*3 result, glucose is unable cells, to enter the LOURIE, BRYSON, Before DYK, and thereby depriving the body of its main Circuit Judges. source energy. Type 2 diabetes is the common most form of diabetes—affecting Opinion the court by for filed Circuit over 90% of diabetic individuals. Judge Concurring LOURIE. opinion filed 1990s, a class of drugs known as by Circuit Judge DYK. (“TZDs”) thiazolidinediones intro- LOURIE, Circuit Judge. duced on the market as a treatment for Type 2 diabetes. Takeda Chemical Indus- Alphapharm Pty., and Genpharm, Ltd. tries, Ltd., and Takeda Pharmaceuticals Inc. (collectively “Alphapharm”) appeal America, North Inc. (collectively “Take- from the decision of the United States da”) first invented certain TZDs in the District Court for the Southern District of 1970s. Takeda’s research revealed that York, New following trial, a bench TZDs acted sensitizers, ie., insulin com- 4,687,777 U.S. Patent was not shown to be pounds that ameliorate insulin resistance. invalid § under U.S.C. 103. Takeda Although the function of TZDs was not Indus., Chem. Mylan Ltd. v. Labs., 417 completely understood, appeared TZDs (S.D.N.Y.2006). F.Supp.2d 341 Because glucose lower blood by levels binding to a we conclude that the district court did not molecule in the nucleus of the cell known err in determining that the claimed com- as PPARgamma, which activates insulin pounds would not have been obvious receptors and stimulates the production of light art, and hence that the glucose transporters. patent has not been invalid, shown be 348-49. The transporters we affirm. then travel to the cellular surface and en- glucose
able to enter the from cell BACKGROUND bloodstream. Id.
Diabetes is a disease that is character- Takeda developed the ACTOS®, drug by ized body’s inability to regulate which is used to control sugar blood sugar. blood It generally caused patients who suffer from Type diabetes. inadequate levels of. insulin—a hormone ACTOS® has enjoyed substantial commer- produced in pancreas. Insulin allows cial success since its launch in 1999. By used as practically can be market, pounds TZD 47% it held safety having a broad agents antidiabetic year exceeded $1.7 gross sales effect pharmacological margin between ingredient active Id. at 386. billion. unfavorable side reactions.” toxicity or compound piogli- TZD is the ACTOS® The asserted col.1 ll.34-37. tazone, 1, 2, and 5. Claim claims claims are suit. Claim 5 genus claims a (the 4,687,777 Patent con compositions owns U.S. pharmaceutical compounds. Those genus taining “Thiazolidinedione entitled patent”) “'777 follows: claims read as Derivatives, As Antidiabetic Useful *4 formula: compound A of the 1. to “com is directed Agents.” composition which An antidiabetic 5. acceptable salt pharmacologically aor essentially compound of a consists thereof. the formula: (C2 H5) drawn to pictorially stituent acceptable salt pharmacologically aor ring, indicates pyridyl thereof, pharma- with center of in association carrier, excipi- com possible acceptable covers four cologically the structure ethyl sub- viz., ent or diluent. an compounds with pounds, posi available at the four located stituent Id., 1 & 5. Takeda, 417 ring. pyridyl tions on critical appeal, purposes For includes The formula is the structure compound portion 4-ethyl compound, 3-ethyl compound, molecule, namely, the moiety of the left and 6- (pioglitazone), 5-ethyl compound ring.1 That ethyl-substituted pyridyl ethyl compound. structure, ethyl sub- has an chemical F.Supp.2d at 351. nitrogen.” carbon-con- Pyridine is a "six-membered 1. replaced by a taining ring with one carbon Claim 2 of the '777 patent covers the that is referenced in Table 1 of the '777 single compound pioglitazone. claim, patent That as compound b. The left moiety of which depends 1, from claim consists a pyridyl reads: ring with (CH3) a methyl group attached to the 6- A claimed in claim position ring. portion That of its wherein is 5-{4-[2- chemical structure is illustrated as follows: (5-ethyl-2-pyridyl)ethoxy] benzyl}- 2,4-thiazolidinedione.
