Intellectual property in drug discovery and development

Chapter 19 Intellectual property in drug discovery and development



P. Grubb


As is clear from the rest of this book, it costs a great deal of effort and money to discover and develop a new drug. No one would make such an investment if the results could simply be copied by an imitator who had invested nothing. The best way to protect the investment is by obtaining a patent for the drug. In this chapter we will look at what patents are, what kinds of inventions can be patented, and how a patent may be obtained and enforced.


Patents are not the only form of intellectual property (IP), but they are by far the most important for the pharmaceutical industry. Many patents that are filed and granted prove to be worth nothing, but a patent protecting a blockbuster drug against generic competition may be worth millions of dollars for each day that it is in force. An unexpected loss of patent protection may have a much larger effect upon the market value of the company holding the patent. In August 2000, when a US patent covering Prozac was held invalid by the Court of Appeal for the Federal Circuit, thereby reducing by about 3 years the expected term of exclusivity for this drug, 29% of the value of Eli Lilly stock was lost in 1 day – over $35 billion. This is serious money by any standards.



What is a patent?


A patent is the grant by a nation state of the exclusive right to commercialize an invention in that state for a limited time. During that time (the ‘term’ of the patent, usually 20 years from the filing date) the patent owner can go to the courts and enforce his or her rights by suing an infringer. An owner who wins the infringement suit can get damages or other compensation, and more importantly can obtain a court order (an injunction) to stop any further infringement. Note that although the state grants the patent right, the state does not check whether the right is being infringed – the patent owner must do that.


It is important to realize that the rights given by a patent do not include the right to practise the invention, but only to exclude others from doing so. Many inventors and business managers think that having a patent gives them freedom to operate, but this is not so. The patentee’s freedom to use the invention may be limited by laws or regulations having nothing to do with patents, or by the existence of other patents. For example, owning a US patent for a new drug does not give the right to market that drug in the USA without permission from the FDA (see Chapter 20).


What is less obvious is that having a patent does not give the right to infringe an earlier existing patent. To take a simple example, if A has a patent for a process using an acid catalyst, and B later finds that nitric acid (not disclosed in A’s patent) gives surprisingly good results, B may be able to get a patent for the process using nitric acid as catalyst. However, because this falls under the broad description of acid catalysis covered in A’s patent, B is not free to use his invention without the permission of A. On the other hand, A cannot use nitric acid without a licence from B, and in this situation, cross-licensing may allow both parties to use the improved invention.


Patents are important to industry because they give the innovator a period during which imitations can be excluded and the investment in R&D can be recovered. They are of particular importance to the pharmaceutical industry because once the chemical structure of a drug is published it is usually rather easy to copy the product, and because the manufacturing cost of a pharmaceutical is only a small part of the selling price, an imitator who has no R&D costs to recover can sell the product cheaply and still make a profit.



The patent specification


A patent (which strictly speaking is just a one-page certificate of grant) is in most countries published with a printed patent specification, which typically will be 10–100 pages long, or even more. The patent specification consists of three parts, the bibliographic details and abstract, the description, and the claims. Each part has a different purpose.



Bibliographic details


The title page usually sets out the bibliographic details, giving information such as the names of the inventors, the owner or assignee of the patent, the title, the dates of priority, filing, publication and grant, and the name of the attorney, if any, who acted for the patentee. It may also give the international search classification, and a list of prior published documents considered by the Patent Office when examining the application. Generally it will also have an abstract summarizing the invention; this is meant as a tool for searching purposes and is not used in determining the scope of protection given by the patent.



Description


The longest part of the specification is the description, the purpose of which is to give enough information about the invention to enable a reader who is technically qualified in the relevant field to reproduce it. This ensures that when the patent is no longer in force the invention will be fully in the public domain and able to be used by anyone having the necessary skills. The description will usually start with a brief account of the background to the invention, followed by a summary of the invention, then present full details, with actual examples where appropriate. There may also be figures (drawings, structural formulae, graphs, photographs, etc.) and if DNA or amino acid sequences are disclosed there will be sequence identifiers in standard form.



