Combination Products - Patent Issues and Remedies

Noël Akers reviews patent laws and practice for the protection of drug-device combination products.

Noël Akers is the principal of NJ Akers & Co, a firm of chartered patent attorneys and European patent and trade mark attorneys based in Cornwall, UK. Email: [email protected].

The investment required to bring any medical product to market is considerable. As a result, the need to ensure that any commercial product is free from patent infringement issues and, ideally, fully protected by patents in its own right is an important one. The arena of drug-device combination products is no exception to these principles. This article provides an overview of the key issues relating to patenting developments in relation to a new combination product and, more importantly, to the overriding requirement of ensuring freedom from infringement of any third-party patents.

Drug-device combination products

As a general rule, drug-device combination products seek to combine the positive effects of one or more drugs on the intended patient and the technical advantages offered by the device. Such a product combines the technical intricacies and complexities of the pharmaceutical component as a chemical on the one hand and the physical aspects of the apparatus or device on the other hand.

Technical issues

In many respects, these two aspects can be kept largely separate. In many instances, however, the combination of the chemical substance with the physical device requires a range of new, specific behaviours and interactions to be understood and accommodated.

For example, a novel slow release implant for delivering a particular drug may employ a well-known pharmaceutical compound, with the intention of having the active ingredient perform its well-known and understood function once in the patient's body. Such an implant, however, will likely need to address a range of wholly new technical issues relating to the active ingredient that are hitherto irrelevant to the known use of the drug, for example as administered orally or intravenously. For instance, how the implant will ensure that the drug is delivered to the required site at the appropriate dosage rate. The chemo-physical properties of the active ingredient, its formulation, its interaction with the physical structure of the implant device and its behaviour within the body once the device has been implanted are just some of the new technical issues to be addressed and understood.

This simple example demonstrates the complexities that frequently arise as soon as one starts to consider combining a pharmaceutical with a device of any kind. The complexities do not end with the technical issues. The legal issues in general relating to such a combination device are correspondingly complex. The patent legal issues are no exception to this.

Legal issues

A question that is asked in relation to combination devices is to what extent patents are interpreted differently when considering a device that combines a pharmaceutical with a device. The answer is, in principle, that the patents and the relevant legal issues are no different for such a product as they are for other products. The complexities arise because, whatever the patent issue, it is necessary to consider both the pharmaceutical aspects and the physical aspects of the device as an apparatus. A wide range of legal principles apply across all of these aspects. However, certain aspects have their own specific legal peculiarities, the patent law and practice relating to pharmaceutical products being a perfect example.

In short, the basic legal and practical approaches to considering patents relating to combination devices remain the same as for other medical products. The nature of the combination device, however, requires that a wider range of issues be addressed and covered, than say would be required when considering a pure pharmaceutical product or a simple medical device.

Freedom to operate

A patent is a right granted in respect of a technical invention. The right granted by a patent is not, in the main, a right to do anything, but rather is a right to prevent others from practising the patented invention. Whether or not a company may commercialise its own inventions does not depend upon the number or scope of the patents it obtains for its inventions. Rather, this freedom is determined by the patents held by others.

A patent infringement clearance study, often called a freedom to operate study, is conducted to identify any patents that are held by third parties that would be infringed by the commercialisation of a product. It is recommended that such a study is conducted before any product is placed on the market. The cost of such a study, even including the costs of the patent attorney, generally are very low in comparison with the overall investment made in the product as a whole and in all likelihood would pale into insignificance compared with the costs of defending a legal action for patent infringement and the likely effects on the commercial operation if such an action were to be lost.

As indicated above, the patents of third parties could potentially be infringed by the development and commercialisation of a combination product. The specific legal provisions as to what acts constitute patent infringement will vary from country to country, depending upon the relevant patent law. In general, acts likely to give rise to a potential liability for patent infringement include the following:

where the patent relates to a product, the manufacturing, selling, offering for sale or importing the product;

where the patent relates to a method, the use of the method; and

where the patent relates to a method of preparing a product, the importation, sale or offer for sale of the product prepared directly by the patented method.

While not exhaustive, it will be appreciated that a third-party patent can effectively curtail all commercial activities relating to a new combination product, if infringement of the patent is to be avoided. The penalties for being held by a court to have infringed a patent can be severe and may include an injunction or court order preventing further infringing acts from being committed, the destruction of any infringing goods or products and an award of damages for the infringing acts, to be paid to the patent holder.

