Ethical Pharmaceutical Limited v Napp Pharmaceutical Group Limited

[1994] APO 20

official notice

decision of a delegate of the commissioner of patents

Application        :    No. 589254 in the name of ETHICAL PHARMACEUTICALS LIMITED

Title:    Pharmaceutical Matrix-Type slow release formulations

Action: Opposition under Section 59 of the Patent Act 1952 by NAPP PHARMACEUTICAL GROUP LIMITED

Decision:    Issued              .  The opposition failed on the grounds of novelty, prior publication and manner of manufacture, but, succeeded on the ground of lack of compliance with Section 40.  The description of the invention contains serious ambiguity.

patents act 1990

decision of a delegate of the commissioner of patents

Re:Patent Application No. 589254 by ETHICAL PHARMACEUTICAL LIMITED and an opposition under section 59 of the Patents Act 1990 by NAPP PHARMACEUTICAL GROUP LIMITED

background

Patent application No. 589254 by Ethical Pharmaceuticals Limited (Ethical) was lodged under the Patents Act 1952 on 13 February 1987 as a convention application claiming priority of 13 February 1986 from GB Application No. 8603523. The application was advertised accepted under the Patents Act 1952 on 5 October 1989. A Notice of Opposition was filed on 22 December 1989 by Napp Pharmaceutical Group Limited (Napp). The claims of the specification were subsequently amended under section 104 of the Patents Act 1990.

The opposition is proceeding as provided for in section 234(3) of the 1990 Act and regulation 23.3 of the 1991 Regulations.  All evidence stages were completed by 21 December 1992 and the matter heard in Canberra on 2 December 1993.

The grounds relied on in the Notice of Opposition are all the grounds available under section 59(1) of the Patents Act 1952.

At the hearing submissions were only made on sub-sections 59(1) (e), (f), (h), (i), and there were no submissions made in relation to obtaining, prior claiming and obviousness.

Ethical was represented at the hearing by Dr Peter A Stearne of Davies Collison Cave (Patent Attorneys) Sydney.  Napp was represented by Mr Raymond Walton of Griffith Hack & Co. (Patent Attorneys) Sydney.

EVIDENCE

Evidence-in-support consists of declarations by:

-Raymond Walton of 74 Fallon Drive, Dural NSW who is a partner in the Patent Attorneys firm Griffith Hack & Co. together with a number of exhibits.

-Ronald Alexander Anderson of 11 Eulbertie Avenue, Warrawee in NSW who currently holds the title Professor Emeritus and formerly held the position of Professor of Pharmaceutics in the Pharmacy Department of The University of Sydney.

-Ian Richard Buxton of 29 Youngman Avenue, Histon, Cambridge England, a scientist employed by Napp Research Centre Limited and involved with controlled release tablets.

Evidence-in-answer consists of declarations by:

-David John Trigger of the Old School House, The Green, Shouldham Norfolk, England, a scientist who is a Member of the Royal Pharmaceutical Society of Great Britain and a Member of the Controlled Release Society and who is employed by Ethical Pharmaceuticals Limited as a Technical Director responsible for pharmaceuticals development.

-William Neil Charman of 58 The Parade, Ascot Vale 3032 in the State of Victoria who is a senior lecturer in the School of Pharmaceutics at the Victorian College of Pharmacy Ltd.

Evidence-in-reply consists of a declaration by Ian Richard Buxton who made an earlier Statutory Declaration on behalf of Napp Pharmaceutical Group Limited in the evidence-in-support.

THE SPECIFICATION

The accepted specification describes a slow release formulation for pharmaceutical or veterinary use.  On page 3 (line 10) it is stated that the applicants have now appreciated

"that there remains a need for an economical slow release formulation.  In particular, it would be desirable to provide slow release formulations which need only include cheap and readily available excipients and which can be made using existing machinery."

