introduction

the scientific field of biotechnology is dramatically changing the world in which we live. tremendous new discoveries this past decade have fundamentally changed the way we think about biotechnology and the way we use it to improve our lives. many biotechnology uses create legal issues, and patent law is evolving to address these issues. however, since the field of biotechnology is new, the body of case law is small, problems have arisen about the certainty in the patent law on the patentability concerning biotechnology.

one of the biggest issues involving biotechnology and the law is the patentability of ests. the patentability of ests has become an important major object of discussion over the last years in patent literature.[1] in u.s, the ongoing discussion led to the u.s to acknowledge, in principle, the patentability of ests.[2] however, questions still exist to patent ests. in eu, to the best of the author’s knowledge, there is no decision of an appeal board of the european patent office (epo) that addresses the patentability of ests.

this article will examine the patentability of ests in both us and eu regimes in accordance with the statutory requirements. the second part will define what ests are. the third part will discuss the patentability of ests in the u.s regime. the fourth part will exam the patentability of ests in the eu regime. finally, i will conclude the essay.

what are ests

“an est(expressed sequence tag) is a partial sequence of a clone picked at random for cdna library and used in the identification of [so far unknown]genes being expressed in a particular tissue. the technique exploits recent advances in automated dna sequencing and sequence date handling, and a remarkably high numbers of ests turn out to represent previously unknown genes. the predicted primary structure of the proteins that would be expressed and their relation to proteins of known structure identify these. ests have proved extremely valuable in mapping the human genome.”[3]

patentability of ests in us regime

1.patent application process in the united states

in the united states, patents are granted on application to the pto (u.s. patent and trademark office) when the invention meets the requirements of patentability. each application should not only contain a specification which describes the invention and explains how it works, but also contain claims which are the actual patentable features of the invention. if the application is rejected twice by the examiner, the applicant can appeal to the board of patent examiners, if he is not satisfied with the board’s decision, he may further appeal to the united states court of appeals for the federal circuit or the united states district court for the district of columbia.[4]

the court of appeals for the federal circuit is a specialized court established in 1982 to deal with disputes concerning grants and infringements of patents. the court has played a major role in developing a pro-patent legal environment.[5]

2.patentability of ests

a. statutory requirements for patentability

to obtain a patent under the current patent statute, an invention must be new, nonobvious, and useful.[6]the inventor must also describe the invention in an enabling disclosure.[7]

novelty

the newness or novelty requirement is provided at 35 u.s.c. s102. this provision of the patent act requires that a patentable invention was new at the time of its discovery and that its inventor was the person who conceived of and reduced the invention to practice.[8] according to section 102, an invention is patentable so long as the invention is not identical to a product or a process already relegated to the public domain.

nonobviousness

the nonobvious requirement is codified at section 103. it is often the most difficult requirement of patentability to apply, involving a subjective determination.[9] the procedure is set forth in graham v john deere co. which requires an initial appreciation of “ the scope and content of the prior art”[10] if the invention, as a whole, would have been non-obvious to an ordinary worker in the pertinent field at the time the invention was made, then the claimed invention is patentable. a u.s patent is prior art as of its filing date even though it is not available to the public.[11]after identification of the prior art, the next step involves determining its scope and content, that is, what does it disclose or suggest to a person reasonably skilled in the applicable art.[12]

enabling disclosure

the enabling disclosure requirement can be found at section 112 of patent act. under s 112, an inventor have to provide a description of the invention as well as clear and complete instructions in his patent specification, so as to enable others to recreate and use the invention. the adequate disclosure requirement guarantees that the patent specification dedicates to society the inventive concept on patent issuance and the invention itself on patent expiration.[13]

utility

the utility requirement is derived from the constitution, which grants patent right to “useful arts”, [14]and from the patent act, section 101. to satisfy the utility requirement, an invention must first be “operable,” and secondly, must have “practical utility.” if an invention is a chemical process, the third requirement must be met: the product of the claimed process must also be useful.[15] an invention is “operable” if it works to solve the problem it is designed to solve.[16] to satisfy this requirement, however, the inventions need not be completely successful in solving the problem: “to violate s101 the claimed device must be totally incapable of achieving a useful result.”[17]an invention satisfies the second requirement of utility, “practical utility”, when the claimed subject matter has a “real-world” value.[18]

b. patentability of ests

to determine whether ests are patentable, one should apply the tests set forth for each prone of the patent statutes. to obtain patent protection, ests must be shown that they are new and nonobvious, described in an enabling disclosure and of some utility.

