Allergan, Inc. v. Apotex Inc.

INC., ALLERGAN, Duke

University, Plaintiffs-

Appellees,

v. Sandoz, INC., Apotex Corp.,

APOTEX Co.,

Inc., Pharmacal and Hi-Tech Defendants-Appellants.

Inc., University, Inc.,

Allergan, and Duke

Plaintiffs-Appellees, Inc., Pharmaceuticals, now

Watson Actavis, Inc., Labo Watson

known as Pharma,

ratories, and Watson

Inc., Defendants-Appellants. 2013-1245, 2013-1246,

Nos.

2013-1247, 2013-1249. Appeals, Court of

United States Circuit.

Federal 10, 2014.

June En Banc

Rehearing Rehearing Sept.

Denied Pharmaceuticals, Inc.,

Watson al. et Of T. counsel were Luke Shannon Har- Deshield, Rakoczy ven V. Mazzochi Molino LLP, Chicago, Siwik IL. PROST,*

Before Chief Judge, REYNA CHEN, Judges. Circuit Opinion for court filed Chief Judge Opinion part PROST. dissenting by Judge filed Circuit CHEN. PROST, Judge.. Chief Inc., Apotex Sandoz, Inc., Apotex Corp., Co., Inc., Actavis, Hit-Tech Pharmacal Inc., Laboratories, Inc., Watson and Wat- Pharma, (collectively son Inc. “appellants”) appeal judgment from a final of the U.S. District Court for the Middle District of North Carolina that appellants had infringed 7,388,- claims of U.S. Patent Nos. (“'029 (“'404 7,351,404 patent”) and patent”) they and had failed to establish Singer, Jonathan E. Fish & Richardson invalid. were For reasons stated be- P.C., MN, Minneapolis, argued of for low, we the district findings reverse court’s him on the plaintiffs-appellees. With brief validity respect with to the of each Reichel; were Deanna J. and Juanita R. Brooks, Diego, of San CA. Of counsel was Background Gibson, Thomas, Jeffrey T. Dunn & (“Aller- Plaintiff-appellee Allergan, Inc. Crutcher, LLP, Irvine, of CA. has and gan”) Drug U.S. Food Administra- Mazzochi, Rakoczy M. Deanne Molino (FDA) Latisse®, approval tion to sell a LLP, IL, Chicago, Mazzochi Siwik of ar- solution, bimatoprost ophthalmic 0.03% gued defendants-appellants Apotex for topical solution to treat hypotrichosis Inc., et al. With her on the brief were (i.e., reduction) eyelash- hair of loss Rakoczy, Molino, William A. Paul J. and by hair stimulating growth. es Alul, Inc., al; Apotex Andrew for et M. Filarski, Addy, synthetic Bimatoprost prostaglandin Meredith Martin Thomas (“PGF”) Helms, F-2-alpha and C. & Steptoe analog. Prostaglan- Brandon Johnson LLP, IL, Inc.; Chicago, occurring of for are naturally Sandoz Ste- dins molecules Co., Roth, ven Hi-Tech Pharmacal on the of receptors bind surface cells. NY, Vetter, Amityville, and prostaglandins recep- Thomas J. Lu- bind to a cell’s When tors, Mercanti, LLP, York, NY, they signals change cas & generate New Co., Inc.; functions, way for example, by Hi-Tech Pharmacal and that the cell for Hood, Gary Robyn controlling E. H. Ast Mark T. cell Because PC, Chicago, ability Deming, prostaglandins Polsinelli IL for to control cell * position Judge May Sharon assumed the of Chief on 2014. Prost targets optical approv- received FDA solution also they significant

properties, treatment, glaucoma variety in a al for use research pharmaceutical type prosta- marketed particular is a continues be as Xalatan®. areas. PGF FP receptor. with the that binds Dr. Johnstone observed in the course glandin glaucoma patients latanop- of treating naturally oc- structure The chemical eyedrops, rost a substantial fraction of illustrated below: curring PGF eye- grew longer them much denser lash hair. Dr. Johnstone filed on application latanoprost the use of 17-phenyl promote other PGF February to the The work that led by appel- of the two asserted patents first case, in this was conducted re- lees & led Dr. searchers Proctor Gamble “cyclopentane The structure includes Dr. DeLong. DeLong Mitchell his atoms, which illustrated ring” carbon range a team studied the effects of wide at the pentagonal above as structure the in prostaglandin compounds mice. In the the chains of atoms diagram. left of Two they of their course studies observed top ring. the The chain is are attached to administration compounds of PGF chain,” and chain “alpha called the FP receptor were selective for the resulted “omega it is chain.” below called in hair. growth longer and thicker On mid-1980s, By the it was established 21, 2000, DeLong March Dr. and others allevi- naturally occurring PGF could provisional application on patent filed (IOP), pressure ate intraocular which is topical application that bind glaucoma. eye disease associated with receptors FP to treat hair loss. The To effective treatment and min- develop an patent priority provi- '029 claims to this effects, on imize scientists worked side application. During prosecution, sional in de- synthesizing testing more selective 2003, parent application '029 particular A analogs rivatives and of PGF. patent assigned University, to Duke ana- analog, 17-phenyl kind of PGF PGF 17, issued on June 2008. in the logs, proved particularly to be useful glaucoma. Bimatoprost treatment of by appellees The second asserted analog, synthetic 17-phenyl one such PGF this suit is the '404 which is in the course of emerged research assigned Allergan. to The 2001, by Allergan Allergan scientists. during from arises observations made approval Lumigan®, received FDA to sell Lumigan®. trials had clinical for As been bimatoprost ophthalmic a 0.03% solution- pa- for latanoprost, glaucoma observed eyedrop an identical to Latisse®—as bimatoprost eyedrops tients treated with glaucoma, treat mar- which it continues to spontaneously grew longer ey- and thicker ket. elash hair. See patent col.ll 11.5-62. The '404 covers the treatment of Hair another area loss treatment was eyelash through applica- hair topical loss proved which certain PGF useful. 1990s, bimatoprost, priority tion of claims Murray per- In the Dr. filed on Febru- latanoprost, provisional application formed on another studies 4, analog. Latanoprost ary kind of 17-phenyl (collec University ordinary meaning as understood

Allergan per and Duke appel each of the art. tively “appellees”) Phillips sued son of skill v. 271(e)(2)(A) (Fed.Cir. 1303, § after Corp., lants under 35 U.S.C. AWH 2005) (en banc). Drug Abbreviated New they exception submitted There is an (ANDAs) FDA seeking to the Applications general patentee this rule when sets out generic Allergan’s to market a version of a definition lexicographer. and acts as her own product. Appellees Latisse® asserted Sony Computer rner Entm’t Tho 1, 8, 14, 18, and 20 of the '029 Am., LLC, (Fed.Cir. claims claim 14 of the '404 patent and 2012). After a bench trial the consolidated Appellants single raise a claim construc- action, the district court Hatch-Waxman appeal concerning tion issue on held, aha, inter that the asserted claims of patent. The '029 asserted claims patents the '029 and '404 invalid are directed towards a of “treating method obviousness, insufficient anticipation, Appellants challenge hair loss.” the dis- enablement, description, written or lack of trict court’s construction of this term as and, moreover, infringed. that appellants “ loss, loss, ‘arresting hair reversing hair 1:10-CV-681,

