Alza Corporation v Cygnus Research Corporation

[1993] APO 9

official notice

decision of a delegate of the commissioner of patents

Application        :    No. 565177 in the name of ALZA
  CORPORATION

Title             :    Device for Transdermal Administration
  of Fentanyl

Action : Opposition under s.59 by CYGNUS
  RESEARCH CORPORATION

Decision           :    Issued            .  Section 40
  defects.  Applicant given the
  opportunity to amend.

patents act 1990

decision of a delegate of the commissioner of patents

Re:Patent Application No. 565177 by ALZA CORPORATION and Opposition under S.59 of the Patents Act 1952 by CYGNUS RESEARCH CORPORATION

background

ALZA CORPORATION (Alza) lodged patent application no 565177 under the Patents Act 1952 on 3 July 1985. This was a Convention application based on an earlier application lodged in the USA on 23 July 1984.

The Office advertised acceptance of the application on 10 September 1987.  CYGNUS RESEARCH CORPORATION (Cygnus) lodged notice of its opposition to the acceptance of the application on 10 March 1988 after being given a three months extension of time within which to lodge notice of opposition.

Following service of the evidence-in-support, evidence-in-answer and evidence-in-reply, all of which required several extensions of time for filing, the Office set down the matter for hearing in Canberra on 27 August 1992.  Dr A Bennett of counsel assisted by Dr Ian T Ernst, patent attorney of Shelston Waters, represented the applicant at the hearing.  Mr B Hess of counsel assisted by Mr Ian A Scott, patent attorney of Watermark, represented the opponent.

As the application was both filed and advertised accepted before the commencement of the Patents Act 1990, the provisions of section 234(3) of the 1990 Act, and regulation 23.3, are applicable.

The notice of opposition states the grounds of opposition are those specified in paragraphs (e), (g), (h) and (i) of sub-section (1) of section 59 of the Patents Act 1952. The opponent also reserved the right to base its opposition on the grounds specified in paragraphs (c), (d) and (f). At the hearing all submissions were directed to the grounds of novelty, obviousness, manner of manufacture and compliance with s.40 ie grounds (f), (g), (h) and (i).

SPECIFICATION

The specification commences by indicating that the invention relates to the administration of fentanyl for analgetic purposes, and more particularly to a method and device for administering fentanyl to a subject through intact skin over an extended period of time.
This is followed by a discussion of the prior art where it is admitted that:

a)Fentanyl is a known drug which is normally administered as the citrate either as a bolus injection or infusion or a continuous infusion for the purposes of producing anaesthesia or analgesia.

b)The transdermal drug delivery technology as discussed in US patents 3598122, 4144317, 4201211, 4262003 and 4379454 incorporated into the specification by reference are representative of various transdermal drug delivery systems of the prior art.

I note that, according to the specification, none of the above patents nor any other prior art of which the inventors were aware describes a transdermal delivery system which is intended to deliver fentanyl or its derivatives.  Furthermore the inventors were not aware of any data on skin permeability or therapeutic transdermal delivery rates adequate to design such a system.

c)Fentanyl and its derivatives are highly potent, rapidly metabolized drugs having a relatively narrow therapeutic index which produce extremely undesirable side effects on overdosage.  The applicants found that these characteristics impose numerous and sometimes conflicting design constraints on a practical transdermal delivery device.  For example the specification indicates that:

1. it would be desirable that the device deliver the drug at a substantially constant rate for at least about 24 hours while at the same time keeping the amount of drug within both the unused and depleted systems to a minimum; and

ii)the degree to which the system controls the release rate should be relatively high in order to ensure that excessive amounts of the drug are not delivered in the event that the skin of a patient has been damaged or has an abnormally high permeability.

