Patent Baristas

“The U.S. patent system has shown a remarkable ability for identifying flaws and implementing self-correcting, substantive policy changes within existing authority.”  ~Barfield and Calfee

On September 16, 2011, President Obama signed the Patent Reform Act of 2011 into law (“America Invents Act”).  It is the first major reform of the patent system in decades.  The new law provides for a conversion to a first-inventor-to-file system and an introduction of enhanced post-grant review procedures conducted in the USPTO.  The Act also addresses pre-issuance submissions by third parties, supplemental examination, reissue, elimination of the best mode defense,  special post-grant review for business method patents and USPTO authority to prioritize examination.

In this week’s Book Review, we look at “Biotechnology and the Patent System: Balancing Innovation and Property Rights” by Claude Barfield and John Calfee (AEI Press, 132 pp).   This book, published in 2007, analyzes the role of intellectual property protection in biotechnology and how patent law encourages research and venture capital investment.  The authors then evaluate whether the current system could potentially impede genomic research and the development of new treatment and diagnostic tools. Then, they set out a series of recommendations and cautionary notes.

Given the passage of the America Invents Act, I wondered how the book held up.  While Calfee passed away earlier this year, Barfield pondered the same thing in an article this fall.  The authors suggested three criteria by which to judge the legislative proposals:

First, do no harm. We were quite aware of the unintended consequences of earlier legislative and administrative “reforms”—for instance, the creation of a separate court for patent litigation (Court of Appeals for the Federal Circuit), which in its early years tilted the system heavily in favor of patent holders. We also argued that the U.S. patent system had shown a remarkable ability for identifying flaws and implementing self-correcting, substantive policy changes within existing authority.

Our second, and most important, suggestion was to increase information flow through “bounded adversarial proceedings.”  “Bounded” because we were very aware of the potential for increased costs and protracted delays in any new institutional proceedings.

Third, we acknowledged long-standing substantive and interest group clashes over key elements of the existing patent system.

So, how’d they do?  Barfield thinks not too bad:

Reviewing the new legislation, it becomes clear that Congress demonstrated remarkable restraint—it did not push the envelope in areas where the system is self-correcting. For instance, the courts have tightened patent eligibility requirements by overturning patents that are “obvious” and lack inventiveness. Similarly, they have made it more difficult to obtain huge damages when a claim is only against a single patent in a multi-patent product.

With regard to greater information flow and a “bounded adversarial process,” the new law establishes a limited post-grant administrative review process that will be much less costly and time-consuming than litigation. Henceforth, during a short window after a patent has been granted, any outside party may challenge the initial determination of the Patent Office before a newly created review board. The act also provides for a more restricted reexamination procedure (a so-called “second window”) that can be requested after the conclusion of the first appeal.

On consensus-based reforms, the legislation moves forward with several important changes. It switches the United States from a first-to-invent system to a first-to-file system, which brings the country into line with most of the rest of the world. More important, this change will eliminate inconclusive and expensive proceedings to discern just when the “Eureka moment” occurred. 

Agree or not, it would be good to see an updated version of the book in light of the law changes.

“Biotechnology and the Patent System: Balancing Innovation and Property Rights” is available from Amazon.

About the Authors

Economist John E. Calfee (1941-2011) studied the pharmaceutical industry and the Food and Drug Administration (FDA), along with the economics of tobacco, tort liability, and patents. He previously worked at the Federal Trade Commission’s Bureau of Economics. He had also taught marketing and consumer behavior at the business schools of the University of Maryland at College Park and Boston University.

Claude Barfield, a former consultant to the office of the U.S. Trade Representative, is a resident scholar at the American Enterprise Institute and researches international trade policy (including trade policy in China and East Asia), the World Trade Organization (WTO), intellectual property, and science and technology policy.

In the on-going saga of the patentability of correlations between blood test results and patient health, Prometheus Laboratories submitted its brief to the U.S. Supreme Court.  The Court granted cert for the second time in Mayo Collaborative Services v. Prometheus Labs., Inc, Supreme Court No. 10-1150, to consider whether to set limits on when inventors can patent medical diagnostic tests.

An earlier judgment was vacated and the case remanded to the U.S. Court of Appeals for the Federal Circuit for further consideration in light of Bilski v. Kappos, 561. The Federal Circuit, reversing the district court, upheld Prometheus’s patent claims covering a means to measure the level of 6-thioguinine (6-TG) and 6-methylmercaptopurine (6-MMP), which indicates that an adjustment in drug dosage may be required at certain metabolite levels.

