | Permalink | Comments (2)

November 06, 2022

Supreme Court Grants Certiorari in Amgen v. Sanofi

High Court Will Tackle Proper Enablement Standard

By Kevin E. Noonan --

Constituting something of a surprise, the Supreme Court on Friday, November 3rd granted Amgen's petition for certiorari on the second of the Questions Presented in its petition:

(The Court did not deign to consider the first Question, regarding whether enablement should be a question of law for the court, as it is under current Federal Circuit precedent, or a question of fact for the jury.)

To recap, the petition was filed after en banc review was denied by the Federal Circuit after the Court affirmed the District Court's grant of JMOL below, overturning a jury's decision that the asserted claims were not invalid for non-enablement. The case arose when Amgen sued Sanofi and Regeneron over sales of Praluent® (alirocumab), which allegedly competes with Amgen's Repatha™ (evolocumab) product; Amgen's asserted patents, U.S. Patent Nos. 8,829,165 ("'165 patent") and 8,859,741 ("'741 patent"), claim a genus of antibodies that encompass Praluent®. As background, blood plasma contains low-density lipoproteins that bind cholesterol and are associated with atherosclerotic plaque formation. Liver cells express receptors for LDL (LDL-R) wherein binding thereto reduces the amount of LDL cholesterol in blood and reduces the risk of plaque formation and cardiovascular disease. PCSK9 (proprotein convertase subtilisin kexin type 9) is a molecule that binds to and causes liver cell LDL-R to be destroyed, thus reducing the capacity and effectiveness of the liver cell's ability to reduce serum LDL-cholesterol. The antibodies at issue in this suit bind to PCSK9 and prevent PCSK9 from binding to LDL-R, preventing their destruction and resulting in lower serum cholesterol. It is important to note that, while reciting the structure of the residues on PCSK9 (the antigen) that are bound by the claimed antibody, the claim does not recite any structural limitations of the antibody. The only antibody characteristics recited as limitation are functional, i.e., the ability to bind (and not even specifically bind) to at least one of the recited PCSK9 residues and block PCSK9's interaction with the LDL-R.

The Federal Circuit's decision affirming the District Court's JMOL of non-enablement was based on its determination that "[t]he claimed antibodies are defined by their function: binding to a combinations of sites (residues) on the PCSK9 protein, in a range from one residue to all of them; and blocking the PCSK9/LDLR interaction." The panel relied on its decision in In re Wands (and its famous "Wands factors"), the dispositive factor in the Court's decision being the amount of experimentation required to encompass the full scope of the claims at issue. Calling In re Wands the Court's "go to" precedent, the opinion stated that while itself a monoclonal antibody case, "Wands did not proclaim that all broad claims to antibodies are necessarily enabled" because "[f]acts control." The panel considered the facts (and the findings of invalidity) in more recent cases, including Wyeth & Cordis Corp. v. Abbott Laboratories, Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. In all these cases, of course, the Federal Circuit found that the claims were not enabled, due to the broad scope of embodiments the claims in these cases encompassed and the amount of undue experimentation required to satisfy the enablement requirement throughout its full scope. The panel set forth its synthesis of the Federal Circuit's analysis regarding satisfaction of the enablement requirement arising from these cases:

What emerges from our case law is that the enablement inquiry for claims that include functional requirements can be particularly focused on the breadth of those requirements, especially where predictability and guidance fall short. In particular, it is important to consider the quantity of experimentation that would be required to make and use, not only the limited number of embodiments that the patent discloses, but also the full scope of the claim.

This precedent is well grounded in the Federal Circuit's concern that a patentee must satisfy the quid pro quo of the patent grant, so that the specification supports its claims throughout their entire scope, whether on enablement or written description grounds.

In its petition for certiorari, Amgen's argument regarding the second Question Presented was that it was contrary to ancient Supreme Court precedent, citing Mowry v. Whitney, 81 U.S. 620, 644-645 (1871); The Telephone Cases, 126 U.S. 1, 536 (1888); Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 271 (1916); Schriber-Schroth Co. v. Cleveland Tr. Co., 305 U.S. 47, 57 (1938); and Universal Oil Prods. Co. v. Globe Oil & Refin. Co., 322 U.S. 471, 484 (1944). Amgen argued that the Federal Circuit's standard for statutorily compliant enablement, what it termed cumulative disclosure that reached the full scope (even to the most remote corners of the claimed invention), is "a standard of its own devising" that is "impossible to satisfy" citing the Karshtedt paper. This standard requires the claims to be enabled throughout their full scope even if there is no evidence that there is any particular species that would require undue experimentation to achieve, Amgen argued. The proper standard, according to Amgen, consistent with the statutory text, the history of how enablement has been considered, and Supreme Court precedent, is disclosure sufficient to be able to make and use the invention, which does not require disclosure throughout entire scope of the claim. "The Federal Circuit identified no reason why patent validity should depend on the cumulative effort required to ferret out every conceivable implementation of the invention," Amgen argued in its petition, asserting that the requirement was contrary to Minerals Separation, Ltd. v. Hyde, 242 U.S. 261, 271 (1916). The test creates an impossibility that prevents a patentee from protecting her invention because a claim can be avoided by an infringer who makes a minor (structural) change, according to Amgen. And as a consequence, "[t]he Federal Circuit routinely lays waste to innovative patents that juries upheld at trial" by imposing its test, according to the petition.

The Solicitor General presented the government's views that the Court should not grant certiorari in this case. The SG's brief argued that this case is not an appropriate vehicle for Supreme Court review (being limited to its narrow factual predicate) and that Amgen is wrong in its legal arguments because what must be enabled is the invention (which necessitates disclosure throughout its full scope). The brief in particular cited Consolidated Electric Light Co. v. McKeesport Light Co., 159 U.S. 465, 476 (1895), wherein the Court rejected the proposition "that one, who had discovered that a certain fibrous or textile material answered the required purpose, should obtain the right to exclude everybody from the whole domain of fibrous and textile materials." And with regard to Amgen's reliance on Minerals Separation, the SG stated that the principle enunciated in that case was merely that "the need to tweak an invention to accommodate differing circumstances—without changing the basic principles on which the invention operates—does not render a patent claim invalid for lack of enablement," which is not the situation in this case.

As always, it is impossible to discern the Court's reasoning for granting certiorari, particularly when it is against the recommendations of the SG. (The last patent case where these circumstances arose was in LabCorp v. Metabolite; in that case the Court ultimately decided certiorari had been improvidently granted and after oral argument dismissed the writ.) Here the Court will wade into a question that involves balancing the scope of genus claims and their preclusive preemptive effect on future development of related but not expressly disclosed species, on one hand, and the need for a patentee of an invention capable of a multiplicity of (relatively) minor structural changes to be able to protect her invention from trivial infringers, on the other hand. One alternative to restricting the scope of genus claims can be appreciated by recognizing that the law leaves room for others to patent independently non-obvious (and not expressly disclosed) species falling within the scope of a claimed genus (thus protecting future innovation while permitting the genus patentee to protect against infringers). The doctrine of equivalents provides perhaps a less certain but not entirely toothless weapon against trivial changes in undisclosed species claims (e.g., substituting a valine for a leucine in the amino acid sequence of a claimed protein). It is undoubtedly the case that the briefing in this case will provoke a broad range of amici curiae on both sides of the question, and ultimately that the Court will have the opportunity to stimulate the patent community on an issue that isn't subject matter eligibility under Section 101. Which in some ways is in itself blessing (at least until the decision is rendered).

*Sadly, the first author, Professor Dmitriy Karshtedt, died recently and suddenly; see D. Kass, "'Brilliant' GW Law Patent Scholar Dmitriy Karshtedt Dies at 45," IPLaw 360 November 2, 2022.

Posted at 09:56 PM in Enablement, Supreme Court | Permalink | Comments (5)

June 15, 2022

District Court Rules PureCircle Steviol Glycoside Patents Invalid

By Kevin E. Noonan --

On May 23rd, U.S. District Court Judge James V. Selna of the Central District of California granted summary judgement to Defendant Sweegen, Inc. on its motion that Plaintiff Pure Circle USA Inc.'s claims in suit were invalid for reciting patent ineligible subject matter and for failing to satisfy the written description and enablement requirements of 35 U.S.C. § 112(a), in PureCircle USA Inc. v. SweeGen, Inc. Neither judgment was surprising in the current patent environment, but the District Court's reasoning is illustrative of the current state of U.S. patent law.

