Patent Law Weblog
As part of its series of quarterly updates on IP developments in China, the U.S. Patent and Trademark Office will offer a webinar entitled "China IP: Quarterly Legislation and Case Law Update" on March 24, 2022 from 1:00 pm to 2:00 pm (ET). The webinar will feature presentations by senior U.S. Patent and Trademark Office IP attorneys with extensive China IP experience.
Those interested in registering for the webinar can do so here.
But Not All the Judges Are Happy About It
By Kevin E. Noonan —
On March 16th, the Federal Circuit denied Biogen's petition for panel rehearing and rehearing en banc in Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc. Judges Cunningham and Stoll did not participate in the decision, which was issued per curiam and supported by Judges Dyk, Prost, Reyna, Taranto, Chen, and Hughes. Judge O'Malley (who dissented in the panel decision) participated (and putatively supported) the decision to deny the petition for panel rehearing (perhaps related to her decision to leave the Court on March 11th). Judge Lourie, joined by Chief Judge Moore and Judge Newman (constituting two of the remaining most senior Judges on the Court) wrote an opinion in dissent.
To recap, the case arose over Mylan's attempt to get regulatory approval and come to market with a generic equivalent of Biogen's Tecfidera® (dimethyl/monomethyl fumarate) multiple sclerosis drug. Biogen asserted Orange Book-listed U.S. Patent Nos. 6,509,376; 7,320,999; 7,619,001; 7,803,840; 8,399,514; and 8,759,393, but the parties dismissed their causes of action on all patents except the '514 patent, where Biogen asserted claims 1-4, 6, 8-13, and 15-16; claim 1 is representative:
1. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a pharmaceutical composition consisting essentially of (a) a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, and (b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.
(Wherein the italicized limitation was the entirety of the basis for the District Court's decision and the Federal Circuit majority's affirmance.)
The District Court held that the asserted claims were invalid for failure to satisfy the written description requirement of 35 U.S.C. § 112(a). The grounds for the District Court's decision, and the bases for Mylan's arguments that were persuasive, stemmed from certain characteristics of the prosecution history, which Mylan used to create an impression that Biogen had obtained claims based on clinical trial results for an invention not adequately disclosed in the application as filed in its earliest priority document (without such priority the claims perhaps would have been obvious). Moreover, certain claim limitations (importantly, the effective dose) were recited only as part of a range and only once in the specification, which in the main was directed to methods for identifying compounds for treating neurological diseases and mentioned the specific disease treated by the claimed method, multiple sclerosis, only as one disease amongst many. The District Court summed up the basis for its opinion succinctly, stating "[i]n sum, Biogen has attempted to satisfy the written description requirement of § 112 by selectively plucking specific words from the specification that correspond to each element of the claimed invention."
The Federal Circuit affirmed, in an opinion by Judge Reyna joined by Judge Hughes, with Judge O'Malley dissenting. Biogen was hampered by its burden of showing clear error by the District Court as well as the apparent "equities" between their position and Mylan's. The majority considered Biogen to have ""cast[] a wide net for a myriad of neurological disorders, including neuro-degenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, and Huntington's disease; demyelinating neurological diseases, such as various forms of MS and at least twenty-eight other disorders related to demyelination; polyneuritis; and mitochondrial disorders with demyelination" (something Judge O'Malley herself termed a "laundry list" form of disclosure). The relevant elements of the claim (the disease treated, the drug used, and the dose) were each recited once in the specification, according to the majority, and those citations were scattered in different portions of the specification.
Judge O'Malley's dissent was based on her appreciation of the majority misunderstanding the differences between therapeutic and clinical efficacy and the differences between what is required to obtain a patent and what is required for FDA approval of a drug. This error, she contended, led the majority to apply the Court's Nuvo Pharms. (Ireland) Designated Activity Co. v. Dr. Reddy's Lab'ys Inc., 923 F.3d 1368, 1377, 1381 (Fed. Cir. 2019), precedent, also in error according to the Judge. And the Judge stated that in her view the specification contained an adequate written description based on this reasoning:
The majority's decision affirming the district court partially rests on the fact that the '514 patent only mentions the claimed DMF480 dose once. . . . But the majority cites no case law (and I know of none) for the proposition that the written description requirement demands that a patentee recite a claim element repeatedly to pass written description muster. The majority does not, and cannot, deny that the claimed DMF480 dose is expressly disclosed. To the extent the majority's opinion may be read to establish a requirement that a claim element must be disclosed multiple times, I dissent from that holding as well.
