Merck & Co., Inc. v Bernard Charles Sherman - [2007] APO 9

ABSTRACTS OF DECISIONS
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 697696 in the name of Bernard Charles Sherman

Title: Stable solid formulation of enalapril salt and process for preparation thereof

Action: Opposition to the grant of a patent by Merck & Co., Inc.

Decision: Issued 01 March 2007.
Abstract

The opposition succeeds on all grounds.
a)Novelty: The citation discloses a tablet that is coated with a polymer. The tablet prior to coating with the polymer is produced by a process that falls squarely within the scope of claim 1.
b)Inventive step: In order to solve the problem of the present application, all that is necessary is to follow the teaching of the citation.
c)Entitlement: The evidence shows that Dr Sherman learned all of the steps of the process from Merck. Consequently, Dr Sherman is not an inventor. Dr Sherman is a co-inventor of the form of the invention using the alkaline sodium compound dissolved in water.

Application refused.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 697696 by Bernard Charles Sherman, and an opposition to the grant of a patent by Merck & Co., Inc.

BACKGROUND

Patent application 697696 in the name of Bernard Charles Sherman (‘Sherman’) has been opposed by Merck & Co., Inc. (‘Merck’). The matter was heard in Canberra on 4 and 5 December 2006. Dr Sherman was represented by Tony Bannon QC, assisted by Paul Jones and Kirstie Murdoch of Freehills. Merck was represented by Katrina Howard SC, assisted by Shahnaz Irani and Linda Govenlock of Spruson and Ferguson.
The opposition proceeded on the basis of only two grounds of opposition. First, it is alleged that the application lacks novelty and inventive step in the light of WO 94/01093. Second, it is alleged that Dr Sherman lacks entitlement.
A very large body of evidence has been served in this matter. The evidence in support consists of declarations by Paul Anthony Power (two declarations), Peter James Stewart, George Crank, Gregory John Cox and Michael Brian McGuinness. Evidence in answer consists of declarations by Mark Llewellyn Egerton, Zak T Chowhan, Robert A McLelland, Istvan Toth, Philip A Marshall, George A Olah and Robert S Langer. Evidence in reply consists of declarations by George Crank, Peter James Stewart and Michael McGuinness.
Many pieces of further evidence have been served by both parties. Evidence on behalf of the applicant consists of declarations by Robert S Langer, Zak T Chowhan (two declarations), George A Olah, James B Hendrickson, Istvan Toth, Philip Marshall, Robert McLelland, Mark Llewellyn Egerton and Paul William Jones (two declarations). Evidence on behalf of Merck consists of declarations by Paul Anthony Power (two declarations), George Crank (two declarations), Peter James Stewart and Edward W. Murray.
Throughout this decision, a reference to the Jones declaration means the final declaration of Mr Jones, dated 2 November 2006. The letters EWM refer to exhibits to the Murray declaration.
DECISION
1. The specification
The specification relates to the known pharmaceutical enalapril. Enalapril in the form of the maleate salt was used for the treatment of hypertension. However the preparation of stable tablets of enalapril maleate had proved difficult. The specification describes a method for producing stable tablets of enalapril, by converting enalapril maleate to enalapril sodium.
The process described involves wet granulating a composition containing enalapril maleate and an alkaline sodium compound (such as sodium bicarbonate). Enalapril maleate is acidic (it has three acid groups), and water allows the acid to react with the alkaline sodium compound. Dry granulation does not allow the acid base reaction to take place.
2. The claims
Claim 1 is the key claim for the present opposition. The claim reads:
A process of manufacture of a pharmaceutical solid composition comprising enalapril sodium, which process comprises the steps of:
i)a) mixing enalapril maleate with an alkaline sodium compound and at least one other excipient, adding water sufficient to moisten, and mixing to achieve a wet mass, or
b)mixing enalapril maleate with at least one excipient other than an alkaline sodium compound, adding a solution of an alkaline sodium compound in water, sufficient to moisten and mixing to achieve a wet mass;
thereby to achieve an essentially complete reaction without converting the enalapril maleate to a clear solution of enalapril sodium and maleic acid sodium salt in water, and without significant formation of enalaprilat;
ii)drying the wet mass, and
iii)further processing the dried material into tablets.
The key feature of the claim is that enalapril maleate is wet granulated with an alkaline sodium compound (where the sodium compound is either pre-mixed with the enalapril maleate or dissolved in the water).