Allergan, Apotex, Inc. v. Nos. promoting or both and hair growth’ mean- V-650, 1:11-CV-298, 1:11-C loss, ing may that the invention arrest hair (M.D.N.C. 2013). at *1 Jan. WL loss, promote reverse hair subsequently enjoined court district parties, the alternative.” All as well as appellants, along any persons with or enti court, agreed specifi- the district that the privity appellants ties who are in or to provides express cation definition for ANDA, whom transfer the from appellants “ ‘Treating the term: hair loss’ includes manufacture, use, commercial offer to sell loss, arresting reversing hair loss or hair proposed products sale of the until and/or both, promoting growth.” or hair '029 and expiration the latest of the dates of the Appellants argue, col.3 11.29-30. patents. Allergan, '029 and '404 Inc. v. however, conjunctive that use of the “and” Inc., No. Permanent Apotex, 1:10-CV-681 lexicography the inventor’s own ex- 2-3, Inj. and Final J. ECF No. 231. pressly provides that the method for treat- followed, appeal appellees This in which ing hair loss both arrest or reverse must raise issues of claim construction for the loss, promote hair hair as well as also invalidity '029 as well as the of the growth. Appellants argue that under their and '404 pat- asserted claims construction, proposed generic version of jurisdiction ents. have under 28 We infringe Latisse® La- would because 1295(a)(1). § U.S.C. by lengthening, tisse® treats hair loss thickening, darkening existing healthy Discussion appellants argue hair—which means hair promotion growth. I. Claim Construction agreed appel- Claim construction is an issue of The district court with the Lighting law we review de novo. lees that the use of the word “includes” Philips “treating plainly Ballast Control LLC v. Elecs. N. the definition of hair loss” (Fed. 1272, 1276-77, Corp., patentee Am. 744 F.3d means that the intended to define Cir.2014) (en banc); Cybor Corp. treating possibility v. FAS hair loss to include the Techs., (Fed. loss, arresting hair 1454-55 of one or all of revers- Cir.1998) (en banc). loss, construing ing promoting growth. In a claim hair or hair term, plain Appellees argue comports we look at the term’s this loss,” of a va presumption “treating hair meaning of plain § 282 can be rebut lidity under 35 U.S.C. in the art as understood

which would be convincing evidence. Mi ted clear and exclusively pro- including treatments — P’ship, Ltd. U.S. Corp. compellingly, Most mote hair i4i crosoft 2238, 2245-46, -, 180 L.Ed.2d 131 S.Ct. may ambiguity be some if there even (2011). does proof The standard of term, numer- defined the patentee how the fall with the facts of each not “rise and in the describe examples ous particular, Id. at 2250. case.” to “induce hair compositions claimed use of previously con a reference eyelashes,” “[w]hether and thicken growth,” “darken PTO, proof the burden of sidered “promote eye- growth,” hair “promote convincing evidence of See, the same: clear and at cols. e.g., growth.” lash 11.61-62, Lupin Pharma Inc. v. 43-44, invalidity.” Sciele 11.17-19, 59 11. (Fed.Cir. Ltd., 1253, 1259-61 11.31-32, nothing 60 11.11-12.There sug- or the claims specification either the 2012). ex- patentee that the would have

gesting patent, appel- to the '029 respect With examples scope from the cluded these allegedly anticipatory refer- lants raise two claimed methods. (i) patent application published ences: Dr. aforemen- arising from Johnstone’s lexi Reading patentee’s own promoting growth hair tioned research on light specifica of the whole cography compounds, and related using latanoprost tion, that a method of “treat we conclude (ii) Allergan’s earlier on the use may include a method of ing hair loss” and related hair without also arrest promoting each refer- glaucoma. treat We discuss Accordingly, ing reversing loss. ence in turn. the district court’s construction. we affirm Application a. Johnstone PCT Invalidity II. filing Dr. research led to the Johnstone’s A. '029 Patent Application International Patent No. (“Johnstone”) on Febru- PCT/US98/02289 Anticipation 1. 3, dis- ary particular, Johnstone anticipa A invalid stimulating closes methods for single § 1021 if a tion under 35 U.S.C. genus prostaglandin ana- using a broad each and ev prior art reference discloses that, an logs among properties, other have ery limitation of the claimed invention. following structure alpha chain with Pharm., Schering Corp. v. 339 Geneva 11.16-22): (see at 16 Johnstone (Fed.Cir.2003). 1373, single A 1377 F.3d may prior anticipate art reference without of the claimed inven

disclosing feature necessarily present,

tion if such feature is inherent, art of the '029 includes in that reference. Id. Antici The cited or Johnstone, 6,262,105 to of fact that we review U.S. Patent No. pation question Ireco, its disclosure with the John- Atlas Powder which shares for clear error. Co. (Fed.Cir.1999). Inc., 1342, application. The Johnstone 1346 stone PCT ("AIA”), case were filed before that Act Pub.L. ents at issue in this 1. The America Invents 16, date, 112-29, pre-AIA September we refer to the versions took effect on No. pat- §§ applications for the 102 and 103. 2012. Because the application during PCT was also raised the would not have been thought to have a therapeutic prosecution patent. Following effect because it would not se allowance, lectively FP receptor. issue of the initial notice of bind Aller 286251, gan, 2013 at patentee filed an amendment to add a WL *5. The district supported court further proviso independent claims with the aim its determination by citing to the '029 expressly excluding compounds dis- notice of allowance, in which the examiner The indicated closed Johnstone. J.A. 4130-37. Johnstone “lacks modify motivation to accepted examiner the amendment and is- prostaglandins taught therein in order to sued a notice of allowance for the presently obtain the prostaglan- claimed with the claims amended to include the Id.; dins.” J.A. 5559-65 at 5564. The provisos. found, therefore, district court Appellants argue that Johnstone antici- disclosure on which appellants rely does above, As illustrated pates nevertheless. “clearly unequivocally disclose” expressly Johnstone discloses PGF struc- the use of compounds with the saturated chain alpha tures which the includes a 286251, bond. Allergan, 2013 WL at *6 (also “unsaturated”) double known as bond (citing MoneyIN, Net Inc. v. VeriSign, position, at the C5-C6 shown as a doubled Inc., (Fed.Cir.2008)). 545 F.3d diagram. provisos line the above expressly within the '029 claim exclude persuaded light We are that in Appellants such structure. contend that very disclosure, limited the court did so, goes even on to also disclose not commit Appellants clear error. (also single with a known as correct that where a disclosure was writ “saturated”) position: bond at the C5-C6 ten provide optional ingredient, preferably “The chain could be a structure, step, we have held C6-C10 chain can be saturated or unsatu- optional component anticipates. still See rated, bonds, having one or more double Labs., Pamlab, Upsher-Smith Inc. v. alienes, triple L.L.C., (Fed.Cir. or a bond.” Johnstone 1320-21 added). (emphasis 2005) (“[A] 11.22-24 As a composition that ‘op disclosure, result of this additional in ap- tionally ingredient includes’ an anticipates view, pellants’ Johnstone also teaches a a claim for the same composition that ex saturated, single, or bond at the C5-C6 pressly that ingredient.”); excludes Bris position, which would not be Labs., excluded tol-Myers Squibb Co. v. Ben Venue provisos consequently (Fed.Cir.2001) reads on the independent claims of the '029 (“[A]nticipation require does not actual performance suggestions of in the disclo Johnstone, however, contains no other sure.”). Indeed, even if the reference dis single, disclosure of a structure with a option closes the within the context of a saturated, bond at that location. All of the that “disparages” reference or “teaches examples of Johnstone are drawn to com- away,” we not in do consider those issues positions in which a the C5-C6 bond is anticipation analysis. the context of an double bond. The district court moreover Upsher-Smith, 412 F.3d at 1323. agreed with appellees and found that art, erroneous, person clearly the context of the state of the The court not was however, of ordinary skill would not read Johnstone in its determination that in this case, disclosing single as bond sparse structure. The the disclosure was too accepted district court appellees’ ambiguous evidence of skill to that a analog comprehend PGF with such a structure Johnstone’s disclosure as an- at reported eyelash growth. Id. MoneyIN, eyedrops patent. '029 Net

