The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 69

Primary structure
Amino acid composition
N & C terminal analysis
Peptide mapping & full sequencing
Identify & locate any disulfide linkages present
Secondary structure
Determine major elements of secondary structure
(e.g. % α-helix present)
Tertiary/quaternary structure
Determine biologically active format (e.g. monomer, dimer, etc)
Determine full 3D structure, if possible
Post translational modifications
Identify & locate any carbohydrate side chains
Oligosaccharide structural analysis (if present)
Identify & characterize any additional PTMs
(e.g. carboxylation, hydroxylation, amidation, etc.)
Figure 4.5 Task tree for the structural characterization of a therapeutic protein. A more detailed examina-
tion of many of these characterization studies is undertaken in chapter 7
In addition to the studies listed in Figure 4.5, stability characteristics of the protein with regard
to e.g. temperature, pH and incubation with various potential excipients are studied. Such infor-
mation is required in order to identify a suitable fi nal product formulation, and to give an early
indication of the likely useful shelf-life of the product (Chapter 6).
4.9 Patenting
The discovery and initial characterization of any substance of potential pharmaceutical applica-
tion is followed by its patenting. The more detail given relevant to the drug's physicochemical
characteristics, a method of synthesis and its biological effects, the better the chances of success-
fully securing a patent. Thus, patenting may not take place until preclinical trials and phase I clini-
cal trials are completed. Patenting, once successfully completed, does not grant the patent holder
an automatic right to utilize/sell the patented product; fi rst, it must be proven safe and effective in