Patent Docs

Regents of the University of Minnesota v. Gilead Sciences, Inc. (Fed. Cir. 2023)

By Kevin E. Noonan --

The Supreme Court's (re)consideration of the enablement requirement expected in its decision later this year in Amgen v. Sanofi may be the most closely watched patent case since AMP v. Myriad Genetics.  But in a decision handed down on Monday, Regents of the University of Minnesota v. Gilead Sciences, Inc., the Federal Circuit reminded us that the principles and considerations that form the basis for the Federal Circuit's recent enablement jurisprudence originated in that Court's analysis of the other side of Section 112(a), the written description requirement.

The case arose in an inter partes review decision by the Patent Trial and Appeal Board involving Gilead's challenge of claims 1−9, 11−21, and 23−28 of U.S. Patent 8,815,830.  The issue was reached in the only way it can be in an IPR:  Gilead challenged Minnesota's right to priority to applications earlier filed than Gilead's patent on its commercial product, sofosbuvir used to treat hepatitis C infections.  The temporal relationships between the patents and applications at issue are set forth in this table in the opinion:

Claim 1 was considered representative of the claims challenged in the IPR and illustrate the legal principles that formed the basis for the Court's opinion:

1.  A compound of formula I:

wherein:

R₁ is guanine, cytosine, thymine, 3-deazaadenine, or uracil, optionally substituted by 1, 2, or 3 U; wherein each U is independently halo, hydroxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyloxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, trifluoromethyl, hydroxy(C1-C6)alkyl, -(CH₂)_1-4P(=O)(OR_w)₂, aryl, aryl(C1-C6)alkyl, or NR_xR_y;

R₂ is halo;

R₆ and R₇ are independently H or (C1-C6)alkyl;

R₃ is hydroxy;

R₄ is hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, aryl, aryl(C1-C6)alkyl, or 2-cyanoethyl;

R₅ is an amino acid;

X is oxy, thio, or methylene;

each R_w is independently hydrogen or (C1-C6)alkyl;

R_x and R_y are each independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, phenyl, benzyl, phenethyl, or (C1-C6)alkanoyl; or R_x and R_y together with the nitrogen to which they are attached are pyrrolidino, piperidino or morpholino;

wherein any (C1-C6)alkyl of R₁, R₄-R₇, R_w, R_x, and R_y is optionally substituted with one or more halo, hydroxy, (C1-C6)alkoxy, (C3-C6)cycloalkyloxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, trifluoromethyl, azido, cyano, oxo(=O), (C1-C6)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C6)alkyl, (C1-C6)alkyl-S-(C1-C6)alkyl-, aryl, heteroaryl, alkyl(C1-C6)alkyl, or heteroaryl(C1-C6)alkyl, or NR_ajR_ak; wherein each R_aj and R_ak is independently hydrogen, (C1-C6)alkyl, (C3-C6)cycloalkyl, phenyl, benzyl, or phenethyl;

and wherein any aryl or heteroaryl may optionally be substituted with one or more substituents selected from the group consisting of halo, hydroxy, (C1-C6)alkyl, (C3-C6)cycloalkyl, (C1-C6)alkoxy, (C3-C6)cycloalkyloxy, (C1-C6)alkanoyl, (C1-C6)alkanoyloxy, trifluoromethyl, trifluoromethoxy, nitro, cyano, and amino;

or a pharmaceutically acceptable salt thereof.

It should be noted that this claim and the notational complexity thereof is not that different from many claims in chemical and biotechnological patents.

There was no dispute that the Sofia patent discloses every limitation of the claims challenged in the IPR and thus the '830 patent claims would be invalid if the patent was not entitled to priority to one of the three Minnesota patent applications (designated "P1," "NP2," and "NP3" in the opinion) that preceded it (as shown in the table).

As discussed in the opinion, the disclosure of the NP3 application was the same as the NP2 application, and the Board "focused its priority analysis on the disclosures of NP2 and P1, each of which was filed before Sofia was published."  The PTAB held that the challenged claims were invalid for anticipation by Gilead's Sofia publication because the disclosures of the NP2 and P1 prior applications did not provide an adequate written description of the claims in the '830 patent.  Thus the '830 patent was not entitled to the priority date of any of these applications and the Sofia patent publication was anticipating prior art.  The basis of the Board's decision was that "these documents contained neither ipsis verbis support nor sufficient blaze marks to guide the skilled artisan to the claims of the '830 patent."  The Board issued a Final Written Decision invalidating the challenged claims of the '830 patent and this appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Lourie joined by Judges Dyk and Stoll.  (It should be remembered that Judge Lourie almost single-handedly developed the modern application of the Court's written description jurisprudence, particularly for biotechnology claims, in cases including Amgen, Inc. v. Chugai Pharmaceutical Co., Fiers v. Revel, Enzo Biochem, Inc. v. Gen-Probe Inc., University of Rochester v. G.D. Serle Co., and most particularly Regents of California v. Eli Lilly & Co. and Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co.)  The opinion addressed Minnesota's three grounds for appeal in order:  first, that the Board erred in finding no adequate written description for the '830 claims in the priority documents; second, that the decision was contrary to the Administrative Procedures Act; and third, that Minnesota as a sovereign State was immune from the Board's jurisdiction.

With regard to the written description question per se, the opinion sets forth a brief but informative synopsis of the standard properly applied by the Board.  As part of the patent "quid pro quo," the panel noted that the "judicial gloss" imposed by the courts is that a disclosure must show that the applicant made what was claimed.  In the context of claims to a chemical genus, the Court apprehends "particular issues" to be raised because such claims must be supported by disclosure of "either a representative number of members of the genus or structural features common to the members of the genus, in either case with enough precision that a relevant artisan can visualize or recognize the members of the genus," citing Ariad.  Minnesota's argument sounded in the second basis for an adequate written description, setting forth "blaze marks" sufficient to disclose the genus.  Under the substantial evidence standard applied to factual questions decided by the Board (which for written description issues "must be assessed on a case-by-case basis" under Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1562 (Fed. Cir. 1991)), the Federal Circuit agreed that the Board did not err in finding against Minnesota.  Minnesota contended that a collection of dependent claims, each being directed to species for one of the several substituents (P1 Claim 47 for R₇ substituents, P1 Claim 45 for R₆ substituents, P1 Claim 33 for R₅ substituents, P1 Claim 21 for R₃ substituents, P1 Claim 13 for R2 substituents, and P1 Claim 2 for R₁ substituents, and P1 Claim 1 for R₄ substituents and X) provided ipsis verbis disclosure of the subgenus claimed in the '830 patent.  Calling this recitation a "maze-like path" needing to be followed, with "each step providing multiple alternative paths," this is "not a written description of what might have been described if each of the optional steps had been set forth as the only option."  The inadequacy in the argument (and the written description) is its indeterminacy and lack of direction because "all those optional choices do not define the intended results of claim 1 of the'830 patent."  The panel states that the situation before them was analogous to the claims invalidated on written description grounds in Fujikawa v. Wattanasin, 93 F.3d 1559, 1571 (Fed. Cir. 1996), which provided what the Court characterized in that case to be an assertion of "laundry list disclosure of every possible moiety for every possible position" as providing an adequate written description, which the Court rejected because "such a disclosure would not 'reasonably lead' those skilled in the art to any particular species."*  Here, the panel asserts that the disclosure relied upon by Minnesota recited "a compendium of common organic chemical functional groups, yielding a laundry list disclosure of different moieties for every possible side chain or functional group" and "[i]ndeed, the listings of possibilities are so long, and so interwoven, that it is quite unclear how many compounds actually fall within the described genera and subgenera."  On this basis, the Federal Circuit held that the P1 priority document does not provide sufficient ipsis verbis support for the challenged '830 patent claims to entitle these claims to its priority date.

Turning to the question of whether the prior applications provided the requisite "blaze marks" to satisfy the written description requirement, the Federal Circuit again agreed with the PTAB that they did not.  In doing so (after stretching the "tree in the forest" analogy about as far as it could be taken), the opinion rejects Minnesota's attempted reliance on rubrics from Ariad, stating that Ariad stood for the principle that what is required is:

[A] description of a claimed genus disclosing either (1) "a representative number of species falling within the scope of the genus," which the parties do not dispute is lacking here, or (2) "structural features common to the members of the genus," either of which must enable "one of skill in the art [to] 'visualize or recognize' the members of the genus" [emphasis in opinion].

In the applications considered here (P1 and NP2) "the structures here are so extensive and varied that the structures of P1 claim 47, which, through its multiple dependencies, encompasses a significantly larger genus than that claimed in the '830 patent, are not sufficiently common to that of claim 1 of the '830 patent to provide written description support."  Under these circumstances there are no "blaze marks" in the P1 nor NP2 applications to the subgenus claimed in the '830 patent for the skilled worker to appreciate.  Having failed to satisfy either alternative basis for an adequate written description, the Federal Circuit held that the PTAB properly invalidated the challenged claims as being anticipated by the Sofia publication.

Minnesota's remaining grounds for appeal were dealt with by the Court more expeditiously.  With regard to the APA challenge, the opinion rejects there being an APA basis for objection to the Board "disregard" for Minnesota's experts, because the Court states "[i]t is within the discretion of the Board to weigh the evidence of record," citing Tiger Lily Ventures Ltd. v. Barclays Cap. Inc., 35 F.4th 1352, 1365−66 (Fed. Cir. 2022), and regardless the record showed that the Board had cited Minnesota's experts "more than a dozen times" in its FWD.  Nor does the APA require the Board to perform a "creditability determination" for expert witness testimony according to the panel.  The Court also rejected Minnesota's claim that the Board's decision was contrary to an earlier decision involving Gilead, the opinion reciting five ways in which the earlier case was different from this one.  And the panel rejected Minnesota's objections on certain procedural grounds, stating that they had been given an adequate opportunity to respond during the IPR.

Finally, the opinion summarily rejected Minnesota's sovereign immunity claims based on its earlier decision in Regents of the University of Minnesota v. LSI Corp., 926 F.3d 1327 (Fed. Cir. 2019), on collateral estoppel and stare decisis grounds.

As with enablement, the Federal Circuit (albeit supported by over thirty years of precedent) has established a standard requiring heightened disclosure supporting claims to chemical and biological inventions.  The inherent complexity in these arts provides a logical basis for the distinctions drawn in this case and in earlier written description cases, and the Court's concern over a patentee receiving claims of broader scope than what is expression disclosed is a consistent theme in these cases and the more recent enablement cases before the Federal Circuit.  This parsimony is likely to resonate with the Supreme Court and thus encase in stone the disclosure requirements for written description developed for a generation by the Federal Circuit.

*Such an objection has not, sadly, prevented the Patent Office from making arguments encompassing prior art laundry list disclosures in asserting lack of patentability.

Regents of the University of Minnesota v. Gilead Sciences, Inc. (Fed. Cir. 2023)
Panel: Circuit Judges Lourie, Dyk, and Stoll
Opinion by Circuit Judge Dyk

Minerva Surgical, Inc. v. Hologic, Inc. (Fed. Cir. 2023)

By Kevin E. Noonan --

Minerva and Hologic, competitors selling devices used for ablating uterine endometrial tissue, are notable for their dispute last year that gave the Supreme Court an opportunity to reassess an established patent law doctrine, assignor estoppel (reminiscent of the Court's review of the Federal Circuit's standard for obviousness in KSR Int'l v. Teleflex).  As with KSR and obviousness, the Court's decision on assignor estoppel did not do significant violence to the doctrine, but made it less certain and more difficult for courts to apply it consistently.

But Hologic and Minerva are, after all, competitors, and while they had a role to play in influencing patent law, their interests are properly their private businesses and fortunes, and in addition to the earlier case they were also embroiled in patent litigation over a different patent, U.S. Patent No. 9,186,208.  Minerva had no more luck with that case, however, the District Court deciding on summary judgment that the patent was invalid for having been used in public more than a year before its earliest priority date (under the "public use" bar in pre-AIA 35 U.S.C. § 102(b)).  Yesterday, the Federal Circuit affirmed the District Court judgment in a decision captioned Minerva Surgical, Inc. v. Hologic, Inc. & Cytyc Surgical Products, LLC.

The claimed device was illustrated in the opinion by Figure 9 in the patent:

and the claims represented by Claim 13:

A system for endometrial ablation comprising:
    an elongated shaft with a working end having an axis and comprising a compliant energy-delivery surface actuatable by an interior expandable-contractable frame;
    the surface expandable to a selected planar triangular shape configured for deployment to engage the walls of a patient's uterine cavity;
    wherein the frame has flexible outer elements in lateral contact with the compliant surface and flexible inner elements not in said lateral contact, wherein the inner and outer elements have substantially dissimilar material properties.

(where the underlined terms were the subject of the Court's analysis of invalidity).

