Stoll, Circuit Judge.
This case arises under the Hatch-Waxman Act. Appellees UCB, Inc.; UCB BioPharma SPRL; Research Corp. Technologies, Inc.; and Harris FRC Corp. (collectively, "UCB") own and/or license U.S. Patent No. RE38,551. The '551 patent covers lacosamide, an anti-epileptic drug, which treats epilepsy and other central nervous system disorders. UCB holds New Drug Applications ("NDAs") that cover its lacosamide anti-epileptic drug approved by the Food and Drug Administration ("FDA") and marketed under the tradename Vimpat®. The '551 patent is listed in the FDA's Approved Drug Products With Therapeutic Equivalence Evaluations ("Orange Book") as covering Vimpat®.
Appellants are generic drug manufacturers who filed Abbreviated New Drug Applications ("ANDAs"), seeking approval for generic versions of Vimpat®. Pursuant to the governing Hatch-Waxman provisions, Appellants certified in their ANDAs that the '551 patent is invalid, unenforceable, or that their proposed generic lacosamide products will not infringe the '551 patent. Consequently, UCB sued Appellants for patent infringement in the United States District Court for the District of Delaware. Appellants stipulated to infringement of claims 9, 10, and 13 of the '551 patent but maintained that these claims are invalid for obviousness-type double patenting, obviousness, and anticipation.
Following a bench trial, the district court made exhaustive fact findings based on the trial evidence and concluded that the asserted claims of the '551 patent are not invalid. Appellants appeal that decision, arguing that the district court misapplied the legal standards for obviousness-type double patenting, obviousness, and anticipation, and that the prior art anticipates and/or renders the '551 patent obvious.
As explained more fully below, we hold that the district court applied the correct legal standards in its obviousness-type double patenting, obviousness, and anticipation analyses. And because we discern no clear error in its underlying fact findings, we affirm the district court's ultimate conclusion that the asserted claims are not invalid.
The '551 patent discloses and claims lacosamide, the active ingredient in Vimpat®. Lacosamide belongs to a class of compounds known as functionalized amino acids ("FAAs") having the following general structure:
The R, R
As disclosed in the '551 patent, lacosamide is the R-enantiomer of N-benzyl-2-acetamido-3-methoxypropion-amide. See '551 patent col. 3 ll. 65-67, col. 38 ll. 9-40. Enantiomers, a type of stereoisomers, are compounds that have the same chemical structure — i.e., the same atoms are connected to each other in the same way — but differ in orientation in three-dimensional space. These orientations are designated as either "R" or "S." A 50-50 mixture of two enantiomers is known as a "racemate" or "racemic mixture."
For its R, R
As of the March 1996 effective filing date of the '551 patent, no FAA had been approved as an anti-epileptic drug nor had any FAA advanced to clinical trials. Also, prior to the '551 patent, there was no public disclosure of pharmacological efficacy or safety data to support the use of any FAA as an anti-epileptic or anticonvulsant drug. To date, Vimpat® remains the only approved FAA for the treatment of epilepsy.
