McCoy Russell was pleased to participate in a focus group as part of the feasibility study. The HTC is utilizing these focus groups to connect with health technology leaders across the state of Oregon. Approximately 36% of these interviews have been conducted with women in tech and as a women-owned firm, we were happy to assist in providing additional expertise as to what will be needed to create this new healthcare specific “invention space.”

The Health Technology Inventor Space will be a lab-like facility where healthcare product innovators, practitioners, students and entrepreneurs can bring their ideas, questions or product prototypes to engage in iterative development. The lab will offer industry expertise, software tools, refinement capabilities, testing, and professional prototyping equipment that can ultimately decrease the time between iterations, ensure compatibility with regulatory and data standards, and allow for cross-platform device checking and graphical/human interface validation. 

From our standpoint, participating in forums such as these is an important investment. We have been listening to our Oregon clients, hearing what their friction points are in product development and what services they have had difficulty locating. By being a part of these conversations, we are better able to assist our clients in acquiring the resources they need to succeed, increasing their ability to develop the products they envision and thereby increasing the scope and value of each patent filing.

During yesterday’s USPTO Biotechnology, Chemical and Pharmaceutical Partnership Meeting, the USPTO addressed two priorities of the USPTO Strategic Plan 2018-2022:

                                (1) optimize patent quality and timeliness; and

                                (2) issue highly reliable patents. 

Under Secretary Andrei Iancu’s specific priorities are to address subject matter eligibility under 35 U.S.C. §101 and improve the search capabilities of the agency, finding the most relevant prior art early in prosecution.  This includes testing new semi-automated tools for data mining in specific technology areas.

While new guidelines for rejections under 35 U.S.C. §101 were released January 4, 2019, these changes do not address the problems with rejections in the life sciences.   There is also still a question as to whether the Federal Circuit will agree with these new guidelines.

Current strategies for overcoming 35 U.S.C. §101 frequently do not work well for research institutions and cutting edge life science technologies.  For example, many diseases do not yet have treatments and therefore claims that include both a diagnostic step and  a treatment step, which would be patent eligible, as illustrated by Vanda Pharmaceuticals Inc. v. West-Ward Pharmaceuticals, 887 F.3d 1117 (Fed. Cir. 2018) (and as covered by our earlier post here), are not possible. 

As summarized by Kathleen Chaffee, PhD, Washington University in St. Louis, Office of Technology Management, known strategies to overcome 35 U.S.C. §101 rejections in life sciences typically don’t work because:

o   Academics use conventional methods in the discovery of a new invention to ensure their experiments are reproducible or can be validated

o   Academics typically rely on industry to move research/commercialize

o   Commercial engagement typically occurs after patent filing

o   Unnecessarily adding unconventional steps to satisfy an eligibility requirement render claims commercially less valuable

o   Additional steps reciting elements (e.g., comparing, diagnosing), often necessary to satisfy 35 U.S.C. §102 and §103, can trigger a 35 U.S.C. §101 rejection

Dr. Chaffee went on to enumerate a number of potentially impactful diagnostics that Washington University in St. Louis has abandoned due to problems with 35 U.S.C. §101.  For example:

o   Bacterial Vaginosis Diagnostics –discovered a new enzyme to predict adverse  pregnancy outcomes, preterm birth, infertility

o   Alzheimer’s Disease Diagnostics

 o   Diagnostics for autism, diabetes, lysosomal storage diseases, autoimmune conditions,  allergy, infection, arthritis, inflammatory disease, kidney disease, skin disease, heart disease, cancer, neurodegenerative diseases, etc.

Diagnostics also remain risky ventures for potential commercial partners of educational/research institutions.  The uncertainty regarding their patentability/validity inhibits commercial development and practical exploitation of potentially important discoveries.  Diagnostic claims are being dissected and overgeneralized into foundational laws of nature or natural phenomenon and restated at a high level of generalization so as to be regarded as conventionally known techniques.

