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Microbiological Inventionsand the Patent Law-theInternational DimensionR. S. Crespi aa British Technology Group , 101 NewingtonCauseway, SE1 6BU , London , UKPublished online: 15 Apr 2013.

To cite this article: R. S. Crespi (1985) Microbiological Inventions and the Patent Law-the International Dimension, Biotechnology and Genetic Engineering Reviews, 3:1,1-38, DOI: 10.1080/02648725.1985.10647808

To link to this article: http://dx.doi.org/10.1080/02648725.1985.10647808

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1Microbiological Inventions and the PatentLaw-the International Dimension

R. S. CRESPI

British Technology Group, 101 Nelilillgton C(luse~'vay, London SEJ 6BU, UK

Introduction

Unlike most papers which appear in this series to review the state of the art"this contribution reviews the state of the law. It is focused narro\vly" however.on the Patent la\\', one particular species of the legal genus of ~Industrial

Property" which covers also Trademarks .. Designs .. Plant Variety Rights andCopyright. The blW of industrial property ~ both national and international .. iscontrolled by written statutes as well .as court...made case la\v and sets dO"Jnwhat sorts of invention cind innovation may be protected and the procedureby which the appropriate protection may be secured. As against protection bymeans of patents .. there has to be set the option of industrial or trade secrecy ..the main broad alternative method of ensuring protection against piracy orimitation of ideas and valuable new technology.

Although the microbiological inventor may not expect to have a specialpatent la\v for his subject .. he might well assume that this technology \vould betreated in nluch the same way by patent law from one country to another. Hewill be surprised by the diversity that exists anlong the different nationalsystems and the variety of attitudes towards what may" or may not~ bepatentable. In the la\v of the European patent. for example" "programs forcomputers" are specifically excluded from patentubility. In contrast" thepatentability of micro-organisnls and other lo\ver life forms is not expresslyallowed or denied in any patent statute" yet the pre.judice against patentingorganisms has existed for many years and still survives in various parts of the\:vorld.

Biotechnology is rooted in classical microbiology" for which trade secrecyhas often provided sufficient protection for the industrial innovator. but in itsmodern phase biotechnology has extended into areas in \vhich patent

Ahhreviations: CCPA. Court of CustonlS and Patent Appeals: EPC. Europe,)n Patent Conven­tion: EP(). European P<ucnt Office: IDA. International Depositary Authority: NRDC. NationalResearch Development Corporation: NRRL. Agricultural Research Service Culture C()llcCli(}n~

RPC. Reports of P~Hcnt Design and Tradcrnark C~ISCS; UP()V. International Convention forProtection of Nc\v V~lrictics or Phtnts: WIPO. World Intcllcctucll Property Organization.

BiCJudm%gy (mil (j(~"t.~/i(' EII~i,,(~erill~ R(·,·ic'u:-, - Vol. 3. September 19H5U26.t-S725/N5/U)/OI-37$HUMJ + so.un © Intercept Ltd

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protection can make a significant contribution to scientific and businessenterprise. Scientists and businessmen have accordingly looked to the patentla\v to provide forms of protection properly geared to the emerging ideas'tprocesses and products of this new technology. But the patent law also has itstraditions and these pre-date the newer biotechnology by a considerablemargin. Moreover ot patent la\\' is based on general concepts which arerequired to apply to the whole range of inventions--ehemical, mechanical"electrical .. etc.-which come vlithin its purview and therefore the microbiolo­gical invention must be fitted into this established conceptual framework asbest it can. Although there is no separate patent statute law governing what ispatentable in microbiology .. there are special official regulations governingprocedural matters for the patenting of microbiological inventions.. e.g. thedeposition of new strains in Culture Collections for patent purposes, and thereis an international Convention which deals with this particular problem.There is also a substantial volume of case law on the subject" which will beoutlined bclo\v.

l"he present state of the patent law can be best understood by tracing itsevolutionary history. Before doing so_ however't certain basic concepts mustbe clarified which are vital to an understanding of the current debate aboutthe adequacy or otherwise of the patent law in relation to the more recentdevelopments in biotechnology.

THE NATURE OF PATENTS

A patent is a fOflTI of property right granted by appropriate state authority inrespect of an invention and legally enforceable by its owner against unautho­rized exploitation by others. To obtain patent protection an application mustbe made to the Patent Office and this is usually done by the inventor or\\'hoever claims the o\vnership and benefit of the invention. The patentapplication will be officially examined and~ after a process of negotiationbetween the applicant and the Patent Office Examiner ~ it will be accepted orrejected. This examination is principally concerned with the written specifica­tion of the invention. which must be filed with the application and \vhich nlustdefine the scope of the protection sought (the claims of the patent).

Among the criteria for patentability there are four basic requirements.three of which the invention itself must fulfil.. namely .. it must have (1)novelty .. (2) inventiveness and (3) practical utility or industrial applicability\vhile the other (4) concerns the specification; this nlust be adequate incontent to enable those of ordinary skill and experience in the field to followthe directions and obtain the promised results. The application of thesecriteria in practice often involves legal subtleties~ as will be described later ..but they may be simply sUlnnlarized as foHows.

Novelty

This condition requires that the invention must not already be available toothers by any kind of public disclosure or use before the date of filing of the

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Microbiological inventions and the patent lalv 3

patent application. Although the rule is commonly expressed in terms of'publication' it is important to note that this includes all forms of publicdisclosure and is not limited to literature publication. It covers all forms ofpublication, disclosure and use previous to the patent application, even thosemade by or due to the inventor himself! All such prior knowledge etc. isknown as the ~state of the art' or 'prior arf. Prior experimental use whichoccurs within the privacy of the research laboratory is not part of the state ofthe art as long as the details remain as private or restricted information. Adisclosure by an inventor can sometimes be confidential.. as distinct frompublic, and this does not destroy novelty. This outline of the novelty rulesapplies to most countries; however, the United States, Canada~ Japan and afew others are exceptions in allowing grace periods for filing patent applica­tions in their respective countries after publication or use by the inventor.

In ventiveness

The invention Inust not be 'obvious' to the ordinary skilled worker over thestate of the art, i.e. it must not follow plainly or logically from what is alreadyknown. Research workers \vho \vrite literature publications which presenttheir work as a natural logical scientific development from prior publishedpapers make it difficult for themselves to argue that it has inventive character.

Utility or industrial application

Utility is a crucial concept in US patent law but is not limited to industrialutility and any other sort of practical utility can suffice. In European law aninvention must be capable of industrial application.

Adequate disclosure

The description of the invention must be such as to permit repetition of thework by a person of normal skill. This criterion has Jed to special problems\vith biological inventions in that it is often difficult, or even impossible. todefine living organisms or their products with sufficient precision to ensurereproducibility. l"his review will describe some of the changes which havetaken place in the interpretation of patent law in response to a growingrealization of these important features of patents concerned with biotech­nology.

These four criteria can be interpreted in different \vays by the differentnational patent authorities and nlay have to be confornled to meet ne\vrequirements or modified in the light of the findings of courts of Jaw. For suchreasons there are differences in patent law and its interpretatiqn in variouscountries although international agreements have done much to nlinimizethese inconsistencies.

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SCOI)E AND TYPES OF PROTECTION

A patent confers a monopoly \vithout establishing of itself a situation \vhichcan be described as Monopoly. That is" a patent provides an exclusive right tothe use and enjoyment of a j){lrticular invention. It does not nlonopolizeanything nlore than the specific invention, does not preclude alternative anddifferent methods of solving the same problem. and is not anti-conlpetitivebut on the contrary stimulates competition and the search for ways to "designaround' the patent. It is therefore a reasonable right to allov,' to those whoinvent and thereby enrich the state of the art. Moreover, the right isconditional upon any prior and wider embracing rights which may be held byothers and is therefore not an automatic guarantee of the freedom to useone"s o\vn invention. The precise extent of the right in technological terms isgoverned by the patent claims~ a topic to be discussed below. The writing of apatent specification is always a highly individual work tailored to theparticular invention and the experimental data available but inevitably acertain stereotype structure acceptable to Patent Offices has enlerged overmany years. It is standard practice:

1. To state the problem at which the ~esearch has been ainled;2. To discuss and assess previous attempts to solve it;3. To describe the novel particular solution in broadest terms;4. To provide data and worked Examples to instruct the reader how to

apply the invention in practice. (The extent to which the invention isexemplified by actual data covering a wide range of possible application iscrucial in detennining the scope of the claims that will be granted), and

5. To present claims defining the scope of protection sought.

Patent CllliJ'rIS

The claims of a patent have a purely legal function and although this is notprecisely the same under all national patent systems it is broadly true that thewording of the clainls is a guide to the scope of protection obtained. It is forthe applicant to devise these clailTIs and to do so wisely in order to cover allconceivable methods, forms and embodinlents in which the invention can beexploited conlmercially. If this is not done comprehensively, the patenteecannot assunle that a court of law \vill subsequently fill in for hiln the gaps heInay have left in his protection inadvertently or through lack of foresight.Thus, in an early case about a patent for the manufacture of a cordite-likecomposition on \vhich the inventor (Nobel) had sued an infringer" a Britishcourt pointed to the importance of the invention as clabned--not theinvention which the patentee might have claimed if he had been "veil advisedor bolder but that which he has in fact and substance claimed on a fairconstruction of the specification ~. Nowadays there is nlore latitude in theinterpretation of patent claiJns but liberality cannot be taken for granted.Therefore the applicant usually through his patent agent, argues the case\vith the Patent Office Examiner, and strives for allowance of the broadestpossible clainls and the greatest variety of claim types in order that his

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interests are properly protected. In this the applicant does not have unlimitedfreedom~ however, because the claims must be 'supported by the description'and therefore the experimental data and technical teaching in the specifica­tion provide some check on how many different types of claim can beobtained and what their scope may be. The famous Chakrabarty case decidedby the United States Supreme Court in 1980 was essentially about what canproperly be the subject of a patent claim in the domain of lower life forms.

Types of clairn. The types of claim open to the applicant in relation tomicrobiological inventions will be discussed in detail later but for the presentit \vill be sufficient to indicate their general character. l"he most usual forms ofclaim in microbiology are claims to new processes, products, compositionsand uses. These are written in the form now well established for cheJnicalinventions. Indeed, there is a considerable body of precedent in the case lawof chemical patents that is taken over into its microbiological counterpart.Some of this will have to be mentioned below as background to our mainfocus of interest.

The product clabn. This is of pre-eminent importance. Product claims ar~ oftwo main types, known as the product per se claim and the product-by-processclaim. A product per se claim is one that extends to a substance ornlicro-organism as such and is independent of any defined process ofpreparation or derivation. Such a claim is said to provide absolute productprotection. A product-by..process claim, on the other hand~ defines a subst­ance or micro-organism in terms of some particular method of production.Hence the product---by-process claim is of more limited scope than the per seclaim and can be avoided by the use of a production method differing fromthat defined in the claim.

Absolute product protection. This is available only 'A'here the product is anew substance~ Le. not disclosed or available to others by any kind of publicdisclosure or use before the date of filing of the patent application. Thus,prior written or oral disclosure of a compound, or indeed any other invention~

and any other method of making the knowledge available in a public mannerbefore seeking patent protection makes it part of what is termed the ~prior

arf.

The product-by-process clairn. This is used prinlarily where the novelty liesin the process, the product itself being known from earlier work and obtainedby some previous process. Sometimes this fornl of claim has to be used whenthe product is in fact new but is of such complex and imperfectly knownconstitution that it cannot be adequately characterized in a product jJer seclainl. Difficulties of this kind arose when the first atternpts \yere nlade topatent enzymes and other large molecules including those produced by othertechnology .. e.g. synthetic polyJner chemistry. Definition of a substance interlTIS of biological function alone was usually not accepted by Patent OfficeExaminers conditioned by many years of experience \vith inventions in thefield of simpler organic chemistry.

