PPG Industries Inc. v Stauffer Chemical Company

[1985] APO 24

In the Matter of the Patents Act 1952 - and - In the Matter of Application No. 522675 for a Patent by PPG INDUSTRIES INC. - and - In the Matter of Section 59 Opposition thereto by STAUFFER CHEMICAL COMPANY.

DECISION OF A SUPERVISING EXAMINER:

Patent application No. 522675 entitled "Antidotal Compounds for Use with Herbicides" was lodged on 9 December, 1980 and is a convention application based on two U.S. applications both with a priority date of 26 December, 1979. Acceptance of the application was advertised in the Official Journal dated 17 June, 1982.

Stauffer Chemical Company lodged notice of opposition under section 59 on 21 September, 1982. The service of evidence was completed on 8 November, 1984 and the matter was heard in Canberra on 18 April, 1985. Dr. J.MCL. Emmerson of Counsel advised by Mr. A. Thomas, patent attorney of Collison & Co. , represented the applicant and Mrs. P. Moore of Counsel advised by Mr. J. O'Connor, patent attorney of Spruson & Ferguson, represented the opponent. Although the notice of opposition specified grounds (c) to (i) of sub-section 59(1) the only grounds argued at thy hearing were that the invention, so far as claimed in any claim lacks novelty, has been anticipated and prior claimed and that the complete specification does not comply with the requirements of section 40.

The Specification

The specification states that the invention relates to N-(2,2-dialkoxyethyl)-N-substituted-2,2-dichloroacetamides and to N-(optionally substituted 1,3-dioxolan- or dioxane-2-methyl)-N-substituted-2,2-dichloroacetamides, their use as antidotes, herbicidal compositions containing these compounds and methods of preparation of these compounds.

The dioxolan and dioxane dichloroacetamides are described in similar terms to those used in claim 1 and the dialkoxyethyl acetamides are described in similar terms to those used in claim 6. The preparation of the compounds is described in similar terms to those used in claims 5 and 10. Specific details are described for the preparation of four of the compounds.

The application of the compounds is described as follows:

"The compounds of this invention, as represented in Formulae I and II, have been found eminently well-suited for protecting growing crops, for example, corn from the phytotoxic effects of active herbicides particularly S-alkyl thiocarbamate herbicides and chloroacetanilide herbicides."

The antidotal compounds may be separately incorporated into the soil but are preferably formulated with the herbicidal composition. The preferred weight ratio of herbicide to the antidote lies in the range of 18:1 to 6:1. The formulation may contain more than one herbicide as well as other commonly used agricultural compounds, for example, fertilisers. The formulation may be applied to the soil in any manner well known in the art, for example, as a dust or as an emulsion.

The effects of S-ethyl dipropylthiocarbamate on hybrid field corn were compared in the absence and presence of the compound defined in claim 2 or claim 7. After 42 days the corn crop whose treatment included the claimed compounds was healthy and normal whereas the corn crop treated with the herbicide alone showed reduction in growth, hormonal distortion and necrosis.

The claims read as follows:

1. A compound of the formula:

wherein:

R is ethyl, propyl, 1-methyl ethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-propynyl, or 2-methyl-2-propynyl; R¹, R², R³ and R⁴ are independently hydrogen or methyl; and n is 0 or 1.

2. A compound of claim 1 wherein R is 2-propenyl, R¹ and R² are hydrogen, and n is 0.

3. A composition containing a herbicidally effective amount of S-alkyl thiocarbamate herbicide or chloroacetanilide herbicide and an antidotally effective amount of a compound defined in claim 1 wherein the weight ratio of herbicide to antidotal compound ranges from 18:1 to 6:1.

4. In a method of controlling weed growth among crops wherein a herbicidally effective amount of S-alkyl thiocarbamate herbicide or chloroacetanilide herbicide is used to control said weeds, the improvement residing in controlling said weeds with said herbicide in the presence of an antidotally effective amount of an antidotal compound defined in claim 1 to reduce the phytotoxic effect of the herbicide on the said crops and wherein the weight ratio of herbicide to antidotal compound ranges from 18:1 to 6:1.

5. A process for preparing a compound of claim 1 by reacting a substituted N-(2,2-dialkoxyethyl)amine of the formula:

wherein R is as defined in claim 1 and R⁵ and R⁶ are alkyl of up to 4 carbon atoms with an at least equimolar amount of dichloroacetyl chloride in an inert organic solvent and in the presence of an acid acceptor to form a diacetal of the formula:

and reacting, under anhydrous conditions and in the presence of an acid catalyst, the acetal with at least an equimolar amount of a diol of the formula:

wherein R¹, R², R³, R⁴ and n are as defined in claim 1.

6. A compound of the formula:

Wherein:

R is ethyl, propyl, 1-methylethyl, 2-propenyl, 2-butenyl, 2-methyl-2-propenyl, 2-propynyl, or 2-methyl-2-propynyl; R⁵ and R⁶ are alkyl of up to 4 carbon atoms.

