`Trials@uspto.gov
`Entered: July 12, 2018
`Tel: 571-272-7822
`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`
`
`
`
`
`
`
`CIPLA LTD.,
`Petitioner,
`v.
`ABRAXIS BIOSCIENCE, LLC,
`Patent Owner.
`
`Case IPR2018-00163
`Patent 7,923,536 B2
`
`
`Before JEFFREY N. FREDMAN, RAMA G. ELLURU, and
`SUSAN L. C. MITCHELL, Administrative Patent Judges.
`
`ELLURU, Administrative Patent Judge.
`
`
`
`
`DECISION
`Request for Rehearing
`37 C.F.R. § 42.71
`
`
`
`Petitioner, Cipla LTD., filed a request for rehearing (Paper 11,
`“Req.”) of the Decision Denying Institution (Paper 10, “Dec.”) of an inter
`partes review of claims 1–16 of U.S. Patent No. 7,923,536 B2 (Ex. 1001,
`“the ’536 patent”). Petitioner seeks rehearing on both of its anticipation and
`obviousness challenges. Req. 1. Specifically, Petitioner contends the
`Decision misapprehended or overlooked that
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`
`(1) the Petition argues anticipation based on what Desai discloses
`to a POSA, and not necessarily inherency (§ II.A.1 below); (2)
`the law does not limit anticipation to ipsis verdis disclosure and
`inherency (§ II.A.2 below); (3) Dr. Berkland’s testimony, which
`the Decision cites as supporting Patent Owner’s position,
`actually refutes it (§ II.A.3 below); (4) Dr. Desai’s letter
`submitted during prosecution of an Indian Patent Application is
`irrelevant and excludable (§ II.A.4 below); and (5) for both
`anticipation and obviousness, the Board misapplied Rule
`42.108(c) by crediting Patent Owner’s declarants over
`Petitioner’s declarant (§§ II.A.5 and II.B.1 below).
`Id. at 1–2. After reviewing Petitioner’s request for rehearing, we find that we
`did not misapprehend or overlook any matter set forth in the Petitioner, and
`therefore, the request for rehearing is denied.
`ANALYSIS
`When rehearing a decision on institution, the Board will review the
`decision for an abuse of discretion. 37 C.F.R. § 42.71(c). The applicable
`standard for a request for rehearing is set forth in 37 C.F.R. § 42.71(d), which
`provides in relevant part:
`A party dissatisfied with a decision may file a request for
`rehearing, without prior authorization from the Board. The
`burden of showing a decision should be modified lies with the
`party challenging the decision. The request must specifically
`identify all matters the party believes the Board misapprehended
`or overlooked, and the place where each matter was previously
`addressed in a motion, an opposition, or a reply.
`
`(A)(1) - Desai Anticipation
`Petitioner asserts that its anticipation challenge is “based on two
`
`premises. First, Example 1 of Desai indisputably teaches the mixing of
`paclitaxel (30 mg) and albumin (270 mg)––literally a 9:1 ratio. Pet. at 27–
`28. Second, a POSA would not expect any change in the final ratio after
`
`2
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`completing the process of Example 1. Id. at 32[.]” Req. 3. Petitioner
`contends that we misapprehended Petitioner’s main argument as one of
`inherency. Id. at 4. In support, Petitioner asserts: “Whether the process of
`Example 1 inherently produces a final 9:1 weight ratio is irrelevant to
`Petitioner’s anticipation argument: Regardless of inherency, a POSA reading
`Example 1 in light of his or her knowledge and experience would understand
`the final ratio to be 9:1. See Pet. at 27–28.” Id.
`
`We find Petitioner’s argument unpersuasive. We interpret the “weight
`ratio” phrase as “the ratio of albumin to paclitaxel in the final composition,
`i.e., the composition injected into the patient.” Dec. 7. Thus, in order for
`Desai to anticipate, it is not sufficient for Desai to simply mix paclitaxel
`and albumin in a particular ratio, but rather Desai must formulate the
`composition into particles as well because a particle formulation is required
`for the final pharmaceutical composition that is injected into patients (see
`’536 patent, Claim 1).