The specification then includes a consistory statement which corresponds to claims 1 and 22.  In the subsequent description of the invention it is stated that fentanyl or its derivatives should be administered to the human body via the transdermal route preferably through about 5-100 cm2, and more preferably about 10-50 cm2, of intact skin over an extended period of time at the rate within the range of about 0.5 to 10 ug/cm2/hour and more preferably within the range of approximately 1-5 ug/cm2/hour.

Furthermore the applicant discovered that fentanyl citrate, the form in which fentanyl was previously administered, had such a low skin permeability that it was not at all suitable for transdermal delivery even with the use of permeation enhancers.  Therefore, in order to obtain the delivery rates given above, the drug was incorporated in the transdermal therapeutic system in the form of the base.  Permeation enhancers could be used to increase the permeability of fentanyl.

The applicant also found that skin contains fentanyl binding sites which must be saturated before any significant absorption of the drug into the bloodstream occurs.  To provide rapid onset of analgesia initial saturation of these sites should proceed rapidly.  The transdermal systems of the invention are capable of delivering the drug at initial rates which should induce the onset of analgesia within 2 to 4 hours after application.  The skin binding sites also establish an upper limit on the size of the transdermal system and a lower limit on the usable delivery rate.

The specification goes on to describe various specific embodiments of the invention.  In the examples of the invention the permeation rates of the fentanyl base are in vitro tested in relation to human cadaver skin.

The specification ends with 58 claims of which claims 1, 16, 22 and 28 are independent claims.  These independent claims read as follows:

1. A process for inducing and maintaining analgesia which comprises administering through an area of intact skin, a skin permeable form of a material selected from the group consisting of fentanyl base and its analgetically effective derivatives at an analgetically effective rate and continuing the administration of said material at a substantially constant rate for an extended period of time at least sufficient to induce analgesia.

16.A process for the transdermal administration of a material selected from the group consisting of fentanyl base and its analgetically effective derivatives which comprises:-

(a)contacting a predetermined area of intact skin with a source of skin permeable form of said material;

(b)maintaining said source in material transmitting relationship to said area of intact skin for an administration period of at least 12 hours; and

(c)delivering said material into the skin at a substantially constant rate within the range of 0.1-10 ug/cm2/hour for at least 12 hours.

22.A medical device for the transdermal administration of a material selected from the group consisting of fentanyl base and its analgetically effective derivatives at a substantially constant analgetically effective rate for an extended period of time of at least 12 hours which comprises:-

(a)reservoir means containing a skin permeable form of said material in an amount sufficient to deliver said material at said analgetically effective rate for said extended period of time and,

(b)means for maintaining a said reservoir means in material transmitting relationship to intact skin.

28.A medical device for continuous transdermal administration of a material selected from the group consisting of fentanyl base and its analgetically effective, derivates comprising, in combination:

(a)a reservoir for said material having a skin proximal, material releasing surface area in the range of 5-100 cm2, said reservoir containing between 0.1 and 50% by weight of a skin permeable form of said material in amounts and at a concentration adequate to permit delivery of said material through intact human skin at a substantially constant rate within the range of from 0.5 to 10 ug/cm2/hr for at least 12 hours and

(b)means for maintaining said reservoir in material transmitting relationship to the skin.

evidence

The evidence lodged in support of the opposition consists of:

1. A statutory declaration by Dr Igor Gonda, a senior lecturer in the Department of Pharmacy, University of Sydney.  This declaration has 3 Exhibits of which Exhibit IG-3 includes 22 prior art references.  The declaration discusses the claims of the specification in the light of those references and draws particular attention to references 8 (Michaels), 14 (Chien) and 7 (Shaw).

ii)A statutory declaration by Dr Peter J Stewart, a senior lecturer in the Department of Pharmacy, University of Queensland.  This declaration has 3 Exhibits of which Exhibit PJS-3 includes 21 prior art references.  Dr Stewart explains why, in his opinion, the invention described and claimed in patent application no 565177 is obvious in the light of the prior art.

iii)A statutory declaration by Ian Alexander Scott, a registered patent attorney.  This declaration establishes the publication dates of the prior art references in the Gonda and Stewart declarations.

