Genelabs Diagnostics Pte Ltd v Institut Pasteur and Another

• Jurisdiction: Singapore
• Judge: Chao Hick Tin JA
• Judgment Date: 02 November 2000
• Neutral Citation: [2000] SGCA 60
• Docket Number: Civil Appeal No 14 of 2000
• Date: 02 November 2000
• Published date: 19 September 2003
• Year: 2000
• Plaintiff Counsel: Tan Tee Jim SC and Jason Chan (Allen & Gledhill)
• Citation: [2000] SGCA 60
• Defendant Counsel: Tony Yeo, Gerald Koh and Celeste Ang (Drew & Napier)
• Court: Court of Appeal (Singapore)
• Subject Matter: Whether specification enabled invention to be understood and carried into effect by person skilled in art,s 80(1)(c) Patents Act (Cap 221),Whether party stood by as to induce another to commit the act,Acquiescence,Infringement,ss 13(1), 14(1 & 14(2) Patents Act (Cap 221),Whether insufficient disclosure because immuno-reactive portions of amino acid sequence not revealed,Inventive step,State of art at priority date from mantle of person skilled in art,s 15 Patents Act (Cap 221),Novelty,Whether prior art disclosed existence of HIV-2,Equity,Patents and Inventions,Whether process used by test kit entailed process which fell within claim of patent,Defences,Whether prior art documents should be read collectively or individually,Whether relevant claims of patent infringed -Whether addition of five amino acids in test kit to 18mer a material difference,Whether trial judge had sufficient regard to state of art,Whether there was change of position in reliance on acquiescence,Whether prior art anticipated invention,Sufficiency of disclosure

(delivering the judgment of the court): This is an appeal against the decision of Tay Yong Kwang JC where he held that the respondents` patent in respect of, inter alia, the Human Immunodeficiency Virus-2 (`HIV-2`) and an antigen of HIV-2 of a stated amino acid sequence, is valid, and that the appellants had infringed that patent when they manufactured and sold their diagnostic kits for the HIV-2.

The facts

The first respondents are a private, non-profit making foundation in France. They are the proprietor of European patent No 0239425, which covers, inter alia, the HIV-2, a retrovirus capable of causing acquired immune deficiency syndrome (`AIDS`) in man. The patent relates to a discovery made by Professor Luc Montagnier and his team at the premises of the first respondents in 1986. The European patent application was filed on 22 January 1987 and granted on 2 November 1989, and claims priority from its French application, which was filed on 22 January 1986 (`the priority date`).

One of the countries designated in the European Patents Office (`EPO`) filing was the United Kingdom. The patent was subsequently re-registered in Singapore under the Registration of United Kingdom Patents Act on 15 January 1993 under No 9190285-8.

The claims of the patent cover the following aspects:

Claims 1 to 9	-	the HIV-2 and variants thereof;
Claims 10 to 19	-	the antigens of HIV-2;
Claims 20 to 32	-	the compositions for the in vitro detections of HIV-2 antibodies;
Claims 33 to 37	-	the processes for the in vitro detection of, inter alia, HIV-2 antibodies;
Claims 38 to 40	-	diagnostic kits for the in vitro detection of inter alia, HIV-2 antibodies.

The second respondents are a company incorporated in France. The first and second respondents entered into a collaboration agreement on 26 March 1981, which was renewed on 11 July 1990 (`collaboration agreement`). Under the terms of the collaboration agreement, the second respondents are the exclusive licensee of the first respondents` patent.

The appellants are a local subsidiary of an American biopharmaceutical company, Genelabs Technology Inc. They make and sell, inter alia, diagnostic kits that utilise a laboratory technique known as Western Blot to detect HIV-2. Their kits are known as `Genelabs Diagnostics HIV-2 Western Blot 1.2` (`Blot 1.2`) and `Genelabs Diagnostics HIV-2 Western Blot 2.2` (`Blot 2.2`).

The Western Blot is a variation of a procedure devised in the 1970s to detect deoxyribonucleic acid (`DNA`) fragments, known as Southern Blot. When the technique was adapted to detect ribonucleic acid (`RNA`) fragments, it was called Northern Blot. When the technique was subsequently adapted to detect proteins, it was termed Western Blot.

In a Western Blot analysis, HIV proteins are separated by a standard laboratory technique known as gel electrophoresis. This technique makes use of an electric current to separate the proteins. The smaller proteins would move through the gel faster than the larger proteins, thereby allowing for separation according to size. The separated proteins, such as gp41 and gp120, are then transferred to a strip of special nitrocellulose paper paper by blotting the paper to the gel. Each nitrocellulose strip would thus contained several discrete proteins of HIV.

The testing process operates on the principle of antigen-antibody reaction. In very basic terms, antibodies are formed and released by the body in response to the introduction of antigens into the body. An antigen is a substance foreign to the body that stimulates the production of antibodies. The antibody is a protein created to neutralise the harmful effects of the antigen. It is highly specific for the antigen that elicited its production and will interact only with that antigen.

