UNITED STATES PATENT AND TRADEMARK OFFICE
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`APOTEX INC.
`Petitioner
`V.
`ALCON PHARMACEUTICALS, LTD.
`Patent Owner
`
`CASE IPR: Unassigned
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 6 9716,830
`UNDER 35 U.S.C. §§ 311-319 and 37 C.F.R. §§ 42.1-.80, 42.100-.123
`
`Mail Stop "PATENT BOARD"
`Patent Trial and Appeal Board
`U.S. Patent and Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`

`

`TABLE OF CONTENTS
`
`PETITION FOR INTER PARTES REVIEW OF U.S. PATENT NO. 6,716,830
`UNDER 35U,S.C.311-319 and 37C.F.R. §42.1-.80,42.100-.123 .......
`INTRODUCTION ..........................................................................................1
`I.
`OVERVIEW ................................................................................................... 1
`II.
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS...............................................................................................4
`5
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1)).....................................
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`V.
`REASONS THEREFOR (37 C.F.R. § 42.22(a))............................................6
`THE ’830 PATENT.........................................................................................6
`VI.
`VII. PERSON OF SKILL IN THE ART & STATE OF THE ART......................7
`IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))..................8
`VIII.
`1942 Patent...........................9
`Ground 1: Claim 1 Is Anticipated by the
`Ground 2: Claim 1 Would Have Been Obvious Over the
`’942 Patent in View of OCUFLOf PDR.............................................16
`Ground 3: Claim 1 Would Have Been Obvious Over the
`’942 Patent in View of OcuFLoxfi PDR and Petersen
`Abstract...............................................................................................21
`Ground 4: Claim 1 Would Have Been Obvious Over the
`’942 Patent in View of CIL0xANfi PDR..............................................23
`Ground 5: Claim 1 Would Have Been Obvious Over the
`’942 Patent in View of CILOXAN fi PDR and Petersen
`Abstract...............................................................................................28
`Ground 6: Claim 1 Would Have Been Obvious Over Daihoff
`in View of OCUFLOXfi PDR and Petersen Abstract............................29
`Ground 7: Claim 1 Would Have Been Obvious Over Dalhoff
`in view of CIL0xANfi PDR and Petersen Abstract . ............................ 34
`The Art Does Not Teach Away from the Claimed Invention . ........... 38
`Secondary Considerations Do Not Rebut the Prima Facie
`Case. ................................................................................................... 43
`
`A.
`B.
`
`C.
`
`D.
`
`E.
`
`F.
`
`G.
`
`H.
`I.
`
`1. (cid:9)
`
`No Unexpected Results Over the Closest Prior Art ................. .45
`
`11
`
`

`

`No Long-Felt and Unmet Need (cid:9)
`2. (cid:9)
`No Skepticism by Experts........................................................
`3.
`No Commercial Success . ......................................................... 59
`4.
`CONCLUSION.............................................................................................60
`
`. 55
`57
`
`IX. (cid:9)
`
`111
`
`

`

`I.
`
`INTRODUCTION
`
`APOTEX INC.’s ("Petitioner") Petition for Inter Partes Review ("Petition")
`
`challenges U.S. Pat. No. 6,716,830 to Cagle et al., titled "Ophthalmic Antibiotic
`
`Compositions Containing Moxifloxacin" ("the ’830 patent") (APX 1001).
`
`II.
`
`OVERVIEW
`
`The raison d’Œtre of inter partes review is straightforward: to improve patent
`
`quality and, if warranted, cancel unpatentable issued patent claims. Claim 1 of the
`
`’830 patent never should have been allowed, and Petitioner is reasonably likely to
`
`prevail in establishing that the claim is unpatentable. Claim 1 recites "[a] topical
`
`ophthalmic pharmaceutical composition comprising moxifloxacin or a
`
`pharmaceutically useful hydrate or salt thereof in a concentration of 0.1 to 1.0 wt %
`
`and pharmaceutically acceptable vehicle therefor." (APX 1001, 7:29-32.) Prior art
`
`U.S. Patent No. 5,607,942 to Petersen et al. ("the ’942 patent") (APX 1002)
`
`discloses the exact same composition - moxifloxacin - but the original Examiner
`
`failed to appreciate the full scope of the ’942 patent’s disclosure.
`
`The specification of the ’942 patent clearly conveys to a person of ordinary
`
`skill in the art ("POSA") the subject matter of claim 1 of the ’830 patent without the
`
`need for picking, choosing, and combining various disclosures not directly related.
`
`See Net MoneylN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). The
`
`’942 patent is directed to antibacterial formulations, and claim 3 of the ’942 patent is
`
`1
`
`