3. Novelty
The sole citation relied upon is WO 94/01093, referred to as the Rork citation. It is well established that the general test for anticipation is the reverse infringement test. The classic formulation of this test is that given by Aickin J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd (1977) 137 CLR 228, at page 235:
“The basic test for anticipation or want of novelty is the same as that for infringement and generally one can properly ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement”
This test is satisfied if the alleged anticipation discloses all the essential features of the invention as claimed (see Nicaro Holdings Pty Ltd v Martin Engineering Co (1990) 91 ALR 513 at page 517; 16 IPR 545 at page 549). A citation is part of the prior art base for the purposes of novelty if it was published before the priority date of the claim (see definition of "prior art base" in Schedule 1 of the Act).
The essential features of claim 1 are readily identified from the plain words of the claim:
a) wet granulating enalapril maleate and an alkaline sodium compound with water, or wet granulating enalapril maleate with a solution of an alkaline sodium compound;
b) granulating sufficiently to achieve essentially complete reaction without forming a clear solution, and without significant formation of enalaprilat;
c) drying; and
d) forming into tablets.
It is these features that must be found in the citation.
Rork is directed to a controlled release enalapril formulation. The enalapril composition is enclosed within a permeable wall. It is the nature of the enalapril composition that is most relevant to the present opposition. Page 5 of the description states:
“In preparing the granulation of the core composition, about three (3) moles of sodium bicarbonate are added to the granulation for each mole of enalapril when enalapril maleate is utilized. In the presence of the granulating solvent, water, the sodium bicarbonate reacts with the acidic functional groups of the enalapril maleate and carbon dioxide is released.”
Merck particularly drew attention to example 7, which describes the preparation of enalapril maleate tablet cores. It is worth quoting the relevant part of this example in full.
“EXAMPLE 7
Enalapril maleate tablet cores were prepared with dose strengths of 5, 10 and 20 mg per tablet. The range of ingredients is given in Table II.
TABLE II
Range of Ingredients for Enalapril Maleate Cores
Ingredients  mg per Tablet
Enalapril Maleate  5 to 20
Sodium Bicarbonate                2.5 to 10
Lactose  198 to 154
Starch  22.8 to 22
Pregelatinized Starch                5 to 2.2
Iron Oxide Colorants               q.s.
Magnesium Stearate                0.9 to 1.1
Water  q.s.
The ingredients listed above in appropriate batch sizes were mixed in a high intensity mixer except for the magnesium stearate and water. The water was added at 85°C with mixing at a spray rate sufficient to add all the water in 1 to 1.5 minutes. The material was then mixed for 4 minutes. The material was then discharged into a fluidised bed dryer and dried at 50°C until the moisture content was less than 1%.”
It is clear that the process used involves the mixing of enalapril maleate and sodium bicarbonate, with the subsequent addition of water. There is no reference to alkaline sodium compounds other than sodium bicarbonate. What is not apparent is whether an essentially complete reaction of enalapril maleate to enalapril sodium takes place. The amount of bicarbonate used gives an enalapril:bicarbonate weight ratio of 2:1. Taking account of their different molecular weights, a weight ratio of enalapril:bicarbonate of 2:1 will give a mole ratio of 1:3. Clearly the quantity of bicarbonate used is capable of achieving a complete reaction if the wet granulation is carried out appropriately. The passage on page 5 of Rork makes it clear that it is intended that the acid-base reaction take place. The only sensible construction of Example 7 is that it is carried out in a way that enables the acid-base reaction to take place, and this is presumably why the water is heated to 85°C. The next question is whether the Rork document involves the production of a clear solution, and whether it results in the significant formation of enalaprilat. The material produced in Rork is dried on a fluidised bed dryer. A fluidised bed suspends solid material using jets of air, necessitating the production of a damp mass rather than a solution.
The next question is whether the Rork process proceeds without significant formation of enalaprilat. I can find no reference to the formation of enalaprilat in Rork. I note that the opposed application does not mention enalaprilat formation as a problem with the prior art. None of the examples refer to the amount of enalaprilat in the product, it being presumed that enalaprilat is not present. It seems fair to conclude that enalaprilat is not normally produced, and in the absence of evidence to the contrary it can be safely presumed it is not present in the Rork product.
