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`UNITED STATES PATENT AND TRADEMARK OFFICE
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`_____________
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`BEFORE THE PATENT TRIAL AND APPEAL BOARD
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`____________
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`COMPLEX INNOVATIONS, LLC,
`Petitioner,
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`v.
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`ASTRAZENECA AB,
`Patent Owner.
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`____________
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`IPR2017-00631
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`Patent 7,759,328 B2
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`PATENT OWNER PRELIMINARY RESPONSE
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`Preliminary Response
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`IPR2017-00631
`Patent 7,759,328 B2
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`I.
`II.
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`TABLE OF CONTENTS
`INTRODUCTION ................................................................................ 1
`LEVEL OF SKILL AND CLAIM CONSTRUCTION ....................... 1
`A.
`Person of Ordinary Skill in the Art ............................................ 1
`B.
`Claim Construction..................................................................... 1
`III. EACH GROUND HAS FATAL GAPS IN EVIDENCE ..................... 2
`A. Anticipation by Mistry ............................................................... 2
`1.
`Petitioner’s anticipation case requires picking every
`ingredient and every concentration from generic
`disclosures ........................................................................ 2
`2. Mistry does not disclose 0.09 mg/mL formoterol
`fumarate dihydrate ........................................................... 8
`Anticipation by Rogueda .......................................................... 17
`1.
`Petitioner fails to justify cobbling together different
`embodiments from Rogueda to meet the claims ............ 18
`Rogueda does not disclose 0.09 mg/mL formoterol
`fumarate dihydrate ......................................................... 19
`Obviousness over Mistry, Rogueda, and Carling .................... 27
`C.
`D. Obviousness of claims 2 and 3 over Mistry, Rogueda,
`Meade, and Lewis..................................................................... 29
`IV. CONCLUSION ................................................................................... 30
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`B.
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`2.
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`Patent 7,759,328 B2
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`2002
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`2003
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`PATENT OWNER’S LIST OF EXHIBITS
`Exhibit No. Description
`D.R. Defibaugh and M.R. Moldover, “Compressed and
`2001
`Saturated Liquid Densities for 18 Halogenated Organic
`Compounds.” J. Chem. Eng. Data 42, 160–168 (1997).
`X-J Liu et al., “Liquid Viscosity of 1,1,1,2,3,3,3-
`Heptafluoropropane (HFC-227ea) along the Saturation
`Line.” J. Chem. Eng. Data 44, 688–692 (1999).
`M. Dolovich, “New delivery systems and propellants.”
`Can. Respir. J. 6, 290–295 (1999).
`US Pat. No. 6,475,467, iss. Nov. 5, 2002.
`WO Pub. No. 00/07567, pub. Feb. 17, 2000.
`US Pat. No. 3,283,012, iss. Nov. 1, 1966.
`A.L. Henne and M.A. Snook, “Fluorinated Ethers.”
`J. Am. Chem. Soc. 72, 4378–4380 (1950).
`US Pat. No. 3,965,148, iss. Jun. 22, 1976.
`US Pat. No. 5,874,469, iss. Feb. 23, 1999.
`US Pub. No. 2011/0207893, pub. Aug. 25, 2011.
`US Pub. No. 2016/0310641, pub. Oct. 27, 2016.
`
`2004
`2005
`2006
`2007
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`2008
`2009
`2010
`2011
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`ii
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`IPR2017-00631
`Patent 7,759,328 B2
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`Preliminary Response
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`INTRODUCTION
`The Petition should be denied because each challenge depends on
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`I.
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`erroneous and unsupported factual assumptions as detailed below. Petitioner’s
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`key assertion—that a canister containing 10–19 mL of HFA227, in which
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`small amounts of other ingredients are mixed, would have a fill weight of 6–
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`10 grams—is plainly erroneous. HFA227 has a liquid density at room
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`temperature of about 1.4 g/mL, making Petitioner’s assertion a physical
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`impossibility. Several other defects further taint the Petition, as discussed
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`herein.
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`II. LEVEL OF SKILL AND CLAIM CONSTRUCTION
`Person of Ordinary Skill in the Art
`A.
