UNITED STATES pATENT AND TRADEMARK OFFICE
`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`www .uspto.gov
`
`APPLICATION NO.
`
`FILING DATE
`
`FIRST NAMED INVENTOR
`
`ATTORNEY DOCKET NO.
`
`CONFIRMATION NO.
`
`14/575,566
`
`12/18/2014
`
`Suni1GUPTA
`
`FR2009/121 US CNT2
`
`3758
`
`06/09/2016
`
`7590
`5487
`ANDREA Q. RYAN
`SANOFI
`55 Corporate Drive
`MAllo CODE: 55A-505A
`BRIDGEWATER, NJ 08807
`
`EXAMINER
`
`ANDERSON, JAMES D
`
`ART UNIT
`
`PAPER NUMBER
`
`1629
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`06/09/2016
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address(es):
`andrea. ryan@ sanofi.com
`eFlow@frasappmossll2.pharma.aventis.com
`GlobalPatent.eFlow@ Sanofi.com
`
`PTOL-90A (Rev. 04/07)
`
`MYLAN - EXHIBIT 1040
`
`

`
`Application No.
`14/575,566
`
`Applicant(s)
`GUPTA, SUNIL
`
`Office Action Summary
`
`AlA (First Inventor to File)
`Status
`No
`-- The MAILING DATE of this communication appears on the cover sheet with the correspondence address -(cid:173)
`Period for Reply
`
`Examiner
`JAMES D. ANDERSON
`
`Art Unit
`1629
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE ;2 MONTHS FROM THE MAILING DATE OF
`THIS COMMUNICATION.
`Extensions of time may be available under the provisions of 37 CFR 1.136(a). In no event, however, may a reply be timely filed
`after SIX (6) MONTHS from the mailing date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHS from the mailing date of this communication.
`Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133).
`Any reply received by the Office later than three months after the mailing date of this communication, even if timely filed, may reduce any
`earned patent term adjustment. See 37 CFR 1.704(b).
`
`Status
`1 )~ Responsive to communication(s) filed on 51312016.
`0 A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on __ .
`2a)~ This action is FINAL.
`2b)0 This action is non-final.
`3)0 An election was made by the applicant in response to a restriction requirement set forth during the interview on
`__ ;the restriction requirement and election have been incorporated into this action.
`4)0 Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Ex parte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`Disposition of Claims*
`5)~ Claim(s) 1.6.9. 17.19.24 and 34-40 is/are pending in the application.
`5a) Of the above claim(s) __ is/are withdrawn from consideration.
`6)0 Claim(s) __ is/are allowed.
`7)~ Claim(s) 1.6.9. 17.19.24 and 34-40 is/are rejected.
`8)0 Claim(s) __ is/are objected to.
`9)0 Claim(s) __ are subject to restriction and/or election requirement.
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
`participating intellectual property office for the corresponding application. For more information, please see
`http:ilvvww.uspto.gov!patents/init events/pph/index.jsp or send an inquiry to PPHfeedback(wuspto.oov.
`
`Application Papers
`1 0)0 The specification is objected to by the Examiner.
`11 )0 The drawing(s) filed on __ is/are: a)O accepted or b)O objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12)0 Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`a)O All b)O Some** c)O None of the:
`Certified copies of the priority documents have been received.
`1.0
`Certified copies of the priority documents have been received in Application No. __ .
`2.0
`Copies of the certified copies of the priority documents have been received in this National Stage
`3.0
`application from the International Bureau (PCT Rule 17.2(a)).
`** See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment{s)
`1) 0 Notice of References Cited (PT0-892)
`
`2) ~ Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date 5/3/2016 and 5/20/2016.
`
`3) 0 Interview Summary (PT0-413)
`Paper No(s)/Mail Date. __ .
`4) 0 Other: __ .
`
`U.S. Patent and Trademark Off1ce
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20160519
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 2
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`The present application is being examined under the pre-AlA first to invent
`
`prOVlSlOnS.
