4.0 THE PATENT
25 The Patent is entitled "Pyrazolopyrimidinones for the Treatment of Impotence". It begins by identifying its subject matter as relating to "the use of a series of pyrazolo [4,3-d] pyrimidin - 7 - ones for the treatment of impotence" (page 1 lines 3-5). Although reference is made to the use of particular compounds and groups of compounds for the treatment of impotence, the critical claim for the purposes of the present case, claim 10, is, as will be seen, framed differently.
26 The specification then discusses impotence and the prevalence of the condition (page 1 lines 6-18). There is a discussion of the prior art and methods of treatment (page 1 line 19 to page 2 line 9). It is then said (page 2 lines 10-33):
"The compounds of the invention are potent inhibitors of cyclic guanosine 3',5'-monophosphate phosphodiesterases (cGMP PDEs) in contrast
to their inhibition of cyclic adenosine 3',5'-monophosphate phosphodiesterases (cAMP PDEs). This selective enzyme inhibition leads to elevated cGMP levels which, in turn, provides the basis for the utilities already disclosed for the said compounds in EP-A-0463756 and EP-A-0526004, namely in the treatment of stable, unstable and variant (Prinzmetal) angina, hypertension, pulmonary hypertension, congestive heart failure, atherosclerosis, conditions of reduced blood vessel patency e.g. post-percutaneous transluminal coronary angioplasty (post-PTCA), peripheral vascular diseases, stroke, bronchitis, allergic asthma, chronic asthma, allergic rhinitis, glaucoma, and diseases characterised by disorders of gut motility, e.g. irritable bowel syndrome (IBS).
Unexpectedly, it has now been found that these disclosed compounds are useful in the treatment of erectile dysfunction. Furthermore the compounds may be administered orally, thereby obviating the disadvantages associated with i.c. administration. Thus the present invention concerns the use of a compound of formula (I)"
The earlier disclosures referred to are two European patent applications made by Pfizer. In
the present case they have been designated Bell I and Bell II. The structure of "a compound of formula (I)" is then set out and the specification continues (page 4 lines 20-24):
"or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the curative or prophylactic treatment of erectile dysfunction in a male animal, including man."
The words underlined (including the word "Unexpectedly" above) were added by amendment on 13 May 1994 (PCT application). By reason of the numerous permissible permutations and combinations, the number of compounds which might fall within formula (I) is of astronomic proportions.
27 After a discussion of various aspects of the formula (I) compounds there is a discussion at page 5 lines 7-16 of the salts of formula (I) in these terms (this passage was also added on 13 May 1994):
"The pharmaceutically acceptable salts of the compounds of formula (I) which contain a basic centre are, for example, non-toxic acid addition salts formed with inorganic acids such as hydrochloric, hydrobromic, sulphuric and phosphoric acid, with organo-carboxylic acids, or with organo-sulphonic acids. Compounds of formula (I) can also provide pharmaceutically acceptable metal salts, in particular non-toxic alkali metal salts, with bases. Examples include the sodium and potassium salts."
28 The specification then goes on to identify subsets of the compounds of formula (I). Each is smaller but more desirable than its predecessor. There is a "preferred group of compounds", a "more preferred group", a "particularly preferred group" and "especially preferred individual compounds". The last group is said to "include" nine compounds, one of which is a compound known as sildenafil. The citrate salt of that compound, sildenafil monocitrate, is the active ingredient of Viagra.However sildenafil monocitrate itself is not one of the nine "especially preferred" compounds identified.
29 The specification then states (page 7 lines 22-28) that the compounds of formula (I), and their pharmaceutically acceptable salts, processes for their preparation, in vitro test methods for determining their cGMP and cAMP inhibitory activities, pharmaceutical compositions of them and routes for their administration for human use are described in Bell I and Bell II.
30 Commencing on page 7 line 29 there is a discussion of a "preliminary investigation" carried out to isolate and characterise the cyclic nucleotide PDEs of the human corpus cavernosum. It is said at page 9 line 23 that the investigation identified three PDE isoenzymes. The cGMP-specific PDEVis said to be predominant. However PDEII and PDEIII are also present. In discussing the results of the investigations it is said (page 9 lines 7-8) that the first fraction "was found to be insensitive to stimulation by calcium/calmodulin". Pfizer says that the skilled reader would understand by this that PDEI was not present.
31 On page 9 line 28 it is said:
"The compounds of the invention have been tested in vitro [emphasis in original] and found to be potent and selective inhibitors of the cGMP-specific PDEV."
