Document ID: s3://data.kl3m.ai/documents/govinfo/USCOURTS/USCOURTS-ca13-16-01146/USCOURTS-ca13-16-01146-0/pdf.json

Parties Involved:
Actavis Laboratories UT, Inc.
Appellant
Endo Pharmaceuticals Inc.
Appellee
Strakan International S.a.r.l.
Appellee

Document Text:

NOTE: This disposition is nonprecedential. 

United States Court of Appeals 

for the Federal Circuit ______________________ 

ENDO PHARMACEUTICALS INC., STRAKAN 

INTERNATIONAL S.A.R.L.,

Plaintiffs-Appellees

v.

ACTAVIS LABORATORIES UT, INC.,

Defendant-Appellant

______________________ 

2016-1146

______________________ 

Appeal from the United States District Court for the 

Eastern District of Texas in No. 2:13-cv-00192-JRG, 

Judge J. Rodney Gilstrap.

______________________ 

Decided: October 14, 2016

______________________ 

BARRY P. GOLOB, Cozen O'Connor, Washington, DC, 

argued for plaintiffs-appellees. Also represented by KERRY 

BRENDAN MCTIGUE, WILLIAM BLAKE COBLENTZ, AARON S.

LUKAS, DONALD R. MCPHAIL. 

GEORGE C. LOMBARDI, Winston & Strawn LLP, Chicago, IL, argued for defendant-appellant. Also represented 

by MICHAEL KEENAN NUTTER, IVAN MICHAEL POULLAOS,

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KURT A. MATHAS, JOHN REYNOLDS MCNAIR; GEOFFREY P.

EATON, Washington, DC.

______________________ 

Before MOORE, TARANTO, and HUGHES, Circuit Judges.

TARANTO, Circuit Judge.

Strakan International S.à r.L. owns U.S. Patent Nos. 

6,579,865 (issued in 2003) and 6,319,913 (issued in 2001), 

with priority dating to 1997. Endo Pharmaceuticals Inc. 

is the exclusive United States licensee of those patents. 

In December 2010, Endo obtained final approval from the 

Food and Drug Administration to market its testosterone 

gel product, called Fortesta®, which is used by applying it 

to the skin to deliver testosterone transdermally. 

In 2013, Watson Laboratories filed an Abbreviated 

New Drug Application with the FDA, seeking to market a 

generic version of Fortesta. Upon receiving Watson’s 

notification under 21 U.S.C. § 355(j)(2)(A)(vii)(IV), Endo 

and Strakan (collectively, Endo) filed suit against Watson 

under 35 U.S.C. § 271(e)(2), alleging that Watson’s marketing of its proposed generic product would infringe 

claims 1, 3, 4, 6, 11, 18, 22, and 28 of the ’865 patent and 

claims 19 and 20 of the ’913 patent. Soon after, Watson 

transferred its relevant interests to Actavis Laboratories

UT, Inc., which was substituted for Watson in this case. 

For convenience, we refer to Actavis as if it, rather than 

Watson, had always been the named defendant and had 

filed the application for FDA approval of a generic version 

of Fortesta. 

In this action, Actavis alleged that all of the Endoasserted claims of both patents are invalid based on 

anticipation and obviousness. Actavis also alleged that 

the product described in its FDA application does not 

meet a limitation of claims 1, 3, 4, 6, 11, 18, and 22 of the 

’865 patent and, therefore, its marketing would not infringe those claims. Actavis stipulated to infringement of 

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the other three claims asserted by Endo. After a bench 

trial, the district court ruled that the asserted patent

claims are not invalid for either anticipation, J.A. 30–35, 

or obviousness, J.A. 46–54, and that Actavis’s marketing 

of its product would infringe all of the asserted claims, 

J.A. 65–68. 

Actavis appeals the district court’s decision regarding 

obviousness and infringement. We have jurisdiction 

under 28 U.S.C. § 1295(a)(1). We affirm.

I 

The claims at issue involve combinations of testosterone (or a derivative) and penetration-enhancing systems designed to allow testosterone to enter the body 

through the skin. Even before the 1997 priority date for 

the patents here, there was interest in producing a successful transdermal delivery system for testosterone 

because “there had been issues with delivery of testosterone through pill form (e.g. testosterone was largely 

destroyed by the digestive system) and through injections 

(e.g. patient compliance and dosage issues).” J.A. 46; see 

J.A. 539–42. In 1993 and 1995, the FDA approved transdermal testosterone patches—Testoderm and Androderm. 