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The discovery oj' biologically useful properties in a substance already knol-vll initself. This could often be protected by means of a claim to a composition inwhich the known substance is present as an active ingredient~ e.g. apharmaceutical or insecticidal composition. An alternative to claiming thecomposition might be to claim the actual new use of the known substance, butthis could not be done if the use was medical because of the specific exclusionof medical treatment patents in most countries (USA being the most notableexception). A further drawback to the use claim would be that, generally, thedirect infringer of the claim would be the doctor ~ farmer or other end user,and legal action against these would not usually be worth while or desirable.For the patentee, the real target is always the commercial promoter orinducer of the infringement.

New methods of various kinds. These comprise another noteworthygroup of inventions in the context of patent claims. Thus a method oftreatment or processing of an industrial material is clearly an acceptable formof claim, as is also a claim to a method of testing where the method can beseen as applicable to manufacture in some way. Methods of assay wereconsidered of uncertain patentability some 20 years ago., or it was thoughtslightly unethical to patent them, but these are now regularly patented andsuccessfully licensed or otherwise exploited in the developing field of diagnos­tics.

Depending on where the novelty of the invention resides, therefore~ thepatenting strategy is to secure claims of the kind which give the patentee thegreatest manreuvrability against those who might invade his lawful territory.This strategy is in some countries constrained by the fact that the relevantnational law refuses in principle to allow product-per se claims and offers onlyprocess protection or product-bywprocess claims~ thereby forcing the appli­cant to investigate and claim alternative processes so that no obvious loophole\vill be left to his competitors.

This basic outline of the subj eet of patent clailns should assist in theunderstanding of the case law to be discllssed below. An illustrative selectionof specific examples of claims found in chemical and biological patents of theclassical type has been given by the author (Crespi, 1982).

Historical perspective

For Europe, October 1973 marks a point of departure from centuries-oldpatent law for, in that month ~ the European Patent Convention (EPe) wassigned in Munich by 14 signatory states and has since been ratified by 11 ofthem. EPC provides for a single centralized process of prosecution of a patentapplication and the eventual grant of a European patent in any contractingstate selected by the applicant. Its importance in the present context is that itwas the first statute to take specific account of Jnicrobiological inventionsinVOlving nc\v micro-organisms~ and provided a model procedure whichsubsequently has been emulated in many of the national systems of patent law

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Microbiological inventions and the patent law 7

in Europe, which continue to exist alongside the European (regional) system,and also by national systems outside Europe. In fact, EPC cannot claimcomplete originality on this point because a United States court had, threeyears earlier, laid down a similar procedure which is now established practicefor patent applications in the USA (see later). It wiH be helpful to anunderstanding of legal thinking on inventions in the biological sciences, firstto outline progress up to 1973 and then to examine subsequent developments.This method of study cannot be applied to the law of all countries but thedevelopment is particularly clear in the case of British law and exposesimportant issues which have arisen in other countries too. The nlajordecisions and developments in United States, German and Japanese patentlaw must also be highlighted in order to appreciate the internationaldimension in the patenting of microbiological inventions.

In English law, the origin of the patent system is the Statute of Monopolies1624. This was an abolitionist statute, banning all previous forms of monopolygranted by the Crown but making an exception in favour of any LettersPatent granted for the 'making of any manner of new manufactures \¥ithinthis realm·. It was succeeded by the first United States and French patentstatutes towards the end of the eighteenth century, with most other Europeancountries following suit from the middle of the nineteenth century onwards.British Commonwealth Countries modelled their patent la\vs on the Britishprototype.

Although these la\vs have been successively modernized up to presenttimes, one characteristic feature of the original legislation was retained andsurvives to this day. This concerns the nature or type of invention which canbe covered by a patent. Thus the English statute had defined it as a 'mannerof new manufacture' and this archaic phrase remained as the definition of~inventjon~ contained in subsequent legislation until its final appearance inthe UK Patents Act 1949, which has now given \vay to the Patents Act 1977.This definition continued to give rise to problelns because of its restrictive­ness. The term ·manufacture' was officially interpreted as relating to. the sortof activity that takes place in a factory. Hence agricultural methods. forexample .. \vere held to be outside its scope and therefore unpatentable.Moreover, it was considered essential for there to be a 'vendible producf atthe end of the claimed process and this gave rise to difficulties for inventionsin other technologies too. This key phrase arose in 1942 in the case of GEe'sapplication* in which the claim \\'as directed to a "method of extinguishingincendiary bombs' by applying a solution of known chemical reagents. It washeld that a method or process is a manner of nlanufacture if it (a) results inthe production of some vendible product or (b) improves or restores to itsformer condition a vendible product or (c) has the effect of preserving fronldeterioration SOOle vendibJe product to which it is applied. Many otherinventions involving Jiving matter were also held excluded by the terlTI

*Such British cases arc reported in Reports of Pllleni Design and Tradenzllrk (~{ISeS and can betnlccd by their RPC reference. A list of selected British and other cases is given ~lt the end of thisreview. .

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'manner (or kind) of manufacture' and a body of case law grew around thisconcept.

Another factor, not so much of the early laws but of the late nineteenth­century versions, concerned the written specification. This became of increas­ing importance in deciding the legal scope of the patent. I-Iere the claims wereof primary significance. However, the concept of a patent as a privilegegranted in return for the disclosure of something new and of practical valuemeant that the specification should be sufficiently clear and detailed for theperformance of the inventive process, or the preparation of the inventiveproduct, by a worker of ordinary skill. Eventually, one of the grounds onwhich a patent would stand or fall in a court of law \vas that of 'sufficiency ofdescription' and this has become a virtually universal feature of twentieth­century patent law. In Germany the courts stressed the sanle idea in terms of~reproducibility',a term which although particularly apt for biological inven­tions is nevertheless used essentially in relation to the \vritten description~andthis alone.

BRITAIN AND THE COMMONWEALTH

In the British case law the main thrust of the "nlanllfacture~argument \vas feltin the agricultural field. A case reported in 1951 concerned an attempt byStandard Oil Conlpany to protect ~a method of producing an improved tractof arable land' by application of a known hydrocarbon composition as aselective weed-killer. This application was rejected for lack of a vendibleproduct directly related to the method defined. Thus the crop gro\vn on theland could not be described as the product of the process. In addition, it wasconsidered that the crop itself was not improved or preserved froIn deteriora­tion by the treatment. Furthermore" neither the land~ nor the land plus thecrop, could be regarded as the product. In Lellarlfs application a claim to a'Inethod of offsetting disease in clove trees' by long pruning together \vith asterilizing treatment was simply refused on the ground that agricultural orhorticultural treatments \vere not within the Act. Similarly in the case of N.V. Phillips' Gloeilampenfabriekens application directed to a method ofproducing a new forJTI of poinsettia by the use of a sequence of artificiallong-day and short-day conditions of specific duration and temperature~ thejudge considered that the invention resided in drastically changing theclimatic conditions, whereupon something inherent in the plant itself wouldresult in the production of a neVi variety. The modification of conditionsunder which natural phenomena pursue their inevitable course \vas held notto be a method of manufacture. In contrast, in SZllec's application a methodof pelletizing mushroom tissue \vas allo\\'ed because this \vas in the san1e classas the Inanufacture of yeasts or other micro-organisnls and \vas not a naturalphenomenon of the kind found in the Phillips case. Again, the actual steps ofthe process \vere typical factory procedures so that this application could beaccepted. Another attempt to obtain method protection for producingiInprovcd soil was involved in the case of Virginia C"arolina (?henlica!Corporatioll ts application in "vhich the method step involved treating the soil

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Microbiological inventions anti the patent Lalil 9

with a known chemical substance discovered to have properties as a nemato­cide. This suffered the same fate as the Standard Oil case. An attempt byAlllerican Chelnical Paint Co. to patent a method for obtaining ra\v cotton bytreating the plant with a defoliant was rejected on the grounds that thetreatment did not affect the cotton but only removed the leaves of the plant.The process therefore did not produce cotton free of contamination_ butmerely the conditions whereby such material could be cultivated. Theseillustrative examples show that the mental gynlnastics involved in drawing aline between manufacture and non-manufacture and in the rigid applicationof the ~vendible product' test were becoming rather exacting.

By 1961, British Patent Office practice in relation to processes involvingliving matter had become established. This \vas stated in the General Electriccase \vhere the claim was to ~a process for artificially inducing heritablevariations' in the properties of micro-organisms by subjecting the culture to adefined electrical shock treatment whereby mutant strains were produced.Thus .. the Patent Office explained that they had allo\ved claims to processesfor producing vaccines and other cOlupositions \vhich included the treatlnentof an animal as a preliminary step. In the case of lower fornls of life, claitnshad been allowed for the cultivation and treatment of yeast and of moulds forantibiotic production. Certain patents had also been granted where theproduct of the process was a living substance~ the justification being that suchsubstances would be regarded by the ordinary person as something boughtand sold and used like many other commodities. In the General Electric case,ho\vever, the mutation process did not in general lead to useful results in thecontext of manufacture. Only in one instance .. the mutation of lactic strepto·coccus (sic) for cheese manufacture .. was there a" nlanufacturing applicationdisclosed and this had been specifically claimed in an earlier patent. The otherexamples (E. coli and Micrococcus ctlntlidus) were of academic interest only.

In the face of the established l.manner of manufacture't tradition. a suitabletest case had long been needed to break the nlould in \vhich British andCommonwealth patent law had become set. The turning point came with thedecision of the National Research Developl11en/ C'orporation to contest thedoctrine in the High Court of Australia. l"he particular invention involvedwas based on the discovery by R. L. Wain that certain substituted phenoxy­butyric acids \verc converted into the corresponding toxic phenoxyacetic acidsby means of f3-oxidase enzymes present in certain comnlon \veeds.. thusenabling the parent compounds to be used as selective herbicides. Many ofthe compounds found to function in this way \vere nevv and therefore could beprotected strongly by a product patent; however .. an important group \verekno\vn compounds. For the latter" claims to -selective herbicidal cOlllposi­tions" \vere presented and allowed vvithout difficulty. It \vas consideredinlportant .. however. also to protect the l11ethod of use. as in the following

. typical claitll:

A nlcthod for eradicating \veeds froln crop areas containing a growingcrop selected froIn leguminous fodder crops of the genera Trl:ro!i1l111 andA1edicago .. celery and parsnip which comprises applying to the crop

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areas a herbicide of the class consisting of the w-(2,4..dichlorophenoxy)­butyric and -caproic acids., their salts, esters, nitriles and amides.

Other method claims were also presented in \vhich the crop was specified aslucerne or clover and the weeds were specified as charlock, creeping thistleand annual nettle. The Australian Patent Office had raised the usualobjection and rejected these method claims on the basis of the GEe andStandard Oil cases decided under corresponding UK practice. The AustralianHigh Court, after reviewing the entire legal history of this doctrine~ consi­dered it to be a mistake to limit ones' thinking to the making of tangibleproducts by hand or machine, simply because the everyday word ~manufac­

ture' covered such an idea. It would be folly to fetter the underlying principleof the patent system by means of an exact verbal formula of this kind. Thebetter approach would be to concentrate upon the idea of the useful arts. asdistinct from the fine arts~ and the corresponding idea of value in the field ofeconomic activity. Similarly, the writing-off of agricultural and horticulturalprocesses as outside the area of patentability could not be supported as ageneralization. The appeal was therefore upheld.

The success ~f the NRDC case had rapid consequences. It was followed inthe same year (1960) in New Zealand in the case of Slvift & Co~s applicationin which the claim was for a method of meat tenderizing by injection ofproteolytic enzymes into the circulatory system of the animal prior toslaughter, in order to distribute the tenderizing agents effectively (the priorart being pumped infusion of the enzyme into the carcass). The Patent Officerejection of this claim was taken to the Supreme Court of New Zealand whichendorsed the enlightened approach of the Australian court and extended it toembrace ~biological or physiological' inventions, as \vell as those in thecategories of agriculture and horticulture. The tenderizing invention wasclearly a manner of manufacture as 'interpreted in relation to a modernworld's ever expanding and increasing knowledge of science and technology~.