In some countries, the courts have the power to order the payment of significant monetry payments as damages. Of particular note in this respect is the US, where the courts not infrequently make substantial, punitive awards of damages, where the case involves an act of wilful infringement. In short, a company ignores the possible outcome of infringing the patents of a competitor at its significant peril.

To ensure that patent infringement is not likely, a freedom to operate study is best performed before the combination product is launched. The nature of the combination product, combining as it does a pharmaceutical composition with a mechanical device, results in the freedom to operate study having to consider a wide range of technical areas, in order to identify any potential patent obstacles.

Examples of patents and applications that should be reviewed and studied include the following:

patents relating to the active pharmaceutical ingredient, including:

• the active compound per se;
• use of the compound as a medicament (first and second medical uses);
• formulations of the active compound; and
• methods of manufacture of the active compound;

patents relating to the device, including:

• the entire device per se;
• key components of the device; and
• methods of manufacture of the device and/or its components;

medical methods, including:

• methods of the device's use and its interaction with the human or animal body;
• methods of treating the target condition;
• diagnostic methods using the device; and
• methods of dosing the active compound.

Whether patents in some or all of the above categories will exist depends in part on the patent law in the country or countries of interest. For example, the patenting of medical methods is generally a problem under the existing patent laws in Europe. However, the law of the US is more generous in this respect and medical methods are patentable. The freedom to operate study must be configured to take into account the various differences in the patent laws of the countries of interest.

So far, we have considered infringement of patents by so-called “direct” or “primary” infringement. The law of many countries around the world also recognises that the supply of an essential part or component of a patented product may also constitute patent infringement, so-called “contributory” or “secondary” infringement. Thus, in the case of a combination product comprising a device containing an active pharmaceutical compound for implant and slow release, the supply or offer to supply the basic device, with the intention of having the customer load the active ingredient, may still constitute infringement of patents relating to the complete combination product.

Whether such infringement arises will depend on the circumstances of the sale or offer for sale and the end use or intention, and will differ from country to country. A detailed study of this issue is outside the scope of the present article. However, it should be recognised that there is potential for secondary infringement to arise.

Patent term extensions

The normal patent term in most countries is 20 years from the filing date of the patent application. Thus, in general it is possible to ignore any patents that were filed more than 20 years prior to the intended date of launch of the new combination product. An important exception to this rule is in the pharmaceutical arena.

The time taken to develop a new pharmaceutical product, ensure its efficacy and safety and convince the regulatory authorities of the same is extensive. Indeed, the time taken is long enough in many cases to seriously erode the 20 years of protection offered by the basic patents obtained to protect the basic active compound. As a result of this set of circumstances, the legislators in many countries provide for the term of pharmaceutical patents to be extended, typically by up to five years. The actual length of the extension is determined on a case by case basis and is related to, amongst other factors, the time taken to obtain the first marketing authorisation for the pharmaceutical product.

The relevant law in Europe is at the European Community level and provides for a pharmaceutical patent to be extended by up to five years by a so-called supplementary protection certificate. Again, a detailed review of the law and practice relating to SPCs is outside the scope of this article. However, it is important to note that the issues of patent infringement generally arise in respect of a patent with an extended term, in just the same way as they would with a patent still within its normal term of 20 years. Again, any freedom to operate study must be conducted to take into account the possibility of patents relating to the basic pharmaceutical component being extended. Pharmaceutical companies are, in general, very sophisticated users of the system for obtaining patent term extensions, for obvious commercial reasons. Again, patent term extensions are ignored at a company's peril.

Opportunities for patent protection

As a separate issue to the freedom to make and sell a new combination product, the opportunities for obtaining exclusivity for one or more aspects of the new development by way of patents should also be considered.

As already discussed, a combination product is likely, by its very nature, to be a complex combination of different technologies. It will come as no surprise, therefore, that this is reflected in the strategy for obtaining commercially relevant and useful patent protection. As a general checklist, the following aspects of the combination device should be considered for patenting opportunities:

aspects of the device, its operation and construction;

aspects of the pharmaceutical composition;

interaction between the device and the chemical composition; and

medical methods.