`Example 1 of Desai does show a mixture of 30 mg of paclitaxel to 270
`mg of human serum albumin. See Ex. 1006, 60:25–271. However, that
`mixture is not the final pharmaceutical composition because the mixture is
`then homogenized to form a crude emulsion at low RPM, emulsified in a
`high pressure homogenizer, and subjected to a rotary evaporator in order to
`obtain the particulate form. See Id. at 60:27 to 61:6. Example 4 of Desai
`disclosed a further filtering step to obtain a sterile composition. See Id. at
`63:23–25. Examples 1 and 4 of Desai provide no information regarding the
`
`
`1 Cites to Ex. 1006 refer to original page numbers.
`
`3
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`final paclitaxel/albumin ratio found in the final pharmaceutical compositions
`in particulate form relative to the starting ratio. See Id. at 61:8–12, 64:1–3.
`The Decision, therefore, analyzes the evidence regarding whether the
`initial ratio shown in Example 1 remained within the scope of the claim after
`final formulation into particulate form as required by Claim 1. The Decision
`contrasts Petitioner’s argument, supported by Dr. Berkland’s unsubstantiated
`opinion, that Example 1 of Desai does not result in any paclitaxel loss (see
`e.g., Dec. 13 (citing Ex. 1002 ¶ 106)) with Patent Owner’s experimental
`evidence that paclitaxel was lost during processing such that a starting 9:1
`albumin/paclitaxel ratio resulted in a final 13.3:1 albumin/paclitaxel ratio
`after formulation (see Dec. 19 (citing Ex. 2069 ¶¶ 5, 9)). In essence,
`Petitioner contends that a skilled artisan would have understood that there
`was no paclitaxel loss in the 9:1 albumin/paclitaxel starting ratio of Desai’s
`Example 1 and relies solely on Dr. Berkland’s unsubstantiated opinion for
`that assertion.
`
`Thus, the evidence of record does not support, but instead contradicts
`Petitioner’s assertion that “a POSA would not expect any change in the final
`ratio” after completing the process of Example 1. Req. 6. In fact, the Desai
`Declaration states the “weight ratio of albumin to paclitaxel in the starting
`components was 9:1. . . . Taking into account loss of paclitaxel during the
`nanoparticle preparation process, the estimated albumin/paclitaxel ratio in
`the resulting nanoparticle albumin-bound paclitaxel composition was about
`13.3:1.” Ex. 2069 ¶ 5. The Desai Declaration similarly shows that Example
`16 starts with a 13:1 ratio of albumin/paclitaxel but obtains a final 19:1 ratio
`of albumin/paclitaxel. See id. ¶¶ 9–10.
`
`4
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`To the extent that inherency was at issue, the Decision found
`
`inherency inapplicable because “Dr. Desai’s statements expressly rebut any
`reading of either of Desai’s Examples 1 or 16 as necessarily resulting in a
`final composition with an ‘about 1:1 to about 9:1’ weight ratio of albumin to
`paclitaxel..” Dec. 19.
`
`(A)(2) - Law of Anticipation
`Petitioner asserts the “Board misapprehended the law of express
`anticipation by treating express anticipation as requiring ipsis verbis
`disclosure in the prior art.” Req. 5.
`
`We do not agree that the Decision misapprehended the anticipation
`analysis. See Dec. 8–9. We recognize Petitioner’s point that the prior art
`need not “‘expressly spell out’ all limitations combined as in the claim if a
`POSA would ‘at once envisage’ the arrangement or combination.”
`Microsoft Corp. v. Biscotti, Inc., 878 F.3d 1052, 1069 (Fed. Cir. 2017).
`However, “anticipation is not proven by ‘multiple, distinct teachings that the
`artisan might somehow combine to achieve the claimed invention.’” Id.