Example 7 goes on to state that the material is compressed into tablets. These tablets are then coated with a rate controlling polymer coating to produce an osmotic pump. I conclude that Rork discloses a process involving all of the essential features of the present claim 1. The tablets prior to coating with the polymer are produced by a process that falls squarely within the scope of claim 1. Consequently claim 1 is not novel in the light of Rork. Turning to the other claims, I consider that the additional features in the other claims are also disclosed by Example 7. Consequently, all claims are not novel.
Claim 1 also includes the option of granulating enalapril maleate with a solution of an alkaline sodium compound. I can find no mention of this aspect in the Rork document.
4. Inventive step
It is also asserted that the invention lacks inventive step in the light of the Rork document. The test for inventive step is laid out in section 7(2): an invention is taken to involve an inventive step unless it would have been obvious to a person skilled in the art. The relevant prior art is the common general knowledge, considered on its own or together with information in a document that could reasonably have been expected to be ascertained, understood and regarded as relevant.
The normal approach to obviousness is the problem-solution approach. Once the problem has been formulated, and the common general knowledge and the prior art base have been determined, the question of whether the claimed solution is obvious must be addressed. The test for obviousness is whether it would have been a matter of routine to proceed to the claimed invention.
“The test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have led from the prior art to the invention, whether they be the steps of the inventor or not.”
[Wellcome Foundation Ltd v V.R. Laboratories (Aust.) Pty Ltd (1981) 148 CLR 262 286]
The problem in the present case is the production of a stable enalapril formulation. The citation is directed to an osmotic pump containing enalapril. An osmotic pump is a controlled delivery means for the enalapril. The enalapril is present as a composition made from enalapril maleate and sodium bicarbonate (plus other ingredients), enclosed within a microporous wall. On the face of it, this document is directed to a different problem, and is not relevant. At page 5 it is stated that the amount of sodium bicarbonate is “sufficient to provide greater than 50% of the drug release zero order and stabilize the enalapril maleate of the core composition”. This is the only portion of the text that I was referred to which indicates that a stabilised enalapril composition is involved. Although the suggestion that Rork deals with stable enalapril compositions is brief, the meaning of the statement is clear. I am satisfied that a skilled person could have reasonably regarded Rork as relevant to the problem. I consider that Rork could reasonably have been ascertained, understood and regarded as relevant to the problem.
In order to solve the problem, all that is required is to follow the teaching of Example 7. Given that nothing more is needed, I am satisfied that this would have been a matter of routine. As noted above, the features of the other claims are also disclosed by Example 7. Consequently, all claims lack inventive step in the light of the citation.
The claims of the present application extend to the use of alkaline sodium compound dissolved in the water used for the wet granulation. This is not disclosed in Rork, and I was not referred to any evidence that this would have been a matter of routine. The written submissions provided by Merck do not refer to this matter. On the basis of the submissions, it has not been established that this aspect of the invention is obvious.
5. Entitlement
The question of entitlement is somewhat moot as a consequence of my findings in relation to novelty and inventive step. However, the parties pressed the issue forcefully, so I will deal with the issue briefly.
It is a ground of opposition to the grant of a patent that the nominated person is “not entitled to a grant of a patent for the invention” (section 59(a)(i)). Merck alleges that Dr Sherman did not invent the invention, but instead obtained the invention from Merck.
A person is entitled to a patent if they are the inventor or a person who derives title from the inventor. This is clear from section 15 of the Patents Act. The contribution to an invention that a person must make in order to be an inventor has been considered in a number of cases. Although these cases focussed on joint inventors, they were necessarily dealing with the notion of what is required to be an inventor. In Row Weeder Pty Ltd v Nielsen (1997) 39 IPR 400, the hearing officer considered a number of decisions on entitlement and concluded:
“a person has entitlement to an invention if that person’s contribution, either solely or jointly with others, had a material effect on the final concept of the invention” [at page 405]
In assessing whether a person is an inventor, it is necessary to decide whether they contributed in a material way to the invention. The US decision of Mueller Brass Co v Reading Industries 17 USPQ 361 has often been referred to for guidance in these cases. At page 372 it is stated:
“The exact parameters of what constitutes joint inventorship are quite difficult to define. It is one of the muddiest concepts in the muddy metaphysics of the patent law. On the one hand, it is reasonably clear that a person who merely followed instructions of another in performing experiments is not a co-inventor of the object to which those experiments are directed. To claim inventorship is to claim at least some role in the final conception of that which is sought to be patented. Perhaps one need not be able to point to a specific component as one’s sole idea, but one must be able to say that without his contribution to the final conception, it would have been less - less efficient, less simple, less economical, less something of benefit. This Court has found no case in which co-inventorship status was not deemed in some way, at least presumptively, to have beneficially affected the final concept of the claimed invention, and if such a case exists, it would be so anomalous as to warrant little attention.”
