Apotex Pty Ltd v AstraZeneca AB

Case •

[2013] APO 62

•

27 November 2013

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Apotex Pty Ltd v AstraZeneca AB [2013] APO 62

Patent Application:                   2005202392

Title:Pharmaceutical compositions

Patent Applicant:  AstraZeneca AB

Opponent:  Apotex Pty Ltd

Delegate:  Nicole Howard

Decision Date:  27 November 2013

Hearing Date:  Initial hearing took place on 4 – 5 April 2012 in Melbourne.  Further evidence was allowed on 7 September 2012, and evidence in response was completed on 4 October 2012.  Further submissions from the parties were sought on 10 April 2013, and submissions were provided on 24 April 2013.

Catchwords:  PATENTS – opposition to the grant of a patent – lack of inventive step in the light of the common general knowledge – lack of inventive step in the light of UK patent application 2262229 – opportunity to amend

Representation:  Patent applicant:  Tony Bannon SC and Christian Dimitriadis of counsel, instructed by Michael Caine and Andrew Scott of Davies Collison Cave and Ian Pascarl of Davies Collison Cave Law

Opponent:Katrina Howard SC and Craig Smith of counsel, instructed by Nicole Watling of Freehills

IP AUSTRALIA

AUSTRALIAN PATENT OFFICE

Patent Application:                   2005202392

Title:Pharmaceutical compositions

Patent Applicant:  AstraZeneca AB

Date of Decision:  27 November 2013

DECISION

Claims 1-27 lack an inventive step.  AstraZeneca AB is allowed two months from the date of this decision to propose amendments.  Costs according to Schedule 8 awarded against AstraZeneca AB.

REASONS FOR DECISION

Background

  1. The present application was filed by AstraZeneca AB (AstraZeneca) on 2 June 2005 as a divisional application of 781269 (the parent patent).  The divisional application was examined and advertised accepted on 20 November 2008.  A notice of opposition was subsequently filed by Apotex Pty Ltd (Apotex) on 20 February 2009.  A hearing was held on 4 April 2012 and 5 April 2012 in Melbourne.  AstraZeneca was represented by Tony Bannon SC and Christian Dimitriadis of counsel, instructed by Michael Caine and Andrew Scott (patent attorneys of Davies Collison Cave) and Ian Pascarl of Davies Collison Cave Law.  Apotex was represented by Katrina Howard SC and Craig Smith of counsel, instructed by Nicole Watling (patent attorney of Freehills).  Following the hearing, there was a request to serve further evidence, which was ultimately allowed (see my decision in Apotex Pty Ltd v AstraZeneca AB [2012] APO 95). On 10 April 2013 I sought further submissions from the parties, which were supplied on 24 April 2013.

  2. The parent patent was the subject of infringement proceedings brought by AstraZeneca and AstraZeneca Pty Ltd against Apotex, Watson Pharma Pty Ltd and Ascent Pharma Pty Ltd.  Subsequent to the hearing, the Federal Court issued its decision wherein Justice Jagot found the parent patent was invalid, as the claims were not novel and lacked an inventive step (Apotex Pty Ltd v AstraZeneca AB (No 4) [2013] FCA 162; 100 IPR 285). The decision was appealed to the Full Bench of the Federal Court and heard on 31 July – 2 August 2013.

    Grounds of opposition

  3. The statement of grounds and particulars specified the following grounds of opposition:

    • Manner of manufacture
    • Novelty
    • Inventive step
    • Inutility
    • Section 40 issues of full description and best method of performance, clarity and fair basis.

    Standard of proof

  4. The onus of proof in opposition proceedings rests with the opponent, who must demonstrate that it is clear that a valid patent cannot be granted (F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283 at [67]; 50 IPR 305; Commissioner of Patents v Sherman [2008] FCAFC 182 at [18]; 79 IPR 426).

    Evidence

  5. Apotex’s evidence in support consisted of declarations by:

    • Philip Andrew Marshall dated 29 September 2009 (PAM-1) and Exhibits PAM-1 and PAM-2
    • Nicole Lyndal Watling dated 18 May 2010 (NLW-1) and Exhibits NLW-1 to NLW-8
    • Philip Andrew Marshall dated 27 May 2010 (PAM-2) and Exhibits PAM-3 to PAM-21.