On page 3 line 16 et seq of the specification the invention is stated as follows:

"According to the present invention there is provided a slow release formulation to be administered to humans or animals which uses water soluble/dispersable binder or binders (which must inherently take time to dissolve or disperse) to control the release of the active ingredient.  The formulation comprises secondary granules which comprise primary granules within a secondary matrix of a water soluble/dispersable slow release material, the primary granules themselves comprising particles comprising an active ingredient within a primary matrix of a water soluble/dispersable slow release material."

However the last paragraph of page 4 makes the following statement:

"The slow release formulations of the invention may alternatively be defined as comprising particles which comprise an active ingredient and are arranged as clusters of relatively densely packed particles dispersed in water soluble/dispersable matrix material.  The matrix material at the clusters (ie the primary matrix) may be the same as or different to the matrix material between the clusters (ie the secondary matrix).

The method of the invention is a "building up" process in which, because the second granulating step produces larger granules than the first step there is built up the non-uniform or discontinuous multi-matrix structure.  This method should be distinguished from the homogenising multi-stage granulations process of US Patent No. 2809916 in which each granulation is to the same size and there is no building up and a uniform structure is achieved which is continuous in the sense that there are not sharp changes in the pattern of medicament dispersion."

The accepted specification contains twenty five claims with claims 1,10 and 17 being the important independent claims.

1.   A slow release formulation to be administered to humans or animals, comprising (1) granules which comprise particles comprising an active ingredient and a primary matrix of water soluble/dispersible slow release material in which are dispersed and the particles comprising the active ingredient, and (2) a secondary matrix of a water soluble/dispersable slow release material in which the granules are dispersed.

10.  A slow release formulation to be administered to humans or animals, comprising particles which comprise an active ingredient and are arranged as clusters of relatively densely packed particles dispersed in water soluble/dispersable matrix material, the matrix material at the clusters being the same as or different to the material between the clusters.

17.  A method of making a slow release formulation to be orally administered to humans or animals, comprising mixing particles comprising an active ingredient and a solution or dispersion of a water soluble/dispersible slow release material to form an agglomerate and granulating the agglomerate, drying the resultant primary granules and then mixing them with a solution or dispersion of a water soluble/dispersable slow release material to form an agglomerate and granulating the agglomerate to form secondary granules of a larger size than the primary granules, and drying the secondary granules.

However the claims as accepted were amended and new claims 1 to 20 were lodged 2 January 1992 and subsequently accepted.

The new independent claims were claims 1 and 12.

1.   A slow release formulation to be administered to humans or animals, comprising

(a)  primary granules which comprise particles comprising an active ingredient and a primary matrix of water soluble slow release material in which are dispersed the particles comprising the active ingredient, and

(b)  a secondary matrix of a water soluble slow release material in which the granules are dispersed, the secondary matrix and the primary granules forming secondary granules.

12.  A method of making a slow release formulation to be orally administered to humans or animals, comprising mixing particles comprising an active ingredient and a solution or dispersion of a water soluble/dispersible slow release material to form an agglomerate and granulating the agglomerate, drying the resultant primary granules and then mixing them with a solution or dispersion of a water soluble/dispersable slow release material to form an agglomerate and granulating the agglomerate to form secondary granules of a larger size than the primary granules, and drying the secondary granules.

SUBMISSIONS

In summary, the major submissions made on behalf of the opponent by Mr Walton were:

Section 40 issues

a)The scope of the invention is ambiguous.  The last paragraph of page 4 of the specification is inconsistent with page 3 lines 16 to 28 and the claims as amended.  That paragraph purports to provide an alternative definition of the invention but rather defines a different invention.

b)Claim 7 lacks clarity and is indefinite.  It also renders claim 1 ambiguous.  Is "the granule" of claim 7 additional to the "secondary granule" of claim 1?

c)Claim 11 is unclear in its appendency to claim 1.  Claim 11 specifies that the matrix is "water soluble/dispersable" whereas claim 1 only specifies that the matrix is "water soluble".  Either claim 11 is ambiguous or else it renders claim 1 ambiguous.