Basic standards for patentability

Before considering the specific issues arising in the patenting of inventions relating to combination products, it is perhaps useful to briefly review the basic requirements for patenting a technical invention.

The first key requirement is novelty, that is that the invention is new at the filing date of the patent application. To be new, an invention must be known or have been made available to the public in such a way that the invention is to be understood and useable by a third party. As a general rule, any form of disclosure may take away the novelty of an invention, including an oral disclosure at a seminar, conference or the like, a written disclosure, such as a paper or article, display of the product at an exhibition, and, in many cases, actual sale and/or public use of the product.

Some countries provide so-called “grace periods” in their laws, allowing for a valid patent to be obtained on an application filed after a public disclosure. The US is a key example of such a country. However, the law in many countries, for example across Europe, is much more strict and particularly unforgiving in this respect. As a result, the safest mode of operation for any company is to ensure that all relevant patent applications are filed before any form of public disclosure of the new product is made.

Once it is established that an invention is new, the second key requirement is, in general, that the invention is indeed inventive. In other words, it is a requirement that the invention is not merely an obvious variation or modification to something that is already known and in the public domain. In this respect, the approach to establishing the presence of an inventive can depend upon the particular technical field of the invention. In many cases, it is possible to argue the case for inventive step when dealing with an invention relating to a device. However, in the case of a patent or application relating to aspects of the pharmaceutical component of the combination product, it will generally be necessary to produce some form of experimental data demonstrating the efficacy of the medicament composition, if necessary with comparative data showing how the performance compares with those known compounds or compositions considered to be relevant.

In general, it may be difficult to persuade many patent offices to grant a patent for a pharmaceutical component or composition without some experimental data. Simple arguments for an inventive step may well not be sufficient.

Patenting aspects of the device

Turning to the particular aspects of a new combination product to protect by way of one or more patents, let us first consider the device itself. The patent laws of every country will, almost without exception, to a large extent allow a patent to be obtained for a new apparatus or device that may be used in a medical application. The patent may be directed to the features of the apparatus or device itself and/or the manner in which the various components function and operate. Problems may arise when trying to protect the use of the device as a medical device, where the use is considered as a method of treating the human or animal body.

As already noted, the patent laws of many countries exclude such medical methods from patent protection. Accordingly, the end use of the device may not be protectable in all countries. However, such exclusions do not generally prevent aspects of the device itself from being patented.

Patenting aspects of the pharmaceutical composition

The innovative aspects of the active pharmaceutical components may be protected by applying established laws and practice relating to the patenting of chemical compounds or compositions. If a novel compound or a novel composition containing the active ingredient can be identified, a patent to the compound or composition may be filed for. A novel composition may arise from the development of an entirely new formulation of the active compound, necessary for it to function with the device in the combination product. The patent laws of most countries allow for patents to be obtained for such compounds and compositions.

Historically, the laws of some countries contained exclusions for patenting chemical and/or pharmaceutical compounds or compositions. However, the laws in many countries have developed to allow such patents, or they are currently undergoing change. The mere identification of a new chemical compound or even a composition may be considered to be a routine matter without any inventive merit (a position often taken by the European Patent Office). The applicant is, therefore, expected to have to provide experimental data showing some form of efficacy and/or improvement over known similar or analogous compounds, in order to stand a reasonable chance of achieving the grant of a patent.

Other aspects of the pharmaceutical ingredient that may be patented include new methods of preparing the active compound itself or methods of preparing the formulation.

As the patenting of medical methods has been widely excluded in the laws of many countries, problems can arise where the invention to be protected resides in the recognition of the first or a further medical application of a known compound or composition. The use itself is generally regarded as being a medical method and a patent application directed to such use may well struggle to reach acceptance and grant.

To compensate for this exclusion and to allow for patents to be obtained for inventions that reside in the discovery of new medical applications of known chemical substances, many countries have developed a practice of allowing patents directed to the substances themselves, but limited in terms of purpose or use. A leader in this aspect of patent law and practice has been the EPO, which was one of the first major patent offices to find that a patent may define an invention in terms of the known compound or substance with a limitation as to its use as a medicament. Such patents directed to the first or further medical uses of a known compound have found wide recognition and acceptance in many countries around the world and often provide the only means of getting around the exclusions to patenting medical methods themselves. Again, pharmaceutical companies are very sophisticated users of these practices to protect newly developed drugs around the world.