`Patent Owner does not acquiesce in Petitioner’s characterization of the
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`level of skill possessed by one of ordinary skill in the art (Pet. 25), but takes
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`the position that this issue does not require resolution at this stage of the
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`proceeding.
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`B. Claim Construction
`Patent Owner agrees with Petitioner (at Pet. 26), though solely for
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`purposes of this preliminary response, that no claim terms require express
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`construction.
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`1
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`III. EACH GROUND HAS FATAL GAPS IN EVIDENCE
`A. Anticipation by Mistry
`Petitioner has failed to show a reasonable likelihood that Mistry
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`anticipates claims 1 and 4–15 because (1) Petitioner’s argument requires
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`picking and choosing every recited ingredient and every recited concentration
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`from various generic disclosures; and (2) Petitioner’s elaborate calculations
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`to show that Mistry discloses the recited formoterol fumarate dihydrate
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`(“FFD”) concentration are both unsupported by evidence and erroneous.
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`1. Petitioner’s anticipation case requires picking every
`ingredient and every concentration from generic
`disclosures
`Petitioner cannot point to a single embodiment in Mistry that discloses
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`all five recited ingredients and the recited concentrations. In fact, there isn’t
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`even a single embodiment containing more than two of the recited ingredients,
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`let alone the concentrations. Petitioner’s argument thus requires one of
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`ordinary skill to have made a protracted series of arbitrary selections of
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`ingredients and concentrations to reach the claimed formulation.
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`2
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`For example, Mistry discloses at least 8 different bronchodilators,1 6
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`different reversible obstructive airway drugs,2 4 orders of magnitude of
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`concentrations
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`for each of
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`them,3 over 100 different
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`forms of
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`polyvinylpyrrolidone (“PVP”),4 4 orders of magnitude of concentrations for
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`1 Ex. 1003 at 3:36–38 (“bronchodilators, eg salbutamol, reproterol,
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`terbutaline, formoterol, pirbuterol, isoprenaline, salmeterol, fenoterol and
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`salts thereof”).
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`2 Id. at 3:31–35 (“drugs for use in the prophylactic or remedial treatment of
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`reversible obstructive airways disease, eg drugs such as sodium cromoglycate,
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`nedocromil sodium, inhaled steroids, eg beclomethasone dipropionate,
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`fluticasone propionate, budesonide and tipredane”).
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`3 Id. at 3:64–67 (“However, the composition preferably comprises from 0.01
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`to 15% w/w, preferably from 0.1 to 10% w/w, and most preferably from 0.5
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`to 5% w/w medicament.”).
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`4 Id. at 2:7–9 (“we prefer the polymer to have a K value of from 10 to 150,
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`more preferably 15 to 120”).
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`3
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`PVP in the preferred range,5 6 identified molecular weights of PEG,6 2 orders
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`of magnitude of concentrations for them,7 and 3 propellants along with a
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`mathematical formula for identifying many more.8 Aside from Mistry’s
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`Examples A, B, and C, which include both HFA227 and budesonide
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`(Ex. 1003, 7:4–8:11), and Example K, which includes HFA227 and PEG-
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`1000 (though not in the recited concentration) (id. at 11:26–59), no other
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`examples combine even two of the claimed ingredients.9
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`5 Id. at 2:27–28 (“in general the amount of polymer is from 0.00001 to 10%
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`w/w, more preferably 0.001 to 5% w/w and especially 0.001 to 1% w/w.”).
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`6 Id. at 2:34–36 (“We prefer polyethylene glycol having a mean molecular
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`weight of from 200 to 3000, preferably 400 to 2000, eg 1500.”); id. at 11:40
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`(“PEG 1000”).
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`7 Id. at 2:45–47 (“In general, we prefer a concentration of 0.01 to 4% w/w and
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`more preferably 0.1 to 2% w/w.”).
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`8 Id. at 2:56–65 (giving formula, identifying 3 preferred propellants, and
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`identifying HFA227 as particularly preferred).
