Repurposing, Repositioning and Rescue of Drugs and Pharmaceuticals
Following on from our News Article of 6 April 2020 “Personalised Medicine Patents at the EPO”, regarding a case law summary of the patent protection available for existing pharmaceuticals in terms of dosing regimens and specific patient groups, we now look to explore repurposing, repositioning and rescue (DRPx) of existing drugs and pharmaceuticals.
The soaring costs, lengthy time frames associated with, and high failure rates of de novo drug discovery and development (DDD), along with the well documented problem of the “Patent Cliff”, has driven Big Pharma to look at failed drugs previously considered to be lost causes. Failed drugs, previously written off, are now being reconsidered as possible therapies for different indications than those for which they had originally been considered. It is estimated that up to 30% of annual revenues of the entire Pharma industry comprises DRPx. No wonder, as drug “repurposing” provides researchers and clinicians with a cost-effective way to identify potential new therapies without needing to start from scratch.
Many of these previously failed drugs have already had their relative safety established in Phase I clinical trials, which can simplify and reduce the cost of obtaining regulatory approval should a new indication be found.
Drug repurposing is not just limited to failed drugs but is also being considered for currently marketed drugs, as well as “off patent” generic compounds, to expand and extend their usefulness. Some notable examples are listed in the non-exhaustive list below:
|Drug||Original Disease||New Disease|
|Arsenic||TB & syphilis||Promyelocytic lukemia|
|Aspirin||Pain or fever||Antiplatelet|
|Azathioprene||Rheumatoid arthritis||Renal transplant|
|Atomoxetine||Antidepressant||Attention deficit disorder|
|Ceftriaxone||Antibiotic||Amyotrophic lateral sclerosis|
|Cycloserine||Urinary tract infection||Tuberculosis|
|DB289||Pneumocystis||Malaria & trypanosomiasis|
|Everolimus||Renal cancer||Renal transplant|
|Finasteride||Prostate hyperplasia||Male pattern blindness|
|Fosmidomycin||Urinary tract infections||Antimalarial|
|IFN alpha||Hepatitis B&C||Cancers|
|Minocycline||Antibiotic||Amyotrophic lateral sclerosis|
|Naltrexone||Opioid addiction||Alcohol withdrawal|
|Pentamidine||Pneumonia||Trypanosomiasis & leishmaniasis|
|Raloxifene||Osteoporosis||Postmenopausal breast cancer|
|Retinoic acid||Acne||Promyelocytic leukemia|
|Serotonin antagonists||Antipsychotic||Multifocal leukoencephalopathy|
|Sildenafil||Angina & hypertension||Erectile dysfunction|
|Thalidomide||Morning sickness||Leprosy, multiple myeloma|
Perhaps, the most notorious of these repurposed drugs is Thalidomide. Thalidomide is a sedative drug discovered in the 50s, which went on to cause a worldwide tragedy. The drug was prescribed to many pregnant women in the early 60s in order to relieve pregnancy nausea. However, it caused a plethora of foetal defects and was withdrawn and spawned a change in drug toxicity testing as, prior to this, there was no formal toxicity testing for reproductive effects. It now finds use as a drug of choice for the treatment of leprosy and multiple myeloma. A similarly notorious example of a repurposed drug is Sildenafil (Viagra) which was originally developed by Pfizer for the treatment of hypertension (high blood pressure) and angina pectoris (chest pain due to heart disease). During the heart clinical trials, researchers discovered that the drug was more effective at inducing erections than treating angina. It remains one of the top drugs of choice for erectile dysfunction.
By its very nature, drug repurposing primarily concerns previously known drugs. Obtaining patent protection can therefore be challenging. In some cases, a drug to be repurposed might still be protected by an existing patent that can be acquired and/or in-licensed, but often the drug itself is not protected by patent. Without patent protection, commercialization of a repurposed drug is neither realistic nor attractive for Big Pharma.
Drug repurposing will always rely on a previously known drug. This makes obtaining a granted patent challenging. Both the EPO (G5/83 and G2/08) and USPTO (35 U.S.C. § 101) consider that the repurposing of drugs constitutes patentable subject matter, providing that the “new” use has not been disclosed are also considered novel. In this space, at both the EPO and the USPTO novelty does not seem to the major issue to patentability, rather inventive step/obviousness hurdles must be overcome.
DRPx can help in patent life extension and thus aid in prolonging lifecycle management of product portfolios. So, while drug repurposing and DRPx products offer solutions to many industry problems, there are major issues with IP protection and regulations. Whilst medical method patents are patentable in the US and Australia, for instance as “methods of treating a particular condition”, in Europe and China, such claims are excluded from patentability. What is, however acceptable, are claims in the form of “product for use” claims, also known as “second medical use claims”. For example:
“Compound X for use in the treatment of disease Y” or
“Compound X for use as a disease Y agent”.
Alternatively, one can consider patenting novel formulations and different dosing regimens and patient groups (see TLIP Ltd News Post 6 April 2020).
As such, there are ways to overcome these patent related obstacles in order to obtain protection for repurposed drugs and DRPx products. A mindful pre-planned approach to the prosecution of repurposed drugs and DRPx patents can really go a long way in order to provide a basis for a novel, non-obvious claim. Professional thoughtful preparation of the application done by experts with the specific knowledge and know-how in obtaining protection for repurposed drugs and DRPx products will lead to better, stronger protection.
Turning to the present day, there are at least 150 different known DRPx drugs being researched around the world. Most are existing drugs that are being trialled against the COVID-19 virus. The latest clinical trials of Remdesivir, an anti-viral drug originally developed to treat Ebola, has received the most publicity. The US Food and Drug Administration is moving quickly to fast-track authorize the use of Gilead’s experimental anti-viral drug Remdesivir as an emergency treatment for coronavirus, following news that a preliminary trial of the drug showed positive results. Of course, whilst experts believe that a drug or repurposed drug may assist in reducing the infection period, it will likely only be a vaccine that will truly provide protection in the future.
Again, wishing you are all well, safe and healthy with best wishes from all at TLIP Ltd.