ticipating 5855-71). 525-33, Accordingly, (citing we affirm. J.A. 545 F.3d at moreover, includes as '404 Patent b. '819 the administration of enabling example its by eyedrop study pa- in a bimatoprost (“'819 5,688,819 patent”) Patent No. U.S. As col.10 1.38-col.l2 1.3. patent tients. '404 by Allergan scien emerged from research such, link recites direct specification that could PGF tists on selective eyedrop administration and the between pat glaucoma. The '819 effectively treat “the topical application: directed to claims of a set of selective the use ent discloses eye drops” re- course of treatment which analogs, including bimatoprost, PGF gathering in the lid sults in excess fluid by its chemical specifically identified area, wiped gets in turn once to “the col. 7 11.44-46.The patent '819 structure. adjacent skin of the lid area.” Id. col.10 hair not refer to '819 does argue that if the '819 Appellants 11.51-56. loss, treating hair nor does disclose or eyedrop a method of ad- patent discloses Ap topical application compounds. that suffi- bimatoprost ministration of (i) however, argue, that because pellants pat- cient to enable the claims of the '404 patent’s disclosure teaches ent, inherently then that method must also com eyedrops containing application anticipate. scope within the of the asserted pounds claims, particular bimatop- rejected appellants’ court The district (ii) rost, eyedrops application that arguments. The district court found in the containing bimatoprost results witness, Noecker, appellees’ expert Dr. eyelashes, the method growth of disclosed that a persuasively “properly had testified inherently anticipates not applied drop” would transfer 286251, at *6. Allergan, skin. 2013 WL promoting At is whether issue additionally court found that The district growth through topical application of bima- Lumigan® clinical trials showed that necessarily present toprost on the skin is eyelash patients experience a fraction of applying eye- in the method of or inherent Id. The district court found containing bimatoprost.2 Schering, drops only may bimatoprost eyedrop because a dispute at 1377. There is no skin, contact does not in application eyedrops containing bi- inherency herently anticipate “may matoprost promotion can result by probabilities possibili be established description eyelash Allergan’s hair. own Indus., (citing ties.” Id. Bettcher Inc. v. conception (Fed. USA, Bunzl first observed that after scientists Cir.2011)). monkeys were treated with Appellants argue enhanced that the district court eyes, their some them showed (citing erroneously required certainty pre- as a eyelash growth. Appellees’ Br.13 5624). 396-98, 5617-29, requisite anticipation. re- for inherent J.A. Similar trials, view, court should not during sults were found clinical their the district finding only relied on the that some patients bimatoprost which some who used have ticipated by patent's disclosure of 2. all claims of the '029 the '819 Not asserted Appellants topical application, systemic administration. do not are limited to and irre- issue, event, appellees spective narrow raise this and in answer to this more 14, may inherently which is so limited. question, those claims be an- assert claim