`

`directed to an antibacterial composition comprising a therapeutically effective
`
`amount of moxifloxacin and a diluent,
`
`i.e., a pharmaceutically acceptable vehicle.
`
`(APX 1002, 99:21-23.) The ’942 patent discloses that "[t]he compounds according
`
`to the invention ... exhibit a broad antibacterial spectrum against Gram-positive and
`
`Gram-negative germs." (Id., 53:21-23.) The compounds are "particularly suitable in
`
`human ... medicine for the prophylaxis and chemotherapy of local and systematic
`
`infections caused by [bacterial] pathogens." (Id., 53:42-44.) For example the
`
`compounds are effective against "local and/or systemic diseases caused by" various
`
`bacteria, such as S. aureus, S. epidermidis, S. pneumoniae, H. influenza, and P.
`
`aeruginosa. (Id., 53:45-61.) The compounds of the ’942 patent can treat "eye
`
`infections,"
`
`(Id., 54:22), and can be combined with "[n]on-toxic inert
`
`pharmaceutically suitable excipients" to form "[o]phthalmological ... formulations
`
`[such as] eye ointments," (Id., 54:65; 56:27-29.) In addition, the compounds of the
`
`invention "should preferably be present in the ... pharmaceutical formulations in a
`
`concentration of about 0.1 to 99.5% ... by weight." (Id., 56:7-10.)
`
`Comparing the disclosure in the ’942 patent to claim 1 of the ’830 patent, the
`
`weight % range recited in claim 1 is entirely subsumed within the weight % range
`
`disclosed in the ’942 patent, and there is nothing critical about the claimed range as
`
`compared with the prior art range. Thus, the ’942 patent discloses a topical
`
`ophthalmic pharmaceutical composition comprising moxifloxacin in a concentration
`
`2
`
`

`

`of 0.1 to 1.0% by weight and a pharmaceutically acceptable vehicle. Claim 1 is
`
`therefore anticipated.
`
`The Examiner accepted Alcon’s arguments in reversing her original decision
`
`to reject claim 1. To overcome the Examiner’s rejection, Alcon made meritless
`
`arguments, such as claiming alleged unexpected results. However, the Examiner
`
`erred in considering that argument because unexpected results are irrelevant to
`
`anticipation. See Cohesive Techs., Inc. v. Waters Corp., 543 F.3d 1351, 1364 (Fed.
`
`Cir. 2008). Alcon also argued that the claimed range of "0.1 to 1.0 wt %" was not
`
`disclosed by the ’942 patent. However, the Examiner erred in relying on this
`
`argument because the claimed range (0.1 to 1.0%) is subsumed by the range
`
`disclosed in the ’942 patent (0.1 to 95%). Further, to avoid anticipation in the case of
`
`overlapping or subsumed ranges, Alcon had to demonstrate criticality of the claimed
`
`range and a considerable difference between the claimed range and the range
`
`disclosed in the ’942 patent. See Clear Value, Inc. v. Pearl River Polymers, Inc., 668
`
`F.3d 1340, 1344-45 (Fed. Cir. 2012). Alcon never showed the requisite criticality or
`
`any considerable difference. Because the Examiner failed to appreciate the
`
`deficiencies in Alcon’s arguments, Petitioner seeks to rectify the Examiner’s error of
`
`issuing claim 1 of the ’830 patent.
`
`Should the Board find that the ’942 patent does not anticipate claim 1 of the
`
`’830 patent, claim 1 certainly would have been obvious over of the ’942 patent in
`
`3
`
`

`

`view of various references not previously before the Examiner, nor any other
`
`tribunal (see §§ VIII(B)-(E)). Also, claim 1 would have been obvious in view of a
`
`set of other references not previously before the Examiner, nor any other tribunal
`
`(see §§ VTII(F)-(G)). Alcon’s previously-presented arguments alleging secondary
`
`indicia of nonobviousness are both factually and legally meritless and do not
`
`overcome Petitioner’s strong case of prima facie obviousness. Moreover, the "mere
`
`recognition of latent properties in the prior art does not render nonobvious an
`
`otherwise known invention." In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed.
`
`Cir. 1991). "To hold otherwise would allow any formulation - no matter how
`
`obvious - to become patentable merely by testing and claiming an inherent
`
`property." Santarus Inc. v. Par Pharm., Inc., No. 2010-3160, 2012 WL 3797966, at
`
`*9 (Fed. Cir. Sept. 4, 2012).
`
`In view of clear errors made during original examination, and in view of the
`
`newly-presented grounds for unpatentability set forth herein, Petitioner requests
`
`inter partes review of claim 1 of the ’830 patent and cancelation of the claim.
`
`III. GROUNDS FOR STANDING (37 C.F.R. § 42.104(a)); PROCEDURAL
`STATEMENTS
`
`Petitioner certifies that (1) the ’830 patent is available for
`
`inter partes review;
`
`and (2) Petitioner is not barred or estopped from requesting
`
`inter partes review of
`
`any claim of the ’830 patent on the grounds identified in this Petition.
`
`This Petition is filed in accordance with 37 CFR § 42.106(a). Concurrently
`
`