J.A. 507. The district court found that patients found the

first problematic because of the location where the patch 

had to be worn and that the second “used a penetration 

enhancing system,” in order for the testosterone to cross 

the outer skin barrier in less sensitive body locations, “but 

had significant side effects of irritation.” J.A. 10–11. The 

’913 and ’865 patents resulted from attempts to find a 

combination of a penetration enhancer and testosterone 

that was effective in delivering the testosterone while 

keeping irritation to acceptable levels. The claims at 

issue, as relevant here, claim combinations of specified 

penetration enhancers (sometimes in specified concentrations) with specified concentrations of testosterone or its 

derivatives.

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The makeup of the claimed penetration enhancers differs in certain respects from claim to claim, though much 

remains constant. The claim-by-claim variations are 

significant for the obviousness analysis, but not for the 

usual reason that the challenger argues for invalidity on a 

claim-by-claim basis. Here, Actavis makes no argument 

that some claims are invalid even if others stand. Presumably reflecting the content of its generic-Fortesta 

application to the FDA, Actavis makes a single, all-ornothing, across-the-board obviousness argument: as 

Actavis argues its case, if any one of the asserted claims 

survives, all do. As a result, the prior-art analysis called 

for by Actavis’s approach properly considers differences 

between prior art and any of the asserted claims. 

Oleic acid is required in all of the claimed penetration 

enhancers, as are a glycol and an alcohol, but the specific 

alcohol and glycol used varies in the claims. Claim 1 of 

the ’865 patent claims a composition “consisting essentially of” (a) testosterone (or a derivative) having a concentration of about 0.1% to about 2% and (b) a penetration 

enhancing system consisting of oleic acid, a C1-C4 alcohol, 

and a glycol. ’865 patent, col. 14, lines 34–44. C1-C4

alcohols include ethanol, isopropanol, and propanol. J.A. 

424. The claimed composition also includes a gelling 

agent. 

Claims 3, 4, 6, 11, 18, and 22 of the ’865 patent depend on claim 1. Claim 3 limits the active agent to testosterone (rather than a derivative). Claim 4 limits the 

concentration of testosterone to a range of “about 1% to 

about 2%” (only a part of the claim 1 range). Claim 6 

limits the concentration of oleic acid to a range of “about 

0.1% to about 5%.” Claim 11 limits the “C1-C4 alcohol” to 

a mixture of ethanol and isopropanol. Claim 18 limits the 

“glycol” to propylene glycol. Claim 22 limits the composition to one in which the claim 1 “glycol is present from 

about 30% to about 40%” of the composition’s weight. 

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Independent claim 28 is similar to claim 1 but also requires “inert carriers.”

As to the ’913 patent, independent claim 19 claims a 

method of topically administering a composition “comprising” (a) testosterone at a concentration “of about 0.1% to

about 2%” and (b) “a penetration-enhancing system 

comprising: (i) oleic acid; (ii) a C3 alcohol; and (iii) propylene glycol.” ’913 patent, col. 15, line 31, through col. 16, 

line 4. C3 alcohols include propanol and isopropanol. J.A. 

434. Claim 20 depends on claim 19 and differs only in 

that it includes specific concentrations of testosterone. 

’913 patent, col. 16, lines 5–9. 

II

Having decided not to appeal the district court’s finding of no anticipation, Actavis no longer disputes the 

novelty of the claimed compositions (’865 patent) and 

methods (’913 patent). It argues, however, that it proved 

by clear and convincing evidence that the inventions 

defined by all of the asserted claims would have been 

obvious in 1997. It does so by pointing to multiple pieces 

of prior art. 

The evidence and arguments presented to us permit 

findings that, for each reference, there is a gap between 

its teaching and at least one of the asserted claims—

something in at least one claim not disclosed in the reference. That is significant because of Actavis’s all-ornothing approach to arguing obviousness. We describe 

examples of the gaps here, before discussing, in the next 

section, the findings and evidence regarding whether a 

relevant skilled artisan would have bridged those gaps. 