The development of FAAs as anticonvulsants began in the 1980s with the inventor of the '551 patent, Dr. Kohn. In 1985, Dr. Kohn first disclosed the anticonvulsant activity of a compound identified as "AAB," which provided the proof of concept for the use of FAAs as anti-epileptic drugs. In 1987, Dr. Kohn published a paper ("Kohn 1987"), which disclosed the anticonvulsant activity of different structural analogs of the parent AAB compound. Kohn 1987 reported results of different groups at each of the different R positions of the general FAA chemical structure. Kohn 1987 showed that the placement of an aromatic group at the R
In 1988, Dr. Kohn also reported data on the racemate and individual enantiomers of AAB and APB (a similar compound to AAB except that it contained a phenyl group at R
Finally, in 1991, Dr. Kohn evaluated "compound 3l," a racemate ("Kohn 1991"). Compound 3l contained a methoxyamino group at R
In addition to Dr. Kohn's own publications, his research was disclosed in a 1987 thesis completed by his graduate student, Philippe LeGall ("LeGall"). LeGall focused on 15 new FAAs and their potential anticonvulsant activities. Relevant here, Le-Gall disclosed compound 107e. Compound 107e is the racemate of the lacosamide compound claimed in the '551 patent, meaning that instead of the isolated R-enantiomer (lacosamide) claimed in the '551 patent, compound 107e is a mixture of both the R and S enantiomers. In the study, compound 107e belonged to a class of compounds called "polar analogues" of a parent compound 68a. Similar to lacosamide, LeGall replaced the R
LeGall discloses and provides anticonvulsant efficacy data for all 15 compounds except for compound 107e. The class of compounds to which compound 107e belonged all contained nonaromatic groups, and as a class, these compounds showed little to no potency, resulting in ED
Dr. Kohn's research led to the filing of U.S. Patent No. 5,378,729 in 1991, which is prior art to the '551 patent. The '729 patent issued to Dr. Kohn in 1995 and discloses a genus of FAAs. Its specification explains that the claimed compounds exhibit "central nervous system (CNS) activity which are useful in the treatment of epilepsy and other CNS disorders." '729 patent col. 1 ll. 30-33. The compounds of the '729 patent share the following general formula:
Id. at col. 1 ll. 37-43. The '729 patent lists many different compounds and groups that can be placed at each R position, which the district court found could form millions of possible compounds. Important to the issues here, the '729 patent teaches that "[t]he preferred values of R is aryl lower alkyl, especially benzyl" and "[t]he most preferred R
The '729 patent also discloses Table 1 containing pharmacological data for 54 FAAs. None of the compounds listed in Table 1 are lacosamide, compound 107e disclosed in LeGall, or any FAA compound with a methoxymethyl group at R
U.S. Patent No. 5,654,301 is a continuation-in-part of the '729 patent and was filed in 1993. The '301 patent is not prior art to the '551 patent. Appellants rely on the '301 patent only for their argument that the '551 patent is invalid for obviousness-type double patenting. Like its parent '729 patent, the '301 patent claims compounds of a general structure and recites several different groups that can be placed at the R and R
'301 patent col. 93 l. 3 — col. 94 l. 21.
Independent claim 39 permits a large number of groups at R, R
Claim 45, which depends from claim 44, recites that R
The asserted '551 patent discloses and claims lacosamide, a species of the genus disclosed in the '729 and '301 patents. The claims of the '551 patent at issue in this case are claims 9, 10, and 13, which are reproduced below along with the claims from which they depend.
Claim 9 recites the lacosamide compound with 90% or greater purity. For its R positions, lacosamide has an unsubstituted benzyl at R, an unsubstituted methyl at R
Before the district court, Appellants asserted that claims 9, 10, and 13 of the '551 patent are invalid for obviousness-type double patenting, alleging that they are not patentably distinct from claims 44-47 of the '301 patent. Appellants argued that the compound described in the asserted claims of the '551 patent is merely an obvious species of the genus claimed in the '301 patent.
Following a bench trial, the district court found that the differences between claim 45 of the '301 patent and the asserted claims of the '551 patent rendered the claims patentably distinct. See UCB, Inc. v. Accord Healthcare, Inc., 201 F.Supp.3d 491, 530-36 (D. Del. 2016) ("District Court Opinion"). Relying on, among other things, the lack of supporting efficacy data investigating the impact of placing an unsubstituted benzyl and methyl at R and R
Appellants also asserted that LeGall's disclosure of the racemic mixture compound 107e alone, or in combination with the '729 patent's disclosure of the genus of FAAs and Kohn 1991's disclosure of compound 3l rendered the asserted claims of the '551 patent obvious. Id. at 540. The district court applied a lead compound analysis and concluded that, as of March 1996, a skilled artisan would not have selected any FAA, let alone compound 107e (LeGall) or compound 3l (Kohn 1991), as a lead compound. Id. at 542-43. The district court based this finding on the complete lack of data to support that these compounds were effective and Kohn 1991's disclosure that nonaromatic compounds were generally disfavored. Id.
