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 2231371450
`www.uspto.gov
`
`15/917,742
`
`03/11/2018
`
`Lloyd Johnston
`
`S 1681.70093US01
`
`6109
`
`Selecta B10Sc1ences, Inc.
`c/o Wolf, Greenfield, & Sacks, P.C.
`600 Atlantic Avenue
`Boston MA 02210-2206
`
`PAGUIO FRISING' MICHELLEF
`
`1651
`
`PAPERNUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`03/02/2021
`
`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):
`
`Patents_eOfficeAction @ WolfGreenfield.com
`S 1681_eOfficeAction @ WolfGreenfield. com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`0/7709 A0170” Summary
`
`Application No.
`15/917,742
`Examiner
`MICHELLE F PAGUIO FRISING
`
`Applicant(s)
`Johnston, Lloyd
`Art Unit
`AIA (FITF) Status
`1651
`Yes
`
`- The MAILING DA TE of this communication appears on the cover sheet wit/7 the correspondence address -
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLY IS SET TO EXPIRE g 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.
`|f 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 RCE filed 12/10/2020.
`III A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
`
`2a)D This action is FINAL.
`
`2b)
`
`This action is non-final.
`
`3)[:] 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)[:J 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 Expade Quay/e, 1935 CD. 11, 453 O.G. 213.
`
`Disposition of Claims*
`
`5)
`
`Claim(s)
`
`1—13,15 and 18—19 is/are pending in the application.
`
`5a) Of the above claim(s)
`
`is/are withdrawn from consideration.
`
`
`
`CI Claim(s) _ is/are allowed.
`
`Claim(s) 1—13,15 and 18—19 is/are rejected.
`
`Claim(s) l is/are objected to.
`
`) ) ) )
`
`)
`are subject to restriction and/or election requirement
`[:1 Claim(s
`* 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://www.jjgptgng/patents/init_event§/pph/index.'sp or send an inquiry to PPeredhack@gsptg.ggv.
`
`Application Papers
`
`10)D The specification is objected to by the Examiner.
`
`is/are: a)[:| accepted or b)D objected to by the Examiner.
`11):] The drawing(s) filed on
`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):] Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d) or (f).
`Certified copies:
`
`a)I:I All
`
`b)C] Some**
`
`c)C] None of the:
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`11:] Certified copies of the priority documents have been received.
`
`213 Certified copies of the priority documents have been received in Application No.
`
`SD Copies of the certified copies of the priority documents have been received in this National Stage
`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)
`
`Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mai| Date 12/11/2020; 12/11/2020_
`U.S. Patent and Trademark Office
`
`3) E] Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`4) CI Other-
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mai| Date 20210222
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 2
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`DETAILED ACTION
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`Notice of Pre-AIA or AIA Status
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`The present application, filed on or after March 16, 2013, is being examined
`
`under the first inventor to file provisions of the AIA.
`
`Continued Examination Under 37 CFR 1. 1 14
`
`A request for continued examination under 37 CFR 1.114, including the fee set
`
`forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this
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`application is eligible for continued examination under 37 CFR 1.114, and the fee set
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`forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action
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`has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on
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`12/10/2020 has been entered.
`
`Amendments
`
`Claim 1 has been amended to specify that the synthetic nanocarriers comprise
`
`“poly(D.L lactide) (PLA) and poly(D,L lactide) poly (ethylene glycol) (PLA-PEG)”, the
`
`immunosuppressant is “a rapalog”, and the uricase is “pegylated”. Consequently, claims
`
`2, 11-13, 15, and 18 have also been amended. Claims 14, 16-17, and 50 have been
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`canceled.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 3
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`Election/Restrictions
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`With the cancelation of claim 50 (Invention ll), claims 1-13, 15, and 18-19 remain
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`pending and have been examined on the merits.
`
`Power of Attorney
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`A Power of Attorney still has not yet been submitted.
`
`Information Disclosure Statement
`
`The two information disclosure statements (lDSs) filed on 12/11/2020 are in
`
`compliance with the provisions of 37 C.F.R. 1.97. All cited references have been fully
`
`considered.