This was reinforced by Crennan J in JMVB Enterprises Pty Ltd v Camoflag Pty Ltd (2005) 67 IPR 68 at [132]:
“Rights in an invention are determined by objectively assessing contributions to the invention, rather than an assessment of the inventiveness of respective contributions. If the final concept of the invention would not have come about without a person's involvement, then that person has entitlement to the invention. One must have regard to the invention as a whole, as well as the component parts and the relationship between the participants.”
If a person learns information from another and merely follows their instruction, they cannot be said to be an inventor. However, if a person is given part of the information necessary to make an invention, and then applies their own endeavours they will be an inventor if their contribution produces a material effect. [Of course, they would likely be a joint inventor and not a sole inventor.] This is the principle that I will apply to decide the present matter.
In assessing whether a contribution produces a material effect, it is necessary to look at the process leading to the invention. The starting point is the state of the art prior to the work of the alleged inventor(s). The end point is the production of the invention as claimed. The contributions made to the process of moving from the starting point to the end point will reveal who are the inventors.
The end point is clear, as it is set out in claim 1 (quoted above). It needs to be borne in mind that the end point is the process of preparing enalapril tablets, and not enalapril tablets per se. There are three aspects to that invention. First, there are the components that are used (i.e. enalapril maleate and an alkaline sodium compound). Second, there is the process for mixing the components (i.e. the use of wet granulation is critical). Third, there is the understanding of why this produces a stable composition (i.e. an acid-base reaction takes place).
A person who receives information as to the components and the process has the invention, and there is no material effect in merely putting the process into practice. On the other hand, a person who receives information about the composition and works out the process for themselves has had a material effect (since a stable composition is not produced without the use of wet granulation). The way in which Dr Sherman is said to have obtained the invention from Merck relates to events during a trial in Canada in 1994 between Merck and Apotex (hereafter referred to as the Canadian trial). Apotex is Dr Sherman’s company, and Dr Sherman attended the Canadian trial. The trial related to Merck’s product called Vasotec, which contains enalapril.
The starting point - prior to the Canadian trial
The situation prior to the Canadian trial is largely not in dispute. The following facts are apparent from the evidence.
a)Merck had been manufacturing the product Vasotec since about 1983. (EWM-14 at page 3)
b)Vasotec is a stable product containing enalapril. (Jones para 16 (b))
c)Dr Sherman wanted to manufacture a stable enalapril product. (Jones para 16 (c))
d)Dr Sherman analysed Vasotec and identified that it contained enalapril and a sodium compound. (Jones para 16 (c))
e)Dr Sherman used dry granulation to make enalapril containing tablets.
f)Dr Sherman was aware of the ingredients in Vasotec as listed in the US Physicians’ Desk Reference: enalapril maleate, lactose, magnesium stearate, starch, iron oxides and other ingredients (Jones para 16 (a)).
g)Dr Sherman prepared tablets from enalapril maleate and sodium bicarbonate using a dry granulation, but the product was not stable (Jones para 13).

It is clear that it was known that a stable enalapril composition could be produced (i.e. the product Vasotec). The way to produce such a stable enalapril composition was not known. Looking specifically at Dr Sherman, he knew that Vasotec contained enalapril maleate, and that there was also a sodium compound present. He was of the view that the sodium compound was not sodium bicarbonate. Dr Sherman routinely used dry granulation to prepare enalapril containing tablets.
Dr Sherman asserts that in 1990 he became aware that Vasotec is made by wet granulation (para 9 of the Declaration of Dr Sherman that appears as Exhibit PWJ-1 of the Jones declaration). He learned this by examining Vasotec tablets:
“In 1990, I made a close inspection of the Vasotec tablets. I noted their uniformity of colour. Based upon this observation and my general knowledge, it was apparent to me that Vasotec tablets were probably made by a wet granulation process.”
What happened during the Canadian trial
During the Canadian trial evidence was given relating to the Vasotec product. The two key pieces of evidence are the Vasotec Product Monograph, and the testimony of Mr McLeod. The Product Monograph states that Vasotec contains sodium bicarbonate. The McLeod testimony includes a reference to the fact that Merck use a wet granulation process. These pieces of information provide the components and the process for Vasotec production.