The suit involved methods for making particular glucosylated forms of the natural sweetener steviol obtained from the Stevia rebaudiana plant. The plant produces a variety of rebaudioside variants having various levels of glycosylation; the most predominant of these in the plant is termed "RebA" but this is not the most commercially valuable form. That form, termed variably "RebX" and "RebM" contains six glucose residues on the steviol core, illustrated in the opinion by this diagram:

(As will become evident from the claims, there are several intermediate glycosylated rebaudioside derivatives, termed RebB, RebC, RebD, etc.) The opinion sets forth that RebM is preferred due to its sweetness but that it only exists as "less than about 0.1% by weight of the total steviol glycoside content . . . in the natural stevia plant."

PureCircle asserted all claims in U.S. Patent Nos. 9,243,273 (claims 1-14) and 10,485,257 (claims 1-7), and Sweegen moved for summary judgment that the '257 patent and '257 patent were invalid under 35 U.S.C. § 101 and § 112(a); the opinion set forth these claims as representative:

Claim 1 of the '257 patent:

1. A method for adding at least one glucose unit to a steviol glycoside substrate to provide a target steviol glycoside, comprising contacting the steviol glycoside substrate with a recombinant biocatalyst protein enzyme comprising UDP-glucosyltransferase, wherein the target steviol glycoside is Rebaudioside X.

Claim 1 of the '273 patent:

1. A method for making Rebaudioside X comprising a step of converting Rebaudioside D to Rebaudioside X using a UDP-glucosyltransferase, wherein the conversion of Rebaudioside D to Rebaudioside X is at least about 50% complete.

As stated in the opinion, "the method of the Asserted Patents makes Reb M by using UGT enzymes to add sugar units to a steviol glycoside with less than six sugar units until it has six, thereby converting it to Reb M," wherein the UGT-glucosyltransferase enzymes used in the claimed methods are produced recombinantly in yeast cells.

The District Court granted PureCircle's motion that Sweegen's commercial product, Bestevia Reb M, infringed claims 1-7 of the '257 patent, which Sweegen did not dispute "to the extent that the claims are valid." With regard to invalidity, Sweegen contended that the product of the claims was naturally occurring and that the method for making them merely replicated what occurs natively in the stevia plant. Accordingly, Sweegen maintained, the claims were invalid for being direct to laws of nature under the Supreme Court's subject matter eligibility jurisprudence, which the District Court recognized to include Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347, 2350 (2014); Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 577 (2013); Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66, 89 (2012); and Diamond v. Diehr, 450 U.S. 175, 185 (1981). In addition, Sweegen asserted that the claims lacked an inventive concept base on five distinctions asserted in response by PureCircle:

1) the use of "recombinant" UGT enzymes in Claims 1-7 of the '257 Patent;
2) the use of "host microorganisms" to "express" the UGT enzymes in Claims 6-7 of the '257 Patent and Claims 12-13 of the '273 Patent;
3) the purity percentages for Reb M in Claims 3-5 of the '257 Patent and Claims 4-6 of the '273 Patent;
4) the conversion percentages of Reb D to Reb M in Claims 1 and 7-11 of the '273 Patent; and
5) the use of the UGT76G1 UGT enzyme in Claim 14 of the '273 Patent.

For the first two of these, Sweegen contended that the structure and function of the UDP-glucosyltransferases recited in the claims were identical to these enzymes as they exist in nature and did not recite "any non-natural role the enzyme plays in the claimed process" (which is a frequent source of invalidating comparison for any naturally occurring compound, insofar as changing the structure and/or function reduces or eliminates the desired biological activity). Regarding the third and fourth allegations of subject matter eligibility, Sweegen argued that the asserted claims contained no "steps or methods for achieving the claimed purity or completion percentages" (although this argument appears more fitting for a non-enablement or indefiniteness arguments). Finally, as to the fifth allegation, Sweegen argued that the disclosed enzyme, termed UGT76G1 was also naturally occurring.

PureCircle argued that the preparation methods did not occur in nature, with regard to taking an isolated RebA preparation and using a recombinant UDP-glucosyltransferase, analogizing these claims to the claims found patent-eligible in Rapid Litig. Mgmt Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1047 (Fed. Cir. 2016), and Illumina, Inc. v. Ariosa Diagnostics, 967 F.3d 1319, 1325-29 (Fed. Cir. 2020). PureCircle also pointed out that, in nature, the plant contains enzymes that deglucosylate steviol glycosides, thus making impossible production of RebM in quantities achieved using the claimed methods.

Sweegen countered by arguing that claims reciting man-made elements can be ineligible under Federal Circuit precedent, citing Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743, 750, 753-54 (Fed. Cir. 2019); Roche Molecular Systems, Inc. v. CEPHEID, 905 F.3d 1363, 1371-73 (Fed. Cir. 2018); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1373-74, 1376-77 (Fed. Cir. 2015), and further that the recited enzymes are "structurally and functionally identical to the naturally occurring UGT enzymes" and accordingly do not overcome patent-ineligibility of the asserted claims. Moreover, Sweegen argued that the purity and percentage of conversion to RebM do not in themselves change the "underlying natural process[es]." Finally, Sweegen argued that "methods of preparation" are not per se patent-eligible under the cited precedent.

The District Court agreed with Sweegen, finding claims 1-5 of the '257 patent and claims 1-11 and 14 of the '273 patent invalid for reciting patent-ineligible subject matter. According to the Court, the claims were directed to the natural law of converting rebaudiosides, and specifically RebD, into RebM. In the Court's view, "there is no dispute that the conversion of steviol glycosides and Reb D to Reb M using UGT enzymes is a natural process." The Court found this characterization to be supported by disclosure in the specification, which was expressed as disclosing a "biocatalytic process," defined as "the use of natural catalysts, such as protein enzymes, to perform chemical transformations on organic compounds" (emphasis added). The Court relied on Athena for the proposition that "[s]ynthetically-created chemical compositions that are structurally and functionally identical to their naturally-occurring counterparts . . . are not patent eligible" and the admission in the specification that the recombinant enzymes were structurally and functionally "identical" to the naturally occurring enzymes. The District Court rejected the distinction PureCircle attempted to draw for "method of preparation" claims analogous to CellzDirect and expressly with regard to any suggestion that such claims are per se patent eligible, as being inconsistent with precedent particularly the Supreme Court's rationale in Alice.

The claims of the '257 patent not invalidated on Section 101 grounds recited:

6. The method of claim 1, wherein the UDP-glucosyltransferase is expressed in a host microorganism.

7. The method of claim 6, wherein the host microorganism is selected from the group consisting of: Escherichia coli, Saccharomyces species, Aspergillus species, and Pisehia species.

And the claim of the '273 patent not invalidated on Section 101 grounds recited:

13. The method of claim 12, wherein the UDP-glucosyltransferase host microorganism is selected from the group consisting of: Escherichia coli, Saccharomyces species, Aspergillus species, and Pischia species.

The District Court recognizing these recited limitations as providing "something more" than the natural law as required under Supreme Court and Federal Circuit precedent, that something being in this case "a particular step performed by a human for achieving a particular result," which the Court finds "takes those claims beyond the natural law itself."

Turning to Sweegen's motion for an invalidity finding on written description grounds, the District Court agreed with Sweegen that the recited claim element "UDP-glucosyltransferase" is a "broad, functionally-defined genus" and thus can embrace "not just naturally occurring UDP-glucosyltransferases, but 'any' UDP-glucosyltransferase mutant, fusion, and UDP-glucosyltransferase known or discovered after the patents' . . . filing date" (estimated by Sweegen to encompass a trillion (1012), molecules, "a limitless number," citing Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337 (Fed. Cir. 2021)). The District Court also agreed with Sweegen that the specification does not recite a "a representative number of species or identify any common structural features for UGT enzymes" and that the sequence similarities between different UDP-glucosyltransferase were not correlated with enzymatic activity. In evidence was a comparison between 12 UGT enzymes wherein only 4 had shown an enzymatic activity that added glucose to steviol glycoside molecules. PureCircle countered this evidence by asserting that the term ""UDP-glucosyltransferase" is structural because, inter alia, there are other UGT enzymes that do not add glucose residues to rebaudiosides and that the Court's claim construction limits the scope of the claims to those UGT enzymes that do transfer glucose moieties into rebaudiosides as disclosed and claimed. Finally, PureCircle argued that there are disputed material facts that preclude summary judgment, including that the term "UDP-glucosyltransferases" was itself structural and the structure of functional UGT enzymes had been determined by crystallographic comparisons (unfortunately for PureCircle, the District Court found that none of these crystallographically determined common structural features were disclosed in the specification). Sweegen countered that the specification did not provide (express) written description support for "every" UGT enzyme capable of converting inter alia RebD to RebM (which was the construction the Court gave to the claim element "UDP-glucosyltransferase"). In addition, Sweegen asserted that neither of the specifications disclosed structural features common to members of the genus of UDP-glucosyltransferases.

