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
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
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
 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