Patenting medical methods

As has already been noted, the patenting of medical methods is a particular problem that arises with combination products. The end use of the product, while itself in many cases being particularly innovative, is in essence a method of treating the human or animal body. As such, the laws of many countries exclude such methods from patent protection. A notable exclusion to this is the law of the US, where medical methods may be patented.

Accordingly, while a patent directed to the method of using of the combination product may be not achievable in all countries of interest, patents of significant commercial value may still be obtained in some key markets in the world. Companies that do not have their first place of operation in the US may well be making decisions on patenting based on the law and practice in countries where medical methods cannot be protected. Such companies should be aware of the limited, but potentially very important, opportunities for patent protection in certain key markets, such as the US.

Exclusions from patentability

One final comment in this regard is that the law relating to the exclusions from patentability is developing constantly. The boundary of what constitutes an excluded medical method and what constitutes patentable subject matter is constantly being challenged.

As a result, the law and practice of such patent offices as the EPO and many national patent offices around the world is changing. In general, the exclusions are interpreted narrowly by the patent offices and the courts, meaning that opportunities for obtaining patents in this field open up from time to time, as a new challenge to the law is successfully raised. Companies should keep abreast of such developments, in order to become aware of new opportunities for obtaining patent protection as they arise.

Strategy for seeking patent protection

Overall, the strategy for protecting a new combination product will share similar principles to a strategy for any other product. A natural place to start considering a patent strategy is for a company to review the commercial operations and objectives with regards to its own products. In particular, a company will identify which products it wishes to commercialise and where, taking into account such factors as the countries of manufacture, as well as the likely key markets for sales.

However, a patent strategy should recognise the basic nature of the patent right. As noted above, a patent is not a right to do anything, but rather a right to stop others from practising the invention. As a result, the patent strategy should also consider the likely activities of competitors. A patent has considerable value to a company when it prevents competitors from entering the market with a competing product. This may be a product using the same technology or one using an alternative, but equally viable technology.

Ideally, a patent strategy secures for a company a virtual monopoly in the product in question. To appreciate the importance of considering the activities of competitors when designing a patent strategy, consider the case of a patent that, while perhaps of cast iron validity, does not cover anything that a competitor or another company would wish to do. In such a case, the rights granted by the patent have no practical effect. It can be argued that a patent in such a scenario has no value. If pursued and maintained, the patent would merely represent a financial burden and could hardly be considered as an asset contributing to the profitability of the project in question. This may be something of an over-simplification. However, it serves to highlight the need to look to the actual and potential activities of others in order to develop a patent strategy that can add value to a company.

Providing patent obstacles to rivals

In particular, the strategy should take into account what competitors may wish to manufacture and sell by way of competing products and where such activities will take place. The strategy should aim to provide patent obstacles to the competitors, in order to minimise the competition which the new product will face in the market place. As noted, this may include seeking patent protection for technical alternatives to the particular combination product being developed, if such alternatives offer a viable route for a competing product to reach the market. In many cases a development programme will produce various alternatives to one or more aspects of the final product. The path to commercialisation will involve a selection of one of the alternatives for ultimate commercial implementation. However, the rejected alternatives should be considered as to whether they provide a commercially viable alternative to the aspect chosen. Patenting all the commercially viable alternatives can provide an effective “ring fence” around the final product, ensuring that competitors will struggle to bring an alternative competing product to market.

By bridging a number of different technical disciplines, as we have discussed, a combination product requires the attention of a multifaceted team for its development and commercialisation. The team must have an in-depth understanding of both the technical aspects of the device and its operation, as well as the physico-chemical aspects of the pharmaceutical component of the product. The development and implementation of a successful patenting strategy will require a corresponding range of skills in the patenting and protection of all the various aspects of the product. The patenting of combination products combines tried and trusted areas of traditional patent law and practice with the requirement to work at the cutting edge of the law, in particular concerning the protection of medical methods.

While this is challenging for all concerned, a robust strategy can be developed in all cases, providing personal rewards to the individuals involved and potentially significant commercial gains for the company. Failure to recognise the complexities inherent in the protection of combination products can result in significant technical developments going unprotected, with the eventual product facing major competition in the market place with a consequent loss of revenue.