Finally, Appellants asserted that the '551 patent was anticipated by LeGall's disclosure of the racemic mixture of compound 107e, which necessarily discloses the enantiomers of that mixture, including the
Appellants appeal the district court's fact findings and conclusions on double patenting, obviousness, and anticipation. Invalidity under any of these three theories must be established by clear and convincing evidence. Microsoft Corp. v. i4i Ltd. P'ship, 564 U.S. 91, 95, 131 S.Ct. 2238, 180 L.Ed.2d 131 (2011). Thus, in order to prevail on appeal, Appellants must show that the district court clearly erred in failing to find clear and convincing evidence of invalidity. We have jurisdiction pursuant to 28 U.S.C. § 1295 (a)(1).
OBVIOUSNESS-TYPE DOUBLE PATENTING
We first address Appellants' argument that the district court erred in holding that the asserted claims of the '551 patent are not invalid for obviousness-type double patenting.
By statute, only a single patent may issue for the same invention. See 35 U.S.C. § 101 ("Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor....") (emphasis added); In re Lonardo, 119 F.3d 960, 965 (Fed. Cir. 1997) ("[Section 101] thus permits only one patent to be obtained for a single invention, and the phrase `same invention' refers to an invention drawn to substantially identical subject matter.").
Nonstatutory double patenting, however, is a judicially-created doctrine, which "prohibits an inventor from obtaining a second patent for claims that are not patentably distinct from the claims of the first patent." Id. at 965. It "prevent[s] the extension of the term of a patent, even where an express statutory basis for the rejection is missing, by prohibiting the issuance of the claims in a second patent not patentably distinct from the claims of the first patent." Otsuka Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1297 (Fed. Cir. 2012) (quoting In re Longi, 759 F.2d 887, 892 (Fed. Cir. 1985)) (alteration in original).
The obviousness-type double patenting analysis involves two steps: "First, the court `construes the claim[s] in the earlier patent and the claim[s] in the later patent and determines the differences.' Second, the court `determines whether those differences render the claims patentably distinct.'" AbbVie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Tr., 764 F.3d 1366, 1374 (Fed. Cir. 2014) (quoting Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 1385 (Fed. Cir. 2010)). The second part of this analysis is analogous to the obviousness inquiry under 35 U.S.C. § 103 in the sense that if an earlier claim renders obvious or anticipates a later claim, the later claim is not patentably distinct and is thus invalid for obviousness-type double patenting. Id. at 1378-79. In chemical cases, the double patenting inquiry is not whether a person of ordinary skill in the art would select the earlier compound as a lead compound, but rather whether the later compound would have been an obvious or anticipated modification of the earlier compound. Otsuka, 678 F.3d at 1297. Unlike in an obviousness analysis, the underlying patent in the double patenting analysis need not be prior art to the later claim. See id.
We review the district court's ultimate legal conclusion of obviousness-type
Before the district court, the parties disagreed as to the correct legal test for obviousness-type double patenting. Appellants argued that only the differences between claims 44-47 of the '301 patent and claims 9, 10, and 13 of the asserted '551 patent are to be considered. UCB argued that the claims as a whole should be considered, including the commonalities between the claims and whether a person of ordinary skill in the art would have been motivated to also modify any of those commonalities when modifying the differences between the claims. Specifically, UCB argued that the court should consider whether the commonly shared R
We agree with Appellants that the obviousness-type double patenting inquiry requires consideration of the differences between the claims in the reference '301 patent and the '551 patent. As we stated above, the focus of the double patenting analysis entails determining the differences between the compounds claimed in the reference and asserted patents and then "determin[ing] whether those differences render the claims patentably distinct." AbbVie, 764 F.3d at 1374 (emphasis added). In this case, both claims recite a methoxymethyl group at R
At the same time, as we explained in Eli Lilly & Co. v. Teva Parenteral Medicines, Inc., 689 F.3d 1368 (Fed. Cir. 2012), "those differences [between the claims] cannot be considered in isolation — the claims must be considered as a whole." Id. at 1377. Indeed, "just as § 103(a) requires asking whether the claimed subject matter `as a whole' would have been obvious to one of skill in the art, so too must the subject matter of the [asserted claims] be considered `as a whole' to determine whether the [reference patent] would have made those claims obvious for purposes of obviousness-type double patenting." Id. at 1377 (quoting Gen. Foods Corp. v. Studiengesellschaft Kohle mbH, 972 F.2d 1272, 1278 (Fed. Cir. 1992)). Thus, the district court did not err by focusing its double patenting analysis on the claims' differences, as well as the claims as a whole.
