Legally Protecting & Exploiting Developments in Bioinformatics

 

Dr. Robert Harrison

Huber & Schüssler Patent & Trade Mark Attorneys

Truderinger Str. 246

81825 Munich (Germany)

E-Mail: rob.harrison@germanpatent.de

 

Abstract

 

Introduction

 

In the field of molecular biology, the importance of the protection of intellectual property is widely known and acknowledged. Whilst there might be differences in agreement over the extent to which genes and proteins should be the exclusive property of a company, university or individual for all properties that these substances might possess, it is generally acknowledged that the inventors should be rewarded for their work by the grant of patents.

 

Increasingly, patents are also being awarded for research tools or enabling technologies used in the development and discovery of genes and proteins. Initially researchers developed these tools to help them in their work of, for example, sequencing the genome or screening potential drug candidates. More recently, researchers and their employers are realising that the tools developed may indeed be potentially highly valuable intellectual property assets in their own right. The current dispute between Affymetrix and its competitors over patents relating to microarrays is just one example of the value that it placed on such tools[1]. Just as importantly, ESTs and SNPs are also being patented because of their potential applications in drug development and application[2].

 

One research tool that has until recently not been the subject of many patents is the computer program. A recent study[3] carried out by the London-based consulting firm Silico Research reported that there were very few patent applications filed in the bioinformatics field. The reasons cited for the lack of patents included the fact that many of the current bioinformatics products merely combine together existing data sources into a single product or the difficulties of proving infringement of the software patent. A further reason noted was the fact that the industry was so new that many patent applications may still be pending. In many countries, there is also a popular misconception that software is “not patentable” because it is apparently excluded from patent protection[4].

 

On the other hand, one of the key factors, which investors take into account when investing in technology companies, is the intellectual property that these companies possess which will give them a competitive advantage. The intellectual property does not just comprise patents but may also include copyrights, trade marks and trade secrets. When carrying out research, investigators should therefore keep in mind how they can maximise their intellectual property without limiting their freedom to operate and how they can attract more funds to further their work. This article will attempt to provide guidance on successful strategies for achieving these goals in bioinformatics.

 

Almost all of the relevant legal decisions are taken from the case law of the United States or of the European Patent Office. This is not meant to imply that the laws in these countries are superior in any way and, indeed, many countries throughout the world have almost identical laws[5]. The courts and the patent offices in both Europe and in the United States have, however, been the most active in interpreting these laws and the courts in other countries often follow their reasoning.

 

Copyright versus Patents

 

One argument often heard against the granting of patents on software-implemented inventions, such as in bioinformatics, is that software is adequately protected by copyright and that therefore there is no need for a further legal tool to protect innovation in this area. The argument fails, however, to understand the difference between legal protection available under copyright laws and the legal protection available under patent laws.

 

It is often said that copyright protects the expression of an idea whilst a patent protects a technical idea. Such broad generalisations may seem easy and be of use to lawyers arguing a case in court, but in practice they are difficult to understand. An example can, however, illustrate how these different concepts can be applied in every day research.

 

Much genomic screening these days is carried out using microarrays in which target cDNA sequences or oligonucleotides are placed at a number of sites on a chip and the material to be analysed is washed over the chip. At a number of the sites some of the genetic material becomes bound to the cDNA or the oligonucleotides. The position of the sites is detected by fluorescence or some other means. The shear number of sites[6] on a chip means that detection of those sites in which genetic material is bound to the target is impossible for a human to carry out. Instead the detection is carried out automatically and the results are fed into a computer. The computer contains software that processes the data and produces it in a form that can be understand and interpreted by a human.

 

Clearly, the construction of the chip with its cDNA or oligonucleotide targets can be protected by patents – and, as mentioned above, a number of companies are currently involved in a legal tussle over patent rights. Some of the cDNA or oligonucleotide targets may themselves be the subject of individual patents. The manner in which the presence or absence of genetic material on a site is detected can also be patented as can the construction of the detector. More complicated is the protection of the software that analyses the results.

 

The developer of the software will have written a program that consists of a number of lines of code fed into a computer and that will implement an algorithm to analyse the data produced by the microarray. The expression of the program, i.e. the lines of code and indeed any flow charts or pseudo-code which the developer produced while writing the program, are entitled to copyright protection. This means that anyone copying the lines of code or using the flow charts of the computer program will infringe the copyright in that computer program unless he or she has been given permission to copy by the owner of the copyright.

