Established late in 2007, External Basic Research (EBR) is MRL's newest, and virtual, laboratory. Focused explicitly on external sources of science and innovation, EBR is developing and implementing a strategy to expand the scope and size of Merck’s early pipeline through collaborations with external partners. Like MRL's other research sites, EBR contributes to all stages of Merck's discovery pipeline, collaborating with external partners to discover and validate novel targets, access new technologies and bring forth preclinical candidates for Merck's development pipeline. EBR is staffed by scientific leaders with expertise in each of Merck's franchise and functional areas. These Merck scientists work with scientists from external labs on joint discovery projects, increasing the diversity of our scientific approaches and ideas for the Merck pipeline. Our virtual lab has a global footprint, with major partnerships in all corners of the world. The EBR portfolio includes partnerships with academic collaborators to identify and access novel targets, as well as biotechnology, shared risk and contract partnerships to deliver preclinical candidates for our pipeline. EBR's portfolio of collaborations is diverse and includes drug discovery programs in all six of Merck's franchise areas, with a goal of delivering 25 percent of the early pipeline from external sources of science within 3-5 years.

Merck BioVentures

Using scientific innovation to improve value and access to quality biological medicines

In December 2008, the Company announced it launched a new division called Merck BioVentures, or MBV. This division is aimed at developing biosimilar products that will capitalize on the upcoming patent expirations of many currently-marketed biologic therapeutics.

Background on biologics

Biological medicines are large molecules that are produced using living organisms, unlike small molecule pharmaceuticals that are generally produced from chemical synthesis. The first broadly available recombinant biologic medicine was insulin and other examples include erythropoietin for treating anemia associated with kidney failure, and granulocyte colony stimulating factor (GCSF) for preventing infections associated with the immunosuppression of chemotherapies used to treat cancer. In comparison to small molecule pharmaceuticals, biologics are more complex. These are large molecules with significantly higher molecular weights and often modified by the addition of sugar groups which influence the therapeutic properties of these products. Unlike small molecules where an established pathway already exists to develop and introduce generic copies, the laws and policies governing development of biosimilars are still emerging around the world. It is anticipated that biosimilars will offer great value and improved access to these classes of medicines.

GlycoFi provides innovation

A critical component of Merck’s entry into biosimilars was enabled by the acquisition of a New Hampshire-based company named GlycoFi in 2006. This very talented group of scientists genetically engineered a type of yeast, called Pichia, to produce glycosylated proteins with human sugars rather than yeast sugars. Importantly, the yeast strains that they engineered are capable of producing proteins with a selected and specific human glycoform. This is in striking contrast to the mixture of glycoforms that result when proteins are produced in a mammalian cell culture system. Through the GlycoFi acquisition, Merck obtained a strong intellectual property position for the production of protein therapeutics, including monoclonal antibodies and vaccines, that are of a particular glycoform and that constitute new compositions of matter.

The fact that the work is conducted with yeast also provides major advantages compared to working with mammalian cells. The cycle times and the cost of producing proteins in yeast are faster and cheaper than in mammalian cells, and this will facilitate both development and manufacturing. There are also tremendous advantages with regard to having scalable and portable bioprocesses, with the ability to carry out precise analytical comparability studies that will help ensure the quality and safety of molecules produced with this methodology. The homogeneity of products produced in humanized GlycoFi Pichia strains is greatly enhanced and substantially improves the ability to characterize with analytical precision.

The superior GlycoFi platform will provide MBV with a competitive advantage in the biosimilars area as well. It seems likely that one of the key issues for biosimilars in the future will be quality control and quality assurance, with a focus on reproducibility. Therefore, having exquisite control of glycosylation and the ability to precisely characterize a glycoprotein product will give Merck BioVentures a significant advantage in the regulatory and commercial arenas.