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`9 Mistry’s Examples A, B, C, G, I(37-48), and K include HFA227 and PVP,
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`but each example uses a form of PVP with a K value other than the recited
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`Reaching the challenged claims from this disclosure requires the sort of
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`random picking and choosing of multiple ingredients and parameters, using
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`the claim itself as guide, that the Federal Circuit and its predecessor court have
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`prohibited consistently. For example, in Akzo N.V. v. U.S. Int’l Trade
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`Comm’n, 808 F.2d 1471, 1480 (Fed. Cir. 1986), the Court affirmed a finding
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`of no anticipation where one of ordinary skill would have had “randomly to
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`pick and choose among a number of different polyamides, a plurality of
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`solvents, and a range of inherent viscosities.” Similarly, the CCPA reversed
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`an anticipation rejection because the prior-art reference did not “clearly and
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`unequivocally disclose the claimed compound or direct those skilled in the art
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`to the compound without any need for picking, choosing, and combining
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`various disclosures not directly related to each other by the teachings of the
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`K25. Petitioner does not explain how one of ordinary skill would understand
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`Mistry to have disclosed K25 from among the many possible forms of PVP,
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`especially when Mistry directs attention to specific values other than K25.
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`Ex. 1003, 2:9–11 (specifically citing K values of 10–14, 15–18, 29–32, 88–
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`100, and 115–125). Example D includes HFA-227 and PEG, but it is PEG-
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`600, not the claimed PEG-1000. Id. at 8:13–35.
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`5
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`cited reference.” In re Arkley, 455 F.2d 586, 587 (CCPA 1972) (emphasis in
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`original). The present case is even more aggravated than Akzo and Arkley
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`because it involves many more ingredients (and also concentrations) than they
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`did.
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`Petitioner’s attempts to justify the many arbitrary selections and
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`combinations required to reach the claim also fall flat because Mistry simply
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`does not disclose what Petitioner says it does.
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`For example, Petitioner incongruously argues that Mistry’s range of
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`0.01 to 15% w/w for active ingredients—a range spanning four orders of
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`magnitude—anticipates the particular concentration recited in the claims.
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`Specifically, Petitioner argues that the claimed 0.09 mg/mL FFD converts to
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`0.015% to 0.017% w/w and that this percentage is anticipated because it falls
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`within Mistry’s range. Pet. 30; Ex. 1012 ¶ 62 (citing Ex. 1003 3:62–67).
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`Even if the claimed 0.09 mg/mL fell within Mistry’s range (it doesn’t ;
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`Petitioner miscalculated it, as explained below), Petitioner offers no credible
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`explanation for how that broad range meets the specific concentration
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`claimed. A generic disclosure does not anticipate a species unless one of skill
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`in the art could “at once envisage” the species (In re Petering, 301 F.2d 676,
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`681 (CCPA 1962)) from the generic disclosure or if the species is disclosed
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`6
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`with “sufficient specificity.” Atofina v. Great Lakes Chem. Corp, 441 F.3d
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`991, 999 (Fed. Cir. 2006). Here, Mistry’s passing reference to a wide range
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`does not call out any particular concentration with any specificity.
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`Petitioner’s confused argument that Mistry discloses and claims “upwards
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`from 0.01%” FFD (Pet. 30), an argument repeated without elaboration by
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`Petitioner’s expert Dr. Beasley (Ex. 1012 ¶ 66), does nothing to explain how
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`one of ordinary skill in the art would have understood “0.01 to 15% w/w” to
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`be a specific disclosure of any value within the range.
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`Petitioner similarly fails to explain why the concentration ranges Mistry
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`discloses for PEG-1000 (0.01% to 4% w/w, preferred 0.1% to 2% w/w;
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`Ex. 1003, 2:45–47) anticipate the recited 0.3% w/w for that ingredient.
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`Petitioner simply states that Mistry anticipates because it discloses PEG-1000
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`concentration ranges “encompassing” the limitation, a conclusion Dr. Beasley
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`again repeats without elaboration. Pet. 33 (citing Ex. 1012 ¶ 80). This
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`argument is insufficient to show anticipation for the same reasons given
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`above.