The district court decided as a matter of law that the asserted claims were drawn to non-statutory subject matter and as such, unpatentable.  However, the Federal Circuit held that methods of treatment claims fall within the realm of patentable subject matter. Prometheus Laboratories, Inc. v. Mayo Collaborative Services (08-1403).   The Supreme Court will review that ruling.

The question presented is:

Whether the Federal Circuit correctly held that concrete methods for improving the treatment of patients suffering from autoimmune diseases by using individualized metabolite measurements to inform the calibration of the patient’s dosages of synthetic thiopurines are patentable processes under 35 U.S.C. §101.

Brief Highlights:

“Mayo’s brief distorts the record and ignores the Federal Circuit’s unchallenged construction of the patents-in-suit. Prometheus’s claims are not drawn to scientific facts in the abstract, and they do not “preempt” broad principles like the laws of chemistry or the idea of measuring metabolites. No one can infringe these claims merely by thinking about correlations. The claims describe concrete and specific physical processes, employing synthetic drugs and machines, that are used only to improve the clinical treatment of seriously ill patients.

Mayo argues that the claims’ physical steps should be disregarded because they were old in the art, but that is precisely the discredited “point-of-novelty” approach to 35 U.S.C. §101 that this Court flatly rejected thirty years ago in Diamond v. Diehr, 450 U.S. 175 (1981), and again recently in Bilski v. Kappos, 130 S. Ct. 3218 (2010). This Court has made clear that a process must be evaluated for patent eligibility under §101 as a whole. Novelty and non-obviousness are distinct, fact-intensive questions that are not before this Court. And there certainly is no reason, at the dawn of the 21^st century, for this Court to adopt special rules that would render personalized medicine inventions, or other processes designed to produce useful information, uniquely unpatentable under §101.”

The method claims in the patent at issue typically include two separately lettered steps: (a) administering a drug that provides 6-TG to a subject and (b) determining the levels of the drug’s metabolites, 6-TG and/or 6-MMP, in the subject. The measured metabolite levels are then compared to pre-determined metabolite levels, wherein the measured metabolite levels indicate a need to increase or decrease the level of drug to be administered so as to minimize toxicity and maximize efficacy of treatment.

Mayo, in its brief, continues to play up the harm to patients tactic saying:

Prometheus’s patents, which the district court invalidated but the Federal Circuit upheld, give Prometheus a sweeping monopoly on a biological correlation between drug administration and natural changes in blood chemistry. If these patents are sustained, health care providers, such as Mayo Clinic, cannot improve the numbers Prometheus has assigned to this correlation and provide more accurate drug monitoring services to patients at a lower cost, without permission from Prometheus.

In my mind, this argument is disingenuous.   The term “monopoly” is often misused in the context of patent law, but has a better-defined meaning in antitrust laws. A patent does provide the owner a limited monopoly to the claimed invention granted by the government for the term of the patent.

Patents are granted by governments in exchange for making a invention public. Once an invention is made public, others can improve upon it by making further inventions.  Thus, patents encourage research and development of ideas and concepts, which can improve our quality of life.

Saying that someone could provide a product or service for lower price but for a patent is just crying “WHAAAAAAA!” over the patent owner exercising legal patent rights.  To the extent that Prometheus is engaged in conduct permitted by patent laws, Prometheus cannot be construed as the bad guy.

The question here is whether the patent claims fail under 35 U.S.C. § 101 if it preempts all practical use of an abstract idea, natural phenomenon, or mathematical formula.  Mayo is arguing that the Prometheus patents claim a naturally occurring correlation between metabolites of a drug and the toxicity or efficacy of that drug, without specifying any concrete use of this correlation, which would preempt all practical use of the naturally occurring correlation.