`

`filed herewith are a Power of Attorney and Exhibit List pursuant to § 42.10(b) and §
`
`42.63(e), respectively. The required fee is paid through online credit card payment.
`
`The Office is authorized to charge any fee deficiency, or credit any overpayment, to
`
`Deposit Acct. No. 19-0036 (Customer ID No. 45324).
`
`IV. MANDATORY NOTICES (37 C.F.R. § 42.8(a)(1))
`
`Each Real Party-In-Interest (37 C.F.R. § 42.8(b)(1)) is: APOTEX INC.,
`
`APOTEX CORP., and APOTEX HOLDINGS, INC.
`
`Petitioner Provides Notice of Related Matters (37 C.F.R. § 42.8(b)(2)):
`
`udicial matters: A/con Pharms. Ltd. et al. v. Apotex Inc. et al., Civ. No. 12-960-
`
`SLR (D. Del.); A/con Pharms. Ltd. et al. v. Watson Labs. Inc. et al., Civ. No. 11-
`
`293-SLR (D. Del.); A/con Pharms. Ltd. et al. v. Lupin Ltd. et al., Civ. No. 11-587-
`
`SLR (D. Del.); and A/con Pharms. Ltd. et al. v. Lupin Ltd. et al., Civ. No. 11-973-
`
`SLR (D. Del.). Administrative matters: U.S. Appi. No. 12/611,5 10 and U.S. Patent,
`
`No. 7,671,070 ("the ’070 patent"), a continuation of the ’830 patent.
`
`Designation of Lead and Back-Up Counsel (37 C.F.R. § 42.8(b)(3)):
`
`Lead Counsel
`Eldora L. Ellison (Reg. No. 39,967)
`STERNE, KESSLER, GOLDSTEIN & Fox
`P.L.L.C.
`1100 New York Avenue, NW
`Washington, DC 20005
`202.772.8508 (telephone)
`202.371.2540 (facsimile)
`eellison@skgf.com
`
`Back-Up Counsel
`Richard P. Hadorn (Reg. No. 58,537)
`STERNE, KESSLER, GOLDSTEIN & Fox
`P.L.L.C.
`1100 New York Avenue, NW
`Washington, DC 20005
`202.772.8890 (telephone)
`202.371.2540 (facsimile)
`rhadorn@skgf.com
`
`5
`
`

`

`Petitioner Provides Notice of Service Information (37 C.F.R. §
`
`42.8(b)(4)): Please direct all correspondence regarding this Petition to lead counsel
`
`at the above address. Petitioner consents to service by email at: eellisonskgf.com
`
`and rhadom@skgf.com .
`
`STATEMENT OF THE PRECISE RELIEF REQUESTED AND THE
`V.
`REASONS THEREFOR (37 C.F.R. § 42.22(a))
`
`Petitioner requests inter partes review under 37 CFR § 42.108 as to claim 1 of
`
`the ’830 patent and ruling that claim 1 is unpatentable based on one or more of the
`
`grounds under 35 U.S.C. §§ 102 or 103 set forth herein. Petitioner’s detailed
`
`statement of the reasons for the relief requested is set forth in § VIII below.
`
`VI.
`
`THE ’830 PATENT
`
`The ’830 patent issued on April 6, 2004, and asserts priority back to
`
`September 30, 1998. According to the USPTO’s electronic-assignment records,
`
`ALCON PHARMACEUTICALS, LTD. ("ALcoN") owns the ’830 patent by assignment.
`
`The ’830 patent specification is directed to ophthalmic, otic, and nasal compositions
`
`containing moxifloxacin and the use of these compositions to treat ophthalmic, otic,
`
`and nasal infections, particularly bacterial infections, by topically applying the
`
`compositions to the affected tissues. (APX 1001, Abstract.)
`
`In accordance with 37 C.F.R. § 42.100(b), claim 1 must be given its broadest
`
`reasonable interpretation ("BR!") in light of the specification of the ’830 patent.
`
`Because the terms of claim 1 are clear on their face, they are presumed to take on
`
`

