Nektar Therapeutics v Advanced Inhalation Research, Inc
[2006] APO 22
•9 June 2006
ABSTRACTS OF DECISIONS
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No. 757337 in the name of Nektar Therapeutics
Title: Perforated Microparticles and Methods of Use
Action: Opposition under section 59 by Advanced Inhalation Research, Inc
Decision: Issued 9 June 2006
Abstract
Opposition partly successful.
None of the claims are entitled to claim priority from the priority documents PD-1 or PD-2 and hence documents D4, D5, D11 and D12 (all published after the filing date of one or both of those documents) become part of the prior art base for the purposes of novelty in addition to D1-D3, D6-D10 and D13 which were published prior to PD-1.
Despite this, the opponent has not established that any of the citations D2-D13 deprive the claims of their novelty. There is however a technical novelty problem with D1 (which shares common inventors with the opposed application). One of the surfactants used in the ultrasound imaging contrast agents disclosed in D1 also happens to be used in the treatment of lung problems in infants. As a consequence, the microparticles (disclosed in D1) inadvertently fall within the scope of claims 1, 2, 4-19.
There are no inventive step or section 40 problems with the opposed application.
PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re:Patent Application No. 757337 in the name of Nektar Therapeutics and an opposition under section 59 by Advanced Inhalation Research, Inc.
BACKGROUND
Patent application 757337 in the name of Nektar Therapeutics was filed on 29 September 1998 under the provisions of the PCT. It claimed priority from three US basic applications 60/060,337 (filed on 29 September 1997), 09/106,932 (filed 29 June 1998) and 09/133,848 (filed on 14 August 1998). The Australian application was advertised accepted on 20 February 2003 and a notice of opposition was filed on 20 May 2003 by Advanced Inhalation Research, Inc.
Evidence in support was completed on 1 March 2004 and amendments were proposed to the specification on 14 March 2005 just prior to evidence in answer being finalised (on 22 March 2005). All evidence stages were completed by 21 June 2005 and the matter was set for hearing in Canberra on 8 November 2005 with the proposed amendments advertised allowed on 3 November 2005.
The applicant was represented by Mr Brendan Nugent, patent attorney from Griffith Hack, Brisbane and the opponent was represented by Dr Thomas M. Boyce and Mr Bill Bennett, patent attorneys from Pizzeys Patent and Trade Mark Attorneys, Canberra. Representatives from both the opponent and the applicant attended the hearing (in the case of the applicant, their attendance was by phone).
SPECIFICATION
The specification as amended after acceptance relates to perforated microparticles which are used for the targeted delivery of a bioactive agent to the respiratory tract of a patient. The specification notes that targeted delivery is particularly desirable where toxicity or bioavailability of a pharmaceutical compound is in question. Such drug delivery effectively deposits the compound at the site of action and this potentially serves to minimize toxic effects, lower dosing requirements and decrease therapeutic costs.
One of the most common systems presently used to deliver drugs to the air passages are dry powder inhalers (DPIs). DPIs rely on the patient's inspiratory effect to introduce a dry powder medicament into the lungs. However, conventional powdered preparations for use in DPIs often fail to provide accurate reproducible dosing over extended periods because they tend to aggregate due to hydrophobic or electrostatic interactions between the fine particles. Fine particle aggregation disrupts the aerodynamic properties of the powder thereby preventing large amounts of the aerosolised medicament from reaching the deeper airways of the lung where it is most effective.
In order to overcome these problems, the specification notes that prior art formulations have typically used large carrier particles containing lactose. These larger particles have less tendency to aggregate because of lower interparticle forces but they are not as effective in drug delivery because substantial amounts of the drug are deposited in the throat (after apparently failing to disengage from the large lactose particles).
One particular prior art solution discussed in the specification is that proposed in patent specification WO 98/31346. This document describes particles which have relatively large geometric diameters (ie: preferably greater than 10µm) but which are light enough to avoid the problems of throat deposition which occurred in other prior art formulations. However, according to the opposed specification, these types of particles still have potentially long dissolution times which can result in dosing limitations in standard DPIs. As a consequence, the main object of the invention as outlined on page 3, lines 10-11 indicates that there is a need for standard sized particles that resist aggregation and preserve the flowability of the resulting powder.