`
`In the instant case, under the proper anticipation standard that we
`applied in our decision on institution, Petitioner does not identify a
`disclosure in Desai of a final pharmaceutical formulation of albumin and
`paclitaxel that satisfies the requirements of claim 1 of the ’536 patent
`for a pharmaceutical composition for injection with a 9:1 ratio of
`albumin/paclitaxel and a formulation comprised of particles less than
`200 nm. See Ex. 1001, 37:20–29. There is also no sufficient persuasive
`evidence that the person of ordinary skill would “at once envisage” a final
`
`5
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`pharmaceutical formulation with the 9:1 albumin/paclitaxel ratio solely
`based on a starting ratio of these materials.2
`Indeed, the record includes evidence to the contrary. See Ex. 2001
`¶ 28 (“In my opinion, a POSA would understand and expect that these
`manufacturing steps described in Example 1 of Desai would lead to a
`significant loss of paclitaxel in the final composition obtained from
`practicing the example.”); Ex. 2066 ¶ 46 (“A POSA would not expect the
`starting ratio of albumin-to-paclitaxel to be the same as the final ratio.
`Paclitaxel is a relatively hydrophobic substance with poor water solubility
`that would be preferentially lost during the steps of Example 1.”); Ex. 2069
`¶ 5 (“[M]ore paclitaxel than albumin would be lost during the preparation
`process, which would alter the ratio of the components in the finished
`product.”).
`Thus, the Decision applied the proper anticipation standard and
`correctly found that there is no sufficient persuasive evidence that Desai
`disclosed a final pharmaceutical formulation with a 9:1 albumin/paclitaxel
`ratio either expressly or inherently, nor did Desai provide a disclosure from
`which a person of ordinary skill would “at once envisage” or recognize
`alternative language disclosing a final pharmaceutical formulation with a 9:1
`albumin/paclitaxel ratio.
`
`2 We note that Dr. Berkland interprets the claim to include “the ratio of
`albumin to paclitaxel in the starting ingredients.” Ex. 1002 ¶ 53.
`Dr. Berkland states “the ‘ratio’ in the challenged claims includes at least the
`ratio of the starting ingredients used to make the composition.” Id. ¶ 112.
`These statements regarding starting ingredients do not evidence that a
`person of ordinary skill would envisage a final pharmaceutical ratio with a
`9:1 albumin/paclitaxel ratio consistent with the claim interpretation in the
`Decision. See Dec. 6–8.
`
`6
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`
`(A)(3) - Dr. Berkland’s testimony
`Petitioner argues that we misapprehended Dr. Bekrland’s testimony.
`Req. 6. According to Petitioner, Dr. Berkland’s original declaration
`testimony is clear that a skilled artisan “would have understood Example 1
`to teach a 9:1 final weight ratio of albumin to paclitaxel” and that his
`deposition testimony articulated the same opinion. Id. Petitioner asserts that
`“Berkland’s opinion is simply that given [a starting ratio of 9:1], a POSA
`would expect and understand the final ratio to be 9:1.” Id. at 8. Petitioner
`further argues
`Patent Owner mischaracterized Berkland’s testimony as an
`admission that Example 1 does not teach a final 9:1 ratio. Dec.
`at 16–18. A review of his entire transcript, however, shows there
`was no “gotcha” admission. Berkland stated the trivial facts that
`Example 1 fails to provide measurement data on final ratio; but
`also that a POSA would have understood Example 1 to disclose
`a 9:1 final weight ratio.
`Id. at 10.
`We are not persuaded because the issue is not whether there is a
`“gotcha” admission, but rather, whether Dr. Berkland’s testimony
`sufficiently and reliably supports the evidentiary finding that Desai does not
`disclose a 9:1 albumin/paclitaxel ratio for the final pharmaceutical
`composition. See Dec. 15–16. As discussed in the Decision,
`Dr. Berkland testifies that “the only thing that’s disclosed [in
`Desai] is the starting ingredients.” Ex. 2070, 133:7–14.
`Specifically, with respect to Example 1, Dr. Berkland responded
`to the question “Example 1, it doesn’t tell you what the final ratio
`is, right?” with “[t]hat’s correct.” Id. at 133:14– 17. Dr. Berkland
`further responds to a question “of the ratios you cite in paragraph
`145, 9:1, 9.8:1 and 12.9:1, those are all starting ratios, right?”
