IVDT_In Vitro Diagnostics Technology

IVD Technology, Spring 2013

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ASSAY DEVELOPMENT tidic epitope presenting mechanism described previously may provide an explanation. Small molecules such as drugs, steroid hormones, lipids or glycolipids, and food or environmental contaminants with a molecular weight less than 1 kDa are too small to be appropriately processed and presented to the immune system. As a result, they are not immunogenic. However, if the small molecule is chemically linked to a large protein molecule, a specifc antibody to small molecules or chemical groups can be generated. Studies have shown that any alteration in the shape, size, or charge of a hapten changes its ability to bind to antibodies; thus, it is essential to have a large diversifying antibody repertoire combined with comprehensive nonpeptidic epitope presenting molecules as a basis for developing high-quality antibodies to these haptens. Apparently, the rabbit immune system is developed to fulfll this purpose. A lot of surface antigens from pathogenic microbes are carbohydrates, lipids, or glycolipids. Seemingly, rabbits possess a well-suited immune system to fght these microbes and are able to produce high quality antibodies for IVD applications Applications in Diagnostics Anatomic pathology. One of the most widely used applications for RabMAbs is IHC for anatomic pathology. RabMAbs are well-recognized in pathology labs as best-in-class reagents for IHC, and have taken the majority of market share from mouse monoclonal antibodies for many important markers. Two RabMAbs received FDA approval as companion diagnostic antibodies Feature Endogenous H Endogenous L Average chromosome # Fusion efficiency Hybridoma stability 240E-1 + + 60 71,810,000 37,200,375 low poor for IHC tests of Her-2 and c-Kit for cancer drugs Herceptin (Genentech) and Gleevec (Novartis), respectively. One RabMAb to estrogen receptor (ER) received FDA 510K approval as a Class II diagnostic reagent for breast cancer prognosis. Major players in anatomic pathology diagnosis have adapted RabMAbs in their automated immunostainer systems. EP Clones, a new generation of RabMAbs provided by Epitomics, are recognized as premium antibodies for anatomic pathology. For example, the RabMAb against ETS TMPRSS2-ERG fusion protein is a gold-standard clone for prostate cancer diagnosis and prognosis. Companion diagnostics. RabMAbs have been demonstrated to be superior reagents for detecting subtle protein modifcations such as phosphorylation, methylation, acetylation, and glycosylation. Te posttranslational modifcations of proteins play central roles in cell-signal transduction and other cellular activities, which could refect a change of disease status as both a disease target and/or biomarker. In addition, the pathogeneses originates not only from changes in protein sequence or expression level but also from changes in protein conformational structure or even abnormal interactions among proteins such as prion disease. Terapeutic companies have discovered or identifed a large number of disease targets in these categories and are developing companion diagnostic antibodies for patient selection and therapy efcacy monitoring as they develop therapeutic products. We believe RabMAb technology will allow the development of antibodies that quantitatively measure subtle changes 240E-W + + 84 33,400,000 17,302,500 high intermediate 240E-W2 + 89 5 3 high good 240E-W3 73 high good Table I. This table provides a summary of the characteristics of different rabbit fusion partner cell lines. 26 IVD TEC HNOLO G Y | SP RIN G 2013 magenta cyan black in biomarkers with better specifcity and sensitivity than current techniques. Indeed, RabMAbs are becoming the frst choice of reagent for companion diagnosis, and more products are expected to enter the market in the years ahead. Immunoassays for small molecules. Immunodiagnostics in body fuids such as blood, urine, and saliva is the largest IVD segment. Most pointof-care tests belong to this category. From an antigen perspective, immunodiagnostic tests include microbial antigens such as viral, bacterial, fungal, and parasitic antigens; nonmicrobial antigens such as tumor antigens and autoantigens; and nonclinically relevant antigens such as food toxins or environmental contaminants. Antibodies to small molecules have vast diagnostic applications such as steroid hormone test, food safety assessment, drug abuse detection, and drug metabolite concentration monitoring. A set of RabMAbs to steroid hormones such as estradiol, estriol, and progesterone and food toxic substances such as chinolone, enrofoxacin, fumequine and neomycin have been developed. Typically these RabMAbs demonstrate better sensitivity and specifcity in comparison with rabbit polyclonal antibodies or mouse monoclonal antibodies. We have developed a RabMAb to THC (a marijuana substance) for a drug test with 1000 times the sensitivity that can be achieved through commercial mouse monoclonal antibodies (data not shown). RabMAbs to multiple epitopes of polyethylene glycol (PEG) have allowed us to develop unique detection kits that are widely used in the pharmaceutical feld. Te RabMAb to thiophosphate esters has advanced scientifc research.14 Te diagnoses of many bacterial infectious organisms such as strep A, tuberculosis, legionella, H. pylori, and chlamydia detect glycolipids, polysaccharides, or lipids on bacterial surfaces. Normally, mouse is not the ideal species for generating antibodies to this type of antigen, and RabMAb technology presents a great opportunity for i v d t e c hnol ogy. com ES236234_IV1305_026.pgs 04.23.2013 23:42 UBM

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