United States Court of Appeals 

for the Federal Circuit ______________________ 

UCB, INC., UCB BIOPHARMA SPRL, RESEARCH 

CORPORATION TECHNOLOGIES, INC., HARRIS 

FRC CORPORATION,

Plaintiffs-Appellees

v.

ACCORD HEALTHCARE, INC., INTAS 

PHARMACEUTICALS LTD., MYLAN 

PHARMACEUTICALS INC., MYLAN INC., ZYDUS 

PHARMACEUTICALS (USA) INC., CADILA 

HEALTHCARE LIMITED, AMNEAL 

PHARMACEUTICALS LLC, AMNEAL 

PHARMACEUTICALS OF NEW YORK, LLC, 

AUROBINDO PHARMA LTD., AUROBINDO 

PHARMA USA, INC., BRECKENRIDGE 

PHARMACEUTICAL, INC., SUN PHARMA GLOBAL 

FZE, SUN PHARMACEUTICAL INDUSTRIES, LTD., 

WATSON LABORATORIES, INC. - FLORIDA, NKA 

ACTAVIS LABORATORIES FL, INC., WATSON 

PHARMA, INC., NKA ACTAVIS PHARMA, INC., 

MSN LABORATORIES PVT. LTD., ALEMBIC 

PHARMACEUTICALS LTD., APOTEX CORP., 

APOTEX INC.,

Defendants-Appellants

ALEMBIC PHARMA LIMITED, ACTAVIS, INC., NKA 

ALLERGAN FINANCE, LLC,

Defendants

______________________ 
2 UCB, INC. v. ACCORD HEALTHCARE, INC. 

2016-2610, 2016-2683, 2016-2685, 2016-2698, 2016-2710, 

2017-1001 

______________________ 

Appeals from the United States District Court for the 

District of Delaware in Nos. 1:13-cv-01206-LPS, 1:13-cv01207-LPS, 1:13-cv-01208-LPS, 1:13-cv-01209-LPS, 1:13-

cv-01210-LPS, 1:13-cv-01211-LPS, 1:13-cv-01212-LPS, 

1:13-cv-01213-LPS, 1:13-cv-01214-LPS, 1:13-cv-01215-

LPS, 1:13-cv-01216-LPS, 1:13-cv-01218-LPS, 1:13-cv01219-LPS, 1:13-cv-01220-LPS, 1:14-cv-00834-LPS, Chief 

Judge Leonard P. Stark. 

______________________ 

Decided: May 23, 2018 

______________________ 

 DIMITRIOS T. DRIVAS, White & Case LLP, New York, 

NY, argued for plaintiffs-appellees. Also represented by

ADAM GAHTAN, CHRISTOPHER J. GLANCY, ERIC M.

MAJCHRZAK, LAURA MORAN, JAMES TRAINOR; JACK B.

BLUMENFELD, MEGAN DELLINGER, MARYELLEN NOREIKA, 

Morris, Nichols, Arsht & Tunnell LLP, Wilmington, DE; 

PRISCILLA GRACE DODSON, JEFFREY B. ELIKAN, GEORGE 

FRANK PAPPAS, Covington & Burling LLP, Washington, 

DC; ALEXA HANSEN, San Francisco, CA. 

 RICHARD G. GRECO, Albany, NY, argued for defendants-appellants Accord Healthcare, Inc., Intas Pharmaceuticals Ltd. Also represented by JOHN W. SHAW, Shaw 

Keller LLP, Wilmington, DE; GURPREET SINGH WALIA, 

Cohen & Gresser LLP, New York, NY. 

MAUREEN L. RURKA, Winston & Strawn LLP, Chicago, 

IL, argued for defendants-appellants Alembic Pharmaceuticals Ltd., Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York, LLC, Apotex Corp., Apotex Inc., 

Aurobindo Pharma Ltd., Aurobindo Pharma USA, Inc., 
UCB, INC. v. ACCORD HEALTHCARE, INC. 3

Breckenridge Pharmaceutical, Inc., Cadila Healthcare 

Limited, MSN Laboratories Pvt. Ltd., Mylan Inc., Mylan 

Pharmaceuticals Inc., Sun Pharma Global FZE, Sun 

Pharmaceutical Industries, Ltd., Watson Laboratories, 

Inc. - Florida, Watson Pharma, Inc., Zydus Pharmaceuticals (USA) Inc. Defendants-appellants Amneal Pharmaceuticals LLC, Amneal Pharmaceuticals of New York, 

LLC, Aurobindo Pharma Ltd., Aurobindo Pharma USA, 

Inc., Breckenridge Pharmaceutical, Inc., MSN Laboratories Pvt. Ltd., Sun Pharma Global FZE, Sun Pharmaceutical Industries, Ltd., Watson Laboratories, Inc. – Florida, 

Watson Pharma, Inc., LLC, also represented by GEORGE 

C. LOMBARDI, JOHN REYNOLDS MCNAIR, SAMUEL S. PARK;

CHARLES B. KLEIN, EIMERIC REIG-PLESSIS, Washington, 

DC. 

 M. JEFFER ALI, Carlson, Caspers, Vandenburgh, 

Lindquist & Schuman, P.A., Minneapolis, MN, for defendant-appellant Alembic Pharmaceuticals Ltd. Also 

represented by SARAH STENSLAND, Patterson Thuente 

Pedersen, PA, Minneapolis, MN. 

