The Andhra Journal of Industrial News, February 2010, Issue 72, Vepachedu Educational Foundation

Alzheimer’s Blues for J&J and Pfizer
Elan and Wyeth had started Phase III for bapineuzumab back in 2007. They launched a late-stage program even before the Phase II data was in, hoping that an aggressive development timeline would lead to a swifter approval. Van Renterghem estimates top potential worldwide sales at $8 billion, adding that there are a number of pitfalls for this program that would significantly cut that back. J&J obtained the drug for its portfolio when it bought out Elan's rights to the Alzheimer's program last year. Full, late-stage results for the closely-watched therapy may not be available for two years. Read more: http://www.bloomberg.com/apps/news?pid=20601202&sid=aXS1gHGICFr4

On the other hand, Pfizer’s dimebon has an interesting history, beginning in Russia where it was approved as an antihistamine designed to be taken orally. When other antihistamines entered the market, dimebon was removed for commercial reasons, and now it is not marketed anywhere. However, researchers maintained interest in the drug due to its ability to block the N-methyl-D-aspartate receptor signaling pathway and cholinesterase - neurological pathways that are important in neurodegenerative diseases. As interest in the pathway-blocking ability of dimebon subsided, researchers were able to show that the drug has neuroprotective effects in models for AD and Huntington's disease. This evolution of dimebon has led Pfizer to acquire and continue clinical trials for AD. However, dimebon, failed to meet the main goals in a highly anticipated late-stage clinical trial for Alzheimer's disease. Dimebon also failed to meet its secondary efficacy goals in the 598-patient Phase 3 trial, known as Connection. A smaller earlier trial had generated excitement about Dimebon, also known as latrepirdine, because it strongly suggested the medicine can improve memory and functioning among patients with mild to moderate Alzheimer's disease. But the drug has generated controversy because it had only previously been tested in Russia and because there is uncertainty about how Dimebon works in Alzheimer's patients. http://money.cnn.com/news/newsfeeds/articles/reuters/MTFH45641_2010-03-03_13-29-50_N03217130.htm

Dimebon is a small molecule mitochondrial permeability transition pore (MPTP) blocker, as well as an NMDA receptor antagonist and cholinesterase inhibitor. Unlike Dimebon, the majority of the other pipeline candidates are targeted towards the hypothesized Alzheimer's disease etiology. Drug developers' focus has shifted from neurotransmitter replacements to biological agents that affect beta-amyloid and tau protein, both hallmarks of the disease. The next eagerly awaited compound for which Phase III results will be announced is likely to be bapineuzumab (Johnson & Johnson/Pfizer), a humanized monoclonal antibody for beta-amyloid. However, given the high attrition rate in the pipeline, expectations will be tempered.

There remains an enormous unmet need in the treatment of Alzheimer's disease. For the millions of elderly people worldwide, there are just four drugs available to them that can only offer a modest symptomatic effect. Even so, these treatments cannot slow or modify the course of this neurodegenerative disease, which is the ultimate goal in Alzheimer's therapy. However, despite this need, drug developers have struggled to get new agents to market and the pipeline over the past 10 years is littered with late-stage failures. Indeed, excluding reformulations, no new drugs have launched for Alzheimer's disease since Namenda (memantine; Forest/Merz/Lundbeck) arrived in 2002. Since then, around 20 products have failed Phase III trials. http://www.biospace.com/news_story.aspx?NewsEntityId=172943

Roche’s Pipline
Roche's scientists believe that the pipeline currently includes 10 new molecules with the potential to emerge as a best-in-class therapy. And the company says that it can move 20 programs into late-stage trials by 2015. Among its top prospects, Bloomberg highlights: Taspoglutide, a new GLP-1 drug for Type 2 diabetes; Aleglitazar, also for diabetes; The ‘good cholesterol' drug dalcetrapib and PLX4032 for melanoma. All are believed to have solid blockbuster potential. http://www.bloomberg.com/apps/news?pid=20601202&sid=aw9Tw5Ujka.E