I note that the skilled worker would understand that "standard sized particle" in this context would mean a particle with a particle having a geometric diameter of less than 10µm (see page 26, lines 17-18). However, the rest of the specification makes no mention of geometric diameter being an important feature of the invention. The specification as a whole describes the particles of the invention in terms of their mean aerodynamic diameter (MAD or daer) which unlike the geometric diameter (d) depends substantially on the particle density (ρ):
daer = d √ ρ
The claims also define the particle of the invention in terms of its aerodynamic diameter and not its geometric diameter. Claim 1 (as amended after acceptance) is the only independent claim of the 19 claims that end the specification. It reads as follows:
1.A powder composition comprising a plurality of perforated microstructures, said microstructures comprising a bioactive agent selected from the group consisting of anti-allergics, bronchodilators, pulmonary lung surfactants, analgesics, antibiotics, anti-infectives, leukotriene inhibitors or antagonists, antihistamines, anti-inflammatories, anti-neoplastics, anti-cholinergics, anaesthetics, anti-tuberculars, cardiovascular agents, enzymes, steroids, genetic material, viral vectors, anti-sense agents, proteins, peptides and combinations thereof, a mean aerodynamic diameter of less than 5µm, and a bulk density of less than about 0.5g/cm3, wherein, when suspended in a fluid medium, the volume of the medium displaced by the perforated microstructures comprises less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid.
This claim clearly includes both large geometric diameter (ie: greater than 10µm) and small geometric diameter particles (provided their mean density was sufficiently small). While the specification notes that particularly preferred microstructures have small or average particulates (ie less than 10µm - see page 26, line16-18), the specification does not suggest that large particles are excluded from the invention. In fact, the preferred microparticle embodiments described on page 24, lines 12 et seq have a wide range of geometric diameters (between 0.5µm and 50µm). As a consequence, a skilled worker (in reading the specification as a whole) would understand a "standard sized" particle was not an essential feature of the invention. The implication otherwise in the stated main object of the invention appears to be a consequence of poor drafting rather than intention.
The specification notes that the claimed particles reduce aggregation in carrier particles in dry state formulations (which is the broad stated object of the invention). The specification suggests that this reduction is not related to the geometric diameter but rather is a consequence of the "unique particle" morphology of the structure (see page 26, lines 16-18). The key advance of the invention appears to be the use of hollow, porous microstructures with very low bulk density in pulmonary delivery devices. The pores, voids, hollows, defects or other interstitial forces in such particles reduce the surface contact area between the particles. This minimises interparticle adhesive forces such as van der Waal's forces which in turn ensures good flowability characteristics (see page 25, line 13-15).
According to the specification, such microstructures also have the advantage of minimising throat deposition during drug delivery. This allows drugs to be deposited in the pulmonary air passages where it may be more efficiently absorbed. The specification theorised (on page 30, lines 6-15) that the hollow and porous nature of the particles slows the velocity of the particles in the propellant/gas stream enabling them to be carried along in the flow of gases during inhalation. This ensures that the drug is administered deep into the lungs rather than being impacted on the back of the throat.
The specification states that these microparticles can be used in dry state formulations [used in DPIs] or in stabilised dispersions (used in other types of pulmonary drug delivery devices such as metered dose inhalers (MDI) or nebulisers). MDIs are currently the most popular form of inhalation administration of pulmonary drugs. They use a relatively high vapour pressure propellant (such as Freon) that forces aerosolised medication into the respiratory tract. According to the specification, the microparticles of the invention allow the fluid suspension medium in MDIs to freely permeate the particulate boundary thereby creating a "homodispersion" wherein particle aggregation and sedimentation are minimised and the suspension is more stable (see page 33, lines 12 et seq).
The examples showed microparticles made by a spray drying technique which were used in MDI and DPI devices and nebulisers and found to effectively deliver pulmonary drugs in each of the three systems.
DECISION
Priority date
As noted above, the opposed specification claims priority from three US basic applications:
60/060,337 (filed on 29 September 1997) [PD-1];
09/106,932 (filed 29 June 1998) [PD-2]; and
09/133,848 (filed on 14 August 1998) [PD-3].
Two of the citations relied on by the opponent for novelty (D4 and D5) have publication dates after the filing date of PD-1 but before the filing date of PD-2. Another two citations (D11 and D12) have publication dates after the filing dates of both PD-1 and PD-2 but before the filing date of PD-3. This means that if the claims are not entitled to claim priority from PD-1 or PD-2, then D4, D5, D11 and D12 become part of the prior art base for novelty. It therefore became important in this decision to determine whether the claims are entitled to claim priority from either PD-1 or PD-2.
As noted in the recent Full Federal decision of Pfizer Overseas Pharmaceuticals v Eli Lilly and Company [2005] FCAFC 224 [at paragraph 268], the test for determining the priority date of a claim is basically the same as the internal fair basis test between the description and claims of a specification. While UK law requires an enabling disclosure to establish a priority date (see Asahi Kasei Kogyo KK’s application [1991] RPC 485), Australian law appears to have no such requirement. The role of a priority document is merely to provide fair basis for a more detailed description of the same subject matter in the complete specification. As noted in Anaesthetic Supplies v Rescare Ltd 28 IPR 383 (at 401):
“All that the provisional specification needs to do is describe generally and fairly the nature of the invention, and not to enter into all the minute details as to the manner in which the invention is to be carried out. It is a mode of protecting the inventor until the time of filing the final specification. It is not intended to be a complete description of the invention, but simply to disclose the invention fairly, though in a rough state. The interval of time between the provisional and the final is intended to provide an opportunity of development and precise expression of the invention foreshadowed in the provisional.”
