Trials@uspto.gov
`571-272-7822
`
` PUBLIC VERSION
`
`Paper 100
`
`Entered: June 30, 2022
`
`UNITED STATES PATENT AND TRADEMARK OFFICE
`_____________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`REGENERON PHARMACEUTICALS, INC.,
`Petitioner,
`v.
`NOVARTIS PHARMA AG,
`NOVARTIS TECHNOLOGY LLC,
`NOVARTIS PHARMACEUTICALS CORPORATION,
`Patent Owner.
`____________
`
`IPR2021-00816
`Patent 9,220,631 B2
`____________
`
`Before ERICA A. FRANKLIN, ROBERT L. KINDER, and
`JAMIE T. WISZ, Administrative Patent Judges.
`
`KINDER, Administrative Patent Judge.
`
`PRELIMINARY GUIDANCE
`PATENT OWNER’S MOTION TO AMEND
`
`

`

` IPR2021-00816
`Patent 9,220,631 B2
`
`I. INTRODUCTION
`On October 26, 2021, we instituted trial as to claims 1–26 of U.S. Patent No.
`9,220,631 B2 (Ex. 1001, “the ’631 patent”). Paper 13. After institution, Patent
`Owner filed a Contingent Motion to Amend on January 18, 2022. Paper 37
`(“Motion” or “Mot.”). Should we find in a final written decision that the
`challenged claims are unpatentable, Patent Owner proposes substitute claims 27–
`52, each of which corresponds to a respective one of challenged claims 1–26. Mot.
`6–11. Petitioner filed its Opposition to the Motion. Paper 74 (“Opposition” or
`“Opp.”).
`In the Motion, Patent Owner requested that we provide preliminary
`guidance concerning the Motion in accordance with the Board’s pilot program
`concerning motion to amend practice and procedures. Mot. 1; see also Notice
`Regarding a New Pilot Program Concerning Motion to Amend Practice and
`Procedures in Trial Proceedings under the America Invents Act before the Patent
`Trial and Appeal Board, 84 Fed. Reg. 9,497 (Mar. 15, 2019) (providing a patent
`owner with the option to receive preliminary guidance from the Board on its
`motion to amend) (“Notice”). We have considered Patent Owner’s Motion and
`Petitioner’s Opposition.
`In this Preliminary Guidance, we provide information indicating our initial,
`preliminary, non-binding views on whether Patent Owner has shown a reasonable
`likelihood that it has satisfied the statutory and regulatory requirements associated
`with filing a motion to amend in an inter partes review and whether Petitioner (or
`the record) establishes a reasonable likelihood that the substitute claims are
`unpatentable. Notice, 84 Fed. Reg. at 9,497 (“The preliminary guidance . . .
`provides preliminary, non-binding guidance from the Board to the parties about the
`[motion to amend].” Further, “the preliminary guidance will provide an initial
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`IPR2021-00816
`Patent 9,220,631 B2
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`discussion about whether there is a reasonable likelihood that the MTA meets
`statutory and regulatory requirements for an MTA,” and “also will provide an
`initial discussion about whether petitioner (or the record then before the Office,
`including any opposition to the MTA and accompanying evidence) establishes a
`reasonable likelihood that the substitute claims are unpatentable.”).
`For purposes of this Preliminary Guidance, we focus on the proposed
`substitute claims, and specifically on the amendments proposed in the Motion. See
`Notice, 84 Fed. Reg. at 9,497. We do not address the patentability of the
`originally challenged claims. Id. Moreover, in formulating our preliminary views
`on the Motion and Opposition, we have not considered the parties’ other
`substantive papers on the underlying merits of Petitioner’s challenges. We
`emphasize that the views expressed in this Preliminary Guidance are subject to
`change upon consideration of the complete record, including any revision to the
`Motion filed by Patent Owner.  Thus, this Preliminary Guidance is not binding on
`the Board when rendering a final written decision. See id. at 9,500.
`II. PRELIMINARY GUIDANCE
`
`A. Statutory and Regulatory Requirements
`For the reasons discussed below, at this stage of the proceeding, and based
`on the current record, it appears that Patent Owner has shown a reasonable
`likelihood that it has satisfied the statutory and regulatory requirements associated
`with filing a motion to amend.
