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
`
`09/1 1/2020
`
`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
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`following e—mail address(es):
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`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 7/10/2020.
`CI A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/were filed on
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`2a). This action is FINAL.
`
`2b) D This action is non-final.
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`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.
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`4):] 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.
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`Disposition of Claims*
`
`5)
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`Claim(s)
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`1—19 and 50 is/are pending in the application.
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`5a) Of the above claim(s) @ is/are withdrawn from consideration.
`
`
`
`[I Claim(ss)_is/are allowed.
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`CIaim(s)—1_—19is/are rejected.
`
`[:1 Claim(ss)_ is/are objected to.
`
`) ) ) )
`
`S)
`are subject to restriction and/or election requirement
`C] Claim(s
`* If any claims have been determined allowable, you may be eligible to benefit from the Patent Prosecution Highway program at a
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`participating intellectual property office for the corresponding application. For more information, please see
`
`httpfiwww.”smogovmatentszinit_events[pph[index.'sp or send an inquiry to PPeredhack@gsptg.ggv.
`
`Application Papers
`
`10):] 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:
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`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.
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`2.[:] 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) [3 Notice of References Cited (PTO-892)
`
`Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`2)
`Paper No(s)/Mail Date 7/10/2020.
`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 20200904
`
`

`

`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
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`under the first inventor to file provisions of the AIA.
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`Amendments
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`Applicant has amended claims 5 and 16 to obviate claim objections. It has been
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`verified that no new matter has been added.
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`Election/Restrictions
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`Claim 50 remains withdrawn from further consideration pursuant to 37 CFR
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`1.142(b) as being drawn to a nonelected invention, there being no allowable generic or
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`linking claim. Claims 1-19 have been examined on the merits.
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`Information Disclosure Statement
`
`One of the information disclosure statements (lDSs) submitted on 7/10/2020 fails
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`to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign
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`patent document; each non-patent literature publication or that portion which caused it
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`to be listed; and all other information or that portion which caused it to be listed. It has
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`been placed in the application file a cited NPL has not been considered.
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 3
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`RE: Objection to the claims
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`Claim Objections
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`The corrections on the minor informalities in claims 5 and 16 are sufficient to
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`overcome the claim objections.
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`Claim Rejections - 35 USC § 103
`
`In the event the determination of the status of the application as subject to AIA 35
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`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.
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`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:
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`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 aI.
`
`Traversal of rejections is based on lack of reason for combining an anti-
`
`inflammatory therapeutic with a composition comprising immunosuppressant—containing
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`synthetic nanocarriers and a composition comprising uricase. Referring to Renders et
`
`al.’s statement (left col., page 547), Applicant argues that the Phase III results
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`demonstrate the unpredictability of administering an anti-inflammatory therapeutic
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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 4
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`composition. It is also asserted that the Office’s finding of obviousness stems from an
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`improper application of hindsight reasoning.
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`The traversal has been fully considered but is found unpersuasive. First, the
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`examiner recognizes that obviousness may be established by combining or modifying
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`the teachings of the prior art to produce the claimed invention where there is some
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`teaching, suggestion, or motivation to do so found either in the references themselves
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`or in the knowledge generally available to one of ordinary skill in the art. See In re Fine,
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`837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21
`
`USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S.
`
`398, 82 USPQ2d 1385 (2007). As discussed in the last office action, there is a
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`recognized need to avert antibody formation leading to infusion reactions and to avoid
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`gout flares. Renders et al. states that antihyperuricemic therapy is preferably given with
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`inflammatory protection (left col., page 545). Accordingly, Renders et al. teaches
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`treating gout using pegylated uricase while also preventing inflammation using
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`colchicine or nonsteroidal anti-inflammatory drugs. The combined treatment was found
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`to be effective in decreasing serum urate concentrations and dissolving tophi, which has
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`never been shown before in randomized controlled trial for any urate-lowering agent.
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`Although gout flare was significantly higher during the first 3 months of a 6-month
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`treatment, the incidence and frequency became significantly lower during later months
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`for subjects treated every 2 weeks and those treated every 4 weeks (Table 3, page
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`547). It should be noted that gout flares are known to occur during antihyperuricemic
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`treatment alone due to mobilization of urate and that is why an anti-inflammation
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`therapeutic agent is necessary to prevent immunologic responses. Renders et al.
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 5
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`concludes, “Although long-term data are awaited, an anti-immunologic or anti-
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`inflammatory strategy is needed to prevent antipegloticase formation, which is
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`associated with IRS and diminished or shortened efficacy, and the strategy might also
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`prevent gout flares induced by urate mobilization at the same time” (Summary, right
`
`col., page 548). These teachings provide the motivation to a person with ordinary skill in
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`the art to combine anti-inflammatory therapy with Kishimoto et al.’s method of co-
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`administering pegylated uricase and SVP-rapamycin. Thus contrary to Applicant’s
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`argument, the conclusion of obviousness is supported by the cited prior art.
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`With regards to the argument that the conclusion of obviousness is based upon
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`improper hindsight reasoning, it must be recognized that any judgment on obviousness
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`is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long
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`as it takes into account only knowledge which was within the level of ordinary skill at the
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`time the claimed invention was made, and does not include knowledge gleaned only
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`from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin,
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`443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
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`Hence, the rejections of record have been maintained.
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`Maintained rejections
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`Claims 1-19 are rejected under 35 U.S.C. 103 as being unpatentable over
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`Kishimoto et al. (Nature Nanotechnology 2016, Vol. 11, pages 890-899) in view of
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`Reinders et al. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages
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`543-550).
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 6
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`According to Kishimoto et al., one common cause for failure of biotherapeutic
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`treatments and adverse hypersensitivity reactions is the development of antidrug
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`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