The recent High Court decision of Lockwood Security Products Pty Ltd v Doric Products Pty Ltd (2004) 62 IPR 461 ruled that the test for fair basis merely requires consistency between the invention described and claimed. This proposition is consistent with the tests applied in Rehm Pty Ltd v Western Security Systems (International) Pty Ltd (1988) 81 ALR 79 and CCOM Pty Ltd v Jiejing Pty Ltd (1994) 122 ALR 417 which require a "real and reasonably clear" disclosure of the claimed invention in the priority document for the complete specification to claim priority from the earlier document [as per Societé des Usines Chimiques Rhône-Poulenc v Commissioner of Patents (1958) 100 CLR 5)].
Both PD-1 and PD-2 describe formulations and methods for targeted drug delivery to the lung involving stabilised dispersions which contain perforated microstructures. The documents teach that these dispersions are more stable than those of the prior art because the perforated microstructures are permeated by the surrounding fluid medium in the dispersion which significantly reduces the disruptive attractive inter-particle forces between the microparticles. The invention in its broadest form is defined in the claims of both PD-1 and PD-2. Claim 2 of PD-1 defines:
"A stable respiratory dispersion for the pulmonary delivery of a bioactive agent comprising a suspension medium having dispersed therein a plurality of perforated microstructures comprising a bioactive agent wherein said suspension medium substantially permeates said perforated microstructures".
Claim 1 of PD-2 is almost identical but it envisages having more than one bioactive agent in the dispersion.
There are 4 significant differences between the invention as disclosed in PD-1 and PD-2 and that now defined in claim 1 of the opposed specification. In contrast to the invention broadly claimed in the PD-1 and PD-2, claim 1 of the opposed specification specifically defines:
§powder compositions (not just stabilised dispersions);
§particular active ingredients (not just any active ingredient);
§particular MAD (less than 5µm) and bulk density (less than about 0.5g/cm3) values; and
§a particular volume displacement value (less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid)
I will assess each of these differences in turn to determine if there has been a “real and reasonably clear” disclosure of them in either PD-1 or PD-2.
powder compositions
The claims of both PD-1 and PD-2 do not define the microparticles by themselves but only as part of a stabilised dispersion. The applicant’s understanding of the invention at the time (as set out in PD-1, page 13, lines 29 et seq) was that the dispersion was resistant to degradation because the particulate volume defined by the fluid permeated microstructures (my emphasis) has approximately the same density as the surrounding suspension medium. The key advance of the invention could only be realised in a liquid delivery system and neither PD-1 nor PD-2 contemplated a dry powder formulation containing the microparticles.
The applicant argued that prior to being reconstituted into stabilised dispersions, the microparticles were powder compositions. According to the applicant, this “starting material” was the same as later exemplified in the opposed specification and therefore provided a "real and reasonably clear" disclosure of powdered microparticles. However, the priority document did not “plainly foreshadow” that this starting material should be used on its own outside the stabilised suspension system. Defining the microparticle outside its suspension environ is a “significant departure” from the original invention disclosed in the priority document and “places a very different complexion on the character of the invention” (as per Coopers Animal HealthAustralia Ltd v Western Stock Distributors Pty Ltd (1987) 11 IPR 20).
In addition, the fair basis test of Lockwood v Doric (supra) requires a comparison between what the earlier specification says is the invention and what the later claims define as the invention. PD-1 and PD-2 clearly disclose and define the invention as a suspension system containing fluid-permeated microparticles. The dry powder formulations envisaged by the opposed claims are not the same invention as the stabilised dispersions containing the microparticles disclosed in the priority documents. Hence, all the claims in the opposed specification (as they encompass powder composition per se) are not fairly based on either PD-1 or PD-2.
particular active ingredients
Both PD-1 and PD-2 envisaged that any suitable active ingredient could be used in the drug delivery method of the invention. The list of specific active ingredients defined in claim 1 of the opposed specification are all known to be useful in treating lung conditions and in my view, the earlier broad disclosure in PD-1 and PD-2 is sufficient to provide a "real and reasonably clear" disclosure of the classes of drugs now specifically defined in the claims of the opposed specification.
particular MAD (less than 5µm) and bulk density (less than about 0.5g/cm3) values
The applicant argued that the inclusion of specific values for the mean aerodynamic diameter and bulk density was merely defining extra parameters which were already inherent in the exemplified microstructures. According to the applicant, this provided a “real and reasonably clear” disclosure to support a claim to priority.
However the invention disclosed in PD-1 and PD-2 was a plurality of perforated microstructures through which suspension medium could substantially permeate. PD-1 states at page 8, lines 5 et seq that any biocompatible material can be used for the microstructures (including heavy particles with high MAD). It is not sufficient that the exemplified microstructures of the priority document inherently had the features now claimed. There was no recognition or teaching in either document that the microstructures should also have a low bulk density and low MAD because neither feature was considered important in the stabilised suspension system. As a consequence, the priority documents did not “plainly foreshadow” the invention now claimed in the opposed specification.