Later in 1960 the Swift case fell to be decided on the corresponding patentapplication in the UK where., in spite of the NRDC and Swift precedentselsewhere, it was necessary to take a ·certiorarr appeal to the High Court.The court held that, there being no prior English High Court decisions on thepoint~ the Australian and Ne\v Zealand decisions must at least have posed adoubt, and one \l/hich the British Patent Office should have resolved in favourof the applicants. The desirability of a homogeneous development of law inall countries was also given as reason for quashing the decision to reject theapplication. Although the ·Inanner of manufacture' doctrine \vas not exp'"ressly jettisoned by the court~ the practical effect of the Swift case was that itceased to be applied on anything like its former scale.

The ~mannerof manufacture~doctrine had not been applied to reject claimsto specific mutants of yeast and other industrially useful organisnls and, fromthis tilne onward, claims to other types of organism began to appear. Thecrucial issue of whether a product claim to a new micro.-organisnl could bevalid seems never to have been contested very far in the UK. Some applicantsproceeded cautiously and claimed new strains in some particular form .. e.g.

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freeze-dried or mixed with a maintenance medium~ to avoid the issue but,with the spread of confidence, claims to new strains in undisguised form werepresented and the British Patent Office simply accepted theln. Some exam­ples are:

868~621 : Yeast (ATCC 13601)1,015 ..262 : BHK 21 cells (hamster kidney) plus culture medium1,085~798 : Sabnollella dublin (ATee 15480) freeze ..dried1J)90,794 : E. coli eN 53641,286,250 : Feline heterodiploid cell line. beyond 40th passage1.292,803 = Marek's disease virus free of A antigen1..300~391 : Human liver cell line CL 991,346.061 : Fusariu.rn graln;nearul11 IMI 14542514436.,573 : Chakrabarty pseudomonad (multiple plasmid)

An even earlier and perhaps more remarkable patent was one for thesynthesis of ne\v strains of micro-organism (UK 719.313. mainly processclaims) which covered the parasexual breeding technique described byPontecorvo and his colleagues.

This liberal practice continued for about 10 years. Then an important casewas taken to the House of Lords upon a petition to revoke AI11ericClnCyanamid UK patent 934853 covering a new antibiotic named porfiromycinand the process for preparing it. The process depended on the use of newstrains of Streptolnyces verticillatus, samples of which had been deposited withATee and identified in the specification. The case was concerned only \\liththe question whether. under the UK 18\\1 as it then existed (1971) ~ it wasnecessary to deposit a new strain in a Culture Collection in addition toproviding a written description of the strain in the patent specification.However one of the judges. in discussing the centraJ question, remarked that~the priceless strain. being something Iiving~ found in nature, cannot bepatented·. This was an obiter diclll1n. and therefore not Jegally binding~ but itbegan to be quoted against applications claiming new strains of naturallyoccurring organisms. This objection \\las frequently overcome" hO\'vever'l andclaims to isolates of naturally occurring Inicro-organisms \\'ere generallyaccepted. By this time Britain had wholeheartedly cOlnmitted itself toparticipation in a ne\v system of patent law for Europe in which specificprovisions for olicrobiological inventions \vould be present. Britain alsointended to harmonize its national law with the future European patent lawand" in these circumstances .. it was in no...one·s interest to promote any ma.iorcontroversy during the last years of the oJd law.

CONTINENTAL EUROI)E

In continental European countries .. the equivalent to the British "nlanner ofmanufacture· doctrine was the concept of technical character and industrialapplicability. Of these. technical character was the donlinant influence ..

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excluding not only purely scientific discoveries but also ITIuch of biologicalinnovation in agriculture .. plant and animal breeding~ and medical treatment.

In Germany .. for example, the necessity for an ·instruction for technicalactivity· within a field of technology required official interpretation. TheGerrnan Patent Office considered that ~ for the purposes of the patent law,technology was limited to inanimate substances and objects and the applica­tion to these of the techniques of physics and chemistry. However~ classicalfermentation processes were considered patentable because the final productof such processes was inanimate.

It \vas not until the 1930s that agricultural cultivation processes and newplant varieties \vere considered suitable subject matter for patents in Ger­many. This \videning of the range of patentability so as to embrace the truebiological invention was put on a firmer footing" at least in principle. by thedecision of the German Supreme Court in the celebrated Red Dove case in1969. The invention \vas for the breeding of a large dove, vvith particularlybeautiful red plumage and other desirable physical characteristics.. by adefined process of cross·breeding. The German Patent Office had rejectedthe clainl on the ground that the process was not technical and its repeatabil­ity questionable. The Supreme Court supported the Patent Office on therepeatability argument \'vith the result that the application was" in fact,rejected. I-Iowever, the Court overruled the technical character argument~

finding no basis in the law for excluding the utilization of biological forces andphenomena. The decision therefore nlade patents available for biologicalinventions~ subject to the requirement of reproducibility. Ho\\'ever ~ becauseof the great difficulty of complying \vith this requirement .. in a very highproportion of cases the Red Dove has had the paradoxical effect of closing adoor that the decision appeared to have opened.

l'he German court had specifically considered the argunlcnt that thereproducibility requirement could be met by the fact that the product of thebreeding method could be propagated and \vould Inaintain its desiredcharacteristics. This argument \vas rejected. however .. on the ground that theability of the animal to propagate itself \vas not equivalent to providing ateaching which would enable the skilled \vorker to repeat the breedingInethod for himself. 'These deve)oplnents have been reviewed in depth byGerman authors (Duttenhi)fer .. 1971 ; Beier .. 1972).

UNITED STATES AND CANADA

United States patent la\\' defines the subject nlatter eligible for patentprotection in a \vay \vhich has evolved through successive statutes into itscurrent fornl (US Code Title 35 Section 101) as:

any nc\v and llseful process .. nlachine _1l1anufacture .. or composition ofnlatter .. or any nc\v and lIseful inlprovelnent thereof.

"fhis does not spell out the meaning of the term "ne\\" but in Section 102o(thestatute the novelty condition is defined by a rather complex fornlula. The most

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pertinent parts of the formula for present purposes appJy the test for novelty inthe light of what, previously, was known or used by others" or patented ordescribed in printed publications or put to public use or on sale. Entitlement toa patent is also accorded by Section 101 to ~\\'hoever invents or discovers'something falling within the above definition and it is clear that" of these t\VO

terlns .. one or the other is more appropriate as a description of the innovativeact for the particular categories listed. For the present discussion'l the criticalpart of the definition is the phrase ~manufacture.. or composition of matter'.

The patent usually considered to be the first US patent granted for amicro-organism is the Pasteur patent US 141,072 of July 22 1873 .. includingthe claim to 'yeast free from organic germs of disease. as an article ofmanufacture'. It may be surtnised that the last fe\\' words of the clainl werefelt necessary to avoid covering the natura) product. Between the Pasteurpatent and the Chakrabarty patent allowed by the US Supreme Court in 1980with a claim to a genetically manipulated strain of Pseudomonas (see later) ..there have been many cases involving the 'product of nature" problem. Thissubject has attracted the attention of many authorities including Europeanwriters (Utermann, 1978; White, 1980) who have discussed it internationally,and a much greater number of United States authors who have focused uponthe particular legal problem in their own country (e.g. Wegner .. 1976.. 1978;Dunner and Lipsey~ 1979; Biggart" 1981; Cooper, 1982a).

Of the many decisions bearing upon the patentability of natural products ..the opposing strands of opinion can be seen from the follo\ving four cases. InA/1zerican Fruit Gro~,vers Inc. v. /3rogdex ("0. in 1931 the US Supreme Courtheld a borax-impregnated orange unpatentable as a product of nature. Theclaim was in the forJn ~fresh citrus fruit of \vhich the rind or skin carries boraxin amount that is very small but sufficient to render the fruit resistant to bluemould decay~. Even though the borax-impregnated orange does not occurnaturally .. the prejudice against patenting such objects \vas expressed in thecourt's statement that the borax conferred no new distinctive form~ quality orproperty on the fruit but Jnerely protected it against deterioration: ioIt remainsit fresh orange fit only for the sanle beneficial uses as before'!.

~rhe inlportant case of Funk Bros. Seed (,"0. v. Kalo Inoculant Co. decidedin 1948 was one of the main precedents which figured in the Chakrabarty caseand therefore deserves detailed attention. The invention was based on thediscovery that there were certain strains of nitrogen-fixing rhizobia \vhichwere not mutually inhibitory and therefore could be combined into a .nixedinoculant for legulnes. In the prior art it \vas considered necessary toinoculate separately \vith single...strain inoculants to avoid the problem ofinhibition. The actual non-inhibitory cOlnbinations discovered \vere ratherlimited in nunlber but the patent contained the following broHd claim ..amounting virtually to a clairn to the principle involved:

an inoculant for leguminolls plants comprising a plurality of selectednlutually non-inhibitive strains of different species of bacteria of thegenus Rhizobiu111 such strains being unaffected by each other in respect

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to their ability to fix nitrogen in the leguminous plant for which they arespecific.

The Suprelne Court held this patent to be invalid because the qualities in thestrains \vere the handiwork of nature and the mere aggregation of thesestrains was considered to produce nothing over and above the sum of theirindividual properties. Thus 'the bacteria involved perfornled in their naturalway and their combination did not improve their natural function which wasto serve the ends nature originally provided~ independently of any effects bythe patentee· (abbreviated quotation). As in the case of the borax-treatedorange. the mixed inoculant culture claimed in the patent was not shown tooccur in nature. Nevertheless" the natural occurrence of the main cOlnponentor components of the claim seems to have influenced the court against whatwould appear to have been the strict logic of the situation.

The classic case in which a claim to a natural product was upheld is that of thevitamin B l2 patent US 2 i 563,794, Merck & Co. Inc. v. Olin MathiesonChefnical Corporation. The vitamin occurs in liver, and certain liver extractshad been tried in the treatment of pernicious anaemia .. but rather unsuccessful­ly. l"he patentees had produced B 12 by fermentation of certain strains ofStreprornyces griseus and this had led to the production of therapeutically usefulquantities of the pure substance. The product claim defined the substance as·the compound vitamin B ll.... ' in terms of elemental analysis .. solubility incertain solvents. spectral absorption data and a numerical specific activity. Theproperties recited in the list are., of course, inherent in the substance inwhatever state it may be found or presented, but they are determinable only inthe purified material. The patent was attacked on the ground that it claimed aproduct of nature which was merely a purified form of the natural substance. Inrejecting this attack. the court relied on previous cases where the isolation of anatural product had effectively contributed a new utility to the art and theystated the principles as follows:

"fhe step from complete uselessness to great and perfected utility is along one. That step is no mere advance in the degree of purity of aknown product. From the natural fermentates \vhich for this purposewere wholly useless and \vere not known to contain the desired activityin even the slightest degree. products of great therapeutic and commer­cial worth have been developed. The new products are not the same asthe old but new and useful compositions entitled to the protection of thepatent.

Before Rickes and Wood made it available to the world .. purecrystalline vitamin B12 as described and claimed in the '794 patent did .not exist. No-one had produced even a comparable product. The newproduct had such advantages over the earlier liver extracts that it notonly replaced them but became .. and remains to this day ~ the universaltreatment for perniciolls anaelnia.

Another inlportant case was that of f)arke-Dllllis {~ C~o v. H. D. Mulford('0. in \vhich a clailn to adrenalin was vindicated. The claim \\las directed to a

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substance possessing the 'physiological characteristics and reactions of thesuprarenal glands in a stable and concentrated form and practically free frominert and associated gland tissue'. It was held that the inventor -\vas the first tomake it available for any use by removing it from the other gland tissue inwhich it was found and ~ while it is of course possible logically to call this apurification of the principle, it became for every practical purpose a ne\v thingconlJnercially and therapeutically~.

In the vitamin B 12 case there \vas clear merit in making the substanceavailable by fermentation but it is important to note that. in the adrenalincase, the process of production was by extraction from the natural source.Many natural products have to be produced by extraction rather than bysynthesis, but this is not necessarily to depreciate the step forward \vhich hasbeen made in the art, and should in no way detract from patentability.

