United States Court of Appeals 

for the Federal Circuit ______________________ 

ANACOR PHARMACEUTICALS, INC.,

Appellant

v.

ANDREI IANCU, UNDER SECRETARY OF 

COMMERCE FOR INTELLECTUAL PROPERTY 

AND DIRECTOR OF THE UNITED STATES 

PATENT AND TRADEMARK OFFICE,

Intervenor

______________________ 

2017-1947

______________________ 

Appeal from the United States Patent and Trademark 

Office, Patent Trial and Appeal Board in No. IPR2015-

01776.

______________________ 

Decided: May 14, 2018 

______________________ 

 MICHAEL N. KENNEDY, Covington & Burling LLP, 

Washington, DC, argued for appellant. Also represented 

by EVAN SMITH KRYGOWSKI, ANDREA GAY REISTER. 

 SARAH E. CRAVEN, Office of the Solicitor, United 

States Patent and Trademark Office, Alexandria, VA, 

argued for intervenor. Also represented by NATHAN K.

KELLEY, THOMAS W. KRAUSE, LORE A. UNT. 
2 ANACOR PHARMACEUTICALS, INC. v. IANCU

 JAMES CARMICHAEL, Carmichael IP, PLLC, Tysons, 

VA, for amicus curiae FlatWing Pharmaceuticals, LLC.

______________________ 

Before REYNA, BRYSON, and STOLL, Circuit Judges.

BRYSON, Circuit Judge. 

This is an appeal from a decision of the Patent Trial 

and Appeal Board in an inter partes review proceeding. 

The Board held all of the claims of a patent owned by 

Anacor Pharmaceuticals, Inc., to be unpatentable for 

obviousness. Anacor has appealed with respect to only 

one of the rejected claims. We affirm.

I 

A 

The patent in suit, U.S. Patent No. 7,582,621 (“the 

’621 patent”) is entitled “Boron-containing Small Molecules.” The patent is directed to the use of 1,3-dihydro-5-

fluoro-1-hydroxy-2, 1-benzoxaborole, also known as 

tavaborole, to treat fungal infections. In particular, the 

patent teaches the use of tavaborole as a topical treatment for fungal infections that develop under fingernails 

and toenails. When applied topically, tavaborole can 

penetrate the nail plate and treat the underlying fungal 

infection.

The ’621 patent teaches that tavaborole can be used to 

treat a fungal infection known as onychomycosis, which is 

a disease of the nail that is responsible for approximately 

half of all nail disorders in humans. ’621 patent, col. 28, 

ll. 18–20. Onychomycosis can be caused by a variety of

yeasts and molds, but it is most frequently caused by 

dermatophytes, a group of fungi that includes the genus

Trichophyton and the species Trichophyton rubrum (“T. 

rubrum”). Id., col. 28, ll. 23–27. Onychomycosis is also 
ANACOR PHARMACEUTICALS, INC. v. IANCU 3

sometimes caused by another fungus, a yeast known as 

Candida albicans (“C. albicans”).1 

The single claim of the ’621 patent that is at issue in 

this appeal is claim 6, which depends from claims 1 and 4. 

The three related claims recite as follows:

1. A method of treating an infection in an animal, 

said method comprising administering to the animal a therapeutically effective amount of 1,3-

dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole, or a 

pharmaceutically acceptable salt thereof, sufficient to treat said infection.

4. The method of claim 1, wherein said infection 

is onychomycosis.

6. The method of claim 4, wherein said onychomycosis is tinea unguium.

Id., col. 67, ll. 34–38; id., col. 68, ll. 20–21; id., col. 68, ll. 

25–26. Tinea unguium is the term for onychomycosis that 

is caused by a dermatophyte. Id., col. 28, ll. 24–25. 

B 

In 2015, the Coalition for Affordable Drugs X LLC 

filed a petition requesting inter partes review of all 12 

claims of the ’621 patent. The Board instituted review

and found that the claims would have been obvious in 

light of the combination of Int’l Pat. Appl. No. 

PCT/GB95/01206 (“Austin”) and U.S. Pat. Appl. No. 

10/077,521 (“Brehove”). Both Austin and Brehove teach 

the use of boron heterocycles as antifungal agents that 

inhibit C. albicans, among other fungi. Boron heterocy-

 

1 The evidence before the Board showed that dermatophytes are responsible for approximately 90 percent

of all cases of onychomycosis, while C. albicans is responsible for approximately five percent of all such cases.
4 ANACOR PHARMACEUTICALS, INC. v. IANCU

cles are organic compounds that contain both boron and 

carbon in a ring structure.2 

Austin teaches the use of oxaboroles—boron heterocycles that include a five-member ring containing three 

carbon atoms, one oxygen atom, and one boron atom—as 

fungicides. Austin discloses tavaborole as one of a small 

group of oxaboroles that were tested for antifungal activity and teaches that tavaborole is a highly effective agent 

that inhibits a variety of fungi, including C. albicans. 