Claims


At the end of the specification come one or more claims, which have the legal purpose of setting out exactly what is covered by the scope of the exclusionary right. Readers who see that what they wish to do clearly falls within the claims of someone else’s patent are put upon notice that if they go ahead they may be sued for infringement, and will have to stop their activities unless they can prove that the patent is invalid. Unfortunately the reverse situation is not so clear. In many countries, particularly the USA, even an activity that does not fall within the literal wording of a patent claim may nevertheless be held to infringe by ‘equivalence’. The consequence is that before doing anything in the USA that is even close to the claims of a granted US patent, you must make sure that you get a written opinion from a US patent attorney that you are not infringing any valid claims. If you do not, and infringement is found, you may find yourself having to pay triple damages for ‘willful infringement’.



What can be patented?


There are basically only two categories of subject matter that can be patented – products and processes. Products are broadly anything having physical reality, including machines, manufactured articles, chemical compounds, compositions comprising a mixture of substances, and even living organisms. A process may be a process for manufacturing an article or synthesizing a compound, or may be a method of using or testing a product. However, a patent for a process for making something, for example a chemical compound, also covers the direct product of that process. A patent claiming simply ‘the compound of formula X’ covers X however it is made, but a process claim to ‘a method of production of X by reacting Y and Z’ covers X only when made by that process, and not in any other way. A claim to the compound itself covers the compound not only however it is made but also however it is used. Thus a claim to a compound invented as a dyestuff will also cover the compound when used as a pharmaceutical.


There are also some types of subject matter for which the grant of patents is specifically excluded, and these exclusions vary from country to country. For example, some countries do not grant patents on any plants or animals, whereas in Europe only specific plant and animal varieties are excluded, and in the USA there is no such restriction. Similarly, the USA allows patents for methods of surgical or medical treatment or diagnosis, whereas most other countries do not. Nevertheless, the invention that a known drug may be used for a new indication may usually be protected in these countries by patents having a different form of claim. Generally, patents will not be granted in any country for aesthetic creations, mathematical and scientific theories, and discoveries without any practical application.



Pharmaceutical inventions


Within the pharmaceutical field, patentable inventions may include not only new chemical compounds of known structure, but also, for example, biopolymers and mixtures the structure of which has not been fully elucidated. Isolated DNA sequences and genes are also patentable as chemical compounds, although in some countries the scope of protection given by the patent is limited to the disclosed use. Even if a chemical compound is already known, it may be possible to patent variants, such as new optical isomers and crystal forms of the compound, as well as new galenic formulations, mixtures with other active ingredients, manufacturing and purification processes, assay processes, etc.


If a known compound, not previously known to have any pharmaceutical use, is found to be useful as a drug, this invention may be protected by claiming a pharmaceutical composition containing the compound, or, in Europe, the use of the compound as a pharmaceutical. Such claims will cover all pharmaceutical uses of the compound, not only the one found by the inventor. If the invention is that a known drug has a new and unexpected indication, such an invention may be protected in the USA by a ‘method of medical treatment’ claim (‘method of treating a human suffering from disease Y by administering an effective amount of a compound X’), or in Europe by a use claim (‘use of compound X for the treatment of disease Y’).



Requirements for patentability


For an invention in any of the above categories to be patentable, it must meet three basic criteria:



• It must be novel


• It must involve an inventive step (must not be obvious)


• It must be industrially applicable (must have utility).



Novelty


The first and clearest requirement is that nothing can be patentable which is not new. If a patent were to be granted for something already known, then the grant of a patent in respect of this information would violate the fundamental principle that a patent cannot deprive the public of rights that it already has. There are, however, different definitions of ‘novelty’. The most straightforward is that of ‘absolute novelty’ applied in Europe, Japan, China, and the majority of other countries, which provides that an invention is new if it is not part of the ‘state of the art’, the state of the art being defined as everything that was available to the public by written or oral publication, use or any other way, in any country in the world, before the priority date of the invention. For example, if it could be proved that the invention had been described before that date in a public lecture given in the Mongolian language in Ulan Bator, a European patent application for the invention would lack novelty even if no European had heard or understood the lecture.


