Cognis Corporation v Makhteshim Chemical Works Ltd - [2003] APO 32

OFFICIAL NOTICE
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Application : No 705467 in the name of COGNIS CORPORATION

Title: Pharmaceutical compositions comprising lycopene

Action: Opposition by MAKHTESHIM CHEMICAL WORKS LTD under section 59 of the Patents Act 1990

Decision: Issued 18 August 2003.
Abstract
All of the claims are clear.
Claims 1, 2, 5, 6, 7, 8, 14 and 15 lack novelty in the light of Australian Patent Application

660630. This citation gives clear and unmistakable directions to use an effective amount of any one of a small list of named biologically active analogues to treat heat disease by lowering cholesterol. One of the listed compounds was the natural lycopene claimed in the opposed specification.

All of the claims lack an inventive step in the light of Australian Patent Application 660630 when combined with the common general knowledge as it existed in Australia before the relevant date.
As the application was found to have no patentable subject matter, the application was refused.
Costs were awarded against the applicant

PATENTS ACT 1990
DECISION OF A DELEGATE OF THE COMMISSIONER OF PATENTS
Re: Patent Application No.705467 by Cognis Corporation and opposition thereto by Makhteshim
Chemical Works Ltd under section 59 of the Patents Act 1990
BACKGROUND

Henkel Corporation originally filed patent application 705467 (47421/96) as a PCT application on 22 December 1995. It claims priority from application number 08/362,617 filed in the USA on 22 December 1994. The application was advertised accepted on 20 May 1999 and on 20 August 1999 Makhteshim Chemical Works Ltd (Makhteshim) filed a notice of opposition. The application was assigned to Cognis Corporation (Cognis) on 11 July 2001.
On 16 August 2001 the applicant proposed amendments to the specification. After allowing the opponent time to comment, these were advertised accepted on 20 December 2001.
Following completion of the evidentiary and amendments stages the matter came for hearing in Sydney on 13 February 2003. Mr Richard Baddeley, patent attorney of Watermark Perth represented the applicant. Dr Peter Stearne, patent attorney of Davies Collison Cave, Sydney represented the opponent.
SPECIFICATION
The specification and claims are directed to a method of prevention or treatment of cardiovascular disease by lowering serum cholesterol levels. The specification is directed to both a method and a composition for treating or preventing high serum levels of cholesterol and lipids in a mammal, including human beings. This is achieved, according to the invention, by administering an effective amount of natural lycopene, which occurs in fruit such as tomatoes, optionally with natural tocopherol. Lycopene can also be produced synthetically but this patent application is limited to naturally occurring lycopene. The only reference in the specification to a source of natural lycopene, other than the single line that it is found in tomatoes, is the statement on page 5 of the specification. This reads:

“The natural carotenoids are a mixture of compounds. These include beta-carotene, alpha-carotene, lutein, cryptoxanthin and lycopene”.

As a result of the amendments of 16 August 2001 the feature that the composition is in unit dosage form was added to the method claims. In addition all of the composition claims now include natural tocopherol and new claim 12 includes the feature of a carotenoid suspension in vegetable oil. There is no indication anywhere in the specification of how natural lycopene is prepared or any indication of how or even if it is purified from the only stated source which is the natural carotenoid mixture containing amongst other things b-carotene. The specification ends with fifteen claims that read as follows:

1.   A method of preventing or treating high serum levels of cholesterol and/or lipids in a mammal, said method comprising orally administering to a mammal in need of such prevention or treatment a composition in unit dosage form, said composition comprising an effective amount of natural lycopene to prevent or treat high serum levels of cholesterol or lipid.
2.   The method according to claim 1 wherein the composition comprises 1mg to 10mg of natural lycopene.
3.   The method according to claims 1 or 2, wherein the composition further comprises a natural carotenoid mixture.
4.   The method according to claim 3 wherein the natural carotenoid mixture comprises two or more components selected from the group consisting of a-carotene, b-carotene, lutein, cryptoxanthin and zeaxanthin.
5.   The method according to any one of the preceding claims, wherein the composition further comprises a natural tocopherol component.
6.   The method according to claim 5 wherein said natural tocopherol component comprises d-alpha-tocopherol.
7.   A composition comprising natural lycopene and natural tocopherol in amounts effective to treat or prevent high serum levels of cholesterol and/or lipids when administered orally to a mammal.
8.   The composition according to claim 7, further comprising a natural carotenoid mixture.
9.   The pharmaceutical composition according to claim 8 wherein the natural carotenoid mixture comprises two or more components selected from the group consisting of a-carotene, b-carotene, lutein, cryptoxanthin and zeaxanthin.
10. The composition according to claim 8 or 9, wherein the natural carotenoid mixture comprises a suspension of two or more carotenoids in vegetable oil.
11. The composition according to claim 10, wherein the two or more carotenoids are present in an amount of at least 20% by weight, based on the total weight of the suspension.
12. The composition according to any one of claims 8 to 11, wherein the natural carotenoid mixture comprises a suspension of a-carotene, b-carotene, lutein, cryptoxanthin and zeaxanthin, in vegetable oil.
13. The composition according to claim 12 wherein the a-carotene, b-carotene, lutein, cryptoxanthin and zeaxanthin are present in a combined amount of at least 20% by weight based on the total weight of the suspension.
14. The composition according to any one of claims 7 to 13, wherein the natural tocopherol comprises a mixture of natural tocopherols and natural tocotrienols.
15. The composition according to any one of claims 7 to 14, wherein the natural lycopene is present in an amount of from 1mg to 10mg.

[a-tocopherol is another name for vitamin E.]
From the evidence as a whole I understood the so called “natural lycopene” as claimed in the opposed specification to be the “as extracted” material, which was not pure but was known to be a mixture of carotenoid compounds, which were known to include b-carotene, a-carotene, leutin, cryptoxanthin, zeaxanthin and of course lycopene itself. I note at this point that the specification in suit teaches that natural lycopene, along with other natural carotenoids, is a mixture of cis and trans isomers whereas synthetic carotenoids are all trans isomers.
THE EVIDENCE