961 patent, the claims of the '029 eyedrops experi- anticipate received patients who and we affirm.3 eyelash growth. enced that inherent an- are correct Appellants 2. Obviousness based on a trace can be found ticipation that a example, we have held amount. For Appellants alternatively allege process produces that chemical aforementioned that the references render inherently compound “trace” amounts of obvious asserted claims the '029 compound. SmithKline anticipates A patent. patent is invalid for obviousness F.3d Corp. Apotex Corp., v. 403 Beecham subject “if the differences between the (Fed.Cir.2005). 1331, All that needs 1344 sought patented prior matter to be and the that the outcome of the to be shown is subject art are such that the matter as a flowing a “natural result from process be have been obvious at the time whole would prior in the art.” taught as operation a person having the invention was made to Oelrich, 578, F.2d (citing In re 666 581 Id. ordinary in the art to which said skill 1981)). (CCPA that a We have also held subject matter pertains.” 35 U.S.C. inherently anticipated product would be 103(a). § conclu legal Obviousness is prior where it was a natural result underlying sion based on facts. Graham process, possible art even when it would be Co., 1, 17, v. John Deere 383 U.S. 86 S.Ct. prevent product the formation of the (1966). 684, 15 L.Ed.2d 545 through “extraordinary measures.” Atlas Powder, trial, appeal 190 F.3d at 1349. On from a bench of fact underlying findings we review the court’s find We review the district error, for clear and we review de novo the anticipation for ings of fact on inherent legal court’s ultimate conclusion of wheth case, court clear error. In this the district er the claimed invention would have been to ad possible found that it was at least obvious. Novo Nordisk v. Caraco A/S way in a as to reduce eyedrops minister Labs., Ltd., 1346, Pharm. 1354 eye to the to close to liquid the flow (Fed.Cir.2013). Underlying inqui factual Ltd., Novopharm v. zero. Glaxo Inc. Cf. (i) scope ries include and content of the (Fed.Cir.1995). (ii) art; prior the differences between express found no teach district court also (iii) issue; prior art and the claims at how ing described level of skill the field of the transfer eyedrop fluid from the could (iv) invention; secondary con relevant MEHL/Biophile Corp. Int’l v. the skin. success, including commercial siderations (Fed.Cir. Milgraum, 192 F.3d needs, long-felt but unsolved failure of oth 1999). say cannot either of these find We ers, unexpected results. KSR Int’l that the ings, nor the conclusion 398, 406, 127 Teleflex, 550 U.S. Co. necessarily not include the claimed does (2007); L.Ed.2d Gra S.Ct. limitations, clearly erroneous. Accord ham, 17-18, 684. 383 U.S. 86 S.Ct. persuaded that the dis ingly, we are finding The district court held that trict court committed clear error non-obvious, principally inherently patent was based does not court's Appellants arguments We affirm the district raise the same re- garding anticipation anticipation inherent of the asserted of no inherent similarly claim of the '404 grounds explained for the '029 same on the application topical claims the eyelash specifically promoting as a method of mysterious,” point- unpredictable that there was no motivation finding on its patent and the '819 glau- that certain ing to combine Johnstone to data that showed differences” be- “pharmacological due to ana- drugs prostaglandin coma based on that each reference compounds tween eyelash in low levels of logs only result 286251, at Allergan, 2013 WL discloses. Allergan, 2013 at WL patent the '819 discloses Specifically, *9. that *10. The district court determined compositions chemical list of thirteen additionally secondary considerations which were like analogs, PGF 17-phenyl non-obviousness, based weighed favor of they that disclosed Johnstone those that the invention of the '029 on its double bond and have contain a C5-C6 (for patent unexpected was an result pharmaceutical activity demonstrably high that it found a lack of rea- same reasons mini- pressure intraocular treating success), as well as expectation sonable of 11.9-18, patent '819 col.3 mal effects. side of Latisse® and the commercial success However, col.7 11.19-57. hair paucity competing growth of compounds group contain a Cl-amide treatments. generally discloses whereas carboxylic esters or acids compounds with The court reached its conclusion district at the location. The district court was Cl only at by looking prop- of nonobviousness by Allergan’s expert that it was persuaded and, group particu- of the erties Cl-amide at the time of the invention of understood so, larly, bimatoprost. doing the dis- patent because of this Cl- '029 by failing trict erred to take into court other group, bimatoprost and the amide patent account the full of the '029 scope analog compositions PGF dis- 17-phenyl person ordinary of skill claims.4 “[T]he patent thought in the '819 were closed expectation need have a reasonable FP receptor bind to a other than the re- developing success of the claimed inven- ceptor. Inc., Allergan, tion.” Inc. v. Sandoz result, though patent even As a (Fed.Cir.2013) (emphasis were like the Johnstone com- compounds added). The '029 is not limited to they pounds 17-phenyl in that were PGF compounds group, with a Cl-amide such proved that had effective treat- or the broader class of ing agreed glaucoma, district court described in the '819 ordinary that a skill would not scope independent claims have been motivated to use Cl-amide patent encompasses per- thousands of compounds to treat hair loss. The district analogs, including mutations of PGF struc- “pharmacological that such dif- court found groups all of functional tures with kinds especially significant ferences are in the acids, field,” location, carboxylic growth as “hair is and the Cl such as 6-7, 11-12, Law) (contending demonstrate ECF No. 94 4. The record before us does not arguments appellants’ obviousness that the asserted claims of the '029 regarding to the were limited over Johnstone alone in view the obvious Rather, bimatoprost. ap- obviousness of knowledge in the of those skill pears the district court failed to account for art); Allergan, Apotex, see also Inc. No. scope of the '029 claims de- full Opening 1:10-CV-681 Defs.’ Post-Trial spite appellants’ raising such an assertion in Br.47-48, (arguing plain- ECF No. 190 brief, brief, proposed pretrial post-trial its unexpected a nexus to re- tiffs did not show findings Appellants, of fact. See Letter from secondary sults and other considerations (Excerpt Pro- Ex. A of Defendants' Amended claims). scope within the posed Findings Fact and Conclusions court conclusion. The district needed hydroxyls.5 and Given alkyl carboxylates, falling claimed have found that other embodiments patent’s the breadth in the “same invention, have the ex- within the claim will behave appellants did not manner” with Cl-amide showing compounds a reasonable ex- as burden of acting groups, in order to establish that evidence using the narrow of success pectation unexpected results “is analogs with Cl-amide commensurate class of PGF loss, re scope alone a rea- with the of the claims.”7 In treat hair let groups to Kao, using Huai-Hung expectation of success sonable (Fed.Cir.2011). failed, court Appellants in- The district bimatoprost particular. however, finding make a on how the showing Cl- stead had the burden compounds’ property binding amide genus the broad claimed compounds within necessarily receptor ap- that did the variant FP by patent, including the '029 those expectation of groups, plied were obvious to the reasonable suc- not have Cl-amide scope patent’s cess for the full of the invention. at the time invention, utili- claimed which included the reasoning espe- court’s The district ty compounds that bound the normal FP feature of cially problematic because the receptor to treat hair loss. that it relied on was that it bimatoprost compounded court its error analogs with a Cl- district and the other PGF taking overly cramped view of what disclosed the '819 group amide FP art teaches. The of ordi- receptor.6 to a variant of the bind reading have appellees nary court nor skill Johnstone would the district Neither replete it with references to the the nexus between this and found explain using PGF com- patent’s advantages 17-phenyl claimed scope the broad car- pounds generally, including claimed in- those with patent’s invention. The '029 acids, esters, other related boxylic unique vention is not to PGF location—all covered receptor. groups FP The '029 Cl bind the variant agree the '029 claims. do also claims that do bind We not the district court that Johnstone does garden-variety receptor, FP such as “clearly unequivocally disclose” com- Cl-carboxylic acids. In- Cl-esters saturat- deed, every exemplar pounds that also include C5-C6 almost disclosed antici- latter ed to the extent that would describes one of the bond explained above in improper- pate patent, court’s compounds. The district diminish, This not that it section ILAl.a. does ly analysis limited meant did however, sug- the fact that Johnstone does question prerequisite answer the to its receptor in which the sub-units of example, which of the FP 5. For claim 1 of '029 group rearranged. receptor at the Cl loca describes functional have been the structure "R1,” Br.19, that it claims structures tion as recites Appellees' See n.2. group "wherein R1 is selected from the con C(0)0H, C(0)NHOH, C(0)0R3, sisting of with circumstances such 7.This is in contrast C(0)NHR3, C(0)NHS(0)2 CH2OH, S(0)2R3, Institute, in Genetics LLC v. Novartis as those tetrazole, R4, moiety, phar- a cationic salt Diagnostics, Vaccines & maceutically acceptable amine or ester com There, (Fed.Cir.2011). court 1308-09 atoms, prising a biometa- to 13 carbon applied unexpected across noted that results comprising amine 2 to 13 bolizable or ester structure, scope protein the full of a claimed atoms.” any exceptions were limited to minor since of the claimed variations within "10%” Appellees position, appel- take the structure. dispute, that interacts with lants i.e., splice receptor, a form variant of the FP added). a prefer- sis Johnstone discloses using analog a PGF gest possibility the bond, a analogs already include such that had structure that would ence for PGF adequate explanation with merely without were in the art been identified and known at in itself. See Johnstone the reference pharmacological activity, to have selective may to combine 12 11.22-24.A motivation activity such was irrespective of whether prior in the art—silence does implicit be binding receptor due to to the FP or (U.S.A.) away. Syntex imply teaching variant, as as whether there was a well 407 F.3d Apotex, LLC v. unsaturated bond at the C5- saturated or (Fed.Cir.2005); Corp. Mylan Alza inappositely em- C6 location. The dissent (Fed.Cir. Labs., Inc., 1286, 1291 464 F.3d complexity changing the phasizes 2006) necessity express the of an (rejecting location, that implying bond at this “may it be disclosure of motivation where that patent represents compounds art”). prior implicitly found John- synthesized newly isolated or over those of pref mere disclosure of alternative stone’s Dissenting Op. Johnstone. at 972-73. does not teach a of ordi erences However, Johnstone, following there was nary away from the swath of skill broad nothing left for a chemist to do. As dis- compounds scope within the of the '029 above, taught squarely cussed Johnstone Fulton, In re utility towards a new finite set of (Fed.Cir.2004). already compounds and isolated identified away