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`For another example, Petitioner’s argument that Mistry teaches the
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`combination of FFD and budesonide (Pet. 31) is misleading for at least two
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`reasons. First, Mistry does not disclose FFD, which is a molecular complex
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`of formoterol, fumarate, and water. Instead, Mistry discloses plain formoterol
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`(Ex. 1003, 3:37). Mistry refers to “and salts thereof” (id. at 3:38), but it is at
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`best ambiguous whether this phrase refers to formoterol or merely modifies
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`the last drug in the list, fenoterol. Yet it is “well established that …
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`anticipation … cannot be predicated on an ambiguous reference.” In re
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`Turlay, 304 F.2d 893, 899 (CCPA 1962). Second, Mistry says only that a
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`prophylactic agent may be combined with a bronchodilator. Pet. 31 (citing
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`Ex. 1003, 3:40–42; Ex. 1012 ¶ 85). Mistry does not specify the combination
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`of budesonide and formoterol; Dr. Beasley’s liberal use of ellipses in ¶ 85
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`amounts to a deceptive misquotation of Mistry that demonstrates just how
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`contrived Petitioner’s argument is.10
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`2. Mistry does not disclose 0.09 mg/mL formoterol
`fumarate dihydrate
`Petitioner also has failed to show that Mistry discloses the particular
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`10 Dr. Beasley quotes Ex. 1003, 3:31–40 as: “Such medicaments include drugs
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`for us[e] in the prophylactic or remedial treatment of reversible obstructive
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`airways disease, eg … budesonide … and bronchodilators, eg … formoterol
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`… and combinations of two or more of these agents ….” (emphasis
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`Dr. Beasley’s).
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`8
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`concentration of FFD claimed.
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`a. Petitioner’s “canister volumes” and “fill
`weights” are not supported by any evidence
`In its attempt to show that the claimed 0.09 mg/mL FFD is within
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`Mistry’s range of 0.01 to 15% w/w, Petitioner converts the 0.09 mg/mL figure
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`to a weight percent using canister volumes and fill weights. Pet. 29–30 (citing
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`Ex. 1012 ¶¶ 29, 62–66). The specific numbers Petitioner asserts—10 to 19
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`mL for volume and 6 to 10 g for fill weight—are critical to this calculation.
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`But Petitioner cites only Dr. Beasley’s declaration in support of its
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`assertion that the canister volumes range from 10 to 19 mL and that the fill
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`weights range from 6 to 10 g. Pet. 29 (citing Ex. 1012 ¶ 65). Dr. Beasley’s
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`declaration echoes the Petition but points to no evidence supporting his
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`assertion that these numbers are correct. Regarding canister volumes,
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`Dr. Beasley merely states: “A POSITA would understand that a typical
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`pressurized metered dose inhaler canister, of the type a POSITA would
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`understand would be used by the Mistry and the 328 Patent, is one of the
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`standard sizes of 10 ml, 14 ml, 17 ml, and 19 ml.” Ex. 1012 ¶ 65. Petitioner
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`has supplied no other evidence to support Dr. Beasley’s naked and
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`unsupported contention that these are standard sizes of pressurized metered
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`dose inhaler canisters. Moreover, Dr. Beasley does not even assert that these
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`sizes were known at the time the invention was made.11 As the Board has
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`admonished countless times, conclusory expert testimony is entitled to little
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`or no weight. 37 C.F.R. § 42.65(a). No evidence in the record demonstrates
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`that such “standard sizes” were known in the art at the relevant time.
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`Petitioner similarly offers no evidentiary support for Dr. Beasley’s
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`assertion that the typical fill weight for a canister is 6 g to 10 g or that it was
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`known or disclosed at the time the invention was made. There is nothing in
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`the record to show that Petitioner’s expert did not simply make these numbers
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`up.
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`Petitioner has failed to offer any evidence supporting its expert’s
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`assertions. The expert does not even establish his assertions to be indicative
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`of the state of the art at the time of the invention. Because these assertions are
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`the only evidence Petitioner relies on to justify its unit conversion from
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`Mistry’s % w/w to the claimed mg/mL, and these calculations are essential to
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`Petitioner’s challenge, the challenge should be denied.
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`11 Dr. Beasley’s statement from ¶ 65, quoted immediately above, uses the
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`present tense and thus associates the POSITA’s knowledge with present day.
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`b. “Typical” canister volumes and fill weights are
`not enough to show inherency.