`
`Claim Objections
`
`Claim 1
`
`is objected to because of the following informalities: (i) the period in the
`
`term “poly(D.L lactide)” should have been a comma; (ii) a hyphen is missing between
`
`“D.L” and “Iactide” in the term “po|y(D,L lactide)”; (iii) a hyphen is missing between “D,L”
`
`and “Iactide” as well as before the second “poly” in the term “poly(D,L lactide) poly
`
`(ethylene glycol)”; and (iv) there should be no space before the parenthesis in “poly
`
`(ethylene glycol)”.
`
`To obviate these objections, the new limitation in lines 3-4 should be amended as
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`“poly(D,L-lactide) (PLA) and poly(D,L-lactide)-poly(ethylene glycol) (PLA-PEG)”.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 4
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`Claim Rejections - 35 USC § 103
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`In the event the determination of the status of the application as subject to AIA 35
`
`U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any
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`correction of the statutory basis for the rejection will not be considered a new ground of
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`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
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`the same under either status.
`
`The following is a quotation of 35 U.S.C. 103 which forms the basis for all
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`obviousness rejections set forth in this Office action:
`
`A patent for a claimed invention may not be obtained, notwithstanding that the claimed
`invention is not identically disclosed as set forth in section 102, if the differences between
`the claimed invention and the prior art are such that the claimed invention as a whole
`would have been obvious before the effective filing date of the claimed invention to a
`person having ordinary skill in the art to which the claimed invention pertains.
`Patentability shall not be negated by the manner in which the invention was made.
`
`RE: Rejection of claims 1-19 under 35 us. C. 103 as being unpatentable over
`
`Kishimoto et al. in View of Reinders et al.
`
`Applicant traverses the rejections because they allegedly stem from an improper
`
`application of hindsight reasoning and do not establish why the compositions of
`
`Reinders et al. would have been used with those of Kishimoto et al.. Applicant points
`
`out that the medical strategy by Reinders et al. is “merely conjecture” as said prior art
`
`does not show that administering an anti-inflammatory therapeutic would reliably reduce
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`or eliminate infusion reactions (IR) and gout flares. The observed results during months
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`1-3 and months 4-6 supposedly indicate unpredictability of the combination treatment. It
`
`is asserted that the inventors of the present application were the ones who determined
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`that the claimed method surprisingly resulted in better efficacy and gout flare reduction.
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`In addition, Applicant argues that Reinders etal. only teaches administering pegylated
`
`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 5
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`uricase with either an anti-inflammatory treatment or an anti-immunological treatment,
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`and not both. Lastly, there is supposedly no reason for a person with ordinary skill in the
`
`art to particularly utilize synthetic carriers comprising PLA, PLA-PEG, and rapalog.
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`All arguments have been fully considered but are found unpersuasive. The office
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`action is not based on improper hindsight reasoning as only what was known in the art
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`before the effective filing date of the claimed invention is taken into consideration when
`
`determining obviousness. It is also respectfully submitted that the rejections of record
`
`do establish why it would be obvious to combine the teachings of Kishimoto et al. and
`
`Reinders et al..
`
`Kishimoto et al. discloses a method comprising co-administering SVP-rapamycin
`
`with a pegylated uricase. Even though the disclosed method does not include
`
`administering an anti-inflammatory therapeutic, Reinders etal. acknowledges the need
`
`to minimize unwanted side effects caused by antihyperuricemic treatment. To prevent
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`gout and IR, Reinders etal. teaches using colchicine or nonsteroidal anti-inflammatory
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`drugs (NSAIDs), as well as fexofenadine, paracetamol, and hydrocortisone,
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`respectively, prior to administration of pegylated uricase. Thus, Reinders etal. provides
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`the motivation to administer anti-inflammatory therapeutics when utilizing
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`antihyperuricemic treatment like pegylated uricase.