The District Court considered the issue to be whether the genus of UDP-glucosyltransferases was defined (and described) structurally or functionally and, deciding it was the latter, found that the claims did not provide adequate written description support. This determination was supported by the stipulated meaning of the term, i.e., "[a] type of enzyme that is capable of transferring a glucose unit from a uridine diphosphate glucose molecule to a steviol glycoside molecule." Accordingly, the fact that these claims reciting this limitation were "original" claims they were not entitled to a presumption of adequate written description support. Under these circumstances, the Court held, precedent requires a showing that "the applicant has invented species sufficient to support a claim to the functionally-defined genus," citing Juno, or "structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus," citing Ariad Pharma. Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010). The opinion states that there is no dispute between the parties that the specification does not expressly disclose "structural features common to all UGT enzymes" having the recited function; in fact only 4 UGT enzymes are disclosed (UGT76G1, UGT91D2, UGT91D2e, and UGT91D11) and the specification further states that "the particular UDP-glucosyltransferase used in each reaction can either be the same or different, depending on the particular site on the steviol glycoside substrate where glucose is to be added." Amino acid sequence comparisons, which had been sufficient to overcome a written description rejection before the Patent Office were not persuasive before the Court, based on an understanding that "[a]n enzyme's amino acid sequence does not necessarily predict the enzyme's activity (or functionality) and, therefore, testing is always required to determine the enzyme's activity (or functionality)," from which the Court concluded that "two enzymes with the similar sequences can have different functions and two enzymes with very different sequences can have the same function" (which, to be candid overstates what is a relatively weak biological rule of thumb). But here, the Court found that a comparison of two of the disclosed UDP-glucosyltransferases (UGT76G1 and UGT91D2) did not disclose common structural features sufficient to satisfy the requirement for an adequate written description. Finally, the District Court found that as of the filing date common structural features between different UDP-glucosyltransferases were not known in the art (and what features that were known were not universally associated with UDP-glucosyltransferase function). Accordingly, the District Court granted Sweegen's motion that all asserted claims were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a).

The Court dismissed as moot a third ground of invalidity asserted by Sweegen, sounding in non-enablement. However, in view of the District Court's rationale in its written description determination, and the recent trend at the Federal Circuit in applying the enablement standard in chemical, pharma, and biotechnology cases (see, e.g., Amgen Inc. v. Sanofi and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc.) it is unlikely that PureCircle would have received any different outcome if the Court had considered this ground on the merits.

While the District Court's decision is likely to be followed by an appeal to the Federal Circuit, PureCircle should expect an uphill battle. On the written description issue, as a question of fact the District Court is entitled to "clear error" deference which should prove difficult to overcome in view of the reasoning based on evidence cited in the opinion. And no patentee having had their claims invalidated under Section 101 has had any reason to be sanguine on appeal for the past ten years (although the recent Solicitor General's amicus brief recommending the Supreme Court revisit the subject matter eligibility issue in Am. Axle & Mfg., Inc. v. Neapco Holdings LLC at least raises the possibility that there may be (perhaps just faint) hope for the standard to be reconsidered).

Posted at 10:43 PM in District Court, Enablement, Patentable Subject Matter, Written Description | Permalink | Comments (3)

January 11, 2022

May 20, 2021

Pacific Biosciences of California, Inc. v. Oxford Nanopore Technologies, Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

The Federal Circuit continues its recent run of decisions extending the reach of the enablement requirement of 35 U.S.C. 112(a) to invalidate patents in Pacific Biosciences of California, Inc. v. Oxford Nanopore Technologies, Inc. (albeit in this case, affirming denial of motion for JMOL in the face of a jury verdict of non-enablement).

The matter arose when Pacific Biosciences asserted U.S. Patent Nos. 9,546,400 and 9,772,323 directed to methods for sequencing nucleic acid (DNA) using nanopore technology. As explained in the opinion, the DNA being sequenced passes through the nanopores causing a change in electrical current specific for each nucleotide base (which is then recognized by the machine). Pacific Biosciences asserted Claim 1 of the '400 patent:

1. A method for sequencing a nucleic acid template comprising:
    a) providing a substrate comprising a nanopore in contact with a solution, the solution comprising a template nucleic acid above the nanopore;
    b) providing a voltage across the nanopore;
    c) measuring a property which has a value that varies for N monomeric units of the template nucleic acid in the pore, wherein the measuring is performed as a function of time, while the template nucleic acid is translocating through the nanopore, wherein N is three or greater; and
    d) determining the sequence of the template nucleic acid using the measured property from step (c) by performing a process including comparing the measured property from step (c) to calibration information produced by measuring such property for 4 to the N sequence combinations.

A jury found that Oxford infringed the asserted claims but that the claims were invalid for failure to satisfy the enablement requirement, based in part on conflicting testimony from each party's experts. The District Court denied Pacific Biosciences' pos-trial motion for judgment as a matter of law (JMOL), leading to this appeal.

The Federal Circuit affirmed, in an opinion by Judge Taranto, joined by Judges Lourie and Stoll. According to the opinion, "[w]hat matters is the scope of the asserted claims," which in relevant part extended to determining the sequence of a template nucleic acid without any limitation regarding the "character" of the nucleic acid, including differentiating between "particular types of DNA" (what the Court understood any of this to mean is unclear). The opinion discusses the relevance of the "N nucleotides" limitation in the claims, which was one basis for Oxford's expert's testimony that the claims were not enabled. The opinion also notes testimony from more than one witness that nanopore sequencing technology was not performed in the art until 2011 (after the 2009 priority dates of the patents at issue) and not based on the disclosures of those patents. The opinion notes also that Pacific Biosciences' specification was constructive and that there was no "real-world reduction to practice" achieved at the time of filing. (There was also evidence presented to the jury that Pacific Biosciences had intended to "'tangle . . . up' and 'fool' competitors with its patents" which the opinion understood might have pointed the jury away from deciding that Pacific Biosciences had an enabled method.) The remainder of the panel's opinion on enablement was focused on whether the District Court properly denied Pacific Biosciences' motion for JMOL and whether the jury could reasonably have arrived at its verdict in view of the conflicting testimony of the witnesses. The panel stated that in its opinion "there was ample evidence to support a finding that, before the 2009 priority date of the '400 and '323 patents, relevant artisans did not know how to perform nanopore sequencing for more than a narrow range of the full scope of nucleic acids covered by the asserted claims," citing Idenix Pharms. LLC v. Gilead Sciences Inc., 941 F.3d 1149 (Fed. Cir. 2019), Enzo Biochem, Inc. v. Calgene, Inc., 188 F.3d 1362 (Fed. Cir. 1999), and Union Carbide Chems. & Plastics Tech. Corp. v. Shell Oil Co., 308 F.3d 1167 (Fed. Cir. 2002), in support.

But as Paul Harvey used to say, here's the rest of the story (which has nothing to do with patent law and as such is discussed herein subservient to the patent law aspects of the decision). The trial was held beginning on March 9, 2020, and Pacific Biosciences was concerned that Oxford not be able to intimate to the jury that finding its patents infringed and not invalid would hamper efforts to combat COVID-19 (specifically based on Pacific Biosciences' status as a non-practicing entity or its patent being a "paper patent"). To this end, Pacific Biosciences sought and received a motion in limine that Oxford not be able to make or hint any such conclusion to the jury. Both parties mentioned the pandemic in their opening statements, but Pacific Biosciences objected to how Oxford made its mention of the issue (and obtained a curative instruction from the Court the next day). The judge also admonished both parties not to "'turn this really into a trial about an ongoing global health crisis that has to be on the minds of the jury,' which would be 'unfair' and 'improper' and would 'inflam[e] the jury' and 'would create a real risk of a verdict' not based on the evidence." Pacific Biosciences raised similar objections to Oxford's closing argument. In addition to its motion for JMOL, Pacific Biosciences moved under Rule 59 for a new trial, based on undue prejudice caused by Oxford's violation of the motion in limine; the District Court denied this motion because Pacific Biosciences did not provide evidence that Oxford had violated the in limine motion after its statements in its opening argument or that the jury had been inflamed by those statements.