Evidence in support consists of:
· A statutory declaration by Professor Paul Nestel accompanied by exhibits PJN-1 to PJN-6
· A statutory declaration by Dr Michael Aviram accompanied by exhibits MA-1 and MA-2
Evidence in Answer consists of
· A statutory declaration by Richard H. Baddeley accompanied by exhibit RHB-1
· A statutory declaration by George Britton accompanied by exhibit GB-1.
Evidence in reply consists of:
· A second statutory declaration by Professor Paul Nestel
At the hearing only novelty, inventive step and section 40 were argued.
NOVELTY
A test for determining whether an invention lacks novelty is the "reverse infringement test" as set out in Meyers Taylor Pty Ltd v Viccar Industries (1977) 137 CLR 228 at page 235 Judge 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).
See also General Tire & Rubber Co v Firestone Tyre & Rubber Co Ltd, (1972) RPC 457 at pages 485, 486.
Thus: “To anticipate the patentees claim, the prior publication must contain clear and unmistakable directions to do what the patentee claims to have invented ... 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.”
The opponent relied on two documents. The first is:
Australian Patent Application No 88621/91 (660630) to Brigham and Women’s Hospital published on 16April 1992. (Hereafter referred to as the 630 patent)
This application is published well before the priority date of the application in suit and thus forms part of the prior art base. The citation discloses:
A method for inhibiting the occurrence of a major vascular event in mammals and particular in human beings by administration [including oral administration], of b-carotene and/or vitamin E, [i.e. a-tocopherol]. It seems to indicate that this may be due to the b-carotene and/or vitamin E acting to prevent oxidation of low-density lipoprotein. It also states clearly two other important facts. Firstly that the term b-carotene is intended to include b-carotene itself and biologically active analogues thereof. It then states that typical analogues include molecules, which demonstrate equivalent biological function but differ structurally. Such analogues include canthaxanthin, astaxanthin, zeaxantin, leutin and lycopene [my emphasis]. The specification only exemplifies the use of b-carotene itself and only refers to other analogues in the dictionary on page 7.
The compositions in this citation are specified on page 8 as “the unit oral dose may comprise from about 0.25 to about 500mg, preferably about 3 to about 100mg of b-carotene; about 5 to about 5000mg, preferably about 100mg to about 1000mg of vitamin and about the same relative amounts of each for the composition combining b-carotene and vitamin E”. This clearly encompasses the dosage range claimed by the present application and must therefore be an “effective amount.”
The question then is would the instructed reader understand this specification to be teaching about the use of lycopene? The person skilled in the art in this case would be the person treating the disease that is the cardiologist. The only evidence from such a skilled worker is from Professor Nestel who provides evidence for the opponent. He notes that whilst b-carotene and lycopene are chemically different he would understand the citation to teach that the two chemicals act in the same way and were both specifically named as a member of a small list of biologically active analogues. He states that he would have read the citation as clearly teaching the use of lycopene to treat heart disease in the same way that b-carotene had been exemplified.
The applicant did not provide any contradictory evidence from a cardiologist. The applicant’s sole expert declarant Dr Britton is a biochemist who is an expert in carotenoids. He attests that b-carotene and lycopene are chemically quite different compounds, which I accept and which was not disputed. However, his evidence does not address the point made by Professor Nestel that the skilled worker despite the 2 molecules being dissimilar, would nonetheless have considered lycopene and b-carotene to be biologically interchangeable for the treatment of heart disease in light of the teaching of the citation. In the absence of any contradictory declarations, from another cardiologist, I must believe what Professor Nestel states in his declarations
Prima facie this disclosure deprives claims 1, 2, 5, 6, 7, 8, 14 and 15 of novelty. It does not disclose the feature of active compound being dissolved or suspended in suitable liquids as per claim 12
The applicant argued that the lycopene disclosed in the citation was not natural as required by the claims. However the citation states that b-carotene is a naturally occurring substance, thus in my view it only contemplates the use of the natural rather than the synthetic form of the substance. [Likewise the Vitamin E is stated to be a fat-soluble vitamin found in vegetable oils, egg yolk, milk, fats nuts and cereal grains, all of which are natural products]. The citation clearly states that this includes all analogues including all other tocopherols.
The applicant also argued at the hearing that inhibiting the occurrence of a major vascular event was not the same as preventing or treating high serum levels of cholesterol as in the opposed patent specification. However the citation and the evidence in Professor Nestel’s declarations clearly indicates that in the medical community in Australia, as of the priority date, that it was well known that cholesterol build up and vascular events are related. It was also known that the reduction of cholesterol levels is a vital factor in preventing major vascular events such as heart attack or stroke. This was backed up by the declaration of Dr Michael Aviram. In addition the citation at page 7 specifically states that “the invention comprises both a therapeutic and prophylactic modality”.
In my view from Professor Nestel’s evidence there were clear and unmistakable directions in the citation to treat or prevent major vascular events by preventing or treating high serum levels of cholesterol or lipids. This is done in mammals, by administering b-carotene [which is this citation is defined as including lycopene] at dose rates which correspond to the patent in suit. There is also teaching to do this in conjunction with vitamin E [tocopherol]. The b-carotene of the citation is clearly stated as being a naturally occurring compound so it meets the criterion of being natural lycopene. Thus all the essential integers of claims 1 and 2 have been disclosed. Likewise claims 5, 6, 7, 8 ,14 and 15 which add the feature of tocopherol are also not novel.
The second citation relied by the opponent is:
Tan et al (1991) Am J Clin Nutr, 53:1027-30S published in at some unspecified date in 1991. (hereafter referred to as the Tan paper)
This is a technical article in the journal of the American Society for Clinical Nutrition. It is specifically directed at the effect of a mixture of a capsulated palm oil-vitamin E concentrate [so called “palmvitee”] in lowering both serum cholesterol and low density lipoprotein cholesterol in human subjects. Although the opponent did not provide the exact publication date, the journal is dated sometime in 1991. The applicant did not dispute the exact publication date. As such it I am satisfied that it is part of the prior art base and may be considered for novelty purposes.
The citation does not specifically mention lycopene at all. However the citation may be read in the light of the common general knowledge as it existed in Australia as of it its publication date in Australia. Thus for it to anticipate the method claims the opponent must both show that it was common general knowledge that palm oil contains lycopene and that that the citation teaches the use of an effective amount of lycopene to prevent or treat high serum levels of cholesterol and/or lipids in a mammal. Similarly to anticipate the composition claims the opponent must show that the “palmvitee” contains natural lycopene and natural tocopherol in amounts effective to prevent or treat high serum levels of cholesterol and/or lipids in a mammal.
Dr Stearne at the hearing merely submitted that it was “well known” that palm oil contains a variety of carotenoids including lycopene and and this view is not contradicted by anything in Professor Nestel’s declaration. However whilst I am prepared to believe that “palmvitee” contains both natural lycopene and natural tocopherol, this alone is not sufficient to anticipate the claims of the opposed specification. All the opponent has established is that an effective amount of “palmvitee” is able to prevent or treat high serum levels of cholesterol and/or lipids in a mammal, and that this may be due to the presence of any one or more of its constituents. What the opponent has not established is that natural lycopene or tocopherol are present in the “palmvitee” in an “effective amount” to prevent or treat high serum levels of cholesterol and/or lipids in a mammal.
Thus I am of the view that this citation neither gives clear and unmistakable directions to use an effective amount of natural lycopene, nor does it disclose a composition with an effective amount of lycopene and tocopherol, able to prevent or treat high serum levels of cholesterol and/or lipids in a mammal.

