Trials@uspto.gov
`571-272-7822
`
`
`
`
`
`
`Paper No. 10
`Entered: November 15, 2017
`
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_________________________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`ARADIGM CORPORATION,
`Petitioner,
`
`v.
`
`INSMED INCORPORATED,
`Patent Owner.
`
`Case PGR2017-00021
`Patent 9,402,845 B2
`
`
`
`
`
`
`
`
`
`Before GRACE KARAFFA OBERMANN, RAMA G. ELLURU,
`and MICHELLE N. ANKENBRAND, Administrative Patent Judges.
`
`OBERMANN, Administrative Patent Judge.
`
`
`DECISION
`Denying Institution of Post Grant Review
`35 U.S.C. § 324; 37 C.F.R. § 42.208
`
`

`

`PGR2017-00021
`Patent 9,402,845 B2
`
`
`I. INTRODUCTION
`
`Petitioner filed a Petition for post grant review of claims 1–26 of U.S.
`
`Patent No. 9,402,845 B2 (Ex. 1001, “the ’845 patent”). Paper 1 (“Pet.”).
`
`Patent Owner filed a Preliminary Response. Paper 8 (“Prelim. Resp.”). Based
`
`on the information presented, we hold that Petitioner has not demonstrated
`
`adequately that the ’845 patent is eligible for post grant review.
`
`Accordingly, we deny the Petition.
`
`A. Related Proceedings
`
`Petitioner identifies as a related matter a pending continuation
`
`application of the ’845 patent. Pet. 7 (citing Application No. 15/376,086).
`
`Petitioner states that it “is unaware of any other judicial or administrative
`
`matter that would affect, or be affected by, a decision in this proceeding.” Id.
`
`
`
`B. The Priority Application Chain Relating to the ’845 Patent
`
`The filing dates of the parent applications pertaining to the ’845 patent
`
`are critical to our analysis because, if claims 1–26 are entitled to claim priority
`
`based on the filing date of a parent application filed before March 16, 2013,
`
`the ’845 patent is not eligible for post grant review. See infra § II.A (statutory
`
`analysis pertaining to post grant review eligibility).
`
`The ’845 patent issued from an application (No. 14/987,508, “the ’508
`
`application”) that was filed on January 4, 2016, but claims an earliest possible
`
`priority date of December 8, 2005, based on the filing of a provisional
`
`application (No. 60/748,468, “the ’468 provisional application”). Ex. 1001,
`
`Related U.S. Application Data (60). The ’845 patent also claims the benefit of
`
`filing dates associated with a chain of non-provisional continuation
`
`applications stemming from the ’468 provisional application. Id. at (63).
`
`
`
`
`2
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`

`

`PGR2017-00021
`Patent 9,402,845 B2
`
`
`The first non-provisional application (No. 11/634,343) was filed on
`
`December 5, 2006, and issued as U.S. Patent No. 8,226,975. Ex. 1007. The
`
`second non-provisional application (No. 13/527,213) was filed on June 19,
`
`2012, and issued as U.S. Patent No. 8,632,804. Ex. 1008. The third non-
`
`provisional application (No. 13/666,420) was filed on November 1, 2012, and
`
`issued as U.S. Patent No. 8,642,075. Ex. 1009. The fourth non-provisional
`
`application (No. 14/080,922, “the ’922 application”) was filed on
`
`November 15, 2013, and is pending. Ex. 1010. The ’508 application, from
`
`which the ’845 patent issued, is a continuation of the ’922 application.
`
`Ex. 1001.
`
`The parties agree that the earliest-filed priority application (that is,
`
`the ’468 provisional application) and each non-provisional parent application
`
`have essentially the same specification as the ’845 patent. Pet. 22, 47; Prelim.
`
`Resp. 47. Accordingly, our discussion of the disclosure of the ’845 patent
`
`applies with equal force to the disclosure of each priority application.
`
`C. The Claimed Subject Matter of the ’845 Patent
`
`The ’845 patent, entitled “Lipid-Based Compositions of Antiinfectives
`
`for Treating Pulmonary Infections and Methods of Use Thereof,” relates to a
`
`pharmaceutical formulation comprising a mixture of free and liposome-
`
`encapsulated antiinfectives. Ex. 1001, Title, Abstract. According to the
`
`specification, an objective of the invention is to use lipid-based encapsulation
`
`to improve the therapeutic effects of the antiinfectives when administered via
`
`the pulmonary route to treat pulmonary infections. Id. at 2:34–41.