`Petitioner’s argument is fundamentally one of inherent anticipation,
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`because Mistry does not expressly disclose the 0.09 mg/mL FFD limitation,
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`among others. But to show inherent anticipation, Petitioner must prove that
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`the relied-upon features are inevitably and necessarily present in the
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`disclosure. Continental Can Co. USA v. Monsanto Co., 948 F.2d 1264, 1268
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`(Fed. Cir. 1991); Atlas Powder Co. v. IRECO, Inc., 190 F.3d 1342, 1349
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`(Fed. Cir. 1999).
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`Petitioner has not done this. Instead, Petitioner argues only that the
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`canister volumes and fill weights on which it hinges its arguments are
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`“typical,” not inherent. Critically, Dr. Beasley repeatedly states that the
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`canister size and fill weights on which he bases his calculations are merely
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`“typical.” Ex. 1012 ¶ 65 (“A POSITA would understand that a typical
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`pressurized metered dose inhaler canister … is one of the standard sizes of 10
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`ml, 14 ml, 17 ml, and 19 ml”; “The total fill weight of a 10 ml canister will
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`typically be as low as 6 grams. The total fill weight of a 19 ml canister will
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`typically be as high as 10 grams.”) (emphases added). Dr. Beasley and
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`Petitioner then simply assume that these numbers are true of Mistry without
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`explaining why or giving any facts on which to base that conclusion.
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`11
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`Petitioner’s unwarranted assumptions here are especially unreasonable
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`because the total fill weight of a canister’s contents depends simply on the
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`density of the material with which the canister is filled. That is, the mass of a
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`known material is directly derivable from its volume. If a 10 mL canister
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`were filled with liquid water, the fill weight would be about 10 g, because the
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`density of water is about 1 g/mL. If that 10 mL canister were instead filled
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`with liquid HFA227, which has a density of about 1.4 g/mL at room
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`temperature, it would have a total fill weight of about 14 g, not 6 g.12 As will
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`12 The density of HFA227 is a well-known physical property reported in
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`numerous prior patents and printed publications. E.g., Ex. 2001, 165, Table
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`5 (density 1400.6 kg/m3 for R227ea at 295 Kelvin); Ex. 2002, 690, Table 3
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`(density 1408.26 for HFC-227ea at 293.15 Kelvin); Ex. 2003, 292, Table 1
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`(density 1.41 g/cc of HFA-227 at 20°C); Ex. 2004, 7:44–46 (“density … about
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`1.4 g/ml for HFA 227”); Ex. 2005, 15:6–8 (identical to Ex. 2004, though in
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`German). Although several of these references call HFA227 by slightly
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`different names, they all refer to the same compound: 1,1,1,2,3,3,3-
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`heptafluoropropane. Ex. 2001, 160 (Abstr.); Ex. 2002, 688 (Abstr.);
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`Ex. 2003, 292 (Table 1); Ex. 2004, 1:31–32.
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`12
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`be shown in the next section, Petitioner’s unwarranted assumption that a
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`10 mL canister of propellant HFA227 weighs 6 g instead of 14 g is the basis
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`of its erroneous calculation of the supposed weight percentage of FFD
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`disclosed in Mistry.13
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`For anticipation, it is not enough to show that the claimed features were
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`typical, preferred, obvious, or anything less than necessary and inevitable in
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`the prior art. Petitioner has waived its one-and-only opportunity to provide
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`evidence supporting this aspect of its case-in-chief. For this reason as well,
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`trial on the ground of anticipation by Mistry should be denied.
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`c. Petitioner’s calculations to reach 0.09 mg/mL
`are incorrect
`Petitioner argues that the claimed 0.09 mg/mL concentration for FFD
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`is equivalent to 0.015–0.017% w/w (Pet. 30), but Petitioner’s calculation is
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`wrong. The correct calculation shows that 0.09 mg/mL corresponds to
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`0.0064% w/w, which is outside Mistry’s disclosed range of 0.01 to 15% w/w.
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`Pet. 30.
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`Petitioner bases its analysis on assumed values of canister volume and
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`13 Petitioner’s calculations are predicated inextricably on an assumption that
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`the canister is full, as Patent Owner explains in the next section.
