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`
`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and TrademarkOffice
`Address; COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`
`15/917,742
`
`03/11/2018
`
`Lloyd Johnston
`
`§1681.70093US01
`
`6109
`
`Selecta BioSciences, Inc.
`c/o Wolf, Greenfield, & Sacks, P.C.
`600 Atlantic Avenue
`Boston, MA 02210-2206
`
`PAGUIO FRISING, MICHELLE F
`
`1651
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`10/04/2021
`
`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
`$1681_eOfficeAction @ WolfGreenfield.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`
`
`Disposition of Claims*
`1-2,5-13 and 18-19 is/are pending in the application.
`)
`Claim(s)
`5a) Of the above claim(s) ___ is/are withdrawn from consideration.
`C] Claim(s)__ is/are allowed.
`Claim(s) 1-2,5-13 and 18-19 is/are rejected.
`(1 Claim(s)__is/are objectedto.
`C} Claim(s)
`are subjectto restriction and/or election requirement
`* If any claims have been determined allowable, you maybeeligible 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.uspto.gov/patents/init_events/pph/index.jsp or send an inquiry to PPHfeedback@uspto.gov.
`
`) ) ) )
`
`Application Papers
`10) The specification is objected to by the Examiner.
`11)0) The drawing(s) filedon__ is/are: a)(J accepted or b)() 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)1) Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d)or (f).
`Certified copies:
`c)Z None ofthe:
`b)() Some**
`a)C All
`1.2 Certified copies of the priority documents have been received.
`2.1.) Certified copies of the priority documents have been received in Application No.
`3.1.) Copies of the certified copies of the priority documents have been receivedin 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)/Mail Date 9/01/2021 (2 IDSs).
`U.S. Patent and Trademark Office
`
`3) (J Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`(Qj Other:
`
`4)
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20210928
`
`Application No.
`Applicant(s)
`15/917,742
`Johnston, Lloyd
`
`Office Action Summary Art Unit|AIA (FITF) StatusExaminer
`MICHELLE F PAGUIO FRISING
`1651
`Yes
`
`
`
`-- The MAILING DATEofthis communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLYIS SET TO EXPIRE 3 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available underthe provisions of 37 CFR 1.136(a). In no event, however, may a reply betimely filed after SIX (6) MONTHSfrom 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) MONTHSfrom 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, evenif timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1) Responsive to communication(s) filed on 9/01/2021.
`C} A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/werefiled on
`2a)¥) This action is FINAL.
`2b) (J This action is non-final.
`3)02 An election was madeby the applicant in responseto 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 Exparte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 2
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`DETAILED ACTION
`
`Notice of Pre-AlA or AIA Status
`
`The present application, filed on or after March 16, 2013, is being examined
`
`under the first inventor to file provisions of the AIA.
`
`Amendments
`
`Applicant has amendedclaim 1 to limit the pegylated uricase to “pegadricase’”
`
`and to specify that the composition comprising an anti-inflammatory therapeutic is
`
`administered “at least once at least one week prior’ to the other two compositions.
`
`Claims 2 and 11-13 have also been amended, while claims 3-4 and 15 have been
`
`cancelled. No new matter has been added.
`
`Claims 1-2, 5-13, and 18-19 are pending and have been considered on the
`
`merits.
`
`Powerof Attorney
`
`Applicant is reminded that a Power of Attorney is missing.
`
`Information Disclosure Statement
`
`The information disclosure statements (IDSs) submitted on 9/01/2021 are in
`
`compliance with the provisions of 37 C.F.R. 1.97. Accordingly,all referenceslisted in
`
`these IDSs have been fully considered.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 3
`
`RE: Objection to claims
`
`Claim Objections
`
`The minor informalities in claim 1 have been corrected, thereby obviating claim
`
`objections.
`
`Claim Rejections - 35 USC § 103
`
`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
`
`correction of the statutory basis for the rejection will not be considered a new ground of
`
`rejection if the prior art relied upon, and the rationale supporting the rejection, would be
`
`the same under either status.
`
`The following is a quotation of 35 U.S.C. 103 which forms the basis for all
`
`obviousnessrejections setforth 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 mannerin which the invention was made.
`
`RE: Rejection of claims 1-19 under 35 U.S.C. 103 as being unpatentable over
`
`Kishimotoetal. in view of Reinderset al.
