Dr Renschler Biotechnologie Gmbh v Boehringer Ingelheim International Gmbh

[1995] APO 15

official notice

decision of a delegate of the commissioner of patents

Application        :  No. 581027 in the name of DR RENTSCHLER BIOTECHNOLOGIE GMBH

Title:  Process for treatment of rheumatic diseases

Action: Opposition under S. 59 of the Patents Act 1952 by BOEHRINGER INGELHEIM INTERNATIONAL GMBH

Decision:  Issued            .

Abstract:   Opposition successful in part.

Claims 1, 2, 5-9 (as accepted) and claims 1, 2, 5-8 (as proposed to be amended) lack novelty in light of a citation raised;

The opponent has not established that the claims are obvious in light of the common general knowledge;

Defects in the specification under Section 40 were identified.

patents act 1990

decision of a delegate of the commissioner of patents

Re:Patent Application No. 581027 by DR RENTSCHLER BIOTECHNOLOGIE GMBH and Opposition thereto by BOEHRINGER INGELHEIM INTERNATIONAL GMBH

background

Patent Application 581027 by Dr Rentschler Biotechnologie GmbH was lodged on 7 October 1985, relying on 3 basic documents (dated 5 October 1984, 1 June 1985 and 4 September 1985) the first filed in the Federal Republic of Germany and the latter two in Europe to establish priority.

The application was advertised accepted on 9 February 1985 and on 5 May 1989, Boehringer Ingelheim International GmbH filed a Notice of Opposition to the grant of the patent.

The formal stages of evidence were completed on 8 March 1994.  On 4 August 1992, the applicant filed a statement of amendments under section 104 (Patents Act 1990).

As the application was both lodged and advertised accepted before the commencement of the Patents Act 1990, the provisions of section 234(3) and regulation 23.3 of the 1990 Act are applicable - that is the opposition to the grant of the patent under section 59 is governed by the provisions of the 1952 Act and regulations.

The opposition under section 59 was heard in Canberra on 24 October 1994. The applicant relied on written submissions prepared by their patent attorney (Cullen and Co, Brisbane) and the opponent was represented by Dr Peter Stearne from Davies Collison Cave Sydney.

At the Hearing, the Opponent submitted a copy of a translation of a decision from the German Patent Office dated 28 September 1989 on a related case.  However, I know the law in Europe to be different to that in Australia and I think it inappropriate to have regard to the German decision (see Winner & Anor v Ammar Holdings Pty Ltd (1992) AIPC 90-916).

SPECIFICATION

The specification as accepted relates to a method of treating rheumatic diseases using interferon-gamma.  It ends with 9 claims, only one of which (claim 1) is independent.  Claim 1, as
accepted, defines:

"A process for treating rheumatic diseases comprising the step of administering to a mammal a pharmaceutically effective amount of interferon-gamma."

Both rheumatic diseases and interferon-gamma are further defined in the specification.  A rheumatic diseases is defined as any disease which is (i) characterized by inflammation or degeneration of musculo-skeletal or connective tissue structures of the body, particularly the joints, and including muscles, tendons, cartilage, synovia and fibrous tissues, (ii) accompanied by pain, stiffness or impairment of locomotion or function of these structures and, in some cases, (iii) often accompanied by serological evidence of rheumatoid factor.

Interferon-gamma is defined as including all proteins, polypeptides and peptides which are natural or recombinant interferon-gammas, or derivatives thereof, and which are characterized by the biological activity of those interferon-gammas against rheumatic diseases.  These include interferon-gamma-like compounds from a variety of sources such as natural interferon-gammas, recombinant interferon-gammas and synthetic or semi-synthetic interferon-gammas.

The proposed amendments filed on 4 August 1992 have the effect of removing claim 6 (as accepted) and a section of the description which corresponded to that claim.  Although the opponent was invited (and chose not) to comment on the proposed amendments, the amendments have not as yet been further processed by the Patent Office.  Thus, I will not consider whether they are allowable under section 102 and, in the first instance, I will consider the accepted specification and then comment on whether the deficiencies (if any) would be overcome by the proposed amendments.