d)Pages 5 to 6 of the specification are unclear in relation to whether there is a distinction between "water soluble" and "water dispersible" and how the term "water soluble/dispersible" should be read.

e)Claim 11 embraces formulations described by the last paragraph of page 4 of the specification and thus defines an invention inconsistent with claim 1.

f)At page 6 of the specification it is unclear what is meant by "can be applied in an aqueous medium" and whether this should be an essential feature of the material or whether it is an inherent feature of the material.

g)The specification asserts that the purpose of the invention is to achieve an unexpected enhancement of slow release properties associated with slow release formulations.  One of the opponent's experts tried to repeat the experiments described in the specification but failed to achieve a significantly slower rate of release.  Both of the opponent's experts dispute that an improved result is achieved.  The claims defining the invention are not limited to formulations capable of fulfilling the promise of the invention.  The specification is silent with regard to the selection of an appropriate gum to achieve the alleged improved result.  The specification and claims should disclose and define the invention with sufficient precision to accurately delimit the scope of the invention.

Mr Walton referred to Mond Nickel Company Ltd's Application (1956) RPC 189 at 194, Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at 193, American Cyanamid Company v Ethicon Limited [1979] RPC 215 at 261 and 269, Standards Brands Incorporated's Patent (No. 2) [1981] RPC 499 at 535.

h)The best method of performing the invention is not disclosed.

Novelty Issues

The opponent asserts that there is no substance to the present invention.  It is merely by the choice of selective wording in the claims that the applicant provides the illusion of an invention.  Stripped of verbiage the claims fail to define a novel invention or one that fulfils the requirements for a new manner of manufacture.

Mr Walton referred to Meyers Taylor Pty Limited v Vicarr Industries Limited and Others 137 CLR 228 at 235, RD Werner & Co Inc v Bailey Aluminium Products Pty Ltd [1989] AIPC 90-568 at 38,945, Griffin v Isaacs [1942] AOJP 739 at 740, British Celanese Ltd v Courtaulds Ltd 52 RPC 171 at 193-194, International Paint Co Ltds Application [1982] RPC 247 at 275.

Costs

The opponent submitted that:

The specification as accepted was flawed.  This fact has been acknowledged by the applicant by virtue of their post-acceptance amendments made after receipt of the opponent's Evidence-in-Support.  The opponent submitted that at least for this reason it should be entitled to an award of costs in its favour.

In addition to lack of novelty there are still outstanding flaws in the application which require, at least, further amendment. 

Having established a case against the application in this regard the opponent seeks costs against the applicant.

In summary, the major submissions made on behalf of applicant by Dr Stearne were:

A.Section 40 - Clarity/Fair Basis

1. "Housekeeping amendments" were inadvertently overlooked when claim 1 was amended in the claim set filed on 3 January 1992 and subsequently allowed by the Patent Office.  These minor oversights were the major thrust of the opponent's case with regard to Section 40 considerations.  Clarifying amendments will shortly be filed at the Patent Office for the purposes of amending references to "water/soluble" and "solution" of slow release material, for the purposes of consistency with claim 1 of the application.  Amendments to the specification will be proposed to:

-The statement of invention at page 3 second full paragraph and the paragraph bridging pages 3 and 4.

-The penultimate paragraph on page 4.

-Page 5 last paragraph.

-Page 6 first and second paragraph.

-Method claims 11,12,14,16 and 17.

1. Insofar as references to "soluble/dispersible" slow release materials are concerned, these are clearly alternative characteristics not manifested by the same material under the same conditions.  A clear aspect of the invention as described in the application as originally filed is the use of water soluble slow release materials and amendments have been proposed for the sake of clarity to so limit the claimed invention and supporting description.

1. Claim 7 contains a minor error in referring to a "secondary matrix/granule composition which in itself is in the form of granules in a binder ...".  It is clear from the preceding claims from which this claim depends that the correct recitation should be "secondary granule".  This is a trite point which will be clarified by amendments.