`
`Traversal of rejections is based on “pegadricase’” (also known as pegsiticase)
`
`being different from Reinders ef a/.’s pegloticase. Referring to Garay et al., Applicant
`
`points out that PEGylated uricase derived from Candida utilis has a short half-life of 8
`
`hours whereas pegloticase hasa half-life of 10-20 days. Thus, it is argued that
`
`teachings pertaining to pegloticase would not necessarily extend to pegadricase.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 4
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`Applicant further asserts that the claimed method is unexpectedly found to be
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`significantly better than other therapies (Table 4, page 61 of Specification).
`
`All arguments have been fully considered but are deemed unpersuasive. First,
`
`the PEGylated uricase discussed by Garay et a/. is indeed derived from Candida utilis
`
`like pegadricase. But upon reviewing the source of the information regarding its half-life
`
`(Davis et al., The Lancet 1981, Vol. 318, p. 281-283), it found that the former is
`
`synthesized by covalently attaching 5 kDa PEG to uricase (fourth par. in left column, p.
`
`282). On the other hand, pegadricase has 20 kDa PEG molecules attached to said
`
`enzyme. It is therefore respectfully submitted that the C. utilis PEGylated uricase
`
`described by Garayefal. is not structurally the same as pegadricase and its shorter
`
`PEG groups maybethe reason whythe half-life is only 8 hours.
`
`Second, the prior art rejections are based on Kishimoto eta/. as the primary
`
`reference, which discloses a method comprising co-administering SVP-rapamycin and
`
`pegsiticase to a subject. Pegisticase is another name for pegadricase, hence Kishimoto
`
`et al. meets the new requirement that the pegylated uricase is “pegadricase”. Reinders
`
`et al. was only applied in the rejections as a secondary reference to show the
`
`obviousness of administering an anti-inflammatory agent (/.e., not for its use of
`
`pegloticase). According to Reinders ef a/., anti-inflammatory therapy helps reduce gout
`
`flare that occurs due to urate mobilization induced by urate-lowering agents. So even
`
`though Reinders et a/. describes a study wherein an anti-inflammatory agent like
`
`colchicine or an NSAID was administered to patients receiving pegloticase and not
`
`pegadricase as claimed, a person with ordinary skill in the art would have recognized
`
`that pegadricase also functions as a urate-lowering agent like pegloticase and would
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 5
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`therefore also cause goutflare. Thus regardlessof the specific type of PEGylated
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`uricase being used, it would have been obvious to administer an anti-inflammatory
`
`agentlike colchicine or an NSAID to the subject prior to being administered with SVP-
`
`rapamycin and pegsiticase in Kishimoto et a/.’s method since the latter is expected to
`
`rapidly metabolize urate and trigger gout flare.
`
`Second, Applicant's assertion of unexpected results is not commensurate in
`
`scope with the claims. The data shownin Table 4 is based on: (1) Applicant's
`
`experiments that involve administering colchicine at an initial dose of 1.2 mg one week
`
`prior to infusing subjects monthly with SEL-212 (pegsiticase combined with PLA/PLA-
`
`PEG nanocarriers comprising rapamycin) followed by one daily dose of 0.6 mg
`
`throughout the study (second par., p. 59 of Specification); and (2) Sundy et a/.’s Phase
`
`3 clinicaltrial that includes administering colchicine amounting to 0.6 mg of colchicine
`
`once or twice daily starting one week before infusing subjects biweekly/monthly with
`
`pegloticase (second par., p. 60 of Specification). Given the differences in dosage
`
`regimen of colchicine (ex. Applicant initially administered 1.2 mg of colchicine before
`
`giving a daily colchicine dose of 0.6 mg while Sundyef a/.’s clinical trial did not), it
`
`cannot be established that the reduced number of flares per patient per month is indeed
`
`due to the SVP-rapamycin and/or specific type of PEGylated uricase. And even if the
`
`dosage regimen of colchicine were the same, the claims of the instant application
`
`broadly recite using any anti-inflammatory therapeutic (/.e., not limited to colchicine) at
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`any amount(/.e., not limited to 0.6 mg/day) prior to administering the two other
`
`compositions. There is no evidence demonstrating that other amounts of colchicine, as
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`well as other anti-inflammatory agents, can give the same results. Thus although
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 6
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`subjects treated with SEL-212 experienced less flares per month comparedto those
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`treated with pegloticase, it cannot be determined if the same outcome would be
`
`observedif a lower (or greater) colchicine amount, or if a different anti-inflammatory
`
`agent, is administered prior to infusion with the SEL-212.
`
`The rejections of record are therefore being maintained, but have been modified
`
`to address all amendments including claim cancellations.