Prometheus notes that “[a] patent system that recognizes thiopurine compounds themselves as potentially patentable subject matter, allowing preemption of all uses of these compounds, cannot be concerned that a process patent may preempt some of their uses. ”

Merits Briefs for the Petitioners

• Brief of Mayo Laboratories and Mayo Clinic Rochester
• Reply brief for Mayo Laboratories and Mayo Clinic Rochester

Amicus Briefs in Support of the Petitioners

• Brief for Verizon Communications, Inc., and Hewlett Packard Company
• Brief for Nine Law Professors 
• Brief for the CATO Institute et al.
• Brief for Arup Laboratories, Inc., and Laboratory Conporation of America Holdings 
• Brief for the of American College of Medical Genetics et al.
• Brief for the American Civil Liberties Union 
• Brief for AARP and the Public Patent Foundation

Amicus Briefs in Support of Neither Party

• Brief for the International Association for the Protection of Intellectual Property
• Brief for the United States of America 
• Brief for Roche Molecular Systems, Inc. et al.
• Brief for the New York Intellectual Property Law Association
• Brief for Microsoft Corporation, EMC Corporation, and Intel Corporation
• Brief for Association Internationale Pour La Protection De La Propriété Intellectuelle et al.

Merits Briefs for the Respondent

• Brief for Prometheus Laboratories

Amicus Brief in Support of the Respondent

• Brief for SAP America, Inc., in Support of Affirming the Federal Circuit’s Opinion
• Brief for the Pharmaceutical Research and Manufacturers of America
• Brief for Myriad Genetics, Inc.,
• Brief for the Biotechnology Organization 
• Brief for the Association of University Technology Managers
• Brief for the American Intellectual Property Law Association

James Madison submitted to the framers of the Constitution a provision “to secure to literary authors their copyrights for a limited time.”  ~August 18, 1787

The various forms of intellectual property (patents, copyrights, trademarks, etc.) all have roots in European laws developed over centuries.  The precursor of modern copyright law first appeared in Britain in the fifteenth century in response to Gutenberg’s printing press (a form of mass copying).

The first copyright law was a censorship law, which established a guild of private-sector censors, the London Company of Stationers.  The Stationers were granted a monopoly over all printing, old works as well as new, in return for keeping a eye on what was printed.

Hence, copyright laws are often not the most straight-forward topics to discuss.  They have their own sets of unique and arcane rules to remember, each with their own pitfalls and traps for the unwary.  Therefore, it is foolhardy to practice in such minutia-filled legal practices without being well-versed in the particulars.

And so it is that the book “An Associate’s Guide to the Practice of Copyright Law” by Meaghan Hemmings Kent and Joshua J. Kaufman covers the task of getting associates — or anyone new to the field — up to speed and what to look for and where to find the answers.

An Associate’s Guide provides readers with guidance on conducting legal tasks and research.  The authors give practice-oriented advice on topics such as what questions to ask a client, what research to conduct, what elements must be met for various causes of action, the potential repercussions for various actions and the proper alternatives to be considered.

This is a great desk handbook for anyone working with clients who are in an industry that produces copyrightable materials.  While it starts off with basics, it quickly plunges neck-deep in ares like copyright transfers, the Digital Millennium Copyright Act (DMCA), cease and desist letters as well as a detailed coverage of the steps in copyright litigation from steps to take prior to filing a claim to initial motions to counterclaims to post-trial motions.  The section includes detailed discussions of remedies, depositions and the use of experts.

The book is well laid out and contains handy call-outs of practice tips all along the way.  The book is structured so that it can be read by skipping around to the sections of interest and contains a very thorough review of the topics while pointing the way to more in-depth sources where needed.

Practice Tip

Discuss the declaratory judgment standard with your client before sending a cease and desist letter.  You do not want to have to explain after the fact how you got her sued in a faraway state because of your letter.

The book also includes some sample documents and pleadings, references to secondary sources and key cases in copyright law. A CD-ROM containing some forms in electronic format, is included.  (*Why don’t all books don’t come with such supplementary material??)  The dozen or so forms won’t replace the standard forms books but is a nice addition for the selected forms included such as samples of a cease and desist letter, complaint and interrogatories.

We highly recommend this desk reference to practitioners at any stage who are not familiar with all the nuances of copyright laws.  The practice tips are invaluable.

“An Associate’s Guide to the Practice of Copyright Law“ 344 pages (Oxford University Press, USA; 2009) is available from Amazon.

About the Authors

Meaghan Hemmings Kent is a senior associate at Venable, LLP, where she focuses her practice on intellectual property litigation, including patent, trademark and copyright claims. She also has experience in trademark prosecution before the USPTO, and proceedings before the Trademark Trial and Appeal Board.