`
`1. Reasonable Number of Substitute Claims
`
`Does Patent Owner propose a reasonable number of substitute claims?
`(35 U.S.C. § 316(d)(1)(B))
`
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`IPR2021-00816
`Patent 9,220,631 B2
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`Yes, Patent Owner proposes no more than 1 substitute claim for each
`challenged claim. See Mot. 6–11. Petitioner does not argue otherwise.
`
`2. Respond to Ground of Unpatentability
`
`Does the Motion respond to a ground of unpatentability involved in the
`trial? (37 C.F.R. § 42.121(a)(2)(i))
`
`Yes. Patent Owner responds to the grounds of unpatentability. See Mot.
`12–25. Petitioner does not argue otherwise.
`
`3. Scope of Amended Claims
`
`Does the amendment seek to enlarge the scope of the claims? (35 U.S.C.
`§ 316(d)(3); 37 C.F.R. § 42.121(a)(2)(ii))
`
`No. Each of the proposed substitute claims includes narrowing limitations
`or additional limitations. See Mot. 3–4. Petitioner does not argue
`otherwise.
`
`4. New Matter
`
`Does the amendment seek to add new subject matter? (35 U.S.C.
`§ 316(d)(3); 37 C.F.R. § 42.121(a)(2)(ii))
`
`No. On this record, and having considered Petitioner’s contrary arguments
`(Opp. 1–10), we find Patent Owner provides written description support
`for the added limitations according to their plain meaning.
`Patent Owner asserts that the proposed substitute claims are supported by
`the specification of the original application, No. 13/750,352 (“the ’352
`Application” (Ex. 2227)) and the priority application EP 12189649 (“EP
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`Patent 9,220,631 B2
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`’649,” (Ex. 2014)).1 Mot. 6. Patent Owner asserts that the added
`limitation of “from about 1 μg to about 25 μg silicone oil” in proposed
`substitute claims 27 and 48 is supported in the original application at page
`6, lines 13–20, and claims 7 and 8.2 Mot. 7, 10. Patent Owner cites the
`same disclosure for supporting proposed substitute claim 29, reciting a
`range “of from about 3 μg to about 25 μg silicone oil.” Id. The cited
`portion of the ’352 Application discloses that
`in one embodiment a syringe according to the invention
`comprises less than about 800 μg, (i.e. about less than
`about 500 μg, less than about 300 μg, less than about 200
`μg, less than about 150 μg, less than about 75 μg, less than
`about 50 μg, less than about 25 μg, less than about 15 μg,
`less than about l0 μg) silicone oil in the barrel. If the
`syringe comprises a low level of silicone oil, this may be
`more than about 1 μg, more than about 3 μg, more than
`about 5 μg, more than about 7 μg or more than about 10 μg
`silicone oil in the barrel.
`Ex. 2227, 6:13–20. Original claim 7 recites the maximum amounts of
`silicone oil for internally coating a syringe barrel (less than about 500 μg,
`100 μg, 50 μg, 25 μg, and 10 μg). Id. at 18. Original claim 8 recites the
`minimum amounts of silicone oil for internally coating a syringe barrel
`(more than about 1 μg, 3 μg, 5 μg, 7 μg, and 10 μg). Id.
`As to the new limitation that the VEGF solution “has a shelf life of at least
`twelve months after terminal sterilization” in proposed substitute claim 27,
`Patent Owner cites the original application at page 12, lines 15–17. Mot.
`7. The cited portion of the specification recites: “[t]hus, in one
`embodiment, a syringe according to the invention (whilst in its blister
`pack) may have a shelf life of up to 6 months, 9 months, 12 months, 15
`months, 18 months, 24 months or longer,” following a description of a
`sterilization process. Ex. 2227, 12:13–17.
`Patent Owner argues that Dr. Sigg testifies that he developed syringe
`barrels comprising amounts of silicone oil range from
`. Mot.
`
`1 Both applications appear to disclose the same subject matter. See generally,
`Ex. 2227; Ex. 2014. The parties do not argue otherwise. For expediency, we cite
`to Ex. 2227.
