Source: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-14-01635/USCOURTS-ca13-14-01635-0/pdf.json

Nature of Suit Code: 830
Nature of Suit: Patent
Cause of Action: 

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United States Court of Appeals 

for the Federal Circuit ______________________ 

PROMETHEUS LABORATORIES, INC.,

Plaintiff-Appellant

v.

ROXANE LABORATORIES, INC., CIPLA, LTD.,

Defendants-Appellees

______________________ 

2014-1634, 2014-1635

______________________ 

Appeals from the United States District Court for the 

District of New Jersey in Nos. 2:11-cv-00230-FSH-MAH, 

2:11-cv-01241-FSH-MAH, Judge Faith S. Hochberg.

______________________ 

Decided: November 10, 2015 

______________________ 

NEAL KUMAR KATYAL, Hogan Lovells US LLP, Washington, DC, argued for plaintiff-appellant. Also represented by JACLYN DILAURO, MATTHEW A. SHAPIRO; THOMAS 

SCHMIDT, New York, NY.

HENRY C. DINGER, Goodwin Procter LLP, Boston, MA, 

argued for defendants-appellees. Also represented by 

KEITH A. ZULLOW, MARTA E. GROSS, MICHAEL B. COTTLER,

TIMOTHY J. DOYLE, New York, NY; WILLIAM M. JAY, 

Washington, DC. 

______________________ 

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Before DYK, TARANTO, and HUGHES, Circuit Judges.

DYK, Circuit Judge. 

Prometheus Laboratories, Inc. (“Prometheus”) appeals 

a judgment of the U.S. District Court for the District of 

New Jersey holding the amended claims of U.S. Patent 

No. 6,284,770 (“the ’770 patent”) invalid. The district

court found the claims would have been obvious over the 

prior art or, in the alternative, invalid on grounds of 

obviousness-type double patenting over U.S. Patent No. 

5,360,800 (“the ’800 patent”). We affirm the district 

court’s decision because the claims of the ’770 patent are 

invalid as obvious over the ’800 patent and other prior 

art, and do not reach the issue of double patenting. 

BACKGROUND

Irritable bowel syndrome (“IBS”) is a condition defined and diagnosed by its constellation of symptoms. 

Patients may suffer from diarrhea-predominant IBS 

(“IBS-D”), constipation-predominant IBS (“IBS-C”), or, 

less often, mixed IBS (“IBS-M”) or alternating IBS (“IBSA”). A patient’s symptoms define the type of IBS with 

which a patient is diagnosed. 

In this case, Prometheus, the owner of the ’770 patent, sued Roxane Laboratories, Inc. (“Roxane”) and Cipla, 

Ltd. (“Cipla”) (together “defendants”), alleging infringement of claims 5, 6, 10, 13, and 14 of the ’770 patent. As 

described below, the ’770 patent claims a method of 

treatment for IBS-D utilizing alosetron (known by the 

brand name Lotronex). The question is whether these 

claims of the ’770 patent would have been obvious over 

various prior art references or are invalid for obviousnesstype double patenting over the prior ’800 patent.

Prometheus also owns the ’800 patent, which also covers the use of alosetron for treatment of IBS. The ’800 

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patent issued on November 1, 1994, and has now expired.1 The ’800 patent is prior art to the ’770 patent 

asserted here. Claim 17 of the ’800 patent is directed to 

“[a] method of treating a condition [such as IBS] which is 

ameliorated by antagonism of 5-HT3 receptors which 

comprises administering to a patient an effective amount 

of [alosetron].” ’800 patent col. 38 ll. 7–12. Claim 27 of the 

’800 patent covers “[a] method according to claim 17 for 

the treatment of irritable bowel syndrome.” Id. at col. 38 

ll. 50–51. 

The ’770 patent, entitled “Medicaments for the 

Treatment of Non-Constipated Female Irritable Bowel 

Syndrome,” is also directed to a method of treating IBS 

patients using alosetron. The ’770 patent has a priority 

date of October 7, 1997. After the ’770 patent issued, 

Prometheus initiated an ex parte reexamination of the 

’770 patent, and a reexamination certificate was issued on 

October 19, 2010. During reexamination, Prometheus 

amended claim 5 to add new claim limitations (those new 

limitations are underlined below) and added, inter alia, 

claims 10 and 13. 

