Chemistry

Plant Safety: Fatal accident is second recently to befall a Louisiana chemical facility

The Supreme Court has another ruling that affects the drug industry: FTC v. Actavis took up the question of "pay to delay", the practice of paying generic companies to go away and not challenge a branded drug. Actavis was in the process of bringing a version of Solvay's AndroGel to market, claiming that the Solvay patent was invalid. They won that case, and the FDA approved their generic version, but Solvay turned around and paid them (and Paddock, another generic firm) to not bring any such drug to the market. The Federal Trade Commission (FTC) filed suit, alleging that re- spondents violated §5 of the Federal Trade Commission Act by unlawfully agreeing to abandon their patent challenges, to refrain from launching their low-cost generic drugs, and to share in Solvay’s monopoly profits. The District Court dismissed the complaint. The Eleventh Circuit concluded that as long as the anticompetitive effects of a settlement fall within the scope of the patent’s exclusionary potential, the settlement is immune from antitrust attack. Noting that the FTC had not alleged that the challenged agreements excluded competition to a greater extent than would the patent, if valid, it affirmed the complaint’s dismissal. It further recognized that if parties to this sort of case do not settle, a court might declare a patent invalid. But since public policy favors the settlement of disputes, it held that courts could not require parties to continue to litigate in order to avoid antitrust liability. And now the Supreme Court reverses the Eleventh Circuit. The FTC, they hold, should have been given a chance to make its antitrust case. The Court makes a point out of declining to hold such agreements "presumptively unlawful", but gives a guide to breaking them down. There are both patent validity questions and anticompetitive questions involved, they point out, and these are separate issues (and because of that, they might not take forever to litigate, as the Eleventh Circuit decision worried about). Besides, as the justices note, a sudden large payment in such a case could be a reasonable indication of the underlying patent's validity (and chances of holding up to a determined challenge). The Hatch-Waxman Act has a generally pro-competitive bent to it, and that should operate in this situation as well. I think this is the decision that most people expected (it's certainly the one I did). Pay-to-delay has always had an antitrust-violation smell to it. The Supreme Court has now gone on record as saying that this scent may well be no illusion, and at the very least, the FTC should be able to make a case if it can. I suspect that we're going to see fewer of these deals now - perhaps none at all - because I doubt many of them would hold up.

Read all about it: Misleading headlines can even plague presidential elections. Credit: Byron Rollins/AP/Wikipedia The Newscripts blog would like to be closer Internet buddies with our glossy print Newscripts column, so here we highlight what’s going on in the print issue of C&EN. There's an unfortunate trend that seems to be becoming increasingly popular in today's science news world. The recipe goes like this: Take one misleading headline, add an introductory sentence that takes liberties with the subject matter it's covering, and stir in one gullible blogosphere, and before you know it, you have a distorted science news story that appears to be popping up everywhere. That's the controversy that C&EN Senior Editor Carmen Drahl took on in last week's Newscripts column. Carmen stumbled upon a press release purporting to have found a way to analyze human health through the measurement of genetic material. She called bullocks on the claim, and the journal responsible for the press release apologized. According to Carmen, this incident is nothing new. She says National Geographic blogger Ed Yong and many others have been leading a battle against misleading public relations for years. She also remembers stumbling across two particularly dubious “news stories” herself. One centered on the ENCODE (ENCyclopedia Of DNA Elements) Project. As Carmen remembers, the project's attempts to catalog the pieces that make up the genome led to press releases that claimed so-called junk DNA served a life function, which in turn led to a barrage of articles both deriding the articles as hype and asking for clarification on what constitutes as “junk.” --> --> --> The second “news story” centered on the 2010 claim that a bacterium had somehow replaced phosphorus in its DNA backbone with arsenic. “I can tell you the effect this second release had on me—lots of sleepless hours covering the backlash to what became known as #arseniclife,” Carmen says. “Misleading news releases, and the misleading reportage that often goes hand in hand with them, are bad for science,” she continues. “With oversimplification or omitted information, readers and viewers (whether they're fellow scientists or laypeople) never hear about the real reasons why scientists are excited about findings—the beauty and importance are often in the details.” As Carmen puts it, misinformation can lead to “science whiplash,” where readers are left oscillating between two debatable claims with no resolution. Think of the endless debate about whether red wine is good for you, she says. “That's the kind of thing that breaks down people's trust in science in general.” For the second part of her column, Carmen focuses on the lighter subject of Prince Harry's recent visit to the U.S. and the three-dimensional printed doll he received during his travels. To celebrate the royal visit, Carmen says she busted out “a proper cup of tea” that she brewed using the teamaker she bought in London last year. And Carmen's Newscripts connection with British royalty doesn't stop there. She is already looking for ways to incorporate the new royal baby into her next Newscripts column. “Maybe Harry will give his little niece or nephew the 3-D printed doll as a gift,” she wonders. --> Related Posts:In Print: Horse. It's What's For DinnerIn Print: Europe's Got A Stink ProblemIn Print: Droplets of Rain, Strands of HoneyIn Print: Cooking With CicadasIn Print: Chemistry Labs Sound Like Music

