Inherent Anticipation in the Pharmaceuticaland Biotechnology Industries

Michael Goldman, Georgia Evans, and Andrew Zappia

LeClairRyan, A Professional Corporation, Rochester, New York 14625

Correspondence: andrew.zappia@leclairryan.com

Pharmaceutical and biotech research often involves discovering new properties of, or newmethods to use, existing compositions. The doctrine of inherent anticipation, however, pre-vents the issuance and/or validity of a patent for discoveries deemed to have been implicitlydisclosed in the prior art. This can be a barrier to patent rights in these technologies. Inherentanticipation therefore creates uncertainty for patent protection in the pharmaceutical andbiotech sciences. Despite this uncertainty, Federal Circuit jurisprudence provides guidanceon the boundaries of the inherent anticipation doctrine. In view of the case law, certainstrategies may be employed to protect inventions that may potentially be viewed as inherentin the prior art.

It is a fundamental principle of patent law thatto obtain a valid patent, the invention claimed

must be novel and nonobvious over the existingart. Generally, to be novelty-destroying, a priorart reference must disclose all the features of theclaimed invention. Explicit disclosure, however,is not always required. The doctrine of inherentanticipation may preclude the issuance of a pat-ent or serve to invalidate a previously issuedpatent, despite the lack of a reference that ex-plicitly discloses each and every limitation of theclaim at issue. The Federal Circuit, the federalappeals court with exclusive jurisdiction overpatent issues, has summarized this doctrine asfollows:

Humans lit fires for thousands of years beforerealizing that oxygen is necessary to create andmaintain a flame. The first person to discover thenecessity of oxygen certainly could not have ob-tained a valid patent claim for “a method of

making fire by lighting a flame in the presenceof oxygen.” Even if prior art on lighting fires didnot disclose the importance of oxygen and oneof ordinary skill in the art did not know aboutthe importance of oxygen, understanding thislaw of nature would not give the discoverer aright to exclude others from practicing the priorart of making fires (EMI Group North America,Inc. v. Cypress Semiconductor Corp. (268 F.3d1342) (Fed. Cir. 2001)).

Not all cases of inherent anticipation are asstraightforward as the hypothetical example ad-vanced by the Federal Circuit above. In fact, in-herent anticipation creates a level of uncertaintyon where the line is to be drawn between a pat-entably distinct limitation and an inherent char-acteristic of a claimed invention. This issue isparticularly prevalent in patents related to phar-maceutical and biotech technologies. In that re-gard, the courts as well as the U.S. Patent and

Editors: Salim Mamajiwalla and Rochelle Seide

Additional Perspectives on Intellectual Property in Molecular Medicine available at www.perspectivesinmedicine.org

Copyright # 2015 Cold Spring Harbor Laboratory Press; all rights reserved; doi: 10.1101/cshperspect.a021006

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Trademark Office (USPTO) have provided guid-ance on the scope and application of the inher-ent anticipation doctrine. This guidance raisesparticular issues of interest with respect to phar-maceutical and biotech inventions, as discussedin detail below.

STANDARD FOR INHERENTANTICIPATION

The express, implicit, and inherent disclosures ofa prior art reference may be relied on in the re-jection or invalidation of patent claims under35 U.S.C. §§ 102 (anticipation) and 103 (ob-viousness) (U.S. Patent and Trademark Office2007) (Manual of Patent Examining Procedure[MPEP]). Thus, prior art references must be an-alyzed with respect to both their express andinherent teachings. The basis for the inherentanticipation doctrine has been repeatedly reiter-ated by the Federal Circuit, noting that the dis-covery of a previously unappreciated property ofa prior art composition, or of a scientific expla-nation for the prior art’s functioning, does notrender the old composition patentably new tothe discoverer (see, e.g., Atlas Powder Co. v. Ireco,Inc. (190 F.3d 1342, 1347, 51 U.S.P.Q.2d 1943,1947) (Fed. Cir. 1999)).

Inherency arguments are most often en-countered for anticipation pursuant to 35U.S.C. §102; however, the inherent disclosure ofa combination of references can also be used un-der 35 U.S.C. §103, which requires that a claimedinvention be nonobvious.1 This is because theinherent teaching of a reference is a question offact, which may arise under both 35 U.S.C. §§102 and 103 (In re Grasselli (713 F.2d 731, 739,218 U.S.P.Q. 769, 775) (Fed. Cir. 1983)). More-over, the Federal Circuit has held that it is properfor the USPTO to make separate rejections under35 U.S.C. §§ 102 and 103 or concurrent rejec-tions for obviousness under 35 U.S.C. §103 andfor anticipation by inherency under 35 U.S.C.

§102 (In re Best (562 F.2d 1252, 195 U.S.P.Q.420) (C.C.P.A. 1977)).