DECISION

Common General Knowledge

A key element in this decision is to establish the common general knowledge of the person skilled in the art in Australia at the priority date of the claims.  In particular, I need to determine what involvement interferon-gamma was thought to have in rheumatic disease.

The applicant argued that given interferon-gamma's immunoregulatory activity, one of ordinary skill in the art would have logically expected that its administration would stimulate the immune system and intensify the disease, not mediate it.  However, the evidence before me clearly shows that interferon-gamma is an immunomodulator and can be an immunostimulant or immunosupressant depending on the circumstances.  Because of this, the person skilled in the art could only have speculated about the role of interferons in rheumatic disease and, for example, could equally have hypothesized that interferon-gamma was a known immunosupressant and might be useful in the treatment of the disease.

The opponent suggested that the field of interferon treatment was moving so fast at the priority date of the claims that the common general knowledge was reflected more in the scientific literature rather than textbooks (or in other more "conventional" forms of common general knowledge).  This may be true but I do not accept the opponent's further submission that a particular scientific paper:

Kajander et al., The Lancet, 5th May 1979, pp. 984-985 (hereafter "Kajander").

which was published before the priority date was necessarily part of the common general knowledge because that paper was published in a well-known journal.

Kajander is a key reference.  It shows that despite any theoretical conjecture about interferon exacerbating rheumatic diseases, a clinical study had found interferon may be useful in the treatment of rheumatic arthritis in humans.  Kajander found that interferon produced considerable improvement in grip strength and morning stiffness.  However, the authors noted that this improvement did not reach statistical significance, and reported their experiments were inconclusive.

In my opinion, although the reference is a key one, the opponent has not succeeded in showing that it is part of the common general knowledge.  A scientific paper only becomes part of the common general knowledge if the conditions outlined in British Acoustic Films (53 RPC 221 at 250) are met. Luxmore J. said in that decision that:

"In my judgement it is not sufficient to prove common general knowledge that a particular disclosure is made in an article or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates.  A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated.  Such a piece of knowledge only becomes general knowledge when it is generally known and accepted by the bulk of those engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art."

The court in General Tire and Rubber Company Ltd v Firestone Tyre and Rubber Company Ltd [1972] RPC 457 agreed generally with Luxmore's statement although reserved for further consideration whether the words "accepted without question" may not be putting the position rather high and substituted the words "generally regarded as a good basis for further action".

The opponent has established that Kajander was in a well-known and widely circulated journal and that it was widely read.  However the opponent has not demonstrated that Kajander was "generally regarded as a good basis for action" by the person skilled in the art at the priority date.  The statement of Dr MacCay, for example, that Kajander was "a prominent signal of the possible usefulness of interferons in the treatment of rheumatoid arthritis" may simply be ex post facto analysis.  There is certainly no independent verification of his statement such as evidence suggesting that the reference was widely quoted or discussed before the priority date of the claim.

There also appears to be a lot of circumstantial evidence which indicates that Kajander was not as prominent as Dr MacCay suggests:

(a)Theoretical conjecture about interferon being involved in the pathogenesis of disease continued after the publication of Kajander;

(b)There is no evidence of further clinical trials on interferon treatment of rheumatic diseases by Kajander (or any one else);

(c)In the evidence before me, later papers published before the priority date of the claims did not refer to Kajander's work;

(d)Kajander's results were mainly negative and although the authors warned that their results should not be overestimated, they did not appear to herald a great breakthrough in the treatment of rheumatic diseases.

I also note that in the evidence before me, the reference most akin to a textbook in the field ("Interferon, volume 1: General and Applied Aspects" - A. Billiau (ed) (1984) at page 178) discussed the role of interferon in rheumatic diseases and referred to the uncertainty of the field suggesting that interferon could a pathogenic factor or just be a symptom of the disease.  It did not refer to Kajander and did not mention a possible role for interferon in treatment.

