The cost of developing a single new prescription drug is incredibly high, ranging from hundreds of millions to a few billion dollars. As a consequence, finding any and all possible means of extending the life of patent protection is imperative to ensuring the profitability of a drug.
There are many ways the drug companies can extend the patent protection for a soon-to-be expiring megahit drug by implementing “evergreening strategies” in order to continue revenue generation from the drug. These ever-greening strategies involve creating new formulations by improving the patented formulation, discovering new indications of the patented formulation and making a new combination by combining the patented formulation with other drugs.
New Formulations
A very popular way of extending the life of the patented drug is to improve the formulation of the drug, yet retaining sufficient similarity to the patented formulation so as to avoid delays to get FDA approval. Some of the improvements over the patented formulation used to produce a new formulation, and examples of each, are summarized below:
- Extended period of effectiveness: Adderall XR, a reformulation of the already patented drug Adderall, improves on its predecessor by offering an extended period of effectiveness.
- Administering a drug in a new way: Imitrex, a migraine drug originally sold in tablet form, was later reformulated and patented for intranasal delivery.
- Making the drug more effective: This can take the form of reducing the dosage while increasing the bioavailability, and/or reducing adverse side effects. The drug Nexium is a single-enantiomer version of the drug Prilosec that only includes the effective form of the active molecule. See the “Chiral Switch” section below for more information.
New Indications
When a new drug is developed, it is typically patented for the original compound and method of use for a specific application, or “indication.” Indication patents allow for old drugs to be granted new patents for novel applications.
For instance, the drug bupropion was originally indicated for the treatment of depression under the brand name Wellbutrin. However, it was also found to be effective in helping people to quit smoking (which resulted in doctors frequently prescribing Wellbutrin for that specific off-label use). After the patent on Wellbutrin expired, GlaxoSmithKline successfully obtained a new indication patent for its use in the treatment of smoking, under the name Zyban.
New indication patents are a powerful means of granting new patent protection to drugs that may be many decades old.
Chiral Switches
Many drugs are chiral in nature, meaning that there are two mirror, non-superimposable forms of the molecule that form the active ingredient. These forms are known as R and S enantiomers (sometimes referred to as left- and right-handed enantiomers). Most active drug compounds are racemic, meaning that they contain both R and S enantiomers of the active molecule. Typically, one enantiomer is effective, while the other is less effective, ineffective, or even harmful.
The most (in)famous example of a drug with a harmful enantiomer is the sedative thalidomide. Several decades after its introduction, it was discovered that one of the drug’s enantiomer’s caused terrible birth defects.
Drug companies often breathe new life into older, racemic products by producing a single-enantiomer version, thereby increasing the effectiveness of the drug. They then apply for a new patent for the new single-enantiomer derivative. This replacement of an older racemic drug with a newly patented single-enantiomer version is known as a “chiral switch strategy.”
A well-known example of a chiral switch is the drug esomeprazole, a heartburn medication marketed under the name Nexium. Esomeprazole is a single-enantiomer form of the drug omeprazole, which was marketed under the name Prilosec. Nexium was introduced to the market after the patent for Prilosec expired in 2001.
New combinations
It’s quite common for multiple drugs to be prescribed together because they control different aspects of a condition, or they have a magnified effect when taken together—known as synergism—that is more than the sum of its parts. In either case, this provides an attractive opportunity for drug companies to create combinations of patented drugs and bring them to market as a newly patented product. A recent example of this is Symbyax—a combination of the drugs olanzapine (Zyprexa) and fluoxetine (Prozac)—that is indicated for the treatment of bipolar disorder.
Typically, more than one strategy is implemented. For example, the drug bupropion was not only patented for a new indication, smoking cessation, but it was also reformulated into a slow-release formula, creating a justification for two new patents. It is critical for pharmaceutical companies to prudently devise and implement strategies to extend the profitable lifespans of their popular products.