Trials@uspto.gov
`571-272-7822
`
`
`
`
`
` Paper No. 20
` 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 IPR2015-01571
`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. 20
` 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 IPR2015-01571
`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
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`
`I. INTRODUCTION
`
`
`
`Fresenius Kabi USA LLC (“Petitioner”) filed a corrected Petition
`
`(Paper 7, “Pet.”) requesting institution of inter partes review of claims 1–19,
`
`21–44, 48–51, 53, 92–107, 112–146, 151–167, 176, 177, 179, and 183–189
`
`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 claims 98 and 187. Paper 15, 3. Cubist Pharmaceuticals LLC (f/k/a
`
`Cubist Pharmaceuticals, Inc., “Patent Owner”) timely filed a Preliminary
`
`Response (Paper 18, “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 claims 98 and 187. Accordingly, pursuant to
`
`35 U.S.C. § 314, we authorize an inter partes review to be instituted as to
`
`these claims 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 19, 1. The ’238 patent is also at issue
`
`
`
`2
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`in inter partes review proceedings: IPR2015-01566, IPR2015-01570, and
`
`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
`
`antibiotic with potent bactericidal activity against gram-positive bacteria.”
`
`Ex. 1001, 1:21–24, 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 3:50–52.
`
`
`
`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.
`
`Ultrafiltration is preferred for purifying lipopeptides using this size
`
`separation technique. Id. at 6:11–13.
`
`
`
`
`
`C. Illustrative Claims
`
`Dependent claims 98 and 187 are the only claims challenged in this
`
`proceeding. Claims 98 and 187, as well as the independent and dependent
`
`claims from which these claims depend, 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.
`
`
`
`
`3
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`
`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.
`
`98. The composition of claim 97, wherein the size selection
`technique is ultrafiltration or size exclusion chromatography.
`
`Id. at 43:7–30
`
`183. A purified daptomycin composition of greater than or
`about 93% purity relative to impurities 1-14 defined by peaks
`1-14 shown in FIG. 12, wherein the percent purity is measured
`by HPLC analysis, and the purified daptomycin composition is
`obtained from a lipopeptide aggregate comprising daptomycin.
`
`
`
`
`4
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`
`187. The composition of claim 183, wherein the daptomycin
`composition is at least or about 97% pure.
`
`Id. at 48:54–59, 49:6–7.
`
`
`
`
`
`D. Prior Art Relied Upon
`
`Petitioner relies upon the following prior art references, as well as the
`
`declaration testimony of Dr. Ralph Tarantino (Ex. 1005):
`
`U.S. Patent No. 4,874,843, issued October 17, 1989 (Ex. 1007, “the ’843
`patent).
`
`Catherine N. Mulligan & Bernard F. Gibbs, Recovery of Biosurfactants by
`Ultrafiltration, 47 J. CHEM. TECH. BIOTECHNOLOGY 23–29 (1990) (Ex. 1013,
`“Mulligan”);
`
`Lin et. al., General Approach for the Development of High-performance
`Liquid Chromatography Methods for Biosurfactant Analysis and
`Purification, 825 JOURNAL OF CHROMATOGRAPHY A 149–159 (1998)
`(Exhibit 1015, “Lin II”); and
`
`Jeremy H. Lakey and Marius Ptak, Fluorescence Indicates a Calcium-
`Dependent Interaction Between the Lipopeptide Antibiotic LY146032 and
`Phospholipid Membranes, BIOCHEMISTRY 27, 4639–4645 (1988) (Exhibit
`1033, “Lakey”).
`
`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
`
`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).
`
`
`
`5
`
`
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`IPR2015-01571
`Patent 8,058,238 B2
`
`
`Product-by-Process Limitations
`
`The parties agree that challenged claims 98 and 187 are product-by-
`
`process claims. Pet. 5–6; Prelim. Resp. 6–7. The general rule when
`
`determining 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., 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 the general rule should apply with respect to
`
`claims 98 and 187 and, therefore, the claims should be “analyzed through
`
`the composition only, and not through the claimed process steps.” Pet. 6.
`
`Patent Owner disagrees, asserting that “Petitioner has not sufficiently
`
`established” that the process limitations do not impart distinctive structural
`
`characteristics to the final product. Prelim. Resp. 7.