Johnstone does not even teach properties already with that had been that bind variant compounds from forms example, characterized—for as disclosed in contrary, receptor. the FP On the John- patents. the '708 and '819 provides prefer- stone even an alternative any The district court also did not find analogs ence for the that were known PGF express teaching away in the art as a receptor binding FP have different court did that whole. district find vasodilatory properties—the compounds analogs art other than included PGF patent, taught parent those disclosed in that had iden- Johnstone 5,352,708. at U.S. Patent No. Johnstone effects, tical physiological as evinced The conclusion of Johnstone’s 11.13-15.8 the '819 disclosure of thirteen description detailed makes this clear. compounds, including bimatoprost, such unequivocally teaches is What reducing that intraocular could be used “[pjrostaglandin derivatives ex- pressure thereby glaucoma. treating high pharmacological activity hibit However, the district court concluded that only very effects, side no small such growth general- in the of hair as a esters, context [latanoprost] carboxylic and its acid art, ly “unpredictable mysterious” presently particularly preferred, are also activity difference in chemical of a of the skin especially large use areas scalp.” (empha- analog, and the Id. at 11.21-23 PGF even one with structure sure, (and agree appellees progeny, including 8. To be we and its the '819 dissent, length, which addresses this issue at patent, had different chemical structures 973-74) Dissenting Op. appellants see example, properties—including, for the bind- sufficiently fail to show that this is a clear ing receptors. especially of variant FP This is itself, reference to the '819 since the court's salient because district conclusion compounds expressly being list of disclosed as heavily relied so on its that—even in vasodilatory in the '708 exclude the light utility disclosure—the of a Johnstone's analogs 17-phenyl PGF that the '819 receptor compound that a variant FP binds discloses, Rather, bimatoprost. such as unexpected an result. point is that the disclosed in the '708 skill in guided persons one claimed very similar to away. to teach would be sufficient with similar structures that scope fall would within the But, not matter whether does patent’s claims. See Altana AG Pharma unpredictable en- generally USA, Inc., v. Teva Pharm. narrowly question is more deavor—the (Fed.Cir.2009) (“Obviousness 1007 based using the success of selective whether similarity may proven by on structural be hair loss would be analogs PGF to treat that the identification of some motivation The district reasonably unpredictable. would have led one of skill commit the same court and the dissent modify art to select and a known com- art examining of the state of the error pound particular way in a to achieve the the time of the invention. See Dis- before compound.”). claimed While success was senting Op. at 974. Once Johnstone employing the disclosed characteristics of published, general may guaran- treat hair loss not have been art ceased to be relevant. the hair teed, teaching provided Johnstone’s suffi- taught analogs that PGF could Johnstone guidance parameters cient as to what Indeed, grow be used to hair. Johnstone expectation lead to a of would reasonable taught that PGF specifically even more success. glaucoma that were effective analogs Therefore, drugs grow could hair. findings The district court’s on second '029 question, correct at the time of ary from considerations suffer the same invention, whether there was

patent’s infirmity lacking scope of a nexus with the mysterious” anything “unpredictable It patent’s claimed invention. glau- analog about a PGF that could treat “objective is the established rule that evi hair. growing coma must com dence of non-obviousness be the district court point, On this the claims which scope mensurate with the failure of certain thera chiefly cited support.” Appli the evidence is offered to analogs grow PGF hair—remark peutic 1420, Tiffin, cation 58 C.C.P.A. 448 F.2d of eyelash growth was a ably, though even (1971); 791, 792 see also MeadWestVaco of one of the potential known side effect Closures, Inc., Beauty v. Rexam & Corp. so, examples.9 two cited Even “[o]bvious 1258, (Fed.Cir.2013); In 731 F.3d 1264-65 require predictabili not absolute ness does Kao, 1068; In Huai-Hung re 639 F.3d O’Farrell, In F.2d ty of success.” re 853 (Fed.Cir. Peterson, 1325, 1331 re 315 (Fed.Cir.1988). 894, mat What does Co., 2003); In re Hiniker gives direction ter is whether the (Fed.Cir.1998). above, As discussed parameters are critical and as to what findings unexpected court’s on the district many may choices be possible which of results, closely which were intertwined Id,; Pfizer, Apotex, successful. Inc. v. analysis of motivation to combine with its (Fed.Cir.2007). success, of expectation and reasonable general Johnstone did not make a exhorta scope with the full were not commensurate covering possibilities—its tion thousands of claims. patent’s specific on classes of com teaching focused sum, even if the district court did specifically positions of PGF fact, findings error in its of properties commit clear described structures ("The eyelashes, length had de- Allergan, WL at *10 increased of 7% 9. See length eyelashes, and showed glaucoma drug creased label for the Rescula® in- 80% whatsoever.”). warning patients response had no cludes 10-14% scope to treat hair loss. Even if we appropriate failure to consider claimed invention in eval- were to determine that the aforementioned patent’s expectation of suc- reasonable uating analysis flaws in court’s the district do not secondary considerations consti- error, cess and rise to the level of clear evidence we review without legal tutes a error cannot on commercial success its own deference. remedy the district court’s other errors leading conclusion to its overall of non- Taking appropriate view of the obviousness.10 claimed inven scope tion, by the court the facts found district We therefore reverse the district court’s the conclusion of obvious weigh towards that the asserted claims validity rests ness. The non-obvious. on that exclude certain PGF provisos scope, from its claim analog structures B. '404 Patent designed anticipation to avoid which were above, by As discussed Johnstone. howev 1. Brandt References er, plethora a contains of teach patent emerged The '404 from the re- analog that ing towards PGF structures sults of Allergan’s clinical trials evaluating scope of in provisos, are outside the safety efficacy bimatoprost eye- and of suggestion cluding express employ treatment, drops for glaucoma which were bonds, saturated compositions with C5-C6 subsequently as Lumigan®. marketed teaching as to PGF that analogs well as Appellants identify publications four in having are selective maximized thera they allege clinical that trials disclose the peutic minimized effect with side effects. ability of bimatoprost promote eyelash claims many The '029 different hair (collectivelythe “Brandt refer- structures, analog including kinds PGF ences”). that, Appellants argue among both and analogs PGF with unsaturated grounds invalidity, other for Brandt bonds, as saturated C5-C6 well as PGF references render the '404 patent would analogs receptor that both bind FP obvious light in of Johnstone. The Brandt and its variant. The district court’s find following: references include the and the ing bimatoprost patent’s that a presentation given by Dr. James compounds only other disclosed bind the Brandt, investigator a clinical working receptor variant FP relevant to the on Lumigan®, to the American Acade- actual claimed Ac invention. my of Ophthalmology Meeting court on cordingly, the district made no find Octo- 23, 2000, disclosing ber three ing probative that would diminish the month re- more trial, sults a from a supporting eyedrop facts drug only expectation skill’s substantial reasonable identifies the stating motivation to use name that “Lumigan,” success and PGF more than high pharmacological activity patients experience and 5% eyelash growth; to those structures similar disclosed finding long-felt The district court made further commercial success or need. event, however, drug approved that Latisse® was the by Allergan’s it is undercut eyelash FDA and marketed exclusive license of the issued latanoprost, It further noted Co., from the Johnstone PCT. See Merck & PCT, subject of the Johnstone has not been USA, 1364, Inc. TevaPharm. 395 F.3d approved. It is unclear from the district (Fed.Cir.2005). 1376 opinion court’s whether this related

