Sime Darby Singapore Ltd and Another v Beecham Group Ltd

• Judge: Tan Ah Tah FJ
• Judgment Date: 10 August 1968
• Neutral Citation: [1968] SGFC 9
• Citation: [1968] SGFC 9
• Defendant Counsel: JP Graham QC and AC Ferguson (Drew & Napier)
• Published date: 19 September 2003
• Date: 10 August 1968
• Docket Number: Civil Appeal No Y55 of 1967
• Court: Federal Court (Singapore)
• Plaintiff Counsel: RK Fullagar QC and AP Godwin (Donaldson & Burkinshaw)

The High Court of Singapore granted an interlocutory injunction against both defendants restraining them until judgment in the action from advertising, offering for sale, selling or supplying the antibiotic hetacillin or any preparation containing the same or otherwise infringing either or both of the plaintiffs` United Kingdom Letters Patent No 870395 and No 873049 which have been registered in Singapore under the provisions of the Registration of United Kingdom Patents Ordinance under Number 99 of 1965 and Number 34 of 1962 respectively.

The defendants now appeal against this decision. The first defendants are Sime Darby Singapore Ltd (hereinafter referred to as Sime Darby), a Singapore company who have imported into and sold in Singapore the antibiotic hetacillin. The second defendants an Bristol-Myers Co (hereinafter referred to as Bristol), an American corporation incorporated in Delaware, who manufactured the hetacillin imported into Singapore by Sime Darby.

The plaintiffs, Beecham Group Ltd (hereinafter referred to as Beecham), in 1957, through their research chemists, succeeded in isolating the penicillin nucleus, 6-aminopenicillanic acid, (hereinafter referred to as 6-APA). This achievement has been universally accepted as a fundamental break-through in antibiotic research and has opened the way to the making of a whole series of new penicillins which are conventionally known as semi-synthetic penicillins and which are formed by the addition to the nucleus of what is known to organic chemists as `side-chains`.

One such semi-synthetic penicillin which Beecham discovered is generally known as ampicillin which Beecham manufacture and sell under the trade name `Penbritin`. The processes by which ampicillin is manufactured and the product itself are protected by inter aliathe two Beecham`s patents No 870395 and No 873049 which patents have been registered in the United Kingdom, the United States of America, Singapore and many other countries.

It is common ground that following on Beecham`s discovery of ampicillin, which has earned world-wide acceptance as being effective against both Gram-positive and Gram-negative organisms over a broad spectrum, Bristol were licensed, under a licence agreement and a supplemental licence agreement, to manufacture and sell ampicillin in the United States of America and Canada. It is also not in dispute that Bristol in the course of research by their chemists in the preparation and methods of manufacture of ampicillin discovered the substance hetacillin and that it has a different chemical structure to ampicillin. It is however not in dispute or at any rate in our opinion clear beyond doubt that hetacillin is a derivative of 6-APA. One method of its preparation being the reaction of acetone with ampicillin and another method consisting in treating 6-APA in aqueous acetone at a pH between 2.5 and 3 with the acylating agent, D-alpha-aminophenylacetyl chloride hydrochloride and then adjusting the pH to 7.5 with triethylamine, an alkaline, and storing the solution at 5-10[deg ]C for 20 hours.

Beecham claim that hetacillin is in substance the equivalent of ampicillin and they also claim that hetacillin is manufactured by the use of their patented process as to amount to an infringement of both their patents.

More specifically Beecham say that as hetacillin is in substance the medical equivalent of ampicillin there is infringement of claims 1, 2, 3, 5 and 20 of Patent No 873049, which are product claims, by the sale of hetacillin in Singapore. Beecham also say, that having regard to what is generally known as the Saccharine [1901] 1 Ch 414 principle, there is infringement of the same five product claims 1, 2, 3, 5 and 20 of Patent No 873049 by the importation and sale in Singapore of hetacillin.

With regard to their process claims, Beecham say that on the Saccharine principle, there is infringement of claim 1 of Patent No 870395 and claim 12 of Patent No 873049 by the importation and sale in Singapore of the product, hetacillin, because in the course of the process of making hetacillin, ampicillin plays an important part or, to put it another way, hetacillin is made by a process which is almost identical, except for an addition which is of no real value or significance medically, with the process for making ampicillin.

We will first deal with the process claims. Claim 1 of Patent No 870395 reads as follows:

A process for the preparation of 6-acyl-amino derivatives of penicillanic acid in which 6-aminopenicillanic acid ... or a salt thereof, is reacted with a carboxylic acid chloride or bromide, a sulphonic acid chloride, an ester or chlorocarbonic acid, and acid anhydride of a carboxylic acid or a mixed acid anhydride derived from a carboxylic acid.

Claim 12 of Patent No 873049 reads as follows:

The process for the preparation of penicillin derivatives ... which comprises coupling 6-aminopenicillanic acid with an acid of the general formula XOH having its amino group ... protected, or a salt thereof, and thereafter removing the protecting group ... under sufficiently mild conditions to avoid destruction of the penicillin nucleus.

Claim 1 of Patent No 870395 is a general claim to a process for the preparation of 6-acyl amino derivatives of penicillanic acid whereby 6-APA is reacted with a carboxylic acid chloride and this claim protects the process by which ampicillin is manufactured. The full chemical name of ampicillin is alpha-aminobenzyl-penicillin and ampicillin is the product of the reaction of 6-APA with alpha-aminophenylacetyl chloride, which is the chloride salt of alpha-aminophenylacetic acid. In terms of chemistry, amninophenylacetic acid is a carboxylic acid.

In the commercial manufacture of hetacillin the method used by Bristol is described by Mr Sadoff, one of Bristol`s chemists, thus:

6-aminopenicillanic acid (6-APA) is dissolved in water and a large quantity of acetone. The solution is then cooled, made acidic by addition of hydrochloric acid, after which D(-)-2-aminophenylacetyl chloride hydrochloride is added in small portions with concomitant addition of aqueous sodium hydroxide to maintain the solution at the desired acidity. These steps lead to the formation (by reaction of molecules of 6-aminopenicillanic acid with molecules of D(-)2-aminophenylacetyl chloride hydrochloride) of the hydrochloride salt of D(-)-alpha-aminobenzylpenicillin as one of the solute constituents of the solution ...

From this description it is clear that Bristol`s manufacturing process starts with 6-APA which is reacted with aminophenylacetyl chloride hydrochloride. The first chemical reaction admittedly then is the reaction of 6-APA with a carboxylic acid chloride and therefore uses the process protected by claim 1 of Patent No 870395.

Claim 12 of Patent No 873049 is a claim to the process for the preparation of penicillin derivatives of the general formula: where X is an amino-substituted acyl group containing up to 20 carbon atoms and having the formula:

R (CH 2)n CH. CO -

NH2

where R is hydrogen or an amino carboxyl or substituted or unsubstituted aklyl, aryl, aralkyl or heterocyclic group and N is zero or an integer, and non-toxic salts thereof, which comprises coupling 6-APA with an acid of the general formula XOH having its amino group or groups protected, or a salt thereof, and thereafter removing the protecting group or groups under sufficiently mild conditions to avoid destruction of the penicillin nucleus.

Without going into the detailed chemistry in relation to claim 12, the evidence before us shows that Bristol coupled 6-APA with the salt of an acid having the general formula XOH where X is...