Trials@uspto.gov
`571.272.7822
`
`
`
`
`
`
`
`
` Paper No. 13
`
` Entered: November 30, 2016
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LUYE PHARMA GROUP LTD., LUYE PHARMA(USA) LTD.,
`SHANDONG LUYE PHARMACEUTICAL CO., LTD., and
`NANJING LUYE PHARMACEUTICAL CO., LTD.,
`Petitioner,
`
`v.
`
`ALKERMES PHARMA IRELAND LTD. and
`ALKERMES CONTROLLED THERAPEUTICS, INC.,
`Patent Owner.
`____________
`
`Case IPR2016-01096
`Patent 6,667,061 B2
`____________
`
`
`Before LORA M. GREEN, ROBERT A. POLLOCK, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`GREEN, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`
`571.272.7822
`
`
`
`
`
`
`
`
` Paper No. 13
`
` Entered: November 30, 2016
`
`
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`LUYE PHARMA GROUP LTD., LUYE PHARMA(USA) LTD.,
`SHANDONG LUYE PHARMACEUTICAL CO., LTD., and
`NANJING LUYE PHARMACEUTICAL CO., LTD.,
`Petitioner,
`
`v.
`
`ALKERMES PHARMA IRELAND LTD. and
`ALKERMES CONTROLLED THERAPEUTICS, INC.,
`Patent Owner.
`____________
`
`Case IPR2016-01096
`Patent 6,667,061 B2
`____________
`
`
`Before LORA M. GREEN, ROBERT A. POLLOCK, and
`JACQUELINE T. HARLOW, Administrative Patent Judges.
`
`GREEN, Administrative Patent Judge.
`
`
`
`DECISION
`Institution of Inter Partes Review
`37 C.F.R. § 42.108
`
`
`
`
`
`
`
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`
`
`INTRODUCTION
`Luye Pharma Group Ltd., Luye Pharma (USA) Ltd., Shandong Luye
`Pharmaceutical Co., Ltd., and Nanjing Luye Pharmaceutical Co., Ltd.
`(collectively “Petitioner”) filed a Petition requesting an inter partes review
`of claims 1‒13 and 17‒23 of U.S. Patent No. 6,667,061 B2 (Ex. 1001, “the
`’061 patent”). Paper 5 (“Pet.”). Alkermes Pharma Ireland Limited and
`Alkermes Controlled Therapeutics, Inc. (collectively, “Patent Owner”) filed
`a Preliminary Response to the Petition. Paper 11 (“Prelim. Resp.”).
`Institution of an inter partes review is authorized by statute when “the
`information presented in the petition . . . and any response . . . shows that
`there is a reasonable likelihood that the petitioner would prevail with respect
`to at least 1 of the claims challenged in the petition.” 35 U.S.C. § 314; see
`37 C.F.R. §§ 42.4, 42.108. Upon considering the Petition and the
`Preliminary Response, we determine that Petitioner has demonstrated a
`reasonable likelihood that it would prevail in showing the unpatentability of
`claims 1‒13 and 17‒23. Accordingly, we institute an inter partes review of
`those claims.
`
`Related Proceedings
`A.
`Petitioner states that it has filed a second request for inter partes
`review seeking cancellation of claims 1‒13 and 17‒23 of the ’061 patent on
`other grounds. Pet. 1; Prelim. Resp. 1 n.1. That petition for inter partes
`review, IPR2016-01095, is being decided concurrently with the instant
`proceeding.
`
`The ’061 Patent (Ex. 1001)
`B.
`The ’061 patent issued on December 23, 2003, with J. Michael
`
`Ramstack, M. Gary I. Riley, Stephen E. Zale, Joyce M. Hotz, and Olufunmi
`
`2
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`L. Johnson as the listed co-inventors. Ex. 1001. According to the ’061
`patent, it is drawn “to injectable suspensions having improved injectability.”
`Id. at 1:12‒14.
`
`The ’061 patent discloses:
`Injectable suspensions are heterogeneous systems that
`typically consist of a solid phase dispersed in a liquid phase, the
`liquid phase being aqueous or nonaqueous. To be effective and
`pharmaceutically acceptable, injectable suspensions should
`preferably be: sterile; stable; resuspendable; syringeable;
`injectable;
`isotonic; and nonirritating.
