Live Blogging: Post-Trial Responsibilities Conference, Session 2

By Zachary Shapiro

Hello from the Post-Trial Responsibilities conference! I will be live blogging session 2: where speakers will be providing important perspectives on PTA. Barbra Bierer is monitoring the discussion.

We started with Richard Klein calling in from FDA:

Richard is talking about post-trial responsibilities. He points out that there is a justice issue here with ensuring access to health care and up to date interventions. He points out that while the FDA can encourage Post-Trial Access (PTA), it has no authority to require or ensure it. He points to moral authority, rather than legal. Foreign trials, however, are a different story, as the FDA has sway over protocol applications that are submitted in the US. Richard begins highlighting some specific considerations for protocol drafters and IRBs: particularly focusing on determining monitoring plans, as well as figuring out financial responsibilities for the provision of PTA.

He moves on to highlight that there is more of a moral obligation than a legal obligation. FDA is supportive of the provision of PTA. He believes that enthusiasm must be tempered, as there are situations when PTA is not appropriate. These include studies that have significant safety concerns, studies of bio-markers as well as validation studies that do not specifically examine safety and effectiveness. There are also situations where PTA is simply not feasible, particularly if additional drugs do not exist (one thinks of the recent Ebola treatment), if there is insufficient safety data, or if there is no practical capacity or resources to provide safety monitoring. We must also be aware of financial limitations, especially for start-up biotech firms that might not have deep pockets.

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Gilead Announces Access Program for Hepatitis C Drug

For all those who are interested in issues of global health, access to medicines, and drug pricing, yesterday Gilead formally announced its access program for enabling many developing countries to purchase its new Hepatitis C drug, Sovaldi, at low prices. This announcement is particularly noteworthy because Sovaldi represents a significant improvement over the current standard of care for Hepatitis C, as it can cure a much greater percentage of sufferers than could standard therapies, and it does so with many fewer negative side effects. Gilead’s partnership-based program will permit seven Indian generic drug companies to produce and sell the drug in 91 developing countries. The discounts are significant: although Gilead formally charges $1,000 a pill (or $84,000 for a course of treatment) for Sovaldi in the United States, it will charge just 1% of that, or $10 a pill, in India (the total cost there is estimated at $1,800, given the difference in strain prevalence).

The global health community has reacted to the announcement with mixed reviews. The 91 countries in the program include more than half of the world’s Hepatitis C patients. But tens of millions of other patients in large nations like China, Brazil, Mexico, and Thailand are left out of the program. Going forward, some of the excluded nations may seek to issue compulsory licenses in an effort to expand access to Sovaldi.

Gilead has also drawn fire in the United States for Sovaldi’s $84,000 sticker price (which, for various reasons, very few if any will actually pay), to the degree that members of both houses of Congress have asked Gilead to justify the price of the drug. Those opposing Sovaldi’s price have generally not come out publicly against the high price of many orphan drugs, which can cost $250,000-$350,000 per year. But because Hepatitis C afflicts about 2.7 million people in the US, as compared to the few thousand people with one of the relevant orphan diseases, its impact on insurers (both public and private) is likely to be much larger (as this very blog has previously noted).  Continue reading

Post-Trial Access and Responsibilities (and Upcoming Conference, Sept. 18 at HLS)

By Zachary Shapiro

Post-Trial Access (PTA) is emerging as an important topic in the design of ethical clinical trial protocols. PTA refers to the provision of study drug to the participants in a successful clinical trial (and maybe others) during the crucial period after a clinical trial phase is over, but before the drug is widely available or approved for the market (or maybe longer/in other circumstances). At issue is the question of the commitment a clinical trial sponsor owes the participants of their trial (and maybe others) in the period after a clinical trial phase, but before market approval of the tested pharmaceutical (or maybe longer).

While the provision of Post-Trial Access may seem to be an ethical “no-brainer,” there are numerous variables that make the decision of whether to provide PTA difficult. One major question is whether all arms of the trial deserve access to the therapy, even those who were on placebo or in the control arm. If the therapy tested shows less efficacy than a more or less expensive treatment modality, is there a responsibility to provide the more effective treatment, regardless of the cost? What if said therapy is far beyond the standard of care for the condition in the particular country where the trial took place? Furthermore, how long do PTA obligations extend? While the simple answer is that they end after market approval, the truth is that many drugs have long approval processes, with complicating factors that can result in significant delays. This is an even more difficult question if the trial is a multi-regional study, and takes place in a country where the sponsor does not intend to market the product.