1. Claim 11 contains the recitation "... other than as prior art" and claim 19 contains the recitation "... other than with references to the prior art".  These recitations come from the European derivation of these omnibus claims and amendments will be proposed to delete the language in question to conform them to Australian practice.

1. A significant proportion of the opponent's Section 40 case centred on the penultimate paragraph at page 4 of the specification discussed at paragraph 2 above.  It is submitted that a person skilled in the art, reviewing this paragraph not in isolation but in the context in which it is found, would understand that it is referring to the same invention defined in the consistory clause and claimed in the claims of the application.  The applicant is, however, prepared to delete this paragraph from the specification.

1. The first full paragraph on page 6 of the specification makes reference to "water soluble matrixes which can thus be applied in aqueous mediums."  The key word here is matrixes.  There are two matrixes in the formulations of the invention (a primary and a secondary matrix which may or may not comprise the same material).  It is readily apparent that a water soluble matrix can be applied in an aqueous medium based on its inherent properties.

1. Reference was made in the opponent's submission to Olin Mathieson v Biorex (supra) in the context of speculative claiming.  Dr Buxton's own experiments show that he was able to repeat the invention from the description.  It is clear from the evidence of Dr Charman and Dr Trigger, Ethical's experts, that a person skilled in the art would be equipped with the common general knowledge in the field of control release formulations, with regard to the preparation of solutions as sustained release material, inherent batch variations between sustained release materials, and the mixing and general processing of pharmaceutical formulations.  It is the applicant's position that the claims are fully supported by the detailed description provided in the application.

B.Section 40 - Sufficiency

1. The Opponent's evidence comprising two declarations by Dr Buxton served in these proceedings clearly shows that he has been able to put the invention as claimed into practice - see Table 2 on page 6 of the Buxton declaration made 18 March, 1991, and Table 1 of Annex A of the Buxton declaration made on 24 November, 1992, where double matrix preparations made according to the examples of the Ethical application release active material much more slowly than single matrix preparations.  The differences are so obvious and dramatic that little more need be said.  However, a telling factor is that the ratio of release of Dr Buxton's double matrix preparations compared to the single matrix preparations prepared by him (0.7) is effectively the same as that of the examples of the Ethical application.  See Dr Trigger's declaration in this regard at paragraphs 32 and 33.

1. An important argument for insufficiency advanced by Napp was that the amount of material released from Dr Buxton's double matrix preparations made according to examples 1 and 3 of the Ethical application, was not identical to the data set forth in the Ethical application at specific time points.  Our submissions focus on three key points.  First, the double matrix material produced by Dr Buxton in his repeats of examples 1 and 3 of the Ethical application have definite control release properties superior to the single matrix preparations by him.  Secondly, the variation in absolute release rates is most probably associated with variation in the source of the water soluble control release binder.  Thirdly, the law clearly recognises (No-Fume v Pitchford & Co., Ltd [1935] 52 RPC at 248) that a patent is not bad simply because further experiments are required to obtain the best results.

10)Dr Buxton failed to repeat Examples 2 and 4 of the Ethical application and his process variations of Example 1 gave unclear results.  Ethical's technical experts, Dr Trigger and Dr Charman evidence in their declarations (Trigger paragraph 34 and Charman paragraph 4.08) that Dr Buxton simply failed to take into account the processing requirements well known in the field for producing solutions of low viscosity methyl cellulose which explains Dr Buxton's inability to repeat Example 2.

C.Novelty/Prior Publication/Manner of New Manufacture

11)The opponent principally relies on two patent documents in its assertion of want of novelty, namely, UK patent specification 1,137,379 to Dow (hereafter "Dow") and EP097,523.

The Dow patent is directed to a highly specific method for producing slow release preparations, and preparations produced by such methods.  It is clear that the Dow formulation is different to the invention claimed in claims 1-11 of the Ethical application and hence would not infringe these claims.  There is no anticipation of the Ethical claims by the Dow patent.