Before dealing in detail with this evidence, it is necessary to consider a claim of legal professional privilege that was made in relation to some of the evidence of Mr Murray.
Legal professional privilege
The parties are in dispute as to whether one portion of the evidence of Mr Murray should be excluded on the basis of legal professional privilege. The specific evidence relates to comments made by Dr Sherman to Mr Johnston, his counsel, during a recess in the Canadian trial. The comments were overheard by Mr Murray, and are recorded in his declaration.
It is well established that legal professional privilege should be respected by administrative tribunals. It is settled law that privilege applies to confidential communications between a client and their legal advisor, if made for the dominant purpose of advice or use in an existing or anticipated litigation [Halsburys Laws of Australia, 195-7450]. Whether legal professional privilege applies is a question of fact, and as such it must be established by evidence and not merely asserted. In the present case the communication was overheard by Mr Murray, potentially removing the confidentiality of the communication. Dr Sherman has asserted through Mr Jones (para 14 of the Jones declaration, quoted below) that his comment was intended to be confidential. Given the circumstances of a discussion with counsel, that is a reasonable assertion. I am prepared to proceed on the assumption that the communication was intended to be confidential, and that it is still capable of protection by privilege.
The real difficulty in the present case is that the purpose of the communication is not apparent. Mr Jones declared (at para 14)
“I am informed by Dr Sherman that all communications relating to those proceedings between Dr Sherman and his counsel were for the dominant purpose of providing instructions or seeking advice in relation to the conduct of the proceedings and he denies that any such communications were intended to be heard by any other person and were privileged communications and remain so and he objects to any purported disclosure of such communications.”
The words reportedly used by Dr Sherman are surprising: “for the dominant purpose of providing instructions or seeking advice”. This is not the language that would be expected from a lay person, but are the words that appear in legal textbooks. There is no explanation of the facts surrounding the making of the comment, only Dr Sherman’s conclusion. I am concerned that Dr Sherman has merely repeated an expression without fully understanding it. Consequently I must give little weight to Dr Sherman’s reported statement.
The other evidence of the purpose of the communication is the words themselves and the context. The words of Dr Sherman were:
“Now I know how they do it. They use a wet granulation.” … “It must react with the water.”
The words were exchanged between client and counsel, during a trial. To my mind, this raises the likelihood that they were for the purpose of instruction or advice. The words do not clearly illuminate their purpose. The wet granulation was a fact disclosed during the trial, and as such would have been known by Mr Johnston. Dr Sherman goes on to explain why wet granulation is used - “it must react with the water”. In fact, every chemist would know that it is not a reaction with water that is taking place, but rather the water enables the acid and base to react by allowing at least one of them to dissolve. As a consequence, the tablets contain enalapril sodium rather than enalapril maleate. This distinction was a matter that Apotex later tried to introduce in the Canadian trial. Consequently, it is possible that the words overheard by Mr Murray were part of a larger communication for the purpose of advice from Mr Johnston on whether the nature of the enalapril species in Vasotec was important for the trial. Despite the absence of an explanation from Dr Sherman, I am satisfied that legal professional privilege should be accorded to the discussions between Dr Sherman and Mr Johnston. Those comments will not be taken into account in making my decision.
The Vasotec Product Monograph
The evidence shows that the Product Monograph relating to Vasotec was publicly available since October 1992 (EWM-3), which is prior to the Canadian trial. However, Dr Sherman’s evidence is that he first saw the Product Monograph in the courtroom on 30 March 1994 (see the Statement of Facts prepared by Dr Sherman, which appears as EWM-5). I will proceed on the basis that Dr Sherman only became aware of the contents of the Product Monograph on 30 March 1994.
The relevant part of the Product Monograph states:
“In addition to the active ingredient, enalapril maleate, each tablet contains non-medicinal ingredients including iron oxides, lactose, magnesium stearate, sodium bicarbonate and starch.”
Dr Sherman admits that he saw the Product Monograph on 30 March 1994:
“on March 30, 1994, I saw in the courtroom a Product Monograph of Merck Frosst”
Para 10 of the Sherman declaration of 13 July 1998, appearing as Exhibit 1 of the Jones declaration.
Dr Sherman further declares that he thought the information that Vasotec contains sodium bicarbonate was incorrect, based on his previous experiments. However, he quickly came to the view that sodium bicarbonate was used, but that it underwent a reaction [para 13 of the declaration of 13 July 1998]. It is clear that on 30 March 1994 Dr Sherman was aware of the contents of the Product Monograph, including that statement that Vasotec contains sodium bicarbonate. I conclude that Dr Sherman received information about the composition on 30 March 1994.
