Trials@uspto.gov
`571-272-7822
`
`
`
`
`
` Paper No. 17
` Entered: January 28, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FRESENIUS KABI USA LLC,
`Petitioner,
`
`v.
`
`CUBIST PHARMACEUTICALS LLC,
`Patent Owner.
`____________
`
`Case IPR2015-01570
`Patent 8,058,238 B2
`____________
`
`
`
`Before BRIAN P. MURPHY, JON B. TORNQUIST, and
`TINA E. HULSE, Administrative Patent Judges.
`
`
`TORNQUIST, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`571-272-7822
`
`
`
`
`
` Paper No. 17
` Entered: January 28, 2016
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`FRESENIUS KABI USA LLC,
`Petitioner,
`
`v.
`
`CUBIST PHARMACEUTICALS LLC,
`Patent Owner.
`____________
`
`Case IPR2015-01570
`Patent 8,058,238 B2
`____________
`
`
`
`Before BRIAN P. MURPHY, JON B. TORNQUIST, and
`TINA E. HULSE, Administrative Patent Judges.
`
`
`TORNQUIST, Administrative Patent Judge.
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`IPR2015-01570
`Patent 8,058,238 B2
`
`
`I. INTRODUCTION
`
`
`
`Fresenius Kabi USA LLC (“Petitioner”) filed a Petition (Paper 2,
`
`“Pet.”) requesting institution of inter partes review of claims 3–7, 21–25,
`
`27–33, 35–44, 48–52, 55–57, 61–63, 66, 85, 87–89, 92–109, 113, 115–121,
`
`123–151, 153–159, 161, 162, 164–167, 175–184, 189, and 190 of U.S.
`
`Patent No. 8,058,238 B2 (Ex. 1001, “the ’238 patent”). On September 15,
`
`2015, we granted the parties’ joint motion to limit the Petition to claim 98.
`
`Paper 12, 3. Cubist Pharmaceuticals, LLC. (f/k/a Cubist Pharmaceuticals,
`
`Inc., “Patent Owner”) timely filed a Preliminary Response (Paper 15,
`
`“Prelim. Resp.”) to the limited Petition.
`
`
`
`We have jurisdiction under 35 U.S.C. § 314(a), which provides that an
`
`inter partes review may not be instituted “unless . . . there is a reasonable
`
`likelihood that the petitioner would prevail with respect to at least 1 of the
`
`claims challenged in the petition.” For the reasons given below, we
`
`determine that Petitioner has demonstrated a reasonable likelihood of
`
`prevailing with respect to claim 98. Accordingly, pursuant to 35 U.S.C.
`
`§ 314, we authorize an inter partes review to be instituted as to claim 98 on
`
`the ground set forth below.
`
`
`
`
`
`A. Related Proceedings
`
`The parties indicate that the ’238 patent is at issue in: Cubist
`
`Pharms., Inc. v. Hospira, Inc., 1:12-cv-00367-GMS (D. Del.); Cubist
`
`Pharms., Inc. v. Agila Specialties Inc. and Mylan Laboratories Limited,
`
`1:13-cv-01679-GMS (D. Del); Cubist Pharms., Inc. v. Fresenius-Kabi USA
`
`LLC, 1:14-cv-00914-GMS (D. Del.); and Cubist Pharmaceuticals, Inc. v.
`
`Hospira, Inc., 805 F.3d 1112 (Fed. Cir. 2015) (pending request for
`
`rehearing). Pet. 3–4; Paper 5, 2; Paper 16, 1. The ’238 patent is also at issue
`
`
`
`2
`
`
`
`IPR2015-01570
`Patent 8,058,238 B2
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`in inter partes review proceedings: IPR2015-01566, IPR2015-01571, and
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`IPR2015-01572. Pet. 4; Paper 5, 3.
`
`
`
`
`
`B. The ’238 Patent
`
`The ’238 patent, titled “High Purity Lipopeptides,” discloses a highly
`
`purified form of daptomycin (also known as LY146032), “a lipopeptide
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`antibiotic with potent bactericidal activity against gram-positive bacteria.”
`
`Ex. 1001, 1:21–24, 1:58–61. More particularly, the ’238 patent is directed to
`
`“providing commercially feasible methods to produce high levels of purified
`
`lipopeptides,” such as daptomycin. Id. at 3:50–54.
