I-MAK's Quest To Trim The Biopharmaceutical Patent Thicket
By Ben Comer, Chief Editor, Life Science Leader
How long should a new drug be protected against lower- cost generic or biosimilar competitors? Established patent law provides an answer, and mechanisms exist in the U.S. to challenge patents believed to be invalid, unduly broad, obvious, or otherwise problematic. However, members of the American public — commonly known as patients, caregivers, and others without a direct business interest at stake — do not have meaningful channels for challenging patents that effectively determine drug access and affordability, a situation that the Initiative for Medicines, Access, and Knowledge (I-MAK) is fighting to change.
“We believe the patent system can work; what we are against is patent abuse,” says Priti Krishtel, cofounder and co-executive director at I-MAK and a 2022 MacArthur Fellow. “It is time for an honest national, and global, conversation about the period of exclusivity that the industry is trying to get. Hiding behind patent manipulation is eroding the integrity of the patent system, which has negative effects on scientific progress and negative effects on healthcare costs and access to medicines.”
It’s an argument that certain leaders in the biopharmaceutical industry have supported. Jeremy Levin, chairman and CEO at Ovid Therapeutics and former BIO board chairman, told Life Science Leader in 2019 that “perpetual franchises are the enemy of innovation, and these need to be called out.” Protecting old drugs through incremental patents is not the way to stimulate innovation, continued Levin, adding that “companies should be using their cash flow to drive innovation to replace the older products rather than spending money to litigate with the intent to secure a perpetual franchise.”
There is no shortage of ideas about how to improve the function of the United States Patent & Trademark Office (USPTO). Examples that I-MAK supports include opening lines of communication between the FDA and the USPTO, making Patent Trial and Appeal Board (PTAB) rulings more transparent, and providing legal standing in the courts to American patients struggling for survival. But without amending current law and making significant policy changes to the way the USPTO makes decisions about drug patents, it is hard to imagine that a majority of publicly traded biopharmaceutical executives will start to leave money on the table and walk away from available IP protections in the name of better access and lower prices for consumers. Don’t public company leaders have a fiduciary responsibility to maximize shareholder value, as Martin Shkreli once opined, as long as they are operating within the existing legal framework? (Shkreli’s conviction on securities fraud and conspiracy, as a reminder, was not related to raising the price of Daraprim by 5,000%.)
Money Talks
The problem with the existing legal framework, says Tahir Amin, cofounder and co-executive director of I-MAK, is that large corporations have made it bend to their will. “If you have deep pockets, you can shape the law in many different ways.” Amin, who in the 1990s and early 2000s worked in private practice in the U.K. as an IP attorney, saw firsthand how large corporations pressure patent laws over and over again until “by attrition, you get the law that you want.” Last summer, a bipartisan group of six U.S. senators sent a letter to USPTO Director Kathi Vidal decrying patent thickets’ ability to harm competition. “In the drug industry, with the most minor, even cosmetic, tweaks to delivery mechanisms, dosages, and formulations, companies are able to obtain dozens or hundreds of patents for a single drug. This practice impedes generic drugs’ production, hurts competition, and can even extend exclusivity beyond the congressionally mandated patent term,” the letter said.
The number of patents protecting many of the best-selling drugs in the world has indeed ballooned in recent years. In an analysis of the patents supporting the top 10 best-selling drugs in the U.S., published in September 2022, I-MAK found that drugmakers filed more than 140 patents on average per drug, and that on average, 66% of those patent applications were filed after the drug received FDA approval. Compared with Europe, four times as many patents were granted in the U.S. across the top 10 best-selling drugs. Those patent thickets translate into very real dollars: Primary patents for Humira, the best-selling drug of all time, expired in 2016, but the first biosimilar version of Humira didn’t enter the U.S. market until earlier this year. Between 2016 and the launch of the first biosimilar, Humira earned roughly $100 billion, or two-thirds of its all-time total U.S. sales, according to the I-MAK analysis.
