United States Court of Appeals 

for the Federal Circuit 

__________________________ 

ELI LILLY AND COMPANY AND TRUSTEES OF 

PRINCETON UNIVERSITY, 

Plaintiffs-Appellees, 

v. 

TEVA PARENTERAL MEDICINES, INC. 

AND BARR LABORATORIES, INC., 

Defendants-Appellants, 

and 

APP PHARMACEUTICALS, LLC, 

Defendant-Appellant. 

__________________________ 

2011-1561, -1562 

__________________________ 

Appeals from the United States District Court for the 

District of Delaware in consolidated Case Nos. 08-CV0335, 08-CV-0384, 08-CV-0860, and 09-CV-0272, Chief 

Judge Gregory M. Sleet. 

__________________________ 

ELI LILLY AND COMPANY AND TRUSTEES OF 

PRINCETON UNIVERSITY, 

Plaintiffs-Appellees, 

v. 

APP PHARMACEUTICALS, LLC, 

Defendant-Appellant. 
ELI LILLY v. APP PHARMA 2

__________________________ 

2012-1037 

__________________________ 

Appeal from the United States District Court for the 

District of Delaware in Case No. 11-CV-0628, Chief Judge 

Gregory M. Sleet. 

____________________________ 

Decided: August 24, 2012 

____________________________ 

ADAM L. PERLMAN, Williams & Connolly, LLP, of 

Washington, DC, argued for plaintiff-appellee. With him 

on the brief were BRUCE R. GENDERSON, KANNON K.

SHANMUGAM, DOV P. GROSSMAN, and DAVID M. KRINSKY. 

Of counsel was ELLEN E. OBERWETTER. 

JOHN C. ENGLANDER, Goodwin Procter, LLP, of Boston, Massachusetts, argued for defendants-appellants. 

With him on the brief were DARYL L. WIESEN and EMILY 

L. RAPALINO. Of counsel on the brief were ERIC H. YECIES 

and MICHAEL B. COTTLER. 

__________________________ 

Before LOURIE, DYK, and WALLACH, Circuit Judges. 

LOURIE, Circuit Judge. 

Appellants Teva Parenteral Medicines, Inc., Barr 

Laboratories, Inc., and APP Pharmaceuticals, LLC appeal 

from the judgment of the United States District Court for 

the District of Delaware holding that U.S. Patent 

5,344,932 (the “’932 patent”) is not invalid for obviousness-type double patenting. See Eli Lilly & Co. v. Teva 

Parenteral Meds. Inc., No. 08-335-GMS, 2011 U.S. Dist. 
3 ELI LILLY v. APP PHARMA

LEXIS 83124, 2011 WL 3236037 (D. Del. July 28, 2011). 

We affirm. 

BACKGROUND

This patent infringement dispute concerns applications filed by several generic pharmaceutical manufacturers seeking regulatory approval to market generic 

formulations of the chemotherapy agent pemetrexed. To 

begin, we outline the necessary background information 

and procedural history, as set forth below. 

A. Antifolate Drugs 

Folates, which include the B vitamin folic acid and its 

derivatives,1 play a critical role in nucleic acid synthesis 

within human cells and, as such, are required for cell 

growth and division. To that end, numerous cellular 

enzymes recognize and process folates—some folatespecific enzymes such as dihydrofolate reductase 

(“DHFR”) and glycinamide ribonucleotide formyltransferase (“GARFT”) catalyze biochemical reactions important for making both DNA and RNA, while others such as 

thymidylate synthetase (“TS”) selectively affect DNA 

production.2 

 1

 Although folic acid itself predominates in most 

dietary supplements and fortified foods, the compound 

naturally occurs in various other chemical forms including folic acid salts and esters. For convenience, we refer 

to folic acid and such related compounds collectively as 

“folates.” 