 IAN SCOTT, Taft, Stettinius & Hollister, LLP, Chicago, 

IL, for defendants-appellants Apotex Corp., Apotex Inc. 

Also represented by STEPHEN AUTEN, RICHARD T. RUZICH. 

 NICOLE W. STAFFORD, Wilson, Sonsini, Goodrich & 

Rosati, PC, Austin, TX, for defendants-appellants Mylan 

Pharmaceuticals Inc., Mylan Inc. Also represented by 

ADEN M. ALLEN; ADAM WILLIAM BURROWBRIDGE, Washington, DC; JOSHUA B. KUSHNER, Los Angeles, CA; DAVID S.

STEUER, Palo Alto, CA. 

 MICHAEL JOHN GAERTNER, Locke Lord LLP, Chicago, 

IL, for defendants-appellants Zydus Pharmaceuticals 

(USA) Inc., Cadila Healthcare Limited. Also represented 

by DAVID BRIAN ABRAMOWITZ, HUGH S. BALSAM, TIMOTHY 

FLYNN PETERSON; ANDREA LYNN WAYDA, New York, NY. 
4 UCB, INC. v. ACCORD HEALTHCARE, INC. 

______________________ 

Before PROST, Chief Judge, BRYSON and STOLL, Circuit 

Judges.

Opinion for the court filed by Circuit Judge STOLL. 

Dissenting opinion filed by Chief Judge PROST. 

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. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 5

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. 

BACKGROUND

A. 

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, R1, and R3 positions are variables, representing the many different chemical groups that can be placed 

at each position resulting in a vast number of possible 

FAA compounds. These groups may be aromatic, heteroaromatic, or nonaromatic. Aromatic groups have a 

two-dimensional structure, typically organized into rings, 

such as benzene. Heteroaromatic groups, such as oxygen 
6 UCB, INC. v. ACCORD HEALTHCARE, INC. 

or nitrogen, are also aromatic but contain at least one 

heteroatom, i.e., any atom other than carbon. Nonaromatic groups have three-dimensional structures and are 

not organized into rings. 

As disclosed in the ’551 patent, lacosamide is the Renantiomer of N-benzyl-2-acetamido-3-methoxypropionamide. 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, R1, and R3 positions, lacosamide has an unsubstituted benzyl at R, an unsubstituted methyl at R1, 

and a nonaromatic methoxymethyl at R3. The specification teaches that “the R stereoisomer is unexpectedly 

more potent than the corresponding S stereoisomer and 

the racemic mixture.” Id. col. 23 ll. 31–33. 

As of the March 1996 effective filing date of the 

’551 patent, no FAA had been approved as an antiepileptic 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 antiepileptic drugs. In 1987, Dr. Kohn published a paper 

(“Kohn 1987”), which disclosed the anticonvulsant activity 

of different structural analogs of the parent AAB com-
UCB, INC. v. ACCORD HEALTHCARE, INC. 7

pound. 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 R3 position showed improved 

anticonvulsant activity. Relevant to the issues here, the 

compounds studied in Kohn 1987 used an unsubstituted 

benzyl at R and an unsubstituted methyl at R1. A substituted molecule replaces one of the hydrogen atoms of the 

parent molecule with another atom or structure. 

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 R3). This data showed that the R enantiomers of AAB 

and APB were 10 times more potent than their S enantiomers. In 1990, this was confirmed by Dr. Kohn in a 

study (“Kohn 1990”) in which he concluded “that the 

anticonvulsant activity [of AAB and APB] resided primarily in the R stereoisomers.” J.A. 3240. In this study, 

Dr. Kohn also kept the R and R1 positions constant as 

benzyl and methyl, respectively, while testing the effect of 

different substituents at the R3 position. 

Finally, in 1991, Dr. Kohn evaluated “compound 3l,” a 

racemate (“Kohn 1991”). Compound 3l contained a methoxyamino group at R3 and exhibited superior anticonvulsant properties. Notably, like lacosamide, compound 3l 

contained a nonaromatic group at R3. Compound 3l had 

instability problems, however, which were of concern for 

pharmaceutical formulations.

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, LeGall 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 
8 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 R3 position in compound 107e with a 

nonaromatic methoxymethyl group. 

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 ED50

values ranging from above 100 mg/kg to above 300 

mg/kg.1 By comparison, LeGall reported that other proven anticonvulsants had ED50 values of 14.0, 18.7, 20.1, 

and 61.0 mg/kg, and some other FAAs had ED50 values of 

51.0 and 62.0 mg/kg. Despite not disclosing any pharmacological data for compound 107e, LeGall speculated that 

because of its structural similarities to compound 86b in 

the study, which had an ED50 of 62, compound 107e “may 

have good anticonvulsant activity.” J.A. 5001, 5050. 

LeGall concluded that the most active compounds studied 

had heteroaromatic groups in the R3 position whereas 

compound 107e had a nonaromatic group. 

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 epi-

 

1 Anticonvulsant activity, i.e., efficacy, is determined based on ED50, which in LeGall represents the dose 

at which half of the animals tested did not have a convulsion. A lower ED50 value represents higher potency. 