`2 Patent Owner cites the Bates numbers of the exhibit.
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`IPR2021-00816
`Patent 9,220,631 B2
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`12 (citing Ex. 2206 ¶ 50). Patent Owner argues that “[t]hese syringes
`showed break loose forces of less than 11N, and a slide force of less than
`5N, at time zero and after storage for at least twelve months following
`terminal sterilization, with minimal change in such forces between these
`timepoints.” Id. (citing Ex. 2206 ¶ 51; Ex. 2224, 41).
`Petitioner contends that the proposed substitute claims introduce new
`matter because the original application does not convey possession of the
`claimed invention as an integrated whole. Opp. 1–2. Specifically,
`Petitioner contends that the original application fails to “disclose
`possession of a syringe having 1–25 μg or 3–25 μg of silicone oil on the
`syringe barrel and that maintained a break loose force of less than 11N for
`at least twelve months after terminal sterilization.” Id. at 4 (citing
`Ex. 1101 ¶¶ 34–51). Rather, Petitioner argues that the specification lists
`each of these limitations as part of a “laundry list” of features. See id.
`(citing Ex. 2227, 6:13–20, 7:10–11, 12:15–17; Nuvo Pharm. (Ir.)
`Designated Activity Co. v. Dr. Reddy’s Labs. Inc., 923 F.3d 1368, 1380
`(Fed. Cir. 2019)).
`Specifically, Petitioner argues that the specification discloses an example
`of “syringe having ‘<100 μg silicone oil’ with average and maximum
`break out forces below 3N,” but does not disclose any specific amount of
`silicone oil within the claimed range, nor a break loose force of below 11
`N after twelve months of storage. Opp. 5–6 (citing Ex. 2227, 7:14–16;
`15:25–16:3). Petitioner argues that Patent Owner seeks an interpretation
`of “shelf life” that requires maintaining the break loose force over a period
`of time. See id. at 2, n.1. However, Petitioner argues that “a POSITA
`would not interpret ‘shelf life’ in the [specification] as relating to the break
`loose force of the syringe, let alone a break loose force of less than 11N.”
`Id. at 6.
`Petitioner separately argues that the original specification does not convey
`possession of the full scope of the claims encompassing syringes having a
`fill volume of between about 0.5 ml and about 1 ml, combined with the
`claimed amount of silicon oil, break loose force, and shelf life. Opp. 8.
`Specifically, Petitioner argues that a 1 ml syringe would “(i) require more
`silicone oil as compared to a 0.5 ml syringe because of the larger surface
`area of the barrel; and (ii) still yield a higher break loose force by a factor
`of approximately 1.37 or 1.86, respectively.” Id. at 9 (citing Ex. 1011
`¶ 54).
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`Finally, Petitioner argues that Dr. Sigg’s declaration is not part of the
`specification and cannot provide written description support. Opp. 7
`(citing Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1309 (Fed. Cir.
`2015)) (“The written description requirement requires possession as shown
`in the specification, not as shown by prior experimental work.”).
`Petitioner further argues that Dr. Sigg’s declaration does not provide
`written description support for the full scope of the claims. Id. at 7–8.
`Specifically, Petitioner argues that “[n]one of the data in Ex. 2224
`indicates that the syringes with a break loose force of less than 11N after
`twelve months also had about 1 μg or about 3 μg of silicone oil on the
`syringe barrel,” as claimed. See id. at 8 (citing Ex. 1101 ¶¶ 47–48).
`On this record, it is our preliminary and non-binding guidance that Patent
`Owner has shown written description support for the proposed substitute
`claims, according to their plain meaning. To satisfy the written
`description requirement, the original disclosure does not have to provide in
`haec verba support for the claimed subject matter at issue. Purdue
`Pharma L.P. v. Faulding Inc., 230 F.3d 1320, 1323 (Fed. Cir. 2000).
`However, “one skilled in the art, reading the original disclosure, must
`immediately discern the limitation at issue in the claims.” Id. In Purdue
`Pharma, the Federal Circuit found lack of written description for claims
`reciting specific values that selected from a multitude of pharmacokinetic
`parameters without any suggestion that the values were an important
`defining quality of the invention. See id. at 1326–1327. Unlike the claims
`in Purdue Pharma, it is our preliminary and non-binding guidance, that
`the original specification defined low amounts of silicone as one of the
`defining qualities of the invention. We address this finding below.