The Federal Circuit also affirmed the District Court's denial of the motion for a new trial. One solid basis for this decision is that the panel opined that the District Court's views of the matter should be given "considerable weight" in view of that court's being in a better position to observe the demeanor of the jury, party counsel, and witnesses, citing Draper v. Airco, Inc., 580 F.2d 91, 97 (3d Cir. 1978) (the Federal Circuit applying Third Circuit law to this question). Another basis in the opinion was that Pacific Biosciences did not object when presented with advance notice that Oxford intended to make the purportedly inflammatory statements. Further, the opinion notes that the District Court gave just the curative instruction Pacific Biosciences requested the day after the purported violation occurred, and required each party inform each other of any further instances of argument or testimony related to COVID-19 before eliciting testimony or making arguments to the jury. Accordingly, the opinion asserts that "[g]iven all the circumstances, we do not see a basis for disturbing the district court's assessment that there was an insufficient likelihood that the improper opening remarks had an adverse impact on the ultimate verdict to justify a new trial in this case."

Pacific Biosciences of California, Inc. v. Oxford Nanopore Technologies, Inc. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Taranto, and Stoll
Opinion by Circuit Judge Taranto

Posted at 11:14 PM in Enablement, Federal Circuit | Permalink | Comments (2)

April 18, 2021

Raytheon Technologies Corp. v. General Electric Co. (Fed. Cir. 2021)

By Michael Borella --

The legal concept of obviousness is tricky. A claimed invention is found obvious if the prior art teaches or suggests all claim limitations and one of ordinary skill in the art would have been motivated to combine the relevant teachings of the references. The inherent subjectivity of such an analysis can lead to reasonable people disagreeing on whether an invention is ultimately patentable. But it does not end there -- like an onion, obviousness has layers.[1] Normally, whether the references themselves provide enabling disclosure is not relevant. Except when it is.

Raytheon is the owner of U.S. Patent No. 9,695,751, which was challenged by General Electric (GE) in an inter partes review before the Patent Trial and Appeal Board (PTAB). Of note are claims 1-3 of the patent, shown in part below.

1. A gas turbine engine comprising:
    a fan including a plurality of fan blades . . . ;
    a compressor section;
    a combustor in fluid communication with the compressor section;
    a turbine section in fluid communication with the combustor, the turbine section including a fan drive turbine and a second turbine . . . ; and
    a speed change system configured to be driven by the fan drive turbine to rotate the fan about the axis; and
    a power density at Sea Level Takeoff greater than or equal to 1.5 lbf/in³ and less than or equal to 5.5 lbf/in³ and defined as thrust in lbf measured by a volume of the turbine section in in³ measured between an inlet of a first turbine vane in said second turbine to an exit of a last rotating airfoil stage in said fan drive turbine.

2. The gas turbine engine as recited in claim 1, wherein the fan drive turbine has from three to six stages.

3. The gas turbine engine as recited in claim 2, wherein said number of fan blades is less than 18 and the second turbine has two stages.

In the words of the court, "[t]he '751 patent generally claims a geared gas turbine engine with two turbines and a specific number of fan blades and turbine rotors and/or stages." Further, the "key distinguishing feature of the claims is the recitation of a power density range that the patent describes as being 'much higher than in the prior art.'" Here, power density is defined as sea-level-takeoff (SLTO) thrust divided by the engine turbine volume.

During the proceeding, Raytheon disclaimed claims 1 and 2 (among others), leaving claim 3 as representative. GE's obviousness contentions for claim 3 relied only on a single reference, a non-patent literature document by Knip.

Knip is "a 1987 NASA technical memorandum that envisions superior performance characteristics for an imagined advanced turbofan engine incorporating all composite materials." It is undisputed that such an engine could not be built in 1987 and still cannot be built today. But such speculation allowed Knip "to assume aggressive performance parameters for an advanced engine, including then-unachievable pressure ratios and turbine temperatures." Nonetheless, Knip does not disclose SLTO thrust, turbine volume, or power density for this hypothetical engine. GE asserted that "because power density is a result-effective variable, even if Knip did not disclose a turbine section volume and/or SLTO thrust that resulted in a power density within the claimed range, it would have nevertheless been obvious to a skilled artisan to modify the thrust and/or turbine volume for Knip's engine to optimize the power density."

Before the PTAB, Raytheon argued that "GE's expert employed a flawed methodology in deriving the power density of Knip's advanced engine from the parameters that Knip disclosed," and that Knip's disclosure failed to enable a skilled artisan to make the claimed invention. GE countered by stating that "the issue of whether Knip enabled its advanced engine was irrelevant to the question whether a skilled artisan reviewing Knip could make the '751 Patent's engine (using any already available materials) without undue experimentation." Note the subtle difference in the points being made -- Raytheon is alleging that Knip does not enable one to make the invention of the '751 patent, while GE is addressing whether Knip enables one to make Knip's own engine.

In any event, the PTAB ultimately found Knip enabling because it allowed "a skilled artisan to "determine a power density as defined in claim 1, and within the range proscribed in claim 1." As a result, the PTAB concluded that Knip rendered the claims obvious.

On review, the Federal Circuit set forth the delicate interactions between obviousness and enablement. Writing for the Court, Judge Chen noted that "[i]n general, a prior art reference asserted under § 103 does not necessarily have to enable its own disclosure, i.e., be 'self-enabling,' to be relevant to the obviousness inquiry." To that point, "a reference that does not provide an enabling disclosure for a particular claim limitation may nonetheless furnish the motivation to combine, and be combined with, another reference in which that limitation is enabled." Further, "such a reference may be used to supply claim elements enabled by other prior art or evidence of record."

Thus, the point at issue in this case was whether a skilled artisan could have made the claimed invention regardless of whether the cited references are self-enabling. Of particular relevance to single-reference obviousness contentions such as one made by GE, is that "a standalone § 103 reference must enable the portions of its disclosure being relied upon."

The Court found that the PTAB erred by focusing on whether Knip enabled determination of a power density. The PTAB should have considered "whether Knip enabled a skilled artisan to make and use the claimed invention." The PTAB's conclusion of obviousness could have been supported "if GE had presented other evidence to establish that a skilled artisan could have made the claimed turbofan engine with the recited power density." But that did not happen. Therefore, according to the Court, "Knip's self-enablement (or lack thereof) is not only relevant to the enablement analysis, in this case it is dispositive."

The Court also found GE's use of expert testimony to be lacking, because its expert constructed "a computer model simulation of Knip's imagined engine" rather than the actual engine. In contrast, Raytheon's expert presented unrebutted evidence of non-enablement -- the "unavailability of the revolutionary composite material contemplated by Knip." Raytheon also "submitted evidence that the exceptional temperature and pressure parameters cited in Knip had not been achieved through other means as of the priority date."

Moreover, GE argued that a skilled artisan could achieve the claimed power density by optimizing Knip's engine. But the Court rejected this notion, stating that "[i]f a skilled artisan cannot make Knip's engine, a skilled artisan necessarily cannot optimize its power density."

For these reasons, the Court reversed the PTAB's finding of claim 3 to be obvious.

This case is interesting, though it presents an avenue for arguing for non-obviousness that is unlikely to be available in practice very often. Here, the Knip reference was admittedly speculative, and gaps between Knip's speculation and reality matched up with the gaps in GE's arguments. By adding in other references or reasoning, the outcome may have differed. Perhaps the holding here is best summarized by Judge Chen writing "if an obviousness case is based on a non-self-enabled reference, and no other prior art reference or evidence would have enabled a skilled artisan to make the claimed invention, then the invention cannot be said to have been obvious."

[1] Also like an onion, obviousness as a legal principle has the ability to make one involuntarily cry.