Conversely, a higher ED50 value represents lower potency. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 9

lepsy 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 R1 group is methyl.” Id. at col. 5 ll. 17–19. For the 

R3 position, the ’729 patent lists a number of preferred 

heterocyclics and alkyl and lower alkoxy groups but does 

not list methoxymethyl. Id. at col. 6 ll. 13–31. 

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 R3. All of the compounds listed in 

Table 1 of the ’729 patent have a methyl at R1 and 49 of 

them have an unsubstituted benzyl at R, all with varying 

potency, ranging from 3.3 mg/kg to over 300 mg/kg. Of 

the top ten compounds with the most potency (i.e., lowest 

ED50), eight had heteroaromatic groups at R3 and two had 

nitrogen-based groups. Unlike lacosamide, none of the 

most potent compounds in Table 1 had a nonaromatic 

group at R3. The four compounds with nonaromatic 

groups at R3 showed moderate to weak potency. 

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 
10 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 R1 positions. The relevant 

claims at issue for purposes of double patenting are 

claims 39–47 of the ’301 patent, which are reproduced 

below: 

39. A compound of the formula 

or the pharmaceutically acceptable salts thereof 

wherein 

R is aryl, aryl lower alkyl, heterocyclic, heterocyclic lower alkyl, cycloalkyl or lower cycloalkyl lower alkyl, wherein R is unsubstituted or is 

substituted with at least one electron withdrawing group or an electron donating group; 

R1 is hydrogen or lower alkyl and R1 is unsubstituted or substituted with at least one electron 

withdrawing group or at least one electron donating group; 

A and Q are both O; 

one of R2 and R3 is hydrogen and the other is lower alkyl which is substituted with an electron donating group or a electron withdrawing group and 

n is 1–4. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 11

40. The compound according to claim 39 wherein 

one of R2 and R3 is hydrogen and the other is lower alkyl substituted with an electron donating 

group. 

41. The compound according to claim 40 wherein 

one of R2 and R3 is alkyl substituted with an electron donating group wherein alkyl is methyl, 

ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, 

amyl or hexyl. 

42. The compound according to claim 41 wherein 

one of R2 and R3 is methyl substituted with an 

electron donating group. 

43. The compound according to claim 42 wherein 

the electron donating group is lower alkoxy. 

44. The compound according to claim 43 wherein 

lower alkoxy is methoxy. 

45. The compound according to any one of 

claims 39–44 wherein n is 1. 

46. An anti-convulsant composition comprising an 

anti-convulsant effective amount of a compound 

from any one of claim 37–42 and a pharmaceutical 

carrier therefor. 

47. A method of treating CNS disorders in an animal comprising administering to said animal an 

anti-convulsant effective amount of a compound of 

any one of claims 39–44. 

’301 patent col. 93 l. 3 – col. 94 l. 21. 

Independent claim 39 permits a large number of 

groups at R, R1, and R3, where each group can comprise a 

large number of substituents and can be either unsubstituted or substituted. Hence, the district court found that 

claim 39 could be thousands, if not millions, of possible 

group combinations. Although the specification does list 
12 UCB, INC. v. ACCORD HEALTHCARE, INC. 

some of the most preferred groups, the list also contains 

generic categories of substituents, creating a large scope 

of possible groups. Although lacosamide is not specifically 

disclosed in the ’301 patent, it is undisputed that lacosamide falls within the broad genus of claim 39 of the ’301 

patent. 

Claim 45, which depends from claim 44, recites that 

R3 is a methoxymethyl group, which is the substituent at 

R3 in lacosamide and claimed in the ’551 patent. Claim 

45 does not recite the molecules at R and R1, however. As 

stated above, claim 45 depends from claim 39, which 

recites a genus of groups that can be located at R and R1. 

B. 

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. 

1. A compound in the R configuration having the 

formula: 

wherein 

Ar is phenyl which is unsubstituted or substituted with at least one halo group; 

Q is lower alkoxy, and 

Q1 is methyl. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 13

8. The compound according to claim 1 which is (R) 

N-Benzyl 2-Acetamido-3-methoxypropionamide. 

9. The compound according to claim 8 which contains at least 90% (w/w) R stereoisomer. 

10. A therapeutic composition comprising an anticonvulsant effective amount of a compound according to any one of claims 1–9 and a 

pharmaceutical carrier therefor. 

11. A method of treating central nervous system 

disorders in an animal comprising administering 

to said animal in need thereof an anticonvulsant 

effective amount of a compound according to any 

one of claims 1–9. 

12. The method according to claim 11 wherein the 

animal is a mammal. 

13. The method according to claim 12 wherein the 

mammal is a human. 

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 R1, 

and a nonaromatic methoxymethyl group at R3.2

C. 

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 

 

2 As shown in the formula of claim 1, the ’551 patent uses “Ar”, “Q”, and “Q1” to designate the location of 

substituent groups corresponding to the “R”, “R1”, and 

“R3” positions in the asserted art. For ease of comparison, we use the R, R1, and R3 designations in discussing 

corresponding substituents in lacosamide. 
14 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 R1, 

the district court concluded that it would not have been 

obvious to a person of ordinary skill in the art to make 

lacosamide by placing an unsubstituted benzyl at R or an 

unsubstituted methyl at R1 in combination with methoxymethyl at R3. Id.

