THE ADAPTABLE CHALLENGE
Bioconjugates are versatile and can be used for a number of different applications. Most importantly, they are being used
for extending the half-life of the peptide. Despite their many uses they face a number of challenges. Depending on the type
of conjugate, there may be safety issues with their toxicological profile as is the case with PEGs. In the case of polypeptide-based
conjugates, there is concern over immunogenicity. Economic hurdles, although not a major concern at early stages of development,
are certainly a concern at larger scale and at later stages of clinical development of the bioconjugates. The ability to purchase
these conjugates from several sources is important for risk mitigation. The analytical hurdles encountered with bioconjugates
are of paramount concern, especially with regulatory bodies. Advances in linker technology or analytical methods are vital
to deal with these analytical challenges. Bioconjugates are the adaptable challenge.
ACKNOWLEDGMENTS
The author would like to thank the colleagues who provided ideas and comments during preparation of this paper. The author
would also like to provide special thanks to Dr. Sheri Barrack, PhD, for her support, information and guidance during preparation
of this article. Dr. Barrack is the senior vice-president of pharmaceutical development for Cebix, Inc.
Trishul Shah is the business development key account manager for the PolyPeptide Group, North America, Torrance, CA. trishul.shah@polypeptide.com
.
REFERENCES
1. Pharma Exec News, "PEGylation: Advantages And Potential," Apr. 7, 2009,
http://www.pharmaexecnews.com/biotechnology/pegylation-advantages-potential accessed Aug. 10, 2012.
2. J.M. Harris and R.B. Chess, Nature Rev. Drug Discov. 2, 214–221 (2003).
3. P. Taupin et al., "PEG and PEG Conjugates Toxicity: Towards an Understanding of the Toxicity of PEG and its Relevance to
PEGylated Biologicals," in PEGylated Protein Drugs: Basic Science and Clinical Applications (Birkhäuser Verlag, Basel, Switzerland, 2009), pp. 127–146.
4. Peptide Therapeutics Foundation, Peptide Therapeutics Foundation Database 2010.
5. F.M. Veronese, Biomaterials 22, 405–417 (2001).
6. J.M. Harris, M.D. Bentley, and M.J. Roberts, Adv. Drug Deliv. Rev. 54, 459–476 (2002).
|