Raytheon Technologies Corp. v. General Electric Co. (Fed. Cir. 2021)
Panel: Circuit Judges Lourie, Chen, and Hughes
Opinion by Circuit Judge Chen

Posted at 11:40 PM in Enablement, Federal Circuit, Obviousness | Permalink | Comments (2)

March 08, 2021

Bayer Healthcare LLC v. Baxalta Inc. (Fed. Cir. 2021)

By Kevin E. Noonan --

Last week, the Federal Circuit affirmed a jury verdict against Baxalta Inc., Baxalta US Inc., and Nektar Therapeutics for infringing Bayer Healthcare's patent to human blood clotting factor conjugates in Bayer Healthcare LLC v. Baxalta Inc.

Bayer Healthcare sued Defendants on U.S. Patent No. 9,364,520, alleging willful infringement by Baxalta's product, Adynovate®. This product is a recombinant human Factor VIII (the blood clotting factor responsible for causing Hemophilia A) having the protein structural domains A1-A2-B-A3-C1-C2, wherein the B portion was specifically modified by addition of polyethylene glycol (PEG). PEGylation is important because Factor VIII has an 11-hour half-life which requires frequent injections and leads to reduced patient compliance. The prior art had disclosed "random" modification of Factor VIII with PEG, which had "several drawbacks" due to the multiplicity of PEGylations sites ("158 lysines, the two N-termini, and multiple histidines, serines, threonines, and tyrosines") in the Factor VIII protein, which led to heterogeneity in the species produced, including ones having deleterious effects on Factor VIII activity and ones having a multiplicity of PEG residues conjugated to the protein.

The '520 patent specification disclosed site-specific PEGylation at a site not at an N-terminal amine; claim 1 is representative:

1. An isolated polypeptide conjugate comprising a functional factor VIII polypeptide and one or more biocompatible polymers, wherein the functional factor VIII polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or an allelic variant thereof and has a B-domain, and further wherein the biocompatible polymer comprises polyalkylene oxide and is covalently attached to the functional factor VIII polypeptide at the B-domain.

(wherein the italicized portions of the claim identify claim language disputed in the litigation).

At trial, the District Court construed the term "isolated polypeptide conjugate" to mean "a polypeptide conjugate where conjugation was not random." Specifically, the District Court held that during prosecution of the '520 patent, Bayer had disclaimed embodiments having random PEGylation. Further, the District Court construed the term "at the B-domain" to mean "attachment at the B-domain such that the resulting conjugate retains functional factor VIII activity," rejecting Baxalta's proposed construction that the phrase should be construed to mean "at a site that is not any amine or carboxy site in factor VIII and is in the B-domain." The District Court granted Defendants' pre-trial motion as a matter of law that there was no willful infringement, and a jury found that Defendants infringed claims 1-3 and 8 of the '520 patent. The jury found against Defendants' counterclaim of non-enablement, and awarded Bayer $155,190,264 in reasonable royalty damages, based on a 17.78% royalty rate for $872,836,128 in Defendants' profits. The District Court also denied Defendants' JMOL motions on the issues of infringement, enablement, and damages. Bayer filed a motion under Federal Rule of Civil Procedure 59(a) for pre-verdict supplemental damages, which the District Court granted and awarded Bayer another $18,324,562. The District Court also denied Bayer's motion for JMOL on willful infringement. Both parties appealed.

The Federal Circuit affirmed, in an opinion by Judge Stoll, joined by Judges Newman and Linn. The opinion first opined on the District Court's claim construction, which (because the District Court had not relied upon extrinsic evidence) was performed de novo, with regard to the interpretation of the terms "at the B-domain" and "random" PEGylation of the B portion of Factor VIII. The opinion rejected Defendants' argument that the term "at the B-domain" should have been interpreted to exclude amine/lysine PEG conjugation. The opinion sets forth its claim construction analysis by way of the factors enunciated in Phillips v. AWH Corp., 415 F.3d 1303 (Fed. Cir. 2005) (en banc): plain meaning of the claim terms, the specification, and the prosecution history. The Federal Circuit found the plain meaning of the term "'[a]n isolated polypeptide conjugate' in which PEG 'is covalently attached to the functional factor VIII polypeptide at the B-domain'" does not require any particular amino acid residue to be PEGylated, saying that the claim "broadly requires PEGylation at the B-domain as a region." The panel identified statements in the specification that supported this construction, and while acknowledging that PEGylation at cysteine residues was expressly disclosed, held that this disclosure did not limit the scope of site-specific PEGylation to just cysteine residues. The Federal Circuit also disagreed with Defendants that the specification disparaged amine/lysine PEG conjugation, expressly based on Indivior Inc. v. Dr. Reddy's Laboratories, S.A., 930 F.3d 1325 (Fed. Cir. 2019); Gaus v. Conair Corp., 363 F.3d 1284 (Fed. Cir. 2004); and SciMed Life Systems, Inc. v. Advanced Cardiovascular Systems, Inc., 242 F.3d 1337 (Fed. Cir. 2001) (although the opinion states that it was a close question). Rather than disparaging or disclaiming any particular type of conjugation with PEG, the panel held that the '520 patent specification disparaged random PEGylation (which is not the same thing). Finally, the opinion held that nothing in the prosecution history was to the contrary, specifically in that it did not contain "a clear and unmistakable surrender of claims directed to non-random amine/lysine PEGylation." While art cited by the USPTO included amine/lysine conjugation sites, taken as a whole and as understood by a person of ordinary skill in the art, the Federal Circuit held the rejection and cited art was directed to random PEGylation. (And Defendants' citation of statements made in the prosecution of related European Patent Application No. 11153287.4 were unavailing, both on the merits and, in agreement with the District Court, "varying legal and procedural requirements for obtaining patent protection in foreign countries might render consideration of certain types of representations inappropriate for consideration in a claim construction analysis of a United States counterpart.")

With regard to the term "random," the Federal Circuit rejected Defendants' argument that the District Court had erred by not expressly defining the term, thus improperly leaving construction of this term to the jury. The panel held that the District Court had "resolved the parties' differences" with regard to this term by addressing (and rejecting) Defendants' arguments that "(1) that 'random' conjugation means any conjugation at amines or carboxy sites; and (2) that 'random' conjugation means all heterogenous conjugation." The Federal Circuit understood the District Court's construction did not exclude any degree of heterogeneity from PEG conjugation but rather that Bayer had disparaged embodiments with "a high degree of heterogeneity" (which was the problem with prior art embodiments of PEGylated Factor VIII preparations that distinguished Bayer's invention). Reciting the District Court's construction, the opinion states that the District Court found (correctly) that "non-random conjugation neither required that each FVIII protein in a product such as Adynovate® be PEGylated in the same places (homogeneity among conjugates in the product) nor required that every PEG on each FVIII protein be in the B-domain (homogeneity within each conjugate)." Accordingly, the Federal Circuit held that limiting the term "random" with reference to construction of the term "isolated polypeptide conjugate" to mean "a polypeptide conjugate where conjugation was not random" sufficiently defined the meaning of the word "random" in the claimed context, and that this was consistent with other district court decisions, including denial of Defendants' motion in limine on this issue.

The panel also affirmed as being supported by substantial evidence the jury's infringement decision, and consequently, that the District Court did not err in denying Defendants' motion for JMOL. The opinion provided a synopsis of the parties' evidence, including differing expert witnesses on infringement, supported by Baxalta's submissions to FDA regarding the specificity with which its Factor VIII product comprised "controlled, targeted chemical addition of 20 [kilodalton] PEG conjugates to this FVIII B-domain" (emphasis in opinion), statements inconsistent with random PEGylation.

Similarly, the Federal Circuit held that there was substantial evidence for the jury's rejection of Defendants' non-enablement defense, particularly with regard to embodiments comprising non-random lysine PEGylation. According to the opinion, "Bayer presented substantial evidence from which a reasonable juror could find that the specification's disclosure of instructions as to the reaction conditions required to practice the claimed invention using cysteine PEGylation were sufficient to enable not only non-random cysteine PEGylation at the B-domain, but also non-random lysine PEGylation at the B-domain." Somewhat in contrast to recent, more stringent applications of the Federal Circuit's standards for enablement (see Amgen Inc. v. Sanofi and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc.), this panel held that "the specification need not include a working example of every possible embodiment to enable the full scope of the claims," citing Alcon Rsch. Ltd. v. Barr Labs., Inc., 745 F.3d 1180, 1189–90 (Fed. Cir. 2014), and Amgen Inc. v. Hoechst Marion Roussel, Inc., 314 F.3d 1313, 1336–37 (Fed. Cir. 2003).