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 R enantiomer (lacosamide). Id. at 544. Relying on our decision in SanofiSynthelabo v. Apotex, Inc., 550 F.3d 1075, 1084 (Fed. Cir. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 15

2008), the district court held that LeGall does not anticipate the asserted claims because, while it discloses the 

racemic mixture compound 107e, it does not explicitly 

disclose the R-enantiomer or its characteristics. Id. 

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 (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). 

I 

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 
16 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 double patenting de novo and 

review its underlying fact findings for clear error. AbbVie, 

764 F.3d at 1372. “A factual finding is clearly erroneous 

if, despite some supporting evidence, we are left with the 

definite and firm conviction that a mistake has been 

made.” Otsuka, 678 F.3d at 1290. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 17

A. 

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 R3 methoxymethyl group in 

the ’301 and ’551 patents would have been substituted 

with another substituent when considering which substituents to place at the R and R1 positions. The district 

court adopted Appellants’ theory, but held that the asserted claims are not invalid for obviousness-type double 

patenting under either theory. 

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 R3. 

Thus, the double patenting analysis requires determining 

whether the claims’ differences, i.e., unsubstituted benzyl 

and methyl at R and R1, would have been obvious to one 

of skill in the art. 

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 
18 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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. 

B. 

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 R3 position, 

the question before us is whether a person of ordinary 

skill in the art, starting with claim 45 of the ’301 patent, 

would have been motivated to place an unsubstituted 

benzyl at R and an unsubstituted methyl at R1 in combination with the methoxymethyl group at R3 with a reasonable expectation of success. We acknowledge that this 

is a close case, but because we discern no clear error in 

the district court’s underlying fact finding that there 

would have been no reasonable expectation of success in 

placing an unsubstituted benzyl and methyl in the 

claimed combination, we agree with the district court that 

the asserted claims of the ’551 patent are patentably 

distinct from the ’301 patent. 

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 
UCB, INC. v. ACCORD HEALTHCARE, INC. 19

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 R1 to be a 

substituted or unsubstituted hydrogen or lower alkyl with 

at least one electron withdrawing or donating group, the 

’551 patent requires R1 to be an unsubstituted methyl. 

Compare ’301 patent col. 93 l. 3 – col. 94 l. 15, with 

’557 patent col. 38 ll. 8–39. 

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 R1 with a methoxymethyl group at R3 would 

have yielded an efficacious anticonvulsant FAA. The 

district court recognized that in the context of drug development, “‘predictability is a vital consideration in the 

obviousness analysis,’ including obviousness-type double 

patenting.” District Court Opinion, 201 F. Supp. 3d at 

531 (quoting Otsuka, 678 F.3d at 1298). We agree that 

proving that a claim is invalid for obviousness-type double 

patenting “requires identifying some reason that would 

have led a chemist to modify the earlier compound to 

make the later compound with a reasonable expectation of 

success.” Eli Lilly, 689 F.3d at 1378 (emphasis added) 

(quoting Otsuka, 678 F.3d at 1297); see also Amgen Inc. v. 

F. Hoffman-La Roche Ltd, 580 F.3d 1340, 1362 (Fed. Cir. 

2009) (“An obviousness determination requires that a 

skilled artisan would have perceived a reasonable expectation of success in making the invention in light of the 

prior art.”). Here, the district court, relying on the prior 

art and expert evidence, found no reasonable expectation 

of success. That is a fact finding that we review for clear 

error following a bench trial. Par Pharm., Inc. v. TWI 

Pharm., Inc., 773 F.3d 1186, 1196 (Fed. Cir. 2014). We 
20 UCB, INC. v. ACCORD HEALTHCARE, INC. 

hold that the district court’s fact finding of no reasonable 

expectation of success is sufficiently supported by the 

evidence presented at trial and is not clearly erroneous. 

We are not left with “the definite and firm conviction that 

a mistake has been made.” Otsuka, 678 F.3d at 1290. We 

are satisfied that the district court did not clearly err. 

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 R1 in combination with a 

methoxymethyl group at R3. Out of all the work performed by Dr. Kohn and others, not a single reference 

disclosed any anticonvulsant data for any compound 

comprising a methoxymethyl group at R3 let alone lacosamide. And most of the FAAs studied prior to the 

priority date only experimented with modifying the substituents at the R3 position while holding constant the 

unsubstituted benzyls at R and unsubstituted methyls at 

R1. See District Court Opinion, 201 F. Supp. 3d at 504, 

531. Thus, the district court reasonably found that the 

prior art data studying FAAs did not provide sufficient 

insight into the effectiveness of placing benzyl and methyl 

at those positions relative to other substituents that could 

have been placed at the R and R1 positions. Id. at 531. 

This finding was supported by Dr. Roush, who explained 

that the prior art was silent as to what role benzyl and 

methyl played in the activity of the FAAs studied in the 

prior art. The district court buttressed its finding with 

the data disclosed in the ’729 patent showing that compounds with benzyl and methyl at R and R1 with different 

R3 groups had a varying range of effectiveness. Id. (citing 

’729 patent at Table 1). Thus, 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. Because 
UCB, INC. v. ACCORD HEALTHCARE, INC. 21

these findings are supported by expert testimony and the 

record, we conclude that they are not clearly erroneous. 

See Eli Lilly, 689 F.3d at 1378 (affirming the district 

court’s obviousness-type double patenting determination 

based on its fact finding of no reasonable expectation of 

success); see also Amgen, 580 F.3d at 1362–63 (affirming 

the district court’s judgment as a matter of law that the 

asserted claims were not invalid for obviousness-type 

double patenting where the trial evidence supported a 

finding of no reasonable expectation of success). 