The question of how to provide PTA also poses logistical issues, as many sponsor sites close after a clinical trial is finished. This can make provision of post-trial access extremely expensive, and perhaps unduly burdensome, especially if the trial is sponsored by a biotech start-up without the deep pockets of a large pharmaceutical company. These costs can skyrocket depending on whether we believe the sponsor should be responsible for costs that might result from improper use of the therapy, or failure of the participants to comply with proper treatment. Continue reading

Harvard Effective Altruism: an event today, Michael Kremer on Sept. 10, and a fellowship opportunity

A message from Harvard Effective Altruism:

On Saturday, Sept. 6 at 3pm in Sever 111, we are holding a giving game / donation discussion and an information session for Harvard students interested in our organization. We’ll explain what effective altruism is and what HCEA does here on campus. If you’re new to HCEA, you should definitely check it out!

Wednesday, Sept. 10 at 4:30pm in Science Center Hall A: Prof. Michael Kremer – a development economist at Harvard – will give a talk entitled “How can individuals reduce global poverty?” He’ll discuss the ways that individuals can use both their money and their careers to contribute to poverty reduction and international development.

All semester long! HCEA is hosting its third Philanthropy Fellowship program for Harvard undergrads and graduate students. Fellows will attend talks from speakers like Harvard professor Steven Pinker, Rob Mather of the Against Malaria Foundation, and Center for Applied Rationality president Julia Galef; learn about effective altruism at weekly dinners with other fellows and speakers; get to know likeminded students at discussions and social events; and fundraise for effective charities! You can find more information and apply on our website before 11:59pm on Sunday, Sept. 14th.

We hope to see soon! Altruistically yours,
Ales and John

Art Caplan: Is It Fair That Americans Received the Ebola Treatment?

Art Caplan has a new video on Medscape laying out the principles behind rationing limited supplies of experimental ebola treatments. As he explains:

I believe the answer to the question of who should receive the drug is: people we can both learn from and potentially help the most. I believe those are the 2 values we use when trying to ration access to an experimental drug. If we do not learn whether something is safe and effective, then we have missed an opportunity, even in the middle of an epidemic, to find out whether it is worth giving out drugs that are new, untested, and unapproved. People who should be included are those who can be observed and kept under surveillance — not for a day or a week but probably for months and years. That favors people who are not in rural villages. That favors people who will have access to hospital facilities. Those criteria will drive the selection of who receives a new, unapproved drug.

Click here to see the video and read more.

Ethics of experimental Ebola interventions

In “Ethical considerations of experimental interventions in the Ebola outbreak“, published yesterday by The Lancet, Zeke Emanuel and I discuss what we take to be the key ethical questions about the use of Zmapp and other investigational agents in the current Ebola epidemic. In essence, we argue that the national and international response to the epidemic should focus on containment and strengthening health systems, rather than experimental treatments and vaccines; that experimental interventions, if they are used, should be distributed fairly and only in the context of clinical trials; and that advance planning is needed for research in future Ebola and other epidemics, as well as for making any proven interventions against Ebola accessible in affected regions.

The full article is available open access. Be sure to check out the Lancet’s new Ebola Resource Centre as well, which includes many other interesting pieces and a podcast (access here podcast) covering—among other things—our paper.

Is it ethical to hire sherpas when climbing Mount Everest?

By Emily Largent

In “Is it ethical to hire sherpas when climbing Mount Everest?,” a short piece out today in the British Medical Journal, I suggest that the question of whether it is ethical to pay sherpas to assume risks for the benefit of relatively affluent Western climbers is a variant of cases–common in medical ethics–where compensation and assumption of risk coincide.  Consider offers of payment to research subjects, organ sales, and paid surrogacy.  As a result, medical ethics can offer helpful frameworks for evaluating the acceptability of payment and, perhaps, suggest protections for sherpas as we look forward to the next climbing season on Everest.

I owe particular thanks to Nir Eyal, Harvard Medical School Center for Bioethics and Harvard School of Public Health Department of Global Health and Population; Richard Salisbury, University of Michigan (retired); and Paul Firth, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital.