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`As pointed out in the last office action, it is known in the art that gout flares occur
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`during antihyperuricemic treatment because of urate mobilization caused by rapid urate
`
`metabolism. This explains why the experimental results of Reinders et al. show gout
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`flare initially increased during the first three months of the treatment. But eventually, it
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`decreased during subsequent months for patients pretreated with anti-inflammatory
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 6
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`drugs and then treated with pegloticase every 2 weeks and those treated every 4 weeks
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`(Table 3, page 547). Reinders etal. states that consultation with the FDA led to the
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`determination that the distribution of severe adverse events is not unusual because it
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`occurred in patients predisposed to such events and there was unequal randomization
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`in the clinical trials (last par. in right column, page 547).
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`In addition, the differences in the observed number of gout flares between the
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`patient groups can be attributed to the different administration regimen of pegylated
`
`uricase and not to the anti-inflammatory drugs themselves (which were presumably
`
`given in the same amount among the various patients groups). It should also be noted
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`that in both groups of pegloticase-treated patients, gout flares decreased as the
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`treatment continued from months 1-3 (77% & 81%) to months 4-6 (41% & 57%) unlike
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`the placebo group which exhibited increased gout flares (from 54% on months 1-3 to
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`67% on months 4-6). More importantly, more patients in both pegloticase-treated
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`groups reached the target serum urate concentration of <6 mg/dL and showed tophus
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`dissolution compared to the placebo group. Overall, Reinders et al.’s data show the
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`effectiveness of treating gout using pegylated uricase with anti-inflammatory drugs as
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`gout and IR prophylaxis. Reinders et al. concludes that “a strategy on prevention of
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`immunologic responses is warranted, eg, by prescribing anti-inflammatory regimen”
`
`(first par. in right column, page 548). Thus while long term data was missing before the
`
`effective filing date of the claimed invention, it does not negate the fact that Reinders et
`
`al. provides a reason to modify Kishimoto et al.’s method by also administering an anti-
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`inflammatory therapeutic to the subject.
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 7
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`Reinders et al.’s statement that “an anti-immunologic or anti-inflammatory
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`strategy is needed to prevent antipegloticase antibody formation” (Summary, page 548)
`
`does not necessarily mean these two strategies cannot be combined together. Based
`
`on the teachings of the cited prior art, a person with ordinary skill in the art would have
`
`recognized that using both strategies along with antihyperuricemic treatment would
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`address the problems of gout in multiple fronts: an anti-immunologic agent like
`
`rapamycin would inhibit the formation of antibodies; anti-inflammatory agents would
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`minimize the occurrence of gout flares and IR; and an antihyperuricemic treatment such
`
`as pegylated uricase would reduce serum concentration of urate.
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`Indeed, Kishimoto etal. demonstrates that administering SVP-rapamycin in
`
`combination with pegylated uricase not only reduces serum uric acid levels below target
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`threshold but also inhibits antibody response (Figure 5, page 896). Since Reinders etal.
`
`teaches that IR is associated with the presence of antibody response (first par. in right
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`column, page 546), the absence of antibodies is expected to lower the risk for IR.
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`It can
`
`also be predicted by one with ordinary skill in the art that administering anti-
`
`inflammatory agents would help prevent gout flares. In other words, the claimed
`
`method’s greater efficacy (relative to treatment using pegloticase alone) and lower gout
`
`flares is predictable, contrary to Applicant’s assertion.
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`With regards to the composition of synthetic nanocarriers, it should be noted that
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`Kishimoto etal.’s rapamycin-carrying nanoparticles comprises PLA and PLA-PEG,
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`thereby satisfying the new limitation.
`
`Hence, the claimed invention is obvious over Kishimoto etal. and Reinders etal..
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`To properly address all amendments, the rejections of record have been modified.
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 8
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`Modified rejections
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`Claims 1-9, 11-13, 15, and 18-19 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Kishimoto et al. (Nature Nanotechnology 2016, Vol. 11, pages
`
`890-899) in view of Reinders et al. (Therapeutics and Clinical Risk Management
`
`2010, Vol. 6, pages 543-550).