Judge Lourie's dissent from the Court's decision not to rehear the case en banc cites four grounds of error by the District Court (and by not subtle implication the Federal Circuit Judges constituting the panel majority). The dissent begins by noting that a proper written description analysis rests on the Court's en banc decision in Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010), but Judge Lourie sets out Federal Circuit precedent involving the variety of cases where an adequate written description was not found (many of them written by the Judge himself) and based, according to the dissent, on the CCPA case In re Ruschig, 379 F.2d 990, 995 (C.C.P.A. 1967), and (somewhat provocatively) on O'Reilly v. Morse, 56 U.S. 62, 113 (1853). This case, according to the dissent, is an "outlier" "at the farthest end of the spectrum" because "every claim limitation is expressly described in the disclosure." And the consequence is that the Court has "let a panel majority opinion stand that imports extraneous considerations into the written description analysis and blurs the boundaries between the written description requirement and the other statutory requirements for patentability. In doing so, the court has contributed to the muddying of the written description requirement."
The basis for an adequate written description is always what is disclosed, according to Judge Lourie, and here Example 4 was expressly directed to treating MS; accordingly, "from any perspective, including that of a person of ordinary skill in the art, the '514 patent describes the invention of a method for treating multiple sclerosis." What is recited in claim 1, the dissent asserts, is "precisely what the specification discloses—treatment of multiple sclerosis with a 480 mg per day dose of DMF or MMF." "Whatever shortcomings exist in this unfocused patent specification, failure of written description with respect to claim 1 is not one of them" according to Judge Lourie's dissenting opinion.
So why did the panel majority go so astray in the dissenting Judges' opinion? The dissent sets out the four grounds of error by the District Court and the panel majority that provide the basis for why the District Court's opinion should have been reversed by the panel. The first is the "undue emphasis that the panel majority and the district court placed on unclaimed disclosures in the specification," engaging in "irrelevant comparisons between the amount of disclosure of the claimed subject matter versus the unclaimed subject matter," reciting as examples the majority's focus on the number of other neurological diseases set forth in the specification and the frequency (once) with which the 480mg dose was set forth. Agreeing with Judge O'Malley's dissent, Judge Lourie faults the panel majority for relying on In re Ruschig for the use of "blazemarks" in performing a written description requirement, because they thereby neglected the important distinction that in Ruschig the specification did not disclose the claimed embodiment. Discussing the extent of disclosure in genus/species claims, Judge Lourie recited portions of the body of precedent developed by the Court for making sufficiency determinations (a "representative number of species falling within the scope of the genus or structural features common to members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus," citing Regents of the Univ. of Cal. v. Eli Lilly & Co., 119 F.3d 1559, 1568–69 (Fed. Cir. 1997). It is only when a claimed species is not expressly disclosed in the context of a disclosed genus that a blazemarks analysis is needed according to the dissenting Judges, something expressly set forth in Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336, 1349 (Fed. Cir. 2013): "'[b]laze marks' are not necessary where the claimed species is expressly described in the specification." That is not the case here, Judge Lourie asserts, where the disease to be treated, the drug used for the treatment, and the administered dose is expressly disclosed. In such cases, whatever else is disclosed in the specification does not support a finding of inadequate disclosure according to the dissent, citing Scriptpro, LLC v. Innovation Assocs., Inc., 762 F.3d 1355, 1359 (Fed. Cir. 2014), nor is the fact that there was only a single mention of the 480 mg dose contrary to a finding of an adequate written description ("once is enough" according to the dissent, citing Vanda Pharms. Inc. v. W.-Ward Pharms. Int'l Ltd., 887 F.3d 1117, 1137 (Fed. Cir. 2018). Summing up this ground of error, the dissent states:
The panel majority opinion implies that a patent fails the written description requirement of 35 U.S.C. § 112 when it contains too much disclosure beyond the claimed invention, which is incorrect. The opinion implies that a patentee must disclose the claimed subject matter more than once, which is also incorrect. And the opinion implies that a court may arbitrarily count the number of times the claimed subject matter is disclosed in the specification relative to the number of times unclaimed subject matter is disclosed, which is incorrect.
The second ground of error (again in agreement with Judge O'Malley) is that Federal Circuit precedent does not require a patentee to show that "the specification proves the efficacy of the claimed pharmaceutical composition," citing Nuvo Pharms. (Ir.) Designated Activity Co.; In re Brana, 51 F.3d 1560, 1567 (Fed. Cir. 1995) (that the requirements for patenting and the requirements for drug marketing approval were different); and Scott v. Finney, 34 F.3d 1058, 1063 (Fed. Cir. 1994). Merely stating the claimed dose is enough, according to Judge Lourie because it "leaves nothing for the skilled artisan to deduce; it expressly states that 480 mg per day is an effective amount."
The third error made by the District Court and panel majority was importing "extraneous legal considerations into the written description analysis" contrary to Ariad. For example, the dissent notes that while operability can be raised with regard to enablement, Ariad stands for the distinction between the written description and the enablement requirements of the statute. "By focusing on whether the patentee proved that 480 mg per day is an effective amount to treat multiple sclerosis—as distinct from whether the '514 patent specification discloses that 480 mg per day is an effective amount to treat multiple sclerosis—the panel majority and the district court erroneously imported operability considerations into the written description analysis" (emphasis in dissenting opinion). Even further the dissent criticizes the District Court and the panel majority for considering inventorship issues, which is also separate from a proper written description requirement analysis. The dissent also appreciates the majority to have introduced a best mode issue, in reference to whether the skilled artisan would have been "drawn to" the 720 mg dose (emphasis in dissenting opinion). Once again, the dissent asserts that "[b]y incorporating extraneous legal standards into the analysis, the panel majority opinion creates confusion for future patent applicants and litigants regarding what is required to meet the written description requirement of 35 U.S.C. § 112."