The specification then gives an example of what is meant by this potent and selective inhibition, saying that "one of the especially preferred compounds of the invention" (although the compound is not identified) strongly inhibits PDEVbut "demonstrates only weak inhibitory activity" against PDEII and PDEIII. It is then said (page 9 line 35):
"Thus relaxation of the corpus cavernosum tissue and consequent penile erection is presumably mediated by elevation of cGMP levels in the said tissue, by virtue of the PDE inhibitory profile of the compounds of the invention."
32 At page 10 line 5 the specification discusses toxicity testing of some of the compounds of the invention in rat, dog and mouse. The compounds are not identified.
33 At page 10 line 13 there is reported oral administration to volunteers of "certain especially preferred compounds" in both single dose and multiple dose studies. It is stated that these studies have confirmed that "one of the especially preferred compounds induces penile erection in impotent males". Again, the compounds are not identified.
34 The matters discussed in [30]-[33] above were added to the Patent on 13 May 1994.
35 At page 10 line 25 it is said that oral administration of "the compounds of the invention is the preferred route being the most convenient and avoiding the disadvantages associated with i.c. administration" and that a preferred dosing regimen for a typical male is 5mg-75mg of compound three times daily.
36 From page 11 line 4 to page 12 line 5 there is what is, arguably at least, a consistory clause. It is made up of six components.
37 First, it is said the invention
"… includes a pharmaceutical composition for the curative or prophylactic treatment of erectile dysfunction in a male animal, including man, comprising a compound of formula (I), or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable diluent or carrier".
38 Secondly, there is "further provided" a process for preparing such a composition.
39 The first and second components were added on 13 May 1994.
40 Thirdly, the invention
"… also provides a method of treating a male animal, including man, to cure or prevent erectile dysfunction which comprises treatment with an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable composition containing either entity".
41 Fourthly, it is said that "in a further aspect" the invention
" …includes the use of a cGMP PDE inhibitor, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the oral treatment of erectile dysfunction in a male animal, including man` in man."
This is the first mention in the Patent of a substance other than the "compounds of the invention" or "the compounds of formula (I)". The words underlined were added on 13 May 1994. The words double underlined were added on 4 April 1995 (PCT application amendments) and on the same date the words struck out were deleted.
42 Fifthly, it is said the invention
"…also includes a method of orally treating a male animal including man, to cure or prevent erectile dysfunction, which comprises treating said male animal with an effective amount of a cGMP inhibitor treatment with an orally effective amount of a cGMP inhibitor, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity."
The dates of addition and deletion are as previously indicated.
43 Sixthly, it is said the invention
"…includes the use of a cGMP PDE inhibitor, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity, for the manufacture of a medicament for the curative or prophylactic oral treatment of erectile dysfunction in a male animal, including man."
The dates of addition and deletion are as previously indicated.
44 Claim 1, commencing on page 13 line 2, is as follows:
"A method of treating a male animal requiring such treatment, including man, to cure or prevent erectile dysfunction which comprises treating said male animal with an effective amount of a compound of formula (I) wherein:…"
These words in their present form were added on 3 October 1996 (Australian national phase amendments in response to the Examiner's report). There follow chemical formulae which were added on 13 May 1994.
45 Claims 2, 3 and 4 narrow claim 1 by limiting various groups of formula (I). Claim 5 specifies nine particular compounds. These are the "especially preferred individual compounds" already referred to. The formulae in claims 2 to 5 were added on 13 May 1994.
46 Claims 6, 7 and 8 each specify one particular compound of formula (I). Claim 7 specifies the freebase known as sildenafil and claim 8 specifies sildenafil monocitrate. As already mentioned, it is the active ingredient of Viagra. Sildenafil has previously been claimed in the patent granted on the Bell I application. In each of claims 2 to 8 the claim is for "The method according to" the previous claim, the words "The method" having been added on 3 October 1996.
47 Claims 6, 7 and 8 were added on 6 January 1997 (Australian national phase amendments in response to the Examiner's report).
48 Claim 10 is critical for the present case since the allegedly infringing product of Lilly (Cialis), does not contain any of the compounds of the earlier claims.
49 Claim 10 takes its present form from an amendment which I ordered, on the application of Pfizer, on 19 September 2003: Eli Lilly and Company v Pfizer Research and Development Company [2003] FCA 988.
50 Prior that amendment claims 9 and 10 read as follows:
"9. A method of orally treating man to cure or prevent erectile dysfunction in man in need of such treatment, which comprises treatment with an orally effective amount of a cGMP PDE inhibitor, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity.
10. The method according to claim 9 wherein the inhibitor is cGMP PDEVinhibitor."
51 The amendment deleted claim 9 and altered claim 10 so that it read:
"10. A method of orally treating man to cure or prevent erectile dysfunction in man in need of such treatment, which comprises treatment with an orally effective amount of cGMP PDEVinhibitor, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing either entity."
There follow seven further claims but they are not relevant for the present case.