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`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and Trademark Office
`Address: COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`
`16/908,426
`
`06/22/2020
`
`Gregory I. OSTROW
`
`46682-701.317
`
`5508
`
`WILSON SONSINI GOODRICH & ROSATI
`650 PAGE MILL ROAD
`PALO ALTO, CA 94304-1050
`
`SHOWALTER, ALEXANDER KEITH
`
`ART UNIT
`
`1629
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`04/01/2024
`
`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):
`
`patentdocket @ wsgr.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`
`
`Disposition of Claims*
`31-35,37,39-45 and 49-53 is/are pending in the application.
`)
`Claim(s)
`5a) Of the above claim(s) _ is/are withdrawn from consideration.
`CL] Claim(s)__is/are allowed.
`Claim(s) 31-35,37,39-45 and 49-53 is/are rejected.
`(] 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)7) 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
`1.1.) Certified copies of the priority documents have been received.
`2.2) 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
`U.S. Patent and Trademark Office
`
`3)
`
`4)
`
`(LJ Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`(Qj Other:
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20240317
`
`Application No.
`Applicant(s)
`16/908,426
`OSTROWetal.
`
`
`Office Action Summary Art Unit|AIA (FITF)StatusExaminer
`
`ALEXANDER K SHOWALTER__|1629 Yes
`
`-- The MAILING DATEof this communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORYPERIOD FOR REPLYIS SET TO EXPIRE 3 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensionsof 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 9/28/2023.
`C} A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/werefiled on
`
`2a)() This action is FINAL. 2b)¥)This action is non-final.
`3) 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)(2) 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: 16/08 ,426
`Art Unit: 1629
`
`Page 2
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`DETAILED ACTION
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`Notice ofPre-AIA or AIA Status
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`The presentapplication, filed on or after March 16, 2013, is being examined underthe
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`first inventorto file provisions of the AIA.
`
`Priority
`
`The present Application is a continuation of U.S. Application No. 15/568,381, filed
`
`October 20, 2017, which is a §371 U.S. National Stage Application of International Application
`
`No. PCT/US2016/029222, filed April 25, 2016, which is a continuation of International
`
`Application No. PCT/US2015/037249, filed June 23, 2015, which is a continuation of U.S.
`
`Application No. 14/726,139, filed May 29, 2015, now U.S. Patent No. 9,421,199, issued August
`
`23, 2016, which claims the benefit of U.S. Provisional Application No. 62/151,926,filed April 23,
`
`2015; U.S. Provisional Application No. 62/096,433, filed December 23, 2014, and U.S.
`
`Provisional Application No. 62/016,502, filed June 24, 2014.
`
`Status ofthe Claims
`
`In the amendmentfiled September 27, 2023, claims 34-35 are amended. Claims 31-35,
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`37, 39-45, and 49-53 are currently pending and subject to examination herein.
`
`Information Disclosure Statement
`
`The information disclosure statements (IDSs) submitted on September 28, 2023 and on
`
`December19, 2023 are acknowledged.
`
`Response to Arguments/Amendments
`
`Applicant’s arguments presented on pgs. 5-10 of Applicant’s response of September27,
`
`2023 have been fully considered. Without rendering an opinion on the persuasiveness or lack
`
`thereof of Applicant’s arguments,the rejectionsin the Non-final Office Action of March 28, 2023
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`are withdrawn, and new rejections are presented herein. This is not intendedas an indication that
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`the prior rejections were incorrect, but the new rejections are presentedin the interestof clarity of
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`the record. Dueto the withdrawal of the prior rejections and rendering of the new rejections,
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`Applicant’s arguments of September 27, 2023 are moot. Because the present Office Action
`
`

`

`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 3
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`includes one or morerejections that could have beenissued prior to Applicant’s previous response,
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`the present Office Action is Non-final.
`
`Claim Rejections - 35 USC § 112
`
`The following is a quotation of 35 U.S.C. 112(b):
`(b) CONCLUSION.—Thespecification shall conclude with one or more claims particularly pointing
`out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the
`invention.
`
`The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph:
`The specification shall conclude with one or more claims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`Claim 44 is indefinite for reciting the improper Markushgroup, “wherein the preservative
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`is selected from benzalkonium chloride...polyhexamethylene biguanide, or combinations
`
`thereof.” The conjunction “or” should be replace with “and.” Claim 45 is indefinite for reciting
`
`that the solution is “essentially free of procaine and benactyzine, or pharmaceutically acceptable
`
`salts thereof.” This phrasing suggests that exclusion of thesalts is in the alternative, rather than in
`
`addition to exclusion of procaine and benactyzine. This should be correctedto, “essentially free
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`of procaine, benactyzine, and pharmaceutically acceptable salts thereof.”
`
`Claim Rejections - 35 USC § 103
`
`The following is a quotation of 35 U.S.C. 103 which formsthe basis for all 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.
`
`The factual inquiries for establishing a background for determining obviousness under 35
`
`U.S.C. 103 are summarized as follows:
`
`1. Determining the scope and contents of the priorart.
`2. Ascertaining the differences betweentheprior art and the claimsat issue.
`3. Resolving the level of ordinary skill in the pertinentart.
`4. Considering objective evidence presentin the application indicating
`obviousness or nonobviousness.
`
`