Take a look and let me know what you think.

Art Caplan: WHO Ethics Committee on Ebola Just a Start

Art Caplan has a series of new opinion pieces out on the WHO ethics advisory committee meeting that approved the use of experimental drugs to treat patients ill with Ebola.

He suggests deeper exploration of issues of informed consent, corporate responsibility, and resource allocation in this blog post for The Health Care Blog. As he writes in his piece in NBC News Health:

It is important that the WHO committee affirmed the morality of compassionate use. This addresses the concern that any use of unapproved drugs is inherently exploitative. But there are huge ethical issues that still remain unaddressed and unanswered regarding experimental interventions.

In the wake of the Canadian government’s offering 1,000 doses of an experimental Ebola vaccine to the stricken nations, he also extends the argument from allocation of treatment to allocation of prophylaxis in this opinion piece in NBC News Health:

It is ethically appropriate in the midst of a deadly contagious epidemic to try both untested treatments and experimental preventative vaccines that have shown some promise in animals and no safety issues. But with only 1,000 doses of vaccine available, who should get them? And what do they need to be told?

The most ethical way to distribute limited experimental vaccine, is, as the WHO ethics group noted, with an eye toward collecting information on safety and efficacy. Rather than just handing out vaccine to a small group of people in countries that have seen Ebola outbreaks, it is important to learn as much as possible about whether the vaccine has any efficacy in humans and is safe.

You can read more at the links above.

Art Caplan: Ebola Treatment Distribution is Troubling

Amidst news from Spain that a 75-year-old Catholic priest has received the experimental treatment ZMapp for Ebola, Art Caplan critiques what he describes as the “bad science” behind choosing its recipients:

ZMapp is not the answer to the Ebola epidemic ravaging West Africa. There is no chance of getting a significant amount of this drug made for many months. Deploying more health care workers, face guards, moon suits, gloves and antiseptic, along with restrictions on travel and burying the dead, is the only way to get the epidemic under control. [...]

The fact that a 75-year-old has been given the scarce drug is especially disturbing, not because he is 75 but because 75-year-olds do not have strong immune systems — something very important in battling a virus like Ebola. Moreover 75-year-olds often have other medical problems that complicate the ability of scientists to figure out if the drug is safe and if it is really working.

In testing unapproved, highly risky drugs like ZMapp, it is crucial that recipients not be so sick that they may well die regardless of whether they get the drug or not. Indeed, the recipients ought not be very sick so that side-effects can be seen and efficacy determined. To do that, doctors need to be able to monitor experimental subjects for months to make sure the drug does not damage their livers or cause any other fatal side-effect. So not every person infected with Ebola makes for the best recipient — younger, those more recently infected and those who can be closely monitored are among the “best” candidates.

You can read more of Art Caplan’s perspective on NBC News Health here.

Ebola, Ethics, and the WHO Getting to Yes

Earlier this week, the World Health Organization, responding both to the international outcry over the rapidly rising number of Ebola cases and deaths across sub-Saharan Africa (and critiques of the speed of their action), and the news that western health care workers and ministry had found ways to get access to the untested-in-humans Ebola drug ZMapp, convened a panel of ethicists to offer recommendations on more widespread use of experimental Ebola treatments.

The issues considered by the ethicists included:

1) Whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis. If it is, what criteria and conditions need to be satisfied before they can be used?

2) If it is ethical to use these unregistered interventions in the circumstances mentioned above, then what criteria should guide the choice of the intervention and who should receive priority for treatment or prevention?

Continue reading

Art Caplan: Why do two white Americans get the Ebola serum while hundreds of Africans die?

As the WHO announced today that medical ethicists will convene next week in New York to discuss the use of experimental medicines in the West African Ebola outbreak, Art Caplan has a timely new opinion piece in the Washington Post asking why only white American victims of the Ebola outbreak have been treated with an experimental serum. Caplan argues that the decision was a question of economics:

The reasons for different treatment are partly about logistics, partly about economics and, partly about a lack of any standard policy for giving out untested drugs in emergencies. Before this outbreak, ZMapp had only been tested on monkeys. Mapp, the tiny, San Diego based pharmaceutical company that makes the drug stated two years ago: “When administered one hour after infection [with Ebola], all animals survived…Two-thirds of the animals were protected even when the treatment, known as Zmapp, was administered 48 hours after infection.”