We turn next to the district court's double patenting analysis. Appellants assert that claims 9, 10, and 13 of the '551 patent are not patentably distinct from claims 44-47 of the '301 patent and are thus invalid for obviousness-type double patenting. Because these claims only have a common methoxymethyl group at the R
The differences between claim 45 of the '301 patent and claim 9 of the '551 patent are that: (1) unlike claim 45 of the '301 patent, claim 9 of the '551 patent requires the R-enantiomer with 90% or greater purity; (2) while claim 45 of the '301 patent allows for any substituted or unsubstituted "aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, cycloalkyl, or lower cycloalkyl lower alkyl," at R, the '551 patent requires an unsubstituted benzyl at R; and (3) while claim 45 of the '301 patent allows R
Focusing on these differences, the district court found that as of the priority date, a person of ordinary skill in the art would not have had a reasonable expectation that placing an unsubstituted benzyl at R or an unsubstituted methyl at R
As the district court found, by the priority date, there was little to no data from which a person of ordinary skill in the art could have formed reasonable expectations about the effect of placing an unsubstituted benzyl at R and an unsubstituted methyl at R
The dissent states that the district court erred by not considering LeGall in its primary double-patenting analysis. Dissent Op. at 1334. We disagree with the dissent's characterization of the district court's opinion. The district court's fact findings regarding LeGall spanned thirteen paragraphs. District Court Opinion, 201 F.Supp.3d at 508-09. In what the dissent characterizes as the district court's "primary" double patenting analysis, the district court also relied on Dr. Roush's expert testimony specifically discussing LeGall. That portion of Dr. Roush's testimony explained that because R and R
The "presence or absence of a reasonable expectation of success is ... a question of fact," Par Pharm., 773 F.3d at 1196, and after considering the prior art and expert testimony presented at trial, the district court found no reasonable expectation of success. We cannot reweigh the evidence, make credibility findings, or find facts. The district court, relying on LeGall and crediting expert testimony, made extensive fact findings regarding the LeGall Thesis. As the district court found, LeGall discloses no data whatsoever for compound 107e or any compound with a methoxymethyl group at the R
Appellants argue that the '729 patent's disclosure that benzyl is "especially preferred" and that methyl is "most preferred" for this genus of compounds itself renders the asserted claims obvious. We disagree. The '729 patent describes other possible variants as "preferred compounds," "preferred embodiments," or preferred groups for each position, indicating a large variety of possible compounds. See '729 patent cols. 5-10. As we held in Eli Lilly, complex compounds like the FAAs disclosed in the '729 patent provide for many opportunities for modification. As the district court found here, there was no indication that out of the millions of possible choices, an unsubstituted benzyl at R and an unsubstituted methyl at R
Appellants also argue that the district court erred by requiring them to prove that benzyl and methyl were the "best" substituents from which to choose. This is a mischaracterization of the district court's decision. The district court merely quoted Dr. Roush's expert testimony that in the prior art "[t]here is no data to say whether benzyl is best or something else would be the best." District Court Opinion, 201 F.Supp.3d at 532 (quoting Dr. Roush's trial testimony). In context, however, it is clear that the district court merely relied on this testimony to support its finding that the prior art data demonstrated a range of effectiveness such that the effectiveness of prior art compounds could not be attributed to benzyl. We do not read the district court's opinion to have required Appellants to prove that benzyl was the best selection.
