Michelle Hoffman, editorial director of Pharmaceutical Technology.

Michelle Hoffman

I recently attended a press conference sponsored by BIO, the Biotechnology Industry Organization. BIO President and CEO Jim Greenwood called the media together to talk about some proposed changes at the United States Patent and Trademark Office (USPTO). Overwhelmed by the crush of patents coming out of US industry and academia, the patent office is seeking to lighten its workload by, among other things, reducing the number of continuances a petitioner can file. Continuances essentially allow a patent filer to add claims to a patent that's already been filed—effectively broadening the scope of the original patent. 

This procedure is important in biotechnology and drug discovery, where patents are filed when the technology is at a fairly early stage, before the technology's potential has been fully explored. Blocking the number of continuances a drug developer can file forces an inventor to file a new patent for each new application of the technology—a process that, because of its expense, can discourage follow-on inventions, especially for young, poorly capitalized companies, which nevertheless may be extremely innovative. 

I have heard from several patent attorneys that the USPTO is considering other changes as well. For example, the office may limit the damages a patent holder can seek from an infringer. The office is also considering granting patents that represent an incremental change, rather than a radical departure, over an existing patent. The attorneys I've spoken with have explained to me that the proposed changes are being supported by the high-tech and software industries, where innovations tend to be incremental and frequent, and where commercialization timelines (and the time to obsolescence) are short.  

In contrast, the changes are perceived as inhospitable to the drug-making industry, where innovations are slow in coming and commercialization times run decades, rather than months.  

The BIO press conference was held at the JP Morgan Healthcare Investors conference last month. The meeting gives investment bankers, venture capitalists, and Wall Street analysts an opportunity to hear from executives of (mostly) publicly traded companies their projections and expectations for their company's strategic and financial performance over the coming year. For me, it was an opportunity to size up the US pharmaceutical industry and get a glimpse of the trends to look out for in 2008. 

It will come as a surprise to no one that globalization continues to be a major theme. Many companies are looking to a growing middle class in developing nations to consume more of their drugs. At the same time, they're taking advantage of the excellent scientific talent and lower wages to set up research and development (R&D) centers in these nations. Take GlaxoSmithKline, for example, which in the words of CEO Jean-Pierre Garnier, has put together a "full-fledged, integrated R&D center in Asia to discover drugs for the world."  

Companies are doing more and more of their R&D overseas. And why shouldn't they? In addition to finding outstanding scientific talent in this region at lower wages, companies are also capitalizing on the region's improved patent protections. 

So, what does the entire picture reveal? The US is considering weakening its patent protection for novel drugs and discovery tools at a time when the scientific expertise overseas is at its most competitive and sophisticated, and at a time when countries in the developing world are strengthening their patent protections for these discoveries. In sum, it would seem to be a bad time for the USPTO to make such changes. Such a strategic move may very well diminish America's ability to compete on the world stage. 

As I mentioned, the rationale for altering the US system is to lighten the burden on the overtaxed patent office. But as Jim Greenwood stated, "If we have an overload of patents coming to the Patent Office, we should celebrate it. Congress should be thinking about how to accommodate and not strangle innovation." We simply can't afford that. 

Articles

Can an overload of patent applications lead to the US' demise as a scientific leader?

Patents "R" Us

Text sirtuins are the new kinases, according to a presentation given last month at the JP Healthcare Investors Conference in San Francisco by Sirtis CEO Christoph Westphal. Sirtuins are a class of proteins that seem to modulate aspects of the aging process. Researchers had noted some time ago the increased longevity of animals on highly calorie-restricted diets. These animals also enjoy better sugar regulation than do animals on higher-calorie, higher-fat diets. Within the past year, scientists have shown that sirtuins in general, and the protein SIRT1 in particular, are activated in calorie-restricted animals. 

All of this has led investigators to initiate studies of the sirtuins in order to someday mitigate some of the effects of aging. Westphal predicted that the sirtuins may even merit the kind of attention now enjoyed by the kinases—a family of proteins in which some of its members have been implicated in cancer and autoimmune diseases, and which have been the focus of intense scrutiny by drugmakers for most of the past decade. 

Indeed, many of the health benefits of a calorie-restricted diet can be simulated by resveratrol, a small molecule found in red wine. Scientists now understand that resveratrol also activates SIRT1. 