But privileged humans were always going to be the first ones to try it. ZMapp requires a lot of refrigeration and careful handling, plus close monitoring by experienced doctors and scientists—better to try it at a big urban hospital than in rural West Africa, where no such infrastructure exists. [...]

But it’s about more than logistics. Drugs based on monoclonal antibodies usually cost a lot—at least tens of thousands of dollars. This is obviously far more than poor people in poor nations can afford to pay; and a tiny company won’t enthusiastically give away its small supply of drug for free. It is likely that if they were going to donate drugs, it would be to people who would command a lot of press attention and, thus, investors and government money for further research—which is to say, not to poor Liberians, Nigerians or Guineans. [...]

To get Caplan’s full perspective, read the full article.

Art Caplan: The Real Reasons for Worrying About Ebola

Art Caplan has a new opinion piece on NBC News responding to the recent media coverage of Ebola. He makes the case that although this has been the worst recorded outbreak of the disease, citizens of developed countries have little reason to panic:

Ebola is not going to run amok in downtown Boston, Cape May or Myrtle Beach or anywhere else in the U.S. It is running amok in poor African nations because local authorities did not have the will or the resources to respond quickly, because no one confronted local funeral customs that expose people to Ebola, mainly because the world did not care much if hundreds died in poor, politically insignificant nations.

The harsh ethical truth is the Ebola epidemic happened because few people in the wealthy nations of the world cared enough to do anything about it.

Read the full article.

Good news for many South African HIV patients—with a big glitch

On Wednesday, South African Health Minister Aaron Motsoaledi announced that, as of January 2015, HIV-positive patients in the country would start receiving free antiretroviral treatment once their CD4 count fell below 500, instead of current threshold of less than 350. Some patient groups would start receiving antiretrovirals immediately upon being diagnosed with HIV infection, regardless of their clinical stage.

Last month, Till Bärnighausen, Dan Wikler and I predicted in PLoS Medicine that sub-Saharan nations would move in the direction that South Africa is now moving, and pointed out a big complication. This policy change might make several gigantic trials of so-called treatment-as-prevention in sub-Saharan Africa impossible to complete successfully. As we explained, these trials remain important for assessing the potential of treatment-as-prevention to curb the spread of HIV in general populations (with many different relationship types and different levels of care delivery and support).

In treatment-as-prevention, antiretrovirals are offered to patients immediately upon their diagnosis with HIV. The hope is that very early treatment would be better for these patients and prevent them from infecting others. We also offered some ways out of this mess, but they involve untraditional approaches to research conduct and to policy. Our piece was featured in the June issue of UNAIDS’ HIV This Month.

The Right to Health at the Public/Private Divide: A Global Comparative Study

In the U.S., the right to health is often held up as a utopian legal principle that other countries manage to embrace and that we shortsightedly spurn.  What I learned working on a new project is that the right to health does not always lend itself to admirable ends.  In some countries, a formal right to health is not used to advance equity but rather for the opposite.  In other words, having a right to health can lead to a less equitable distribution of health care resources because, for example, people who are better able to navigate the legal system can claim more resources for themselves.

This insight and others are featured in an excellent book that just came out from Cambridge Press, The Right to Health at the Public/Private Divide: A Global Comparative Study, edited by Colleen M. Flood, University of Toronto, Faculty of Law and Aeyal Gross, Tel-Aviv University, Faculty of Law.  This book is worth reading, in part, because it features chapters on countries that are not the usual suspects, including Hungary, Venezuela, Nigeria, New Zealand, and Taiwan.  Two of the chapters are by U.S. health care scholars: one I wrote on the U.S. system and the Affordable Care Act (A Vision of an Emerging Right to Health Care in the United States: Expanding Health Care Equity through Legislative Reform) and one Christina Ho wrote on China (Health Rights at the Juncture between State and Market: the People’s Republic of China).

In my chapter, I argue that while the U.S. does not have a formal right to health, the ACA could provide the vision and foundation for an evolving American conception of a right to health care.

High Noon for Population-Wide Mammography Screening?

