We developed a unique technology platform called dual variable domain-immunoglobulin (DVD-Ig), which allows one drug to block two targets. This is in contrast to a typical monoclonal antibody (mAb), which has one unique binding domain with a single target to interrupt a disease process. A DVD-Ig, utilizing an immunoglobulin backbone, incorporates two pairs of distinct binding domains that can bind to two different targets independently. Simply, a DVD-Ig is capable of engaging two different molecules.
Addressing a single disease target with a traditional mAb can result in limitations of the therapeutic profile for immune-mediated inflammatory conditions, as many of these disorders can involve multiple disease mediators. For example, in rheumatoid arthritis, distinct disease mediators can contribute to various aspects of the disease: inflammation, angiogenesis and bone and cartilage erosion.
When delivering next-generation therapies to our patients, we focus on solutions that work in the most efficient and effective ways.
Small molecules are therapeutic agents chemically synthesized in the laboratory. They are formulated to be taken orally in the form of a pill or a tablet, usually once or twice a day. Small molecules can be designed to block the activity of a particular enzyme, such as a kinase on the inside of a cell or a cell surface receptor. They can also be designed to disrupt interactions between proteins or to stimulate the response of a cell.
Biologic therapies are substances derived from living organisms, such as bacteria and yeast cells. These living cells are genetically modified to produce therapeutic proteins (monoclonal antibodies or DVD-Ig), which are then harvested and purified as medicines.
Biologic therapies are often used to target interactions between soluble proteins and their cognate receptors on the cell surface or in cell-to-cell interactions. The biologic therapies are able to disrupt these interactions by binding to specific sites on the surface of proteins. Biologics are typically administered by intravenous infusion or by subcutaneous injection because they would be rapidly digested if taken orally.
Antibody-drug conjugates (ADCs) represent a proven technology platform that delivers a therapeutic agent using precise targeting of an antibody. ADCs combine the precision and specificity of antibodies with potent, intracellular small molecules to deliver a drug where it is needed.
ADCs are versatile delivery vehicles—the antibody, combined with a chemical agent, identifies the target on the surface of a cell and is actively taken up by that cell. Once inside the cell, the chemical agent is released to either reduce the activity of the cell or to kill the cell. The ADC is only taken up by targeted cells, limiting the effect on other cells.
See how we’re using ADCs to target cancer cells.
We are investigating several targets as part of our robust immunology pipeline.
Tumor necrosis factor-α (TNF-α) is a cytokine that plays a role in several immune-mediated, inflammatory conditions. TNF mediates a wide range of cellular activities, including proliferation, survival, differentiation and apoptosis (cell death). TNF-α is a contributor to the induction and maintenance of the inflammatory immune response.
Interleukin-1 (IL-1), which includes the two related cytokine proteins IL-1a and IL-1b, has a role in acute and chronic inflammation. IL-1 is produced in the body mainly by certain immune cells called macrophages and monocytes.
Interleukin-6 (IL-6) is a pro-inflammatory cytokine that plays a key role in immune-mediated, inflammatory disease. In rheumatoid arthritis, IL-6 contributes to both joint destruction and systemic manifestations. IL-6 is one of the cytokines that signals through the JAK/STAT pathway, which is involved in a number of chronic inflammatory diseases. Overproduction of IL-6 is involved in inflammatory, immune-mediated diseases. IL-6 and transforming growth factor-β are necessary for differentiating naïve T cells into Th17 cells; Th17 cells can lead to inflammation.
Interleukin-13 (IL-13) is an inflammatory cytokine that may play a role in asthma. IL-13 is primarily produced by a subset of T cells called T-helper cells 2 (Th2). IL-13 induces tissue inflammation, epithelial hypertrophy, mucus hypersecretion, goblet cell hyperplasia, subepithelial airway fibrosis, Charcot-Leyden-like crystal deposition, airway obstruction and airway hyperresponsiveness.
Interleukin-17 (IL-17) may play a role in a variety of immune-mediated, inflammatory diseases. IL-17A and IL-17F can mediate pro-inflammatory responses when produced in excess. IL-17 is produced primarily by specialized T cells called Th17 cells.
Proteins in the B cell lymphoma 2 (BCL-2) family regulate apoptosis, the natural process by which aged, damaged and unnecessary cells are removed.
 Correia I, Sung J, Burton R, et al. The structure of dual-variable-domain immunoglobulin molecules alone and bound to antigen. mAbs. 2013; 5(3): 364-372.
 Samanen J. Similarities and differences in the discovery and use of biopharmaceuticals and small-molecule chemotherapeutics. In: Ganellin CR, Jefferis R, Roberts SM, eds. Introduction to Biological and Small Molecule Drug Research and Development: Theory and Case Studies. 1st edition. Waltham, MA: Elsevier; 2013: 161-200.
 Panowksi S, Bhakta S, Raab H, Polakis P, Junutula JR. Site-specific antibody drug conjugates for cancer therapy. mAbs, 2014; 6(1):34-35.
 JAK: Janus Kinases; **STAT: Signal transducer and activator of transcription protein