`
`DETAILED ACTION
`
`Formal Matters
`
`Applicants' response, filed 5/3/2016, is acknowledged and entered.
`
`No claims have been amended, cancelled, or added.
`
`Claims 1, 6, 9, 17, 19, 24, and 34-40 are pending and under examination
`
`pursuant with the latest claim set filed 8/3112015.
`
`Response to Arguments
`
`Applicants' arguments, filed 5/3/2016, have been fully considered but they are
`
`not deemed to be persuasive. Rejections and/or objections not reiterated from
`
`previous office actions are hereby withdrawn. The following rejections and/or
`
`objections are either reiterated or newly applied. They constitute the complete set
`
`presently being applied to the instant application.
`
`Information Disclosure Statement
`
`Receipt is acknowledged of the Information Disclosure Statements filed
`
`5/3/2016 and 5/20/2016. The Examiner has considered the references cited therein
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 3
`
`to the extent that each is a proper citation. Please see the attached USPTO Form
`
`1449.
`
`Declaration under Rule 1.132
`
`The Examiner acknowledges receipt of the Rule 1.132 Declaration of Dr.
`
`Alton Oliver Sartor ("Sartor" Declaration) and has carefully considered the
`
`information provided therein. The Examiner's response to the Sartor Declaration is
`
`set forth below in response to Applicants' arguments pertaining to the 35 U.S. C. 103
`
`rejection.
`
`The Examiner also notes Applicants' citation of the Mylan Petition of Inter
`
`Partes Review of U.S. Patent No. 8,927,592, which includes a Declaration of Dr.
`
`Rahul Seth. As the Seth Declaration is directly applicable to the instant claims and
`
`refutes points raised in the Sartor Declaration, the Sartor Declaration will be
`
`considered in light of the Seth Declaration, particularly those matters that are a
`
`matter of opinion and not fact, e.g., predictability of the art and reasonable
`
`expectation of success.
`
`Claim Rejections- 35 USC§ 103
`
`The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all
`
`obviousness rejections set forth in this Office action:
`
`(a) A patent may not be obtained though the invention is not identically disclosed or
`described as set forth in section 102 of this title, if the differences between the subject
`matter sought to be patented and the prior art are such that the subject matter as a
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 4
`
`whole would have been obvious at the time the invention was made to a person
`having ordinary skill in the art to which said subject matter pertains. Patentability
`shall not be negatived by the manner in which the invention was made.
`
`This application currently names
`
`joint
`
`inventors.
`
`In considering
`
`patentability of the claims under 35 U.S. C. 103(a), the examiner presumes that the
`
`subject matter of the various claims was commonly owned at the time any
`
`inventions covered therein were made absent any evidence to the contrary.
`
`Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor
`
`and invention dates of each claim that was not commonly owned at the time a later
`
`invention was made in order for the examiner to consider the applicability of 35
`
`U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35
`
`U.S.C. 103(a).
`
`Claims 1, 9, 17, 19, 24, and 34-40 remain rejected under 35 U.S.C. 103(a) as
`
`being unpatentable over BOUCHARD ET AL. (USP No. 5,847,170; Issued Dec. 8,
`
`1998) and PIVOT ET AL. (Annals of Oncology, September 2008, vol. 19, pages
`
`1547-1552) in view of BEARDSLEY ET AL. (Curr. Opin. In Supportive and
`
`Palliative Care, September 2008, vol. 2, pages 161-166), RODRIGUES ET AL.
`
`(The Canadian J. of Urology, December 2007, vol. 14, no. 6, pages 3779-3786),
`
`MITA ET AL. (Clin. Cancer Res., 2009, vol. 15, no. 2, pages 723-730) (Published
`
`Online January 15, 2009), NATIONAL HORIZON SCANNING CENTRE
`
`("NHSC") (University of Birmingham, April 2009, pages 1-6), and BERTHOLD
`
`ET AL. (J. Clin. Oncol., January 2008, vol. 26, no. 2, pages 242-245).