In 2015, the White House launched a precision medicine initiative.  Rising health care costs are under constant scrutiny.   Diagnosing by exclusion can be an expensive and time consuming undertaking and frequently leads to delayed intervention and poorer clinical outcomes.  However, diagnostics inform treatment and drive personalized medicine.  They improve clinical outcomes and decision making, decreasing costs and benefiting patients.  As Dr. Chaffee observed, diagnostics frequently represent cutting edge applications in science and biotechnology.  They are ‘useful Arts’ that the patent system is supposed to be promoting and securing for public use and benefit. However, the issue with 35 U.S.C. §101 is something that will probably have to be addressed through legislative change.

On April 17, 2019, U.S. Senators Chris Coons and Thom Tillis and Representatives Doug Collins, Hank Johnson, and Steve Stivers released a framework for 35 U.S.C. §101 reform.  They suggested a “practical application” test to ensure that statutorily ineligible subject matter is construed narrowly.  But it remains unclear what “integrated into a practical application” would mean for a diagnostic invention.  Do they only apply to method claims or would formulations also be considered practical applications?  Is diagnosing a specific disease a practical application of the discovery of the underlying natural phenomenon?  Current case law would suggest not.

The Supreme Court is considering petitions for certiorari in decisions generally viewed as favorable to patent holders and has asked the Solicitor General to submit a brief in both Berkheimer v. HP Inc., 881F.3d1360 (Fed. Cir. 2018) and the Vanda decision.  In the meantime, many potentially game changing diagnostics and treatment opportunities are being abandoned due to the continued uncertainty.

Consider the example of US 2014/0244292, which disclosed a method of ranking and recommending treatments for an individual’s medical condition, a determination clearly in the public interest.  This application was ultimately abandoned, but not before receiving a pair of §101 rejections for reciting the abstract idea of “comparing new and stored information and using rules to identify options.”

That characterization certainly sounds like any generic ranking methodology.  Yet, several applications have managed to clear this hurdle.  Consider US 8,898,174, which discloses a method for ranking lawyers and their practices.  Or US 9,177,349, which patents a method for rating patents (“and other intangible assets”).  At first glance, these certainly seem just as abstract as a medical treatment recommendation method.  Yet, both of these patents were issued in due course (the latter overcoming a §101 rejection in a single round of prosecution, the former not receiving a §101 rejection at all).

Indeed, under the continually developing case law and guidance concerning subject matter eligibility, such inconsistency at the USPTO has been debated even at the highest levels.  In an effort to address this, the recent 2019 Revised Patent Subject Matter Eligibility Guidance has standardized some of the more loosely interpretable and challenging aspects of §101 rejections.

Of particular interest to this discussion is the new, two-pronged approach for determining whether or not a claim is directed to a judicial exception, including consideration of whether or not a recited judicial exception is integrated into a practical application (and therefore possibly constituting eligible subject matter).  This reveals a path for future prosecution strategies for comparison- and rules-based ranking methodologies.  Examples provided in the Revised Guidance include integrating judicial exceptions into the improvement of a technology or technical field, implementing the judicial exception with a particular machine or manufacture, and effecting a transformation/reduction of an article to a different state/thing.  Most hopeful for cases such as the ‘292 application is the potentially patentable utilization of a judicial exception to effect a particular treatment for a disease or medical condition.

The potential for ranking methodologies (and similar subject matter) under the Revised Guidance is hardly unlimited.  The Revised Guidance clearly states that judicial exceptions are not integrated into a practical application merely because the claim recites the words “apply it,” or an equivalent.  However, by constructing claims in such a way as to integrate the generation of ranked lists into “real world” practicality, there may yet be opportunities in this space.

Why can this be advantageous?

Patent drafting inevitably requires some amount of learning. Inventions are, by definition, new and anyone other than the inventors is not an expert. Traditional firms might think it is beneficial to assign these inventions only to attorneys and/or agents considered experts in a particular field that seems closest to the new invention. However, they bring their own preconceived notions and experiences in a narrow field which may result in a tunnel-view of the problem and technical solution of the invention. When I work with a team having diverse backgrounds to prepare a new patent application, past experiences are used to deepen and broaden the scope of an invention and the scope of the description, thereby setting up the application to enable a diverse range of arguments in support of patentability. Interdisciplinary review ensures that the traditional aspects of the invention are described while strengthening the patent application as different eyes with different backgrounds learn the invention and provide their own spin.