`

`their ordinary and customary meanings. Petitioner proposes that the BRI for the
`
`term "ophthalmic" is "of or relating to the eye," and the BRI for "pharmaceutically
`
`acceptable vehicle" is "a composition for delivery of an active ingredient." Although
`
`a court construed certain terms of the ’830 patent in Bayer Healthcare AG et al. v.
`
`Teva Pharms, USA, Inc., Civ. No. 06-234-SLR (D. Del.) (the "Teva litigation"), the
`
`Board is not bound by that construction because courts apply narrower claim-
`
`construction standards. See In re Trans Texas Holdings Corp., 498 F.3d 1290 (Fed.
`
`Cir. 2007); In re Baxter Intern., Inc., 678 F.3d 1357 (Fed. Cir. 2012). Further, the
`
`Petitioner was not a party to the Teva litigation nor in privity with a party to that
`
`litigation. But even under the court’s narrow construction, claim 1 is unpatentable on
`
`the grounds set forth herein.
`
`VII. PERSON OF SKILL IN THE ART & STATE OF THE ART
`
`A POSA is presumed to be aware of all pertinent art, thinks along
`
`conventional wisdom in the art, and is a person of ordinary creativity. With respect
`
`to the ’830 patent, a POSA would have had knowledge of the scientific literature
`
`concerning pharmaceutical compositions for the treatment of eye infections as of
`
`1998. A POSA typically would have a Doctor of Medicine (MD) degree, a Ph.D., or
`
`another degree relating to ophthalmic infections (e.g., pharmacy, microbiology,
`
`etc.), and such a POSA would have substantial familiarity, training, or experience
`
`with compositions for treating ophthalmic infections.
`
`7
`
`

`

`As of September 30, 1998, the fluoroquinolone moxifloxacin and its use for
`
`topically treating eye infections were well known in the art, as evidenced by the ’942
`
`patent which issued in 1997 and is thus reflective of the state of the art. (APX 1002,
`
`98:52-99:2 (claim 1); cols. 23-24, first grouping of substituents enumerated in line
`
`1.) The chemical structure and International Union of Pure and Applied Chemistry
`
`(TUPAC) name of moxifloxacin (1 -cyclopropyl-7-([S,S]-2, 8-diazabicyclo-
`
`[4.3.0] non-8-yl)-6-fluoro- 1 ,4-dihydro-8-methoxy-4-oxo-3 -quinolinecarboxylic acid)
`
`are shown, and moxifloxacin is claimed in claim 1, in the ’942 patent. (APX 1002,
`
`98:52-99:2.) The ’942 patent also claims an antibacterial composition comprising
`
`moxifloxacin and a diluent (claim 3), as well as a method of combating bacteria in a
`
`patient comprising administering moxifloxacin to the patient in need thereof (claim
`
`5). (APX 1002, 99:21-100:8.) As of September 30, 1998, CIL0xAN fi and OCUFLOXfi
`
`were the main fluoroquinolone products marketed for the treatment of bacterial eye
`
`infections. (APX 1007, ¶25.) CILOXANfi contains 0.3% of ciprofloxacin as the active
`
`ingredient, and OcuFLox fi contains 0.3% of ofloxacin as the active ingredient. (Id.)
`
`VIII. IDENTIFICATION OF CHALLENGE (37 C.F.R. § 42.104(b))
`
`Inter partes review of claim 1 of the ’830 patent is requested on the grounds
`
`for unpatentability listed in the index below. Per 37 C.F.R. § 42.6(d), copies of the
`
`references are filed herewith. In support of the proposed grounds for unpatentability,
`
`this Petition is accompanied by declarations of technical experts Drs. Michael J.
`
`[’I
`
`