An inherent feature need not be recognizedby one of ordinary skill in the art at the timeof the invention (Schering Corp. v. GenevaPharmaceuticals, Inc. (339 F.3d 1373, 1377, 67U.S.P.Q.2d 1664, 1668) (Fed. Cir. 2003)). As setforth by the Federal Circuit, “[a]n inherentstructure, composition, or function is not nec-essarily known” (Atlas Powder Co. v. Ireco, Inc.(190 F.3d at 1348–1349, 51 U.S.P.Q.2d at 1947)(Fed. Cir. 1999)). It is only required that thesubject matter is, in fact, inherent in the priorart reference (Schering Corp. v. Geneva Pharma-ceuticals, Inc.).2

To establish inherency, the missing des-criptive matter must necessarily be present inthe thing described in the reference (Continen-tal Can Co. USA, Inc. v. Monsanto Co. (948 F.2d1264, 1268, 20 U.S.P.Q.2d 1746, 1749) (Fed. Cir.1991), quoting In re Oelrich (666 F.2d 578, 581,212 U.S.P.Q. 323, 326) (C.C.P.A. 1981)). Inher-ency may not be established by probabilities orpossibilities.3 Moreover, the mere fact that a cer-tain thing may result from a given set of circum-stances is not sufficient.4

Defendants in patent cases or the USPTOrely on inherency arguments to challenge patent

1Examples of cases discussing inherency rejections under 35U.S.C. §103 include In re Zurko (258 F.3d 1379, 59U.S.P.Q.2d 1693) (Fed. Cir. 2001); In re Napier (55 F.3d610, 34 U.S.P.Q.2d 1782) (Fed. Cir. 1995); and In re Grasseli(713 F.2d 731, 218 U.S.P.Q. 769) (Fed. Cir. 1983).

2Some ambiguity arises with older Federal Circuit cases thatmake general statements regarding a reference being deemedto anticipate a subsequent claim if the missing element isnecessarily present in the thing described in the reference,and that it would be so recognized by persons of ordinaryskill. These cases often cite Continental Can Co. USA,Inc. v. Monsanto Co. (948 F.2d 1264, 20 U.S.P.Q.2d 1746)(Fed. Cir. 1991) for this proposition. However, the issue ofthe requirement of contemporary knowledge was specifi-cally addressed in Schering Corp., in which the Federal Cir-cuit stated that Continental Can did not require past recog-nition of the inherent feature, but only allowed recourse toopinions of skilled artisans to determine the scope of theprior art reference (Schering Corp. (339 F.3d at 1378, 67U.S.P.Q.2d at 1667–1668)). But see EMI Group North Amer-ica, Inc. v. Cypress Semiconductor Corp. (268 F.3d 1342, 60U.S.P.Q.2d 1423) (Fed. Cir. 2001) and Rosco, Inc. v. MirrorLite Co. (304 F.3d 1373, 64 U.S.P.Q.2d 1676) (Fed. Cir. 2002)(rejection under 35 U.S.C. §102(g), requiring corroboratedevidence that the accused infringer recognized and appreci-ated the varying radius feature).3948 F.2d at 1268, 20 U.S.P.Q.2d at 1749 (quoting In reOelrich (666 F.2d 578, 581, 212 U.S.P.Q. 323, 326)(C.C.P.A. 1981)).4948 F.2d at 1268, 20 U.S.P.Q.2d at 1749.

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claims when a relevant prior art reference con-tains an incomplete description of the subjectmatter at issue. For example, the prior art mayinclude a description of a claimed invention butmay be missing a certain element. The conceptof inherency is used to supply the element miss-ing from the description, and inherency canoperate to anticipate entire inventions as wellas single limitations within an invention (Scher-ing Corp. v. Geneva Pharmaceuticals, Inc. (339F.3d at 1380, 67 U.S.P.Q.2d at 1669) (Fed. Cir.2003)). The extent of the inherent disclosuredoes not limit its anticipatory effect.5 In otherwords, a single limitation or the entire inven-tion can be inherent in a prior art reference.However, the concept of “inherent disclosure”does not alter the requirement that all elementsmust be disclosed in an anticipatory reference inthe same way as they are arranged or combinedin the claim (Therasense, Inc. v. Becton, Dickin-son & Co. (593 F.3d 1325, 1332, 93 U.S.P.Q.2d1481, 1485) (Fed. Cir. 2010)).

Also, an invitation to investigate is not aninherent disclosure (Metabolite Laboratories,Inc. v. Laboratory Corp. of America Holdings(370 F.3d 1354, 1367, 71 U.S.P.Q.2d 1081,1091) (Fed. Cir. 2004)). For example, the priorart disclosure of a genus, such as a genus ofcompounds or a genus of potential applications,does not inherently disclose all species withinthat broad genus.6 Rather, one must examinethe prior art to see if a disclosure of the claimedspecies has been made. However, the disclosureof a pattern of preferences in the prior art, whichdirects one of ordinary skill in the art to theclaimed invention, may support an inherencyargument (see, e.g., Sanofi-Synthelabo v. Apotex,Inc. (470 F.3d 1368, 81 U.S.P.Q.2d 1097) (Fed.Cir. 2006) [distinguishing older United StatesCourt of Customs and Patent Appeals caseswhere a pattern of preferences was found]).

Inherency arguments arise in a number ofsituations. One common type of inherency is-sue arises when a composition, product, or ap-paratus is claimed in terms of a property or

characteristic or function. If the prior art teach-es an identical chemical structure, a party mayargue that the claimed characteristic or func-tion is necessarily disclosed (In re Spada (911F.2d 705, 709, 15 U.S.P.Q.2d 1655, 1658) (Fed.Cir. 1990)). Moreover, if product and apparatusclaims are substantially identical to prior artproducts or produced by substantially identicalprocesses, parties can argue that the claimedproperties or functions should be presumed tobe inherent.7 In other words, where a compo-sition is claimed in terms of a function, prop-erty, or characteristic and the composition is inthe prior art, but the function or property orcharacteristic is not explicitly disclosed, theremay be grounds for an inherency argument un-der 35 U.S.C. §§ 102 and 103.8 This same ratio-nale applies to product, apparatus, and processclaims claimed in terms of function, property,or characteristic.