Indian Generics
Pfizer has entered into a collaboration with India’s Strides Arcolab on the supply of 40 generic products. Pfizer’s new deal with Strides Arcolab follows two similar alliances last year with Aurobindo and Claris LifeSciences of India. Under the new collaboration Pfizer will commercialize Stride’s off-patent sterile injectable and oral products in the United States through its Established Products Business Unit. In May, Pfizer acquired rights to 55 generic pills and 20 injectables for more than 70 emerging and developed markets through new deals. Pfizer will commercialize the 60 products in phases tailoring its approach for different regions. Pfizer will gain rights to 60 products to be sold in developing markets, where it is seeking to add $3 billion in annual sales by 2012. http://www.dancewithshadows.com/pillscribe/pfizer-strikes-deal-with-strides-arcolab-on-40-generic-products/

Pfizer is reportedly in talks to buy a stake in India’s leading generic firm Dr Reddy’s Laboratories. Pfizer is keen to acquire the Hyderabad, south India-based Dr Reddy’s generic formulations business, reports quoting unconfirmed sources said. http://www.dancewithshadows.com/pillscribe/pfizer-eyes-dr-reddys-rs-1000-cr-branded-generics-business-reports/

AstraZeneca has entered into a license and supply agreement with Indian firm Torrent Pharmaceuticals Ltd tol supply 18 generic products to nine emerging markets. As per the deal Torrent will supply a portfolio of generic medicines to AstraZeneca for which the Indian company already has licenses in a range of countries. AstraZeneca will brand Torrent generics and sell them in many of its emerging markets, using its marketing force. Initially, AstraZeneca will purchase from Torrent the licenses and market authorizations for 18 products in nine countries. The AstraZeneca-Torrent agreement allows the flexibility to add further products and new countries, the Anglo-Swedish company said in a press statement. http://www.dancewithshadows.com/pillscribe/indias-torrent-pharma-to-supply-18-generic-drugs-to-astrazeneca-for-9-emerging-markets/

The Relevance of Invention Date in Patent Prosecution
The US first-to-invent patent regime is unique in that it allows a patent applicant to assert priority rights back to the invention date. The level of reliance on inventorship rights is important because it informs the longstanding policy debate over whether the US should conform to a first-to-file system as well as for patent applicant strategy. Prior studies have considered the use of inter partes interference proceedings. However, that approach necessarily ignores ex parte prosecution.

This paper presents a normative study of patent applicant use of invention-date rights during ex parte prosecution. Three sources inform the primary results: the prosecution history files of 21,000 patent applications filed in the past decade; a survey of 1,000 patent practitioners regarding their use of the novelty provisions of the Patent Act; and a collection of 11,000,000 prior art references cited in recently-issued patents. Additional compilations of prosecution file histories for patents identified as either (1) valuable or (2) worthless supplement these data sets and allow for an evaluation of the differential importance of the novelty rights. Finally, a set of opinions from the Board of Patent Appeals and Interferences (BPAI) evidences the difficulty of proving a prior invention date.

During prosecution, most patent applicants are faced with non-102(b) prior art that could be antedated. Yet, very few applicants actually attempt to assert prior-invention rights. A miniscule 0.1% of cases in my large sample included an assertion of novelty rights that directly led to an issued patent. The process of claiming priority to a pre-filing invention-date requires that an applicant prove prior conception and due diligence or reduction-to-practice. The difficulty of attempting to prove these elements are laid-out in a set of administrative patent appeal decisions where 77% of attempts to antedate references were rejected by the administrative court.