7. A compound of claim 6 wherein R is 2-propenyl and R⁵ and R⁶ are methyl.

8. A composition containing a herbicidally effective amount of S-alkyl thiocarbamate herbicide or chloroacetanilide herbicide and an antidotally effective amount of a compound defined in claim 6 wherein the weight ratio of herbicide to antidotal compound ranges from 18:1 to 6:1.

9. In a method of controlling weed growth among crops wherein a herbicidally effective amount of S-alkyl thiocarbamate herbicide or chloroacetanilide herbicide is used to control said weeds, the improvement residing in controlling said weeds with said herbicide in the presence of an antidotally effective amount of an antidotal compound defined in claim 6 to reduce the phytotoxic effect of the herbicide on the crops and wherein the weight ratio of herbicide to antidotal compound ranges from 18:1 to 6:1.

10. A process for preparing a compound of claim 6 by reacting a substituted N-(2,2-dialkoxyethyl)amine of the formula:

wherein R, R⁵ and R⁶ are as defined in claim 6, with an at least equimolar amount of chloroacetyl chloride in an inert organic solvent and in the presence of an acid acceptor.

11. A compound as in Claim 1, substantially as hereinbefore described with reference to the accompanying examples.

In claims 1 and 6, as well as the description, 2-methyl-2-propynyl is included as a substituent for R but this radical cannot exist. I note that in the basic documents this substituent does not occur but rather there is a 1,1-dimethyl-2-propynyl substituent, which does not occur in the present specification. Dr. Emmerson conceded that this impossible radical was a printing error.

I also note that claim 10 contains an obvious error because the compounds defined in claim 6 cannot be prepared from chloroacetyl chloride and this reactant should be dichloroacetyl chloride. It is also apparent that the second formula in claim 5 is erroneously referred to as a diacetal in line 7 of the claim.

Evidence

The evidence in support of the opposition consists of statutory declarations made by Deborah Margaret Houghton, Dr. Andrew George Netting, Professor Barry Baughan Milborrow and Dr. John Lawrence Huppatz.

Dr. Netting is a Professional Officer in the School of Biochemistry at the University of New South Wales and the research aspect of his employment is concerned with plant physiology. He discusses the disclosures in patent application No. 522675 and concludes that there is substantial equivalence between the two types of compounds described in the specification because there is no differentiation in the biological effects. Dr. Netting considers that the article entitled "Antidotes to Protect Corn from Thiocarbamate Herbicide Injury" (exhibit AGN-3 but henceforth called the Pallos article) teaches that "an N,N-disubstituted dichloroacetamide is very likely to be a compound which would protect plants from thiocarbamate herbicide injury". He also argues that because of the similarity between the compounds described in Australian patent No. 467379 (exhibit AGN-4, henceforth tie Stauffer patent) and those defined in the present claims that the claimed compounds "would be very likely to possess antidotal activity to thiocarbamate herbicides". He points out that the Stauffer patent discloses a generic formula with a broad range of substituents and in particular he refers to compound No. 340 which has the following structural formula:

On the basis of this structural formula Dr. Netting concludes that the terms alkoxyalkyl and halolkyl which are used in claim 1 of the Stauffer patent, include within their scope a dialkoxyalkyl group and a dihaloalkyl group respectively.

Exhibit AGN-5 to Dr. Netting's declaration consists of U.S. patent No. 4,113,464 which describes dioxalane substituted monochloro amides and U.S. Patent No. 4,116,670 which describes dioxane substituted monochloro amides. I do not intend to consider either of these U.S. patents any further because the compounds in suit are substituted dichloro amides rather than monochloro amides.

The final exhibit to Dr. Netting's declaration (AGN-6) is an article entitled "Effects of Variations in the Acyl Moiety on Herbicidal Activity of N-Substituted Alpha-Chloroacetamides". Dr. Netting declares that this article teaches that if the compounds disclosed in the above U.S. patents were converted to dichloro amides they would be less effective as herbicides. Moreover he considers that the Pallos publication suggests that these same dichloro amides would be effective antidotes. This notional conversion would produce compounds which are within the scope of the present claims.

Professor Milborrow is a professor of Plant Biochemistry at the University of New South Wales and he has extensive research experience in the chemistry and biochemistry of biologically active compounds. He discusses the nomenclature describing the substituents used in the generic formula in the Stauffer patent. He gives his opinion on the scope of the terms haloalkyl, alkyl, alkenyl, alkynyl and alkoxyalkyl as they are used in the Stauffer patent. He also points out that the 2-methyl-2-propynyl radical which is used in the present description and claims cannot exist.

Professor Milborrow submits that the scopes of the terms haloalkyl and alkoxyalkyl include polyhaloalkyl and polyalkoxyalkyl radicals respectively and he points to several examples of these radicals in the Stauffer specification. In particular he refers to compound No. 340 and compound No. 472 which has the following structure:

He also declares that the scope of the tern alkoxyalkyl includes cyclic alkoxyalkyl radicals but he does not refer to examples of these in the Stauffer patent. He also points out that the IUPAC publication entitled "Nomenclature of Organic Chemistry" (exhibit BVM-3) states that "acetal" is an alternative name for a dialkoxyalkyl group in which both alkoxy radicals are attached to the same carbon atom.