` The
`foregoing
`characteristics result in manufacturing, storage, and usage
`requirements that make injectable suspensions one of the most
`difficult dosage forms to develop.
`Id. at 1:17‒25.
`
`The ’061 patent teaches that viscosity enhancers are added to injection
`vehicles to prevent settling of particles, but notes that viscosity is kept low to
`facilitate mixing and make the suspension easier to inject. Id. at 2:25‒30.
`According to the ’061 patent, it was “unexpectedly discovered that
`injectability is improved, and in vivo injectability failures significantly and
`unexpectedly reduced, by increasing the viscosity of the fluid phase of an
`injectable suspension.” Id. at 4:57‒60. The ’061 patent teaches that “is in
`contrast to conventional teachings that an increase in the viscosity hinders
`injectability and syringeability.” Id. at 4:60‒62.
`
`The ’061 patent specifically teaches that “microparticles” and
`“microspheres” refer to “particles that contain an active agent or other
`substance dispersed or dissolved within a polymer that serves as a matrix or
`binder of the particle,” wherein the “polymer is preferably biodegradable
`and biocompatible.” Id. at 5:14‒19.
`
`3
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`The ’061 patent specifically teaches the following injection vehicles:
`
`Vehicle A: 0.9% saline and 0.1% Tween 20; Vehicle B: 1.5% CMC, 30%
`sorbitol, and 0.2% Tween 20; and Vehicle C: 3% CMC, 0.1% Tween 20,
`and 0.9% saline. Id. at 9:38‒46. According to the ’061 patent, Vehicle A
`had a viscosity of 1.0 cp, Vehicle B had a viscosity of 24 cp, and Vehicle C
`had a viscosity of 56 cp. Id. at 10:Table 4. The ’061 patent specifically
`teaches that CMC is a viscosity enhancing agent. Id. at 12:14‒20.
`C.
`Challenged Claims
`Petitioner challenges claims 1‒13 and 17‒23 of the ’061 patent.
`Claim 1, the only independent claim of the ’061 patent, is representative:
`1.
`A composition suitable for injection through a needle
`into a host, comprising:
`microparticles comprising a polymeric binder; and
`an injection vehicle, wherein said microparticles are suspended
`in said injection vehicle at a concentration of greater than about
`30 mg/ml to form a suspension, wherein a fluid phase of said
`suspension has a viscosity greater than about 20 cp and less
`than about 600 cp at 20º C., wherein the viscosity of said fluid
`phase of said suspension provides injectability of the
`composition through a needle ranging in diameter from 18–22
`gauge.
`Ex. 1001, 18:6‒16 (emphasis added).
`D. The Asserted Grounds of Unpatentability
`Petitioner challenges the patentability of claims 1‒13 and 17‒23 of the
`’061 patent on the following grounds (Pet. 4):
`
`4
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`
`References
`Johnson1 and Kino2
`Gustafsson,3 Ramstack,4 and
`the Handbook5
`
`Petitioner relies also on the Declaration of Patrick Deluca, Ph.D.
`(Ex. 1002).
`
`Basis
`§ 103
`§ 103
`
`Claims Challenged
`1‒13 and 17‒23
`1‒13 and 17‒23
`
`
`
`ANALYSIS
`Claim Construction
`A.
`In an inter partes review, claim terms in an unexpired patent are
`interpreted according to their broadest reasonable construction in light of the
`specification of the patent in which they appear. See 37 C.F.R. § 42.100(b);
`Cuozzo Speed Techs., LLC v. Lee, 136 S. Ct. 2131, 2144–45 (2016)
`(upholding the use of the broadest reasonable interpretation standard).
`Under that standard, we presume that a claim term carries its “ordinary and
`customary meaning,” which “is the meaning that the term would have to a
`person of ordinary skill in the art in question” at the time of the invention.
`
`1 Johnson et al., U.S. Patent No. 5,654,010, issued August 5, 1997
`(Ex. 1009) (“Johnson”).
`2 Kino et al., U.S. Patent No. 5,656,299, issued August 12, 1997 (Ex. 1010)
`(“Kino”).
`3 Gustafsson et al., WO 97/14408, published April 24, 1997 (Ex. 1011)
`(“Gustafsson”).
`4 Ramstack et al., WO 95/13799, published May 26, 1995 (Ex. 1005)
`(“Ramstack”).