The fourth point of error in the dissenting Judges' view was consideration of extrinsic evidence by the District Court and the panel majority. Under Ariad, "[t]he test for written description 'requires an objective inquiry into the four corners of the specification.'" While considerations outside the four corners can be relevant (regarding, for example, the understanding of one or ordinary skill in the art), such considerations need to be limited to "an objective inquiry into what is meant by the disclosure in the patent specification" according to the dissent. Where, as here, "the disclosure in a patent's specification plainly corresponds to what is claimed, extrinsic evidence should not be used to cast doubt on the meaning of what is disclosed."
The dissent concludes by stating that the best reason for the en banc Court to hear this case is that the panel majority had "affirmed a district court's erroneous broadening of the written description inquiry" and by denying rehearing the case the Court "lost an opportunity to provide clarity for future litigants by reaffirming the proper boundaries of the written description requirement in 35 U.S.C. § 112."
It would be good to remember that satisfaction of the written description requirement is a question of fact, and such questions do not easily lend themselves to readily applied, rigid rules. Thus the strength of Judge O'Malley's dissent and the dissenting Judges here is directed at the proper application of the law to the question before the Court, which if in the unlikely event it ever arises again would be persuasive but is not likely to be binding precisely because such future facts are unlikely to be entirely on all fours with the question before the Court here. More significant, perhaps, is that the Court has trended towards a more stringent application of written description questions during Judge Prost's tenure as Chief Judge, and with the appointment of Judges Cunningham and Stark and Judge Moore taking the position of Chief Judge that may change, perhaps to a greater consistency with what was presumed to be settled Federal Circuit law.
Biogen Int'l GmbH v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2022)
Panel: Chief Judge Moore and Circuit Judges Newman, Lourie, Dyk, Prost, O'Malley, Reyna, Taranto, Chen, and Hughes (Circuit Judge O'Malley retired on March 11, 2022, and participated only in the decision on the petition for panel rehearing)
Order per curiam; opinion dissenting from the denial of the petition for rehearing en banc by Circuit Judge Lourie, joined by Chief Judge Moore and Circuit Judge Newman
By Donald Zuhn —
According to a Reuters report published earlier today, the United States, European Union, India, and South Africa have reached an agreement on a waiver with respect to patents for COVID-19 vaccines (see Andrea Shalal and Emma Farge, "U.S., EU, India, S.Africa reach compromise on COVID vaccine IP waiver text," Reuters). Progress on the compromise appears to have been made during a recent meeting of the Council for Trade-Related Aspects of Intellectual Property Rights (TRIPS) on March 9-10. In a statement issued by the World Trade Organization (WTO) on March 10, the WTO noted that:
Some of the members participating since December 2021 in the high-level talks — the European Union, India, South Africa and the United States — expressed cautious optimism about a possible outcome and asked for patience from the rest of the membership. These members said that the small-group discussions continue to take place in good faith, with the objective of finding a landing zone that delivers on the common purpose of ensuring equitable access to vaccines, therapeutics, and diagnostics.
As we reported last year, India and South Africa proposed in the fall of 2020 that the WTO TRIPS Council recommend "a waiver from the implementation, application and enforcement of Sections 1, 4, 5, and 7 of Part II of the TRIPS Agreement in relation to prevention, containment or treatment of COVID-19" to the General Council of the WTO. The two countries also recommended that "[t]he waiver should continue until widespread vaccination is in place globally." As we reported last May, United States Trade Representative Katherine Tai announced "the Biden-Harris Administration's support for waiving intellectual property protections for COVID-19 vaccines."
Although the details of the waiver proposal are still being finalized, and the text of the compromise proposal has not been released, the Biotechnology Innovation Organization (BIO) and U.S. Chamber of Commerce both issued statements this afternoon on the reported compromise. A statement released by Chief Policy Officer John Murphy noted that:
While we have seen the reported outlines of an alleged compromise on the TRIPS waiver, we still need to see and review the full text before rendering a final judgment. However, the irrational fixation on weakening IP is simply a distraction from the real challenge of overcoming global vaccine hesitancy, removing actual trade barriers, and helping countries to strengthen their healthcare infrastructure so that we can get more shots in arms. In 2021 alone, companies produced more than 11 billion doses of COVID vaccines, enough to give two shots to every adult on the planet.
Strong, predictable intellectual property protections are what allowed biopharma companies to produce COVID vaccines and therapeutics in record time. It laid the foundation for cross-border partnerships, global scientific collaboration, and an unprecedented manufacturing scale-up that ensured vaccines could reach every corner of the world. Dismantling the foundation of innovation—a strong and predictable IP system—will only make us less prepared to respond to the next pandemic and weaken our ability to develop new classes of medicines the world needs.
