Groundbreaking Technologies and Approaches

When it comes to technological breakthroughs in biotech research, MedImmune is a visionary company that is helping to shape the industry. We have successfully discovered, developed, and applied an impressive range of innovative technologies, including antibody engineering, cell culture production, live viral vaccines, reverse genetics, and virus-like particle technology. The integration of MedImmune with Cambridge Antibody Technology and other biologics work being done within AstraZeneca in 2007 brought together a broad suite of antibody, protein generation, and optimization tools.

Monoclonal antibodies

Found naturally in the human immune system, antibodies are proteins produced in response to antigens. These highly specific molecules bind strongly to their target antigen.

All antibodies share the same basic structure. They are large "Y" shaped molecules, comprising two chains, a "heavy" chain and a "light" chain. The tips of the forked area, or variable region that come into contact with the antigen are highly variable in structure, enabling the antibody to be specific for a particular antigen.

Antibody-based therapeutics mimic and harness the body's own immune system and act by utilizing their acute specificity for their target antigen. At MedImmune, antibody drugs are generated using three core technologies:

  • Phage display
  • Ribosome display
  • VelocImmune® (human monoclonal antibody-producing mice)*

Antibodies generated by these three techniques are currently produced from a single clone of cells, and are therefore called monoclonal antibodies. The majority of approved monoclonal antibodies marketed today are humanized and chimeric monoclonal antibodies. However, human monoclonal antibodies which are less likely to cause adverse immunological responses in patients now form the largest group in research and development pipelines and are expected to be the fastest growing segment of antibody therapeutics in the future.

*Regeneron

Vaccines

MedImmune has the expertise to address target diseases with a wide variety of vaccine technologies. We are instrumental in the discovery and development of these cutting-edge biologics.

Live attenuated vaccine
MedImmune has developed a prudent and comprehensive strategy to apply its unique live attenuated influenza vaccine (LAIV) technology to the development of pandemic vaccines, prioritizing the subtypes based on current epidemiology.

Seasonal LAIV attributes suggest that a pandemic LAIV formulation may be an important component of pandemic preparedness for both industrialized nations and developing countries.

Reverse genetics
Reverse genetics is a method by which viruses such as influenza can be generated from segments of DNA. Reverse genetics can be particularly useful in the development of pandemic vaccines because the process does not require manufacturers to work directly with potentially highly infectious strains such as H5N1, rather only with segments of the virus's genome. Reverse genetics is also being applied in the development of seasonal influenza vaccines.

Viral vectored vaccines
Advances in molecular virology have facilitated an understanding of the regulation of viral replication, gene expression and molecular pathogenesis. At the same time, this understanding has enabled the development of novel viral vectors useful for vaccination. A variety of such vectors are now being advanced in preclinical and clinical studies.

Virus-like particles
Virus-like particles (VLPs) consist of viral protein(s) derived from the structural proteins of a virus. In some cases these proteins are embedded within a lipid bilayer. These particles resemble the virus from which they were derived, but lack viral nucleic acid, meaning that they are not infectious. The VLPs used as vaccines are often very effective at eliciting both T-cell and B-cell immune responses. The human papillomavirus and hepatitis B vaccines are the first VLP-based vaccines approved by the FDA.

Subunit vaccines
Subunit vaccines contain purified antigens rather than whole organisms. These vaccines are not infectious, so they can be given to immunosuppressed people, and they are less likely to induce unfavorable immune reactions that may cause side effects.

Next generation proteins

As a forward-thinking company, we are constantly exploring alternative technologies to discover compounds effective against new and challenging therapeutic targets.

While the majority of MedImmune's current drug projects are based on either antibody or vaccine technology, we have a dedicated team that works on next generation proteins, collaborating with other biotechnology companies and academic institutions.

Some of the approaches include:

  • Design and generation of very small, stable, antibody-like scaffolds that offer new routes of administration
  • Engineering of antibodies into multispecific compounds capable of interacting with several targets simultaneously
  • Drug complex G-protein coupled receptors, ion channels and intracellular protein-protein interactions
  • Use of protein-digesting enzymes to remove a specific target of interest
  • Exploring the potential of developing RNA inhibitor (RNAi)-based therapeutics and improved delivery methods
  • Developing peptides as a drug class
  • Engineering or selecting antibodies for their ability to penetrate the blood-brain barrier, or to be delivered by inhalation

In all of these efforts we are guided by the target selection teams of our five key therapy areas so that we can ensure that technical success will have the potential to result in a meaningful product with substantial patient benefit.

Translational sciences

MedImmune's Approach to Translational Science

At MedImmune, translational science is a "mindset" embedded throughout the organization.

But what is translational science? It is an integral innovative approach to development of a new generation of drugs, in which we are seamlessly bringing knowledge and information from early discovery to the clinic and back again. This methodology enables us to translate the findings of basic research quickly and more efficiently into clinical practice, thereby improving patient care and enabling science driven drug development and decision making.

Critical to the success of our entire drug development process are science driven approaches that utilize a better understanding of disease and patient subsets, drug mechanism of action and effective use of biomarkers, which are continually being identified through our translational research. Biomarkers are biological indicators–such as certain genes or gene mutations, proteins or cells–that are used to measure biological functioning, the underlying disease pathology, or response to a medical intervention. From bench to bedside and back, we are using the information gleaned from biomarkers and a better understanding of characterization of disease and patient subsets to help investigators identify potential drug candidates, better select patients, more accurately predict clinical outcomes, and manage potential drug safety problems. Biomarker research may help speed the availability of important drugs to patients and enable treatments to be directed to patient populations that may yield the highest benefit, thereby potentially reducing overall healthcare costs.

One example of a biomarker directed approach is through targeting PDGFRα (platelet-derived growth factor receptor alpha). PDGFRα is a pathway that may play a role in regulating transformation, tumor microenvirnonment, progression and metastasis of solid cancer tumors. Early stage research has shown that our fully human monoclonal antibody to PDGFRα (MEDI-575) inhibits signaling from this pathway on some cancer cells and supportive stroma. MEDI-575, currently in Phase I clinical development is scheduled to be tested in cancer patients that have a high prevalence of either tumor expression and/or tumor stromal cell expression of PDGFRα. Furthermore, PK/PD modeling of MEDI-575 utilizing preclinical pharmacology and toxicology models has enabled dose selection for clinical testing. MEDI-575 is in Phase 1 development in patients with advanced solid tumors.