`5 HANDBOOK OF PHARMACEUTICAL EXCIPIENTS, 78‒81, 135‒138, 294‒298,
`329‒330, 375‒378, 420‒421, 439‒442, 477‒482 (Ainley Wade and Paul J
`Weller, ed., Am. Pharm. Ass’n & Pharm. Press 2nd ed. 1994) (Ex. 1008)
`(“the Handbook”).
`
`5
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed. Cir. 2007). See also
`Trivascular, Inc. v. Samuels, 812 F.3d 1056, 1062 (Fed. Cir. 2016) (“Under
`a broadest reasonable interpretation, words of the claim must be given their
`plain meaning, unless such meaning is inconsistent with the specification
`and prosecution history.”). 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).
`Petitioner offers explicit constructions of several claim terms (Pet. 19‒
`22), as does Patent Owner (Prelim. Resp. 9‒12). On the present record, we
`determine that none of the claim terms require explicit construction for
`purposes of this Decision. See, e.g., Wellman, Inc. v. Eastman Chem. Co.,
`642 F.3d 1355, 1361 (Fed. Cir. 2011) (“[C]laim terms need only be
`construed ‘to the extent necessary to resolve the controversy.’”) (quoting
`Vivid Techs, Inc. v. Am. Sci. & Eng’g, Inc., 200 F.3d 795, 803 (Fed. Cir.
`1999)).
`
`Obviousness over Johnson and Kino
`B.
`Petitioner asserts that claims 1‒13 and 17‒23 are rendered obvious by
`the combination of Johnson and Kino. Pet. 23‒38. Petitioner presents a
`claim chart demonstrating where the limitations of the challenged claims
`may be found in the relied upon references. Id. at 32‒38. Patent Owner
`contends that Petitioner has not established a reasonable likelihood that
`claims 1‒13 and 17‒23 is rendered obvious by the combination of references
`relied upon by Petitioner. Prelim. Resp. 14‒32.
`i.
`Overview of Johnson (Ex. 1009)
`Johnson “relates to a composition, and methods of forming and using
`
`said composition, for the sustained release of biologically active, stabilized
`
`6
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`human growth hormone (hGH).” Ex. 1009, 1:42‒45. The method of
`forming the composition includes the steps of “dissolving a biocompatible
`polymer in a polymer solvent to form a polymer solution, dispersing
`particles of biologically active, stabilized hGH in the polymer solution, and
`then solidifying the polymer to form a polymeric matrix containing a
`dispersion of said hGH particles.” Id. at 1:52‒57. Johnson teaches that “[a]
`preferred size range for microparticles is from about 1 to about 180 microns
`in diameter.” Id. at 4:60‒62.
`
`Example 7 of Johnson evaluated “the pharmacokinetic profiles of
`different hGH sustained release formulations as compared to more
`traditional methods of administering hGH.” Id. at 12:19‒24. Monkeys were
`administered a dose of 160 mg of hGH sustained release microspheres in
`1.2 ml of injection vehicle using a 20 gauge needle. Id. at 12:37‒42.
`Johnson teaches that the “injection vehicle was an aqueous vehicle
`containing 3% w/v Carboxymethyl Cellulose (sodium salt), 1% v/v Tween
`20 (Polysorbate 20) and 0.9% sodium chloride.” Id. at 12:42‒45.
`ii.
`Overview of Kino (Ex. 1010)
`Kino teaches:
`With the aim of improvement in compliance at the time of
`maintenance therapy with hydrophobic antipsychotic drugs, the
`present inventors have conducted intensive studies on the
`development of a sustained release pharmaceutical preparation
`in which a drug itself is used as an active ingredient without
`modification. As the result, it was found that a drug can be
`released at an almost constant rate extending over 1 week or
`more by including a hydrophobic antipsychotic drug in the form
`of microcrystals having an average particle size of 10 µm or less,
`desirably 5 µm or less, into a base comprising a biodegradable
`high molecular weight polymer having in vivo histocompatibility
`to make a sustained release microsphere preparation and
`administrating it by subcutaneous or intramuscular injection.
`
`7
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`Ex. 1010, 1:66‒2:12.
