We need a Public Domain Day for drug patent expirations

“This Jan. 1, readers, archivists, and creatives in the United States celebrated a special holiday: the largest Public Domain Day in 21 years. The legal ownership of hundreds of works of classic literature — this year including well-loved Robert Frost poems like “Nothing Gold Can Stay” and “Stopping by Woods on a Snowy Evening” — was transferred into the hands of the people.

We suggest a plot twist: Let’s celebrate the same way when drug patents expire.

Every year, patents on high-profile branded drugs expire and these compounds “go generic,” allowing competitors to make and sell these same treatments at lower prices. Unlike literature, where copyright protection can last a whopping 95 years or more after initial publication, most drugs are under patent protection for just 10 to 15 years. Companies that successfully bring a drug to market have only that time to charge high prices before the drug goes generic. Patent protection is their window to profit from their investments and to plow some of that money back into developing new treatments. This system of incentives keeps the biotechnology innovation engine churning, rather than allowing it to milk cash-cow drugs forever….

Public Domain Day is clearly something to celebrate. The expiration of a copyright on a literary work merits a moment to admire its beauty, contemplate our gratitude to its creator, and mark the place it has held and will continue to hold in our collective human story.

 

We should do the same when branded drugs enter the public domain. These therapies keep working just as well as before, but they become much less expensive. In the case of oral drugs, there’s an average 90 percent drop in price within a few years as multiple generics come into the market. By anticipating when a branded drug is set to enter the public domain and publicizing the date as it approaches, the public might not only show innovators that they are appreciated but also apply some healthy social pressure to let them go generic with grace, instead of tying up patent expirations in complicated legislative battles that delay the entry of generics. In short, we need a Public Domain Day for drugs….”

For Innovation, Open Science Means Open for Business | Centre for International Governance Innovation

“Last week, Celgene – an American biotech company – invested the most ever for a Canadian-discovered early-stage drug. The US$40-million down and potentially US$1-billion deal only came about because of strategic funding by governments both for “open science” partnerships and for risk-taking, IP-generating research and commercialization centres. Open science partnerships openly share data and research results with the scientific community and do not seek patent rights over their results.

The Celgene deal is the fruit of a new innovation path – from open science to Canadian IP – that involves the Ontario government-funded Ontario Institute for Cancer Research (OICR) and its commercialization partner, FACIT Inc. This “made in Canada” approach does not copy U.S. approaches, which commonly result in Canadian IP rights being transferred to foreign firms for pennies on the dollar, as we are doing in the cases of Sidewalk Labs and investments in artificial intelligence. Rather, it leaves the IP in Canada for much longer, within a locally owned company that will continue to develop the drug and conduct clinical trials here, and thus extract fuller scientific and economic value from our investments….

Five years ago, OICR embraced open science as an early innovation strategy and partnered with the SGC. Both OICR and SGC appreciated that although IP is a key pillar of the innovation economy, seeking it too early or by the wrong entity creates barriers to collaboration, leads to redundant research, introduces significant transaction costs and, perhaps counterintuitively, slows down innovation. The open science collaboration allowed knowledge, materials and data to flow freely and enabled OICR and SGC to develop a new chemical probe against the WDR5 protein and to share it freely and rapidly with research groups around the world. Those groups revealed WDR5’s therapeutic role in leukemia, breast cancer and neuroblastoma….”

Ultra-large library docking for discovering new chemotypes | Nature

Abstract:  Despite intense interest in expanding chemical space, libraries containing hundreds-of-millions to billions of diverse molecules have remained inaccessible. Here we investigate structure-based docking of 170 million make-on-demand compounds from 130 well-characterized reactions. The resulting library is diverse, representing over 10.7 million scaffolds that are otherwise unavailable. For each compound in the library, docking against AmpC ?-lactamase (AmpC) and the D4 dopamine receptor were simulated. From the top-ranking molecules, 44 and 549 compounds were synthesized and tested for interactions with AmpC and the D4dopamine receptor, respectively. We found a phenolate inhibitor of AmpC, which revealed a group of inhibitors without known precedent. This molecule was optimized to 77 nM, which places it among the most potent non-covalent AmpC inhibitors known. Crystal structures of this and other AmpC inhibitors confirmed the docking predictions. Against the D4 dopamine receptor, hit rates fell almost monotonically with docking score, and a hit-rate versus score curve predicted that the library contained 453,000 ligands for the D4 dopamine receptor. Of 81 new chemotypes discovered, 30 showed submicromolar activity, including a 180-pM subtype-selective agonist of the D4 dopamine receptor.

Ultra-large virtual molecular libraries throw open chemical space

“A paper published this week demonstrates the power of ultra-large virtual libraries in helping researchers to look into the unknown (J. Lyu et al. Nature https://doi.org/10.1038/s41586-019-0917-9; 2019). In it, the authors built a virtual library of around 350 million drug-like molecules. They used this to simulate the ways that these molecules could interact with two therapeutically relevant proteins — AmpC ?-lactamase, a target for antibiotics, and the D4dopamine receptor, linked to several neurological disorders and a member of the pharmacologically important family of G protein-coupled receptors….

After this virtual screening, the team synthesized the top-scoring compounds and tested them against the two targets. One of the compounds turned out to be the most potent inhibitor of AmpC ?-lactamase known, and is chemically distinct from all other known inhibitors.