967 (Fed. Labs., Inc., 1052, by Allergan on tech issued press release Cir.2005). 23, 2000, containing Conception the same is “the formation October inventor, of a as the October the mind of the definite and information permanent complete opera idea of the presentation; invention, tive is hereafter to be by Drs. Sherwood publication applied practice.” Burroughs Wellcome Comparison entitled “Six-Month Brandt Labs., Inc., Co. v. Barr Onee-Daily and Twice- Bimatoprost (Fed.Cir.1994). concep The issue of the Twice-Daily in Pa- Timolol Daily with legal of an invention is a conclu Pres- tion date Elevated Intraocular tients with findings. factual underlying in sion based on Survey Ophthalmology sure” IP, DaimlerChrysler in a month Taurus LLC v. May disclosing six (Fed.Cir.2013). was re- study, eyelash growth Corp., 726 F.3d glaucoma pa- 48% of per in between 35 and While defendants bear the burden of ported bimatoprost, depending receiving tients suasion to show that the Brandt references dose; patent by on art to the '404 clear evidence, patentee nev Brandt, convincing by Drs. VanDen- publication (a produc ertheless must meet its burden of burgh named inventor conception tion to demonstrate an earlier Chen, Whitcup Ophthal- patent), Bard, Inc., 79 date. Mahurkar v. C.R. in a disclosing 2001 that mology June (Fed.Cir.1996). 1572, 1577 F.3d study, eyelash growth was three month 25.6% and 33.7% of reported between evaluating patentee’s In evi bimatoprost, depend- patients receiving date, conception dence of courts “must ing on dose. give regard oppor due to the trial court’s in- two Brandt references are The first credibility.” tunity judge to the witnesses’ 102(b), § prior art under disputably 52(a)(6). inquiry Fed.R.Civ.P. The court’s year they published were more than one guided by principle is that is well “[i]t priority date of the '404 before party established that when a seeks 4, February 2002. These references do testimony via the oral of prove conception however, not, bimatop- expressly refer inventor, proffer must party putative A of skill hence rost. testimony.” corroborating that evidence report- be unaware that the results would Bouchard, 347 F.3d Chen v. Shu-Hui bimatop- ed therein were associated with (Fed.Cir.2003). particular, In 1309 respect to the more fulsome rost. With permanent” required idea the “definite references, May 2001 the district and June by cor conception supported “must be in- that the '404 court found Burroughs roborating evidence.” Well and, publication to their date prior vented come, 40 at 1230. therefore, were not that the references 102(a).11 concep- § that the prior art under court found The district '404 was mid- tion date of the a. Date of Invention (i) facts: Dr. following on the based testimony that he credible The invention date is the date Woodward’s topi- a “concrete conclusion” Invitrogen Corp. v. Clon reached conception. of year priority date suggests ed more than one before opinion that it 11. The district court Allergan, WL patent. that all four "Brandt references are not found of 102(a),” § even prior art under 35 U.S.C. at *7. publish- though were the first two references court, therefore, com grow would The district application cal (ii) finding mid-2000, mitted clear error corroboration VanDenburgh’s Dr. hair in date in documents priority earlier testimony meeting credible any collectively do not include de early 2001 attorneys late 2000 and between scription of the claimed invention of the (iii) invention, and internal to discuss the only potentially As the other eyelash Allergan reporting memoranda corroborating conception evidence is the trials, which were re- growth in clinical co-inventor, testimony oral of a we reverse and VanDen- ceived Drs. Woodward court’s the district Allergan, 2013 WL burgh early prior to the patent was conceived date 286251,at *7. publication May and June that to the extent there problem Brandt references. evidence, documentary it does not relate to the claimed invention Authorship b. of the Brandt References bimatop- patent—the topical application of argue that if Appellees even eyelash hair promote rost for use to priority cannot claim an earlier Allergan refer growth. The memoranda date, the later Brandt references are still only eyelash growth resulting from the 102(a) they represent § art as The memo- eyedrops. administration work inventors themselves. reported bimatop- randa the side effects of own is not “[0]ne’s work under eyedrops rost used in and did not disclose 102(a) though § even it has been disclosed topical application the claimed invention of public to the in a manner or form which therapeutic for intended effect. The 102(a).” § otherwise would fall under evidence that corroborates Dr. Wood (CCPA 1982). Katz, re testimony topi that he conceived of ward’s Appellees claim that the Brandt references bimatoprost in mid2000 application cal product are the co- co-inventor, testimony the oral of his Dr. is VanDenburgh’s inventor Dr. work de VanDenburgh. This is not one of the signing directing Lumigan® clini by appellees in cases cited which corrobo Appellees rely predominately cal trials. rating through multiple evidence is found testimony VanDenburgh’s regard on Dr. documents, trials, ing such clinical written as collection of her role supervising she described her role engineering Spansion, notebooks. Inc. v. Comm’n, managing being by the work done various Int’l Trade 629 F.3d locations, study including writing clinical (Fed.Cir.2010); Pittsburgh Univ. of This, reports. internal memoranda and Hedrick, (Fed.Cir. 573 F.3d contend, appellees amounts to Dr. Brandt 2009). Rather, this is a case in which and other authors of the Brandt references corroborating there is no document that being “pair pat of hands” for the '404 anything shows about the claimed inven inventors, particular ent’s Dr. VanDen tion. The corroboration of the Coolegem, burgh. Mattor v. 530 F.2d testimony invention the oral claimed is (CCPA 1976). 1391, 1395 inventor, an which we must treat with in skepticism possibility due to the of an that, Appellants argue as an initial mat- in obtaining ventor’s self-interest or main ter, appellees timely did not raise this taining existing patent. Shu-Hui that appellees issue. To the extent did Chen, 1309; Symsek, argue appears Price v. to have been point, this (Fed.Cir.1993). 1187, 1194 during closing arguments post-trial However, 2,” Group referring long under Fourth Circuit to a briefing.12 list law, the issue appellees may study group have waived members—a list in which Dr. authorship references’ VanDenburgh’s appear. of the Brandt name does not pretrial briefing, it in even presenting not J.A. 2413-14. The fact that a reference authors, if raised it later. See McLean appellees does not list co-inventors as Steamship Contracting authors, Co. v. Waterman or that it lists other certainly is (4th Cir.2002) Corp., 277 F.3d However, dispositive not in itself. in this (“Failure worthy of identify legal issue ease, VanDenburgh super- whether Dr. pretrial pretrial trial in conference or logistics vised the of the clinical trial on party’s right to have that order waives the not, appellees pro- her own or have not tried.”). issue respon- duced evidence that shows she was directing production sible for of either if did not waive appellees Even content, design, article’s which includes the issue, arguments raised this their belated trial, analysis of results. There no unavailing. towards the end of trial are evidence, therefore, appellees’ expla- foremost, question First and nation of the Brandt in any references is whether, argue, seem to Dr. appellees way consistent the content of the VanDenburgh or Dr. Brandt was the first publications. articles and the nature of the recognize bimatoprost’s potential ther Katz, In re 687 F.2d at 455. apeutic eyelash value for Appellants argue do not that the Brandt appellees produced Since have no evi expressly bimatoprost’s references teach dence—unsurprising given their belated is, they hair-—-that grow intentional use to argument—and provided recourse this inventorship. The argue do not relevant supported explanation demonstrating no be whether the Brandt ref inquiry must the Brandt references were in fact methods, erences, which describe the de printed publications authored Dr. Van- results, analysis and dis tailed statistical 102(a), § Denburgh purposes for the we trials, clinical cussion of were no to remand to make further see reason solely VanDenburgh’s Dr. work and hers findings question on this issue. The Katz, alone. In re 687 F.2d at 455. On whether a reference is a work of others for this, appellees’ explanations strain reason. 102(a) is, §of that of purposes like inventorship, question of law based on

First, testimony Dr. VanDenburgh’s was Ethicon, underlying facts. Inc. U.S. equivocal at best as to whether she alone (Fed. 1456, Surgical Corp., 135 F.3d 1460 directed clinical trials and wrote internal Cir.1998). appellees Even if had not 508, Second, reports. J.A. 540-41. while arguments point, on this the waived their she was at least a co-author of one Brandt at trial could appellees presented evidence dispute, along reference in with two other support legal not the conclusion that the scientists, VanDenburgh Dr. Allergan represented Dr. references Van at all in the Brandt not listed as a co-author other Denburgh’s own work. See journal Soverain May one. Brandt’s 2001 article Soft co-author, Sherwood, Newegg ware LLC v. includes one Dr. also (Fed.Cir.2013) reh’g, amended on Allergan. unaffiliated with The author (Fed.Cir.2013) and cert. line of the latter article describes it as F.3d 1332 de —nied, -, Study being Bimatoprost written “for the U.S. 134 S.Ct. (attach- post-trial findings Appellees, Allergan