`
`Kino teaches that the microspheres may be made into a sustained
`release injection by preparing an aqueous suspension along with a dispersing
`agent, such as polysorbate 80 or CMC, a preservative, and an isotonic agent,
`such as sodium chloride or sorbitol. Id. at 4:38‒44. In addition, according
`to Kino, the sustained release injection may be made more stable by adding
`a filler such as sorbitol or mannitol, drying to form a solid preparation,
`which is then used by adding a dispersion medium, such as water, before
`injection. Id. at 4:52‒60.
`
`Kino teaches also that when used as a suspension for injection, the
`particle size of the microparticles “may be a range which can satisfy their
`dispersibility and needle-passing property, for example, in the range of from
`about 0.5 to about 400 µm, more preferably from about 0.5 to about 200 µm,
`most preferably from about 15 to 50 µm as an average particle size.” Id. at
`4:32‒37.
`
`Analysis
`iii.
`Claims 1‒3, 6‒9, 12, and 13
`a.
`Petitioner relies on Johnson for teaching “microspheres suspended in
`
`an aqueous injection vehicle.” Pet. 24 (citing Ex. 1009, 10:64‒66; Ex. 1002
`¶¶ 54, 59). Petitioner contends that “Johnson teaches a solution of 3% w/v
`carboxymethyl cellulose (low viscosity), polysorbate 20, and sodium
`chloride used as the injection vehicle; the same components as used in
`Vehicle C of the ’061 Patent.” Id. (citing Ex. 1009, 12:39‒42; Ex. 1002
`¶¶ 55, 59). Petitioner asserts further that Johnson teaches that a
`concentration of microparticles of 133 mg/ml, which, Petitioner argues, is
`greater than the concentration of a minimum of 30 mg/ml required by the
`
`8
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`challenged claims. Id. at 24‒25 (citing Ex. 1009, 12:39‒42; Ex. 1002 ¶¶ 54,
`59). In addition, Petitioner notes that the “formulation is suitable for
`injection into a patient via a 20 gauge needle, which is within the claimed
`range of 18–22 gauge.” Id. at 25 (citing Ex. 1009, 12:39-42; Ex. 1002 ¶¶ 54,
`59).
`Petitioner acknowledges that “Johnson is silent as to the viscosity of
`
`the . . . formulation.” Id. Petitioner contends, however, that the ordinary
`artisan would understand that CMC is a viscosity enhancing agent, and that
`it “would be considered the viscosity-controlling component of an injection
`vehicle.” Id. (citing Ex. 1008, 78; Ex. 1002 ¶ 61).
`
`Petitioner notes further that during prosecution, the applicants relied
`on the Declaration of Dr. Mark A. Tracy (Ex. 1018), in which Dr. Tracy
`“offered the conclusion that Kino taught a viscosity less than 7 cp based
`solely on the amount of CMC present in the Kino examples.” Pet. 25. Thus,
`Petitioner asserts, the ordinary artisan “would appreciate that the injection
`vehicle disclosed in Johnson would have substantially the same viscosity of
`the preferred embodiment of the ’061 Patent and as a result fall within the
`scope of claim 1.” Id. (citing Ex. 1002 ¶¶ 60, 61).
`According to Petitioner:
`Based on the Patent Owner’s admission during prosecution of
`the ‘061 Patent, the Tracy Declaration, and what would be known
`to [the ordinary artisan], [the ordinary artisan] would reasonably
`expect the injection vehicle of Johnson — having 3% CMC —
`to have a viscosity greater than 27cp at 20°C and certainly within
`the claimed range of 20-600cp at 20°C. Johnson therefore
`teaches every limitation of claims 1-3. (Ex. 1002 ¶ 60, 61)
`Id. at 25‒26.
`
`Patent Owner responds that neither Johnson nor Kino teaches the
`required viscosity limitation. Prelim. Resp. 14. Moreover, Patent Owner
`
`9
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`asserts that Petitioner is relying on Johnson’s disclosure of the injection
`vehicle, and the claimed suspension is formed after the microparticles are
`suspended in the injection vehicle. Id. at 15. Patent Owner contends,
`therefore, that Petitioner has not explained how the ordinary artisan “would
`have determined the viscosity of the fluid phase of the suspension[ ] of
`Johnson . . . from disclosures related to the compositions of their injection
`vehicles prior to formation of a suspension or to show that the viscosity of
`the injection vehicle[ ] of Johnson . . . would be the same as that of the fluid
`phase of their suspensions.” Id. at 15‒16. Specifically, Patent Owner
`asserts that Petitioner has failed to account for how the microspheres may
`affect the viscosity of the injection vehicle. Id. at 16. In addition, Patent
`Owner argues that the challenged claim require measuring the viscosity at
`20°C, and Johnson does not specify the temperature at which the viscosity
`should be measured. Id. at 16‒17.