'777 patent, claim 2. Pioglitazone is re-
ferred to 5-ethyl as the compound because CH2CH2— ethyl substituent is attached to the 5- position ring. portion That asserted the claimed depicted as: compounds would have been obvious over
compound b.
The district court found that Alphap- harm prove failed clear and convinc- *5 ing evidence that the asserted claims were invalid as obvious § under 35 U.S.C. 103. The court first concluded that there was no prior motivation to select Alphapharm, generic a drug manufac- compound b as the lead compound for turer, filed an Abbreviated Drug Ap- New research, antidiabetic and that prior (“ANDA”) plication pursuant to the art taught away from such, its use. As Hatch-Waxman Act seeking U.S. Food court concluded that Alphapharm failed to and Drug (“FDA”) Administration approv- make prima a facie case of obviousness. al § under 355(j) U.S.C. seq. et to man- The court continued analysis its and found ufacture and generic sell a of piog- version that even if Alphapharm succeeded in litazone. Alphapharm filed a Paragraph making a facie showing, Takeda IV certification with its ANDA pursuant to would still prevail any prima because facie § 505(j)(2)(B)(ii), asserting that the '777 case of obviousness was rebutted patent is invalid as obvious under 35 unexpected results pioglitazone’s of non- § U.S.C. In response, Takeda sued toxicity. The court then judg- rendered Alphapharm, along with three gener- other ment in favor of Takeda. The district ic drug manufacturers who sought also court also held that the '777 had FDA approval to generic market pioglita- not been procured though inequitable con- zone, alleging that the defendants have duct. That decision has been separately infringed or will infringe the '777 patent. appealed and has been affirmed ain deci- sion today. issued 17,
On January 2006, the district court Alphapharm timely appealed. haveWe commenced a bench trial solely on the jurisdiction pursuant 28 U.S.C. issues of validity and enforceability of the 1295(a)(1). § patent. '777 Alphapharm advanced its in- n validity argument, asserting that DISCUSSION would have been obvi- A. Standard Review ous at the time of the alleged invention. of Alphapharm’s obviousness contention rest- In this appeal, we presented are entirely ed on a prior art TZD issue, with one namely, whether the as- art, in prior of the scope and content patent- would serted prosecu- to include the particular, whether § 103 35 U.S.C. under been obvious have patent. Last- -history tion An was made. the invention the time numerous assigns error to ly, Alphapharm alia, “if inter patentable, is invention and cer- legal and factual determinations subject matter between the differences the court evidentiary rulings tain art are patented be sought to course of the trial. during made a whole subject matter as such at the time have been obvious would responds that the district having person to a was made invention correctly determined U.S.C. in the art.” ordinary skill convincing by clear and prove failed to 103(a). presumed is Because § are inval- the asserted claims evidence that evidentiary § valid, 35 U.S.C. be that there Takeda contends id as obvious. a conclu supporting to show facts burden presented at overwhelming evidence ac which rests invalidity, sion conclusion that support the court’s trial con one of clear and infringer, is cused art for existed in the no motivation v. Corp. AK Sollac Steel vincing evidence. art to select one (Fed.Cir. 1234, 1238-39 Ugine, 344 F.3d compound, & and even compound b as a lead 2003). invention an was, Whether unexpected that the results if there § U.S.C. under 35 toxicity obvious would have improved been pioglitazone’s novo, law, based de showing reviewed facie of obvi- “question any prima rebutted questions argues factual that all of underlying Takeda further upon ousness. following challenges to the remaining clear error Alphapharm’s reviewed for *6 Labs., rulings are Mylan legal and factual Corp. v. district court’s trial.” Alza bench (Fed.Cir.2006). merit. 