Joshua Kaufman is a partner at Venable, LLP, where he is the head of the firm’s Copyright and Licensing group. He counsels and litigates in the fields of copyright, e-commerce, licensing, art, intellectual property, software, on-line issues, trademark, entertainment, media and literary law.

“There are 10,000 baby boomers entering Medicare every day… If you could delay the onset of Alzheimer’s by five years, you’d save Medicare $50 billion a year. That’s what biotechnology companies do.”  ~Jim Greenwood

James Greenwood, President & CEO of the Biotechnology Industry Organization (BIO) gave the keynote speech at the BioOhio conference yesterday outlining his conviction that biotechnology is not the enemy in the global economic crisis but may be a great tool to help curb it.

First, it’s important to know that new drug approvals are not keeping pace with R&D spending.  While global biotech R&D spending more than doubled to $127 million in the last ten years, the number NME + BLA FDA approvals went from 29 in 2000 to just 24 in 2010.

At the same time, drug development times are steadily increasing. During the period 1982-89, the average time for the clinical phase was 2.5 years and the average approval time was 1.6 years.  Contrast that with the period 2005-09 where the average time for the clinical phase was 7.1 years and the average approval time was 1.1 years.  The time for approval has actually gotten shorter but the time required to satisfy the approval requirements has lengthened considerably.

Simultaneously, 39% of VC firms reported decreases in their healthcare investments in the last 3 years versus just 17% that saw an increase.  And it’s very easy to see where that money is going.  Venture capitalists reported that, in the next three years, they expect to shift investments away from technologies having high FDA regulation (biopharma, medical devices, diagnostics) to technologies having low FDA regulation (healthcare services, consumer health, healthcare IT).

Of all the factors cited as having the highest impact on VC investment, FDA regulatory challenges were cited as the greatest impact on VC investment decisions over reimbursement concerns, availability of capital and capital requirements.

With $14 trillion in debt, Greenwood expressed concerns that the recent deficit troubles and the actions of the Joint Select Committee on Deficit Reductions, the so-called “super committee” that is charged with finding $1.5 trillion in savings over the next ten years, means there could be an across-the-board cut of some $1.2 trillion — putting drug reimbursement and medical innovation in the crosshairs.

On Jan. 1, 2011, the first 6,000 of eligible Baby Boomers will turn 65 and begin receiving Medicare. The number of beneficiaries is expected to increase by 3% annually. The government estimates 76 million baby boomers in all will enroll in Medicare, causing the program to grow from 47 million beneficiaries to 80 million beneficiaries in 2030.

The total cost of Medicare is expected to expand to $929 billion in 2020 — an 80% increase over 10 years. The program is slated to become insolvent in 2017, but the federal health law could extend funding until 2029 if payments to physicians and other providers are cut back.  What’s really scary is the cost of treating chronic disease:  75 cents of each health care dollar goes to treating patients with chronic disease.

How do we help fight this monster?

Greenwood is advocating that we act quickly to promote investment in innovation.  Greenwood is proposing the following incentives:

• Angel investor tax credit
• R&D partnership structures
• Improved capital gains treatment
• Matching grants for start-up investments
• Net operating loss reform
• Tax holiday for repatriated investments
• Faster cost recovery for intangible assets

How do you get involved?  Contact your congressperson.  All federal officials have offices in their home districts as well as an office in Washington, DC.   A face-to-face meeting has the potential to have more impact than a letter; a letter, more than a phone call; a phone call, more than an e-mail.

For details about your U.S. Representative — including mailing address for the district and capitol offices — use the House of Representatives, Find Your Representative page.

The Senate website contains an alphabetical list of all Senators, with their capitol addresses and a link to their Senate website, which will have information about state offices and telephone numbers.

OK, maybe not explode but at least some terrible, Armageddon-like fate.  According to a study by the Federal Trade Commission, pharmaceutical companies are engaging in anti-competitive tactics of paying potential generic rivals to delay the introduction of lower-cost prescription drug alternatives.  The report summarizes data on patent settlements filed with the FTC and the Department of Justice during FY 2011 under the Medicare Modernization Act of 2003.

The FTC staff report claims that drug companies entered into 28 potential pay-for-delay deals in FY 2011.  Emphasis on the word “potential“.  I think this report is idiotic and not because it has to do with complaining about patents.  It’s that this so-called study is completely flawed in its logic.  And, if there’s one thing patent attorneys hate, it’s the illogical.