`The original disclosure of the ’631 patent directs the skilled artisan to a
`small volume syringe suitable for intravitreal injections and comprising a
`low level of silicone as a lubricant that provides a break loose force of less
`than 20 N. Ex. 2227, 2:7–11. The specification further directs the skilled
`artisan to maximum amounts of silicone oil, of which “about 25 μg” is one
`prophetic example. See id. at 6:5–26. That amount falls within the
`experimental examples siliconized with <100 μg silicone oil. Id. at 15:25–
`16:5. Similarly, the original disclosure directs the skilled artisan to a
`pharmaceutical product having an appropriate shelf life, e.g. at least
`twelve months after terminal sterilization. Id. at 12:13–17. Accordingly,
`it is our preliminary, non-binding, guidance that the specification as whole
`
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`IPR2021-00816
`Patent 9,220,631 B2
`
`would have directed one skilled in the art to low levels of silicone oil as an
`important defining quality of the claimed invention. See Purdue Pharma,
`230 F.3d at 1327. Thus, it is our preliminary and non-binding guidance
`that the written description supports the claims including a maximum
`amount of silicon of about 25 μg, and a shelf life of at least twelve months
`after terminal stabilization.
`Despite our finding that the proposed substitute claims have written
`description support, we agree with Petitioner that the specification does
`not explicitly describe shelf life correlated with break loose force. See
`Opp. 5–6. For example, the specification does not describe any effect of
`terminal stabilization on break loose force, unlike the description of
`alkyation of the VEG antagonist and sterilant residue (EtO or hydrogen
`peroxide). See Ex. 2227, 12:13–13:2. Likewise, the specification does not
`describe terminal stabilization of the experimental examples which test
`break loose force. See id. at 15:25–16:3. Dr. Sigg’s testimony on
`experimental results cannot fill this absence in the specification. See
`Allergan, 796 F.3d at 1309. Finally, the plain language of claim 27 recites
`break loose force and shelf life as separate limitations (joined by “and”)
`not as one limitation being a subset of the other. See Mot. 3. Accordingly,
`we construe the term “has a shelf life of at least twelve months after
`terminal sterilization” according to its plain and ordinary meaning, as
`supported by the specification and without correlation to break loose force.
`We emphasize that our position on written description is preliminary, and
`invite the parties to address this issue in further briefing.
`
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`IPR2021-00816
`Patent 9,220,631 B2
`
`B. Patentability3
`For the reasons discussed below, at this stage of the proceeding, and based
`on the current record,4 it appears that Petitioner (or the record) has shown a
`reasonable likelihood that proposed substitute claims 27–52 are unpatentable.
`
`Does the record establish a reasonable likelihood that the proposed
`substitute claims are unpatentable?
`
`1. Written Description
`No. On this record, and having considered Petitioner’s contrary arguments
`(Opp. 1–10), we find Patent Owner provides written description support
`for the added limitations according to their plain meaning. See supra 4–8
`(discussion of “new matter” for proposed substitute claims 27, 29, and 48).
`2. Enablement
`No. On this record, Petitioner has not shown a reasonable likelihood of
`establishing that proposed substitute claims 27–52 are unpatentable for
`lack of enablement.
`
`Petitioner argues that the specification does not enable the proposed
`substitute claims’ two limitations related to: 1) “shelf life” and 2) about
`
`3 The Leahy-Smith America Invents Act, Pub. L. No. 112-29, 125 Stat. 284 (2011)
`(“AIA”), amended 35 U.S.C. § 103. Because Patent Owner asserts an effective
`filing date before the effective date of the applicable AIA amendments for the
`proposed substitute claims of the ’631 patent, we refer to the pre-AIA version of 35
`U.S.C. § 103 in this Guidance.
`4 As noted above, in this Preliminary Guidance, we express no view on the
`patentability of original claims 1–26 in this Preliminary Guidance. Instead, we
`focus on limitations added to those claims in Patent Owner’s Motion to Amend.