 

The technical features of the program, such as algorithms used to analyse the data collected, the structure of the database or program interfaces can be protected by patents. The advantage of patent protection over copyright protection can be understood if one considers a unique algorithm developed to analyse the data from the microarray. The algorithm is implemented in lines of code that might be written, for example, in the PERL language. If another programmer reprograms the algorithm using, for example, an implementation of the BASIC language, then there will be no infringement of the copyright of the PERL implementation of the algorithm since the lines of code have not been copied. Had the original developer been granted a patent on the application of the algorithm to the analysis of data from the microarray, however, then a BASIC implementation of the algorithm would infringe the patent.

 

Patenting Computer Programs as such

 

The European Patent Convention – and many other national patent laws throughout the world – states that patents cannot be granted to computer programs as such. This limitation is, however, neither to be found in the United States patent law nor in the TRIPS agreement[7]. This provision seems to rule out the patentability of any invention in which computer programs play a role. However, given the importance that computers and the fact that a general-purpose computer has often replaced a specialised piece of equipment, it is clearly outdated to exclude computer programs from patentability. In Europe, the European Patent Office realised fairly soon after its foundation in 1978 that this exclusion was illogical and in its famous VICOM decision[8] pointed out that the wording of the European Patent Convention excluded only the patenting of computer programs as such[9]. A general-purpose computer programmed for a special purpose was, however, not excluded from patentability as long as it produced a technical effect.

 

The VICOM decision and other ones that followed it in Europe opened the way to the patenting of inventions implemented by means of computers. The reasoning behind these decisions has often been adopted by courts in other countries. In 1984, the word bioinformatics had probably not been coined. However, much of the case law developed by courts in Europe on computer-implemented inventions is highly relevant to bioinformatics developments.

 

Protection of Databases

 

Much of the early interest in bioinformatics lay in the construction of databases to record the data that was generated by gene sequencing experiments. The original data – such as that used in GenBank – was stored as a flat file structure. Later more sophisticated relational database structures were developed to allow more efficient and significant analysis of the data stored therein. Some of the relational databases have been put into the public domain, i.e. the developers have renounced their rights to the databases, and they can be used without charge by all researchers and commercial companies. Other database developers have reserved their rights and will only provide free access to, for example, academic institutions. Commercial companies wishing to exploit the database and the information contained within it have to negotiate a contract with the database  developers.

 

Protection of the information contained within the database is obtained either by copyright protection or by so-called database rights. In many countries, however, copyright protection is not granted to the information contained within a database. Some countries, however, such as Australia[10], consider that the arrangement and collection of the information may be so significant that copyright is granted on the database. The United States Supreme Court, on the other hand rejected some years ago the so-called “Sweat of the Brow” test[11] in which copyright was previously given to collections of information which had been put together. In Germany copyright protection has never been accorded to a collection of items of information.

 

In order to harmonise protection within its member states, the European Union adopted the European Database Rights Directive on 11 March 1996[12] that protects “a collection of independent works, data or other materials arranged in a systematic or methodical way and individually accessible by electronic or other means”[13]. Thus a developer of a database can prevent the extraction and/or reutilisation of the whole or of a substantial part…of the contents of the database[14]. This means that somebody who creates, for example, a database comprising genome sequence data or protein structure data can stop others from using this data without permission. Unfortunately protection under the European Database Rights Directive is limited only to those persons or legal entities resident in the European Economic Area[15] or in countries having similar protection schemes. Proposals to introduce a similar protection right in the United States have, despite several bills in the US Congress, not yet been successful.

 

Protection of the structure of the database can be obtained through patents. One of the earliest cases on patent protection for data structures was in 1994 in the United States. The Federal Circuit, which is the Appeal Court in the United States for decisions in patent matters, considered a patent claim having a data structure that organised the information in a database in accordance with a so-called attributive data model. In such a model, the information used by one or more application programs was organised in terms of attributes and the relationships of each attribute to the other attributes was stored in the database. This case, and other subsequent cases, established the principle in the United States that a database structure was in principle patentable. The database structure still had to be examined to see that it was new and non-obvious when compared to other known database structures.

 

The European Patent Office’s Boards of Appeal have also considered the question of the patentability of a data structure[16] in a patent application that claimed a picture retrieval system having data stored on or in a record carrier having a particular structure. The Board pointed out that there was a difference between the functional data, which controlled the technical working of the system, and the cognitive information, which represented the picture that could be retrieved and displayed[17].