The District Court's decision on summary judgment was based on Minerva's behavior satisfying the prongs of the test enunciated by the Supreme Court in Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 67–68 (1998), that the invention was in public use by being disclosed to the public without any restrictions or confidentiality provisions more than one year from its earliest priority date, and that the invention was "ready for patenting" (i.e., what was disclosed was the claimed invention) when it was disclosed.  With regard to the latter prong, the device had ""the inner and outer elements have substantially dissimilar material properties" (abbreviated in the opinion as the "SDMP" term) which the District Court construed as meaning that the "inner and outer frame elements have different thickness and different composition."  The facts establishing the public disclosure prong recited Minerva's participation in a trade show -- the 38th Global Congress of Minimally Invasive Gynecology sponsored by the American Association of Gynecologic Laparoscopists and held November 16-19, 2009 (abbreviated in the opinion as "AAGL 2009") and testimony by one of the inventors that after some failures by the time of AAGL 2009 the device disclosed at the trade show were nearly "perfect."  Minerva had a booth at the show and several (15) "fully functional" devices that were extensively demonstrated on ex vivo uteri to an audience of doctors and industry participants, a presentation by the Chairman of Minerva's Medical Advisory Board, and an "Investigator's Brochure" that "provided a detailed description of the Aurora device and identified that its frame elements were made of 'Stainless steel (420 and 17-4)'" (consistent with CAD drawings prepared during development by Minerva and that the District Court found disclosed the SDMP feature recited in the claims).

Based on these facts, the District Court found no disputed material facts and granted Hologic's motion for summary judgment of invalidity.

In the Federal Circuit's opinion by Judge Reyna, joined by Judges Prost and Stoll, the Court agreed with the District Court that Hologic had established evidence satisfying the requirements for invalidating public use more than a year before Minerva's earliest priority date.  Relying on Delano Farms Co. v. California Table Grape Comm'n, 778 F.3d 1243, 1247 (Fed. Cir. 2015), and Dey, L.P. v. Sunovion Pharms., Inc., 715 F.3d 1351, 1355 (Fed. Cir. 2013), the panel asserted that the standard was the invention was "accessible to the public or was commercially exploited" by the inventor, "shown to or used by an individual other than the inventor under no limitation, restriction, or obligation of confidentiality" under Am. Seating Co. v. USSC Grp., Inc., 514 F.3d 1262 (Fed. Cir. 2008).  As to the "ready for patenting" prong, the Court cited Hamilton Beach Brands, Inc. v. Sunbeam Prods., Inc., 726 F.3d 1370, 1379 (Fed. Cir. 2013), for the persuasiveness of there being drawings and working prototypes of the claimed invention at the time of the disclosure.

The Court rejected Minerva's three assertions of error:  that the disclosure at AAGL 2009 was not a public disclosure; that the disclosure of the device did not have the claimed SMDP feature; and that the invention was not ready for patenting because Minerva was still improving the invention at the time of AAGL 2009.  As for the nature of the disclosure, the panel found dispositive that the "nature of and public access to activities involving" the disclosure were consistent with a public use because the audience consisted of "attendees who were critical to Minerva's budding business—such as potential investors and physicians—and Minerva had every incentive to showcase the Aurora devices to these attendees as best as it could."  The extensiveness of the disclosure also supported a determination of public use, disclosing the operation of fifteen functional devices at Minerva's booth over several days of the trade show, as well as "meetings with interested parties" and a technical presentation.  This was more than "mere display," according to the Federal Circuit in contrast to Motionless Keyboard Co. v. Microsoft Corp., 486 F.3d 1376 (Fed. Cir. 2007) cited by Minerva.  The panel rejected Minerva's contention that the disclosure was insufficient because observers were not permitted to "closely observe[] or physically handle[]" them, stating that "public use may also occur where, as here, the inventor used the device such that at least one member of the public without any secrecy obligations understood the invention," citing Netscape Commc'ns Corp. v. Konrad, 295 F.3d 1315, 1319–21 (Fed. Cir. 2002).  Summarizing, the opinion states that "[t]he inescapable conclusion of the detailed feedback Minerva received on the Aurora device is that Minerva allowed knowledgeable individuals to scrutinize the invention enough to recognize and understand the SDMP technology Minerva later sought to patent."

In addition, the opinion cites in support of the activities at AAGL 2009 constituting a public disclosure that on the record at the District Court "there were no 'confidentiality obligations imposed upon' those who observed the . . . device," nor did Minerva assert that the trade show had in place the "type of informal confidentiality obligations we have recognized in prior cases" to constitute sufficient confidentiality to rebut the existence of public disclosure, citing Bernhardt, L.L.C. v. Collezione Europa USA, Inc., 386 F.3d 1371, 1380–81 (Fed. Cir. 2004).

Finally on the disclosure prong, the Court found no genuine issue regarding disclosure of devices having the claimed SMDP feature, which was conceived prior to AAGL 2009 and regarding which there was evidence that the devices that were displayed had this feature (based inter alia on evidence that Minerva brought "fully functional" devices to the trade show).

With regard to the "ready for patenting" prong, the Court considered the record to show that the devices disclosed were "working prototypes" supported by inventor testimony explaining their function and incorporation of the SMDP feature and how they were used (i.e. with extirpated uteri).  To Minerva's argument that what it did not demonstrate was ablations on "live humans" the opinion counters (somewhat weakly) that "nothing in the intrinsic record indicating that the '208 patent is limited to devices only usable on live human tissue" (what else would be the device's "intended purpose"?) despite additional "fine tuning" and "later refinements" which did not rebut reduction to practice under Hamilton Beach and Atlanta Attachment Co. v. Leggett & Platt, Inc., 516 F.3d 1361, 1367 (Fed. Cir. 2008).  Similarly unavailing was Minerva's contention that the device was not ready for patenting because it was not FDA approved.  And the opinion states that, regardless of these considerations the disclosed devices were ready for patenting because the evidence of "drawings and detailed descriptions" in the inventors' notebooks were "more than enough to enable a person of skill in the art to practice the claimed invention" under the Court's Hamilton Beech precedent.

Minerva Surgical, Inc. v. Hologic, Inc. (Fed. Cir. 2023)
Panel: Circuit Judges Prost, Reyna, and Stoll
Opinion by Circuit Judge Reyna

Chromadex, Inc. v. Elysium Health, Inc. (Fed. Cir. 2023)

By Kevin E. Noonan --

Judge Giles Sutherland Rich, famous for many things (including being the principal author of the 1952 Patent Act and in particular Section 103, which cabined at least for a while the Supreme Court’s penchant for invalidating patents to such an extent that Justice Jackson remarked that the only valid patent was one the Court had not had an opportunity to invalidate, Jungersen v. Ostby & Barton Co., 335 U.S. 560, 572 (1949)) is perhaps most well-known for his aphorism that "the name of the game is the claim."  An illustration of the wisdom of this phrase is the recent decision by the Federal Circuit affirming the District Court's invalidation of asserted claims on subject matter eligibility grounds in Chromadex, Inc. v. Elysium Health, Inc.

The case arose over U.S. Patent No. 8,197,807, directed to dietary supplements comprising nicotinamide ribonucleotide (which is converted in the body to nicotinamide adenine dinucleotide, or NAD+), a co-enzyme commonly known as vitamin B3:

Representative claim 1 at issue was set forth in the opinion:

1.  A composition comprising isolated nicotinamide riboside in combination with one or more of tryptophan, nicotinic acid, or nicotinamide, wherein said combination is in admixture with a carrier comprising a sugar, starch, cellulose, powdered tragacanth, malt, gelatin, talc, cocoa butter, suppository wax, oil, glycol, polyol, ester, agar, buffering agent, alginic acid, isotonic saline, Ringer’s solution, ethyl alcohol, polyester, polycarbonate, or polyanhydride, wherein said composition is formulated for oral administration and increased NAD+ biosynthesis upon oral administration.

After construing the term "isolated nicotinamide ribonucleotide" (or "[NR]") to mean "[NR] that is separated or substantially free from at least some other components associated with the source of [NR]," the District Court granted summary judgment to defendant Elysium for failure of the claims to recite patent eligible subject matter under 35 U.S.C. § 101, on the grounds that isolated nicotinamide ribonucleotide is a product of nature declared ineligible under the rubrics set forth by the Supreme Court in Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589 (2013).

The Federal Circuit affirmed in an opinion by Judge Prost joined by Judges Chen and Stoll.  The opinion sets forth a comparison between the elements of the claim and milk, a natural product the panel considered manifestly patent ineligible as a product of nature:

The opinion characterizes the claims as being "very broad" and to read on milk with only one difference, i.e., that the nicotinamide ribonucleotide is not isolated.

The Federal Circuit relied on the Supreme Court's Myriad decision and contrasted it with the Court's decision in Diamond v. Chakrabarty, 447 U.S. 303, 309 (1980), in reaching its decision.  In Chakrabarty, the claimed microorganism was not naturally occurring, having been genetically manipulated to encode enzymes capable of digesting "multiple components of crude oil," inter alia, in oil spills, citing as the standard that the claimed bacterium was "a nonnaturally occurring manufacture or composition of matter—a product of human ingenuity having a distinctive name, character and use."  Here, as in Myriad, the claimed nicotinamide ribonucleotide while having been "isolated" was not different and distinct enough "structurally or functionally from its natural counterpart in milk" to be patent eligible.  The Federal Circuit recognized in this opinion one important distinction expressly introduced into subject matter eligibility considerations for natural products by the Supreme Court in its Myriad opinion, that "mere" isolation is not enough to confer eligibility.  This rubric was at odds with how Judge Rich understood natural product eligibility to be determined; after all, in his most famous eligibility case (the companion to Chakrabarty, a case captioned In re Bergy) there was no question raised that "merely" isolated lincomycin antibiotic was eligible.

The opinion also references another post-Myriad natural product opinion, Natural Alternatives Int'l, Inc. v. Creative Compounds, LLC, 918 F.3d 1338, 1342 (Fed. Cir. 2019), where the Federal Circuit held the claims patent eligible.  In Natural Alternatives, the Court recognized that claims to a natural product (beta-alanine) were patent-eligible for reciting "specific treatment formulations that incorporate[d] natural products" and that those formulations "ha[d] different characteristics and c[ould] be used in a manner that beta-alanine as it appears in nature cannot."  Moreover, in that case "natural products ha[d] been isolated and then incorporated into a dosage form"—"between about 0.4 grams to 16 grams"—"with particular characteristics"—namely, to "effectively increase[] athletic performance."  The Court found those "markedly different characteristics distinguished the claimed supplements from natural beta-alanine and preserved the claims' validity."

Those distinctions made all the difference for the Federal Circuit, wherein the opinion noted that the distinctions argued by Chromadex did not require that the claimed composition contained any minimum quantity of nicotinamide ribonucleotide or that the claimed composition increased NAD+ biosynthesis (something that milk itself also did).  The primary deficiency recognized by the panel is that "the claims simply do not reflect the distinctions Appellants rely on," including that "they do not require any specific quantity of isolated NR" and that the term nicotinamide ribonucleotide as construed by the District Court did not require purification from lactalbumin whey protein argued as a distinction by Chromadex.

Having arrived at its determination, the panel went on to apply the formalism of the two-part test enunciated by the Supreme Court in Mayo Collaborative Servs. Prometheus Labs., Inc., 566 U.S. 66, 77–80 (2012), and Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217 (2014), in support of its decision.  Not surprisingly, the Federal Circuit came to the same conclusion, finding reliance on the "natural law" that nicotinamide ribonucleotide compositions cause an increase in NAD+ in vivo.

There may be some comfort for the patentee in that the application resulting in this patent has an earliest priority date of April 20, 2005, many years prior to the Supreme Court's Myriad decision, or that there is another patent in the family, U.S. Patent No. 8,383,086, that claims oral pharmaceutical formulations of nicotinamide ribonucleotide.  But an analysis that patent lawyers have been doing long before Myriad's enhanced considerations of subject matter eligibility were those concerning novelty and non-obviousness.  The table contained in the opinion suggests that the claims had "bare-bones" novelty at best and the lone distinction, incorporation of "isolated" nicotinamide ribonucleotide, appears a thin reed to support an assertion of non-obviousness.  While this is just another illustrative example of how the Court could have reached the policy goals in Mayo and Alice (and perhaps Myriad, come to that) using other portions of the patent statute, it also shows that Justice Breyer's apprehension about the "clever draftsman" were both warranted and perhaps the best (only?) bulwark innovators have against summary invalidation of their patents under Section 101.