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Claimed Invention
`
`Page 5
`
`The instant claims recite methods for treating a patient with castration
`
`resistant or hormone refractory, metastatic prostate cancer that has progressed
`
`during or after treatment with docetaxel, comprising administering to said patient a
`
`dose of 20 to 25 mg/m2 of cabazitaxel, or a hydrate or solvate thereof, as a one- hour
`
`infusion, in combination with 10 mg/day of prednisone or prednisolone, wherein the
`
`administration of cabazitaxel, or hydrate or solvate thereof, is repeated as a new
`
`cycle every 3 weeks.
`
`Teachings ofBOUCHARD ETAL.
`
`Bouchard et al. disclose new taxoids of formula (I):
`
`in which Z represents a radical of formula (II):
`
`~0
`
`O.H
`
`that display "noteworthy antitumour and antileukemic properties. See Abstract;
`
`col. 1, line 7 to col. 4, line 33.
`
`Bouchard et al. disclose cabazitaxel, and specifically claim cabazitaxel m
`
`independent claim 1. See Claim 1.
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 6
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`Bouchard et al. disclose that the new products have antitumor properties,
`
`and more especially activity against tumours which are resistant to
`
`Taxol® (paclitaxel) or to Taxotere® (docetaxel). See col. 11, lines 49-51.
`
`Bouchard et al. disclose that the new products of general formula (I) in which
`
`Z represents a radical of general formula (II) manifest significant inhibitory activity
`
`with respect to abnormal cell proliferation, and possess therapeutic properties
`
`permitting the treatment of patients having pathological conditions associated with
`
`abnormal cell proliferation including, inter alia, cancer of the prostate. See col. 26,
`
`lines 33-51.
`
`Bouchard et al. disclose that the therapeutic treatment may be performed
`
`concurrently with other therapeutic treatments including, inter alia, hormones and
`
`antagonists such as adrenocorticosteroids such as prednisone. See col. 27, line 37 to
`
`col. 28, line 3.
`
`Bouchard et al. disclose general dose ranges for administering products
`
`according to the invention. With regard to intravenous administration in man,
`
`Bouchard et al. disclose for intravenous administration, the doses generally range
`
`from 0.1 to 50 mg/kg, preferably from 0.1 to 5 mg/kg and still more specifically from
`
`1 to 2 mg/kg.l See col. 28, lines 5-41.
`
`1 For an average human male weighing about 80 kg and having a body surface area of
`about 2.0 m 2 , the dose ranges taught in Bouchard et al. are about 4 to 2000 mg/m2 ,
`preferably 4 to 200 mg/m 2 , and more specifically 40 to 80 mg/m2 .
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 7
`
`Bouchard et al. differ from the instant claims in that they do not specifically
`
`combine the various teachings disclosed therein in the manner claimed by
`
`Applicants, i.e., treating castration resistant or hormone refractory metastatic
`
`prostate cancer that has progressed during or after treatment with docetaxel
`
`comprising administration of 20 to 25 mg/m2 of cabazitaxel as a 1-hour infusion in
`
`combination with prednisone and repeating the cycle every 3 weeks.
`
`Teachings of PIVOT ET AL.
`
`Pivot et al. disclose a Phase II study of XRP6258 (cabazitaxel) in taxane-
`
`resistant metastatic breast cancer patients. See Title; Abstract.
`
`Regarding a dose of 20 to 25 mg/m2 cabazitaxel administered as a one-hour
`
`infusion every 3 weeks as recited in Claims 1, 9, 24, 35, 37, and 38, Pivot et al. teach
`
`that XRP6258 was administered as a 1-hour intravenous (i.v.) infusion on
`
`day 1 every 3 weeks at 20 mg/m2 (then, in the absence of severe toxicity, at
`
`25 mg/m2 from cycle 2). See Abstract; page 1548, right column, "treatment
`
`assignment and schedule".