In my view, both PD-1 and PD-2 fail to mention the importance of MAD or bulk density in the working of the invention and does not teach the skilled worker to produce microstructures with the properties defined in the opposed claims. The invention disclosed in the priority documents is different to that disclosed in the opposed specification with respect to both the MAD and bulk density values. There is not a “real and reasonably clear” disclosure of either feature in PD-1 or PD-2.
a particular volume displacement value (less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid)
The opponent argued that both PD-1 and PD-2 suggest that microparticles should displace less than 50% of the liquid medium (compared with an analogous solid microparticulate structure) and this was broadened to 70% in the opposed specification. The opponent therefore suggested that there was no disclosure of microparticles which displace liquid medium between 50 and 70%.
I note that there is nothing “special” about microparticles with displacement values between the two ranges which had not been contemplated in the earlier priority documents. Further, while the priority document discusses a preferred particulate volume of less than 50% (later referred to in the opposed specification as the "displacement volume"), it broadly claims a dispersion containing perforated microstructures which can be substantially permeated by the suspension medium. I have nothing before me to suggest that this would not also include a microparticle with a displacement volume less than 70%. Given this, the specific inclusion of the range 50-70% appears to be a clarification of the range broadly described in the priority documents rather than an expansion of the range as argued by the opponent. My view is that the broad disclosure does provide a “real and reasonably” clear disclosure of the full range and that there is a “real and reasonably clear” disclosure of a volume displacement volume of less than 70% of the average volume defined by the microstructure boundary.
Are the claims of the opposed specification entitled to the priority date of PD-1 or PD-2?
Based on the analysis above, I found that there is not a "real and reasonably clear" disclosure of either powder compositions or particles with particular MAD and bulk density values in PD-1 or PD-2. As a consequence, none of the claims as they encompass either feature are entitled to the priority date of either PD-1 or PD-2. D4, D5, D11 and D12 (all published after the filing date of one or both of those documents) therefore become part of the prior art base for the purposes of novelty.
Novelty
Law relating to Novelty
The test for novelty has been discussed recently in the Full Federal Court decisions of Pfizer Overseas Pharmaceuticals v Eli Lilly and Company [2005] FCAFC 224 (see paragraphs 311 et seq) and Bristol-Myers Squibb Company v FH Faulding & Co Limited (2000) 97 FCR 524. As noted in both decisions, the basic test for novelty is the "reverse infringement test" as set out in Meyers Taylor Pty Ltd v Vicarr Industries (1977) 137 CLR 228 at page 235 where Aickin J stated:
"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 invention would if the patent were valid, constitute an infringement."
Infringement is said to occur where "each and every one of the essential features of that claim have been taken" (Rodi and Wienenberger AG v. Henry Showell Ltd (1969) RPC 367).
However, as Pfizer noted it is not sufficient for a citation to contain all the essential features of the claim, there must be “clear and unmistakable” directions to the claimed invention. In that regard, the Full Court referred to three key decisions:
Canadian General Electric Co v Fada Radio Limited [1930] AC 97:
“…it is not enough to prove that an apparatus described in an earlier specification could have been used to produce this or that result. It must also be shown that the specification contain clear and unmistakeable directions to use it.”
General Tire & Rubber Co v Firestone Tyre and Rubber Co Ltd [1972] RPC 45:
“a signpost, however, clear, upon the road to the patentee’s invention will not suffice. The prior inventor must be clearly shown to have planted his flag at the precise destination before the patentee”
ICI Chemicals v Lubrizol Corp (2000) 106 FCR 214
‘... skilled addressees are not required to rummage through the prior patentee’s "flag locker" to find a "flag which the [prior patentee] possessed and could have planted".’
Novelty can however be found where a feature is not explicitly mentioned but nonetheless present as an inherent feature as an inevitable result of the disclosure. As noted in General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd (supra) at page 486:
"if in carrying out the directions contained in a prior inventor's publication will inevitably result in something being made or done which, if the claim of the opposed specification were a claim of a valid patent, would constitute and infringement of that claim, then that claim would have been anticipated".
However as also observed by the same court:
"If ... the prior publication contains a direction which is capable of being carried out in a manner which would infringe the patentee's claim, but would be at least as likely to be carried out in a way that would not do so, the patentee's claim will not be anticipated."
In addition, as noted in the Pfizer decision, a citation to deprive a claim of its novelty must be the same as the claimed invention for the purposes of “practical utility”. In other words, the citation has to “enable” the skilled worker to produce the invention from the written disclosure. The basic principle is explained in Hill v Evans (1862) 4 De G F & J 288; 45 ER 1195be where the court noted
“…the antecedent statement must be such that a person of ordinary knowledge in the subject would at once perceive, understand, and be practically able to apply the discovery without the necessity of making further experiments and gaining further information before the invention can be made useful. If something remains to be ascertained which is necessary for the useful application of the discovery that affords sufficient room for another valid patent”.