`
`
`
`The ’238 patent describes several methods of purifying lipopeptides,
`
`and daptomycin in particular, to achieve a highly pure composition. One
`
`method involves a size separation technique, where a lipopeptide is
`
`converted from a monomer to a micelle (aggregate) and back to a monomer
`
`during the purification process, in order to separate the lipopeptide from low
`
`molecular weight and high molecular weight impurities. Id. at 5:56–6:10.
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`Ultrafiltration is preferred for purifying lipopeptides using this size
`
`separation technique. Id. at 6:11–13.
`
`
`
`In Example 15 of the ’238 patent, daptomycin is purified by repeated
`
`column chromatography on HP-20 and HP-20ss resin. Ex. 1001, 36:42–45.
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`The resulting product is 93% pure, but contains “visible impurities on HPLC
`
`chromatographs and measurable pyrogen.” Id. at 36:46–47. The 93% pure
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`daptomycin is then passed through a 10,000 NMW ultrafiltration membrane
`
`in monomeric form. Id. at 36:50–53. According to the ’238 patent, “[t]he
`
`resulting product remains 93% pure, but several impurities that had been
`
`present at 0.1-0.2% are removed by the ultrafiltration membrane” and
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`“pyrogen content is reduced to undetectable levels.” Id. at 36:52–55.
`
`
`
`3
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`
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`IPR2015-01570
`Patent 8,058,238 B2
`
`
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`C. Illustrative Claims
`
`
`
`Claim 98 depends from claims 49 and 92–97. These claims are
`
`reproduced below:
`
` 49. A purified daptomycin composition comprising
`daptomycin of greater than or about 93% purity relative to
`impurities 1–14 defined by peaks 1–14 shown in FIG. 12, the
`daptomycin being obtained by a process comprising the step of
`forming an aggregate comprising daptomycin.
`
`Ex. 1001, 40:34–38.
`
`92. The composition of claim 49, wherein the purity of
`daptomycin is at least 93%.
`
`93. The composition of claim 92, wherein the daptomycin is
`obtained by a process comprising:
`
`a) subjecting a daptomycin solution to conditions forming a
`daptomycin aggregate;
`b) separating the daptomycin aggregate from low molecular
`weight contaminants; and
`c) subjecting the daptomycin aggregate to conditions in which
`the daptomycin aggregate dissociates into daptomycin
`monomers.
`
`94. The composition of claim 93, wherein the daptomycin
`aggregate of step b) is separated from the low molecular weight
`contaminants by a size selection technique.
`
`95. The composition of claim 94, wherein the size selection
`technique is ultrafiltration or size exclusion chromatography.
`
`96. The composition of claim 95 further comprising separating
`the daptomycin monomers obtained from step c) from high
`molecular weight contaminants.
`
`97. The composition of claim 96, wherein the daptomycin
`monomers are separated from the high molecular weight
`contaminants by a size selection technique.
`
`
`
`4
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`
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`IPR2015-01570
`Patent 8,058,238 B2
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`98. The composition of claim 97, wherein the size selection
`technique is ultrafiltration or size exclusion chromatography.
`
`Id. at 43:7–30.
`
`
`
`D. Asserted Ground of Unpatentability
`
`
`
`Petitioner contends that claim 98 of the ’238 patent is unpatentable
`
`under 35 U.S.C. § 102(b) as anticipated by U.S. Patent No. 4,874,843,
`
`issued October 17, 1989 (Ex. 1007, “the ’843 patent). Pet. 5, 14–19, 23–24.
`
`In support of its patentability challenge, Petitioner relies upon the
`
`declaration testimony of Dr. Ralph Tarantino (Ex. 1005).
`
`II. ANALYSIS
`
`A. Claim Construction
`
`In an inter partes review, “[a] claim in an unexpired patent shall be
`
`
`
`
`
`given its broadest reasonable construction in light of the specification of the
`
`patent in which it appears.” 37 C.F.R. § 42.100(b); In re Cuozzo Speed
`
`Tech., LLC, 793 F.3d 1268, 1275 (Fed. Cir. 2015). Under this standard, we
`
`may take into account definitions or other explanations provided in the
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`written description of applicant’s specification. See In re Morris, 127 F.3d
`
`1048, 1054 (Fed. Cir. 1997). Any special definition for a claim term must
`
`be set forth in the specification with reasonable clarity, deliberateness, and
`
`precision. In re Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994). Only those
`
`terms that are in controversy need be construed, and only to the extent
`
`necessary to resolve the controversy. Vivid Techs., Inc. v. Am. Sci. & Eng’g,
`
`Inc., 200 F.3d 795, 803 (Fed. Cir. 1999).