`
`The specification describes an embodiment in which “the lipid-based
`
`composition is a liposome.” Id. at 3:22–23. Claims 1–26 are directed to a
`
`method that employs “a plurality of liposomes” for encapsulating a specific
`
`
`
`
`3
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`

`

`PGR2017-00021
`Patent 9,402,845 B2
`
`antiinfective—namely, “quinolone antibiotic agent.” Id. at 14:55–57 (claim 1,
`
`the only independent claim). The claimed method includes administering a
`
`mixture of free and liposome-encapsulated “quinolone antibiotic agent” to the
`
`lungs of a patient via an inhalation delivery device. Id. at 14:51–57. The
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`encapsulated form is “encapsulated in a plurality of liposomes” that “consists
`
`of electrically neutral lipids.” Id. at 14:56–62. The free quinolone provides
`
`for immediate bactericidal activity, while the encapsulated quinolone provides
`
`a slow release that results in sustained levels of drug in the lungs for
`
`prolonged activity between administrations. Id. at 2:52–59, 14:66–15:4.
`
`The ’845 patent informs that the antiinfective “is selected from the
`
`group consisting of antibiotic agents, antiviral agents, and antifungal agents.”
`
`Id. at 3:11–13. Quinolones are among the antibiotic agents expressly
`
`identified as antiinfectives suitable for use in the claimed invention. Id.
`
`at 3:15, 4:9, 9:21. The specification lists specific quinolones, including
`
`ciprofloxacin, that are useful in the claimed method. Id. at 9:43–48. The
`
`specification also describes with particularity lipids suitable for encapsulating
`
`the antiinfectives. Id. at 3:27–31, 4:16–26, 6:35–8:54. On that point, the
`
`specification teaches that suitable “[l]iposomes can be produced by a variety
`
`of methods,” and identifies at least five U.S. patents that disclose methods for
`
`producing liposome-encapsulated antiinfectives. Id. at 7:53–8:3.
`
`The ’845 patent discloses two working examples, neither of which uses
`
`a quinolone as the antiinfective. Id. at 13:35–14:35. Both working examples
`
`employ amikacin as the antiinfective. Id. at 13:42–43, 14:11–15. Amikacin is
`
`an aminoglycoside, which, like quinolone, is identified in the specification as
`
`an antiinfective suitable for use in the claimed invention. Id. at 4:13–15.
`
`
`
`
`4
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`PGR2017-00021
`Patent 9,402,845 B2
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`
`D. Illustrative Claim
`
`
`
`Claim 1, the only independent claim, is illustrative of the claimed
`
`subject matter and is reproduced below:
`
`1. A method for treating or providing prophylaxis against a
`pulmonary infection in a patient in need thereof, comprising:
`
`administering to the lungs of the patient via an inhalation
`delivery device, a pharmaceutical formulation comprising a
`mixture of free quinolone antibiotic agent, a quinolone
`antibiotic agent encapsulated in a plurality of liposomes, and a
`pharmaceutical excipient, wherein the formulation is a solution
`or a suspension, the ratio by weight of free quinolone antibiotic
`agent to the encapsulated quinolone antibiotic agent is between
`about 1:10 and about 10:1 and the lipid component of the
`plurality of liposomes consists of electrically neutral lipids,
`
`wherein the pharmaceutical formulation is administered
`as an aerosolized pharmaceutical
`formulation, and
`the
`aerosolized pharmaceutical
`formulation
`comprises
`free
`quinolone antibiotic agent in an amount effective to provide
`immediate bactericidal activity against the pulmonary infection
`and liposomal encapsulated quinolone antibiotic agent in an
`amount effective to provide sustained bactericidal activity
`against the pulmonary infection.
`
`Ex. 1001, 14:51–15:4 (indention added).