`
`Pivot et al. disclose that XRP6258 appears to be active m docetaxel- or
`
`paclitaxel-resistant breast cancer, even when the most stringent criterion of
`
`resistance (PD on therapy) was used. The ORR was 14% (95% CI 7% to 24%) in the
`
`treated population. In addition, 18 patients (25%) had SD lasting for >3 months
`
`(range 3.4-14.6 months). Long-lasting SD may be an indicator of activity, especially
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 8
`
`in heavily pretreated patients, who did not respond or had responses of short
`
`duration to the previous line of chemotherapy. The 14% ORR reported is
`
`comparable to that described by Dieras et al. for larotaxel in a similar population.
`
`See page 1551, left column, "Discussion".
`
`Pivot et al. thus teach that the administration of cabazitaxel in base form in
`
`amounts of 20 and 25 mg/m2 as a 1-hour intravenous infusion every three
`
`weeks was safe and effective in treating docetaxel-resistant metastatic
`
`breast cancer.
`
`Pivot et al. differ from the instant claims in that they do not disclose treating
`
`castration resistant or hormone refractory, metastatic prostate cancer that has
`
`progressed during or after treatment with docetaxel and do not disclose combining
`
`cabazitaxel with prednisone.
`
`Teachings of BEARDSLEY ET AL.
`
`Beardsley et al. disclose that there is an urgent need for systemic treatment
`
`options for patients with castration-resistant prostate cancer who have
`
`progressed after receiving first-line docetaxel therapy. Beardsley et al.
`
`disclose that the purpose of this article is to review recent developments in this
`
`area. See page 161, "Purpose of review".
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 9
`
`Beardsley et al. disclose that XRP2658 2 (Sanofi-Aventis, Paris, France) is a
`
`semi-synthetic taxoid compound with low affinity for the P-glycoprotein drug efflux
`
`transporter and cytotoxic in cell lines with acquired resistance to paclitaxel
`
`or docetaxel. A phase II study of XRP6258 was conducted in patients with
`
`docetaxel refractory metastatic breast cancer and an objective response rate of 14%
`
`was observed. Two patients achieving a complete response with a median response
`
`duration of 7.6 months. See page 163, right column, fourth paragraph.
`
`Beardsley et al. disclose that a phase II trial with XRP6258 has not been
`
`performed in patients with CRPC; however, given its activity in the docetaxel
`
`refractory setting described above, this agent is currently being investigated in
`
`a phase III multi- center, randomized superiority trial comparing 3-weekly
`
`XRP6258 with prednisone to mitoxantrone with prednisone in patients with
`
`castrate resistant metastatic prostate cancer previously treated with
`
`docetaxel-containing treatment. The aim is to recruit 720 patients with a
`
`projected completion date of May 2010. See page 163, right column, fifth paragraph.
`
`Beardsley et al. thus expressly suggest treating patients with castration-
`
`resistant prostate cancer that has progressed after treatment with docetaxel
`
`comprising administration of cabazitaxel and prednisone on a 3-weekly cycle.
`
`Beardsley et al. differ from the claims only in that they do not disclose the
`
`dosing regimen of cabazitaxel and prednisone.
`
`2 Cabazitaxel as recited in the instant claims is also known in the art as XRP2658.
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Teachings ofRODRIGUES ET AL.
`
`Page 10
`
`Rodrigues et al. disclose specifics of the phase III multi -center study
`
`comparing 3-weekly XRP6258 with prednisone to mitoxantrone with prednisone in
`
`patients with castrate resistant metastatic prostate cancer previously treated with
`
`docetaxel-containing treatment disclosed in Beardsley.
`
`In this regard, Rodrigues et al. disclose a randomized, open-label multicentre
`
`study of XRP-6258 at 25 mg/m2 in combination with prednisone every 3
`
`weeks compared to mitoxantrone in combination with prednisone for the
`
`treatment of hormone-refractory metastatic prostate cancer previously
`
`treated with a taxotere-containing regimen. Rodrigues et al. teach that the
`
`study is a randomized Phase III study with a sample size of n = 720. See page 3784.