Cooper ’872. This reference teaches the delivery of 

corticosteroids, not testosterone (which is not a corticosteroid). The district court found that the reference 

teaches that an alcohol such as ethanol should be used, 

but not as part of the penetration enhancer, only as a 

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solvent. J.A. 32. The court relied in part on the reference’s statement that the alcohol, “if used, should not 

significantly interfere with the penetration action of the 

binary combination” of “a diol and a cell-envelope disordering compound.” J.A. 578, 577, quoted at J.A. 20, 22. 

The court also found that there is no teaching of the 

combination of isopropanol and ethanol required by claim 

11 of the ’865 patent. J.A. 32. 

Cooper ’934. The advance described and claimed in 

this reference is a penetration-enhancing vehicle containing a “binary” mixture of 1-dodecylazacycloheptan-2-one 

(azone) and either “a C3-C4 diol, such as propylene glycol, 

or a second N-substituted azacycloalkyl-2-one.” J.A. 590. 

Although there was evidence that azone and oleic acid 

have some similar properties, it is undisputed that they 

are not the same compound. The points made above 

about Cooper ’872, concerning the role of relevant alcohols 

and the absence of an isopropanol-ethanol combination,

apply as well to Cooper ’934. J.A. 34. The district court 

found that Cooper ’934 does not specifically identify 

testosterone, including in any of its Examples, which 

discuss a significant number of differently constituted 

penetration vehicles. J.A. 33; J.A. 600–05. The court 

noted that Cooper ’934 does include “male sex hormones” 

among the potential active ingredients listed in a multipage, unelaborated recitation of conditions and active 

ingredients—which the district court found “enumerates 

‘without limitation’ a list of what appears to be every 

condition or ailment one might seek to apply a pharmaceutical agent to.” J.A. 33; see J.A. 28; J.A. 505 (testifying to Cooper ’934’s “very long or comprehensive list of 

different drug classes, and . . . pretty much every known 

drug within those classes at the time of the invention”). 

Patel ’970. This reference mentions testosterone 

among many other potential active ingredients, but 

Actavis has not pointed to evidence showing that it discloses the three-part penetration enhancers of all of the 

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asserted claims here, as required for Actavis’s argument. 

The penetration-enhancing vehicle of the Patel ’970

patent, as described in the Abstract, has three components: (i) a cell-disordering compound such as oleic acid; 

(ii) specific lower alkanols, namely, ethanol, propanol, 

isopropanol, or mixtures of them; and (iii) an optional 

“inert diluent.” J.A. 615. But Actavis has cited to no 

evidence that the patent discloses a three-part penetration enhancer of oleic acid, a C1-C4 alcohol such as ethanol, and propylene glycol, as required by claim 18 of the 

’865 patent and claims 19 and 20 of the ’913 patent. 

Actavis points to certain testimony of its expert, Dr. 

Potts, but neither that nor other cited testimony says that 

Patel ’970 teaches the three-part enhancer with propylene 

glycol. Thus, Dr. Potts noted that the Abstract of Patel 

’970 discloses a three-part composition including oleic acid 

and ethanol and, also, polypropylene glycol (PPG) and 

polyethylene glycol (PEG)—which Patel ’970 identifies as 

among the “inert diluents” required by component (iii). 

J.A. 431; see J.A. 615, 624, 625. Dr. Potts noted that PPG 

and PEG are “glycols” under the ’865 and ’913 patents, J.A. 431, but he did not say, and Actavis has identified no testimony stating, that the disclosed PPG or PEG 

is “propylene glycol,” as required by the above-identified 

claims. When Patel ’970 discusses propylene glycol (PG), 

it is not as an “inert diluent” in the claimed compound, as 

with PPG and PEG, but only in comparing its own combination of oleic acid and component (ii)’s lower alkanols 

favorably, with respect to skin irritation, to combinations 

of oleic acid and PG. J.A. 621 (“[T]his combination of oleic 

acid and propylene glycol causes severe skin irritation. . . . 

[T]he combinations of 80% glycerol dioleate and/or oleic 

acid with 20% ethanol provide penetration enhancement 

similar to that obtained with propylene glycol and oleic 

acid and, as will subsequently be demonstrated, does not 

possess the skin irritation properties of propylene glycololeic acid combinations.”); see J.A. 615, 617, 618, 624, 625.