Given the difficulty of asserting invention-date-based novelty rights, it is unsurprising that applicants are more likely to assert such rights in cases of highly valuable inventions, choosing not to waste money in less valuable cases. Furthermore and perhaps contrary to conventional wisdom, my findings suggest that individual inventors assert invention-date-based novelty rights relatively less often and less successfully than large, publicly traded companies. Lastly, a practitioner survey of 1000 patent law professionals reveals, inter alia, a shared concern that attempts to antedate prior art leave patents open to challenge during litigation by providing “fodder” for validity challenges. http://papers.ssrn.com/sol3/papers.cfm?abstract_id=1576564

Hiring in India
Becton, Dickinson and Company (BD), one of the world’s leading syringe suppliers, is planning to add close to 100 people its India team each year, reports said. Becton Dickinson is proposing significant expansions in the manufacturing operations. The company is planning to transfer 10 manufacturing lines of IV catheter from Sweden to India. The company has also plans to expand its marketing operations as well by adding more workforce, reports said quoting senior official from Becton. Becton Dickinson has been operating in India since 1997. Currently India accounts for $100 million of its global annual income. Becton’s Indian business had grown 20 per cent two years ago. It currently sells 80-90 per cent of the company’s global product portfolio in India, except for the high-end medical diagnostics. In future, Becton would like to have a few pilot development opportunities in India.

Bayer Schering Pharma AG, Germany’s largest pharmaceutical company is planning to double its sales force in India as part of its strategy to make Asia an important market through making huge investments in the region, reports said. Over 20% of Bayer’s healthcare division’s 2009 sales were generated from the Asia Pacific region. Bayer Schering Pharma is currently one of the largest pharmaceuticals suppliers in China. As of now, Bayer’s business in India is focused majorly on its CropScience pesticides unit. In the next 4-5 years time Bayer wants to be among the top 10 pharma groups in India by 2015. Bayer aims tripling its workforce and a sixfold increase in sales in Vietnam by 2015. The company also targets to become one of the top three pharmaceutical groups in South Korea by 2013 by increasing its staff by 20%.

Despite serious layoffs in the developed markets, an increasing number of pharma multinational companies (MNC) from Europe and the US are planning to bolster their workforce in India. Big Pharma, which is incurring steady losses in the major markets, see the emerging pharma destinations like India as valuable hedges to offset their setbacks. Pharma sector employment opportunities better as Aventis, GSK, Merck looking fill hundreds of jobs in field & marketing.

GlaxoSmithKline (GSK) is another leading European pharma major looking to hire in India. The world’s second largest drug company plans to bolster its field force by employing at east 200 people. GSK India, which currently has 2,250-strong sales and marketing team, wants to enhance its field-force support in its vaccines, oncology and other specialty segments, the company said recently while announcing quarterly financial performance in India. http://www.dancewithshadows.com/pillscribe/pharma-jobs-in-india-mncs-on-a-hiring-spree-in-india/

Clinical Trials in India
The Clinical Trials Registry- India (CTRI) has been set up by the ICMR’s National Institute of Medical Statistics (NIMS) and is funded by the Department of Science and Technology (DST) through the Indian Council of Medical Research (ICMR). The idea behind setting up of the Clinical Trials Registry-India (CTRI) is to encourage all clinical trials conducted in India to be prospectively registered before the enrollment of the first participant and to disclose details of the 20 mandatory items of the WHO International Clinical Trials Registry Platform (ICTRP) dataset. Clinical trial outsourcing market in India is forecasted to grow at a CAGR of over 30% during 2010-2012 to around US$ 600 million by 2012, says new report by RNCOS. India will become one of the highest growing clinical trial destinations in the world, with this kind of growth, according to the study titled “Booming Clinical Trials Market in India”.