`
`Rodrigues et al. differ from Claims 1 and 24 only in that they do not disclose
`
`that the 25 mg/m2 cabazitaxel is administered as a 1 hour infusion and the
`
`prednisone is administered at a dose of 10 mg!day.
`
`Teachings of MITA ET AL.
`
`Mita et al. disclose a Phase I and pharmacokinetic study of cabazitaxel
`
`(XRP6258), administered as a 1-hour intravenous infusion every 3 weeks in
`
`patients with advanced solid tumors. See Abstract.
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 11
`
`Mita et al. disclose that cabazitaxel (XRP6258) has shown broad spectrum
`
`antitumor activity in mice bearing s.c. implanted human xenografts, including Du-
`
`145 prostate cancers. See page 724, left column, first full paragraph.
`
`Mita et al. disclose that the encouraging spectrum of antitumor activity of
`
`XRP6258 in experimental tumor models, particularly its notable activity
`
`against docetaxel-resistant, Pgp-expressing malignancies, served as a
`
`rationale to clinical evaluations. See page 724, left column, second full paragraph.
`
`Regarding the administration regime recited in Claims 1 and 24, Mita et al.
`
`disclose that XRP6258 was administered as a 1-hour i.v. infusion every 3 weeks
`
`at a starting dose of 10 mg/m2, with subsequent incremental increases to
`
`15, 20, and 25 mg/m2 dose levels. See page 724, right column, "Drug
`
`administration" and "Dose escalation".
`
`Regarding claims 17, 19, and 39-40, Mita et al. disclose monitoring blood
`
`neutrophil counts, i.e., absolute neutrophil counts (ADC), and that at the highest
`
`dose level (25 mg/m2), the ADC was 1,500 cells/mm3 (990) and at that dose level
`
`there were cases of Grade 3 and Grade 4 neutropenia. Mita et al. disclose that the
`
`rate of dose limiting toxicity (DLT) exceeded the predefined limits of tolerability at
`
`the 25 mg/m2 dose level. See Table 3; page 726, left column, second full paragraph.
`
`Regarding anticancer activity, Mita et al. disclose that evidence of anticancer
`
`activity was observed in a patient with prostate cancer metastatic to liver and bones
`
`whose disease had progressed through surgical castration, bicalutamide, diethyl
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 12
`
`stilbestrol, and mitoxantrone and prednisone. Further evidence of anticancer
`
`activity was observed in a patient with hormone- and docetaxel-refractorv
`
`prostate cancer metastatic to bone and iliac lymph nodes. See page 727, left
`
`column, "Anticancer activity"
`
`Mita et al. thus teaches the administration of cabazitaxel in amounts of 20
`
`and 25 mg/m2 as a 1-hour intravenous infusion every three weeks to treat docetaxel-
`
`refractory metastatic castration-resistant prostate cancer.
`
`Teachings of NHSC
`
`NHSC describes the specifics of the Phase III clinical trial of cabazitaxel
`
`(XRP-6258) discussed in Beardsley et al. and Rodriguez et al. supra.
`
`(:~llmzitR,.;:d.(.XU.l}'~6258) for honn<.me refnu~tOQ't mct.1cstatk
`rn·osl~lf:{~ cancer- second Hne after d.ocetaxei
`
`NHSC discloses that the Target Group is hormone refractory prostate cancer
`
`(HRPC): metastatic - second line; after docetaxel-based treatment. See page 2,
`
`"Target group".
`
`T<lrogd Jlr:Oup
`~
`ll(g'tnon:(~ refh:~ct<wy pro:s.t~~h.':: C(tnt.~r {Ilt~.?(:):
`d<l>X~tm;d-b~~ ... ~~r tw<~tm~mt.
`
`NHSC discloses that cabazitaxel in combination with prednisone is intended
`
`to provide a further treatment option for patients with progressive disease following
`
`or during docetaxel-based
`
`treatment.
`
`Cabazitaxel
`
`is administered by
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 13
`
`intravenous (IV) infusion at 25 mg/m2 every 3 weeks. See page 2, "Technology
`
`description"; page 3, "Efficacy and safety".