Reexamined claims 5, 10, and 13 provide:

5. A method for treating a diarrhea-predominant 

female IBS patient, while excluding those with 

predominant constipation, said method comprising: 

assessing whether said diarrhea-predominant female IBS patient has experienced symptoms for 

at least six months; and 

1 Prometheus acquired the ’770 and ’800 patents, 

along with other rights relating to the Lotronex franchise, 

from Glaxo Group Ltd. in 2007. 

 

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administering an effective amount of alosetron or 

a pharmaceutically acceptable derivative thereof 

to said patient who has experienced symptoms for 

at least six months, wherein said effective amount 

is dependent on the condition of the patient and is 

at the discretion of the attendant physician. 

10. The method for treating according to claim 5, 

further comprising assessing whether said female 

IBS patient has experienced at least moderate 

pain prior to administration of alosetron.

13. A method for treating a diarrhea-predominant 

female IBS patient, while excluding those with 

predominant constipation, said method comprising: 

assessing whether said diarrhea-predominant female IBS patient has experienced symptoms for 

at least six months; 

assessing whether said nonconstipated female 

IBS patient experiences at least moderate baseline pain from IBS; and 

administering an effective amount of alosetron or 

a pharmaceutically acceptable derivative thereof 

to said patient who has experienced symptoms for 

at least six months and who experiences at least 

moderate baseline pain from IBS, wherein said effective amount is dependent on the condition of 

the patient and is at the discretion of the attendant physician.

Ex Parte Reexamination Certificate, ’770 patent. Claims 6 

and 14, which depend from claims 5 and 13, respectively, 

limit alosetron to its hydrochloride salt form. Id.

Some background information on the history of Lotronex is helpful to understanding the issues here. Shortly 

before the issuance of the ’770 patent, Lotronex was

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approved by the FDA as a treatment for IBS and was

launched in 2000. That same year, the drug had to be 

taken off the market because of serious side effects, 

including death. The drug was re-launched in 2002, with 

a new, more restrictive label, new warnings about side 

effects, and a risk management program. After reintroduction, the label specified that Lotronex is indicated only 

for women with severe IBS-D who have, inter alia, chronic 

symptoms generally lasting six months or longer, and 

should not be used on patients with constipation—

indications that correspond to the limitations of the

amended ’770 patent claims. The label also included socalled “black box” warnings regarding the potential for 

serious side effects and repeated that Lotronex should 

only be prescribed to women with severe diarrheapredominant IBS who have not responded adequately to 

conventional therapy. 

Following reintroduction, the number of severe incidents associated with Lotronex dropped, but the rate of 

adverse events did not change. The district court found

that “[l]imiting the patient population to women with 

severe IBS-D did not change the risk profile for Lotronex. 

Even when limited to that cohort of the patient population, Lotronex’s incidence of complications did not decrease.” J.A. 12. The district court also found that the 

decrease in the number of severe incidents is less likely 

due to the more restrictive label, and: 

more likely attributable to other changes in how 

Lotronex is prescribed. For example, Lotronex can 

only be prescribed pursuant to a REMS (Risk 

Evaluation and Mitigation Strategies), which requires patients and doctors to complete a form 

that highlights the risks; Lotronex’s label now has 

“black box” warnings about the drug’s potential 

side effects and instructs doctors that it should 

only be prescribed to patients with severe IBS-D 

who have not responded to conventional therapy; 

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and its prior removal from the market caused doctors to be more vigilant with respect to complications. These cautionary steps are not claimed in 

the ’770 patent.

J.A. 13 (citations omitted). 

In 2009, Roxane filed an Abbreviated New Drug Application (“ANDA”) with the Food and Drug Administration (“FDA”) seeking approval to commercially market a 

generic version of Lotronex prior to the expiration of the 

’770 patent. In 2010, following the relisting in the Orange 

Book of the ’770 patent after its reexamination, Roxane 

submitted to the FDA a paragraph IV certification that 

the patent was non-infringed or invalid. 