`In addition, Patent Owner quotes Continental Can Co. U.S.A. v.
`
`Monsanto Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991) for the proposition that
`in order to establish inherency, “the missing characteristic must be
`necessarily present, or inherent, in the single anticipating reference.”
`Prelim. Resp. 17. Patent Owner contends that Petitioner has “failed to
`establish that [the ordinary artisan] would have inevitably measured the
`viscosity of the Johnson . . . formulations at 20ºC or that viscosity of the
`formulations would be between 20 cp and 600 cp.” Id. at 18.
`Challenged independent claim 1 requires that the “fluid phase of said
`suspension has a viscosity greater than about 20 cp and less than about 600
`cp at 20º C.” (emphasis added). We acknowledge that Johnson does not
`specifically teach that viscosity limitation. As noted by Petitioner, however,
`
`10
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`Johnson teaches an injection vehicle comprising 3% w/v CMC, 1 %
`polysorbate 20, and 0.9% sodium chloride. Pet. 24; Ex. 1009, 12:42‒45.
`The ’061 patent teaches Vehicle C, which comprises 3% CMC, 0.1% Tween
`20 (i.e., polysorbate 20), and 0.9% saline, has a density of 56 cp. Ex. 1001,
`9:45; 10:Table 4. As the injection vehicle of Johnson and Vehicle C are
`substantially the same, except for the concentration of polysorbate 20, the
`injection vehicles would be expected to have similar, if not the same
`viscosities, especially as the ’061 patent teaches that CMC is a viscosity
`enhancing agent. Id. at 12:14‒20.
`Petitioner further relies on the Declaration of Dr. Tracy (Ex. 1018),
`submitted during prosecution, to demonstrate that the viscosity of the
`injection vehicle of Johnson would have a viscosity greater than about 20 cp.
`Pet. 25. The Tracy Declaration looked at test Example 2 of Kino. Dr. Tracy
`declared:
`Test Example 2 of the Kino patent uses a 0.5% sodium
`carboxymethyl cellulose (CMC) solution
`isotonized with
`mannitol as the injection vehicle. Based upon my knowledge·
`and experience, the CMC is the viscosity-controlling component
`of the injection vehicle of Test Example 2 of the Kino patent.
`That CMC is the viscosity-controlling component is exemplified
`by the two injection vehicles disclosed on page 10, lines 10-17
`of the ’875 application as originally filed. The Formula 1
`injection vehicle described on page 10 of the ’875 application
`contains 1.5% CMC, and has a viscosity of approximately 27 cp
`at 20°C. The Formula 2·injection vehicle described on page 10
`of the ’875 application contains 0.75% CMC, and has a viscosity
`of approximately 7 cp at 20°C. By reducing the CMC from 1.5%
`to 0.75%, the viscosity dropped from 27 cp to 7 cp. Based upon
`my knowledge and experience, and the disclosure on page 10,
`lines 10-17 of the ’875 application, the viscosity of the CMC
`injection vehicle as the fluid phase of a suspension containing the
`
`11
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`
`microspheres of Test Example 2 of the Kino patent is less than 7
`cp at 20°C.
`Ex. 1018 ¶ 5.
`
`Thus, Dr. Tracy based his estimate of the viscosity of the injection
`vehicle of Kino solely on the amount of CMC in the injection vehicle. The
`Tracy Declaration, therefore, is further evidence that the injection vehicle of
`Johnson would have a viscosity at 20ºC close to that of Vehicle C of the
`’061 patent, as each has 3.0% CMC.