Defendants also appealed the jury's damages calculations and the basis thereof. While agreeing with the District Court in rejecting Bayer's expert's 50-50 split royalty rate, the panel disagreed with several other assertions of error by Defendants. These included the basis for the 17.78% reasonable royalty rate, which Defendants' argued relied on a "a flawed and speculative methodology—namely, asking the jury to pick a rate between the range of feasible rates presented by [Bayer's expert] as the reasonable rate." The Federal Circuit held that "[t]he district court properly exercised its discretion in allowing Bayer to ask the jury to select a rate between the range presented," within the confines of a damages expert using "reliable methodology for determining the range of possible hypothetical negotiation royalty rates." When, as here, a jury's damages award "fell within the range suggested by the patentee's damages expert" the Federal Circuit stated it was supported by substantial evidence, citing Rembrandt Wireless Techs., LP v. Samsung Elecs. Co., 853 F.3d 1370, 1382 (Fed. Cir. 2017), and that the District Court had not erred in permitting the jury to received Bayer's damage expert's testimony. Defendants had had (and had exercised) the opportunity to cross-examine Bayer's expert on his methodology and damaged calculation, according to the opinion, and "ultimately, the jury evaluated his opinions and adopted a rate within his proposed range." In the Federal Circuit's opinion there was nothing improper about the jury's damages calculation or award.

Finally, Defendants argued that the District Court had violated their Seventh Amendment rights by awarding pre-judgment damages under Fed R Civ Pro 59. In doing so, according to the Federal Circuit, the District Court used actual sales data instead of projected amounts and applied the same 17.78% royalty rate on the amount of these actual sales. "Under these circumstances," said the Federal Circuit, "we are not persuaded that the District Court's award constitutes an impermissible additur or an otherwise 'bald addition of something which in no sense can be said to be included in the verdict,'" citing Dimick v. Schiedt, 293 U.S. 474, 486 (1935) (the remainder of the Court's opinion making it clear that its judgment was limited to the facts in this case).

Regarding Bayer's appeal on the District Court's grant of Defendants' motion for JMOL on willful infringement, the panel held that there was insufficient evidence of the necessary "state of mind" having "a specific intent to infringe at the time of the challenged conduct" to support willfulness, citing Halo Elecs., Inc. v. Pulse Elecs., Inc., 136 S. Ct. 1923, 1933 (2016) ("willful, wanton, malicious, bad-faith, deliberate, consciously wrongful, flagrant, or—indeed—characteristic of a pirate"). The panel affirmed the District Court's decision even though "there was no dispute that Baxalta was 'aware of the '520 patent,'" because "Bayer merely 'assume[d] that [Baxalta] knew Adynovate[®] infringed because it involved pegylation at the B-domain of factor VIII." The Federal Circuit rendered this opinion even in the face of testimony by Defendants' witnesses "concerning their awareness of the patent application that issued as the '520 patent" and representations to FDA regarding non-random PEGylation in Defendants' Adynovate® product.

Bayer Healthcare LLC v. Baxalta Inc. (Fed. Cir. 2021)
Panel: Circuit Judges Newman, Linn, and Stoll
Opinion by Circuit Judge Stoll

Posted at 11:59 PM in Claim Construction, Damages, Enablement, Federal Circuit, Infringement - Literal or DOE | Permalink | Comments (2)

February 21, 2021

Amgen Inc. v. Sanofi (Fed. Cir. 2021)

By Kevin E. Noonan --

A little less than four years ago, the Federal Circuit rendered a decision in Amgen Inc. v. Sanofi that brought clarity to how the Court (and U.S. Patent and Trademark Office) should apply the written description requirement in 35 U.S.C. § 112(a) to properly circumscribe the scope of claims to monoclonal antibodies. Earlier this month, on an appeal from remand, the Court took aim at the enablement requirement for antibody claims, with similar, scope-limiting results.

The case arose when Amgen sued Sanofi and Regeneron over sales of Praluent® (alirocumab), which allegedly competes with Amgen's Repatha™ (evolocumab); Amgen's asserted patents, U.S. Patent Nos. 8,829,165 ("'165 patent") and 8,859,741 ("'741 patent"), claim a genus of antibodies that encompass Praluent®. As background, blood plasma contains low-density lipoproteins that bind cholesterol and are associated with atherosclerotic plaque formation. Liver cells express receptors for LDL (LDL-R) wherein binding thereto reduces the amount of LDL cholesterol in blood and reduces the risk of plaque formation and cardiovascular disease. PCSK9 (proprotein convertase subtilisin kexin type 9) is a molecule that binds to and causes liver cell LDL-R to be destroyed, thus reducing the capacity and effectiveness of the liver cell's ability to reduce serum LDL-cholesterol. The antibodies at issue in this suit bind to PCSK9 and prevent PCSK9 from binding to LDL-R, preventing their destruction and resulting in lower serum cholesterol.

The following claims were recited in the opinion as being relevant to the issues before the Court:

Claims of the '165 patent:

1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDL[-]R.

19. The isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO:3.

29. A pharmaceutical composition comprising an isolated monoclonal antibody, wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3 and blocks the binding of PCSK9 to LDLR by at least 80%.

Claims of the '165 patent:

1. An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

2. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is a neutralizing antibody.

7. The isolated monoclonal antibody of claim 2, wherein the epitope is a functional epitope.

It is important to note that, while reciting the structure of the residues on PCSK9 (the antigen) that are bound by the claimed antibody, the claim does not recite any structural limitations of the antibody. The only antibody characteristics recited as limitation are functional, i.e., the ability to bind (and not even specifically bind) to at least one of the recited PCSK9 residues and block PCSK9's interaction with the LDL-R.

Evidence at the first trial showed that Amgen had produced a plurality of anti-PCSK9 antibodies and screened them for the ability to inhibit PCSK9 binding to LDL-R. This screening was done using a "trial and error" process that reduced 3,000 human monoclonal antibodies down to 85 antibodies that "blocked interaction between the PCSK9 . . . and the LDLR [at] greater than 90%," of which the specification illustrated the three-dimensional binding arrangement for two (one of which became the Repatha™ antibody) by x-ray crystallography. The specification of the Amgen patents in suit disclose amino acid sequence information for twenty-two human anti-PCSK9 antibodies able to compete for PCSK9 binding with these two more fully characterized antibodies. Regeneron's patents (not at issue here) recited antibody-specific amino acid sequences for its claimed anti-PCSK9 antibodies.

The jury in the earlier case found Amgen's patents not to be invalid. The District Court had excluded evidence relating to written description and enablement based on Praluent® and other post-priority-date antibodies (i.e., that were produced after Amgen's earliest priority date). The District Court, relying on Noelle v. Lederman as precedent, instructed the jury that an applicant can be entitled to claim scope encompassing generically described antibodies (as was the case for Amgen's claims) provided that the applicant provided a full characterized, novel antigen.

The Federal Circuit reversed in part, affirmed in part, vacated in part, and remanded, in an opinion by Chief Judge Prost, joined by Judges Taranto and Hughes. With regard to the written description question, the Court vacated and remanded, on the grounds that the District Court had instructed the jury based on the Court's pre-Ariad Noelle v. Lederman precedent, which was inconsistent with the Court's later en banc decision in Ariad v. Eli Lilly & Co. The Court also found it to be error for the District Court to have excluded evidence regarding enablement, related to the "lengthy and potentially undue experimentation" Amgen needed to employ to arrive at its antibodies that fell within the scope of the claims of the '165 and '741 patents. The Federal Circuit ordered a new trial for the District Court to consider post-priority-date evidence for the purposes of both enablement. The District Court remanded for a new trial on written description as well, based on the jury instruction and evidentiary errors.

On remand, the jury found that claim 7 of the '741 patent and claims 19 and 29 of the '165 patent were not invalid. The District Court granted Sanofi's motion for JMOL with regard to enablement for these claims but denied JMOL on written description. This appeal followed.