 Brehove teaches the use of boron heterocycles in a 

topical composition to treat onychomycosis. Specifically, 

two dioxaborinanes—boron heterocycles that include a 

six-member ring containing three carbon atoms, two 

oxygen atoms, and one boron atom—were determined 

through in vitro testing to have powerful potency against

C. albicans. Brehove also reports the results of five in 

vivo tests, each involving a single individual, in which the 

individual’s onychomycosis was successfully treated by 

the topical application of Brehove’s two dioxaborinanes. 

Brehove does not identify whether each individual’s 

onychomycosis was caused by C. albicans or some other 

microorganism, such as a dermatophyte.

The petition posited that the combination of Austin 

and Brehove would have rendered all the claims of the 

 

2 The Board also instituted review on a second 

ground, the combination of Austin with Int’l Pat. Appl. 

No. PCT/US02/23252 (“Freeman”). The Board found that 

all the claims of the ’621 patent were unpatentable for 

obviousness in light of that combination. Because we 

affirm the Board’s conclusion that claim 6 would have 

been obvious in light of the combination of Austin and 

Brehove, we need not address Anacor’s additional arguments on appeal challenging the Board’s decision on the 

second ground.
ANACOR PHARMACEUTICALS, INC. v. IANCU 5

’621 patent obvious. According to the petition, a person of 

ordinary skill would have had a reason to combine Austin 

and Brehove because the compounds in both references 

are boron heterocycles that are effective as fungicides 

and, in particular, in inhibiting C. albicans. The petition 

argued that a skilled artisan would have expected that 

those compounds would share other fungicidal activity, 

such as treating onychomycosis caused by dermatophytes. 

In addressing claim 6, the petition referred to Brehove’s 

in vivo tests, which reported the successful use of Brehove’s compounds to treat onychomycosis, a condition that 

is most often caused by dermatophytes. In addition, the 

petition pointed out that tavaborole has a lower molecular 

weight than the Brehove compounds, and would therefore 

be expected to be more likely than those compounds to 

penetrate the nail barrier at lower concentrations. 

In its patent owner’s response, Anacor argued that 

the combination of Austin and Brehove would not disclose 

treating onychomycosis caused by a dermatophyte, and 

that a person of ordinary skill would not have combined 

Austin and Brehove because they concern structurally 

different compounds. In addition, Anacor argued that a 

person of ordinary skill would not have had an expectation of success in treating a dermatophyte infection with 

tavaborole, because such a person “could not have predicted activity against dermatophytes based on activity 

against a yeast such as C. albicans.”

In support of that argument, Anacor cited an article 

by Dr. Rina Segal (“Segal”).3 Among other things, Anacor 

noted that the Segal article reported that a compound 

known as terbinafine was very effective against dermato-

 

3 Rina Segal et al., Treatment of Candida nail infection with terbinafine, 35 J. Am. Acad. Dermatology 958 

(1996).
6 ANACOR PHARMACEUTICALS, INC. v. IANCU

phytes but had “variable and species-dependent” effectiveness against different species of the Candida genus. 

The petitioner also relied on Segal, introducing that 

article during the deposition of the petitioner’s expert, Dr. 

Narasimha Murthy. In his deposition, Dr. Murthy explained that terbinafine was effective against both dermatophytes and various Candida species. Dr. Murthy

testified that the information in the Segal article supported his opinion that a person of ordinary skill would have 

understood that “most antifungal drugs are found to be 

active against different strains over a broad spectrum of 

organisms.”4 

As part of its patent owner’s response, Anacor also included declarations from several experts, including Dr. 

Marjella Lane and Dr. Mahmoud A. Ghannoum. Dr. Lane 

addressed whether a person of ordinary skill would have 

expected tavaborole to be suitable for topical application 

to a human nail. In the course of her testimony, Dr. Lane 

cited two installments of a study by Dirk Mertin and 

Bernhard C. Lippold that was published in 1997 in the 

Journal of Pharmacy and Pharmacology. Dr. Lane argued that those articles supported her view that a person 

of ordinary skill would not have expected the combination 

of Austin and Brehove to be successful. 