Consequently none of the claims lack novelty in the light of this document.
INVENTIVE STEP
Subsections 7(2) and 7(3) of the Patents Act of 1990, when read in the light of the definition of “prior art base” provided in schedule 1 of the Act, relevantly indicate that a claimed invention will lack an inventive step when compared with the prior art base, if it is obvious in the light of:
common general knowledge existing in the art before the priority date considered alone; or
common general knowledge when considered with information in a single document, provided that document could be reasonably be expected to have been ascertained, understood and regarded as relevant to work in the relevant art in the patent area before the priority date by the person skilled in the art.
A frequently used approach by the courts to the determination of an inventive step is the so-called “problem/solution” approach.
“…the test is whether the hypothetical addressee faced with the same problem would have taken as a matter of routine whatever steps might have lead from the prior art to the invention whether they be the steps of the inventor or not.”
Aickin J in Wellcome v VR Laboratories (Aust)
The problem faced by the inventor was how to treat high serum cholesterol and or lipid levels in mammals. The inventors solution was to administer an effective amount of natural lycopene and alternatively to administer an effective amount of natural lycopene and tocopherol.
What the opponent has not established is that it is common general knowledge to use an effective amount of natural lycopene to prevent or treat high serum levels of cholesterol and/or lipids in a mammal. Nor have they established that a composition containing an effective amount of natural lycopene and tocopherol to prevent or treat high serum levels of cholesterol and/or lipids in a mammal is part of the common general knowledge.
Consequently in my view the opponent has not established that the state of the common general knowledge in Australia before the priority date of the claims is sufficient by itself to demonstrate that the claims lack an inventive step
The opponent argued at the hearing that if I was unable to find a lack of inventive step based on the common general knowledge alone, then I should combine common general knowledge with each of the citations relied on for novelty. Considering the criteria set out in the Patents Act 1990 for finding lack of inventive step I do not think there is any doubt that both the 630 Patent and the Tan paper, which were both in the public domain before the priority date, would have been understood by the person skilled in the art.
In my view the person skilled in this art would have considered the patent literature. There has been no suggestion from the applicant that they would not. I therefore also consider that the 630 patent would have been “ascertained” and “regarded as relevant” because it is related to treating cardiovascular disease by dosing the patient with a composition, which cardiologists understand to be achieved by lowering cholesterol and or lipids, as claimed in some of the claims. Indeed it renders a number of the claims not novel and I have so found in this decision in respect of most of the claims.