Chromadex, Inc. v. Elysium Health, Inc. (Fed. Cir. 2023)
Panel: Circuit Judges Prost, Chen, and Stoll
Opinion by Circuit Judge Prost

Astellas US LLC v. Hospira, Inc. (Fed. Cir. 2022)

By Kevin E. Noonan --

A change in the weather is known to be extreme
But what's the sense of changing horses in midstream?
I'm going out of my mind, oh, oh
With a pain that stops and starts
Like a corkscrew to my heart
Ever since we've been apart

"You're a Big Girl Now," Blood on the Tracks, Bob Dylan

In perhaps one of his most infelicitous lyrics* Bob Dylan inserted the adage that it is unwise to change horses in midstream.  This lesson comes to mind with regard to the Federal Circuit's decision late last year regarding an attempt to pursue a new theory of infringement just weeks before trial would commence (which attempt failed) in Astellas US LLC v. Hospira, Inc.

The case involved ANDA litigation brought by Gilead Sciences, Inc., Astellas US LLC and Astellas Pharma US, Inc. against Hospira for infringement of U.S. Patent Nos. 8,106,183; RE47,301; and 8,524,883 claiming a particular polymorph (termed Form A, a monohydrate) of regadenoson, an A2A adenosine receptor agonist that is a coronary vasodilator used to mimic cardiac stress and sold as Lexiscan®.  The formula for Hospira's generic regadenoson contained Form G as its active pharmaceutical ingredient (API) that would not infringe Astellas's asserted claim (the basis for Hospira's Paragraph IV certification), made by a process converting crude regadenoson to Form F (another polymorph) to Form G.  Plaintiff's initial theory of the case was that Hospira's generic drug nevertheless infringed the asserted claims, because Form A was made inadvertently by Hospira's third party supplier of an intermediate product and consequently the Form A polymorph was incorporated into Hospira's final generic product (on the basis that when these compounds "are exposed to a sufficient amount of water, including water in the air . . . and in reagents, they will convert to Form A").  In response to Hospira amending the Drug Master File (DMF) portion of its ANDA prior to trial (in an attempt to make Astellas's infringement showing harder to establish, wherein the new DMF recited that its manufacturing process had been optimized to "limit the presence of water"), Astellas asserted an alternative theory alleging that Form A arose as part of Hospira's compounding process in making its generic regadenoson.

The District Court granted Hospira's motion to strike Astellas's newly presented infringement contentions and expert testimony and evidence, with the case going to trial on Astellas's original infringement theory.  The District Court found Hospira did not infringe according to Astellas's original infringement contentions, and Astellas appealed solely on the issue of whether the District Court's preventing their assertion of their alternative infringement theory and contentions and expert evidence associated therewith was an abuse of discretion.

The Federal Circuit ruled that the District Court had not abused its discretion and affirmed the judgment in favor of Hospira, in an opinion by Judge Dyk joined by Judges Reyna and Cunningham.  The opinion notes that the District Court granted Astellas extra fact discovery in response to Hospira's change in its ANDA, but in addition to taking this discovery, Astellas submitted its new infringement contentions and expert evidence related to these contentions.  On the procedural issue of whether Astellas's motion was untimely, the Court recited the circumstances the panel relied upon in finding no abuse of discretion by the District Court.  These included testimony by Astellas's expert in the initial discovery phase that he was offering no opinion regarding whether Form A was made during Hospira's compounding process as well as several timing issues.  These included that Astellas proffered its alternative theory a year after the close of fact discovery and six months after expert discovery closed, and waited 14 months after Hospira's document disclosure, six months after learning of Hospira's ANDA change and two months after receiving Hospira's actual ANDA amendments.  In addition, Astellas waited "more than a month" after the District Court's grant of supplemental discovery prompted by Hospira's ANDA change.  Under these circumstances, the Federal Circuit stated that:

There was no reason, other than Astellas's own litigation choices, that the compounding infringement theory could not have been asserted earlier.

This is not a case where Astellas relied on new information disclosed in the ANDA amendment to craft a new theory of infringement.  Instead, Astellas simply decided that the ANDA amendment would make it harder to prove its original infringement theory and decided to try a new theory related to a process not changed by the amendment.

Based in a supplementary discovery order the District Court had issued against another defendant (who later settled) in this case who had amended its ANDA, the Federal Circuit considered the supplementary discovery order here to have been limited to Hospira's changes to its ANDA and was not broad enough to be used to develop Astellas's alternative infringement theories or proffer expert evidence in support thereof, as well as representations by Astellas to the District Court regarding the limited extent of this discovery.  On this issue the Federal Circuit based its affirmance of the District Court striking Astellas's alternative infringement contention and expert evidence on  the "great deference . . . given to a district court's interpretation of its own order," citing WRS, Inc. v. Plaza Entertainment, Inc., 402 F.3d 424 (3rd Cir. 2005).

The Federal Circuit similarly rejected Astellas's arguments that, timely or not, it was an abuse of the District Court's discretion to exclude its alternative theory of infringement.  Applying Third Circuit law, the Court considered whether Astellas had not satisfied the factors required in the Third Circuit under Meyers v. Pennypack Woods Home Ownership Assn, 559 F.2d 894 (3rd Cir. 1977):

(1) "the prejudice or surprise in fact of the party against whom the excluded witnesses would have testified" or the excluded evidence would have been offered; (2) "the ability of that party to cure the prejudice"; (3) the extent to which allowing such witnesses or evidence would "disrupt the orderly and efficient trial of the case or of other cases in the court"; (4) any "bad faith or willfulness in failing to comply with the court's order"; and (5) the importance of the excluded evidence.

Here, the Federal Circuit held that, while there was no finding under factor (4) of bad faith, the other factors supported the exercise of the District Court's discretion to preclude Astellas's alternative infringement theory.  These included clear evidence that Hospira was surprised by the alternative theory and was prejudiced thereby in view of the time remaining before trial, particularly in view of Astellas's expert's earlier testimony that he had no opinion regarding whether the Form A polymorph arose in Hospira's compounding process and there being insufficient time to perform the testing necessary to show that this conversion did not take place.  The Court also considered the prejudice to other parties to the litigation if the District Court postponed trial long enough for Hospira to complete this testing.  The opinion states that regarding factor (3) Astellas had not presented any persuasive evidence that the District Court erred in finding disruption of the court's calendar, and that Astellas had not shown that the evidence was sufficiently important to satisfy factor (5) (the opinion voicing reasons why the panel was not convinced that the excluded evidence would have been helpful for Astellas in establishing infringement).

Ultimately the decision came down to the District Court's discretion, and the Federal Circuit was unwilling to second guess that court absent more compelling evidence than Astellas was able to provide.

Astellas US LLC v. Hospira, Inc. (Fed. Cir. 2022)
Nonprecedential disposition
Panel: Circuit Judges Dyk, Reyna, and Cunningham
Opinion by Circuit Judge Dyk

* Of course he also wrote this lyric on that album, so maybe it was just a phase:

They say I shot a man named Gray
And took his wife to Italy
She inherited a million bucks
And when she died they came to me
Can I help it if I'm lucky?

"Idiot Wind"

Top Stories of 2022: #5 to #7

By Donald Zuhn –-

After reflecting upon the events of the past twelve months, Patent Docs presents its 16th annual list of top patent stories.  For 2022, we identified ten stories that were covered on Patent Docs last year that we believe had (or are likely to have) a significant impact on patent practitioners and applicants.  On Monday, we counted down stories #10 to #8, and today we count down stories #7 to #5, as we work our way towards the top four stories of 2022.  As with our other lists (2021, 2020, 2019, 2018, 2017, 2016, 2015, 2014, 2013, 2012, 2011, 2010, 2009, 2008, and 2007), links to our coverage of these stories (as well as a few links to articles on related topics) have been provided in case you missed the articles the first time around or wish to go back and have another look.  As always, we love to hear from Patent Docs readers, so if you think we left something off the list or disagree with anything we included, please let us know.  In addition, we will be offering a live webinar on the "Top Patent Law Stories of 2022" on January 24, 2023 from 10:00 am to 11:15 am (CT).  Details regarding the webinar, which will focus on a few of the most important stories on this year's list, can be found here.

7.  PTAB Issues Decisions in CRISPR Interferences and University of California/Berkeley Appeals to Federal Circuit

Seven years ago, the journal Science picked the CRISPR (clustered regularly interspaced short palindromic repeats) technology as its "Breakthrough of the Year," declaring that the technology had "matured into a molecular marvel."  Not surprisingly, CRISPR's status as breakthrough molecular marvel has resulted in a battle over who has the best patent position with respect to this technology.  Interferences between the Broad Institute, Harvard University, and the Massachusetts Institute of Technology (as Senior Party) and the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (as Junior Party) (No. 106,115), between Toolgen as Senior Party and the parties in Interference No. 106,115 as Junior Parties, and between Sigma-Aldrich as Senior Party and the parties in Interference No. 106,115 as Junior Parties continued to move forward in 2022.

In February, in Interference No. 106,115, the Patent Trial and Appeal Board granted priority for eukaryotic CRISPR to the Broad Institute, Harvard University, and MIT ("Broad") as Senior Party and against Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier ("CVC").  Accordingly, all of Broad's patents and applications in interference remain and CVC's applications having claims directed to eukaryotic CRISPR were finally rejected for lack of priority.  In November, CVC filed its brief on appeal to the Federal Circuit seeking to convince the Court that correction of the PTAB's decision is in order.

CRISPR interferences have now made five of our last six top stories lists, and the dispute over the protection of this technology could very well be on next year's list as well.

For information regarding this and other related topics, please see:

• "PTAB Redeclares Interference No. 106,132 and Suspends Priority Phase Proceedings," December 26, 2022
• "PTAB Decides Parties' Motions in CRISPR Interference," December 22, 2022
• "A Better, CRISPR World Assayed in The New York Times," December 13, 2022
• "Regeneron Files Amicus Brief in Support of CVC and Reversal in Interference No. 106,115*," November 16, 2022
• "Oral Arguments Scheduled in CRISPR Interferences," November 13, 2022
• "Scientists File Amicus Brief in Interference No. 106,115," November 8, 2022
• "CVC Files Appeal Brief in Interference No. 106,115," November 2, 2022
• "PTAB Renders Decisions in Interference No. 106,127," October 23, 2022
• "PTAB Renders Decisions in Interference No. 106,126," October 18, 2022
• "PTAB Suspends ToolGen Interferences," October 17, 2022
• "Oral Hearing in Interference No. 106,127," September 21, 2022
• "Oral Hearing in Interference No. 106,126," September 20, 2022
• "Oral Arguments Rescheduled in CRISPR Interferences," August 28, 2022
• "Oral Arguments Scheduled in CRISPR Interferences," August 4, 2022
• "Tell Us What You Really Think: CVC Asserts Board Decision in '115 Interference Negates Jurisdiction in Interference Nos. 106,127 and 106,132," June 9, 2022
• "Junior Party Broad Files Reply to Sigma-Aldrich Opposition to Broad Preliminary Motion No. 3 in Interference No. 106,133," June 1, 2022
• "Junior Party Broad Files Reply to Sigma-Aldrich Opposition to Broad Contingent Motion No. 2," May 30, 2022
• "Junior Party Broad Files Reply to Sigma-Aldrich Opposition to Substantive Preliminary Motion No. 1 in Interference No. 106,133," May 22, 2022
• "Sigma-Aldrich Files Reply to Broad’s Opposition to Sigma's Substantive Preliminary Motion No. 1 to Deny Priority Benefit in Interference No. 106,133," May 19, 2022
• "CVC Files Reply to Sigma-Aldrich Opposition to CVC's Responsive Motion No. 1," May 16, 2022
• "Junior Party CVC Files Reply to Sigma-Aldrich's Opposition to Its Preliminary Motion No. 4," May 15, 2022
• "CVC Files Reply to Senior Party Sigma-Aldrich's Opposition to CVC's Substantive Preliminary Motion No. 3 in Interference No. 106,132," May 11, 2022
• "CVC Files Reply to Sigma-Aldrich Opposition to CVC Substantive Preliminary Motion No. 1 to be Accorded Priority Benefit," May 9, 2022
• "Senior Party Sigma-Aldrich Files Reply to Junior Party CVC'S Opposition to Its Substantive Preliminary Motion No. 1 to Change Count in Interference No. 106,132," May 8, 2022
• "Senior Party Sigma-Aldrich Files Opposition to Junior Party's Preliminary Motion No. 3 in Interference No. 106,133," May 4, 2022
• "Senior Party Sigma-Aldrich Files Opposition to Broad Contingent Motion No. 2," April 21, 2022
• "Senior Party Sigma-Aldrich Files Opposition to Junior Party Substantive Preliminary Motion No. 1 in Interference No. 106,133," April 18, 2022
• "Junior Party Broad Files Opposition to Senior Party Sigma-Aldrich's Substantive Preliminary Motion No. 1 in Interference No. 106,133," April 11, 2022
• "CVC Files Opposition to Senior Party Sigma-Aldrich's Substantive Preliminary Motion No. 1 to Change Count in Interference No. 106,132," March 27, 2022
• "Senior Party Sigma-Aldrich's Opposition to CVC's Substantive Preliminary Motion No. 4 in Interference No. 106,132," March 22, 2022
• "Senior Party Sigma-Aldrich's Opposition to CVC's Substantive Preliminary Motion No. 3 in Interference No. 106,132," March 20, 2022
• "Sigma-Aldrich Files Opposition to CVC Substantive Preliminary Motion No. 1 to be Accorded Priority Benefit," March 15, 2022
• "PTAB Holds for Broad in CRISPR Interference: The Reasoning," March 7, 2022
• "PTAB Grants Priority for Eukaryotic CRISPR to Broad in Interference No. 106,115," February 28, 2022
• "Sigma-Aldrich Files Substantive Preliminary Motion No. 2 to Remove Broad Application from Interference," February 20, 2022
• "Sigma-Aldrich Files Substantive Preliminary Motion No. 1 to Deny Broad Priority Benefit to Its Earliest-filed Provisional Application," February 16, 2022
• "Broad Files Substantive Preliminary Motion No. 3 to Designate Claims as not Corresponding to Count in Interference No. 106,133," February 13, 2022
• "Broad Files Contingent Preliminary Motion No. 2 to Designate Claims Corresponding to Substitute Count 3," February 10, 2022
• "PTAB Hears Oral Argument in Interference No. 106,115," February 7, 2022
• "Broad Files Substantive Preliminary Motion No. 1 to Substitute the Count," February 2, 2022
• "CVC Files Responsive Preliminary Motion No. 1 for Priority Benefit," January 31, 2022
• "Patent Trial and Appeal Board Set Date for Oral Hearing in Interference No. 106,115," January 30, 2022
• "Sigma-Aldrich Files Substantive Preliminary Motion 1 to Change the Count in Interference No. 106,133," January 19, 2022
• "CVC Files Substantive Miscellaneous Motion No. 4 to Add Senior Party Patents and Designate Claims Corresponding to the Count," January 13, 2022
• "CVC Files Substantive Preliminary Motion No. 3 to Substiture the Count," January 12, 2022
• "CVC Substantive Preliminary Motion No. 1 for Priority Benefit," January 10, 2022

