Case IPR2016-01096
`Patent No. 6,667,061
`Resp. POs’ Observations on Cross-Examination of Patrick DeLuca, Ph.D.
`Attorney Docket No. 9LUYE 7.1R-004
`
`
`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.,
`Petitioners,
`
`v.
`
`ALKERMES PHARMA IRELAND LTD and
`ALKERMES CONTROLLED THERAPEUTICS, INC.,
`Patent Owners.
`
`Patent No. 6,667,061 to Ramstack et al.
`Issue Date: December 23, 2003
`Title: PREPARATION OF INJECTABLE
`SUSPENSIONS HAVING IMPROVED INJECTABILITY
`____________________________
`Inter Partes Review No. IPR2016-01096
`__________________________________________________________________
`
`RESPONSE TO PATENT OWNERS’ OBSERVATIONS
`ON CROSS-EXAMINATION OF PATRICK DeLUCA, PH.D.
`
`
`
`
`Mail Stop: Patent Board
`Patent Trial and Appeal Board
`U.S. Patent And Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`Patent No. 6,667,061
`Resp. POs’ Observations on Cross-Examination of Patrick DeLuca, Ph.D.
`Attorney Docket No. 9LUYE 7.1R-004
`
`
`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.,
`Petitioners,
`
`v.
`
`ALKERMES PHARMA IRELAND LTD and
`ALKERMES CONTROLLED THERAPEUTICS, INC.,
`Patent Owners.
`
`Patent No. 6,667,061 to Ramstack et al.
`Issue Date: December 23, 2003
`Title: PREPARATION OF INJECTABLE
`SUSPENSIONS HAVING IMPROVED INJECTABILITY
`____________________________
`Inter Partes Review No. IPR2016-01096
`__________________________________________________________________
`
`RESPONSE TO PATENT OWNERS’ OBSERVATIONS
`ON CROSS-EXAMINATION OF PATRICK DeLUCA, PH.D.
`
`
`
`
`Mail Stop: Patent Board
`Patent Trial and Appeal Board
`U.S. Patent And Trademark Office
`P.O. Box 1450
`Alexandria, VA 22313-1450
`
`
`
`
`
`Case IPR2016-01096 (Patent No. 6,667,061) Attorney Dkt. 9LUYE 7.1R-004
`Resp. POs’ Observations on Cross-Examination of Patrick DeLuca, Ph.D.
`
`Johnson And Gustafsson Inherently Teach The Viscosity Limitation
`I.
`1: The cited testimony is irrelevant, incomplete, and does not confirm that
`
`Petitioners should have accounted for all grades of CMC to prove inherency. The
`
`testimony was given with respect to Example 7 of the Johnson vehicle. DeLuca
`
`testified that although Example 7 did not explicitly state low CMC, Johnson stated
`
`“low . . . 3 percent” CMC for all of the other examples, thus, it “would be unlikely
`
`that he would use a high in one case and low in another.” (Ex.2081, 122:8-19; see
`
`also 119:21-24, 154:17-19, 123:24-124:5.) DeLuca testified that the low CMC in
`
`the Handbook (Ex.1008) “would be more appropriate for parenteral suspensions”
`
`(Ex.2081, 121:16-21), and that a POSA “for a parenteral suspension would have
`
`picked the low grade [CMC]” (id. 195:14-19).
`
`2: The cited testimony is irrelevant, incomplete, and does not contradict
`
`Petitioner’s argument. DeLuca’s testimony only sets forth his understanding as to
`
`what Ex.2073 states on its face. Despite listing “all the different CMCs from
`
`Aqualon” (Ex.2081, 132: 2-9), DeLuca’s testimony is only related to one specific
`
`CMC, “Aqualon CMC 7HF” (id. 135:4-137:4). DeLuca testified that a POSA “for
`
`a parenteral suspension would have picked the low grade [pharmaceutical CMC].”
`
`(Ex.2081, 194:20-195:19.)
`
`
`
`
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`3: The cited testimony is irrelevant, incomplete, and does not “confirm” POs’
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`assertion. DeLuca testified that whether he used high and low grade CMCs in his
`
`study, “may be irrelevant . . . [b]ecause we are not talking about parenteral use.”