Professor Milborrow asserts that in the light of the Stauffer patent it is likely that the compounds described in the present application would possess antidotal activity. He considers that the following partial formula:

is the toxiphore or "warhead" portion of the molecule which is intimately involved with the biological efficacy of the compounds. The other radicals are "decorations" and by varying these within the limits which are outlined in the Stauffer patent the molecule can be "tuned" for activity. The manner in which the "decorations" effect the activity is described as follows:

"The effect of the "decorative" portion could be due to the bulkiness of the substituent which affects the ease with which the molecule will fit into an enzyme pocket; it may be due to the effect of the radical on the molecule's partition coefficient which will affect the way in which the molecule can pass through the surface of leaves or through the cell membrane and reach its site of action."

He describes how the toxiphore was determined for compounds with a vastly different structural formula to the present compounds (exhibit BVM-4). He also considers that the Pallos publication describes the toxiphore for the present compounds. Professor Milborrow considers that the difference in structural formula between the present compounds and those described in the Stauffer patent would only have a secondary effect on the molecule's activity as a whole and the degree of antidotal activity could easily be determined by field tests similar to those described in the Stauffer patent.

Dr. Huppatz work in the Division of Plant Industry in CSIRO and his research is concerned with the biological activity of agricultural chemicals. He also compares the compounds described in the Stauffer patent with those described in the present specification and he interprets the terms haloalkyl and alkoxyalkyl in a similar way to Professor Milborrow. He also considers that the claimed compounds are prepared by standard methods.

Ms. Houghton's declaration states that she has been informed that exhibit AGN-6 and the Pallos publication were accessioned in the Library of N.S.W. before tie present priority date. She also states that the "Journal of Agricultural and Food Chemistry" which published both these articles is widely distributed throughout Australian libraries and she provides evidence of the distribution by exhibiting "Scientific Serials in Australian Libraries".

The evidence in answer consists of a statutory declaration made by John Melvin Swan. Professor Swan, who is currently Dean of the Faculty of Science at Monash University, has research interests in the design and synthesis of biologically active molecules. He commences his declaration by calculating that the scope of the present claims is limited to 384 distinct compounds whereas the Stauffer patent exemplifies only 513 compounds of the "many thousands of millions of different compounds" within the scope of its generic formula. He concedes that tie 2-methyl-2-propynyl radical cannot exist and also that the tern haloalkyl includes polyhaloalkyl. Professor Swan points out that compounds Nos. 340 and 472 described in the Stauffer patent have the most similar chemical structure to the claimed compounds. But he also notes that both these compounds "retain one hydrogen attached to the nitrogen atom" and that compound 472 is a monochloro amide. Moreover he goes on to argue that neither of these compounds is encompassed within tie very broad definitions given in the Stauffer patent. This argument is based on Professor Swan's interpretation of the scope of the term alkoxyalkyl as not including a .--dialkoxyalkyl group. He points out that in the structure of compounds Nos. 340 and 472 the alkoxy radicals are attached to the same carbon atom and compounds containing this feature are known to have different chemical properties to those containing an alkoxyalkyl group. This difference in properties is so marked that dialkoxylalkyl groups with the two alkoxy groups attached to the same carbon atoms are known as acetals instead of ethers. Professor Swan considers that the situation is still more sharply defined when the dialkoxyalkyl group is a cyclic acetal because these do not lie within the scope of the tern alkoxyalkyl group.

Professor Swan disputes Professor Millbrook's conclusion that the compounds defined in claims 1 and 6 of application No. 522675 contain substantially equivalent radicals merely because the compounds possess similar activity, by pointing to the absurdity of suggesting that all the radicals listed in the generic formula of the Stauffer patent must similarly be equivalent.

He also disagrees with Dr. Netting's assertion that given the disclosures of the Stauffer patent it would be very likely that the compounds of the invention would possess antidotal activity because:

"nothing is obvious or predictable in the difficult task of trying to establish a relationship between molecular structure and biological activity. The chemical and biological literature is replete with examples where even very small changes in structure make a dramatic difference to the use or efficacy of a drug."

The evidence in reply consists of further statutory declarations made by Professor Milborrow and Dr. Netting and one made by Ferenc Marcus Pallos.

Professor Milborrow points out that Dr. Swan has not commented on the conclusions relating to the active portion of the molecule or "war head". He also suggests that Professor Swan uses a contradictory approach in his interpretation of the terms haloalkyl and alkoxyalkyl because he includes polyhaloalkyl in the former and excludes polyalkoxyalkyl from the latter. Furthermore he argues that the terminology used to refer to classes of compounds is much less exact than that which is used to refer to a particular compound. Thus the generic terminology used in the Stauffer patent should be realistically interpreted in the light of the specification as a whole. Professor Milborrow considers that compounds Nos. 340 and 472 are embraced by the terms in the claims chosen to define the classes of compounds. He also interprets the Stauffer patent as envisaging the nitrogen atom in these compounds being substituted by a broad range of different radicals because there are compounds exemplified which contain a substituted nitrogen atom. He disagrees with Professor Swan's interpretation of the tern alkoxyalkyl and points out that the differentiation from acetals may be sound insofar as chemical behaviour is concerned but it is not sound insofar as nomenclature is concerned.