the argument against patenting ests always focuses on the utility requirement.  typically, the function of the gene from which the est was derived is unknown. therefore, the est does not have a specific utility. however, ests are useful tools for obtaining the entire sequence of genes.[19] as a result, there has been much debate about the patentability of ests.

in brenner case, the supreme court held that patentability required disclosure of a practical utility -- not merely a use for further research.[20] based on the rule of the brenne, there would be an argument that claims to partial dna sequences whose only disclosed utility is for further research -- gene mapping or probing to isolate a full-length sequence whose function is unknown -- are patentable. but as in the case of the incyte “est” patent, the full sequence of the corresponding gene is known as well as the function of the protein coding from this gene, the utility requirement will almost be found to be met.[21]

in the clarified utility requirement of pto, the utility standard requires that ‘[a] claimed invention must have a specific and substantial utility’[22]this requirement precludes the inventor of an est from patenting the est without providing a substantial utility.[23]under the new standard, this would likely require that inventor know the identity of the gene that corresponds to the est.[24]

turning to novelty requirement, a previously published est would be considered prior art (part of the state of the art) with respect to a claim to a later discovered full-length gene.[25] in the context of priority of invention, the court of appeals for the federal circuit has held that conception of a full-length gene does not occur until the inventor can describe the gene "by structure, formula, chemical name, or physical properties." [26] under this rationale, the prior disclosure of an est would not anticipate (destroy novelty) of a later discovered full-length gene that comprises the sequence of the est.[27] to anticipate a patent claim, the prior art must disclose each limitation of the claim in the same manner as set forth in the claim.[28] because a claim to a full-length gene would contain limitations (sequences) not disclosed by the previously published est, it would not be anticipated.[29]

the standards for nonobviousness on ests are not different from inventions in other fields because ests are chemical compounds.[30] the court of appeals for the federal circuit has held that in regards to claims to dna, as with claims to other chemical compounds, unpatentability requires that the teachings of the prior art suggest the claimed compound to a person of ordinary skill in the art.[31] where the prior art discloses structurally related compounds, obviousness requires that there must be a suggestion of making the specific molecular modifications necessary to achieve the claimed invention.[32] the federal circuit has rejected the contention that the availability of a method for isolating dna renders a claim to a specific dna molecule obvious.[33]

these rules suggest that an est would not be considered obvious absent a suggestion in the prior art of the specific sequences being claimed. the fact that the methods for generating and sequencing ests are known is irrelevant to the patentability of the specific dna molecules.[34] moreover, the fact that it is obvious to try to create these molecules does not render them obvious.[35]

as to enabling disclosure requirement, inventions relating to ests can present unique issues, depending on the claim scope sought by the applicant. the patent applicant [36]always attempts to obtain broader claims that cover not only the est, but also longer molecules, including the full-length gene, that contain the est sequence. claims of this scope present difficult enablement issues, because they presumably would encompass a longer dna molecule, including a full-length gene whose structure and function are unknown at the time of filing.

enabling requires that a person of ordinary skill in the art be capable of following the teachings of the specification to practice the claimed invention without engaging in undue experimentation.[37]. the enabling teaching provided by the specification must be commensurate in scope with the claims.[38]

it is questionable if an inventor who discovers an est, without knowledge of the gene from which it is derived or the tissue in which such gene is expressed can give an enabling description of the full-length gene.[39] a further problem is whether an inventor of an est can satisfy the written description requirement with respect to claims that encompass the full-length gene. in case fiers v revel, the court stated that"an adequate written description of a dna . . . 'requires a precise definition, such as by structure, formula, chemical name, or physical properties,' not a mere wish or plan for obtaining the claimed chemical invention." [40] in this case, the court held that possession of a partial sequence of an interferon gene and a general method for obtaining the full-length cdna was not sufficient to constitute conception of the full-length gene.[41]

this precedent suggests that a claim that encompasses a full-length gene based on disclosure of only an est would not be patentable because of lack of sufficient written description. unless the applicant can describe the full-length gene by structure, formula or distinguishing characteristics, then the claim scope should be limited to the particular dna molecules that have been isolated.[42]

patentability of ests in t he eu regime

1.patent application system in the eu

the european patent convention (epc) governs patentability of ests in the eu. a patent application must be submitted to the epo with a list of states in which the inventor wishes to secure patent rights.[43]upon application, the examining division of the epo determines whether the invention is patentable. if the patent is granted, it is subjected to a nine month opposition proceeding during which any person may challenge its validity.[44]if the patent is revoked as a result of a successful opposition, the inventor may appeal the decision to a technical board of appeals. the technical board of appeals also reviews initial rejections of patent rights by the epo.[45]