`Patent Owner’s argument premised on Continental Can does not
`
`convince us otherwise. Inherency does not require intent or recognition that
`a prior art process achieve a result which is claimed. “Inherency is not
`necessarily coterminous with the knowledge of those of ordinary skill in the
`art. Artisans of ordinary skill may not recognize the inherent characteristics
`or functioning of the prior art.” MEHL/Biophile Intern. Corp. v. Milgraum,
`192 F.3d 1362, 1365 (Fed. Cir. 1999). Thus, “[m]ere 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). Thus, the fact that the ordinary artisan may not have recognized that
`the injection vehicle of Johnson may have a viscosity greater than about 20
`cp at 20ºC does not affect the inherency analysis.
`
`Patent Owner’s argument that Petitioner does not take into account
`how the microspheres may affect the viscosity of the injection vehicle is also
`not convincing at this stage of the proceeding. Claim 1 specifies that the
`“fluid phase of said suspension has a viscosity greater than about 20 cp and
`less than about 600 cp at 20º C.” (emphasis added). The fluid phase of the
`suspension would be the injection vehicle. That is supported by the
`Specification of the ’061 patent, as, for example, Table 4 provides the
`
`12
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`viscosity of Vehicles A, B, and C, and not the viscosity of suspension after
`the microparticles were added. Ex. 1001, 10:Table 4; see also id. at 10:12‒
`13 (noting that “[d]ensities were measured for Vehicles A, B, and C”). In
`that regard, as we noted above, the Declaration of Dr. Tracy only took into
`account the amount of CMC in stating that the fluid phase of Test Example 2
`of Kino would have a viscosity less than 7 cp at 20ºC. Ex. 1018 ¶ 5.
`
`As to Petitioner’s use of the Declaration of Dr. Tracy, Patent Owner
`argues also that the Declaration does not support Petitioner’s contention that
`the ordinary artisan would have understood that the injection vehicle of
`Johnson meets the claimed viscosity limitation. Prelim. Resp. 19‒20.
`According to Patent Owner, that Declaration was directed to the formulation
`of Kino, and “Dr. Tracy did not state that [the ordinary artisan] could always
`determine viscosity based solely on the concentration of CMC in an
`injection vehicle or fluid phase of a suspension, without accounting for
`additional components, such as polysorbate 80, sodium chloride or
`microspheres of various active ingredients.” Id. at 20. In addition, Patent
`Owner argues that the Tracy Declaration is not a patent or printed
`publication under 35 U.S.C. § 311(b), as it was filed during prosecution
`more than two years after the earliest filing date of the challenged patent. Id.
`at 20.
`
`Patent Owner argues further that Dr. Tracy is not an ordinary artisan,
`but exceeds the knowledge of the ordinary artisan, and thus his Declaration
`does not reflect what would have been known by the ordinary artisan. Id. at
`20‒21. Thus, Patent Owner asserts, Petitioner offers “no independent
`evidence that [the ordinary artisan] would have understood the formulations
`in Johnson . . . to necessarily meet the claimed viscosity limitation present in
`
`13
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`each challenged claim of the ’061 patent.” Id. at 21. Patent owner argues
`that although Petitioner relies on its declarant, Dr. DeLuca, Dr. DeLuca
`relies only on the Tracy Declaration for support. Id. (citing Ex. 1002 ¶¶ 60,
`61). According to Patent Owner, that reliance is in error, because, as argued
`above, the Tracy Declaration is not prior art, and nor is it a patent or printed
`publication, and thus Dr. DeLuca’s testimony is unsupported. Id.
`
`Patent Owner asserts further:
`Petitioners use impermissible hindsight to selectively rely
`on the Tracy declaration. Dr. Tracy clearly states that, assuming
`measurement at 20ºC and consistent with the art at the time of
`the invention, the viscosities of the injection vehicles in Kino are
`significantly less than 20 cp.
` (Exh. 1018 at ¶¶ 4-5.)
`Nevertheless, Petitioners ignore this teaching and ask the Board
`to focus only on Dr. Tracy’s statements elsewhere in his
`declaration. Petitioners, however, cannot pick and choose one
`portion of his declaration to support a viscosity disclosure while
`blatantly ignoring another portion, relied upon by the Examiner,
`that proves Kino is not invalidating prior art with respect to the
`invention. See, e.g., Abbott Labs. v. Sandoz, Inc., 544 F.3d 1341,
`1348 (Fed. Cir. 2010) (warning against relying on hindsight to
`pick and choose among isolated elements from the prior art).
`Id. at 22.