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`13
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`fill weight. Petitioner uses two specific examples: a 10 mL canister having a
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`fill weight of 6 g, and a 19 mL canister having a fill weight of 10 g. Pet. 30
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`(citing Ex. 1012 ¶ 65). In each case, Petitioner assumes that the full volume
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`of the canister is used. This is shown most clearly in Dr. Beasley’s
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`declaration, where he multiplies 0.09 mg/mL by 10 or 19 to get a total mass
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`of 0.9 mg or 1.7 mg FFD. Ex. 1012 ¶ 65 (“Figuring that the formoterol
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`fumarate dihydrate concentration is 0.09 mg/ml, then multiplying the
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`concentration by the canister ranges, such a canister would have a total mass
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`of formoterol between 0.90 mg to 1.7 mg.”) (emphasis added). Because
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`Dr. Beasley obviously is multiplying 0.09 by 10 to get 0.9, and multiplying
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`0.09 by 19 to get 1.7, his calculations are based on the assumption of a 10 mL
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`or 19 mL volume, i.e., a full canister.
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`Petitioner, through Dr. Beasley, then divides that total mass of FFD14
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`14 Note that Dr. Beasley refers to a “total mass of formoterol,” not FFD
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`(Ex. 1012 ¶ 65). Patent Owner assumes for the sake of argument, at the present
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`stage of this proceeding only, that Dr. Beasley meant FFD. But this confusion
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`only further highlights Mistry’s shortcomings as an anticipating reference.
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`Mistry does not disclose FFD, as discussed above at page 7.
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`14
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`by the 6 g “typical” fill weight to get 0.015% w/w for a 10 mL canister or by
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`10 g to get 0.017% w/w for a 19 mL canister. Pet. 30 (citing Ex. 1012 ¶ 65).15
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`But this is where Petitioner’s calculations go astray. As discussed
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`above, a full 10 mL canister of HFA227 cannot have a fill weight of 6 g. It
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`has a fill weight of 14 g (10 mL × 1.4 g/mL). The canister in Petitioner’s
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`calculations must be full, because Dr. Beasley expressly assumed it to be so.
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`The weight percentage of FFD therefore would be 0.9 mg (which corresponds
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`to 0.0009 g) divided by 14 g, giving 0.000064, which multiplied by 100 gives
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`0.0064%. 0.0064% is outside Mistry’s range of 0.01 to 15%. Mistry therefore
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`does not anticipate.16
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`15 Dr. Beasley does not lay out his calculation, but the only way his numbers
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`work out as he states them is to divide 0.9 mg (which equals 0.0009 g) by 6 g,
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`giving 0.00015, then multiplying by 100 to give a percentage of 0.015%.
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`Similarly, 1.7 mg (which equals 0.0017 g) divided by 10 g and multiplied by
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`100 equals 0.017%.
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`16 It certainly is possible that a 10 mL canister with HFA227 in it could have
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`a fill weight of 6 g, but only if it is not full. For example, about 4.3 mL of
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`HFA227 would weigh 6 g (4.286 mL × 1.4 g/mL = 6 g). Petitioner’s argument
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`15
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`Preliminary Response
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`IPR2017-00631
`Patent 7,759,328 B2
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`Nor can Petitioner dispute that the canister is principally filled with
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`HFA227 and not some other material (or mixture of materials) with a density
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`of 0.6, low enough to give 10 mL a total weight of 6 g. First, Petitioner itself
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`relies on the canister being filled principally with HFA227. Pet. 29 (citing
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`Ex. 1012 ¶ 65 (“the vast majority of the total fill weight would be from the
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`propellant, or the propellant and other ingredients.”) Second, every single
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`example in Mistry that includes HFA227 includes no other ingredients except
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`in tiny amounts. In each of Examples A, B, C, D, F(b), G, H, I nos. 13–24
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`and 37–48, J, K, the mixture is described as being “in propellant 227” and
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`everything else (active ingredients, stabilizers, excipients, etc.) is present in
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`just a few milligrams per milliliter, or a few hundredths of a percent.