6.  Federal Circuit Continues to Focus on Written Description

In 2017, the Federal Circuit's decision in Amgen Inc. v. Sanofi 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, and that decision came in at #11 on our top stories list.  Last year, the Federal Circuit issued several decisions implicating the written description and enablement requirements, and the Federal Circuit's continuing development (and limitation of) § 112 made it to #5 on our top stories list.

Last year, the Federal Circuit continued to focus on the written description requirement.  For example, in June, in Novartis Pharmaceuticals Corp. v. Accord Healthcare, Inc., the Federal Circuit granted a panel rehearing and vacated a panel decision between these parties that had been decided in January.  In the panel rehearing, Chief Judge Moore (who dissented in January) was joined by Judge Hughes (who replaced Judge O'Malley, who left the Court in May) in vacating the January decision (over a dissent by Judge Linn, who had joined Judge O'Malley in the majority in January).  The panel majority opinion tracks the Chief Judge's dissent in the Court's earlier decision, that negative limitations do bear a burden of disclosure different from affirmative ones.  According to the Chief Judge, this burden can be satisfied, for example, by including "a reason to exclude the relevant [element]," or by including "'statements in the specification expressly listing the disadvantages of using' that element," or by distinguishing among the excluded element and advantageous alternatives.  The opinion calls "the common denominator" of all these rubrics disclosure of the element to be excluded, repeating the Chief's aphorism from her earlier dissent that "silence is not disclosure."  While not disputing the principle that "a negative limitation need not be recited in the specification in haec verba," the majority opinion asserts the need for "something" to be disclosed in the specification "that conveys to a skilled artisan that the inventor intended the exclusion, such as a discussion of disadvantages or alternatives."

For information regarding this and other related topics, please see:

• "Novartis Pharmaceuticals Corp. v. Accord Healthcare, Inc. (Fed. Cir. 2022)," June 21, 2022
• "Federal Circuit Denies Petition for Rehearing en Banc in Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc.," March 17, 2022
• "Novartis Pharmaceuticals Corp. v. Accord Healthcare, Inc. (Fed. Cir. 2022)," January 4, 2022

5.  UPC Postpones Start of Sunrise Period

Last month, the Unified Patent Court (UPC) announced that the start of Sunrise Period –- when patent owners can begin to remove European patents and European patent applications from the jurisdiction of the UPC, i.e., opt-out -- was being postponed by two months from January 1, 2023 to March 1, 2023.  The UPC indicated that the initial plan called for the Sunrise Period to begin on January 1, 2023, with the Agreement on a Unified Patent Court (UPCA) coming into force on April 1, 2023.  However, following the UPC's adjustment, the Sunrise Period will begin on March 1, 2023, and the UPCA will come into force on June 1, 2023.  The UPC also noted that it "expect[s] no further delay of the start of the UPC beyond 1 June 2023."

For information regarding this and other related topics, please see:

• "UPC Postpones Start of Sunrise Period to March 1, 2023," December 12, 2022

Dionex Softron GmbH v. Agilent Technologies, Inc. (Fed. Cir. 2023)

By Kevin E. Noonan --

As the dodo of patent practice, the number of interferences has been steadily dwindling since enactment of the Leahy-Smith America Invents Act in 2012 abolished the practice in favor of a "first inventor to file" regime and a derivation proceeding for instances where a patentee is found to have taken the invention from the true inventor (35 U.S.C. § 135).  And while the various CRISPR interferences between The Broad Institute and the University of California (Nos. 105,048 and 105,115) and those parties and ToolGen (Nos. 106,126 and 106,127) and Sigma-Aldrich (Nos. 106,132 and 106,133) have garnered more attention than other interferences combined, there remain a few other remaining interferences and in one of them, Dionex Softron GmbH v. Agilent Technologies, Inc., the Federal Circuit affirmed a determination by the Patent Trial and Appeal Board in favor of the Junior Party.

This interference was in an interesting procedural posture, wherein both parties copied each other's claims to provoke an interference.  Agilent made the first attempt and failed, copying claims to Dionex's U.S. Application No. 15/596,738, now U.S. Patent No. 10,031,112.  After Agilent amended its claims in U.S. Application No. 15/965,402, Dionex copied those claims in its U.S. Application No. 16/016,866, and the interference was declared.  The Count in Interference No. 106,109 was Claim 1 of Agilent's application:

A method of operating a liquid chromatography system, the liquid chromatography system comprising a liquid chromatography column and an injection valve, the method comprising:
    isolating a sample loop of the liquid chromatography system from a high-pressure fluidic path in fluid communication with the liquid chromatography column, wherein the high-pressure fluidic path is at a pump pressure, wherein the sample loop is in fluid communication with the injection valve and the sample loop comprises a metering device for loading a sample on the sample loop, and isolating the sample loop comprises placing the injection valve in a PRESSURE COMPENSATION position, wherein a volume of the metering device is defined by a chamber in which a piston is reciprocatingly mounted;
    determining a movement amount of the piston within the chamber from a first position to a second position to increase a pressure in the sample loop from an essentially atmospheric pressure to the pump pressure, based on the pump pressure; and
    while the sample loop is isolated from the high pressure fluidic path, decreasing the volume of the metering device to increase the pressure in the sample loop from the essentially atmospheric pressure to essentially correspond to the pump pressure of the high-pressure fluidic path;
    wherein decreasing the volume includes forwarding the piston within the chamber by the determined movement amount from the first position to the second position;
    wherein the metering device and the sample loop are in fluid communication in each position of the injection valve.

(wherein the italicized limitations were relevant to the issues before the Federal Circuit on appeal).

The PTAB denied Dionex's motion that Agilent's claims were not supported by an adequate written description under 35 U.S.C. § 112, first paragraph, finding that the specification whose adequacy was required was Agilent's '402 application because that was the application from which the claim was copied.  The issue, regarding the italicized limitation above was whether "determining a movement amount" needed to occur before "forwarding the piston" based on the disclosure of Dionex's '116 application (although Dionex conceded that certain terms, like "determining," should be construed under Agilent's '402 specification).  The Board held that Agilent's '402 specification provided an adequate written description under § 112, first paragraph, because using the "broadest reasonable interpretation" standard there was no basis for Dionex's asserted temporal limitation (i.e., that there was a movement determination prior to piston movement).  Under the Board's construction, there could be such a determination while the piston was moving and the limitation under this interpretation was adequately described by the '402 specification.

On the priority merits, the Board held for Agilent on corroborated evidence that its inventor had reduced the invention to practice (June 1, 2007) prior to Dionex's earliest asserted conception date (December 4, 2007).  The evidence was provided by testimony of one of two co-inventors, Kretz, corroborated by two co-workers, Berndt and Bäuerle.  Their corroborating testimony was that Kretz had successfully tested a prototype of the claimed invention by his asserted June 1, 2007 reduction to practice date.  This testimony was consistent with documentary evidence initially created on April 4, 2006 and having modifications as late as November 11, 2008, which document was attested by Agilent's expert to describe a functional apparatus falling within the interference Count.  The Board rejected Dionex's argument that the described apparatus did not have a pressure sensor needed to provide equalized pressure as recited in the Count, based on testimony by Bäuerle that the pump used in the prototype had an internal pressure sensor.  Finally, the Board refused to draw an adverse inference against Agilent from the failure of the second named inventor, Glatz, to testify or from the absence of contemporaneous technical drawings, schematics, and other documentary evidence in light of the adequacy of the testimony introduced by Agilent.  This appeal followed.

The Federal Circuit affirmed, in an opinion by Judge Stark joined by Judges Reyna and Chen.  Regarding the § 112, first paragraph, issue, the Federal Circuit agreed with the PTAB that the '402 application was the proper source of an adequate written description, as the "originating specification" under Agilent Techs., Inc v. Affymetrix, Inc., 567 F.3d 1366, 1374 (Fed. Cir. 2009); Rowe v. Dror, 112 F.3d 473 (Fed. Cir. 1997); and In re Spina, 975 F.2d 854 (Fed. Cir. 1992).  Agilent's earlier failure to provoke an interference by coping Dionex's claims did not change this result according to the panel.  The Federal Circuit also agreed with the PTAB's claim construction regarding whether there was a temporal component in the claim language, i.e., whether the "determining" activity must antecede "forwarding" of the piston.  While conceding the general rule that a method claim does not necessarily require steps to be performed in the order they are recited in the claim, the opinion notes that there are instances where "logic or grammar" requires a particular order, citing Mformation Techs, Inc v. Rsch. in Motion, Ltd., 764 F3d 1392 (Fed. Cir. 2014).  This was not such a case, the panel concluded, and thus the Board's determination was supported by substantial evidence (including expert testimony) as a question of fact.

The Federal Circuit also affirmed the Board's priority determination, based on actual reduction to practice having been achieved prior to Dionex's conception date and being supported by sufficient corroborating evidence.  The panel affirmed the Board's application of the "rule of reason" regarding corroborating testimony under Cooper v. Goldfarb, 154 F.3d 1321 (Fed. Cir. 1998), where there is "sufficient circumstantial evidence of an independent nature" to support inventor Kretz's testimony concerning his actual reduction to practice.  The opinion characterizes Dionex's arguments on these issues to be "mistaken" insofar as the Board properly credited testimony of contemporary witnesses of inventor Kretz's work and actual reduction-to-practice of an apparatus within the scope of the interference Count.  While the witnesses, particularly Bäuerle, may not have known every detail of the apparatus the Court held that "omniscience is unnecessary under the rule of reason" in Cooper and that any inadequacy in witness Berndt's understanding that was the basis of his testimony was not disqualifying because it was independent of inventor Kretz's testimony and the Board could find "some collaborative value" in it.  Regarding the exhibit, the panel rejected Dionex's challenge, saying it was "without merit" because the Board relied on the exhibit "as it existed at the relevant date" (emphasis in opinion), as corroborated by witness Bäuerle.  Finally, the Court rejected Dionex's argument that the Board should have drawn an adverse inference from second inventor Glatz's failure to provide testimony, saying there is no per se requirement to infer that an inventor's failure to testify should be considered harmful to her co-inventor, citing Borror v. Herz, 666 F.2d 574 (C.C.PA. 1981), and that the Board had discretion that it had not abused on this record regarding inventor Glatz's failure to testify.  In the absence of such a mandate that the Board draw the adverse inference, the Court held there was no error by the Board in not doing so and thus affirmed the Board's priority determination in favor of Agilent.