Appellants further argue that lacosamide falls within the broad scope of claim 45 of the '301 patent, and is thus presumed enabled. Appellants argue that this presumption establishes a reasonable expectation of success as a matter of law. We disagree. Appellants do not cite any authority for the proposition that the presumption of an enabled genus of compounds precludes the district court from finding that there was no reasonable expectation of success of creating a species falling within that genus. Moreover, such a result would have a chilling effect on genus claiming in the chemical arts as there would be double patenting in all chemical compound cases where a parent patent claims a genus.
Because we hold that the district court's finding regarding no reasonable expectation of success was not clearly erroneous, we are compelled to affirm the district court's conclusion that the asserted claims of the '551 patent are not invalid for obviousness-type double patenting.
Next, we address obviousness. We review the district court's ultimate determination that the asserted claims of the '551 patent would not have been obvious de novo and review its underlying fact findings for clear error. Otsuka, 678 F.3d at 1290.
Appellants assert that claim 9 of the '551 patent would have been obvious based on LeGall's disclosure of compound 107e as a racemic mixture. Appellants further assert that LeGall alone, or in combination with the '729 patent and Kohn 1991, render claim 9 obvious. Applying a lead compound analysis, the district court concluded that a person of ordinary skill in the art would not have selected any FAA, let alone the compounds disclosed in LeGall and Kohn 1991, as lead compounds in the lead compound analysis. Relying on our decision in Aventis Pharma Deutschland GmbH v. Lupin, Ltd., 499 F.3d 1293 (Fed. Cir. 2007), Appellants argue that the district court erred by using a lead compound analysis because this case merely involves purification (not structural modification) of a known compound. We disagree.
"In cases involving the patentability of a new chemical compound, prima facie obviousness under the third Graham factor generally turns on the structural similarities and differences between the claimed compound and the prior art compounds." Otsuka, 678 F.3d at 1291. We have held that to demonstrate that a new chemical compound would have been prima facie obvious over a particular prior art compound based on a lead compound analysis, the court follows a two-part inquiry. First, "the court determines whether a chemist of ordinary skill would have selected the asserted prior art compounds as lead compounds, or starting points, for further development efforts." Id. Second, the court determines "whether the prior art would have supplied one of ordinary skill in the art with a reason or motivation to modify a lead compound to make the claimed compound with a reasonable expectation of success." Id. at 1292. A lead compound is "a compound in the prior art that would be most promising to modify in order to improve upon its ... activity and obtain a compound with better activity." Id. at 1291 (quoting Takeda Chem. Indus., Ltd. v. Alphapharm Pty., Ltd., 492 F.3d 1350, 1357 (Fed. Cir. 2007)).
Appellants argue, however, that this court has never required a lead compound analysis in chemical purification cases. Appellants further cite Aventis, where we addressed whether the pure 5(S) stereoisomer of ramipril, in a form substantially free of other isomers, would have been obvious over the prior art disclosing its racemic mixture. Aventis, 499 F.3d at 1300. There, we held that the "structural similarity between claimed and prior art subject matter, proved by combining references or otherwise, where the prior art
Appellants argue that because Aventis did not apply a lead compound analysis, no such analysis is required in this case. We agree. A lead compound analysis is not required in analyzing obviousness of a chemical compound when, in the inventing process, there was no lead compound. An inventor may not have tried to improve a compound known to have desirable properties. See, e.g., Otsuka, 678 F.3d at 1291 ("New compounds may be created from theoretical considerations rather than from attempts to improve on prior art compounds."). And an obviousness rejection by an examiner, or a challenge in court, may be based on the closest prior art, which may not have been a lead compound that the inventor had in mind.
We are not aware of any authority holding that a lead compound analysis is or is not required in cases involving purifying mixtures. Aventis simply required proving that a person of ordinary skill in the art would have been motivated to purify a mixture of compounds based on some known desirable property. See Aventis, 499 F.3d at 1301 (holding that "if it is known that some desirable property of a mixture derives in whole or in part from a particular one of its components, or if the prior art would provide a person of ordinary skill in the art with reason to believe that this is so, the purified compound is prima facie obvious over the mixture").