2

 Purines and pyrimidines are key building blocks 

in the production of both RNA and DNA. DHFR and 

GARFT participate in global purine synthesis, so those 

enzymes affect both DNA and RNA production. In contrast, TS serves only in the production of deoxythymidine 

monophosphate, a pyrimidine nucleotide that is incorporated into DNA but not RNA. 
ELI LILLY v. APP PHARMA 4

Given the key role of folates in DNA synthesis, and 

thus in cellular replication, folate metabolism presents an 

attractive target for cancer treatments because cancerous 

cells characteristically exhibit rapid, unchecked division 

and proliferation. Accordingly, researchers and physicians have developed numerous compounds, known as 

“antifolates,” intended to inhibit one or more of the folatespecific enzymes necessary for DNA synthesis. Structurally analogous to natural folates, antifolates induce initial 

recognition by one or more of the folate-specific enzymes 

yet contain important structural differences that prevent 

the target enzyme from carrying out its normal function. 

For example, the chemical structure of folic acid is represented below—highlighting key structural features including the bicyclic core, bridge region, aryl position, and 

glutamic acid domain—along with the closely related 

structure of methotrexate, a well-known antifolate that 

was first introduced around 1950. 

Folic Acid 
5 ELI LILLY v. APP PHARMA

Methotrexate 

Methotrexate is used as a chemotherapy agent for 

treating certain cancers, including leukemias, lymphomas, and osteosarcoma, among others. In addition to its 

anticancer effects, however, methotrexate, like many 

antifolates, exhibits significant toxicity due to deleterious 

effects on non-cancerous, healthy cells. Such toxicity is 

thought to arise at least in part because methotrexate 

primarily inhibits DHFR and therefore substantially 

impairs DNA and RNA synthesis. While DNA synthesis 

is of principal importance for actively dividing cells (e.g., 

cancer cells), ongoing RNA synthesis is necessary for 

essentially all living cells in the body. Methotrexate and 

other antifolate drugs that inhibit both the DNA and RNA 

synthesis pathways are thus prone to undesirable offtarget effects. 

In the 1980s, researchers sought to develop antifolates capable of inhibiting TS, which would selectively 

impede DNA synthesis and presumably mitigate the 

toxicity issues associated with methotrexate and other 

then-existing antifolates. One such effort led by Prof. 

Edward Taylor, a chemist at Princeton University, 

yielded pemetrexed, the antifolate at the heart of this 

appeal: 
ELI LILLY v. APP PHARMA 6

Pemetrexed 

As with methotrexate, pemetrexed exhibits some structural similarity to folic acid. One key difference that 

distinguishes pemetrexed from folic acid and methotrexate is that pemetrexed contains a pyrrolo[2,3-

d]pyrimidine bicyclic core, characterized by a five-member 

ring fused with a six-member ring, rather than the dual 

six-member rings found in the pteridine cores of folic acid 

and methotrexate. After synthesizing pemetrexed, the 

Princeton group collaborated with researchers at Eli Lilly 

to test the new compound for antifolate activity, and the 

results soon revealed that pemetrexed acts as a potent 

inhibitor of TS. Princeton and Eli Lilly (together, “Lilly”) 

thereafter began exploring for related compounds with 

similar activity as TS inhibitors and pursuing preclinical 

and clinical studies to evaluate promising candidates for 

therapeutic use. 

Among the many pemetrexed-related compounds that 

were developed and tested, pemetrexed itself proved to be 

the best therapeutic candidate and ultimately won FDA 

approval in 2004 for use in treating mesothelioma and 

then in 2008 for treatment of non-small cell lung cancer. 
7 ELI LILLY v. APP PHARMA

Lilly manufactures and distributes pemetrexed under the 

brand name Alimta®. 

B. Lilly’s Patents 

In conjunction with their antifolate research, the inventors filed U.S. patent application 07/448,742 (the “’742 

application”) on December 11, 1989. The ’742 application 

disclosed and claimed pemetrexed as well as a broader 

group of related antifolates containing pemetrexed’s 

characteristic core structure. The ’742 application, 

though itself eventually abandoned, founded a family of 

related applications that ultimately yielded the three 

patents at issue in this appeal. 