In 2011, Prometheus filed suit against defendants alleging infringement of reexamined claims 5, 6, 10, 13, and 

14 of the ’770 patent based on the filing of the ANDA, an 

artificial act of infringement. See 35 U.S.C. § 271(e)(2). 

Prometheus alleged, inter alia, that Roxane’s label would

encourage doctors to prescribe alosetron in a manner that 

infringes the claims. Cipla, a defendant-appellee, manufactures the active pharmaceutical ingredient, alosetron 

hydrochloride, used in Roxane’s ANDA products. 

After a bench trial, the district court held that the asserted claims of the ’770 patent would have been obvious 

when considering the prior art and secondary considerations of nonobviousness. The district court found that “the 

elements of the ’770 patent were present in the prior art, 

and the differences between the prior art and the claims 

of the ’770 patent are insubstantial . . . [as] some of the 

prior art is virtually identical to the claimed inventions.” 

J.A. 44. The district court also found that the asserted 

claims of the ’770 patent would have been obvious in light 

of secondary considerations. The district court found that 

it was not unexpected for alosetron to exhibit greater 

efficacy in IBS-D patients, who have exhibited symptoms 

for greater than six months, and who have experienced at 

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least moderate pain. The district court held that the 

limited evidence at trial did not establish that there is an 

unexpected result of greater efficacy in women. The 

district court concluded that, “[a]t best, the claims at issue 

are a combination of known elements, combined in a 

known way, to produce expected results.” J.A. 47. As 

noted above, the district court found that the clinical 

improvement of reintroduced Lotronex was due to factors 

other than the ’770 patent. Moreover, the district court 

found that any commercial success of reintroduced Lotronex could not be attributed to the method claimed in 

the ’770 patent, but rather was due to Prometheus’ marketing and sales practices. Finally, the district court 

found that the method claimed in the ’770 patent did not 

satisfy a long-felt but unmet need. Thus, “[a]fter considering the knowledge of one of ordinary skill in the art, the 

scope and content of the prior art compared to the claimed 

invention, and the objective considerations of nonobviousness,” the district court held that “the claims of ’770 

patent, considered as a whole, are obvious.” J.A. 44. In the 

alternative, the district court held that the claims were 

invalid for obviousness-type double patenting in light of 

the claims of the ’800 patent.2 Given its invalidity rulings, 

the district court did not reach the issue of infringement. 

Prometheus appeals. We have jurisdiction pursuant to 

28 U.S.C. § 1295(a)(1). “On appeal from a bench trial, this 

court reviews the district court’s conclusions of law de 

novo and findings of fact for clear error.” MeadWestVaco 

2 The parties stipulated below that if the district 

court found independent claim 5 of the ’770 patent invalid 

due to, inter alia, obviousness or obviousness-type double 

patenting, then dependent claims 6, 11, and 12 would be 

invalid for the same reason. The same stipulation was 

entered with respect to independent claim 13 and dependent claims 14, 15, and 16. 

 

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Corp. v. Rexam Beauty & Closures, Inc., 731 F.3d 1258, 

1266 (Fed. Cir. 2013). Both obviousness and double patenting are questions of law based on underlying facts. 

Power Integrations v. Fairchild Semiconductor Int’l, Inc., 

711 F.3d 1348, 1355–56 (Fed. Cir. 2013) (obviousness); 

AbbVie Inc. v. Mathilda & Terence Kennedy Inst. of 

Rheumatology Tr., 764 F.3d 1366, 1372 (Fed. Cir. 2014)

(double patenting). 