`As such, we do not address Patent Owner’s arguments as to the subject matter of
`claims 50–52 (see Mot. 23–24) because those proposed substitute claims do not
`recite the added limitations (apart from their dependency).
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`IPR2021-00816
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`1 μg or about 3 μg silicone oil. Opp. 20–25. We address each argument
`below.
`
`Shelf life
`Petitioner argues that the proposed substitute claims, reciting “a shelf life
`of at least twelve months after terminal sterilization,” cover an unbounded
`shelf life. Opp. 20–22 (citing MagSil Corp. v. Hitachi Global Storage
`Techs., Inc., 687 F.3d 1377, 1381 (Fed. Cir. 2012) (finding non-
`enablement of an “open-ended” claim range)). Petitioner argues that the
`specification lists out the number of months that the syringe may remain
`sterile, including 24 months or longer. Id. at 21 (citing Ex. 2227, 12:13–
`17). Petitioner argues that the “specification, however, includes nothing to
`suggest that an ordinarily skilled artisan could achieve a shelf life of
`greater than 24 months for a pre-filled syringe containing a VEGF-
`antagonist without undue experimentation.” Id. (citing Ex. 1105 ¶¶ 364–
`367). Nevertheless, Petitioner argues that “a shelf life of 6, 9, 12, 15, 18
`or 24 months is consistent with what a POSITA would have expected
`based on the prior art.” Id. at 22 (citing Ex. 1015, 210).
`
`On this record, we are not persuaded by Petitioner’s argument. “To be
`enabling, the specification of a patent must teach those skilled in the art
`how to make and use the full scope of the claimed invention without
`‘undue experimentation.’” MagSil Corp., 687 F.3d at 1380. Petitioner
`argues that those skilled in the art would have expected a pre-filled syringe
`for a therapeutic biologic to have a minimum shelf life of 18 to 24 months
`at the intended storage condition. See Ex. 1015, 195. The original
`specification describes a method for sterilizing the syringe so that it has
`the claimed shelf life. See Ex. 2227, 12:13–17. Accordingly, it does not
`appear that undue experimentation would have been required to obtain the
`claimed product, having the claimed shelf life of at least 12 months after
`terminal stabilization.
`
`Syringe having about 1 μg or about 3 μg silicone oil
`Petitioner argues that “the specification fails to provide adequate
`disclosure across the full range of silicone oil,” including the lower ends of
`the claimed ranges of about 1 μg or about 3 μg. Opp. 22. Specifically,
`Petitioner argues that the specification does not disclose any process for
`
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`Patent 9,220,631 B2
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`applying silicone oil in low amounts (1 μg or 3 μg) to a syringe barrel. Id.
`at 23 (citing Ex. 1101 ¶ 94 ). Petitioner further argues that the
`specification does not disclose working examples of syringes with 1 μg or
`3 μg silicone oil that also display the claimed break loose and slide force.
`See id. (citing Ex. 1101 ¶¶ 91–111; Ex. 1001, 12:21–45).
`
`Petitioner argues that in the absence of an express disclosure in the
`specification, one of ordinary skill in the art would look to the prior art for
`the minimum amounts of silicone oil. See Opp. 23–24. Petitioner argues
`that the prior art, including Boulange5, describes syringe barrels with
`silicone oil as low as 20 μg, but not as low as about 1 μg or about 3 μg.
`See id. at 24 (citing Ex. 1101 ¶¶ 97–99; Ex. 1162, 2). Petitioner argues
`that “nothing in the prior art demonstrates that achieving 1 μg or 3 μg of
`silicone oil on the syringe barrel while also maintaining break loose and
`slide forces of less than 11N would be routine or attainable without undue
`experimentation.” Id. (citing Ex. 1001 ¶¶ 99–111). Rather, Petitioner
`argues that “it took more than
` of design and experimentation for the
`Vetter employees to develop a siliconization process and define the
`minimum amount of silicone oil that would achieve a break loose force of
`less than 11N.” Id. (citing Ex. 1001 ¶¶ 108–109).