The evidence lodged in answer consists of:

1. A statutory declaration by Laurence E Mather, a professor of anaesthesia and analgesia research at the School of Medicine, the Flinders University of South Australia.  This declaration has 3 Exhibits.  Prof Mather explains why, in his opinion, the invention is not obvious in the light of the prior art and argues against the conclusions reached by Drs Gonda and Stewart.

ii)A statutory declaration by Dr Mary A Southam, product registration manager and research scientist at Alza Corporation.  This declaration has 6 Exhibits of which Exhibit F includes 8 prior art references.  Dr Southam discusses the clinical studies conducted to establish the safety and efficacy of the transdermal dosage form of fentanyl.

iii)A statutory declaration by Dr David Enscore, senior research scientist, senior project development manager and area director, Physical Sciences at Alza Corporation.  This declaration has 4 Exhibits of which Exhibit D includes 11 prior art references.  Dr Enscore discusses the transdermal delivery of drugs, particularly in relation to the disclosure in his prior art reference 2 (Michaels), and the screening of compounds for use as permeation enhancers.

The evidence lodged in reply consists of:

1. A further statutory declaration by Dr Igor Gonda.  Dr Gonda considers in turn each of the 3 declarations of the evidence-in-answer and indicates why he disagrees with the conclusions reached.

ii)A further statutory declaration by Dr Peter J Stewart.  Dr Stewart also considers the applicant's 3 declarations and indicates where he disagrees with that evidence.

At the hearing Dr Bennett objected to certain passages in the declarations filed as evidence-in-support and evidence-in-reply.  These mainly concerned assertions as to what was common general knowledge and what would have been obvious to a person skilled in the art.  Dr Bennett submitted that the declarants were not entitled to make these assertions and therefore certain passages should be omitted from the evidence.  Mr Hess for the opponent agreed that these passages would no longer form part of the opponent's evidence and therefore I shall have no regard to them in my decision.

I will not discuss the evidence further here but will refer to the relevant parts of the evidence at the appropriate points in my decision.

submissions

At the hearing Dr Bennett gave an account of the invention, focussing special attention on the independent claims 1, 16, 22 and 28.  She indicated that if any of these claims were found to be deficient, the applicant did not agree the appendant claims would fall with them.  She sought to amend an error in claims 49 and 51-58 by inserting "u" before "g/cm2/hr".  Mr Hess for Cygnus agreed to this amendment.  I note that a section 104 request has now been filed in relation to these amendments.

On behalf of the opponent Mr Hess considered the prior art references of Exhibit IG-3 of the first Gonda declaration, pointing out that there was no one publication which disclosed and taught the applicant's invention.  In other words the invention defined by the claims was not prior published.  However a consideration of the prior art showed that fentanyl was a known substance with known properties.  Reference 8 (Michaels) relates to drug permeation through human skin and includes fentanyl in the list of compounds which were tested.  Transdermal administration of drugs was also known.  Reference 14 (Chien) summarises all the material known to Chien about transdermal application, and includes a cross reference to the Michaels article.  Therefore, in Mr Hess' submission, the invention defined by the claims failed for lack of novelty since it was merely a combination of a known substance and a known device.  The specification at page 2 refers to design constraints on a practical transdermal delivery device, but does not indicate any new or unexpected result from using fentanyl in a transdermal device.  It merely describes design desiderata for the device at page 3, which desiderata are well canvassed in Chien, for example the use of permeation enhancers.

Furthermore Mr Hess submitted that the 3 US patents 4201211, 4262003 and 4379454 referred to at page 2 of the specification were common general knowledge since the inventor had incorporated them into the specification.  In Mr Hess' opinion any one of the transdermal devices disclosed in those US patents could be used to administer fentanyl.  Therefore he submitted the patent application was merely directed to the reorientation of a known device to deliver a known substance in a known way for a known purpose.  The variation from the known device involved the use of a different drug ie fentanyl.  This made no substantial contribution to the working of the device and therefore the claims were not novel.  In reaching this conclusion Mr Hess relied on the test in Griffin v Isaacs (1942) 12 AOJP 739 which was endorsed by Lockhart J in R D Werner & Co Inc v BaileyAluminium Products Pty Ltd 85 ALR 679.