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Patel ’190. This reference discloses a combination of 

testosterone, glycerin (which the ’913 and ’865 patents

define as a glycol), oleic acid, and ethanol. J.A. 613. But 

Actavis points to no such combination that does not also 

include methyl laurate, and it neither identifies evidence, 

nor even argues, that Patel ’190 discloses a combination 

“consisting essentially” of glycerin, oleic acid, and ethanol, 

i.e., with no other material components. J.A. 612. Actavis 

likewise points to no evidence that Patel ’190 discloses the 

use of propylene glycol, as required by claim 18 of the ’865 

patent and claims 19 and 20 of the ’913 patent, or the use 

of an ethanol-isopropanol mixture, as required by claim 

11 of the ’865 patent.

Aungst. Both the 1989 and 1995 Aungst references 

teach the combination of fatty acids, such as oleic acid, 

with propylene glycol, but Actavis does not show that they 

disclose the combination of those ingredients with an 

alcohol. See J.A. 50. And while the 1995 Aungst reference mentions testosterone with a different fatty acid and 

propylene glycol, Actavis does not show that either reference discusses the use of testosterone with an oleic-acid 

penetration-enhancing system. See J.A. 1333–34, 1357. 

Other References. The Santus reference, not specifically addressed by the district court, discusses the use of 

oleic acid, propylene glycol, and “ethyl alcohol,” another 

name for ethanol, as one example among many different 

penetration enhancers shown in patents. J.A. 750. 

Actavis identifies in Santus no mention of testosterone, 

for this or any other enhancer, or of a mixture of ethanol 

and isopropanol. The district court found, and it is not 

disputed, that the Francoeur and Touitou references do 

not disclose the use of testosterone. J.A. 51. Cormier 

teaches the use of cytotoxic agents such as 5-flourouracil 

as the active ingredient, and the district court found no 

evidence that testosterone is a cytotoxic agent or substantially similar to one. J.A. 51. And Actavis does not 

demonstrate, or even clearly argue, that any of those 

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references discloses the subject matter of all of the Endoasserted claims—not just some claimed combinations, not 

just elements of claimed combinations, but all the specific 

combinations claimed, together with “consisting essentially of” for the ’865 patent. In particular, the Actavis-cited 

testimony of Endo’s expert is fairly read as making only 

more limited points than that. See J.A. 519–20, 522–25. 

III

The district court concluded that a relevant skilled 

artisan would not have considered it obvious to bridge the 

gaps that separate the prior art from (at least one of) the 

claimed compositions and methods. The only relevant 

problem identified in the record was balancing delivery 

effectiveness with acceptable irritation for testosterone. 

J.A. 36. And while it would have been obvious to pursue a 

transdermal delivery mechanism for testosterone, and to 

consider using a penetration enhancer, the district court 

determined, it would not have been “obvious how to select 

and configure a particular penetration enhancer to combine with a particular level of testosterone.” J.A. 47–48. 

Actavis “has not established that it was obvious that a 

person of ordinary skill in the art, which in this case is a 

highly and specifically educated person, would have, 

considering the art of the time, including the art presented to the Court, found the inventions of the patents-insuit to be obvious either alone or in combinations of the 

numerous various references [Actavis] puts forward in the 

specific way that would yield the inventions of the patents-in-suit.” J.A. 52–53.

Actavis has not presented a persuasive showing of 

prejudicial factual or legal error in the district court’s 

determination. Notably, sufficient evidence supports the 

finding that “there were tremendous numbers of penetration enhancers that were known in the relevant time 

period and that one of ordinary skill, in this case, could 

have combined with testosterone.” J.A. 52; see, e.g., J.A. 

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40, 47; J.A. 441–43, 739–58, 1606–10.1 So too for the 

finding that the desired balance of effects varies “unpredictabl[y]” according to the “specific” makeup of the 

particular enhancer and the choice of active ingredient 

with which it was to be combined. J.A. 33; see, e.g., J.A.