`
`
`
`On this record, Patent Owner presents no intrinsic evidence tending to
`
`show that the process limitations impart distinctive structural characteristics
`
`to the final product. As such, we apply the general rule and analyze the
`
`patentability of claims 98 and 187 based on the claimed product and not the
`
`claimed process of making it.
`
`
`
`6
`
`
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`IPR2015-01571
`Patent 8,058,238 B2
`
`
`
`
`B. Obviousness of Claims 98 and 187 over the ’843 patent, Mulligan,
`Lin II, and Lakey
`
`
`
`
`Petitioner asserts that claims 98 and 187 would have been obvious
`
`over the ’843 patent, Mulligan, Lin II, and Lakey. Pet. 14–48. In support of
`
`this argument, Petitioner relies upon the declaration testimony of Dr.
`
`Tarantino. Ex. 1005. Patent Owner opposes. Prelim. Resp. 6–10.
`
`
`
`
`
`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, 43–45; Ex. 1005 ¶ 79.
`
`2. Mulligan
`
`Mulligan published in 1990 and is prior art under 35 U.S.C. § 102(b).
`
`Pet. 9. Mulligan discloses the use of ultrafiltration to purify and concentrate
`
`micelle-forming biosurfactants, such as surfactin. Ex. 1013, Abstract.
`
`Mulligan reports that the “ability of surfactant molecules to form micelles at
`
`concentrations above the critical micelle concentration allows these
`
`aggregates to be retained by relatively high molecular weight cut-off
`
`membranes.” Id. Mulligan further reports that the use of certain identified
`
`ultrafiltration membranes increased surfactin yields to over 97 percent and
`
`“dramatically reduced” recovery costs. Id. at 26 (Table 1), 27; Ex. 1005
`
`¶ 90. Mulligan notes that the disclosed method of ultrafiltration may be used
`
`
`
`7
`
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`IPR2015-01571
`Patent 8,058,238 B2
`
`for any “molecules that tend to aggregate above certain concentrations.”
`
`Ex. 1013, 28.
`
`
`
`
`
`3. Lin II
`
`Lin II was published in November 1998 and is prior art under
`
`35 U.S.C. § 102(b). Pet. 11. Lin II discloses the use of ultrafiltration (size
`
`separation) and HPLC (High Performance Liquid Chromatography) to
`
`purify biosurfactant molecules. Ex. 1015, 151, Abstract; Ex. 1005 ¶¶ 99–
`
`100. The Lin II method first separates biosurfactant micelles from small
`
`molecule impurities using ultrafiltration. Ex. 1015, 151. The biosurfactant
`
`micelles are then dissociated through the addition of alcohol to form
`
`monomers that pass through an ultrafiltration membrane, thereby separating
`
`the monomeric biosurfactant molecules from larger macromolecule
`
`impurities. Id. at 153–154, 156. Lin II discloses that these size-separated
`
`biosurfactant molecules may be further purified using HPLC to form
`
`“homogeneous biosurfactant samples useful for biophysical and chemical
`
`analysis.” Pet. 11 (quoting Ex. 1015, 150–51, Abstract); Ex. 1005 ¶¶ 98–
`
`100.
`
`
`
`Lin II notes that the described method “can be applied for the
`
`development of a HPLC assay for any biosurfactant as long as the
`
`concentration of biosurfactants in the fermentation broth is higher than the
`
`critical micelle concentration.” Ex. 1015, Abstract.
`
`
`
`
`
`4. Lakey
`
`Lakey published in 1988 and is prior art under 35 U.S.C. § 102(b).
`
`Pet. 11. Lakey discloses that daptomycin may exist in either monomeric or
`
`aggregate form, with aggregation of daptomycin occurring at
`
`“concentrations higher than 10-3 M.” Ex. 1033, 4643; Ex. 1005 ¶ 104. Dr.
`
`
`
`8
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`Tarantino testifies that one of ordinary skill in the art would understand the
`
`aggregates reported in Lakey “were in fact micelles.” Ex. 1005 ¶ 104.
`
`5. Analysis
`
`
`
`Claim 98 requires a purified daptomycin composition that is “at least
`
`93% pure” relative to impurities 1–14 defined by peaks 1–14 shown in
`
`Figure 12. Ex. 1001, 40:33–38, 43:7–8, 43:29–30. Claim 187 requires a
`
`daptomycin composition that is “at least or about 97% pure.” Id. at 48:54–
`
`59, 49:6–7.