In any event, even if a lead compound analysis is required here, we hold that the district court did not clearly err in finding that a person of ordinary skill in the art would not have selected compound 107e as a lead compound. As we have stated, the district court found that LeGall contains no data that would have led a person of ordinary skill in the art to select compound 107e among the many compounds disclosed in LeGall as a lead compound. The district court further found that the data provided in LeGall for that class of compounds showed little potency. Dr. Roush also testified that based on LeGall's disclosure, a person of ordinary skill in the art would not have been motivated to develop compound 107e. We see no clear error in the district court's factual findings based on such evidence.
We also see no clear error in the district court's fact finding that a person of ordinary skill in the art would not have selected Kohn's 1991 compound 3l as a lead compound. Kohn's compound 3l is also a nonaromatic compound like compound 107e, and Dr. Roush testified that nonaromatic compounds were not of interest as of 1996. The district court's fact finding was also supported by additional expert testimony, which established that compound 3l had properties making it less stable and that medicinal chemists would have avoided investigating its potential use in a pharmaceutical product.
Based on this evidence, we see no clear error in the district court's fact findings and sustain its conclusion that the asserted claims of the '551 patent would not have been obvious.
Finally, we address anticipation. Only Appellants Accord Healthcare, Inc. and Intas Pharmaceuticals Ltd. (the "Accord
Relying principally on our decision in Sanofi, 550 F.3d at 1084, the district court found claim 9 of the '551 patent not anticipated, concluding that LeGall discloses neither the R-enantiomer of compound 107e nor any of its characteristics. Anticipation is also a question of fact, which we review for clear error. See Sanofi, 550 F.3d at 1082.
We hold that the district court did not clearly err in finding that LeGall does not anticipate claim 9 of the '551 patent. As the district court recognized, we have held that "[t]he knowledge that enantiomers may be separated is not `anticipation' of a specific enantiomer that has not been separated, identified, and characterized." Id. at 1084. We have also stated that "the novelty of an optical isomer is not negated by the prior art disclosure of its racemate." In re May, 574 F.2d 1082, 1090 (CCPA 1978). Although LeGall discloses the chemical structure of the racemic compound 107e, it does not disclose its separation into individual enantiomers nor does it disclose any pharmaceutical data of the R enantiomer recited in claim 9 of the '551 patent. As the Accord Appellants point out, LeGall expressly stated that he "prepare[d] the racemic amino acid derivatives rather than the individual enantiomers," and that "[i]n each case, the functionalized amino acid racemate was prepared rather than, the individual enantiomers." J.A. 4942; J.A. 5030 (emphasis added). Thus, we discern no clear error in the district court's finding of no anticipation.
We have considered the parties' remaining arguments and find them unpersuasive. For the foregoing reasons, we affirm the district court's judgment that the asserted claims of the '551 patent are not anticipated, obvious, or invalid for obviousness-type double patenting.
Costs to Appellees.
Prost, Chief Judge, dissenting.
Because I believe that the district court clearly erred when it found there would not have been a reasonable expectation of success in selecting unsubstituted benzyl for R and unsubstituted methyl for R
The parties focused their double-patenting presentations to the district court on whether claim 9 of the '551 patent (asserted claim) is invalid for obviousness-type double patenting over claims 44 and 45 of the '301 patent (reference claims). UCB, Inc. v. Accord Healthcare, Inc., 201 F.Supp.3d 491, 528 (D. Del. 2016) ("District Court Opinion"). Reference claim 45 covers a genus of compounds known as functionalized amino acids ("FAA") having the following general structure of the formula:
Id. at 512.