From a legal standpoint, USPTO guidelines are continuously changing, further requiring attorneys and agents to, again, learn and adapt. My experience working in a collaborative team-based environment helps understand these changes from different points of view. For example, by being included in monthly continued legal learning events which include analysis of recent cases, I can get a better feel for the direction the USPTO is going and then adapt drafting strategies today for the USPTO guidelines changes of tomorrow.

The structure and strategy of a collaborative approach enables technical team members and legal team members to maximize their individual skills and the resulting patent application is more of a melting pot of these ideas due to the collaborative approach.  Collaboration occurs not only during the searching, evaluation  and drafting phases, but is also carried through during prosecution affording not only more robust patent applications with a smorgasbord of concepts with varying scope, but better ideas for developing a range of options to respond to Office action rejections by the USPTO. Inclusion of these types of diverse strategies in each patent application increases a client’s stronghold around technology, and builds a stronger and higher quality patent portfolio.

Though the number of new drugs receiving FDA approval is relatively small, many drugs that are already FDA-approved receive expanded FDA approval each year. Expanded approval may include use of already FDA-approved drugs for new therapies and for new patient populations, such as children, for example.

Depending on how long the drug has been used, there may be substantial historical data which can be used to provide guidance in developing protocols for the expanded therapy or population of the already FDA-approved drug. As an example, Lithium (first approved in 1980) obtained expanded approval from the FDA last year for use in treating several new adult illnesses,[1] likely taking advantage of over twenty years’ worth of historical data and reports to guide the development of these new therapies.

Given the advantages of historical data for substantial savings in research, expansion of FDA approval can be an attractive option for companies once initial FDA approval has been received.

So what does this all mean from an IP perspective? Can you receive any patent protection for new use of your known drug? What is the best strategy to protect the expanded approval of the drug?

As discussed in Patent Docs’ “Patenting Repurposed Drugs”  by John E. Conour, new uses for a known drug can be patent-eligible if the use is novel and non-obvious. Thus, so long as the manner in which the drug is being used is new, the main remaining concern is providing sufficient evidence to support that the new use for the known drug is not obvious. To establish that the new use of the drug is non-obvious, detailed discussion as to the specific unexpected benefits achieved via the new use of the drug may be particularly helpful. Furthermore, if available, trial data showing unexpected advantages can be another powerful tool to support non-obviousness of a new use for a known drug.

From an overall patent portfolio standpoint, coordinating patent coverage of the new drug itself with patent coverage on various uses for the new drug may be a wise strategy to protect a drug from initial FDA approval and through expanded approval.

At least one way to coordinate patent coverage over the initial approval of the drug and into subsequent expansion approvals is to file an initial patent application for the new drug with disclosure directed towards the new drug composition and any contemplated therapies for which the new drug may be used. Then, although the initial patent application may only include claims directed towards a composition of the new drug for example, child patent applications directed towards the various therapies may be filed at a later time.

Via the above approach to coordinating patent coverage, patent protection may be more easily catered to the new drug as the new drug progresses through various FDA approval stages. Moreover, coverage may be provided with as early of filing dates as possible, to help protect the new drug against potential competitors as FDA approval is expanded for the new drug.

Clearly, even though there are not many new drugs approved each year by the FDA, patent portfolio maintenance can be a key strategy for protection of downstream expanded FDA approvals.

[1] “Novel Drug Approvals for 2018.” U.S. Food & Drug Administration, FDA, 15 Jan. 2019, www.fda.gov/drugs/developmentapprovalprocess/druginnovation/ucm592464.htm.

            However, the medical community has debated the efficacy of fish oil supplements for years.  The debate appeared to culminate in July of this year, when a study published in the Cochrane Database of Systemic Reviews that included analysis on more than 112,000 participants over the course of 10 years, reported that omega-3 supplements had essentially no effect on cardiovascular health.