2.patentability of ests

1.statutory requirements for patentability under epc

in eu regime, a patentable invention must satisfy four basic requirements: novelty; inventory step; industrial application and not be excluded from patentability by the statute (epc articles 54 and 55; 56; 57 and 52(3) and (4); 52(2)). besides, a european patent must satisfy several additional requirements. with respect to est patent applications, article 83 and 84 concerning the substantive requirements of sufficiency of disclosure and support by the specification, article 82 concerning the formal requirement of unity of the application should be considered additionally.

novelty: article 54

under article 54 epc, an invention is considered to be new if it is not part of the “state of the art”, the “ state of art ” is defined as everything that was available to the public by means of written or oral description, by use or any other way.[46]

inventory step: article 56

article 56 provides “an invention should be considered as involving an inventive step if, having regard to the state of the art, it is not obvious to a person in the art”[47]

industrial application: article 57

article 57 states: “ an invention should be considered as susceptible of industrial application if it can be made or used in any kind of industry, including agriculture.”[48]

not excluding from the patentability

article 52(2) states “ the following in particular should not regarded as inventions within the meaning of paragraph 1:a) discoveries…”

patentability of ests under epc

to determine whether ests are patentable under epc, the requirements have to be met for patenting ests.

as to novelty requirement, it is easy to determine the novelty of an est, one can check the sequence against the known sequences in dna libraries in order to ascertain whether the sequence has already been made public.[49]as in t301/87 alpha-interferon/biogen, [50]an appeal board stated that the public availability of a cdna library did not render each clone of the c-dna library to be state of art.  it should be further noted that if the prior art disclose the existence of the full-length gene containing the est sequence, it would not render the actual est sequence non-novel.[51] as in t886/91 hepatitis b virus/biogen, inc[52], the board stated under item8.1.3: “document (1)…does not report any definite sequence date which can be said affect the novelty of the claims at issue. in fact, although the nucleotide sequences referred to in the latter are likely to be contained in the said fragments, they are not identified and characterized in the exact primary structure, thus they are not made available in the sense of article 54(2) epc.”

turning to the requirement of inventory step, different situations have to be considered in patenting the ests.if a patent application provides an est and does not indicate any function and if no related est is known in the prior art, it can be argued that this provision of a new chemical compound is lack of inventory step because it would not solve a technical problem[53]. in decision t22/82 the board stated that a chemical compound is not patentable merely because it potentially enriched chemistry.[54] in addition, in the agrevo decision,[55] the technical board of appeal established held that the technical effect of the claimed subject matter is inherently linked to the assessment of inventive step. an invention that does not solve a technical problem would probably not involve an inventive step.[56] thus, gugerell argues, ‘if the technical problem underlying the alleged invention is to be considered as the provision of human genes probed by the ests but these genes have not yet provided and have unknown functions, it could be argued that the invention as disclosed does not solve this problem.’[57]

in the situation that patent application provides an est and discloses a function, the invention solves the problem of providing a new chemical compound that can be used for the disclosure purpose. under such a situation, inventory step ought to be acknowledged if no related est is known in the prior art.[58]

as for the industrial application requirement, as mentioned before, an est can be used to map the human genome. in addition, an est could be made e.g. by chemical synthesis in a pharmaceutical company, which would be one kind of industry. as a result the industrial application would be fulfilled.[59]

in order to be patentable, ests should not be discoveries under epc. guidelines for examinations in the epo clearly acknowledge the patentability of natural products under certain circumstances. it sates that “if a substance found in nature has first to be isolated from its surroundings and a process for obtaining it is developed, that process is patentable. moreover, if the substance can be properly characterized, either by structure, by the process which it is obtained or by other parameters….and it is “new” in the absolute sense of having no previously recognized existence, then the substance per se may be patentable.”[60] since an est can be properly characterized by its structure, i.e the nucleotide sequence is not merely “discovery” but an invention in the sense of epc.[61]

to be patentable, the four basic requirements are not enough for ests, other articles of epc have to be considered additionally.

sufficiency of disclosure: article 83

article 83 epc requires: “the european patent application must disclose the invention in a manner sufficiently clear and complete for it to be carried out by a skilled person in the art”[62]the requirement of a sufficient and enabling disclosure can be met with the disclosure of the sequence of the claimed est and a statement concerning its use[63]

unity: article 82

article 82 provides: “the european patent application should relate to one invention only or to a group of inventions so-linked as to form a single general inventive concept.”