Canadian patent law has a definition of invention identical in \vording tothat of the US statute~ although it recognizes precedents in British case law aswell as those in US decisions. It was a long...standing official practice until 1972to reject certain claims, process or product .. \vith the stock objection that:

Living organisms, ranging from the lower forms of life~ such as viruses ..bacteria and fungi, to the higher animals and plants are self-propagatingentities and have evolved by processes of self-variation and reproduc­tion which only the particular organism itself is capable of performing.They cannot therefore be regarded as products of human manufacture.In the live state, either alone or in association with inanimate material..they do not fall within the definition of invention according to Section2(d). Since living plants and animals whether /Jer se or in compositionalform may not be patented, the more primitive forms of life .. which sharethe same property of self-reproduction~ are like\vise unpatentable.Being manifestations of natural phenomena they lie outside the sphereof patent monopoly.

In October 1972 a change of policy \vas declared. In the \vriter~s experiencethis occurred in connection with two NRDC patent applications in \vhich anappeal was lodged against the Examiner's rejection of claims to pig and calf5'tabnone/la vaccines comprising attenuated strains of Sabnol1ella cholerlle-suisand Sabnonel/a dublin respectively .. in association \vith a pharmaceuticallyacceptable carrier. At about the same tinle other applicants \\'erc alsocontesting the establishment view and there \vas therefore a strong case forreconsideration by the Patent Office. After the revision ~ "processes and theproducts thereof in the microbiological field were not necessarily excludedfrom patentability'. It is important to note that clainls to nlicro-organisms Ile,.se \vcrc not specifically in issue at that particular tinle.

JAPAN

It is often said that. when Japan began to industrialize in the early years ofthis century to it \vas influenced by the patent systenl of the United States ofAmerica which .. the Japanese believed .. \vas a contrihutory factor in the

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renlarkable economic progress made in America. However" in establishing itsown system Japan was also influenced by German ideas of patent law. Thusan invention is defined as ·highly advanced creation of technical ideas bywhich a law of nature is utilized' and this concept can be traced back toGerman legal scholars. In practice it is the idea of technical content which hascome into the foreground .. together \vith industrial applicability" which is alsoa specific criterion in the Japanese statute. Furthermore~ as in Germanthought, the technical content idea has become closely associated with thenecessity for reproducibility of the teaching and this latter requirement hasbeen stressed repeatedly,

The Japanese Patent Office is unique in its propensity for issuing guidelinesfor the patenting of inventions in various branches of technology. These arcknown as +Examination Standards" and, again .. some of this uniqueness lies inthe readiness of the Patent Office to consult \vith industry and other users ofthe patent system in the preparation of such guidelines. Some commentatorsolltside Japan suggest that the Examination Standards are over...detai1ed~require too nluch from the applicant and tend towards rigidity of practice.Whatever opinion one adopts.. guidelines have the advantage that theapplicant and inventor kno\v from the beginning \vhat sort of data \vill helptheir case.

In the 1950s" Japanese litigation on patents for chlortetracycline producedby Streptofnyces aureoj'aciells ~ and other disputes about the identification ofcertain micro-organisms referred to in patents for the production of glutamicacid. led to a general realization in Japanese official circles and industry thatclarification of nomenclature and the general procedure for the patenting ofmicrobiological inventions \vas necessary. In 1965 the first ExaminationStandard for 'inventions concerning micro-organisms and the ferlnentationindustry' \vas issued. In 1970 this \vas re-titled as a standard for the ·appliednlicrobiological industry~.

Processes utilizing micro-organisrTIs presented no difficulty over patentabil­ity. At that date., however.. micro-organisms ~7ere officially regarded asunpatentable on the ground that they were not industrially applicable andalso because the invention could not be reproduced (sic) ~in the same mannerthat plants and anilnals are not patentable", This policy was reversed in a newguideline issued in 1979.

Patentability conditions: their impact on microbiolog}'

Technical character and industrial applicability are not the only criteria forpatentability of an invention. As noted earlier 'I the subject Inatter of thepatent claims must also be both new and inventive when cOJnpared with the .pre-existing state of the art Cprior arf). However ~ novelty is not conceivedand formulated identically in all patent la\vs. In the European PatentConvention. for exanlple .. the novelty condition is expressed in a differentform fronl that in \yhich it is presented in the United States and Canadianstatutes. As this revie\v has so far followed a chronological approach.discussion of the legal concept of novelty \vill be postponed until the question

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of the patentability of micro-organisms is dealt \Yith. In the order in \vhichthey have more recently arisen as contentious issues in relation to microbiolo...gical inventions, novelty a'nd inventiveness have given place to the majordebate over the application of the fourth main criterion of patentability ..namely.. the adequacy of the patent specification as an instruction to theskilled worker for practical performance of the invention.

Adequacy ofdescription

This requirement is usually expressed as sufficiency of disclosure .. enablingdisclosure 4 reproducible teaching" or in siolilar terms. The belief is sonletimesstated by research \vorkers that patents frequently do not fulfil this expecta­tion~ i.e. that they leave out something essential. either deliberately orthrough lack of appreciation on the part of \vriters of patent specifications.Whatever the extent to \vhich this belief is jllstified~ a patent must not bedefective in this way if it is to stand up in court.

In mechanics, physics and classical organic chemistry it is usually possibleto define an invention and to transfer adequate information to the skilledperson by means of the patent specification. With cOlnplex biological materialsuch as enzymes and cells .. however .. our knowledge and descriptive powersare often insufficient for this purpose. Not only does a complete descriptionrequire Inassive alTIOunts of data .. but in addition the description must ensurethe possibility of performance of the described procedure by the skilledworker in order to obtain the product or result, be it a new product or result~

or a known one produced in some better way by the new process. Where anew Inicro-organism (i.e. one not already available to the public) is anessential elenlent of the invention .. and it cannot adequately be described Of arepeatable method of obtaining it cannot be given. it was considered that thedifficulty could be solved by depositing the ne\v microworganisrn in a CultureCollection \vhich was sufficiently public in nature to provide an objectivesource of reference and supply. Patent practice on this expedient has givenrise to a new dimension in the case la\\' and statute law of patents over the lastdecHde and more and deserves special attention in this review.

THE DEPOSITION OF MICRO-ORGANIS1\1S IN CULTURE COLLECTIONS FOR I>ATENT

PURPOSES

The first legal decision bearing upon this subject was given in 1970 by theUnited States Court of Customs and Patent Appeals (CePA) ill re: Argoulle­lis. Ho\vever" bearing in mind the basic principle that a patent is granted tothe inventor in return for the useful and usable ne\v infonnation he provides~

the need for deposition and availability of the micro-organism had beenrealized intuitively much earlier and the practice of depositing strains hadbegun voluntarily frolll 1949 onwards in the United States and clsc\vhere (seealso Chapter 13. page 431). "fhe question immediately arises as to whena deposit should be nlade in the Culture Collection and \vhen the cultureshould be nlade available to the public jn the time-scale of patenting

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procedure. Before practice became stereotyped there \vas some variation ofthinking in this respect, but the prevailing view was that deposition of themicro-organism, before the filing of any patent application, was desirable andprobably necessary in order to identify the strain in the specification as firstfiled. On the more controversial part of the question, i.e. on the release of thestrain to third parties~ a choice of three alternative dates must be made: thedate of filing, the date of publication or the date of grant of the patent. It isclearly in the interests of the applicant to delay release of a new strain tocompetitors for as h;>ng as possible and at least until the grant of anenforceable right. In the USA, publication and grant of the patent occur atabout the same time and this is, therefore~ a convenient stage at \vhich releaseof the deposited strain will meet the legitimate wishes of all parties. However.,many other countries have adopted a dual publication system in which theunexamined application is published early" followed by a second publicationof the finally accepted specification at the time of grant., and there has beendisagreement as to which of these two dates should apply in such circumst­ances.

In the Argoudelis case the claimed inventions were two new antibiotics anda microbiological process for their production. The process was dependent ona new StreptoTnyces strain which had been isolated from nature and depo­sited, before the filing of the US Patent Application, with a public depository(the Agricultural Research Service Culture Collection~ NRRL) in the USA.l"he micro-organism had been deposited under the condition that it would notbe distributed to n1embers of the public (other than applicanfs nominees)before the patent \vas granted, at which time it could then become accessibleto alL The US Patent Office had argued that this deposit was secret andconfidential and therefore that the application was defective because thernicro-organisln had not been made available to the general public at the timeof filing of the patent application. The Court held that there was no need for amicro-organisln to be available at the time of filing the application. It \vas notnecessary for the public to have access to the culture before issuance of thepatent. The disclosure was 'sufficient to permit a thorough examination by thePatent Office and to preclude the possibility that a patent could issue withoutany person skilled in the art being henceforth enabled to make and use theinvention~. l"he applicant had set up a procedure whereby~ at the time thepatent \vas issued" there would be no doubt that a person of ordinary skillwould be able to make the claimed antibiotics \vith the critical nlicro­organism which would then be readily available to him.

l"he procedure laid down as acceptable in this case has long since been theestablished offlcial practice in the United States and it commands \vide assent.In the same year as the Argoudelis decision a similar point had arisen inBritain in the previously mentioned case of A 111eric(ln (~}'llll{lrl1id (!Jalllt 's)

patent and was taken to the House of Lords. It \vas held that the la\v existingat the time silnply did not cover the situation. Thus the highest English Courtdid not define a pragnlatic solution along the lines of the US decision but, intrue common la\\' fashion~ declared a hiatus; all the law required was a \vrittcndescription. The court therefore refrained frOITI devising a rule to cover the

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situation. The Gernlan Suprenle Court felt under no such inhibiti()n~ howev­er. \vhen a related poin t arose in the IJaker·s Yeast case in 1975. This case is ofspecial importance on the patentability of Inicro-organisms .. but its ruling onthe date of public availability of the deposited culture has also been highlyinfluential and still stands. In adopting the early publication date (firstpublication of the unexamined appJication) as the crucial date for availabilityof the culture to the public. the Gernlan court \vas no doubt influenced by theidentical posjtion taken in the European Patent Convention \vhich had beensigned t\VO years previously. l"he issue involved here concerns the effective­ness of the patent specification as a publication and emphasizes the inforlna­lion'll purpose of the patent systenl.

PUBLICATION AND PATENT I)ROCEDURES

To those \vho see a conflict bet\veen patenting and publishing .. it nlust bepointed out that it is of the essence of patenting to involve publication .. butthrough the offi.cial channel. Those whose only nl0tivatioo is to achievescientific priority by publishing in the journals.. will find that this usuallyprecludes subsequent patenting. Ho\vever~ the real incompatibility is bet\veenpublication and a policy of total secrecy which \vill not tolerate even thepublication which flo\vs fronl the patenting process. In the past .. and in mostcountries. this process iesulted in publication of the specification only at theend of negotiation between applicant and Examiner .. as it still does in theUSA and Canada. Ho\vever .. nlany countries considered that long delays indisclosure of the infornlation in patent specifications ~'ere against the publicinterest and so adopted a practice of publishing the application at an earlydate .. even hefore its cxanlination had begun .. e.g. in Australia .. Netherlands.Japan and Gerrnany. This practice \vas taken over \vhen the European patentla\v \vas created in ]973. and other countries have since follo\ved suit .. so thatit is now COnl1110n to find patent applications published at about 18 monthsafter their o\vn filing date or the filing date of an earlier application on whichthey rely for priority .. as will nO\\I be explained4

An application for patent protection is nornlally first 1l1adc in the country ofresidence or place of business of the applicant. This establishes a so-calledpriority date \vhich \vill be recognized in most of the other countries of the\vorld under the provisions of an international convention kno\vn as the ParisConvention. In practice this tlleans that the 111ajor expense of a foreignpatenting progranlJ11C can be postponed un til to\\.'ards the end of one yearafter the initial tHing date in the home country. For this purpose anapplication for a European (regional) patent is on the sanle footing asnational applications in other countries filed under the Paris (~onvention. l'hevalue of this one..ycar intcrinl period .. both to industry and to other organiza­tions \vhich have the problclTI of assessing the potential industrial importanceof nc\v research results .. is considerable. Bet\vccn conlpeting interests there isal\vuys a race to establish the earliest priority date .. but this eagerness has tohe h~lnpered by the uncertain evaluation of the conlnlercial prospects of theinvention at such an early stage. The one-year breathing space offered by the

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Paris Convention is of S0l11C help and focuses the minds of those engaged inresearch and devclopnlcnt and also of those who authorize expenditure onpatenting. Figure I SUITIlnarizes these procedural points. The other nlajoradvantage given by the Paris Convention is that the inventor can publishdetails of his invention at any time after his priority date without detriment tohis patent prospects. The only provisos here are that the invention is clearlydefined and well supported by data in the first application and that the foreignapplications are filed no later than one year after the first application.