Another claim type susceptible to inherencyarguments is a process claim using a knowndevice. If a prior art device in its normal andusual operation would necessarily perform theclaimed method, then the method is arguablyinherently anticipated by the prior art device (Inre King (801 F.2d 1324, 1326, 231 U.S.P.Q. 136,138) (Fed. Cir. 1986)). Yet another claim typesusceptible to inherency arguments is a “meth-od of use” claim where the “use” is directed to aresult or property of a known composition orstructure. For example, in In re May (574 F.2d1082, 197 U.S.P.Q. 601) (C.C.P.A. 1978), theUnited States Court of Customs and Patent Ap-peals held that a method of effecting nonad-dictive analgesia was inherently anticipated bya prior art disclosure of the same compoundsfor effecting analgesia, but silent as to addic-tion.9 The court stated that applicants hadmerely found a new property of the compoundand that this discovery did not constitute a new

5339 F.3d at 1380, 67 U.S.P.Q.2d at 1669.6370 F.3d at 1367, 71 U.S.P.Q.2d at 1091.

7MPEP §2112.01; In re Best (562 F.2d 1252, 1255, 195U.S.P.Q. 430, 433) (C.C.P.A. 1977); In re Schreiber (128F.3d 1473, 1478, 44 U.S.P.Q.2d 1429, 1432) (Fed. Cir.1997) (conical shape of spout for oil can in the prior art isthe “same general shape” as the claimed conical top fordispensing popcorn).8MPEP §2112(III).9574 F.2d at 1090, 197 U.S.P.Q. at 607.

Inherent Anticipation in Pharma and Biotech

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use.10 However, the court reversed the rejectionof claims directed to a process of using a newcompound, relying on evidence showing thatthe nonaddictive property of the new com-pound was unexpected.11

CURRENT PHARMACEUTICAL/BIOTECHCASE LAW RELATING TO INHERENCY

Numerous cases have analyzed inherent anti-cipation related to inventions involving phar-maceutical and biotech applications. The caseshave dealt with both inherent properties of com-positions as well as inherent uses of particularcompounds or methods. Several recent deci-sions related to these inherent anticipation is-sues regarding pharmaceutical and biotechtechnologies are discussed below.

Inherent Properties

A patent may be deemed anticipated if a prior artreference teaches a composition with the sameproperties. The properties themselves, how-ever, are not required to be disclosed in orderfor inherent anticipation to apply. There are nu-merous cases dealing with inherent propertiesof pharmaceuticals and biotech technologies.

In SmithKline Beecham Corp. v. Apotex Corp.(403 F.3d 1331, 74 U.S.P.Q.2d 1398) (Fed. Cir.2005), for example, the technology related toparoxetine, which is used to treat depression.The original form of paroxetine was anhydrousparoxetine hydrochloride (PHC). The patentat issue, assigned to SmithKline, covered crys-talline paroxetine hydrochloride hemihydrate(Paxilw), a new and more stable crystallineform of PHC.

The case arose out of an Abbreviated NewDrug Application (ANDA) by Apotex for anantidepressant including PHC anhydrate asan active ingredient. In response, SmithKlinefiled an infringement action alleging that Apo-tex would infringe claim 1 of its patent, directedto crystalline paroxetine HCl hemihydrate,

by manufacturing PHC anhydrate that neces-sarily contains, by a conversion process, at leasttrace amounts of PHC hemihydrate.12 The dis-trict court interpreted the claim to require thePHC hemihydrate in commercially significantamounts and found the claim valid but notinfringed.13

The Federal Circuit rejected the districtcourt’s claim interpretation and held that theclaim covered PHC hemihydrate without fur-ther limitation.14 As a factual matter, the courtheld that PHC anhydrate made in accordancewith a cited prior art patent converts into at leasttrace amounts of PHC hemihydrate.15 However,based on this claim interpretation and factualfinding, the Federal Circuit found the claim in-herently anticipated by the earlier patent to themethod of making PHC anhydrate.16 The courtheld that Apotex did not need to prove that itwas impossible to make PHC anhydrate thatcontained no PHC hemihydrate, but merelythat the disclosure of the prior art was sufficientto show that the natural result flowing fromthe operation as taught would result in theclaimed product.17 Whether it was actually pos-sible to make pure PHC anhydrate before thecritical date was held to be irrelevant.18 Rather,the court stated that the prior art suffices as ananticipatory prior art reference if it discloses inan enabling manner the production of PHChemihydrate.19 Moreover, the court emphasizedthat the first known existence of PHC hemihy-drate resulted from an attempt to produce PHCanhydrate according to the prior art method.20

Similarly, in Schering Corp. v. Geneva Phar-maceuticals, Inc. (339 F.3d 1373, 67 U.S.P.Q.2d1664) (Fed. Cir. 2003), the Federal Circuit ap-