 

The reasoning behind the European Board’s decision can be applied not only to video or television systems. If we return to the original example of the microarray data, the Board’s decision suggests that a data structure is patentable in which the data relates to control of the microarray experiment or to display of the information obtained from the microarray experiment. Furthermore, since data relating to the DNA sequences or protein structure is not merely “cognitive information”, it is possible to argue that data structures containing this information are patentable.

 

Patenting of Algorithms

 

Much of the original analysis of DNA sequence data was carried out by manual processing of the sequence data. In many of the early gene matching experiments, experienced operators compared the newly discovered DNA sequences to detect similar known sequences. As the amount of data grew in databases such as GenBank, it was necessary to automate such techniques and develop algorithms such as the Smith-Waterman algorithm.

 

Neither the United States Patent Office nor the European Patent Office will allow the patentability of an algorithm per se without any reference to its application. However, the Federal Circuit of the United States recently emphasised that in order to include an algorithm as part of a patent claim, it is necessary that the algorithm be applied to produce a “useful, concrete and tangible result[18]”. Similarly the European Patent Office points out in its Guidelines for Examination[19] that an electrical filter designed using a mathematical method would not be excluded from patentability. In a decision relating to the interactive rotation of displayed graphic objects on a screen[20], the Appeal Board stated that the invention did not relate to a mathematical method as such but stated that the “calculating steps mentioned are only means, or tools, used within the overall method claimed, for entering a rotation angle value into a draw graphic system.”[21]

 

This certainly suggests that an algorithm used in the analysis of DNA sequence or protein data should be patentable as long as it is not couched in purely mathematical terms but is applied to the real world. So, for example, an algorithm to identify homologies among genes should be patentable since it offers a useful, concrete and tangible result and is only a means for obtaining information about the homologies.

 

An algorithm to mine existing data for potentially useful properties would also be protectable. Examples of such a data mining algorithm could be one which matched similarities in protein structures with identical annotations of properties in order to determine which protein structures might have also have the same properties.

 

As explained above, the lines of code, which implement the algorithm, will be protected by copyright protection.

 

Interfaces

 

The need for bioinformatics programs to interact with a human user or with other programs means that the interfaces to the program have to be documented. The European Patent Office considered the patentability of a user interface in a decision dating from 1988[22]. In the case in hand a method was claimed for displaying one of a set of predetermined messages indicating a specific event which may occur in an input/output device of a word-processing system. The Board of Appeal stated that giving visual indications automatically about conditions prevailing in an apparatus or system is basically a technical problem[23] and thus not excluded from patentability. Thus it is probable that the European Patent Office would more generally consider to be patentable an interface in which information is exchanged about conditions prevailing in an apparatus or system. In the microarray experiment described above, the information exchanged between the computer program which analysed the microarray data and the microarray itself relates to the conditions prevailing in the apparatus and therefore the interface should be patentable. Similarly, displays on an output device of DNA or protein sequence data give information about the conditions prevailing in the microarray experiment and a method for displaying this information should, in accordance with the Board’s reasoning, be patentable.

 

Exploiting Patents and Copyright

 

Exploitation of the patents and copyrights can be carried out in a number of ways. The simplest manner is placing the computer program or database on the web and inviting anybody who wants to use it to do so. This can save the costs of filing for patent and/or copyright registration. However, the developer cannot necessarily expect any financial return for his or her efforts – if a drug development company uses the program or the information in the database in its own research, then there is generally no obligation for the drug development company to return any profit to the developer.

 

There is therefore an increasing emphasis on obtaining formal intellectual property protection for the programs or databases developed. Filing a patent application or applying for copyright protection does not necessarily mean that the developer is obliged to enforce the rights and go against unauthorised users of the software, data or ideas. Rather, they allow the holder to selectively chose to whom he licences the work without charge and from whom he can collect royalty fees. So, for example, the holder of a patent or copyright can choose to licence it free of charge to other academic users for non-commercial purposes whilst entering into an agreement with a company for the use of the patent or data in developing new drugs.

 

Banks and Venture Capitalists are also often interested in which patents and copyrights a company holds when choosing to invest in a newly formed company. These can be used to stop other companies from competing in the same field, or can be licensed to competitors to increase revenue. Experience shows that a company with patents filed in major countries such as the United States or Europe is generally more successful than one without any protection whose business can be easily copied by competitors.

 

Potential Pitfalls

 

When considering a strategy to protect developments in bioinformatics for later exploitation, it is important to ensure that the value of the intellectual property is not accidentally destroyed. In all countries but in the United States[24], a patent must on its filing be new and not obvious. If the idea has been disclosed at a conference, in a Ph.D. thesis, or published in a journal by the developer, then it can no longer be patented.