The dissent states that the district court erred by not 

considering LeGall in its primary double-patenting analysis. Dissent Op. at 10. 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 R1 were held 

constant in the compounds studied in LeGall, one could 

not tell what role benzyl and methyl had in the activity of 

the compounds disclosed. Id. at 531–32 (citing Roush Tr. 

681–82). Moreover, in its analysis under UCB’s proffered 

alternative double patenting test, the district court rejected Appellants’ argument that the claims of the ’551 patent 

are indistinguishable from the discussion of compound 

107e in LeGall. Id. at 535–536. The district court explained that LeGall’s reference to compound 107e lacks 

any data or discussion that would have motivated a 

person of ordinary skill in the art to use a nonaromatic 

compound such as a methoxymethyl at R3. Id. at 535–36. 

Thus, far from ignoring LeGall, as the dissent suggests, 

the district court squarely considered and addressed 

LeGall in its double patenting analysis. 
22 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 R3 position. 

District Court Opinion, 201 F. Supp. 3d at 508. In fact, 

the data LeGall did disclose for similar polar analogue 

compounds showed little to no potency. Id. The district 

court acknowledged that LeGall speculated that compound 107e “may” have good anticonvulsant activity 

based on its structural similarity to another compound. 

Id. at 509. Dr. Roush testified, however, that a person of 

ordinary skill in the art looking to LeGall would have had 

no interest in pursuing that compound and that a person 

of ordinary skill would not have had a reasonable likelihood of success in pursuing an FAA with a methoxymethyl group at R3 as an anticonvulsant drug. The district 

court did not clearly err in crediting this testimony. 

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 
UCB, INC. v. ACCORD HEALTHCARE, INC. 23

R1 would have been selected in combination with a methoxymethyl group at R3 to arrive at lacosamide. See Eli 

Lilly, 689 F.3d at 1378. Because the district court did not 

clearly err in finding that there was no motivation to 

modify the ’301 patent’s claims to arrive at lacosamide or 

a reasonable expectation of success in doing so, we uphold 

the district court’s conclusion that claims 9, 10, and 13 of 

the ’551 patent are not invalid for obviousness-type double patenting. 

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 
24 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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.3 Also, for this reason, we need not reach the 

district court’s findings regarding secondary considerations and Appellants’ argument that the district court 

failed to find a nexus between the asserted secondary 

considerations and lacosamide. 

 

3 We note that the USPTO instituted an ex parte 

reexamination and inter partes review of the ’551 patent. 

While this appeal was pending, the USPTO issued its 

final written decision in the inter partes review, concluding that the petitioner failed to demonstrate that claims 

1–13 of the ’551 patent would have been obvious over 

certain prior art, including Kohn 1991 and the ’729 patent. See Argentum Pharm. LLC v. Research Corp. Techs., 

Inc., IPR2016-00204, 2017 WL 1096590 (PTAB Mar. 22, 

2017). The USPTO also recently concluded its reexamination proceeding and confirmed that claims 9, 10, and 13 

are not unpatentable for obviousness-type double patenting over the ’301 patent, Kohn 1991, and the ’729 patent. 

 

The dissent contends that the USPTO did not consider the LeGall Thesis in its reexamination. Dissent Op. 11 

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. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 25

II 

OBVIOUSNESS

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 
26 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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 gives reason or motivation to 

make the claimed compositions, creates a prima facie case 

of obviousness.” Id. at 1301. We stated further that 

where a claimed composition is a purified form of a mixture that existed in the prior art and “if the prior art 

would provide a person of ordinary skill in the art with 

reason to believe [it had desirable properties], the purified 

compound is prima facie obvious over the mixture even 

without an explicit teaching that the ingredient should be 

concentrated or purified.” Id. (emphasis added). 

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 
UCB, INC. v. ACCORD HEALTHCARE, INC. 27

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 
28 UCB, INC. v. ACCORD HEALTHCARE, INC. 

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. 

III 

ANTICIPATION

Finally, we address anticipation. Only Appellants Accord Healthcare, Inc. and Intas Pharmaceuticals Ltd. (the 

“Accord Appellants”) raise anticipation on appeal. They 

argue that because LeGall discloses the chemical structure of the racemic compound 107e, it necessarily discloses the R-enantiomer (lacosamide) recited in claim 9 of the 

’551 patent. 

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 
UCB, INC. v. ACCORD HEALTHCARE, INC. 29

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. 

CONCLUSION

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. 

AFFIRMED 

COSTS

 Costs to Appellees. 
United States Court of Appeals 

for the Federal Circuit ______________________ 

UCB, INC., UCB BIOPHARMA SPRL, RESEARCH 

CORPORATION TECHNOLOGIES, INC., HARRIS 

FRC CORPORATION,

Plaintiffs-Appellees

v.