10574 F.2d at 1090, 197 U.S.P.Q. at 607.11574 F.2d at 1090, 197 U.S.P.Q. at 608–610.

12403 F.3d at 1334–1335, 74 U.S.P.Q.2d at 1400. SmithKlineput forth a rather complex argument regarding PHC anhy-drate morphing into the hemihydrate and the general envi-ronment then being seeded with hemihydrate crystals.13403 F.3d at 1335, 74 U.S.P.Q.2d at 1400.14403 F.3d at 1339, 74 U.S.P.Q.2d at 1403.15403 F.3d at 1338, 74 U.S.P.Q.2d at 1402–1403.16403 F.3d at 1343, 74 U.S.P.Q.2d at 1406.17403 F.3d at 1343, 74 U.S.P.Q.2d at 1406.18403 F.3d at 1344, 74 U.S.P.Q.2d at 1406.19403 F.3d at 1344, 74 U.S.P.Q.2d at 1406.20403 F.3d at 1344, 74 U.S.P.Q.2d at 1407.

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plied the inherent anticipation doctrine to inval-idate a patent based on the formation of a me-tabolite as anticipated based on prior art disclo-sure of administering the base compound. Thetechnology at issue related to the antihistamineloratadine (Claritinw). The patent involvedin this case, which was assigned to ScheringCorporation, covered a metabolite of loratadinecalled descarboethoxy-loratadine (DCL), itsfluorine analog, and their salts.21 Schering Cor-poration also owned a patent covering a class ofcompounds including loratadine itself, whichwas prior art to the DCL patent. This prior artpatent did not expressly disclose DCL and didnot refer to metabolites of loratadine.22

This case arose after Geneva Pharmaceuti-cals, Inc. and others sought to market genericversions of loratadine, alleging invalidity ofSchering’s DCL patent. Schering filed suit forinfringement. The district court found that theclaims covered DCL in all of its forms, includingforms metabolized in the human body.23 How-ever, the district court found that Schering’s pri-or patent for loratadine inherently anticipatedthe metabolite claim.24

A Federal Circuit panel affirmed. In partic-ular, the court held that the prior art referenceshowing administration of loratadine to a pa-tient inherently anticipated claims to a metab-olite. At the outset the court specifically rejectedthe contention that inherent anticipation re-quires recognition in the prior art.25 Rather,the court held that recognition by a person ofordinary skill in the art before the critical dateof the patent at issue was not required to showanticipation by inherency.26 In addition, thecourt distinguished cases dealing with “acci-dental, unwitting, and unappreciated” anticipa-tion, stating that DCL is not formed accidental-ly or under unusual conditions when loratadineis ingested.27

Moreover, the Federal Circuit found inher-ent anticipation even though the prior art pat-ent did not expressly disclose the claimed me-tabolite or refer to metabolites of loratadine.The Federal Circuit held that the inherent dis-closure of the entire claimed subject matteranticipates as well as inherent disclosure of asingle feature of the claimed subject matter.28

Further, the court noted that, in contrast to Inre Seaborg (328 F.2d 996, 51 C.C.P.A. 1109)(C.C.P.A. 1964), in which the prior art processproduced at most one-billionth of a gram of theclaimed isotope in 40 tons of radioactive mate-rial, in this case DCL formed in readily detect-able amounts upon ingestion of loratadine.29

The Federal Circuit also held that antic-ipation does not require the actual creation orreduction to practice of the prior art subjectmatter (i.e., it was irrelevant if actual adminis-tration of loratadine to patients occurred beforethe critical date of the patent at issue).30 All thatwas required for the prior art patent to suffice asan anticipatory prior art reference was an en-abling disclosure.31

Another Federal Circuit decision made clearthat statements made by the prior art inventoror owner regarding the inherent disclosure in itsprior art may be used to establish inherency. InAstra Aktiebolag v. Andrx Pharmaceuticals, Inc.(In re Omeprazole Patent Litigation) (483 F.3d1364) (Fed. Cir. 2007), the technology at issuerelated to omeprazole (Prilosecw). Omeprazoleis a proton pump inhibitor that inhibits gas-tric acid production. However, omeprazole de-grades in acidic and neutral environments.Therefore, an omeprazole formulation needs aprotective coating to prevent contact with gas-tric juices. The patent at issue, assigned to Astra,covered a process for preparing an oral pharma-ceutical formulation including a protective en-teric coating around a core containing a protonpump inhibitor and an active alkaline reactingcompound and a separating layer between the21339 F.3d at 1375–1376, 67 U.S.P.Q.2d at 1665–1666.

22339 F.3d at 1376, 67 U.S.P.Q.2d at 1666.23339 F.3d at 1376, 67 U.S.P.Q.2d at 1666.24339 F.3d at 1376, 67 U.S.P.Q.2d at 1666–1667.25339 F.3d at 1377, 67 U.S.P.Q.2d at 1667.26339 F.3d at 1377, 67 U.S.P.Q.2d at 1667.27339 F.3d at 1378, 67 U.S.P.Q.2d at 1668.

28339 F.3d at 1379, 67 U.S.P.Q.2d at 1668.29339 F.3d at 1379, 67 U.S.P.Q.2d at 1669.30339 F.3d at 1380, 67 U.S.P.Q.2d at 1670.31339 F.3d at 1380, 67 U.S.P.Q.2d at 1670.

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core and coating. In particular, the process in-volved creating an in situ separating layer in thegastric acid–inhibiting drug.