Professor Milborrow declares that it is by no means correct to say that nothing is obvious or predictable in the difficult task of trying to establish a relationship between molecular structure and biological activity.

He continues as follows:

"although the chemical and pharmacological literature is replete with examples where very small changes in the structure make a dramatic difference to the efficiency of a drug, the chemical and pharmacological literature is equally replete with examples where small changes in the structure do not make a dramatic difference to the use or efficiency of a drug. As I pointed out previously, small changes in stereo chemistry in the warhead or active site of a molecule, which interacts with an active site of an enzyme or receptor molecule, would very predictably make dramatic changes to the biological activity of the molecule. However, equally small changes at a site in the molecule which does not interact with the active site of an enzyme will usually make little difference to the biological activity of the compound."

In support of the view that there are relationships which allow predictions to be made about the activity of the compound from its structure, he refers to an exhibit in which such a relationship has been demonstrated for synthetic auxins.

Dr. Netting declares that the Stauffer patent teaches that a large number of compounds of the general formula given in the patent would possess antidotal activity and comments that it would be totally unrealistic to expect a patentee to provide an example of each and every compound they wished to cover in a patent. He comments that Professor Swan's distinction between compounds Nos. 340 and 472 and the claimed compounds is only appropriate if the compounds are looked at in isolation rather than in the context of the whole of the Stauffer specification. He asserts that the specification teaches that monochloro amides are less active than dichloro amides and he also states:

"There is no doubt in my mind that the Stauffer Patent not only teaches the specific compounds 340 and 472 as possessing antidotal activity but it also teaches me that a substitution of the hydrogen atom on the amide nitrogen by another group such as a small alkyl group, a small alkynyl group or a small alkynyl group would result in compounds which possessed antidotal activity."

Dr. Netting considers that because a dialkoxyalkyl group is disclosed by the Stauffer patent it is reasonable to expect that the cyclic analogue would also be a suitable substituent. He disagrees with Professor Swan with respect to the interpretation of the scope of the term alkoxyalkyl and points out that because the activities of compounds Nos. 340 and 472 were tested the patentee intended these compounds to be embraced by the claims. Dr. Netting whilst agreeing with Professor Swan's description of the chemistry of acetals submits that the nomenclature used in the Stauffer patent should be interpreted realistically and he considers that the interpretation should not be obscured by arguments concerning the finer points of nomenclature and chemical reactivity. With respect to the relationship between molecular structure and biological activity, Dr. Netting says:

"There are numerous examples throughout the technical literature where predictions have been made about the relationship between molecular structure and biological activity. To say that in this field everything is unpredictable is to negate the basis of science, being that nature is predictable once the basic criteria are elucidated. Therefore, certain relationships between molecular structure and biological activity become predictable once a certain amount of work has been done in the area."

In his opinion, it is reasonable to predict that the claimed compounds would have antidotal activity in the light of the disclosures in the Stauffer patent.

Dr. Pallos is employed by Stauffer Chemical Company in the U.S.A. as a Research Associate and he is co-inventor of the Stauffer patent and coauthor of the Pallos publication. He explains the research program which led to the invention described in the Stauffer patent and attests to its commercial success. He considers that the patent provides sufficient support to predict antidotal properties within the class of compound recited therein and he justifies the broad generic claims on the basis of the invention being a break- through.

Dr. Pallos then refers to exhibits FMP-2, FMP-3 and FMP-4 to illustrate the fact that persons skilled in the art recognised that dichloro amides had antidotal properties in the presence of thiolcarbamate herbicides before the present priority date. Even though there is no evidence that these exhibits have been published in Australia before the priority date I shall consider them later in this decision.

Dr. Pallos also refers to a declaration dated 28 July, 1983 (exhibit FMP-5) which was filed with the U.S. Patent Office as part of the proceedings in respect of U.S. patent No. 4,415,353. He relies on this declaration to substantiate his predictions of antidotal activity for the broad class of dichloro amides disclosed in the Stauffer patent. Whilst U.S. patent No. 4,415,353 is a divisional of a divisional of a divisional, of the basic documents of the Stauffer patent there is no evidence that the results described in exhibit FMP-5 were published in Australia before the present priority date. I will therefore disregard this declaration.

Dr. Pallos then compares the compounds disclosed in the Stauffer patent with those disclosed in application No. 5k2675. He points out that the --compounds described as having the highest activity in the Stauffer patent are dichloro amides in which the nitrogen atom does not have a hydrogen substituent. He also states that he would have predicted that substituting an organic residue for a hydrogen atom on the nitrogen atom of compounds Nos. 340 and 472 of the Stauffer patent would enhance their respective antidotal activity. He would have been able to make this prediction on the basis of the Pallos article. He then points out that the only difference between compound No. 340 and the compounds defined in claim 7 is that an organic residue is substituted for the hydrogen atom on the nitrogen atom of compound No. 340.