1286, simply Inc., 1289 F.3d 464 without that the dis with Takeda agree We B. Obviousness concluding did not érr in trict court claims of the asserted argu three main Alphapharm raises The Su been would not have obvious. the its contention support in ments the issue recently addressed preme Court First, have been obvious. Co. v. in KSR International of obviousness court that the district asserts Alphapharm - -, Inc., 127 S.Ct. U.S. Teleflex law, law particularly misapplied the (2007). The 1727, Court L.Ed.2d 705 167 the context obviousness governing Co. v. Deere John stated that Graham compounds. chemical structurally similar 684, 15 86 S.Ct. City, 383 U.S. Kansas es Alphapharm, to record According an (1966), control factors still 545 L.Ed.2d most b was tablished 1) are: Those factors inquiry. obviousness pri antidiabetic effective 2) art”; prior and content “the scope failing art, by erred and thus the or art and between the “differences ordi that one of apply presumption to 3) claims”; ordinary skill “the level of been moti in the would have nary skill 4) art”; objective and pertinent compounds. to make the vated KSR, 127 of nonobviousness. evidence a conclusion that such Alphapharm asserts Graham, U.S. (quoting at 1734 383 S.Ct. law, including our by case mandated our 684). 17-18, S.Ct. 86 Dillon, F.2d In re banc decision in en opinion, (Fed.Cir.1990). Second, thorough In a well-reasoned was decided before KSR determining albeit erred in rendered that the court argues Court, the Supreme the district court We elaborated on requirement made findings extensive of fact and conclu- Deuel, case of In re 1552, 1558 51 F.3d sions of as to the four law Graham factors. (Fed.Cir.1995), where we stated that Alphapharm’s arguments challenge the “[n]ormally facie case of obvious court’s determinations respect with to cer- ness is based upon similarity, structural factors, tain of these which we now ad- ie., an established structural relationship dress. a prior between
claimed compound.” That is so because close or Between the established “[structural Prior Art relation Differences ships Claims may provide the requisite motivation or suggestion modify to known compounds a. Compound Selection to obtain compounds.” new Id. A known Compound Lead compound may suggest its homolog, ana Alphapharm’s argument first challenges log, or isomer because such the court’s regard determination with “often have similar properties and there the “differences- between art and fore chemists of ordinary skill would ordi the claims.” Alphapharm contends that narily contemplate making try them to the court erred as a matter of law obtain compounds with improved proper holding ethyl-substituted TZDs ties.” Id. clarified, We however, that were nonobvious in light of the closest order to find a prima facie case of unpa- prior art compound, by mis- tentability instances, in such a showing applying the law relating obviousness of “prior that the art would suggested chemical making specific molecular modifica necessary tions to achieve the claimed in
We disagree. Our case law concerning vention” was also required. Id. (citing In prima facie obviousness of structurally Jones, re 347 (Fed.Cir.1992); Dil similar is well-established. We lon, 688; Grabiak, 919 F.2d 729; 769 F.2d have held that similarity “structural be- Lalu, In re (Fed.Cir.1984)). F.2d 703 tween claimed and art subject mat- *7 ter, proved by combining references or That test prima facie obvious
otherwise, where the art gives reason ness for chemical compounds is or consistent motivation to make the compo- claimed with the legal sitions, principles enunciated in prima a creates facie case of obvi- KSR.2 While Dillon, the KSR rejected ousness.” Court F.2d at a 692. In rigid application of addition to the similarity teaching, structural sugges between tion, (“TSM”) or compounds, prima a motivation facie case in of obvi- test an obvi requires ousness ousness inquiry, also a showing of “ade- Court acknowledged quate in support art” importance for the of identifying “a reason change in Grabiak, structure. In re that would prompted have person a (Fed.Cir.1985), 731-32 ordinary skill in the relevant field to corn- 2. We Supreme mined, note that the Court in its KSR we consider that the did Court not in opinion referred to issue as reject whether KSR the standard statutory formulation subject claimed matter "was” or not” inquiry "was whether the subject claimed obvious. § Since U.S.C. 103 uses lan- matter "would have been obvious at the time guage obvious,” have "would been the invention made.” § was 35 U.S.C. Supreme Hence, Court KSR par- did consider the we will continue to statutory use the ticular time at which obviousness is . deter- “would have language. been” Thus, Alphap- discovery pioglitazone. way the claimed in the elements bine clearly de- argument harm’s