Novelty determination in the current case
Documents relied on at the hearing
In their statement of grounds and particulars, the opponent alleged that there were 13 documents which deprived the current claims of their novelty. However, the opponent limited their arguments at the hearing to 5 documents which were published before the earliest priority date of the opposed specification:
D1:International Patent Application WO 96/26746 by Alliance Pharmaceutical Corp published on 9 September 1996;
D3:D.A Edwards et al, "Large Porous Particles for Pulmonary Drug Delivery" Science 276: pp 1868-1871 (published 20 June 1997);
D4:Published Ph.D. thesis by Justin Haynes at the Massachusetts Institute of Technology (MIT) entitled "Polymer Microspheres for Vaccine Delivery" dated September 1996, archived by the MIT library on 31 July 1997 (at which time the thesis could have been viewed at the Institute Archives) and catalogued there on 5 December 1997 (at which time the cataloguing record was made public) (after the filing of PD-1 but before the date of filing of PD-2);
D5:International Patent Application WO 97/44013 by Massachusetts Institute of Technology and The Penn State Research Foundation published on 27 November 1997 (after the filing of PD-1 but before the date of filing of PD-2);
D11:International Patent Application WO 98/31346 by Massachusetts Institute of Technology and The Penn State Research Foundation published 23 July 1998 (after the filing of PD-1 and PD-2 but before the date of filing of PD-3).
D1 discloses a gas emulsion forming composition which contains dry, hollow, particulate, approximately microspherical material permeated with a gas or gas mixture and which is used as a contrast enhancement agent for ultrasound technology. Four of the inventors of the opposed application are also inventors on D1 and (as conceded by the applicant at the hearing) the microparticles used in D1 are made by the same spray drying process and would inevitably have the same structural properties as those used in the current specification (ie: a mean aerodynamic diameter of less than 5µm, and a bulk density of less than about 0.5g/cm3, wherein, when suspended in a fluid medium, the volume of the medium displaced by the perforated microstructures comprises less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid).
I note that D1 does not suggest that the powder composition could be used as a pulmonary drug delivery agent. However the composition disclosed in D1 is surrounded by a layer containing at least two surfactants. One of the surfactants disclosed in D1 also happens to be used in the treatment of lung problems in infants and therefore inadvertently falls within the scope of the current claims. The problem affects claims 1, 2, 4-19 and the applicant agreed to amend the claims to overcome the problem.
The remaining citations are D3, D4, D5 and D11. These are all similar publications having emanated from the same research group. For convenience, I will refer to this group as the “Edwards’ group” after the first listed author on three of the citations and will refer to the citations as a whole unless I need to discuss a particular feature of one of the citations. The Edwards’ group was the first group to publish the use of aerodynamically light microparticles as carriers in the pulmonary delivery of therapeutic agents particularly in dry powder aerosols. The Edwards’ citations noted that the increased aerosol efficiency of large, light particles lowers the probability of deposition losses before particle entry into the lungs, thereby increasing the systematic bioavailability of an inhaled drug.
Each citation disclosed a preferred embodiment containing particles with a large mean diameter (greater than 5 µm) but a small mass density (a tap density less than 0.4 g/cm3). Calculating the MAD from this data, the density and MAD values fall within the range defined in claim 1 of the opposed specification. The applicant did not argue otherwise. While the applicant noted that there was slight difference between the terms “tap density” (as used in the citations) and “bulk density” (as defined in the opposed specification), they did not suggest that this would have then translated to a different density value which was outside the range defined in the opposed claims.
Instead, the applicant argued that the difference between the Edwards’ citations and the opposed claims is the requirement that the volume of the medium displaced by the perforated microstructures comprises less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid (I will refer to this as “the volume displacement limitation”).
Given the evolution of the invention (from liquid suspension to dry formulation), I had some concerns that the volume displacement limitation may not be an essential integer of the dry powder claims. I could see that the limitation was important in a liquid environment where the surrounding medium needs to penetrate the microparticle but outside this environment, it is not immediately apparent what advantage this feature would confer. This issue was not raised by the opponent at the hearing. Given this, and the fact that there could be some advantage in the dry powder formulation that I am not aware of (such as increasing surface roughness and thereby reducing agglomeration), I am prepared to accept that volume displacement limitation is an essential integer of the claims. As a consequence, a citation will need to disclose this feature (in addition to the other essential integers) in order to deprive the claims of their novelty.