In Dr. Pallos' opinion the generic name alkoxyalkyl embraces dialkoxyalkyl radicals and he indicates other examples in the Stauffer patent where a generic name covers instances of multiple substitutions. He also points out that Professor Swan has been inconsistent in his interpretation of the term alkoxyalkyl with respect to his interpretation of the term haloalkyl. He also disagrees with Professor Swan's statement concerning the relationship between molecular structure and biological activity. He continues as follows:

"The specification of the Stauffer Australian Patent is a well exemplified specification which predicted antidotal activity for a very broad range of compounds. Given the broad basis of the patent and the nature of the compounds disclosed therein, there was provided a very good basis from which to predict the antidotal properties of other compounds not exemplified."

Finally he concludes that it was only practical for Stauffer to market one of the compounds disclosed in the patent and the compound which it has chosen is as follows:

Stauffer Patent

The majority of the submissions concerning anticipation are in respect of the Stauffer patent, i.e. Australian patent No. 467379.

The Stauffer patent which was available for public inspection on 18 October, 1973 is entitled "Herbicide Compositions". This invention concerns herbicidal compositions consisting of an active herbicidal compound and an antidote therefor and the methods of use of the herbicidal compositions. The antidote compounds are described by the following generic formula:

in which R can be selected from a large group of substituents including haloalkyl; R, and R2 can be the same or different and can be selected from a large group of substituents which includes hydrogen, alkenyl, alkyl, alkynyl, cycloalkyl, alkylcycloalkyl, alkoxyalkyl, cycloalkenyl and tetrahydrofurylalkyl provided that when R₁ is hydrogen R₂ is other than hydrogen and halophenyl.

The Stauffer patent explains that the background to the invention is that commercially available herbicidal compounds, e.g. thiolcarbamates and anilides, can cause serious injuries to the crop plant as well as weed pests. The crop plant can be protected against injury or their tolerance substantially increased by adding the antidote compounds to the soil.

The antidote compounds can be synthesised by mixing together an appropriate acid chloride with an appropriate amine. The Stauffer patent then gives detailed instructions describing the preparation of 42 compounds. The substituents for a further 513 compounds are listed in Table I and this includes compounds Nos. 340 and 472 which have been mentioned previously.

The results of growing representative crops in the presence of various herbicides when some of the antidote compounds were incorporated into the soil are reported in Table II. Similarly Table III reports the results when corn seeds, which had been treated with the compounds listed in Table 1, were grown in the presence of various herbicides.

The Stauffer patent states that the antidote compounds can be used in any convenient form and also states that in the preferred form the antidote is --admixed with the herbicide and the amount of antidote is in the range of .0001 to 30 parts by weight for each part of herbicide.

The specification defines the phrase active herbicidal compound to include a herbicidal compound alone or admixed with other active compounds. The herbicides are of a general type and are effective against a wide range of plant species with no discrimination between desirable and undesirable species. Thus by using the antidote compounds it is possible to prevent injury to a desired crop species in the presence of a specific herbicidal compound or combination.

Claim 1 of the Stauffer patent claims a herbicidal composition comprising an active herbicidal compound and an antidote defined by the generic formula given above except several combinations of a particular kind of herbicide and a group of antidotes are excluded from the scope of the claim. Claims 2 to 7 limit the range of the substituents of the antidote compound and claim 8 defines a composition restricted to a range of named herbicidal compounds. The composition defined in claim 9 contains the antidote compound in an amount of .0001 to 30 parts by weight per each part by weight of the active herbicide whilst claim 10 is directed to a method of controlling weed pests.

Mrs. Moore submitted that the compounds claimed in claims 1 and 6 of application No. 522675 fell within the scope of the generic formula of the Stauffer patent. This submission was based on the following interpretations of the structural formula in the two specifications:

(1) The present formulae include a dichloromethyl substituent and this lies within the scope of R in the Stauffer patent being haloalkyl.

(2) The groups R in the present formulae are disclosed in Vie broad generic terms of R₁ or R₂ in the Stauffer patent.

(3) The acetalalkyl group of the formula in the present claim 6 falls within the scope of the term alkoxyalkyl group which is an alternative choice for R₁ or R₂ in the Stauffer patent.

(4) The cyclic acetalalkyl group of the formula in the present claim 1 is a cyclic analogue of the alkoxyalkyl group which is an alternative choice for R₁ or R₂ in the Stauffer patent.

In reply Dr. Emmerson argued that the compounds defined in claims 1 and 6 did not lie within the scope of the generic Stauffer formula.

With respect to paragraph (1) above Dr. Emmerson conceded that the scope of the term haloalkyl included a dihaloalkyl group and therefore he agreed that the dichloromethyl group in the present formulae lay within the scope of R in the Stauffer patent. He also agreed with the interpretation in paragraph (2) above although he pointed out that R in claims 1 and 6 could not be hydrogen even although this was a possibility for R₁ and R₂ in the formula in the Stauffer patent. However Dr. Emmerson's disagreement with Mrs. Moore's submission was in the interpretation of the scope of the alkoxyalkyl group. His interpretation of the alkoxyalkyl group was that this group consisted of two alkyl groups bonded together by an oxygen atom and did not include a dialkoxyalkyl group. Dr. Emmerson supported this interpretation with a reference to the distinct chemical properties of acetals referred to by Professor Swan.