            The conclusion that omega-3 supplements are worthless however, was recently turned on its head with the report that Vascepa, a purified version of EPA produced by the biopharmaceutical company Amarin Corporation, remarkably lowered the risk of heart attacks and strokes in patients with very high levels of a type of fat in the blood called triglycerides.  Specifically, patients on Vascepa who were also on a statin drug for lowering cholesterol showed a 25 percent reduction in the relative risk of a heart attack, stroke, or death due to a cardiovascular event, etc.  Remarkably, the 25 percent reduction in risk is on top of a 25 percent reduction in risk that historically has been associated with taking statins.  Thus, there appears to be enormous potential for this particular drug when taken in combination with conventional statin treatment.

The critical reason for the success appears to lie in the fact that Vascepa lowers triglycerides, without increasing so-called bad cholesterol (low-density lipoprotein-cholesterol, or LDL-cholesterol).  Other supplements previously examined in studies assessing cardiovascular health included DHA along with EPA, and it is thought that because DHA is known to elevate bad cholesterol, that is the reason the previous trials failed.  Alternatively, as mentioned, Vascepa is pure EPA. 

            Upon learning of these incredibly promising results, we were interested in looking into Amarin’s intellectual property holdings regarding this subject matter.  Certainly with the overwhelming amount of information out there pertaining to the relationship between statins, cholesterol, triglycerides and omega-3 supplements including EPA and DHA, the prosecution history would provide valuable lessons from which to glean how to overcome Examiner rejections in this space.

            Thus, we looked into patents filed in this space by Amarin.  Specifically, United States Patent Application No. 14/411815 assigned to Amarin was directed to:

 A method of reducing a risk of cardiovascular death, coronary revascularization, and unstable angina in a subject on statin therapy, the method comprising:

Administering to the subject a pharmaceutical composition comprising about 1 g to about 4 g of ethyl icosapentate per day, wherein the subject has a fasting baseline triglyceride level of about 135 mg/dL to about 500 mg/dL and optionally has established cardiovascular disease.

            The primary rejection during prosecution included a 35 U.S.C. 102 rejection based on prior art teachings of US 2012/0121698, which included all the elements of the method claim of US 14/411815, but which failed to specifically teach the limitations related to “reducing a risk of cardiovascular death, coronary revascularization, and unstable angina in subjects having a baseline triglyceride level of about 135 mg/dL to about 500 mg/dL”, even though methods for treating a cardiovascular-related disease were disclosed.  This fact was argued by the Applicant, and was enough to persuade the Office to allow the claims without any further rejections.  We were surprised that no further rejections were applied in this case, given the frequency with which the KSR decision (KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007)) has been recently readily applied to claims simply by an Examiner finding all the elements in a particular claim in one or more pieces of prior art, and then asserting the claim as being obvious to one skilled in the art.

            At any rate, the take-home message is that method of treatment claims directed to specific aspects of disease can in some cases be sufficient to overcome close prior art.  The success of Amarin’s trial is good news for investors, as well as patients with high triglyceride levels, which Amarin estimates to be over 50 million adults in the United States alone.  More good news is the current list price of Vascepa, which is around $2400 per year, as compared to much higher pricing for other drugs that reduce cardiovascular events in high-risk populations.

This means that any third party seeking to commercialize the CRISPR-cas9 technology in the U.S. for use in eukaryotic cells (which, based on the nearly 2000 U.S. patent applications filed since 2014, using or otherwise developing, CRISPR-cas9 technology, is a lot)  will need a license from both the University of California and the Broad Institute.

And as for the stock prices, EDITAS (licensed from Broad Institute), CRISPR (licensed from Dr. Emannuelle Charpentier who is on the University of California's patents and has also retained her own rights in the patents), and INTELLIA (licensed from Caribou Biosciences who licensed the technology from the University of California and University of Vienna)  all seem to have recovered from a drop yesterday and the effective impact of this decision on R&D and the ensuing therapeutic tools remains to be seen. 17-1907

Part of receiving the limited monopoly of a patent is a contribution to the body of scientific knowledge.  In some ways, a patent can be viewed as a teaching document. In order for an invention to be enabled, as required for patentability, the specification must include enough information to allow someone of skill in the art to make and use the claimed invention.  In other words, your invention needs to be reproducible to be valid.