`
`(Ex.2081, 130:5-10.) Similarly, with respect to Ex.2031, DeLuca testified that the
`
`work did not involve the injectable suspension of microparticles (Ex.2081,
`
`240:11-241:25) and that matrices were “solid” and “certainly not injectable” (id.
`
`242:2-18). The Tracy Declaration did not consider anything other than the amount
`
`of CMC used by Kino. (Ex.1018.) DeLuca utilized the Tracy Declaration in the
`
`exact same manner as the POs in obtaining the ’061 Patent. (Pet. 17-18; Ex.1002
`
`¶44.)
`
`4: The cited testimony is irrelevant, incomplete, lacks foundation, and does not
`
`contradict Petitioners’ testing criticism. DeLuca’s testimony only sets forth his
`
`understanding as to what Exs.2074-2077 state on their face. DeLuca testified that
`
`the disclosure “may not be accurate.” (Ex.2081, 166:21-167:3.) Exs.2074-2077 are
`
`nonanalogous art. DeLuca testified that ultra low Blanose 7UL® and extra low
`
`Blanose 7EL® are not low viscosity CMCs as taught in the Handbook for low
`
`CMCs (Id. 121:16-21; Ex.1008, 79).
`
`5: The cited testimony is irrelevant, incomplete, and does not contradict
`
`Petitioner’s testing criticism. DeLuca’s testimony only sets forth his understanding
`
`2
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`as to what Exs.2039, 2078, and 2079 state on their face. None of these references is
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`prior art.
`
`6: The cited testimony is irrelevant, incomplete, does not contradict Petitioners’
`
`testing criticism. DeLuca’s testimony only sets forth his understanding as to what
`
`Ex.2038 states on its face. DeLuca testified that ultra low Blanose 7UL® and extra
`
`low Blanose 7EL® are not low viscosity CMCs (Ex.2081, 121:16-21; 1008, 79).
`
`7: The cited testimony is irrelevant, incomplete, lacks foundation, does not
`
`contradict Petitioners’ testing criticism. DeLuca’s testimony only sets forth his
`
`understanding as to what Ex.2076 states on its face. Ultra low Blanose 7UL® is not
`
`a low viscosity CMC. (Ex.2081, 121:16-22; Ex.1008, 79.)
`
`8: The cited testimony is irrelevant, incomplete, and does not “confirm[] the
`
`generic nature of Gustafsson’s disclosure.” DeLuca’s prior testimony explained
`
`that Gustafsson’s vehicle would have a viscosity in the claimed range of the
`
`’061 Patent based on the Tracy Declaration. (Pet. 39; Ex.1002 ¶70.) The Tracy
`
`Declaration did not consider anything other than the amount of CMC used by
`
`Kino. (Ex.1018.)
`
`9: The cited testimony is irrelevant, incomplete, and does not “confirm[] the
`
`generic nature of Johnson’s disclosure.” DeLuca testified that the CMC in
`
`Johnson’s Example 7 is low viscosity CMC. (Ex.2081, 76:9-12, 122:14-19.)
`
`DeLuca’s prior
`
`testimony explained
`
`that Johnson’s vehicle would have
`
`3
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`substantially a viscosity in the claimed range as of the ’061 Patent. (Pet. 25-26;
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`Ex.1002 ¶¶44, 60-61.)
`
`10: The cited testimony is mischaracterized, irrelevant, incomplete, does not
`
`“confirm[] that order of addition of ingredients can impact viscosity,” nor does it
`
`“support[] that Petitioners should have accounted for this factor in proving
`
`inherency.” DeLuca testified that sodium chloride does not impact viscosity in any
`
`significant way when it is used for the isotonic concentration of a preparation.
`
`(Ex.2081, 190:4-9.) DeLuca testified that a POSA would dissolve CMC in the
`
`water and then add the sodium chloride (id. 191:3-192:22, 195:20-196:24) and that
`
`“Dr. Gehrke prepared his solutions using a method that would not be used by a
`
`POSA by adding the CMC after sodium chloride” (id. 191:7-10; see also id.