DISCUSSION

We conclude that the asserted claims of the ’770 patent are invalid as obvious under 35 U.S.C. § 103. A 

patent would have been obvious “if the differences between the claimed invention and the prior art are such 

that the claimed invention as a whole would have been 

obvious before the effective filing date of the claimed 

invention to a person having ordinary skill in the art to 

which the claimed invention pertains.” Id. Obviousness is 

based on underlying factual findings, including: (1) the 

level of ordinary skill in the art; (2) the scope and content 

of the prior art; (3) the differences between the claims and 

the prior art; and (4) secondary considerations of nonobviousness, such as commercial success, long-felt but unmet 

needs, failure of others, and unexpected results. See KSR 

Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 406 (2007); Graham v. John Deere Co., 383 U.S. 1, 17–18 (1966). 

The primary prior art reference relied on by the district court was the ’800 patent. In addition to the ’800 

patent, the district court relied on a number of research 

publications that predated the October 7, 1997, priority 

date of the ’770 patent as prior art references. 

The district court determined, and the parties agreed, 

that the relevant person of ordinary skill in the art is a 

gastroenterologist with three years of experience. The 

district court also found, and Prometheus and defendants

agreed, that the claims of the ’770 patent recite a species 

of the genus method claimed in the ’800 prior art patent. 

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The ’800 patent claims the use of alosetron to treat patients suffering from IBS. The ’770 patent claims treating 

a subset of those IBS patients—those who (1) are women 

(2) with IBS-D (3) who have experienced symptoms for at 

least six months and (4) who have had moderate pain. 

While the parties dispute whether the claims of the ’770 

patent operate as exclusions defining patient categories 

that should not be treated with alosetron, we need not 

decide this question. Even treating the limitations of the 

’770 claims as exclusions, we conclude that before October 

7, 1997, it would have been obvious to a person of ordinary skill to treat those sub-species claimed here.

To be sure, “[i]t is well-settled that a narrow species 

can be non-obvious and patent eligible despite a patent on 

its genus.” AbbVie, 764 F.3d at 1379. An “earlier disclosure of a genus does not necessarily prevent patenting a 

species member of the genus.” Eli Lilly & Co. v. Bd. of 

Regents of Univ. of Wash., 334 F.3d 1264, 1270 (Fed. Cir. 

2003). 

The genus-species distinction may have particular 

relevance in the field of personalized medicine, where, for 

example, a particular treatment may be effective with 

respect to one subset of patients and ineffective (and even 

harmful) to another subset of patients. See, e.g., Margaret 

A. Hamburg & Francis S. Collins, The Path to Personalized Medicine, 363 New Eng. J. Med. 301, 301 (2010). 

Singling out a particular subset of patients for treatment 

(for example, patients with a particular gene) may reflect 

a new and useful invention that is patent eligible despite 

the existence of prior art or a prior art patent disclosing 

the treatment method to patients generally. An obviousness rejection likely would not be appropriate where the 

new patient subset displayed unexpected results. 

But that is not the situation here. In this case, the 

district court’s factual findings make clear that, at the 

time of the ’770 patent, it would have been obvious for a 

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person skilled in the art to have separately treated the 

limited subset claimed in the ’770 patent with alosetron, 

and that any unexpected results were attributable to 

factors exogenous to the ’770 patent. 

The first limitation of asserted claim 5 of the ’770 patent pertains to treating women. Prometheus argues that 

the district court erred in framing its inquiry as whether 

alosetron was administered to women with IBS-D in the 

prior art, rather than as whether it was obvious to focus 

on treating women rather than men. It is not disputed 

that it was well known in 1997 that a majority of IBS 

patients were women. As the district court found, it was

well known that “approximately 75% to 80% of IBS-D 

patients . . . have always been[] women.”3 J.A. 9. For 

example, the 1992 Thompson article reported that female 

IBS patients predominate in Western countries. Even if 

the claims should be read as focusing treatment on women, as Prometheus urges, the district court found the prior 

art taught precisely that. The Hysu study (1995) taught 

that females taking alosetron “had higher concentrations 

of alosetron in their blood and total amount of the drug 

absorbed compared to [males taking alosetron]” and the

district court found that “[t]his could reasonably suggest 

that women would have a greater response to the drug 

than men.” J.A. 25. At the time of the ’770 patent’s priority date, it would have been obvious to a person having 

ordinary skill in the art to treat women as a separate 

group of IBS patients. 