`
`We do not find Patent Owner’s arguments in this regard convincing at
`this stage of the proceeding. It is irrelevant that Dr. Tracy may not be one of
`ordinary skill in the art. Dr. Tracy is testifying as to the inherent property of
`an injection vehicle, and inherency need not be coterminous with the
`knowledge of those of ordinary skill in the art. MEHL/Biophile Intern.
`Corp., 192 F.3d at 1365. Thus, the challenge is based on Johnson and Kino,
`and the Declaration of Dr. Tracy, as discussed above, is evidence that the
`injection vehicle of Johnson would inherently meet the viscosity limitation
`of challenged claim 1.
`
`14
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`As to claims 6‒9, 12 and 13, Petitioner notes that claim 6 adds a
`
`tonicity agent, and claim 7 specifies that the tonicity agent is sodium
`chloride. Pet. 27. Claims 8 and 12 depend from claims 2 and 6,
`respectively, and add a wetting agent, and claims 9 and 13 “specify that the
`wetting agent is ‘selected from the group consisting of polysorbate 20,
`polysorbate, 40, and polysorbate 80.’” Id. at 27‒28. According to
`Petitioner, “Johnson teaches carboxymethyl cellulose (sodium), a viscosity
`enhancing agent, sodium chloride, a tonicity agent, and polysorbate 20, a
`wetting agent, alone or in combination, and therefore teaches every element
`of claims 6-9 and 12-13.” Id. at 28 (citing Ex. 1009, 12:42‒45; Ex. 1002
`¶ 63).
`After considering the Petition and Preliminary Response, we
`
`determine that Petitioner has demonstrated a reasonable likelihood that
`claims 1‒3, 6‒9, 12, and 13 are obvious over the cited prior art.
`b. Claims 4, 5, 10, and 11
`Petitioner notes that claim 4 adds the limitation of a density enhancing
`agent, and claim 5 specifies that the density enhancing agent is sorbitol. Pet.
`26. As to claim 10, Petitioner notes that that it depends from claim 4, and
`adds a wetting agent, and claim 11 specifies “that the wetting agent is
`‘selected from the group consisting of polysorbate 20, polysorbate, 40, and
`polysorbate 80.’” Id.
`
`Petitioner relies on Kino for teaching the addition of fillers, such as
`sorbitol, and wetting agents, such as polysorbate 80, to microparticle
`suspensions, and that sorbitol is known to enhance the stability of such
`suspensions. Id. at 27 (citing Ex. 1010, 4:38‒40, 4:52‒56; Ex. 1002 ¶¶ 56,
`62).
`
`15
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`Patent Owner responds that Petitioner has not established why the
`
`ordinary artisan would have combined Johnson and Kino, with a reasonable
`expectation of success of arriving at the claimed invention. Prelim. Resp.
`24‒25. At best, Patent Owner asserts, Petitioner relies on impermissible
`hindsight. Id. at 25.
`
`Specifically, as to claims 4, 5, 10, and 11, Patent Owner asserts that
`the reason provided by Petitioner is to increase the density to stabilize the
`formulation; however, Patent Owner argues, neither Johnson nor Kino
`suggest that the formulation need to be stabilized, or that increasing the
`density would be desirable. Id. at 26.
`
`We agree with Patent Owner that the Petition does not point to any
`teaching in Johnson or Kino that establishes that increasing the density
`would be desirable. As noted by Petitioner (Pet. 27), however, Kino teaches
`that adding a filler such as mannitol or sorbitol to microspheres before
`freezing allows for more stable sustained release injections. Ex. 1010, 4:52‒
`60. Thus, Petitioner has sufficiently demonstrated on this record that the
`ordinary artisan would have had a reason to use a filler such as mannitol or
`sorbitol in the final sustained release compositions of Johnson.
`
`Patent Owner argues that Johnson and Kino are directed to “vastly
`different subject matter,” as Johnson is drawn to compositions for sustained
`release of hGH, which is soluble in a water-based system, whereas Kino
`relates to microspheres containing risperidone, which lacks affinity for
`water. Prelim. Resp. 28. Moreover, Patent Owner asserts, Kino is drawn to
`low viscosity compositions, which comprise 0.5% CMC, whereas the
`compositions of Johnson contain 3% CMC. Id. at 28‒30. Thus, given the
`conventional wisdom that low viscosity compositions were better for
`
`16
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`injectable compositions, Patent Owner asserts that the ordinary artisan
`would not have combined Johnson and Kino as suggested by Petitioner. Id.