Alternatively Mr Hess submitted that the use of fentanyl in a known transdermal delivery device was a mechanical equivalent or workshop variation of what was known in the art, and again the claims lacked novelty.  In this event he relied on NicaroHoldings Pty Ltd and Others v Martin EngineeringCo and Another 16 IPR 545.

In response Dr Bennett put to me that I should decide the issues in the opposition on the evidence, and pointed out that there was no evidence to show any publication had become common general knowledge.  She referred me to the Enscore declaration which, inter alia, made the following points:

.Prior to fentanyl only 4 drugs had transdermal delivery devices approved for systemic administration in the United States (para. 5).

.Not all drugs suggested in the prior art as possible candidates for transdermal administration actually possess the properties required to safely produce the desired therapeutic effect when administered transdermally (para.6).

.The administration pattern for transdermal drug delivery is significantly different from conventional dosage forms (para. 7).

.The Michaels reference (supra) teaches away from the use of fentanyl for transdermal administration (para. 11).

.Alza has not identified a "universal" permeation enhancer (para 19).

.Use of a permeation enhancer complicates the design and development of a transdermal delivery device (para. 22).

Dr Bennett submitted that the invention was a combination patent, the inventors having to work out how to administer fentanyl through a transdermal device by considering features such as administration rates, flux and permeation enhancers.  She also relied on the decision in Nicaro v Martin (supra), in particular at page 549 where Lockhart J endorsed the "reverse infringement" test as the test for novelty whereby all the essential features of the invention must be disclosed in the prior art. She pointed out that there was no evidence of what the skilled addressee would perceive from the prior art publications. Furthermore it is the interaction of integers producing a new result which constitutes the invention in a combination patent (Lockhart J at page 553).

On the question of mechanical equivalents and workshop improvements Dr Bennett submitted that the use of fentanyl, which had previously been used only as an injection or orally, in a transdermal device could not be a mechanical equivalent since the device had to be manipulated before it would work.

Mr Hess then considered the question of obviousness.  Following the test proposed by Aickin J at page 237 in Meyers Taylor Pty Limited v Vicarr Industries Limited and Others (137 CLR 228), he submitted that since fentanyl was a known drug with known characteristics it was a matter of routine to use it in a known transdermal device. Furthermore the addition of fentanyl to a known transdermal device produced no unexpected result or benefit, the inventor merely achieving the desired result without the exercise of inventive skill. Therefore in Mr Hess' view the invention was obvious.

For similar reasons Mr Hess considered the invention was not a manner of manufacture since the claims merely put together 2 known things, namely fentanyl and a transdermal delivery device.  He submitted that the device required no adaptation because of special difficulties in using fentanyl and hence the use of fentanyl was an analogous use.

Dr Bennett submitted that since the opponent had not established by evidence what was common general knowledge it could not rely on the ground of obviousness.  She pointed out that, per Nicaro vMartin (supra) at page 558:

.It was not possible to mosaic publications where they were not common general knowledge; and

.There was no evidence from the non-inventive skilled worker, which was vital for a combination patent.

She further submitted that the use of fentanyl in the transdermal device was a new use.  Dr Bennett referred to various passages in the early part of the specification where the problems which had to be overcome in getting the device to work with fentanyl were mentioned.  Therefore, in her view, the invention lay in working out how to administer fentanyl through a transdermal device, and so it followed that the use of fentanyl was not an analogous use.