'finle

o

1 year

18 months

tVariableperiod

J

Action

1st application, houle filingl (establishes priority date)

2nd application, consolidating protectionin home country

l~"oreign applications - Routes:(\-\lith priority) National,

t:uropean,International(Patent Co-operation 'rreaty)

Official prior art searc}l

lPublication of application (some countries)

~Official exam inationand prosccuiion

~c.;rant or refusal of patent

Fil!ure 1. Palcilling proccdun.'.

THE EUROPEAN PATENT CONVENTION

.;1 Plli!ability 0." JlO vel orgaJl iSJJ1S

~rhc European Patent C~onvcntion (EP(~) 1973 provided for the deposit of anc\v I1licro-organisn1 in Rule 2H of the 1~£'glllatioJls. "rhis required an applicantto nlake the deposit in a (~llhllre C"ol1cction not later than the Europeanpatent application date .. to add to the application identifying details of thedeposit. and to l11akc the deposited Inicro-organism available fronl theC"ulturc C"ollcction to any person fronl the date of first publication of thepatent application. l"'hc European Patent SystClll had C0l1101itted itself to apolicy. of duaJ publication of the kind 1l1cntioncd above. "rhc release of the

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deposited strain at the 18-nl0llth stage _at \vhich time there is no certainty ofthe grant of patent rights. was clearly controversial. but the nlajority officialvie\v prevailed and Rule 28 came into existence as the model for thesubsequent amendment of NationaJ laws in Europe in harmony \\,ith the EPe.

A deposit under Rule 28 gave irrevocable consent to the availability of thedeposited culture under the rule and this could be withdrawn only byabandoning the patent application before preparations for its early publica­tion had been completed. Availability to third parties was sUb.iect to certainundertakings: while the patent application \vas pending, or as long as theeventual patent lasted. the culture could not be passed on to others by thethird party~ in addition .. during the pendency of the application (but not aftergrant) the third party undertook to use the culture for experimental purposesonly. Both conditions ceased· upon refusal or withdrawal of an application.The identity of the person obtaining a sample would be comnlunicated to theapplicant.

THE BUDAPEST TREATY

The EPe \vas signed in October 1973 but did not come into operation untilJune 1978. Meanwhile .. the need had been recognized in official circles toestablish arrangenlcnts for deposition procedure \vhich \\/ould be adopted onan international scale \vider than the area ernbraced by the EPe signatorystates. Under the auspices of the World Intellectual Property Organization(WIPO) .. preparations began in 1974 towards this objective. As a result .. the~Budapest "rreaty on the International Recognition of the Deposit of Micro­organisms for the Purposes of Patent Procedure" \vas signed at Budapest in1977 and entered into force three years later.

According to the Budapest Treaty .. a Culture Collection may becomedesignated as an International Depositary Authority (IDt'\) and therebybecome recognized for the deposit of rnicro-organislTIs for the purposes ofpatent applications in any of the contracting states. A single such depositary ..whatever its location .. can therefore be chosen by an applicant to hold adeposit relevant to a single patent application or to a fanlil y of related patentapplications fiJed in any number of contracting states.

The Budapest Treaty covers the forrnalities of deposit and maintenance ofthe culture and the possibility of re..deposit \vhere the original depositedstrain has lost viability upon storage. An IDA must store a depositedmicro-organism for at least 5 years after the most recent request for thesample and for at least 30 years from the date of the original deposit. Theprocedure for release of samples of the deposited culture to various parties iscovered in detail.

The cl1llendtnenl o.f EJ~C' Rule 28

In June 1980 an <lll1cndrnent of Rule 28 \-vas nl<lde to hring the original ruleinto alignment vvith the ternlinology and procedures of the Budapest Treaty.Further changes \\fere rnade as an aCCOJlllTIodation to the vie\vs of interested

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22 R. S. CRESPI

circles \vhich had maintained that the original rule was in certain respects tooharsh to the applicant. This standpoint has been discussed by Europeanworkers (1~liini~ 1977; Crespi, 1981, 1983).

The main target of criticism of the original Rule 28 was the requirement tomake the deposited culture available to an)' person at the date of firstapplication of the European patent application .. Le. at 18 months after theapplication date or priority date. At this date the applicant has no certainprospect of obtaining patent protection and no right of any kind which is thenenforceable. "fhe only protection the applicant has at this stage is that givenby the above-mentioned undertakings of third parties. Furthermore~ thepredominant role of the micro-organism itself in producing the end-productof the microbiological process, and also the ease of replication of themicro-organism, combine to give an unfair advantage to competitors at suchan early stage by physically putting into their hands the chief instrument ofperforming the process of the invention. A further problem arises from therelative ease \vith which micro-organisms can be modified .. either by conven­tional mutagenic treatment or by direct chemical treatment of DNA mole­cules. These present the applicant with substantial problems of proof ofderivation from the deposited strain. In any case the legal question of patentinfringement by modification of deposited organisms is by no means clear andsettled. The question of derivation, for example" must be decided by expertscientific evidence~ which may be conflicting. In the case of AmericanCyanamid v. Berk Pharlnacellticals~ on a process for producing tetracycline~

there was contradictory evidence upon whether the strain used by thedefendants was a Stre/J(ornyces (lureofaciens of the kind claimed in the patent ..or whether it could have been derived (as alleged) by mutation of amicro...organism which. both sides agreed, was not of this species. In spite ofthe very considerable enlinence of the patentee's \vitnesses .. who concludedthat the strain was aureoj"aciens, the British judge accepted the defendants·account of its origin. It is no exaggeration to state that problems of this kind~

which are inherent in the typical biotechnology invention that involvesdeposition of highly valuable biological material, are unprecedented in thehistory of patent law.

Interested circles argued that the Inost logical time for making thedeposited strain available was that at \vhich publication occurs .. upon or afterthe grant of the patent. A compromise alternative vvould be one in \vhich theavailability of the deposited strain at the early publication date could berestricted to an independent expert acting on behalf of a third party. Theindependent expert \vould be bound by all of the conditions attaching tooriginal Rule 28 and he would therefore not be free to transmit the culture tothe third party for \vhom he \vas acting. He could. nevertheless~ perfornl allthe experilnents requi red on behalf of his principal to assess the sufficiency ofthe patent description and to enable the latter to fOflll an opinion of the meritof the invention and its relevance to his o\\'n activities. This \vould Ineet theinfonnational function of the patent disclosure and \vould enable conlpetitorsand others to prepare \vell in advance for the eventual filing of an Oppositionto the granted patent.

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The European Patent Organisation accepted the 'independent expert"proposal and introduced it into a new version of Rule 28. Provided that theapplicant informs the Patent Office before preparations for publication of theapplication are completed, he may take advantage of the independent-expertoption .. according to which, in the interim between early pubHcation and theeventual mention of the grant of the European patent .. the deposited strainwill be available only to an independent expert nominated by a third partyfrom a list of experts recognized by the European Patent Office for thesepurposes.

In addition to the above amendment .. ,the rule was modified by extendingthe scope of the undertakings made by persons obtaining a sample of thedeposited organism. These now apply also to cultures ~derived' fronl thedeposited culture .. such being defined as those \vhich are so derived and whichstill exhibit the characteristics of the deposited culture essential to carryingout the invention. This must include sub-cultures of the deposited strain andmodifications thereof which meet the terrns of the definition. Should any suchmodifications constitute or contribute to a further invention .. however .. theirown deposition for the purposes of patent procedure is permitted.

Finally. an inlportant amendment was made to the opening clause of therule \vhich specified the kind of micro~organism to \vhich the ruJe isapplicable. Originally this was simply defined as a micro-organism not alreadyavailable to the public, but no\v there has been added the qualification "andwhich cannot be described in the European patent application in such amanner as to enable the invention to be carried out by a person skilled in theart". This amendment makes explicit the possibility of avoiding the need todeposit the ne\v micro-org~nism \\Ihere the applicant can justifiably rely onthe reproducibility of a written description of the method of producing andidentifying the Illicro-organisnl .. e.g. by a repeatable technique of geneticmanipulation.

The present situation on the release of deposited strains is summarized inFigure 2. UK.. Germany and S\vitzerland are examples of countries \vhichhave maintained the original Rule 28 practice .. \vhereas the current EPapractice. offering the independent-expert solution.. has been adopted byFrance and S\veden and will be follo\ved by others.

The current fornl of Rule 28 still falls short of being totally satisfactory tomany applicants. The irrevocable nature of the deposit. even \vhere no patentis obtained .. is viewed as giving a\vay a proprietary right in the biologicalmaterial. independent of the patent right. Moreover. there is no restriction onthe location of the independent expert \\Iho ITIay obtain the culture. Formicrobiological inventions of the kind involved in the present discussion. theinventor who desires patent prote~ti()n cannot avoid at some stage eithermaking his new strain available to others or putting others in the position toreproduce the strain .. i.e. to re-isolate or re-create it. The present dra\vbacksof depositing strains and accepting their consequential early availability toothers have understandably given risc to discussion of the possibility ofavoiding this requirenlent. In relation to recombinant strains and otherorganisms prepared by ne\v biological techniques.. it is being stated with

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24 R. S. CRESPI

'finlC

o

1 year

Basic application (hlme filing)

Foreign filings (Convention priority)

18 months

I IUK, LTSf\,Germany etc Japan etc

Il)ublication(release of strain)

1EP()etc

1Publication(option of releaseto independentexpert only)

Non... transmission* ,experimental use,unless application--~abandoned orrefused

No releaseuntil

~i\.cceptance Oapan)I)atent grant (US1\)(General release)

No release unlessapp licationabandoned orrefused

Grant Grant(General release)

Figure 2.. Rclcusc of deposited strains. "':S(~e page 2l for conditions of release.

increasing confidence by SOITIe that the methods are beconling perfected tothe stage at \vhich they are reproducible fronl a \vritten description alone.When such a consunlmation is achieved it \\liB be a great relief to all \vho areinvolved in patents and the existing rules can be modified or reserved for thedoubtful cases. The purist Inay say that the technique in different hands cannever give rise to the identical ne\v organism. However .. absolute identity maynot be fundanlen tal for patent lel\\'. All that lnatters is that the inventionclaimed can be repeated but the bl\V may not necessarily dClnand identicalcopies of \vhat the inventor has achieved in his O\"ll1 laboratory. Ho\vever ..these are still uncharted \vaters.

l\'licro-organisnl patents

I n both classical Inicrobiology and the ne\v biotechnology the follo\ving typesof clairn are encountered:

I. Process of producing a nC\\J Iniero-organism.

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Microbiological inventions and the patent Itn'v 25

2. The ne\v micro-organism as produced by the defined process.3. The new micro-organism /lel" Sf.

4. Process of cultivating or otherwise using a defined nlicro-organisnl toproduce an end-product \vhich Inay be:(a) a form of the multiplied Inicro-organisln itself.. for exanlple vaccine or

edible biomass:(b) a by-product of microbial gro\vth .. for exalllple an antibiotic ..

enzyme ~ toxin 'I or an other\vise useful inclustrial product (even jf

inactive biologically): or(c) SOllle other product Of substrate \vhich is produced or inlproved by

the culturing process, for cxanlple a purified industrial product oreffluent.