European Patent No. 097523 describes slow release formulations where the active moiety in its free or base form is combined with the salt form thereof in a slow release matrix.  It is unnecessary to consider the reverse infringement test in any detail as this disclosure is manifestly a single matrix preparation.

12)The opponent's "manner of manufacture" arguments were predicated on their contention that the invention was not new or novel, and that the results achieved by the invention were not "significant".  These premises are flawed and the invention as claimed clearly represents a manner of new manufacture.

Costs

It was submitted by Dr Stearne that costs should follow the event.

DECISION

Section 40 issues

I agree with Mr Walton's submissions about the last paragraph of page 4 of the specification.  I believe it is inconsistent with the invention defined on page 3 lines 16 to 28 and leads to an unclear understanding of the invention and to ambiguity because both descriptive passages appear to describe different slow release formulations.

The inconsistency has arisen because the accepted claims were amended with claim 10 as accepted deleted and consequent amendments were not made to clarify the description, in particular to remove the inconsistency contained in the last paragraph of page 4.  I do not agree with Dr Stearne's submission that a person skilled in the art reviewing this paragraph, not in isolation, but in the context in which is it found would understand that it is referring to the same invention defined in the consistory clause and claimed in the claims in the application.  In my opinion this statement defines a formulation wherein clusters of active ingredients are dispersed in a matrix material which is different to that defined on page 3 lines 16 to 28 wherein the active ingredient is contained in a primary matrix and is in the form of a granule which is then separately embedded in a secondary matrix.

I believe the problem can be overcome by deleting the penultimate paragraph on page 4 and I note that Dr Stearne is prepared to make such an amendment.

With respect to other submissions made by Mr Walton on behalf of the opponent, I agree with the clarity problems he raised in relation to the lack of clarity of "the granule" of claim 7 and its effect on claim 1.  The claims should presumably refer to the "primary granule".

I do not agree that there is a problem with the distinction between "water soluble" and "water dispersible" and the meaning of the term "water soluble/dispersible" as used in pages 5 and 6 of the description.  I note that only "water soluble" is used in the claim 1 but both terms are used in claims 11, 12, and 14.  I agree with Dr Stearne that insofar as references to "soluble/dispersible" slow release materials are concerned, these are clearly alternative characteristics not manifested by the same material under the same conditions.  It follows from this that the meaning of "can thus be applied in an aqueous medium" used on page 6 line 4 and 5 is clear in its context as a material can be applied either as a solution or a dispersion and depends on the materials used.

However, I agree that claims 11 and 19 which refer, in part, to "substantially as hereinbefore described other than as prior art" are unclear as they include within their scope the inconsistency between page 3 lines 3 to 16 and the last paragraph on page 4 mentioned above.

It appears to me from Dr Stearne's submissions that the applicant is willing to address these clarity problems by amending the relevant parts of the specification.

In relation to the opponent's submission that the specification contained speculative claiming, which in essence is that the description of acacia gum as a matrix was not sufficiently precise to accurately delimit the scope of the invention (the specification being silent with regard to the appropriate particular type of acacia gum required to achieve the alleged improved result, there being a large number of different acacia gums available), Dr Stearne made the point that page 5 of the specification describes four different binders three of which need not be acacia gum.  Furthermore he noted that although the properties of acacia gum may vary according to their source they still fulfilled the promise of the invention (Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd (supra)).  He pointed out that the opponent's expert (Dr Buxton) when repeating the examples of the Ethical application obtained results for the double matrix formulation which were superior to the single matrix formulations.

It seems to me that Dr Buxton's own experiments show that he was able to repeat the invention from the description.  I agree with Dr Sterne's contention that a skilled addressee would understand what materials could be used in slow release formulations, the conditions under which the materials would be used and the limits of the claims in this context.  Hence I believe that there is no speculative claiming.

