Background
The Delenex PENTRA® technology enables the development of high quality antibody therapeutics. This technology is based on combining stable, fully human antibody frameworks with highest affinity CDRs of different origins. Our approach circumvents antibody display technologies such as phage, yeast, mammalian cell, ribosomal and retroviral display as well as immunisation of humanized mice.
Generation of PENTRA®antibody fragments
To generate PENTRA®fragments directed against a specific target, Delenex starts from its proprietary set of human antibody frameworks and combines them with highest affinity CDRs from various sources such as mouse, rabbit or human B cells as well as from synthetic libraries. The unique Delenex frameworks had been identified by an exhaustive selection of yeast cells engineered with more than 10e7 human antibody sequences to pan for antibodies with unsurpassed characteristics. By an elegant, cost-efficient and optimized work flow clinical grade PENTRA® fragments are readily obtained:
Model of a PENTRA®antibody fragment
The following model pictures the VH (blue) and VL (green) region of a PENTRA® scFv fragment. The key features of the technology provide an optimized surface area (orange) for highest solubility of the fragment and confer a strong VH/VL interface (buried) for best-in-class stability.
PENTRA® antibodies offer a number of advantages such as:
1. High affinity. Low picomolar monovalent affinities (KD) are obtained without affinity maturation.
“Relative potency”: Ratio of the concentrations at which a marketed control antibody and the DLX scFV display half-maximum potency.
2. High stability and solubility. PENTRA® fragments are based on pre-selected ultrastable human antibody frameworks leading to monomeric molecules with exceptional stability and solubility.
3. Small size. The low molecular weight facilitates tissue penetration and diffusion within confined body compartments. Rapid clearance from systemic circulation reduces adverse effects and minimizes the risk of anti-drug antibodies.
4. Preferred format for neutralisation of noxious targets. PENTRA® fragments harbor the target neutralisation capability and lack the so-called Fc region. Thus, unwanted ADCC (antibody-dependent cellular cytotoxicity) and CDC (complement-dependent cytotoxicity) reactions are avoided.
5. Topical/local application. The exceptional stability and the small size allow novel formulations and administration routes to target, e.g., the CNS, skin, joint and lung tissue.
6. Minimized immunogenicity. Clinical safety studies prove a very low risk of immunogenicity of antibodies.
7. Bacterial expression and production. Homogeneous clinical product is rapidly obtained from high yield, low cost bacterial fermentations (e.g., no glycosylation heterogeneity). One hundred gram batches of GMP material were successfully manufactured for clinical trial supply.