This case arose out of an attempt by Andrxto market a generic version of Prilosecw. Thedistrict court found the claims of Astra’s patentinfringed, but inherently anticipated by or ob-vious over a published Korean patent applica-tion by Chong Kun Dan Corporation (CKD).32

CKD’s Korean patent application described anomeprazole composition with no enteric coat-ing process conditions.33 Moreover, the CKDapplication expressly disavowed the presenceof a separating layer.34

On appeal, Astra argued that its patent con-tained an additional limitation requiring per-formance of the claimed process at a tempera-ture below 42˚C.35 In response, the FederalCircuit noted that the 42˚C “limitation” wasonly an example from the specification andheld that reliance on a nonclaimed distinctionwas inappropriate.36 Moreover, the court notedthat the specification suggested variable tem-peratures, not a 42˚C requirement.37

In addition, Astra argued that prior art didnot disclose “forming in situ a separatinglayer.”38 However, the Federal Circuit relied onstatements made by Astra in a Korean litigationregarding another Astra patent39 that the pro-cess in the CKD application resulted in the insitu formation of a separating layer.40 “DespiteCKD’s denials, [Astra] realized and explainedthat CKD’s OMP tablet’s formation of a sepa-rating layer was a natural result flowing from thecombination of certain ingredients listed. . . .”41

Moreover, the court noted that Astra neitherdenied the statements made in the Korean liti-gation nor provided scientific proof to rebutor refute its prior admissions of inherency.42

Relying on the fact that the record showed for-mation of the in situ separating layer in the priorart even though that process was not recognizedat the time, the Federal Circuit held that the trialcourt correctly found inherent anticipation.43

Intended Use

The Federal Circuit has also rejected claims un-der inherent anticipation where the claims re-late to a method of use directed to a knownproperty.

In King Pharmaceuticals, Inc. v. Eon Labs,Inc. (616 F.3d 1267, 95 U.S.P.Q.2d 1833) (Fed.Cir. 2010), the technology at issue relatedto metaxalone, which is a muscle relaxant thatis used to treat musculoskeletal conditions.Metaxalone was first discovered in the 1960s.There were two patents assigned to King Phar-maceuticals, Inc. at issue in this case. The pat-ents covered methods of increasing the bioavail-ability of metaxalone. The first patent requiredthe administration of an oral dosage form ofmetaxalone with food. In the specification ofthe patent, administration with food was shownto increase both the rate and extent of absorp-tion. The second patent required a step of in-forming a patient that taking metaxalone withfood increases the bioavailability of the drug.44

In certain independent claims the informingstep was recited as a method step, and in cer-tain claims, including one independent claim,a container provided information that ad-ministration of metaxalone with food increasesthe drug’s bioavailability. Certain independent

32483 F.3d at 1367, 1371, and 1373–1374.33483 F.3d at 1370.34483 F.3d at 1370.35483 F.3d at 1371.36483 F.3d at 1372.37483 F.3d at 1372.38483 F.3d at 1371.39The Korean litigation arose with regard to a Korean pro-cess patent that was a sister to Astra’s U.S. Patent No.4,786,505, which required a separate application of a sub-coating (i.e., separating layer).40483 F.3d at 1372–1373.41483 F.3d at 1373.

42483 F.3d at 1372. Astra specifically stated in the Koreanlitigation that the method of the CKD application formeda separating layer and that such formation is inherent in theprocess.43483 F.3d at 1373.44One dependent claim of the first patent also included an“informing” limitation, and one dependent claim of the firstpatent required a container with printed labeling advisingthat taking metaxalone with food increases the drug’s bio-availability.

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claims also required administering/ingestingmetaxalone.

This case arose out of an ANDA by EonLabs, Inc. alleging noninfringement and inval-idity of King’s patents. In response to theANDA, King filed suit against Eon alleging in-fringement of King’s two patents. Before thedistrict court, Eon presented six references toinvalidate King’s patents, three of which wererelied on by the district court and disclosed ad-ministration of metaxalone with food to reducegastric upset or nausea. The district court foundthe independent claims of the first patent in-herently anticipated by the three prior art ref-erences and stated that “an increase in thebioavailability of metaxalone is inherent whenthe drug is taken with food.”45 The dependentclaims were also found anticipated or obvious.The district court found the independent claimsof the second patent invalid under 35 U.S.C.§101 (the requirement for patentable subjectmatter), stating that the “informing” limitationwas not patentable under In re Bilski (545 F.3d943, 88 U.S.P.Q.2d 1385) (Fed. Cir. 2008) (af-firmed sub nom., Bilski v. Kappos (130 S. Ct.3218, 177 L. Ed. 2d 792) (2010); (616 F.3d at1273, 95 U.S.P.Q.2d at 1837)), and, for the in-dependent claim requiring a container provid-ing information regarding bioavailability, thisclaim was held to be anticipated (inclusion ofwritten material with a known compound didnot make the claim patentably distinct from theprior art).46

