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.