`with “[y]es,
`that’s my recollection.” Id. at 195:16–19.
`Dr. Berkland also could not confirm that the 97% recovery rate
`
`7
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`
`disclosed in Desai’s Example 4 was based on the entire
`manufacturing process, from start through filtration, as opposed
`to, for example, based on only the process immediately before
`filtration to immediately after filtration. Id. at 174:24–178:1.
`That is, Dr. Berkland acknowledged that Example 4 does not
`necessarily demonstrate 97% recovery of the complete Example
`1 production process. See id.
`Dec. 16.
`Therefore, we remain persuaded that the reasonable interpretation of
`Dr. Berkland’s testimony does not demonstrate a final pharmaceutical
`formulation with a 9:1 albumin/paclitaxel ratio. Rather, Dr. Berkland’s
`testimony is ambiguous as to whether a final pharmaceutical formulation
`containing about 1:1 to about 9:1 ratio of albumin to paclitaxel in Example 1
`of Desai inherently results from, or would have been reasonably envisaged
`based on, performance of the manufacturing process disclosed in Desai with
`the disclosed starting ratio for albumin to paclitaxel. See Dec. 17–18.
`(A)(4) - Dr. Desai’s letter
`Petitioner argues that we misapprehended Dr. Desai’s statements in
`his letter submitted in an Indian proceeding. Req. 10. Petitioner asserts
`Desai’s statement
`does not address the critical question for Petitioner’s anticipation
`argument: Would a POSA have understood the disputed ratio
`limitation to be disclosed by Example 1 when read in the light of
`a POSA’s knowledge and experience? Desai is not giving an
`opinion as to what a POSA would understand, and therefore, his
`statement is immaterial.
`Id. at 10–11. Petitioner further asserts “Desai’s unsubstantiated and self-
`serving guestimate as to the final ratio without personal knowledge is
`excludable.” Id. at 11. According to Petitioner, the “Desai Letter is neither
`
`8
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`a witnessed affidavit nor sworn declaration. 37 C.F.R. §§ 1.68, 42.2, 42.63.
`The letter is technically excludable because it does not indicate that he was
`‘warned that willful false statements and the like are punishable by fine or
`imprisonment. . . .’ 37 C.F.R. § 1.68.” Id.
`We are not persuaded because Dr. Desai does address the critical
`question of whether the starting ratio of albumin/paclitaxel changes to a
`different albumin/paclitaxel ratio in the final pharmaceutical product. See
`Dec. 19–20. Dr. Desai states that “I provide information about the
`nanoparticle albumin-bound paclitaxel products we developed and disclosed
`in the above referenced patent application and in WO00/71079.” Ex. 2069
`¶ 4. As noted in the Decision, Dr. Desai specifically addresses the question
`of whether the starting and final ratios would be the same, showing that in
`their experiments, there was a change from a starting 9:1 albumin/paclitaxel
`ratio to a final 13.3:1 albumin/paclitaxel ratio. See id. ¶ 5. Dr. Desai also
`shows in another example that “the 13:1 starting ratio was indeed what we
`had used when manufacturing the nanoparticle albumin bound paclitaxel
`formulation” but that based on a Certificate of Analysis, the “amount of
`albumin in the finished product was 644 mg/vial. This makes the
`albumin/paclitaxel ratio in the finished product to be about 19:1.” Id. at ¶¶
`9–10. Thus, Dr. Desai provides experimental evidence showing that a
`starting ratio of 13:1 albumin/paclitaxel changed, after manufacturing, to a
`final pharmaceutical ratio of 19:1 albumin/paclitaxel. This evidence is not a
`“guesstimate,” but rather based on specific data regarding the starting
`materials and based on a Certificate of Analysis of the final materials. See
`id. ¶¶ 9–10.