I conclude that Kajander was not part of the common general knowledge before the priority date of the claims.  In my opinion, from considering all the evidence in front of me (including a gamut of references which ranged from implicating interferon in the pathogenesis of the disease to suggesting it was a symptom of the disease to inferring it was a possible treatment), the only reasonable conclusion I can draw seems to be that the common general knowledge in Australia at the priority date was that the role of interferon in rheumatic diseases was uncertain.  The person skilled in the art:

(a)did not fully understand the etiology or pathogenesis of rheumatic diseases but recognized that there was an immune dysfunction component in the disease;

(b)thought there may have been an involvement of interferon in the disease but did not understand the nature of the involvement;

(c)knew that interferon was an immunomodulator and could be an immunostimulant or immunosupressant depending on the circumstances;

(d)considered that interferons may be useful in treatment but equally may have no effect; and

(e)thought it, at least theoretically possible, that interferon could exacerbate the disease.

I also consider (again, from the evidence before me) that the person skilled in the art applied the above statements to all three interferons and not just interferon-gamma.

NOVELTY

The test for determining whether an invention lacks novelty is the " reverse infringement test" as set out in Meyers Taylor Pty Ltd v Vicarr Industries (1977) CLR 228 at page 225 where Aiken 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 anticipation would if the patent were valid, constitute an infringement".

Infringement of a claim has been said to occur where "each and every one of the essential integers of that claim have been taken" (Rodi and Wienenberger AG v Henry Showell Ltd (1969) RPC 367).

Essential features of the claims

Claim 1 is the broadest (or leading ) claim of the instant specification and contains the following features:

1.  A process for treating rheumatic diseases comprising

2.  the step of administering to a mammal

3.  a pharmaceutically effective amount of interferon-gamma.

The only contentious issue in determining the essential features of this claim is whether the type of interferon (i.e. interferon-gamma as opposed to any other interferon) is essential.

Prima facie, each of the features in claim 1 is essential, simply because they are in the leading claim (as per Catnic Components v Hill and Smith Ltd, (1982) RPC 183 (at page 227)).

It is also clear from a construction of the specification that interferon-gamma is regarded as an essential feature.  Interferon-gamma, for example, is the only difference between the interferon-alpha treatment of Kajander (reportedly ineffective) and the claims of the instant specification.  Further, the specification clearly distinguishes interferon-gamma from the other types of interferons and all the examples and claims refer to interferon-gamma.

Under these circumstances I find that interferon-gamma and each of the other features of claim 1 are "essential features" of the claim.  I do not consider that claims 2, 5, 7, 8 or 9 (as accepted) add any further essential features since neither the method of making (nor type of) interferon-gamma nor the method of administering (nor dose of) interferon-gamma nor the type of mammal to which interferon-gamma is administered "materially affects the working of the invention" (as per Catnic Components v Hill and Smith Ltd, (supra)).  There is also no evidence before me that a further compound co-administered with interferon-gamma could have a synergistic effect on interferon-gamma treatment.  It seems to me that without this synergistic effect, the "further compound" would be working independently of interferon-gamma and could not materially affect the working of the invention.  It follows that the further compounds defined in claim 6 (as accepted) are also inessential.  Claims 3, 4 (as accepted) define particular rheumatic diseases.  Since interferon-gamma may differ in efficacy in treating each of these diseases, the type of disease can materially affect the working of the invention and potentially be an essential feature.

The net effect of the proposed amendments is to delete claim 6 and renumber claims 7, 8 and 9 to claims 6, 7, and 8.  The same analysis will apply to the claims (as proposed to be amended), resulting in claims 1-5 having the same essential features as the corresponding accepted claims and claims 6, 7, and 8 adding no extra essential features over and above claim 1.

Applying the reverse-infringement test

The opponent relied primarily on the following references to submit that the claims were not novel.

European Application No. 077063 by Viral Genetics Inc(published on or before 31 May 1983) (hereafter "Viral Genetics");

Pearson, C.M. et al., Perspect. Information. Proc. Int. Meet. 3rd, 131-146, 1977 (hereafter "Pearson") ((published in Australia on or about 30 November 1977)

Kajander et al., The Lancet, 5th May 1979, pp. 984-985 (hereafter "Kajander") ((published in Australia on or before 26 November 1979)

Viral Genetics discloses a topical administration of 102-108 I.U. of human interferon for treating inter alia psoriasis in humans.  It discusses the 3 types of interferons (alpha, beta and gamma) and states that any of these would be suitable, using alpha (or leukocyte) interferon in each of the examples.  The citation also teaches (pages 25 and 26) that a significant amount of interferon would be absorbed into the blood stream and may have a favourable effect on the systemic aspects of psoriasis (i.e. psoriatic arthritis).