`
`E. Evidence Relied Upon
`
`
`
`Petitioner raises seven grounds of unpatentability. Pet. 8–9. Our
`
`decision, however, turns on the threshold question of whether the ’845 patent
`
`is eligible for post grant review. Pet. 45–55. Because we ultimately conclude
`
`that the patent is not post grant review eligible, we do not reach the merits of
`
`any asserted ground of unpatentability. Given that they form no part of our
`
`decision, we decline to enumerate the grounds here. See id. at 8–9
`
`(Petitioner’s recitation of the seven grounds).
`
`
`
`
`5
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`

`

`PGR2017-00021
`Patent 9,402,845 B2
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`
`
`The Petition is supported by a declaration of A. Bruce Montgomery,
`
`M.D. Ex. 1020. Based on Dr. Montgomery’s statement of qualifications and
`
`curriculum vitae, for the purposes of this decision, we find that he is qualified
`
`to opine from the perspective of a person of ordinary skill at the time of the
`
`invention. See Ex. 1020 ¶¶ 4–12 (Dr. Montgomery’s statement of
`
`qualifications); see also Ex. 1020, Exhibit A (Dr. Montgomery’s curriculum
`
`vitae). We are not persuaded by Patent Owner’s argument that
`
`Dr. Montgomery is unqualified due to a lack of liposome-specific experience.
`
`On that point, even Patent Owner acknowledges that Dr. Montgomery is a
`
`named inventor on nine patents related to liposomes. Prelim. Resp. 65–66
`
`(observing that “only” nine of twenty-four U.S. Patents, which list
`
`Dr. Montgomery as an inventor, “include the term ‘liposome’”).
`
`
`
`The Preliminary Response is supported by a declaration of Robert J.
`
`Lee, Ph.D. Ex. 2001. Based on Dr. Lee’s statement of qualifications and
`
`curriculum vitae, for the purposes of this decision, we find that he also is
`
`qualified to opine from the perspective of a person of ordinary skill at the time
`
`of the invention. See Ex. 2001 ¶¶ 3–9 (Dr. Lee’s statement of qualifications);
`
`see also Ex. 2001, Appendix A (Dr. Lee’s curriculum vitae).
`
`II. ANALYSIS
`
`A. Statutory Analysis Pertaining to Post Grant Review Eligibility
`
`Post grant review is available only for patents “described in
`
`section 3(n)(1)” of the Leahy-Smith America Invents Act (“AIA”), Pub L. No.
`
`112-29, 125 Stat. 284 (2011). AIA § 6(f)(2)(A). Those are patents that issue
`
`from applications “that contain[] or contained at any time . . . a claim to a
`
`claimed invention that has an effective filing date in section 100(i) of title 35,
`
`
`
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`6
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`PGR2017-00021
`Patent 9,402,845 B2
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`United States Code, that is on or after” “the expiration of the 18-month period
`
`beginning on the date of the enactment of” the AIA. Id. § 3(n)(1).
`
`Because the AIA was enacted on September 16, 2011, post grant review
`
`is available only for patents that issue from applications that, at one point,
`
`contained at least one claim with an “effective filing date,” as defined by
`
`35 U.S.C. § 100(i), on or after March 16, 2013. Our rules require a petitioner
`
`for post grant review to certify that the challenged patent is available for post
`
`grant review. 37 C.F.R. § 42.204(a) (“petitioner must certify that the patent
`
`for which review is sought is available for post-grant review”). Petitioner
`
`includes the requisite certification and, further, asserts that at least one claim
`
`of the ’845 patent has an effective filing date of January 4, 2016, which is the
`
`actual filing date of the ’508 application. Pet. 8.
`
`
`
`Petitioner advances two independent arguments in support of its
`
`position that at least one claim of the ’845 patent has an effective filing date
`
`after March 16, 2013. First, Petitioner argues that claims 1–26 are not enabled
`
`by the priority applications and, therefore, none of the claims is entitled to
`
`claim priority back to a date earlier than the actual filing date of the ’508
`
`application—namely, January 4, 2016. Pet. 47–53. Second, Petitioner argues
`
`that claims 1–26 lack written description support in the priority applications;
`
`thus, in Petitioner’s view, no claim is entitled to the benefit of the filing date
`
`of any application filed before March 16, 2013. Pet. 53–55.
