Patent Docs

BRCA2 Gene Mutations Associated with Risk of Childhood Lymphoma

November 11, 2019

By Kevin E. Noonan —

The BRCA2 gene is one member of a pair of genes that changed the patent landscape several years ago, when the Supreme Court ruled that "mere" isolation was insufficient to render genomic embodiments thereof patent eligible, in Association of Molecular Pathologists v. Myriad Genetics. As understood at the time patents on these genes were granted, certain mutations occurring in human populations were correlated with a higher risk of breast and ovarian cancer. Recently, a group of researchers found this gene seems to be involved with risk of non-Hodgkins lymphoma in children and adolescents.

The paper was published in JAMA Oncology, entitled "Association of Germline BRCA2 Mutations with the Risk of Pediatric or Adolescent Non-Hodgkins Lymphoma," by a research group* from St. Jude Children's Research Hospital. Spurred on by prior studies showing BRCA2 gene mutations were the third most frequent germline mutations identified in survivors of childhood lymphomas, these researchers studied an additional 794 lymphoma survivors by whole-genome sequencing of DNA from peripheral blood and buccal or saliva samples. Both single-nucleotide variants and insertion/deletion mutants (indels) were detected. These researcher reported detection of 177 mutants predicted to result in loss of function. The total number of survivors (1380) were made up of 815 Hodgkin lymphoma patients and 565 non-Hodgkins lymphoma patients. Of these, 748 were male and disease onset (median) was 13.4 years (although the range is wide: 1.1-22.7 years); 81 percent were Caucasian.

A total of thirteen mutations were detected in this population (although not expressly disclosed in their paper), five coming from Hodgkin lymphoma survivors and the rest from non-Hodgkins lymphoma survivors (the paper notes that all of the non-Hodgkins lymphoma survivors were male). There was a statistical significance in non-Hodgkins lymphoma not found in the Hodgkin lymphoma patients. These authors note that these patients are also at risk for adult neoplastic disease previously associated with cancer risk, as well as risk of pancreatic cancer, prostate cancer, and melanoma.

One reality illustrated by this paper is that the claims that Myriad's BRCA2 gene test would inhibit research and development of medical science were flatly false. This blog has discussed how the "gene" claims themselves would not be infringed by interrogating genomic DNA (see "The ACLU, Working for the Man"), and the detection method claims in the Myriad patents were limited to detecting BRCA2 gene mutations predictive of ovarian and breast cancer. Nowhere in the Myriad patents was there disclosure that would support a claim to a method of detecting a risk for childhood or adolescent non-Hodgkins lymphoma. And nowhere was there ever a risk that the Myriad patents would have prevented or even inhibited the research disclosed in this paper or any commercial application of it. Sadly, the ACLU's false narrative (recently reiterated during Senate hearings over proposed statutory reforms directed to ameliorating the most deleterious consequences of judicial persuasion to this erroneous point of view; see "ACLU (Predictably) Opposes Patent Subject Matter Eligibility Proposal") now limits such commercial development to the very companies least in need of exclusivity and who might reasonably choose to stick to already developed diagnostic methods rather than take the commercial risks associated with this new knowledge, no matter how much of an improvement it might provide. So much for the Court's decisions ensuring progress is promoted under its interpretation of the Patent Act.

* Wang, Zhaoming, PhD, Wilson, Carmen L., PhD, Armstrong, Gregory T., MD, Hudson, Melissa M., MD, Zhang, Jinghui, PhD, Nichols, Kim E., MD, Robison, Leslie L., PhD
Berkeley Files Opposition to Broad’s Substantive Motion No. 1 in Interference

November 10, 2019

By Kevin E. Noonan —

On October 18th, Junior Party (the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier (collectively, "CVC") filed its authorized opposition to Substantive Motion No. 1 from Senior Party the Broad Institute (and its partners as Senior Party, Harvard University and MIT), which asked for judgment in Interference No. 106,115 on the basis that CVC was estopped by prior judgment of no interference in fact in Interference No. 106,048 between these parties.

To recap, the Broad's motion asserted these arguments in favor of judgment:

CVC is estopped from getting a "second bite at the apple" in this interference by the provisions of 37 C.F.R. § 41.127(a)(1) and MPEP § 2308.03(b) (interference estoppel) because:

- this interference is directed to the same subject matter as the previous '048 patent (using the inclusion of the same Broad patents in this interference and the correspondence between the count in the '048 interference and claim 1 in involve U.S. Patent No. 8,697,359 in support)

- CVC is estopped from pursuing this interference on the grounds of judgment estoppel regarding issues that were raised or could have been raised in the earlier interference:

Judgment. (a) Effect within Office—(1) Estoppel. A judgment disposes of all issues that were, or by motion could have properly been, raised and decided. A losing party who could have properly moved for relief on an issue, but did not so move, may not take action in the Office after the judgment that is inconsistent with that party's failure to move, except that a losing party shall not be estopped with respect to any contested subject matter for which that party was awarded a favorable judgment [emphasis added].

The Broad argued that CVC had the opportunity in the '048 interference to file a responsive motion to the Broad's motion of no interference-in-fact to add claims directed to eukaryotic applications of CRISPR technology but did not. The Broad argues that this was a strategic decision by CVC to have only its "environment-free" claims in the interference. Furthermore, the Broad contends that it was intentional, citing to CVC's colloquy before the Board when the parties discussed which motion the Board would authorize, where CVC expressly "reserved" the ability to file such responsive motions.

The Broad's motion also asserts that the Board should not permit CVC to maintain the "cloud of uncertainty" regarding its patents, in its public statements and by pursuing "serial" interferences against the same Broad patents.