The next claim limitation in asserted claim 5 of the

’770 patent pertains to only treating patients suffering 

from IBS-D. The district court concluded that several pre3 The district court also found that “the limited evidence at trial . . . did not actually show that there is a 

greater efficacy [of alosetron] in women compared to 

men.” J.A. 40. 

 

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1997 publications taught that “alosetron and other 5-HT3 

antagonists slow colonic transit” and “taught that 

alosetron would be beneficial to prescribe to those with 

IBS-D and potentially harmful to those with IBS-C.” J.A. 

30. For instance, the district court found that the Talley 

study (1992) “taught that 5-HT3 antagonists slowed 

colonic transit and would be helpful in treating IBS-D and 

harmful in treating IBS-C.” J.A. 30. The district court 

found that the Sanger study (1996) taught that “5-HT3 

antagonists have the potential to treat diarrhea and 

recommends that they only be used with severe patients 

because of the potential to cause constipation.” J.A. 22. 

Prometheus’ basic objection is that the district court

simply relied on studies suggesting that the class of 5-HT3 

antagonist drugs, of which alosetron is a part, should be 

used to treat IBS-D and not IBS-C. While those studies 

were not focused on alosetron, but the class of drugs, 

there is ample testimony that a person of ordinary skill 

would have understood the studies as equally applicable 

to alosetron. See, e.g., J.A. 1747–51, 1760. We do not think 

the district court clearly erred in concluding that the 

lessons drawn with regard to a class of drugs (5-HT3 

antagonists) are applicable to a species (alosetron) within 

that class. 

Prometheus submits that the district court relied on 

references in which alosetron was administered to healthy 

volunteers instead of IBS patients, and that studies that 

did test alosetron in IBS patients suggested only that 

alosetron would be helpful in treating IBS generally. But 

the district court did not extrapolate those study results 

on its own; rather, this conclusion was informed by expert 

testimony. E.g., J.A. 1763. And the studies cited by Prometheus specifically state that alosetron delays colonic 

transfer. J.A. 866, 868. We see no clear error in the district court’s conclusion that it would have been obvious to 

a person of ordinary skill in the art reading the claims of 

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the ’800 patent and the prior art to limit treatment to 

patients suffering from IBS-D. 

As to the claim limitation requiring symptoms for “at 

least six months” before administering alosetron, J.A. 71,

it was common practice at the time of the ’800 patent to 

determine whether a patient had suffered symptoms for 

longer than six months. Dr. Lucak, Prometheus’ own 

expert, testified that the benefit of the six-month limitation was having “a greater confidence in the diagnosis.” 

J.A. 1372. Pre-October 1997 studies suggest using a sixmonth standard for the diagnosis of IBS. The so-called 

Manning criteria (named after a 1978 study) call for 

symptoms lasting at least 6 months. The Kruis study 

(1984) “specifically teaches using the existence of symptoms for over two years as a basis for increasing the 

confidence in a diagnosis of IBS.” J.A. 20. The Francis 

paper (February 1997) “discloses the use of a 6-month 

duration criterion to reduce the margin of error” in diagnosing IBS. J.A. 21. In fact, the district court found that 

“most IBS-D patients will have symptoms for more than 6 

months” and “it has always been true that waiting a 

longer period of time to observe a patient’s symptoms 

decreases the likelihood of a false positive.” J.A. 9. In 

1997, it would have been obvious for a person having skill 

in the art to treat patients displaying IBS symptoms for 

more than six months as a separate group. Although 

Prometheus argues that three months was the diagnostic 

standard in 1997, the district court’s finding as to the sixmonth standard is amply supported by the record and is 

not clearly erroneous. 