For the reasons given in the decision on novelty claims 1, 2, 5, 6, 7, 8, 14,and 15 lack an inventive step. The feature of the natural carotenoid mixture being added in claims 3, 4, 8, 9, 10, 11,12 and 13 is common general knowledge. This is particularly so as it has been established that natural lycopene in the “as extracted state” is itself a natural carotenoid mixture. In addition the 630 citation discloses that the list of carotenoids labelled for the purposes of that patent as “b-carotene” were considered interchangeable as far as their clinical affect was observed in that instance. To use a mixture of them to me does not appear to involve any degree of inventiveness.
In addition the feature of active compound being dissolved or suspended in suitable liquids as per claim 12 in also not inventive. The 630 citation at page 10 teaches that in certain circumstances the active compounds are preferably dissolved or suspended in suitable liquids, such as fatty oils or liquid paraffin. Whilst it does not specifically teach the addition of natural carotenoid mixtures, suspended in vegetable oil, to the lycopene, or lycopene tocopherol mixtures, this appears to be a situation where the carotenoids have to be suspended in something and vegetable oils come under the general heading of fatty oils and are commonly used in the pharmaceutical industry. [I note also that the specification teaches that palm oil is itself a source of carotenoid mixtures. I also note that the claims that include this feature were added by amendment after acceptance, and consequently can hardly be claimed by the applicant to be the main inventive concept.].
I am therefore of the view that all of the claims lack an inventive step in the light of the 630 citation when combined with the common general knowledge.

There is evidence from all the declarants that they were in the habit of reading technical papers. Since the main thrust of the Tan paper is a method of lowering cholesterol in humans to reduce the incidence of heart problems by the use of palm oil with increased vitamin E content, I am confident that it would have been “ascertained”, and be “regarded as relevant” It details how palm oil is rich in vitamin E. There seems to be some suggestion that the researchers are not sure whether the benefit derives from the vitamin E, or the palm-olein TGs. It is a matter of fact that lycopene is one component of the mixture of natural carotenoids obtained from palm oil. However there is no evidence teaching that it would be obvious from this paper, combined with the common general knowledge, to reach the present invention of using natural lycopene, rather than any of the other components in palm oil, to lower cholesterol in mammals.
Consequently I am of the view that none of the claim lack an inventive step in the light of the Tan paper.
SECTION 40.
The opponent argued at the hearing that the present application was not clear. In particular Dr Stearne argued that the specification and claims as a whole are unclear due to the use of the terms “natural lycopene” and “natural carotenoid mixture”. However the opponent’s own witness Professor Nestel seems to have had no trouble with them.
Therefore in my view the claims are clear.
CONCLUSION
Claims 1, 2, 5, 6, 7, 8, 14 and 15 as presently drafted lack novelty in the light of the 630 patent. All of the claims also lack an inventive step in the light of the 630 patent combined with common general knowledge. As I believe there is no patentable subject matter present, I refuse the application.
COSTS
Costs normally follow the event. I see no reason to vary that practice. As in this case the opposition has succeeded I award costs against Cognis.
R. A. Melvin
Delegate of the Commissioner of Patents
18 August 2003
Patent attorneys for the applicant: Watermark, Perth
Patent attorneys for the opponent: Davis Collison, Cave Sydney