As is required under the procedural rules in interferences, CVC's opposition addresses each of these contentions in turn, including any disagreement over the facts the Broad put forward in support. Thus, CVC's first asserted opposition argument was that "judgment estoppel" (quotation marks in opposition brief) does not exist in any form that would prelude this interference. CVC's counter to the Broad's argument focuses on the existence vel non of a "losing" party in cases where no interference-in-fact are found. The brief characterizes as false the assumption that the subject matter of this interference is the same as the subject matter of the '048 interference. In the prior interference, it is undisputed that the Broad's claims were limited to practicing CRISPR in eukaryotic cells while CVC's claims-in-interference had no such restriction. That restriction (embodied in the Count) was imposed by the Board when the '048 interference was declared (and the Board never ruled on CVC's motion to change the count to remove this restriction. The scope of that earlier interference is different from this one, which is frankly directed towards using CRISPR solely in the eukaryotic background. According to CVC, this is the first time the priority question on practicing CRISPR solely in the eukaryotic cell context has been before the Board, and thus there should be no estoppel.

With regard to the Broad's arguments related to Rule 127, CVC contends that the Broad has misconstrued the meaning of the first sentence of the Rule. There is no per se "failure to move" requirement devoid of the need for a losing party in the prior interference (which does not exist in this case). The brief takes the opportunity to assert its priority argument in this section, arguing that CVC was "the first party to file a patent application identifying the necessary and sufficient components of a CRISPR-Cas system that cleaves or edits DNA," starting with its May 25, 2012 filing date, importantly encompassing its use without regard to cellular milieu.

The brief further addresses the assertions made that CVC was executing a "tactical decision" to "wage [a] serial interference campaign." On the contrary, CVC argues that it had suggested a count in the '048 interference that was cellular milieu-free, and it was the Board that restricted the count to use in eukaryotic cells. Nor, CVC contends, can its efforts to obtain patents on systems and uses of CRISPR in eukaryotic cells as "a mere attack" on the Broad's claims. CVC is jut doing what it was always intending to do, obtain broad and specific claim coverage for uses of CRISPR broadly. CVC also reminds the Board that, unlike in the '048 interference in this interference the Board declared it sua sponte (further blunting any allegations of manipulation or scheming, according to CVC). Having found interfering subject matter CVC argues that the Board ha a responsibility to declare an interference to resolve the priority issue under 35 U.S.C. §§ 102(g) and 135. CVC further argues that it is the Broad that has sought to avoid Board determination of the priority question, and points to its alleged motivation to do so: "[the] Broad was actually the fourth entity to file a patent application directed to CRISPR in eukaryotes" (citing facts CVC filed in support of tis opposition). The brief also makes sub silentio an argument regarding the Broad's (perfectly proper) prosecution strategy that accelerated examination of its CRISPR patents, and by "changing its applications' designation from post-AIA to pre-AIA during prosecution so that it could swear behind CVC's earlier-filed application." And CVC turns the Broad's victory in the earlier '048 interference against it, characterizing the Broad's successful pursuit of a finding of no interference-in-fact as another way to avoid final Board determination of the priority question (and similarly turns the Broad's allegations that CVC had a responsibility to move that the Board include claims to eukaryotic cell embodiments of CRISPR against the Broad, by alleging that it was the Broad that "could and should have moved to add a eukaryotic claim to CVC's involved application" as the proper alternative to seeking a finding of no interference-in-fact). Reminding the Board of the purported advantages of its alleged strategy, the brief states that:

Broad has enjoyed the benefits of its issued patents for five-and-a- half years but must now finally face the unresolved question of priority of invention for CRISPR in eukaryotes; no principles of collateral estoppel or res judicata prohibit the PTAB from resolving the issue now via this interference. Broad and the public have long been on notice that this issue remained unresolved as between Broad and CVC. The present interference, mandated by §§ 102(g) and 135, presents the proper vehicle for finally resolving priority of invention.

CVC's brief also addresses the estoppel issue, stating that interpreting estoppel as the Broad seeks in its motion would "invite the Office to commit legal error by exceeding its authority." Interference estoppel comes in two flavors, according to the brief: those set forth expressly in the enabling statute and those arising from common law. The latter are impliedly present in the statute because "Congress may be presumed, when enacting a statute granting to an agency adjudicatory authority, to mandate adherence to the doctrine of collateral estoppel," citing Duvall v. Atty. Gen., 436 F.3d 382, 387 (3d Cir. 2006). Here, the statute does not affirmatively set forth an estoppel and thus, according to CVC, any estoppel (including the "judicial estoppel" that is the basis for the Broad's prayer for relief in its motion, must arise from these common law principles. In addition, CVC argues that once Congress gives an agency authority to act, it "cannot promulgate or apply procedural rules in a manner that unilaterally contracts its jurisdiction to make it more narrow than what Congress has provided," citing Union Pac. R. Co. v. Bhd. 13 of Locomotive Engineers & Trainmen, 130 S. Ct. 584, 590 (2009). These arguments are relevant to CVC brief in two ways: first, the PTAB is not capable of promulgating rules on estoppel that go beyond the common law (absent express statutory authority absent here). Nor can the PTAB fail to satisfy its statutory mandate (here) to make priority determinations when priority of invention is in conflict.

With regard to the proper scope of estoppel, CVC argues that the Broad's interpretation of Rule 127 is contrary to these common law estoppel principles. CVC's first argument in support of its opposition in this regard is that this interference does not involve the same subject matter as the prior, '048 interference (making arguments substantially as set forth above on this point). While it is true that the Broad's claims in the earlier interference were limited to eukaryotic cell applications of CRISPR, CVC's were not, and thus this interference considering eukaryotic cell claims of both parties defines different subject matter. CVC's claims limited to eukaryotic cells in this interference are (and must be) patentably distinct from its claims in the '048 interference, because after all that distinction was the basis for the Broad having the PTAB (and the Federal Circuit) decide there was no interference-in-fact in the '048 interference:

The PTAB is now poised to answer who was first to invent CRISPR in eukaryotes. That question was not (and could not have been) litigated or decided in the previous interference given the no interference-in-fact determination. No principle of collateral estoppel or res judicata prevents deciding an issue that was not previously litigated,

according to CVC’s brief, citing B&B Hardware, Inc. v. Hargis Indus., Inc., 135 S. Ct. 1293, 1303 (2015); Biogen MA, Inc. v. Japanese Found. for Cancer Research, 785 F.3d 648, 658 (Fed. Cir. 2015); Purdue Pharma L.P., et al. v. Iancu, 2019 U.S. App. LEXIS 11205 (Fed. Cir. 2019); and Cromwell v. County of Sac, 94 U.S. 351, 353 (1877).