On appeal, King argued that the prior artdisclosure was vague as to the conditions underwhich the food was administered, such thatthe court could not assume that an increase inbioavailability was necessarily disclosed.47 Incontrast to the cited prior art, King’s writtendescription included specific conditions forfood consumption. The Federal Circuit heldthat reliance on a nonclaimed distinction wasinappropriate.48 The court also noted that the

written description did not suggest that the spe-cific food conditions were necessary for increas-ing bioavailability.49 Rather, the court held that,according to the first patent, the natural resultof taking metaxalone with food is an increasein the bioavailability of the drug.50 The courtemphasized that the only steps taught in King’sfirst patent as required to increase metaxalone’sbioavailability were (1) ingesting metaxalone(2) with food.51 The court dismissed testimo-ny of King’s expert that disclosure of takingmetaxalone with food would not inherentlydisclose increasing bioavailability, stating thatthe prior art need only meet the inherently dis-closed limitation to the extent the patentedmethod does.52 The Federal Circuit also heldthat the dependent claims reciting time framesfor ingesting metaxalone and food were anti-cipated.53

With regard to the claims requiring an in-forming step, the Federal Circuit held that al-though the district court erred when focusingsolely on the “informing” limitation in inval-idating the claims under 35 U.S.C. §101, ad-dition of the informing limitation “adds nonovelty to the method, which is otherwise an-ticipated by the prior art.”54 Accordingly, theseclaims were found invalid under the alterna-tive ground that the claims were anticipated bythe prior art. In particular, the court notedthat the informing limitation was not func-tionally related to the otherwise anticipatedmethod.55

The Federal Circuit also applied inherentanticipation to a method of treatment in Perri-cone v. Medicis Pharmaceutical Corporation (432F.3d 1368, 77 U.S.P.Q.2d 1321) (Fed. Cir. 2005).There, the technology related to methods of

45616 F.3d at 1272, 95 U.S.P.Q.2d at 1837.46616 F.3d at 1273, 95 U.S.P.Q.2d at 1837.47616 F.3d at 1274, 95 U.S.P.Q.2d at 1838–1839.48616 F.3d at 1275, 95 U.S.P.Q.2d at 1839.

49616 F.3d at 1275, 95 U.S.P.Q.2d at 1839.50616 F.3d at 1275, 95 U.S.P.Q.2d at 1839.51616 F.3d at 1276, 95 U.S.P.Q.2d at 1840.52616 F.3d at 1276, 95 U.S.P.Q.2d at 1840.53616 F.3d at 1276–1277, 95 U.S.P.Q.2d at 1840–1841.54616 F.3d at 1278, 95 U.S.P.Q.2d at 1842. The Federal Cir-cuit analogized these claims to the “printed matter” series ofcases, where it has recognized that printed matter is notindependently patentable (citations omitted).55616 F.3d at 1279, 95 U.S.P.Q.2d at 1842.

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treating or preventing sun damage through top-ical application of ascorbic acid (vitamin C) in afat-soluble form. The two patents at issue cov-ered methods of treating or preventing sunburnand methods of treating skin damage or disor-ders. Specifically, the patents disclosed the top-ical application of ascorbyl fatty acid ester (e.g.,ascorbyl palmitate, ascorbyl laurate, ascorbylmyristate, and ascorbyl stearate) with a derma-tologically acceptable carrier.56

Dr. Perricone sued Medicis for infringe-ment of two patents based on a line of skindepigmenters made by Medicis. Certain claimsof Perricone’s second patent were found invalidby the district court for nonstatutory obvious-ness-type double patenting over Perricone’s firstpatent.57 The district court also found the in-dependent claims, as well as certain dependentclaims, of Perricone’s patents inherently antici-pated by a prior art patent disclosing a cosmeticcomposition for topical applications.58 The pri-or art patent disclosed skin benefit ingredients,including ascorbyl palmitate.59 In addition, theprior art patent identified the disclosed compo-sitions as suitable for topical application to theskin or hair.60

On appeal, the district court’s finding ofinvalidity for nonstatutory obviousness-typedouble patenting over Perricone’s first patentwas affirmed.61 With regard to anticipation,Perricone argued that the prior art’s disclosedskin benefit ingredients included ascorbyl pal-mitate among many others, so the prior art didnot anticipate the specific claimed use of as-corbyl palmitate.62 Further, Perricone arguedthat the prior art did not disclose any benefitdirected to skin sunburn.63

The Federal Circuit held that the prior artdid not merely disclose a genus of skin benefitingredients without disclosing the particular

claimed ingredient.64 In contrast, ascorbyl pal-mitate was specifically identified in a list of 14skin benefit ingredients.65 Moreover, the courtdistinguished cases in which a broad genus wasdisclosed without reference to the specific po-tentially anticipating species.66 Accordingly, theFederal Circuit found claims to methods oftreatment or prevention including applying to“exposed skin surfaces” or “affected skin/tissueareas” inherently anticipated.67

However, the Federal Circuit held that aclaim to a method for treating skin sunburnincluding topically applying to the skin sunburnwas not inherently anticipated.68 The court heldthat skin sunburn is not analogous to skin sur-faces generally.69 Because the prior art was silentabout any sunburn prevention or treatmentbenefits, not to mention the mechanisms un-derlying such uses, the court held that the priorart did not anticipate Perricone’s claim to amethod for treating sunburn.70 Moreover, thecourt did not take the position that a particularprevention method necessarily anticipates atreatment method, as proposed in the dissent.71

The court stated that such a prior art preven-tion method may render subsequent treatmentclaims obvious; however, these were unrealizedpossibilities that did not alter the analysis in thiscase, where the prior art did not disclose topicalapplication to skin sunburn.72