`
`9
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`
`We also do not find persuasive Petitioner’s assertion that Dr. Desai’s
`statement3 is excludable for lacking a statement under 18 U.S.C. § 1001
`because 37 CFR 42.62(a) states “the Federal Rules of Evidence shall apply
`to [an inter partes review] proceeding” and Rule 603 states “a witness must
`give an oath or affirmation to testify truthfully.” Fed. R. Ev. 603. Dr. Desai
`makes such a statement. See Ex. 2069, 5 (“Verified at Los Angeles on the
`9th day of April, 2014 that the contents of paragraphs 1 to 12 of my affidavit
`are true to the best of my knowledge and belief and nothing material or
`relevant has been concealed therefrom.”).
`(A)(5) and (B)(1) - Rule 42.108(c)
`We next turn to Petitioner’s argument that the “Board overlooked
`Rule 42.108(c) in this case. In particular, the Board viewed Dr. Desai’s
`unsworn statements more favorably than Dr. Berkland’s testimony.” Req.
`12, cf. Req 13 (“The Board again overlooked Rule 42.108(c) when it
`credited Patent Owner’s declarants over Petitioner’s declarant.”).
`Under § 42.108(c), when a patent owner submits testimonial evidence
`with a preliminary response, the Board views any “genuine issue of material
`fact created by such testimonial evidence” “in the light most favorable to the
`petitioner solely for purposes of deciding whether to institute an inter partes
`review.” 37 C.F.R. § 42.108(c).
`
`
`3 We note that Dr. Desai’s statement was not generated to provide support
`for any proceeding before the USPTO, and therefore, was not written
`necessarily in compliance with USPTO rules. Also, because Dr. Desai has
`provided evidence based on personal knowledge as already noted above, the
`affirmation required must be consistent with that required by the Federal
`Rules of Evidence.
`
`10
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`
`Petitioner asserts:
`The only new evidence relied upon by the Board in its Decision
`on Ground I against Cipla was Patent Owner’s submission of the
`Desai Letter and Dr. Berkland’s testimony. In reaching the exact
`opposite conclusion for Cipla’s Petition, the Board viewed
`testimonial evidence in light most favorable to the Patent
`Owner––the opposite of Rule 42.108(c).
`Req. 12. Similarly on the obviousness ground, Petitioner asserts: “The only
`new portion of the record was Patent Owner’s addition of new testimonial
`evidence, including Oupicky, Vellturo, Desai, and Tkaczuk––in addition to
`its original expert, Peppas. It should not matter if Patent Owner hired twenty
`declarants.” Id. at 13. Petitioner is essentially asserting that because the
`preliminary record included conflicting opinion testimonies, the Board was
`obligated to institute trial to resolve the conflict. See id.
`Petitioner’s analysis does not account for the words “genuine” and
`“material” in the terms of Rule 42.108(c). In addition, Rule 42.108(c) does
`not undercut the statutory mandate that precludes trial institution where, as
`here, the information presented in a petition, when viewed in light of
`information presented in a preliminary response, fails to make out the
`threshold showing for review. See 35 U.S.C. § 314(a) (authorizing review
`only upon a showing of “a reasonable likelihood that the petitioner would
`prevail with respect to at least 1” challenged claim). Taken to its natural
`end, Petitioner’s view of the rule would compel the Board to institute trial
`whenever a preliminary record includes declarations that reflect differing
`opinions—which is, of course, an untenable result.
`In the obviousness analysis, the “genuine issue of material fact” is
`whether the prior art teachings provide reason to reduce albumin amounts in
`Desai’s Example 1 starting materials in order to obtain a final composition
`
`11
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`falling within the scope of Claim 1 of the ’536. We address this issue in the
`Decision. See Dec. 28–31. As noted above, reviewing these facts by
`looking “in the light most favorable to the petitioner” does not undercut the
`statutory mandate that precludes trial institution where, as here, the
`information presented in a petition when viewed in light of information
`presented in a preliminary response fails to make out the threshold showing
`for review. See 35 U.S.C. § 314 (a) (authorizing review only upon a
`showing of “a reasonable likelihood that the petitioner would prevail with
`respect to at least 1” challenged claim).