While the citations D3, D4, D5 and D11 all disclose the broad principle of making aerodynamically light particles, none explicitly teach that the microparticles must also be permeable to the surrounding media. As the citations all focus on dry powder formulations, it is likely that permeability to the surrounding medium was not considered a relevant factor. Thus, while the citations all use the term “porous” to describe a microparticle, this is referring to the hollow (light) nature of the particle in the context of the citation rather than its permeability. As Dr Tarara noted in evidence in answer (at paragraph 28), a closed pore system may well contribute to the reduction of density of the certain particles but would not allow a fluid medium to enter these particles. Hence, the feature “porosity” cannot be taken to be “clear and unmistakeable directions” to the volume displacement limitation of the opposed claim 1. Further, any “porosity” values in the citations cannot be directly compared to the volume displacement limitation referred to in the current specification.
The opponent did not dispute this construction but argued instead that the volume displacement limitation was an inherent property of the microparticles exemplified in the citations. According to the opponent, the scanning electron micrographs (see figure 7-1 of D4), the confocal micrographs (see figure 7-2 of D4), and the computer enhanced image of a micrograph of the particles (see D3 - next to the table of contents in the Science issue in which D3 appears) all indicate a highly porous microstructure containing a large number of external pores. Given this, the opponent argued these structures would necessarily be able to absorb enough surrounding medium to fall within the claimed volume displacement limitation parameters defined in claim 1 of the opposed specification and that the particles disclosed in the citation would therefore fall within the scope of the opposed claims.
The applicant disputed the opponent’s allegation that a skilled worker could determine “by eye” from a micrograph whether a particular microparticle would have a certain volume displacement value (see Dr Tarara’s declaration at paragraph 35). I note that the opponent did not attempt to estimate how much volume would likely be displaced by the microparticles from these and I agree that the scanning and confocal micrographs do not give any indication of how much volume is likely to be absorbed by the particles because neither show how if (or how much of) the internal pore network is accessible from the external pores. As a consequence, the apparent morphological similarity between the microparticles of the prior art and figures 1, 2 and 3 of the current specification (shown in the scanning and confocal micrographs) is not sufficient to show that the prior art also had the same volume displacement limitations.
The opponent argued that the computer enhanced image in D3 discussed at the hearing showed that the prior art microparticles have a “wiffle ball-like” structure which is likely to be highly permeable. However, the image was merely an “advertising teaser” for the Science article (next to the table of contents of the main journal) and not part of the Science article itself. There was therefore no discussion about how the image was generated and what it was intended to represent – either next to the image itself or in the Science article. The opponent’s evidence in support also failed to explain the image (which is particularly surprising given that the opponent’s expert was also the lead author of the citation). Without such explanations, the opponent’s view (presented from the bar table at the hearing) of what the image might represent has little weight.
My view is that it is not possible from the evidence before me to conclude from the image or any of the micrographs that the microparticles were highly permeable and had the volume displacement limitations imposed in the claims of the opposed specification. As noted in the decision of F. Hoffmann-La Roche AG v New England Biolabs, Inc. (2000) 99 FCR 56, the role of an opposition is only to refuse a patent application if it is clearly invalid. The onus is therefore on the opponent to prove that the citation disclosed the volume displacement limitation.
Rather than providing experimental evidence to demonstrate that prior art particles produced under the conditions of the citations were necessarily permeable, the opponent has assumed that the particles are the same and have relied on micrographs to support their view. However, there is no clear teaching in the citations to generate a permeable microparticle. Further the methodology used in the citations to generate their microparticles is not the same as that used in the opposed specification and therefore there can be no underlying presumption that the microparticles produced in the citations are necessarily the same as those exemplified in the current specification.
Given this, the only evidence before me to show that the microparticles of the citations are the same as those now claimed is the micrographs themselves in the citations. However, as noted above, it is not possible to conclude from these alone that the microparticles have a certain volume displacement limitation. As a consequence, the opponent has failed to establish that any of the citations contain this essential integer of the claimed microparticles. As a consequence, none of the claims lack novelty in light of the citations D3, D4, D5 or D11.
Documents not relied on at the hearing
The opponent made no specific submissions at the hearing about the other 8 documents cited in the statement of grounds and particulars but nonetheless argued that these documents also deprived the claims of their novelty. These documents are as follows:
D2International Patent Application WO 96/32149 by Inhale Therapeutic Systems published 17 October 1996;
D6 US patent number 5, 611,344 by Bernstein et al published 18 March 1997;
D7 US patent number 4,180,593 by Cohan published 25 December 1979;
D8International Patent Application WO 94/07514 by Inhale Therapeutics Systems published on 14 April 1994;
D9International Patent Application WO 95/01324 by Glaxo Group Limited published on 12 January 1995;
D10 UK patent application GB 2 105 189 by Fisons plc published on 23 March 1983;
D12International Patent Application WO 98/29096 by Inhale Therapeutics published on 9 July 1998 (after the filing of PD-1 and PD-2 but before the date of filing of PD-3);
D13J.G. Weers "Colloidal particles in drug delivery" published in Current Opinion in Colloidal and Interface Science Vol. 3:540-544 dated 1998
However, despite this, they nonetheless still maintained that the current claims were not novel in light of the additional documents. I therefore need to deal with each of these citations in this decision.