  6. AstraZeneca’s evidence in answer consisted of declarations by:

    • Desmond B Williams dated 12 August 2010 (DBW-1) and Exhibits DBW-1 to DBW-10
    • Desmond B Williams dated 16 November 2010 (DBW-2) and Exhibits DBW-11 and DBW-12
    • Desmond B Williams dated 8 February 2011 (DBW-3) and Exhibit DBW-13
    • Desmond B Williams dated 28 February 2011 (DBW-4) and Exhibit DBW-14.

  7. Apotex’s evidence in reply consisted of a declaration by

    • Philip Andrew Marshall dated 12 December 2011 (PAM-3).

  8. Apotex filed further evidence consisting of declarations by:

    • Philip Andrew Marshall dated 13 April 2012 (PAM-4)
    • James Steven Rowe dated 16 April 2012 (JSR) and Exhibits JSR-1 to JSR-3
    • Emma Elizabeth Lees dated 16 April 2012 (EEL) and Exhibits EEL-1 to EEL-10
    • Nicole Lyndal Watling dated 16 April 2012 (NLW-2) and Exhibits NLW-1 to NLW-4.

  9. AstraZeneca’s evidence in response to the further evidence consisted of a declaration by:

    • Desmond B Williams dated 3 October 2012 (DBW-5) and Exhibit DBW-14.

    The subject matter of the specification

  10. The specification relates to pharmaceutical compositions containing (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R, 5S)-3, 5-dihydroxyhept-6-enoic acid (rosuvastatin) or a pharmaceutically acceptable salt thereof.  The sodium and calcium salts of rosuvastatin are preferred.

  11. Rosuvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) and is useful in the treatment of hypercholesterolemia, hyperlipidproteinemia and atherosclerosis.

  12. Rosuvastatin is sensitive to degradation under certain conditions.  Major degradation products are the corresponding lactone and an oxidation product (“B2”) in which the hydroxy group adjacent to the carbon-carbon double bond is converted to a ketone functionality.  Consequently, rosuvastatin is difficult to formulate and provide in the form of a pharmaceutical composition with an acceptable storage life.

  13. The specification states on page 2 that the stability of rosuvastatin is:

    “improved by selection of an inorganic salt to be added to the composition which contains one or more multivalent inorganic cations.  Whilst not wishing to be bound by theory we believe that the multivalent inorganic cation stabilises the structure of the Agent [rosuvastatin] and makes it less susceptible to oxidation and/or lactonization.”

  14. In discussing the formulation of the pharmaceutical compositions at page 6, the specification further states:

    “Coatings containing ferric oxides are especially preferred as they reduce the rate of formation of photodegradation products of the Agent [rosuvastatin].”

    The claims of the specification

  15. The specification ends with 27 claims.  Four of these are independent and are as follows:

    “1.       A pharmaceutical composition comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R, 5S)-3, 5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof as the active ingredient, the composition having a ferric oxide light protective coating.

    2.        A pharmaceutical composition comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R, 5S)-3, 5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof as the active ingredient and an inorganic salt in which the cation is multivalent; the composition having a coating containing a ferric oxide.

    22.      A pharmaceutical tablet composition comprising (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R, 5S)-3, 5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof as the active ingredient and tribasic calcium phosphate; the tablet composition having a coating containing a ferric oxide.

    26.      The use of a coating containing a ferric oxide to reduce the rate of formation of degradation products of the compound (E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-[methyl(methylsulfonyl)amino]pyrimidin-5-yl]-(3R, 5S)-3, 5-dihydroxyhept-6-enoic acid or a pharmaceutically acceptable salt thereof in a pharmaceutical composition containing the compound.”

  16. Claims 3 to 21 and 23 to 25 are directed to pharmaceutical compositions and claim 27 is an omnibus claim.

    Claims construction

  17. The approach to claims construction was considered by Bennett J in H Lundbeck A/S v Alphapharm Pty Ltd [2009] FCAFC 70 at [118]-[120]; 81 IPR 228:

    “the end point is that the words in a claim should be read through the eyes of the skilled addressee in the context in which they appear.  …  While the claims define the monopoly claimed in the words of the patentee’s choosing, the specification should be read as a whole …  It is not permissible to read into a claim an additional integer or limitation to vary or qualify the claim by reference to the body of the specification …  However, terms in the claim which are unclear may be defined or clarified by reference to the body of the specification …”

    Claim 1

  18. Claim 1 is directed to a pharmaceutical composition comprising rosuvastatin, “the composition having a ferric oxide light protective coating.”  The claim is construed to define a composition that is coated with a ferric oxide, wherein the ferric oxide protects rosuvastatin from light.