`
`On this record, we are not persuaded by Petitioner’s argument. “[P]atent
`applicants are not required to disclose every species encompassed by their
`claims, even in an unpredictable art.” In re Vaeck, 947 F.2d 488, 496
`(Fed. Cir. 1991). But “the disclosure must adequately guide the art worker
`to determine, without undue experimentation, which species among all
`those encompassed by the claimed genus possess the disclosed utility.” Id.
`The disclosure provides a range of silicone oil amounts and a desired
`target of break loose force, as well as a method for testing breaking loose
`force. See Ex. 2227, 15:25–16:3. Even if it took more than
` of
`design and experimentation to develop a siliconization process and define
`the minimum amount of silicone oil within the claimed range, Petitioner
`has not shown on this record that the amount of experimentation was
`undue given the nature of the art.
`
`5 PCT Patent Publication No. WO 2009/030976 (Ex. 1008).
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`Indefiniteness
`3.
`No. On this record, Petitioner has not shown a reasonable likelihood of
`establishing that proposed substitute claim 27 is unpatentable for being
`indefinite.
`
`Petitioner argues that the “shelf life” limitation renders indefinite the
`proposed substitute claims. Opp. 25–28. Petitioner argues that Patent
`Owner proposes a claim construction of “shelf life” as including 1) long-
`term storage stability of the active agent and 2) maintaining a stopper
`break loose force for the duration of the product’s shelf life. Id. (citing
`Mot. 19). Petitioner argues that “[i]t is unclear, however, based on the
`intrinsic or extrinsic record, whether—and to what degree—any
`additional product characteristics must be maintained to satisfy the shelf
`life limitation.” Id. at 25–26 (citing Ex. 1105 ¶ 371).
`
`Petitioner presents three specific arguments that “shelf life” is ambiguous.
`See id. at 25–28. First, Petitioner argues that the claims recite various
`product characteristics relating to shelf life. See id. at 26–27. For
`example, proposed substitute claim 46 refers to ≤ 5% alkylated VEGF
`antagonist but claim 47 requires a “Sterility Assurance Level of at least
`10- 6.” Id. (citing Mot. 10). Second, Petitioner argues that the
`specification describes different variables related to shelf life, including
`sterility of the outer surface of the syringe and low alkylation of the VEGF
`antagonist. See id. at 27–28 (citing Ex. 2227 12:17–22, 12:23–26;
`Ex. 1105 ¶¶ 368–372). Third, Petitioner contends that shelf life was never
`addressed during prosecution. See id. at 28.
`
`On this record, we do not find Petitioner’s arguments persuasive.
`“[D]efiniteness is to be evaluated from the perspective of someone skilled
`in the relevant art.” Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S.
`898, 908 (2014). As discussed with respect to enablement above and
`obviousness below, Petitioner asserts that those of ordinary skill in the art
`would have sought to achieve a minimum shelf life of 18 to 24 months at
`the intended storage condition. See Opp. 32 (citing Ex. 1015, 210;
`Ex. 1105 ¶¶ 155–156). Likewise, Petitioner argues that the known prior
`art, including the Macugen PFS, had a shelf life of
`. See id.
`(citing Ex. 1120, 59; Ex. 1105 ¶ 187). The references show that “shelf
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`life” was a term known to those of ordinary skill in the art as applied to
`therapeutic biologics, such as the VEGF antagonist recited by the claims.
`On this record, neither the claims nor the specification define “shelf life”
`contrary to the plain meaning of the term. Accordingly, it is our
`preliminary and non-binding analysis that the “shelf life” limitation
`informs those skilled in the art about the scope of the invention with
`reasonable certainty. See Nautilus, 572 U.S. at 910.
`
`Inventorship
`4.
`On this record, Petitioner raises substantial questions as to the inventorship
`of the proposed substitute claims. Patent Owner has not had an
`opportunity to respond to that argument. Thus, we decline to take a
`preliminary position on this issue. We encourage the parties to further
`brief this issue. Nevertheless, we summarize Petitioner’s arguments
`below.
`
`Petitioner argues that the ’631 patent does not list all of the inventors and
`therefore the proposed substitute claims are unpatentable under 35 U.S.C.