`
`Daptomycin, or LY146032, is an antibiotic intended for therapeutic
`
`use. Ex. 1007, 1:5–8, 1:36–38; Pet. 18–19; Ex. 1005 ¶ 137. Given this
`
`intended therapeutic application, Petitioner contends a person of ordinary
`
`skill in the art would have been motivated to increase the purity of
`
`daptomycin compositions to levels “suitable for pharmaceutical and/or
`
`analytical use.” Pet. 18–19; Ex. 1005 ¶¶ 75 (asserting that high purity levels
`
`for pharmaceutical preparations of antimicrobial agents would have been a
`
`target goal for one of ordinary skill in the art), 137. To achieve this goal,
`
`Petitioner contends one of ordinary skill in the art would have accessed the
`
`“extensive tool-box” known in the art for purifying lipopeptide
`
`biosurfactants. Pet. 16. In particular, Petitioner contends that one of
`
`ordinary skill in the art—starting with the 93% pure daptomycin
`
`composition of the ’843 patent—would have purified daptomycin to purity
`
`levels above 97% using the biosurfactant purification methods of Mulligan
`
`and Lin II. Pet. 18–20, 34–37, 47–48.1
`
`
`1 Petitioner provides a claim chart identifying where the asserted
`combination of references discloses each of the process steps of claims 98
`and 187 of the ’238 patent. Pet. 34–37, 47–48.
`
`
`
`9
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`
`In support of Petitioner’s arguments, Dr. Tarantino testifies that one of
`
`ordinary skill in the art would have been motivated to increase the purity of
`
`daptomycin compositions “as much as reasonably possible.” Ex. 1005
`
`¶ 137. Dr. Tarantino further testifies that, given the disclosure in Lakey that
`
`daptomycin forms aggregates (in the form of micelles), one of ordinary skill
`
`in the art would have understood that the purification methods of Mulligan
`
`and Lin II could be used to obtain daptomycin compositions with purity
`
`levels greater than 99%. Ex. 1005 ¶¶ 71, 137, 141–144.
`
`
`
`Patent Owner contends that Petitioner provides insufficient reason or
`
`motivation to combine the asserted references. Prelim. Resp. 8–9.
`
`According to Patent Owner, “[w]hile the Petition makes general assertions,
`
`such as that a person of skill in the art would have sought to obtain
`
`daptomycin compositions of high purity, it fails to explain with particularity
`
`why” a person of ordinary skill in the art “would have selected, combined,
`
`and modified the specific group of asserted references” to obtain the claimed
`
`invention. Id. at 8–9. On this record, however, we are persuaded that
`
`Petitioner provides sufficient reasoning with rational underpinning to
`
`support its assertion that one of ordinary skill in the art would have sought to
`
`purify daptomycin compositions to purity levels above 99% using the
`
`disclosures of the ’843 patent, Mulligan, Lin II, and Lakey.
`
`Accordingly, we are persuaded that Petitioner demonstrates a
`
`reasonable likelihood of prevailing on its argument that claims 98 and 187
`
`would have been obvious over the ’843 patent, Mulligan, Lin II, and Lakey.
`
`III. CONCLUSION
`
`
`
`For the reasons set forth above, we institute an inter partes review as
`
`set forth in the Order. At this stage of the proceeding, we have not made a
`
`
`
`10
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`final determination with respect to the patentability of the challenged claims
`
`or any underlying factual or legal issues.
`
`For the foregoing reasons, it is
`
`IV. ORDER
`
`ORDERED that pursuant to 35 U.S.C. § 314, an inter partes review of
`
`
`
`
`
`the ’238 patent is hereby instituted on the following ground:
`
`
`
`Whether claims 98 and 187 would have been obvious under 35 U.S.C.
`
`§ 103 over the ’843 patent, Mulligan, Lin II, and Lakey;
`
`
`
`FURTHER ORDERED that the trial is limited to the ground identified
`
`above and no other grounds are authorized; and
`
`
`
`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.
`
`
`
`11
`
`
`
`IPR2015-01571
`Patent 8,058,238 B2
`
`
`
`PETITIONER:
`
`Elizabeth J. Holland, Esq.
`eholland@goodwinprocter.com
`
`Robert V. Cerwinski, Esq.
`rcerwinski@goodwinprocter.com
`
`Cynthia L. Hardman, Esq.
`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
`
`
`
`
`
`12
`
`
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