 

4 Dr. Stephen Kahl, another of the petitioner’s experts, testified to the same effect. He stated, “I think a 

[person of ordinary skill] would presume that if a compound showed significant antifungal activity against any 

of a variety of fungi, would have reasonable reason to look 

at those against a specific fungus and expect some success. . . . [F]ungi are rather simple organisms. And it’s 

not unusual that a compound that . . . has antifungal 

activity in one fungus, might be expected or at least

evaluated in another fungus.”
ANACOR PHARMACEUTICALS, INC. v. IANCU 7

During the depositions of Anacor’s experts, the petitioner introduced the third installment of the study by 

Mertin and Lippold, which was published in 1997 as part 

of the same series of articles (“Mertin”).5 The petitioner 

used the third Mertin article to challenge Dr. Lane’s 

testimony regarding the relationship between a compound’s molecular weight and its ability to penetrate the 

nail plate. When questioned about the study, Dr. Lane 

explained that she was aware of the article, but that she 

disagreed with its findings about the inverse relationship 

between permeability and molecular weight. 

The petitioner also used the third Mertin article during Dr. Ghannoum’s deposition. Dr. Ghannoum relied on 

a paper by Kazuhiro Nimura (“Nimura”), which teaches 

that some antifungals, such as ketoconazole, are effective 

against C. albicans but ineffective against dermatophytes 

such as T. rubrum.6 Based on Nimura, Dr. Ghannoum

testified that a person of ordinary skill would not have 

predicted activity against dermatophytes based on activity against other microorganisms such as C. albicans. In 

challenging Dr. Ghannoum’s testimony on that issue, the 

petitioner directed his attention to a statement from the 

third Mertin article that “[d]ermatophytes are usually 

more sensitive to antimycotics than yeast.”7

 

5 Dirk Mertin & Bernhard C. Lippold, In-vitro Permeability of the Human Nail and of a Keratin Membrane 

from Bovine Hooves: Prediction of the Penetration Rate of 

Antimycotics Through the Nail Plate and Their Efficacy, 

49 J. Pharmacy & Pharmacology 866 (1997).

6 Kazuhiro Nimura et al., Comparison of In Vitro 

Antifungal Activities of Topical Antimycotics Launched in 

1990s in Japan, 18 Int’l J. Antimicrobial Agents 173 

(2001).

7 The various Candida species are fungi that are 

classified as yeasts.
8 ANACOR PHARMACEUTICALS, INC. v. IANCU

In its reply brief to the Board, the petitioner responded to Anacor’s argument that a person of ordinary skill 

would not have predicted a compound’s activity against 

dermatophytes based on its activity against C. albicans. 

In the course of that discussion, the petitioner discussed

Mertin’s conclusion that antimycotics are often more 

effective against dermatophytes than against yeasts. The 

petitioner’s expert, Dr. Murthy, also noted in his reply 

declaration that Segal and Nimura teach that a number 

of antifungal drugs are equally or more effective against 

dermatophytes than against C. albicans.

C 

In its final written decision, the Board observed that 

Austin teaches that tavaborole is a known fungicide with 

particular potency against C. albicans. The Board also 

found that molecular weight was the most important 

factor in predicting whether a molecule would penetrate 

the nail plate. The Board then pointed out that, of the 16 

tested compounds listed in Tables 8 and 9 of Austin, 

tavaborole was the most effective against various fungi, 

including C. albicans, of any of the seven compounds in 

Table 9 and that it had a lower molecular weight than 

any of the nine compounds in Table 8. Based on the 

evidence before it, the Board found that a person of ordinary skill in the art would have considered tavaborole as 

a promising candidate for treating onychomycosis. 

The Board found that Brehove taught the treatment 

of onychomycosis with boron heterocycles and, in particular, that Brehove’s compounds were effective against C. 

albicans, which Brehove characterized as a common cause 

of onychomycosis. In light of Brehove’s test results, the 

Board concluded that a person of ordinary skill in the art 

would have used Austin’s tavaborole in Brehove’s topical 

treatment of onychomycosis with a reasonable expectation 

of success. The Board acknowledged that “there are 

obviously structural differences between the dioxa-
ANACOR PHARMACEUTICALS, INC. v. IANCU 9

borinanes of Brehove and the benzoxaboroles of Austin,” 

and it recognized that “small structural differences can 

cause different biological actions and activities.” Coal. for 

Affordable Drugs X LLC v. Anacor Pharm., Inc., No. 