Dionex Softron GmbH v. Agilent Technologies, Inc. (Fed. Cir. 2023)
Panel: Circuit Judges Reyna, Chen, and Stark
Opinion by Circuit Judge Stark

Genentech, Inc. v. Sandoz Inc. (Fed. Cir. 2022)

By Kevin E. Noonan --

The Federal Circuit recently affirmed a district court judgment of invalidity for obviousness and for noninfringement for a series of patents challenged in ANDA litigation, in Genentech Inc. v. Sandoz Inc.  In doing so, a majority of the panel illustrated perhaps unintentionally how initial impressions regarding the issues before the Court can influence the final outcome in circumstances where the Federal Circuit is compelled to give deference to the lower court.

These issues arose in ANDA litigation brought by Genentech and InterMune against ANDA filer Sandoz and its supplier LEK Pharmaceuticals.  The drug at issue was pirfenidone used to treat idiopathic pulmonary fibrosis (IPF), an incurable, chronic, irreversible disease whose patients have a 2- to 5-year average survival length.  There is one other drug, nintedanib that has been approved for treating IPF and the two drugs split the marker evenly (approximately).  Pirfenidone had a long development time (more than 30 years) before obtaining orphan drug approval in 2004 and was approved for IPF treatment in 2014 as Esbriet®, the drug sold by Genentech and the proximal subject of this lawsuit.

Unlike most ANDA suits, the patents at issue here were not directed at the drug, formulations thereof, or methods of treatment, but rather towards administration methods for ameliorating or avoiding certain drug side effects.  There were two categories of patents at issue in the ANDA litigation and this appeal.  The first, termed the "LFT patents," were directed at administration methods for patients having liver abnormalities as detected by biomarker alterations.  These patents were U.S. Patent Nos. 7,566,729 (the "'729 patent"), 7,635,707 (the "'707 patent"), 8,592,462 (the "'462 patent"), and 8,609,701 (the "'701 patent") and the claims at issue are set forth in this table:

The asserted LFT patent claims:

The opinion summarizes the claimed subject matter into five categories:  administration methods that (1) temporarily reduce the administered dose followed by return to the "full" therapeutic dose; (2) maintain the full administered dose; (3) reduce the dose (and maintain the reduced dose); (4) discontinue administration for a week and then return to the full therapeutic dose; and (5) discontinue administration for a week and then administer a reduced dose.

Infringement was assessed as to these claims based on Sandoz's proposed label, which recited how the drug should be administered to patients showing sufficiently severe liver abnormalities:

Dosage modifications or interruptions may also be necessary when liver enzyme and bilirubin elevations are exhibited.  For liver enzyme elevations, modify the dosage as follows:

If a patient exhibits >3 but ≤5 x the upper limit of normal (ULN) ALT and/or AST without symptoms or hyperbilirubinemia after starting pirfenidone tablets therapy:

• Discontinue confounding medications, exclude other causes, and monitor the patient closely.
• Repeat liver chemistry tests as clinically indicated.
• The full daily dosage may be maintained, if clinically appropriate, or reduced or interrupted (e.g., until liver chemistry tests are within normal limits) with subsequent re-titration to the full dosage as tolerated.

wherein the italicized language was particularly relevant to Genentech's allegations sounding in inducement of infringement under 35 U.S.C. § 271(b).

Sandoz asserted invalidity for obviousness over three references:  a scientific journal article by Azuma related to a clinical trial of pirfenidone; a label for Shionogi's pirfenidone product approved in Japan, Pirespa®; and "known, standard medical practices."  The Federal Circuit's opinion characterized the teachings of the Azuma reference to specify a "stepwise" reduction in pirfenidone administration up to and including discontinuing the drug in response to severity of liver-associated side effects, and that the Pirespa® label specified discontinuing the drug.  The District Court had found that four of the five liver-associated side-effect induced alterations in pirfenidone administration were disclosed in the Pirespa® label, and furthermore found that Genentech's asserted claims in the LFT patents were invalid for obviousness in light of the references relied upon by Sandoz.

Sandoz also argued that there was no specific intent to induce infringement and thus its label did not induce infringement.

The other category of patents asserted by Genentech were directed to adverse interactions with another drug, fluvoxamine (termed "the DDI patents").  Fluvoxamine inhibits an enzyme, CYP1A2, that is involved in liver detoxification and metabolism of drugs including pirfenidone, where administration of pirfenidone to a patient taking fluvoxamine would result in what the opinion calls "supertherapeutic" drug levels in the patient's body.  The claims at issue for these patents were as follows:

The opinion summarizes the instructions in Sandoz's label (which forms the basis for Genentech's direct (literal) infringement allegations) as directing that fluvoxamine administration be discontinued prior to administering pirfenidone or reducing the amount of pirfenidone administered to a specified dose (267mg/3 time per day).  The District Court found this label to be insufficient to support Genentech's direct infringement allegations by a preponderance of the evidence because, despite Genentech showing that the label "encourages, recommends, or promotes an infringing use" Genentech failed to show that "such an infringement will in fact occur" (which seems at least odd in view of the function of the label as enshrining FDA determinations regarding how an approved drug can be safely and effectively used).  The basis for the District Court's decision was that Genentech failed to show that any patient would be prescribed both drugs to be administered together or at the same time, a prohibition that if it deemed necessary, the FDA would be capable of requiring, particularly insofar as the label expressly stated that:

The concomitant administration of pirfenidone and fluvoxamine or other strong CYP1A2 inhibitors (e.g., enoxacin) is not recommended because it significantly increases exposure to pirfenidone.  . . .   Use of fluvoxamine or other strong CYP1A2 inhibitors should be discontinued prior to administration of pirfenidone and avoided during pirfenidone treatment.  In the event that fluvoxamine or other strong CYP1A2 inhibitors are the only drug of choice, dosage reductions are recommended.  Monitor for adverse reactions and consider discontinuation of pirfenidone as needed [emphasis added].

The Federal Circuit affirmed, in an opinion by Judge Lourie who was joined by Judge Prost; Judge Newman dissented without an opinion (perhaps getting to the point where the Judge is not willing to waste her judicial breath in cases where her opinion has proven to be unavailing).  With regard to the District Court's finding that the asserted claims of the LFT patents were obvious, the majority displayed the mindset brought to the question by stating that "it is worth noting our initial perception that, as the district court noted, varying doses in response to the occurrence of side effects would seem to be a well-established, hence obvious, practice.  Thus, claiming it as an invention would appear to be at best a long shot" before stating that, like the District Court, the Federal Circuit would give the matter "careful scrutiny."  Perhaps not surprisingly in view of the majority's preconceptions, the Court agreed with Sandoz that these claims were obvious, despite Genentech's objections regarding what Azuma and the Pirespa® label taught to the skilled artisan (which as questions of fact the District Court's findings were due "clear error" deference by the Federal Circuit).  The District Court's findings as to the teachings of the asserted prior art were supported in the majority's view by "record evidence" and expert testimony.  Finally, the majority relied upon the Federal Circuit's rubric following KSR v. Teleflex that "weak secondary considerations [as the District Court and the majority considered Genentech's secondary considerations arguments to be] generally do not overcome a strong prima facie case of obviousness," citing W. Union Co. v. MoneyGram Payment Sys., Inc., 626 F.3d 1361, 1371 (Fed. Cir. 2010).  These arguments included skepticism in the art and long-felt but unmet need; none of these were sufficiently established by Genentech in the majority's view nor had Genentech established that the District Court clearly erred in arriving at its conclusions in this regard.

Having affirmed the District Court's obviousness determination, the panel did not reach the District Court's non-infringement decision.

With regard to the DDI patents, despite citing precedent that "a patentee does not need to prove an actual past instance of direct infringement by a physician to establish infringement in an ANDA case," Vanda Pharms. Inc. v. W.-Ward Pharms. Int'l Ltd., 887 F.3d 1117, 1129–30 (Fed. Cir. 2018), the majority nevertheless opined that the question of direct infringement requires "'consideration of all the relevant evidence,' including the proposed label's instructions and physician practice," citing Ferring v. Watson Lab'ys, 764 F.3d 1401, 1408 (Fed. Cir. 2014), because "past conduct is relevant to what will happen in the future" (a position the opinion acknowledges Sandoz argued).  The majority's affirmance relied upon expert witness testimony that the two drugs (pirfenidone and fluvoxamine) would not be administered together or at the same time based on "decades of treating IPF patients" (which testimony is at least curious in view of the 2014 approval date of Genentech's Esbriet® product) and that there was an alternative product on the market (nintedanib) that the physicians would prescribe instead.  The majority characterized as speculation without evidentiary support Genentech's argument that instructions regarding co-administration were important enough that the FDA included them on Sandoz's label, and in any event were not enough to sufficiently support Genentech's direct infringement arguments according to the majority.  (And in what appears to be something of a "Hail Mary" argument, the majority rejected Genentech's assertion that fluvoxamine can be used to treat COVID-19 infection in an IPF patient as speculation.)

Based on the totality of the evidence relied upon by the District Court, the Federal Circuit majority affirmed the District Court's finding that Sandoz would not necessarily directly infringe the claims of Genentech's DDI patents.

Genentech, Inc. v. Sandoz Inc. (Fed. Cir. 2022)
Panel: Circui9t Judges Newman, Lourie, and Prost
Opinion by Circuit Judge Lourie; dissent without opinion by Circuit Judge Newman

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

Scientists File Amicus Brief in Interference No. 106,115

By Kevin E. Noonan --

Early last month, a group of scientists* filed an amici curiae brief in support of the appeal by Junior Party the University of California/Berkeley, the University of Vienna, and Emmanuelle Charpentier (collectively, "CVC") of the Patent Trial and Appeal Board's decision to award priority to Broad Institute, Harvard University, and MIT (collectively, "Broad") as Senior Party for claims reciting eukaryotic embodiments of CRISPR-Cas9 (see "PTAB Grants Priority for Eukaryotic CRISPR to Broad in Interference No. 106,115").

The scientists state in preface:

Science is not perfect.  A perfectly designed experiment can fail for a host of reasons before subsequent experiments vindicate the underlying theories.  Likewise, experiments may succeed (or appear to succeed) even when they are designed using incorrect or incomplete theories.  Luck, human error, and unaccounted-for variables all play a role in determining the results of an experiment.  It is impossible to control for all of these factors.

This reality has led to development of the scientific method, wherein "scientists have developed rigorous procedures for testing their initial results and moving past initial failures."  And these failures are of two types, the scientists argue:  one, mundane failures arising from biological variability, experimental imprecision, and the play of chance; and two, fundamental failures, where "well-designed and well-executed series of experiments fails to support a scientist's expectations despite efforts to optimize or improve the experimental design and execution, suggesting the scientist has not actually made a discovery."

With these principles as backdrop, the scientists argue that the PTAB "fundamentally misunderstood how skepticism and failure operate within the scientific method."  For inventions like CRISPR that "involve[] complex biological systems with many variables," the scientists maintain that "experimental failures are common and are not necessarily indicative of a problem in the underlying theories or experimental design."  After all, the scientists note, "Broad Institute reported only two positive results out of 265 sequencing reads in its first 'successful' use of the CRISPR-Cas9 system to cleave DNA in eukaryotic cells, a gene modification rate of less than one percent."  The PTAB's mistake was to take the CVC scientists' "ordinary skepticism" (that is a part of how experimental scientists evaluate their results and ensure they are reliable) with doubt regarding the experimental data (and hence whether the CVC inventors had conceived of operable embodiments for practicing CRISPR in a eukaryotic cell).

The scientists' brief then recites some of this skepticism (in their view) that the PTAB misinterpreted, from the evidence Broad asserted in arguing incomplete conception from statements by the CVC inventors.  These statements, coupled with the five- to eight-month delay in getting eukaryotic embodiments of CRISPR to cleave target DNA effectively, convinced the Board that CVC's conception was incomplete.  This was error, according to the scientists, because the Board "mistakes mundane failures—part of everyday lab work—for fundamental failures—which might suggest the inventive idea is inoperative or incomplete."  Contrary to an admission of defeat, the scientists identify these statements to indicate that "the CVC inventors remained objective and open-minded in considering whether they needed to tweak their experimental design."