Regarding the limitation directed to at least moderate 

pain, at the time the ’800 patent issued, it was wellknown to evaluate patients for pain in order to diagnose 

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IBS. The Rome criteria4 for diagnosing IBS are standard 

criteria used to diagnose IBS and inquire into pain and its 

severity. Pain is in fact a main symptom of IBS (along 

with diarrhea and constipation). The Manning study 

(1978) states that “[a]bdominal pain, constipation, and 

diarrhoea are the main symptoms [of IBS].” J.A. 822. The 

Kruis study (1984) defines IBS as “a cluster of chronic 

symptoms that include abdominal pain.” J.A. 815. The 

Steadman study (1992) states that “[c]linically, patients 

with IBS experience fluctuations in bowel habit, abdominal pain, and other symptoms.” J.A. 839. And the 

Talley study (1992) states that “[p]atients with irritable 

bowel syndrome typically have a chronic but erratic 

disturbance of defecation and associated abdominal pain.”

J.A. 855. In the Manning study, all but one of the thirtytwo patients diagnosed with IBS had pain. In the Kruis 

study, 96% of patients diagnosed with IBS had abdominal 

pain. 

Prometheus concedes that doctors commonly assess 

IBS patients for pain, and does not dispute that it would 

have been obvious to use alosetron to treat pain. Instead, 

Prometheus argues that it would not have been obvious to 

administer alosetron only to patients suffering from at 

least moderate pain. But as the district court noted, 

Prometheus’ own expert, Dr. Lembo, testified that because a candidate for Lotronex was a patient with severe 

IBS, “it’s pretty obvious that [a physician] will assess for 

at least moderate pain.” J.A. 1303. The expert testimony 

also shows that a person of ordinary skill would have 

adopted a conservative approach in treating IBS patients, 

and avoided drug intervention for a patient with mild 

symptoms. The district court did not err in finding that it 

would have been obvious for a person having skill in the 

4 According to the district court, the Rome criteria 

are described in the Thompson reference (1992). 

 

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art to single out IBS patients displaying at least moderate 

pain. 

Relevant here is our decision in AbbVie. There, a prior 

art genus patent claimed a method of co-administering 

two drugs to treat rheumatoid arthritis. AbbVie, 764 F.3d. 

at 1378–79. The later patent contained a species claim 

limiting the prior art genus to a more specific patient 

group: individuals with “active disease.” AbbVie, 764 F.3d 

at 1378–79. Borrowing from “the law of obviousness 

generally,” we noted that “if the later expiring patent is 

merely an obvious variation of an invention disclosed and 

claimed in the reference patent, the later expiring patent 

is invalid.” Id. at 1378–79 (quotation marks and citation 

omitted). This case is analogous. Here, it would have been 

obvious for a person having ordinary skill in the art 

reading the ’800 patent to treat female patients with IBSD who had symptoms for at least six months and who had 

experienced at least moderate pain. As discussed above, 

these limitations are directed to a known type of IBS, to 

treating the gender that predominantly experiences IBS, 

to treating patients with a characteristic that is always or 

almost always evaluated in establishing IBS, and to 

assessing symptoms for a duration of time that was 

common in diagnosing patients with IBS. 

While this case, unlike AbbVie, involves a few different variables, the district court found that it would have 

been obvious to combine the teachings of the prior art in 

the form of the ’770 patent. The record contains abundant 

evidence that there was a limited number of known 

parameters and it would have been obvious to combine 

the teachings as to each parameter. 

Finally, the district court carefully considered secondary considerations of nonobviousness as required by our 

precedent, In re Cyclobenzaprine Hydrochloride ExtendedRelease Capsule Patent Litig., 676 F.3d 1063, 1079 (Fed. 

Cir. 2012), and found that the secondary considerations 

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did not support a conclusion of nonobviousness. Prometheus first argued that the reintroduced Lotronex’s commercial success can be attributed directly to the ’770 

patent, noting that from 2003 to 2007, net sales of Lotronex increased each year and the original patent owner 

was able to sell the Lotronex franchise to Prometheus for 

$120 million. The district court recognized that sales 

revenue of Lotronex increased from the time of its reintroduction into the market in 2002 until 2012, but observed that “by 2011, there were just over 42,000 

prescriptions of Lotronex written per year for about 

10,000 patients. This was only about 2,100 more prescriptions compared to its peak year of sales with [the original 

patent owner].” J.A. 14. The district court determined 

that the ’770 patent was not responsible for the commercial success of reintroduced Lotronex, but instead that the 

