Transition from Genentech to Biogen

Since its birth, the biotechnology boom has only experienced an upswing. Biotechnology has created an independent knowledge-based economy of its own, which affects economies the world over. Patents in biotechnology have gained ever more importance over the last three decades, as research and development in biotechnology has tremendous monetary ramifications and involves a great amount of time and energy.

Patents in biotechnology have aroused a lot of controversies owing to the complicated nature of the subject-matter involved. The laws and standards regularizing biotechnological patents are country based. Some countries have more rigorous standards as compared to others. For example in Europe, even though, all countries have framed their domestic legislations on patents on the lines of the European Patents Convention, 1973 (EPC), their respective interpretations of the various provisions and requirements on granting of patents differ, from case to case and jurisdiction to jurisdiction. This varied interpretation has deeply affected the progression of patent laws and their understanding.

It is this variance and evolution in patent laws that the researcher aims to focus on, by studying the transition between two very important cases, Genentech Inc.’s Patent [1] and Biogen v. Medeva [2] It can be very well contended that these two cases laid down the foundation of the law regarding patentability of biotechnological inventions. The researcher for the purpose of her study has chosen to restrict the scope of her research to the change in the approach of the courts towards the concept of ‘invention’. The researcher also intends to highlight the difference in the interpretation of similar provisions of law under different jurisdictions.

Concept of Invention

Genentech Inc.’s Patent, [1989] R.P.C. 147 (C.A.)

In this case, the patentee discovered the DNA sequence of the human protein comprising tissue Plasminogen Activator (‘t-PA’). This human protein was known to have important medical uses against blood clots in the treatment of thrombosis, but was not naturally available in useful quantities so as to be used for medical purposes. However, with the discovery of its DNA structure, t-PA could be artificially synthesized. A particular advantage of using recombinant DNA technology to produce t-PA was that the artificially produced t-PA would lack the impurities which exist if the protein is extracted from human tissue. Genentech sought monopoly rights over t-PA [3] (which essentially is a type of protein existing in the human body). [4] The dispute came before the English Court of Appeal comprising of Lord Justices Purchas, Dillon and Mustill, who framed the following criteria to review whether a patent could be granted in this case:

Whether there was an invention;

Whether the invention was of a type capable of being patented by reference to section 1(2) of the Patents Act,1977 (‘the 1977 Act’) ;

Whether the invention involved an inventive step?

With regards to the determination of the first question of whether the 1977 Act requires the applicant to have made an invention, as distinguished from an invention that is new, involves an inventive step and is capable of industrial application, Mustill LJ commented that the initial words of section 1(1), ‘A patent may be granted only for an invention in respect of which the following conditions are satisfied …’, and the final words, ‘and any reference in this Act to a patentable invention shall be construed accordingly’ were clear enough to indicate that it is required of the applicant to establish the existence of an invention, separate from the other four criteria specified in section 1(1), i.e. before determining whether a claim complies with paragraphs (a) to (d) of section 1(1), the question whether the claim discloses anything which can be described as an invention must be answered in the affirmative. [5]

Now, the description of a previously unknown genetic structure of a known, naturally occurring substance (t-PA) was not in harmony with Mustill LJ’s view of invention as being the creation of a product, or a process for the production of a product [6] , i.e., he found it difficult to understand how the acknowledgment of a previously unknown property of a known substance could be either the invention of that “product” or the invention of a “process. He went onto state that, “a properly framed claim for a process for synthesising, refining or transforming the substance should be capable of founding a patent”, i.e. though he was willing to regard a process for synthesizing the substance as an invention, but a mere claim asking for patent over a naturally occurring substance was not worthy of being granted a patent. [7]

Biogen Inc. v. Medeva Plc [1997] R.P.C. 1

This is a landmark case in the field of patents in biotechnological inventions as it was in this case that the House of Lords, considered patentability of genetically engineered products for the first time.