5. The products of any of the processes defined in (4 )-defined by a /Jer seclaim or product-by-process clainl as appropriate.

6. Particular formulations of ne\v strains or cultures thereof.. includingcombinations \vith other substances .. designed to utilize and exploit theirspecial properties .. for exanlple .. in hUJTlan or anirllal foods or forindustrial uses.

Patents for process technology and specific applications of n1icro-organisnlshave been relatively uncontroversial as cOlllpared \vith those sought for themicro-organisnls thenlselves. "rhus for the Chakrabarty technology the pro­cess patent US 3..813.316 was granted \vithin t\VO years of its application date~

\vhereas for the bacteriunl itself US patent 4,25Y .. 4-1-4 cillcrgcd only after anine-year legal odyssey. This is another exanlplc of the occasional need foraltruism by the fc\v (in this case the General Electric (\>I11pany) to take anexpensive tcst case on an iInportant point of principle.

The general excitclncnt caused by the judgelllcnt of the lJnitcd StatesSUprCITIC Court (!Jillnlond v. C"hakrabarty /980) in upholding the claim to aman-made organiSJll has tended to overshado\v the fact that the firsthigh-level .judicial decisions on the patentability of nlicro-organisn1s haveCOJne fronl Europe. In Germany .. in keeping \vith the principles laid do\vn inthe Red Dove case described above. the Suprcnlc (~ourt has approved ordenied per se claiJns in accordance \vith its ground rule of rcproducihility.Again .. follov"ing the chronological 1l1cthod. SOlllC of the Illain (jcflllan

decisions \vill be outlined.In the Baker's Yeast case (]')75) the applicants clailllcd t\\'O J11ulanl strains

of yeast by reference to their specific culture-collection accession nunlhersand a variety of process clainls and use clainls directed to the propagation ofthe defined strains by conventional 1l1cthods and their usc for pressed yeast or<lctive dry yeast or for the production of baked goods. T'he f'cdcral Suprcll1cCourt held that in order to obtain protection for a nlicro-organislll per se(including one found in nature) the organiSt11 Illust he capable of hcingobtained by disclosure of a repeatable Tllcthod of producing it \vithoutdependence on biological nlatcrial provided by the applicant (such as bypropagation fro III a sample deposited by the applicant). In the patentspecification no nlcthod \\'ClS disclosed for producing the 111utants other th"n

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26 R. S. CRESPI

through propagation of a culture of these same mutants. l""his \vas insufficientto meet the req uiren1ent of the prevailing patent lay.'.

In the 7-chloro-6-llelnethyltetracyclin case (1977) ~ the invention v"as con­cerned with the production of lnutant strains of Strepu)Jnyces aUre(~fllCiells

which \vould selectively produce the title conlpound in preference to reJatedtetracyclines~ thereby obviating substantial purification problenls. The micro­organism clainls \vere directed to mutants of the type strain A-377 (NRRL22(9) characterized by selectivity for producing the desired conlpound andalso by the colour of the fermentation nlash expressed in terms of anumerically defined reflection curve. The latter paralnetcr \\'<.\5 a disting­uishing mark by \vhich strains having the desired properties could berecognized. In the appeal to the Gerlnan Suprenlc Court~ 'llnended clainlSwere presented \vhich included culture-collection deposition numbers ofexenlplary nlutant strains. Ho\vever.. these deposits had not been Inade untilalmost 3 years after the filing date of the application. Important though it \vas ..the non-deposit of the strains at the proper date was not the central issue inthis casco The primary ground of objection \vas that the mutants \vcreobtained by treatment of the type strain \vith ultraviolet radiation or chen1icalITIutagens .. but no details of the process \vere given \\lhich \\'ould have been ­reproducible with reasonable certainty of success and \\'ith the expenditure ofreasonable effort and cost. The characteristic colour of the fernlentation tllClShwas alleged to be a marker for recognizing suitable mutants once they hadbeen produced. However .. the randoo1 use of a 1l111tagenic procedure follo\vedby recognition of suitable mutants did not cunount to a reproducible chain ofsteps \vhich would be reasonably certain to produce the mutants. This lack ofa reproducible process for the production of the 111utants \vas fatal to thepatentability of the mutant strains per se.

In the Lactobacillus bavaricus case (1978) .. ho\vever .. the Gennan FederalPatent Court upheld a claim to a group of naturally occurring Inicro­organislTIs to v"hich the applicants gave the species nanle Lactobacillusbavariclls. The clainl defined the nlicro-organisills as "obtainable' by carryingout certain specified selection steps \\lhich resulted in the production ofbacteria \vhich predOJ1linantly produced the L( +) isomer of lactic acid. Theclaitn \vas therefore to a nc\v species of lactic acid bacteria characterized by acertain method of producing strains of this species but not linlited to the liseof such Inethods of production.

Although naturally occurring .. the nc\v nlicro-organislns had previouslybeen undiscovered and required hun1an technical intervention to recognizethem and produce thenl in a reproducible manner. 'fhe subject rnattcr of theapplication \vas therefore an invention and not a 1l1Cre discovery. The court\vas persuaded that a reproducible description enabling the skilled person toproduce (i. e. isolate) strains of this species had been given in the specifica­tion. l"hc court 'llso stated that the isolated pure cultures of the nc\v speciesupon addition to the vegetable to be fennented (Sauerkraut) had a differenteffect compared \vith that achieved at naturally occurring concentrations inthe vegetable source.

l"'he insistence 011 the reproducibility issue is perhaps the reason \vhy theGernlan cases have not had as great an intlucnce on the international

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Microbiological inventions and tlte /Jutent latv 27

development of nlicrobiological patent 1£1\\' as the Chakraharty decision in theUnited States. Also" in Chakrabarty vve are close to the nc\v biotechnology ..as the following rnain claiJn of the patent sho\\'s:

A bacteriunl from the genus Pselldol1'zollas containing therein at leastt\VO stable energy-generating plasmids .. each of said plasillids providinga separate hydrocarbon degradative path\\.'ay.

The United States Patent and ~rradenlark Office had maintained the argu­ment that Congress had not intended Jiving organisms to be encornpassed bythe tcrlTIS "nlanufacture· or "conlposition of matter" under the US PatentStatute (35 USC~ 1(1). In addition they had argued that Inicro-organisnls areproducts of nature and as such unpatentable. "rhe first proposition \vassupported by the argulnent that the Plant Patent Act of 1930 and the PlantVariety Protection Act of 1970 sho\ved the intention of Congress to linlit thelegal protection for living organisms to those specifically covered by thesestatutes and therefore to exclude bacteria fronl \vithi n the categories ofpatentable subject nlatter. In rejecting this argunlent the court held thatCongress plainly contemplated that the patent la\vs would be given \videscope. The clailll \vas not to a hitherto unkno\vn natural phenonlenon hut to anon-naturally occurring nlanufacture or composition of matter. a product ofhUlnan ingenuity having a distinctive kno\vn character and usc. In alsorejecting the -product of nature" argulncnt" the court held that the patenteehad produced a new bacteriunl with tllarkedly different characteristics fronlany found in nature and one having the potential for significant utility. This\vas not nature"5 h<lndiwork but that of the inventor.

This decision has addressed the crucial question of novelty in patent ht\v inthe context of "product of nature·~ Had it been possible to sho\v the fortuitousand even previously unkno\vn occurrence in nature of a PSCudolllonadcontaining t\VO or Inore different plasrnids of the kind clainlcd .. the decision\vouJd presumably have been othervvisc. Fortunately .. such ,\~as not the caseand the decision stands as one of nl0nU1l1entai illlportancc to the futuredevelopnlcnt of patent la\v in the lJSA and beyond.

Bct\veen the Baker·s Yeast and (~hakrabarty cases~ negative decisions onthe patentability of nlicfo...organisrTIs nc\vly isolated frOITI soil \verc given inAustralia ()976) and Ireland (1978) in the I~({llk //o,:is 1\1c[)Oll1!.(l11 casco

-rhe cJahns rejected by the Australian (~()nlrllissionerof Patents \\!erc of thefoHo\ving type:

fllsariunl grarnlllearuI11 Sch\vahe deposited ,,,lith the (~oJl1nl()n\vealth

Ivtycological Institute and assigned the nunlber ItvlI 14525 and variantsand nlutants thereof.

'l'hcse novel strains had heen developed as suitable for the production ofedible protein. "'rhey \verc adnlittedly isolated frorn soil sanlplcs but nodisclosure of the p,lrticular soil or particular 111cthod of isolation had heengiven. 'rhe specification \Vas held insufficient because it did not describe any1l1cthod of perfonnancc of the invcntion~ i.e. it did not describe any nlcthod

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28 R. S. CRESPI

of producing the micro-organisms. This requirement was not satisfied by meredeposition in a Culture Collection. even if a deposited strain was available bythat means. The view was also taken that as the organism was isolated from asoil sample "l"here may at best have been a discovery. No invention wasinvolved in the mere discovery or the nlere identification or the mere isolationby an unspecified method of something that occurs in nature. ~ In asking therhetorical questions ·What has the inventor done .. \vhat contribution has hemade?' the reply \vas "He has discovered Cl naturally occurring micr()~

organism and by altering its conditions of growth he has changed itsn1orphological characteristics. If that is all that he has done he has made nouseful contribution to the art. ~ The decision indicated that the situation \vouJdbe quite different if in producing the micro...organism by some man-controlledmicrobiological process the inventor were to have produced a new micro...organislTI having improved or altered useful properties. In the latter circulnst­ances it would be wrong to refuse a patent for such an invention on theground that such a micro-organism .. being something Hving.. \\tas not a mannerof nlanufacture.

The identical claim \vas also refused in the Irish High Court but fordifferent reasons.

The Chakrabarty case is generally assessed as definitive in disposing of theobjection that patents should be denied for micro-organisms simply becausethey are alive. In the Abitibi PalJer Corporation case in Canada decided in1982.. the Commissioner of Patents \vas undoubtedly influenced by theattitude of the US Supreme Court and by other foreign case hl\\'. The Abitibiclaim \vas to a combination of five micro-organislns acclimatized to spentsulphite liquor. Combination clailTIS have not usually provoked the oppositionreserved for clairns in naked per se fornl to a single strain and the decision istherefore not remarkable on that ground as such. But .. in allo\ving the clain1,the decision discusses the subject as a whole and sees no reason why patentsfor life forlns nluch higher than bacteria should be refused.

1"'0 the positive attitude now shown to\vards n1icro-organism patents in thenlajor industrial countries mentioned so far .. we must add the view of theEuropean Patent Office explained in its official Guidelines .. and the thoroughanalysis of the issue under European patent hl\V given by an EPO officer\vriting in his personal capacity Creschemacher .. 1(82). The European patentsystem has gone a fair \vay towards accomnlodating microbiological inven­tions although there is still room for greater perfectjon~ As regards biologicalinventions nlore generally. the main surviving problem is one rooted in pastobjections to the patenting of Jnethods of treatment and diagnosis carried outon the hun1an or nnilnal body. Method clain1s of this type \\'ould be used\vhere the substances or apparatus involved are not themselves patentable."fhe explicit rejection of these claims applies both to humans and otheranimals \vhere the nlethod has a therapeutic us distinct from an econoJnicpurpose. ·The exclusion of such methods frOITI patentability .. \vhich is based onlack of industrial applicability ~ has inevitably also passed into those nationalhl\VS that have harmonized \vith the EPC. Attelnpts to evade this exclusion bypresenting claims in the form of "use of substance X in trc,ltment of disease Y"have been supported by European \vriters (see especially White .. I YH4).