12. Letter from ECF No. 93 and Duke’s ing "excerpts closing argument regarding from the tran- fact and conclusions of law” this brief, issue). script, Allergan post-trial and Duke’s (2014) bimatop- to remand Brandt reference’s disclosure of (declining L.Ed.2d 779 hair, eyelash in findings growing for further factual on obviousness rost’s effect material factual dis- in ordinary where there was no skill the art would legal appar- conclusion was pute and the have had substantial motivation to follow ent). Accordingly, we hold the application Johnstone and use topical to the prior references are art eyelash Brandt hair. grow Likewise, provid- the Brandt references expectation ed a reasonable of success for Invalidity topical application bimatoprost. findings on the The district court’s nearly Clinical trials showed that 50% were limited obviousness patients using bimatoprost eyedrop May and June 2001 reiterating experiencing eyelash form were hair (as prior Brandt references were not additionally taught Johnstone finding on the mid-2000 consequence of its contacting eyelid eye- that fluid from and that patent) invention date of the '404 drops likely was the mechanism of hair light was not obvious growth. Appellees’ remaining argu- Allergan, Johnstone alone. 2013 WL in light ment for nonobviousness of the 286251, at *10. The district court did secondary Brandt references is the consid- findings regarding anticipa make inherent success, eration of commercial which is in light tion of the two earlier Brandt unavailing on its own. Paralleling reasoning references. its on overwhelming weight Given the of evi- anticipation by inherent as dence, here, unnecessary remand is “as III.A.l.b, discussed above section art, scope content district court found that the disclosure of claim, and the level of skill eyelash growth incidence of did not 48.4% in the art are not in dispute, material inherently anticipate. Id. at *8. While we apparent the obviousness of the claim is question need reach the of whether the Soverain, light of these factors.” represents district court’s inference clear KSR, (citing at 1337 at 550 U.S. error, we do note that the Brandt refer 1727). Accordingly, S.Ct. we reverse the eyelash ences disclose a substantial rate of district court’s that the '404 patent using as side effect of bima is not invalid for reasons of obviousness. toprost eyedrops. eye- length details how (marketed Conclusion drops containing latanoprost Xalatan®) glaucoma drug promote reasons, foregoing For the we reverse eyelash hair growth through the invalidity findings the district court’s on containing latanoprost mechanism of fluid the asserted claims of both the '029 and making topical eyelid. contact with the patents, '404 and we vacate the court’s 22 Johnstone at 11.28-35.Johnstone also injunction accordingly.13 topical application discloses the of lata- noprost to In light treat hair loss. REVERSED AND VACATED invalidity description 13. Because we reverse the court's ten for the asserted claims of the patents inadequate on both asserted on the '029 and enablement of grounds of and vacate the claim 14 the well obviousness thus as as the injunction, appel- question court's we need not reach of whether the court abused its dis- arguments regarding granting permanent injunction. lants’ insufficient writ- cretion in a

971 CHEN, Judge, dissenting-in- pounds—citing latanoprost particular, Circuit part. treating for hair loss. But that reference sufficiently suggest does not teach using or opinion except for join majority

I the (i.e., a prostaglandin with a saturated sin- II.A.2, reverses the district Part chain, gle) alpha bond on the Appellants failed to court’s that conclusion C5—C6 proving prior Instead, the meet their burden claimed the John- patent. by art obvious rendered seemingly up stone serves a menu of un- Johnstone, or in either alone combination possibilities. example, limited For when it view, my John- patent. with the '819 chain, alpha comes to the Johnstone states simply too teachings vague stone’s are good that the are those ones characterized invalidating equivocal justify the presence “the lack of various modifi- or Therefore, I dissent. respectfully alpha cations the chain.” J.A. 2293. with, patents enjoy a begin To issued Then, chain, omega for the Johnstone validity, only which can be presumption of again states that preferred prostaglandins convincing by clear and evidence. rebutted “presence are those characterized — P’ship, Ltd. Corp. v. U.S. i4i Microsoft lack of omega or modifications to their 2245-46, -, 2238, 180 L.Ed.2d S.Ct. 131 broad, generic chain.” Id. Such a disclo- (2011). challenging 131 A a party sure would almost appear to cover validity do so with “evidence which must among prostaglandin. conceivable And a mind of the trier of fact an produces variety of modifications possible other abiding the truth of [the] conviction chains, vaguely Johnstone states that highly probable.” factual contentions alpha be a preferably chain “could C6- Indus., Inc., Inc. v. Kason Buildex chain which can be either saturated or C10 (Fed.Cir.1988) (citing F.2d Col unsaturated, more having one or double Mexico, 310, 316, orado New 467 U.S. bonds, triple bond.” J.A. alienes or (1984)). 81 L.Ed.2d 247 S.Ct. provide 2293. This does not lone sentence easily that is This not a burden satisfied. using a sufficient blaze mark for saturat- Moreover, majority heavily relies on Cg—Cg ed bond. For the same reason that alone, spe- but the Patent Office Johnstone majority that agree I with the cifically during that reference considered com- anticipate does not the claimed prosecution of “clearly unequivo- pounds—it does not came conclusion that the fact- to the same cally” compound disclose a with saturat- finder did below: Johnstone does not ren- Og—Cq ed bond—I would find does a reviewing der obvious. As the claims suggest specification one either. The court, particularly careful we should be examples no language contains other overturning before the verdict under these certainly alpha saturated chains and no Corp. See Tokai v. Easton circumstances. specific saturating references to bond Enterprises, figures and sum- (Fed.Cir.2011) issue. dozens (explaining that burden mary only depict unsat- proof claim is invention to invalidate double) (i.e., bond, more the challenge difficult to meet when and John- urated C5-C6 is based on the same considered stone’s claims cover examination). during the Patent Office steady persistent this bond. mes- The sage entirety from of Johnstone’s the majority The correct Johnstone the it comes to teachings is clear: when contemplates large prostaglan- a class C6 bond, it unsaturated. analog keep PGF2 com- 17-phenyl dins—the —C6 Also, majority recognizes, compounds as the the bond Johnstone’s would C6 during pros- destroyed claims patentee binding proper amended the have the critical (“Before ty proviso carving compounds. add a out the Id. at 30 ecution to patent] in a inventor of the '029 compounds, [the Johnstone which resulted discov prostaglandin The notice of allow- that saturated F ana ered] notice of allowance. bind, logs out that the amended could this double bond pointed ance even was vital thought FP-receptor binding.”). claims were not obvious over Johnstone: for patent’s compounds The '029 have saturat prosta- art teaches the use of prior The do, fact, ed bonds but bind to the (see glandins treating for hair loss for C6-C6 FP-receptor (contrary popular to at belief [Johnstone]). example, WO 98/33497 time), suggests the which further nonobvi- However, prior the art lacks motivation ousness. DePuy Spine, See Inc. v. Med modify prostaglandins taught the Danek, Inc., tronic presently therein order to obtain the Sofamor (Fed.Cir.2009) (“An 1314, 1326 inference of thus, prostaglandins, claimed does especially strong nonobviousness is where suggest presently teach or prior teachings art’s undermine the claimed invention. very being proffered reason why as to a light of the particularly J.A. 5564. person ordinary skill would have com heavy burden to obviousness a show over elements.”). majori bined the known during prosecution reference disclosed ty finds no clear error in the district examiner, Appellants discussed acceptance undisputed court’s of this fact have not shown that Johnstone now some- purposes anticipation. Majority See suggests very how teaches or structur- Op. at 959. I would also find patentee al feature that claimed to correctly district court concluded that it distinguish the compounds. Johnstone would not have person been obvious to a Nothing in the record compels a differ- ordinary skill at the time of invention to ent Allergan’s expert, result. Dr. Mac- change the unsaturated bond C5-C6 Donald, testified that a Johnstone’s to a saturated skill would not have saturated Johnstone’s DePuy, bond. See (sug double bond because was con- “[i]t C5-C6 gesting nonobviousness “if the art very sidered to be a important parameter indicated that the invention would not have in binding receptor.” to the FP J.A. 1773. purpose worked for its intended or other Prostaglandins receptors bind to on the invention”); taught away wise from the Eli cells, surface of and that binding creates a Pharm., Lilly & Co. v. Zenith Goldline signal to change properties the cell to its Inc., (Fed.Cir.2006) invention, or functions. At the time of prior art (holding supplied no motivation to that identifying well-understood modify compound to include claimed struc receptors prostaglandin can bind to is tural features because no reasonable ex key designing drug that affects the success). pectation of (“Studying receptors cells. See J.A. 23 pharmacology—the central science of This is not a situation in which there are identified, drug therapeutics—because knowing predictable what finite number of receptors biological are associated with a solutions. See KSR Int’l Co. v. Teleflex 398, 421, in designing drug effect aids to [bind 550 U.S. 127 S.Ct. to] (2007). Rather, receptors produce those or inhibit that single L.Ed.2d 705 effect.”). And, time, actually at that the state of proposes sentence thousands, millions, suggested saturating hundreds or even CB-

