Ways to Patent a ‘Drug-Device Combination

It is known that a patent can be obtained for a combination of two or more active ingredients if the applicant proves that they work in combination to produce a new way to treat a disease or condition. This fact must be supported by the clinical trial results. This means clinical trials are looking to discover unexpected results. This unexpected result must be based on the finding that each ingredient that is already known and used for the treatment of disease individually to a certain extent, and if these ingredients are combined, they interact functionally to produce a new effect or what is called synergistic effect under patent law practice. Such a combination qualifies for patents in all jurisdictions. With a rise in trends to adopt personalised medicines, there has been a growing tendency to use combination products.

Lately, the tendency to mix biologics, small-molecule drugs, and even medical devices to optimise patient treatment has grown, and such experimental combinations result in better and faster recovery of patients. The combination of drugs with medical devices is increasingly gaining importance with pharmaceutical inventors, and many devices with drugs have gained patent protection. Types of ‘Drug-Device Combination’ patents include (a) Device patents to cover the medical device component, such as an inhaler or implant or transdermal/thermal patch, (b) pharmaceutical patents to protect the drug or active ingredient used therein, (c) drug-device combination patents to include the specific combination of the device and drug and (d) method patents to seek the protection of methods of using the drug-device combination product.

Medicine Device Combination Patents

The medicine device combination patents may include inhalation devices, auto-injectors, prefilled syringes, insulin pump systems, transdermal patches, nebuliser systems, ophthalmic devices, and dry powder inhalers. To be more specific, we may come across many types of medicine device combination products involving combinations of drugs, biological products, and medical devices that are becoming increasingly prominent. Such medicine device combination products may involve components that are physically, chemically, or otherwise combined to get an enhanced effect on the recovery of the patient. These components can be packaged together (e.g., a drug packaged with a delivery device), or the components are provided separately but intended to be used together (e.g., a photosensitising drug and activating light source). Patenting drug-device combinations involves patenting innovative medical products meant to be combined with medical devices.

Patentability Issues and Remedies

The patentability of medical devices was never an issue with the patent office, as medical device patents are allowed in all jurisdictions if they are novel and inventive. Similarly, patents on technological advances related to a novel drug-device combination for its new formulations, dosage forms, or combinations with other drugs were not denied provided it meets the criteria of novelty, inventive step. However, the legal concepts of obviousness and unexpected results, particularly in emerging drug-device combination therapies, are reshaping the patenting strategies of the pharmaceutical innovation trends.

Pharmaceutical companies seek patent protection for drug-device combinations of cancer therapeutics based on unexpected results. But what constitutes an ‘unexpected result’ for the purpose of an appropriate patent is not an easy question to answer. To obtain a patent for the drug-device combination, the inventor must prove through research what constitutes unexpected results (positive or negative) in clinical trials. Similarly, routine experimental results are not considered advancement. This makes the patenting of drug-device combinations a little tricky and challenging in various jurisdictions. The challenges in patenting drug-device combinations include (a) Subject matter exceptions, (b) obviousness (Demonstrating the combination is non-obvious) and (c) claims for method of treatment.

Role of Clinical Trials

This also brings to the forefront the need for clinical trial elements that gain importance in the thoughtful evaluation of the non-obviousness of combination therapy patents. In the Indian context, unexpected results are key to the grant of a combination or minor modification patents. In the Green Cross Holdings Vs Deputy Controller of Patent and Designs appeal case, the IPAB ruled that “Even though the applicant’s modification results in some degree of improvement and utility over the prior art, it may  still not be patentable if the substitution of stabilizer was within the capabilities of one skilled in the art unless the claimed mixture produces a  new unexpected result which is different in kind and not merely in degree from the results of the prior art….”[IPAB 78 of 2014]. In this case, the patent office refused a patent for the invention relating to ‘Pharmaceutical preparation of recombinant factor VIII lyophilized without Albumin as a stabilizer’.