MBV and the future regulatory environment

The regulatory landscape for biosimilars is still evolving. In the past, small process changes in the production of some biologics led to changes in immunogenicity, with resultant significant adverse clinical consequences, including pure red cell aplasia in one case, and thrombocytopenia in another case. Issues like this lead to regulatory concerns about a simple generic-type biosimilar approval process. We understand these concerns and, therefore, our strategy is to conduct a thorough development program, including a preclinical toxicology package and Phase III clinical studies for each of our biosimilars and submit Biologic License Applications to obtain approval. We will, of course, adapt our approach as new legal requirements are implemented.

The fact that proteins can be produced that are more homogeneous and more amenable to thorough characterization will be important to payors, physicians, and patients as they choose from the available biosimilar products for a given indication.

Merck's first biosimilar, MK-2578, which is our version of pegylated erythropoietin with controlled humanized glycosylation, is now in clinical development for anemia associated with kidney failure. We anticipate launching this product in 2012.

Merck BioVentures will have a well-diversified product portfolio across many clinical indications. We are committed to having at least five biosimilars in late-stage development in 2012, and to launching at least six of these products between 2012 and 2017. The Company announced it plans to invest over $1.5 billion in Merck BioVentures by 2015. Of course, the experience that we are gaining with biosimilars, and the proprietary technology that we continue to establish, will further enhance our launch into novel biologics as well.

Genetic Research

Genetic research examines how variations in the system of human biomolecules — such as DNA, RNA and proteins — affect disease and an individual patient's response to drugs. The advent of DNA sequencing methodology that allowed sequencing of human genome, combined with advances in microarray technology, powerful computing hardware and software, and high-throughput analysis of biomolecules have made it practical to initiate studies that attempt to understand which genetic determinants cause a disease or drug response.

Merck scientists have a strong commitment to understanding how genes work and how they are linked to diseases and drug treatments. For example, Merck scientists identified two genes in mice that could someday be targets for obesity prevention drugs.  For additional information on this research please go to the publication in Nature Genetics.  Finding genes that can be influenced with drugs is very complex because in addition to environmental and behavioral factors, many different genes may contribute to each individual's obesity.

We may collect genetic samples in Merck clinical trials and analyze data from such trials so that we can apply new technologies to improve the development of new medicines and vaccines. The collection of samples represents the critical foundation of all clinical genetic research strategies. We obtain appropriate subject consent for use of the genetic samples in accordance with applicable domestic and international laws and regulations.

Regenerative Medicine Research

Some of the most advanced scientific technologies in regenerative medicine involve animal or human embryonic stem cells or stem cells developed through somatic cell nuclear transfer. Merck believes that such research has the potential to help identify important new medicines and therapies for currently unmet needs.

Merck has been conducting research into the biology of stem cells for more than a decade. This research has involved the use of animal or human adult stem cells.

Merck recently formed a Regenerative Medicine Oversight Committee comprised of Merck and external experts. This committee helps oversee Merck's research involving stem cells, including highly targeted research using human embryonic stem cells.

Merck, along with the scientific community, believes that research using stem cells, including human embryonic stem cells, has the potential to help identify medicines and therapies that will treat or cure diseases and alleviate the suffering of patients. Examples would include neurodegenerative conditions such as Parkinson's disease, cancer, cardiovascular disease, diabetes, osteoarthritis or trauma.

Merck conducts research using stem cells in full accordance with all applicable laws and regulations and with our own research policies. Research involving human embryonic stem cells is guided by National Academy of Sciences guidelines.

Merck is opposed to the reproductive cloning of human beings.

Bioprospecting

In the course of our drug discovery, we believe that it is important to protect and preserve the environment in which we operate. Merck no longer is actively involved in research on natural products. However, through external collaborations, Merck assays may be used to screen natural products, in which case Merck adheres to the Convention on Biological Diversity.

The content on this page was last modified on September 15, 2009.

Merck & Co., Inc., Whitehouse Station, NJ, USA, and Schering-Plough Corporation, Kenilworth, NJ, USA, are now one company. We have combined our global operations under the name Merck & Co., Inc. We are working to update our corporate responsibility Web site to reflect our new, combined, global organization.