In a survey published in the journal Nature in January 2017, more than 70% of researchers revealed that they have tried and failed to reproduce another scientist’s results based on the information published in scientific literature (Munafò, Marcus R., Brian A. Nosek, Dorothy V. M. Bishop, Katherine S. Button, Christopher D. Chambers, Nathalie Percie Du Sert, Uri Simonsohn, Eric-Jan Wagenmakers, Jennifer J. Ware, and John P. A. Ioannidis. "A manifesto for reproducible science." Nature Human Behaviour1, no. 1 (2017): 0021. doi:10.1038/s41562-016-0021).  This reproducibility failure can call into question the validity of a patent that is based on research published in a paper.  If someone in the field cannot reproduce a claimed invention, then arguably the claimed invention is not enabled by the patent and therefore the claims are invalid.

As research becomes increasingly computerized, it is important to stay cognizant of software developments and updates as using outdated software may lead to conclusions that are not scientifically valid, and thus such conclusions may not be reproducible when updated software is utilized.  While it may be human nature to continue to rely on procedures and software you learned when you first started out, doing so may impact the patentability and any valuations attached to your discovery.

As an example, in the realm of computational biology, the website for TopHat, a spliced read mapper for RNA-Seq originally published in 2009, now states: “[p]lease note that TopHat has entered a low maintenance, low support stage as it is now largely superseded by HISAT2 which provides the same core functionality . . . in a more accurate and much more efficient way.” (Emphasis TopHat’s, https://ccb.jhu.edu/software/tophat/index.shtml).” TopHat has not been updated since February, 2016.  

In a letter to the editor published in Nature Methods in 2016 (Wadi, Lina, Mona Meyer, Joel Weiser, Lincoln D. Stein, and Jüri Reimand. "Impact of outdated gene annotations on pathway enrichment analysis." Nature Methods13, no. 9 (2016): 705-06. doi:10.1038/nmeth.3963), the authors wrote that “the use of outdated resources has strongly affected practical genomic analysis and recent literature: 67% of ∼3,900 publications we surveyed in 2015 referenced outdated software that captured only 26% of biological processes and pathways identified using current resources.”  What this means is that competitors using more advanced tools and methods have access to differentiating data and models that can be used, either in whole or part with existing knowledge, to more completely describe inventions. This may allow them to either to design around your claims or claim complete novelty.

Enablement is a requirement of patentability.  When “the claimed subject matter is inoperable, the patent may indeed be invalid for failure to meet the utility requirement of § 101 and the enablement requirement of § 112,” Process Control Corp. v. HydReclaim Corp. 190 F. 3d 1350 (Fed. Cir. 1999) citing Brooktree Corp., 977 F.2d at 1571, 24 USPQ2d at 1412 (citing Raytheon Co., 724 F.2d at 956, 220 USPQ at 596). Using the most modern tools and methods not only helps increase the breadth of your discovery, it also helps with reproducibility and validation of your claims.  Your insights and research are cutting edge, make sure your tools are, too. 

The following table summarizes the procedural differences among the various third party submission practices in both the U.S. and China.

The most noticeable difference between the U.S. and China practices is that the window for filing the third party submission in China is much broader than in the U.S.  In the U.S., there are two types of third party submissions that may be filed after the publication and before the issuance of a patent: the third party pre-issuance submission and the third party protest.  Both of them have a relatively tight window to file.  In China, there are three types of patent applications: invention, utility models, and design applications.  The public opinion is only accepted during the prosecution of the invention application, which is analogous to the utility application in the U.S.  The window for filing the public opinion in China is during the entire prosecution period of the application.  It is anonymous and it is free!  Thus, even with potential risks in the future (such as that the unaccepted prior art may not be relied in future invalidation procedure), filing the public opinion in China may be a very cost effective way to block the competitor’s potential coverage.

One way to monitor a competitor’s progress in patent applications in China is through the Global Dossier (https://globaldossier.uspto.gov/#/).  The Chinese patent Office has made impressive progress in digitizing and publishing the patent document database.  Currently, the amended claims entered after each Office action can be accessed through the Global Dossier while the application is still pending.  As to how to know whether the competitor has filed a related patent, one way may be to monitor if any patent application in your patent portfolio have been cited by others. 