Subject Matter Exceptions: Therapeutic Method/Medical Treatment

The management and care of a patient to combat any disease or disorder is considered medical treatment. Patenting medical therapeutic methods is the toughest task for inventors in some jurisdictions where these methods are excluded from patentable subject matter. For example, in India, any method or process for medical, surgical, curative, prophylactic or other treatment of human beings or animals is excluded from patentability under Section 3(i) of the Indian Patent Act.

Most jurisdictions restrict inventors from patenting therapeutic methods. However, whether the drug-device combination is a method of treatment does not have a clear answer. Some countries, such as the United States and Australia, allow patents related to therapeutic methods. The primary reason for denying patents for such inventions is to protect medical practitioners from the fear of infringement, and it is believed that such a monopoly over a method of medically treating a patient could affect physicians’ skill and judgment when treating patients.

Position in the US

There is no statutory bar in the US for patenting drug-device combinations, including drug transdermal/thermal patches. In the US, patents for methods of treatment are also allowed. A list of a few representative Drug device combination patents in the US is given below:

Position in India: Section 3(i) Exclusions

Like in other jurisdictions in India, a drug-device combination invention should meet the eligibility criteria viz novelty, non-obviousness, and industrial applicability under (sec 2 (1) (j). However, under section 3(d), subject matter covering new use for a known substance or mere use of a known process, machine, or apparatus unless such a known process results in a new product or at least employs one new reactant is not patentable in India. Section 3(i) exclusion includes methods of treatment but not devices or their combinations with drugs. New forms of known substances (e.g., polymorphs, salts, etc.) are also excluded under the explanation, provided new uses of known substances show significant efficacy compared to the known substance.

Leading Cases in India

Pizer “Use of a Compound in Dry Inhaler”

Most applicants in India and elsewhere follow a direct approach to protect their inventions by directing their claims towards medical treatment methods. For example, in India, one such typical application was filed by Pizer for “Use of a compound in dry inhaler” (110/MUMNP/2004 and 216/MUMNP/2006 (divisional to 110/MUMNP/2004) and the claims covering medical treatment 17-22 were drafted as under

17. The use of an inhaled formulation according to any one of claims 1 to 15 in the manufacture of a medicament for the treatment of a disease treatable by the inhibition of PDE4.
18. The use according to claim 17, wherein the disease is a respiratory disease.
19. The use, according to claim 18, wherein the respiratory disease is asthma or chronic obstructive pulmonary disease. (use claims )
20. A method of treatment of a disease treatable by the inhibition of PDE4 comprising the administration of an inhaled formulation according to any one of claims 1 to 15 to a mammal.
21. A method of treatment, according to claim 20, wherein the disease is a respiratory disease. (medical treatment)

On examination, objections were:

7. Claims 16-19 and 23-25 are not an invention U/S 2 (j) of the Indian Patent Act, 1970.
8. Claims 20-22 are not patentable U/S 3 (i) of the Indian Patent Act, 1970.

The objection relating to section 3(i) was raised as the applicant directly claimed the method of treatment. The use claims were also objected to as the definition of the invention under section 2(1) (j) says ‘invention’ means ‘new product or process’. It does not cover the ‘use.’ The applicant later filed a divisional application with a similar set of claims. The applicant did not pursue the parent application and allowed it to be deemed abandoned under section 21(1).

The applicant, in fact, did not pursue the divisional application as well. The patent for the above applications was not allowed. This case shows that following a direct approach to protecting such inventions by directing the claims towards the use or methods of the medical treatment itself in India may not be a good drafting strategy.

Novartis AG “Use of Pleuromutilin Derivatives for Transdermal Treatment of Bacterial Diseases’ Case

Similarly, the application by Novartis AG for “use of pleuromutilin derivatives for transdermal treatment of bacterial diseases” faced the same fate when the IPO raised the following objections

1. The subject matter does not constitute an invention under section 2(1)(j) of the Patents Act, 1970.
2. 2. Claims fall within the scope of such clause (i) of section 3 of the Patents Act.

