Opinion ID: 382067
Heading Depth: 3
Heading Rank: 1

Heading: Structural Obviousness and the Unanticipated Trait

Text: 24 The Patent Act of 1952 17 sets forth three general requirements for patentability: novelty and utility as defined in § 101 and § 102, and nonobviousness as defined in § 103. The first two sections express the traditional prerequisites of patentability that in this country date back at least to the Patent Act of 1790. 18 There is no dispute in this case regarding novelty or the utility of cephalexin. Rather, Premo's primary claim is focused on the nonobviousness requirement of § 103, which was explicitly added to the patent laws in 1952. 19 25 Section 103 provides:Conditions for patentability; non-obvious subject matter 26 A patent may not be obtained . . . if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made. 20 27 Although the ultimate question of validity is one of law, 21 the Supreme Court has stated that the determination of obviousness entails several factual inquiries. In Graham v. John Deere Co., 22 the Court held that under § 103 28 the scope and content of the prior art are to be determined; differences between the prior art and the claims at issue are to be ascertained; and the level of ordinary skill in the pertinent art resolved. 23 In addition, the Court observed that 29 (s)uch secondary considerations as commercial success, long felt but unsolved needs, failure of others, etc., might be utilized to give light to the circumstances surrounding the origin of the subject matter sought to be patented. As indicia of obviousness or nonobviousness, these inquiries may have relevancy. 24 30 In cases dealing with the patentability of chemical compounds, the question of obviousness is particularly difficult because the differences between the molecular structure of the new drug and the prior art frequently are slight. Hence, the structure of the new compound may well be obvious when compared with the structure of related drugs that were in existence at the time the new drug was synthesized. Under these circumstances, if the patent law were to define a drug solely by its chemical structure, few new drugs would be patentable. As a consequence, the weight of authority-including every court of appeals that has addressed this question-holds that the structural obviousness of a new chemical compound does not, by itself, render the compound non-patentable. Instead, most courts have taken the view that the determination whether a new drug is nonobvious should be based on a consideration of the properties exhibited by the drug as well as the chemical structure of the drug. 31 The Court of Customs and Patent Appeals was the first appellate court explicitly to adopt this approach. That court's leading opinion on structural obviousness and § 103 is In re Papesch, 25 dealt with the validity of a patent on several trialkyl compounds. The hearing examiner had rejected the patent application on the ground that the new compounds were obvious homologues of the methyl groups shown in the reference compound and the method of preparation (was) substantially the same. 26 The court held that although the new compounds were closely related chemically to the prior art, and therefore were structurally obvious, the drugs nevertheless were patentable. After reviewing a number of its own decisions, 27 in which patentability was found . . . in spite of close similarity of chemical structure, the court declared: 32 From the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing. The graphic formulae, the chemical nomenclature, the systems of classification and study such as the concepts of homology, isomerism, etc., are mere symbols by which compounds can be identified, classified, and compared. But a formula is not a compound and while it may serve in a claim to identify what is being patented, as the metes and bounds of a deed identify a plot of land, the thing that is patented is not the formula but the compound identified by it. 28 33 The court concluded that (t)here is no basis in law for ignoring any property in making such a comparison. 29 Patentability therefore depends on the outcome of a comparison of both the chemical and pharmacological properties of the old and new compounds. 34 In subsequent cases, the Court of Customs and Patent Appeals has reaffirmed and, perhaps broadened the Papesch principle. In In re Stemniski, 30 it overruled the so-called Hess-Henze doctrine. The Hess and Henze cases, decided before the passage of the Patent Act of 1952, held that the existence of a homologue was evidence that the new compound was obvious in light of prior art, 31 and that a presumption of obviousness arose where a homologue was disclosed in the prior art. 32 To rebut the presumption, an applicant must have demonstrated that the claimed compound possesse(d) nonobvious or unexpected beneficial properties not actually possessed by the prior art homologue. 33 In Stemniski, the structures of the tin compounds at issue were very similar to the structures known to exist in the prior art. Under the principle set forth in Hess and Henze, the court observed, the petitioner had the burden of rebutting the presumption of obviousness. But Henze, its predecessors and its progeny, the court asserted, have met with their share of criticism over the years, both in this court, in other courts and elsewhere. 34 The court, believing that progress in the useful arts is ill-served by denying patents to inventors in the circumstances at bar, rejected the Hess-Henze rule. 35 In its stead, it held that structural similarity, or the existence in the prior art of a homologue, merely establishes a prima facie case of obviousness. 