And of course, "despite initial setbacks, the inventors eventually reduced to practice their invention—in the form in which they had conceived of it—using only those routine materials and techniques known to persons of ordinary skill in the art."  This is evidence that "the CVC inventors never fundamentally doubted their invention; their expression of uncertainty was just ordinary scientific skepticism," according to the scientists.  The brief hammers home the scientists' fundamental message that "scientific skepticism is not fundamental doubt" with regard to the PTAB's acceptance of Broad's expert witness, Dr Mirkin, on the potential reasons "why a person of ordinary skill in the art (i.e., a skeptical scientist) might have believed, prior to the successful implementation of CRISPR-Cas9 systems in eukaryotic cells, that routine laboratory techniques might not work due to theoretical obstacles such as RNA degradation in eukaryotic cells, differences in the environment of eukaryotic and prokaryotic cells, and toxic effects of prokaryotic RNAs on eukaryotic cells."  The PTAB's error, the brief argues, was to misunderstand the scientists' skepticism regarding the absence of empirical data.  This was just a scientist's prudent practice, CVC argues, that "[w]hen presented with a discovery (such as the use of CRISPR-Cas9 to cleave eukaryotic DNA in vitro, as disclosed in P1), responsible scientists will reserve judgment that the discovery works in other slightly different situations (such as eukaryotic cells) until experimental results demonstrate that it actually works."  This just reflected the requirement for "tough, sustained scrutiny" that the scientific method requires, the scientists argue.  While it is easy for the skilled worker to "come up with a list of any number of theoretical obstacles to reducing to practice an invention . . . that does not mean that clearing those obstacles requires additional disclosures or anything more than routine methods."

Turning to the putative consequences of the PTAB's decision in this interference, the scientists predict that if upheld the Board's decision will "discourage collaboration, slow scientific progress, and reward confirmation bias."  In view of the collaborative nature in modern scientific labs, the scientists argue, the Board's decision to deny CVC's scientists with priority benefit to their invention will "discourage the free flow of communication between collaborators."  Prudently, future scientists "may choose not to speculate openly with their colleagues about why an experiment failed or brainstorm next steps" and, should this closed mouth behavior extend to students, cripple scientific education.  These concerns apply with at least equal risk to communication with the scientific community as a whole, the scientists argue.  As they put it, "[s]cience is a conversation: an iterative process that allows for one idea to build and shape the next through refinement of the last.  Sharing experimental results with the wider scientific community can launch a slew of new research."  But the lesson from the PTAB's decision against CVC will encourage future scientists "to secret away their inventions until they can muster enough evidence to convince others that their inventions will work."  Proposing the hypothetical, the scientists argue that the CVC inventors could have keep secret the discovery that CRISPR-Cas9 could be used to cleave DNA in vitro, waiting for the in vivo data to be later produced.  This would have delayed the progress of CRISPR research with deleterious effects on progress.

The broader picture painted in the scientists' brief is that "the PTAB's decision will encourage bad science."  This means that:

If the minor missteps and changes in strategy characteristic of routine bench work can later be used as evidence that an inventor lacked a definite and permanent idea of the invention, as the PTAB found here, scientists will avoid rigorously testing their own settled expectations.  Instead, they will be tempted to look for evidence that supports their view, building a case in favor of their invention for fear that proceeding objectively will result in denial of valuable intellectual property rights.  Such confirmation bias is antithetical to the very core of the scientific method, which demands steadfast skepticism.

It is hard to say what the effects of this amicus brief will be.  But what the scientists provide for the Court is context for the statements, e-mails, and other evidence Broad adduced during the interference that proved persuasive to the PTB in awarding priority to the Broad due to perceived failures of the CVC inventors to have had complete conception of eukaryotic CRISPR.

* The scientists on the brief are Thomas Cech (Nobel Prize winner, Chemistry, 1989), Titia de Lange, Michael Levine, David Jay Segal, and Jack Szostak (Nobel Prize Winner, Physiology/Medicine, 2009).

Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp. (Fed. Cir. 2022)

By Kevin E. Noonan --

The Federal Circuit affirmed the Patent Trial and Appeal Board's (PTAB) Final Written Decision (FWD) in an inter partes review (IPR) that Mylan Pharmaceuticals failed to show the claims of U.S. Patent No. 7,326,708 were either anticipated or rendered obvious by the asserted prior art, in Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp.

The claimed subject matter at issue was sitagliptin dihydrogenphosphate ("sitagliptin DHP"), a dihydrogenphosphate salt of 4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine:

This compound is useful for treating non-insulin dependent (Type 2) diabetes based on its activity as a dipeptidyl peptidase-IV inhibitor.  Claims 1-4, 17, 19, and 21-23 of U.S. Patent No. 7,326,708 were challenged in the IPR.

Mylan argued that International Patent Publication No. WO 2003/004498 (equivalent to another Merck patent, U.S. Patent No. 6,699,871) anticipated the claims at issue in the IPR.  Specifically, the '498 application disclosed dipeptidyl peptidase-IV inhibitors for treatment of diseases such as Type 2 diabetes.  The application disclosed 33 species of these inhibitors, including sitagliptin.  Also disclosed were the preparation of pharmaceutically acceptable salts (as a class) and hydrates thereof, including but not specifically directed to phosphoric acid.  The Board rejected Mylan's anticipation argument because the '498 application did not disclose all of the limitations in the challenged claims (specifically a 1:1 sitagliptin DHP salt), based inter alia on "evidence, both experimental and from the technical literature, undeniably showed that 1:1 sitagliptin DHP does not form every time sitagliptin and DHP were reacted" (which was the basis for the Board rejecting Mylan's inherent anticipation argument).

The Board also rejected Mylan's obviousness assertions, based on the combination of the '498 application with two scientific publications:  Brittain, which disclosed the "pharmaceutical importance and prevalence of crystalline hydrates of pharmaceutical compounds"; and Bastin, which disclosed "salt selection and optimization procedures during the development of pharmaceutical compounds."  For claims 1, 2, 17, 19, and 21-23 the Board held that Merck was able to antedate the '498 application under pre-AIA 35 U.S.C. § 102(a), and while the related '871 patent was available as prior art under pre-AIA § 102(e), application of the reference was prohibited under pre-AIA § 103(c) because the '871 and '708 patents were commonly owned or subject to an obligation for assignment.

With regard to claim 3 (directed to the (S)-configuration of sitagliptin) and claim 4 (directed to the (R)-configuration), the Board found that none of the cited references disclosed (S)-sitagliptin and thus claim 3 was not obvious.  Regarding (R)-sitagliptin recited in claim 4 the Board found that "Mylan provided no rationale to explain why a person of ordinary skill would have been motivated to make the claimed crystalline monohydrate form of 1:1 sitagliptin DHP of claim 4 and failed to show that a skilled artisan would have had a reasonable expectation of success in making the crystalline monohydrate form of the 1:1 sitagliptin DHP salt."

The Federal Circuit affirmed in an opinion by Judge Lourie, joined by Judges Reyna and Stoll.  Regarding Mylan's anticipation argument, the Court held the Board's decision was supported by substantial evidence, based in part on the testimony of Mylan's own expert witness that the '498 application did not expressly disclose sitagliptin DHP nor the production of dihydrogenphosphate salts.  The panel also found substantial evidence supported the Board's determination that the '498 application did not inherently anticipate the sitagliptin dihydrogenphosphate claimed in the '708 patent.  This decision distinguished the circumstances here from those in In re Petering (relied upon by Mylan), on the basis that Petering was based on their being only a limited number of members of the class of compounds. 301 F.2d 676, 681 (C.C.P.A. 1962).  In this case, the evidence of record showed that the 33 disclosed dipeptidyl peptidase inhibitors could result in 957 combinations with various pharmaceutically acceptable salts, under circumstances where another Mylan expert admitted that "salt formation is an unpredictable art that requires a 'trial and error process.'"  While not ruling on what would or could constitute a limited class that would satisfy the Petering standard the Court held that the proper standard was not met under these circumstances.

In considering the Board's decision on obviousness grounds, the Court first considered and rejected Mylan's argument concerning whether Merck's experimental evidence and the status of the '871 and '708 patents under pre-AIA §§ 102(a) and 102(e) precluded assertions of the '498 application as prior art.  Once again, the Court held that the Board's decision was supported by substantial evidence, including that the '498 application did not disclose 1:1 sitagliptin DHP and thus could not and did not disclose a monohydrate of the salt.

Finally, with regard to claims 3 ((S)-sitagliptin) and 4 ((R)-sitagliptin), the panel also found the Board's decision supported by substantial evidence.  The FWD held that Mylan failed to establish a motivation to combine the '498 application and the Bastin reference and that the skilled artisan would not have had any reasonable expectation of success had the reference been combined.  Considering claim 3 (again relying on Mylan's expert's testimony that the (S)-sitagliptin enantiomer was not disclosed in the '498 application, the panel held the Board was correct in concluding that Mylan had "advanced no expected or theoretical benefit to making the (S)-enantiomer of 1:1 sitagliptin DHP, and that the general disclosure on diastereomers in [the '498 application] encompasses millions of potential compounds and salts with no motivation to make the (S)-enantiomer with a reasonable expectation of success, particularly in an unpredictable activity like salt formation."  Similarly, the Court held the PTAB's decision regarding claim 4 was also supported by substantial evidence that there would have been no motivation to combine the cited references nor any reasonable expectation of success in doing so (yet again relying on Mylan's expert's testimony in this regard and also Merck's expert regarding the art teaching away from hydrates due to their unpredictability).  (In an aside, the opinion also affirms the Board's consideration of secondary indicia of non-obviousness).

While there is nothing particularly earth-shattering or precedent-setting in the Court's precedential opinion, it does illustrate once again the difficulty parties have in overcoming the presumption of substantial evidence in IPRs (and the advantages to be accrued by attempting to avoid IPR institution in the first place).

Mylan Pharmaceuticals Inc. v. Merck Sharp & Dohme Corp. (Fed. Cir. 2022)
Panel: Circuit Judges Lourie, Reyna, and Stoll
Opinion by Circuit Judge Lourie

SawStop Holding LLC v. Vidal (Fed. Cir. 2022)

By Donald Zuhn --

Earlier this month, the Federal Circuit affirmed the grant of summary judgment in favor of the U.S. Patent and Trademark Office by the U.S. District Court for the Eastern District of Virginia, finding that the USPTO did not err in its interpretations of 35 U.S.C. § 154(b)(1)(C)(iii) and did not violate the Administrative Procedure Act by refusing to award additional patent term adjustments for (C) delay for U.S. Patent Nos. 9,522,476 and 9,927,796.  At issue in the consolidated appeal was subsection (C) of § 154(b)(1), which provides patent term adjustments for delays associated with appellate review, and which reads as follows:

Subject to the limitations under paragraph (2), if the issue of an original patent is delayed due to . . .
    (iii) appellate review by the Patent Trial and Appeal Board or by a Federal court in a case in which the patent was [1] issued under a decision in the review [2] reversing an adverse determination of patentability,
    the term of the patent shall be extended 1 day for each day of the pendency of the proceeding, order, or review, as the case may be.

(The meanings of the two numbered and italicized were at issue in the consolidated appeal.)

The issuance of the '476 and '796 patents, which are directed to power saws having a safety feature that stops the saw blade upon contact with flesh, was delayed by appeals to the Patent Trial and Appeal Board before allowance.  With regard to the '476 patent application, claim 11 was finally rejected by the Examiner as being obvious, and SawStop appealed the rejection to the Board.  The Board concluded that the Examiner failed to make the initial factual findings required to demonstrate a prima facie case of obviousness of claim 11, but nevertheless affirmed, finding the claim to be obvious based on a new ground of rejection.  On remand, SawStop reopened prosecution, filed several amendments and a Request for Continued Examination, and eventually secured an allowance of claim 11.  The USPTO did not award any PTA for the time on appeal, SawStop sought reconsideration of the Office's determination, the Office denied that request, and SawStop filed a complaint in the Eastern District of Virginia to challenge the Office's determination.  The District Court granted summary judgment to the USPTO, finding that because claim 11 was subject to a new ground of rejection on appeal, the '476 patent was not "issued under a decision in the review reversing an adverse determination of patentability," and therefore was not eligible for PTA under § 154(b)(1)(C)(iii).

With regard to the '796 patent, claim 1 was finally rejected by the Examiner for anticipation and provisional non-statutory double patenting, and claim 2 was finally rejected for anticipation.  SawStop appealed the rejections to the Board, which affirmed the rejections of claim 1 and reversed the rejection of claim 2, and SawStop appealed the anticipation rejection of claim 1 to the District Court for the District of Columbia, which reversed that rejection.  On remand, the Board noted that claim 1 remained rejected for provisional non-statutory double patenting, and rather than filing a terminal disclaimer or rewriting claim 2 as an independent claim, SawStop filed an RCE and continued prosecution, filing several amendments to the claims, and eventually secured an allowance.  The USPTO again did not award any PTA for the time on appeal and SawStop filed a complaint in the Eastern District of Virginia to challenge the Office's determination.  The District Court granted summary judgment to the USPTO, finding that because claim 1 remained subject to the outstanding provisional double patenting rejection and was thus unpatentable both before and after appeal to the District Court, the '796 patent was not entitled to PTA for SawStop's appeal because the appeal did not "revers[e] an adverse determination of patentability" as required by 35 U.S.C. § 154(b)(1)(C)(iii).  The District Court also found that because claim 1 was eventually cancelled and thus did not issue in the patent, the '796 patent did not "issue under" an adverse determination of patentability as that phrase is used in 35 U.S.C. § 154(b)(1)(C)(iii).