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`Ex. 1003, 7:11–11:60. Thus, as Petitioner has done, everything other than
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`HFA227 can be disregarded when figuring the mass of the total mixture,
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`would not have been any better if Petitioner had assumed these numbers,
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`because concentration and weight percent are of course independent of
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`whatever volume happens to be used. In this case, 0.09 mg/mL FFD
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`multiplied by the volume 4.286 mL and divided by mass 6 g (equal to 6,000
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`mg) gives 0.000064 = 0.0064%, just as before.
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`16
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`Preliminary Response
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`IPR2017-00631
`Patent 7,759,328 B2
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`because those ingredients contribute only tiny fractions to the total.
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`But more to the point, Petitioner has not identified any example in
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`Mistry, or for that matter, to any combination of teachings in Mistry, however
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`arbitrarily cherry-picked, that would lead to a mixture having a density of 0.6,
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`i.e., low enough to have a 6 g fill weight for a 10 mL canister. Dr. Beasley
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`simply proclaims that a full 10 mL canister typically has a fill weight of 6 g
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`without explaining how that possibly could be achieved with the ingredients
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`disclosed in Mistry. It can’t, for the reasons given here. When the proper
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`numbers are used, as shown above, it is clear that even the smallest active
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`ingredient weight fraction Mistry discloses (0.01%; Pet. 30) is larger than the
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`weight fraction corresponding to the recited concentration of FFD. Thus
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`Mistry is wholly outside the scope of the claims. Petitioner has failed to meet
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`its burden of showing a reasonable likelihood that Mistry discloses this
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`limitation.
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`For these reasons, trial on the challenge to claims 1 and 4–15 for
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`anticipation by Mistry should be denied.
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`B. Anticipation by Rogueda
`Petitioner has failed to show a reasonable likelihood that Rogueda
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`anticipates claims 1 and 4–15 for similar reasons as discussed above. In
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`17
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`Preliminary Response
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`Patent 7,759,328 B2
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`particular, (1) Petitioner fails to justify cobbling together different
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`embodiments from Rogueda to meet the claims; and (2) Petitioner’s
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`calculations to show that Rogueda discloses the recited FFD concentration are
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`both erroneous and unsupported by evidence.
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`1. Petitioner fails to justify cobbling together different
`embodiments from Rogueda to meet the claims
`Petitioner acknowledges that Rogueda fails to disclose a single
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`embodiment with all five recited ingredients, let alone the recited
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`concentrations. Pet. 37. Petitioner’s subsequent arguments do not overcome
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`this admission.
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`Petitioner acknowledges in particular that Rogueda teaches no example
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`that includes both FFD and budesonide. Id. Petitioner argues instead that a
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`person of ordinary skill “would understand” that a combination of the two
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`“could be achieved” because Rogueda expressly discloses the combination of
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`budesonide and formoterol. Pet. 38.
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`But, as discussed above, it is irrelevant to the anticipation inquiry
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`whether one of ordinary skill “would understand” that a modification “could
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`be achieved.” The standard for anticipation is more stringent than that.
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`Nothing in Rogueda “clearly and unequivocally” directs one of skill in the art
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`to combine the recited ingredients to reach the claimed formulation. See In re
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`18
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`Patent 7,759,328 B2
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`Arkley, 455 F.2d at 588. Rogueda does not anticipate for this reason.
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`Petitioner’s arguments justifying the combination of formoterol and
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`budesonide at particular concentrations because a person of ordinary skill
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`might choose to use known molar ratios between these two substances
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`(Pet. 39–40; id. at 41) similarly runs afoul of this basic principle of
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`anticipation.
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`2. Rogueda does not disclose 0.09 mg/mL formoterol
`fumarate dihydrate
`As with Mistry, above, Petitioner errs in its showing that Rogueda
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`discloses 0.09 mg/mL, by ascribing physical properties to Rogueda that are
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`not supported by evidence, that are not shown to be inherent, and that are used
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`incorrectly in calculations.
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`Petitioner again asserts that the fill weight of a canister is 6 to 10 g, or
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`more specifically, 6 to 7 g, but cites as support only the pronouncements of
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`Dr. Beasley, who again does not explain where those values come from or
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`how they are inherent in Rogueda. Pet. 39 (citing Ex. 1012 ¶ 96). His
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`testimony therefore should be given little or no weight. See 37 C.F.R.