In a statement released by the U.S. Chamber of Commerce Global Innovation Policy Center, Senior Vice President Patrick Kilbride, the Chamber contended that:
This proposal is fundamentally misguided and should be rejected. It ignores that the overwhelming problem is not vaccine production, it is last-mile delivery, and it will erode the ability of innovative companies to develop the cure for the next pandemic or global health threat.
Business is delivering on the promise to manufacture safe and effective COVID-19 vaccines for the whole world. Vaccine production is estimated to reach over 20 billion doses this year, enough for everyone. As of March, over 65% of global population has received at least one dose, and this number is growing every day. Some patients remain hard to reach. Governments and international organizations should avoid political distractions and more quickly achieve comprehensive global vaccination against COVID-19, by focusing on real, practical ongoing issues with last-mile distribution.
Intellectual property waiver proposals distract from the real issues preventing more shots in arms such as logistical hurdles, supply chain bottlenecks, and vaccine hesitancy. Worse yet, dismantling IP rights threatens the licensing arrangements that are enabling rapid global production and technology transfer. Any WTO action undermining IP will harm multiple U.S. industries, who are global leaders in their fields, and who depend on IP protections. Any agreement of this kind would bargain away US competitiveness.
For additional information regarding this topic, please see:
• "Sen. Tillis Writes to U.S. Trade Representative (Again) Regarding TRIPS Waiver," December 12, 2021
• "U.S. Trade Representative Responds to Letters from Senators Regarding TRIPS Waiver," November 14, 2021
• "U.S. Chamber of Commerce Urges Administration to 'Double Down' on Global Vaccine Distribution," November 3, 2021
• "Is This the WTO Waiver End Game?" July 25, 2021
• "BIO Declaration on Global Access to COVID-19 Vaccines and Treatments and Role of IP," June 24, 2021
• "GOP Legislators Write in Opposition to Proposed TRIPS Waiver," May 16, 2021
• "Population of Patents at Risk from Proposed WTO Patent Waiver," May 12, 2021
• "Sen. Daines Urges Biden Administration to Withdraw Support for COVID-19 IP Waiver," May 12, 2021
• "Pfizer CEO Pens Open Letter on COVID-19 Vaccine IP Waiver," May 10, 2021
• "If the Devil of the WTO IP Waiver Is in the Details, What Are the Details?" May 9, 2021
• "The Road to Hell Is Paved with What Everybody Knows," May 6, 2021
• "BIO & IPO Issue Statements on Biden Administration's Support for Proposed WTO Waiver," May 6, 2021
• "Biden Administration Supports Waiver of IP Protection for COVID-19 Vaccines," May 5, 2021
• "Suspending IP Protection: A Bad Idea (That Won't Achieve Its Desired Goals)," April 26, 2021
• "Sen. Tillis Asks Biden Administration to Oppose WTO Waiver Proposal," April 21, 2021
• "IP Organizations Support Continued Opposition to Waiver Proposal," April 5, 2021
• "Industry Coalition Supports Continued Efforts to Oppose Waiver Proposal," March 29, 2021
• "BIO and PhRMA Urge Biden Administration to Oppose Proposed WTO TRIPS Waiver," March 11, 2021
• "IPO Sends Letter on IP Law and Policy to President-Elect and Vice President-Elect," January 4, 2021
By Kevin E. Noonan —
On February 18th, Sigma-Aldrich filed its Opposition to Junior Party's (the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier; collectively, "CVC") Substantive Preliminary Motion No. 1 in Interference No. 106,132, asking the Patent Trial and Appeal Board for benefit of priority to U.S. Provisional Application No. 61/652,086, filed May 25, 2012 ("P1"), U.S. Provisional Application No. 61/716,256, filed October 19, 2012, ("P2"), and U.S. Provisional Application No. 61/757,640, filed January 28, 2013 ("Provisional 3"), pursuant to 37 C.F.R. §§ 41.121(a)(1)(ii) and 41.208(a)(3) and Standing Order ¶ 208.4.1. The relationships between the patents and applications in the '132 interference are set forth in this chart (filed in CVC's earlier preliminary motion in Interference No. 106,115):
To recap, CVC argued that "CVC invented a eukaryotic cell comprising a single-molecule guide RNA ("sgRNA") CRISPR-Cas9 system capable of cleaving or editing target DNA, as defined by the count" to define the issue, and then gives the Board a basis for coming to a different conclusion here. Specifically, CVC argues that (as a result of the '115 Interference) it now has additional evidence in support of this motion. (CVC made a similar argument in the '127 Interference.)