The ’932 patent issued on September 6, 1994, from an 

application filed on March 22, 1991, claiming priority 

from the ’742 application through a series of continuations. Claim 3 of the ’932 patent claims pemetrexed. 

Claims 1, 2, and 7 are generic, Markush-style claims that 

encompass pemetrexed as well as other structurally 

related antifolates. 

U.S. Patent 5,028,608 (the “’608 patent”) issued on 

July 2, 1991, from an application filed on May 24, 1990, as 

a continuation-in-part of the ’742 application. The ’608 

patent claims, inter alia, an antifolate (the “’608 Compound”) that differs from pemetrexed only in its aryl 

region—the ’608 Compound contains a five-member 

thiophene ring in place of pemetrexed’s six-member 

benzene ring.3 

 3

 The parties use the expressions “thienyl group” 

and “phenyl group”; accordingly, we will also. 
ELI LILLY v. APP PHARMA 8

The ’608 Compound 

U.S. Patent 5,248,775 (the “’775 patent”) issued on 

September 28, 1993, from an application filed January 31, 

1992, as a continuation-in-part of the application that led 

to the ’932 patent. The ’775 patent discloses a family of 

chemical intermediates that can be used to make a variety of antifolates, including pemetrexed, that contain a 

pyrrolo[2,3-d]pyrimidine bicyclic core. Among others, the 

’775 patent claims a compound (the “’775 Intermediate”) 

that is used as an intermediate in one method for making 

pemetrexed. The ’775 Intermediate differs from pemetrexed in having a carbon-carbon triple bond in its 

bridge region and three protecting groups at substituent 

positions in its core and glutamate domains.4 In addition, 

 4

 Protecting groups are selectively reversible 

chemical modifications often used to prevent unwanted 

side reactions during multistep organic syntheses. In 

general, protecting groups are introduced at one or more 

particularly reactive positions in a complex molecule to 

stabilize or “protect” those parts of the molecule during 

later chemical manipulation of other target sites. Once a 

desired modification has been achieved elsewhere in the 

molecule, the protecting groups can be removed to reconstitute a reactive substituent at each protected position. 

The ’775 Intermediate contains a pivaloyl protecting 

group (denoted “t-BuCO”) in its core region and two 

methyl ester protecting groups (denoted “OMe”) in its 

glutamate domain. 
9 ELI LILLY v. APP PHARMA

Examples 6 and 10 of the ’775 patent disclose reduction 

and hydrolysis reactions, respectively, that could together 

be used to derive pemetrexed from the ’775 Intermediate. 

’775 patent col. 9, l. 59 – col. 10, l. 5; col. 12, ll. 51–66.

The ’775 Intermediate 

The ’932, ’608, and ’775 patents were assigned to the 

Trustees of Princeton University and exclusively licensed 

to Eli Lilly. The ’608 and ’775 patents have expired, but 

the ’932 patent remains in effect until July 24, 2016, due 

to a patent term extension of over four years to compensate for delays in the regulatory approval of Alimta®. See

35 U.S.C. § 156. Lilly holds a further six months of 

market exclusivity over pemetrexed pursuant to 21 U.S.C. 

§ 355a. 

C. District Court Proceedings 

Teva Parenteral Medicines, Inc., Barr Laboratories, 

Inc., and APP Pharmaceuticals, LLC (collectively, “Teva”) 

filed abbreviated new drug applications (“ANDAs”) seeking approval to manufacture and sell generic versions of 

Alimta® before the expiration of the ’932 patent. Those 

ANDAs each included a Paragraph IV certification asserting that the ’932 patent was invalid, unenforceable, or 

would not be infringed by the proposed generic products. 
ELI LILLY v. APP PHARMA 10

See 21 U.S.C. § 355(j)(2)(A)(vii)(IV). In response, Lilly 

brought suit in the United States District Court for the 

District of Delaware, alleging infringement of claims 1, 2, 

3, and 7 of the ’932 patent pursuant to 35 U.S.C. 

§ 271(e)(2)(A). 