 

So-called non-disclosure agreements are often used before a patent is filed in order to discuss the idea with a potential investor. These agreements are fine as long as both sides keep to them. However, if they are broken, then an opportunity to file a patent application may be lost. Many larger pharmaceutical companies are not prepared to accept non-disclosure agreements since they will have to reveal the idea to a large number of people in their company or in affiliate companies. The companies know that the chances of maintaing confidentiality of the idea within the company are almost impossible.

 

The choice of countries in which the patent application or copyright registered[25] is filed is also important. Patents filed only in one country are often worth very little. In the bioinformatics field it is vital to have a patent in the United States and probably also in Europe. These must be filed within one year of the filing in the first country, although it may be possible to use the so-called patent co-operation treaty to extend this deadline to 30 months after the initial filing. Missing the deadline, even accidentally, can means loss of the opportunity to obtain patent protection in other countries.

 

Conclusion

 

The legal protection of developments in bioinformatics can be successful if time and effort is put into identifying which developments are protectable by copyright and which developments are patentable. The developments can be successfully exploited by either licensing them to companies or by using them to obtain investment to start up a company. Care, however, has to be taken that the opportunity to obtain patent registration is not thrown away by filing the application too late.

 

Robert Harrison

Munich, 15 December 2001.



[1] See, for example, “Affymetrix, OGT settle Infringement Dispute; Affy to Post $19M Charge” by Marian Moser Jones, www.genomeweb.com/articles/view-article.asp?Article=20013261123, and “California Judge Dismisses Affy Claims Against Incyte”, www.genomeweb.com/articles/view-article.asp?Article=200101575128.

[2] “Patenting expressed sequence tags and single nucleotide polymorphisms” by Gerald Flattmann & Jonathan M. Kaplan, Nature Biotech, vol 19, August 2001, pp 777-778.

[3] “Bioinformatics Patents Remain a Rarity in IP-Heavy Biopharmaceutical Industry” By Bernadette Toner http://www.genomeweb.com/articles/view.asp?Article=200110863736

[4] Art. 52 (2) of the European Patent Convention states, for example, that the following in particular shall not be regarded as inventions … (c) schemes, rules and methods for performing mental acts, playing games or doing business, and programs for computers; (d) presentations of information.

[5] In particular, member countries of the World Trade Organisation are obliged under the so-called TRIPS agreement to introduce minimum starndards for trademark, copyright and patent laws. The minimum standards are modelled on those in Europe and in the United States.

[6] Affymetrix have, for example, a chip with 400,000 sites.

[7] See footnote 5.

[8] T 0208/84 of 15 July 1986 “Computer-related Invention/VICOM” published in the Official Journal of the European Patent Office, 1987, pp 14-23.

[9] See point 6 of T0108/84 (footnote 8).

[10] Telstra Corporation Limited v Desktop Marketing Systems Pty Ltd [2001] FXA 612 (15 May 2001)

[11] Feist Publications v. Rural Telephone Service Corp, 1991

[12] Directive 96/9/EC of the European Parliament and of the Council adopted on 11 March 1996 on the legal protection of databases. OJ European Uion No. L77, 27 March 1996, 20.

[13] Art. 1, §2, of the Directive

[14] Art. 7 §1 of the Directive

[15] The European Economic Area consists of the European Union, Norway, Iceland and Liechtenstein.

[16] Decision T 1194/97 – 3.5.2 of 15 March 2001. “Data Structure Product/PHILIPS”.

[17] See point 3.3. of decision T 1194/97 (footnote 10).

[18] State Street Bank & Trust Co. v. Signature Fin. Group, Inc., 149 F.3d 1368, 47 USPQ2d 1596 (Fed. Cir. 1998).

[19] Part C, Chapter IV, 2.3

[20] T 0059/93 – 3.5.1. of 20 April 1994.

[21] See point 3.2 of T 0059/93 (Footnote 14)

[22] T0115/85 of 5 September 1988 “Computer-related Invention/IBM” published in the EPO Official Journal, 1990, pp 30-34.

[23] See Point 7 of T0115/85 (footnote 19).

[24] In the United States, the inventor can still file a patent one year after disclosure. However, no patent rights can be obtained outside of the United States.

[25] Only a few countries, such as the United States and Japan, provide special registration systems for computer programs. In most other countries, copyright is established by the author of the program on writing the program. In a court case, the programmer needs, however, to demonstrate that he or she was the original author of the program. This can often be done by filing a copy of the program with a lawyer or notary. In the United States it is also advisable to register documentation associated with the computer program.