Now, it seems, Sirtis has found a small molecule that it is calling SRT1720, which is more potent than resveratrol, and which might be useful in the treatment of Type II diabetes. Westphal reported at the meeting that the experimental drug lowered blood glucose levels and improved glucose homeostasis and insulin sensitivity in mouse models of diabetes and obesity. Late last year, Sirtis researchers, in collaboration with investigators at the University of California at San Diego and Harvard Medical School also reported these results in 

J.C. Milne, P.D. Lambert, S. Schenk, et al., "Small Molecule Activators of SIRT1 as Therapeutics for the Treatment of Type 2 Diabetes," 

Text sirtuins are the new kinases, according to a presentation given last month at the JP Healthcare Investors Conference in San Francisco by Sirtis CEO Christoph Westphal.

Coming Down the Pike: Sirtuins

The most significant early-stage discovery to hit the journals in late 2007 (or at least the most highly publicized) were the dual announcements from two independent research groups that they had managed to turn adult human skin cells into cells with properties that are seemingly identical with human embryonic stem (hES) cells. The teams each inserted four genes (only two of which overlap) into the adult cells to make them revert to the embryonic-like state. Among other things, the achievement may allow US scientists to explore the properties of hES cells—and their potential uses in regenerative medicine—while circumventing the debate on the morality of destroying human embryos to get the cells. Of course, both teams a nd scientific commentators stress that it will take a while to determine how similar the so-called induced pluripotent cells are to true hES cells. For now, however, it may allow US scientists to catch up to foreign counterparts studying hES cells. 

1. J. Yu, M. A. Vodyanik, K. Smuga-Otto, J. Antosiewicz-Bourget, J. L. Frane, S. Tian, J. Nie, G. A. Jonsdottir, V. Ruotti, R. Stewart, I. I. Slukvin, J. Thomson, "Induced Pluripotent Stem Cell Lines Derived from Human Somatic Cells," SCIENCEXPRESS, 

2. K. Takahashi, K. Tanabe, M. Ohnuki, M Narita, T. Ichisaka, K. Tomoda, and S. Yamanaka, "Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors," Cell (2007), doi: 10.1016/j.cell.2007.11.019. 

The most significant early-stage discovery to hit the journals in late 2007 were the dual announcements from two independent research groups that they turned adult human skin cells into cells with properties that are seemingly identical with human embryonic stem (hES) cells.

Coming Down the Pike: hES cells

At some point in this editorial, I may feel the need to utter something like "Surely the richest country in the world can find the resources to...." If you're sick of hearing that, you may choose to stop reading. But for the rest of you, I find myself wondering about the sorry state of the US Food and Drug Administration. 

A scientific subcommittee appointed by FDA Commissioner Andrew von Eschenbach to study the agency's fitness, released a report in December that concluded "...science at the FDA is in a precarious position...and is not positioned to meet current or emerging regulatory responsibilities." 

The subcommittee cited an imbalance between supply and demand: Essentially, the report said, "Resources have not increased in proportion to the [increased] demands. The result is that the scientific demands on the Agency far exceed its capacity to respond."   

In response to this report and other criticisms of FDA's ability to ensure the safety of the nation's food and drug supply, the 

 reported that President George W. Bush, in an executive order, said that improvements would have to be made with existing resources. Surely, the richest country in the world can find the resources to ensure the safety of its food and drug supply. 

In a previous editorial, I had to conclude that we didn't see Nobel Laureates on news shows, because the Prize is simply not a priority. Could it be that FDA is so underfunded because food and drug safety is also not a priority? Well, what better time to air national priorities than in the run-up to a national election? And who better to ask than the candidates for president? These people are—at the moment—exquisitely attuned to the public's priorities. 

So, to find out, we got in touch with the press offices for all of the leading presidential candidates of both major parties. How do they feel about the current level of FDA funding? We asked. And, How do they feel about the way FDA is funded—in part, through user fees? Finally, If they were to become president, would they change these things and how? 

You're probably wondering how they answered. So are we. Not a single one answered our request. (That's not exactly accurate. The Richardson campaign did send us an email thanking us for our interest in the candidate. But that's not really the kind of reply we were hoping for.) 

I don't know why they didn't reply. I am aware that 

, and so maybe the press officers didn't feel compelled to respond to us. I actually hope that's the reason, because the other options are pretty frightening.  

Perhaps the candidates know the FDA's in trouble, and they do have a solution but don't want to talk about it because issues related to the pharmaceutical industry are controversial and/or polarizing and therefore dangerous to the campaign. Or maybe they do know it's in trouble but don't have a solution. Finally, it's possible the candidates don't know FDA is in trouble—even the ones who have made healthcare an issue. 