In the instant appeal, the Federal Circuit affirmed in an opinion by Judge Lourie, joined by Chief Judge Prost and Judge Hughes. The panel grasps the nettle of the question before it immediately, stating that "[t]he claimed antibodies are defined by their function: binding to a combinations of sites (residues) on the PCSK9 protein, in a range from one residue to all of them; and blocking the PCSK9/LDLR interaction." This aspect of the issue before the Court was just as important and dispositive for the enablement question as it has become for the question of written description, under the reasoning set forth in this opinion. The panel reverted (as it must) to its decision in In re Wands (and its famous "Wands factors"), the dispositive factor in the Court's decision being the amount of experimentation required to encompass the full scope of the claims at issue. Albeit being a question of law, enablement depends particularly on the facts from which conclusions of law are based. The opinion is sensitive to the requirement for patenting that the specification enable practice of the claimed invention throughout its full scope, and with the Wands rubrics that the scope of the claims can determine the extent of experimentation required and whether such experimentation is undue. The opinion then focused on claims 19 and 29 of the '165 patent and claim 7 of the '741 patent in rendering its decision.

Amgen's arguments were grounded in the disclosure in the specification regarding the type of experimentation required and the guidance provided therein on the extent of such experimentation, while Defendants argued that the scope of these claims encompassed "millions of antibody candidates," that antibody production was unpredictable, and that the specification lacked sufficient guidance because, inter alia, "practicing the full scope of the claims requires substantial trial and error." Defendants emphasized not the antibodies Amgen had actually made but "the number of candidates that must be made and tested to determine whether they satisfy the claimed function."

Calling In re Wands the Court's "go to" precedent, the opinion states that while itself a monoclonal antibody case, "Wands did not proclaim that all broad claims to antibodies are necessarily enabled" because "[f]acts control." Here, the panel considered the facts (and the findings of invalidity) in more recent cases, including Wyeth & Cordis Corp. v. Abbott Laboratories, Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. In all these cases, of course, the Federal Circuit found that the claims were not enabled, due to the broad scope of embodiments the claims in these cases encompassed and the amount of undue experimentation required to satisfy the enablement requirement throughout its full scope. The panel set forth its synthesis of the Federal Circuit's analysis regarding satisfaction of the enablement requirement arising from these cases:

And citing a footnote in McRO, Inc. v. Bandai Namco Games Am. Inc.:

In cases involving claims that state certain structural requirements and also require performance of some function (e.g., efficacy for a certain purpose), we have explained that undue experimentation can include undue experimentation in identifying, from among the many concretely identified compounds that meet the structural requirements, the compounds that satisfy the functional requirement [emphasis added].

This precedent was controlling here: "[w]hile functional claim limitations are not necessarily precluded in claims that meet the enablement requirement, such limitations pose high hurdles in fulfilling the enablement requirement for claims with broad functional language." As applied to Amgen's claims, the panel recognized each of them to be "a composition claim defined, not by structure but by meeting functional limitations." This outcome is consistent with Wands, according to the opinion, because the "functional breadth" of these claims is "indisputably broad" and "the claims are far broader in functional diversity than the disclosed examples." Taking a real property analogy from AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., the opinion states that "[i]f the genus is analogized to a plot of land, the disclosed species and guidance 'only abide in a corner of the genus.'" The opinion also referenced the unpredictability of the antibody arts as a relevant (and supportive) Wands factor in favor of invalidity. And the quantum of guidance factor from Wands was also deficient, according to the opinion, because "any reasonable factfinder would conclude that the patent does not provide significant guidance or direction to a person of ordinary skill in the art for the full scope of the claims."

Importantly, the panel cabined its decision by stating that while the "substantial amount of time and effort" required to produce the scope of antibodies claimed here is undue, "[w]e do not hold that the effort required to exhaust a genus is dispositive" (emphasis in opinion). The Court struck a balance: "[t]he functional limitations here are broad, the disclosed examples and guidance are narrow, and no reasonable jury could conclude under these facts that anything but 'substantial time and effort' would be required to reach the full scope of claimed embodiments." But the facts here (which distinguish this decision from Wands) are that "the evidence showed that the scope of the claims encompasses millions of candidates claimed with respect to multiple specific functions, and that it would be necessary to first generate and then screen each candidate antibody to determine whether it meets the double-function claim limitations." Under these facts, the substantialness of such time and effort was sufficient to be considered undue experimentation by the Court.

While providing yet another fact-bound basis for invalidating (or limiting the scope of) claims to biotechnological inventions, it is unlikely to have been a coincidence that the opinion is authored by Judge Lourie, the architect of the Court's emphasis on structure in applying the written description requirement to biotechnology claims. As the Judge emphasized in his seminal Regents of the University of California v. Eli Lilly case:

Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention," citing Lockwood v. American Airlines, Inc. (Fed. Cir. 1997).

An adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the '525 patent, "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention. Fiers v. Revel (Fed.Cir.1993). Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself." Id.

A written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name," of the claimed subject matter sufficient to distinguish it from other materials. Fiers; In re Smythe ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus․").

This precedent is thus well grounded in the Federal Circuit's concern that a patentee must satisfy the quid pro quo of the patent grant, so that the specification supports its claims throughout their entire scope, whether on enablement or written description grounds. It has been a bane for the biotechnology industry that the courts (and to a lesser extent, Congress) have played "catchup" in determining the proper application of these standards to biotechnology inventions, resulting in claims either invalidated under such changing standards or failing to encompass the activities of accused infringers. But this decision provides a consistent standard ("structure, structure, structure," as recited by former Chief Judge Rader on several occasions) and one that can be applied with consistency even though the resulting scope may prove insufficient to provide enough support to justify the costs of commercialization. Which will be a bane on everyone.

Amgen Inc. v. Sanofi (Fed. Cir. 2021)
Panel: Chief Judge Prost and Circuit Judges Lourie and Hughes
Opinion by Circuit Judge Lourie

Posted at 11:59 PM in Enablement, Federal Circuit | Permalink | Comments (4)

October 31, 2019

Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. (Fed. Cir. 2019)

By Kevin E. Noonan --

Section 112 of the Patent Act as codified, entitled "Specification" in the statute, specifies the amount of disclosure required to support a patent claim (among other requirements). Section 112(a) contains three requirements: written description, enablement, and best mode (although the latter has been in something of a state of limbo since the Leahy-Smith America Invents Act (AIA) disabled it as a defense). Today in Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., the Federal Circuit held that Idenix's patent was invalid on both grounds, affirming the District Court's overturning of a jury verdict on enablement and the District Court's post-trial denial of judgment as a matter of law (JMOL) regarding satisfaction of the written description requirement. In doing so, the Court illustrated ways in which it has been able to impose its views (and recently, the Chief Judge's views) on both aspects of Section 112 requirements despite its reliance on fact finding by the jury or district court below (with Judge Newman characteristically dissenting from what she viewed as appellate court overreach by her brethren).

The case arose in litigation over Idenix's U.S. Patent No. 7,608,597 that was directed to drugs for treating hepatitis C virus (HCV), which Idenix alleged Gilead would infringe by launch of its sofobuvir (Solvadi®) HCV treatment. Independent claim 1 of the '759 is representative of Idenix's invention:

1. A method for the treatment of a hepatitis C virus infection, comprising administering an effective amount of a purine or pyrimidine β-D-2'-methyl-ribofuranosyl nucleoside or a phosphate thereof, or a pharmaceutically acceptable salt or ester thereof.

The opinion illustrates the structure of the purine or pyrimidine β-D-2'-methyl-ribofuranosyl nucleoside as disclosed in the '759 patent:

which differs from naturally occurring embodiments by the substitution of a methyl group at the 2' position on the ribofuranosyl sugar, cis to the nitrogenous base (or in the "up" position as understood by the Federal Circuit). Gilead argued (and the District Court and Federal Circuit agreed) that the '759 specification did not provide guidance regarding the "billions" of possible molecules falling within the scope of the claims. This argument was based on the acknowledged difference between the compounds exemplified in the '759 patent (having a hydroxyl, -OH, group at the 2' "down" position) while Gilead's accused infringing compound had a fluorine atom at that position. After protracted ("years," according to the opinion) litigation, the District Court conducted a jury trial in which Gilead conceded infringement but challenged the '759 claims as failing to satisfy the Section 112(a) enablement requirement. This trial resulted in a jury verdict that Idenix's '759 patent claims were not invalid for failure satisfy the enablement requirement of Section 112(a). The Court granted Gilead's JMOL motion overturning the jury's verdict but denied Gilead's JMOL motion that the claims were invalid for failing to satisfy the written description requirement. This appeal followed.