The brief makes a distinction between termination of an interference because no interference-in-fact is found (which, according to CVC, is a dismissal for lack of jurisdiction), which is not the same as a judgment and "does not preclude a second action based on the same cause of action that includes claims that overcome the initial defect of jurisdiction," citing, inter alia, Hughes v. U.S., 71 U.S. 232, 237 (1866). The proper analogy for a finding of no interference-in-fact is dismissal of a district court action for failure to state a claim, where res judicata arises only where the defect in the pleadings has not been cured.

CVC further faults the Broad's estoppel argument by noting that according to its terms Rule 127 raises an estoppel in the context of provoking an interference, whereas the '115 interference was declared sua sponte by the Board (exactly the type of procedural argument that frequently resonates with the Board; see "Sigma-Aldrich Tried Again"). Similarly, CVC's brief distinguishes MPEP 2308.03(b) from MPEP 2308.03(c) on the basis that the former rule of practice bars "any further interference between the same 2 parties for claims to the same invention as the count of the interference, [and] not any subsequent interference that presents a new question not previously litigated" (emphasis in brief). (And even if the PTAB disagrees with how CVC has parsed the MPEP, the brief asserts that "[t]o the extent that MPEP 2308.03(b) is construed to bar the present interference, the MPEP is contrary to the law and therefore invalid.") Finally, on these matters CVC disagrees that the scope of the count of the '048 interference has any weight or relevance, because if there was no interference-in-fact in the '048 interference there was no count that properly defined interfering subject matter.

CVC's brief then turns to the Broad's argument that CVC was under an obligation to move to include claims in the '048 interference directed to eukaryotic embodiments of CRISPR and that failing to do so raises an estoppel. Here CVC again raises objection to the Broad's interpretation of Rule 127, asserting (again) that the Rule requires there to be a losing party for estoppel to arise and a finding of no interference-in-fact does not produce a losing party. (The brief cites voluminous authority regarding the proper relationship between clauses or provisions of rules or statutes and their interpretation in support of this argument.) The brief notes (at least in part in contrast) that the Broad cited no authority for its (mis)interpretation of the Rule, and that its citation of commentary on the rulemaking that resulted in the provisions of the MPEP cited in the Broad's brief either does not support the Broad's interpretation of the Rule nor is the Board bound by them. CVC's conclusion is that:

[N]either Rule 127's text nor the rule-making comments state or imply that, following a judgment of no interference-in-fact, a non-losing party "who could have properly moved for relief on an issue, but did not so move, may not take action in the Office after the judgment that is inconsistent with the party's failure to move." 37 C.F.R. § 41.127(a)(1). That kind of failure-to-move estoppel is expressly reserved for a losing party, and limited to issues for which the losing party was not awarded favorable judgment. Id. Applying estoppel any more broadly would impose an inequitable result on a party that had not lost the prior proceeding.

CVC further blunts (or attempts to do so) in this portion of the brief the Broad's allegations that CVC's actions or inaction in the prior '048 interference were somehow improper or merely strategic, calling these characterizations a "mischaracterize[ation of] the facts." At least one set of these facts set forth in CVC's brief is that the Broad accuses CVC of not moving to include eukaryotic cell CRISPR claims in the '048 interference, when CVC had no such claims in condition for allowance (a requirement for the PTAB to make a priority determination) at that time. CVC also cites a Board Order in the prior interference, which stated that "[u]nder the facts and circumstances of this interference, where [CVC] believes all of its current claims interfere with all of Broad's claims, there is no reason why [CVC] should need to add a new claim. If [CVC]'s claims in other applications are ultimately found to be allowable, [CVC] may suggest additional interferences to the examiner" (emphasis in brief). Clearly, the position argued by the Broad is contrary to the terms of the Board's prior Order (at least as CVC interprets it) and may provide a basis for the Board to disregard this portion of the Broad's argument at a minimum and perhaps deny Substantive Motion No. 1.

The final Sections of CVC's brief address the Broad's assertion of equitable estoppel (which, according to CVC, would result in the Board to "abrogate its statutory mandates to decide interferences under § 135 and to issue patents to all those entitled to them under § 102); certain "policy considerations" that support the PTAB deciding the priority question ("it would contradict the PTAB's legislative mandate if it were to refrain from deciding the outstanding priority of invention issue, particularly where Broad's patents are facially invalid in view of CVC's earlier filed patent applications disclosing CRISPR in eukaryotes"); and that the Board must resolve certain disputed factual issues before deciding to grant the Broad's Substantive Motion No. 1.

Final Section VI of the brief provides CVC with an outcome that could snatch (ultimate) victory from the jaws of a defeat should the Board grant the Broad's Substantive Motion No. 1. Under those circumstances, CVC argues that the PTO has determined that CVC's claims are in condition for allowance but for the priority issues that have arisen under 35 U.S.C. §102(g). Thus, should the Board grant the Broad's motion the impediments to patentability raised by the Examiner would be overcome (i.e., there would be no violation of § 102(g)) and accordingly the Office should issue CVC's patents in due course. This would then give CVC the right to file an action in district court under § 291 to determine which of CVC and the Broad should properly have priority to the subject matter of eukaryotic cell embodiments of CRISPR. While not exactly a poison pill, such an outcome would not necessarily be estopped, because there would be two parties having granted claims to eukaryotic embodiments of CRISPR, and the public interest at a minimum would favor final resolution of the priority question. Of course the Broad recognized the possibility of this outcome and has asserted § 101 as a basis to preclude the Office from granting CVC's patents. While § 101 has been put to a great many uses during the past ten years, it clearly does not apply here (as CVC asserts), because "§ 101 simply bars issuing two patents to the same inventive entity; it says nothing about issuing a patent to a different inventive entity" (which is the provenance of § 102(g)).