 

Of the 500 or so molecules the group made that targeted the D4 dopamine receptor, one had an unprecedented ability to stimulate it. This compound’s selectivity over other dopamine receptor types, and its preferential activation of the G protein signalling pathway, are both important properties that might help to minimize unwanted side effects when, and if, it’s used as a drug….”

Richard Smith: Pharmaceutical companies follow public funders of research in efforts to reform science publishing – The BMJ

Funders of research are the one group who have the power to change the slow, inefficient, old-fashioned, wasteful, arbitrary, and, some would say, iniquitous way that we publish science. About half of biomedical research is funded by pharmaceutical companies, but they have been much slower than public funders of research to use their influence. Open Pharma, which “works with pharma to drive fast and transparent medical publishing,” is encouraging pharmaceutical companies to use their influence more. The group met last week and discussed promoting open access and finding ways to link together the material on particular issues—perhaps a single clinical trial, a drug, or a disease—that currently is widely scattered and hard to find. (I chaired the meeting: see conflict of interest statement below.)

On the day of the meeting only one pharmaceutical company—Shire had mandated open access for the research it funds, whether undertaken by its employees or outsiders. Indeed, remarkably it seemed to be the only for-profit company to have done so—despite hundreds, probably thousands, of public bodies having mandated open access. (The day after the meeting another pharmaceutical company, Ipsen, also mandated open access.) One ironic reason for pharmaceutical companies being so slow is that they are heavily regulated and uncertain how regulators will view mandatory open access….

We agreed that for a patient, researcher, reviewer, or journalist it could be useful to have all the material together, and for a funder, including a pharmaceutical company, it would be good to be able to easily access all material related to research it had funded. There was also a hope expressed at the meeting that ensuring all material was available would increase trust in pharmaceutical companies.

At the moment, six major pharmaceutical companies are part of Open Pharma, along with six publishers—and the hope is that more may join and that the companies can work with public funders of research in improving the publishing of science.”

Making Evidence Affordable: Get Ready For The Citizen Science Revolution

“Take the most rigorous study possible – a large double blind clinical trial. It can cost tens of millions of dollars to conduct such a trial, and (depending on what assessment is being conducted) take years of bureaucratic wrangling to complete.

This creates (some would argue by design) a “monopoly of proof,” leaving billion dollar companies among the few who can (quite literally) afford to prove their products work.

So how does a new wellness product company provide solid evidence that their products are the real deal?…

Every purchaser of Qualia Mind or Qualia Focus gets free access to the assessment tools from Cambridge Brain Sciences used in the pilot study so consumers can test their personal mental performance before and after use to see if the products work for them….”

How Shared, Open Data Can Help Us Better Overcome Disasters | WIRED

“Hopefully, interest in data about air quality and the difficulty in getting a comprehensive view will drive more people to consider an open data and approach over proprietary ones. Right now, big companies and governments are the largest users of data that we’ve handed to them—mostly for free—to lock up in their vaults. Pharmaceutical firms, for instance, use the data to develop drugs that save lives, but they could save more lives if their data were shared. We need to start using data for more than commercial exploitation, deploying it to understand the long-term effects of policy, and create transparency around those in power—not of private citizens. We need to flip the model from short-term commercial use to long-term societal benefit….”

Be open about drug failures to speed up research

It can take 20 years or more to get a drug to market, from testing compounds in animals to running late-stage (phase III) clinical trials in thousands of subjects. More than 80% of drugs that are tested in humans fail to demonstrate safety and efficacy1 (see ‘High failure rate’); the rate for Alzheimer’s treatments is estimated at more than 99%2 (see ‘Alzheimer’s drug attrition’).

Yet the data behind these failures are generally not seen by regulators, or considered deeply by anyone outside the company sponsoring the trial. Without this information, learning is unlikely….

Initiatives for private companies to share biomedical data and ideas have expanded in the past decade. Some, such as the Biomarkers Consortium and the Structural Genomics Consortium, bring together many companies and academics to design experiments for the benefit of the community, such as identifying disease markers or characterizing tool compounds to understand how target proteins work. Others ask companies and academic groups to pool data in a common repository. For instance, the Project Data Sphere Initiative is a platform to share de-identified data from people who were enrolled in the control, placebo or even experimental arms of more than 180 cancer trials….

Information that is not shared is arguably the most important: data that failed to meet drug developers’ hopes are most likely to help progress. Large clinical trials are multimillion-dollar experiments to validate a hypothesis that an experimental drug will be effective and safe. Results that go against these expectations must be made available to refine hypotheses and to elaborate alternative ones.

Data from negative research can reveal whether a trial adequately tested the intended hypothesis. …”

FDA fails to collect over one billion dollars in fines from law-breaking pharma companies and universities | transparimed

“The FDA Amendments Act was originally introduced to prevent companies from burying research results that show their drugs to be harmful or ineffective. Negative publicity around past disasters linked to hidden clinical trials seems to have pushed pharma companies into compliance. Today, the leading drug companies publish their trial results as required by law nearly all of the time, though some of the less prominent commercial trial sponsors continue to do badly.

In contrast, even some of the major universities and nonprofits perform dismally….

If the FDA was enforcing the law, New York University School of Medicine alone would be facing a $7,647,109 fine for its illegal and unethical behaviour. However, to date, the FDA has not collected a single cent in fines….

The FDA has recently signalled that it may in future start selectively imposing fines on some occasions. Transparency advocates have sharply criticized the FDA’s plan for lacking teeth. …”