`§ 102(f) (pre-AIA). Opp. 10–20. Specifically, Petitioner argues that
` and
` made significant contributions to
`conceiving the numerical ranges of silicone oil, but were not joined as
`inventors. See id. When a party asserts invalidity under 102(f), a court
`should first determine whether there exists proof that the alleged unnamed
`inventor was in fact a co-inventor. Pannu v. Iolab Corp., 155 F.3d 1344,
`1350 (Fed. Cir. 1998). Accordingly, we summarize Petitioner’s arguments
`that
` and
` should have been joined as co-
`inventors below.
`
` were employees of
`and
`Petitioner argues that
`Vetter Pharma-Fertigung GmbH & Co. KG (“Vetter”). Opp. 10.
`Petitioner argues that
` and
` collaborated with
`the named inventors as part of a joint development agreement between
`Patent Owner (Novartis) and Vetter to develop a syringe pre-filled with
`Lucentis. Id. at 12 (citing Ex. 2132, 2); see also Kimberly-Clark Corp. v.
`Procter & Gamble Distrib. Co., 973 F.2d 911, 916 (Fed. Cir. 1992) (“It is
`undisputed that this language required some form of collaboration in order
`that an ‘invention’ be ‘made by two or more persons jointly.’”). Petitioner
`
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`presents evidence—from before, during, and after the collaboration
`between Patent Owner and Vetter—that allegedly corroborates conception
`by
` and
`. See id. at 12–20 (citing Ex. 1158;
`Ex. 1159; Ex. 1112–1113; Ex. 1101; Ex. 2143; Ex. 1119; Ex. 1121–1127;
`Ex. 1128; Ex. 2002).
`
`On this preliminary record, Petitioner’s argument may have merit as to
`whether
` and
` contributed to the conception of
`the proposed substitute claims. However, as discussed above, we decline
`to provide a preliminary analysis here, as Patent Owner has not had an
`opportunity to respond. Again, we encourage the parties to further brief
`this issue.
`
`5. Obviousness
`Yes. On this record and at this stage of the proceeding, Petitioner has
`shown a reasonable likelihood of establishing that the proposed substitute
`claims are unpatentable as having been obvious over the combined prior
`art. We focus our discussion on proposed substitute claims 27, 29, and 48,
`which include limitations added by Patent Owner’s Motion. The
`remaining proposed substitute claims have not been amended other than
`by virtue of their reliance on proposed substitute claim 27.
`
`Petitioner argues that claims 27, 29, and 48 would have been obvious over
`the Macugen pre-filled syringe (PFS), and Boulange or BD 1 ml Hypak
`(Ground 1). Opp. 28. Petitioner cites to the Macugen 2008 Label6 to
`argue that Macugen PFS was in public use and on sale in the United States
`before July 2011. Id. at 29. Alternatively, Petitioner argues that claims
`27, 29, and 48 would have been obvious over Sigg7 or Lam8, Boulange or
`BD 1 ml Hypak, and Nema9 (Ground 6). Id. at 29. Because we find the
`
`6 Internet Archive WayBack Machine, March 7, 2011 Record of Drugs.com,
`Macugen Prescribing Information, available at https://web.archive.org/web/
`20110307065238/http://www.drugs.com:80/pro/macugen.html (Ex. 1009).
`7 PCT Patent Publication No. WO 2011/006877 (Ex. 1007).
`8 PCT Patent Publication No. WO 2008/077155 (Ex. 1029).
`9 S. Nema & J. D. Ludwig, Pharmaceutical Dosage Forms: Parenteral
`Medications, Volume 1: Formulation and Packaging (3rd ed. 2010) (Ex. 1015); S.
`14
`
`

`

`IPR2021-00816
`Patent 9,220,631 B2
`
`combination of Sigg, Boulange, and Nema dispositive for this preliminary
`guidance, we focus our discussion on that combination as we address the
`limitations added by the Contingent Motion below.
`
`Maximum amount of about 25 μg silicone oil (claims 27, 29, 48)
`
`Petitioner relies on the teachings of Boulange for this limitation. Relying
`on the testimony of Mr. Koller, Petitioner argues that “Boulange describes
`applying 4 ± 1 μg/cm2 baked-on silicone oil to a 1 ml syringe barrel.”
