Celebrating the 20 years of Expert Opinion on Therapeutic Patents

This month celebrates the 20th anniversary of Expert Opinion on Therapeutic Patents. Behind this slightly esoteric title, EOTP has for two decades offered a bird’s eye view of the latest advances in the discovery of therapeutically promising molecules. During this period the scientific and regulatory landscapes in drug R&D inevitably evolved, the number of peer-reviewed publications worldwide increased steadily and the Expert Opinion journals changed hands. Yet, I think it is fair to say that EOTP’s distinct approach and relevance have remained unaltered.

Expert Opinion on Therapeutic Patents’ launch aimed at filling a gap in the life science literature by explicitly including patents within the scope of its review articles. Key to a legal system designed to promote innovation, patents provide exclusive rights to the inventor in return for the full disclosure of the invention to the public. In the specific context of the pharmaceutical and biotechnology industries, this makes patents a particularly valuable source of information for medicinal chemists and other researchers involved in drug discovery. In effect, to protect their promising compounds, companies reveal them at an early preclinical stage and for the first time in patents. Not only do patents divulge the novel compounds, but they also show which are deemed to show clinical potential and offer insights into the competitors’ research programmes.

Patents are not alien to researchers in the industry. However, despite being largely freely available and easily searchable, patents present the information in a somewhat cryptic way. They don’t follow the rules of scientific writing and extracting the relevant knowledge can be time consuming. Patents are long documents worded in legal jargon by specialist attorneys. They often cover dozens of compounds, only a few of which are of genuine interest. These compounds need to be reconstructed from generic structures and of course, they need to be put into context with other related patents as well as the scientific literature.

EOTP’s review articles provide a dramatic shortcut to the essential information by summing up the important scientific content of dozens of patents, putting it into a wider perspective and, of course, expressing the authors’ own critical opinion. They answer fundamental questions such as “what are the structural types of inhibitors? “ and “who are the major players in the field?,” but also go beyond and suggest which compounds are likely to progress to the clinic. In that respect, Expert Opinion on Therapeutic Patents’ reviews offer exceptional added value.

I know from many first-time authors that preparing a manuscript for the journal is a surprisingly taxing undertaking. I can but acknowledge this and I would like to thank our authors for their hard work. The constant increase in EOTP’s usage testifies that the drug discovery community clearly values such efforts. Moreover, the readership is very likely to continue to grow as EOTP has eventually been accepted for indexing on Medline last year – an unfortunately tardy development.

Last year, Expert Opinion’s editorial team gathered feedback from the advisory boards and our readers. This 20th volume of EOTP should reap the first benefits of this consultation. First, the abstract’s structure has been redesigned to better reflect the content of the article. Second, an ‘article highlights’ box has been added to guide the reader through the main points of the paper. Third, EOTP will start publishing one to two themed issues in each volume. The first one, guest-edited by Dr Herbert Kirst from our Editorial Board, will cover antibacterials and will be due later this year.

I expect in 2010 the acceleration of another more gradual addition to the journal. The biotechnologies are now fully integrated to the pharmaceutical area and bear novel promises of therapeutic advances. Expert Opinion on Therapeutic Patents will logically increase its coverage of biologicals to echo this trend.
I hope this agenda meets our readers’ expectations and that EOTP will remain, above all, a useful resource to professionals in the field.

Joris Roulleau
Senior Editor

New Informa Healthcare website

Informa Healthcare has moved this week the content of its 180 peer-reviewed journals to a new online delivery platform at www.informahealthcare.com.

The site combines all the Informa Healthcare journal titles listed on InformaWorld.com and InformaPharmaScience.com to help simplify the customer experience. The new site utilizes the online content management and delivery system provided by Atypon Systems, Inc. – an e-publishing solutions supplier for a number of leading information providers including JSTOR, New England Journal of Medicine and the American Chemical Society.

The Atypon system enables Informa Healthcare to integrate a comprehensive archive service dating back to 1918 giving pharmaceutical, medical and healthcare professionals one central, high-quality source of information.

The new platform offers the option of online trials, advanced searching, alerting, and single article purchases. The site also provides COUNTER-compliant reports and statistics to help subscribers analyze usage.