`
`196:25-197:25). When asked if his concern was “that the order of addition of
`
`sodium chloride could impact viscosity,” he testified that “[He has] no concern
`
`with viscosity.” (Id. 197:14-25.)
`
`11: The cited testimony is irrelevant, incomplete, and does not undermine
`
`Petitioners’ assertion. DeLuca testified that the injection vehicle used in the animal
`
`model could be optimized in the human model. (Ex.2081, 58:15-59:11.) Both
`
`Johnson’s Examples 6 and 7 are administered by subcutaneous injection into
`
`animals. (Id. 77:8-79:7) DeLuca testified that CMC in Johnson’s Example 6 is the
`
`4
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`same
`
`low viscosity CMC as Example 7. (Id. 114:5-15, 116:24-117:12,
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`118:22-119:10.)
`
`12: The cited testimony is irrelevant, incomplete, and does not “confirm[] that the
`
`supplier of CMC can impact viscosity” and it does not support POs’ assertion.
`
`DeLuca testified that even though a CMC could be different depending on a
`
`supplier, the CMC is added for suspendability. (Ex.2081, 154:20-155:2.)
`
`Therefore, “you want to have a sufficient concentration . . . you have to balance the
`
`suspendability property with the . . . viscosity.” (Id. 155:2-12.) In overcoming
`
`Kino, the Tracy Declaration did not consider different suppliers, different viscosity
`
`ranges, or order of addition of ingredients. (Ex.1018.)
`
`13: The cited testimony is irrelevant, incomplete, and does not “confirm[] that
`
`polysorbates can impact viscosity” or that Petitioners should have accounted for
`
`this. DeLuca agreed with the scientific statements, but was never asked, however,
`
`whether these scientific principles would impact the viscosity. DeLuca’s testimony
`
`explained that polysorbates would minimally impact viscosity of an injectable
`
`suspension. (See Ex.1024 ¶68; see also Ex.2059 Tables 1, 2.)
`
`14: The cited testimony is mischaracterized, irrelevant, incomplete, does not
`
`“confirm[] that the method of dissolution and mixing can impact viscosity,” or that
`
`“Petitioners should have accounted for this. There was no need for DeLuca to
`
`5
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`address the “dissolution and mixing” issue since the Tracy Declaration did not
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`consider dissolution or mixing overcoming Kino. (Ex.1018.)
`
`15: The cited testimony is irrelevant, incomplete, and does not “establish[] the
`
`standard DeLuca applied in his inherency analysis.” The testimony relied upon has
`
`nothing to do with the inherency standard that was applied by DeLuca in reaching
`
`his conclusion concerning the Johnson and Gustafsson references. (Ex.2081,
`
`148:19-154:6.) DeLuca’s prior testimony explained that the Johnson and
`
`Gustafsson vehicles would have a viscosity in the same range as claimed in the
`
`’061 Patent based on his reliance on Alkermes’ admission in the Tracy
`
`Declaration. (Pet. 17-18, 39-40; Ex.1002 ¶¶44, 70.)
`
`II. Gustafsson Teaches The Microparticle Of The ’061 Patent
`16: The cited testimony is mischaracterized, irrelevant, incomplete, and does not
`
`contradict Petitioners’ assertions concerning the DeLuca’s testimony concerning
`
`the disclosure in the ’061 Patent is consistent in that it differentiates between
`
`“polymer” and “polymeric binder.” (Exs.2081, 233:17-235:12; 1001, 5:15-18,
`
`14:10-18.) The claim requires a “microparticle comprising a polymeric binder” and
`
`“microparticle” is defined by the ’061 Patent as “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.” (Ex.1001, 5:15-18.) DeLuca testified that it is his
`
`opinion that the polymeric binder does not have to have any sort of function
`
`6
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`(Ex.2081, 229:25-232:5), whereas DeLuca testified that the polymer, in the
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`definition of “microparticle,” functions as a binder or matrix (Ex.2081,
`
`234:15-235:12).