In this formula, R, R
Lacosamide is one species of this genus. Id. at 512. Lacosamide has a methoxymethyl group at R
With respect to the district court's double-patenting analysis, much like the majority, I would leave undisturbed nearly all of the district court's findings. To the extent, however, the district court found that a person of ordinary skill in the art would not have had a reasonable expectation of success in selecting an unsubstituted benzyl for R and an unsubstituted methyl for R
The obviousness-type double-patenting analysis involves determining whether the differences between the claims in the reference patent and the claims in the asserted patent render the claims patentably distinct. AbbVie Inc. v. Mathilda & Terence Kennedy Inst. of Rheumatology Tr., 764 F.3d 1366, 1374 (Fed. Cir. 2014). This part of the obviousness-type double-patenting analysis is analogous to an obviousness analysis under 35 U.S.C. § 103. Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340, 1361 (Fed. Cir. 2009). An obviousness determination requires that a
The district court found that a person of ordinary skill in the art would not have had a reasonable expectation of success in selecting an unsubstituted benzyl for R and an unsubstituted methyl for R
Although we cannot reject the district court's finding that drug development is unpredictable, "obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success." Pfizer, 480 F.3d at 1364. In reality, "there were many tests conducted on FAAs with benzyl at R and methyl at R
In 1985, Dr. Kohn published the anticonvulsant activity of his first FAA compound, AAB. District Court Opinion, 201 F.Supp.3d at 505. AAB contained a benzyl at R, and a methyl at R
In Dr. Kohn's 1990 paper, he also kept "R
Dr. Kohn then summarized his prior FAA work in a 1991 paper. Id. All twenty-six compounds reported in that paper had unsubstituted benzyl at R and unsubstituted
Dr. Kohn continued to explore and publish data for many other compounds with different groups at R
On this record it is clear that Dr. Kohn's extensive study of FAAs provides copious amounts of information from which a person of ordinary skill would form a reasonable expectation that the selection of an unsubstituted benzyl for R and an unsubstituted methyl for R
The district court recognized that "there were many tests conducted on FAAs with benzyl at R and methyl at R
It was clear error for the district court to require testing to provide "insight into the effectiveness of benzyl and methyl relative to other structures that could be placed at R and R
Further, if, as the district court found, all the testing focused on R
In dismissing the data resulting from the many tests conducted with unsubstituted benzyl at R and unsubstituted methyl at R
The district court also erred when it found that the limited data that did exist at the time would not have led a person of ordinary skill to place an unsubstituted benzyl at R or an unsubstituted methyl at R
For example, Dr. Kohn, in his 1985 paper, used unsubstituted benzyl at R and unsubstituted methyl at R
Dr. Kohn also considered, in his 1990 paper, the effect of replacing an unsubstituted benzyl at R and found that placing a fluoro-substituted benzyl at R yielded only a comparable anticonvulsant effect. Id. Fluoro-substituted benzyl at R did, however, provide a "far superior" protective index. Id. Yet, this must be balanced against Dr. Kohn's 1991 paper (where all 26 compounds reported had unsubstituted benzyl at R and unsubstituted methyl at R
Thus, the data that were available showed that unsubstituted benzyl at R and an unsubstituted methyl at R
Accordingly, the district court clearly erred when it found that the data specific to R and R
Finally, and perhaps most importantly, the district court erred when it did not consider the LeGall Thesis in its primary double-patenting analysis.
Importantly, the LeGall Thesis disclosed compound 107e which, exactly like lacosamide, has a methoxymethyl group at R
The LeGall Thesis is highly relevant to the obviousness analysis. For example, the majority concluded that "the trial evidence supports the district court's finding that there was no prior art that would have provided a person of ordinary skill reason to believe that unsubstituted benzyl and methyl would have been successful with a methoxymethyl group." Majority Op. 1326. Not so. The thesis disclosed a compound having, like lacosamide, a methoxymethyl group at R
Certainly this evidence, especially when considered along with the other evidence before the district court, would have strongly contributed to a person of ordinary skill in the art's having a reasonable expectation of success in creating an FAA with anticonvulsant activity by selecting an unsubstituted benzyl for R and an unsubstituted methyl for R
* * *
The dissent contends that the USPTO did not consider the LeGall Thesis in its reexamination. Dissent Op. 1335 n.3. We note, however, that the USPTO did consider LeGall and determined that LeGall was not prior art because it was not publically accessible before the priority date. See Argentum Pharm., IPR2016-00204, Paper No. 19 at 12 (PTAB May 23, 2016); District Court Opinion, 201 F.3d at 523.