`

`Barza (APX 1007) and Richard Fiscella (APX 1012), which explain what the art
`
`would have conveyed to a POSA.
`
`Ground
`1
`
`2
`
`3
`
`4
`
`5
`
`6
`
`7
`
`35 Usc
`§ 102(b)
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`§ 103(a)
`
`Index of Reference(s)
`’942 patent (APX 1002)
`’942 patent (APX 1002) in view of OCUFLOX fi PDR
`(APX 1006)
`’942 patent (APX 1002) in view of OCUFLOX fi PDR
`(APX 1006) and Petersen Abstract (APX 1005)
`’942 patent (APX 1002) in view of CILOXAN fi PDR
`(APX 1004)
`’942 patent (APX 1002) in view of CIL0xANfi PDR
`(APX 1004) and Petersen Abstract (APX 1005)
`Daihoff (APX 1003) in view of OCUFLOX fi PDR (APX
`1006) and Petersen Abstract (APX 1005)
`Dalhoff(APX 1003) in view of CILOxAN fi PDR (APX
`1004) and Petersen Abstract (APX 1005)
`
`A. (cid:9)
`
`Ground 1: Claim 1 Is Anticipated by the ’942 Patent.
`
`The ’942 patent (APOTEX 1002), titled "7-(1-Pyrrolidinyl)-3-Quinolone- and
`
`-Naphthyridone-Carboxylic Acid Derivatives as Antibacterial Agents and Feed
`
`Additives," issued on March 4, 1997. Thus, the ’942 patent is prior art to the ’830
`
`patent under at least 35 U.S.C. § 102(b) because it issued more than one year before
`
`September 30, 1998.
`
`As shown by the following claim chart and discussion herein, each and every
`
`element of claim 1 is disclosed in the ’942 patent, arranged as claimed, so as to
`
`enable a POSA to make and use the invention in claim 1 without the need for undue
`
`experimentation in light of the general knowledge available in the art.
`
`

`

`Claim 1
`1. A topical
`ophthalmic
`pharmaceutical
`composition
`
`Disclosure of the ’942 Patent
`"Possible suitable formulations are ... emulsions,
`ointments or drops. Ophthalmological and dermatological
`formulations ... eye ointments ... can be used for local
`therapy." (APX 1002, 56:24-30.)’
`
`Moxifloxacin is "active against a very broad spectrum of
`microorganisms. Gram-negative and Gram-positive
`bacteria and bacteria-like microorganisms can be
`combated and the diseases caused by these pathogens can
`be prevented, alleviated and/or cured with the aid of
`[moxifloxacin]." (APX 1002, 53:34-39.)
`
`"For example, local and/or systemic diseases caused by the
`following pathogens or by mixtures of the following
`pathogens can be treated and/or prevented: Gram-positive
`cocci, for example Staphylococci (Staph. aureus and
`Staph. epidermidis) and Streptococci (... Strept.
`pneumoniae ... ). The antibacterial spectrum moreover
`includes the genus Pseudomonas (Ps. aeruginosa ... ) and
`Mycobacteria, for example Mycobacterium tuberculosis."
`(APX 1002, 53:45-67.)
`
`As confirmed by Dr. Barza, a POSA would have
`understood that a reference to "local therapy," "local
`diseases," or "eye ointments" in the context of an
`ophthalmic formulation, means a topical ophthalmic
`pharmaceutical composition. (APX 1007, ¶30.)
`The ’942 patent discloses and specifically claims the
`fluoroquinolone moxifloxacin (1-cyclopropyl-7-([S,S]-
`2, 8-diazabicyclo- [4.3. 0]non- 8-yl)-6-fluoro- 1 ,4-dihydro- 8-
`methoxy-4-oxo-3-quinolinecarboxylic acid) (APX 1002,
`cols. 23-24, the substituents enumerated in line 1; and at
`98:52-99:2 (claim 1).)
`in a concentration of Moxifloxacin "should preferably be present in the above-
`
`comprising
`moxifloxacin or a
`pharmaceutically
`useful hydrate or
`salt thereof
`
`The citation format used throughout this document is: (Exhibit Number, page or
`
`column number:line number-line number), e.g. (APX 1002, 5:5-12.)
`
`10
`
`

`

`0.1 to 1.0 wt %
`
`mentioned [sic] pharmaceutical formulations in a concen-
`tration of about 0.1 to 99.5, preferably about 0.5 to 95% by
`weight of the total mixture." (APX 1002, 56:7-10.)
`
`The concentration range in the ’942 patent overlaps with
`the range of moxifloxacin in claim 1. According to Dr.
`Barza, he is not aware of any information that establishes
`that the claimed range is critical. (APX 1007, ¶30-3 1.)
`
`Therefore, a POSA would have understood that many
`values outside the claimed range of 0.1 to 1.0 wt % of
`moxifloxacin, up to moxifloxacin’s limit of aqueous
`solubility, would have been as efficacious as the claimed
`range, if not more efficacious. (Id.)
`"Possible suitable formulations are ... emulsions,
`ointments or drops. Ophthalmological and dermatological
`formulations ... eye ointments ... can be used for local
`therapy." (APX 1002, 56:24-30; see also APX 1007.)
`
`and
`pharmaceutically
`acceptable vehicle
`therefor.
`
`The ’942 Patent Inherently Discloses a "Pharmaceutically Acceptable
`
`Vehicle": As noted above, the ’942 patent discloses "[p]ossible suitable
`
`formulations are ... emulsions, ointments or drops. Ophthalmological and
`
`dermatological formulations ... eye ointments ... can be used for local therapy."
`
`(APX 1002, 56:24-30.) As confirmed by Dr. Barza, a POSA would have understood
`
`that a reference to "local therapy," "local diseases," or "eye ointments" in the context
`
`of an ophthalmic formulation, necessarily means a topical ophthalmic
`
`pharmaceutical composition. (APX 1007, T30.) Furthermore, a POSA would have
`
`understood that emulsions, ointments or drops are pharmaceutically acceptable
`
`vehicles. (Id. at ¶31) Therefore, as supported by Dr. Barza, a pharmaceutically
`
`acceptable vehicle is necessarily present in the ’942 patent. As such, the ’942 patent
`
`11
`
`