`
`17: The cited testimony is mischaracterized, irrelevant, incomplete, and does not
`
`contradict Petitioners’ assertion regarding the microparticle limitation. DeLuca’s
`
`prior testimony explained that Gustafsson teaches that any active may be used in
`
`its formulation, which includes an injection vehicle that aids in suspension of
`
`microparticles, teaches PLGA is a useful polymeric binder as a coating, and that a
`
`POSA would use Ramstack’s microparticles in Gustafsson’s vehicle (Pet. 39,
`
`45-47; Ex.1002 ¶¶78, 80).
`
`III. A POSA Would Combine The Prior Art
`18: The cited testimony is irrelevant, incomplete, and does not “confirm[] there is
`
`no reason to combine” Gustafsson’s microparticles and Ramstack’s risperidone.
`
`DeLuca testified that based on the prior art, a POSA would know how to choose a
`
`suitable viscosity to balance suspendability and injectability (Ex.2081, 9:11-23,
`
`15:15-16:9, 38:24-39:3, 154:23-155:12) and how to choose a suitable vehicle (id.
`
`41:8-20), and that Gustafsson teaches that any active may be used in its
`
`formulation, which includes an injection vehicle that aids in suspension of
`
`microparticles (Ex.1024 ¶107), and that a POSA could combine Ramstack’s
`
`7
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`risperidone with the microparticles and injectable suspension of Gustafsson with a
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`reasonable expectation of success (Ex.1024 ¶112).
`
`19: The cited testimony lacks foundation, is irrelevant, incomplete, and does not
`
`“contradict[] any motivation to replace or modify Ramstack’s microspheres or
`
`vehicle.” DeLuca
`
`testified
`
`that a POSA would use either Ramstack’s
`
`microparticles in Gustafsson’s vehicle or Ramstack’s risperidone in Gustafsson’s
`
`microparticles and vehicle with a reasonable expectation of success. (Ex.2081,
`
`9:11-23, 15:15-16:9, 38:24-39:3, 41:8-20, 154:23-155:12; Pet. 39, 45-47; Ex.1002
`
`¶¶ 78, 80; Ex.1024 ¶106.)
`
`20: The cited testimony is irrelevant, incomplete, and does not “contradict[]
`
`Petitioners’ assertion that a POSA would be motivated to combine components of
`
`Ramstack with Gustafsson’s injection vehicle.” DeLuca testified that a POSA
`
`would use either Ramstack’s microparticles in Gustafsson’s vehicle or Ramstack’s
`
`risperidone in Gustafsson’s microparticles and vehicle with a reasonable
`
`expectation of success. (Ex.2081, 9:11-23, 15:15-16:9, 38:24-39:3, 41:8-20,
`
`154:23-155:12; Pet. 39, 45-47; Ex.1002 ¶¶ 78, 80; Ex.1024 ¶106.)
`
`21: The cited testimony is irrelevant, incomplete, and does not contradict
`
`Petitioners’ assertions that a POSA would combine components of Ramstack with
`
`Gustafsson’s injection vehicle. DeLuca testified that a POSA would use either
`
`Ramstack’s microparticles in Gustafsson’s vehicle or Ramstack’s risperidone in
`
`8
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`Gustafsson’s microparticles and vehicle with a reasonable expectation of success.
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`(Ex.2081, 9:11-23, 15:15-16:9, 38:24-39:3, 41:8-20, 154:23-155:12; Pet. 39,
`
`45-47; Ex.1002 ¶¶78, 80; Ex.1024 ¶106.)
`
`22: The cited testimony is irrelevant, incomplete, and does not “contradict[]
`
`Petitioners’ assertion that Ramstack and Gustafsson would be combined.” DeLuca
`
`testified that a POSA would use either Ramstack’s microparticles in Gustafsson’s
`
`vehicle or Ramstack’s risperidone in Gustafsson’s microparticles and vehicle with
`
`a reasonable expectation of success. (Ex.2081, 9:11-23, 15:15-16:9, 38:24-39:3,
`
`41:8-20, 154:23-155:12; Pet. 39, 45-47; Ex.1002 ¶¶78, 80; Ex.1024 ¶106.)