It’s easy to point a finger at biopharmaceutical companies that successfully prevent generic or biosimilar competition, sometimes for years, using aggressive IP strategies and pay-for-delay tactics. Amin admits to a degree of sympathy for biopharmaceutical CEOs, given the financialization of the industry, including constant market pressure from Wall Street and shareholders to deliver growth quarter after quarter, year after year. “But when you think about the fact that 34 million Americans know someone who died because they couldn’t afford a prescription, that is not an outcome that CEOs want, but that is what is happening,” he says. “The conversation that we need to have now is, how much is enough to sustain your R&D programs so that you can develop new drugs?”
Finding the right balance between extending patents through additional indications or making incremental improvements to products — which benefit some patients but also can create access and affordability issues for others — versus investing in the development of new innovative drug candidates is a challenge for the industry. There are clear benefits, in terms of cost and risk, to building out existing products. “I am concerned that companies aren’t focusing on real R&D; they are instead focusing on life cycle management strategies,” says Amin. “They find a winner, and then milk it until they can milk it no more.” The challenge, boiled down, is in balancing patient access and affordability with an obligation to shareholders. As a nonprofit organization, I-MAK’s priority is patients.
Gaining Visibility
Similar to what the Institute for Clinical and Economic Review (ICER) has done to influence drug pricing practices in the U.S. by setting a benchmark price for drugs that a growing number of insurers incorporate into drug formulary decision-making, I-MAK is exerting its influence on the drug patenting system. I-MAK’s Drug Patent Book database, its reports on top-selling drugs and the patent thickets that back many of them, and its policy “blueprint for reforms” have been cited by a growing number of national media outlets and Congressional investigations. Last year, the New York Times Editorial Board endorsed I-MAK’s proposed reforms to the patent system.
Founded by Krishtel and Amin in 2006, I-MAK began in India, advocating for patent reform and access to HIV drugs. Before that, Krishtel worked at the Lawyers Collective, an NGO advocating for patients and public health in the context of shifting patent law under the World Trade Organization’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). Krishtel met Amin in 2004, and with the help of scientists and other experts — notably Dr. Joseph Fortunak, a professor of chemistry and pharmaceutical sciences at Howard University — succeeded in challenging patents and improving access to HIV drugs in India, which in turn improved access to HIV medications across the Global South.
I-MAK’s experience in India opened Krishtel’s and Amin’s eyes to similar issues in Brazil, Argentina, Thailand, South Africa, and Ukraine. By the time I-MAK set its sights on the U.S. patent system, it was already working in 50 countries. In its early days, I-MAK sustained itself through consultancies with organizations like the World Health Organization and the Clinton Foundation, among others, performing tasks like global patent landscaping and identifying where specific patents exist in different countries. Amin served as an intellectual property advisor to the European Patent Office and UNITAID. I-MAK also received seed funding from the Echoing Green Foundation, a group that provides early-stage funding for social entrepreneurs. When I-MAK focused its work on the U.S. in 2016, it found a system with “less openness, less transparency, and less access to justice than any other country we’ve worked in,” says Krishtel. “In the U.S., there is no legal standing for patients to challenge patents in court, and it is prohibitively expensive to file patent challenges at the USPTO.” Outside of the U.S., Krishtel and Amin had witnessed the power of patient access to patent information, combined with an understanding of patent law, as well as partnerships with lawyers and patent agents as a means for broadening drug access and reducing prices.
Participatory Changemaking
To bring public participation and new voices into USPTO decision-making, I-MAK started a program called “participatory changemaking,” which Krishtel describes as building a table for people who are not politically or ideologically aligned to get together and discuss specific policies. “It’s very rare for patients or affected communities to sit down together with policymakers, and it’s just as rare for someone at the USPTO to sit down with people from other government agencies, like the FTC or FDA.” Amin says I-MAK works with organizations including T1International (a type 1 diabetes advocacy group), the National Multiple Sclerosis Society, and Patients For Affordable Drugs, among others, that understand the need to learn policy and participate in order to improve drug access and affordability.
During a listening session on interagency collaboration held by the FDA and USPTO in February, Amin says the extent of public participation, in the form of comments and testimony on how the patent system affects various communities, was powerful. “It was interesting to see how the industry responded to that, because usually they occupy these spaces by themselves.”