`
`We address these two arguments in turn below. As an initial matter,
`
`however, we observe that no claim term requires express construction for the
`
`purposes of this decision. See, e.g., Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999) (only claim terms in controversy need
`
`be construed, and then only to the extent necessary to resolve the dispute).
`
`
`
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`7
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`PGR2017-00021
`Patent 9,402,845 B2
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`B. Eligibility Based on Lack of Enablement of Claims 1–26
`
`We first turn to Petitioner’s argument that the ’845 patent is post grant
`
`review eligible because the priority applications do not enable the ’845 patent
`
`claims. Pet. 47–53. We organize our discussion into four subparts:
`
`(1) Petitioner’s analysis of the relevant filing dates of the priority applications;
`
`(2) Petitioner’s treatment of binding Federal Circuit precedent; (3) Patent
`
`Owner’s treatment of that binding Federal Circuit precedent; and
`
`(4) conclusions pertaining to undue experimentation.
`
`(1) Petitioner’s Analysis of the Relevant
`Filing Dates of the Priority Applications
`
`
`
`As Patent Owner points out, the ’845 patent claims priority to at least
`
`five parent applications. Prelim. Resp. 29. The Petition, however, does not
`
`adequately account for the state of the prior art on the individual filing dates
`
`of the priority applications. Stated differently, the information presented in
`
`the Petition is insufficient to establish the state of the art on the filing date of
`
`each priority application filed prior to March 16, 2013. If claims 1–26 are
`
`enabled by those applications, the ’845 patent is not eligible for post grant
`
`review. Accordingly, Petitioner’s failure to adequately address each relevant
`
`date, standing alone, justifies denial of the Petition. See id. at 29–31 (citing
`
`Mylan Pharms. Inc. v. Yeda Research & Dev. Co. Ltd., PGR2016-00010,
`
`Paper 9, 10 (PTAB Aug. 15, 2016) (denying petition for post grant review
`
`where petitioner did not address how intervening priority applications failed to
`
`support a priority date earlier than March 16, 2013)).
`
`Patent Owner, for its part, directs us to persuasive evidence that the
`
`level of ordinary skill in this particular field of endeavor was “not static in
`
`time” and that new methods for producing liposome-encapsulated quinolones
`
`were developing during the period between the filing of the ’468 provisional
`
`
`
`
`8
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`PGR2017-00021
`Patent 9,402,845 B2
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`application and the filing of subsequent priority applications. Prelim
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`Resp. 29; 30–31 (citing Ex. 1030). The Petition only generally argues that
`
`one would have needed to perform undue experiments to determine which
`
`lipids, quinolones, and loading methods were useful for performing the
`
`invention—without tethering that argument to any particular point in time.
`
`Pet. 50–51 (citing Ex. 1020 ¶¶ 99–101). The Petition is deficient for failure to
`
`adequately analyze, from the perspective of an ordinary artisan on each
`
`relevant filing date, whether claims 1–26 are enabled by the priority
`
`applications filed after the ’468 provisional application but before March 16,
`
`2013. Accordingly, on that basis, we deny the Petition for failure to establish
`
`that the ’845 patent is post grant review eligible.
`
`(2) Petitioner’s Treatment of
`Binding Federal Circuit Precedent
`
`A second, independent rationale supports our denial of the Petition.
`
`The Petition asserts that the priority applications provide “little guidance” that
`
`would have equipped an ordinary artisan to carry out the claimed invention
`
`without undue experimentation—given the lack of “quinolone-specific
`
`embodiments” or “examples of any quinolone-containing formulations” in the
`
`disclosure. Id. at 50. But the Petition does not adequately address undue
`
`experimentation under applicable binding Federal Circuit precedent.
`
`Our reviewing court has held that undue experimentation is analyzed by
`
`applying the factors set forth in In re Wands, 858 F.2d 731 (Fed. Cir. 1988).
`
`Petitioner argues that the Wands factors are “illustrative, not mandatory.”
`
`Pet. 46 (citing Amgen, Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 1213 (Fed.
`
`Cir. 1991)). We are not persuaded that the Amgen court held that a party,
`
`asserting undue experimentation in a post grant review, may circumvent an
`
`
`
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`9
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`PGR2017-00021
`Patent 9,402,845 B2
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`analysis based on the Wands factors by arguing that those factors are
`
`“illustrative” only. Id.