    Claim 2

  19. Claim 2 is directed to a pharmaceutical composition comprising rosuvastatin and an inorganic salt in which the cation is multivalent, “the composition having a coating containing a ferric oxide.” 

  20. Although the claim states that a ferric oxide is present in the coating, it does not specify an amount.  Reading the specification as a whole, it is apparent that the whole thrust of the specification is to use ferric oxide in a light protecting amount.

  21. The specification at page 6, lines 11-16 states:

    “Coatings containing ferric oxides are especially preferred as they reduce the rate of formation of photodegradation products of the Agent [rosuvastatin].

    Accordingly we present as a feature of the invention a pharmaceutical composition comprising the Agent, the composition having a ferric oxide light protective coating.”

  22. Thus, the ferric oxide is present in the coating in an amount sufficient to provide light protection. 

  23. Claim 2 does also not specify the amount of the inorganic salt present in the composition.  However, this issue may be resolved in an analogous manner.  The specification indicates at pages 1A to 2 that:

    “We have found that with the Agent [rosuvastatin] stability is improved by selection of an inorganic salt to be added to the composition which contains one or more multivalent inorganic cations.  Whilst not wishing to be bound by theory we believe that the multivalent inorganic cation stabilises the structure of the Agent and makes it less susceptible to oxidation and/or lactonization.

    We present as a feature of the invention …

    …

    (2)       The use of an inorganic salt in which the cation is multivalent as a stabilising agent in a pharmaceutical composition comprising the Agent.”

  24. Thus, the inorganic salt is present in an amount sufficient to function as a stabiliser.  It is also noted that the inorganic salt may itself be a ferric oxide, i.e. ferric oxide may be a component of both the coating and the composition.  This is consistent with the finding of the Federal Court in Apotex Pty Ltd v AstraZeneca AB (No 4) supra at [271]). 

  25. Claim 2 is therefore construed to define a composition comprising rosuvastatin and an inorganic salt and having a coating containing a ferric oxide, wherein the inorganic salt and ferric oxide are present in amounts sufficient to act as a stabiliser and provide protection from light respectively.  A similar construction also applies to the tablet composition defined by claim 22.

    Priority date

  26. The priority date of the present divisional application was not raised at the hearing, however this issue was considered in relation to the parent patent during the Federal Court proceedings. 

  27. The claims of the parent patent are directed to pharmaceutical compositions comprising rosuvastatin and an inorganic salt in which the cation is multivalent, provided the counter anion to the inorganic salt is not a phosphate.

  28. The parent patent claims a priority date of 26 January 2000 from the priority document GB 0001621.  The priority document relates to pharmaceutical compositions comprising rosuvastatin and a tribasic phosphate salt in which the cation is multivalent.  The use of ferric oxide coatings is also described.  However, there is no disclosure of inorganic salts wherein the counter ion is other than a tribasic phosphate. 

  29. The Federal Court found that as none of the claims of the parent patent are limited to a composition comprising rosuvastatin and a tribasic phosphate salt, the claims are not fairly based on the priority document (Apotex Pty Ltd v AstraZeneca AB (No 4) supra at [418]).  Consequently, the earliest priority date for the parent patent is the date of filing of the corresponding application, i.e. 4 August 2000.

  30. Consistent with this finding, the priority dates of the claims of the present divisional application are as follows:

Claimed Composition Earliest Priority Date
rosuvastatin and a ferric oxide coating 26 January 2000
rosuvastatin, a ferric oxide coating and an inorganic salt wherein the counter anion is a tribasic phosphate 26 January 2000
rosuvastatin, a ferric oxide coating and an inorganic salt wherein the counter anion is not a tribasic phosphate 4 August 2000

Novelty

  1. Under subsection 7(1), an invention is taken to be novel unless it is not novel in the light of the prior art base.  A document forms part of the prior art base for the purposes of novelty if it was published before the priority date of a claim.

  2. 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 Aicken J in Meyers Taylor Pty Ltd v Vicarr Industries Ltd [1977] HCA 19 at [20]; 137 CLR 228:

    “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”.