IPR2015-01776, at 21 (P.T.A.B. Feb. 23, 2017) (“Final 

Written Decision”). Nonetheless, the Board was persuaded by the petitioner’s experts that “the combination of the 

structural similarities and the similar fungicidal activity

against C. albicans would have led a person of ordinary 

skill in the art to combine Brehove’s method of treating 

onychomycosis using Austin’s tavaborole.” Id. The Board 

explained that “a person of ordinary skill in the art would 

have been less concerned about the possibility of differences in biological function given Brehove and Austin’s 

disclosure confirming that [Brehove’s compounds] and 

tavaborole have similar fungicidal activity against C. 

albicans.” Id. at 21–22. 

Addressing claim 6, the Board noted that “neither 

Austin nor Brehove expressly teaches whether the disclosed compounds exhibit any activity against dermatophytes.” Id. at 29. Accordingly, the Board identified the 

question posed by claim 6 as whether “a person of ordinary skill in the art would have expected that tavaborole, 

which shares functional activity with the compounds of 

Brehove” against C. albicans would also share functional 

activity against other fungi responsible for onychomycosis, i.e., dermatophytes. Id. at 29. 

On that issue, the Board concluded that “the weight of 

the evidence favors Petitioner’s argument.” Id. at 30. In 

support of that conclusion, the Board cited evidence that 

included Segal, Nimura, and Mertin. The Board noted 

that Segal shows that terbinafine, an antifungal, is highly 

potent against dermatophytes and also active (albeit less 

so) against C. albicans; that although Nimura discloses 

that ketoconazole has potent antifungal activity against 

C. albicans but poor activity against dermatophytes, 

another antifungal, amorolfine, exhibits potent antifungal 
10 ANACOR PHARMACEUTICALS, INC. v. IANCU

activity against all fungal species tested, including both 

C. albicans and T. rubrum; and that Mertin teaches that 

dermatophytes are usually more sensitive to antimycotics 

than yeasts are. 

In light of all the evidence of record, the Board concluded that a person of ordinary skill “would have had a 

reasonable expectation that a compound with activity 

against C. albicans would also have activity against 

dermatophytes, particularly given the teaching that 

dermatophytes are usually more sensitive to antimycotics 

than yeast.” Id. at 31. The Board therefore held that “the 

combination of Austin and Brehove teaches each limitation of” the claims and that the claims of the ’621 patent, 

including claim 6, were invalid for obviousness. Id.; see 

also id. at 37.

II

A 

On appeal, Anacor first argues that the Board violated due process and the procedural requirements of the 

Administrative Procedure Act (“APA”) by failing to provide Anacor with adequate notice of, and an opportunity 

to respond to, the grounds of rejection ultimately adopted 

by the Board. 

Under the APA, a patent owner involved in an inter 

partes review is entitled to notice of and a fair opportunity to address the grounds of rejection. 5 U.S.C. §§ 554(b)–

(c), 557(c); Dell Inc. v. Acceleron, LLC, 818 F.3d 1293, 

1301 (Fed. Cir. 2016). Therefore, an agency “may not 

change theories in midstream without giving respondents 

reasonable notice of the change and the opportunity to 

present argument under the new theory.” Genzyme 

Therapeutic Prod. Ltd. P’ship v. Biomarin Pharm. Inc., 

825 F.3d 1360, 1366 (Fed. Cir. 2016) (quoting Belden Inc. 

v. Berk-Tek LLC, 805 F.3d 1064, 1080 (Fed. Cir. 2015)). 
ANACOR PHARMACEUTICALS, INC. v. IANCU 11

Anacor argues that the Board’s decision violated the 

APA and due process in two related ways. First, Anacor 

contends that the petitioner abandoned one prior art 

reference in its reply (Brehove) and shifted to a new 

theory of invalidity (relying on Austin in light of Segal 

and Mertin), and that the Board adopted that new theory 

without giving Anacor proper notice or an opportunity to 

respond to it. Second, Anacor argues that, in bolstering 

this new theory of obviousness, the petitioner impermissibly relied on new evidence, not included in the petition, to 

satisfy its burden of showing a prima facie case of obviousness.

We reject Anacor’s argument that the Board violated 

the APA or due process by adopting a new theory of 

obviousness not presented in the petition. Unlike in In re 

NuVasive, Inc., 841 F.3d 966 (Fed. Cir. 2016), on which 

Anacor relies, the Board’s final written decision was

based on the same combination of references—Austin and 

Brehove—and the same series of inferences that the 

petition proposed. 