Mrs. Moore further supported her interpretation of the scope of the alkoxyalkyl group by pointing out that compounds Nos. 340 and 472 in the Stauffer patent contained a dialkoxyalkyl group in the form of an acetalalkyl group. Therefore she considered that it was clear that the broad term included acetalalkyl groups. In order to show that cyclic acetalalkyl groups were also included Mrs. Moore pointed to the many examples of cyclic substituents found in the Stauffer patent. She suggested that her interpretation of the nomenclature used in the Stauffer patent would be that used by a plant biochemist rather than a purist organic chemist.

Dr. Emmerson responded by pointing out that the Stauffer patent listed cyclic substituents as possibilities for R, R₁ and R₂, for example cycloalkyl.

Whilst I am aware that there are various methods for naming organic compounds, including the systematic nomenclature proposed by IUPAC, I consider that the nomenclature of the Stauffer patent should be given a purposive construction in the context of the specification (Catnic Components Ltd. v. Hill and Smith Ltd. (1982) RPC 183 at page 243). Thus compounds Nos. 340 and 472 contain a dimethoxyethyl group, which is represented in the generic formula by R1 or R2- The most appropriate substituents listed under R₁ or R₂ for a dimethoxyethyl group is alkoxyalkyl. Thus I interpret the scope of the alkoxyalkyl group to include dialkoxyalkyl groups including acetalalkyl groups. In the context of the Stauffer specification I do not think that the different chemical properties of acetal groups should modify this interpretation of the nomenclature. Thus I am satisfied that the compounds defined in claim 6 of patent application No. 522675 fall within the scope of the generic formula in the Stauffer patent.

However the compounds prepared in Examples 4 and 27 of the Stauffer patent contain a tetrahydrofurylmethyl group, which is represented by R₁ or R₂ in the generic formula. Whilst this group might be considered as a cyclic alkoxyalkyl group it is listed under R₁ or R₂ as a tetrahydrofurylalkyl substituent. Therefore in the context of the Stauffer patent my interpretation of the scope of the alkoxyalkyl group does not include cyclic alkoxyalkyl groups and certainly does not include cyclic dialkoxyalkyl groups. Therefore I consider that the compounds defined in claim 1 of patent application No. 522675 do not fall within the scope of the generic formula in the Stauffer patent.

In the light of this interpretation I now have to consider whether the Stauffer patent anticipates, prior claims or renders not novel claim 6 and appended claims in patent application No. 522675.

Anticipation

Mrs. Moore submitted that the Stauffer patent anticipated claims 6 to 11 of patent application No. 522675 because the claimed compounds fell within the scope of the generic formula of the citation and had the same use. She argued that the Stauffer patent should be construed in the light of the fact that it concerned a pioneering invention. Mrs. Moore also directed my attention to the compounds described in the Stauffer patent which illustrate the individual functional groups found in the compounds claimed in claim 6. In particular she directed my attention to the similarity between the structures of the claimed compounds and compounds Nos. 340 and 472 in the Stauffer patent.

Mrs. Moore submitted that the Stauffer Patent disclosed that all the compounds within the scope of its generic formula possessed antidotal activity. She based this submission on Professor Milborrow's evidence by arguing that the invention described in this patent was that the partial formula

was the "war head" for antidotal activity. Thus she considered the substituents bonded to the nitrogen atom in the compounds defined in the present claim 6 are "decorations" which merely alter the antidotal activity. Therefore she argued that the presently claimed compounds do not possess a special advantage beyond the compounds described in the Stauffer patent.

Dr. Emmerson commenced his submissions with respect to anticipation by stating that some of the opponent's witnesses had interpreted the disclosures of the Stauffer patent by forming a mosaic with other documents. He argued that this was not permissible in the light of "the four corners rule" (Rose Holdings Pty. Ltd. v. Carlton Shuttlecocks Ltd. (1957) CLR 444 at page 450). I agree that the interpretation of the Stauffer patent should not be modified by combining its disclosures with other documents filed in support of the opposition, unless that document is part of common general knowledge. However I am satisfied that none of the documents filed in support of this opposition have been shown to form part of the common general knowledge in Australia.

Dr. Emmerson stated that there were a very large number of compounds which were comprehended by the generic formula in the Stauffer patent and he claimed that this generic formula satisfied "the gorilla test" (Beecham Group Ltd. v. Bristol-Myers Company (1980) 1 NZLR 192 at page 218). That is, its countless permutations and combinations of chemical formulae could have been produced by a gorilla mindlessly producing chemical formulae with no knowledge of what they mean, nor whether any suggested formula was capable of manufacture. He contrasted this vast number of compounds with the much smaller number of compounds claimed by the present claims.

