Pharmacy Industry News: Super resolution microscopy for pharmaceutical industry: Patents granted for 3D complex labeling

Super resolution microscopy for pharmaceutical industry: Patents granted for 3D complex labeling

Mechanism of action of drugs in body cells becomes transparent – the LIMON 3D microscopy (LIght MicroscOpical Nanosizing) of Prof. Dr. Dr. Christoph Cremer opens new possibilities for pharmaceutical research. 3D molecular complexes so-called biomolecular machines, targets of drugs can thus be studied in vivo.
“By means of these issued patents, our super resolution microscopy is especially important for molecular biotechnology and the pharmaceutical industry, with emphasis on target identification and personalized medicine,” according to Dr. Andrea Nestl, innovation manager of the Technology Licensing Office (TLB) and responsible for the patent management and the commercialization.
Biomolecular machines (BMM) are highly complex nanostructures consisting of several large molecules and which are responsible for basic functions in the body cells. Depending on their functional status they have a defined 3D structure. Examples of biomolecular machines are nucleosomes which enable the DNA, a two meter long carrier of genetic information, to fold in the body cells in a space of a few millionth of a millimeter in diameter only. Therefore, the DNA can serve as an information and control center.

By using Professor Christoph Cremer`s LIMON 3D in combination with LIMON complex labeling it is possible for the first time to make hidden proteins or nucleic acids of a 3D-molecule complex of the so-called biomolecular machines visible without destroying the complex. Up to now, the problem in most cases was that the complex had to be destroyed for detailed analysis of the individual macromolecules therein. Alternatively, virtual computer simulation models or expensive nuclear magnetic resonance methods were used to visualize the three-dimensional structure of such complexes.
The issued LIMON patent family allows the identification and the spatial positioning of individual components of the complex in its original native i.e. in a biologically relevant composition.
Besides the usual labeling of a macromolecule with a single fluorescent molecule, LIMON offers the option to label the target molecule with a variety of fluorescent markers of the same type in order to highlight several different areas. This is especially important for the investigation of such complexes in which not all binding sites for labeling probes are accessible, and thus it is difficult to visualize the individual partners.
“The pharmaceutical industry can trace in this way the interactions of biomolecular machines with pharmaceutically active compounds specifically and answer fundamental mechanistic questions about drugs”, according to Dr. Andrea Nestl, responsible for the development of patenting and marketing strategy on behalf of the University of Heidelberg. The mechanism of drug action in the cells becomes thus transparent, and the expensive development of drugs, which reaches the region from 500 million up to 2 billion U.S. dollars and usually lasts for 10 to 12 years, can take place in less time, and additionally, it is less cost-intensive.
The 3D Super Resolution Microscopy LIMON is an excellent tool for the development and validation of therapeutically active substances. As an example for the importance in pharmaceutical industry by using LIMON, it was possible for the first time to investigate in detail the gene product which is responsible for 20 percent of inherited metastatic breast cancer. The aim is the patient-specific optimization of the existing Herceptin therapies.
Due to individual genetic equipment patients with an identical diagnosis often respond very differently to treatment with the same medicine. Personalized medicine considers and takes into account all diagnostic possibilities for characterizing the personal particularities. Thus the Super Resolution Microscopy LIMON patents will offer a significant contribution. The results of this breast cancer study were recently published in the notable Journal of Microscopy (“Analysis of Her2/neu membrane protein clusters in different types of breast cancer cells using localization microscopy”).
To realize the 3D LIMON Super Resolution Microscopy Professor Christoph Cremer combines two of his 2D Super Resolution Microscopy methods: the localization microscopy SPDM (Spectral Precision Distance Microscopy) and the structured illumination SMI (Spatially Modulated Illumination), both patented by TLB as well. The main LIMON patents are issued in Europe and in the USA. With this European divisional patent application the third member of the LIMON patent family is being granted.
Christoph Cremer is full Professor and Chair of Applied Optics and Information Processing at the Kirchhoff Institute of Physics, and the Institute of Pharmacy and Molecular Biotechnology (IPMB), both at the University of Heidelberg, and he is group leader in the field of Super Resolution Microscopy at the Institute of Molecular Biology gGmbH (IMB) at the University of Mainz. In addition he is scientific member of the US-American Jackson Laboratory in Bar Harbor / Maine.
Professor Christoph Cremer is longtime coordinator of the BMM-network “Biomolecular Machines / Biomolecular microscopy” of the Rhine-Neckar bioregion, where numerous working groups in Heidelberg participated in the in the fields of medicine, mathematics / computer science, chemistry, pharmacy, physics and biology. Objective target is the quantitative analysis and modeling of “biomolecular machines” outside the cell and within the living cell itself.

