Protein Therapeutics: a summary and pharmacological classification
Benjamin Leader, Quentin J. Baca and David E. Golan
Yiben Wang11/16/11
Protein Therapeutics:
-25,000-40,000 different genes in the human genome-Alternative splicing of genes-Post-translational modifications-Very high number of functionally distinct proteins
Disease View:-Immense challenge:
-One protein is mutated or abnormal-Present in high or low concentrations
Therapeutic View:-Tremendous opportunity
130 different proteins or peptides – FDA approval
Advantages of protein therapeutics:
1.Proteins – highly specific and complex set of functions-Chemical compounds can’t mimick
2.Specificity -Less chance of interference; reduce adverse effects
3.Natural production -Well tolerated; no immune response
4.Diseases – gene is deleted or mutated-Replacement treatment – no gene therapy (Unavailable)
•Faster FDA approval time-2003: 1980-2002 33 therapeutic proteins, 294 small-molecule
drugs (>1year)
•Unique form and function-Companies – patent protection
Functional classification of protein therapeutics:
Group I -Protein therapeutics with enzymatic or
regulatory activity
Group II-Protein therapeutics with special targeting
activity
Group III-Protein vaccines
Group IV-Protein diagnostics
Group I: Protein therapeutics with enzymatic or regulatory activity
Ia: Replacing a protein that is deficient or abnormal
Ib: Augmenting an existing pathway
Ic: Providing a novel function or activity
Group II: Protein therapeutics with special targeting
IIa: Interfering with a molecule or organism
IIb: Delivering other compounds or proteins
Group III: Protein vaccines
IIIa: Protecting against a deleterious foreign agent
IIIb: Treating an autoimmune disease
IIIc: Treating cancer
Group IV: Protein diagnostics
Challenges for protein therapeutics:
1.Protein solubility, route of administration, distribution, and stability.
2.Immune response.
3.Physiologically active – post-translational modifications.
4.Costs
5. Ethics
Recombinant human proteins:
-FDA – biotechnology medicines:-Monoclonal antibodies-Natural interferons-Vaccines-Hormones-Modified natural enzymes-Cell therapies
More work needs to be done.
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