The Broad's Reply brief is due March 20, 2020 unless the Board specifies an earlier date (which is likely).
USPTO Seeks Comments on Intersection of Intellectual Property and Artificial Intelligence in Second Federal Register Notice

November 7, 2019

By Aaron Gin —

On October 30, 2019, the U.S. Patent and Trademark Office released a Federal Register Notice requesting comments on issues of artificial intelligence (AI) and intellectual property, the second such request in the past three months.

In a blog post on the USPTO "Director's Forum", USPTO Director Andrei Iancu and Deputy Director Laura Peter stated that "[t]he fields of copyright, trademark, database protections, and trade secret law, among others, may be . . . susceptible to the impacts of developments in AI." As such, the USPTO has requested public feedback by way of thirteen questions involving topics ranging from whether an AI, without human intervention, can create a copyrightable work to whether and how AI might impact trade secret law. The Notice questions are summarized as follows:

1. Should a work produced by an AI algorithm or process, without the involvement of a natural person contributing expression to the resulting work, qualify as a work of authorship protectable under U.S. copyright law?

2. Assuming involvement by a natural person is or should be required, what kind of involvement would or should be sufficient so that the work qualifies for copyright protection? For example, should it be sufficient if a person (i) designed the AI algorithm or process that created the work; (ii) contributed to the design of the algorithm or process; (iii) chose data used by the algorithm for training or otherwise; (iv) caused the AI algorithm or process to be used to yield the work; or (v) engaged in some specific combination of the foregoing activities? Are there other contributions a person could make in a potentially copyrightable AI-generated work in order to be considered an "author"?

3. To the extent an AI algorithm or process learns its function(s) by ingesting large volumes of copyrighted material, does the existing statutory language (e.g., the fair use doctrine) and related case law adequately address the legality of making such use?

4. Are current laws for assigning liability for copyright infringement adequate to address a situation in which an AI process creates a work that infringes a copyrighted work?

5. Should an entity or entities other than a natural person, or company to which a natural person assigns a copyrighted work, be able to own the copyright on the AI work? For example: Should a company who trains the artificial intelligence process that creates the work be able to be an owner?

6. Are there other copyright issues that need to be addressed to promote the goals of copyright law in connection with the use of AI?

7. Would the use of AI in trademark searching impact the registrablity of trademarks?

8. How does AI impact trademark law? Is the existing statutory language in the Lanham Act adequate to address the use of AI in the marketplace?

9. How does AI impact the need to protect databases and data sets? Are existing laws adequate to protect such data?

10. How does AI impact trade secret law? Is the Defend Trade Secrets Act (DTSA), 18 U.S.C. 1836 et seq., adequate to address the use of AI in the marketplace?

11. Do any laws, policies, or practices need to change in order to ensure an appropriate balance between maintaining trade secrets on the one hand and obtaining patents, copyrights, or other forms of intellectual property protection related to AI on the other?

12. Are there any other AI-related issues pertinent to intellectual property rights (other than those related to patent rights) that the USPTO should examine?

13. Are there any relevant policies or practices from intellectual property agencies or legal systems in other countries that may help inform USPTO's policies and practices regarding intellectual property rights (other than those related to patent rights)?

In August, the USPTO previously requested comments on AI inventions with respect to patent law and policy. The questions from the first Notice covered a variety of patent-related topics, including whether revisions to patent laws may be needed. The current Notice extends similar inquiries to ask how AI may affect non-patent areas of IP (e.g., copyright, trademark, and other intellectual property rights). Notably, some of the questions could even foreshadow how examination procedures might evolve at the USPTO to include AI-based trademark searches. The Notice stated that public comments in these areas would aid the USPTO to evaluate whether further guidance to the Examining Corps is needed and to assist in the development of any such guidance with respect to intellectual property policy and its relationship with AI.

The USPTO has clearly made understanding the benefits/drawbacks of AI an action item for itself in the near future, on the policy front, and possibly in its own examination practice. The Notice itself pledges that "[t]he USPTO is committed to keeping pace with this critical technology in order to accelerate American innovation." Furthermore, the Patent Office has an open job posting for a "Senior Level Artificial Intelligence Technical Expert" whose responsibilities may include "operational implementation of Artificial Intelligence (AI) infrastructure/architecture throughout the enterprise." Going forward, it will be interesting to see how AI impacts existing patent and non-patent IP law and policy, as well as how AI-based innovations will be incorporated into the operation of the USPTO.

Written comments can be provided by email to AIPartnership@uspto.gov until December 16, 2019. Written comments will be made available for public inspection.