The McLeod testimony
On March 28 1994 Mr McLeod gave evidence in relation to the process used to prepare Vasotec. A video was shown in the court, showing the basic processing steps and the equipment used. A copy of this video was provided as evidence in the present opposition. The video was shown during the present hearing, and Mr McLeod’s testimony was read while the video was running. Consequently I consider that I have a good understanding of the information that was conveyed by this part of Mr McLeod’s evidence.
The McLeod testimony does not disclose the specific ingredients used in preparing Vasotec, or the amounts. However, it is clear that water is added during granulation, and that the product is subsequently dried. Mr McLeod refers to this step as a wet granulation. A person skilled in the art would have understood that wet granulation was used, although there is no suggestion of the significance of this step. This is the critical piece of process information.
Merck’s allegation that Dr Sherman learned of wet granulation from the McLeod testimony is speculation, as only Dr Sherman knows when he learned about wet granulation. However, the short time period between Mr McLeod’s evidence and Dr Sherman’s breakthrough in using wet granulation to prepare a stable enalapril composition raises the reasonable suspicion that the two are connected. Dr Sherman has not given direct evidence in this matter, but he has given evidence in numerous other actions and I have copies of documents from those actions. It is appropriate for me to consider these documents to assess the truth of Dr Sherman’s contention.
Dr Sherman has stated that he did not become aware of what Mr McLeod said in his testimony until he read Merck’s submission in opposition to his Canadian patent, which was no earlier than 1997. Instead, Dr Sherman has asserted that he became aware of the wet granulation process in 1990 by studying the uniformity of colour of the tablets (paragraph 9 of the Sherman declaration of 13 July 1998, appearing as Exhibit 1 of the Jones declaration). However, Dr Sherman also declares that analysis cannot reveal how a tablet is made:
“As to processing steps used by Merck, not only was it not known to me what steps Merck used, but there was no way to determine what the steps were by analysis of the tablets. That is to say, analysis can show only what is in the tablets and not what the steps were that caused it to be there.”
(paragraph 15 of the Sherman declaration of 13 July 1998, appearing as Exhibit 1 of the Jones declaration)
On the one hand Dr Sherman says that he could determine that wet granulation was used by simple inspection of the tablets. On the other hand he says that the processing steps were not known to him and could not have been determined. On the face of it, these statements are inconsistent, and Dr Sherman has not provided an explanation of the inconsistency. In addition, Dr Sherman used dry granulation when attempting to replicate the Vasotec product. This in itself seems inconsistent with the assertion that he knew Vasotec was prepared by wet granulation.
If Dr Sherman was aware in 1990 that Merck used wet granulation, then when he read the Product Monograph on 30 March he had all the information necessary to prepare a stable enalapril composition. This is made clear in the Statement of Facts appearing as Exhibit 5 of the Murray declaration (under a covering letter dated 8 April 1994), where Dr Sherman states:
“5. On March 30, 1994, when I saw that the Product Monograph purported that Vasotec tablets contain enalapril maleate and sodium bicarbonate, I immediately recognised that what was purported could not be correct, as it contradicted my findings that sodium bicarbonate would decrease and not increase the stability.
6. As I know that Vasotec tablets are made by a wet granulation process, it immediately occurred to me that there was only one plausible explanation. That explanation is that the enalapril maleate and sodium bicarbonate used by Merck react with each other in the wet granulation process, so that the final product does not contain enalapril maleate plus sodium bicarbonate.”
However, Dr Sherman has elsewhere declared that in 1990 he did not reach this conclusion:
“In 1990, I made a close inspection of the Vasotec tablets. I noted their uniformity of colour. Based on this observation and my general knowledge, it was apparent to me that Vasotec tablets were probably made by a wet granulation process. However, it did not then occur to me that, if the combination of enalapril maleate, sodium bicarbonate, lactose and other inert ingredients were subjected to a wet granulating process, the result would be a tablet containing, as the active ingredient, enalapril sodium, a more stable compound than enalapril maleate.”