To demonstrate effectiveness against dermatophytes, 

the petition cited Brehove’s in vivo tests to demonstrate 

that boron heterocycles can be effective against onychomycosis, which is most often caused by dermatophytes. 

The petition suggested that Brehove’s compounds would 

likely show effectiveness against dermatophytes and that, 

therefore, Austin’s tavaborole would do so also, since the 

compounds in both references were effective against C. 

albicans. 

The Board’s final written decision was based on the 

same combination of references, and it concluded that the 

weight of the evidence supported the inferences drawn by 

the petition. The Board stated that “[f]or the reasons 

stated in the Petition and by Dr. Murthy, we are persuaded that the combination of Austin and Brehove teaches or 

suggests each limitation of dependent claims 2–10.” Final 
12 ANACOR PHARMACEUTICALS, INC. v. IANCU

Written Decision, at 28; see also id. at 31 (concluding that 

“a person of ordinary skill in the art would have had a 

reason to combine Austin and Brehove with a reasonable 

expectation of success”). In particular, the Board concluded that “a person of ordinary skill in the art would have 

had a reasonable expectation that a compound with 

activity against C. albicans would also have activity 

against dermatophytes,” id. at 30–31, which was the same 

argument raised in the petition.

We also reject Anacor’s argument that the Board improperly relied on new evidence to which Anacor did not 

have an opportunity to respond. Anacor argues that the 

Board improperly cited two references—Mertin and 

Segal—that were not cited in the petition. There is, 

however, no blanket prohibition against the introduction 

of new evidence during an inter partes review proceeding. 

In fact, “the introduction of new evidence in the course of 

the trial is to be expected in inter partes review trial 

proceedings and, as long as the opposing party is given 

notice of the evidence and an opportunity to respond to it, 

the introduction of such evidence is perfectly permissible 

under the APA.” Genzyme, 825 F.3d at 1366; see also 

Novartis AG v. Torrent Pharm. Ltd., 853 F.3d 1316, 1325–

26 (Fed. Cir. 2017) (finding no APA violation because 

patent owner was not “surprised” where a reference was 

discussed in patent owner’s response, in depositions, and 

at the hearing, because “it is quite clear that [the patentee] had more than sufficient notice and opportunity to be 

heard on [the reference’s] potential relevance”).

In addition, the petitioner in an inter partes review 

proceeding may introduce new evidence after the petition 

stage if the evidence is a legitimate reply to evidence 

introduced by the patent owner, or if it is used “to document the knowledge that skilled artisans would bring to 

bear in reading the prior art identified as producing 

obviousness.” Genzyme, 825 F.3d at 1369 (quoting Ariosa 
ANACOR PHARMACEUTICALS, INC. v. IANCU 13

Diagnostics v. Verinata Health, Inc., 805 F.3d 1359, 1365 

(Fed. Cir. 2015)).8

It was not improper for the Board to cite Segal and 

Mertin (along with Nimura) as evidence of the knowledge 

that a skilled artisan would bring to bear in reading 

Austin and Brehove, even though those references were 

not cited in the petition. Anacor argues that Segal, Mertin, and Nimura “surfaced for the first time in Petitioner’s 

Reply,” but that is not so. Anacor discussed both Nimura 

and Segal in its patent owner’s response and related 

submissions; indeed, Anacor spent three pages of its 

patent owner’s response addressing Segal. For that 

reason, it was not improper for the Board to rely on those 

references to show what a person of skill in the art would 

believe about whether a compound effective against a 

yeast such as C. albicans would be likely to be effective 

against a dermatophyte. 

As for Mertin, the first two installments in Mertin

and Lippold’s three-part series of articles were first introduced and addressed by Anacor in the declaration of Dr. 

 

8 Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d 1359 (Fed. Cir. 2016), cited by 

Anacor, is not to the contrary. In that case, the court 

upheld the Board’s refusal to consider the petitioner’s 

reply brief on the ground that the reply brief presented a 

new argument for the first time. The Board found that 

the reply violated a Board regulation, 37 C.F.R. 

§ 42.23(b), which provides that a reply “may only respond 

to arguments raised in the corresponding opposition or 

patent owner response.” Id. at 1369–70. In this case, the 

reply appropriately responded to arguments made in the 

patent owner’s response and evidence elicited in the 

course of the proceeding through the depositions of the 

parties’ experts, and the Board accordingly did not refuse 

to consider the petitioner’s reply. 
14 ANACOR PHARMACEUTICALS, INC. v. IANCU

Lane. The third installment was introduced by the petitioner during the deposition of Anacor’s experts and was 

then referred to in the petitioner’s reply. But the third 

installment did not come as a surprise to Anacor. As 

noted, Dr. Lane admitted she was familiar with the 

article, which related to the first two installments she had 

cited in her declaration. Moreover, the third Mertin 

article was offered in direct response to testimony by Dr. 