This application was also deemed to have Abandoned U/s 21(1) as no response to the objections raised by the IPO was filed by the applicant.

Purdue Pharm L.P. “A “TRANSDERMAL PATCH” Case        

However, in the application (4747/DELNP/2005) by Purdue Pharm L.P. for “A “TRANSDERMAL PATCH“, similar objections relating to section 3(i) were raised (marked in bold)

“2. Claims 1- 21, 22-40, 41-54, 58-62, 64-68 & 71-72 fall within the scope of such clause (d) &(e) of section 3, Claims 55-57 & 70 fall within the scope of such clause (i) of section 3 and Claims 1- 21, 22-40, 41-54, 58-62, 64-68 & 71-72 appears to fall within the scope of such clause (i) of section 3 as worded.”

The applicant, in reply to the objections, amended claims 1-22, and claims 22-72 were deleted. The patent for the amended claims listed below was granted.

Granted claims

“1. A transdermal patch (100) comprising an active agent component (110) comprising a polymeric material (115) and an active agent said active agent component having a proximal surface (120) and a distal surface (130) said proximal :::::::::::::::::::::: active agent and adverse agent, ::::::::::::::::::::: (190) of said patch (100); and an adhesive component connecting the adverse agent component (160) and the barrier (150); wherein the active agent component :::::::::: substantially from the proximal surface to the distal surface.

:    :      :           :           :           :           :           :           :           :           :

14. A transdermal patch, as claimed in claim 1, wherein the active agent is an opioid agonist.
15. A transdermal patch as claimed in claim 1, wherein the active agent is selected from the group consisting of alfentanil, ::::::::::::::::: normorphine, norpipanone, opium, oxycodone, :::::::::::::::::::::::, phenadoxone, ::::::::: phenomorphan, phenazocine, :::::::::::: piritramide, ::::::::::::::::::;, propylliexedrine, sufentanil, tilidine, tramadol, a pharmaceutically acceptable salt thereof, and mixtures of two or more of the foregoing.
16. A transdermal patch, as claimed in claim 1, wherein the active agent is more preferably being fentanyl or a pharmaceutically acceptable salt thereof.
17. A transdermal patch, as claimed in daim 1, wherein the adverse agent is an opioid antagonist.
18. A transdermal patch, as claimed in claim 1, wherein the adverse agent is selected from the group consisting of naloxone, naltrexone, nalrnefene, nalbuphine, nalorphine, cyclazacine, cyclazocine, levallorphan, a pharmaceutically acceptable salt thereof, and mixtures of two or more of the foregoing.
19. A transdermal patch as claimed in claim 1, wherein the adverse agent is more preferably being naltrexone or a pharmaceutically acceptable salt thereof.”

:           :           :           :           :           :

In all, 22 claims as amended were allowed, but the claims falling under section 3(i) method treatment viz 22-40, 41-54, 58-62, 64-68 & 71-72 were deleted by the applicant, and patent for device and drug combination falling under claim 1 to 22 as amended were allowed (IN 233567).

The Purdue Pharm case clearly indicates that the Indian patent office permits drug-device combination patents where the applicants do not claim a method of treatment. There is no statutory bar in India on drug-device combination patents. Many such patents are granted under the Indian Patents Act, 1970. In simple words, products such as devices, pharmaceuticals, or a combination thereof or process patents or method of manufacture and method patents such as specific uses or applications may form the subject matter of such patent applications. It may be noted that many patents of drug-device combinations are allowed in India. A representative list of such patents is given below:

Changing Trends of Patenting Therapeutic Methods in Australia

In Australia, the patentability of therapeutic methods has undergone a sea change. Initially, like India, the Australian Patent Office also used to deny patents claiming methods of medical treatment as the examiners found them generally inconvenient and essentially non-economic. However, in Joos v Commissioner of Patents (1972) HCA 38, Barwick CJ ruled that a process for the cosmetic treatment of hair and nails could be patentable but distinguished this from medical treatment of disease, malfunction or incapacity.