With respect to section 40 Mr Hess made the following submissions:

.The specification is insufficient in relation to the promise of the invention, which is to achieve a transdermal drug delivery system with fentanyl for analgetic purposes.  The specification therefore ought to describe in vivo testing in humans or animals to show the efficacy of the device to induce analgesia.  However the examples are directed solely to in vitro testing.  The declaration of Enscore at paragraph 13 mentions that knowledge of in vitro flux did not necessarily assist in determining the suitability of a drug for transdermal administration.

.Claim 1 is not fairly based since the process of inducing analgesia is not fully described.

.There is no indication in the specification of what constitutes "an analgetically effective rate" in claims 1 and 22.  The description at page 4 refers to a preferable rate of "0.5 to 10 ug/cm2/hour" but there is no reference to this being analgetically effective.  Therefore claims 1 and 22 are not fairly based.

.Claims 16 and 28 are similarly not fairly based because it is not clear whether the delivery rate specifically mentioned is analgetically effective.

.Claim 1 is very broad and could be directed to any process using fentanyl to induce analgesia provided there is continuous administration.  It could therefore include administration by intravenous injection.

.The claims as a whole are not supported by the description.  The features in the dependent claims do not save the fatal defects of the independent claims.  For example in claim 30 there is the first mention of a "release rate controlling means" which, from the specification, is an essential feature of the invention.  Claim 30 is appended to claim 28 which does not refer to analgesia.  Incorporating the features of claim 30 into claim 28 therefore will not save claim 28.

Dr Bennett considered that any doubt in granting the patent should be resolved in favour of the applicant, following the decisions in Commissioner v Microcell (102 CLR 232) and International Business Machines Corporation v Smith (1991 ALR 388). She did not agree with Mr Hess' submission that if the independent claims were found to be wanting the remaining claims also fell.
She then made the following submissions concerning section 40:

.Sufficiency is a question of fact to be determined by the evidence (Asahi Kasei Kogyo Kabushiku Kaisha v W R Grace &Co 22 IPR 491 at page 516). There is no evidence of any insufficiency. The invention concerns the delivery of fentanyl into the body and the specification describes this. The "in vivo" argument raised by the opponent concerns the question of inutility rather than insufficiency, and there is no evidence that the device does not work.

.The claims satisfy the 3 "Mond Nickel" rules (In the matterof the Mond Nickel Company Ltd's Application for a Patent 1956 RPC 189) and are therefore fairly based. The claims must be construed in the light of the specification to resolve any ambiguity.

.The term "an analgetically effective rate" serves to narrow the claims.  The claims would define the invention without reference to this rate.  The specification gives sufficient information to support this rate and there is no evidence that the rate is ineffective.

.Claim 1 refers to "an area of intact skin".  By definition "intact" means untouched and therefore claim 1 cannot include administration by injection.

decision

Novelty

Both Mr Hess and Dr Bennett considered that the invention was a combination patent, but they differed as to whether that combination was new.  The facts that fentanyl was a known drug and that transdermal delivery devices were known at the priority date of the application are not in dispute.  However the question to be answered is whether the combination of fentanyl and a transdermal device is new.

In considering whether a combination is novel I am mindful of the words of Lockhart J in Nicaro v Martin (supra) at page 553:

"Each of the integers of a combination patent may not be novel.  They may be part of the prior art, but it is the interaction of the combined integers to produce a new result which constitutes the invention the subject of a combination patent."

In Mr Hess' view Alza had merely indicated some well known design desiderata which were necessary to incorporate fentanyl into the transdermal device.  However Dr Bennett stated that fentanyl and its derivatives were highly potent drugs which could cause death if left unchecked.  The design parameters were not easily selected and much experimentation was required before a safe fentanyl transdermal device could be made.  Furthermore the Chien reference shows that transdermal drug administration is a very complicated subject.

