Patents and loss of exclusivity
Patents are not the only way a new drug molecule is protected. To understand the factors involved, see our article Understanding generic and biosimilar market entry.
What can be patented
For a discovery to be patentable, it must fulfil all the following criteria:
- something that can be made or used, a technical process or a method of doing something
- new
- inventive
Some things cannot be patented, including:
- scientific discoveries, theories or mathematical methods
- ‘essentially biological’ processes like cross-breeding plants
- methods of medical treatment or diagnosis
Where patents are effective
There is no such thing as a worldwide patent. Inventors apply for a patent in each country or region.
Inventors applying for a ‘European patent’ get a bundle of national patents, including a UK patent. Inventors can also apply directly for a UK patent.
This means medicines can be patent-protected in the UK, but not in other countries, or the other way around.
Duration of protection
A patent lasts for 5 years from the date of filing, not the date of grant. It can be renewed every year up to a maximum of 20 years.
Once a discovery is publicised, such as in a scientific paper, it is not new and cannot be patented. This disadvantages pharmaceutical manufacturers as they cannot begin selling their inventions immediately. Drugs must undergo clinical trials and licensing before revenue can be generated.
Special arrangements have therefore been made to extend protection for new drugs beyond 20 years.
Supplementary Protection Certificate (SPC)
A Supplementary Protection Certificate is not a patent extension. It is a separate intellectual property right protecting a licensed medicine containing the patented active ingredient.
A patent may cover several drugs or chemicals, some of which never become licensed medicines. The patent-holder can only apply for an SPC to extend protection for a licensed medicine containing the patented drug. If a patent covers multiple drugs which become different licensed products, a separate SPC is needed for each.
An SPC extends protection for the shorter of:
- an additional five years, for a maximum of 25 years of combined patent and SPC protection
- the time between patent filing and grant of marketing authorisation, minus five years
SPCs cannot be applied to new formulations or indications.
The patent-holder must pay a fee for an SPC. The SPC can expire early if the correct fee is not paid.
Paediatric Extension (PE)
A PE extends the protection of an SPC by an additional six months. It is intended to encourage manufacturers to license medicines for use in children.
To obtain a PE, a manufacturer must complete a paediatric investigation plan (PIP) and submit a new marketing authorisation application with data from paediatric trials. The PIP results must be included in the Summary of Product Characteristics. A PE may be granted whether the studies result in a new paediatric indication, or show the medicine is not suitable for children.
Protecting new uses for drugs
Methods of medical treatment cannot be patented, but new uses for drugs can be protected.
Second use and ‘Swiss form’ patents
Second-use patents protect new uses for a known drug. They avoid the restriction on patenting medical treatments by focusing on the application of a substance rather than the treatment process. They use wording like ‘Substance X for use in the treatment of disease Y’.
Swiss-form patents were a way of patenting new medical uses by covering the manufacturing process, not the treatment itself. They use wording like ‘Use of X in the manufacture of a medicament for the treatment of Y.’ Swiss-form claims are no longer accepted, but existing patents are valid until expiry.
These patents can prevent generic or biosimilar companies marketing a medicine for the patented use, even if the core drug patent has expired.
Example
Pfizer’s patent for using Lyrica® (pregabalin) to treat neuropathic pain was a Swiss-form patent.
Skinny labels
If protection for a drug molecule has expired but some uses are still patented, generic manufacturers may obtain a licence excluding the patented indications. This cut-down licence is termed a ‘skinny label’ or ‘carve out’.
Example
The first generic pregabalin products had skinny labels. They included epilepsy and generalised anxiety disorder, but not neuropathic pain.
Patents for other aspects of a medicine
Patents can be used in several ways to protect a product after expiry of the patent on the drug molecule.
Protecting the original product
Patents can cover formulations, salts or delivery methods. These patents may be filed several years after the core drug patent. They may therefore extend exclusivity by preventing generic or biosimilar competition even after the drug patent expires.