  3. This test is satisfied if the alleged anticipation discloses all the essential features of the invention claimed (Nicaro Holdings Pty Limited v Martin Engineering Company [1990] FCA 40 at [19]; 16 IPR 545). In order to meet this requirement, the prior art “must contain clear and unmistakeable directions to do what the patentee claims to have invented” (The General Tire & Rubber Company v The Firestone Tyre and Rubber Company Limited [1972] RPC 457 at 486).

  4. Lack of novelty was only pressed at the hearing in view of one document, UK patent application 2262229.

    UK patent application 2262229

  5. Apotex submitted that the invention of claims 1-27 is not novel in the light of UK patent application 2262229 (‘229).

  6. Application ‘229 was published on 16 June 1993 and therefore forms part of the prior art base.  The application relates to pharmaceutical compositions comprising HMG-CoA reductase inhibitor compounds.  Page 1 states that the compounds are of the formula:

    R-X-CH(OH)-CH2-C(OH)-CH2-COOM (I)

    wherein R is an organic radical, X is preferably (E)-CH=CH and M is a physiologically acceptable cation.

  7. R may be selected from numerous groups, including derivatives of pyrimidinyl (page 15, 2nd full paragraph).  However, none of the 28 compounds listed on pages 16 to 18 correspond to rosuvastatin.  Of the 9 preparative examples given on pages 19 to 23, 7 of these relate to fluvastatin (R = substituted indolyl) and the remaining 2 describe different HMG-CoA reductase inhibitors.  Thus, the ‘229 patent application does not provide clear and unmistakeable directions to use rosuvastatin in the pharmaceutical compositions. 

    Conclusion on novelty

  8. It has not been demonstrated that there is a lack of novelty in the light of UK patent application 2262229.

    Inventive Step

  9. Under subsections 7(2) and 7(3), an invention is taken to involve an inventive step unless it would have been obvious to the person skilled in the art in the light of the common general knowledge, either considered alone or together with the prior art.  The prior art is information that the skilled person could, before the priority date of the relevant claim, be reasonably be expected to have ascertained, understood and regarded as relevant.

  10. The test for whether an invention is obvious is whether it would have been a matter of routine to proceed to the claim 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 VR Laboratories (Aust) Pty Ltd [1981] HCA 12 at [45]; 148 CLR 262).

  11. More recently, in Aktiebolaget Hassle v Alphapharm Pty Ltd [2002] HCA 59 at [53]; 212 CLR 411, the High Court accepted the approach taken in Olin Mathieson Chemical Corporation v Biorex Laboratories Ltd [1970] RPC 157 at [187] where Graham J posed the reformulated Cripp’s question:

    “Would the notional research group at the relevant date, in all the circumstances, ….directly be led as a matter of course to try [the claimed combination] in the expectation that it might well produce a [useful or better result]?” (emphasis in original)

    The problem

  12. AstraZeneca submitted that the problem-solution approach does not apply in the present case.  In determining whether the problem-solution approach is appropriate, consideration should be given to the specification.

  13. The specification at page 1 states:

    “A problem associated with the Agent [rosuvastatin] is that it is particularly sensitive to degradation under certain conditions.  The major degradation products formed are the corresponding (3R, 5S) lactone (hereinafter referred to as ‘the lactone’) and an oxidation product (hereinafter referred to as ‘B2’) in which the hydroxy group adjacent to the carbon-carbon double bond is oxidised to a ketone functionality.  The potential for significant degradation of the Agent makes it difficult to formulate and provide a pharmaceutical composition with acceptable storage life for a marketed product.”

  14. It is therefore appropriate to apply the problem-solution approach in the assessment of inventive step.

  15. Apotex submitted that the problem to be solved is the instability of rosuvastatin.  AstraZeneca

    argued it is not permissible to assume a “starting point” or problem identified in the specification if this is not shown to be part of the common general knowledge.  In particular, it was submitted that rosuvastatin is not part of the common general knowledge.

  16. The specification does not discuss the “discovery” of rosuvastatin, nor its preparation in any detail.  Consequently, the “starting point” is rosuvastatin itself.  This is consistent with the approach taken by the Federal Court in Apotex Pty Ltd v AstraZeneca AB (No 4) supra at [454]:

    “As discussed, because I consider that the invention lies in the formulation of a particular composition of rosuvastatin, the invention pre-supposes the existence of the compound, with its particular chemical structure.  In other words, no part of the invention lies in knowing about rosuvastatin or its chemical structure”.

  17. The problem to be overcome therefore relates to providing pharmaceutical compositions comprising rosuvastatin which address the degradation issues.