The Federal Circuit affirmed the District Court's JMOL decision on enablement, and reversed the District Court's denial of JMOL on written description, in an opinion by Chief Judge Prost joined by Judge Wallach; Judge Newman dissented. The majority rendered its decision under the de novo review standard applied to JMOL motions, which permitted the appellate panel to more easily dismiss the jury's factual determinations. The majority opinion characterized the issue before the Court as "whether a person of ordinary skill in the art would know, without undue experimentation, which 2'-methyl-up nucleosides would be effective for treating HCV." The majority held that the answer to this question is no, because "a reasonable jury would not have had a legally sufficient basis to find otherwise." The opinion rendered its decision by applying the factors delineated in In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988):

(1) the quantity of experimentation necessary;
(2) how routine any necessary experimentation is in the relevant field;
(3) whether the patent discloses specific working examples of the claimed invention;
(4) the amount of guidance presented in the patent;
(5) the nature and predictability of the field;
(6) the level of ordinary skill; and
(7) the scope of the claimed invention.

For context in appreciating how the majority applied the Wands factors, it is relevant to consider that the chemical arts have traditionally been considered unpredictable as compared with, for example, mechanical inventions. While a mechanical device comprising a fastener, for example, could have as embodiments a handful of alternatives (a crew, a nail, a rivet, a bolt, glue, Velcro®), chemical compounds can have a multiplicity of substituents at a multiplicity of positions in a molecule, wherein the permutations can quickly exceed hundreds of thousands to millions, while but a few hundred exemplary compounds are disclosed in the specification. The biotechnological arts are even more complex, for at least two reasons. First, the molecules are even larger and have the capacity for additional substitutions, and the effects of those substitutions on function of a biological molecules are themselves unpredictable. These scientific facts engendered the Federal Circuit's explication of the application of the written description requirement of Section 112 that culminated in the Court's en banc Ariad v. Eli Lilly decision (as well as earlier promulgation of Guidance from the U.S. Patent and Trademark Office in 2001). Paradoxically, biotechnology patents (unlike chemical patents) do not disclose hundreds of exemplars (and frequently only one or a few), which has led to the scope of biotechnology claims to be relatively narrow.

These considerations provide an opportunity for the Federal Circuit to apply the factors set out in Wands stringently to find failure to satisfy the enablement requirement of Section 112(a), as the Court did here. Going in order, the majority agreed with the District Court that the amount of experimentation required to support the "billions and billions" of putative species was high, supported by Gilead's expert testimony. The District Court and the majority held that experimentation was too high even if mitigating circumstances would have presented a much smaller number of species (thousands) to the person of ordinary skill in the art. This aspect of Idenix's argument was contradicted by its own evidence that "the field of modifying nucleosides for anti-HCV activity was 'in its infancy' and 'unpredictable'." This conclusion was also supported by evidence that "many" of the candidate nucleosides would need to be synthesized because they were not commercially available, although the majority acknowledges that such synthesis was routine.

The majority then turned to the "working examples" and "amount of guidance" factors, which the opinion not surprisingly held supported non-enablement. The opinion asserts in support of this conclusion that "Claim 1 requires more than just an identification of 2'-methyl-up: it requires identification of which 2'-methyl-up nucleosides will effectively treat HCV" and that "[w]ithout specific guidance on that point, the specification provides "only a starting point, a direction for further research," citing ALZA Corp. v. Andrx Pharm., LLC, 603 F.3d 935, 941 (Fed. Cir. 2010). The (un)predictability prong of the factors was supported by trial testimony from both parties' experts, and the claim scope prong (essentially overbreadth) followed from the majority's conclusions regarding the rest of the factors. The opinion's discussion characterized the situation as the person of skill in the art "the "large number" of 2'-methyl-up nucleosides falls into the 'small' group of candidates that effectively treats HCV."

As a consequence of these analyses, the majority readily concluded that the District Court correctly granted JMOL because no reasonable jury could conclude other than that Idenix did not satisfy the written description requirement. The opinion notes that their decision has "striking similarities" to Wyeth and Cordis Corp. v. Abbott Laboratories based on the "millions of compounds made by varying the substituent groups" in that case wherein "only a 'significantly smaller' subset of those compounds would have the claimed 'functional effects'." The opinion says that the decision here, as in Wyeth, "rests on the 'limits on permissible experimentation'," and states the somewhat new principle that "[w]here, as here, 'practicing the full scope of the claims would have required excessive experimentation, even if routine,' the patent is invalid for lack of enablement."

Turning to the written description issue, the majority readily pivoted from its enablement decision to hold that the '759 patent specification fails to provide an adequate written description because there was insufficient evidence that the Idenix inventors possessed the invention throughout its full scope. In particular, the majority held that there was no evidence that the '759 inventors were in possession of Gilead's product. As has been the case since the Federal Circuit's seminal decision in Regents of the University of California v. Eli Lilly, the absence of explicit disclosure of this species, in the further absence of a sufficient number of species to define a genus comprising Gilead's species, or structure/function relationships that would ensnare this species within the scope of the species expressly disclosed, was enough for the majority to conclude that the specification failed to satisfy the written description requirement.

The majority rejected Idenix's argument that the specification provided "abundant traditional blazemarks for the claims—working examples, formulas, data, synthesis routes, and the target," stating that the flaw in this analysis was that Idenix provided "lists or examples of supposedly effective nucleosides, but do not explain what makes them effective, or why." In almost the reverse of the majority's reasoning regarding enablement, the opinion states that "the specification lists tens or hundreds of thousands of possible nucleosides, substituent-by-substituent, with dozens of distinct stereochemical structures, and yet the compound in question is conspicuously absent."

Judge Newman dissented; it must be said that the tone of the dissent, and that of a footnote in the majority opinion regarding the dissent, denotes a certain impatience on the part of both authors. Judge Newman contends that "[t]he large number of unclaimed chemical variants in the specification are not described, not synthesized, and not tested for antiviral activity" and thus "[i]t is incorrect to include these variants in the claims and then to invalidate the claims because these variants are not described and not enabled." The Judge believes that a reasonable jury could have considered the claims as being limited to the much smaller number of species exemplified in the specification and thus both enabled and adequately described. She characterizes the majority's enablement theory as flawed for requiring description of "unclaimed and unsupported subject matter," and states that "a reasonable jury could have understood that subject matter that is unclaimed is irrelevant to validity under section 112."

In Judge Newman's view, the claims are limited by what is exemplified in the specification, wherein interpreting claim scope necessarily restricts the scope to that disclosure. This is certainly a more parsimonious interpretation than the majority's and has the advantage that it would guard against a patentee expanding the scope of a claim to encompass species that a conscientious competitor pursues in an effort to avoid the claim. The dissent recites copiously (18 separate citations, with the opinion stating there is "much more" ) from the expert testimony in this regard. Judge Newman asserts that "[i]t was undisputed that the '759 specification did not describe and enable products other than those whose synthesis and antiviral properties were shown in the specification, all of which had the narrow formula of three OH groups and a CH₃ group as pictured. A reasonable jury could have so viewed the claims." She further states the jurisprudential principle that "[c]ourts are not free to reweigh the evidence and set aside the jury verdict merely because the jury could have drawn different inferences or conclusions or because judges feel that other results are more reasonable," citing Tennant v. Peoria & P.U. Ry. Co., 321 U.S. 29, 35 (1944). Judge Newman concludes her dissent by stating that, despite Gilead's stipulation of infringement, the proper outcome of this case would be that the '759 patent claims were not invalid (when properly cabined to the scope supported by the specification) and not infringed by Gilead's fluorinated product (based on testimony as well as the absence of this species in the '759 disclosure).

In her own way, Judge Newman is putting her appellate thumb as heavily on the scale as did the majority, but in contrast, her jurisprudence would preserve the patent within the scope of the disclosure while absolving Gilead of infringement, while the majority's approach seems to be to interpret the claims broadly to reach the conclusion that they are invalid. This decision continues the appearance, illustrated most starkly in the Court's decision denying rehearing en banc in Athena Diagnostics v. Mayo Collaborative Services, that the Court is seriously fractured in how it approaches its role as principle arbiter of U.S. patent law.

Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. (Fed. Cir. 2019)
Panel: Chief Judge Prost and Circuit Judges Newman and Wallach
Opinion by Chief Judge Prost; dissenting opinion by Circuit Judge Newman

Posted at 12:48 AM in Enablement, Federal Circuit | Permalink | Comments (4)

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