During testing, serum from a patient is applied directly to the antigenic protein bands located on the nitrocellulose strips. If antibodies are present in the serum, they will bind to their complementary antigenic determinant, forming an immunological conjugate, also called immunological complex. Thus, a HIV gp120 antibody would bind to the HIV gp120 antigenic determinant. A colouring agent is used to detect if an antibody has complexed with any of the banded HIV antigenic proteins located on the nitrocellulose strip. The presence of such colour reaction would indicate that the patient has HIV.

Evidence was led that in about 1996, the respondents became aware that HIV-2 test kits were manufactured and sold by the appellants. In April 1998, the respondents carried out investigations that culminated in trap purchases of the appellants` Blot 1.2 and Blot 2.2 diagnostic kits in July 1998. After testing the diagnostic kits for possible infringement of the patent, the respondents decided to commence action against the appellants, asserting that Blot 1.2 infringed claims 12, 13, 20, 22, 24, 33, 34, 35, 38 and 39 of the patent and that Blot 2.2 infringed claims 19, 20, 33, 34, 35, 38 and 39 of the patent.

In defence, the appellants contended that the patent was not valid. They centred their defence on the lack of novelty and inventive steps in claims 19 and 33. These claims cover:

Claim 19

Antigens having the following amino acid sequence or a part of said sequence, providing that it raises a specific immunological reaction with the antibodies against a HIV-2 retrovirus, according to any one of claims 1 to 9, especially when this antigen is contacted with the serum of a patient infected with HIV-2 ...

Claim 33

Process for the in vitro detection of the presence of antibodies, induced in man infected with a human HIV-2 retrovirus, in a human biological sample such as a serum and more particularly for the in vitro diagnosis of a potential or existing LAS or AIDS due to such a retrovirus and obtained from the person being diagnosed, characterised in that this biological sample is contacted with an antigen recognised by an antibody induced in the infected man, by a human HIV-2 retrovirus as defined in claims 1 to 9 in conditions authorising the formation of an immunological complex between this antigen and the said antibody and in that the possibly immunological conjugate formed between this antibody and antigen used is detected.

The appellants also argued that there was insufficient disclosure in the patent and that the defence of acquiescence applied by virtue of the respondents` unreasonable delay in pursuing relief.

Decision below

The trial judge held that the patent is valid. He found that there was novelty in claim 19 of the patent, as the prior art documents, either individually or collectively, did not clearly and unmistakeably disclose any antigen having the amino sequence or part thereof described in claim 19. It was not logical to suggest that the prior art revealed the function of detecting a virus which was then unknown. Claim 33 is concerned with the process to detect the new virus. It would follow that the process is new when it provides the means to detect a new virus.

The trial judge found that the inventive step requirement was satisfied in respect of claim 19 as it was not obvious to invent an antigen with the specified sequence to detect an as yet unknown virus. The inventiveness manifested in claim 33 was in the recognition that a new virus was responsible for causing AIDS in West Africa and providing the means to detect it by using an antigen.

The trial judge also found that the appellants` diagnostic kits infringed the claims of the patent as the sequence of 18 amino acids (`18mer`) used by the appellants in their diagnostic kits was a highly immuno-reactive portion of the amino acid sequence set out in claim 19, and while the diagnostic kits also used five other amino acids, the latter did not alter the immuno-reactive character of the 18mer but served only as a fixing and stabilising agent for the 18mer on the nitrocellulose strip.

Issues

Before us the appellants canvassed the same issues which were raised in the court below, namely:

(i) were the inventions, as disclosed in claim 19 and 33 of the patent, novel;

(ii) did the inventions, as disclosed in claim 19 and 33 of the patent, involve any inventive steps;

(iii) was there sufficient disclosure in claims 19 and 33;

(iv) did the production/sale of the diagnostic kits by the appellants infringe the patent;

(v) was there any delay/acquiescence on the part of the respondents in commencing proceedings against the appellants;

(vi) as the collaboration agreement between the respondents was not registered at the commencement of the action, is the second respondent precluded from recovering damages or seeking an account of profits in view of s 75 of the Patents Act 1994 (hereinafter referred to as `the Act` or `the 1994 Act` as may be appropriate in the context).

From the appellants` case, it is quite clear that the first two issues are their main contentions. Nevertheless, we will consider each of the issues in turn.

Novelty

Under s 13(1) of the Act an invention, to be patentable, must satisfy the following conditions:

(i) the invention is new;

(ii) it involves an inventive step; and

(iii) it is capable of industrial application.

In relation to the present case, it is not in dispute that condition (iii) is satisfied. It is in relation to the first and second conditions that the present case turns.

Section 14(1) of the Act provides that an invention shall be taken to be new if it does not form part of the state of the art. Subsection (2) elaborates on the concept of the `state of the art` as follows:

The state of the art in the case of an invention shall be taken to comprise all matter (whether a product, a process, information about either, or anything else) which has at any time before the priority date of that invention been made available to the public (whether in Singapore or elsewhere) by written or oral description, by use or

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