4 strategies that pharmaceutical companies employ to protect drug patents

20160801130000, Mak Wen Yao 
drug patent, pharmaceutical, pharmacy
4 strategies that pharmaceutical companies employ to protect drug patents
The costs of developing new pharmaceutical drugs have ballooned to astonishing figures in recent years, owing to much stringent regulations and safety requirements in conducting clinical trials. Latest data suggested a cost of over USD$1 billion is needed for one drug molecule to make it to the market. Although pharmaceutical companies employ drug patents to ensure market exclusivity, this typically only lasts for 20 years (1). While the research and development process itself takes up as much as 10 years, pharmaceutical drug companies have engaged in multiple strategies to extend their drug patents.

1. Improved formulations


Many oral drugs enter the market as a standard, immediate-release dosage forms. It is the most straightforward method to deliver an orally-active pharmaceutical ingredient systematically. When pharmaceutical companies face patent expiry of a blockbuster drug, they often opt to develop alternative formulations which are more efficacious. These new formulations can be developed to reduce dosing frequency, or to improve patients’ compliance. For example, an extended-release formulation can be used to protect the patent of an original, immediate-release drug. Moreover, new improved formulations have an edge when facing increasing competition from generic alternatives.

Several common examples can be used to illustrate this idea. The patent of the blockbuster antidepressant drug Prozac produced by Eli Lilly & Co. expired in August 2001, and the company responded by launching an improved, once-weekly formulation known as Prozac Weekly (2).

2. Stereoselectivity / chiral switching


Enantiomers are two molecules with identical molecular structure and bonding patterns, with the only difference in their spatial orientation. In simple terms, enantiomers are the mirror image of each other (3). However, despite the molecular similarity, these isomers could have distinct chemical and pharmaceutical properties.

Many drugs are marketed as a mixture of enantiomers, i.e. a 50/50 combination of both the S- and R- isomers. Pharmaceutical companies realised certain isomers have a more favourable therapeutic profile such as fewer side-effects, enhanced efficacies, wider therapeutic index or less significant interactions with other compounds. By isolating the single enantiomers, pharmaceutical companies can then extend the drug exclusivity by rebranding the enantiomers under a new patent.

A famous example to this stereoselectivity is the popular acid-reflux blockbuster drug, Nexium. It can be considered as the continuation of another popular drug Prilosec or omeprazole marketed by AstraZeneca. Patent for Prilosec expired in 2002, and the company responded by synthesising the (S)-enantiomer of omeprazole. This enantiomer was later known as the famous Esomeprazole and was accounted for nearly $3 billion sales for the company in the following year after Prilosec lost its market exclusivity (4).

3. New Indications


In addition to modification of the drug formulations, pharmaceutical companies also search for new uses for drugs with near patent expiry. Many compounds are active against multiple targets and these data is available early during the drug development process. By identifying these new targets and further developing the compound into active pharmaceutical drugs, a company can then maximise the return-on-investment of the compound.

Finasteride was initially marketed for the treatment of benign prostatic hyperplasia under the brand name Proscar. However, it was later found to be effective against male pattern baldness and was marketed under a new patent as Propecia (4).

4. Combination of products with near patent expiry into a single product


Pharmaceutical companies have been known to combine two or more related drug compounds into a single dosage form under a new patent. These drugs compound, however, are indicated for similar diseases. In addition, they must exhibit stability when formulated in the same dosage form.

Olanzapine (Zyprexa), a compound used to treat schizophrenia and marketed by Eli Lilly & Co. faced an expensive drop in revenue once the patent expired in 2011. The company responded by combining Zyprexa with another of Lilly blockbuster drug, Prozac, into a new product called Symbyax to treat bipolar disorder (4). MIMS

Reference:
1. Herper M. Solving The Drug Patent Problem [Internet]. Forbes. 2002 [cited 2016 Jul 24]. Available from: http://www.forbes.com/2002/05/02/0502patents.html
2. Burton T. Weekly Prozac Fails to Boost Eli Lilly Despite Pill’s Benefits [Internet]. The Wall Street Journal. 2002 [cited 2016 Jul 24]. Available from: http://www.wsj.com/articles/SB102667268367162520
3. Reusch W. Stereoisomers [Internet]. Michigan State University. 2013 [cited 2016 Jul 24]. Available from: https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/sterisom.htm
4. Cunningham M, Spruill W. Strategies for Extending the Life of Patents. BioPharm Int. 2005;18(3).

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