`
`In any event, Petitioner provides no cogent reasoning that persuades us
`
`to treat the claims of the ’845 patent, or its field of invention, like the
`
`disparate claims and field that were at issue in Amgen. Pet. 46. The cursory
`
`analysis set forth in the Petition is insufficient in that regard. Id.
`
`Accordingly, on that basis, we hold that the Wands factors apply in this case,
`
`and that Petitioner’s failure to adequately address them justifies denial of the
`
`Petition. See Pet. 46–53 (only generally discussing the Wands factors, without
`
`clearly articulating how they support Petitioner’s position on enablement).
`
`(3) Patent Owner’s Treatment of
`Binding Federal Circuit Precedent
`
`Patent Owner, by contrast, shows persuasively that the Wands factors,
`
`when properly applied in this case, support denial of the Petition. The Wands
`
`factors center on “(1) the quantity of experimentation necessary, (2) the
`
`amount of direction or guidance presented, (3) the presence or absence of
`
`working examples, (4) the nature of the invention, (5) the state of the prior art,
`
`(6) the relative skill of those in the art, (7) the predictability or unpredictability
`
`of the art, and (8) the breadth of the claims.” In re Wands, 858 F.2d at 737. A
`
`central dispute in this case is whether the direction and guidance provided by
`
`the disclosures of the priority applications, including the working examples,
`
`would have been adequate at the time of filing to enable an ordinary artisan to
`
`practice the claimed method, given the nature of the invention, the state of the
`
`prior art, and the relative skill of those in this particular field of endeavor.1
`
`
`1 Neither party clearly articulates reasoning directed to the remaining Wands
`factor—the predictability or unpredictability of the art. On this record, we are
`
`
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`10
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`PGR2017-00021
`Patent 9,402,845 B2
`
`
`Patent Owner presents persuasive argument and evidence tethered to
`
`the Wands factors. Patent Owner identifies evidence that the level of ordinary
`
`skill in the art would have been relatively high, and that the ’845 patent claims
`
`are relatively narrow given their focus on specific liposomes for encapsulating
`
`a limited subset of antiinfectives (quinolones). Prelim. Resp. 40–42. Against
`
`that backdrop, Patent Owner identifies evidence, consisting of disclosures
`
`within the priority applications, which, when coupled with information that
`
`was publicly available in the art, would have equipped an ordinary artisan to
`
`practice claims 1–26 at the time of filing of the earliest priority application—
`
`that is, on December 8, 2005, the filing date of the ’468 provisional
`
`application. Id. at 20, 24–25, 33–35 (citing Ex. 2001 ¶¶ 72–77).
`
`Patent Owner directs us to persuasive evidence on that point. For
`
`example, Patent Owner points out that the disclosure of each priority
`
`application sets forth known techniques for making liposomes and electrically
`
`neutral lipids and, further, incorporates by reference five U.S. patents that
`
`teach passive entrapment methods useful for encapsulating antiinfectives in
`
`electrically neutral lipids. Prelim. Resp. 20, 24–25, 33–35 (citing Ex. 2001
`
`¶¶ 72–77); see Ex. 1001, 7:53–8:3 (the ’845 patent, which shares the same
`
`disclosure as all parent applications, incorporating by reference at least five
`
`U.S. patents); Ex. 1002, 10–11 (bridging paragraph). Patent Owner shows
`
`sufficiently that those patents, incorporated by reference into the disclosures
`
`of each priority application, would have informed the selection of lipids and
`
`liposome-encapsulation techniques useful for practicing the claimed
`
`invention. Prelim. Resp. 20, 24–25, 33–35 (citing Ex. 2001 ¶¶ 72–77).
`
`
`left to conclude that this factor is entitled to little weight under the particular
`facts and circumstances of this case.