Most of CVC's arguments are familiar to anyone following parallel motions in the '115 and '127 interferences. These include CVC's contention that once this breakthrough had been achieved, adapting CRISPR to the eukaryotic cell environment would have been "pretty straightforward" (quoting Dr. Luciano Marraffini, who purportedly informed the Broad inventors of the sgRNA embodiment in June, 2012 (see "CVC Files Motion in Opposition to Broad Priority Motion"). CVC supported this assertion with contemporaneous consistent statements from Rodolphe Barrangou, Erik Sontheimer, Samuel Sternberg, and Dana Carroll, as well as Jennifer Doudna; by the existence of "existing platforms that had already been successfully used with the two incumbent systems: zinc-finger nucleases ("ZFNs") and transcription activator-like effector nucleases ("TALENs")"; and by the successful practice of CRISPR by several groups (including Sigma-Aldrich) "[j]ust months after CVC presented this work" and the absence in the reports from any of these groups of "any 'special' adaptations or conditions needed" to achieve CRISPR gene editing in eukaryotic cells. And CVC argued that the Board's contrary conclusion in denying CVC's motion for priority benefit to the P1 and P2 provisional applications in the '115 Interference was that it was made "without the benefit of the now well-developed evidentiary record," specifically, that "[t]he prior decision credited assertions that have been seriously undermined by evidence presented during the priority phase of the '115 interference." That evidence was presented in CVC's Motion, which will not be recapitulated here.
Sigma-Aldrich's Opposition countered CVC's assertions using the same approach successfully used by Broad in persuading the Board to find priority of invention in their favor in the '115 interference (see "PTAB Holds for Broad in CRISPR Interference: The Reasoning")*: that the two provisional applications (filed on May 25, 2012 and October 19, 2012) did not disclose an operative embodiment of CRISPR that could be successfully practiced in eukaryotic cells. (Sigma-Aldrich does not challenge CVC's motion with regard to the P3 provisional application, no doubt because inter alia its status as Senior Party in this interference would not change should the Board do so.) Harkening back to the Board's decision on CVC's motion in the '115 interference, Sigma-Aldrich argued that the Board was correct in its prior determination that those applications only disclosed in vitro CRISPR methods in a "cell-free" environment. According to Sigma-Aldrich, nothing has changed that would have the Board render a decision different from their refusal in the '115 interference to accord CVC benefit to P1 and P2 provisional application, and the Board should come to the same conclusion (the brief noting that CVC has the burden as the party advancing the motion to convince the Board to come to a different conclusion here). Because Sigma-Aldrich contends that most if not all the evidence CVC asserts in its brief supporting its priority benefit motion in this interference had been asserted in the corresponding brief in the '115 motion, Sigma-Aldrich contends CVC has not met that burden.
The cornerstone of Sigma-Aldrich's motion is that neither the P1 nor P2 provisional applications disclosed any "specific instructions or conditions" required for the practice of CRISPR in eukaryotic cells and that such instructions and/or conditions were necessary in view of the several obstacles required (tracking the same distinctions between CRISPR in eukaryotic cells and under other conditions recited by Broad in the '115 interference and Interference No. 105,048; see "PTAB Decides CRISPR Interference in Favor of Broad Institute — Their Reasoning"). Sigma-Aldrich further contends that one basis for CVC's argument is that the ordinarily skilled person would have had a reasonable expectation of success in achieving successful CRISPR in eukaryotic cells in the absence of disclosure in the P1 or P2 provisional applications, in contradiction to the Board's contrary determination in the '048 interference.
In support of its contention that the absence of disclosure of the specific instructions or conditions in the P1 or P2 provisional applications supported its contention that neither disclosed an embodiment within the scope of the Count to satisfy the requirements for priority, Sigma-Aldrich cited Group II introns as analogous embodiments, because:
• Both Group II introns and CRISPR-Cas9 originate in bacteria and function as RNP complexes.
• Both systems use an RNA to interact with a DNA target and to direct the action of the RNP complex.
• The consequences of both CRISPR-Cas9 and Group II introns are sequence-specific changes to prokaryotic DNA that involve endonuclease activities.
And further:
• Group II introns comprise an RNA component and an intron encoded protein.
• LtrA protein encoded by L1.LtrB intron is the best characterized [intron-encoded protein or] IEP . . . . Both LtrA and Cas9 have an HNH endonuclease domain that cleaves a DNA target.
• Group II introns are capable of site-specifically cleaving DNA, or additionally inserting sequences into DNA.
• Because of this, Group II introns have been utilized in prokaryotes for gene targeting applications. This function is mediated by the RNP particle containing the IEP and an excised intron RNA, with DNA target specificity determined by base pairing of the intron RNA to the DNA target sequence, with additional support from the IEP.
But "[d]espite successful use in prokaryotes for gene targeting, only moderate activity of Group II introns has been obtained in eukaryotic cells" Sigma-Aldrich asserts, citing prior art references. Other systems for DNA editing known in the art, such as zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can be distinguished from CRISPR (and expected to act differently in vivo) because these complexes do not require an RNA component for DNA cleavage, Sigma-Aldrich contends. Indeed, Sigma-Aldrich argues, this distinction, the requirement for the sgRNA component of CRISPR recited in the Count, is a reason the skilled person would have considered CRISPR-Cas9 to be unique and not analogous to any prior methods for site-specific DNA cleavage. In addition, Sigma-Aldrich argues that the art did not disclose a set of "common factors and conditions" that would be expected to work with CRISPR because they had worked with other systems for cleaving DNA in eukaryotic cells based on prokaryotic mechanisms.