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Microbiological inventions and the patent la}1v 29

NATURALLY OCCURRING ~nCRO-ORGANISMS

Patent law postulates a division between pure science and the phenomena andcreations of nature on the one hand and the applied or artificial contrivancesdevised for meeting human economic needs on the other. Thus the concept of'discovery~ is primarily intellectual in character, in contrast to that of·invention' which has a practical utilitarian nature, and it has been recognizedin patent Jaw that some such distinction must be made in considering the kindof subject matter which is suitable for patent protection. For example.although the US patent statute does not explicitly treat discovery as differentfrom invention .. the distinction bet\veen them has always been present in caselaw. It is to be found again in the Chakrabarty case in the way the SupremeCourt dealt with the argument that the handiworks of nature are above thepatent law and free for all. The Court \vas able to reject the argument basedon the unpatentability of natural phenomena by observing that the Chakra­barty micro...organism was a new bacterium which was non-naturally occur­ring. The patent law prevailing in Western Europe is typified by the EuropeanPatent Convention wherein ~discoveries~ as such are one of the list of specificexclusions from patentability although the criteria for distinguishing bet\veenunpatentable discoveries and patentable inventions have been left open.presumably. for decision by case law.

For micro-organislns it seems appropriate at first sight to apply the term·discovery~ to organisms pre-existing as such in nature and the term "inven­tion ~ to non-naturally occurring organisms constructed by the ne\\' techniquesof biotechnology., such as the recombinant DNA and hybridoma technolo­gies. This line has the merit of being a clear and simple solution and it appearsto be accepted by Jnany commentators within the patent professionalcommunity and beyond.

An analysis of this issue must begin \'lith the question of novelty. To takethe European patent system as a model for discussion. the test for novelty isapplied to the ~state of the arf \vhich is defined as ·everything made availableto the public by means of a written or oral description. by usc .. or in any other\Yay~ before the date of filing of the European patent application', The samecriterion is used \vhen considering \vhether a micro..organisnl should bedeposited in accordance \vith EPC Rule 28. A ne\y nlicro-organisnl is one notalrcHdy available to the public. e.g. not on open access in a Culture Collectionor not so weB known .. so \vell identified and so ubiquitous in the environrnentthat it may be recovered at \vill "lith Jninimal effort by the skilled 'h'orker. Thenecessary elcrnent of novelty ~ in the sense of previous inaccessibility .. can befulfilled in a variety of \vays. A ne\\' micro-organisln may be produced bypurposive construction from a kno\vn and available organism by incorporat­ing into it foreign genetic nlatcrial. Alternatively .. in the category no\\' beingdiscussed .. a nc\v strain rnay arise in the laboratory by chance rnutation orsonle other fortuitous event. Yet again.. a previously unknown micro­organism may be isolated for the first time fronl soil or other natural source.

At the cxtrenlC negative end of the spectrum of opinion .. the isolation of"found~ nlicro-organislns is regarded as 111Cre discovery and therefore un­patent'lble. l"'he Illiddle ground taken by lnost conlnlentators is that the

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30 R. S. CRESPI

technical teaching of an isolation procedure" or the mere fact of one havingbeen required. adds the element of inventiveness necessary for patentability.Assuming also that some practical utility for the organism is demonstrated"two of the main criteria for patentability have thus been filet. Inventiveness.the other criterion. ftO\VS almost autolnatically fronl the combination ofnovelty and utility. assuming of course that it was not obvious (1) that thespecific organisnl existed" (2) hoYt, to isolate it and (3) that it would have theuseful properties shown for it. The adherents of this position usually suggestthat the claim to the Inicro-organism must not directly cover the organism inits natural state and some kind of purity limitation is called for as~ forexalnple, in USA \vhere the claim must recite a ~bi()logically pure' culture."rhe ITIOst positive approach to patents in this situation regards the puritylinlitation as contrived and really unnecessary. For \\'hat did it profit theskilled \vorker that the micro-organisnl existed in nature. if that existence waspreviously unrecognized and therefore ullutilized? In those circulnstances itcould not be a part of the state of the art as comn1only understood in relationto \vhat is previously kno\vll fronl docunlents or used in the technology. Inpractice .. such a restricted claim nlay give sufficient protection in most cases"but one can conceive cirClunstances in which the purity limitation may beinconvenient and impose a difficult burden of proof on the patentee.

"rhe argunlents outlined here are relevant to the natural-product problemas a \vhole and not only to micro-organisITIs. An important recent contribu­tion to the debate is the decision of the Federal Patent Court in Germany onthe Antllll111nide case. The claim was to a cyclic decapeptide termed antama­nidc .. \vhich was a naturally occurring substance present in the green amanitefungus. Here. the Federal Patent Court addressed itself to the problem ofdifferentiating between discovery and invention. The court \vas convincedthat this \vas not a case of mere discovery because. although the inventor haddiscovered the existence of this valuable peptide in nature.. he had notrestricted hilllscif to a non-patentable discovery but had gone further andprovided a technical teaching of the process of preparing the substance. Thefact that the substance existed in nature \vas not per se a circumstancedetracti ng fr0l11 novelty. provided that the average expert \vas not previously(1\vare of the fact. "fhe court therefore approached the legal problcln on thebasis not of pre-existence but of availability or other\\'isc to the public. i.e. itapplied a strict state-of-the-art test. A naturally occurring substance which,-vas previously available to the public \vauld be no longer novel in the patenthl\V sense" but that \vas not the situation here. As to \vhcther there \vas anydifference of identity bet\vcen the clainlcd conlpound and the dccapeptidc inthe form in \vhich it existed in nature (a question of fact vvhich \vas not

. resolved). the court took the liberal view that this \\rould not in any event bedecisive as regards the allov/ability of a clainl in the per se form used.

l'hc significance of this case is that it is nlodcrn and decided under nationalh.l\v in confornlity \vith the principles laid tkl\Vn in the guidelines of theEuropean Patent Office. Most other 'product of nc.L[lIn.~" cases are no\vrelatively old and \verc decided under United States jurisprudence. l"'his caseis therefore helpful on the \vhole question of "products of nature" under

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Microbiological inventions llnd the {latent !al1} 31

modern patent law and is significant not only for genetic engineering and thevectors and other immediates used therein but also for inventions in a widerresearch area involving the isolation of valuable substances from naturalsources.

PATENTS FOR GENETIC fttfANH)UlATJON

The Cohen...Boyer US Patent 4,,237 ~224 \vas the first patent granted in theUnited States for recombinant DNA techniques~ but others had appearedrelatively unnoticed and unsung in other countries. The grant of the Cohen­Boyer patent opened the log-jam in the US Patent Office and nlany patents inthis field have since issued. The present period is one in \\'hich both thecombined creativity of inventor and patent draftsman and the officialresponse to it will determine the kinds of patent that can CJnerge fromprosecution and examination in Patent Office proceedings. Claims to synthe- .tic genes and plasmids in terms of functional properties and specific restrictionmaps .. as well as those drafted more concretely in ternlS of DNA sequences ..are all appearing .. together with clainls to recombinant strains and otherscientific creations. The categories of patent in this field have been postulatedby some authors (Vossjus~ 1979: Hiini and Buss~ 1982) and many specificexamples have been quoted in an early overview of this developing field(HaJluin~ 1982). A highly perceptive analysis of the legal issues involved invarious types of claim to newly isolated or ne\vly constructed plasmids andother DNA combinations has been given in an academic study (Bendt~ 1982).A summary of a review of published patent applications and patents in geneticengineering up to 1982 and beyond (Knuth et al.. 1984) indicates that a \videvariety of terminology has been used by applicants for the characterization ofthe moJecules and other entities involved~ and these latter authors suggest theneed for more uniformity of definition in this field.

There is clearly inspiration in the writing of genetic engineering patents aswell as in the inventing of \vhat goes into them .. and the observer can onlymarvel at the ingenuity of the pacemakers. It \vill be the case la\\,' \\'hich finallybrings discipline into the draftsnlan's art and so far the signposts are fc\v. Thegreatest interest \vill focus around the level of inventiveness required tosustain clainls of the broad scope that are required to block effectively theloopholes through \vhich competitors can slip \vith their o\vn specific sequ­ences and clones. Inventiveness is the acid test of any patent. Its resolution isan enormous probJern for legal systems in \\'hich judges \vith specitic technicalknowledge are the exception and not the rule. The clainling of vectors andother DNA nl0lecules in broad and purely functional ternlS .. i.e. reciting theend result intended to be produced by the cOlllponents of the systc£l1 (controlregion" structural gene sequences .. etc) is in danger of being held unacceptableas a nlere statement of a problcnl or an ohvious dcsideratulll even thoughsupported by one or 1110rc of the characteristic EX(lI11plcs to he found inpatent specifications.

The classic conception of invention is the finding of sorncthing unexpectedOf the doing of sonlcthing unusual.. proceeding perhaps do\vn a path a\\!ay

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32 R. S. CRESPI

from the normal direction of research. This is not easily equated with thedemonstration of great scientific skill as such. It is likely in this field. however'lthat arguments for inventiveness may place more reliance in future on thedegree of expertise displayed in overcoming problems of scientific experi­mentation than has been done in the past in less complex technologies.

Some of the reconlbinant..DNA patents that have issued may soon betested as the parties begin to shape up for disputes over priority and scope ofpatent claims. In vie\v of the cOlTIplexity of the issues involved~ this writer hasno intention of predicting the case law before any of it happens. As these newgeneral techniques yield their fruits \vhen applied to the production ofparticular biologically useful peptides and proteins by the efficient methods ofthe fermentation industry 'I the inventiveness of specific applications \viIlinevitably be called into question. Much will depend on the scope of ''''hat isclaimed as nc\v and as more than the obviolls application of a new tool tofashion specific end..products.

On the question of inventiveness and claim scope.. one case which isparticularly noteworthy has been decided at Patent Office level. This involvedthe application of cell-fusion techniques to the construction of hybridomas forthe production of monoclonal antibodies. After the discovery of the basictechnique and the subsequent appreciation of its general inlportance. it wasreasonable to assume that the patentability of any application of this generalprocedure ITIUst rest on some special and non-obvious property or advantageof the particular system constructed .. in much the same \\lay as should apply tothe patenting of particular applications of recombinant DNA methodology.Mere novelty should not be enough. This approach has been vindicated in theWistar Institute case in \vhich claims so broadly drafted as to cover theapplication of the basic method to the preparation of viral antibodies couldnot be sustained. Rejection of an attelnpt to re-patent the basic technique asapplied to such a broad sub-class of antibodies is less noteworthy .. ho\vever"than the rejection even of the specific claim to an individual hybridoma on thegrounds of lack of any stated exceptional quality which \vould justify patentprotection.

Patents for plants and other organisms

There is now a clear trend in favour of allowing patents for organisnls of thekind with which the industrial microbiologist is principally concerned. Theseare now \videly seen to be tools as useful to industry as are chenlicalcompounds. An extension of this thinking to certain higher organisnls hasalready been achieved \vithout perceptible difficulty. "rhus. animal and other

.cell cultures and cell lines have not so far been distinguished from bacteriaand other sinlple organislTIs in the consideration of patentability by patent­examining authorities. Cell lines .. for exanlple .. are treated as nlicro-organismsfor the purpose of existing legislation and are regularly deposited in CultureCollections for patent purposes. At sonlC stage in the scale of life fornls.hO\'Jever .. an obstacle is reached either by statute or by a prevailing ethosagainst granting patents for higher organislTIs of a certain size and COlllplcxity.

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Microbiological inventions and the patent lal-v 33

The most explicit legal restriction on patents for plants and animals is to befound in Article 53(b) of the European Patent Conventi()n~ as follows:

European patents shall not be granted in respect of:(a)(b) plant or animal varieties or essentially biological processes for the

production of plants or animals~ this provision does not apply tomicrobiological processes or the products thereof.