I am inclined to agree with Dr Bennett that the selection of certain design parameters so that fentanyl can be used in a transdermal device requires invention and is novel.  If the design features are not carefully chosen the transdermal device can be ineffective or, worse still, deadly.  In reaching this conclusion I have taken account of the evidence of Prof Enscore and in particular the passages of his declaration referred to in my discussion of Dr Bennett's submissions above.  I have also had regard to the evidence of Dr Mather, especially the following:

"7.At the priority date of the patent, regulatory approval had been granted for transdermal drug delivery devices in the form of adhesive patches for only four systemically acting drugs; hyoscine (scopolamine), nitroglycerine, clonidine, and oestradiol, despite the fact that extensive research and development on such transdermal drug delivery devices had been underway throughout the pharmaceutical industry and academia for more than a decade.  None of those drugs were natural or synthetic opiates or other analgesics.  Consequently, it was not obvious that natural or synthetic opiates or other analgesics, generally, or fentanyl and its derivatives, specifically, were suitable for transdermal administration......

1. It is well known by those skilled in the art that not all "feasible candidates" for use in transdermal delivery devices are actually suitable for therapeutic transdermal administration because they must also possess the desired pharmacokinetic, pharmacodynamic and other biological properties on transdermal administration required to produce the desired therapeutic effects safely.  In the absence of data relating to such properties it is not obvious which, if any, of the feasible candidates will actually be suitable for transdermal administration.  At the priority date of this application the pharmacokinetic and pharmacodynamic properties of fentanyl and its derivatives after intravenous administration were not described adequately...."

Both the Enscore and Mather declarations indicate that the Michaels paper teaches away from the selection of fentanyl for transdermal administration, especially in view of the conclusions in the Michaels paper at page 986:

"Of particular medical significance is the conclusion that drugs of high water and oil solubility can be expected to be quite skin permeable and, if sufficiently potent, can be administered at therapeutically effective rates to a relatively small skin area."

Prof Enscore and Dr Mather both point out that fentanyl has low water solubility.

In view of all the above I cannot agree with Mr Hess' submission that the combination of fentanyl and a transdermal device lacks novelty.  It seems to me from the evidence that the design features for the fentanyl transdermal device had to be carefully chosen and that the prior art did not point to fentanyl as being a suitable drug for transdermal delivery.  I believe that the device for the transdermal administration of fentanyl is a unique device which has been specially tailored for its specific function.  The combination of fentanyl and the transdermal device therefore produces a new result which is novel in the light of the prior art.  I believe that the use of fentanyl in a known device does make a substantial contribution to the working of the device in view of the particular design parameters.  It also follows from the above that I do not consider the use of fentanyl in a known transdermal device to be a mere mechanical equivalent or workshop improvement.  Therefore for all these reasons I believe the combination of fentanyl and a transdermal device is novel over the prior art.

Obviousness

It was submitted by Mr Hess that the 3 US patents 4201211, 4262003 and 4379454 formed part of the common general knowledge of the person skilled in the art.  He also submitted that the Michaels article, relating to drug permeation through human skin, would also have become part of the common general knowledge.  Therefore in his view putting fentanyl, whose properties and characteristics were common general knowledge, together with a device which was known and formed part of the common general knowledge resulted in an invention which was obvious.

Dr Bennett replied that the patents and article could only be regarded as public documents.  If they were part of the common general knowledge this would have to be established by evidence from a person skilled in the art.  No such evidence had been provided.

The determination of obviousness depends on the common general knowledge in the field of the invention in Australia, determined at the priority date of the invention (see the judgement of
Aikin J in Minnesota Mining & Manufacturing Co. v Biersdorf(Australia) Ltd. 144 CLR 253). I agree with Dr Bennett that the Michaels article cannot be regarded as common general knowledge since there is no evidence to establish this. Also it seems clear to me from the evidence that the properties of fentanyl which made it suitable for incorporation in a transdermal device were not known prior to the present application. As I stated above in relation to novelty, I believe the fentanyl transdermal device is a unique device which has been specifically tailored for its specific function. Therefore I have no difficulty in deciding that the invention is not obvious.