SawStop appealed both District Court decisions to the Federal Circuit.  The opinion begins by citing the Federal Circuit's decision in Chudik v. Hirshfeld, 987 F.3d 1033, 1039-40 (Fed. Cir. 2021), for the proposition that:

[T]he most natural meaning of the words "appellate review by the Patent Trial and Appeal Board or by a Federal court in a case in which the patent was issued under a decision in the review reversing an adverse determination of patentability," when applied to an examiner's unpatentability ruling, requires that "the patent issue under a Board decision that reversed the examiner's unpatentability ruling or under a court decision that reversed a Board unpatentability ruling in the matter."

Citing Supernus Pharms., Inc. v. Iancu, 913 F.3d 1351, 1353 (Fed. Cir. 2019), the Court also notes that "[t]ype C adjustments are for delays that are . . . due to . . . successful appeals."

Regarding the '476 patent, SawStop contended that because the Examiner's rejection of claim 11 was overturned on appeal, even though the Board issued a new ground of rejection, this qualified as "a reversal of a determination of patentability."  The USPTO countered that there was "no reversal of an adverse patentability determination" because claim 11 was unpatentable before and after appeal, and because the Board maintained the unpatentability of claim 11, the '476 patent could not have "issued under" the Board's decision.  The Federal Circuit agreed with the USPTO, finding that:

The adverse determination of unpatentability remained before and after the appeal to the Board.  The appeal thus resulted in no substantive change in the patentability of claim 11.  Such a substantive change is required by the language of the statute itself: the reversal of a "determination of patentability" requires a determination that the claim in question is substantively allowable, not just free of a particular rejection.

Noting that "the claim as issued was not the same as the claim 'under a decision in the review,'" the Court added that "[t]he statutory requirement [that "the patent was issued under a decision in the review"] is not met if the claim that ultimately issues differs substantively from the claim under review."  "Because claim 11 of the '476 patent application was subject to an adverse determination of patentability both before and after the appeal, and because the claim issued only after significant substantive post-appeal prosecution and amendment," the Federal Circuit affirmed the District Court's determination that the '476 patent did not "issue[] under a decision in the review reversing an adverse determination of patentability" as required by § 154(b)(1)(C)(iii).

Regarding the '796 patent, SawStop contended that § 154(b)(1)(C)(iii) only requires "an adverse determination of patentability," and not "that 'all' rejections of a particular claim be reversed."  The Court noted, however, that "the singular reversal referenced in the statute is the determination of patentability of the claim under appellate review, not a basis for a rejection or number of rejections" (emphasis in opinion).  The opinion states that:

The problem with Sawstop's position is that the PTO's "adverse determination of patentability" of claim 1 of the '796 patent was based on two grounds: double patenting and anticipation.  Sawstop only appealed anticipation without addressing the provisional double patenting rejection.  As a result, the District Court for the District of Columbia understandably did not address the double patenting rejection.  Sawstop's success in reversing the anticipation rejection left the provisional double patenting rejection in place.  Claim 1 of the '796 patent was thus unpatentable both before the appeal (because of anticipation and double patenting) and after the appeal (because of double patenting).

SawStop, however, argued that the remaining rejection did not affect "patentability" because it was non-statutory and provisional, adding that the rejection did not have any force or effect until the obviousness-rendering reference issued and was thus not a rejection that it could appeal or the District Court could affirm or reject.  The Federal Circuit disagreed, noting that SawStop had appealed the double patenting rejection to the Board.  The Court also noted that "the only claim that was subject to the decision under review was claim 1, which was cancelled and thus not part of the issued patent," concluding that "[t]he '796 patent therefore did not issue under a decision in the review."  The Federal Circuit therefore affirmed the District Court's determination that the '796 patent also did not "issue[] under a decision in the review reversing an adverse determination of patentability" as required by § 154(b)(1)(C)(iii).

Finding that the USPTO did not err in its interpretations of § 154(b)(1)(C)(iii) and did not violate the APA by refusing to award additional patent term adjustments for (C) delay for the '796 and '476 patents, the Federal Circuit affirmed the District Court's decisions granting summary judgment in favor of the USPTO.

SawStop Holding LLC v. Vidal (Fed. Cir. 2022)
Panel: Circuit Judges Newman, Linn, and Chen
Opinion by Circuit Judge Linn

In re Cellect*

By Kevin E. Noonan --

The Federal Circuit soon will have the opportunity to decide a question left open during a recent spate of opinions involving the judicially created doctrine of obviousness-type double patenting (OTDP):  the effect patent term adjustment (PTA) can (or should) have on creating circumstances where OTDP will operate to find a patent invalid in the absence of a timely filed terminal disclaimer.

The issue arose in a series of ex parte reexaminations over five patents owned by Cellect, U.S. Patent Nos. 6,424,369; 6,452,626; 6,982,742; and 7,002,621, that involve "solid state image sensors which are configured to be of a minimum size and used within communication devices specifically including video telephones" according to the '621 patent (only 4 of these patents were invalidated, the fifth not having any PTA that raised the issue).  The chronological situation is set forth in an exhibit from Cellect's brief in its Federal Circuit appeal brief:

There was no dispute that the claims in these applications were patentably indistinct.  The Board issued four Decisions on Appeal affirming the reexamination division's invalidation of the '369, '626, '621, and 742 patents, all on the grounds that the provisions of 35 U.S.C. § 154(b)(2)(B),

"No patent the term of which has been disclaimed beyond a specified date may be adjusted under this section beyond the expiration date specified in the disclaimer"

mandated that a terminal disclaimer be filed under circumstances where obviousness-type double patenting arose due to extension of patent term as PTA, i.e., that OTDP must be determined after application of PTA.  (It will be recalled that the Federal Circuit reached a different conclusion with regard to patent term extension (PTE) under 35 U.S.C. § 156 in Novartis AG v. Ezra Ventures LLC, the Court expressly refusing to permit "a judge-made doctrine to cut off a statutorily-authorized time extension.")  Because all of these patents had expired (but Cellect retained the right to sue for prior infringement under 35 U.S.C. § 286), the Board's decision invalidated these patents with no available remedy for Cellect.  In its consolidated decision, the Board emphasized the potential inequities to the public due to the possibility of harassment by different parties owning patents to obvious variants of one another (in the absence of a terminal disclaimer preventing this potentiality) as representing an unjust extension of patent term to the public's detriment; see In re Fallaux, 564 F.3d 1313 (Fed. Cir. 2009)).  Finally, the Board rejected arguments that the Federal Circuit's jurisprudence did not rely on whether or not there was gamesmanship or the potential thereof under Gilead Sciences, Inc. v. Natco Pharma Ltd. but that under In re Longi, the public was entitled to the assumption that it is free to practice what is claimed in the patent and obvious modifications and variants thereof once the patent has expired.  759 F.2d 887 (Fed. Cir. 1985).

The questions before the Court according to Cellect are summarized in five arguments.  The first is based on the Board's putative legal error in interpreting the statute to justify treating term extension under PTA differently from term extension under PTE.  Second, Cellect argued that application of OTDP in this case was inequitable, due to the lack of remedy as well as there being no unjust extension because Cellect had engaged in no gamesmanship.  Third, Cellect argued as a fallback position that OTDP should be used here to cancel the term extended by PTA rather than invalidating the patents in their entirety.  The final two arguments were that the reexamination had been improperly instituted because there was no substantial new question of patentability and that any ancillary obviousness rejections raised in the reexamination was ultimately based on the OTDP of these patents (which argument the Board argued Cellect had waived).

Cellect's first argument was based on statutory interpretation.  Cellect argues that both PTA and PTE are statutory grounds for extending a patent term and there was no legal nor logical basis for treating them differently, i.e., the Court should interpret the PTA statute here as the Court had interpreted the PTE statute in Ezra.  Further, Cellect argues that the statutory language for PTA is that the term "shall" be extended (although there have been other instances, e.g. regarding provisions of the BPCIA, see Sandoz Inc. v. Amgen Inc., where "shall" has not been given commanding effect).  Cellect argues that the provisions the Board relied upon were intended for situations where a terminal disclaimer had been filed, not one where PTA creates OTDP (compare the language of the statute regarding a "patent the term of which has been disclaimed" to how Cellect argues the Board interpreted the language regarding a "patent the term of which [may need to be] disclaimed [if adjustment is granted]").  The consequence of the Board's interpretation creates a situation requiring "preemptive" terminal disclaimer filings, Cellect argues which Congress had not intended.  Cellect also cited several district court cases, including Amgen, Inc. v. Sandoz Inc. (D.N.J. 2021), and Mitsubishi Tanabe Pharma Corp. v. Sandoz Inc. (D.N.J. 2021), that had interpreted the Court's Ezra decision to support giving statutory deference to respecting PTA over a "judge-made doctrine."

Regarding the equities, Cellect argues that the purpose of OTDP was to prevent "unjust timewise extension of patent term" and to prevent "harassing litigation filed by multiple patent owners" for patents on "not-patentably-distinct" inventions.  Cellect's argument emphasizes the unjust extension aspect, which Cellect ties to the gamesmanship the Court recognized in Gilead.  And in this case Cellect contends that "[t]he Board used an equitable doctrine to achieve an inequitable result" because the circumstances provided no basis for Cellect to cure.  In an effort to avoid this outcome, Cellect argues that applying the Board's interpretation to retroactively disclaim the PTA-extended term but not invalidate the patents would not only cure the inequitable effects of the Board's decision but also as precedent notify future applicants who could have the opportunity to decline PTA to avoid invalidation on OTDP grounds.

The Solicitor's argument emphasized the inequities to the public occasioned by any extension of patentably-indistinct inventions (in view of the government's interpretation of the statute).  The brief cites in opposition the Court's decision in Abbvie Inc. v. Mathilda & Terence Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 1373 (Fed. Cir. 2014), that OTDP apples whenever there is an extension of patent term for patents claiming patentably-indistinct invention.  The Solicitor also notes that under circumstances where OTDP would invalidate a patent having PTE will not save it and that the differences in the statutes permit PTA to produce OTDP where PTE cannot (because § 156 does not contain the "disclaimer" in § 154(b)(2)(B)).  Regarding Cellect's arguments for forswearing PTA but preserving the patent, PTO cites Boehringer Ingelheim Int'l. GmbH v. Barr Laboratories Inc. that a patentee that had benefited from notice to public of the later expiration date has already obtained an "unjustified advantage."  Finally, the Solicitor argues that the term extension issue here is not dispositive because OTDP also prevents potential harassment by multiple assignees.

A number of amici filed briefs were filed in favor and against the Board's decision.  Briefs in opposition to the Board's application of OTDP in these circumstance were filed by the Intellectual Property Owners (IPO), the Pharmaceutical Research and Manufacturers of America (PhRMA), and the Biotechnology Innovation Organization (BIO).**  The IPO's brief emphasized that the only reason OTDP arose in this case was the application of PTA, and that the statute mandates extension (and accordingly the Board's decision was contrary to congressional intent).  PhRMA's brief focused on the purpose of OTDP that was to avoid unjust enrichment and that the PTO's "speculative" harassment rationale was inconsistent with Federal Circuit precedent.  BIO's brief discussed the Board's statutory interpretation errors and that the inequitable outcome in this case is inconsistent with the equitable underpinnings of OTDP.

Briefs in favor of the Board's decision were filed by Alvogen, the Association for Accessible Medicines (AAM), and Samsung.  Alvogen's brief argued that there was no reason OTDP should not apply to PTA because the doctrine was intended to establish term limits on patents to patentably-indistinct inventions.  Gamesmanship is not required under the statute and is an "unstable benchmark" in Alvogen's view.  AAM's brief was entirely outcome-oriented, based on the amici's perspective that patents increase drug costs and the Board's decision was a good one because it reduced patent term (no matter that the patents at issue were not related to drug products).  Finally, Samsung's brief argued that the decision was consistent with the policy bases for the OTDP doctrine and that accordingly there was no inequitable result.  (It should be noted that Samsung is a competitor and is involved in litigation with Cellect on other patents.)

The deadline for Cellect's Reply brief has been extended to October 18th, and barring further delay should be heard at oral argument within the next 4-6 months.  Thus a decision can be expected in the first quarter of next year.

From a panel discussion with Jeremy Lowe and Steve Horowitz at the 8th Annual Paragraph IV Disputes Master Symposium in Chicago on September 22, 2022

*On appeal to the Federal Circuit
**Patent Docs authors Kevin Noonan and Donald Zuhn participated in filing the BIO brief

In re Smith (Fed. Cir. 2022)

By Michael Borella --

In a ruling that should surprise absolutely nobody, the Federal Circuit rapidly scrapped an appeal of a PTAB decision that affirmed a 35 U.S.C. § 101 rejection of a business method claim.  This is the latest in a series of cases going back years in which the Court tends to find inventions that improve business processes ineligible for patenting, even if computer implementation is required.