Here’s the supposed data and the conclusions drawn from them, you be the judge:

The FTC looked at 156 final resolutions of patent disputes between a brand-name and a generic pharmaceutical makers. Out of the 156, they found the following:

1. 28 final settlements contain both compensation to the generic manufacturer and a restriction on the generic manufacturer’s ability to market its product;
2. 100 final settlements restrict the generic manufacturer’s ability to market its product, but contain no explicit compensation;
3. 28 final settlements have no restrictions on entry; and
4. of those 28 final settlements that contain both compensation and a marketing restriction, 18 involved generics that were so-called “first filers,” meaning that they were the first to seek FDA approval to market a generic version of the branded drug, and, at the time of the settlement, were eligible to exclusively market the generic product for 18 months.

So far, so good.  Up to this point, these are all just facts.  Now, look at the conclusion the FTC draws:

1. generic drugs help reduce costs for taxpayer-funded health programs such as Medicare and Medicaid.
2. generic drug prices are typically at least 20 to 30 percent less than the name-brand drugs;
3. patent settlements that include a payment or other compensation delay generic entry on average by 17 months longer than those that do not include a payment;
4. the 28 settlements involve 25 different branded pharmaceutical products with combined annual U.S. sales of more than $9 billion; and
5. prohibiting pay-for-delay settlements would reduce the federal deficit by $2.67 billion over 10 years.

Ipso facto, pay-for-delay settlements are at the root of the world financial crisis.  And global warming.  And maybe the war on Christmas.  Well, at least we know the government knows how to work a calculator.  What they lack (purposefully?) is an understanding that patent lawsuit settlements by there very nature are two sides coming up with terms that they can both agree on.

Both sides are for-profit entities with no interest in not making a profit.  Both sides are also being advised by presumably competent counsel.  The brand-name company believes its patent is perfectly valid but aware that anything can happen in litigation.  The generic company may well believe the patent is not valid but aware that anything can happen in litigation.  They have weighed the risks and rewards and decided on a settlement they can live with.

Yet, the FTC concludes that these settlement are wrong and are harming hard-working, God-fearing Americans.  Or, is it that the government really just needs to reduce the deficit and cutting drug costs sounds good?

“While a lot of companies don’t engage in pay-for-delay settlements, the ones that do increase prescription drug costs for consumers and the government each year,” said FTC Chairman Jon Leibowitz.  “Fortunately, Congress has the opportunity to fix this problem through the Joint Select Committee on Deficit Reduction — and save the government and American taxpayers billions of dollars.”

The FTC has challenged a number of these patent settlement agreements in court, contending that they are anti-competitive and violate U.S. antitrust laws.  The agency also has supported legislation in Congress that would prohibit pay-for-delay settlements that increase the cost of prescription drugs.

Inevitably, the FTC must make some difficult decisions about whether or not a particular patent settlement harms com­petition and should be challenged on antitrust grounds. But the broad conclusion that a settlement is anti-competitive if it includes compensation plus market restriction lacks a proper critical analysis.

At least you can like the FTC on Facebook.

A process which involves removal of a stem cell from a human embryo at the blastocyst stage, entailing the destruction of that embryo, cannot be patented.

Last week the Court of Justice of the European Union issued a judgment in the case of Brüstle v Greenpeace e.V (Case C 34/10) in which it banned the issuing of patents for stem cells on ethical grounds.  Mr. Oliver Brüstle is the holder of a patent for isolated and purified neural precursor cells produced from human embryonic stem cells used to treat neurological diseases.

The Federal Patent Court ruled that Mr. Brüstle’s patent was invalid in so far as it covers processes for obtaining precursor cells from human embryonic stem cells.  On appeal, the Court of Justice (CJEU) was asked to interpret the concept of ‘human embryo’ which is not defined in Directive 98/44/EC on the legal protection of biotechnological inventions.

The purpose of Directive 98/44 is to establish a framework for the legal protection of biotechnological inventions. Article 6(1) provides that inventions must be considered unpatentable where their commercial exploitation would be contrary to ordre public or morality. Article 6(2)(c) of the directive cites the use of human embryos for industrial or commercial purposes as an example of inventions which are considered unpatentable.

The question is whether the exclusion from patentability of the human embryo covers all stages of life from fertilization of the ovum or whether other conditions must be met, for example that a certain stage of development be reached.