`
`According to Kishimoto et al., one common cause for failure of biotherapeutic
`
`treatments and adverse hypersensitivity reactions is the development of antidrug
`
`antibodies or ADAs (Abstract, page 890). Not only do ADAs neutralize or alter the
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`pharmacokinetics and biodistribution of biologic drugs, they can also cause
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`hypersensitivity reactions, crossreact with endogenous proteins, or deprive patients of
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`life-sustaining therapies. For example, pegylated uricase enzyme known as Pegloticase
`
`helps treat refractory gout by metabolizing uric acid but it induces ADAs in about 90% of
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`subjects which leads to loss of efficacy and anaphylactic reactions. Prevention of ADA
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`formation in an antigen-specific manner is therefore desirable in order to lessen late
`
`stage clinical failure of biologics (Introduction, left column, page 890).
`
`Previously, nanoparticles carrying rapamycin and an antigen were found to be
`
`effective in inducing durable antigen-specific immunological tolerance in vivo. Kishimoto
`
`et al. then shows that synthetic vaccine particles carrying only rapamycin (SVP-
`
`rapamycin) can be co-administered with any free antigen to induce immunological
`
`tolerance. The tolerogenic dendritic cells and antigen-specific regulatory T cells induced
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`in vivo inhibits the activation of antigen-specific CD4+ T cells and B cells in rodents and
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`non-human primates (Introduction, right column, page 890; Figure 1, page 891).
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 9
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`Kishimoto et al. discloses a method comprising co-administering SVP-rapamycin
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`with a pegylated uricase called pegsiticase in uricase-deficient mice having elevated
`
`levels of serum uric acid. The SVP-rapamycin comprises PLA, PLA-PEG, and
`
`rapamycin (Figure 1A, page 891).
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`While pegsiticase alone did not reduce uric acid levels when administered as
`
`repeated injections indicating development of an anti-uricase lgG response, SVP-
`
`rapamycin + pegsiticase inhibited ADA response thus allowing maintenance of low
`
`serum uric acid levels. Similar results were obtained with cynomolgus monkeys (left
`
`column, page 895; Figure 5, page 896). Kishimoto etal. concludes that biologic
`
`therapies with tolerogenic nanoparticles offer a promising approach to minimize ADA
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`formation that is associated with adverse hypersensitivity reactions and loss of efficacy.
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`Use of SVP-rapamycin with pegylated uricase is being tested in human subjects with
`
`hyperuricemia (Conclusion, left column, page 898).
`
`The method of Kishimoto et al. is similar to the instant application’s method as
`
`explained below:
`
`Regarding claim 1: co-administering SVP-rapamycin, which is a synthetic
`
`nanocarrier comprising the immunosuppressant rapamycin, and pegiticase (a pegylated
`
`uricase also known as pegadricase) to a subject such as a mouse, monkey, or human is
`
`equivalent to “concomitantly administering to a subject in need thereof 1) a composition
`
`comprising synthetic nanocarriers... and 2) a composition comprising a pegylated
`
`uricase”.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 10
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`The SVP-rapamycin being composed of PLA and PLA-PEG meets the
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`requirement that the synthetic nanocarriers comprise “poly(D.L lactide) (PLA) and
`
`poly(D,L lactide) poly (ethylene glycol) (PLA-PEG)”.
`
`The rapamycin in SVP-rapamycin satisfies the stipulation that the synthetic
`
`nanocarriers also comprise “a rapalog”. Applicant defines the term “rapalog” as referring
`
`to “rapamycin and molecules that are structurally related to (an analog) of rapamycin
`”
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`(sirolimus)
`
`(4th par., page 14 of Specification).
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`Kishimoto et al. is different from the claimed method in that it does not entail
`
`concomitantly “administering 3) a composition comprising an anti-inflammatory
`
`therapeutic” with the first two recited compositions.