There will be a dual-hosting period with the InformaWorld platform, which currently hosts the medical content, through 2009 allowing for a gradual migration. Informa Healthcare will set up customer accounts in August and will notify subscribers of the change to ensure a seamless transition to the new site. Customers with journals on InformaPharmaScience.com will be automatically re-directed.

This website will also allow Informa Healthcare to implement new features and improve the layout over the next few months.

To review a list of journal titles on the new site or for more information, visit www.informahealthcare.com.

Ubiquitin - a promising target for new drug development

Where potential approaches to drug discovery are concerned, ubiquitylation might not be the first word that springs to mind. But the 2006 approval of bortezomib (Velcade) and recent research into inhibitors of the ubiquitin-proteasome pathway have raised expectations for this biological process as a target for novel treatments for a range of diseases.

A recent review article published in Expert Opinion on Therapeutic Targets, Targeting the proteasome pathway, by Yokosawa and Tsukamoto explores the emergence of the proteasome and other members in the ubiquitin–proteasome pathway as novel therapeutic targets. In a related piece in Scrip World Pharmaceutical News, Informa Analyst Ian Schofield provides his Expert View on ubiquitylation as an attractive route to novel drug design.

Yokosawa and Tsukamoto review the current understanding of the ubiquitin–proteasome pathway and describe inhibitory mechanisms for tageting it, while Schofield discusses the RUBICON network and the recent creation of the Scottish Institute for Cell Signalling, which with government funding hopes to pinpoint novel drug targets for use in designing medicines for inflammation, cancer and infectious diseases.

Read both articles at:
Expert Opinion on Therapeutic Targets and
Scrip World Pharmaceutical News

Outstanding performance for Informa Healthcare journals

Impressive growth, high world rankings and excellent impact factors demonstrate strength of Informa Healthcare’s comprehensive portfolio of highly respected publications.

LONDON – Monday, 29 June 2009 – Informa Healthcare – one of the world’s leading medical and scientific publishing groups – has announced highlights of its latest journal Impact Factor results, with impressive results across the division’s comprehensive range of titles. The company’s highly respected range of Expert Opinion titles performed notably well, with significant jumps for Expert Opinion on Biological Therapy which is up almost 20% to 3.475 and Expert Opinion on Therapeutic Targets, up more than 21% to 4.038. Expert Opinion on Investigational Drugs leads the series with a 2008 Impact Factor of 4.058 and two new titles – Expert Opinion on Drug Safety and Expert Opinion on Metabolism & Toxicology, registered sensational first ever Impact Factors of 3.073 and 3.069, respectively.

The company’s Critical Reviews in Toxicology also registered an outstanding impact factor of 7.204, up more than 40% and now ranked 2nd out of 75 journals in toxicology – with 1st place being an annual publication as compared with Critical Reviews in Toxicology’s ten issues per year.

Impact factors are a method of measuring the influence which a journal has on the scientific community. They are calculated by Thomson Reuters and are designed to indicate how many times the published articles of a journal are cited during the course of a year, providing an insight to how much ‘impact’ the journal is making on its audiences.

“Impact Factors provide us with a measure for the importance of our journals to the medical and scientific communities we serve,” explains Phil Garner, Publishing Director at Informa Healthcare. “We are delighted with the performance of our market leading titles as well as some new journals which have posted excellent first time results.”

“Our Expert Opinion range of titles – which provides in-depth analysis of the pharmaceutical R&D pipeline – has registered impressive gains across the board and first ever Impact Factors of above three for our two new titles is testament to the quality of information that goes into our journals,” says Phil. “These results give a big ‘thumbs up’ to the comprehensive, intelligent content which make these titles the definitive reference source for leading pharmaceutical scientists.”

Other Informa Healthcare journals that have performed well are the Journal of Drug Targeting – up to 2.771, Inhalation Toxicology – up to 2.403, International Reviews of Immunology with a 37% increase to 4.935, the International Journal of Radiation Biology – up 48% to 2.178, and first ever IF’s for The Aging Male – at 2.622, and Prehospital Emergency Care at 1.248, now ranked in the top half of 13 journals in the emergency medicine category.

Informa’s Scandinavian titles also performed well: Fifteen out of twenty five registered increased impact factors and eighteen with impact factors of over 1.00. The International Journal of Pediatric Obesity registered 3.984 in just its second year, up almost 100% from 2.00 in 2000. World Journal of Biological Psychiatry was also up by more than 111% to 3.582. The division’s flagship journal, Annals of Medicine, registered an impact factor of 5.435 with some 78% of the group’s Scandinavian journals registering impact factors.