For additional information, please see:

• Second Federal Notice: Request for Comments on Intellectual Property Protection for Artificial Intelligence Innovation (FR Doc. 2019-23638).
• First Federal Notice: Request for Comments on Patenting Artificial Intelligence Inventions (FR Doc. 2019-18443).
• Andrei Iancu and Laura Peter, "USPTO issues second Federal Register Notice on artificial intelligence and innovation," Director's Forum: A Blog from USPTO's Leadership, October 30, 2019.
• Senior Level Artificial Intelligence Technical Expert, usajobs.gov, Announcement Number OCIO-2019-0010.
GlobalData Discloses Top 20 Pharma Rankings

November 7, 2019

By Kevin E. Noonan —

As reported in John Carrol's EndPoint News early last month, GlobalData has published a list of the Top 20 Pharmaceutical Companies by market cap as of March 31, 2019. Notable advances include Takeda (up 142% based in part on its Shire acquisition, and jumping in the rankings from 23rd to 17th Q4 2018 – Q1 2019), with several other companies showing robust growth (including Celgene Corp., 37%; Novo Nordisk AS, 17%; Novartis AG, 14%; and Merck KGa, 13%; Hoffmann-La Roche, 12.7%). Companies declining included Bristol-Myers Squibb, 7.9%; Pfizer, 6.9%; and Bayer AG 4.9%. Biogen, the article notes, fell out of the Top 20. Expected acquisitions are expected to change this landscape again in the next several months.
Genetic Basis for Resistance to Toxic Compounds in Monarch Butterflies Elucidated

November 5, 2019

By Kevin E. Noonan —

One of the wonders and satisfactions of modern science has been the elucidation (usually based in genetics) of the wonders of nature that have been famously observed but not explained until the proper tools (again, usually genetic) have been developed. One of these is the ability of certain animals to grow and thrive on a diet comprising otherwise toxic substances. The koala is one example; on a different scale are insects, most noticeably monarch butterflies, that grow on milkweed known to contain cardiac glycosides inimical to life.

Recently an international group published a paper in the journal Nature entitled "Genome editing traces the evolution of toxin resistance in the monarch butterfly" that elucidated the genetic basis of this phenotype. The molecular target for these cardiac glycosides is known to be the alpha subunit of the sodium-potassium ATPase (ATPα) involved in energy generation (in higher animals associated with cardiac tissue but present in other tissues in insects). Genetic analysis of the amino acid sequence of this protein (or more accurately, the nucleotide sequence of the genes encoding them) from several species (including the monarch butterfly, Danaus plexippus) identified mutations in a particular region of the protein (the first extracellular loop, H1-H2) that is associated with target-site insensitivity (TSI), i.e., a loss of the ability for the protein to bind cardiac glycosides. Two resistance phenotypes were known, one that enables feeding on cardiac glycosides and the other that sequesters the toxin to avoid toxicity (and that make such species unpalatably bitter as a food source for birds and other predators). The mutations were detected in amino acid residues at three sites (111, 119, and 122), with mutations at the 111 and 122 sites undergoing frequent parallel substitutions associated with the TSI phenotype. The 119 site showed repeated substitutions in resistant species and co-evolution with mutations at the 111 site; paradoxically, mutations at the 119 were not phenotype-specific, because they are found in non-resistant species as well. Assessing the genetic history of how these mutations arose revealed that mutation in almost all cases arose at site 119 before or in conjunction with mutation at site 122, with "repeated substitutions at the three sites [that] evolved concurrently with specialization." These authors concluded that:

The mutational paths lead to three predictions for how substitutions at sites 111, 119 and 122 affect fitness. First, the mutational paths provide stepwise fitness advantages at increasing toxin concentrations. Second, the mutational paths contribute to sequestration of cardiac glycosides through passive toxin accumulation. Third, given the ordered appearance of the substitutions, interactions between substitutions (epistasis) increase fitness and mitigate the pleiotropic fitness costs of adaptive substitutions.

These researchers then tested the effects of these mutations on resistance by using CRISPR-Cas9 mutagenesis techniques to genetically engineer Drosophila cell lines to encode ATPα having one or more of these mutations, as illustrated in this diagram:

Four genotypes were tested: substitution of glutamine at amino acid 111 with either leucine or valine; substitution of serine at amino acid 119 with serine; and substitution of asparagine at amino acid 122 with histidine (producing mutants represented as LAN, LSN, VSN, and VSH, respectively; the unmutated sequence is QAN). These mutations were chosen because the mimicked the evolutionary progression of the mutations observed in the determination of sequences phylogenetically. Single site mutants were also produced (represented as QSN and QAH). Expression of the ATPα gene and sodium pump activities were unaffected in these mutants. These mutations were then used to produce "knock-in" lines of fruit flies that showed increased resistance to ouabain, a hydrophilic cardiac glycoside familiar for its use as a selective agent against human B cells in conventional hybridoma technology. In larval-adult and adult survival experiments, the LAN mutant showed increased survival in larval-adults only at low ouabain concentrations. Resistance increased in these experiments for LSN mutants, with VSN mutants behaving similarly. The VSH mutant (which is the native monarch butterfly mutant) "was unaffected by even the highest levels of ouabain in larvae and adults," a phenotype not associated merely with reductions in toxin ingestion or feeding rates. Experiments with knock-in eggs using leaves from Asclepais curassavica (milkweed) showed increased survival for the LSN, VSN, and VSH genotypes.

Physiological assessment of enzymatic activity of the mutant sodium ATPases showed a "neutral to positive" effect of TSI to ouabain. Resistance progressed (again, following the observed phylogenetic progression) from a small increase in TSI with the LAN mutant, to a ten-fold increase for LSN and VSN mutants, and a thousand-fold increase for the VSH mutation array. According to these authors, "VSH is sufficient for 'monarch [Drosophila] flies' to achieve the same degree of TSI to ouabain as the monarch butterfly, suggesting that TSI is the predominant biological mechanism for the in vivo toxin resistance observed above."

Returning to the genetics, the paper notes that "[s]ite 119 co-evolves with site 111 . . . and substitutions at site 119 always occurred before or with TSI-conferring substitutions at site 122," from which the authors speculate that "antagonistic pleiotropy and epistasis may have shaped mutational paths to resistance and TSI." To test this hypothesis, the paper reports the results of experiments using QZH and QSN mutants; the former genotype was "often the last substitution to evolve" while the latter occurs in both resistant and sensitive species. While the QSN mutant could not increase larval-adult survival at low ouabain concentrations there was a survival benefit as ouabain concentrations were increased (this effect "dropped sharply" at the higher concentrations). The results with adults were different, with QSN providing "slight" survival benefit. The last mutation to arise (N122H) gave the highest TSI phenotype but was phylogenetically contingent on substitution arising in site 119. Neurological testing showed the QSN flies were least sensitive and QAH flies the least, and the first mutant LAN was more sensitive that LSN.