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`§ 42.65(a).
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`Petitioner performs the unit conversion twice from weight percent to
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`concentration: first using Rogueda Examples 8 and 11 (Pet. 38–39) and then
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`using several Rogueda control samples (Pet. 41). Both are done incorrectly.
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`For Examples 8 and 11, Petitioner begins by noting that each of the
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`samples within these examples include FFD at a weight percentage of around
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`0.016% or 0.017%. Pet. 38 (citing Ex. 1004, 24–25;17 Ex. 1012 ¶ 96).
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`Petitioner also observes that Rogueda teaches the use of a 12 mL canister.
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`Id. at 38–39 (citing Ex. 1004, 22, ll. 13–14). However, in the next steps of the
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`analysis, Petitioner,
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`through Dr. Beasley, proceeds by making
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`the
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`unsupported and therefore impermissible assumptions about canister fill
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`weights. In particular, Dr. Beasley assumes that “[a] POSITA would
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`understand that a 12 ml canister would have a fill weight of at least 6 grams,
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`and would expect a fill weight of between 6 and 7 grams.” Ex. 1012 ¶ 96
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`(cited at Pet. 39). From that footing, Dr. Beasley proceeds to assume
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`whatever fill weight is necessary “between 6 and 7 grams,” as long as the final
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`result is a claimed formoterol concentration of 0.09 mg/mL. See Ex. 1012
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`¶ 96, ll. 12−14 (assuming the fill weight must have been 6.3 g or 6.4 g, and
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`thereby arriving at the claimed concentration of 0.09 mg/mL).
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`17 Petitioner cites Rogueda using exhibit page numbering rather than the
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`publication page numbering. Patent Owner does the same.
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`20
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`Tellingly, Dr. Beasley points to no proof in the record to support these
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`purported fill weights as being “typical” (¶ 65) or “what a POSITA would
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`understand” (¶ 96), or that they were in the prior art, though he nevertheless
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`assumes these values and they are critical for his mathematical analyses. Even
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`more tellingly, inspection of Rogueda’s formulations plainly demonstrates
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`that Dr. Beasley’s values cannot possibly be correct.
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`The simplest way to illustrate this point is by looking at the same
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`example from Rogueda on which Dr. Beasley focused: Example 8.5. See
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`Ex. 1012 ¶ 96, ll. 12–14. Rogueda’s Example 8 table is reproduced below
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`from page 24 of Ex. 1004:
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`Dr. Beasley notes that Example 8.5 discloses the formulation of a 12
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`mL canister, having a formoterol concentration of 0.0172 % w/w. Ex. 1012
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`21
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`IPR2017-00631
`Patent 7,759,328 B2
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`¶ 96, ll. 12–14. However, it is not necessary to do what Dr. Beasley does next,
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`which is to assume a fill weight (relying on wholly unsupported values of 6.3
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`g or 6.4 g) because the fill weight can be calculated by one simple
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`multiplication stepi.e., if one knows the volume (12 mL) and the densities
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`of the components described in Rogueda, then one can calculate the expected
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`fill weight without the need to assume anything.
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`Reference to Example 8 shows that sample 5 contains 0.0172% w/w
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`FFD, 0.521% w/w methoxy-PEG-DSPE-2000, 12.0% w/w 4HPFOH, and the
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`balance HFA227 (87.4618%). Even if one takes into consideration just the
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`two main components by weightHFA227 and 4HPFOH (making up >99%
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`of the formulation’s weight), which have densities of 1.4 g/mL (supra n.12)
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`and 1.68 g/mL (respectively)18the calculated fill weight is much higher than
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`the 6–7 g fill weight that Dr. Beasley assumed in order to make his
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`18 4HPFOH is 1H,1H,2H,2H perfluorooctan-1-ol and has chemical formula
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`CF3(CF2)5CH2CH2OH or (equivalently) F(CF2)6CH2CH2OH. Ex. 1004, 13,
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`l. 7; Ex. 2008, 4:45–47; Ex. 2009, 3:
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