obviousness de- in an obviousness does” invention new finding a that one pends preliminary on KSR, 127 S.Ct. termination. ordinary would have select- skill art there Moreover, that Court indicated compound. as a compound ed b lead inconsistency between necessary “no and the Grar test underlying the TSM idea found, however, that court The district the test is long as analysis.” Id. As ham not in the art would one of skill mandatory” “rigid as applied b as the lead com- compound have selected in- “helpful formula, provide can that test determination, the reaching pound. its inquiry. Id. to an obviousness sight” Pat- Takeda’s U.S. court first considered chemical com- new involving in cases (the 4,287,200 patent”), “'200 ent identify necessary to it remains pounds, 1, 1981, and its September was issued led a chemist have reason would some history. The court found prosecution particu- known in a compound modify a mil- hundreds of patent “discloses facie obvi- manner to establish compounds.”4 lar of TZD lions compound. specifically claimed of a new at 378. The ousness including fifty-four compounds, identified and the district with agree We synthesized accord- that were make that failed to Alphapharm described in the ing procedures, to the argues Alphapharm showing here. experimental but did not patent, disclose one of ordi- led prior art would have any of those com- or test results for data select nary in the art to history, howev- prosecution The pounds. By compound,” “lead compound. a lead er, specific for nine test disclosed results to a to refer Alphapharm understand we That compound b. compounds, including that would be to the examiner provided information im- modify in order to promising most to show rejection order response activity and antidiabetic upon its prove of the '200 activity.3 better with obtain to the known com- superior were antidia- compound for selecting that Upon in a cited refer- that were pounds research, asserts that betic court, however, nothing found ence. the art would ordinary skill in one history, to file pátent, in the '200 or its first, changes: two obvious chemical made ordinary skill in the one of suggest to ie., methyl replacing the homologation, the hun- out of compounds, nine that those ethyl group, which with an covered group of millions dreds *8 and 6-ethyl compound; per- in a were the best patent application, resulted have antidiabetics, and second, moving the eth- as forming compounds or “ring-walking,” im- to seek targets for modification position on hence to another substituent yl proved properties. Id. thereby leading to the ring, 5-position, derive from applications divisional dispute compound b 4. Three parties do not The 3. Thus, applications matured compound. patent. prior art Those the closest was 4,438,- 4,340,605, legal question whether or not U.S. Patent Patent into U.S. subject 4,444,779 (the have been obvi- matter would "'779 Patent and U.S. No. however, will, compound. We ous over Patent”). particular patent '779 is of The terminology com- Alphapharm’s of "lead use be- appeal and is discussed in this relevance deciding appeal opinion, pound” in this low. argued. it has been next considered an compound article b as “especially important,” the published following year was in court found that suggestion any to select al. T. Sodha et entitled “Studies essentially b was negated by the II. Agents. Synthesis Antidiabetic of 5- disclosure of the II Sodha reference. The [4-(l-Methylcyclohexylmethoxy)-benzyl- court reasoned that ordinary one of (ADD-3878) ]thiazolidine-2,4-dione and the art would not compound b, have chosen (“Sodha II”). Its Derivatives” The Sodha notwithstanding the statement in the '779 II reference data relating hy- patent prosecution history, “given the poglycemic activity plasma triglycer- and more exhaustive and reliable scientific ide lowering activity 101 TZD analysis com- presented II, by Sodha pounds. Those did not include taught away b, from compound pioglitazone, but included b. evidence from all of the TZD patents that Significantly, Sodha II identified three Takeda filed contemporaneously with the specific compounds that were deemed [pjatent '779 showing that there were most favorable in toxicity many terms and promising, broad avenues for further activity. Notably, compound b was not research.” Id. at 380. identified as one of the three most favor- The court found that the three com- compounds. able contrary, On the com- pounds that the Sodha II reference identi- pound b, singled causing out as “con- fied as “most favorable” “valuable for body siderable increases weight maturity-onset ' treatment of diabetes,”