Generic or biosimilar manufacturers may be able to ‘avoid’ these patents by:
- using a different salt
- changing the formulation
- using a different delivery device
However, the more changes the generic or biosimilar manufacturer makes, the more difficult it may be to get a licence. If the way the product is used is changed, prescribers and patients may prefer to stay with the familiar version.
Isomers, new formulations, and other iterations
If a manufacturer cannot protect the original product, they may produce and patent a new version or formulation. This is often marketed as having advantages over the original. This does not prevent generic or biosimilar competition for the original product, but the manufacturer hopes that prescribers and patients will prefer the new version.
Example
Doxazosin modified-release tablets, and esomeprazole (isomer of omeprazole).
‘Evergreening’
‘Evergreening’ refers to the practice of a patent-holder using secondary patents to extend market exclusivity.
Example
Phesgo® (trastuzumab-pertuzumab subcutaneous combination) was licensed in December 2020. Phesgo is more convenient than separate intravenous formulations of trastuzumab and pertuzumab, allowing faster administration, so use is increasing. This reduces the use of intravenous formulations and potentially limits use of biosimilars.
Significant innovations
Sometimes, an entirely new presentation of a drug molecule that is no longer patent-protected may be marketed. The differences between the new version and the original may be so great that it is not marketed as a generic or biosimilar. Instead, it is given a new ‘originator’ product licence with all the relevant protections.
If a new presentation is significantly different, expect the innovation to be protected by a patent, which may prevent copies of this new product.
Example
Lytenava® is a formulation of bevacizumab for intravitreal injection. The original bevacizumab product (Avastin®) is given by intravenous infusion. A patent protects the intravitreal formulation, and Lytenava® is entitled to data exclusivity and market protection too. These will prevent copies of Lytenava® for several years despite the availability of biosimilar formulations of intravenous bevacizumab.
Patent litigation and agreements
Patents protect the patent-holder’s investment, but can be challenged. Patent-holders can also permit another company to make or sell their product.
Patent infringement
Patents give the patent-owner the sole right to ‘deal with’ the invention, and to permit other people to deal with it.
Patents can be infringed by dealing with the product without the patent-holder’s permission. This includes making, selling or using it.
If a generic or biosimilar formulation is marketed while a relevant patent is in effect, the patent-holder can take legal action. They may be able to stop the infringing product being marketed. They may also be able to claim damages from its manufacturer.
Example
Celltrion planned to launch biosimilar omalizumab in 2024, but the product was found by the UK High Court to infringe a formulation patent. This delayed launch until expiry of the patent in September 2025.
Patent challenges
Patent applications must include all aspects of the invention to ensure it is protected. However, if an applicant extends the patent beyond what the evidence supports, or includes anything obvious or not innovative, the patent may be challenged.
Prospective generic or biosimilar manufacturers often challenge a patent on grounds of obviousness, or because they believe it exceeds its proper scope (patent overreach).
If the generic or biosimilar manufacturer wins the case, the patent ‘falls’ or is invalidated. This means the patent never had legal effect. The generic or biosimilar manufacturer can market their product immediately. They may also be able to seek damages if they were wrongly prevented from entering the market.
If generic or biosimilar manufacturers think they will win, they may launch their product before litigation has concluded. This is called ‘launching at risk’.
Example
The patent on apixaban was challenged and found to be invalid because it did not sufficiently define the drug. Generic manufacturers were therefore able to market their versions of apixaban four years earlier than expected. The first 18 months of this was ‘at risk’ while the invalidity case went through the courts.
Licence agreements
A patent-holder may allow a generic or biosimilar manufacturer to market their product while the patent is still in force, in return for a fee.
This may happen if the patent-holder cannot or does not wish to make or distribute the product themselves. It may also happen after a patent has been challenged, as part of a settlement agreement between the parties.
This means that a generic or biosimilar product may appear sooner than expected.
Example
Neurim held the patents for Slenyto® (melatonin MR 1mg and 5mg) tablets. They granted Flynn a licence to market Slenyto®.