What are Biopharmaceuticals?

Initially: (early 1980) class of therapeutic products produced by modern

biotechnology techniques (recombinant DNA technology) or by hybridoma .

Mid 2000: monoclonal antibodies not for therapeutic purposes, nucleic acid
based therapeutics.

A biopharmaceutical is a protein or nucleic acid based pharmaceutical

substance used for therapeutic or in vivo diagnostic purposes, which is
produced by means other than direct extraction from a native (non engineered)
biological source

Synonyms: biotechnology products, biotechnology medicines, products of

pharmaceutical biotechnology

The definition includes: recombinant proteins, recombinant antibodies, gene

therapy products, antisense oligonucleotides

Recombinant technology started in the seventies, today, there are 100 products
approved around the world.
The first biopharmaceutical to gain marketing approval was that of humulin
(recombinant human insulin developed and marketed by Genentech and Eli Lilly),
initially approved in the United States in 1982

Approximately 250 million patients had been administered these products and
currently in the region of 1 in 4 new molecular entities approved for medical use
are biopharmaceuticals

The majority of initially approved biopharmaceuticals may be classified as simple

replacement proteins, proteins displaying an identical amino acid sequence to a
native human protein and administered in order to replace or augment levels of
that protein (FIRST GENERATION BIOPHARMACEUTICALS)

Protein Engineering: controlled alteration of the nucleotide sequence of a

gene/cDNA
coding for a polypeptide, such that specific pre-determined changes in amino
acid sequence are introduced with one or more of the following objectives
(a) generation of faster/slower acting product;
(b) alteration of a proteins biological half-life
(c) alteration of product immunogenicity;
(d) generation of novel fused (hybrid) therapeutic proteins

SECOND GENERATION BIOPHARMACEUTICALS

Post translational modifications engineering
This entails covalent attachment of a chemical group to the
polypeptides backbone, or the alteration of a pre-existing
post-translational modification, such as a glycosylation
Pattern

Most common is PEGylation: straightforward and generally

increases the plasma half-life of the protein drug by reducing
the rate of systemic clearance

Engineered monoclonal antibodies

Future trends
Alternative production systems: Escherichia coli, engineered animal
cell lines: CHO, BHK, Saccharomoycese cerevisae

Alternative delivery

Nucleic acid based therapeutics: gene therapy: many

disappointments due to toxic/poor delivery, cancer gene therapy
antisesne oligonucleotides: single stranded nucleic acid-based sequences are
designed to hybridize with mRNAs, thereby preventing translation
siRNA: post translational inhibition of gene expression

Stem cell based therapy