Viral Genetics clearly discloses each of the essential features of claim 1 with regard to the rheumatic disease, psoriatic arthritis.

The applicant argued that the use of the composition in Viral Genetics is as an anti-viral agent and is in no way suggestive of using interferon-gamma as an immunomodulator in the treatment of rheumatic diseases.  Even if this is true, the citation teaches the treatment of rheumatic disease which still falls within the scope of the claim.  The theory behind how a interferon-gamma works in combating rheumatic diseases would be irrelevant unless the claims were limited to rheumatic diseases without a viral etiology.

The applicant also suggested that despite a clear teaching in the citation that all three interferons could be used, the common general knowledge would teach away from using interferon-gamma.  I concluded previously that at the priority date of the claims, the common general knowledge was that the role of interferon in rheumatic diseases was uncertain.  It follows that there could not have been the teaching away that the applicant has suggested.

The applicant also contended that a statement that interferon "may have a favourable effect on the systemic aspects of psoriasis" is mere "fond hope and speculation".  However the statement in the citation is "a clear recommendation" which is sufficient to destroy the novelty of a claim (see WR Grace v Asahi 25 IPR 481). The applicant's argument that interferon might not be able to enter the bloodstream via topical treatment is mere conjecture and I do not give it any weight.

I conclude that Viral Genetics provides a clear teaching that interferon-gamma can be used to treat a rheumatic disease (psoriatic arthritis) and that this falls within the scope of claim 1 (as accepted) depriving it of its novelty.  As I concluded previously, claims 2, 5-9 (as accepted) and claims 2, 5-8 (as proposed to be amended) do not contain any additional essential features and therefore these claims also lack novelty in light of Viral Genetics.  Claims 3 and 4 define specific types of rheumatic diseases (other than psoriatic arthritis).  Viral Genetics does not provide any teaching for the treatment of rheumatic diseases other than psoriatic arthritis and, as a result, claims 3 and 4 are novel over the Viral Genetics reference.

Pearson describes the treatment of adjuvant arthritis (an experimental model of a rheumatic disease) in rats using interferon preparations.  It is not clear whether the Pearson preparation of interferon was alpha, beta or gamma.  However Dr MacCay believes it was probably interferon-alpha.

Kajander describes the treatment of rheumatoid arthritis in humans with interferon-alpha.  Although, the citation reported that there was a considerable improvement in grip strength and morning stiffness, neither change reached statistical significance.

Kajander and Pearson each contains all of the features of claim 1 except that they use interferon-alpha as opposed to interferon-gamma.  The opponent argued that the two interferons were "biological equivalents" and hence mere workshop variations (as per R.D. Werner and Co Inc v Bailey Aluminium Products Pty Ltd (1989) 85 ALR 679).

However, Werner v Bailey (supra) decided that it is only inessential features of a claim which can be substituted by mechanical (or, in this case, biological) equivalents.  I have previously found that interferon-gamma is an essential feature of the claims and since the feature is in neither Kajander nor Pearson, neither citation deprives any of the claims of their novelty.

OBVIOUSNESS

Under the 1952 Act, the determination of obviousness depends on the common general knowledge in the field of the invention in Australia at the priority date (see the judgement of Aiken J. in Minnesota Mining and Manufacturing Co v Beiersdorf (Australia) Ltd 144 CLR 253).

I have previously concluded that the common general knowledge in Australia at the priority date of the claims was that the role of interferons in rheumatic diseases was uncertain.  It follows that the person skilled in the art could only have speculated on the usefulness of interferons in the treatment of rheumatic diseases.  I am not satisfied, given this level of uncertainty, that the opponent has established that interferon would be worth trying (as per WR Grace & Co v Asahi Kasei Kogyo Kabushiki Kaisha (1993) AIPC 90-974 (at page 272)). Hence, they have not established that the claims are obvious in light of the common general knowledge.