if two or more ests are claimed in the application, article 82 will be relevant. it can be assumed that in most cases the ests are contained within one application are structurally and functionally non-related. the applicant can hardly argue that the different ests are linked by a single general inventive concept, especially when no function of the claimed ests is known except as probes.[64] in such a case, the patent office can permit one of the several ests.

however, “the applicant can file an application with several ests and can use this application as a source for filing divisional applications when answering the communication under rule 51(4) epc for those ests not claimed which has become important later on.”[65]

description: article 84

article 84 states: “ the claims define the matter for which protection is sought. they shall be clear and concise and be supported by the description.”[66] the question about to what extent derivatives of an est could be incorporated into the claim can only be answered on a case-by-case basis. if no sufficient information is available to define the function of derivatives, which will often happens to ests, one might decide to broaden the claim by defining their hybridization characteristics to the special est or a degree of homology between the est and the derivatives. therefore, one may obtain a ‘gene’ claim if only one specific sequence is disclosed if all patentability requirements are fulfilled.[67]

scope of claims for an est patent

the scope of the protection is determined by the terms of the claim. the description and drawing have to be used to interpret the claim.[68] one question may be asked as to what desirable form of an allowable est claim. therefore, it must be decided what is a fair and adequate claim scope for an est. in decision t 0694/92 “modifying plant cells/mycogen”, the appeal board stated: “a proper balance must be found between, on the one hand, the actual technical contribution to the state of the art that the invention disclosed in said patent or patent application, if any and , on the other hand, the manner of claiming so that , if patent protection is granted its scope is fair and adequate .”[69]thus, it can be concluded that in order to determine the scope of claims for an est patent, one answer should be that to grand est patents has to be both fair to the patentee and adequate under consideration of the patentee’s contribution to the art. it would be broad for the for a applicant to claim the scope if an est patent would dominate the full-length gene and even could dominate the use of full-length gene for preparing a protein having a desirable biological activity because the only known function of an est is its suitability for screening libraries[70]one possibility for the scope of the claims for an est could be to allow claims covering further embodiment besides the one specific est, such as sequences that are homologous to a certain degree to the given est.[71]

eu directive and patentability of ests

the biotechnology directive of the european union came into force on july 30,1998 and has to be incorporated into the national laws of the member states by july 30,2000.

the epo itself is not bound by e.u. directives. however, the non-biding character of the eu directive for the epo questioned by an appear board of the epo in the decision t 1054/96 “transgenic plant/ novartis”.[72] “on june 15, 1999 the epo administrative council accepted a recommendation from the epo to implement the e.u. biotechnology directive in european patent law by means of amendments to the epc implementing regulations. the new rules provide that the directive "shall be used as supplementary means of interpretation" (which will mean that its recitals can be taken into account) and reflect the provisions of chapter i of the directive, as to which the epo notes that although the principles set forth there regarding the patentability of biotechnological inventions are based on the relevant provisions of the epc and essentially reflect current practice as developed by the office and its boards of appeal in applying the convention, some extensions and clarifications are required in this area to ensure that the patentability provisions of the epc also continue to be interpreted in keeping with the directive.”[73]

assuming that the standards of the eu directive are applied by the epc, the standard for obtaining ests patents might be raised.

according to article 5(1)-(3) of the eu directive, partial gene sequences are not patentable if they are merely discovered and not isolated or otherwise produced by a technical process, and if their industrial application cannot be disclosed.[74] in other words, partial gene sequences can be patented if they are isolated from the human body or otherwise produced by technical means. [75] in addition, recital 24 of the directive requires that where a claimed use of a sequence or partial sequence is to produce a protein or part of a protein, the application must specify which protein or part of the protein is produced or what function it performs.[76]

presently, it is not clear whether the function of the est to be useful as a probe may be sufficient to establish the industrial requirement of the directive. “the industrial application requirements may be satisfied if the est is e.g. useful as a species or tissue specific probe, or for forensic purposes, or as genetic marker etc, and it should not be detrimental to the validity of the patent if some of the several functions indicated in an application should turn out not to be associated with the est.”[77]

conclusion

all in all, in the us regime, for ests to be patentable, the four requirements have to be satisfied. even though the first est patent has been issued which indicates that ests are patentable, questions regarding utility looks like to be revolved, the questions to be answered involve the breadth of claims allowed for ests rather than whether protection should be given.

in eu regime, there is currently no regulation under the epc or case law a priori would prevent an applicant from obtaining a patent for ests. the appeal boards of the epo may raise the standard of the epc for obtaining ests patents by applying the requirement of the eu biotechnology directive to the practice of the epo because the biotechnology directive requires to indicate the industrial application of an est in a patent application which said requirement is not laid down in the epc.