It seems to me that the opponent's submission that the best method of performing the invention is not disclosed, has not been proved.  The opponent's expert (Dr Buxton) carried out the experiments described in the specification.  Dr Buxton's repeated example 1 at page 6 of his declaration made 18 March 1991 shows that at 50 minutes, 68% of active was released for the double matrix composition compared to 92% for the single matrix preparation, and Dr Buxton's repeated example 3 described in his declaration of 24 November 1992 shows that at 3 hours 38% of active had been released from the double matrix formulation compared with 77% of active release from a single matrix preparation.  I believe this represents a significant advantage.

I accept the applicant's explanation that Dr Buxton was unable to successfully repeat example 2 because the mixing process was overdone.  It is uncertain why Dr Buxton's example 4 failed.  Nevertheless I believe it is fair to say that his experiments did show that for the same amount of binder there is a different rate of release when there is a primary and secondary matrix.

Novelty/Prior Publication

The basic test for anticipation is set out in Meyers Taylor Pty Ltd v Vicarr Industries Ltd (supra) at page 235.  That is

"The basic test for anticipation or want of novelty is the same as that for infringement and generally one can ask oneself whether the alleged anticipation would, if the patent were valid, constitute an infringement" .

It follows from the reverse infringement test that if a citation discloses all the features of the claim, the claim will lack novelty.  If the citation does not disclose all the features of the claim, the claim will still lack novelty provided the citation discloses all the essential features of the claim; but if the essential features are not disclosed in the citation, the claim is novel. (Nicaro Holdings v Martin Engineering 16 IPR 545, and Catnic Components Ltd v Hill and Smith Ltd [1982] RPC 183)

In my view the essential features of claim 1 are as follows:

.    primary granules which comprise:

-    an active ingredient;

-a primary matrix of water soluble slow release material in which the particles of active ingredient are dispersed;

.a secondary matrix of a water soluble slow release material in which the granules (the primary granules mentioned above) are dispersed;

.the secondary matrix and primary granules form secondary granules.

The compositions produced in Dow's Patent (GB 1137379) are not granules of a secondary matrix surrounding the granules of active agent in a primary matrix.  I agree that the dried particles of Dow are simply mixed into a dough not unlike currants are mixed into a cake mix and they do not have the complex structure of the slow release granules as presently claimed.  It is clear that the Dow formulation would not infringe the claims of the Ethical application and hence there is no anticipation of the Ethical claims by the Dow patent.

European Patent No 097523 describes slow release formulations where the active moiety in its free or base form is combined with the salt form thereof in a slow release matrix.  Only a single control release matrix is described at steps 1 - 3 of the general method set forth at page 17 line 9 to page 18 line 6.  In step 4, a binder phase of a water insoluble fatty acid slow release material is applied as a melt to the first granulation.  This is clearly distinct from a secondary matrix of water soluble slow release material in which the primary granules of the Ethical application are dispersed.

I agree with Dr Stearne that GB 1137379 and EP 097523 do not disclose the essential features of the present claims and consequently do not prior publish the invention or render it not novel.

The opponent's case alledging no manner of new manufacture relied on lack of novelty.  Therefore, for the reasons given above, I find the opponent has not proved a lack of manner of new manufacture.

CONCLUSION

I have found that the opposition has failed on the grounds of novelty, prior publication and manner of manufacture but succeeds on the ground of lack of compliance with section 40.

I afford the applicant 60 days from the date of this decision to propose amendments to overcome the section 40 deficiencies.

COSTS

Normally in actions of this nature costs follow the event.  I have found that the opposition succeeded on the basis of the section 40 ground and I see no reason to vary this practice.  Consequently, I award costs against Ethical Pharmaceuticals Limited.

(R J SAWYER
Delegate of the Commissioner of Patents

Patent attorneys for the applicant  :  Davies Collison Cave

Patent attorneys for the opponent   :  Griffith Hack & Co