Lane at her deposition: it was brought up in the deposition as part of the petitioner’s challenge to Dr. Lane’s 

testimony regarding the relationship between molecular 

weight and nail permeability.9

Following Dr. Lane’s deposition, the Mertin article 

was brought up again during the deposition of Anacor’s 

expert, Dr. Ghannoum. In that proceeding, the petitioner’s counsel questioned Dr. Ghannoum about the conclusions reached in the Mertin article as part of the petitionpetitioner’s challenge to Dr. Ghannoum’s assertion, based 

in part on Nimura, that compounds that showed activity 

against C. albicans often were not particularly effective 

against dermatophytes. In particular, the petitioner’s 

counsel cross-examined Dr. Ghannoum regarding his 

opinion on that point by referring to the statement in 

Mertin that “[d]ermatophytes are usually more sensitive 

towards antimycotics than yeasts.” 

Finally, Anacor discussed Mertin extensively at the 

hearing before the Board, including discussing Mertin’s 

findings with respect to permeability, and arguing that 

Mertin “highlights the unpredictability of going from 

predicting the activity of one species and going to another 

 

9 In addition, the third Mertin article was cited and 

discussed at some length in another reference relied on by 

Dr. Lane and cited in her declaration. See Sudaxshina 

Murdan, Drug Delivery to the Nail Following Topical 

Application, 236 Int’l J. of Pharmaceutics 1, 9–11 (2002). 
ANACOR PHARMACEUTICALS, INC. v. IANCU 15

species.” In response to the petitioner’s argument that 

Mertin says that dermatophytes are more sensitive to 

antimycotics than yeasts, Anacor argued at the hearing 

that “nowhere in the Mertin article does it talk about 

Candida albicans. So they are extrapolating much beyond 

the teachings of Mertin[.]”

Based on this record, we conclude that Anacor was not 

denied its procedural rights with respect to the theory of 

obviousness adopted by the Board or any evidence relied 

on by the Board. The Board did not materially deviate 

from the theory of obviousness set forth in the petition,

and Anacor had ample notice of and an opportunity to 

respond to the Segal and Mertin references, which in any 

event were properly offered in reply to arguments made 

by Anacor and for the purpose of showing the state of the 

art at the time of the patent application.

B 

Anacor next argues that the Board improperly shifted 

the burden of proof by requiring the patent owner to 

disprove obviousness. Relying on In re Magnum Oil Tools 

International, Ltd., 829 F.3d 1364 (Fed. Cir. 2016), Anacor contends that the record provides no basis to conclude 

that tavaborole’s activity against dermatophytes would be 

expected and that, in adopting the petitioner’s position 

without supporting evidence, the Board necessarily shifted the burden of proof to Anacor.

Unlike in In re Magnum, nothing in the Board’s final 

written decision suggests that the Board improperly

shifted the burden to the patent owner to disprove obviousness. To the contrary, the Board expressly and repeatedly stated that it was the petitioner’s burden to 

“show[] by a preponderance of the evidence that claims 1–

12 of the ’521 patent are unpatentable.” Final Written 

Decision, at 3; see also id. at 9, 10, 18, 22, 23, 37, 42.
16 ANACOR PHARMACEUTICALS, INC. v. IANCU

Notwithstanding those statements, Anacor argues 

that the Board effectively shifted the burden of proof to 

the patent owner because the Board’s conclusions rested 

not on the petitioner’s presentation of evidence in support 

of an argument, but rather on whether Anacor had sufficiently disproved that argument. In particular, Anacor 

contends that the Board failed to require proof from the 

petitioner as to the mechanism of action that would lead 

to the conclusion that tavaborole would kill both C. albicans and dermatophytes, and that the Board did not 

explain why the evidence that dermatophytes are usually 

more sensitive than yeasts to antimycotics applies to 

tavaborole. 

In substance, Anacor’s argument is not that the Board 

shifted the burden of proof to Anacor, but that the Board 

improperly relaxed the burden on the petitioner to prove 

its case. That argument, however, does not suggest that 

the Board shifted the burden of proof to Anacor, but 

instead is directed to the question whether there was 

substantial evidence to support the Board’s finding of 

obviousness.