D2, D8, D9, D10 and D12 all relate to dry powder compositions for targeted pulmonary delivery of pharmaceutical drugs. The powder compositions in each of the citations contain a bioactive agent from the list defined in the opposed claim 1, and a mean aerodynamic diameter of less than 5µm. D9 and D10 also specifically discloses that the powder formulations have a bulk density of less than about 0.5g/cm3. However, none of the citations disclose the feature that the microparticles are perforated. Further, none of the citations indicate that their powder formulations, when suspended in a fluid medium, displace a volume of the medium which is less than 70% of the average volume that would have been displaced if the microstructure were solid. This means that the claims do not disclose all of the essential features of claim 1. Hence this claim (as well as the remaining claims which are all either directly or indirectly dependent on claim 1) are novel in light of D2, D8, D9, D10 and D12.
D6 discloses a microencapsulated fluorinated gas for use as an ultrasound imaging contrast agent. Because the microcapsules are merely used to enhance the image in an ultrasound, there is no suggestion that they contain a bioactive agent as required by claim 1. Hence, claim 1 (and therefore all the claims) are novel in light of D6.
D7 discloses a spray drying process of producing round spherical free flowing beaded food products. The process enables the bulk density of the products to be regulated and ensures that the product is substantially uniform. In addition, the process minimises the presence of vapour holes in the product surface. This citation does not teach the presence of a bioactive agent, a mean aerodynamic diameter of less than 5µm, or bulk density of less than about 0.5g/cm3. Further, the disclosure teaches away from having external pores which allow displacement of media when in suspension. As a consequence, this citation does not deprive any of the claims of their novelty.
There is no evidence before me that D13 was published before the priority date of the current claims. Therefore it does not appear to be part of the prior art base for novelty and I do not need to consider it further. I do note however, that even if the citation were relevant for novelty, it is merely a review of the state of the art and adds nothing over the other citations raised by the opponent.
In my view, the opponent has not established that any of the citations D2-D13 deprive the claims of their novelty. However there is a technical novelty problem with D1 as the applicant conceded at the hearing. The microparticles described in D1 as ultrasound image contrast agents are structurally similar to those disclosed in the current specification used for pulmonary drug delivery. Because one of the surfactants disclosed in D1 happens to be used in the treatment of lung problems in infants, it inadvertently falls within the scope of claims 1, 2, 4-19.
Inventive Step
The opponent did not discuss the ground of inventive step at the hearing and I agree that it is not an issue in the current case. Even assuming that each of the prior art documents raised by the opponent could be considered part of the prior art base for obviousness, there was no motivation from any of those documents or the common general knowledge to use microstructures with the capacity to allow a fluid medium to enter the particle. As a consequence, the skilled worker faced with a problem of stabilising dispersions for use in pulmonary drug delivery would not be directly led to generate a perforated microstructure which, when suspended in a fluid medium, displaced a volume of the medium which was less than 70% of the average volume of a solid microstructure with the same boundary. As a consequence, all of the claims are inventive based on the evidence before me.
Section 40
The opponent raised a number of issues on section 40 in their statement of grounds and particulars but only pursued two clarity/fair basis issues at the hearing in relation to claim 1 (as amended). I will deal with each issue separately.
The term "perforated" as used in the claims is ambiguous and so broad that the claims fail to define the invention and are unclear.
The opponent argued that the definition provided of the term "perforated" in the specification is very broad and unclear. The definition on page 18, lines 19-22 defined “perforated” to include “voids, pores, defects, hollows, spaces, interstitial spaces, apertures, perforations or holes”. According to the opponent, the term “perforated” embraces not only one or more holes in the microstructure shell but also other surface morphologies or defects such as a dimple, dent, bump, crack, deformation and crenulation. As most surface morphologies would have such a defect, the opponent argued that the word has no defining meaning in the claims and therefore the claims lack clarity.
The opponent in criticizing the term “perforated” in isolation has failed to consider the scope of the claim as a whole. As Lindgren J noted in Nesbit Evans Group Australia Pty Ltd v Impro Ltd (1997) 39 IPR 56, there is a danger in considering the integers of a claim individually and in isolation because this can lead to a literal rather than a purposive construction. Even if the term “perforated” is as broad as the opponent suggests, there are a number of additional limitations imposed on the claimed microstructure (including a specific mean aerodynamic diameter, a particular bulk density and a volume displacement limitation) which restrict the claim to a reasonable scope. The term “perforated” is an additional limitation which simply narrows the scope of the claim further.
In any event, I note that the perforations allow liquid to permeate the internal structure of the microparticle. To achieve the volume displacement limitation defined in the claims, the perforations would need to be significant and not the minor “dimples, dents, bumps, cracks, deformations and crenulations” that the opponent alleged. As a result, in the context of the claim, the term “perforated” is not as broad as the opponent suggests.