The brief sets forth all the multiple distinctions between prokaryotic cells and eukaryotic cells used successfully in the '048 and '115 interferences (including structural distinctions with eukaryotic mRNA (caps, poly A); the requirement for proper folding; crowding and lack of chaperones in eukaryotic cells; the packaging by chromatin/histones of eukaryotic genomic DNA; uncertainty regarding the need for PAM sequences in sgRNA; intracellular conditions (including ion concentrations); toxicity, inter alia from dsRNA-triggered interferon production in eukaryotic cells; and non-specific binding). Microinjection, which CVC asserts is an embodiment showing successful eukaryotic CRISPR "would not obviate most technical challenges," because most of the circumstances providing impediments also exist in the microinjected cell. Sigma-Aldrich argues that the existence of these impediments (actual or potential) required disclosure of conditions for addressing them but, on the contrary, CVC's argument was that the skilled artisan could presume eukaryotic CRISPR could be successfully achieved without them.
In support for the deficiencies in the P1 and P2 applications Sigma-Aldrich recites portions of these specifications to illustrate:
Histone proteins are known in the art to bind DNA and form complexes known as nucleosomes. Histones can be modified (e.g., by methylation, acetylation, ubiquitination, phosphorylation) to elicit structural changes in the surrounding DNA, thus controlling the accessibility of potentially large portions of DNA to interacting factors such as transcription factors, polymerases and the like . . . . Thus, a site-directed modifying polypeptide with histone-modifying activity finds use in the site-specific control of DNA structure and can be used to alter the histone modification pattern in a selected region of target DNA. Such methods find use in both research and clinical applications.
And:
In some of the above applications, the subject methods may be employed to induce DNA cleavage and DNA modification in mitotic or post-mitotic cells in vitro and/or ex vivo and/or in vitro (e.g., to produce genetically modified cells that can be reintroduced into an individual). Because the DNA-targeting RNA provide specificity by hybridizing to target DNA, a mitotic and/or post-mitotic cell of interest in the disclosed methods may include a cell from any organism (e.g. a bacterial cell, an archaeal cell, a cell of a single-cell eukaryotic organism, a plant cell, an animal cell, a cell from an invertebrate animal (e.g. fruit fly, cnidarian, echinoderm, nematode, etc.), a cell from a vertebrate animal (e.g., fish, amphibian, reptile, bird, mammal), a cell from a mammal, a cell from a rodent, a cell from a human, etc.). Any type of cell may be of interest (e.g. a stem cell, e.g. an embryonic stem (ES) cell, an induced pluripotent stem (iPS) cell, a germ cell; a somatic cell, e.g. a fibroblast, a hematopoietic cell, a neuron, a muscle cell, a bone cell, a hepatocyte, a pancreatic cell etc.) . . . [emphasis in brief].
These disclosures, according to Sigma-Aldrich, demonstrate that the P1 and P2 applications disclose a "mere wish or plan," citing Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011) and fail to satisfy the requirements for priority.
Again as Broad has done in earlier interferences, Sigma-Aldrich recites statements from CVC's witnesses used to cast doubt their positive assertions in support of CVC's motion. For example, from Dr. Carroll:
What about activity of the system in eukaryotic cells? Both zinc fingers and TALE modules come from natural transcription factors that bind their targets in a chromatin context. This is not true of the CRISPR components. There is no guarantee that Cas9 will work effectively on a chromatin target or that the required DNA–RNA hybrid can be stabilized in that context. This structure may be a substrate for RNA hydrolysis by ribonuclease H and/or FEN1, both of which function in the removal of RNA primers during DNA replication. Only attempts to apply the system in eukaryotes will address these concerns [emphasis in brief].
And Dr. Barranghou:
Although immediate applications of this new tool include customized DNA nicking and/or cleavage in bacteria, there are intriguing possibilities for genome editing and genome engineering of eukaryotes. This will require testing whether crRNA-Cas systems can efficiently cleave chromatin DNA in vivo and be readily transferred into organisms of interest, notably yeast and fungi, but also plants, for crop and agricultural applications, and human cells, for medical purposes. Only the future will tell whether this programmable molecular scalpel can outcompete ZFN and TALEN DNA scissors for precise genomic surgery [emphasis in brief].
And of course the brief cites statements from Jennifer Doudna:
These findings [reported in Jinek 2012] suggested the exciting possibility that Cas9:sgRNA complexes might constitute a simple and versatile RNA-directed system for generating DSBs that could facilitate site-specific genome editing. However, it was not known whether such a bacterial system would function in eukaryotic cells.