`Opp. 30 (citing Ex. 1008, 16:7–10, Tables 5, 7; Ex. 1105 ¶ 166).
`Petitioner argues that “[i]t would have been obvious to apply the same rate
`of silicone oil to a 0.5 ml syringe barrel, resulting in approximately 20.19–
`35.9 μg silicone oil.” Id. (citing Ex. 1105 ¶¶ 167–169). For this amount,
`Petitioner relies on Mr. Koller’s calculations applying “a silicone oil
`spraying rate of 3–5 μg/cm2 for baked-on siliconization.” See Ex. 1105
`¶¶ 166–169. Petitioner further argues that syringes prepared according to
`Boulange would maintain a break loose force of less than about 11 N after
`12 months of shelf life under normal storage conditions for a VEGF-
`antagonist. Opp. 33 (citing Ex. 1105 ¶¶ 174–175). Specifically, Mr.
`Koller declares that Boulange Tables 5 and 7 teaches syringes A, B1, and
`C with break loose forces of less than about 11 N after 1-month
`accelerated aging. Ex. 1105 ¶¶ 173–184. Mr. Koller further declares that
`one of ordinary skill in the art “would have understood that the break loose
`and slide forces after one month accelerated aging at 40° C disclosed for
`Boulange . . . syringes conservatively correspond to forces after storing
`the syringes at 2–8 °C for at least 9.2–13.9 months.” Id. ¶ 179.
`
`Petitioner argues that a person of ordinary skill in the art would have been
`motivated to apply low volume syringes with low baked-on silicone oil
`and low break loose force to the known products to reduce the amount of
`silicon oil. Opp. 31–32 (citing Ex. 1105 ¶ 159; Ex. 1003 ¶¶ 159–167).
`Petitioner argues that low levels of silicon reduce the amount of silicone
`oil injected into a patient’s eyes and minimize negative interaction with
`the drug product. Id. Petitioner further argues that it was known that the
`“baked-on silicone oil process applied less silicone oil to the syringe barrel
`
`Nema & J. D. Ludwig, Pharmaceutical Dosage Forms: Parenteral Medications,
`Volume 2: Facility Design, Sterilization and Processing (3rd ed. 2010) (Ex. 1016).
`15
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`IPR2021-00816
`Patent 9,220,631 B2
`
`that better adheres to the syringe barrel, thus reducing the amount of
`silicone oil that could migrate into the drug product.” Id. at 32.
`
`Patent Owner argues that “Boulange describes syringe barrels with
`coatings of silicone oil in amounts of only 40 μg and 500 μg.” Mot. 14.
`Patent Owner argues that Boulange does not teach a syringe barrel coated
`with silicone oil in an amount from about 1 μg to about 25 μg. Id. at 15
`(citing Ex. 1008, 20:16, 19). Patent Owner argues that Mr. Koller’s
`calculations based on applying 4 μg/cm2 silicone oil to 0.5 and 1.0 mL
`syringes “would result in in a syringe having anywhere from ~28–43 μg of
`silicone oil.” Id. at 15 (citing Ex. 1003, 129–130; Ex. 2208 ¶¶ 78–79).
`
`Patent Owner further argues that one of ordinary skill in the art would not
`have been motivated to use the claimed amount of silicone oil with a
`reasonable expectation of success. Mot. 16–18. First, Patent Owner
`argues that Boulange shows that “syringes with lower amounts of silicone
`oil (e.g., 40 μg) perform worse than syringes with the higher amounts of
`silicone oil (e.g., 500 μg),” and therefore one of ordinary skill would not
`have been motivated to reduce the amount of silicone oil by nearly half to
`reach the claimed upper limit of about 25 μg. Id. at 16–17 (citing
`Ex. 2208 ¶¶ 96–100, 103). Second, Patent Owner argues that Boulange’s
`test results using demineralized water “could not have been extrapolated to
`a syringe with a VEGF antagonist,” because a VEGF antagonist would be
`more viscous than water. Id. at 17 (citing Ex. 1003, 117; Ex. 2208 ¶ 107).
`
`On this record, Petit