brown fat weight.” not would have served as the
The court also Takeda’s considered “starting point best for further investiga- patent. patent That covers a subset of tion” person to a skill in the compounds originally included the '200 art. Id. at 376. Because diabetes is a patent application, namely, TZD com- chronic disease and thus require pounds “where the or thiazolyl long treatment, term the court reasoned groups may be substituted.” Id. at 353. that researchers would have been dissuad- The broadest claim of the '779 cov- ed selecting from a lead ers over one million Id. at effects, exhibited negative toxicity, such as 378. Compound specifically b was claimed or effects, other adverse side especially in claim patent. 4 of the The court noted one that causes “considerable increases that a preliminary pros- amendment body weight and fat weight.” brown Id. at history ecution contained a 376-77. the court determined that statement “the in which art did suggest to one of heterocyclic these rings are substituted ordinary skill in the art that compound b important, become especially [com- would be the best candidate as the lead pound b].” Id. compound for antidiabetic research. whole,
Based on the prior art as a how- Admissions from witnesses *9 ever, the court person found that a of further buttressed the court’s conclusion. ordinary skill in the art would not Rosenberg, have Dr. of Alphapharm’s head in- selected b as a lead compound property tellectual department, testified as for 30(b)(6) antidiabetic treatment. Although the a witness behalf of Alphap- on prosecution history of the '779 in- II, harm. In discussing Sodha Dr. Rosen- cluded the statement that berg characterized admitted that nothing there was particular a acid- covering certain claims that a would recommend that the article salt, directly supports position. its choose addition ordinary in the art of skill person compounds over other compound b disagree. recog- The KSR Court We efficacy rating. the same that had article design that there is a need “[w]hen nized com- acknowledging that Rosenberg, Dr. pressure problem or to solve a and market of negative side effects b had the pound identified, finite number of there are a fat, also and brown body weight increased solutions, ordinary predictable person of with such side that a admitted good pursue reason to the known skill has a suit- not” be “presumably would effects grasp.” his or her technical options within treatment of compound for able candidate KSR, 127 at 1732. In such circum- S.Ct. Alphapharm’s expert, II diabetes. Type stances, “the fact that a combination was at his in that view Mosberg, Dr. concurred might that it was try obvious to show that a medici- he admitted deposition when § 103.” Id. That is not the obvious under effects would find such side nal chemist identify predicta- Rather than case here. “undesirable.” treatment, for antidiabetic ble solutions 30(b)(6) of prior art disclosed a broad selection Moreover, Alphapharm another any which could have compounds one of witness, testified at his Barry Spencer, fur- art, as a lead for been selected reviewing prior that in deposition the clos- investigation. Significantly, ther in the art would have ordinary skill one compound (compound prior II est art in Sodha as three chosen research, 6-methyl) negative properties solely exhibited lead witness, addition, have directed one of Takeda’s that would In compound b. away compound. in the art from that Morton, So- that at the time Dr. testified Thus, present type this case fails to it was known published, II was dha contemplated by the Court when situation to insulin resistance obesity contributed may be deemed it that an invention one of ordi- stated Type diabetes. try.” The if it “obvious to concluded obvious art would have nary skill obvious to showed that it was not away from evidence taught II that Sodha try. it associated adverse compounds because compound b.
side effects with
Similarly, Alphapharm’s
reliance
Pfizer,
we held
fares no better.
asser
accept Alphapharm’s
do not
We
Pfizer
besylate
KSR,
covering
case
that certain
as well as another
tion that
court,
have been obvi-
amlodipine
Inc.
salt of
Pfizer,
recently decided
reference,
(Fed.Cir.
Inc.,
art included
ous.