As to that issue, the Board found that a person of skill 

in the art would have been motivated to combine Austin 

and Brehove and would have had a reasonable expectation of success in doing so. Austin disclosed the use of 

oxaboroles, a subset of boron heterocycles, as fungicides

that were effective against five different species of fungi, 

including C. albicans. It stated that compounds containing an oxaborole ring, such as tavaborole, are particularly 

effective against fungi. Tavaborole, in particular, was 

identified as being especially potent against the various 

species of fungi that Austin tested. Austin also disclosed 

that tavaborole was a low molecular weight compound, 

which would enable the compound to penetrate the nail 

plate covering the locus of the infection. 
ANACOR PHARMACEUTICALS, INC. v. IANCU 17

The compounds of Brehove, also boron heterocycles, 

were shown through in vitro testing to be effective against 

C. albicans. The results of Brehove’s in vivo testing 

showed that Brehove’s compounds were effective against 

onychomycosis in each of the patients suffering from that

condition. In light of the fact that approximately 90 

percent of all onychomycosis cases are attributable to 

dermatophytes, and in the absence of any evidence that 

patients with dermatophyte-based onychomycosis were 

excluded from the in vivo testing, it is highly likely that at 

least some of the five cases discussed by Brehove involved 

dermatophyte infections. 

Beyond that, the evidence in the record before the 

Board showed that persons of skill in the art would have 

known that antifungal agents that are effective against 

one species of fungus are typically effective against others, as reported by the petitioner’s experts, Dr. Kahl and 

Dr. Murthy. In addition, one of skill in the art would 

have appreciated that many antifungal agents are more 

effective against dermatophytes than against yeasts, as 

reported by Dr. Murthy and as indicated by data in the 

Segal, Mertin, and Nimura references.10 In light of the 

full record before the Board, we conclude that substantial 

evidence supports the Board’s findings that a person of 

ordinary skill in the art would have been motivated to 

combine the pertinent teachings of Austin and Brehove 

 

10 As for Anacor’s argument that the Board failed to 

require proof of the mechanism of action that caused the 

boron heterocycles to be toxic to fungi, no such proof is 

required, as it has long been settled that “an inventor 

need not comprehend the scientific principles on which 

the practical effectiveness of his invention rests.” Fromson v. Advance Offset Plate, Inc., 720 F.2d 1565, 1570 

(Fed. Cir. 1983) (citing Diamond Rubber Co. v. Consol. 

Rubber Tire Co., 220 U.S. 428, 435–36 (1911)). 
18 ANACOR PHARMACEUTICALS, INC. v. IANCU

and would have had a reasonable expectation of success in 

doing so.

C 

In its third argument, Anacor challenges what it refers to as the Board’s “conclusion that the compounds of 

Austin are ‘structurally similar’ to the compounds of 

Brehove.” Anacor contends that the compounds are 

structurally dissimilar, and that a person of ordinary skill 

in the art would have expected that even small structural 

differences between tavaborole and the Brehove compounds would result in significant differences in their 

chemical and biological properties.

Anacor’s argument is premised on the misapprehension that the Board viewed structural similarity as a 

binary factor—either present or absent—and that the 

Board found it was present in this case. That is not an 

accurate characterization of the Board’s assessment of the 

issue of structural similarity. 

In its final written decision, the Board viewed the existence of some structural similarity between the compounds in Austin and Brehove as evidence that the 

references might be good candidates to be combined. That 

is, the Board recognized that the structural similarity 

between the boron heterocycles of Austin and Brehove 

provides a useful starting point, but it attributed more 

significance to the functional similarities of the two 

groups of compounds. As the Board observed, Austin 

teaches that oxaboroles, a subset of boron heterocycles, 

are effective fungicides, and Brehove teaches that certain 

dioxaborinanes, a different subset of boron heterocycles, 

are likewise effective fungicides. Moreover, notwithstanding the structural differences between the two subsets of 

compounds, the Board focused on the fact that both were 

shown to be effective against C. albicans, a fungus that 

was known to cause onychomycosis.
ANACOR PHARMACEUTICALS, INC. v. IANCU 19

The Board did not regard the structural similarity between the compounds of Austin and Brehove to be sufficient proof, by itself, that tavaborole would be likely to 

have the same functionality as the compounds in Brehove. 

The Board correctly acknowledged that there “are obviously structural differences between the dioxaborinanes of 

Brehove and the benzoxaboroles of Austin,” but it concluded that “the combination of the structural similarities 

and the similar fungicidal activity against C. albicans 

would have led a person of ordinary skill in the art to 

combine Brehove’s method of treating onychomycosis 

using Austin’s tavaborole instead of [Brehove’s compounds].” Final Written Decision, at 21.