In reaching this conclusion I have been influenced by the decision of Gummow J in Nicaro v Martin (supra) and in particular the passage at page 558 where he says:

"In Australia, where obviousness is put in issue, it is not possible to "make a mosaic" out of existing publications which do not form part of common general knowledge; rather, where what is claimed is a combination, the question is whether it would have been obvious to a non-inventive skilled worker in the field to select from a possibly very large range of publications the particular combination subsequently chosen by the opponent in the glare of hindsight and also whether it would have been obvious to that worker to select the particular combination of integers from those selected publications."

Much of the Gonda and Stewart declarations lodged as evidence-in-support for the opponent seem to be concerned with making a mosaic of publications which have not been established as forming part of the common general knowledge in order to prove the invention is obvious.  It does not seem to me, having regard to all the evidence filed with this opposition, that it would have been obvious to a non-inventive skilled worker to use fentanyl in a transdermal delivery device.

Manner of New Manufacture

I do not regard this invention to be the mere collocation of 2 known things as submitted by Mr Hess.  For the reasons I have stated in my consideration of novelty I regard the product of this invention as being a specifically tailored transdermal device for the administration of fentanyl.  Therefore in my view the fentanyl transdermal device is certainly a manner of manufacture.

Section 40

Mr Hess raised a number of issues concerning compliance with section 40 and I shall consider these in turn, starting with sufficiency.  Mr Hess contended that the specification is insufficient in relation to its description of the transdermal device using fentanyl.  His main basis for this contention appears to be that the specification does not describe in vivo testing of the device.  Dr Bennett responded that the patentee had done all that was required in describing the nature of the invention and the manner in which it was to be performed.  The invention concerned the delivery of fentanyl into the body and the patentee did not have to describe what happened in the body.

It seems to me, from reading the specification, that the invention concerns the transdermal administration of fentanyl to humans to induce and maintain analgesia.  The administration is achieved via a device which must have certain design parameters.  The Examples show the testing of the device on cadaver skin to determine permeation rates.  These Examples show to me that the desired permeation rates can be achieved in vitro using the devices described.  In my view the patentee has done all that is necessary in describing the transdermal device and how it is adapted to use fentanyl.  Certainly examples of in vivo testing would have enhanced that description, but I do not see that such examples are essential.  I would agree with Dr Bennett that the argument concerning in vivo testing goes more to the question of utility rather than sufficiency, and there is no evidence that the device as described does not work.  Finally I note that sufficiency is a question of fact and it is preferable to determine this question by evidence of the addressee of the specification.  In this case there is no evidence from an addressee on the question of sufficiency.

Mr Hess raised two issues in connection with fair basis, one concerning the process of inducing analgesia and the other relating to the meaning of an analgetically effective rate. 
Dr Bennett contended that the claims satisfied the "Mond Nickel" rules.

Section 40(2) requires that the claims be fairly based on the matter described in the specification.  In order to determine this the following tests, known as the "Mond Nickel" rules, are applied:

a)is the invention broadly described in the specification?

b)is the description of the invention inconsistent with the claims?

c)does the claim include as a characteristic of the invention a feature on which the specification is wholly silent?

In my view the specification broadly describes a process of inducing analgesia.  The description of the invention at pages
4-5 refers to the transdermal administration of fentanyl for the purpose of inducing analgesia.  The subsequent description gives details of the device.  While the specification does not include in vivo tests to illustrate the induction of analgesia in humans, I believe the patentee has made a "sound prediction" (per
Graham J in Olin Matheson Chemical Corp v Biorex Laboratories Ltd (1970) RPC 157 at 193). Since Cygnus has not shown that the administration of fentanyl as claimed in claim 1 fails to induce analgesia, then I conclude that claim 1 is fairly based with respect to the process of inducing analgesia.