Based on the record before we con tion, the court relied on Dr. Rosenberg’s clude that the district court’s fact-findings admission person that a skill in clearly were not erroneous and were sup the art would “look at a host of substitu- ported by evidence the record. More ents, chlorides, such as others, halides and over, reject we the assertion that court just methyls” modifying pyridyl failed to correctly apply relating the law to ring. Id. prima facie obviousness of chemical com Pioglitazone from compound differs b in
pounds. Because Alphapharm’s obvious
respects,
two
and one would have to both
argument
ness
entirely
rested
homologate the methyl group of
making
preliminary
finding that
pri-
b and move the resulting ethyl
or art
group
would have
to the
to
led
selection of
5-position
b as
on the
the lead
compound,
ring
order
pioglitazone.
failed to
obtain
assertion,
prove
regard
With
to ho-
the court did not commit
mologation,
reversible error
the court found
nothing
by failing
apply
a presumption
of moti
provide
expecta
reasonable
vation. We thus conclude that the court
tion
adding
methyl
to com
group
did not err in holding that Alphapharm pound b would reduce or
its tox
eliminate
n
failed to establish a prima facie case of
icity. Based o
the test
results
obviousness.
Lilly
See Eli
& Co. v. Zenith
numerous
disclosed in Sodha
(Fed.Cir.
Pharms.,
Goldline
b. Choice Compounds Claimed potency better than compound and one if Alphapharm Even had particular, estab compound 99, that lished preliminary finding, and we had no problems identified signifi- differed *11 skin, the isomer was the human whereas in structure. Id. compound b cantly from court held that “one who claims Moreover, toxic. The Mosberg Dr. n. 51. at 376 se, structurally compound, per a which is expert, Dr. Danish- Takeda’s agreed with a must rebut similar to activities of vari- biological efsky, that the presumed expectation that the struc- “unpredictable” were substituents ous compounds have similar turally similar II. at Id. disclosure of Sodha based on the recogniz- Id. at 460. While properties.” in nothing court also found 384-85. between the iso- ing that the difference to one suggest to patents '200 and '779 nontoxicity of the toxicity and the mer’s in that homolo- ordinary the art of skill compound “indi- homolog and claimed a ex- bring about reasonable gation would degree unpredictability,” of- some cate[d] of success. pectation failed to appellant the court found that the found that the court ring-walking, As for in single a actual difference “point out in the expectation there was no reasonable between the claimed properties of a substi- positions changing art that and thus failed to homologue,” in result ring a would tuent on Wilder, presumption. rebut Mosberg opined changes. Dr. beneficial at 460. ring-walking was process of note that since our Wilder would We Takeda, the court found to but “known” decision, general- cautioned “that we have support testimony inapt as it failed specif- ization should be avoided insofar expectation to one a reasonable alleged to be ic chemical structures are performing that chemi- in the art other,” facie obvious one from the prima a to be would cause change cal Grabiak, F.2d at 731. In addition toxic. Id. at 382. efficacious or less more caution, present case the facts Moreover, Mosberg relied on the effi- Dr. from the facts of Wil- significantly differ Sodha cacy phenyl data of Here, that pioglita- the court found der. II, insuffi- court found those data but the superior prop- unexpectedly zone exhibited would that the same effects cient to show compound b. erties over pyridyl compounds. occur The court Wilder, 563 relies on In re “Preliminary report entitled considered a (CCPA 1977), proposition for the F.2d 457 Ciglita- Toxicological Effects Studies on compound’s in a chemical that differences Rats” that Compounds zone-Related change resulting from a small properties, Dr. February presented was molecule, reasonably ex- made to the Scientist Fujita, then-Chief Takeshi thus are vary by degree and pected to Lab and co- Biology Research Takeda’s facie case insufficient to rebut report That patent. inventor of Wilder, predecessor our obviousness. toxicity preliminary results of contained holding that court affirmed the Board’s compounds, selected studies that involved was discovered compound, b. including pioglitazone and antidegradant to be useful as rubber to the to be “toxic Compound b was shown nontoxic to human liver, among also shown to be other erythrocytes, was heart and skin, light “com- pioglitazone have been obvious was things,” whereas no and “showed statisti- homolog potent” and isomer were paratively its toxicity.” Id. 356-57. cally significant showed art. The