1.
Protein Therapeutics: a summary
and pharmacological classification
Benjamin Leader, Quentin J. Baca and
David E. Golan
Yiben Wang
11/16/11

2.
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

3.
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)
5. Faster FDA approval time
-2003: 1980-2002  33 therapeutic proteins, 294 small-molecule
drugs (>1year)
6. Unique form and function
-Companies – patent protection

4.
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

5.
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

6.
Group II: Protein therapeutics with special targeting
IIa: Interfering with a molecule or organism
IIb: Delivering other compounds or proteins

7.
Group III: Protein vaccines
IIIa: Protecting against a deleterious foreign agent
IIIb: Treating an autoimmune disease
IIIc: Treating cancer

8.
Group IV: Protein diagnostics

9.
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

10.
Recombinant human proteins:
-FDA – biotechnology medicines:
-Monoclonal antibodies
-Natural interferons
-Vaccines
-Hormones
-Modified natural enzymes
-Cell therapies
More work needs to be done.