According to the figures collated with available information collected, as many as 308 persons died in the year 2009 till the month of August, reports said. The total number of trials registered in India was 158 in 2009, down by 30% compared to 229 in 2008. The Central drugs Standard and Control Organization (CDSCO) has granted permissions to about 2000 clinical studies from the year 2004 till December 2009, reports said quoting official sources. All the major pharmaceutical and biotech players as well as major CROs are making India their base for conducting global clinical trials. Clinical trial outsourcing market in India is forecasted to grow at a CAGR of over 30% during 2010-2012 to around US$ 600 million by 2012, says new report by RNCOS. India will become one of the highest growing clinical trial destinations in the world, with this kind of growth, according to the study titled “Booming Clinical Trials Market in India”.
http://www.dancewithshadows.com/pillscribe/india-enforces-stricter-norms-for-pharma-exporters-reports/

New Export Regulations in India
The government of India has brought into effect stricter norms for obtaining No Objection Certificates (NOCs) for pharmaceutical exporters. The Central Drugs Standard Control Organization (CDSCO) – the apex body regulating pharmaceutical industry in India – has issued circular with effect from 1st January 2010, announcing a set new rules for exporters, reports said. Exporters of pharma products now needs to submit documents including a shipping bill along with custom report to obtain no objection certificate (NOC) from the the Assistant Drugs Controller (ADC) for export of drugs and cosmetics. The original copy of the invoice in duplicate should be signed by the authorized authority. Certificate of analysis, current Good Manufacturing Practices (cGMP) certificates, certified copy of permission for production of the drugs and cosmetics in the list approved by the Central FDA or state drugs controller are among the other submissions mandated by the new regulation.

Exporters need also submit a sample of the drugs from the consignment sealed or signed by the customs officer, reports said quoting a circular No. ADC/TECH/BSZ dated January 1, 2010. In the case of bulk drugs, exporters should get thier labels duly signed and stamped by the head of Quality Control or Quality Assurance department. The same practice needs to be followed for outer cartons of subsequent packs.
The Indian pharmaceutical industry now ranks 3rd worldwide by volume of production thereby accounting for around 10% of world’s total pharmaceutical output in terms of volume, according to Srikant Kumar Jena, the Minister of State for Chemicals and Fertilizers, Government of India. Globally, Indian pharma market ranks 4th in terms of generic production and 17th in terms of export value of bulk actives and dosage forms.
Indian pharma companies export their products to more than 200 countries around the globe including highly regulated markets of USA, West Europe, Japan and Australia. The industry now produces bulk drugs or active pharmaceutical ingredients (API) belonging to all major therapeutic groups requiring complicated manufacturing technologies. http://www.dancewithshadows.com/pillscribe/india-enforces-stricter-norms-for-pharma-exporters-reports/

Broken Pharmaceutical Industry
The pharma and biotech industry spent some $65 billion dollars on R & D in 2008, according to the Pharmaceutical Research and Manufacturers Association. FDA only approved 24 new drugs (21 new molecular entities and 3 biologics) that same year, implying that it cost about $2.7 billion per drug approved. However, many of these are not for new molecular entities, but instead are for new indications for old drugs, or new dosing modalities (different formulation, dose, route of administration, syringe design, etc.), which is considered as “ever greening,” by the third world countries who don’t spend any money or spend very little on drug research because they are so-called “poor” to exploit the rich and greedy big pharma.

The Financial Times advises that to “boost success rates, lower costs, and triple returns,” big Pharma should simply buy them from smaller, more nimble and innovative biotech companies. http://www.ft.com/cms/s/0/2ed73272-0eb6-11df-bd79-00144feabdc0.html?nclick_check=1. Big Pharma didn’t wait for this advice. This scheme would certainly fit into the plans of most venture capital (VC) firms, who could cash out large profits if Big Pharma acquires the biotech startups that they have invested in. Thanks to kind of thinking big pharma had embarked on a major job shedding binge, eliminating positions duplicated as a result of mergers and a number of research programs, destroying the institutions that developed innovative drugs. The worst offender is Pfizer eliminating around 19,500 positions after acquiring Wyeth, followed by Merck around 16,000 jobs after buying Schering-Plough, and Roche about 1,500 jobs after purchasing the remainder of Genentech. To stay competitive, Johnson & Johnson is cutting 8,000 jobs this year, Eli Lilly is axing 5,500, and GlaxoSmithKline around 6,000 positions.