By Prof. Dr. med. Dr. phil. Nikola Biller-Andorno

Director, Institute of Biomedical Ethics, University of Zurich, Switzerland

Safra Network Fellow, Harvard University (13-14)

Visiting Professor, Div. Medical Ethics, Harvard Medical School (12-14)

It is amazing how much heat a report can draw that simply states what has been all over town for some time now: We do not know if mammography screening does more good than harm, we do not even know for sure if it does any good at all.

The Swiss Medical Board, an independent health technology assessment initiative that was started in 2008, stated that based on the empirical data availability the introduction of mammography screening all over Switzerland could not be recommended.

As could be expected the report drew fire. Curiously, one of the chief complaints was that it was “unethical” to upset women who might no longer know if screening was good for them or not.

This sounds just a little bit paternalistic – particularly given that we know that most women seriously overestimate the benefits of screening when making their decision, a point that my colleague Peter Juni and myself illustrate in a Perspective piece published on May 22, 2014 in the New England Journal of Medicine.

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What Should Customers Do About Dirty Practices of Big Companies?

The video “Who Pays the Price? The Human Cost of Electronics” recently went viral on social media. It purports to document the suffering of former workers of Chinese electronics factories that supply smartphones to big brands. According to the video, these workers contracted serious occupational illnesses such as cancer and severe nerve damage as a result of exposure to the toxic chemicals benzene and n-hexane. The workers are said to be unaware of the fatal risks; and in any event, many would be too young to consent. The film calls for elimination of toxic chemicals in electronics factories, which it claims can be done at a negligible cost.

Watching this video and learning about this problem, are we, the customers, now under a duty to act?

For instance, in an effort to convince Apple to remove toxic chemicals from their factories, the “Bad Apple” campaign asks customers to sign a petition, call the brand, and maybe re-consider upgrading their phone less often. The campaign targets Apple because of its powerful position in the public eye as well as in the industry, which currently lacks any toxin-free option.

The question is: What is the morally right response of a customer? To put it in more detail, are you morally required to take action? If so, is signing the petition or calling the brand sufficient or should you, for example, boycott the brand?

Here is the answer: You are probably right to do anything, including nothing. Continue reading

WEDNESDAY, 4/23: Reforming Brazilian Pharmaceutical Patent Policy

Reforming Brazilian Pharmaceutical Patent Policy: Lessons from the Past and the Road for the Future

April 23, 12:00pm 

Wasserstein Hall 1010, Harvard Law School, 1585 Massachusetts Ave.

In this lecture by Pedro Paranaguá, he will discuss the report issued by the Brazilian House of Representatives in 2013 as part of an effort to revamp the country’s patent law. Brazil does not want to be a mere exporter of commodities, neither does it want to be a simple consumer of knowledge goods. Brazil wants to be at the cutting edge of innovation; it wants to innovate to compete. Paranaguá’s presentation will introduce the current state of affairs of the Brazilian patent system, with a focus on pharmaceuticals. He will present the main findings and recommendations of the 2013 report, including the tabling of a bill to fix the mistakes of the 1990s.  The talk will be followed by discussion with a panel of experts. Panelists include:

  • Brook K. Baker, Professor of Law, Northeastern University School of Law; Policy Analyst for Health GAP (Global Access Project)
  • Benjamin N. Roin, Hieken Assistant Professor in Patent Law, Harvard Law School; Co-Director, Petrie-Flom Center for Health Law Policy, Biotechnology & Bioethics; Associate Member, Broad Institute

Pedro Paranaguá has been a Lecturer in Law at the LL.M. in Business Law at Fundação Getulio Vargas (FGV), Brazil, since 2007. Mr. Paranaguá is also the lead Advisor to the ruling Workers Party at the Brazilian House of Representatives for Internet, copyright, patent, data privacy, cybercrime, and related matters. He is responsible for drafting the Brazilian Internet Framework Bill (“Marco Civil”) for the rapporteur, including provisions on net neutrality, ISP liability, and privacy. He coordinated the 350-page report, “Brazil’s Patent Reform,” for the Brazilian House of Representatives. He has been an invited instructor at Duke University School of Law (2011), lecturer in law at FGV Rio, and has held numerous other lectureships in Brazil and abroad (Lecturer in Brazil and abroad (Brazil’s Supreme Court and Senate, Yale, UCLA, UNESCO, UNCTAD, WIPO). He was Director of the A2K Brazil Program at the Center for Technology and Society (CTS-FGV), and co-representative of Creative Commons in Brazil (2005-2010). He produced commissioned studies on copyright and technology for the country’s Culture Ministry, and served as FGV-delegate at the World Intellectual Property Organization (WIPO) in Geneva (2005-2009). He has also served as a member of the Brazilian Free Software Project. From 2001 to 2003, he was an IP lawyer at Gusmão & Labrunie, where he was Project Manager on patents and access to medicines. He is the author of the books Copyright Law (Portuguese) (with Sergio Branco) andPatent Law (Portuguese) (with Renata Reis). Mr. Paranaguá holds a LL.M. (cum laude) in Intellectual Property, Internet and Policy (London) and is a Doctoral candidate (S.J.D.) at Duke University School of Law, where he is finalizing his thesis, “Brazil’s Copyright Law Reform: Tropicália 3.0?”, under the supervision of Professor Jerome Reichman.