973 compel able not to properties Eli should us alpha the chain.1 on variations Cf. that this would have been obvious (prior 1376 art reference conclude Lilly, 471 F.3d at invention, especially millions at the of compounds did time when that disclosed or expert testimony limited class of there is no other evi- spell out “a definite and not person ordi record the notion compounds supporting that enabled dence in the envisage to nary skill in the art at once that it be obvious to treat hair loss would class”). The using “high of this limited any prostaglandin each member exhibits have a satu could compound pharmacological activity.” in Johnstone See Sanofi- the any position alpha Inc., on rated bond at F.3d Synthelabo Apotex, v. 550 chain, any position, (Fed.Cir.2008) an bond at unsaturated (“Only hindsight even a any position, at or triple bond dextrorotatory the knowledge that enan- any of bonds. As a combination of these tiomer can highly properties, has desirable result, in the skill art it Apotex that would have been obvi- argue easily or tra not faced with “small to particular ous select this racemate and on options based John versed” number arduous separation.”). undertake its Bayer Schering Pharma stone. See AG majority’s I also from the combi- depart (Fed. Labs., Barr F.3d nation Johnstone with Cir.2009) (“[A]n invention would have Appellants’ argument, Following try to the inventor been obvious when majority links methods of Johnstone’s try all in a possibilities would have had to treating hair loss and by prior of the field direction unreduced treating glaucoma looking methods art.”). instance, covering every In this properties to the shared vasodilation nothing. tells thing effectively us See compounds those references. Ma- (“When at Bayer, what jority at 963-64. I find Johnstone’s Op. would try would been obvious to have have ambiguous too to discussion of vasodilation try vary parameters all each of been amount a clear to combine. motivation possi until one possible numerous choices result, at a where bly arrived successful For example, Johnstone states either no indication of gave cause a alpha “PGF2 can vasodila- or no parameters which were critical di that mechanism through tion effect and many possible rection to which of may provide perfusion to the enhanced to be likely choices successful inven and thus stimulate region bulb obvious.”) (inter tion would not have been activity in the hair folli- trophic increased omitted). quotations nal added). (emphasis 2291-92 cles.” J.A. That frames his vasodilation Johnstone majority further reasons that uncertain terms theory in somewhat select would have been obvious to (“may”) surprising he later they, is not since compounds claimed because like acknowledges representative pros- compounds, high “exhibit his Johnstone’s also derivative, latanoprost, spe- activity very taglandin no or “was pharmacological eliminate ... cifically vasodila- at tailored Majority Op. side small effects.” Ultimately, Johnstone tion.” at 2290. that we know that the Id. But fact now possible there “several surmises that highly claimed contain desir- sug- compounds, majority but Johnstone’s that the maintains classes 1. To extent modifications, majority does not thousands of that Johnstone cover re- gested Majority Op. respectful- possibilities, I on, many variations. lies cover more True, specific ly disagree. reaches may individually Thus, mechanisms that in omega or chain. majority as the con- explain growth cedes, concert the altered pattern “the list of compounds expressly of hair follicles observed the current disclosed being [in Johnstone] vasodila- study.” clinical Id. at 2291. This level of tory in the patent '708 exclude the 17- uncertainty in Johnstone cannot then es- phenyl PGF patent the '819 tablish motivation to combine with the '708 discloses.” Majority Op. at 964 n. 8. Con- patent patent. and then with '819 Unlike sequently, Johnstone’s reference to the references, the Brandt which suggested patent simply '708 does not amount to a that bimatoprost could be grow used to motivation to combine Johnstone with the hair, patents the '708 and '819 have noth- patent. '819 ing to do with hair patents These It undisputed is the field of hair concern glaucoma. treatment methods for growth “unpredictable is mysterious.” Appellants have not established clear majority See J.A. 38. The errs in minimiz- convincing evidence that’ a person of ing this unpredictability. Majority atOp. ordinary skill in the art would look to (“But, it does not matter whether hair these references for solutions in the hair growth generally an unpredictable en- growth field. especially This is true when ...”). deavor. Our case law plain: makes the correlation between vasodilation and unpredictability is a factor. Eisai Co. Ltd. hair growth—the alleged link between Labs., Ltd., Reddy’s v. Dr. Johnstone and the '819 patent—is so spec- (Fed.Cir.2008) (“To the extent an art ulative. Scientific, See Star Inc. v. R.J. unpredictable, as the chemical arts often Co., Reynolds Tobacco ... potential solutions are likely less (Fed.Cir.2011) (reference’s discussion of genuinely predictable.”). be In light of what “might” “may” or “seems” to lead our case law and the unpredictability of to nitrite production and TSNA does not growth, hair Appellants have not satisfied obviousness). suggest their burden of showing clear and convinc- Appellants further assert that one of ing evidence of obviousness. ordinary skill in the art would use the compounds disclosed in Accordingly, the '819 patent looking at the evidence of with Johnstone’s whole, method of obviousness stimulating as a I would find that because Johnstone the district court clearly refers to did not err in the '708 parent holding is the asserted claims of the '029 patent. '819 reasons, nonobvious. For these I respectfully dissent. But Johnstone’s link to the via the is tenuous at best. “preferred describes deriva-

tives” for hair growth as those

lacking phenyl ring structure their chains,

omega such as those described J.A. Any motiva-

tion to combine Johnstone with the com-

pounds via the '708

patent is then confined to those compounds

lacking a phenyl ring structure. The '819

patent, however, teaches bimatoprost,

which has a phenyl ring structure in its

Case Details

Case Name: Allergan, Inc. v. Apotex Inc.

Court Name: Court of Appeals for the Federal Circuit

Date Published: Jun 10, 2014

Citation: 754 F.3d 952

Docket Number: 2013-1245, 2013-1246, 2013-1247, 2013-1249

Court Abbreviation: Fed. Cir.