  18. Apotex submitted that the claimed invention lacked an inventive step either in the light of the common general knowledge or the prior art.  I will firstly consider the common general knowledge and then the prior art.

    Common general knowledge

  19. In relation to coatings for pharmaceutical compositions, the evidence indicates it was common general knowledge at the earliest priority date that:

    • coatings may be used to protect ingredients from the environment, particularly light, air and moisture (PAM-2 at [19]; Exhibit PAM-6 at page 669; Exhibit PAM-7 at page 2; Exhibit PAM-8 at page 1666; Exhibit PAM-10 at page 1; Exhibit PAM-11 at pages 126‑127; Exhibit DBW-12 at page 14).
    • inorganic colours are commonly used in coating formulae, including titanium dioxide and iron (ferric) oxide yellow, red and black (Exhibit PAM-7 at pages 34-36; Exhibit PAM-8 at page 1668; Exhibit PAM-11 at pages 126-127).
    • iron (ferric) oxide pigments in a film provide opacity.  Opaque film coatings prevent degradation of the active substance by light (PAM-2 at [32] and [33]; Exhibit PAM-7 at pages 35, 40-42 and 47; Exhibit PAM-11 at pages 126-127).
    • coatings may include other components such as hydroxypropyl methylcellulose, lactose and triacetin (present description at page 6, lines 6-9; PAM-2 at [76]; Exhibit PAM-7 at pages 9-11, 28, 45 and 46; Exhibit PAM-8 at page 1669; Exhibit PAM-9 at page 365).

  1. The evidence provided by AstraZeneca did not comment on the commonly used components in coating formulations.

  2. The evidence also indicates that when formulating pharmaceutical compositions it was routine to:

    • add fillers, binders, disintegrants, lubricants and other excipients (present description at page 4, lines 22-27; PAM-2 at [69]; Exhibit DBW-12 at page 14).
    • include inorganic salts such as aluminium magnesium metasilicate, dibasic or tribasic calcium phosphate, calcium sulphate, tribasic magnesium phosphate and tribasic aluminium phosphate (PAM-2 at [53] and [58]; Exhibit DBW-12 at page 14).
    • include active ingredient in amounts ranging from 1 to 50% by weight of the composition (PAM-2 at [57]).
    • use coatings in amounts ranging from 0.5% to 10% by weight of the composition (PAM-2 at [64]).

    Claim consideration

  3. The evidence indicates that the use of ferric oxide pigments in coating formulations was known to prevent photodegradation of active ingredients in pharmaceutical formulations.  The expert witnesses from both parties indicated that they would expect rosuvastatin to be susceptible to certain conditions, including light, based on its chemical structure (PAM-2 at [5] and [6]; Exhibit DBW-8 at page 22).

  4. Therefore, the skilled addressee, faced with the problem of providing a pharmaceutical composition of rosuvastatin with improved stability, would have taken the routine step of applying a ferric oxide coating to the composition, in the expectation it would reduce the sensitivity of rosuvastatin to degradation by light.

  5. This is consistent with the finding in Apotex Pty Ltd v AstraZeneca AB (No 4) supra at [459]:

    “The hypothetical skilled addressee, faced with the same problem disclosed in the 842 or cation [parent] patent, immediately would have taken the routine step of applying a conventional coating containing titanium dioxide and ferric oxide to a pharmaceutical composition containing rosuvastatin in the expectation that stability would be improved because improving shelf life, providing protection from degradation by external agents and enhancing tablet stability were three of the recognised potential functions of coatings at all material times.  On the evidence, the skilled person would directly be led to try the step of stabilising a pharmaceutical composition of rosuvastatin by “slapping on a coating” containing titanium dioxide and ferric oxide in the expectation that it may achieve a useful result in terms of improved stability.  The uninventive worker in the field would have taken such a step as a matter of course.”

  6. Consequently, claim 1 lacks an inventive step.

  7. Claim 2 is directed to a pharmaceutical composition comprising rosuvastatin and an inorganic salt in which the cation is multivalent, the composition having a coating containing a ferric oxide.  Having established that the use of ferric oxides in coatings is routine, consideration of the inorganic salt component is now required.

  8. The evidence indicates that the inclusion of inorganic salts, in which the cation is multivalent, in pharmaceutical compositions was common practice.  Therefore, it would have been routine for the skilled addressee to add an inorganic salt to a composition comprising rosuvastatin and subsequently coat the composition with a coating containing a ferric oxide.  The fact that the inorganic salt may contribute to the improved stability of the composition is merely a bonus effect.  Claim 2 therefore does not involve an inventive step.