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`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
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`stage clinical failure of biologics (Introduction, left column, page 890).
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`Previously, nanoparticles carrying rapamycin and an antigen were found to be
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`effective in inducing durable antigen-specific immunological tolerance in vivo. Kishimoto
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`et al. then shows that synthetic vaccine particles carrying only rapamycin (SVP-
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`rapamycin) can be co-administered with any free antigen to induce immunological
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`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).
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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
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`levels of serum uric acid. While pegsiticase alone did not reduce uric acid levels when
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`administered as repeated injections indicating development of an anti-uricase lgG
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`response, SVP-rapamycin + pegsiticase inhibited ADA response thus allowing
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`maintenance of low serum uric acid levels. Similar results were obtained with
`
`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 7
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`cynomolgus monkeys (left column, page 895; Figure 5, page 896). Kishimoto etal.
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`concludes that biologic therapies with tolerogenic nanoparticles offer a promising
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`approach to minimize ADA formation that is associated with adverse hypersensitivity
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`reactions and loss of efficacy. Use of SVP-rapamycin with pegylated uricase is being
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`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
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`explained below:
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`Regarding claims 1-19: co-administering SVP-rapamycin, which is a synthetic
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`nanocarrier comprising the immunosuppressant rapamycin (an mTOR inhibitor), and
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`pegiticase (a pegylated uricase also known as pegadricase) to a subject such as a
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`mouse, monkey, or human is the same as “concomitantly administering to a subject in
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`need thereof 1) a composition comprising synthetic nanocarriers comprising an
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`immunosuppressant and 2) a composition comprising an uricase”.
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`What differentiates Kishimoto et al. from the claimed method is that it does not
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`entail concomitantly “administering 3) a composition comprising an anti-inflammatory
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`therapeutic” with the first two recited compositions.
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`Nonetheless, Reinders etal. states that patients receiving pegylated uricase
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`treatments experience infusion reactions (IR) and gout flares. To address this problem
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`glucocorticosteroids can be used to prevent antibody formation that result in IR and
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`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
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`fexofenadine, paracetamol, and hydrocortisone as lR prophylaxis before infusion with
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`pegylated uricase (right column, page 546). Results demonstrate that incidence and
`
`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 8
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`frequency of gout flare significantly decreased during month 4-6 in subjects treated
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`every 2 weeks of pegylated uricase (left column, page 547). A person with ordinary skill
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`in the art before the effective filing date of the claimed invention would have been
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`motivated by Reinders efal.’s teachings to pretreat subjects in Kishimoto efal.’s method
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`with colchicine/NSAID and fexofenadine, paracetamol, and hydrocortisone. It can be
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`expected that these pre-treatments would advantageously minimize gout flares and IR.
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`The obviousness of the instant claim is based on some teaching, suggestion, or
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`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.
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`See MPEP § 2143.01 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82
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`USPQ2d 1385, 1395-97 (2007).
`
`Hence, claims 1-19 are obvious over Kishimoto ef al. in view of Reinders ef 3]..
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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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`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 9
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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
`
`1.321 (b).
`
`The USPTO Internet website contains terminal disclaimer forms which may be
`
`used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application
`
`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
`
`all requirements is auto-processed and approved immediately upon submission. For
`
`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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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 10
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`RE: Nonstatutory double patenting rejections
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`Applicant requests the rejections be deferred until allowable subject matter has
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`been identified. Since the case is still not allowable, the rejections have been
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`maintained.
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`Maintained rejections
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`Claims 1-19 are provisionally rejected on the ground of nonstatutory
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`double patenting as being unpatentable over the claims of co-pending
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`Application Nos. 14/269042, 14/269048, and 15/456520; each one in view of
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`Reinders et aI. (Therapeutics and Clinical Risk Management 2010, Vol. 6, pages
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`543-550).
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`The co-pending applications are drawn to methods involving administering to a
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`subject (i) synthetic nanocarriers attached to immunosuppressants and (ii) therapeutic
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`molecules. In some embodiments, the immunosuppressant is an mTOR inhibitor and
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`the therapeutic molecule is an enzyme like pegloticase. Although none of these 00-
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`pending applications’ methods also administering an anti-inflammatory therapeutic,
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`Reinders et al. teaches that pretreatments with glucocorticosteroids would help prevent
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`gout flares and IR. 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 drugs (NSAIDs) as gout
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`prophylaxis, as well as fexofenadine, paracetamol, and hydrocortisone as IR
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`prophylaxis. Obviousness is established by combining or modifying the teachings of the
`
`

`

`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 11
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`prior art to produce the claimed invention where there is some teaching, suggestion, or
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`motivation to do so.
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`These are provisional nonstatutory double patenting rejections.
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`Conclusion
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`No claim is allowed. THIS ACTION IS MADE FINAL. Applicant is reminded of
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`the extension of time policy as set forth in 37 CFR 1.136(a).
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`A shortened statutory period for reply to this final action is set to expire THREE
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`MONTHS from the mailing date of this action.
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`In the event a first reply is filed within
`
`TWO MONTHS of the 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.
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`In no event, however, will the statutory period for reply expire later
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`than SIX MONTHS from the mailing 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 whose telephone
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`number is (571)272-6224. The examiner can be reached on 9:00 am. - 6:00 pm.
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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
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`(AIR) at http://www.uspto.gov/interviewpractice.
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`

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`Application/Control Number: 15/917,742
`Art Unit: 1651
`
`Page 12
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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 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 information about PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair.
`
`Should you have questions on access to the Private PAIR system, contact the
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`Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like
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`assistance from a USPTO Customer Service Representative or access to the
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`automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-
`
`1000.
`
`/Michelle F. Paguio Frising/
`Primary Examiner, Art Unit 1651
`
`