The case raised very interesting legal and ethical issues, in particular how the right to human dignity related to the dispute. Although a fundamental right under German constitutional law and jurisprudence, the right to human dignity has been recognized as an unwritten principle of EU law, and undoubtedly played a significant part in the outcome of this case.

The Court was asked “What is meant by the term “human embryos” in Article 6(2)(c) of Directive 98/44 ?”  Directive 98/44 stipulates that patent law must be applied so as to respect the fundamental principles safeguarding the dignity and integrity of the person.  The question then is what form, what stage of development of the human body, must be given the legal categorization of ‘embryo’.

The development from conception begins with a few totipotent cells, which each cell has the capacity to develop into a complete human being. The Court viewed totipotent cells as representing the first stage of the human body and must therefore be legally categorized as embryos.

The Court emphasized that whether that categorization must be recognized from before or only after implantation is irrelevant.  This means that every totipotent cell, whatever the means by which it has been obtained, is an embryo and that any patentability must be excluded.  This definition covers unfertilized ova into which a cell nucleus from a mature cell has been transplanted.

The Court felt that characterizing a totipotent cell as an embryo does not resolve the issue since an embryo quickly develops into a blastocyst made up of pluripotent cells, which can develop into all kinds of cells to form all the organs of the human body. These cells cannot develop separately into a complete human being.  While the court felt that blastocysts as a whole must be categorized as an embryo, an individual pluripotent cells in isolation is not.

Most of the EU Member States take the view that pluripotent stem cells are not human embryos given that embryonic stem cells, taken in isolation, are no longer capable of developing into a complete individual.  However, the Court said it is not possible to ignore the origin of this pluripotent cell.  The pluripotent stem cell in the present case is removed from the blastocyst, which the removal will destroy. The argument is that patentability depends on the way in which it has been removed and the consequences of such removal .

In comparing the situation to prisoners killed in order to remove organs for trafficking, the Court reasoned that even though the claims under the patent did not specify that human embryos are used for the exploitation of the invention, when they actually are, the patentability of such an invention must be excluded.
While the Court agreed that inventions relating to pluripotent stem cells can be patentable if they are not obtained to the detriment of an embryo, the cells at issue are removed from the human embryo at the blastocyst stage and they necessarily entail the destruction of the human embryo.  The Court held that Article 6(2)(c) must be interpreted that a human embryo applies from the fertilization stage to the initial totipotent cells and to the entire ensuing process of the development and formation of the human body, which includes the blastocyst.

The use of human embryos for therapeutic or diagnostic purposes which are applied to the human embryo and are useful to it is patentable, but their use for purposes of scientific research is not patentable.

The Court interpreted Article 6(2)(c) of Directive 98/44/EC on the legal protection of biotechnological inventions as an invention must be excluded from patentability where the application of the technical process for which the patent is filed necessitates the prior destruction of human embryos or their use as base material, even if the description of that process does not contain any reference to the use of human embryos.

The exception to the non-patentability of uses of human embryos for industrial or commercial purposes concerns only inventions for therapeutic or diagnostic purposes that are applied to the human embryo and are useful to it.

The holding and reasons of the case means that inventions making use of deposited cell lines which had originally been obtained by destruction of an embryo within the broad meaning of an embryo are not patentable. This applies even if the origin of the cell line is not part of the claim in question.

If you read the ruling as saying that any invention based on human embryonic stem cells is unethical and therefore cannot be patented, then the ruling will have major implications for the commercialization of stem cell-based technologies in the EU, especially if it fosters the idea that stem cell research is inherently immoral.

It will take several years for the European Patent Office, national patent offices and various courts to take up the issue and interpret the decision. In one view, companies may end up relying on keeping manufacturing processes a trade secret instead of relying on patents since the European Medicines Agency keeps data submitted for regulatory approval private for eight years and blocks others from using this information for two additional years.

While the decision could spur development of therapies since it could free up ES cell research from patent infringement, it could still prove to be harmful since the far-reaching decision bans patents on any downstream products using cell lines that required the destruction of human embryos for violating respect for human dignity.

Read the judgment (in English) here.

As part of our Supporting Sponsorship of the BioOhio Annual Conference: 2020 Vision, we have one complimentary registration to share.

Just be the first person to send us your name and email address by 5:00 pm EST tomorrow, Oct. 19th, and we’ll get your registration fee taken care of on us! We think that’s pretty cool.

