Synthetic antibody libraries tend to yield clones with more homogenous properties and to perform better against highly conserved antigens, since antibody genes have not undergone in vivo negative selection. We chose to concentrate amino acid-diversity in the CDR3 loops of heavy and light chains, since these positions are frequently involved in contact with the antigen. However, we also chose asparagine as residue 52 of VH, as this position is frequently changed during somatic hypermutation and in affinity maturation procedures. Library clones based on the DPL16 germline gene, we inserted at least one proline at positions 91, 92, 93, 95 or 96, according to previously published strategies. Sequence analysis of PHILODiamond- derived clones revealed a preference for a proline insertion at position 95 or 96, which may favor beta turn formation. The DP47 germline VH gene, chosen for library NVS-CECR2-1 construction, presents a number of attractive features. First, it is frequently associated with high thermal stability of the corresponding antibody clones. Second, it confers binding to protein A even in scFv format, a feature, which is particularly attractive for antibody purification and for immunodetection purposes. The PHILODiamond library was found to contain.90% of functional clones. It was tested on more than 15 antigens, ranging from big size molecules like collagen-I or fibrinogen, over a broad range of targets, including small catalytic domains and small toxic organic molecules. The modular design of the library allows a facile reformatting of antibody clones in several functional variants, such as SIPs or full length IgGs Furthermore, the concentration of amino acid diversity in CDR3 loops facilitates the implementation of affinity maturation procedures by randomization of CDR1 or CDR2 region, as recently shown for the selection of antibodies against Placental Alkaline Phosphatase, an ovarian cancer marker. We chose to use the scFv antibody rather than Fab fragments or dAbs, as scFv��s tend to express better and yield higher levels of antibody OAC-2 display on filamentous phage. On the other hand, scFv fragments may form non-covalent oligomers, a feature which is not shared by Fab fragments. Antibody clones based on scFv fragments can be easily reformatted into intact human immunoglobulins, while the same feature is not possible with dAbbased antibodies, which lack the light chain domain. The PHILODiamond library performed better for most antigens, or at least in a similar fashion, when compared in side-by-side selections with the ETH2-Gold library. Only in the case of collagen I, fewer antibody clones were isolated from the PHILODiamond library. The new library presents a number of attractive features, including binding to protein A for all library members. This property cannot be achieved using other synthetic libraries, which make use of various types of germline genes coding for the VH domain.