`at 29‒30. Patent Owner contends, therefore, that Petitioner has not
`established a reasonable expectation of success of combining Johnson with
`Kino to arrive at the claimed invention. Id. at 31. Specifically, Patent
`Owner contends that the prior art “establishes that increased viscosity
`hinders injectability.” Id.
`
`We do not find Patent Owner’s arguments convincing at this stage of
`the proceeding. Both Johnson and Kino are drawn to the use of sustained
`release microsphere compositions. In addition, Johnson teaches an injection
`vehicle containing 3% CMC, and, thus, provides a reasonable expectation of
`success of achieving an injection vehicle containing 3% CMC, as well as a
`filler, such as sorbitol or mannitol. Note that all that is required is a
`reasonable expectation of success, not absolute predictability of success. In
`re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988).
`After considering the Petition and Preliminary Response, we
`determine that Petitioner has demonstrated a reasonable likelihood that
`claims 4, 5, 10, and 11 are obvious over the cited prior art.
`c. Claims 17‒21
`Petitioner notes that claim 17 depends from claim 1, and “requires that
`the microparticles ‘further comprise an active agent encapsulated within said
`polymeric binder.’” Pet. 28. Claim 18 specifies that the polymeric binder is
`selected from a Markush group that includes a copolymer of poly(glycolic
`acid) and poly-d,l-lactic acid, and claim 19, also dependent from claim 17,
`specifies that the “polymeric binder is poly(d,l-lactide-co-glycolide) having
`
`17
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`a molar ratio of lactide to glycolide in the range of from about 85:15 to about
`50:50.” Id. at 28‒29.
`
`As to claims 20 and 21, Petitioner notes that they depend from claims
`17 and 19, and “specify that the ‘active agent is selected from the group
`consisting of risperidone, 9-hydroxyrisperidone, and pharmaceutically
`acceptable salts thereof.’” Id. at 29.
`
`Petitioner relies on Johnson for teaching entrapping active substances
`in microparticles for sustained release, as well as teaches the use of
`poly(lactide-co-glycolide) as a polymeric binder. Id. (citing Ex. 1009, 1:45‒
`49, 3:55‒60; Ex. 1002 ¶ 64).
`
`Petitioner relies on Kino for teaching “that daily dose maintenance
`therapy to treat mental disease is undesirable due to patient compliance and
`that improvements in sustained release antipsychotics are necessary.” Id.
`(citing Ex.1010, 1:12-2:13; Ex. 1002 ¶ 65). Petitioner also relies on Kino as
`teaching that “improvements to compliance of maintenance therapy with
`antipsychotic drugs can be obtained with injections of sustained release
`preparations,” wherein the antipsychotic drug may be risperidone. Id. at 29‒
`30 (Ex. 1010, 1:65‒2:3, 2:41; Ex. 1002 ¶ 65).
`
`Petitioner asserts that the ordinary artisan would have improved the
`injectibility of a suspension of risperidone microparticles to increase patient
`compliance, and, thus, would have looked “to combine sustained release
`microparticles . . . to improve the injectability of the suspension.” Id. (citing
`Ex. 1002 ¶ 66).
`
`Patent Owner responds that “nothing in Johnson or Kino indicates that
`selectively combining their teachings would lead to improved suspension
`injectability or that improved injectability would impact patient
`
`18
`
`
`
`IPR2016-01096
`Patent 6,667,061 B2
`
`compliance.” Prelim. Resp. 27. Patent Owner argues further that “nothing
`in Johnson or Kino suggests the higher viscosity injection vehicle of
`Johnson would be appropriate for the Kino compositions comprising
`risperidone as an active ingredient.” Id. at 30.
`
`We agree with Patent Owner that Petitioner has not demonstrated a
`reasonable likelihood that claims 17‒21 are rendered obvious by the
`combination of Johnson and Kino. Petitioner offers only the conclusory
`statement that the ordinary artisan “would look to combine sustained release
`microparticles . . . to improve the injectability of the suspension.” Pet. 30.
`Such a conclusory statement, without more, is not sufficient to support the
`obviousness analysis. In KSR Int’l Co. v. Teleflex Inc., 550 U.S
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