During the proceedings, Teva conceded infringement 

but maintained that the asserted claims of the ’932 patent 

were invalid for obviousness-type double patenting over 

two earlier-issued claims: (1) claim 3 of the ’608 patent, 

which claims the ’608 Compound, and (2) claim 7 of the 

’775 patent, which claims the ’775 Intermediate. 

Regarding the ’608 Compound, Teva presented evidence that various antifolates known at the time of the 

invention contained a phenyl group in the aryl position, 

and Teva contended that it would have been obvious to 

incorporate a phenyl group into the ’608 Compound 

consistent with such “conventional wisdom” in the field. 

As to the ’775 Intermediate, Teva argued that the asserted claims of the ’932 patent constitute a use for the 

’775 Intermediate—i.e., synthesizing pemetrexed—that 

had already been disclosed in the specification of the 

earlier-issued ’775 patent, rendering such claims invalid 

for obviousness-type double patenting. In addition, Teva 

argued that even ignoring the specification of the ’775 

patent, an ordinarily skilled chemist presented with the 

’775 Intermediate immediately would have recognized 

pemetrexed as an obvious potential end product. 

Following a bench trial, the district court rejected 

Teva’s arguments and held that claims 1, 2, 3, and 7 of 

the ’932 patent were not invalid for obviousness-type 

double patenting over either the ’608 Compound or the 

’775 Intermediate. Eli Lilly, 2011 WL 3236037, at *2–4. 

Specifically, the district court rejected Teva’s “focus[] only 

on the aryl region of the [’608 Compound] in isolation,” 
11 ELI LILLY v. APP PHARMA

finding persuasive other evidence indicating that one of 

skill in the art would have pursued changes outside of the 

aryl region to improve TS inhibition and would have 

avoided introducing a phenyl group into the ’608 Compound based on previous reports of toxicity with analogous antifolate structures. Id. at *4. The district court 

also declined to hold the asserted claims invalid over the 

’775 Intermediate. The court held (1) that the ’932 patent 

“does not claim the use of the [’775 Intermediate],” so the 

teachings from the ’775 patent’s specification were inapplicable to its obviousness-type double patenting analysis, 

and (2) that pemetrexed would not have been obvious 

from the structure of the ’775 Intermediate because, 

among many possible choices, a person of ordinary skill 

would not have made the structural changes necessary to 

derive pemetrexed. Id. at *2–3. 

Accordingly, the district court entered a final judgment in Lilly’s favor and enjoined approval of Teva’s 

proposed generic pemetrexed products until after the 

expiration of Lilly’s exclusive rights on January 24, 2017. 

Eli Lilly & Co. v. Teva Parenteral Meds. Inc., Nos. 08-335-

GMS, 08-384-GMS, 08-860-GMS, and 09-272-GMS (D. 

Del. Aug. 22, 2011) (Am. Final J. Order), ECF No. 115. 

Teva timely appealed, and we have jurisdiction under 28 

U.S.C. § 1295(a)(1).5

 5

 After trial, individual appellant APP Pharmaceuticals supplemented its ANDA to add a further Paragraph 

IV certification relating to a particular pemetrexed dosage 

form. Appellees initiated a new infringement suit to 

address APP’s supplemental ANDA filing, and the parties 

agreed to be bound in that action by any judgment in the 

antecedent litigation. Accordingly, following its August 

22, 2011, judgment in favor of Lilly, the district court 

entered a stipulated judgment against APP as to its 

supplemental ANDA filing. Eli Lilly & Co. v. APP 

Pharm., LLC, No. 11-628-GMS (D. Del. Oct. 17, 2011) 
ELI LILLY v. APP PHARMA 12

DISCUSSION

The sole disputed issue in this appeal is whether the 

asserted claims of the ’932 patent are invalid for obviousness-type double patenting. The doctrine of obviousnesstype double patenting is intended to “prevent the extension of the term of a patent . . . by prohibiting the issuance of the claims in a second patent not patentably 

distinct from the claims of the first patent.” In re Longi, 

759 F.2d 887, 892 (Fed. Cir. 1985). “A later patent claim 

is not patentably distinct from an earlier claim if the later 

claim is obvious over, or anticipated by, the earlier claim.” 