Pharmaceutical Industry at a Cross Roads

The pharmaceutical (pharma) industry, once a thriving sector, has been cutting costs right and left by closing plants, laying off people, outsourcing jobs to third-world countries, and reducing research efforts to the minimum.

“The good old days of the pharmaceutical industry are gone forever. Even an improved global economic climate is unlikely to halt efforts by the developed world’s governments to contain spending on drugs,” according to a December McKinsey Quarterly report, a business journal published by McKinsey & Company.

Despite a strong third quarter financial performance, Novartis International AG, a Swiss-based pharmaceutical giant, announced that it is closing down three of its subsidiaries, resulting in the layoff of 2,000 people. About 35 percent of the jobs will be outsourced to China and India, according to a conference call.

“Novartis is announcing today additional cost reduction activity, which will be executed over three to five years … resulting in closure of two sites in Switzerland and one in Italy. … In total, approximately 2,000 positions will be reduced in the Group … mostly in Switzerland and the US offset by 700 new positions in low cost and other countries,” according to a Novartis press release.

During the third quarter, net sales had increased by 18 percent to $14.8 billion compared to the same time period in 2010. Net income increased by 7 percent to $2.5 billion.

Global giant AstraZeneca, based in London and the world’s seventh-largest pharmaceutical company in terms of revenue, announced in December that it would reduce its U.S. sales force by 1,150 people, about 24 percent of their U.S. sales force, by February 2012.

Cost reduction efforts, including the above reduction in force, saved the company between $50 million and $100 million, resulting in a third quarter profit of $3 billion, an increase of 36 percent over the third quarter 2010 numbers.

Rich Fante, president of AstraZeneca U.S., said in a recent press release, “These are difficult decisions that impact valued employees. The changes we are making, however, will help us deliver better results for our business and, most importantly, continue delivering on our mission of patient health.”

Global Pharmaceutical Firms’ Business Model Flawed

“Profit margins will be substantially lower than they are today. This dramatic situation requires Big Pharma executives to envision responses that go well beyond simply tinkering with the cost base or falling back on mergers and acquisitions,” the McKinsey report advised.

Despite total global 2010 drug sales of $856 billion, the pharmaceutical industry is distressed, given that the industry has not produced a blockbuster drug over the past years. New drugs are just improved copies of existing drugs.

Drug development history suggests that out of 10,000 drugs under development only one or two will hit the market big time, and that each one will take between 10 to 15 years to be developed. Although development costs are hard to assess, suggestions are that it costs more than $1 billion to develop a new drug.

In 2011, there were around 3,000 medicines being tested in clinical trials and/or awaiting Food and Drug Administration evaluation.

Most importantly, the industry is facing the expiration of a large portion of patents, such as Plavix (Bristol-Myers Squibb) and Zyprexa (Eli Lilly & Co.), resulting in the loss of revenue-producing income. Generic drug manufacturers are lurking around the corner and probably already have cheaper generic drugs waiting, which will be sold the day the patents expire.

“The next five years are expected to reflect a significant imbalance between new product introductions and patent losses,” suggested an article on the Zacks Investment Research website.

In response to large corporate inflexibility and bureaucratic environments, the industry has begun to fragment into different segments, including generic, biotech, life-sciences, health-care equipment, and midsize pharma companies.

From 84 companies in 1989, the industry has grown to 192 companies, with 51 midsize pharma and 51 health-care equipment firms being the majority of firms.

“Fragmentation is especially troubling for Big Pharma because it would be natural to expect that economic rents will accrue to an industry’s most innovative companies. Since some Big Pharma players can’t deliver innovations as quickly as biotech players can, only brand strength and a global commercial footprint would allow it to go on charging premium prices,” according to the McKinsey article.

Furthermore, unbridled research and development (R&D) spending are a sore point for investors, who have become vocal as such activities cut into their dividends and just don’t bring value to the investor.

Analysts have been especially honing in on the pharma industry and suggest that most growth will no longer happen in the large global companies, but will be found in the small and midsized firms that have sprung up over the past few years. Most importantly, the best results would be achieved when the industry players work collaboratively in the development of new drugs instead of going at it alone.