evidence showed “the growth in revenue [since Lotronex’s 

reintroduction into the market] is due to Prometheus’s 

actions in marketing, increasing the price of Lotronex, 

and introducing a series of rebates to stimulate sales of 

the drug, rather than from the treatment method claimed 

in the ’770 patent.” J.A. 15. The district court was not 

persuaded by Prometheus’ evidence relating the commercial success of Lotronex to the ’770 patent, because Prometheus did not submit an analysis that would show the 

commercial success for the ’770 patent on its own merits, 

“control[ling] for other variables and separat[ing] the 

treatment instructions from the drug compound and the 

method in the ’800 patent that already existed, nor any 

analysis to control for other changing variables, such as 

marketing campaigns, new drug warnings, pricing changes, etc.” J.A. 41. 

Prometheus argues that the district court erred by 

placing the burden of proof on Prometheus to demonstrate 

the nexus between Lotronex’s commercial success and the 

’770 patent. The party challenging the validity of a patent 

always has the burden of persuading the trial court of 

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invalidity. Microsoft Corp. v. i4i Ltd. P’ship, 131 S. Ct. 

2238, 2242–43 (2011). However, “once a challenger has 

presented a prima facie case of invalidity, the patentee 

has the burden of going forward with rebuttal evidence. 

But, all that means is that even though a patentee never 

must submit evidence to support a conclusion by a judge 

or jury that a patent remains valid, once a challenger 

introduces evidence that might lead to a conclusion of 

invalidity—what we call a prima facie case—the patentee 

would be well advised to introduce evidence sufficient to 

rebut that of the challenger.” Pfizer, Inc. v. Apotex, Inc., 

480 F.3d 1348, 1360 (Fed. Cir. 2007) (quotation marks 

and citations omitted). 

We do not find that the district court improperly 

shifted the burden of proof as to commercial success. 

Although the district court described and rejected Prometheus’ attempts to “prove commercial success of Lotronex 

and that [Lotronex] fulfilled a long-felt but unmet need,” 

J.A. 41, we understand those statements to be in reference to Prometheus’ burden of production. We have found 

that similar imperfect language is not grounds for reversal. Optivus Tech., Inc. v. Ion Beam Applications S.A., 469 

F.3d 978, 991 (Fed. Cir. 2006) (citation and quotation 

marks omitted) (affirming the district court’s holding of 

invalidity despite the court’s statement that “[t]here is no 

indication that the [motivation to combine] was nonobvious,” because the district court’s opinion as a whole 

indicated it “correctly allocated the burden of proof”). The 

district court opinion clearly states the correct standard in 

finding the claims of the ’770 obvious by clear and convincing evidence. J.A. 44.

Prometheus next argued that the ’770 patent met a

long-felt but unmet need and created an unexpected 

result by improving the safety and risk-benefit profiles of 

alosetron. The district court rejected these contentions. 

The district court was not persuaded that any long-felt 

need was satisfied by the instructions claimed in the ’770 

Case: 14-1635 Document: 10-2 Page: 16 Filed: 11/10/2015
PROMETHEUS LABORATORIES, INC. v. ROXANE LABORATORIES,

INC. 

17

patent “as distinguished from . . . the drug itself, which is 

covered by the ’800 patent.” J.A. 41. It found that “it is 

clear that many of the benefits touted by Prometheus 

were attributable to the compound itself rather than the 

’770 patent’s method of treatment.” J.A. 16. The district 

court further found that “any praise or reduction in the 

severity of side effects is more likely attributable to elements from the ’800 patent, the new safety precautions, 

heightened awareness, and warnings issued after Lotronex’s reintroduction.” J.A. 44. We find no clear error in 

the district court’s factual conclusions in this respect. 

We affirm the district court’s holding that the challenged claims of the ’770 patent would have been obvious 

over the ’800 patent and other prior art. 

AFFIRMED

COSTS

Costs to appellees. 

Case: 14-1635 Document: 10-2 Page: 17 Filed: 11/10/2015