The Federal Circuit recently extended theinherent anticipation doctrine to a method oftreatment based on a reference disclosing a planfor a clinical trial that had not yet been carriedout by the effective filing date of the patent. In Inre Montgomery (677 F.3d 1375, 102 U.S.P.Q.2d1881) (Fed. Cir. 2012), the technology related to

56432 F.3d at 1371, 77 U.S.P.Q.2d at 1322.57432 F.3d at 1372–1375, 77 U.S.P.Q.2d at 1323–1325.58432 F.3d at 1376, 77 U.S.P.Q.2d at 1326.59432 F.3d at 1376, 77 U.S.P.Q.2d at 1326.60432 F.3d at 1376, 77 U.S.P.Q.2d at 1326.61432 F.3d at 1372–1375, 77 U.S.P.Q.2d at 1323–1325.62432 F.3d at 1376, 77 U.S.P.Q.2d at 1326.63432 F.3d at 1376, 77 U.S.P.Q.2d at 1326.

64432 F.3d at 1377, 77 U.S.P.Q.2d at 1326.65432 F.3d at 1376, 77 U.S.P.Q.2d at 1326. The court char-acterized this list as a “handful of different compositions.”432 F.3d at 1377, 77 U.S.P.Q.2d at 1326.66432 F.3d at 1376–1377, 77 U.S.P.Q.2d at 1326.67432 F.3d at 1379–1380, 77 U.S.P.Q.2d at 1328–1329.68432 F.3d at 1378–1379, 77 U.S.P.Q.2d at 1328.69432 F.3d at 1379, 77 U.S.P.Q.2d at 1328.70432 F.3d at 1379, 77 U.S.P.Q.2d at 1328.71432 F.3d at 1379, 77 U.S.P.Q.2d at 1328.72432 F.3d at 1379, 77 U.S.P.Q.2d at 1328.

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a method for treatment or prevention of strokesby administering an inhibitor of the renin–an-giotensin system (RAS). The specification notedthat RAS inhibitors had been administered totreat high blood pressure.73 In particular, themethod involved administering the knownRAS inhibitor ramipril.74

The case arose from a decision of the Boardof Patent Appeals and Interferences (BPAI) af-firming the USPTO’s rejection of the claims.75

The USPTO rejected the claims as anticipatedby four prior art references describing the ad-ministration of ramipril to subjects at risk of astroke.76 On appeal, the patentee argued thatnone of the references demonstrated that ra-mipril actually treated or prevented strokes. TheBPAI affirmed the USPTO’s rejections by each ofthe prior art references, determining that eachreference taught administration of ramipril tostroke-prone patients, and that treating or pre-venting stroke was an inherent characteristicbased on the use described in the prior art.77

The Federal Circuit, in a 2–1 panel decision,affirmed the rejection of the claims based onone of the cited references.78 The cited referencedisclosed a clinical trial of utilizing ramipril inthe prevention of myocardial infraction, stroke,or cardiovascular death.79 The study, which ul-timately concluded that administering ramiprilto such patients provided a statistically signifi-cant reduction in the risk of stroke, was notpublished until after the effective filing date ofthe patent at issue.80 The Federal Circuit indi-cated that the contested elements of the claimincluded the administration of ramipril (1) to apatient diagnosed as in need of stroke treatmentor prevention, (2) where such administration isfor the treatment and prevention of stroke or itsreoccurrence.81 The Federal Circuit determined

that even if the recited claims required an effi-cacy requirement, the cited reference anticipat-ed the claims despite the lack of testing results atthe effective filing date as efficacy was inherentin carrying out the steps of the claims.82 TheFederal Circuit therefore disregarded the paten-tee’s argument that inherent anticipation re-quired the claimed method to have been actu-ally performed.83 Thus, a prior art reference thatdiscloses a claimed method can serve to inher-ently anticipate a claim even if the method wasnot carried out in the prior art reference.

PROSECUTION STRATEGIES FORPREVENTING AND RESPONDINGTO INHERENCY REJECTIONS

The USPTO must provide objective evidenceand/or technical reasoning to reasonably sup-port the determination that the allegedly in-herent characteristic necessarily flows from theteachings of the prior art.84 An additional ref-erence or evidence can be used to show an in-herent characteristic of the thing taught by theprimary reference. This can still be an anti-cipation rejection. Once the USPTO has provid-ed objective evidence and/or technical reason-ing, the burden shifts to the applicant to arguethat the inference of lack of novelty was notproperly drawn or show that the prior art andthe claimed invention are different (MPEP§2112(V); In re Spada (911 F.2d at 708, 15U.S.P.Q.2d at 1657) (Fed. Cir. 1990)).

Based on the foregoing, a number of prac-tical considerations for avoiding and respond-ing to inherency rejections can be identified. Forexample, in King Pharmaceuticals, Inc. v. EonLabs, Inc. (616 F.3d 1267, 95 U.S.P.Q.2d 1833)(Fed. Cir. 2010), specific administration condi-tions giving rise to increased bioavailabilityof metaxalone were disclosed in the patent atissue. Similarly, in the In re Omeprazole PatentLitigation, specific process conditions were dis-closed in the patent giving rise to an in situ

73677 F.3d at 1376.74677 F.3d at 1377.75677 F.3d at 1376.76677 F.3d at 1377.77677 F.3d at 1378–1379.78677 F.3d at 1383.79677 F.3d at 1378.80677 F.3d at 1378.81677 F.3d at 1380.