Related links:

君合专题研究报告

http://www.junhe.com/download?filePath=/upload/law-reviews/eeaae1e5a6bceb7ad5f24c5a98b509d9.pdf&fileName=%E4%B8%93%E9%A2%98%E7%A0%94%E7%A9%B6%E6%8A%A5%E5%91%8A-%E4%B8%93%E5%88%A9%E7%94%B3%E8%AF%B7%E4%B8%AD%E7%9A%84%E5%85%AC%E4%BC%97%E6%84%8F%E8%A7%81%E7%A8%8B%E5%BA%8F%E4%B9%8B%E6%B5%85%E6%9E%90%EF%BC%8820151112%EF%BC%89.PDF

Protests: Are Those Still Around?

https://www.finnegan.com/en/insights/blogs/prosecution-first/protests-are-those-still-around.html

Third Party Inquiries and Correspondence in a Published Application

https://www.uspto.gov/web/offices/pac/mpep/s1134.html

Global Dossier

https://globaldossier.uspto.gov/#/

The University of California filed its first provisional patent on CRISPR-cas9 technology in May 25, 2012. The Broad Institute filed its first provisional patent application on December 12, 2012. However, the Broad Institute paid for accelerated examination of the utility application and its patent issued first. 

In March 2013, the America Invents Act changed the requirement for patent applications from the first-to-invent to the first-to-file protocol. Because both the Broad Institute and the University of California’s  patent applications claim priority to provisional patent applications filed prior to March 2013, they fall under the first-to-invent provisions and the University of California instituted proceedings in front of the Patent Trial and Appeal Board (PTAB) in an effort to have the Broad Institute’s patents thrown out.  In February of 2017, the PTAB issued a judgement of no interference-in-fact concluding:

Broad has persuaded us that the parties claim patentably distinct subject matter, rebutting the presumption created by declaration of this interference. Broad provided sufficient evidence to show that its claims, which are all limited to CRISPR-Cas9 systems in a eukaryotic environment, are not drawn to the same invention as UC’s claims, which are all directed to CRISPR-Cas9 systems not restricted to any environment. Specifically, the evidence shows that the invention of such systems in eukaryotic cells would not have been obvious over the invention of CRISPR-Cas9 systems in any environment, including in prokaryotic cells or in vitro, because one of ordinary skill in the art would not have reasonably expected a CRISPR-Cas9 system to be successful in a eukaryotic environment. This evidence shows that the parties’ claims do not interfere. Accordingly, we terminate the interference.

The University of California filed an appeal of the PTAB’s decision with the U.S. Court of Appeals for the Federal Circuit in April 2017 and filed a brief in July of 2017.  The Broad Institute filed its reply brief in October 2017, and the case is expected to be heard soon.  Until a final decision is reached, who owns the technology, as well as the scope of that ownership, is unclear.

The status of the ownership of the CRISPR-cas9 technology is also up for debate in Europe.  In January, 2018, the European Patent Office revoked the Broad Institute’s European Patent No. 2771468 which claims priority to 12 U.S. provisional patent applications including the December 12, 2012 provisional application.  EP 2771468 was revoked in part because of an invalid priority claim due to a disagreement between Rockefeller University and The Broad Institute over the contributions of Luciano Marraffini who is listed as an inventor on the U.S. provisional patent applications, but not the European patent application claiming priority to the U.S. provisional patent application.  The Broad Institute has stated that it plans to appeal the decision, but it is unlikely that the European Patent Office will change its mind.

Nearly 4000 patent applications using or otherwise developing CRISPR-cas9 technology have been filed worldwide since 2014, and many of the commercial developments stemming from such patent applications will require licensing from the Broad Institute or the University of California, or both. The Broad Institute and the University of California both filed patent applications in the US, EU, China and Korea.  The question thus arises: what will need to be licensed, and from whom?