501 (quoted at J.A. 16) (“quite difficult to predict”), 31, 33 

(noting “the extensive record describing how specific and 

unpredictable mixtures are in the context of transdermal 

agents”), 36, 47, 52, 1292–96, 1333. And it is relevant, 

too, in determining what specific course a relevant skilled 

artisan would have had reason to pursue, among a large 

number of possibilities, that some prior art taught that a 

combination of oleic acid and propylene glycol could cause 

“severe skin irritation” whereas certain other enhancers 

would not. J.A. 621, 1355–57.2

That evidence is sufficient to uphold the district 

court’s determination against the arguments Actavis has 

presented for reversal, and we need not go on to review 

 

1 Just as to what is reflected in patents (not other 

publications), the Santus article, from 1993, reviews more 

than 150 enhancer patents, categorizing them into twelve 

groups of different types of enhancers, each type covering 

different individual enhancers—“(a) alcohol enhancers; (b) 

amide enhancers; (c) amino acid enhancers; (d) azone and 

azone-like enhancers; (e) essential oil enhancers; (f) fatty 

acid and fatty acid ester enhancers; (g) Macrocyclic enhancers; (h) phospholipid and phosphate enhancers; (i) 2-

pyrrolidone derivatives; (j) soft penetration enhancers; (k) 

sulphoxide enhancers; (l) miscellaneous enhancers.” J.A. 

741; see J.A. 839–51.

2 When Actavis argues that the irritability of the 

claimed composition is irrelevant because Fortesta is the 

most irritating product on the market, it is impermissibly 

comparing the composition’s irritability to that of products that entered the market after the priority date. 

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certain other determinations made by the district court

that, if sound, could only further weaken, not aid, Actavis’s argument for obviousness. Thus, we need not 

consider whether the prior art’s discussion of irritation 

effects of certain enhancer compositions, beyond supporting the finding of insufficient reason of a relevant skilled 

artisan to pursue the combinations at issue here, actually 

“teach away” from a path such an artisan otherwise would 

pursue with the required expectation of success. Nor need 

we consider whether any otherwise-persuasive showing of 

obviousness could be overcome in this case by objective 

indicia such as unexpected results, long-felt need, or 

others’ failure to arrive at the inventions.

 Finally, we see no basis for reversing the district 

court’s judgment in the court’s statement that “the effectiveness and side effects of using a combination of a 

particular penetration enhancer to deliver a particular 

compound were not readily predictable.” J.A. 47. Unlike 

Actavis, we do not read that statement as applying an 

improperly high threshold for proving obviousness—ready 

predictability rather than a reasonable expectation of 

success—where the requisite motivation to combine is 

otherwise proved. Here, we read the district court’s 

opinion as finding no such motivation to combine, a 

question to which the sheer number of possible combinations and degree of uncertainty are both relevant.

Moreover, the district court recited the expert testimony that the relevant effects are “quite difficult to 

predict,” J.A. 18 (internal quotation marks omitted), and 

that “a person of ordinary skill would not have expected 

success using the penetration enhancing system,” J.A. 36. 

And far from requiring ready predictability, the passage 

Actavis quotes immediately goes on to explain that “experiments were depended upon for the characterization of 

the properties of such a combination” and to credit the 

evidence “that extensive work, including a progression of 

studies, was generally required to characterize such a 

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combination on human subjects.” J.A. 47. In the end, we 

do not read the district court’s passage as raising the 

threshold for proof of obviousness the way Actavis alleges. 

We read the passage as addressing and rejecting one of 

Actavis’s contentions in the very terms of “predictable 

results” and “predictable use” from KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 417 (2007), that Actavis itself 

invoked. Watson’s Proposed Findings of Fact and Conclusions of Law 74–75, ECF No. 130. 

IV

Actavis also argues that the district court’s finding of

infringement was clearly erroneous as to all of the asserted claims of the ’865 patent except claim 28. Its theory is 

that in its accused product water plays a material role as 

part of the enhancer, so that its penetration enhancer

does not “consist[ ] essentially” of the claim-listed components. Actavis agreed at oral argument in this court that 

the infringement issue need not be decided if we affirm 

the district court’s validity determination, because Actavis stipulated to infringement of claim 28 of the ’865 

patent and claims 19 and 20 of the ’913 patent, and it 

needs to succeed on all claims to be permitted to market 

its generic product. Oral Arg. at 2:00–2:55. In any event, 

we do not see clear error in the district court’s finding 

that Endo proved infringement. Actavis, in its filings 

with the FDA, listed only one function for water in its 

product—serving as a solvent—even while it listed dual 

solvent/enhancer functions for other components. It is a 

legitimate inference in the circumstances here that water 

in Actavis’s product does not play a material role in the 

penetration enhancer. See J.A. 17, 66–67. Therefore, we 

refuse to disturb the court’s infringement finding. 

CONCLUSION

For the foregoing reasons, we affirm the judgment of 

the district court. 

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AFFIRMED

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