ACCORD HEALTHCARE, INC., INTAS 

PHARMACEUTICALS LTD., MYLAN 

PHARMACEUTICALS INC., MYLAN INC., ZYDUS 

PHARMACEUTICALS (USA) INC., CADILA 

HEALTHCARE LIMITED, AMNEAL 

PHARMACEUTICALS LLC, AMNEAL 

PHARMACEUTICALS OF NEW YORK, LLC, 

AUROBINDO PHARMA LTD., AUROBINDO 

PHARMA USA, INC., BRECKENRIDGE 

PHARMACEUTICAL, INC., SUN PHARMA GLOBAL 

FZE, SUN PHARMACEUTICAL INDUSTRIES, LTD., 

WATSON LABORATORIES, INC. - FLORIDA, NKA 

ACTAVIS LABORATORIES FL, INC., WATSON 

PHARMA, INC., NKA ACTAVIS PHARMA, INC., 

MSN LABORATORIES PVT. LTD., ALEMBIC 

PHARMACEUTICALS LTD., APOTEX CORP., 

APOTEX INC.,

Defendants-Appellants

ALEMBIC PHARMA LIMITED, ACTAVIS, INC., NKA 

ALLERGAN FINANCE, LLC,

Defendants

______________________ 
2 UCB, INC. v. ACCORD HEALTHCARE, INC. 

2016-2610, 2016-2683, 2016-2685, 2016-2698, 2016-2710, 

2017-1001 

______________________ 

Appeals from the United States District Court for the 

District of Delaware in Nos. 1:13-cv-01206-LPS, 1:13-cv01207-LPS, 1:13-cv-01208-LPS, 1:13-cv-01209-LPS, 1:13-

cv-01210-LPS, 1:13-cv-01211-LPS, 1:13-cv-01212-LPS, 

1:13-cv-01213-LPS, 1:13-cv-01214-LPS, 1:13-cv-01215-

LPS, 1:13-cv-01216-LPS, 1:13-cv-01218-LPS, 1:13-cv01219-LPS, 1:13-cv-01220-LPS, 1:14-cv-00834-LPS, Chief 

Judge Leonard P. Stark. 

______________________ 

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 R1, I disagree with the 

majority that the asserted claims of the ’551 patent are 

patentably distinct from the reference patent claims. I 

therefore respectfully dissent. 

I 

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: 
UCB, INC. v. ACCORD HEALTHCARE, INC. 3

Id. at 512. 

In this formula, R, R1, and R3 are variables, meaning 

that different elements or compounds can be placed at 

each of these three sites. When claim 45 is limited to 

depending from claim 44, the R3 group is defined as 

methoxymethyl. Id. The definition of R includes unsubstituted benzyl and the definition of R1 includes unsubstituted methyl. Id. at 516. 

Lacosamide is one species of this genus. Id. at 512. 

Lacosamide has a methoxymethyl group at R3, id. at 503, 

unsubstituted benzyl at R, and unsubstituted methyl at 

R1, id. at 530. Asserted claim 9 claims lacosamide. Id. at 

502. It “fills in the variables of the claim 44/45 equation, 

so as to narrow the genus of claims 44 and 45 to the 

species of a single compound, lacosamide.” Id. at 515. In 

other words, claim 9 “selects substituents for R (benzyl) 

and R1 (methyl) that fall within the scope of claims 44/45.” 

Id. at 516. These differences are depicted below: 

Id. 

II 

With respect to the district court’s double-patenting 

analysis, much like the majority, I would leave undis-
4 UCB, INC. v. ACCORD HEALTHCARE, INC. 

turbed 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 R1, it clearly 

erred. 

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 skilled artisan would have 

perceived a reasonable expectation of success in making 

the invention in light of the prior art. Id. at 1362. This is 

a question of fact, which we review for clear error following a bench trial. Par Pharm., Inc. v. TWI Pharm., Inc., 

773 F.3d 1186, 1198 (Fed. Cir. 2014). “A factual finding is 

clearly erroneous if, despite some supporting evidence, 

‘the reviewing court on the entire evidence is left with the 

definite and firm conviction that a mistake has been 

committed.’” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 

1359 (Fed. Cir. 2007) (quoting United States v. U.S. 

Gypsum Co., 333 U.S. 364, 395 (1948)).

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 R1. It based this finding largely 

on a lack of data showing the effect of placing these 

substituents at their respective positions. District Court 

Opinion, 201 F. Supp. 3d at 532. The court stated that 
UCB, INC. v. ACCORD HEALTHCARE, INC. 5

“given how unpredictable drug development is, and the 

high likelihood that any formulation will prove unsuccessful, the lack of data strongly contributes to the [c]ourt’s 

finding.” Id. (citations omitted). 

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 R1.” District Court Opinion, 

201 F. Supp. 3d at 531. And indeed, as the district court 

found, 75% of Dr. Kohn’s experimental compounds contained benzyl at R and methyl at R1, and most of these 

were unsubstituted. Id. As I detail below, the district 

court’s findings of fact as to the prior art provided ample 

evidence showing that a person of skill in the art would 

have had a reasonable expectation of success in creating 

an FAA with anticonvulsant activity by selecting an 

unsubstituted benzyl for R and an unsubstituted methyl 

for R1. While it is true that there may be some evidence 

supporting the district court’s view, given the overwhelming evidence to the contrary, I am “left with the definite 

and firm conviction that a mistake has been committed.” 

Pfizer, 480 F.3d at 1359 (quoting U.S. Gypsum, 333 U.S. 

at 395). 