`Our review of the evidence in the Decision, based on a review looking
`in the light most favorable to Petitioner, did not support a finding that the
`prior art rendered at least one of the challenged claims obvious. In
`particular, we noted
`Dr. Berkland’s testimony is conclusory and not supported by
`factual rationale.
` Moreover, Desai
`itself acknowledges
`paclitaxel loss during the manufacturing process of Example 1
`because the final 13.3:1 albumin to paclitaxel ratio of Capxol,
`which Desai teaches is the result of Example 1 (Ex. 1006, 36:16–
`19, 28–29; Ex. 2066 ¶ 49) is different from the starting 9:1 ratio
`of Example 1 (Ex. 1002 ¶ 98). In addition, Patent Owner has
`provided evidence that there is paclitaxel loss, as discussed
`above. See, e.g., 2069 ¶ 5.
`Dec. 21. We concluded based on the evidence that “we do not find a
`genuinely disputed material fact.” Id. Similarly, we do not find a genuinely
`disputed material fact regarding the absence of any disclosure in Kadima for
`albumin/paclitaxel weight ratios below 39:1 or Liversidge’s disclosure of
`crystalline rather than nanoparticle amorphous active agent. See Dec. 34–
`37. We recognize that Dr. Berkland generally states the ordinary artisan
`would have “been motivated to reduce the ratio of albumin to paclitaxel in
`
`12
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`Capxol in order to reduce costs of production.” Ex. 1002 ¶ 155. However,
`this statement is not inconsistent with Dr. Vellturo’s finding that the cost
`reduction motivation would have been balanced by the ordinary artisan
`against the costs of reformulation, supporting our conclusion that this does
`not provide motivation to reduce the albumin/paclitaxel ratio. See Dec. 34–
`35. Indeed, we conclude that this evidence, even when considered in the
`light most favorable to Petitioner, fails to satisfy the threshold of “a
`reasonable likelihood that the petitioner would prevail with respect to at least
`1” challenged claim.
`
`Summary
`As noted in the Decision (Dec. 2), the standard for instituting an inter
`partes review is set forth in 35 U.S.C. § 314(a), which provides:
`THRESHOLD – The Director may not authorize an inter partes
`review to be instituted unless the Director determines that the
`information presented in the petition filed under section 311 and
`any response filed under section 313 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.
`
`As also noted in the decision on institution, we have considered both
`the Petition and Patent Owner Preliminary Response, and determine that the
`information presented in the Petition fails to demonstrate a reasonable
`likelihood that Petitioner would prevail with respect to the challenged
`claims. Dec. 2–3. Therefore, we applied the correct threshold standard for
`instituting the inter partes review.
`As such, Petitioner has not shown that we misapprehended or
`overlooked any matters in instituting inter partes review. See 37 C.F.R.
`
`13
`
`
`
`IPR2018-00163
`Patent 7,923,536 B2
`
`§ 42.71(d). Thus, for the forgoing reasons, Petitioner has not shown that the
`Board abused its discretion in declining to institute this inter partes review.
`
`CONCLUSION
`Petitioner’s request for rehearing is denied.
`
`
`PETITIONER:
`Michael J. Freno
`Jason A. Engel
`Peter L. Giunta
`K&L GATES LLP
`michael.freno@klgates.com
`jason.engel.ptab@klgates.com
`peter.giunta@klgates.com
`
`PATENT OWNER:
`J. Patrick Elsevier
`Anthony M. Insogna
`Cary Miller
`Christopher J. Harnett
`Lisa Marie LoGiudice
`JONES DAY
`jpelsevier@jonesday.com
`aminsogna@jonesday.com
`cmiller@jonesday.com
`llogiudice@jonesday.com
`charnett@jonesday.com
`
`F. Dominic Cerrito
`Andrew S. Chalson
`Daniel C. Wiesner
`Frank C. Calvosa
`QUINN EMANUEL URQUHART & SULLIVAN
`nickcerrito@quinnemanuel.com
`andrewchalson@quinnemanuel.com
`danielwiesner@quinnemanuel.com
`frankcalvosa@quinnemanuel.com
`
`
`14
`
`