evidence months, per- following During homolog similarly nontoxic *12 toxicity formed fifty additional studies on moiety of a compound lead would create compounds already synthe- that had been compounds with the same properties as by Takeda, sized and researched including compounds art; of the it does not pioglitazone. were tested represent that toxicity lower would result. potency and toxicity. The results were And even if the statement so repre- did presented in another report by Fujita enti- sent, it does not any refer to specific sub- tled “Pharmacological and Toxicological any stituent specific position of TZD’s Ciglitazone Studies of and Analogues.” Its left moiety particularly as promising. As Pioglitazone was shown to be the only correctly noted, the court compound that toxicity, exhibited no al- included a though many of the other compounds were variety substituents, including al- lower found to potent. be more Id. at 358. kyls, halogens, hydroxyl groups, at- tached to a pyridyl or thiazolyl group. As court found there that was no discussed supra, the district court found reasonable expectation pioglitazone that that the claims encompassed over one mil- possess would property desirable lion compounds. Thus, disagree we with nontoxicity, particularly in light of the tox- Alphapharm that that statement provided icity of compound b. The court’s character- a reasonable expectation to one of ordinary ization of pioglitazone’s unexpected results skill in the performing specific clearly such, erroneous. As Wilder steps of replacing the methyl group of the does not Alphapharm because, aid unlike 6-methyl compound with an ethyl group, homolog claimed in Wil- and moving that substituent to 5-posi- der that shared similar' properties, pioglita- tion of the ring, would provided a zone was shown to differ significantly from safety margin, broad particularly in light compound b, of which it was not a homo- of the district court’s substantiated find- log, in terms of toxicity. Consequently, ings to contrary. any presumed rebutted expecta- tion that compound- pioglitazone b and We thus conclude that Alphapharm’s would similar properties. share challenges identify grounds fail to for re- versible error. The court properly consid- Alphapharm also points to a state teachings ered the of the art and ment Takeda made during prosecution made credibility regarding determinations as evidence that there the witnesses at trial. any We do not see was a expectation reasonable making error in the district court’s determination changes to region that one of ordinary skill in the art would b would to toxicity lead “better than the not have been prompted modify com- prior art.” During prosecution of the '779 pound using the steps of homologation patent, in response to an enablement re and ring-walking, synthesize jection, Takeda stated that “there should Because court’s be no reason case instant for the clearly conclusions are not erroneous and Examiner to doubt that the claimed com supported by evidence, the record we pounds having specified substituent find no basis disturb them. would function as a hypolipidemic and hy poglycemic agent specified in the in The court properly concluded-that Al- stant statement, disclosure.” That phapharm howev did not make out a facie er, only that changes indicates to the left case of Alphapharm obviousness because history upon which b tion relies to adduce evidence failed position com- of its support selected as the lead have been and, preliminary if that show- would have chosen even been as the lead com pound made, pound. it failed to show ing had been reason, *13 on what was history a based considering prosecution
there existed of the invention, the time of the patent, known at '779 the court noted that Takeda neces- the chemical modifications perform preliminary filed amendment on. March sary 15, 1983, to achieve the in which prosecuting attorney its stated that “the which these Alphap- that of our conclusion light heterocyclic rings are substituted have be that the claimed com- prove harm failed to important, especially 6-methyl come [the facie obvi- prima would have been pounds Alp compound].” rejected Id. The court ous, any objective we need not consider hapharm’s assertion that that statement indicia of nonobviousness.5 supported the conclusion that would have been selected as a lead com Scope and Content the Prior Art Rather, pound. the court found that view- whole, art ing prior prior as assigns also error to Alphapharm actively showed “that Takeda was conduct regard court’s determination district directions, ing many research in and had prior of the ing scope and content not narrowed its focus to b.” Id. the court art. asserts may while the district court