The candidates might reply if you, their constituents and potential voters, ask them. (If they do respond, please let us know what they said.) They still might respond to us, of course, and if they do, we'll post the replies online. But let's all hope they're thinking about this issue, because everyone in the pharmaceutical industry (not to mention everyone who takes drugs or eats) is. 

Send your comments or story ideas to Editor-in-Chief 

Fixing FDA lies in the hands of the government, but is the president-to-be paying attention?

Candidate Copout

close our 30th anniversary celebration. In July, we marked the occasion with a look back at everything that's changed since our magazine's launch in 1977. In a special report on page 40, we ask industry experts to look forward and speculate on what we might expect to see in the coming 30 years. 

So, in keeping with the spirit of things, I'd like to share a fantasy and a wish. Here's the fantasy: I'm at work, when I notice a colleague that I haven't seen for a couple of days. "Where have you been?" I ask. 

 "Oh," replies my colleague, "I was out for a few days with cancer. I'm feeling better now." 

"Good," I answer. "I'm glad it wasn't anything serious."  

The wish is that syndromes that seem difficult to manage now will, within 30 years (less, if I could really have my wish), be as unremarkable as a head cold.  

So, what will it take to make that fantasy possible? I don't know for sure, but I suspect that one factor is for firms to place much greater value on innovation, even if it means putting aside some scientific and fiscal conventional wisdom (after all, that kind of thinking has led to some rather dry pipelines, it seems). 

I also think drug makers, drug inspectors, and drug consumers need to demand that new drugs be effective. Perhaps in the future, animal models of disease will improve and become more actively predictive than they must be right now, especially considering that so many drugs fail in Phase III. (And while we're on that subject, why do we ask about a drug's efficacy at the very end of drug development, anyway?) I am gratified to see that the USFood and Drug Administration and consumers are starting to demand new drugs that offer a quantum improvement and not just incremental improvements over existing drugs. I believe this call to action  will go a long way toward stimulating innovation.  

I would also like to think that by publishing cutting-edge developments in drug formulation and manufacturing, we at 

 are also, in our own way, contributing to the general advancement of pharmaceutical science and drug making. We certainly have expert help. I would like to thank the many members of  our Editorial Advisory Board—some of whom have been with us since the very beginning (Patrick P. DeLuca at the University of Kentucky, and Ram Murty with Murty Pharmaceuticals)—for their continued support and expert critical advice and for keeping us on top of our game. 

I also wish for you, our readers, a productive, fruitful, and innovative 2008.  

Drug makers, drug inspectors, and drug consumers need to demand that new drugs be effective.

Here's to Innovation

"May you live in interesting times," goes the allegedly ancient Chinese curse. Well, these have been "interesting times" indeed for those working in the pharmaceutical industry. Long thought of as the most stable industry, the pharmaceutical industry has in the past few years found itself in the midst of upheavals of all sorts: technological, geographical, strategic, regulatory, and economic. We at 

often hear from readers that globalization has had a profound influence on the industry. The locus of manufacturing, R&D, and sales is slowly shifting from its traditional bases in the US and Western Europe to emerging markets in Asia and Latin America. Technologically, there can be no doubt that the pace of biopharmaceutical development and manufacturing stands to outstrip that of small-molecule development. And many analysts predict the demise of the "blockbuster" one-size-fits-all approach to drug making in favor of more targeted drug development. Of course the largest growth area appears to be in generics, and once regulatory issues are worked out, biosimilars after that. 

Regulatory sands are shifting in uncertain ways both here and abroad. FDA is changing both philosophically and operationally, with initiatives such as Quality by Design, Process Analytical Technology, and the Critical Path. Of course, as the industry abroad matures, so do overseas regulations. And that necessitates efforts to standardize regulations so firms can operate smoothly and efficiently, and so drugs are of uniform quality, in multiple markets. Taken together, the current picture is one of an industry in flux. So, we couldn't resist asking industry experts how they think it will all shake out. What, we asked, will the pharmaceutical industry look like in 2037 when Pharmaceutical Technology celebrates its 60th anniversary? The following is an edited version of their replies. Jim Miller, Pharmaceutical Technology's columnist on outsourcing and president of PharmSource Information Services, may have summed it all up best when he said, "New players, new technologies, new geographies—in 30 years, it won't be your parents'... industry." 

Industry experts give their predictions for the next 30 years. 

"May you live in interesting times," goes the allegedly ancient Chinese curse. Well, these have been "interesting times" indeed for those working in the pharmaceutical industry.