“We are justifiably proud of the performance of all of our journals,” adds Phil. “Our new titles have done very well and our established journals have continued to go from strength to strength, with an impressive number of them moving many places up in their respective rankings.”

Informa’s results, across its wide range of journals, are remarkable: The International Journal on the Biology of Stress is up to 2.952; The Journal of Protein Folding Disorders is up to 1.714; The International Journal of Audiology has an Impact Factor of 1.201; The Journal of Psychosomatic Obstetrics and Gynecology is up 67% to 1.585, and Platelets is up to 2.271 – a rise of almost 20% over last year. In addition, the Journal of Intellectual & Developmental Disability has increased to 0.902 and Pathology to 2.324.

“Our overall performance – together with the outstanding individual performances of many of our titles – ensures that Informa continues to serve as a leading force in medical and scientific publishing, providing the market with the lion’s share of must-read titles,” explains Phil.

Scholar One 'submitting agent' feature activated for Expert Opinion journals

Medical communication agencies can now submit manuscripts to Expert Opinion journals as third party, on behalf of the authors .
The name of the submitting agent will not appear in the authors' list and both the submitting agent and the corresponding author will receive emails from the editorial team regarding the manuscript.

The submitting person must now identify itself as an author or a third-party submitting agent at the first step of the submission process.

This feature has been activated for the following journals using the Scholar One submission platform:

• Expert Opinion on Pharmacotherapy
• Expert Opinion on Therapeutic Targets
• Expert Opinion on Investigational Drugs
• Expert Opinion on Biological Therapy
• Expert Opinion on Metabolism and Toxicology
• Expert Opinion on Drug Safety
  

Award winning research at the Dutch Atherosclerosis Symposium, 2009

The years to come are going to be very busy for persons working in the field of atherosclerosis and cardiovascular disease. Basic-science researchers are hot on the trail of targeted drugs that will be much more focused than available drugs, and some remarkable progress is being made. The 12th Dutch Atherosclerosis Symposium took place on March 12 and 13, 2009 and showcased some of this progress taking place in the Netherlands. I would like to briefly present 4 of the interesting research topics that received jury awards.

Exercise
Meissner et al.1 investigated the effect of exercise on cholesterol metabolism in mice either exposed to voluntary running wheel for 2 weeks or which remained sedentary. Exercise appears to increase cholesterol and bile acids turnover via specific changes in the intestine that decrease intestinal bile acid and cholesterol absorption and promote their fecal excretion. If the same holds true in humans, exercised-induced modulation of bile acids and cholesterol turnover leading to reduced plasma cholesterol levels might contribute to the beneficial effects of exercise on cardiovascular disease.

Cathepsin inhibition
The research aim of Waard et al.2 is to develop pharmaceutical therapies for abdominal aortic aneurysm to prevent surgical intervention in elderly patients. They have previously shown that cathepsins are functionally involved in collagen degradation in human aneurysm tissue. In the present study they showed that E64 (a cathepsin inhibitor) treatment resulted in a decreased number and severity of aneurysms and in a less inflammatory profile in serum in a mouse model. The inhibition of cathepsins may be therefore an attractive therapeutic approach to prevent aortic aneurysms expansion.

Microarray antigen chip
The immune system is thought to play an important role in initiation and progression of atherosclerosis. Den Dekker et al.3 aimed to explore the potential of auto-antibody profiles as a biomarker for a cardiovascular event. A generic version of the antigen microarray was used bearing over 740 proteins related to a variety of conditions including immune regulation, inflammation, angiogenesis, apoptosis and more. The antigen microarray was able to identify patients with previous myocardial infarction with a high sensitivity and specificity. In conclusion, a microarray antigen chip may be used as a novel biomarker for cardiovascular disease.

Nuclear receptor Nurr1
Bonta et al.4 have investigated the role of nuclear receptor Nurr1 in stent restenosis. They found that Nurr1 is expressed in human in-stent restenosis lesions. Nurr1 inhibits inflammatory gene expression in both macrophages and smooth muscle cells and it inhibits proliferation of smooth muscle cells. In vivo Nurr1 reduces neointima formation in mice. Small-molecule drugs have been identified that enhance the transcriptional activity of this nuclear receptor. It seems therefore that Nurr1 may be an attractive novel target for local intervention against in-stent neointima formation.