`
`:;:::.%.t~sc~ fnhibit{~Jr~ ~~f c:t~H dtvis5nn ~H~.d :;.;t~:H
`(}:;:;~d). (~~~n?.it~"X:~~?~ ~~;;. t~.s)~nb9~~~E:s)~3 ~~,·~i:tl
`P..f~~hti.&:;"!:~t~~- ~s ~-nt:~ndl~ t:~] prt)'c/id~: .a ftMth~:r ·tn:!' .. ~tHH~nt ~YptE~)~s ·n:~r- .p;sii\:~~l~.~ '~+th pr(."g~·~:\~l~~t::
`d~&~~~~st.~ f~:Jk~\~~i~ltt -.>r {h._nin;~ d:::.~~-<~J~~~d-.-ba:red tr:e~t!r:~nt. r:~~hB:.:.>:~t~~x~~ jt;;- ad~nin3$t~s·e)1 by
`-::;; -l~~~"i"'<:.-1:.-s_
`~,--i;~-~~::,.->;-:.'~~,~-,.ls~ {j"\}\ .... ;-.~ ... i;;.l.:-·i 1·wl >:(~._.")>-~*-~~=•r/J··o:.,? ....... ~.·~,, .. ..,_.-
`J l.l.L~~ .. ·h-'"1
`~ -~---,.~.{_, • ._,,.,::;:)~ .• ·~~~> ,_:.
`.... vf-~;~ ... -
`:..-")'-.... ')} .,,
`
`·~~..: .... ,,~···"-'=':S':~ .~}
`
`'l-
`
`NHSC thus teaches the administration of cabazitaxel m an amount of 25
`
`mg/m2 m combination with prednisone every three weeks as an intravenous
`
`infusion during or following docetaxel therapy to treat metastatic hormone
`
`refractory prostate cancer as presently claimed.
`
`NHSC differs from instant Claims 1 and 24 only m that they do not disclose
`
`the dose of prednisone (10 mg/day).
`
`

`
`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Teachings of BERTHOLD ET AL.
`
`Page 14
`
`Berthold et al. report on the TAX 327 Study, comparmg docetaxel
`
`administered every 3 weeks, weekly docetaxel, and mitoxantrone, each with
`
`prednisone, in 1,006 men with metastatic hormone-resistant prostate cancer. See
`
`Abstract.
`
`Regarding administration of prednisone at a dose of 10 mg/day as recited in
`
`instant Claim 1, Berthold et al. teach that prednisone was administered at a
`
`dose of 5 mg twice daily, i.e., 10 mg/day as presently claimed. See page 242,
`
`right column, first full paragraph.
`
`Principles of Law
`
`"In rejecting claims under 35 U.S.C. § 103, the examiner bears the initial
`
`burden of presenting a prima facie case of obviousness. Only if that burden is met,
`
`does the burden of coming forward with evidence or argument shift to the
`
`applicant." In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993) (citations omitted). In
`
`order to determine whether a prima facie case of obviousness has been established,
`
`we consider the factors set forth in Graham v. John Deere Co., 383 U.S. 1, 17 (1966):
`
`(1) the scope and content of the prior art; (2) the differences between the prior art
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`and the claims at issue; (3) the level of ordinary skill in the relevant art; and ( 4)
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`objective evidence of nonobviousness, if present.
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
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`Page 15
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`"The combination of familiar elements according to known methods is likely
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`to be obvious when it does no more than yield predictable results." KSR Int'l Co. v.
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`Teleflex Inc., 550 U.S. 398, 416 (2007). "In determining whether obviousness is
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`established by combining the teachings of the prior art, 'the test is what the
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`combined teachings of the references would have suggested to those of ordinary skill
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`in the art."" In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995).
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`Examiner's Analysis and Conclusion of Obviousness
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`A claimed invention is unpatentable if the differences between the claimed
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`invention and the prior art are such that the claimed invention as a whole would
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`have been obvious to one of ordinary skill in the relevant art. 35 U.S.C. § 103.