Dr. Emmerson submitted that a document could not satisfy the well known criteria for anticipation, e.g. clear and unmistakable directions (Flour Oxidizing Co. v. Carr Co. Ltd. (1908) RPC 428 at 457) and the infringement test (The General Tire and Rubber Co. v. The Firestone Tyre and Rubber Co. (1972) RPC 457 at page 485), unless it disclosed compounds with the same structural formula as those claimed. He argued to do otherwise would be to ignore the molecule as an entity and merely regard it as a collection of interchangeable substituents. Dr. Emmerson then pointed out that, although compounds Nos. 340 and 472 both contain a dimethoxy acetalethyl group, they also have a hydrogen atom bonded to the nitrogen atom whereas none of the claimed compounds have this feature; he also noted that compound No. 472 is only a monochloro amide.

Dr. Emmerson also argued that the Stauffer patent did not describe its compounds as having a "war head" and he stated that tie manner in which the specification was drafted led tie reader away from this concept. This was because the generic formula did not specify that the "war head" could be combined with any substituents but limited the number of substituents to those listed for R, and R2- He also referred to Professor Milborrow's admission that the "decorations" could alter the activity of a compound by changing the way the molecule might fit into an enzyme pocket or by altering the ability of the compound to pass through the cell membrane and reach its site of action. He said this admission was relevant in view of the fact that both parties acknowledged that acetal groups were acid sensitive.

Dr. Emmerson submitted that the present situation was very similar to that which occurred in the Amoxycillin case (Beecham Group Ltd.'s Application (1980) RPC 261) wherein the Court of Appeal found that an application describing one optical isomer was not anticipated by a disclosure of the racemate. He also pointed to the similarity between the present situation and that found in the Amoxycillin licence case (Beecham Group Ltd. v. Bristol Laboratories International S.A. (1978) RPC 521). He also submitted that an application claiming a compound could not be anticipated unless the citation described the preparation of the compound and described its properties (E.I. Du Pont Nemours and Co. (Witsiepe's) Application (1982) FSR 303 at page 311). Dr. Emmerson argued that in the light of these decisions there was sufficient room for a patent to be based on the presently claimed compounds because it was clear from the Stauffer patent that the compounds had not been made. Only after a compound had been prepared was it possible to know that it would be eminently well suited for protecting growing crops from the phytotoxic effects of active herbicides.

In reply Mrs. Moore pointed out that in the Amoxycillin cases and Witsiepe's Application the compounds had been selected from a large group of compounds because they had been found to have unexpected properties. She argued that the most relevant case in the present situation was the well known I.G. Farbenindustrie case (1930) RPC 289.

The question I have to consider is whether the claimed compounds represent a true selection from the compounds described in the Stauffer patent or does the present application amount to a mere verification (I. Farbenindustrie case (supra) at page 322). In Witsiepe's Application (supra at page 315) it was decided that a selection from a class, that is a group of products or processes from which some particular result or results may be predicted, may give rise to a valid selection patent:

"If from such a class of related or homologous products or processes a property, quality or use is discovered which could not have been predicted by anyone ordinarily skilled in the art in question."

However the product or process will be specifically patented and as such published in priority, so as to be effectively monopolised and unavailable for any later patent, if it is identified in the earlier specification but it is not in that specification a member of a class. Even then it will not bar a later patent if it is no more than a starting point on the road to a new invention.

I agree with Dr. Emmerson that the Stauffer patent does not describe the compounds it discloses in terms of a "war head", although the Pallos article and exhibit FMP-4 do provide some basis for predicting the antidotal activity of some of the compounds within the scope of the generic formula in the Stauffer patent. However there is no evidence that either of these articles forms part of common general knowledge in Australia and therefore they cannot be used to aid the interpretation of the Stauffer patent. Further I note that Mrs. Moore's interpretation of the "war head" includes all the substituents listed for R in the Stauffer patent whereas the compounds of the present invention are restricted to dichloramethyl amides.

The antidotal activity of the compounds described in the Stauffer patent is reported in Tables II and III but there is no statement in the specification that a structure-activity relationship can be derived from these results. It is apparent from the results described in those tables that the antidotal activity varies widely in relation to the structure of the antidote and the nature of the herbicide. There is no description of that part of the molecule which could be considered as the "war head" neither is there a description of the basic criteria which would establish that there is a relationship between structure and antidotal activity. The Stauffer patent specification does not teach that it discloses compounds wherein small changes ,--in structure do not make a dramatic difference in the antidotal activity.

Therefore I conclude that the Stauffer patent discloses that the compounds within the scope of its generic formula may have antidotal activity but the activity of any particular compound will have to be determined empirically. This conclusion is particularly relevant to compounds containing acetalalkyl and cyclic acetalalkyl groups because those groups are known to be sensitive to acids.

In support of my conclusion I note the fact that the relationship between the structure of chloro amides and antidotal activity was published in Australia after the priority date of the Stauffer patent (the Pallos article and exhibit FMP-4 to the Dr. Pallos' declaration). Moreover before the priority date of the Stauffer patent it appears that it was known in Australia that there was a relationship between the structure of certain chloro amides and herbicidal activity (exhibit AGN-6 to Dr. Netting's declaration).