Eli Lilly & Co. v. Barr Labs., Inc., 251 F.3d 955, 968 (Fed. 

Cir. 2001). As with statutory obviousness under 35 

U.S.C. § 103, obviousness-type double patenting is an 

issue of law premised on underlying factual inquiries. 

Otsuka Pharm. Co. v. Sandoz, Inc., 678 F.3d 1280, 1290 

(Fed. Cir. 2012). Accordingly, we consider the district 

court’s ultimate conclusion on obviousness-type double 

patenting without deference, but we review any predicate 

findings of fact for clear error. Id. 

A. The ’608 Compound 

We first address the ’608 Compound. Claim 3 of the 

’608 patent recites the ’608 Compound, an antifolate that 

is structurally related to pemetrexed but never advanced 

to clinical use. As described, the ’608 patent issued in 

July 1991, more than three years before the ’932 patent 

issued with its claims covering pemetrexed. The question, 

then, is whether the asserted claims of the ’932 patent are 

 

(Stipulation and J. Order), ECF No. 10. We granted 

APP’s unopposed motion to consolidate that action with 

the related matters on appeal. Eli Lilly & Co. v. Teva 

Parenteral Meds. Inc., Nos. 2011-1561, -1562, 2012-1037 

(Fed. Cir. Nov. 29, 2011) (Order Consolidating Appeals). 
13 ELI LILLY v. APP PHARMA

patentably distinct from Lilly’s earlier-issued claim to the 

’608 Compound. 

On appeal, Teva contends that the district court erred 

by failing to invalidate the claims for obviousness-type 

double patenting. Teva’s primary argument concerns the 

appropriate legal standard for evaluating obviousnesstype double patenting. Relying on our decision in Amgen 

Inc. v. Hoffmann-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 

2009), Teva contends that the correct analysis involves 

only the differences between the claims at issue, so that 

any features held in common between the claims—in this 

case, all but the aryl regions of the ’608 Compound and 

pemetrexed—would be excluded from consideration. In 

Amgen, we explained that once the differences between 

claims are established, the obviousness-type double 

patenting analysis entails determining “whether the 

differences in subject matter between the claims render 

the claims patentably distinct.” 580 F.3d at 1361. But 

those differences cannot be considered in isolation—the 

claims must be considered as a whole. Amgen expressly 

noted that “[t]his part of the obviousness-type double 

patenting analysis is analogous to an obviousness analysis under 35 U.S.C. § 103.” Id. And 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 ’932 claims be considered “as a whole” to determine whether the ’608 Compound would have made those claims obvious for purposes 

of obviousness-type double patenting. Gen. Foods Corp. v. 

Studiengesellschaft Kohle mbH, 972 F.2d 1272, 1278 (Fed. 

Cir. 1992) (“Claims must be read as a whole in analyzing 

a claim of double patenting.”). Thus, the district court did 

not err by examining whether one of ordinary skill in the 

art would have been motivated to modify the ’608 Com-
ELI LILLY v. APP PHARMA 14

pound to create pemetrexed, considering the compounds 

as a whole. 

On the merits, Teva also disputes the district court’s 

findings and conclusions in view of the evidence presented. Specifically, Teva contends (1) that placing a 

phenyl group in the aryl position represented inescapable 

“conventional wisdom” in the field based on antifolate 

structures known at the time, (2) that the district court 

erred in finding that one of skill in the art would have 

considered a phenyl group undesirable within the structural context of the ’608 Compound, and (3) that the 

district court erred by discounting its theory that principles of bioisosterism6 would have suggested replacing the 

’608 Compound’s thienyl with phenyl.

Lilly defends the district court’s findings, arguing that 

the evidence amply supported the court’s view that a 

person of ordinary skill would not have had reason to 

manipulate the ’608 Compound to produce pemetrexed. 