Also in this week's C&EN, an interesting set of comments reported by Michael McCoy from the annual meeting of the American Chemistry Council (the chemical industry's trade group) (emphasis mine):Through the end of March, nearly 100 chemical investment projects that capitalize on shale gas had been announced, the report found. Valued at $71.7 billion, the new plants are expected to generate $66.8 billion in annual chemical output and create some 500,000 jobs in chemical plants and surrounding communities by 2020. “There’s been a dramatic change in the past five years,” Calvin M. Dooley, ACC’s chief executive officer, told reporters during a press conference at the event. Dooley was particularly proud that more than half of the announced spending is from companies based outside the U.S. In the decade prior to 2010, he said, investment left the U.S. at a prodigious rate, causing a 20–25% decline in the chemical industry’s employee ranks. Yet ACC’s top officers acknowledged that the full impact of shale gas is yet to be seen and that it can’t offset the effects of a weak overall U.S. economy, stagnation in Europe, or even production woes. On the first day of the meeting, ACC released statistics showing that U.S. chemical production this year through April is up only 0.6%. This comment about manpower was especially interesting:And the blossoming of multiple new plants after many fallow years will strain the engineering and construction industries, executives acknowledged. As it is, companies that scheduled plant maintenance in the spring had trouble finding qualified welders and pipe fitters, Gallogly said, and the problem will only worsen when big ethylene facilities start getting built. “There should be significant manpower shortages,” he said. The ethylene crackers that have been announced won’t all be built, Gallogly predicted, and some of those that are built will be delayed for reasons of manpower and permitting.It seems like there are always shortages of experienced welders.One hopes that, after a while, there will be a boom in the hiring of research chemists in the chemical and polymer industries to take advantage of relatively inexpensive and plentiful natural gas. We've really yet to see evidence of that, though, just a lot of promised jobs. (FWIW, I think there will be.)

Also in this week's C&EN, an interesting set of comments reported by Michael McCoy from the annual meeting of the American Chemistry Council (the chemical industry's trade group) (emphasis mine):Through the end of March, nearly 100 chemical investment projects that capitalize on shale gas had been announced, the report found. Valued at $71.7 billion, the new plants are expected to generate $66.8 billion in annual chemical output and create some 500,000 jobs in chemical plants and surrounding communities by 2020. “There’s been a dramatic change in the past five years,” Calvin M. Dooley, ACC’s chief executive officer, told reporters during a press conference at the event. Dooley was particularly proud that more than half of the announced spending is from companies based outside the U.S. In the decade prior to 2010, he said, investment left the U.S. at a prodigious rate, causing a 20–25% decline in the chemical industry’s employee ranks. Yet ACC’s top officers acknowledged that the full impact of shale gas is yet to be seen and that it can’t offset the effects of a weak overall U.S. economy, stagnation in Europe, or even production woes. On the first day of the meeting, ACC released statistics showing that U.S. chemical production this year through April is up only 0.6%. This comment about manpower was especially interesting:And the blossoming of multiple new plants after many fallow years will strain the engineering and construction industries, executives acknowledged. As it is, companies that scheduled plant maintenance in the spring had trouble finding qualified welders and pipe fitters, Gallogly said, and the problem will only worsen when big ethylene facilities start getting built. “There should be significant manpower shortages,” he said. The ethylene crackers that have been announced won’t all be built, Gallogly predicted, and some of those that are built will be delayed for reasons of manpower and permitting.It seems like there are always shortages of experienced welders.One hopes that, after a while, there will be a boom in the hiring of research chemists in the chemical and polymer industries to take advantage of relatively inexpensive and plentiful natural gas. We've really yet to see evidence of that, though, just a lot of promised jobs. (FWIW, I think there will be.)

That's my take-away from this paper, which takes a deep look at a reconstituted beta-adrenergic receptor via fluorine NMR. There are at least four distinct states (two inactive ones, the active one, and an intermediate), and the relationships between them are different with every type of ligand that comes in. Even the ones that look similar turn out to have very different thermodynamics on their way to the active state. If you're into receptor signaling, you'll want to read this one closely - and if you're not, or not up for it, just take away the idea that the landscape is not a simple one. As you'd probably already guessed. Note: this is a multi-institution list of authors, but it did catch my eye that David Shaw of Wall Street's D. E. Shaw does make an appearance. Good to see him keeping his hand in!