`
`
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`11
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`PGR2017-00021
`Patent 9,402,845 B2
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`Specifically, Patent Owner’s witness, Dr. Lee, cogently explains why
`
`those five incorporated patents, although not specifically discussing
`
`quinolones, would have been recognized in the art as applicable to the
`
`encapsulation of quinolones in electrically neutral lipids. Pet. 24–25 (citing
`
`Ex. 2001 ¶ 77) (Dr. Lee, discussing the five patents and their disclosures of
`
`various passive entrapment methods useful for encapsulating antiinfectives in
`
`electrically neutral lipids); id. at 32–39 (citing Ex. 2001 ¶¶ 68, 70, 71, 74–83,
`
`85) (Dr. Lee, discussing why those patents, coupled with information publicly
`
`available in the prior art, would have enabled a person of ordinary skill in the
`
`art to prepare liposome-encapsulated quinolones suitable for use in the method
`
`of claims 1–26). For example, Dr. Lee directs us to persuasive objective
`
`evidence that an ordinary artisan would not have been required to “‘create’ an
`
`active loading method for ciprofloxacin,” given that the quinolone is “a
`
`weakly basic drug that is ‘ionizable,’” a property that would have
`
`recommended quinolone as suitable to loading via the method disclosed in
`
`U.S. Patent No. 5,059,421,2 which uses “a proton gradient and []
`
`transmembrane gradient for loading of ionizable drugs of various
`
`pharmacological classes.” Ex. 2001 ¶ 74 (citing Ex. 2002, 11; Ex. 2015, 3);
`
`see Prelim. Resp. 21–22 (citing Ex. 2001 ¶ 74).
`
`By contrast, Petitioner’s witness, Dr. Montgomery, observes that the
`
`incorporated patents disclose only “generic methods of preparing
`
`liposomes”—but stops short of opining that those methods would not have
`
`been useful for producing a suitable liposome-encapsulated quinolones.
`
`Pet. 50 (citing Ex. 1020 ¶¶ 99–101). We are not persuaded that any conflict
`
`2 This patent is one of at least five U.S. patents incorporated by reference into
`the disclosure of each priority application and the ’845 patent. See Ex. 1002,
`13 (the ’468 provisional application); Ex. 1001, 7:66–67 (the ’845 patent).
`
`
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`Patent 9,402,845 B2
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`between Dr. Lee’s and Dr. Montgomery’s testimonies on that point justifies
`
`institution of trial, given the further undisputed fact—which appears as an
`
`admission in the Petition—that at least one technique for preparing liposome-
`
`encapsulated quinolones, suitable for practicing the method of claims 1–26,
`
`was well known in the art long before the filing date of the earliest priority
`
`application. Pet. 56–60 (Petitioner, explaining why Finlay3 discloses suitable
`
`liposome-encapsulated quinolones).
`
`Specifically, Finlay, while not a patent publication, is probative of the
`
`knowledge and understanding of a person of ordinary skill in the art at the
`
`time of filing of each priority application. The parties agree that Finlay,
`
`published seven years before the filing date of the earliest priority application,
`
`discloses a remote loading method for encapsulating a quinolone
`
`(ciprofloxacin) with electrically neutral lipids (photophatisdylcholine and
`
`cholesterol). Significantly, the parties further agree that Finlay’s method
`
`would have produced liposome-encapsulated quinolones suitable for use in
`
`the invention of claims 1–26. Pet. 57–58 (Petitioner, explaining why Finlay
`
`would have enabled one to prepare liposome-encapsulated quinolones suitable
`
`for use in the claimed invention); Prelim. Resp. 42 (Patent Owner, explaining
`
`why “Finlay could be used to prepare the liposomal quinolones” required by
`
`the claims) (citing Ex. 2001 ¶ 71).
`
`Patent Owner directs us to additional evidence that this remote loading
`
`technique “was not first disclosed by Finlay,” but had “been published by
`
`
`3 W.J. Finlay & J.P. Wong, Regional Lung Deposition of Nebulized Liposome-
`Encapsulated Ciprofloxacin, 167 INT’L J. PHARMACEUTICS 121–127 (1998)
`(Ex. 1024).
`
`
`
`
`13
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`Oh[4] in 1995” and “generally described in Cullis[5]” even earlier.6 Prelim.
