Anacor Pharm., Inc. v. Iancu

• Citation: 889 F.3d 1372
• Decision Date: 14 May 2018
• Docket Number: 2017-1947
• Parties: 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
• Court: United States Courts of Appeals. United States Court of Appeals for the Federal Circuit

889 F.3d 1372

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

United States Court of Appeals, Federal Circuit.

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.

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 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 heterocycles 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 '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 dermatophytes 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.

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

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...