Active Antibodies on the Cheap

Some statistics on the antibody therapeutics (some of the numbers are couple of years old!):

  • 20 Therapeutic Antibodies have been approved by FDA
  • At least 150 antibody based drug candidates were under development as of 2006
  • Worldwide sales of antibody therapeutics in 2005 was more than 12 billion dollars
  • 55% of the drugs under development are mAbs
  • Pharmaceutical industry is aiming at producing 10 tons of antibodies per years

This intense interest in antibody based therapeutics is driving development of new antibody technologies for purification, production, alternative engineered affinity proteins etc. This interest is also good news for Biosensing because antibodies are most commonly used biomolecular recognition elements used for detection of analytes. See my post for information on antibodies and other bio-molecules used as recognition elements in biosensors.

One major disadvantage of antibody therapeutics is cost: Annual cost for the treatment of rheumatoid arthritis, is approximately $13,500, while that of Rituxan, an anti-cancer MAb, is $10,000. Purification of Antibodies is a multistep, time-consuming and expensive step and methods that can simplify the purification step will be extremely useful. Whitesides Group at Harvard has come up with a simple non-chromatographic method to purify antibodies that are bivalently active (J.Am.Chem.Soc. June 16 2009). The idea is simple as shown below in schematic. Method uses bivalent or trivalent haptens to form dimer, trimer or oligomer antibody complex that precipitate easily at 35% ammonium sulfate concentration. No cumbersome chromatography is needed and purity of >95% is achieved. What is icing on the cake is that method only purifies antibodies that are bivalently active (both of the binding site on antibody is active)

 

 

Primary limitation as pointed out by authors is that this method requires multivalent haptens so may exclude antibodies against proteins, however as authors pointed out small antigenic sequence or domains may be used for this purpose. However there are few other hiccups that are obvious

  • Synthesis of multivalent haptens of very high purity will be very expensive
  • Large excess of monovalent haptens are used to dissociate antibody complex: Can be very expensive
  • Dialysis is used to remove monovalent hapten: Time consuming and high affinity antibodies may nit dissociate completely

But hey method is simple and may prove to be useful for select applications

 

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