`
`Resp. 19 (citing Ex. 1035, 15–17; Ex. 1056, 2; Ex. 2001 ¶ 68); see id. at 36–
`
`37 (citing Ex. 1024, 2; Ex. 1056, 2; Ex. 2001 ¶ 68). We agree with Patent
`
`Owner that the Petition fails to adequately account for these references,
`
`publicly available long before the filing date of the earliest priority
`
`application, which “expressly teach the preparation of liposomal quinolones
`
`with electrically neutral lipids.” Prelim. Resp. 18 (emphasis omitted) (citing
`
`Ex. 2001 ¶¶ 67–68). In that regard, we find significant that Petitioner’s own
`
`exhibits reveal publicly available prior art techniques, useful for preparing
`
`liposome-encapsulated quinolones, but neither the Petition nor
`
`Dr. Montgomery adequately analyzes those exhibits when discussing the state
`
`of the prior art for purposes of establishing post grant review eligibility based
`
`on lack of enablement. Id. at 10–20.
`
`On that point, when addressing the state of the prior art,
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`Dr. Montgomery focuses on Cullis—a reference published in 1987, almost
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`twenty years before the earliest priority application. Pet. 11–12 (citing
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`Ex. 1020 ¶¶ 27–29 (Dr. Montgomery, relying on Ex. 1035, 4, 7, 11); see
`
`
`4 Yu-Kyoung Oh et al., Formulation & Efficacy of Liposome-Encapsulated
`Antibiotics for Therapy of Intracellular Myobacterium avium Infection,
`39 ANTIMICROBIAL AGENTS & CHEMOTHERAPY 2104–2111 (1995) (Ex. 1056).
`Although we provide the original pagination in this citation, like the parties,
`we refer in our discussion to the pagination Petitioner added to the exhibit.
`5 Peter R. Cullis et al., Liposomes as Pharmaceuticals, in Liposomes From
`Biophysics to Therapeutics 39, 60–65 (Marc J. Ostro ed., 1987) (Ex. 1035).
`Although we provide the original pagination in this citation, like the parties,
`we refer in our discussion to the pagination Petitioner added to the exhibit.
`6 The ’845 patent cites Cullis in the context of disclosing methods available
`for producing liposomes suitable for use in the invention. Ex. 1001, 7:53–54
`(“Liposomes can be produced by a variety of methods (for a review, see, e.g.,
`Cullis et al. (1987)).”).
`
`
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`Prelim. Resp. 17 (citing Ex. 2001 ¶¶ 64, 65). But that reference “recognizes
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`that liposomal technology was rapidly developing, and concludes by stating
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`that it ‘appears increasingly likely that a pharmaceutically acceptable
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`liposomal formulation for any given drug can be achieved.’” Prelim.
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`Resp. 17–18 (citing Ex. 1035, 19; Ex. 2001 ¶ 64).
`
`Patent Owner identifies another of Petitioner’s exhibits for disclosure of
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`a technique for encapsulating ciprofloxacin (a quinolone) in electrically
`
`neutral lipids, involving citrate-based remote-loading, which was publicly
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`available before the filing date of the earliest priority application. Id. (citing
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`Ex. 1045 ¶ 10; Ex. 2001 ¶ 68). That reference persuasively shows that, nearly
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`two years before the filing of the ’468 provisional application, it would have
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`been well within the level of ordinary skill in the art to encapsulate
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`“[a]ntibacterial agents,” including “quinolones, such as ciprofloxin” with
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`liposomal compositions for delivery to the lungs by inhalation. Ex. 1045
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`Title, ¶ 31; see id. ¶¶ 36–37, 44–50 (describing lipids and liposomes suitable
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`for encapsulating quinolones), ¶¶ 72–74 (Example 2, directed to “free
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`ciprofloxacin or liposomal ciprofloxacin”), claim 33 (directed to quinolones).
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`In addition, Patent Owner directs us to other known prior art loading
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`techniques useful for encapsulating other quinolones, such as entrofloxacin
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`and ofloxasin, in electrically neutral lipids. Prelim. Resp. 20–21, 36–37
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`(citing Ex. 2012, 3; Ex. 2013, 4; Ex. 2014, 1; Ex. 2001 ¶ 70).
`
`On this record, there is no genuine dispute surrounding the question
`
`whether, before the filing date of the earliest priority application, techniques
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`useful for preparing liposome-encapsulated quinolones, suitable for practicing
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`claims 1–26, were publicly available to a person of ordinary skill in the art.