  9. Independent claim 22 defines a composition comprising rosuvastatin and tribasic calcium phosphate and having a coating containing a ferric oxide, whilst independent claim 26 is directed to the use of a coating containing a ferric oxide to reduce the formation of photodegradation products of rosuvastatin.  These claims similarly lack an inventive step.

  10. The dependent claims define additional features as follows:

    • claims 3-7 and 11 specify the nature of the inorganic salt, or its cation or counter anion components.
    • claims 8 and 21 define the form of the composition.
    • claims 9, 10, 12, 14-19, 23 and 24 indicate the amounts of specific components present in the composition.
    • claim 13 defines the presence of additional excipients.
    • claim 20 indicates that the active ingredient is the calcium salt.
    • claim 25 specifies the type of coating.
    • claim 27 defines specific compositions.

  11. All of the features included by these claims are part of the common general knowledge (see above).  It follows that the preparation of a pharmaceutical composition possessing the features defined by the dependent claims would be readily achieved by the skilled addressee via routine steps.  Claims 3‑21, 23- 25 and 27 therefore lack an inventive step.

    Prior art

  12. Apotex submitted that the claimed invention is not inventive in light of each of EP 521471, AU 30202/89 and UK patent application 2262229.  The first question to consider is whether these documents would have been ascertained, understood and regarded as relevant.  The evidence indicates that the skilled addressee would undertake a search of the patent literature in order to solve the problem (PAM-4 at [4]; JSR at [23]; Exhibit DBW-9 at page 3; Exhibit DBW‑12 at page 7).  Therefore, each document would have been ascertained.

  13. In determining whether the prior art would have been regarded as relevant, I will firstly consider the EP and AU documents.

    EP 521471

  14. EP 521471 was published on 7 January 1993 and therefore forms part of the prior art base.  Example 1 on pages 8-10 describes the preparation of the sodium salt of rosuvastatin.  However, there is no disclosure of any stability or degradation issues associated with the compound.  In view of the problem to be solved, EP 521471 is not considered relevant.

    AU 30202/89

  15. AU 30202/89 was published on 31 August 1989 and therefore forms part of the prior art base.  The document describes a broad range of pyrimidine derivatives.  Although rosuvastatin is disclosed in a generic sense, there is no specific mention or exemplification of the compound.  There is also no discussion of any stability or degradation problems associated with the pyrimidine derivatives.  In light of the problem to be solved, AU 30202/89 is not regarded as relevant.

  16. Having established that the EP and AU documents are not relevant, I will now consider the UK patent application 2262229.

    UK patent application 2262229

  17. The UK patent application 2262229 (‘229) does not specifically disclose rosuvastatin as I have found above.  However, ‘229 relates to a class of HMG-CoA reductase inhibitors, of which rosuvastatin is a member.  The document also discusses instability issues associated with the reductase inhibitors, including pH-related destabilisation and heat and light sensitivity (page 2).  In view of the problem to be solved, ‘229 would be regarded as relevant prior art.

  18. ‘229 indicates that the stability of compositions comprising the reductase inhibitors may be improved by the addition of an alkaline medium, including salts such as calcium dibasic phosphate and tribasic calcium phosphate, i.e. inorganic salts in which the cation is multivalent (page 3, 2nd full paragraph; page 4, 3rd paragraph to page 5, 1st paragraph).  The use of coatings to protect the compositions against moisture and light is also described (page 8, 3rd full paragraph).  The coating may contain opacifiers and colourants (page 8, 3rd full paragraph), including iron oxide (page 9, 2nd paragraph).  Opadry YellowT, which contains ferric oxide and titanium dioxide, is listed as a possible coating (page 8, last paragraph) and exemplified in Example 4 (pages 21‑22).

  19. In view of this disclosure, the skilled addressee, faced with the problem of providing a pharmaceutical composition of rosuvastatin with improved stability, would have taken the routine steps of including an inorganic salt in which the cation is multivalent and applying a coating containing a ferric oxide to the composition, in the expectation it would reduce the degradation of rosuvastatin.