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 R1. Id. According to Dr. Kohn, AAB 

demonstrated the “proof of concept” for FAAs. Id. Two 

years later, Dr. Kohn reported on the anticonvulsant 

activity of sixteen structural analogues of AAB. Id. The 

paper used unsubstituted benzyl at R and unsubstituted 

methyl at R1 as a “reference point,” and considered five 

possible modifications of the unsubstituted benzyl at R 
6 UCB, INC. v. ACCORD HEALTHCARE, INC. 

and three modifications of the unsubstituted methyl at R1. 

Id. at 506. 

In Dr. Kohn’s 1990 paper, he also kept “R1 constant 

and R constant” as methyl and benzyl, respectively. Id. at 

509. He reported that the most potent compound was 2g, 

which had benzyl at R and methyl at R1. Id. Unlike 

lacosamide, 2g had an aromatic 2-furanyl structure at R3. 

Id. Compound 2g “was found to be significantly more 

potent than APB [described in a 1988 paper], and at the 

time in 1990 when this paper was published this was the 

most potent compound in the FAA family.” Id. 

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 methyl at R1 with different compounds at the R3

group. Id. at 506–07. Dr. Kohn explained in this paper 

that “you get potent protection if you have a benzyl on one 

end [at R] and a methyl on the other [at R1].” Id. at 506. 

The 1991 paper also identified compound 3l, which possessed “the best activity to date” for any FAA racemate. 

Id. at 507. Compound 3l had unsubstituted benzyl at R 

and unsubstituted methyl at R1 with methoxyamino at R3. 

Id. 

Dr. Kohn continued to explore and publish data for 

many other compounds with different groups at R3. Id. at 

506. In a 1993 paper, Dr. Kohn published the results of 

an experiment investigating modifications of the 2-

furanyl group at R3 with other heteroaromatic groups. 

Once again, the “starting point” was benzyl at R and 

methyl at R1. Id.

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 R1 would 

lead to the successful creation of an FAA with anticonvul-
UCB, INC. v. ACCORD HEALTHCARE, INC. 7

sant activity. Indeed, Dr. Kohn described unsubstituted 

benzyl for R and an unsubstituted methyl for R1 as the 

“starting point” or “reference point” for nearly every 

experiment he published. Dr. Kohn himself explained in 

his 1991 paper (where all 26 compounds reported had 

unsubstituted benzyl at R and unsubstituted methyl at 

R1) that “you get potent protection if you have a benzyl on 

one end [at R] and a methyl on the other [at R1].”1 Id. at 

506. 

The district court recognized that “there were many 

tests conducted on FAAs with benzyl at R and methyl at 

R1.” Id. at 531. But it dismissed the resulting data 

because “[m]ost of these tests kept the structures at R and 

R1 constant in order to assess changes made at the R3

position” and so “any changes (whether increases or 

decreases) observed in anticonvulsant behavior and/or 

neurotoxicity would be attributed to the structure at R3

rather than to the benzyl at R or the methyl at R1.” Id. 

In dismissing the data resulting from these tests, the 

court clearly erred. Although the experiments may have 

been designed to assess changes made at the R3 position, 

by using unsubstituted benzyl for R and an unsubstituted 

methyl for R1 as the “starting point” or “reference point” 

for these tests, the prior art showed, without question, 

that those substituents would work at those positions. 

And not only did the prior art show that unsubstituted 

benzyl works at R and that unsubstituted methyl works 

 

1 Additionally, I find it significant that unsubstituted benzyl and unsubstituted methyl were most often used 

together at R and R1, respectively. In other words, they 

are presented throughout the prior art as a pair. Thus, a 

person of ordinary skill would not need to independently 

select benzyl for R and then separately select methyl for 

R1, as the district court posited. 
8 UCB, INC. v. ACCORD HEALTHCARE, INC. 

at R1, the prior art showed that FAAs with these substituents so positioned demonstrate anticonvulsant activity. 

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 R1.” Id. Where the prior art teaches that the 

selected substituent will work, even when it is selected 

from thousands of compounds, an inability to predict how 

any one substituent will work in the composition and a 

need for testing will not render that selection nonobvious. 

See In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985) 

(“Although [the inventor] declared that it cannot be 

predicted how any candidate will work in a detergent 

composition, but that it must be tested, this does not 

overcome [the prior art’s] teaching that hydrated zeolites 

will work.”); Pfizer, 480 F.3d at 1364. 

Further, if, as the district court found, all the testing 

focused on R3 and a person of ordinary skill would attribute anticonvulsant behavior to R3, once R3 was fixed in 

the ’301 reference patent genus, plugging in unsubstituted benzyl at R and unsubstituted methyl at R1 (which had 

remained largely constant throughout the prior art testing) would be viewed simply as a trivial selection. Indeed, 

because the ’301 claim is a genus claim, with only two 

variables R and R1, a person of ordinary skill would know 

to select a substituent for each variable. A person of 

ordinary skill would certainly have a reasonable expectation of success when deciding which substituents to select 

if she copied the “75% of Dr. Kohn’s compounds [which] 

contained benzyl at R and methyl at R1, and most of these 

were unsubstituted.” District Court Opinion, 201 F. Supp. 

3d at 531. 

In dismissing the data resulting from the many tests 

conducted with unsubstituted benzyl at R and unsubstituted methyl at R1 and in relying so heavily on what it 

saw as a lack of data, the district court clearly erred. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 9

B 

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 R1. Id. at 532. Indeed, the data that were available showed that unsubstituted benzyl at R and an unsubstituted methyl at R1 were 

comparable to, if not better than, any other substituents 

tested. 