The authors note that "this is, to our knowledge, the first in vivo validation of a multi-step adaptive walk in a multicellular organism, and illustrates how complex organismal traits can evolve by following simple rules."

* Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, USA; Department of Biology, Center for Genomics and Systems Biology, New York University, New York, NY, USA; LAI, U1067 Aix-Marseille Université, Inserm, CNRS, Marseille, France; Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY, USA; Department of Statistics, University of California, Berkeley, Berkeley, CA, USA; Molecular Evolutionary Biology, Zoological Institute, Biocenter Grindel, Universität Hamburg, Hamburg, Germany; Department of Entomology, Cornell University, Ithaca, NY, USA
Board Denies CVC Motion to Seal Priority Statement

November 4, 2019

By Kevin E. Noonan —

On September 11th, Junior Party (Regents of the University of California, University of Vienna, and Emmanuelle Charpentier, collectively "CVC") in Interference No. 106,115 with The Broad Institute et al. filed a motion to file its priority statement under seal. Specifically, CVC's motion requested that it be permitted to have the PTAB seal the priority statement until 45 days after final judgment or indefinitely; CVC also asked for 45 days after judgment to move that the statement be expunged from the record. (In the alternative, CVC requested that its statement remain sealed until a scheduling order issued by the Board for the priority phase of the interference, and that CVC be permitted to file a motion to expunge, e.g., if the count was changed). Last week, the Patent Trial and Appeal Board (PTAB) denied this motion, in a Decision by Administrative Patent Judge Katz, joined by APJs Moore and Lane.

CVC's motion was based on their contention that their priority statement "will contain sensitive research and development information that would be otherwise kept confidential." CVC asserted that there were "several third-party competitors [specifically, Sigma-Aldrich, ToolGen, and Vilnius University] in the field of CRISR-Cas9 gene editing technology and that it will be prejudiced in any potential interference with these parties if its confidential research and development information were to be made public." These competitors, according to CVC, all have competing applications filed within 10 months of CVC's priority date, and have argued that their claims interfere with CVC's claims in this interference (see "Sigma-Aldrich Wants Its Piece of CRISPR Pie").

The Board opined that, in agreement with the Broad, CVC's arguments were "based on speculation," because as yet there have been no other interferences declared between CVC and any of these other parties. Relying as it frequently does on the procedural aspects of the questions before it (see "Sigma-Aldrich Tries Again"), the Board asserts in support of this point that "no count has been used to describe interfering subject matter between any of CVC's applications or patents" and that "CVC presents no evidence that any of the claims it asserts might interfere with CVC's own claims have been determined to be allowable." Under these circumstances, the Board was not persuaded to deviate from its policy that "[t]he record of a Board proceeding [be] available to the public unless a patent application not otherwise available to the public is involved," citing 37 C.F.R. § 41.6(b)(1). In particular, the opinion reminds the parties that the Board "strive[s] towards making all filings in an interference public at least by the time we issue a final judgment," and that CVC has requested that its priority statement be held under seal until 45 days after final judgment (although the Board notes that CVC can file a renewed request once judgment has been entered).

The Board was persuaded by CVC's request to keep its priority statement under seal until the Board issued a schedule for the priority phase, stating that CVC had correctly noted that 37 C.F. R. § 41.120(a) permits the Board to keep priority statements confidential "for a limited time." The Board remained unpersuaded by the Broad's arguments that it would be prejudiced, inter alia, because "Broad's potential licensees, commercial partners, and the public will not be able to evaluate for themselves CVC's claims to priority, and Broad's patents will continue to be subject to the uncertainty CVC has sought to create around them since suggesting the 048 interference four years ago." The opinion states in support that the parties' priority evidence will not be "made in full" until priority motions are filed if there is a priority phase in this interference. And the Board does not see prejudice to the Broad's ability to establish priority if CVC's priority statement is kept in confidence until the priority phase commences.

The opinion mandates that CVC file by November 7th a revised proposed protective order taking into account the Board's decision to keep CVC's priority statement under seal until commencement of the priority phase.
Launch of New Diagnostics and Cancer Advocacy Group Announced

November 3, 2019

A new non-profit advocacy organization, New Cures for Cancers, recently announced its launch and the opening of its website. The mission of the organization is to give cancer patients and their families and friends a podium to tell their stories and to demand judicial and legislative advocacy to motivate new diagnostics, personalized medicines, and drugs to treat cancer.

One goal of the organization is to change the law currently applied by the U.S. Supreme Court that has caused the invalidation of every patent on personalized diagnostics since 2012. Without patent protection for their investments, companies will not be interested in the personalized diagnostics field.

Another goal is to change the U.S. Supreme Court case law that isolated natural products are not eligible for patent protection, because isolated natural products have played a major role in extending and saving the lives of cancer patients. Newer drugs such as checkpoint inhibitors and cell therapy are typically used in addition to or as a second line therapy to conventional chemotherapy, which means that the public should not lose sight that improved chemotherapies, including those based on natural products, are still needed.

A third goal is to counterbalance the narrative of the ACLU and other organizations that the only goal of pharmaceutical drug advocacy is drug pricing. The price of the drug or the diagnostic doesn't matter if it has not been invented. The major advocacy now ongoing about drug prices and "access to medicine" misses the point: our first goal is to demand laws that motivate new and effective diagnostics, personalized medicines and cancer drugs. The details of marketing and pricing don't come until years later.