`

`inherently discloses the limitation "pharmaceutically acceptable vehicle." In re
`
`Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999) (establishing inherent disclosure
`
`requires that the extrinsic evidence "make clear that the missing descriptive matter is
`
`necessarily present in the thing described in the reference, and that it would be so
`
`recognized by [POSAs]"); In re Petering, 301 F.2d 676, 681-82 (C.C.P.A. 1962)
`
`(finding anticipation when a POSA can "at once envisage" each member of a limited
`
`class from a reference).
`
`Claim I’s Wt. % Range Limitation Is Not "Critical" and Is Anticipated by
`
`the ’942 Patent’s Subsuming Range: Claim 1 recites a wt% range of moxifloxacin
`
`that is entirely subsumed within the wt% range disclosed in the ’942 patent. Further,
`
`as confirmed by Dr. Barza, claim l’s wt % range is not critical when compared with
`
`wt %’s outside of the claimed range, and a POSA would have understood that many
`
`values outside claim l’s wt % range, up to moxifloxacin’s limit of aqueous
`
`solubility, would have been as efficacious as the claimed range, if not more
`
`efficacious. (APX 1007, ¶30-3 1.) Controlling case law makes it clear that the claim
`
`is unpatentable in such a situation. Therefore, claim l’s range limitation is met by
`
`the ’942 patent.
`
`It is "an elementary principle of patent law that when, as by a recitation of
`
`ranges or otherwise, a claim covers several compositions, the claim is ’anticipated’ if
`
`one of them is in the prior art." Titanium Metals Corp. v. Banner, 778 F.2d 775, 782
`
`12
`
`

`

`(Fed. Cir. 1985); see King Pharms., Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1277
`
`(Fed. Cir. 2010). And in the absence of extenuating circumstances, a prior art range
`
`that overlaps a claimed range anticipates that claimed range. See Titanium Metals,
`
`778 F.2d at 782. The Federal Circuit recently drew a bright line between a case
`
`where such extenuating circumstances existed and cases with fact scenarios such as
`
`Alcon’s. See Clear Value, Inc., 668 F.3d at 1344-45. In the extenuating-
`
`circumstances case, a patentee was able to defeat a finding of anticipation because
`
`the claimed range was critical to the invention and there was a considerable
`
`difference between the range taught in the prior art and the claimed range.
`
`Id. at
`
`1345 (citing Atofina v. Great Lakes Chem. Corp., 441 F.3d 991 (Fed. Cir. 2006)). In
`
`contrast, the Federal Circuit observed that the patentee in Clear Value did not
`
`establish that the claimed range was "critical" or that there was a considerable
`
`difference between the range taught in the prior art and the claimed range.
`
`Clear Value, 668 F.3d at 1345.
`
`As with the invalid claims in Clear Value, Alcon has neither alleged any
`
`"criticality" of claim l’s range compared to the ’942 patent’s subsuming range, nor
`
`presented any evidence to show a considerable difference at different points within
`
`the ’942 patent’s range. Indeed, Dr. Barza is not aware of any information suggesting
`
`such a criticality or differentiation exists. Therefore, as confirmed by Dr. Barza, a
`
`POSA would have understood the ’942 patent’s range of 0.1 to 99.5 wt % to
`
`13
`
`