Lilly contended, and the district court found, that a 

chemist at the time seeking to develop TS inhibitors 

would have looked specifically to data from that emerging 

sub-discipline rather than attempting to emulate the 

“conventional” antifolates highlighted by Teva. In fact, 

according to Lilly, the contemporary experience and 

understanding in the TS field not only would have failed 

to suggest substituting a phenyl group into the ’608 

Compound, but earlier reports of associated inefficacy and 

toxicity would have actively dissuaded one from doing so. 

Finally, Lilly maintains that bioisosterism provides no 

 6

 Bioisosterism refers to a process that involves replacing one atom or functional group in a molecule with 

another of similar chemical, physical, or electronic properties in hopes that the substitution will result in similar or 

enhanced activity. 
15 ELI LILLY v. APP PHARMA

basis for predicting whether a substituted compound will 

prove more or less effective than the original.

Based on the evidence presented at trial, we discern 

no error in the district court’s findings or its conclusion 

that the asserted claims are patentably distinct from the 

’608 Compound. In the chemical context, we have held 

that an analysis of 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.” 

Otsuka, 678 F.3d at 1297. Here, the district court considered the parties’ arguments and evidence, particularly 

their conflicting expert testimony as to how an ordinarily 

skilled chemist presented with the ’608 Compound would 

have been motivated to proceed at the time. In its decision, the court credited Lilly’s evidence to find that “the 

ways in which a person of ordinary skill in the art would 

modify [the ’608 Compound] would not result in pemetrexed.” Eli Lilly, 2011 WL 3236037, at *4. We owe 

that finding considerable deference on appeal, and we see 

no clear error based on the record before us. Moreover, a 

complicated compound such as the ’608 Compound provides many opportunities for modification, but the district 

court did not find that substituting a phenyl group into 

the aryl position was the one, among all the possibilities, 

that would have been successfully pursued. Thus, absent 

any motivation to derive pemetrexed from the ’608 Compound or reason to expect success in doing so, the district 

court correctly concluded that the asserted claims were 

not invalid for obviousness-type double patenting over the 

’608 Compound. 

B. The ’775 Intermediate 

As with the ’608 Compound, Lilly’s claim covering the 

’775 Intermediate was issued before the ’932 patent. As 
ELI LILLY v. APP PHARMA 16

an independent basis for holding the ’932 claims invalid 

for obviousness-type double patenting, Teva similarly 

contends that pemetrexed is not patentably distinct from 

the ’775 Intermediate. 

Teva’s arguments regarding the ’775 Intermediate can 

be summarized as follows. According to Teva, the ’775 

Intermediate is used to make pemetrexed, and Lilly 

disclosed that use in the ’775 patent. By later claiming 

pemetrexed itself, Teva maintains, the ’932 patent appropriates a previously disclosed use for a previously patented compound, which renders the asserted ’932 claims 

invalid for obviousness-type double patenting under a line 

of our precedent including In re Byck, 48 F.2d 665 (CCPA 

1931), and Sun Pharmaceutical Industries, Ltd. v. Eli 

Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010). We conclude 

that Teva’s reliance on Byck, Sun, and related cases is 

unsound and that the district court did not err when it 

upheld the asserted claims of the ’932 patent over the ’775 

Intermediate. 

As a general rule, obviousness-type double patenting 

determinations turn on a comparison between a patentee’s earlier and later claims, with the earlier patent’s 

written description considered only to the extent necessary to construe its claims. E.g., In re Avery, 518 F.2d 

1228, 1232 (CCPA 1975). This is so because the nonclaim portion of the earlier patent ordinarily does not 

qualify as prior art against the patentee and because 

obviousness-type double patenting is concerned with the 

improper extension of exclusive rights—rights conferred 

and defined by the claims. The focus of the obviousnesstype double patenting doctrine thus rests on preventing a 

patentee from claiming an obvious variant of what it has 

previously claimed, not what it has previously disclosed. 