Similarly, in Anaesthetic Supplies Pty Ltd vs Rescare Ltd (1994) 50 FCR 1 relating the patentability of a method and device for the prevention of sleep apnoea, the court allowed the patent for method and device for the prevention of sleep apnoea. Again, in Bristol-Myers Squibb Co v FH Faulding & Co Ltd (2000) 170 ALR 439. patent for the method of administering a drug used to treat cancer was held to be valid against the contention of the defendant that it is a medical method/treatment.

Later, in 2013, in Apotex Pty Ltd v Sanofi-Aventis Australia Pty Ltd [2013] HCA 50, the High Court confirmed that medical treatment methods involving the administration of therapeutic drugs are patentable subject matter in Australia. In this case, the drug Leflunomide, the preparation and composition of which was the subject of an expired Australian patent, is used for the treatment of psoriatic and rheumatoid arthritis. A method of using Leflunomide is the subject of an Australian Patent No 670491 entitled “Pharmaceutical for the treatment of skin disorders”. A full bench of the Federal Court of Australia affirmed that therapeutic methods of humans can be considered patentable in Australia.

In 2013, in the Apotex case for the first time, the High Court of Australia held that a medical treatment method, specifically the administration of therapeutic drugs to humans, constitutes patent-eligible subject matter in Australia. Since then, the Australian Patent Office has revisited its stand and opened the doors for inventions related to processes or methods of medical treatment of the human body or part of it for patentability.

For example, AU2020217342B2 for a claim “13. The method of claim 12, wherein the THIP or a pharmaceutically acceptable salt thereof is administered by contacting a transdermal patch comprising THIP or a pharmaceutically acceptable salt thereof with the skin of the subject.” was granted to Matthew During Ovid Therapeutics, Inc. Similarly, AU2020200884B2 for ‘Compliance monitoring module for a breath-actuated inhaler’ was granted to Norton Waterford Ltd.

Way Forward

Does this mean that the medical treatment is limited to the medical treatment of disease, malfunction, or incapacity? To that extent where medical treatment is spoken of is not satisfied, any application of a substance to the human body or part of it, particularly those who apply chemical preparations to the skin to prevent sunburn in climates which enjoy sunshine and moderate air temperatures can scarcely be regarded either as, in a relevant sense, treating their bodies or as undergoing treatment. However, the application to the skin of an ointment designed and effective to remove keratoses from the skin would be an instance of medical treatment.

To be treatment, in the strict sense, means that the purpose of the application to the body, whether of a substance or a process, must be the arrest or cure of a disease or diseased condition or the correction of some malfunction or the amelioration of some incapacity or disability. The drug-device combination products are complex, and obtaining patents thereto can be accordingly complex. Innovators of drug-device combination products seek to create a legal “picket fence” around core technology.

This means the applicant should patent individual components of the drug-device combination product as well as the product as a whole. In India, there is no bar as such on patenting drug-device combination patents, but the applicant should stay clear from presenting claims for a method of treatment. Such methods are not permitted in India under section 3(i).

Inventions related to therapeutic methods are comparatively less common due to the objections raised by most jurisdictions regarding patentability. Nevertheless, recent precedents in the US and Australia may trigger an increase in patent filings in the field of therapeutic methods as well. Where the applicant seeks to protect the therapeutic products and their use only, there will not be any difficulty. This particularly happens in cases where drug compounds are known, and their further therapeutic use may be determined after the discovery of a device useful for the delivery of the product.

In this scenario, such claims can be allowed protection only if the claims are directed to (i) the use of a new product and/or (ii) comprise steps of a new method. Recent advances in novel drug delivery systems opened an additional channel for obtaining patents for drug-device combinations. For instance, many patents for ‘drug-device combination’ products like inhalers, injector pens and patches containing one or more pharmaceuticals are granted worldwide, including India. Nevertheless, expert advice would benefit inventors seeking patents for drug-device combinations in India or elsewhere.

Author: DPS Parmar

First Published by: Lexology here