`

`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 4
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`Claims 31-33, 37, 39-45, and 49-53 are obvious over Akorn, Kondritzer, Chia, and
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`Cavanaugh:
`
`Claim(s) 31-33, 37, 39-45, and 49-53 is/are rejected under 35 U.S.C. 103 as being
`
`unpatentable over the non-patent publication FDA Drug Label Archive for Atropine Sulfate
`
`Solution, NDC code 17478-215-02,first published in 2010 (hereinafter, “Akorn’), in view of the
`
`non-patentpublication, Stability ofatropine in aqueoussolution, J. Am. Pharm. Assoc., 46, pgs.
`
`531-535 (1957) by Kondritzeretal. (hereinafter, “Kondritzer”), further in view of the non-patent
`
`publication, Atropine for the treatment of childhood myopia:safety and efficacy of 0.5%, 0.1%,
`
`and 0.01% doses (Atropine for the Treatment ofMyopia 2), Ophthalm., 119, pgs. 347-354 (2011)
`
`by Chiaetal., (hereinafter, “Chia”), and furtherstill in view of U.S. Patent Application Publication
`
`No. 2013/0303502 to Cavanaugh et al. (hereinafter, “Cavanaugh” ). Akorn was obtained from the
`
`DailyMed
`
`website
`
`at
`
`the
`
`url
`
`dailymed.nlm.nih.gov/dailymed/getArchivalFile.cfm?archive_id=25609, anda consolidated copy
`
`of the 2010 version (including label and box on pg. | and description on pgs. 2-3) is appended to
`
`this Office Action.
`
`Claim 31 recites a kit comprising a container having a monotherapeutic pharmaceutical
`
`composition and instructions for use.
`
`The monotherapeutic pharmaceutical composition
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`comprises atropine or atropine sulfate as a sole ophthalmic agent, present at about 0.01 mg/g to
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`about 0.5 mg/g. The composition also includes water; a buffer to provide a pH from about 4.8 to
`
`about 6.4; a tonicity adjusting agent; and a viscosity agent.
`
`Akorn teaches an aqueoussolution containing atropine sulfateas the sole active ophthalmic
`
`ingredient(i.e. a monotherapeutic solution having atropine sulfate; see pg. 2, lines 5-7, describing
`
`atropine sulfate as
`
`sole active ingredient.
`
`Akorn teaches that
`
`the solution contains
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`dibasic/monobasic sodium phosphate (i.e. a buffer) and can have hydrochloric acid and/or sodium
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`hydroxide addedto adjust pH to a pH within a range of from 3.5 to 6.0 (pg. 2, lines 9-11). The
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`sodium phosphate of Akorn is both a buffer of claim 31 (see paragraph [0021] of the instant
`
`application anda tonicity adjusting agent (see paragraph [0021] of the instant application). Akeorn
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`further teaches, at pg. 2, line 9 that the solution contains Hypromellose (i.e. hydroxypropyl
`
`methylcellulose, or HPMC, a viscosity agent).
`
`The pH range of from about 4.8 to about 6.4 of instant claim 31 is obvious over the
`
`overlapping pH range of 3.5 to 6.0 taughtby Akorn. In the case wherethe claimed ranges "overlap
`
`

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`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 5
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`or lie inside ranges disclosed by the priorart," a primafacie case of obviousness exists. See MPEP
`
`§ 2144.05() and cases cited therein. Furthermore, Kondritzer teaches that atropine in aqueous
`
`solution is far morestable against hydrolysis (i.e. degradation) at moderately acidic pH thanitis
`
`at neutral or alkaline pH. See, forexample, Table III of Kondritzer, showing a predicted half-life
`
`of 27 years for atropine at 20 °C and pH 6.0, as opposed to a half-life of 2.7 years at the same
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`temperature and pH 7.0.
`Fave UT
`OWENS by EN Var
`
`~Paenrcrn
`
`t
`ai
`a0
`
`2.7
`OE
`a8
`
`
`
`Assuch, it would have been obviousto select a pH within the recited range of from about
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`4.8 to about 6.4, which overlaps with the pH range of Akorn, and as promptedby the teaching of
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`Kondritzer of significantly improvedstability at moderately acidic pH.
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`Akorn does not explicitly teach that the atropine sulfate is present in the monotherapeutic
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`pharmaceutical composition at about 0.01 mg/g to about 0.05 mg/g.
`
`It would have been obvious
`
`to one of ordinary skill in the art, however,to utilize an atropine sulfate concentration within this
`
`range, because concentrations within this range were knownin theart to be safe and effective for
`
`treating various ophthalmological conditions. See, for example, Chia.
`
`Chia teaches a randomized study of low concentration atropine (0.5%, 0.1% and 0.01%)
`
`for the treatmentof atropine in children (Abstract). Chia further teaches that the 0.01% atropine
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`(approximately 0.1 mg/g) retains efficacy for reducing myopia progression in children, and has
`
`fewer adverse events compared to higher concentrations (pg. 353, right column, last paragraph
`
`continuing to top of left column of pg. 354). It thus would have been obvious to utilize the low
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`concentration of about 0.1 mg/g as taught by Chia, in the ophthalmic solution of Akorn, to treat
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`an ophthalmic condition such as reducing myopia progression in children, with fewer adverse
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`events
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`Akorn, in view of Kondritzer and Chia (modified Akorn), thus teaches all elementsofthe
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`monotherapeutic composition of claim 31, but does not teach incorporating the monotherapeutic
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`composition into a kit that includes a bottle to contain the composition andinstructionsfor use. It
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`