Sponsored by the HLS Brazilian Studies Association, with support from the Petrie-Flom Center.

Art Caplan on “Pediatric Euthanasia in Belgium: Disturbing Developments”

Art Caplan has coauthored a new piece in JAMA on problems with Belgium’s new law allowing terminally-ill children and their families to choose euthanasia. From the article:

The Belgian pediatric euthanasia law seeks to respect the moral status of children as agents who possess the nascent capacity for self-determination. Specifically, the law requires the medical team to demonstrate a patient has the “capacity for discernment,” indicating that he or she understands the consequences of a choice for euthanasia.

What the law does not consider, however, is that adults choose euthanasia for reasons that go beyond pain. For adults, the decision to end their life can be based upon the fear of a loss of control, not wanting to burden others, or the desire not to spend their final days of life fully sedated. These desires might be supported by the experience they have had witnessing a loved one express a loss of dignity or because they understand what terminal sedation is and wish to refuse it. Children, however, lack the intellectual capacity to develop a sophisticated preference against palliative interventions of last resort. Instead, in the case of the new Belgian law, children seem to be asked to choose between unbearable suffering on the one hand and death on the other.

This possibility causes the Belgian euthanasia law to fall short of the standard required for valid assent. The criterion related to the “capacity for discernment” runs the risk of ignoring the fact that children and adolescents lack the experiential knowledge and sense of self that adults often invoke—rightly or wrongly—at the end of their lives.

Read the full article.

The Future of “Country of Origin” Labeling Regulations

By Ching-Fu Lin

The U.S. Court of Appeals for the District Columbia Circuit recently ruled against the meat industry’s challenge to stop the United States Department of Agriculture’s (USDA) implementation of the amended Country of Origin Labeling (COOL) rules.  The current COOL regulations (amended in May 2013) require retailers to identify several types of information on beef, pork, and poultry products that were previously not required.  It now requires labeling of the country where the animals were born, raised, and slaughtered along with the prohibition of the commingling of meat muscle cuts from different origins.

The old and less stringent version of the COOL regulations was published in 2009 by the USDA’s Agricultural Marketing Service (AMS) based on the 2008 Farm Bill (Food, Conservation, and Energy Act of 2008) amending the Agricultural Marketing Act of 1946.  In the same year, Canada and Mexico brought a case in front of the World Trade Organization (WTO) Dispute Settlement Body (DSB), arguing that the old COOL requirements violated relevant WTO rules.  The WTO DSB found that the old COOL requirements were inconsistent with the US’s obligations under Article 2.1 (national treatment principle) of the WTO Agreement on Technical Barriers to Trade (TBT Agreement) as well as Article X:3(a) (uniform, impartial, and reasonable administration) of the General Agreement on Tariffs and Trade (GATT 1994).

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Liveblog of 4/2 panel in European Bio-patent Law, Part III

Third up is Dr. Maaike van der Kooij, discussing medical use claims at the EPO.

In general, methods of medical treatment aren’t patentable under Art. 53(c) of the EPC, but the way around is to claim a relevant product either for medical use (if the substance is known but not medically used (Art. 54(4)) or for a specific medical use (Art. 54(5)).  (From my point of view, this seems like another way that the EPO is trying to address its innovation mandate by working around what appears to be pretty clear language in the EPC, a pattern which we certainly see in the US in both PTO and Federal Circuit practice). Continue reading