  20. Claims 1 and 2 therefore lack an inventive step.

  21. The features of independent claims 22 and 26, and dependent claims 3-21, 23-25 and 27 are discussed above.  These claims all lack an inventive step in view of ‘229 when read in light of the common general knowledge.  However, it is noted that the features of the following claims are disclosed in ‘229:

    • claims 3-5, 7 and 11 (nature of the inorganic salt, or its cation or counter anion components): ‘229 at pages 4 and 5.
    • claims 8 and 21 (form of the composition): page 6, 5th paragraph.
    • claims 9, 10, 12, 14-19, 23 and 24 (amounts of specific components present in the composition): example 1; example 4; page 6, last paragraph to page 8, 1st paragraph; page 9, 1st paragraph.
    • claim 13 (presence of additional excipients): page 6, last paragraph to page 8, 1st paragraph.
    • claim 20 (calcium salt): page 3, 1st full paragraph.

    Conclusion on inventive step

  22. Claims 1-27 lack an inventive step in the light of the common general knowledge.  Claims 1-27 also lack an inventive step in view of UK patent application 2262229. 

    Manner of manufacture

  23. Subsection 18(1)(a) requires that an invention must be a manner of manufacture within the meaning of section 6 of the Statute of Monopolies.  Manner of manufacture is assessed by asking whether the claimed invention lacks the necessary quality of inventiveness on the face of the specification (NV Philips Gloeilampenfabrieken v Mirabella International Pty Ltd [1995] HCA 15 at [9]; (1995) 183 CLR 655).

  24. Apotex submitted that there is no invention on the face of the specification on several grounds.

    Mere use of a known substance

  25. Apotex argued that the “use of a ferric oxide coating to provide a light-protective coating to a formulation comprising rosuvastatin involves the use of ferric oxide for precisely the use for which its known properties were known to make it suitable.”  However, on the face of the specification, it is not apparent that it was known that ferric oxide coatings could be used to address the degradation issues of compositions containing rosuvastatin.

    UK patent application 2262229

  26. Apotex argued that UK patent application 2262229, discussed on page 1A of the specification, discloses the claimed invention.  However, as indicated above, it has not been established that the claimed invention lacks novelty in the light of this document.

    Mere collocation of known integers

  27. Apotex submitted that since the ferric oxide coating and rosuvastatin do not interact in anyway, or have any synergistic effect, claim 1 merely defines a collocation of integers.  However, the ferric oxide coating and rosuvastatin are defined to be in a physical arrangement such that the coating prevents degradation of the rosuvastatin.

    Conclusion on manner of manufacture

  28. It has not been established that the present invention is not a manner of manufacture.

    Utility

  29. The requirements for utility were considered by the Full Court of the Federal Court in H Lundbeck A/S v Alphapharm Pty Ltd supra at [81]; 81 IPR 228:

    “A claim is bad if it covers means that will not produce the desired result, even if a skilled person would know which means to avoid.  That is to say, everything that is within the scope of a claim must be useful, otherwise the claim will fail for inutility”.

  30. Apotex argued that the specification does not suggest that the use of a ferric oxide coating alone will achieve improvement in the stability of pharmaceutical compositions comprising rosuvastatin, and further that the claims are not limited to a stable or stabilised composition.  This is based on the observation that Examples 1-4 described in the specification indicate that the uncoated formulations perform better than the coated formulations in terms of the amount of decomposition products formed (PAM-2 at [91] and [95]).

  31. Examples 1 and 4 relate to uncoated formulations whereas examples 2 and 3 are directed to coated formulations.  The amounts of the degradation products (“B2” and lactone) formed after one week are provided for each example.  Whilst the quantity of lactone produced in the coated formulations is higher than the uncoated formulations, it is not possible to make a direct comparison as the formulations differ in terms of their composition.  Also, the conditions under which the formulations were stored, i.e. 70C at 80% relative humidity for one week, do not reflect the conditions under which the formulations would be stored during normal use, making conclusions on utility inappropriate.

  32. Apotex also submitted that as none of the claims are limited to a composition containing any minimum amount of ferric oxide in the coating, or any minimum amount of an inorganic salt, the claims include subject matter that does not provide any improvement in stability.  However, as indicated above, the independent claims are construed to define compositions with a coating wherein the ferric oxide component has a light protective function and the inorganic salt component, where present, acts as a stabiliser. 