`
`Modified rejections
`
`Claims 1-2, 5-9, 11-13, and 18-19 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Kishimoto etal. (Nature Nanotechnology 2016, Vol. 11, pages
`
`890-899) in view of Reinderset al. (Therapeutics and Clinical Risk Management
`
`2010, Vol. 6, pages 543-550) and Sundyetal. (Journal of American Medical
`
`Association 2011, Vol. 306, pages 711-720).
`
`According to Kishimoto et a/., one common causefor failure of biotherapeutic
`
`treatments and adverse hypersensitivity reactions is the development of antidrug
`
`antibodies or ADAs(Abstract, page 890). Not only do ADAsneutralize or alter the
`
`pharmacokinetics and biodistribution of biologic drugs, they can also cause
`
`hypersensitivity reactions, crossreact with endogenous proteins, or deprive patients of
`
`life-sustaining therapies. For example, pegylated uricase enzyme knownas Pegloticase
`
`helps treat refractory gout by metabolizing uric acid but it induces ADAsin about 90%of
`
`subjects which leadsto loss of efficacy and anaphylactic reactions. Prevention of ADA
`
`formation in an antigen-specific manner is therefore desirable in order to lessen late
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`stage clinical failure of biologics (Introduction, left column, page 890).
`
`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 7
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`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
`
`in vivo inhibits the activation of antigen-specific CD4* T cells and B cells in rodents and
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`non-humanprimates (Introduction, right column, page 890; Figure 1, page 891).
`
`Kishimoto et a/. discloses a method comprising co-administering SVP-rapamycin
`
`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).
`
`While pegsiticase alone did not reduce uric acid levels when administered as
`
`repeated injections indicating development of an anti-uricase IgG 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 et a/. concludes that biologic
`
`therapies with tolerogenic nanoparticles offer a promising approach to minimize ADA
`
`formation that is associated with adverse hypersensitivity reactions and lossof efficacy.
`
`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 a/. is similar to the instant application's method as
`
`explained below:
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 8
`
`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 humanis equivalent to “concomitantly administering to a subject in need thereof 1) a
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`composition comprising synthetic nanocarriers... and 2) a composition comprising
`
`pegadricase”.
`
`The SVP-rapamycin being composed of PLA and PLA-PEG meets the
`
`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
`
`(sirolimus)” (4" par., page 14 of Specification).
`
`Kishimoto et al. is different from the claimed method in that it does not entail
`
`“administering 3) a composition comprising an anti-inflammatory therapeutic... at least
`
`onceat least one week prior’ to administering the first two recited compositions.
`
`Nonetheless, Reinders ef¢ al. states that patients receiving pegylated uricase
`
`treatments experience infusion reactions (IR) and gout flares. To address this problem,
`
`Reindersetal. refers to a clinical study by Sundy ef a/. wherein glucocorticosteroids
`
`were used to prevent antibody formation that result in IR and prevent goutflares
`
`(Abstract, page 543). The clinical study involved administering colchicine or
`
`nonsteroidal anti-inflammatory drugs (NSAIDs) as gout prophylaxis once or twice a daily
`
`starting one week before infusion of the pegylated uricase. In addition, it included
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 9
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`administering fexofenadine as IR prophylaxis the night before and immediately before
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`infusion with pegylated uricase, as well as paracetamol and hydrocortisone immediately
`
`before infusion (first par. in right column, page 712). According to Reinders ef al., the
`
`clinical study’s results demonstrate that incidence and frequencyof goutflare
`
`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 ef a/. and Sundyet a/.’s teachings to
`
`pretreat subjects in Kishimoto et al.’s method with colchicine/NSAID onceor twice daily
`
`starting on week before administering SVP-rapamycin and pegsiticase, as well as
`
`fexofenadine, paracetamol, and hydrocortisone the night before and/or immediately
`
`before said administration. It can be expected that these pre-treatments would
`
`advantageously minimize gout flares and IR. The obviousnessof 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 ef a/. in view of Reinders et a/. and
`
`Sundyefal.
`
`Regarding claim 2: Sundy ef a/.’s teaching that the colchicine or NSAIDsis
`
`administered once or twice daily starting one week prior to infusion of pegylated uricase
`
`fulfills “wherein the composition comprising an anti-inflammatory therapeutic is
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 10
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`administered prior to the composition comprising synthetic nanocarriers comprising a
`
`rapalog and the composition comprising pegadricase”.