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`Whether a claimed invention would have been obvious is a question of law, based on
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`factual determinations regarding the scope and content of the prior art, differences
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`between the prior art and the claims at issue, the level of ordinary skill in the
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`pertinent art, and any objective indicia of non-obviousness. KSR Int'l Co. v. Teleflex
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`Inc., 550 U.S. 398, 406 (2007); Graham v. John Deere Co. of Kansas City, 383 U.S. 1,
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`17-18 (1966).
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`In KSR, the Supreme Court criticized a rigid approach to determining
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`obviousness based on the disclosures of individual prior-art references, with little
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`recourse to the knowledge, creativity, and common sense that an ordinarily skilled
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`artisan would have brought
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`to bear when considering combinations or
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
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`Page 16
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`modifications. KSR, 550 U.S. at 415-22. Rejecting a blinkered focus on individual
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`documents, the Court required an analysis that reads the prior art in context,
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`taking account of "demands known to the design community," "the background
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`knowledge possessed by a person having ordinary skill in the art," and "the
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`inferences and creative steps that a person of ordinary skill in the art would
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`employ." Id. at 418. This "expansive and flexible approach," id. at 415, is consistent
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`with the Courts' pre-KSR decisions acknowledging that the inquiry "not only
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`permits, but requires, consideration of common knowledge and common sense."
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`DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d
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`1356, 1367 (Fed. Cir. 2006). As KSR established, the knowledge of such an artisan
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`is part of the store of public knowledge that must be consulted when considering
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`whether a claimed invention would have been obvious.
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`In recognizing the role of common knowledge and common sense, the Courts
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`have emphasized the importance of a factual foundation to support a party's claim
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`about what one of ordinary skill in the relevant art would have known. See, e.g.,
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`Mintz v. Dietz & Watson, Inc., 679 F.3d 1372, 1377 (Fed. Cir. 2012); Perfect Web
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`Techs., Inc. v. InfoUSA, Inc., 587 F.3d 1324, 1328 (Fed. Cir. 2009). One form of
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`evidence to provide such a foundation, perhaps the most reliable because not
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`litigation-generated, is documentary evidence consisting of prior art in the area.
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`In the present case, it is well established in the art that cabazitaxel is a novel
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`taxoid anticancer agent expressly taught to be effective in treating docetaxel-
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 17
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`resistant cancers, i.e., cancers that have progressed during or after treatment with
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`docetaxel. See Bouchard et al., Pivot et al., Beardsley et al., Mita et al., and NHSC.
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`The prior art establishes that cabazitaxel is clinically effective when
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`administered to patients having docetaxel-resistant breast or prostate cancer
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`using the same dosing regimen recited in the instant claims. See Pivot et al.,
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`Mita et al., and NHSC.
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`The prior art teaches that cabazitaxel is administered in combination with
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`prednisone. See Beardsley et al., Rodrigues et al., and NHSC.
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`It would have been prima facie obvious to one of ordinary skill in the art at
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`the time the invention was made to combine the teachings of the references so as to
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`administer cabazitaxel in combination with prednisone to treat patients with
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`castration resistant or hormone refractory, metastatic prostate cancer that has
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`progressed during or after treatment with docetaxel as expressly taught by the cited
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`prior art. Indeed, NHSC differs from independent Claims 1 and 24 only in that it
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`does not disclose the dose of prednisone administered. However, a dose of 10
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`mg/day prednisone, administered in combination with a taxane (docetaxel) was
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`known in the art. See Berthold et al. It would have been prima facie obvious to one
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`of ordinary skill in the art to administered prednisone in combination with
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`cabazitaxel in known doses of prednisone already administered in combination with
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`other taxanes for the treatment of cancer.