Stewart Lyman, owner & manager of Lyman BioPharma Consulting LLC in Seattle, analyses the numbers and suggests that drug makers need to find a more efficient way of developing medicines: http://www.xconomy.com/seattle/2010/03/05/the-pharmaceutical-rd-model-is-broken-heres-how-to-fix-it/?single_page=true

New Basis for Drug Development
Scientists from the Helmholtz Zentrum München and the Technische Universität München (TUM) under the direction of Prof. Michael Sattler have developed a new strategy allowing them to determine the spatial structure of biomolecules in solution. The method is flexible and generally applicable to obtaining structural information for signal forwarding pathways in the cell or in the regulation of gene expression. The current online issue of the scientific journal Angewandte Chemie reports on their results. http://www.sciencedaily.com/releases/2010/02/100225084636.htm

Snake venom charms science world
The King Cobra continues to weave its charm with researchers identifying a protein in its venom with the potential for new drug discovery and to advance understanding of disease mechanisms. The novel protein named haditoxin has been described in the Journal of Biological Chemistry (March 12, 2010). Haditoxin was discovered in Professor Manjunatha Kini's laboratory at the National University of Singapore. Co-author of the paper Dr S. Niru Nirthanan, now at Griffith University on the Gold Coast, has characterised the pharmacological actions of haditoxin. The editorial board of the journal has selected this work as the "Paper of the Week" recognising it as being in the top one per cent of their published articles in terms of significance and overall importance. While not every new toxin will convert directly into a clinically useful drug, he said there was potential for haditoxin to be a lead compound or template from which to design other drugs. "Because of the high specificity of these toxins, haditoxin may also be useful as a 'molecular probe' which will help us study neurotransmitter receptors and their role in disease." These receptors are important in neurodegenerative conditions such as Alzheimer's and Parkinson's diseases as well as in schizophrenia, anxiety and depressive disorders and nicotine addiction.

Glowing Sperm May Help
Many advances in reproductive and evolutionary biology have been constrained by the inability to discriminate competing sperm of different males and by the challenges of observing live sperm inside the female reproductive tract. What is the solution? Glow-in-the-dark sperm! Whenever a female mates with more than one male—and female promiscuity is more the rule than the exception in nature—there are conflicts between the sexes over paternity, as well as competition between rival ejaculates to fertilize eggs. Such post-copulation sexual selection is a powerful force for evolutionary change. http://www.syr.edu/news/articles/2010/fluorescent-sperm-03-10.html

Abbott Acquisitions
Abbott announced that it has completed its $123 million acquisition of STARLIMS Technologies Ltd., a leader in laboratory information management systems. "STARLIMS gives us access to innovative technologies and technical expertise for our long-term strategy in laboratory informatics," said Edward L. Michael, executive vice president, diagnostics products, Abbott. "The acquisition enables us to provide a common informatics framework across all of our diagnostics businesses and, equally important, will help accelerate STARLIMS's growth strategy in the non-diagnostics market segments it currently serves."

Abbott announced that its wholly-owned subsidiary, Amber Acquisition Inc., has commenced its cash tender offer for all outstanding shares of common stock of Facet Biotech Corporation at a price of $27 per share. The tender offer is being made pursuant to an Offer to Purchase, dated March 23, 2010, and in connection with the Agreement and Plan of Merger, dated March 9, 2010, by and among Abbott, Amber Acquisition Inc., and Facet, which Abbott and Facet announced on March 9, 2010.

Fortune magazine has named Abbott the world's most admired company in the pharmaceutical industry in 2010 in its annual listing, published in the March 22 issue of the magazine. Abbott has risen steadily up the list over the last several years – from #4 in 2008, to #3 last year – among companies competing for the best reputation among their peers. http://abbott.com/