`
`Regarding claims 5-6: colchicine and NSAIDsbeing 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 to prevent IR is analogous to “administering to the
`
`subject one or more compositions comprising an infusion reaction therapeutic”, which is
`
`further limited to “an antihistamine and/or a corticosteroid” (claim 8) such as
`
`“fexofenadine” (claim 9).
`
`Regarding claim 11: the modified method comprising administering colchicine or
`
`NSAIDs once or twice daily starting one week before infusion of correspondsto
`
`“wherein the composition comprising an anti-inflammatory therapeutic is administered
`
`prior to the composition comprising synthetic nanocarriers comprising a rapalog and the
`
`composition comprising pegadricase’”.
`
`Regarding claims 12-13: administering fexofenadine the night before and
`
`immediately before infusion meets “the one or more compositions comprising an
`
`infusion reaction therapeutic is/are administered at least once prior to the composition
`
`comprising synthetic nanocarriers comprising a rapalog and the composition comprising
`
`pegadricase’” (claim 12) and “...administered at least twice prior...” (claim 13).
`
`Regarding claim 18: the rapamycin in SVP-rapamycin is identical to “wherein the
`
`rapalog is rapamycin’.
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 11
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`Regarding claim 19: the embodiment of the subject being a human meets
`
`“wherein the subject is human’.
`
`Claims 1-2, 5-13, and 18-19 are rejected under 35 U.S.C. 103 as being
`
`unpatentable over Kishimoto etal. (Nature Nanotechnology 2016, Vol. 11, pages
`
`890-899) in view of Reinderset al. (Therapeutics and Clinical Risk Management
`
`2010, Vol. 6, pages 543-550), Sundyet a/. (Journal of American Medical
`
`Association 2011, Vol. 306, pages 711-720), and Czocketal. (Clinical
`
`Pharmacokinetics 2005, Vol. 44, pages 61-70).
`
`The teachings of Kishimoto et a/., Reinders et a/., and Sundyet a/. are setforth
`
`above and applied herein. Kishimoto et a/., Reinders et a/., and Sundy et a/. are found
`
`to render claims 1-2, 5-9, 11-13, 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), but only teaches hydrocortisone as an
`
`example of applicable 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 Czockef al.. Czock et
`
`al. states that glucorticosteroids are frequently usedin clinical practice for various
`
`indications such asinflammatory diseases (Abstract, first par., page 63). The most
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 12
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`commonly used systematic glucocorticosteroids are hydrocortisone, prednisolone,
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`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 wouldstill 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
`
`obvious, absent a showing that the result of the substitution yields more than
`
`predictable results. See MPEP § 2143 and KSRInternational Co. v. Teleflex Inc. 550
`
`US 398, 82 USPQ2d 1385 (2007).
`
`Claim 10 is therefore obvious over Kishimoto etal. in view of Reinders etal.,
`
`Sundy ef al., and Czockefal..
`
`Double Patenting
`
`The nonstatutory double patenting rejection is based on a judicially created
`
`doctrine groundedin public policy (a policy reflected in the statute) so as to prevent the
`
`unjustified or improper timewise extension of the “right to exclude” granted by a patent
`
`and to prevent possible harassment by multiple assignees. A nonstatutory double
`
`patenting rejection is appropriate where the conflicting claims are not identical, but at
`
`least one examined application claim is not patentably distinct from the reference
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 13
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`claim(s) because the examined application claim is either anticipated by, or would have
`
`been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46
`
`USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed.
`
`Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum,
`
`686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619
`
`(CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
`
`A timelyfiled terminal disclaimer in compliance with 37 CFR 1.321 (c) or 1.321 (d)
`
`may be used to overcome an actual or provisional rejection based on nonstatutory
`
`double patenting provided the reference application or patent either is shown to be
`
`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
`
`MPEP § 717.02 for applications subject to examination under the first inventor tofile
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`provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(I)(1) -
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`706.02(1)(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).
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`The USPTOInternet 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/AIA/25, or PTO/AIA/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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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
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`more information about eTerminal Disclaimers, refer to
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`www.uspto.gov/patents/process/file/efs/guidance/eT D-info-l.jsp.
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`Page 14
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`RE: Nonstatutory double patenting rejections
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`Applicant proposed deferring the double patenting rejections until allowable
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`subject matter has been identified.
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`Accordingly, the rejections of record are considered proper but have been
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`modified to address claim amendments.
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`Modified rejections
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`Claims 1-2, 5-13, and 18-19 are provisionally rejected on the ground of
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`nonstatutory double patenting as being unpatentable over claims 134 and 136 of
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`co-pending Application No. 15/456520 in view of Reinders et al. (Therapeutics and
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`Clinical Risk Management2010, Vol. 6, pages 543-550) and Sundyet al. (Journal
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`of American Medical Association 2011, Vol. 306, pages 711-720).
