Bayer Aktiengesellschaft v Alphapharm Pty Ltd

[1991] APO 47

PATENTS ACT 1990

DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS

Re:Application 558331 by BAYER AKTIENGESELLSCHAFT - Opposition by ALPHAPHARM PTY LTD

Background
          Patent application No 558331 in the name of Bayer Aktiengesellschaft was lodged on 8 September 1981, claiming priority from a patent application lodged in West Germany on 9 September 1980.  The earliest priority date that any claim could have is therefore 9 September 1980 and this has not been disputed by either party.  On an examination of the basic document and its translation I am satisfied that the claims are all entitled to this priority date.
          Following examination the application was advertised accepted in the Official Journal of 29 January 1987.  The grant of letters patent has been opposed by Alphapharm Pty Ltd under section 59 of the 1952 Act.
          Following the service of evidence the matter was heard in Sydney on 15 March 1991.  Dr Annabelle Bennett of Counsel, assisted by Mr Jim Siely, patent attorney of Arthur S. Cave represented the applicant and Mr Tony Bannon of Counsel represented the opponent.
          Although the notice specified the grounds of opposition as those listed in paragraphs (a) to (i) of sub-section 59(1) the submissions made at the hearing were limited to the grounds specified in paragraph (g); i.e. obviousness.

The Specification
          The specification commences by stating that the invention relates to novel particulate solid medicament formulation containing the known compound nifedipine.
          It goes on to state that the compound has very powerful actions which influence the circulation, but because it is sensitive to light and sparingly soluble, a number of difficulties occur in the formulation of medicamental specialties.  A number of patent specifications are mentioned, all of which relate to various methods of formulating the drug in order to better administer it to patients.
          The specification then alleges that these previous attempts to compensate for the poor solubility of nifedipine and still ensure good bio-availability have certain disadvantages.  Amongst these are stated to be overlarge tablets; the need to form tablets into particular elongate shapes to facilitate swallowing; particularly difficult processing to give liquid formulations and consequently generally expensive preparations.
          The specification then goes on to state that the present invention provides a solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific surface area.  The method of preparation is said to be grinding crystal mixtures obtained from the synthesis of nifedipine.  The solid formulation thus produced is said to have unexpectedly high bio-availability compared to what was previously known.  The specification continues by describing 3 examples of the invention and ending in 6 claims only one of which is independent and reads as follows:

"1.A solid pharmaceutical composition containing as the active ingredient nifedipine crystals with a specific surface area of 1 to 4 m2/g, in admixture with a solid diluent."

Submissions
          Mr Bannon argued his entire submissions on the basis that the claims of the present application were obvious.
          The main evidence before me on behalf of the opponents are three declarations made by Dr Phillip Michael Altman.  Dr Altman is a Director of Pharmco Pty Ltd a pharmaceutical consulting company.  He has wide experience in the pharmaceutical field.  Just prior to the priority date of the patent he appears to have been acting as a consultant to two pharmaceutical companies (Wellcome Australia Pty Ltd and Searle Laboratories Pty Ltd) whilst undertaking research at Sydney University for his Ph.D.
          Dr Altman has supported his declarations by referring to published documents.  These are labelled exhibits PMA 1-9 supporting the first declaration and exhibits PMA 1A-5A supporting the second declaration.  These documents attempt to prove the state of the art before the priority date of the application.
          Dr Altman's main points are as follows:

(a)He asserts that it would have been obvious to an ordinary worker to grind a water insoluble drug such as nifedipine to reduce its particle size and hence improve its bio-availability before 1981;

(b)This method of effecting the size reduction was widely known prior to 1981.