A few countries still have the system of ‘local novelty’, under which a disclosure of the invention before the priority date destroys novelty only if it is available within that country. Rather more countries, including the USA, have an intermediate ‘mixed novelty’ system, according to which a later patent application is invalidated by written publication anywhere in the world, but by oral publication or use of the invention only in the home country. Thus a US patent would not be invalidated by the lecture in Ulan Bator, but would be by an account of it published in a newspaper there. Similarly, prior use in a country outside the USA would not invalidate a US patent if there was no written description, whereas a European patent would be invalidated by prior use anywhere in the world, so long as the use made the invention available to the public – for example the sale of a chemical compound that could be analysed.



Novelty in the USA


A more basic difference between the USA and all other countries is that all countries other than the USA have a ‘first-to-file’ system, whereby if two persons make the same invention the first one to file a patent application gets the patent. The present US system is ‘first-to-invent’, so that irrespective of who files the first application, the person who can prove the earlier invention date gets the patent. A consequence of this is that in most countries, prior art is what is published before the first filing date (the priority date). In the USA, however, prior art is what is published before the invention date. Since by definition an inventor cannot publish his or her invention before it is invented, self-publication cannot normally be prior art. However, if an invention has been published, by the inventor or by another person, after the invention date, a US patent application for the invention is regarded as lacking novelty unless it is filed within 12 months of the date of publication. This means that an inventor may publish the invention and still obtain a valid US patent so long as a US application is filed within this 12-month period. In the past, many US inventors, particularly those working in universities, sought to take advantage of this so-called grace period, only to find that by so doing they had destroyed their chances of getting any protection in other countries. Now most US inventors are aware of the dangers, and unless they are interested only in obtaining a US patent, they will adhere to the first-to-file principle and file an application before publishing their results. Following passage of the America Invents Act in September 2011, the US system will change to first-to-file on March 16 2013.



Inventive step (non-obviousness)


Whereas the concept of novelty is (or should be) an objective matter, the question of whether or not something involves an inventive step is intrinsically much more difficult, as subjective judgement is involved. The basic principle to remember is that the reason for requiring the presence of an inventive step is that ordinary workers in that field should remain free to apply their normal skills to making minor variations of old products.


Thus the person to whom the invention must be non-obvious in order to be patentable is the ‘person skilled in the art’, i.e. a worker who is competent but lacks imagination or inventive capability. In the days when the majority of patents were for simple mechanical devices, the person skilled in the art was usually described as an ‘ordinary workman’. However, for complex inventions in pharmaceutical chemistry and biotechnology, the ‘person skilled in the art’ may be considered to be a team of highly qualified scientists.


It is a legal fiction to suppose that such a team could be competent but non-inventive, considering that its members would, if employed in industry, be expected by their company to make inventions, and if academic scientists, would be expected by their university to produce original scientific work, which amounts to much the same thing. The point is that obviousness should be judged by a person with qualifications and imagination that are average for those in the field. It is tempting for a party attacking a patent on the ground of obviousness to use an expert witness with the highest possible qualifications, but it is not very helpful to have a Nobel laureate testify that something is obvious. It may be obvious to a genius, but the real question is whether it is obvious to the normal worker in the field.


It is often very easy to reconstruct an invention with the benefit of hindsight, as a series of logical steps from the prior art, but it does not necessarily follow that the invention was obvious, especially if there is evidence that the invention was commercially successful, or satisfied a need. The question ‘If the invention was so obvious, why did no one do it before?’ is usually a relevant one to ask.



Industrial applicability (utility)


In Europe it is a requirement that the invention should be capable of industrial application, which is broadly defined and includes making or using the invention in any kind of industry, including agriculture. In the USA, patentable inventions are defined as any new and useful process, machine, manufacture or composition of matter, or any new and useful improvement thereof. The US requirement that the invention be useful has generally been applied no more strictly than the corresponding European requirement, but recently US examination guidelines have been tightened up so as to make more difficult the patenting of DNA sequences for which no real function is known, and the courts both in the USA and the UK have held such patents invalid.

Related posts:

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  3. Choosing the target
  4. The role of information, bioinformatics and genomics

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Oct 1, 2016 | Posted by in GENERAL SURGERY | Comments Off on Intellectual property in drug discovery and development

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