Combining Antibody Functions To Target Two Or More Disease-Causing Processes

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Abbott scientists presented pre-clinical data demonstrating that a single molecule with two antibody functions can target two disease-causing agents implicated in the progression of rheumatoid arthritis, IL-1Alpha and IL-1Beta. The poster presentation, entitled "Anti- IL-1Alpha/Beta Dual Variable Domain Immunoglobulin (DVD-Ig), a Novel Inhibitor of IL-1Alpha and IL-1Beta is Efficacious in Mouse Collagen-Induced Arthritis Model" was presented at the Cytokines, Mediators and Gene Regulation poster sessions during the meeting.

The study builds upon research published in the November 2007 issue of Nature Biotechnology. In that paper, Abbott scientists were the first to report the discovery of a proprietary technology that combines the function and specificity of two or more monoclonal antibodies (mAbs) into one molecular entity that demonstrates drug-like properties and manufacturing feasibility. These molecules, called DVD-Ig, may allow for development of individual drug candidates that target multiple disease-causing agents in a variety of therapeutic categories.

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Study results reported today show that therapeutic effect with the DVD-Ig molecule resulted in a profound inhibition of arthritis in mice as assessed by MAS (p<0.05, by Mann Whitney) and paw swelling (p<0.05, by Student t test). In addition, the DVD-Ig molecule showed a similar efficacy to the monospecific anti-IL-1Alpha and anti-IL-1Beta antibodies in combination, and had a comparable impact on synovial hyperplasia (an overgrowth of the inner layer of an articular capsule surrounding a joint), as well as bone and cartilage damage.

"For years, small molecules have been combined to create more effective medicines, but combining large molecules, or biologics, has been a significant challenge," said Daniel Norbeck, Ph.D., vice president, Global Pharmaceutical Discovery, Abbott. "Abbott's DVD-Ig technology opens up a whole new set of possibilities for drug development and biologic treatments that have the potential to more effectively treat individuals with complicated conditions such as rheumatoid arthritis."

The efficacy of the DVD-Ig molecule, along with the parental monospecific anti-IL-1Alpha and anti-IL-1Beta antibodies, was evaluated in the standard mouse collagen-induced arthritis (CIA) model. The monospecific antibodies and the DVD-Ig molecule were dosed therapeutically two or three times per week, respectively, for eight days. The impact of treatment was evaluated by mean arthritic score (MAS) and paw swelling.

More than five million people worldwide suffer from rheumatoid arthritis, a chronic inflammatory disease that causes pain, stiffness, and swelling around the joints. Effective biologic treatments exist but given the complexity of the disease, there is a medical need to develop new drugs that can simultaneously target two or more pathogenic processes. Such agents may have improved efficacy over monospecific agents and may also be useful for treating patients that do not respond to monotherapy.

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