(Sherman declaration of 13 July 1998, appearing as Exhibit 1 of the Jones declaration)
Dr Sherman asserts that in 1994 he was already aware that Merck used a wet granulation process, and on 30 March 1994 (but not in 1990) it immediately occurred to him that an acid-base reaction took place. It is surprising that he should tell Mr Murray that the information in the Product Monograph was wrong, given that he alleges he immediately grasped the only plausible explanation. Either Dr Sherman was playing his cards close to his chest, or he had not yet realised the only plausible explanation. In the passage of the Jones declaration quoted earlier, Dr Sherman stated that when he spoke to Mr Murray he believed the product monograph was not correct.
Did Dr Sherman immediately recognise the acid-base reaction upon reading the Product Monograph? Dr Sherman’s evidence is inconsistent on this point. It seems more likely that Dr Sherman did not immediately grasp that an acid-base reaction took place, and what he told Mr Murray was true. It follows that Dr Sherman had either forgotten, or had never known, that Merck use a wet granulation process. By some time on 30 or 31 March 1994 Dr Sherman had come to the conclusion that wet granulation was used, and that enalapril maleate was converted to enalapril sodium [para 14 of the declaration dated 13 July 1998, appearing as Exhibit PWJ-1 of the Jones declaration]. Something must have happened to remind him about the wet granulation, or something happened that disclosed it to him.
I am deeply concerned by the multiple inconsistencies in Dr Sherman’s evidence on these critical matters. Additionally, there is a lack of evidence from Dr Sherman about how he alleges the invention occurred to him.
It was suggested that an inference can be drawn from Dr Sherman’s failure to give evidence in the present opposition. It is certainly unexpected that Dr Sherman has not made a declaration. However, the details of the ground of lack of entitlement only became apparent when the Murray declaration was filed in July 2006. The filing of key evidence at such a late stage places an applicant at a severe disadvantage. I accept that Dr Sherman has many responsibilities, which may have made it difficult for him to make a declaration. However, the importance of his evidence would have been obvious to all, and it is expected that it will be produced (for instance, see Somnomed Ltd v Mehta (2005) 67 IPR 422). Dr Sherman has taken the second best option, and communicated with Mr Jones, who fortunately had time to make a declaration. In an age of fax machines and emails, I would have thought that Dr Sherman would have been able to make a short declaration of the facts he conveyed to Mr Jones. The lamentable way in which Merck’s evidence has been presented does not mean that Dr Sherman’s behaviour should be assessed more leniently. I believe it is open to me to draw an adverse inference from Dr Sherman’s failure to give evidence, but I can reach a conclusion without doing so.
The inconsistencies in Dr Sherman’s evidence compel me to place little weight on his evidence of how he learned of the use of wet granulation. The fact that Dr Sherman did not utilise wet granulation in 1990, even though he states he was aware at that time that Vasotec was prepared by wet granulation, seems unbelievable in the absence of explanation. In view of the remarkably short time period between Mr McLeod’s evidence and Dr Sherman’s breakthrough in using wet granulation to prepare a stable enalapril composition, I consider that it is more likely that Dr Sherman learned of wet granulation from the McLeod testimony (either directly from the transcript or indirectly reported by a third person).
Dr Sherman’s contribution
I have determined that Dr Sherman learned both the composition of Vasotec and the method of preparing Vasotec during the Canadian trial. The contribution of Dr Sherman was to confirm that the wet granulation of a mixture of enalapril maleate and sodium bicarbonate produces a stable formulation. Mere confirmation does not have a material effect on the final concept of the invention. It follows that Dr Sherman is not an inventor of this process.
I note that the claims of the present application extend to wet granulation in which an alkaline sodium compound is dissolved in the water rather than included in the dry mix. This form of the invention was not disclosed during the Canadian trial. I conclude that this form of the invention arose from the contribution of Dr Sherman. However, Dr Sherman’s contribution was on top of the information provided by Merck. It follows that Dr Sherman is a co-inventor with Merck.
6. Conclusion
The opposition succeeds on the ground of lack of novelty and lack of inventive step with regard to all claims. The opposition also succeeds on the ground of lack of entitlement in relation to all aspects of the claimed invention. Since the opposition succeeds with respect to all aspects of the invention, it is not possible to overcome these defects by amendment. Consequently, I refuse the application.
7. Costs
The opponent has been successful with regard to all of the claims. It is appropriate for costs to follow the event. I award costs against Dr Sherman.
Dr S.D.Barker
Delegate of the Commissioner of Patents
01 March 2007
Patent attorneys for the applicant : Freehills
Patent attorneys for the opponent : Spruson and Ferguson