When

Thursday, October 27, 2011

Where

Embassy Suites Dublin, Dublin, Ohio, United States 43017

Fine Print

More info about the conference is found at the BioOhio site here.

The UK Patents Court invalidated patent claims to an enantiomer of a known racemate mixture in Generics Ltd. V. Novartis AG [2011] EWHC 2403 (Pat).

Generics (UK) Ltd. (Mylan) filed an action to try to invalidate a Supplementary Protection Certificate (“SPC”) for a drug for the treatment of Alzheimer’s disease called rivastigmine.  An SPC extends the life of a granted “basic patent” in certain circumstances beyond the date on which the patent would otherwise come to the end of its statutory term. Novartis markets rivastigmine under the trade name Exelon.

Rivastigmine is the name for the (-)-enantiomer of N-ethyl-3-[(1- dimethylamino)ethyl]-N-methylphenyl–carbamate. Earlier, scientists at the Hebrew University of Jerusalem, made and tested the unresolved racemic compound (RA7).  A racemate is an equimolar mixture of a pair of enantiomers.  RA7 was one of a number of compounds proposed for the treatment of AD, but the publications made no mention of resolving it into its individual enantiomers.

The sole question in this action is whether a relevantly skilled pharmaceutical development team would find it obvious in the light of the RA7 publications to resolve the racemic mixture of RA7 into its individual enantiomers.

Stereo-isomers or enantiomers have identical physical and chemical properties in every respect, except two. They differ in their optical properties (the direction in which they rotate the plane of polarised light) and they react at different rates with other chiral compounds. Since living systems contain chiral proteins and constitute a chiral environment, the chirality of compounds administered to humans is important in therapy.

Whether to resolve?

The Court dealt witht he question of whether or not one skilled in the art would have resolved the enantiomers from the racemic mixture.

Firstly, it was common ground that the skilled team would consider the question of resolution in relation to its lead compound or compounds taken forward for development. It could scarcely have been otherwise given the fact that, of the chiral medicinal compounds introduced in 1984 and 1985 (excluding semi-synthetic compounds where nature had produced an enantiomerically pure starting point) about 50% were racemates.

Secondly, it was common ground that the actual resolution of RA7 did not involve any problematic chemistry. RA7 is easily resolved into rivastigmine using a standard stereochemical resolving agent. Novartis did not seek to make anything out of the practical chemistry involved. They contended that the skilled team would be aware that resolution could, in some cases, represent a difficult task, and that this would make the skilled team reluctant even to attempt a simple resolution. Although I accept that questions may arise as to the extent of resources which a skilled team might be prepared to devote to difficult resolution, I am not persuaded that in 1987 the skilled team would be hesitant about seeing whether a chiral compound could be easily resolved.

Novartis argued that the skilled team would see no advantage in the present case in an improvement in potency.  However, the Court thought differently:

I am unable to accept that the skilled team would fail to see practical benefits in resolution. Firstly, there is the question of the metabolism of the compound. Whilst the very process of blocking the active site on the AChE results in a breakdown of the drug molecule, this is not the only metabolic process to which the drug might be subjected. Those drug molecules which do not interact with the target enzyme could be broken down by other enzymes, for example pseudo-cholinesterase, in a stereospecific way. Dr Newton was clear that metabolism was an area where there might (not would) be a stereochemical effect between enantiomers. Secondly, the skilled team would be aware that the process of penetration of the blood brain barrier could be stereo-selective. Thirdly, delivering a drug as a resolved enantiomer avoids the possibility of unknown, stereo-specific side effects emerging downstream.

Ultimately, the Court decided that the enantiomer was obvious in light of the racemic mixture:

I think the correct analysis is that a pharmaceutical composition for treatment of AD comprising rivastigmine was conceptually obvious in the light of Weinstock and would immediately occur to the skilled team. The team would consider that resolving RA7 would be a worthwhile step to take for good technical reasons. The team would find that the chemistry involved is trivial. Applying the principles outlined above I have no doubt that the inventive concept is obvious in the light of Weinstock.

I believe that conclusion to be consistent with the “problem and solution approach” employed by the Boards of Appeal. The objective technical effect demonstrated by the patent in comparison with the Weinstock prior art is simply that which one would expect from resolution of a chiral compound. The skilled person would know how to solve the problem of achieving those effects by an application of the common general knowledge about chiral compounds.