Dr Altman also refers to other water insoluble drugs which have been ground to a small particle size to improve their bioavailability, e.g. insulin.  (In this context water insoluble is taken to mean extremely difficult to dissolve other than actually totally insoluble).
          The applicant's evidence-in-answer consisted of three declarations made by Dr Knud Helmut Heinrich Schauerte, Dr Klaus-Dieter Ramsch and Dr Andreas Ohm.  Dr Schauerte's declaration asserted that the invention resides in a pharmaceutical composition with a specifically defined surface area of 1-4m2/g.  He asserted that the advantages of the invention are:

(a)an unexpected longer duration of the physiological effect;

(b)an unexpected plateau effect for the dissolution rate in nifedipine with a surface area of 1-4m2/g; and

(c)maximum dissolution and bioavailability lies within the surface area of 1-4m2/g and this could not be predicted by an ordinary worker.

Doctor Ohm's declaration added that the long duration of physiological effect was most surprising and that Dr Altman appeared to be suggesting a hypothetical consideration where dissolution and bioavailability are inversely proportional to particle size.  He asserted that this did not exist as the nifedipine crystals show high dissolution rates within the specific surface area but lower dissolution rates outside this range at both lower and upper end.  He also asserted that the invention demonstrated a most unexpected plateau effect.  This was supported by test data and graphs which formed part of his declaration.
          Dr Ramsch's declaration added that the nifedipine crystals showed high bioavailability and that insulin cannot be taken as a logical and scientific pointer to the probable behaviour of nifedipine with a specific surface area of 1-4m2/g.  The applicant also asserted that Dr Altman's declaration did not establish publication dates in Australia for his documents.  The applicant further asserted that Dr Altman had not provided sufficient evidence to establish that the documents formed part of the common general knowledge in Australia before the priority date of 9 September 1980.
Decision
          The determination of obviousness depends on the common general knowledge in the field of the invention in Australia (see the judgement of Aicken J in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd 144 CLR 253). The common general knowledge has to be determined at the priority date of the invention, in this case 9 September 1980.
          To ascertain what is the common general knowledge in this present situation I will rely on the evidence adduced in this opposition.
          I consider that Dr Altman has not established publication dates in Australia for most of the supporting exhibits to his declarations.  Exhibit numbers PMA 1-9 supporting the first declaration do not give any indication of being published in Australia at all let alone before the priority date of 9 September 1980 and there is no other evidence before me to establish a publication date in Australia before the priority date.  Likewise exhibit numbers PMA 1A-3A and 5A supporting the second declaration also have no indication that they were published in Australia before the priority date, nor have I any other evidence before me to establish their publication date in Australia.  Exhibit number PMA 4A, however, shows the reference was published in Australia before the priority date.  Because of this and the provisions of 160(2) I will first consider this document for anticipation. The document "Drug Treatment - Principles and Practice of Clinical Pharmacology and Therapeutics" merely shows a table relating to the choice of oral anti-coagulents with emphasis on pharmokinetic considerations.  It makes no reference to nifedipine in any way.  Thus it neither prior publishes or renders not novel the claims. 
          In addition Dr Altman has not in my view established that the document forms part of the common general knowledge at the priority date of the claims.  Therefore I do not consider that the present application is obvious in the light of the limited information in this single document.
          Despite the fact that the opponents have not presented me with evidence to establish publication dates in Australia of the supporting exhibits PMA 1-9 and PMA 1A-3A and 5A it is possible that some of these could have been published in Australia before the priority date.  Therefore I believe it is desirable that I should have regard to section 60(2) and consider whether they would prior publish or render not novel the claimed invention if they were so published.  PMA3A discusses nifedipine in some detail but was not published until 1986 in the UK.
  PMA2A was published in 1988 and only relates to guidelines for Bioavailability and Bioequivalence study.  Since both these documents were published overseas long after the priority date aof the claims I do not think it is likely that the opponent will be able to prove publication in Australia before the priority date, and I do not propose to consider them further for the purposes of anticipation.
          PMA1 is the Article by Dr Sugimoto referred to in the specification itself.  It merely outlines the problems associated with nifedipine which the claimed invention sets out to overcome.
          PMA2 to 7 and 9 relate to pharmaceutical tablet manufacture generally, or pharmaceutical formulations other than nifedipine.
          PMA1A outlines general pharmaceutical concepts about particle size and absorption and makes no reference to nifedipine.
          PMA5A relates to pharmokinetics in general and does not mention nifedipine.
          Thus I do not consider that any of these documents would anticipate the claims of the specification even if publication before the priority date could be proved.
          On the question of obviousness Dr Altman asserts in his first declaration at paragraphs 10, 11, 14, 16 and 19 that it would have been "obvious to an ordinary worker in the field before 1981 to grind nifedipine crystals to a sufficiently small particle size", rather than before the priority date of 9 September 1980.  From this I may assume that Dr Altman is not able to say what he believes would have been obvious before the priority date.
          However, even allowing that Dr Altman's declaration is intended to refer to 1980 and not 1981, I do not believe his statements establish that the claimed invention is obvious.