SECTION 40

Fair Basis

The opponent argued that rheumatic diseases refer to a large number of illnesses of quite diverse causes and that it would be speculative to suggest that all the diseases could be cured by interferon-gamma.

The definition of rheumatic diseases given in the specification is clearly broad, encompassing any disease which is:

(1)characterized by inflammation or degeneration of musculo-skeletal or connective tissue structures of the body, particularly the joints, and including muscles, tendons, cartilage, synovia and fibrous tissues,

(2)accompanied by pain, stiffness or impairment of locomotion or function of these structures and, in some cases,

(3) often accompanied by serological evidence of rheumatoid factor.

I consider the evidence before me establishes the following:

(a)the person skilled in the art did not fully understand the etiology or pathogenesis of rheumatic diseases but recognized that there was an immune dysfunction component in the disease;

(b)the cause, etiology and type of immune dysfunction seem to differ between the various rheumatic diseases, however, some rheumatic diseases were thought to have a viral cause;

(c)the person skilled in the art thought there may have been an involvement of interferon in (at least some) rheumatic diseases but did not understand the nature of the involvement;

(d)the person skilled in the art knew that interferon was an immunomodulator and could be an immunostimulant or immunosupressant depending on the circumstances.  He or she also recognized that interferon had anti-viral activity.

From this evidence, it appears to me that the role of interferon-gamma in rheumatic diseases is unknown and may vary between different types of rheumatic diseases (since these vary in cause and etiology).  It would not be possible to predict whether interferon could treat a particular rheumatic disease from either the common general knowledge or the specification.  Further, it would take an undue burden of experimentation to test the effectiveness of interferon on the range of diseases encompassed by the term "rheumatic diseases".  In my opinion, the only real support for interferon-gamma is with regard to the rheumatic diseases chronic polyarthritis, rheumatoid arthritis and periarthritis humeroscapularis which the examples describe and to claim broader than this is beyond the scope of the invention.  As a result, claims 1-9 (as accepted) and claims 1-8 (as proposed to be amended) are not fairly based.

The opponent also submitted that the term "derivatives" (which appears in claim 1 as a result of the dictionary definition in the specification of "interferon-gamma") is speculative.  The specification contains no examples of derivatives and it is claiming an "unexplored field".  There are a range of techniques well known in the art that produce protein derivatives and I believe that a person skilled in the art would be able to provide at least some derivatives of interferon-gamma using their common general knowledge without needing specific examples.

It is also well known that some derivatives will retain the original protein's activity and some will not.  In the current claims, the term "derivative" is limited to products which are derived from interferon-gamma and whose biological activity against rheumatic diseases is the same as interferon-gamma.  It seems to me that as the biological activity of interferon-gamma is not affected, any differences between interferon-gamma and its derivative are completely cosmetic and the two would be biological equivalents.  It would be predictable that any effect of interferon-gamma on rheumatic diseases would be shared by its derivative and hence the two are part of the same inventive concept.  Using The Mullard Radio Valve Co. Ld. v. Philco Radio and Television Corp. of Great Britain Ltd., (1936) 53 RPC 323 at page 347, I conclude that the term "derivative" in this context is not speculative.

SUMMARY

The opposition succeeds in part.

Claims 1, 2, 5, 6, 7, 8 (as accepted) lack novelty in light of Viral Genetics.

The opponent has not established that any of the claims lack novelty in light of Kajander or Pearson.

The opponent has not established that the claims are obvious in light of the common general knowledge.

Claims 1-9 (as accepted) and claims 1-8 (as proposed to be amended) are not fairly based because the term rheumatic diseases claims beyond the scope of the invention.

The problems identified above are not overcome by the amendment which has been currently proposed.  However I believe that further amendment will easily overcome the problems I have noted above and I give the applicant 60 days in which to propose amendments.

COSTS

In line with the convention that cost follow the event, I award costs against the applicant, Dr Rentschler Biotechnologie Gmbh.

Karen Ayers
Delegate of the Commissioner of Patents

Patent attorneys for the applicant  :  Cullen and Co., Brisbane.

Patent attorneys for the opponent   : Davies Collison Cave, Sydney