`

`constitute a disclosure of claim l’s range of 0.1 to 1.0 wt %. (APX 1007, ¶30-31.)
`
`As such, claim l’s range limitation is met by the ’942 patent.
`
`The ’942 Patent Anticipates Claim 1: As confirmed by Dr. Barza and as
`
`addressed above, each and every element of claim 1 is disclosed in the ’942 patent,
`
`arranged as claimed. (Id. at 32.) And as a prior art patent, everything disclosed in the
`
`’942 patent - whether claimed or unclaimed - is presumed enabled, including
`
`compositions with a moxifloxacin wt % within the wt% range recited in claim 1.
`
`In
`
`re Antor Media Corp., 689 F.3d 1282, 1287 (Fed. Cir. 2012) ("[B]oth claimed and
`
`unclaimed materials disclosed in a [prior art] patent are presumptively enabling,"
`
`and this "presumption applies in the district court as well as the PTO."); MPEP §
`
`2121. And, an anticipatory reference need not demonstrate efficacy to be enabling.
`
`Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1326 (Fed. Cir. 2005).
`
`Likewise, to serve as an anticipating reference, the ’942 patent need not demonstrate
`
`utility or actually perform suggestions in its disclosure.
`
`Id.
`
`Further, as confirmed by Dr. Barza, the ’942 patent’s disclosure sets forth the
`
`elements shown in the above claim chart in a sufficiently detailed manner such as to
`
`enable at least one embodiment within the scope of the invention of claim 1 without
`
`undue experimentation. (APX 1007, ¶32.) For example, the nature of the invention
`
`is topical ophthalmic pharmaceutical compositions, which was a well-developed
`
`field as of September 30, 1998, as evidenced by the ’942 patent, CIL0xAN fi and
`
`14
`
`

`

`OcuFLoxfi . (Id.) Also, the claim is limited to a topical ophthalmic pharmaceutical
`
`composition having a defined quantity of moxifloxacin, a known antibacterial
`
`fluoroquinolone. (Id.) The state of the prior art was also well established with
`
`respect to topical ophthalmic pharmaceutical compositions as evidenced by at least
`
`three topical ophthalmic compositions containing fluoroquinolones being on the
`
`market as of September 30, 1998. (Id.) And although the skill level of a POSA was
`
`high as of September 30, 1998, formulating topical ophthalmic pharmaceutical
`
`compositions could be routinely performed at that time, as evidenced by the ’942
`
`patent, CIL0xAN fi and OcuFLox fi . (Id.) Such formulating would not have required
`
`more than routine experimentation to generate the claimed topical ophthalmic
`
`composition. (Id.) Thus, as confirmed by Dr. Barza, the level of predictability for
`
`formulating new topical ophthalmic pharmaceutical compositions was high.
`
`(Id.)
`
`Additionally, although the ’942 patent does not detail a working example
`
`relating to a topical ophthalmic pharmaceutical composition comprising
`
`moxifloxacin, the ’942 patent does disclose eye ointments and drops such that a
`
`POSA, according to Dr. Barza, would have appreciated that a pharmaceutically
`
`acceptable vehicle suitable for creating the claimed composition was necessarily
`
`present in the ’942 patent. (Id.) Thus, as confirmed by Dr. Barza, when viewed in
`
`light of the general knowledge in the field, the ’942 patent sets forth the elements of
`
`claim 1 in a sufficient manner such that a POSA could have readily made and used
`
`15
`
`

`

`the composition of claim 1 without the need for undue experimentation.
`
`(Id.)
`
`Therefore, claim 1 of the ’830 patent is anticipated by the ’942 patent.
`
`B. Ground 2: Claim 1 Would Have Been Obvious Over the ’942 Patent in
`View of OcuFLoxfi PDR.
`
`Even if the Board somehow determines that claim 1 is not anticipated, it
`
`nonetheless is unpatentable for obviousness. As supported by the declaration of Dr.
`
`Barza, claim 1 would have been obvious to a POSA reading the ’942 patent in view
`
`of OcuFLoxfi PDR. (APX 1007, ¶34-36.) As discussed
`
`infra, it is reasonably likely
`
`that Petitioner will prevail in challenging claim 1 on the basis of Ground 2 despite
`
`any teaching-away arguments (see §VIII(H),
`
`infra) or secondary-consideration
`
`arguments (see § VII(I), infra) asserted by Alcon ("Alcon’s arguments").
`
`Overview of OcuFLoxfi PDR: Product information for OCUFLOXfi (Ofloxacin
`
`ophthalmic solution) 0.3% was published in the printed publication PHYSICIAN’S
`
`DESK REFERENCE 472 (50th ed. 1996) ("OcuFLox fi MR") (APOTEX 1006). Thus,
`
`OcuFLoxfi PDR is prior art to the ’830 patent under at least 35 U.S.C. § 102(b). The
`
`OCUFLOXfi PDR discloses, inter alia, that OCUFLOXfi is a topical ophthalmic
`
`pharmaceutical composition comprising 0.3% ofloxacin and a pharmaceutically
`
`acceptable vehicle. (APX 1006, 481.)
`
`Claim 1: Claim 1 would have been obvious to a POSA reading the ’942 patent
`
`in view of OCUFL0X fi PDR, as shown below. (APX 1007, ¶34-36.)
`
`16
`
`