Our 2012 [Jinek] paper was a big success, but there was a problem. We weren't sure if CRISPR/Cas9 would work in eukaryotes—plant and animal cells. Unlike bacteria, plant and animal cells have a cell nucleus, and inside, DNA is stored in a tightly wound form, bound in a structure called chromatin [emphasis in brief].
The brief also cites the Board's basis for its decision in the '115 interference:
CVC's arguments fail to persuade us that those of ordinary skill in the art would not have considered specific instructions or conditions for a CRISPR-Cas9 activity in a eukaryotic cell to be necessary. Possession of an innovation is not indicated by the need for optimization to obtain it because "[t]he question is not whether a claimed invention is an obvious variant of that which is disclosed in the specification. Rather, a prior application itself must describe an invention, and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date sought," citing Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) [emphasis in brief].
Accordingly, Sigma-Aldrich asks the Board to deny CVC's motion.
* Thus, Sigma-Aldrich made these arguments before the Board ruled in the '115 Interference.
By Donald Zuhn —
Over the past two weeks, the Ukrainian Institute of Intellectual Property (Ukrpatent) has been posting letters of support that it has received from other European IP offices. Among the offices from which Ukrpatent has received such letters are the European Patent Office (EPO), the Patent Office of the Republic of Poland, the Industrial Property Office of the Slovak Republic, the Austrian Patent Office, the Finnish Patent and Registration Office (PRH), the State Patent Bureau of the Republic of Lithuania, and the European Union Intellectual Property Office (EUIPO).
On Friday, Ukrpatent posted a letter of support that it received from the Estonian Patent Office. In the letter, Director General Margus Viher begins by "express[ing] our strong solidarity with the Ukrainian people and particularly with our colleagues and their families in the Ukrainian Intellectual Property Institute," and declaring that "[w]e stand together with the international community in support of Ukraine and its people." Stating that "[d]uring the past weeks, we have witnessed Ukraine and its people being subject to Russian Federation's unprovoked, unjustified and illegal military aggression against your nation, causing loss of life and suffering," the Director General notes that the Estonian Patent Office "is prepared to contribute in support of Ukraine in IP area on EU and international level." The letter concludes that "[w]e sincerely hope that these unjustified military actions by Russia, grossly violating not only international law but the principles of humanity itself, that are unimaginable in our times, will be stopped," noting that the Estonian Patent Office "align[s] our positions with EU in demanding that Russia immediately ceases its military actions, unconditionally withdraws all forces and military equipment from the entire territory of Ukraine and fully respects Ukraine's territorial integrity, sovereignty and independence within its internationally recognised borders," and closing with the message: "Слава Україні!" (Glory to Ukraine!).
Ukrpatent also posted a letter of support that it received from the National Intellectual Property Center of Georgia (Sakpatenti). In the letter, Acting Chairperson Manana Pruidze writes to "express solidarity with Ukraine," stating that Sakpatenti "strongly condemn[s] an act of aggression on the part of Russian Federation" and is "outraged by the ongoing military actions and send[s] wholehearted thoughts . . . to Ukrpatent colleagues and fellow Ukrainians at these terrible and frightening time." After offering Sakpatenti's "condolences to the families of victims and a swift recovery to those injured," Acting Chairperson Pruidze declares that:
Russia's actions are an immediate danger to those living in Ukraine, but also pose a real threat to democracy throughout the world. Please be informed that over the years our office is not engaging in any activity or communication with Russian IP delegation or representatives.
Acting Chairperson Pruidze also notes that Sakpatenti staff are making voluntary contributions to Georgian Government aid campaigns for Ukraine, and concludes by stating "[w]e hope to have peace in the region, as it is the only solid ground for the existence and sustainable development, innovation and prosperity within the EU neighbourhood and in Europe as a whole."
For additional information regarding this and other related topics, please see:
• "Several Law Firms Close Russian Offices," March 13, 2022
• "Russia Permits Uncompensated Use of Certain Patents without Patentee Consent," March 11, 2022
• "Lithuanian Patent Office and EUIPO Join Other Patent Offices in Expressing Support for Ukraine," March 10, 2022
• "USPTO Terminates PPH with Rospatent and Terminates Engagement with NCIP," March 10, 2022
• " Life Sciences Business Leaders Call for Immediate and Complete Economic Disengagement from Russia," March 9, 2022
• "PRH Joins Other Patent Offices in Expressing Support for Ukraine," March 9, 2022
• "USPTO Terminates Engagement with Rospatent and EAPO," March 7, 2022
• "Ukrpatent Continues Normal Operations Despite Russian Aggression," March 6, 2022
By Donald Zuhn —
According to a number of online reports, several global law firms have decided to close their Russian offices in response to Russia's invasion of Ukraine. Among the firms that are reported to have closed their Russian offices (or that are in the process of doing so) are:
• Allen & Overy
• Baker Botts
• Borenius
• Bryan Cave Leighton Paisner
• Clifford Chance
• Debevoise & Plimpton
• Dechert
• Eversheds Sutherland
• Freshfields Bruckhaus Deringer
• Gowling WLG
• Herbert Smith Freehills
• Hogan Lovells
• Latham & Watkins
• Linklaters
• Morgan, Lewis & Bockius
• Norton Rose Fulbright
• Squire Patton Boggs
• White & Case
• Winston & Strawn
Several other firms are reported to have suspended their operations in Russia, including:
• Akin Gump Strauss Hauer & Feld
• Cleary Gottlieb Steen & Hamilton
• Mannheimer Swartling
Information regarding the impact of Russian's invasion of Ukraine on law firm operations can be found here:
• "Law Firms Respond to Russia's Invasion of Ukraine: How the Legal Industry & the Public Can Help," National Law Review, March 13, 2022.