`
`Product-by-Process Limitations
`
`
`
`The parties agree that challenged claim 98 is a product-by-process
`
`claim. Pet. 14–17; Prelim. Resp. 8–11. The general rule when determining
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`
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`5
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`IPR2015-01570
`Patent 8,058,238 B2
`
`patentability of a product-by-process claim is to “focus [] on the product and
`
`not on the process of making it.” Amgen, Inc. v. F. Hoffman-La Roche Ltd.,
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`580 F.3d 1340, 1369 (Fed. Cir. 2009). This general rule embodies the long-
`
`standing principle that “an old product is not patentable even if it is made by
`
`a new process.” Id. at 1370. An exception applies only when process steps
`
`recited in the claim impart “structural and functional differences” to the
`
`claimed product. Greenliant Sys., Inc. v. Xicor LLC, 692 F.3d 1261, 1267–
`
`68 (Fed. Cir. 2012). If the exception applies, the structural and functional
`
`differences implied by the recited process steps “‘are relevant as evidence of
`
`no anticipation’ although they ‘are not explicitly part of the claim.’” Id. at
`
`1268 (citing Amgen, 580 F.3d at 1370).
`
`
`
`Petitioner asserts that no exception to the general rule applies with
`
`respect to claim 98 because “[t]he only apparent effect of the recited process
`
`steps of the ’238 patent would be the claimed purity levels, which is already
`
`reflected in the claims.” Pet. 16–17; Ex. 1005 ¶ 114. Anticipating Patent
`
`Owner’s arguments, Petitioner further asserts that, although Example 15 of
`
`the ’238 patent discloses removing pyrogens and other impurities using a
`
`10,000 NMW ultrafiltration membrane, none of the challenged claims
`
`“specify an ultrafiltration membrane of suitable size to ensure removal of
`
`pyrogens.” Pet. 17. Thus, according to Petitioner, “the claims do not
`
`require any process steps that would create compositions with the alleged
`
`structural differences or any functional differences.” Id.; Ex. 1005 ¶ 119.
`
`
`
`Patent Owner disagrees, asserting that the daptomycin compositions
`
`prepared using the process steps of claim 98 of the ’238 patent (and the
`
`claims from which this claim depends) contain lower levels of “endotoxins”
`
`and “daptomycin-related impurities,” and these structural differences in the
`
`
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`6
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`IPR2015-01570
`Patent 8,058,238 B2
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`final daptomycin composition cannot be disregarded. Prelim. Resp. 8–12.
`
`According to Patent Owner, Example 15 of the ’238 patent discloses
`
`reducing pyrogen content (“endotoxins”) to undetectable levels, which “can
`
`make the difference between a pharmaceutically acceptable composition and
`
`one that is unacceptably toxic and cannot be administered to patients.” Id. at
`
`12. In support of its argument, Patent Owner provides evidence that
`
`pharmaceutical compositions must be tested for endotoxin levels and the
`
`level of endotoxins in commercial pharmaceutical compositions is strictly
`
`limited. Id. at 3 (citing Exs. 2002 and 2003).
`
`
`
`Upon review of Petitioner’s and Patent Owner’s arguments and the
`
`disclosure of the ’238 patent, on this record we are not persuaded that the
`
`process limitations of claims 49 and 92–98 impart structural and functional
`
`differences in the resulting product such that the process limitations should
`
`be considered in determining the patentability of claim 98. In particular,
`
`Patent Owner directs our attention to no persuasive intrinsic evidence to
`
`show that one of ordinary skill in the art would have understood that the
`
`reported reduction in pyrogen levels for the ultrafiltration process described
`
`in Example 15—which results in no disclosed reduction in overall purity—
`
`functionally distinguishes the disclosed daptomycin product from the prior
`
`art. Although Patent Owner directs our attention to extrinsic evidence that
`
`endotoxins (pyrogens) must be measured and may not exceed certain
`
`thresholds in pharmaceutical compositions (Ex. 2002 and 2003), Patent
`
`Owner does not explain what level of endotoxins would be acceptable in a
`
`pharmaceutical composition of daptomycin or demonstrate that the process
`
`limitations of claims 49 and 92–98 would necessarily reduce endotoxin
`
`levels below this clinically acceptable level.
