Our rationale for discovering therapeutic antibodies is that the human immune system produces antibodies to its diseases. Automated Cell is the only company to “mine” this unique antibody source. ACI has the proprietary technology to create libraries of these antibodies, functionally screen them in high volume to identify functional antibodies and their targets, and then convert that knowledge into monoclonal antibody drug candidates. We perform our discovery using a target-independent approach. Our monoclonal antibody discovery engine employs three proprietary technologies, described in detail below, using six issued and six pending patents. Antibody Target Discovery Automated Cell (ACI) has created a high-throughput, function based approach to identification of therapeutically relevant antibodies from patient plasma using a bead-based epitope specific approach. Once antibodies are fractionated onto beads the beads are directly assayed using ACI’s high-throughput functional biology platform. Beads associated with interesting activities, such as apoptosis, cytostasis or inhibition of anchorage independent growth, are then sequenced and scaled up. Scaled up beads are used to affinity purify antibody for functional characterization and target identification. This function based approach to antibody discovery offers several advantages over more typical genomic/proteomic approaches to target identification and validation: 1) Targets identified by this method are suitable for antibody therapeutics; 2) Because targets are selected based on function they are simultaneously validated; 3) Because the approach is function based it is unbiased with regard to target sequence and offers an opportunity to discover truly novel targets or assign new previously unrecognized function to new targets. Once the target is identified ACI will generate fully human monoclonal antibodies using its Immunocreation technology. Identification of functional human monoclonal antibodies is accelerated through the use of ACI’s high throughput, function based screening platform. Functional Biology Platform Our powerful functional biological screening process is called CytoWorks.Ô Living cells are imaged using visual and fluorescent analysis in a normal cell-culture environment without their destruction through fixation, re-suspension or dilution. Drug induced changes in phenotype such as morphology, motility, colony-formation, cytokinesis, or ultra structure can be digitally recorded and quantified with precision and accuracy. Cell subpopulations can be identified and quantified. Multi-parametric analysis of 65 parameters extends the breadth of information obtainable, thereby increasing assay sensitivity. Throughput is achieved through use of high-density, 384-well cell culture plates: The use of high-density cell culture plates facilitates the design of information rich experiments that can address a large number of variables in a single experiment. For antibody discovery, antibody libraries from diseased plasma are plated on 384-well plates with living human cells of the disease chosen. The antibodies are screened for function against the oncology cell line chosen for the primary screen. Data is analyzed with our PhenowareÔ informatic system to identify antibodies that kill or inhibit the growth of cancer cells. This knowledge is then used to identify and prioritize functional antibody candidates and targets. Monoclonal Antibody Creation Based upon the knowledge gained for a specific antibody-target pair, ACI creates human monoclonal antibodies through the reconstitution of the human immune system in immunodeficient mice. This system can be prompted, through immunization, to produce human antibodies against a selected disease target or tissue. Once the system is immunized, the human lymphocytes are harvested from the mice and fused with MFP-2™ fusion partner cell line to create human antibody producing hybridomas. This system has been proven to be effective in generating high quality human antibodies against both foreign (e.g., viral targets such as respiratory syncytial virus (RSV)) and self-disease targets or "antigens" (e.g., cancer and autoimmune targets such as TNF-α). This technology derives a significant part of its functional and proprietary value from our humanized and immortal fusion partner cell line MFP-2™. This cell line effectively and efficiently fuses with otherwise mortal antibody producing human lymphocytes to create human hybridomas that have the antibody producing characteristics of the human lymphocytes and the immortal characteristic of MFP-2™. Technology References For more information please contact: Kevin Sullivan Vice President, Business Development Automated Cell, Inc. 390 William Pitt Way Pittsburgh, PA 15238 E-mail: ksullivan@automatedcell.com Copyright © 2005, Automated Cell, Inc.