The patent in suit primarily related to the exploitation of Hepatitis B virus (HBV) using recombinant DNA technology. The relevant claims covered recombinant DNA molecules coding for proteins displaying HBV antigen characteristics. Claim 1 covered the distinct surface and core proteins and their expression in bacterial, yeast and mammalian host cells. Claim 3 was limited to cover DNA molecules coding for core antigen and their expression in bacterial, yeast and mammalian hosts; Claim 4 was limited to cover molecules coding for surface antigen and their expression in bacterial, yeast and mammalian hosts. Essentially, the claims related to a synthetic molecule of a naturally occurring virus, HBV, which enabled the construction of diagnostic kits for its detection. [8]

Regarding the process, Biogen had carried out a shotgun expression, which involved hacking up HBV DNA in an arbitrary way and cloning and expressing the haphazard segments to determine if the DNA coding for any functional proteins had been chosen. It was a risky plan in that there was a high probability of failure in any trial. The other possible option would have been to sequence the DNA and then pick specific DNA segments to be expressed having the sequence likely to match for the concerned protein. [9]

Medeva argued that HBV using recombinant DNA technology did not disclose any invention at all. The Court of Appeal, considered this argument and held that Biogen’s patent was invalid due to insufficiency, obviousness and failure to pertain to an ‘invention’. It essentially followed the approach adopted in Genentech while addressing whether the 1977 Act requires the applicant to have made an invention, as distinguished from an invention that is new, involves an inventive step and is capable of industrial application and went onto reiterate that an examination as to whether or not the claims constituted an invention should for all purposes be made before reviewing whether the patentability requirements had been fulfilled. [10]

However, in the House of Lords, Lord Hoffmann discarded the approach taken by the Court of Appeal, while dealing with the issue of whether the claims by Biogen constituted an invention as per section 1(1) and concluded that such an approach would lead to unnecessary complexity and would essentially be scholarly and not practical in nature. Lord Hoffman, acknowledged that the four requirements of patentability in section 1(1) not only restrict the class of inventions which may be patented but ‘probably’ also covered every aspect of the meaning of the term invention. [11] He explained his usage of the term ‘probably’ to mean that in the absence of an exact definition of invention, it could not be said with certainty that there might not be something, which satisfied all the conditions of section 1(1) but could not be described as an invention. [12]

He recommended that courts should first consider the conditions for patentability such as novelty, inventiveness, industrial application, plus the excluded categories, before undertaking the issue of whether the claims satisfy the meaning of invention. He rationalized the same on the basis of convenience. He said that since the four conditions were relatively well-known ground, clarified by definitions in the Act and the jurisprudence of the courts and the E.P.O., it would in general be more suitable to start by deciding whether they were fulfilled as normally the same would virtually be the end of an enquiry in every case. [13]

He also clarified Mustil L.J.’s statement (‘You cannot invent water, although you certainly can invent ways in which it may be distilled or synthesised.’) in Genentech by pointing out that there might be cases in which the alleged subject-matter is so obviously not an invention that it is tempting to dismiss the claim without inquiring too closely into which of the conditions has not been satisfied. In such a case (invention of water) it will be obscure to say that water fails the condition in paragraph (a) of section 1(1) because it is not new. He advised judges to put aside their intuitive sense of what constitutes an invention until they have considered the questions of novelty, inventiveness. [14]

Biogen thus over turned the stance adopted in Genentech, denying the need for looking into the existence of an invention per se, before looking into other provisions of section 1(1) of the 1977 Act.

Disparity among courts in determination of ‘inventive step’ in Biogen v. Medeva & Change in the scope of ‘inventive step’ from Genentech to Biogen

The divergence in the outcomes of the EPO’s Technical Board and House of Lords (‘HoL’) on patentability of DNA molecules coding for proteins displaying HBV antigen characteristics in Biogen shows a difference of approaches adopted, between the EPO and the HoL in regard to the issues of inventiveness and support for an invention. This distinction is a clear indication of the difference in stringency norms and other criteria applied by the courts while determining such issues of patentability. This disparity can be attributable to the complex nature of the subject matter in biotechnological patents which leans to exacerbate the difficulties in devising a uniform practical test. [15]

As per section 3 of the 1977 Act, ‘an invention shall be taken to involve an inventive step if it is not obvious to a person skilled in the art’. Article 52 of the EPC states that European patents shall be granted for any inventions which are new and which involve an inventive step. Article 56 of the EPC states that an invention will involve an inventive step if it is not obvious to a skilled addressee.