• John Malpas and Madeline Anderson, "Hogan Lovells latest to announce Moscow office closure as five more US firms reveal Russia withdrawal plans," Global Legal Post, March 11, 2022.
• Sarah Martinson, "4 More BigLaw Firms Close Offices In Russia," Law360, March 11, 2022.
• David Thomas, "Factbox: Global law firms in Russia react to Ukraine invasion," Reuters, March 11, 2022.
• Megan Tribe, "White & Case to Close Moscow Office, Joining Other Exits," Bloomberg Law, March 11, 2022.
• Jonathan Ames, "Freshfields, Eversheds and Gowling close their Russian practices," The Times, March 10, 2022.
• James Booth, "Allen & Overy and Clifford Chance to close Moscow offices as law firms rush for exit in Russia," Financial News, March 10, 2022.
• Louis Goss, "Clifford Chance to wind down Moscow offices amid scrutiny over law firm's links to oligarchs," City A.M., March 10, 2022.
• Kate Ackley, "Big K Street shops will close offices in Russia," Roll Call, March 9, 2022.
• Lachlan Markay and Sarah Mucha, "Big Law exits Russia," Axios, March 9, 2022.
• Rachel Rippetoe, "6 BigLaw Firms Exit Russia As Ukraine War Rages On," LAW360 Pulse, March 9, 2022.
• David Thomas, "More law firms exit Moscow as Russia wages war in Ukraine," Reuters, March 9, 2022.
• Meghan Tribe, "Five Big Law Firms Close Moscow Offices as Ukraine War Rages," Bloomberg Law, March 9, 2022.
March 16, 2022 – 2022 Women's Entrepreneurship Symposium: "Trends and Opportunities" (U.S. Patent and Trademark Office) – 2:00 pm to 3:05 pm (ET)
March 16, 2022 – "Trending Global IP Issues Through the Lens of IPO's Special 301 Comments" (Intellectual Property Owners Association) – 2:00 pm to 3:00 pm (ET)
March 17, 2022 – "Recent Developments in Pharmaceutical Patent Litigation" (Federal Circuit Bar Association Patent Litigation Committee) – 1:00 pm to 2:00 pm (ET)
April 26-27, 2022 – Paragraph IV Disputes Conference (American Conference Institute) – New York City
The U.S. Patent and Trademark Office will be holding the next installment of the 2022 Women's Entrepreneurship Symposium, entitled "Trends and Opportunities," on March 16, 2022, from 2:00 pm to 3:05 pm (ET). Tené Dolphin of the National Women's Business Council and Adji Fatou Diagne of the U.S. Census Bureau will discuss the economic impact of women in business and how social trends are affecting their professional growth and business opportunities.
Additional information regarding the Symposium can be found here. Those interested in registering for the event, can do so here.
The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "Trending Global IP Issues Through the Lens of IPO's Special 301 Comments" on March 16, 2022 from 2:00 pm to 3:00 pm (ET). Stephen Bauer (retired, Medtronic Inc.), Dean Harts of 3M Innovative Properties Co., Sharon Reiche of Pfizer Inc., and Bill Warren of Eversheds Sutherland will provide an overview of significant IP policy concerns across different countries and regions based on IPO's comments made during the U.S. Trade Representative's Special 301 review, note issues that IP practitioners need to be aware of, and point out global trends in IP law and policy.
The registration fee for the webinar is $150 for non-members or free for IPO members (government and academic rates are available upon request). Those interested in attending the webinar should register here.
The Federal Circuit Bar Association (FCBA) Patent Litigation Committee will be offering a remote program entitled "Recent Developments in Pharmaceutical Patent Litigation" on March 17, 2022 from 1:00 pm to 2:00 pm (ET). April Weisbruch of McDermott Will & Emery LLP will moderate a panel consisting of Christopher Bruno of McDermott Will & Emery LLP and Coy Stull of Carlton Fields, PA. The webinar will cover recent developments in pharmaceutical patent litigation and in particular district court and Federal Circuit decisions involving written description, enablement, and skinny labels.
The webinar is complimentary for FCBA members and students, $50 for government/academic/retired non-members, and $175 for private practitioner non-members. Those interested in registering for the program, can do so here.
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