For academic research, the answer is clear.  The University of California, the Broad Institute and other institutions have all agreed to make their CRISPR constructs widely available through AddGene, a nonprofit repository and patent licensor of CRISPR technologies for academic organizations.  

However, for commercial products, the licensing requirements are much murkier.  Both the Broad Institute and the University of California have largely delegated licensing responsibilities to a for-profit surrogate company that is also in the therapeutic development business, but as ownership of the technology is unclear, so are the licensing requirements.

To further complicate matters, all 12 of the Broad Institute patents declare US federal funding and rights in the patents, as does the patent application from the University of California. Under the Bayh-Dole Act, the federal government has worldwide royalty free rights in federally funded patented inventions [35 USC 202(c)(4)], and the public has the ability to petition to government for “march-in” rights” [35 USC 203] to use the patents when the inventions are not made “available to the public on reasonable terms.” [35 USC 201(f)].

While the stock prices of the for-profit surrogate companies holding the respective CRISPR-cas9 patent portfolios fluctuate in part based on legal decisions regarding the validity of the patents, their overall valuation continues to increase.  However, in the U.S. and Europe at least, it is still unclear who owns what, calling any commercialization developments and licensing deals into question. 

U.S. patent law requires that a patent specification contain a written description of the invention and enable the invention, i.e., details of how to make and use the invention. The written description requirement establishes that the applicant had possession of the invention at the time of filing.  The enablement requirement ensures that the inventor has adequately described, to a person of ordinary skill in the art, how to make and use the invention being claimed without undue experimentation.

The production of antibodies specific to an antigen was generally considered to be routine and thus, the USPTO in their MPEP followed the guidance set forth in Noelle v. Lederman (355 F.3d 1343 (CAFC 2004)), where it was held that an applicant satisfies the disclosure requirements for broad claims encompassing generically-described antibodies, provided that the applicant had sufficiently characterized a novel antigen e.g.  by its structure, formula, chemical name, or physical properties, or by depositing the protein in a public depository.

In Amgen v. Sanofi, one of the issues raised on appeal was the district court’s instructions to the jury.  Specifically, the district court instructed the jury, over Appellants’ objection, that written description can be satisfied “by the disclosure of a newly characterized antigen by its structure, formula, chemical name, or physical properties if you find that the level of skill and knowledge in the art of antibodies at the time of filing was such that production of antibodies against such an antigen was conventional or routine.” J.A. 1580 (Amgen, Inc. v. Sanofi, page 6), i.e. instructions based in part on the written description requirements set forth by the USPTO. 

In setting forth its repudiation of the "newly characterized antigen" test, the Federal Circuit declared that the jury instruction provided at the district court level allowed the jury to “dispense with the required finding of a ‘written description of the invention.’” 35 U.S.C. § 112 (Amgen v. Sanofi at page 16).  The court concluded that the test “allows patentees to claim antibodies by describing something that is not the invention, i.e, the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where ‘one describes an invention, and, if the law’s other requirements are met, one obtains a patent.’” (Amgen v. Sanofi at 18, Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010) (en banc)).

The court referred to its discussion of the “newly characterized antigen” test in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011), stating that in Centocor, “[w]e questioned the propriety of the “newly characterized antigen” test and concluded that instead of “analogizing the antibody-antigen relationship to a ‘key in a lock,’” it was more apt to analogize it to a lock and “a ring with a million keys on it.” (Amgen v. Sanofi at 15 citing Centocor Ortho Biotech, Inc., 636 F.3d at 1352 and the testimony of Dr. Jochen Salfeld).

In the memorandum, the U.S. Patent and Trademark Office states that the examples provided in the 2008 Written Description Training Materials are “outdated and should not be relied upon as reflecting the current state of the law regarding 35 U.S.C. §§101 and 112.” The 2015-2016 training slides entitled “Antibody Decision and Their Compliance with the Written Description Requirement” may still be relied upon, except in the portions where they reference the 2008 training materials.  The U.S. Patent and Trademark Office also noted that MPEP 2163 should still be followed, except for where it indicates that disclosure of a fully characterized antigen may provide written descriptive support of an antibody to that antigen.