`

`Claim 1
`1. A topical
`ophthalmic
`pharmaceutical
`composition
`
`The ’942 Patent and OcuFLoxfi PDR
`"Possible suitable formulations are ... emulsions, ointments
`or drops. Ophthalmological and dermatological
`formulations ... eye ointments ... can be used for local
`therapy." (APX 1002, 56:27-30.)
`
`Moxifloxacin is "active against a very broad spectrum of
`microorganisms. Gram-negative and Gram-positive bacteria
`and bacteria-like microorganisms can be combated and the
`diseases caused by these pathogens can be prevented,
`alleviated and/or cured with the aid of [moxifloxacin]."
`(APX 1002,53:34-39.)
`
`"For example, local and/or systemic diseases caused by the
`following pathogens or by mixtures of the following patho-
`gens can be treated and/or prevented: Gram-positive cocci,
`for example Staphylococci (Staph. aureus and Staph. epi-
`dermidis) and Streptococci (... Stept. pneumoniae.... The
`antibacterial spectrum moreover includes the genus Pseudo-
`monas (Ps. aeruginosa... and Mycobacteria, for example
`Mycobacterium tuberculosis." (APX 1002, 53:45-67.)
`
`A POSA would have understood that a reference to "local
`therapy" or "local diseases," in the context of an ophthalmic
`formulation, means a topical ophthalmic pharmaceutical
`composition, as does the disclosure of an "eye ointment".
`(APX 1007, ¶34.)
`
`"OcufloxTM (ofloxacin ophthalmic solution) 0.3% is a sterile
`ophthalmic solution. It is a fluorinated carboxyquinolone
`anti-infective for topical ophthalmic use." (APX 1006, 481.)
`The ’942 patent discloses and specifically claims the
`comprising
`fluoroquinolone moxifloxacin (1 -cyclopropyl-7-( [S , 5] -2,8-
`moxifloxacin or a
`diazabicyclo- [4.3 .0]non-8-yl)-6-fluoro- 1 ,4-dihydro-8 -
`pharmaceutically
`useful hydrate or methoxy-4-oxo-3-quinolinecarboxylic acid) (APX 1002,
`salt thereof
`23-24, the substituents enumerated in line 1; and at 98:52-
`99:2 (claim 1).)
`in a concentration Moxifloxacin "should preferably be present in the
`of 0.1 to 1.0 wt % abovementioned [sic] pharmaceutical formulations in a
`concentration of about 0.1 to 99.5, preferably about 0.5 to
`95% by weight of the total mixture." (APX 1002, 56:7-10.)
`The concentration range in the ’942 patent overlaps with the
`
`17
`
`

`

`and
`pharmaceutically
`acceptable
`vehicle therefor.
`
`range of moxifloxacin in claim 1. (Id.) Therefore, it is prima
`facie obvious.
`
`"OcufloxTM (ofloxacin ophthalmic solution) 0.3% is a sterile
`ophthalmic solution." (APX 1006, 481.)
`"Possible suitable formulations are ... emulsions, ointments
`or drops. Ophthalmological and dermatological
`formulations ... eye ointments ... can be used for local
`therapy." (APX 1002, 56:24-30.)
`
`OcufloxTM contains ofloxacin "with: Benzalkonium chloride
`(0.005%), sodium chloride and purified water." [i.e., a
`pharmaceutically acceptable vehicle] (APX 1006, 481.)
`
`Claim I’s Wt. % Range Limitation Is Prima Facie Obvious In Light
`
`of the
`
`’942 Patent’s Subsuming Range: Because claim l’s range overlaps with the range
`
`disclosed in the ’942 patent, the claimed range is presumed obvious. See Iron Grip
`
`Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004); In re
`
`Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997). And Alcon has not presented
`
`sufficient evidence to rebut this presumption, nor can it. The prior art does not teach
`
`away from claim l’s wt% range, and claim l’s range does not produce new and
`
`unexpectedly superior results compared to the other points within the ’942 patent’s
`
`range. See discussion infra, § VIII(A); Iron Grip, 392 F.3d at 1322; In re Geisler,