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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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`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, wherein said pegylated urate oxidaseis limited to pegsiticase
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`in an embodiment. Although the co-pending application's method does notalso involve
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`administering an anti-inflammatory therapeutic at last once at least one week prior to
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`administering the two recited compositions, Reinders et al. states that pretreatments
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
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`Page 15
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`with glucocorticosteroids would help prevent gout flares and IR based on the study by
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`Sundy ef al/.. Sundy ef a/. teaches providing patients infused with pegloticase with a
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`nonsteroidal anti-inflammatory drug (NSAID) or colchicine once ortwice daily starting 1
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`week before the first infusion as gout prophylaxis. Sundy ef a/. also teaches
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`administering fexofenadine, acetaminophen, and hydrocortisone the night before and/or
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`immediately before infusion as infusion-related reactions (IRs) prophylaxis (right
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`column, p. 712). Thus, it would have been obvious for one with ordinary skill in the art
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`before the effective filing date of the claimed invention to include an additional step of
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`administering colchicine or nonsteroidal anti-inflammatory drug 1-2x/day starting 1 week
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`prior to administering compositions (i) and (ii) in order to prevent gout, as well as
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`fexofenadine, paracetamol, and hydrocortisone to prevent IRs. Obviousnessis
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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 1-2, 5-13, and 18-19 are provisionally rejected on the ground of
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`nonstatutory double patenting as being unpatentable over claims 49 and 113 of
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`co-pending Application No. 16/893153 and over claim 4 of co-pending Application
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`No. 17/092148; each onein view of Reinders et al. (Therapeutics and Clinical Risk
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`Management2010, Vol. 6, pages 543-550) and Sundyet al. (Journal of American
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`Medical Association 2011, Vol. 306, pages 711-720).
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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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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
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`Page 16
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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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`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 et a/. shows
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`that glucocorticosteroid pretreatment aids in preventing gout flares and IRs. Citing
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`Sundy ef al., patients are given a NSAID or colchicine as gout prophylaxis once or twice
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`daily starting 1 week beforethe first infusion of pegloticase, aside from fexofenadine,
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`acetaminophen, and hydrocortisone as IR prophylaxis the night before and/or
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`immediately before the infusion (right column, p. 712). A person with ordinary skill in the
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`art before the effective filing date of the claimed invention would have modified the co-
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`pending application by also administering colchicine/NSAIDs as well as fexofenadine,
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`acetaminophen, and hydrocortisone at least one week prior to administering the two
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`other compositions with reasonable expectation that these substances would
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`beneficially minimize or prevent gout and IRs. Combining or modifying the teachings of
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`the prior art to produce the claimed invention where there is some teaching, suggestion,
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`or motivation to do so is the rationale supporting obviousness.
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`These are provisional nonstatutory double patenting rejections.
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 17
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`Conclusion
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`No claim is allowed.
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`Applicant's amendment necessitated the new ground(s)of rejection presented in
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`this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a).
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`Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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`A shortenedstatutory period for reply to this final action is set to expire THREE
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`MONTHS from the mailing date of this action. In the eventa first reply is filed within
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`TWO MONTHS ofthe mailing date of this final action and the advisory action is not
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`mailed until after the end of the THREE-MONTH shortened statutory period, then the
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`shortened statutory period will expire on the date the advisory action is mailed, and any
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`extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of
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`the advisory action. In no event, however, will the statutory period for reply expire later
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`than SIX MONTHS from the date of this final action.
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`Any inquiry concerning this communication or earlier communications from the
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`examiner should be directed to MICHELLE F PAGUIO FRISING whosetelephone
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`number is (571)272-6224. The examiner can normally be reached on Monday-Friday,
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`8:00 a.m. - 5:00 p.m..
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`Examiner interviews are available via telephone, in-person, and video
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`conferencing using a USPTO supplied web-basedcollaboration tool. To schedule an
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`interview, applicant is encouraged to use the USPTO Automated Interview Request
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`(AIR) at http:/Avww.uspto.gov/interviewpractice.
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
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`Page 18
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`If attempts to reach the examiner by telephone are unsuccessful, the examiner's
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`supervisor, Renee Claytor can be reached on (571)272-8394. The fax phone number
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`for the organization wherethis application or proceeding is assigned is 571-273-8300.
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`Information regarding the status of an application may be obtained from the
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`Patent Ap