The basic technology is fairly easy to understand.  In a nutshell, the MinION works via passing long strands of DNA through a tiny hole, or nanopore.  DNA is comprised of four bases, known by the letters A, C, G, and T.  When an electrical potential is established across the nanopore, as each base passes through the pore, an electrical signal unique to each particular base is generated, enabling deciphering of the DNA sequence.  However, it is well known that there are several factors that render accurate and complete sequencing of human genomes challenging.  These include large size, regions where particular bases repeat for long stretches, duplications, etc. 

Thus, the breakthrough published last week involved the development of a protocol to generate ultra-long reads (read lengths up to 882 kb), enabling sequencing of a human genome with 99.88% accuracy. 

The possibilities for future use of such technology are virtually limitless.  However, despite the breakthrough, there remains significant hurdles to overcome for the technology to become mainstream.  For example, tools to automate phasing from nanopore assemblies is needed, as are improvements to real-time base-calling in order to simplify workflow, as discussed by the scientists involved with the project. 

In summary, this is a very exciting field with room for improvements to the existing technology, and which will be very interesting to follow in terms of how particular companies approach the continued advancement of this technology space. 

Part I: INTRODUCTION TO A NEW FORM OF LIFE

Life on earth is essentially a story about DNA, and the proteins encoded by DNA, which carry out the innumerable molecular reactions that support life itself at every level.  In a nutshell, DNA is a macromolecule with structural similarities to a common double-stranded “zipper”, comprising four base units that form base pairs ((adenine pairs with thymine, cytosine pairs with guanine).  This double-stranded nature of DNA enables instructions stored in a DNA to b­­e transcribed into a single stranded molecule termed messenger RNA, which is then translated into a particular protein according to the instructions. The building blocks of proteins consist of only 20 amino acids.  In other words, all complex life forms are the result of only 2 base pairs encoding proteins comprised of some variation of the 20 amino acids.  The sequence of amino acids for each particular protein is what dictates its molecular three dimensional structure, which relates to the particular function.  As an example, proteins in the brains of vertebrates called dopamine receptors are involved in neurological processes including cognition, memory, learning, pleasure, motivation, etc. 

                Each protein’s three dimensional structure represents a remarkable example of molecular engineering.  A holy grail of molecular biology thus represents the possibility that particular desired proteins could be engineered to have unique functions, outside of what life has provided.  Such an ability would pave the way for medical advances to treat disease via protein therapeutics, or particular organisms could be created to carry out functions their counterparts cannot, such as producing biofuel, for example.

                The problem is that the translation of protein from RNA molecules is based on three-base sequences termed “codons”, where each codon corresponds to a particular amino acid.  So, if each codon corresponds to a particular amino acid, how to encode other unnatural amino acids?  One option is to reprogram particular codons (codons that otherwise encode for “stopping” or finishing the protein being generated) to accept unnatural amino acids.  Another option includes chemically synthesizing a stretch of amino acids where the stretch includes a desired unnatural amino acid, and then using molecular strategies to incorporate the chemically-synthesized stretch into a protein.  In my work as a scientist at Oregon Health Sciences University, I have experience doing both, and thus have first-hand knowledge of the challenges that need to be overcome to engineer proteins and in some examples organisms with new functionality.  However, the above-described approaches are extremely limited in their potential to realize the downstream applications such as those discussed above.

                Thus, in very exciting news this past week a major milestone was reported in the journal Nature http://www.nature.com/articles/nature24659 by scientists in San Diego.   In the report it was shown that a microbe that included instructions to synthesize proteins that include molecules never before used by any life form on earth, could live, reproduce, and synthesize such proteins.  Hailed as a major technical breakthrough, the results pave the way for a potential future where organisms that can synthesize designer proteins useful for widespread applications is a possibility.  The work is part of an ongoing effort that has led to a company Synthoryx, founded by the senior author of the above-mentioned publication, Floyd Romesburg.  The company has filed patent applications that are in various stages of prosecution at the current time.

                With the enormous potential of such developments, as discussed above we will be exploring the technology behind this landmark report, and the legal issues and implications surrounding such technology, in future posts.  Stay tuned!