36 35 In other decisions, the Court of Customs and Patent Appeals has suggested that the existence of but one unexpected property is enough to establish nonobviousness. For example, in In re Ackermann, 37 the prior art disclosed homologues of the claimed compound and provided the suggestion for modifying the homologues to obtain the compound at issue. Following synthesis, however, the new compound was found to be superior as an optical brightener in comparison with the prior art homologues. Inasmuch as the evidence demonstrated that this trait was unexpected, the court concluded, the new compound was nonobvious: 36 The mere fact that such evidence deals with only one of a spectrum of properties possessed by that subject matter does not detract from its relevance. As we alluded to earlier, such evidence tends to prove that the subject matter claimed possesses a difference in properties over that with which it was compared which would have been unexpected. As such it is relevant and, we feel, convincing of unobviousness. 38 37 One commentator has suggested that after Ackermann and its successors it is evident that the court of patent appeals often regards the demonstration of significant unexpected properties as almost conclusive proof of nonobviousness. 39 38 The other two courts of appeals that have considered the question of structural obviousness and § 103 have adopted the Papesch doctrine. In Commissioner v. Deutsche Gold-Und-Silber-Scheideanstalt Vormals Roessler, 40 the issue was whether an ammonia-derivative compound which was selected from a group of compounds described by a general formula was patentable. The applicant had introduced evidence that the new compound possessed novel vermicidal properties that were not disclosed or suggested in the prior art and demonstrated that the new compound was more effective than the prior art as an intermediate in the production of patented sedatives and antihistamines. The Court of Appeals for the District of Columbia Circuit, speaking through Judge (now Chief Justice) Burger, articulated four reasons for adopting Papesch. First, it construed the Supreme Court's admonition in Graham, that a determination of obviousness should depend on several basic factual inquiries, as directing the courts to look to the relative properties of the new compound and the prior art, as well as to their comparative structures. 41 Second, there exist few compounds whose molecular structure is unknowable prior to their synthesis. The court reasoned that, were it to reject Papesch, few pharmaceutical compounds . . . (would) be patent(able), and the incentive aspect of the patent system, which is basic, . . . be lost from an important area. 42 Third, the court observed that the Patent Office traditionally permitted applicants to prove nonobviousness with evidence that the product possessed novel properties. Fourth, the court recognized that another patentability provision, § 101, focuses on what the compound will do, and its properties are of prime consideration for this purpose. 43 Accordingly, it held that the district court correctly considered all properties of the claimed compound in assessing its obviousness. 39 In another case involving Eli Lilly, the Court of Appeals for the Fifth Circuit also adopted the Papesch rule. In Eli Lilly and Co. v. Generix Drug Sales, Inc., 44 Eli Lilly sought preliminarily to enjoin Generix from infringing the patent it owned on a synthetic morphine analgesic compound. The court rejected what it termed a stultifying per se rule of chemical similarity, and held that Eli Lilly was permitted to introduce evidence that the patented compound exhibited unexpected, nonobvious differences from the prior art. A rule banning the patentability of structurally obvious chemical compounds, in the court's view, would be inconsistent with the purpose of the patent laws if applied to the modern drug industry:In the field of drug patents today therapeutic value, not chemical composition, is the substance of all incentive to invent. Except where the state of the medical art and the state of the chemical art have been advanced and coordinated to the point that it is possible for the mind to conceive or predict with some minimal reliability a correlation between chemical analogues, homologues or isomers and their therapeutic value, reason compels us to agree that novelty, usefulness and non-obviousness inhere in the true discovery that a chemical compound exhibits a new needed medicinal capability, even though it be closely related to structure to a known or patented drug. When such a fresh, efficacious, undisclosed use is identified, its inventor deserves the full ambit of statutory protection. 45 40 Anything short of full patent protection for structurally obvious, but biologically nonobvious, new drugs that meet the other statutory criteria, according to the court, would discourage both the inspiration-perspiration process of the laboratory and the incentive to publicly disclose products of value to mankind. 46 41 We too are persuaded that, in determining whether a new drug meets the nonobviousness requirement of § 103, the district courts should consider all of the properties of the drug-including its structure, uses, and other traits-and compare those properties with their counterparts in the prior art. If the new compound, although structurally obvious, exhibits uses or traits that, at the time of their discovery, were not predictable to chemists or other persons skilled in the prior art, such differences indicate that the new compound is nonobvious for purposes of § 103. Whether the existence of an unexpected use or trait should conclusively establish nonobviousness, we need not decide at this time. If the unexpected property results in a substantial improvement over the prior art in respect to the therapeutic effectiveness or usefulness of the drug, however, it would appear to contravene the purposes of the patent laws to deny patentability on the basis of obviousness. 