Comment
Genetics and biochemistry have now become the unchallenged leaders of cardiovascular research. New drugs to be soon perfected together with the immense progress in the invasive field will completely change the cardiology that we all knew.

By: Sandrin C. Bergheanu, MD, Dept. of Cardiology, Leiden University Medical Center, Leiden, The Netherlands (s.c.bergheanu@lumc.nl)

References

1. Maxi Meissner et al., Department of Pediatrics, University Medical Center Groningen, The Netherlands. E-mail: M.Meissner@med.umcg.nl

2. Vivian de Waard et al. Division of Biopharmaceutics of the Leiden/Amsterdam Center for Drug Research, Leiden and Department of Medical Biochemistry, AMC, Amsterdam, The Netherlands. E-mail: v.dewaard@amc.uva.nl

3. Wijnand den Dekker et al. Molecular Cardiology Laboratory, Erasmus Medical Center Rotterdam, The Netherlands.

4. Peter Bonta et al. Department of Medical Biochemistry, Academic Medical Center Amsterdam, The Nertherlands. E-mail: P.I.Bonta@amc.uva.nl

Top 5 reasons why medical associations should maintain ties with industry

In the April 1st issue of JAMA, Rothman, et al. spelled out a proposal for controlling conflicts of interest that calls for professional medical associations (PMAs) to cut all ties with industry. PMA conferences, continuing education and practice guidelines often set the standard for patient care.

The proposal seems reactionary, albeit understandable given how quickly a handful of high-profile cases—particularly those involving failure to disclose—both blackened the eyes of science and eroded public trust.

But should a few bad apples be allowed to spoil the bunch? I say no. And here are the top 5 reasons why I propose just cutting all the bad apples loose and continuing to reap the best possible fruit.

1. Together, PMAs and industry actually do more good than harm. I could go on and on about all the good new drugs and devices have done for patient care, but we don’t have the space. I will say that I once had a 40-plus year old former patient stop me on the street to thank me for helping save his life. In my opinion, the kudos should have gone to the makers of the intra-aortic balloon pump that kept him alive while his heart recouped. Back in the day, he would never have survived that event regardless of how good the care was.

2. Industry doesn’t have as much power as you think. Industry’s power is diluted by nurses, patients and grass-roots patient advocacy groups, who together wield big clubs called prescriptive pressure and noncompliance: if a drug or device doesn’t work, nurses won’t give it, or patients won’t use it. And don’t forget the 800-lb. gorilla in the room—third-party payers—who have more power than drug and device companies over treatment guidelines and who gets what and when.

3. Industry is on the same side of the fiduciary coin as PMAs. Industry wants to save lives, too. They also want safe and ethical care. If you don’t believe that take a look at how pharma manufactures have come together to police themselves. Visit http://www.phrma.org/ and click on their outline for a revised marketing code.

4. Physicians are business people too. Physicians can’t cut ties with industry; they are industry. We like to believe that pure professionalism lies at the heart of medicine, but the drivers of treatment guidelines, namely the individual physicians and their associations, are in business. Profit isn’t a palatable word, so let’s call what they do “earning a living.” Besides, physicians can cross the line without help from the drug and device part of the industry, as evidence by anti-kickback laws that have more to do with unethical patient referrals than branded pens and notepads.

5. Together, PMAs and industry are on the ethically right path. In the Association of American Medical Colleges’ “The scientific basis of influence and reciprocity: A symposium” the authors show how self-interest can unconsciously bias even those of us who have the best of intentions, but they also demonstrate how just being reminded of an honor code stops cheating completely regardless of the amount of reward. Full transparency is a kind of honor-code reminder, and a huge step in the ethically right direction for all parties involved.

Sources:
Rothman DJ, McDonald WJ, Berkowitz CD, et al. Professional Medical Associations and their relationships with industry. JAMA 2009; 301: 1367–72
Korn D, Ehringhaus SH. Association of American Medical Colleges, The scientific basis of influence and reciprocity: A symposium. 2007. Available at: www.aamc.org/publications Association of American Medical Colleges, Industry funding of medical education: report of an AAMC task force. 2008. Available at: www.aamc.org/publications


Written by Terri Metules.