See generally Gen. Foods, 972 F.2d at 1280–82.
17 ELI LILLY v. APP PHARMA

The cases on which Teva relies represent a limited exception to this customary framework. In Byck, our predecessor court considered obviousness-type double patenting 

rejections against claims to an insulated coil made up of a 

conductive winding material coated with an “infusible, 

flexible, phenol-fatty oil composition.” 48 F.2d at 665. 

The patent applicant, Byck, had earlier obtained a patent 

claiming the same phenol-oil composition, and the prior 

art disclosed similar coils coated with other insulating 

compositions. Id. at 665–66. Moreover, Byck’s earlier 

patent had discussed using his phenol-oil composition to 

produce adherent insulating films on metal substrates. 

Id. at 666. The court concluded that, in view of the prior 

art and Byck’s earlier patent, the pending claims were 

drawn not to a second, distinct invention “but only . . . an 

obvious use of the composition there patented.” Id. The 

court explained: 

It would shock one’s sense of justice if an inventor 

could receive a patent upon a composition of matter, setting out at length in the specification the 

useful purposes of such composition, manufacture 

and sell it to the public, and then prevent the public from making any beneficial use of such product 

by securing patents upon each of the uses to 

which it may be adapted. 

Id. Thus, even though Byck’s earlier patent was not prior 

art, the court held that its disclosure of an intended use 

for the previously claimed phenol-oil composition could be 

used in the obviousness-type double patenting analysis to 

reject a later claim directed to that use of the same compound. Id. at 667. 

A trio of our more recent decisions applied the same 

exception to allow limited consideration of teachings in an 

earlier-issued patent’s specification. In Geneva Pharma-
ELI LILLY v. APP PHARMA 18

ceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 

(Fed. Cir. 2003), the plaintiff had patented methods of 

using clavulanic acid to mitigate antibiotic resistance 

when treating bacterial infections. The plaintiff then 

acquired a preexisting patent that claimed clavulanic acid 

compositions and disclosed their utility for treating patients harboring antibiotic-resistant bacteria. Id. at 1377, 

1385. In that case, we relied on Byck to hold the plaintiff’s method claims invalid for double patenting: “Our 

predecessor court recognized that a claim to a method of 

using a composition is not patentably distinct from an 

earlier claim to the identical composition in a patent 

disclosing the identical use.” Id. at 1385–86 (citing Byck, 

48 F.2d at 666). Similarly, in Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353, 1363 (Fed. Cir. 2008), 

we held claims to methods of administering a particular 

anti-inflammatory drug invalid for obviousness-type 

double patenting where the patentee’s earlier patent 

claimed the drug itself and disclosed the same methods of 

administering the drug. And in Sun, the patent holder 

had developed an antiviral compound, gemcitabine, that 

also proved useful for treating cancer. An initial patent 

issued with composition claims covering gemcitabine as 

well as method claims drawn to using the drug to treat 

herpesvirus infections; also mentioned in the specification, but not claimed, was gemcitabine’s potential anticancer activity. Sun, 611 F.3d at 1383. As in Geneva and 

Pfizer, we held the patentee’s subsequent claims to methods of using gemcitabine to treat cancer invalid for double 

patenting, looking to the disclosure of anticancer utility in 

the first patent’s specification. Id. at 1386–89. 

Byck, Geneva, Pfizer, and Sun thus “address the 

situation in which an earlier patent claims a compound, 

disclosing the utility of that compound in the specification, and a later patent claims a method of using that 
19 ELI LILLY v. APP PHARMA

compound for a particular use described in the specification of the earlier patent.” Sun, 611 F.3d at 1389. Furthermore, in each of those cases, the claims held to be 

patentably indistinct had in common the same compound 

or composition—that is, each subsequently patented “use” 

constituted a, or the, disclosed use for the previously 

claimed substance. 

That is not the case before us. Rather than a composition and a previously disclosed use, the claims at issue 

recite two separate and distinct chemical compounds: the 

’775 Intermediate and pemetrexed, differing from each 

other in four respects. That alone suffices to undermine 

Teva’s argument regarding the ’775 Intermediate, for the 

asserted claims of the ’932 patent do not recite a use of the 

same compound, but a different compound altogether. 