47 42 The primary difficulty in ascertaining whether a new chemical compound is obvious is that most new compounds created today are the result of modification of an existing compound. Frequently, the alteration is obtained through the use of a known method of synthesis. Hence, in synthesizing cephalexin, the Eli Lilly scientists modified cephaloglycin by substituting a methyl group for the side chain that attached to the cephaloglycin molecule at the 3-position of the nuclear ring. There is no claim that this type of modification was not obvious to other chemists working in the field at that time, or that the procedure was a difficult one. Thus, the structural composition of the cephalexin molecule might well be termed obvious in light of the prior art. 43 That a new compound such as cephalexin may be the end product of a fairly simple series of chemical reactions and structurally similar to a well-known prior-art compound such as cephaloglycin, however, does not necessarily imply that the synthesis of cephalexin itself was obvious. At the time cephalexin was first produced, chemists at Eli Lilly and other pharmacological companies were searching for a cephalosporin that would retain its potency when administered orally. The eighteen to twenty-two percent absorption rate of cephaloglycin permitted it to be administered orally, but its loss of ninety percent of its activity upon absorption prevented it from becoming a commercially effective oral antibiotic. Thus, industry chemists sought to synthesize a cephalosporin compound that would not lose so much of its activity upon absorption. 44 Eli Lilly chemists testified that they initially focused their attention on the substitution of the 3-methyl group for the side chain, but subsequently rejected this approach because the resulting compound displayed a markedly lower level of activity than cephaloglycin. As a result of the persistence of two chemists, Drs. Morin and Jackson, however, the Eli Lilly research group decided to renew experimentation using the 3-methyl group. The resulting compound-cephalexin-did not, as hoped for, retain a significantly high level of activity. Cephalexin did exhibit, however, the totally unexpected trait of one hundred percent absorption which made it the orally effective cephalosporin for which the chemists had been searching. This unexpected property therefore represented a substantial advancement over the prior art. 45 Under the circumstances, cephalexin may not reasonably be considered merely an obvious alteration of a previously known substance. At the time cephalexin was originally synthesized, the process of substituting a methyl group for the side chain occurring at the 3-position of a cephaloglycin nucleus was known and easily performable. It was not known, or expected by anyone other than Drs. Morin and Jackson, however, that this substitution would yield a compound that possessed the ultimate characteristic for which industry chemists were searching-that is, effectiveness as an oral antibiotic. Additionally, Drs. Morin and Jackson, who hoped that cephalexin would be such an antibiotic, expected that the salutary effects would occur as a result of the sustained activity of the new drug upon ingestion into the bloodstream. Even they did not consider, let alone anticipate, that cephalexin would be effective because of its one hundred percent absorption rate. Hence, the trait that made cephalexin the highly salutary drug that it is was neither expected by those skilled in the prior art nor anticipated by the chemists who synthesized it. 46 Section 103 authorizes the denial of patentability only if the subject matter as a whole was obvious in light of prior art, and provides that (p) atentability shall not be negatived by the manner in which the invention was made. 48 The manner of producing cephalexin was readily predictable and performable, and therefore concededly obvious. But the real advancement over the prior art-cephalexin's one hundred percent absorption rate-was totally unexpected, even by the chemists who proposed its synthesis. Hence, taking cephalexin as a whole, we conclude that it was a nonobvious advancement over the prior art. The lack of expectation or anticipation of the one hundred percent level of absorption, in our view, strongly indicates that the idea of creating the new compound required a creative insight. 49 47 This analysis is strengthened where, as here, the evidence demonstrates that previous attempts to synthesize a cephalosporin compound that performed satisfactorily as an oral antibiotic had exhibited a high degree of unpredictability. Chemists at Eli Lilly and other pharmaceutical companies had worked for years at refining the various cephalosporin compounds in order to obtain an effective oral antibiotic, but were stymied by the last step-finding a compound that would retain a sufficiently high combination of absorbability and activity upon absorption so that it could be produced in orally administerable doses. Against this background, the probability that the Eli Lilly breakthrough was unexpected or nonobvious in relation to the prior art is substantially enhanced. 50 Accordingly, we join our sister courts of appeals in holding that, in cases involving the patentability of chemical compounds, the determination of obviousness under § 103 should be based on a comparison of the structures of all properties possessed by the new compound and the prior art, including their respective structures, uses, and pharmacological traits. For this reason, we conclude that the district court did not err in considering cephalexin's one hundred percent absorption rate during the course of its determination that cephalexin was nonobvious in light of the prior art.