For example, Dr. Kohn, in his 1985 paper, used unsubstituted benzyl at R and unsubstituted methyl at R1 as 

a “reference point,” and considered five possible modifications of the unsubstituted benzyl at R and three modifications of the unsubstituted methyl at R1. Id. at 506. With 

respect to the R position, only one of the five R modifications showed activity comparable to unsubstituted benzyl 

at R. Id. The others showed decreased activity. Id. For 

the R1 position, each of the three modifications decreased

anticonvulsant activity when compared to unsubstituted 

methyl. Id.

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 

R1) explaining that “you get potent protection if you have a 

benzyl on one end [at R] and a methyl on the other [at 

R1].” Id. (emphasis added). 

Thus, the data that were available showed that unsubstituted benzyl at R and an unsubstituted methyl at 

R1 were comparable, if not better, than any other substituents that were tested with respect to anticonvulsant 

activity. Despite the test that demonstrated fluoro-
10 UCB, INC. v. ACCORD HEALTHCARE, INC. 

substituted benzyl’s “far superior” protective index, these 

tests provide strong evidence that a person of ordinary 

skill would have a reasonable expectation of success in 

selecting these substituents in order to create an FAA 

having an anticonvulsant effect. This is especially so with 

respect to selecting unsubstituted methyl for R1 as it was 

the most successful substituent tested. Although these 

data might have shown that there was no guarantee that 

unsubstituted benzyl at R would provide the greatest 

protective index as compared to other possible substituents, “only a reasonable expectation of success, not a 

guarantee, is needed.” Pfizer, 480 F.3d at 1364. 

Accordingly, the district court clearly erred when it 

found that the data specific to R and R1 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 R1. 

C 

Finally, and perhaps most importantly, the district 

court erred when it did not consider the LeGall Thesis in 

its primary double-patenting analysis.2 See District Court 

Opinion, 201 F. Supp. 3d at 530–35. For purposes of this 

 

2 The majority takes issue with my characterization 

of the district court’s opinion on this point. I do not mean 

to imply that the district court did not make any findings 

of fact as to the LeGall Thesis. The court certainly did in 

its introductory “Findings of Fact” section. District Court 

Opinion, 201 F. Supp. 3d at 508–09. But I maintain that 

the district court determined in its primary doublepatenting analysis that there was no reasonable expectation of success without considering the teachings of this 

reference. A citation to two pages of Dr. Roush’s trial 

testimony, stripped of any reference to the LeGall Thesis, 

cannot cure this deficiency. 
UCB, INC. v. ACCORD HEALTHCARE, INC. 11

litigation, the parties agree that the LeGall Thesis constitutes a “printed publication” within the meaning of 35 

U.S.C. § 102(b).3 Id. at 508. 

Importantly, the LeGall Thesis disclosed compound 

107e which, exactly like lacosamide, has a methoxymethyl 

group at R3, an unsubstituted benzyl at R, and an unsubstituted methyl at R1. Id. Compound 107e is identical to 

lacosamide except that it contains both the R- and Senantiomers in a mixture, rather than just the Renantiomer. Id. Although he did not have data for compound 107e, LeGall hypothesized that structural similarities between compound 107e and another compound for 

which he did have data, 86b, suggested that compound 

107e “may have good anticonvulsant activity.” Id. at 509. 

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. 20. Not so. The 

thesis disclosed a compound having, like lacosamide, a 

methoxymethyl group at R3 together with an unsubstituted benzyl at R and an unsubstituted methyl at R1 and it 

provided a reasonable hypothesis, based on structural 

similarities to other compounds, that this compound “may 

have good anticonvulsant activity.” District Court Opinion, 201 F. Supp. 3d at 509. Again, “only a reasonable 

 

3 The majority, in support of its conclusion, notes 

that the USPTO instituted an ex parte reexamination of 

the ’551 patent and concluded that claims 9, 10, and 13 

were not unpatentable for obviousness-type double patenting over the ’301 patent, Kohn 1991, and the ’729 

patent. Crucially, however, the USPTO did not institute 

trial as to grounds relying on the LeGall Thesis. 
12 UCB, INC. v. ACCORD HEALTHCARE, INC. 

expectation of success, not a guarantee, is needed.” 

Pfizer, 480 F.3d at 1364. Thus, to the extent the district 

court found that there was no indication in the prior art 

that benzyl and methyl would have been successful with a 

methoxymethyl group, it clearly erred. 

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 R1. 

* * * 

Considering all of the evidence, despite some supporting evidence identified by the district court, I am “left 

with the definite and firm conviction” that the district 

court made a mistake. Id. at 1359 (quoting U.S. Gypsum, 

333 U.S. at 395). Thus, I conclude that the district court 

clearly erred in finding that one skilled in the art would 

not have had a reasonable expectation of success with 

unsubstituted benzyl at R and unsubstituted methyl at 

R1. Taking the district court’s clear error together with 

the remainder of its fact findings, I would have concluded 

that claims 9, 10, and 13 of the asserted ’551 patent are 

not patentably distinct from the reference claims. Thus, I 

would reverse the district court’s conclusion and hold that 

the asserted claims of the ’551 patent are invalid for 

obviousness-type double patenting. I therefore respectfully dissent.