`
`Compare Ex. 1020 ¶¶ 90–101, with Ex. 2001 ¶¶ 68, 70, 71, 74–83, 85.
`
`
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`(4) Conclusions Pertaining to Undue Experimentation
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`The crux of Petitioner’s argument is that none of the priority
`
`applications teaches a technique that would have enabled an ordinary artisan
`
`to produce liposome-encapsulated quinolones, suitable for practicing the
`
`claimed method; therefore, undue experimentation would have been required
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`to carry out the invention of claims 1–26. Pet. 47–53. As Patent Owner
`
`points out, however, “a patent need not teach, and preferably omits, what is
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`well known in the art.” Prelim. Resp. 16–17 (quoting Hybritech, Inc. v.
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`Monoclonal Antibodies, Inc., 802 F.2d. 1367, 1384 (Fed. Cir. 1986)).
`
`Given the abundant record evidence that techniques for preparing a
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`liposome-encapsulated form of quinolone, as required by claims 1–26, were
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`publicly available to an ordinary artisan, Petitioner’s argument is
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`unpersuasive. Petitioner argues, for example, that one would have needed to
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`select suitable liposomes and quinolones, then work out a loading or trapping
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`method for encapsulation. Id. at 50. Critically lacking, however, is any
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`persuasive objective proof that those tasks would have amounted to undue
`
`experimentation. Id. at 50–51 (citing Ex. 1020 ¶ 100).
`
`Petitioner lays out a number of safety and efficacy tests that, in
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`Petitioner’s view, rise to the level of undue experimentation (Pet. 50–53), but
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`the test for enablement is “not merely quantitative.” PPG Indus. v. Guardian
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`Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996) (citation omitted). We are
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`guided by precedent holding that “a considerable amount of experimentation
`
`is permissible, if it is merely routine.” Id; see Cephalon, Inc. v. Watson
`
`Pharms., Inc., 707 F.3d 1330, 1339 (Fed. Cir. 2013) (“Unsubstantiated
`
`statements indicating that experimentation would be ‘difficult’ and
`
`‘complicated’ are not sufficient” to show that the “experimentation would be
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`
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`undue.”). Here, the record is replete with objective proof that techniques for
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`preparing liposome-encapsulated quinolones, suitable for use in claims 1–26,
`
`would have been routine by the time of filing of the earliest priority
`
`application. Perhaps most telling, in that regard, is that both parties agree that
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`at least one technique, disclosed by Finlay, was available about seven years
`
`prior to the filing date of the ’468 provisional application. See supra p. 13.
`
`Petitioner nonetheless argues that the priority applications do not “teach
`
`how to make a mixture of free and liposome-encapsulated quinolones that
`
`provide both immediate and sustained bactericidal activity” as required by the
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`claims. Pet. 49 (citing Ex. 1020 ¶ 98). In Petitioner’s view, one would have
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`had “to conduct in vitro and in vivo tests to determine whether the liposomes
`
`have integrity to provide sustained bactericidal activity.” Id. at 50–51 (citing
`
`Ex. 1020 ¶ 100). Patent Owner counters that the earliest-filed priority
`
`application “teaches how to measure sustained and immediate activity.”
`
`Prelim. Resp. 38 (citing Ex. 1002, 22; Ex. 2001 ¶ 81). We agree with Patent
`
`Owner that the ’468 provisional application includes a working example that
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`would have provided adequate guidance for assessing the activity of free and
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`encapsulated antiinfective based on pharmacokinetic modeling. Ex. 1002, 21–
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`22 (Example 1). Regarding liposomal integrity, moreover, Dr. Lee directs us
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`to persuasive evidence that “as of December 8, 2005”—the earliest possible
`
`priority date—an ordinary artisan “would have ‘known that increasing the
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`proportion of cholesterol increases liposomes stability and retention of drug in
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`vivo.’” Ex. 2001 ¶ 78 (citing Ex. 1047, 1; Ex. 1037, 10).
`
`Furthermore, Petitioner’s own evidence establishes that at least one
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`method of producing liposome-encapsulated quinolones, capable of providing
`
`the sustained bacterial activity required by claim 1, was well known as