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`Nonetheless, Reinders et al. states that patients receiving pegylated uricase
`
`treatments experience infusion reactions (IR) and gout flares. To address this problem
`
`glucocorticosteroids can be used to prevent antibody formation that result in IR and
`
`prevent gout flares (Abstract, page 543). Reinders et al. teaches using colchicine or
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`nonsteroidal anti-inflammatory drugs (NSAIDs) as gout prophylaxis, as well as
`
`fexofenadine, paracetamol, and hydrocortisone as IR prophylaxis before infusion with
`
`pegylated uricase (last par. in right column, page 546). Results demonstrate that
`
`incidence and frequency of gout flare significantly decreased during month 4-6 in
`
`subjects treated every 2 weeks of pegylated uricase (first par. in left column, page 547).
`
`A person with ordinary skill in the art before the effective filing date of the claimed
`
`invention would have been motivated by Reinders et al.’s teachings to pretreat subjects
`
`in Kishimoto etal.’s method with colchicine/NSAID and fexofenadine, paracetamol, and
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`hydrocortisone. It can be expected that these pre-treatments would advantageously
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 11
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`minimize gout flares and IR. The obviousness of the instant claim is based on some
`
`teaching, suggestion, or motivation in the prior art that would have led one of ordinary
`
`skill to modify the prior art reference or to combine prior art reference teachings to arrive
`
`at the claimed invention. See MPEP § 2143.01 and KSR International Co. v. Teleflex
`
`Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
`
`Hence, claim 1
`
`is obvious over Kishimoto etal. in view of Reinders etal..
`
`Regarding claims 2-3 and 11: Reinders et al.’s teaching that the anti-
`
`inflammatory drugs are administered before infusion of pegylated uricase fulfills
`
`“wherein the composition comprising an anti-inflammatory therapeutic is administered
`
`prior to the composition comprising synthetic nanocarriers comprising a rapalog and the
`
`composition comprising a pegylated uricase” and “is administered at least once prior”.
`
`Regarding claims 4 and 12-13: Although the prior art does not teach exactly
`
`when the anti-inflammatory drugs are administered nor administering them at least
`
`twice beforehand, a person with ordinary skill in the art would have determined the
`
`appropriate dosing regimen for each particular anti-inflammatory drug used through
`
`routine experimentation and optimization.
`
`Regarding claims 5-6: colchicine and NSAle being utilized in the modified
`
`method as anti-inflammatory drugs to prevent gout satisfy “wherein the anti-
`
`inflammatory therapeutic is a nonsteroidal anti-inflammatory drug (NSAID)” and
`
`“wherein the anti-inflammatory therapeutic is colchicine or ibuprofen”.
`
`Regarding claims 7-9: the modified method’s fexofenadine, paracetamol, and
`
`hydrocortisone being employed as anti-inflammatory drugs to prevent IR is analogous to
`
`“administering to the subject one or more compositions comprising an infusion reaction
`
`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 12
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`therapeutic”, which is further limited to “an antihistamine and/or a corticosteroid” such as
`
`“fexofenadine”.
`
`Regarding claim 15: pegiticase, also known as pegadricase, corresponds to
`
`“wherein the pegylated uricase is pegadricase or pegloticase”.
`
`Regarding claim 18: the rapamycin in SVP-rapamycin is identical to “wherein the
`
`rapalog is rapamycin”.
`
`Regarding claim 19: the embodiment of the subject being a human meets
`
`“wherein the subject is human”.
`
`Claims 1-13, 15, and 18-19 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Kishimoto et al. (Nature Nanotechnology 2016, Vol. 11, pages
`
`890-899) in view of Reinders et al. (Therapeutics and Clinical Risk Management
`
`2010, Vol. 6, pages 543-550) and Czock et al. (Clinical Pharmacokinetics 2005, Vol.
`
`44, pages 61-70).
`
`The teachings of Kishimoto et al. and Reinders et al. are set forth above and
`
`applied herein. Kishimoto etal. and Reinders etal. are found to render claims 1-9, 11-
`
`13, 15, and 18—19 obvious.