  33. It has not been demonstrated that there is a lack of utility.

    Sufficiency and best method

  34. Subsection 40(2)(a) requires that a complete specification must describe the invention fully, including the best method of performing the invention.  The High Court in Kimberly Clark Australia Pty Ltd v Arico Trading International Pty Ltd [2001] HCA 8 at [25]; 207 CLR 1 stated that the question to consider is:

    “will the disclosure enable the addressee of the specification to produce something within each claim without new inventions or additions or prolonged study of matters presenting initial difficulty?”

  35. Apotex submitted that the specification fails to explain why synthetic hydrotalcite should not be used as the inorganic salt in which the cation is multivalent.  This feature is referred to on page 2, line 21 of the specification and in claim 11.

  36. Examples 1-4 in the specification describe the preparation of pharmaceutical compositions wherein the inorganic salt is not synthetic hydrotalcite.  Consequently, the specification enables the skilled addressee to produce something within claim 11 without the need for prolonged study.

  37. It has not been established that the specification fails to describe the invention fully.

    Fair basis

  38. Subsection 40(3) requires that the claims must be fairly based on the matter described in the specification.  The test for fair basis was stated by the High Court in Lockwood Security v Doric Products [2004] HCA 58 at [69]; 217 CLR 274 as:

    “Rather, the question is whether there is a real and reasonably clear disclosure in the body of the specification of what is then claimed, so that the alleged invention as claimed is broadly, that is to say in a general sense, described in the body of the specification.”

  39. Apotex submitted that the specification discloses as an invention a composition comprising rosuvastatin and an inorganic salt with a multivalent cation.  It was argued that the ferric oxide coating is an optional feature that is in addition to the rosuvastatin and inorganic salt present in the composition.  Therefore, claims 1 and 26, which only define rosuvastatin and the ferric oxide coating are not fairly based. 

  40. The specification at page 6, lines 15-16 presents “as a feature of the invention a pharmaceutical composition comprising the Agent [rosuvastatin], the composition having a ferric oxide light protective coating.”  This is considered to disclose a pharmaceutical composition comprising rosuvastatin, wherein the composition has a ferric oxide coating.

  41. Apotex also argued that claims 2 and 22 are not fairly based as the claims do not specify that the coating containing a ferric oxide is light protective, or do not specify the amount of ferric oxide that needs to be in the coating in order for the coating to function as a light protective coating.  However, as indicated above, the ferric oxide is considered to be present in an amount sufficient to provide protection against photodegradation.

  42. I am not satisfied that the opposition on the ground of lack of fair basis has been made out.

    Clarity

  43. Subsection 40(3) requires that the claims must be clear.  A claim will lack clarity if a third party could not ascertain whether a proposed action would fall within the ambit of the claim (Monsanto Co v Commissioner of Patents (1974) 48 ALJR 59).

  44. Apotex submitted that claim 4 is not clear as there is no antecedent for “the counter anion” in claims 2 and 3, from which claim 4 depends. 

  45. Claim 2 makes reference to an inorganic salt in which the cation is multivalent.  The skilled addressee would understand that the inorganic salt would necessarily contain a counter anion to balance the charge on the cation.  Claim 4 is therefore clear.

  46. Apotex also argued that claim 8 is not clear in relation to how a pharmaceutical composition in the form of a powder can have a ferric oxide coating when the claim is appended to claim 1 or claim 2. 

  47. The evidence indicates that coatings may be applied to granules or other particulate matter (Exhibit PAM-7 at page 7; Exhibit PAM-10 at page 1).  Claim 8 is therefore clear.

  48. It has not been established that the claims lack clarity.

    Conclusion

  49. Claims 1-27 lack an inventive step in the light of the common general knowledge.  Claims 1-27 also lack an inventive step in view of UK patent application 2262229.  The opposition fails on all other grounds.  It is possible the lack of inventive step could be addressed by amendment.  It is therefore appropriate to allow AstraZeneca a period of two months to propose amendments.

    Costs

  50. Apotex have succeeded in the opposition on the ground of inventive step.  I see no reason to depart from the normal approach that costs follow the event.  I award costs in accordance with Schedule 8 against AstraZeneca.

    Nicole Howard

    Delegate of the Commissioner of Patents

Actions
Download as PDF Download as Word Document
Cases Citing This Decision

0

Cases Cited

12

Statutory Material Cited

0

Apotex Pty Ltd v Astrazeneca AB [2012] APO 95
Apotex Pty Ltd v AstraZeneca AB (No 4) [2013] FCA 162
F.Hoffman-La Roche AG v New England Biolabs Inc [2000] FCA 283