THE LEGAL PROTECTION OF NEW PLANTS

Legal systerns for the protection of ne\v types of plant are of relatively recentorigin compared with patent laws. "fhis is attributable in part to the fact thatscientific plant breeding did not begin until the laws of genetic inheritance,",,'ere recognized in the early part of the present century. In addition .. it wasconlmonly considered that the difficulty of transferring plant-breeding tech­nology reproducibly by means of the \vritten description must remove it fromthe ambit of the patent law. A further reason may be found in the lack ofsufficient pressure from the industry to provide legal fornls of protection ..until more recently. Indeed" trade secrecy is still regarded by sonle as a moreeffective method of achieving protection: for certain hybrid plants 'I forexample .. the ability to retain exclusive possession of the parental lines maygive the breeder all the protection he needs.

In contcnlplating possible systems of protection .. one must consider thewhole plant .. the reproductive material of the plant .. and the flo\vers or fruit orother consuillption material produced by the plant. "fhe traditional patentsystcln has hitherto been viewed in nlost countries as inappropriate for theprotection of new types and varieties of plane but a sJnall minority hasprovided for plant patents. The most well ...known is the special type of plantpatent granted in the United States under the Plant Patent Act of 1930 \vhichis no\v incorporated into the general statute of patents. This type of patent isavailable for asexually reproducing plants and covers the ~Ihole plant: mostplant patents are taken out for rose trees and fruit trees. The otherwell-known system is that in Gcrnlany where patents for plants began to hegranted under the ordinary patent hi\\I in the 1930s.

Plllilt variety rights

The plant variety right is a special type of protection \vhich \vas introducedinto many national laws in the 1960s and \vas also Jnade the suhject of theInternational Convention for the Protection of ne\v Varieties of Plants(UPOV) \vhich was signed in 1961 and became effective froln 1968 onwards.

Whereas with plant patents of the United States type the protection is forthe \vhole plant" it is a general characteristic of plant variety protection that itis directed to the reproductive material of the plant. The plant variety rightcovers the production of the reproductive or vegetative propagating. nlC:lterial

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34 R. S. CRESPI

for the purposes of cOlnmercial marketing. its offer for sale ~ and itsmarketing. l"his fornl of right is adapted so nluch to the special circumstancesof the plant breeding and gro,"'ing industry that its procurenlcnt andexploitation is a highly specialized business. The establishment of the plantvariety right systelTI has been followed by substantial private industrial andpublic investment in plant breeding \vith the resulting developlnent andintroduction into agriculture and horticulture of many ne\\' varieties of plant.Nevertheless. the linlited scope of the right has been the subject of criticalcOlnment in recent years. The UPOV Convention prohibits the possibility ofdouble protection~ i.e. by both patent and plant variety right (Straus~ 1984).The plant variety right is adapted to the traditional operations of the plantbreeder" from \vhich there finally elnerges a variety which has the desiredcOJllbination of traits and is stable and homogeneous. This kind of activity.although it clearly involves intervention by the skilled worker in the naturalprocess ~ is not seen as technical intervention of the kind \l,lhich patentauthorities \vill recognize as coming within their donlain. It is a )ong-dra\vn­out process incapable of realistic comnlitment to \vriting \vith a view toreproducibil ity, a factor which gave rise to frequent difficulty in the protectionof plants under the (Jernlan patent hl\V. The development of nc\v varieties bythese techniques and the prescribed test procedures typically required forplant variety protection and for official certification of the ne\v variety forindustrial use are outside the relnit of patent-examining authorities. For thisreason it is understandable that legislators of the patent la\\' have insisted on aseparation bet\veen the t\VO systClns.

Plant genetic manipulation poses a new situation. It clearly involvestechnical intervention of the kind \vhich may be capable of reproducible\vritten description along similar lines to that used for reconlbinant-DNAinventions. It is therefore appropriate to question \vhether the processes andproducts of plant genetic Inanipulation should be assumed to COll1C autonlati­cally under the present ban in EPC and sinlilar patent hl\\'. A technique \vhichcan be described in a reproducible manner and vvhich leads to geneticallyaltered plants could be vic\vcd as an invention vvithin the scope of the patentla \v. protectable as a process and also by n1eans of product per se clain1s tonc\v plants defined by appropriate characteristics. If genetic 1l1anipulation is a"111icrobiological process' it follo\'vs that its products are patentable. regardlessof \vhether they are plants or animals. Furthennore .. by lilniting the terln"plant variety· to those specific entities \vhich in context are clearly subjectI1latter most appropriate for protection by means of a plant variety right. it\vould then be possible to allo\v patent protection for subject Inattcr \vhich isnlore correctly categorized as ·invention' .. even though the type of protectionsought involved the presentation of claims to plants as such. l'hcse clailnscould be regarded as not directed to a ~plant variety· but rather to an inventiveconcept relevant to a nlllch \\'ider grouping or definition of plant 1l1aterialsthan is connoted by the ternl ·variety·. Such an appro'lch is already possihle ..for eXi.lrl1 ph:~ ~ under United States la\v \vhere the ordinary (utility) patent isavailable for inventions \vhich are amenable to the verbally fornlulatcd putcntclainl and the corresponding enabling disclosure in \vrittcn forn1.

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Microbiological inventions and the patent Jalv 35

The question ofcopyright

It has been suggested that the la\v of copyright may apply to the works of~authorship~of the genetic manipulator (Kayton, 1982). Opinion is divided onthis question among the few US authors who have so far commented on it (seefor example Cooper. 1982b). To most patent experts the notion of copyrightfor, say .. a recombinant plasmid seems bizarre even in spite of the intriguinganalogy with a computer program. As an academic legal possibility thequestion is of interest, but as a practical reality it may evaporate as soon as theproblem of actual enforcement of copyright comes to be considered. Copy­right vests not in a fundamental idea but in a mode of expression of that idea

. and it is therefore essentially a narrow form of legal protection. In addition .. ifit is to be enforced, there must have been actual copying of the original workand not independent invention. In the light of the specific patent disputes thatare now in prospect, it is difficult to envisage copyright as having anyconceivable application to such situations.

References

LITERATURE REFERENCES

BEIER .. F. K. (1972). Future problems of patent la\y. International Rel,rielV of IndustrialProperty lind C."opyright LlllV (lIe") 3.. 423.

BENDT~ s. A. (1982). Patent protection for DNA nlolecules. Journal of the PacenlOffice Society 64" (2) .. 60-86.

BJ(jG,\RT.. W. A. (1981). Patentability in the United States of micro-organisnls"processes utilising micro-organisms" products produced by micro-organisms andl11icro-organism mutational and genetic modification techniques. Journal of L,nvCllld Technology (IDEA) 22, 113-136.

COOPER .. I. P. (1982a). Biotechnology and the LaJil .. chapter 3. Clark Boardman Co.Ltd. New York.

COOPER. I. P. (1982b). Biotechnology {lnd the L{nv~ chapter II. Clark Boardnuln Co.Ltd .. Nevi York.

CRESPI .. R. S. (1981). Biotechnology and patents: past and future. European Intellec­tual Property Rel1iew 3" 134-140.

CRESI)L R. S. (1982). Patenting in the Biological Sciences, chapter 3. John Wiley andSons. Chichester and Ne\v York.

CRESPI .. R. S. (1983). Biotechnology and patents: outstanding issues. EuropeallIntellectual Property Reviel~' 5 .. 201-205.

DUNNER. D. R. AND LIPSEY.. C. E. (1979). The patentability of life fornls~ newtechnologies and other nooks of nature. Anlericon Patenl LCl~il Quarterly Journal7" 190-219.

[)CITENH6Fr::R~ I-I. (1971). Patent protection for biological inventions. Jahre BUlll/es­!Jatentgericht 1971 Festschrift IO.. 171-200.

I-IAJ.l.ulN .. A. P. (1982). Patenting the results of genetic engineering research: anovcrvie\y. In Patenting of Life Farlns. Blll1bur.y Report /0. pp. 67-126. (~()Id

Spring J--Iarbor Laboratory. Ne\v York.I-IONJ .. A. (]977). The disclosure in patent applications for microbiological inventions.

InJerll(J(io!Za! Revie\i.' of Industrial Property and ('ofJJ'righl Llnv (J!() 8~ 500-521_l·IOt':I~ A ...\ND Buss .. V. (1982). Patent protection in the field of genetic engineering.

Industrial Property J982" 356-368.KAYTON" I. (1982). Copyright in living genetically engineered works. George Washillg~

lOll L(I~l' l?elJie~t: 50.. 191-218.

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KNUTH~ S... BELYAKOVA t L. G q VELKOV .. V. V., DEMENTYEV, V. N q LOMMI. H. J ..JvIARPER~ R. A. L. AND GYLLENBERG .. I-I. G. (1984). Characteristics of geneticmaterial with reference to patent documents. Acta Biotechllo!ogica 4 (3).195-208.

STRAUS .. J. (1984). Patent protection for new varieties of plants produced by geneticengineering-should double protection be prohibited? International RevielV ofIndustrial Proper(v and Copyright L{HV (lIe) 15 .. 426-442.

TESCHEMACHER. R. (1982). Patentability of micro-organisms per se. InternationalRevie~~1 of Industrial Property (lnd Copyright LlHV (lIe) 13.. 27-41.

UTERMANN. J. (1978). Reflections on patent protection of products of nature.International Revie'rv of Industrilll Property and Copyright LtllV (lIe) 9~ 409--421;523-541.

VOSSIlJS .. V. (1979). Patent protection for biological inventions-review of recent casela\v in EEC countries. European Intellectual Property Revie~v 1 t 278-282.

WEGNER .. H. C. (1976). Patenting nature's secrets-micro-organisms. InternationalRevielV of Industrial Property llnd Copyright Law (/Ie) 7, 235-246.

WEGNER. H. C. (1978). The Patentability of NelV Maflufactures-the Living Inventio1l.Patent La,v Conference Casebook. US Bureau of National Affairs .. Washington,DC.

WHITE. A. W. (1980). The patentability of naturally occurring products. EuropeallIntellectual Property Rl'vie~v 2~ 37-41.

WHITE 1 A. W. (1984). Patentability of medical treatnlent claims-the Nimodipincases. Europeall bztellectulll Property Revie\v 6, 3~5.

PATENT CASES errED

British cases

German cases

Reported ill 'Reports of Patent Design andTrade/nark cases'GEeStandard Oil Co.LenardN. V. Phillips GloeilanlpenfabriekenSzuecVirginiu Carolina Chemical

CorporationAlnerican Chemical Paint Co.General ElectricNational Research Development

CorporationSwift & Co.American CyananlidAmerican Cyanamid \'. Berk

PharmacellticalsWistar Institute

Reported ill Intel'1uuiollal RevielV ofJntlust­rial Copyright Lan·' (1/(,) or itsGe,.nul1l~I(lllgllllge equivalent (Gel~'e1"b~

lieher Rechlsschutz lind Urheberrectln­ter1Ztllionaler TeiJ)

I~ed DoveBaker~s Yeast7..Ch(or()-6-demethvItetracvclinLactobacillus bava;ic:lls ..Antanamide

60 RPC 169 RPC 11471 RPC 19071 RPC 192

1956 RPC251958 RPC 38

1958 RPC 471961 RPC211961 RPC 134

1961 RPC 1471971 RPC4251976 RPC231

1983 RPC255

lIle 1366 lIe 207

1978 GRUR3 1621978 GRUR 10586

10 IIC 494

Propert)'

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8 USPQ 131

76 USPQ280

116 USPQ 484

:196 Fed. 496(2nd eir. 1912)168 USPQ 99206 USPQ 193

Microbiological inventions and the patent law 37

Reported in United States Patent Quarterly(USPQ)

American Fruit Gro\vers Inc. v.Brogdex Co.

Funk Bros. Seed Co. v. KaloInoculant Co.

Merck Co. Inc. v. Olin MathiesonChemical Corporation

Parke-Davis & Co. v.H.D. Mulford Co.

In Re ArgoudelisDianlond v. Chakrabarty

US cases

Other cases Rank Hovis McDougall: Ireland" 1978Fleet Street Patent Law Reports. 588~Australia. 1976 Official Journal of Pa­tents, Trademarks and Designs 21 Octo­ber ]976. 3915.

Abitibi Paper Corporation: 62 Cana...dian Patent Reports (2D) 81 (1982)

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