EPO Technical Board- The patentability of Biogen’s claim to recombinant DNA sequence for HBV depended on the existence of an inventive step. The EPO’s Technical Board used Article 56 to resolve the issue of obviousness. The Board determined the same by identifying the technical problem that existed and comparing Biogen’s solution of that problem. [16] The Board concluded that the skilled practician would (even before Biogen’s invention was revealed), have faced a lot of uncertainties and it would not have been obvious to him from his general knowledge to resolve these by hacking up HBV DNA in an arbitrary way and cloning and expressing the haphazard segments (the ‘shotgun’ approach) to identify the right selection as was done by Biogen, rather than sticking to the more predictable way of first determining the genetic HBV DNA. As a result, the assessment on the part of Biogen to try creating HBV antigens through expression techniques was held to be an inventive step. [17]

Court of Appeal- Before going into the decision of the HoL, it is important to note that the Court of Appeal had determined that the ‘shotgun’ approach to identify the DNA coding for the HBV antigen, lacked an inventive step because it was ‘a mere commercial decision’ and ‘a matter of business judgment’.

The Court further said that nothing that Biogen did was not obvious if one took the business decision to do it. It was a simple matter of business judgment as no ‘intellectual jump’ was involved. It was not a description of an inventive step. The distinction between what Biogen did and an inventive step lay in the difference between some element of novel insight or discovery and a mere business assessment or choice to pursue an identified goal by known means. [18]

In applying this logic the Court of Appeal was following the tradition set earlier in Genentech [19] , where the fundamental problem was whether the process of determining the amino acid sequences comprising t-PA (this determination included the DNA sequences coding for this protein, involved copying the gene and joining each copy into a ring of DNA which could then be used to incorporate the t-PA gene into suitable host cells for the production of pure t-PA) entailed any inventive step. The Court in Genentech observed that the goal of the research, the sufficiency of the theory and practice of what Genentech was doing was known to it and it was obvious to the person skilled in the art to set out to produce human t-PA by recombinant DNA technology. Therefore, all the steps taken by Genentech in finding out the composition of the sequences and applying that knowledge to produce human t-PA were applications of known technology without any original step. The Court of Appeal in Genentech decided that the alleged invention was in fact a mere discovery which did not involve the use of any inventive step, and was hence non-patentable [20] , and held that all the claims were invalid for obviousness and want of inventive step.

House-of Lords- Though HoL did not reverse the decision regarding the non-patentability of Biogen, but it criticized the approach taken by the Court of Appeal for determining the question of inventive step. Lord Hoffman observed that a given experimental strategy is normally adopted for commercial reasons because the anticipated rewards and thoughts of gains seem to justify the necessary expenditure. He thus concluded that commercial reasoning in itself could not justify lack of inventive step. [21] Lord Hoffman stressed upon the establishment of a link between inventiveness and “the addition of a new idea to the existing stock of knowledge” for the determination of the presence of an inventive step. He said that to assess this link it was necessary to “include some express or implied reference to the problem which it required invention to overcome”. [22]

From the above three judgments, one not only sees the glaring disparity in the stringency of tests used to determine ‘inventive step’, but one can clearly see how the features of the test have undergone a change in less than a decade from Genentech to Biogen.

Conclusion

The aim of the project was to study the variance and evolution in patent laws by analysing the transition from the case of Genentech (1989) to Biogen (1996) and to highlight the difference in the interpretation of similar provisions of patent laws by the EPO, the House of Lords and the Court of Appeal.

At the outset, we saw how section 1(1) of the Patents Act, 1977 is capable of two interpretations, first being, that any innovation which satisfies the four criteria (of paragraphs (a) to (d) of section 1(1)) will be a patentable invention, and, the second being, that the innovation for which the application is made first passes an initial test of being expressible as an ‘invention’, and then satisfies the four conditions laid in section 1(1). This created confusion regarding the correct interpretation of section 1(1). This uncertainty was settled in the case of Biogen, where the House of Lords sided with the first interpretation, denying the need for looking into the existence of an ‘invention’ there by reversing the stance taken by the Court of Appeals in Genentech.

Thereafter, with respect to the determination of the question of ‘inventive step’ and the components to be considered while doing the same, the House of Lords in Biogen discarded the observation of the Court of Appeal which had followed the traditional approach adopted in Genentech, by holding that it is normal for a particular experimental strategy to be adopted for commercial reasons because the expected rewards and thoughts of gains seem to justify the necessary expenditure. Therefore, denying patents on the reasoning that a particular experiment was ‘a mere commercial decision’ and ‘a matter of business judgment’, does not justify lack of inventive step. Biogen also highlighted the difference in approaches between the EPO and the House of Lords as to the validity of patents in the current patent laws.