At paragraph 10 of his first declaration he asserts what would have been "obvious to an ordinary worker in the field of pharmaceutics".  From this I conclude that although Dr Altman is undoubtedly a person skilled in this area, he does not consider himself a non-inventive person in the art.  He is too skilled and the specification is not addressed to such as he.  So when he asserts what he believes would have been obvious to a non-inventive skilled addressee he must rely on the common general knowledge in the relevant art before the priority date in order to support his belief.  In his declarations he refers to various documents, without demonstrating why they form part of the common.  The fact that publication in Australia has only been proved for one document in my view makes it extremely unlikely that any of the documents did form part of the common general knowledge before the priority date (and in this case PMA8 and PMA2A both published after the priority date could not possibly be part of this common general knowledge).
          Common general knowledge is normally proved by reference to commonly used books (see British Oxygen Co v Maine 1924 41 RPC 604 at 605) or by reference to what students in the art are taught (see Automatic Coil Winder Co v Taylor (1944) 61 RPC 41 at 43) or by the evidence of expert witnesses generally. It is not sufficient to show that information was published in a document having wide circulation in the art concerned, unless that information is also shown to have been "generally accepted without question" (or at least generally regarded as a good basis for further action (see General Tire and Firestone [1972] RPC 457 at 483) by the bulk of those in the art). (Patents for Inventions, T.A. Blanco White Fourth Edition at page 147).
          Since Dr Altman has not adduced any evidence to show that the documents which supported his declarations (PMA Exhibits 1-9 and PMA 1A-5A) formed part of the common general knowledge at the relevant time, I do not propose to consider them further  Although Dr Altman has mosaiced these documents together to support his assertions that grinding nifedipine to 1-4m2/g was well known in the art, he has not proved that a non-inventive skilled worker without the benefit of hindsight at the relevant priority date would choose these particular documents in order to demonstrate that the present application lacks an inventive step.
          Aickin J in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd 144 CLR 253 at page 293 stated:

"In the case of alleged lack of an inventive step the question of making a mosaic must operate (if at all) in a very different matter.  An allegation of want of inventive step is not made out by saying you may take one or two, or twenty-one or twenty-two, prior publications and then select from them appropriate extracts or pieces of information, which will add up to the invention claimed and so demonstrate that it was obvious.  So to proceed is to mistake the nature of an invention and the nature of the objection of obviousness.  The question is, is the invention itself obvious not whether a diligent searcher might find pieces from which there might have been selected the elements which make up the patent.  If this were not so, there could never be a valid patent for a new combination of old integers.  The proper question is not whether it would have been obvious to the hypothetical addressee who was presented with an ex post facto selection of prior specifications that elements from them could be combined to produce a new product or process.  It is rather whether it would (my underlining) 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."

On the evidence before me the opponent has failed to establish they were published in Australia before the priority date of the claims (document numbers PMA 1-9 and PMA 1A-5A).  The opponent has also failed to establish that even if the documents were published before the priority date that they formed part of the common general knowledge available to the non-inventive skilled worker before the priority date.  Thus the opponent has failed to establish that the claimed invention is obvious.
          I award costs against the opponent.

(R. MELVIN)
  Delegate of the Commissioner of Patents

Attorneys for the applicant: Arthur S. Cave & Co, Sydney
Attorneys for the opponent : Griffith Hack & Co, Sydney