Ms. Sherry Knowles founded New Cures for Cancers after promising herself that if she made it through breast cancer, she would do everything possible to help cancer patients and their families. In 2019, the American Cancer Society estimates that 1,762,450 Americans will be newly diagnosed with cancer. The American Cancer Society estimates that 606,800 Americans will die of cancer. Men have a 39.66% chance of developing cancer in their lifetime and women have a 37.65% chance of getting cancer. Only 67% of people who have cancer will survive for 5 years. These cancer patients and their families and friends need a direct vehicle for advocacy to make their voices heard. And they need to be able to break through false narratives and force progress to create new diagnostics, personalized medicines, and drugs.

If you have been touched by cancer, either personally or through a family member or friend, New Cures for Cancers asks that you please go to the group's website and post your story. Given the medical sensitivity of cancer matters, you can add your story with "name withheld" or using only your first name if desired. The goal is to raise the voice in any way you feel comfortable doing so.
Federal Circuit Holds APJs Are Principal Officers

October 31, 2019

By Kevin E. Noonan and James L. Lovsin —

Today in Arthrex, Inc. v. Smith & Nephew, Inc., a three-judge panel of the Federal Circuit held that the way the U.S. Patent and Trademark Office has appointed administrative patent judges at the Patent Trial and Appeal Board violates the Appointments Clause of the Constitution (Art. II, sec. 2, cl. 2), in an opinion by Judge Moore, joined by Judges Reyna and Chen. According to the opinion, because APJs are principal officers they must be nominated by the President and confirmed by the Senate. Although the opinion provides a remedy (having Congress abrogate the portion of the Patent Act restricting removal of the APJs), the legitimacy of the PTAB to render decisions in the meantime has been abrogated by the Court, and the effect on (1) pending PTAB proceedings, (2) pending appeals of PTAB decisions at the Federal Circuit and the Supreme Court, and (3) the thousands of judgments by the PTAB since passage of the Leary-Smith America Invents Act is uncertain. District court litigation stayed in favor of a PTAB proceeding may also be impacted.

This decision will be the subject of a future post.
Idenix Pharmaceuticals LLC v. Gilead Sciences Inc. (Fed. Cir. 2019)

October 31, 2019

By Kevin E. Noonan —

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

October 29, 2019

By Kevin E. Noonan —

Ever since the Supreme Court's decision in Dickerson v. Zurko, decisions from the U.S. Patent and Trademark Office (whether in ex parte examination or any of the many varieties of actions before the Patent Trial and Appeal Board) involving questions of fact are treated on appeal with almost overwhelming deference. This lesson was learned again by the losing party in an interference, styled Wilson v. Martin, where the PTAB held the claims corresponding to the count in the interference were anticipated by the prior art.

The interference was declared between Wilson's U.S. Patent No. 8,809,044 and Martin's U.S. Application No. 14/814,267. The claims of the '044 patent were directed to methods for using a cell culture apparatus comprising semipermeable membranes (that permit passage of gas but not liquids like culture media). The culture apparatus comprises multiple vertical shelves with two or more compartments for culturing cells wherein cells and the liquid culture media are placed:

Martin's '276 application is also directed to a liquid cell culture apparatus having two or more compartments having a gas permeable membrane.

The count in the interference is identical to claim 1 of the '044 patent:

1. A method of culturing animal cells in a gas permeable multi-shelf cell culture apparatus, the method comprising:
    adding animal cells and media into a gas permeable multi-shelf apparatus comprising two or more culture compartments, each compartment including a shelf comprised of gas permeable, liquid impermeable material for cells to reside upon, each shelf connected to an opposing surface, a fluid pathway shared by said culture compartments, and each said shelf is in contact with a gas space,
    whereby said apparatus is incubated in the presence of ambient gas suitable for animal cell culture, oriented in a position such that said culture compartments are located one above the other, each said shelf is in a horizontal position with said gas space located below it, animal cells reside upon at least a portion of each said shelf, said culture compartments include media in contact with said shelf and said opposing surface, and ambient gas resides within each said gas space and is in contact with each shelf.

For comparison, the opinion set forth claim 2 of the '267 application:

2. A method of culturing cells in a gas permeable multi-shelf cell culture apparatus, the method comprising:
    adding cells and media into a gas permeable multi-shelf apparatus comprising two or more culture compartments, each compartment including a shelf comprised of gas permeable, liquid impermeable material for cells to reside upon, each shelf connected to an opposing surface, a fluid pathway shared by said culture compartments, and each said shelf is in contact with a gas space,
    whereby said apparatus is incubated in the presence of ambient gas suitable for cell culture, oriented in a position such that said culture compartments are located one above the other, each said shelf is in a horizontal position with said gas space located below it, cells reside upon at least a portion of each said shelf, said culture compartments include media in contact with said shelf and said opposing surface, and ambient gas resides within each said gas space and is in contact with each shelf.

The "ambient gas" term italicized in each claim was the basis for the PTAB's invalidation of Wilson's claims and the Federal Circuit's review.

Martin filed a motion in the interference that a prior art reference to Toner (U.S. Patent No. 6,759,245) anticipated most of Wilson's claims-in-interference corresponding to the Count, supported by two expert witness declarations. The Toner reference discloses "systems and methods for culturing animal cells using modular cell culturing devices with gas-permeable membranes" having structures with common (left, 222) or individual (right, 20) oxygenated fluid compartments:

The parties proposed different constructions for the term "ambient gas" that were not used by the Board, which did not construe the term because the Toner reference, in its opinion, disclosed the "ambient gas' limitation using either of the proposed constructions.

The Board held that the reference disclosed a multiplicity of ports that communicate between the interior and exterior of the device that would permit outside air to enter the device. The Board held that the gas could be air or other oxygenated "fluid" and that "ambient gas" describes "[a]ir passing from the exterior of the device into the interior of the device" supported by Martin's expert who averred that "the common gas space inside the device is open to the ambient environment for venting air or the mixture of air with other gases supplied into the gas space via the inlet."