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
`
`Page 18
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`The indicia of obviousness in the instant case are many and strong, as the
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`prior art teaches all of the limitations of the instant claims. Cabazitaxel was known
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`in the art and taught to be useful in treating cancer, particularly docetaxel-resistant
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`cancer. Clinically effective doses of cabazitaxel were known in the art and are the
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`same doses presently claimed. Taxanes, including cabazitaxel, were known in the
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`art to be administered in combination with prednisone in the dose presently
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`claimed.
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`Applicants disclose in Example 1 a clinical study, which appears to be the
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`same clinical study disclosed in Beardsley et al. and Rodrigues et al., which were
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`published more than 1 year before Applicants' earliest effective filing date.
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`Beardsley et al. disclose that cabazitaxel is currently being investigated in a phase
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`III multi-center, randomized superiority trial comparing 3-weekly XRP6258 with
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`prednisone to mitoxantrone with prednisone in patients with castrate resistant
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`metastatic prostate cancer previously treated with docetaxel-containing treatment.
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`The aim is to recruit 720 patients with a projected completion date of May
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`2010. See page 163, right column, fifth paragraph. Rodrigues et al. likewise
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`disclose a randomized, open-label multicentre study of XRP-6258 at 25 mg/m2 in
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`combination with prednisone every 3 weeks compared to mitoxantrone in
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`combination with prednisone for the treatment of hormone-refractory
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`metastatic prostate cancer previously treated with a taxotere-containing
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`regimen. Rodrigues et al., like Beardsley et al., teach that the study is a
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
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`Page 19
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`randomized Phase III study with a sample size of n = 720. See page 3784.
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`Applicants also disclose that a clinical study was performed wherein patients
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`received either treatment with cabazitaxel or the reference treatment based on
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`mitoxantrone each combined with prednisone or prednisolone in patients over 18
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`years of age with metastatic castration resistant metastatic prostate cancer.
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`Applicants disclose, like Beardsley et al. and Rodrigues et al., that 720 patients
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`were planned to be included in the clinical study: 360 in each cabazitaxel +
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`prednisone and mitoxantrone + prednisone group. See Specification at page 17,
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`Example 1. Thus, more than one year prior to Applicants' invention, Beardsley et
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`al. and Rodrigues et al. disclosed in general terms the same clinical trial used as the
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`basis for the present invention by Applicants.
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`It is unequivocally clear from the teachings of the cited pnor art that
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`Applicants did not invent cabazitaxel (Bouchard et al.), did not invent the claimed
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`dosing regimen of cabazitaxel (see Pivot et al., Mita et al., and NHSC), did not
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`invent combining cabazitaxel with prednisone (see Beardsley et al., Rodrigues et al.,
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`and NHSC), did not discover that cabazitaxel is effective in treating docetaxel-
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`resistant cancers (see Beardsley et al., Pivot et al., and Mita et al.), and did not
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`invent administering cabazitaxel to treat patients with castration resistant or
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`hormone refractory metastatic prostate cancer that has progressed during or after
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`treatment with docetaxel (see Beardsley et al., Rodrigues et al., and NHSC).
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`

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`Application/Control Number: 14/575,566
`Art Unit: 1629
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`Page 20
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`The skilled artisan would have been imbued with more than a reasonable
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`expectation that cabazitaxel, in the dosing regimen presently claimed, administered
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`in combination with 10 mg/day prednisone, would be effective in treating castration
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`resistant or hormone refractory metastatic prostate cancer that has progressed
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`during or after treatment with docetaxel. This is particularly true because the cited
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`prior art teaches that in a Phase II trial, cabazitaxel is clinically effective in
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`treating docetaxel-resistant metastatic breast cancer (Beardsley et al. and
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`Pivot et al.), which led to cabazitaxel being investigated in a phase III multi-center,
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`randomized superiority trial comparing 3-weekly XRP6258 with prednisone to
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`mitoxantrone with prednisone in patients with castrate resistant metastatic
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`prostate cancer previously treated with docetaxel-containing treatment (Beardsley
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`et al., Rodrigues et al., and NHSC). Those skilled in the art would not administer a
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`drug in a Phase III clinical trial if they did