`
`23: The cited testimony is mischaracterized, irrelevant, incomplete, and does not
`
`contradict Petitioners’ assertion. DeLuca testified that Gustafsson was “focused on
`
`avoiding the problem that’s created by dispersing this sensitive active in PLG[A]
`
`an organic solvent,” meaning the BSA. (Ex.2081, 221:11-16.) However, DeLuca’s
`
`prior testimony explains that Gustafsson teaches that any active may be used in its
`
`formulation, and that a POSA would use either Ramstack’s microparticles in
`
`Gustafsson’s vehicle or Ramstack’s risperidone in Gustafsson’s microparticles and
`
`vehicle. (Pet. 39, 45-47; Ex.1002 ¶¶78, 80; Ex.1024 ¶106; see also Ex.2081,
`
`9:11-23, 15:15-16:9, 38:24-39:3, 41:8-20, 154:23-155:12.)
`
`24: The cited testimony is mischaracterized, irrelevant, incomplete, and does not
`
`contradict Petitioners’ asserted motivations. DeLuca actually testified that density
`
`9
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`is “not necessary to really worry about” because “formulating a suspension that’s
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`pretty standard microparticle in a vehicle for injection purposes, . . . a POSA would
`
`know from the prior art how to go about that to suspend it so that its injectable.”
`
`(Ex.2081, 41:8-14.) DeLuca also testified that “[t]he importance of the density is
`
`with regard to sedimentation.” (Id. 33:15-17.)
`
`IV. Viscosity Is A Consequence Of Suspendability
`25: The cited testimony is irrelevant, incomplete, and does not contradict
`
`Petitioners’ assertion. DeLuca testified that a POSA’s “job is to make sure that
`
`something can be suspended and injected through the needle . . . into the patient.”
`
`(Ex.2081, 11:19-12:2; see also id. 12:10-16, 9:11-23, 15:15-16:9). DeLuca testified
`
`“[i]f you are formulating a suspension that’s pretty standard microparticle in a
`
`vehicle for injection purposes, then a POSA would know from the prior art how to
`
`go about that to suspend it so that it’s an injectable . . . [which] involve[s] using a
`
`suspending agent and increasing the viscosity to ensure that the particles remain
`
`suspended until they are injected.” (Id. 41:8-20.)
`
`26: The cited testimony is mischaracterized, irrelevant, incomplete, and does not
`
`contradict Petitioners’ assertion, DeLuca actually testified that “you are adding the
`
`CMC . . . not for viscosity, it’s for suspendability . . . you have to balance the
`
`suspendability property with the . . . viscosity.” (Ex.2081, 154:23-12; see also
`
`9:11-23, 15:15-16:9, 38:24-39:3, 154:23-155:12.)
`
`10
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`Dated:
`
`August 8, 2017
`
`
`
`5097739_1.docx
`
`
`
`
`
`Respectfully submitted,
`By:
`s/ Paul H. Kochanski /
`Paul H. Kochanski
`Reg. No. 29,660
`
`
`
`
`
`11
`
`
`
`Case IPR2016-01096 (Pat. 6,667,061)
`Resp. POs’ Observs. on DeLuca Cross
`
`
`Attorney Dkt. 9LUYE 7.1R-004
`
`CERTIFICATE OF SERVICE
`The undersigned hereby certifies that a copy of the foregoing RESPONSE
`
`TO PATENT OWNERS’ OBSERVATIONS ON CROSS-EXAMINATION
`
`OF PATRICK DELUCA, PH.D., was served on August 7, 2017, as follows.
`
`VIA E-MAIL
`
`Scott K. Reed, Esq.
`Fitzpatrick, Cella, Harper & Scinto
`1290 Avenue of the Americas
`New York, NY 10104-3800
`Tel: 212.218.2100
`E-mail:
`sreed@fchs.com
`
`
`Dated:
`
`5097739_1.docx
`
`August 8, 2017
`
`
`
`By:
`
`
`
`
`
`s/ Paul H. Kochanski /
`Paul H. Kochanski
`Reg. No. 29,660
`
`
`12
`
`
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