At issue was representative claim 1 of U.S. Patent Application No. 14/786,244, which recites:

A method for facilitating asset acquisition, asset management and asset maintenance whereby customers can purchase from multiple vendors comprising:
    providing to vendor and customer users access to consortium management software;
    providing and maintaining in said consortium management software relational data base tables which are linked together, including a vendor/customer database table, whereby vendor users and customer users can enter their identifying and personal data, and a searchable product catalogue database table;
    providing in said searchable product catalogue database for receipt from vendor users, product, product pricing and product maintenance data;
    providing an inventory database table and a customer asset management database table;
    providing customer users access to said searchable product catalogue database, whereby a customer searches the catalogue data base and purchases from any vendor user product selected from said product catalogue database;
    providing for association of any said user's identifying data with information in any database table, which information is pertinent only to a particular said identified user with said users identifying data; [and]
    linking the purchasing customer's identifying information from the customer/vendor database table, and the product, product pricing and product maintenance data for the selected product or products, to one or both of said inventory database table and/or said customer asset management data base table, such that the customer can retrieve, use and manipulate the product, product pricing and product maintenance data in connection with the management of the assets purchased.

In Alice Corp. v. CLS Bank Int'l, the Supreme Court set forth a two-part test to determine whether claims are directed to patent-eligible subject matter under § 101.  One must first decide whether the claim at hand involves a judicially-excluded law of nature, a natural phenomenon, or an abstract idea.  If so, then one must further decide whether any element or combination of elements in the claim is sufficient to ensure that the claim includes an inventive concept amounting to significantly more than the judicial exclusion.  But elements or combinations of elements that are well-understood, routine, and conventional will not lift the claim over the § 101 hurdle.  While this inquiry is generally carried out as a matter of law, factual issues can come into play when determining whether something is well-understood, routine, and conventional.

In practice, either part of the Alice test can be satisfied when a claim recites a specific, technical advance over the prior art.  The Federal Circuit made this explicitly clear for part two in Dropbox Inc. v. Synchronoss Techs. Inc., holding that "an inventive concept exists when a claim recites a specific, discrete implementation of the abstract idea where the particular arrangement of elements is a technical improvement over the prior art."  Similar reasoning can be pieced together for part one through a synthesis of Federal Circuit decisions since 2014.

During prosecution, the Examiner rejected all of Smith's claims as directed to patent-ineligible subject matter.  The Examiner's rationale, tersely set forth, was that the claimed invention was drawn to an abstract method of organizing human activity without reciting significantly more than that.  The PTAB agreed, finding that the claim recited "collection, display, and manipulation of data and was thus directed to an abstract idea, and that it contained no inventive concept that would make it patent eligible."  Regarding the lack of an inventive concept, the PTAB stated that "any such additional elements include only conventional computer components and that these elements, when considered individually and as an ordered combination, are well-understood, routine, conventional activity in the field and are not specified beyond a high level of generality."

On appeal to the Federal Circuit, the Court found no error in the PTAB's reasoning.  The Court observed that claims "directed to collection of information, comprehending the meaning of that collected information, and indication of the results, all on a generic computer network operating in its normal, expected manner are claims to abstract ideas."  The Court went on to determine that there was no dispute that claim 1 did not improve the functioning of a computer.

Nonetheless, Smith made an unusual (and ultimately ill-advised) argument that "the first step in analyzing a claim to a new process or an improvement thereof must be to determine whether it is useful" and if so "it is by law patent eligible."  The Court rejected this notion in full, stating that "utility is not the test for patent eligibility" and that this argument was "inconsistent with the framework set out in Alice."

A somewhat more relevant argument was that the "Board failed to consider the claims as a whole."  The case law has never established exactly what it means to consider claims as a whole.  Often the § 101 inquiry ignores or downplays this requirement, merely allowing conclusory reasoning to win the day.  The PTAB's reasoning was not completely conclusory but it did not go into any significant detail.  Nonetheless, what the Court was likely looking for here is a contention (supported by evidence in the claim itself or in the specification) that the invention improves a computer or some other technological component or process.  Since the PTAB stated that the claim involved, at best, "an improvement in business practice for which generic computer components are used in their ordinary capacity," this was enough for the Court to affirm the rejection.

In re Smith (Fed. Cir. 2022)
Nonprecedential disposition
Panel: Circuit Judges Lourie, Dyk, and Hughes
Per curiam opinion

Guest Post -- AI and Inventorship -- Will Next Blockbuster Drug Be Denied Patent Protection?

By Brian A. Pattengale* and Anthony D. Sabatelli** --

Decades after the science-fiction visions of Stanley Kubrick’s 2001: A Space Odyssey and Isaac Asimov’s I, Robot, artificial intelligence ("AI") is finally moving to the mainstream.  Many of us use digital assistants like Apple's Siri or Google's Alexa every day, and we gape, with a mixture of awe and terror, over videos of the feats of robotic animals and stories over whether AI being developed at Google is displaying signs of sentience.  Along with this, we have finally reached the point in the development of AI where we must confront the legal and policy questions of whether AI can (or should) be able to be an inventor on a patent.

That very question was recently addressed by the Court of Appeals for the Federal Circuit ("CAFC") in Thaler v. Vidal.¹  The patent applicant in the Thaler case argued that he did not invent the subject matter of his patent applications; rather, he asserted they were invented solely by an AI system.²  In its decision, the CAFC swiftly came to the conclusion that the answer to this question is clear from the statute.  U.S. Patent Law clearly and unambiguously states that only natural persons can be named as inventors on patents.  The Court stated ". . . .it might seem that resolving this issue would involve an abstract inquiry . . . however we need not ponder these aphysical matters . . . [i]nstead, our task begins -- and ends -- with consideration of the . . . statute."  The Court reiterated that the Patent Act requires that inventors are "individuals" and therefore limited to human beings.  End of story.

In this article we consider what this very clear pronouncement by the CAFC means for drug discovery:  Will the next blockbuster drug potentially be denied patent protection if it is discovered solely through highly sophisticated AI methods?

According to a 2020 study, it generally takes on the order of 10 years and over a billion dollars to bring a new drug to market, from initial discovery in the lab through preclinical and clinical testing, to eventual approval of the new drug application ("NDA"), and then to marketing and sales.³  Furthermore, the success rate is very low -- only approximately 10% of drug candidates make it all the way through the process to approval for marketing.  The drug discovery process is still very empirical, often involving medicinal chemists and their teams synthesizing and evaluating thousands of compounds.  The process also typically relies upon numerous structure activity relationship ("SAR") decisions by those involved to direct the process.  Computer-aided drug discovery ("CADD") technologies have significantly improved this very empirical process, allowing for more efficient utilization of bio- and chemoinformatic information to propose, screen, and perform target-based analyses on drug candidates.  AI-based technologies represent the next forefront of drug discovery, offering the potential to identify optimized drug molecules based on training data without further human input during the identification process.⁴  To be clear, scenarios such as this are not science fiction -- the German biotechnology company Evotec recently partnered with UK-based Exscientia to use AI to identify a new anticancer drug candidate that is currently in Phase I clinical trials.⁵  Pharma giant Merck is also highly invested in utilizing AI platforms for drug discovery.⁶

Experts in the field generally utilize AI systems to perform machine learning or what is known as "deep learning" to make decisions and predictions based upon correlations in training data provided to the system.  For example, in the field of drug discovery, one could start with a general core structure for a drug compound and add to it a large set of chemical substituents for altering the properties of the compound.  With appropriate training data, AI can be used to predict and sift through several tens of thousands, if not millions, of theoretical substituent combinations to identify a limited set of compounds– or even a single specific compound — having selected  target properties.  In this scenario, would AI then be the rightful "inventor" of the target compound, which otherwise might never have been identified but for the use of AI?

Inventorship in the U.S. is based upon conception of an invention.  Activities undertaken simply to reduce an invention to practice are not sufficient to confer inventorship.  The Manual of Patent Examination Procedures ("MPEP"), provides unambiguous guidance for inventorship, even specifically for chemical compounds.  MPEP § 2109 II states:  "General knowledge regarding the anticipated biological properties of groups of complex chemical compounds is insufficient to confer inventorship status with respect to specifically claimed compounds".⁷  Therefore, in a simplified scenario, a medicinal chemist having expert knowledge of a broad genus of compounds would not necessarily be the inventor of a specific chemical compound falling under that genus, if that compound was discovered by another chemist on the team.  That other chemist would most likely be the inventor.  Suppose now, instead of that compound having been identified by another chemist, it is identified by AI.  Following the same logic, would not AI now likely be the rightful inventor?

For the sake of discussion, let's assume that AI fully predicts a previously unknown compound as a particular drug target.  That target compound is tested for efficacy, safety, etc. and becomes a candidate that is eventually approved for use and reaches blockbuster sales status.  Even though humans were involved in the synthesis, testing, clinical trials, and approval process, none of those activities would constitute conception (i.e., invention) of this drug compound.  The humans were "told" by AI exactly which compound to make and would only be reducers to practice, having therefore not contributed to the original conception of that particular drug compound.

Taking this scenario to its seemingly perverse conclusion, under current U.S. Patent Law as recently pronounced by the CAFC, the AI-discovered target compound would be unpatentable because AI cannot be an inventor on the patent and no human could specifically be identified as the discoverer of that compound.  In the absence of patent protection, this AI-identified compound could then likely end up in the public domain.  This result is at odds with the public policy standpoint of our patent system which rewards innovation by placing patented inventions before the public to encourage further innovation, while providing the patentee with an exclusivity for the term of the patent, which is generally twenty years.⁸

The above thought exercise, to our knowledge, has not yet played out.  But it soon could.  There may, however, be a solution to this apparent dilemma, albeit not one that is completely satisfying or sufficiently tested through litigation.  Because U.S. inventorship is based upon the patent claims, and a co-inventor need only contribute to the conception of a single patent claim to be listed as an inventor on a patent, it is entirely possible that a human inventor could conceive of a single claim or claim limitation, or even an alternative claimed embodiment, in order to be rightfully included on a patent otherwise directed to an AI-generated compound.  For example, the chemists on the AI project may conceive of or discover salts or solvates of the compound, functional limitations related to the compound, closely related compounds, methods of using the compound, methods of synthesizing the compound, etc., which could likely be sufficient for establishing human inventorship — at least to those claims reciting these limitations.

In Thaler, the Federal Circuit intentionally left certain questions unresolved by stating that the Court was " . . . not confronted today with the question of whether inventions made by human beings with the assistance of AI are eligible for patent protection".  It seems that there are arguments that a human being would have contributed to the inventions (i.e., claims) thereby meeting the inventorship threshold of the Patent Act.  Time will only tell how this scenario plays out.  Perhaps the more important million-dollar question (or, rather, multi-billion dollar question with respect to drug discovery) is whether or not a patent claim directed to a drug compound identified solely through AI, and having no human inventor, would be valid in view of Thaler.

¹ Thaler v. Vidal, U.S. Court of Appeals for the Federal Circuit, 2022, case number 21-2347

² Mr. Thaler was issued a patent in South Africa with his AI system DABUS listed as the inventor, a world first, and Europe and Australia both rejected the applications.  An Australian judge initially ruled that AI can be an inventor, and that decision was overturned earlier this year by a higher court.

³ https://www.biospace.com/article/median-cost-of-bringing-a-new-drug-to-market-985-million/

⁴ Paul, D. et al. "Artificial intelligence in drug discovery and development", 2021, Drug Discov. Today, 26:1, pp. 80–93

⁵ https://www.fiercebiotech.com/medtech/merck-selects-saama-add-machine-learning-tech-drug-development-process; https://www.emdgroup.com/en/research/science-space/envisioning-tomorrow/precision-medicine/generativeai.html

⁶ https://www.nature.com/articles/d43747-021-00045-7

⁷ Ex parte Smernoff, 215 U.S.P.Q. 545, 547 (Bd. App. 1982)

⁸ In Thaler v. Vidal, Mr. Thaler did include related policy arguments, which the Federal Circuit dismissed in view of its reliance on the statutory language that Congress chose.


* Dr. Pattengale is a patent agent at Wiggin and Dana.  Dr. Pattengale received his Ph.D., Physical and Materials Chemistry from Marquette University, and his B.S., Biochemistry from Carroll University.
** Dr. Sabatelli is Patent Counsel at Wiggin and Dana.  Dr. Sabatelli received his J.D., cum laude, from the Salmon P. Chase College of Law.  He received his Ph.D., with Honors, in Organic Chemistry from Yale University, and his B.S., summa cum laude, in Chemistry from Fairfield University.

This article was originally published on the Wiggin and Dana website on August 17, 2022.