`
`The modified method is comparable to the following claim:
`
`Regarding claim 10: the corticosteroid of claim 8 is further limited to
`
`“methylprednisolone, prednisone or dexamethasone”
`
`Reinders et al. teaches that glucocorticosteroids (also referred to as
`
`corticosteroids) provide protection from inflammation when used with antihyperuricemic
`
`therapy (second par. in left column, page 545). Reinders etal. differs from the instant
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 13
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`claim in that it only teaches hydrocortisone as an example of applicable
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`glucocorticosteroid (last par. in right column, page 546).
`
`Nevertheless, it is known in the art that methylprednisolone, prednisone, or
`
`dexamethasone are also glucocorticoseroids as substantiated by Czock et al.. Czock et
`
`al. states that glucorticosteroids are frequently used in clinical practice for various
`
`indications such as inflammatory diseases (Abstract, first par., page 63). The most
`
`commonly used systematic glucocorticosteroids are hydrocortisone, prednisolone,
`
`methylprednisolone, and dexamethasone as they have good oral bioavailability and are
`
`mainly eliminated by hepatic metabolism and renal excretion (Abstract, first par., page
`
`62; Table 1, page 64). Since prednisolone, methylprednisolone, and dexamethasone
`
`are recognized as glucocorticosteroids like hydrocortisone, it would have been obvious
`
`for a person with ordinary skill in the art before the effective filing date of the claimed
`
`invention to replace the hydrocortisone in the modified method with methylprednisolone,
`
`prednisone, or dexamethasone, and expect that such substitution would still result in
`
`reducing or suppressing IR during gout treatment. Substitution of one known element
`
`for another known element, both elements having equivalent effect, is considered to be
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`obvious, absent a showing that the result of the substitution yields more than
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`predictable results. See MPEP § 2143 and KSR International Co. v. Teleflex Inc. 550
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`US 398, 82 USPQ2d 1385 (2007).
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`Claim 10 is therefore obvious over Kishimoto etal. in view of Reinders etal. and
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`Czock et al..
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 14
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`Double Parenting
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`The nonstatutory double patenting rejection is based on a judicially created
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`doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the
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`unjustified or improper timewise extension of the “right to exclude” granted by a patent
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`and to prevent possible harassment by multiple assignees. A nonstatutory double
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`patenting rejection is appropriate where the conflicting claims are not identical, but at
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`least one examined application claim is not patentably distinct from the reference
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`claim(s) because the examined application claim is either anticipated by, or would have
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`been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46
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`USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed.
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`Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum,
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`686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619
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`(CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
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`A timely filed terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321 (d)
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`may be used to overcome an actual or provisional rejection based on nonstatutory
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`double patenting provided the reference application or patent either is shown to be
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`commonly owned with the examined application, or claims an invention made as a
`
`result of activities undertaken within the scope of a joint research agreement. See
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`MPEP § 717.02 for applications subject to examination under the first inventor to file
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`provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) -
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`706.02(l)(3) for applications not subject to examination under the first inventor to file
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`provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR
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`1.321 (b).
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 15
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`The USPTO Internet website contains terminal disclaimer forms which may be
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`used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application
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`in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26,
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`PTO/AlA/25, or PTO/AlA/26) should be used. A web-based eTerminal Disclaimer may
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`be filled out completely online using web-screens. An eTerminal Disclaimer that meets
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`all requirements is auto-processed and approved immediately upon submission. For
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`more information about eTerminal Disclaimers, refer to
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`www.uspto.gov/patents/process/file/efs/guidance/eTD-info-l.jsp.
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`RE: Nonstatutory double patenting rejections
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`The rejections are requested to be deferred until allowable subject matter has
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`beenidenfified.
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`But in light of the claim amendments, the double patenting rejections on some
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`co-pending applications have been withdrawn and new ones are set forth.
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`Modified rejections
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`Claims 1-13, 15, and 18-19 are provisionally rejected on the ground of
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`nonstatutory double patenting as being unpatentable over claims 2, 8, 14, 17, 31,
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`40, 48, 55, 58, 116-134, and 136-137 of co-pending Application No. 15/456520 in
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`view of Reinders et aI. (Therapeutics and Clinical Risk Management 2010, Vol. 6,
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`pages 543-550).