It is true that in the case of patents on new chemical 

compounds, the obviousness inquiry “frequently turns on 

the structural similarities and differences between the 

compounds claimed and those in the prior art.” Daiichi 

Sankyo Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1352 

(Fed. Cir. 2010). In such cases, where the properties of 

the new chemical compound are not known, structural 

similarity is often sufficient to create an expectation that 

the “new compound will have similar properties to the 

old.” Altana Pharma AG v. Teva Pharm. USA, Inc., 566 

F.3d 999, 1007 (Fed. Cir. 2009) (quoting Eisai Co. v. Dr.

Reddy’s Labs., Ltd., 533 F.3d 1353, 1357 (Fed. Cir. 2008)).

This case, however, does not involve a patent on a 

new chemical compound. Where the patent is directed to 

a new treatment using a known compound, it is reasonable to assume that similar compounds that share certain 

common properties are apt to share other related properties as well. See In re Merck & Co., 800 F.2d 1091, 1096 

(Fed. Cir. 1986) (the fact that two similar compounds are 

both psychotropic drugs and one possesses antidepressive 

properties suggests that the other may possess antidepressive properties as well); see also In re Mehta, 347 F.2d 

859, 864 (CCPA 1965) (“The similarity of properties of a 

reference compound as compared with a claimed com-
20 ANACOR PHARMACEUTICALS, INC. v. IANCU

pound gives rise to an even stronger inference of obviousness than that of structural similarity alone[.]”); In re 

Rosselet, 347 F.2d 847, 850 (CCPA 1965) (referring to a 

“prima facie showing of obviousness by reason of the 

admitted ‘gross structural similarities’ of the art compounds, coupled with the fact those compounds are shown 

to have utility in the same area of pharmacological activity”).

To be clear, we recognize that structural similarity is 

an important factor in assessing the motivation to combine and reasonable expectation of success. It has been 

long recognized that chemical compounds with similar 

structures often have similar properties and that similarity in properties can be inferred from structural similarity. In re Hass, 141 F.2d 122, 125 (CCPA 1944). Our cases 

have held that the greater the structural similarity between the compounds, the greater the motivation to 

combine and reasonable expectation of success. Eli Lilly 

& Co. v. Zenith Goldline Pharm., Inc., 471 F.3d 1369, 

1377 (Fed. Cir. 2006) (noting that, for a new chemical 

compound, finding obviousness requires “structural 

similarity” and a “reason or motivation to make the 

claimed compositions” (quoting In re Dillon, 919 F.2d 688, 

692 (Fed. Cir. 1990) (en banc))); In re Deuel, 51 F.3d 1552, 

1558 (Fed. Cir. 1995) (“Structural relationships may 

provide the requisite motivation or suggestion to modify 

known compounds to obtain new compounds.”). The 

opposite is true, too: the less the structural similarity, the 

less the motivation to combine and the reasonable expectation of success. In re Jones, 958 F.2d 347, 350 (Fed. Cir. 

1992) (reversing the prima facie obviousness finding 

because of the “lack of close similarity of structure”). 

At the same time, our cases recognize that the chemical arts are unpredictable and that similar structures do 

not always result in similar properties. See Eisai Co., 533 

F.3d at 1359. The obviousness inquiry often depends on 

whether there is evidence demonstrating a nexus between 
ANACOR PHARMACEUTICALS, INC. v. IANCU 21

structural similarities (or dissimilarities) and functional 

similarities (or dissimilarities). In this case, although 

there is only limited structural similarity between the 

compounds disclosed in Austin and Brehove, we conclude 

that, in light of the combination of the structural and 

functional similarities between the compounds, substantial evidence supports the Board’s findings.

The Board understood that the petitioner’s theory was 

“not based on structural similarities alone,” but was 

“based on the combination of structural similarity and 

functional similarity.” Final Written Decision, at 28. And 

the Board agreed with the petitioner that “a person of 

ordinary skill in the art would have expected that tavaborole, which shares functional activity with the compounds 

of Brehove, would have shared other activities as well, 

such as the inhibition of additional fungi responsible for 

onychomycosis.” Id. at 29. The Board thus did not disregard the structural differences between the compounds of 

Austin and Brehove or attribute undue significance to 

their structural similarities.

For the foregoing reasons, we reject Anacor’s challenges to the Board’s reasoning and uphold the Board’s 

conclusion that claim 6 of the ’621 patent is invalid for 

obviousness.

AFFIRMED