On the question of the meaning of "an analgetically effective rate", I agree with Dr Bennett that this term narrows the claims, but I cannot agree that the claims would define the invention without reference to the rate.  The specification at page 1a in describing the field of the invention refers to the administration of fentanyl "at a substantially constant rate" (line 6).  The description at page 3 refers to the delivery rate as part of the design parameters of the device, and suitable rates are indicated at pages 4-5.  I believe that tests (a) and (c) of the "Mond Nickel" rules referred to above have been satisfied, but what I have to determine is whether the administration rates defined in the claims are consistent and whether they accord with the description in the specification.

Claim 1 refers to the administration "at an analgetically effective rate" and continuing the administration "at a substantially constant rate".  It seems to me, from reading the specification as a whole and especially pages 3-5, that these rates are one and the same, although I do not believe this to be apparent from the claim.  I note that claim 22 refers to "a substantially constant analgetically effective rate" which supports my view, but there seems to be some lack of clarity in the claims if different terms are used to mean the same thing.

I cannot find anywhere in the specification a definition of what constitutes an "analgetically effective rate".  Certain preferred administration rates are indicated but I agree with Mr Hess that there is no indication these rates are "analgetically effective".

Claim 16 refers to "a substantially constant rate within the range of 0.1-10 ug/cm2/hour".  This falls outside the broadest range of 0.5 to 10 ug/cm2/hour mentioned at page 4 line 26, and again there is no indication that the rate is analgetically effective.  Claim 28 also refers to a "substantially constant rate" and here the rate corresponds to that given at page 4 line 26.  Again claim 28 makes no mention of the rate being analgetically effective.

It therefore seems to me that there are some inconsistencies between the specification and the claims with respect to the administration rate and the term "analgetically effective".  I therefore believe that test (b) of the "Mond Nickel" rules referred to above has not been satisfied and that claims 1, 16, 22 and 28 lack fair basis.

The fair basis issue appears to me to hinge on the question of what constitutes an analgetically effective rate.  At present the specification does not include a clear definition of what constitutes such a rate, and does not indicate whether the specific rates mentioned, for example at page 4 line 26, are analgetically effective.  Similarly, as I have mentioned above, the claims are inconsistent with each other and with the specification in using different terms and ranges to possibly indicate the same thing.  I therefore believe that it may be possible to overcome these section 40 defects by providing a clear definition in the specification of what constitutes an analgetically effective rate, and by using consistent terminology throughout the claims which clearly reflects this definition.

On the question of the breadth of claim 1, and in particular whether it is limited to transdermal administration, I am inclined to agree with Dr Bennett that the term "intact" means unbroken and therefore does not include administration via injection.  I note that the claim also refers to a "skin permeable form" of fentanyl which implies transdermal administration.  Also the entire specification is directed to transdermal administration, and hence it is clear to me that the claims are intended to be limited to such administration.

Finally, other than on the question of what constitutes an analgetically effective rate, I do not believe that the claims as a whole are unsupported by the description.  In particular I cannot agree with Mr Hess that the "release rate controlling means" in claim 30 is essential to the invention.  This feature is mentioned for example at pages 11-13, where examples of compositions of the invention are described.

conclusion

I have found that the opposition succeeds on the ground that the claims do not meet the requirements of section 40, but that the grounds of novelty, obviousness and manner of manufacture have not been established.  I believe it may be possible to overcome the section 40 defects by amendment.  Consequently I will allow the applicant a period of 60 days from the date of this decision within which to propose amendments to overcome the defects to my satisfaction.

costs

Although I have found that the opposition succeeds, the only ground for this was a relatively minor section 40 issue.  The main grounds of the opposition to which all the evidence was directed, namely anticipation and manner of manufacture, have not been established.  Therefore having regard to all the circumstances in this case I make no award of costs.

JANET WERNER
Delegate of the Commissioner of Patents

Patent attorneys for the applicant  :  Shelston Waters, Sydney

Patent attorneys for the opponent   :  Watermark Patent & Trademark Attorneys, Melbourne