82677 F.3d at 1381.83677 F.3d at 1382.84MPEP §2112(IV); Ex parte Levy (17 U.S.P.Q.2d 1461,1464) (B.P.A.I. 1990).

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separating layer in the gastric acid–inhibitingdrug (Astra Aktiebolag v. Andrx Pharmaceuticals,Inc.). Although the patent holderstried to relyonthese administration/process conditions, theywere unsuccessful, because these conditionswere not recited as limitations in the claims. Ac-cordingly, addition of claim limitations or de-pendent claims setting forth specific reaction/process conditions giving rise to the claimedimprovements, as well as frequency of use or ex-tent of use limitations, may be useful in over-coming or preventing such inherency rejections.

In addition, for a claim covering a new useof a known compound, identification of thesubject of the use by distinct properties can re-move a claim from the scope of the prior art, asshown in Perricone v. Medicis PharmaceuticalCorporation.

As illustrated in King Pharmaceuticals, Inc.v. Eon Labs, Inc., notification limitations shouldbe avoided as the source of distinction over theprior art. Such limitations are given no weightwhere they are not functionally related to theotherwise anticipated method (i.e., where theydo not transform the claimed method).

One technique for distinguishing claims di-rected to a compound or composition over pri-or art in order to overcome an inherency rejec-tion is to recite specific purity limitations andclaim as an isolated form. In Schering Corp. (339F.3d at 1381, 67 U.S.P.Q.2d at 1670), the FederalCircuit explicitly stated that a patentee may ob-tain patent protection for an inherently antici-pated compound through proper claiming. Thecourt further suggested claiming the metaboliteat issue in its pure and isolated form or as apharmaceutical composition.85 In addition, thecourt suggested claiming a method of adminis-tering the metabolite or the correspondingpharmaceutical composition.86

As set forth in Schering Corp., there are aseries of cases relating to accidental, unintend-ed, and unappreciated disclosures (see, e.g., Ei-bel Process Co. v. Minnesota & Ontario Paper Co.(261 U.S. 45, 43 S. Ct. 322) (1923) and Tilgh-

man v. Proctor (102 U.S. 707) (1880) (Chisum2011). These cases hold that results obtainedunder unusual conditions or accidental resultsthat are not intended and not appreciated donot constitute anticipation. Similarly, occa-sional results are not inherent (Mehl/BiophileInt’l. Corp. v. Milgraum (192 F.3d 1362, 1365,52 U.S.P.Q.2d 1303, 1305) (Fed. Cir. 1999); seealso In re Rijckaert (9 F.3d 1531, 1534, 28U.S.P.Q.2d 1955, 1957) (1993) (optimal condi-tions not disclosed explicitly or implicitly donot constitute an inherent disclosure)). Accord-ingly, aligning the facts of your case with thesecases relating to accidental anticipation or oc-casional results may be useful in arguing againstan inherency rejection.

As described above, the disclosure of a pat-tern of preferences in the prior art that directsone of ordinary skill in the art to the claimedinvention may lead to an inherency rejection(Sanofi-Synthelabo v. Apotex, Inc. (470 F.3d at1376, 81 U.S.P.Q.2d at 1102)). However, broadgeneric disclosures that do not specificallydisclose the claimed species and that do notprovide specific preferences for narrowing thegenus do not properly form a basis for an in-herency rejection. This argument is particularlyrelevant where the art is unpredictable and apattern of preferences leading to a narrow classof compounds including the claimed com-pound is lacking.

Once the USPTO makes a prima facie caseof inherency, providing evidence of structuraldifferences, compositional differences, or pro-cess differences may be the response most likelyto result in a successful outcome. The USPTOwill likely cite In re Best (562 F.2d 1252, 1255,195 U.S.P.Q. 430, 433) (C.C.P.A. 1977) for theproposition that where the claimed and priorart products are identical or substantially iden-tical, or are produced by identical or substan-tially identical processes, the USPTO can re-quire an applicant to prove that the prior artproducts do not necessarily or inherently pos-sess the characteristics of the claimed product.Although such comparative evidence may, attimes, be costly and time-consuming to pre-pare, it is most likely to lead to a successful resultin response to an inherency rejection.

85339 F.3d at 1381, 67 U.S.P.Q.2d at 1670.86339 F.3d at 1381, 67 U.S.P.Q.2d at 1670.

M. Goldman et al.

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CONCLUSION

As shown in the above discussion, considera-tion of inherent anticipation issues is criticalwhen attempting to obtain or address enforce-ment of a patent on pharmaceutical or biotechtechnologies. Focusing claims on truly novelaspects and keeping in mind the approach ofthe courts and the USPTO on inherency issueswill aid any effort to ensure a claimed inventionis protectable.

ACKNOWLEDGMENTS

The authors would like to thank Tate Tischner,Esq., Amanda Keys, Esq., and Bryan Smith, Esq.for their assistance with this review.

REFERENCES

Chisum DS. 2011. Chisum on patents, Part 1, §3.03. MatthewBender, New York.

U.S. Patent and Trademark Office (USPTO). 2007. Manualof patent examining procedure (MPEP), §2112.

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