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`The co-pending application is drawn to a method of reducing gout flare
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`comprising concomitantly administering to a subject identified as having had or as being
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 16
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`expected to have gout flare the following: (i) a composition containing rapamycin and
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`synthetic nanocarriers made of PLA and PLA-PEG; (ii) and a composition comprising
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`pegylated urate oxidase. Although the co-pending application’s method does not also
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`involve administering an anti-inflammatory therapeutic, Reinders et al. teaches that
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`pretreatments with glucocorticosteroids would help prevent gout flares and IR. Thus, it
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`would have been obvious for one with ordinary skill in the art before the effective filing
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`date of the claimed invention to include an additional step of administering colchicine or
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`nonsteroidal anti-inflammatory drugs (NSAIDs) as gout prophylaxis, as well as
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`fexofenadine, paracetamol, and hydrocortisone as IR prophylaxis. Obviousness is
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`established by combining or modifying the teachings of the prior art to produce the
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`claimed invention where there is some teaching, suggestion, or motivation to do so.
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`This is a provisional nonstatutory double patenting rejection.
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`Claims 1-13, 15, and 18-19 are provisionally rejected on the ground of
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`nonstatutory double patenting as being unpatentable over claims 97 and 113 of
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`co-pending Application No. 16/893153 and over claims 3-4 of co-pending
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`Application No. 17/092148; each one in view of Reinders et al. (Therapeutics and
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`Clinical Risk Management 2010, Vol. 6, pages 543-550).
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`Co-pending application 16/893153 discloses a method comprising concomitantly
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`administering to a subject having an anti-uricase antibody level below a threshold (i) a
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`composition comprising polymeric synthetic nanocarriers comprising PLA, PLA-PEG,
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`and rapamycin and (ii) a composition comprising uricase. In an embodiment, the uricase
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`is defined as pegsiticase (a pegylated uricase). Similarly, co-pending application
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 17
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`17/092148 teaches a method comprising concomitantly administering to a subject (i) a
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`composition comprising polymeric synthetic nanocarriers comprising PLA, PLA-PEG,
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`and rapamycin and (ii) a composition comprising uricase which is specified as
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`pegsiticase in an embodiment.
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`The co-pending applications are different in that the disclosed methods do not
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`entail administering an anti-inflammatory therapeutic. However, Reinders etal. shows
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`that glucocorticosteroid pretreatment aids in preventing gout flares and IR. A person
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`with ordinary skill in the art before the effective filing date of the claimed invention would
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`have modified the co-pending application by also administering colchicine or NSAle
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`with reasonable expectation that these substances would beneficially minimize or
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`prevent gout. Combining or modifying the teachings of the prior art to produce the
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`claimed invention where there is some teaching, suggestion, or motivation to do so is
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`the rationale supporting obviousness.
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`These are provisional nonstatutory double patenting rejections.
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`No claim is allowed.
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`Conclusion
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`Any inquiry concerning this communication or earlier communications from the
`
`examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone
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`number is (571)272-6224. The examiner can normally be reached on Monday-Friday,
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`8:00 am. - 5:00 pm.
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 18
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`Examiner interviews are available via telephone, in-person, and video
`
`conferencing using a USPTO supplied web-based collaboration tool. To schedule an
`
`interview, applicant is encouraged to use the USPTO Automated Interview Request
`
`(AIR) at http://www.uspto.gov/interviewpractice.
`
`If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
`
`supervisor, Renee Claytor can be reached on (571 )272—8394. The fax phone number
`
`for the organization where this application or proceeding is assigned is 571-273-8300.
`
`Information regarding the status of an application may be obtained from the
`
`Patent Application Information Retrieval (PAIR) system. Status information for published
`
`applications may be obtained from either Private PAIR or Public PAIR. Status
`
`information for unpublished applications is available through Private PAIR only. For
`
`more infor