The opponent also alleged in their statement of grounds and particulars that the term “perforated” was ambiguous. As I understand their argument, the alleged ambiguity arises because of slightly different definitions given to the term “perforated” in the priority documents (PD-1 at page 8; PD-2 at page 6 and PD-3 at page 12) compared with the opposed specification. However a term in a patent specification is construed on a fair reading of the specification itself. There is no basis to import a definition from a priority document to construe a term. The term “perforated” is specifically and unambiguously defined in the opposed specification. It is irrelevant whether the term is defined differently in the priority documents. In my view, the term “perforated” is clear in the opposed specification.
The "volume displacement" feature fails to define the invention, is unclear and not fairly based upon the specification.
In the claims of the opposed specification, the volume of the medium displaced by the perforated microstructures (when suspended in a fluid medium) has to comprise less than 70% of the average volume defined by the microstructure boundary if the microstructure were solid. The opponent argued that this "volume displacement" feature is "meaningless as stated" to the skilled addressee. According to the opponent, the specification failed to provide the test conditions for measuring volume displacement. The opponent alleged that since volume displacement can vary with different test conditions, it is not possible to determine what would or wouldn't fall within the scope of the claims.
However as the applicant argued, volume displacement is simply a measurement of the volume shifted by the introduction of the microparticle. Its measurement would be well within the expertise of the skilled worker without the need for particular test conditions to be outlined in the specification. I also believe that the skilled worker would appreciate the need to select test conditions which would interfere as little as possible with the integrity of the particles in order to accurately determine volume displacement and that these conditions would vary depending on the nature of the particle.
The opponent failed to provide any evidence that the selection of appropriate test conditions was outside the common general knowledge of the skilled worker. Having selected such conditions, it is not clear that the variation referred to by the opponent remains a problem. As a consequence, the opponent has failed to establish that the absence of specific test conditions would render the claim unclear.
The opponent also argued that it would be difficult to calculate the boundary of the solid microparticle (the "virtual particle") where the original particle had an odd shape. Given this problem, the opponent suggested it would also be difficult to obtain an accurate volume displacement measurement for these odd shaped particles. As a result, a skilled worker could not determine whether an odd shaped particle fell within the scope of the claims.
I note that patent claims frequently contain terms that are imprecise. This does not give rise to an objection of lack of clarity if it is possible for the addressee to ascertain whether or not an act falls within the ambit of the claim. This is a practical determination, rather than a strictly literal exercise, and it is acceptable if there is minor uncertainty at the edges of a claim:
"The court will give little weight to puzzles which may arise 'at the edge of the claim' if those puzzles would not, as a practical matter, cause difficulty for the skilled addressee or manufacturer wishing to satisfy himself that what he proposes to do will not infringe that patent."
(Glaverbel SA v British Coal Corp, [1994] RPC 443 at 495)
In the current case, I am not convinced there is a practical problem determining the boundary of the virtual particle. The claim requires a simple comparison between the displacement volumes of a microparticle with perforations with an equivalent microparticle without perforations (solid microparticle). Given that the test conditions are within the common general knowledge of the skilled worker, the comparison would also be straight-forward regardless of whether the exact boundary of the particles could be calculated. I am therefore unable to see the practical problem alleged by the opponent and in my view, the term is clear.
CONCLUSION
None of the claims are entitled to claim priority from the priority documents PD-1 or PD-2 and hence documents D4, D5, D11 and D12 (all published after the filing date of one or both of those documents) become part of the prior art base for the purposes of novelty in addition to D1-D3, D6-D10 and D13 which were all published prior to PD-1.
Despite this, the opponent has not established that any of the citations D2-D13 deprive the claims of their novelty. There is however a technical novelty problem with D1 (which shares common inventors with the opposed application). One of the surfactants used in the ultrasound imaging contrast agents disclosed in D1 also happens to be used in the treatment of lung problems in infants. As a consequence, the microparticles (disclosed in D1) inadvertently fall within the scope of claims 1, 2, 4-19.
Otherwise, there are no inventive step or section 40 problems with the opposed application. As the specification clearly contains patentable subject matter, I allow the applicant 60 days in which to propose amendments to overcome the deficiencies noted in this decision.
COSTS
In matters before the Commissioner, costs generally follow the event. In this case, the opponent was partly successful at the hearing but only in relation to a minor novelty issue. The applicant narrowed their claims earlier in the opposition proceedings in light of evidence served by the opponent. In such circumstances, I allow costs against the applicant up until the date they filed amendments under section 104 (4 March 2005) but award no costs to either party after that date.
Karen Ayers
Delegate of the Commissioner of PatentsPatent attorneys for the applicant : Griffith Hack, Brisbane
Patent attorneys for the opponent : Pizzeys Patent and Trade Mark Attorneys, Canberra
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