Some interesting articles in this week's C&EN:A comprehensive cover story on PARP inhibitors from Lisa Jarvis. Jean-Francois Tremblay has an intriguing article on an American/Chinese pyridine plant collaboration. Two articles about the changes being made for ACS certification of bachelor degree programs, one by CPT members and one by Celia Arnaud.

Some interesting articles in this week's C&EN:A comprehensive cover story on PARP inhibitors from Lisa Jarvis. Jean-Francois Tremblay has an intriguing article on an American/Chinese pyridine plant collaboration. Two articles about the changes being made for ACS certification of bachelor degree programs, one by CPT members and one by Celia Arnaud.

Compound aggregation is a well-known problem in biochemical assays (although if you go back a few years, that certainly wasn't the case). Some small molecules will start to bunch up under some assay conditions, and instead of your target protein getting inhibited by a single molecule of your test compound, the protein could look as if it's been inhibited by virtue of being dragged into a huge sticky clump of Test Compound Aggregate. A group at Boehringer Ingleheim has a paper out in J. Med. Chem. suggesting a simple NMR readout to see if a given compound is showing aggregation behavior. It looks useful, but there's one thing I would add to it. The authors mention that they used a simple sodium phosphate buffer for their experiments, and that similar trends were observed in others (for a "limited set of compounds"). But I've heard Tony Giannetti of Genentech speak on this subject before (with reference to his specialty, surface plasmon resonance assays), and he's been pretty adamant about how situation-dependent aggregation can be. The Shoichet lab's "Aggregator Advisor" page agrees. My worry is that some people might read this new paper and be tempted to clean their screening sets out up front, but you could throw some useful compounds out that way. But aggregation, annoyingly, appears to be a case-by-case thing. Probably the best ways to guard against it are (1) see if your assay can be run with detergent in it to start with, and be prepared to vary the amount, and (2) take your screening hits of interest and check them out individually before you decide that you're on to something. This new NMR assay would be a good way to do that, using the buffer that your screen was run in. Another note that comes up in all discussions of aggregators is that while many of them are condition-specific, others have a wider range. Many "frequent hitter" compounds turn out to aggregate under a variety of conditions. In that case (because you've got empirical data from your own assays), it's really worth going back and flagging those things. It would seem worthwhile to go through any screening collection and pitch out the individual compounds that show up time and time again, since these are surely less likely to lead to anything useful. Some of these will, on closer inspection, turn out to be promiscuous aggregators, but there are other mechanisms for nastiness as well. In extreme cases, whole structural motifs should be given the fishy eye.

Compound aggregation is a well-known problem in biochemical assays (although if you go back a few years, that certainly wasn't the case). Some small molecules will start to bunch up under some assay conditions, and instead of your target protein getting inhibited by a single molecule of your test compound, the protein could look as if it's been inhibited by virtue of being dragged into a huge sticky clump of Test Compound Aggregate. A group at Boehringer Ingleheim has a paper out in J. Med. Chem. suggesting a simple NMR readout to see if a given compound is showing aggregation behavior. It looks useful, but there's one thing I would add to it. The authors mention that they used a simple sodium phosphate buffer for their experiments, and that similar trends were observed in others (for a "limited set of compounds"). But I've heard Tony Giannetti of Genentech speak on this subject before (with reference to his specialty, surface plasmon resonance assays), and he's been pretty adamant about how situation-dependent aggregation can be. The Shoichet lab's "Aggregator Advisor" page agrees. My worry is that some people might read this new paper and be tempted to clean their screening sets out up front, but you could throw some useful compounds out that way. But aggregation, annoyingly, appears to be a case-by-case thing. Probably the best ways to guard against it are (1) see if your assay can be run with detergent in it to start with, and be prepared to vary the amount, and (2) take your screening hits of interest and check them out individually before you decide that you're on to something. This new NMR assay would be a good way to do that, using the buffer that your screen was run in. Another note that comes up in all discussions of aggregators is that while many of them are condition-specific, others have a wider range. Many "frequent hitter" compounds turn out to aggregate under a variety of conditions. In that case (because you've got empirical data from your own assays), it's really worth going back and flagging those things. It would seem worthwhile to go through any screening collection and pitch out the individual compounds that show up time and time again, since these are surely less likely to lead to anything useful. Some of these will, on closer inspection, turn out to be promiscuous aggregators, but there are other mechanisms for nastiness as well. In extreme cases, whole structural motifs should be given the fishy eye.