`
`
`
`7
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`
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`IPR2015-01570
`Patent 8,058,238 B2
`
`
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`As such, on this record we are not persuaded that the intrinsic record
`
`demonstrates that the process steps set forth in claims 49 and 92–98 imply
`
`structural and functional differences in the resulting daptomycin
`
`composition requiring consideration of these steps in determining the
`
`patentability of claim 98. Accordingly, we apply the general rule and
`
`analyze the patentability of claim 98 based on the claimed product and not
`
`the claimed process of making it.
`
`
`
`
`
`B. Anticipation of Claim 98 by the ’843 Patent
`
`Petitioner asserts that claim 98 is anticipated under 35 U.S.C. § 102(b)
`
`by the ’843 patent. Pet. 15. In support of this argument, Petitioner relies
`
`upon the declaration testimony of Dr. Tarantino. Ex. 1005. Patent Owner
`
`opposes. Prelim. Resp. 12–14.
`
`
`
`
`
`1. The ’843 Patent
`
`The ’843 patent issued October 17, 1989, and is prior art under
`
`35 U.S.C. § 102(b). Pet. 7. The ’843 patent is directed to a “new
`
`chromatographic process for purifying fermentation products, particularly
`
`the antibiotic LY146032 [(daptomycin)], from fermentation broths by use of
`
`a non-functional resin in reverse mode.” Ex. 1007, 1:5–8. This “reverse
`
`method” removes impurities from daptomycin and “improves the final purity
`
`from about 80% to about 93%” and the overall yield “from about 5% to
`
`about 35%.” Id. at 2:40–45; Ex. 1005 ¶ 79.
`
`
`
`
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`2. Analysis
`
`Claim 92, from which claim 98 depends, requires a daptomycin
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`composition that is at least 93% pure with respect to impurities 1–14 defined
`
`by peaks 1–14 shown in Figure 12. Ex. 1001, 40:33–38, 43:7–8. Petitioner
`
`
`
`8
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`
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`IPR2015-01570
`Patent 8,058,238 B2
`
`contends that the ’843 patent discloses a daptomycin composition that is
`
`93% pure with respect to these recited impurities. Pet. 15–16.
`
`
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`Patent Owner does not dispute that the ’843 patent discloses a
`
`daptomycin composition that is at least 93% pure with respect to impurities
`
`1–14. Patent Owner argues, instead, that Petitioner has not demonstrated
`
`that the ’843 patent discloses the process steps set forth in claims 49 and 92–
`
`98. Prelim. Resp. 13. As noted above, however, on this record we are not
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`persuaded that the process steps of claims 49 and 92–98 are to be considered
`
`in determining the patentability of claim 98. Accordingly, we are persuaded
`
`that Petitioner has demonstrated a reasonable likelihood that claim 98 of the
`
`’238 patent is anticipated by the ’843 patent.
`
`For the foregoing reasons, it is
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`III. ORDER
`
`ORDERED that pursuant to 35 U.S.C. § 314, an inter partes review of
`
`
`
`
`
`the ’238 patent is hereby instituted as to whether claim 98 is anticipated
`
`under 35 U.S.C. § 102 by the ’843 patent;
`
`
`
`FURTHER ORDERED that the trial is limited to the ground identified
`
`above and no other grounds are authorized; and
`
`
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`FURTHER ORDERED that pursuant to 35 U.S.C. § 314(a), inter
`
`partes review of the ’238 patent is hereby commenced on the entry date of
`
`this Order, and pursuant to 35 U.S.C. § 314(c) and 37 C.F.R. § 42.4, notice
`
`is hereby given of the institution of trial.
`
`
`
`9
`
`
`
`IPR2015-01570
`Patent 8,058,238 B2
`
`
`
`PETITIONER:
`
`Elizabeth J. Holland
`eholland@goodwinprocter.com
`
`Robert V. Cerwinski
`rcerwinski@goodwinprocter.com
`
`Cynthia L. Hardman
`chardman@goodwinprocter.com
`
`Goodwin Procter LLP
`
`
`
`PATENT OWNER:
`
`Emily R. Whelan
`Emily.Whelan@wilmerhale.com
`
`Andrej Barbic
`Andrej.Barbic@wilmerhale.com
`
`Gerard M. Devlin, Jr.
`Gerard.Devlin@merck.com
`
`Lisa A. Jakob
`Lisa.Jakob@merck.com
`
`Wilmer Cutler Pickering Hale and Dorr LLP
`
`
`
`
`
`10
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`
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