Wilson contended before the Board that the Toner reference did not anticipate its claims-in-interference because it required the gas to be "pumped or forced into the device." The Board rejected this interpretation because the reference disclosed "static, as well as directional, flow of the oxygenated fluid." The Board also rejected Wilson's characterization of the nature of the gas disclosed in the Toner reference as having "carefully controlled characteristics different from 'those found in standard ambient cell culture conditions,'" stating that the gas in Toner needs merely to be "ambient" (albeit conceding that Toner does not expressly use the word "ambient" but that it is "inherent or otherwise implicit" in the reference, citing Standard Havens Prods., Inc. v. Gencor Indus., Inc., 953 F.2d 1360, 1369 (Fed. Cir. 1991)).

Finally, the Board refused to preclude Martin from asserting the Toner reference for disclosing the "ambient gas" reference based on judicial estoppel because assignee Corning (the real party in interest) had made inconsistent statements during prosecution of the parent application to the '267 application-in-interference, inter alia because the Board could rely on the expert testimony before it from both parties.

Consequently, the Board held that all Wilson's claims in the '044 patent at issue in the interference were invalid as being anticipated or obvious over the Toner reference. Wilson appealed.

The Federal Circuit affirmed, in an opinion by Judge Reyna joined by Chief Judge Prost and Judge Stoll. With regard to the Board's anticipation determination, the panel found that this conclusion was supported by the written description of the Toner patent and the figures set forth therein. Important in this outcome was Wilson's argument that Toner only disclosed embodiments wherein the gas was provided by a gas tank (and thus not "ambient"), where the Federal Circuit pointed to Figure 8A not showing a gas tank and disclosure that embodiments having a gas tank as the source of gas were "preferable" but not required. Further, the panel credited (and gave deference to) the Board's consideration of Martin's expert. Despite the absence of the conventional bases for giving deference to expert witness testimony at trial (that the factfinder can observe the witness' demeanor, for example, which the Board cannot, relying on only the written record and portions of deposition transcripts), the Federal Circuit states that "the Board was entitled to weigh and credit that testimony," citing Elbit Sys. of Am., LLC v. Thales Visionix, Inc., 881 F.3d 1354, 1358 (Fed. Cir. 2018); Inwood Labs., Inc. v. Ives Labs., Inc., 456 U.S. 844, 856 (1982); and Yorkey v. Diab, 601 F.3d 1279, 1284 (Fed. Cir. 2010). Under the substantial evidence standard, the panel held that the Board's determination was "such that a reasonable mind might accept as adequate to support the Board's conclusion," citing Fleming v. Escort Inc., 774 F.3d 1371, 1375 (Fed. Cir. 2014).

The panel also rejected Wilson's other arguments, that the expert witness testimony was extrinsic evidence, stating that "[e]xtrinsic evidence may be used to interpret the allegedly anticipating reference and to shed light on what it would have meant to a person of ordinary skill in the art," citing Monsanto Tech. LLC v. E.I. DuPont de Nemours & Co., 878 F.3d 1336, 1345 (Fed. Cir. 2018) (citing In re Baxter Travenol Labs., 952 F.2d 388, 390 (Fed. Cir. 1991)). The panel held that the expert's testimony was consistent with the disclosure in the Toner reference and did not "provide missing disclosure of the claimed invention." In like manner, the panel rejected Wilson's arguments regarding differences between "air" as disclosed in the Toner reference and "ambient gas" recited in its claims, based on its previous rejection of Wilson's argument (reiterated here) that Toner required a gas tank, and again in reliance on Martin's expert declarations.

Turning to the question of judicial estoppel (that "where a party successfully urges a particular position in a legal proceeding, it is estopped from taking a contrary position in a subsequent proceeding where its interests have changed," citing Data Gen. Corp. v. Johnson, 78 F.3d 1556, 1565 (Fed. Cir. 1996) (citing Davis v. Wakelee, 156 U.S. 680, 689 (1895)), the panel states that the Board has the authority to apply the doctrine. The opinion then sets forth the factors to be considered in deciding to apply judicial estoppel:

(1) whether a party's later position is "clearly inconsistent" with its earlier position; (2) whether a court has accepted the party's prior position, such that accepting its "inconsistent position in a later proceeding would create the perception that either the first or the second court was misled"; and (3) whether the party changing its position "would derive an unfair advantage or impose an unfair detriment on the opposing party if not estopped,"

citing New Hampshire v. Maine, 532 U.S. 742, 751 (2001). The standard of review for this Board determination is abuse of discretion (an even more deferential standard) and the Federal Circuit held that the Board's decision here satisfied those criteria. The opinion notes two distinctions in support of its decision. The first is that the purported arguments made in the related prosecution were made regarding an embodiment of the Toner invention different from the ones at issue here (specifically, Figure 8b, rather than Figure 8a which the Board relied upon here). The purportedly inconsistent argument is based, according to the opinion, on the different configuration of the two embodiments and are thus not inconsistent and do not raise the estoppel. The second basis for finding no abuse of discretion is that "Martin's current position is not clearly inconsistent with Corning's prior statements because those statements were made in a different context and were part of a different evidentiary record," specifically that the claims in the earlier, related patent were directed to the structural components of the apparatus rather than methods for culturing cells with it. Indeed, according to the panel opinion the claims of this earlier patent did not recite the "ambient gas" limitation. Finally, the Court held that the differences in context between ex parte examination and the interference here (specifically the expert testimony) was sufficient to support the conclusion that the Board did not abuse its discretion.

Of course, anyone familiar with interference practice will recognize that a finding of anticipation of one party's claims in interference will usually result in the moving party's claims also being held to be anticipated, and that is the final conclusion in the opinion, i.e., all claims in interference were held anticipated by the Toner reference. The Federal Circuit, at least, awarded Martin its costs.

Wilson v. Martin (Fed. Cir. 2019)
Nonprecedential disposition
Panel: Chief Judge Prost and Circuit Judges Reyna and Stoll
Opinion by Circuit Judge Reyna

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