The consequence of my conclusion that the Stauffer patent does not disclose that the antidotal activity of a compound can be predicted from its structural formula is that the compounds claimed in the present application do not fall in the class of those described in the Stauffer patent. This conclusion is supported by the Amoxycillin licence case ((supra) at page 567) wherein Lord Wilberforce said:

"Distinctive" and "unexpected" are words of degree and I take "unexpected" (not be it noted, since the words are "it maybe", an essential requirement) to include cases where the maker of the original invention did not known, or was not sure, whether, or to what extent, the properties in question would be found to exist in the selected members of the class."

and he agreed that (page 568):

"the selection of some from a large number of possible compounds, and the exploration of their properties by empirical investigation, is a different thing from verification and leads to different consequences."

Next I have to consider whether the claimed compounds have been published in priority by the Stauffer patent. According to Professor Swan the .-generic formula in the Stauffer patent discloses "unaccountable billions of compounds" of which only 513 are specifically illustrated by choosing a specific substituent for each of R, R₁ and R₂ but there is no description in the citation of preferred substituents. The preferred compounds exemplify combinations of substituents for R, R₁ and R₂ and the structural formulae of compounds Nos. 340 and 472 although similar to the present compounds contain significant differences, a fact to which Dr. Emmerson referred. I do not think the proper approach is to argue that these preferred compounds disclose all the structural formulae which a gorilla might derive by choosing any of the substituents these compounds contain. Rather I consider the preferred compounds exemplify the preferred combinations of substituents which have been chosen for R, R₁ and R₂. Although I have applied the "gorilla test" suggested by Dr. Emmerson, I think that an alternative analysis can be performed by applying the reasoning of the High Court in Ethyl Corp. v. Commissioner of Patents (1969) AQJP 2860). Thus I conclude that the generic formula in the Stauffer patent does not disclose the compounds claimed in the present claim 6 because it may, but it does not necessarily include them.

The consequence of this conclusion is that the claimed compounds have not been published in priority by the Stauffer patent because it does not provide clear and unmistakable directions to use the compounds claimed in claim 6 and acts merely as a starting point on the road to the present invention.

Thus I find that the Stauffer patent does not prior publish claim 6 neither does the patent render the claim not novel. A similar finding applies to claims 7 to 9.

I am also satisfied that the Pallos article and the other exhibits referred to in the declarations made by Dr. Netting and Dr. Pallos do not anticipate application No. 522675.

Novelty

Mrs. Moore also submitted that claim 10 was otherwise not novel in the light of the paragraph in the Stauffer patent which reads as follows:

"The compounds represented by the above formula can be synthesised by mixing together an appropriate acid chloride with an appropriate amine. A solvent such as benzene can be used if desired. The reaction is preferably carried out at reduced temperatures. After the reaction is complete, the end-product is brought to room temperature and can be readily separated."

She argued that the only difference between this paragraph and claim 10 was that the process defined in claim 10 was conducted in the presence of an acid acceptor and, according to the declarations which were served in support of the opposition, this difference was within the common general knowledge of the appropriately skilled person.

Dr. Emmerson submitted that the experts, who had made declarations in support of the opposition, had made inappropriate comments on the process described in the present specification (British Celanese Ltd. v. Courtauld Ltd. 52 RPC 171 at page 196).

Whilst Professor Milborrow and Dr. Huppatz comment on the novelty of the process to produce the claimed compounds there are no exhibits annexed to their declarations which demonstrate what was common general knowledge in Australia at the present priority date. Moreover I have already found that the products of the process defined in claim 10, i.e. the compounds defined in claim 6, are novel in the light of the Stauffer patent. Therefore I am satisfied that claim 10 defines a novel process.

Prior Claiming

Mrs. Moore submitted that claims 8 and 9 were prior claimed by the claims of the Stauffer patent. In reply Dr. Emmerson argued that on the basis of Ethyl Corporation (Cook's) Patent (1970 RPC 227) if I found that the compounds claimed in claim 6 were a valid selection from the Stauffer patent then the appended claims 8 and 9 were not prior claimed. I agree with Dr. Emmerson's argument regarding prior claiming.

Section 40

Mrs. Moore submitted that, if I decided that the Stauffer patent did not disclose the compounds of the present invention, then I should also find that the present claims were not fairly based on the description because the preparation of only four compounds was described and only two of the compounds were tested for antidotal activity. Dr. Emmerson submitted that Mrs. Moore's approach was not the correct one to apply with respect to determining if the claims were fairly based. He said the fact that the Stauffer patent did not disclose or test all the compounds within the scope of its generic formula did not imply that its claims were not fairly based. I also agree with Dr. Emmerson in this respect and I am satisfied that the claims of application No. 522675 are fairly based on the description.

Previously I have noted instances where the specification does not comply with section 40 and Mrs. Moore drew %t attention to the impossible radical although I consider that this only formed a minor part of the opponent's case.

Summary

I have found that application No. 522675 has not been anticipated or prior claimed and is novel. The specification however, does not comply with section 40 in the instances I have noted and I give the applicant 60 days from the date of this decision to propose amendments to overcome these defects. I award the costs of this opposition against the opponent.

(M. KENDALL)

Supervising Examiner of Patents

18 SEP 1985