history of the prosecution excluded the incorrectly implied prosecution have scope prior of the '779 from the public, histories are not accessible to the concluding that it was wrongly art after 59, see id. at n. see also Custom Accesso public. to the Takeda re not accessible Indus., ries, Jeffrey-Allan Inc. v. 807 clearly the court considered sponds (Fed.Cir.1986) (“[t]he person of ordi history, patent prosecution '779 nary hypothetical person is a who is on the first was admitted into evidence pertinent .be aware of all the presumed to testimony. urges that the day of art”), the court nonetheless consid prosecution court’s consideration of prosecution history ered the of the '779 on its extensive history apparent based analysis and ac patent in its obviousness analysis of the '779 and the file weight the statements proper corded history appears opin in the court’s Thus, any contained therein. error com ion. by regard mitted the court in this agree with Takeda that the district We harmless error. court did not err its consideration of Alphapharm’s re- We considered art. As discussed scope and find none that above, maining arguments prosecu- the court considered the court’s de- expressly warrant reversal of district history, tion and even considered cision. key prosecu- one of the statements obviousness, concurrence, agreeing and hence while that the case of
5. The facie question of the "overbreadth” of claims 1 and likely invalid obvious. claims 1 and 5 waived, further that the 6- 5 has been states point Since waiver is sufficient to answer ethyl compound, scope which is within the raised, being no further comment need be 5, possess claims 1 and has not been shown to concerning made its substance. unexpected results sufficient to overcome CONCLUSION claim a subset of that range. Applica See tion Petering, 993, 49 C.C.P.A. 301 F.2d We affirm the district determina- court’s (1962) 676, (species patentable found 1, 2, tion and 5 of the that claims genus when claimed in prior art because patent have not been shown to have been unexpected properties species were and hence invalid. obvious shown); Pfizer, also see Inc. v. Apotex, Inc., 1348, (Fed.Cir.2007) 480 F.3d AFFIRMED (relying on unexpected lack of results determining species claim was obvious Concurring opinion filed Circuit view genus claim); In re Judge DYK. (Fed.Cir. Woodruff, 919 F.2d *14 1990) (when applicant claims a of a subset DYK, Judge, concurring. Circuit range in a prior patent, art the applicant must generally show that “the join I opinion the of the court insofar as range claimed unexpected achieves results upholds it the judgment district court prior relative to the art range”). based on a determination a claim (the pioglitazone 5-ethyl compound) would While 5-ethyl the compound (pioglita- be the prior non-obvious over art. The zone) is scope the pat- within of the '200 problem only is that one ent, of three evidence, there clear is majority as the .the claims involved here—claim finds, 2—is limited correctly of unexpected re- results view, my garding In pioglitazone. compound, the breadth and therefore its claims, validity question is not in ground. of the other two claims of this and 5 However, at (“'777 argument oral 4,867,777 the patentee patent”)— U.S. Patent No. prior admitted that the art also also referenced in judgment- generically 6-ethyl covers the compound, likely renders them invalid. which is scope within the of claims and 5 All of claimed claims patent, of the '777 and admitted that there 1, 2 generic and 5 were included in claims is no of unexpected evidence for results prior 4,287,200 art U.S. Patent No. the 6-ethyl compound. Under such cir- (“'200 patent”). Unfortunately our law cumstances, I believe that 6-ethyl is concerning when a species patentable is obvious, likely and consequently genus over a claimed art is likely and 5 are invalid for obviousness. is, course, less It than clear. of well estab However, argument as to the over- genus lished that a claim to a does not breadth waived, of claims and 5 has been necessarily render invalid a claim later to a because was not it raised in opening species genus. within that See Lilly any event, Eli & brief. In matter, a practical Wash., v. Regents judgment Co. Bd. finding Univ. that the appellants’ (Fed.Cir.2003). 1264, 1270 filing my pioglitazone is an of. ANDA infringement be, a'species barring making view should patentable over pioglitazone supported by genus finding only if unex that claim 2 standing alone is not invalid pected results have been established. Our infringed. and is case law recognizes the vital importance results, a finding of unexpected both in closely context and related con
text where a discloses
numerical range patentee seeks to