Collaboration between the FDA and USPTO on patent decisions hasn’t formally existed in the past, but a Biden administration executive order on Promoting Competition In The American Economy signed in July of 2021 aims to create channels of communication between the two agencies. This is important, says Amin, because drugmakers must provide certain information to the FDA as part of the development process. For example, small molecule drugs must demonstrate stability related to crystalline forms, or polymorphic forms. “If you think about a drug like Celgene’s Revlimid, that information is required prior to the clinical trial stage,” says Amin. Revlimid was approved in 2005 and was working through the investigational drug stages at least five years prior. “Some of the stability data in polymorphic forms was likely known by the FDA in 1999,” he says. “Yet Celgene waited five years to file for that patent, and as a result, today we do not have full generic competition, and we won’t until 2026.” Amin says the industry argument is that early testing data is confidential. “But if you have a trade secret, sit on it for five years, and then file a patent, you are getting your cake and eating it too.”
Near-Term Agenda
I-MAK is engaged on several issues related to how the PTAB operates, with the overarching goal of making PTAB challenges more accessible to the patients impacted by its decisions. One of I-MAK’s blueprint for reforms singles out issues such as the rising number, since 2017, of “discretionary denials” on procedural grounds; the limited scope of options available under Inter Partes Review (IPR) challenges compared with post grant review patent challenges; and the opacity of the FDA’s Orange Book, a compendium of information about approved products.
Krishtel and Amin say that I-MAK’s top priorities in the near term, aside from driving public participation in the system generally, are for the USPTO and FDA to make good on the executive order on promoting competition, which can help to trim existing patent thickets. Both agencies “have a lot of space in their rulemaking capabilities to curb some of those practices,” says Amin. “Unfortunately, my concern is that the can will be kicked down the road.” That concern comes in part from FDA’s foot-dragging on the Orange Book Transparency Act of 2020, which aims to clarify what patent listings should and should not be allowed, says Amin. “They ended up kicking the can down the road for a few more years.”
Regarding the potential impact of the Inflation Reduction Act on promoting patient access and affordability, Amin notes that the price negotiation provision, which would impact certain top-selling single-source drugs (small molecule drugs after nine years, biologics after 13 years), essentially tries to accomplish with pricing what the Hatch-Waxman Act and the Biologics Price Competition and Innovations Act tried to accomplish through patent law. While those laws did establish pathways for generic and biosimilar market entry, drugmakers have successfully shielded some products from competition after those time frames have elapsed.
“Will companies start changing some of their licensing deals, such as opening up the market sooner for limited distribution of generics or biosimilars, as a way to avoid having their drugs negotiated by Medicare?” Amin says that generics and biosimilars companies are also at fault in pay-for-delay deals, since they make money, too, by keeping more affordable options off the market. “That’s where our antitrust laws are toothless, but there is a movement in the antitrust community to fix this truly anti-competitive behavior.”
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Tomorrow’s Advocacy Leaders
In May, Priti Krishtel announced that she would transition out of her current role at I-MAK and serve on its board of directors. Amin will continue as CEO, and Krishtel will continue to help build platforms for tomorrow’s leaders. During the COVID-19 pandemic, Krishtel says she spent more time with young people who are interested in access and affordability of medicines, as well as questions of ethics and equity in science and technology policy. How does she identify a new leader in the making? “I don’t really look for specific characteristics in young people; my approach is to create opportunities and platforms for people to step into,” she says. Krishtel looks for opportunities to put young activists in the spotlight, handing a microphone, for example, to Sernah Essien, a young activist, during an interview with NBC News.
Sharing opportunities helps create the next generation of leaders, a lesson Krishtel learned during her first week on the job with the Lawyers Collective in India, when her boss sent her to an international meeting hosted by the United Nations to present the organization’s multiyear research on trafficking and HIV/AIDS. “I’ve never crammed so hard in my life, but I also learned so much and gained so much confidence from being given the opportunity,” says Krishtel. “It taught me a lot, and I try to open those doors for young people now at this stage of my career.”