The cited cases therefore do not govern. 

Furthermore, even if one composition could somehow 

be considered a “use” of another, the record makes clear 

that, unlike in the cited cases, Lilly’s successive claims 

are wholly independent of one another. For example, 

pemetrexed and the ’775 Intermediate exhibit substantial 

structural differences, and neither embodies or subsumes 

the other. Moreover, pemetrexed can be made via any of 

several synthetic techniques, many of which do not involve the ’775 Intermediate. The ’775 Intermediate and 

pemetrexed are thus separate and independent chemical 

compounds; Lilly’s original claim to the ’775 Intermediate 

offered no protection for pemetrexed, and its claims to 

pemetrexed do not incorporate or require use of the ’775 

Intermediate. The particular concerns motivating our 

prior decisions are thus absent here. In sum, although 

the specification of the ’775 patent discloses one method 

for deriving pemetrexed using the ’775 Intermediate, we 

agree with the district court’s conclusion that that disclo-
ELI LILLY v. APP PHARMA 20

sure does not render Lilly’s claims to pemetrexed invalid 

for obviousness-type double patenting. 

As the district court recognized, the correct double 

patenting analysis in this case turns on an evaluation of 

what Lilly has claimed, not what it has disclosed. Putting 

aside the teachings in the ’775 patent’s specification, 

Teva’s double patenting contentions evaporate. The 

evidence of record characterizes the ’775 Intermediate as 

a versatile compound from which a skilled chemist could 

derive innumerable final products beyond just pemetrexed, and the district court found that there would 

have been “no reason” to pursue pemetrexed among the 

various other avenues that would have been considered 

possible at the time. We see no error in the district 

court’s findings or its conclusion on this point, and, although not controlling, we further note that its analysis 

comports with PTO guidelines on the patentability of 

related products. See Manual of Patent Examining Procedure § 806.05(j) (8th ed., rev. 8, 2010) (“[A]n intermediate product and a final product can be shown to be 

distinct inventions if the intermediate and final products 

are mutually exclusive inventions (not overlapping in 

scope) that are not obvious variants, and the intermediate 

product as claimed is useful to make other than the final 

product as claimed.”). In sum, the district court correctly 

concluded that the asserted claims are not invalid for 

obviousness-type double patenting over the ’775 Intermediate. 

C. Objective Indicia of Nonobviousness 

Finally, Lilly presented evidence at trial that pemetrexed exhibited unexpected clinical properties and 

achieved considerable commercial success. But the district court disregarded that evidence, holding that “secondary considerations are not relevant to the analysis of 
21 ELI LILLY v. APP PHARMA

invalidity for obviousness-type double patenting.” Eli 

Lilly, 2011 WL 3236037, at *1 n.1. For that proposition, 

the district court relied on a footnote in Geneva, in which 

we remarked only that inquiry into secondary considerations is not required in every obviousness-type double 

patenting analysis, not that such evidence is off-limits or 

irrelevant. See Geneva, 349 F.3d at 1378 n.1. The district 

court’s categorical repudiation of Lilly’s evidence was 

therefore erroneous. When offered, such evidence should 

be considered; a fact-finder “must withhold judgment on 

an obviousness challenge until it has considered all relevant evidence, including that relating to the objective 

considerations.” In re Cyclobenzaprine Hydrochloride 

Extended-Release Capsule Patent Litig., 676 F.3d 1063, 

1079 (Fed. Cir. 2012). Given that the district court nonetheless rejected Teva’s double patenting arguments, 

however, such error was, in this instance, harmless. 

CONCLUSION

In view of the foregoing, we hold that the asserted 

claims of the ’932 patent are not invalid for obviousnesstype double patenting over claim 3 of the ’608 patent or 

claim 7 of the ’775 patent. We have considered each of 

Teva’s remaining arguments and find them unpersuasive. 

Accordingly, the judgment of the district court is 

AFFIRMED