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`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 6
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`would have been obvious to one of ordinary skill
`
`in the art, however, to incorporate the
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`monotherapeutic composition of modified Akorn into such a kit, as ophthalmic kits including
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`bottles to contain ophthalmic solutions and instructions for use were well-knownin the art. See,
`
`for example, Cavanaugh.
`
`Cavanaugh teaches, inter alia, a kit that comprises a container containing one or more
`
`ophthalmic solutions or formulations (paragraph [0347]). Cavanaugh further teaches that the kit
`
`can include instructional materials containing directions disclosing means of use of the
`
`formulations (i.e. instructions for use, paragraph [0349]). Cavanaugh further references atropine
`
`as one drug from among manyalternatives that can be included in the formulation or solution
`
`(paragraph [0210]) that is included in the kit, and that the kit can facilitate various aspects of
`
`shipping, use, and storage (paragraph [0347]).
`
`It would have been obvious to incorporate the
`
`monotherapeutic atropine composition of modified Akorninto the kit of Cavanaugh, including
`
`the container andinstructions, to facilitate various aspects of shipping, use, and storage.
`
`With respect to claims 32 and 33, as noted, Chia teaches the benefits of a 0.01% (about 0.1
`
`mg/g) atropine solution. With respect to claim 37, as noted Akorn teaches that the bufferis
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`monobasic/dibasic sodium phosphate and that this may be pH adjusted with hydrochloric acid. It
`
`will be understood that such adjustment would produce sodium ions and chloride ions in solution,
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`i.e. sodium chloride, present as a tonicity-adjusting agent.
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`In addition, Cavanaugh teaches that
`
`the formulations to be used with the kit can include tonicity enhancers such as NaBr or NaCl
`
`(paragraph [0298]).
`
`With respect to claim 39, as noted, Akorn teaches wherein the viscosity agent is HPMC.
`
`With respect to claim 40, while Akorn teaches the presenceof a preservative, Cavanaugh teaches
`
`that the use of single-dose packaging can rendera preservative unnecessary. Cavanaugh further
`
`teaches that this is beneficial because preservatives can at times cause ocular irritation (paragraph
`
`[0343]).
`
`It thus would have been obvious to prepare the kit of Akorn, Kondritzer, Chia, and
`
`Cavanaugh such that
`
`the monotherapeutic composition is
`
`in single dose form without
`
`preservative, thereby reducing ocularirritation.
`
`With respect
`
`to claims 41-44, Akorn teaches that
`
`the solution contains 0.01%
`
`benzalkonium chloride (pg. 2, line 9). With respect to claim 45, Akorn teaches that the solution
`
`does not contain either procaine or benactyzine (the complete list of ingredients at pg. 2 lines 8-11
`
`does not include procaine, benactyzine, or synonymsthereof).
`
`

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`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 7
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`With respect to claims 49-50, Akorn teaches that the solution is a “sterile topical
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`anticholinergic for ophthalmic use”(pg. 2, lines 4-5). With respectto claims 51-53, Akorn teaches
`
`that the solution contains Edetate Disodium (i.e. EDTA, pg.2, line 10).
`
`Claims 34-35 are obvious over Akorn, Kondritzer, Chia, Cavanaugh, and Kumar.
`
`Claims 34-35 rejected under 35 U.S.C. 103 as being unpatentable over Akorn, Kondriter,
`
`Chia, and Cavanaughand further in view of the non-patent publication, Recent Challenges and
`
`Advancesin Ophthalmic Drug Delivery System, The PharmaInnov., 1, pgs. 1-15 (2012) by Kumar
`
`et al. (hereinafter, “Kumar’).
`
`Akorn, Kondritzer, Chia, and Cavanaugh are applied to claims 34-35 as to claim 31,
`
`above. Noneof Akorn, Kondritzer, Chia, or Cavanaugh explicitly teaches the use of a buffer of
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`claim 34. It would have been obviousto one of ordinary skill in the art to use such buffer systems,
`
`however,as citrate, for example, was well-known in the art as a safe and effective buffer for
`
`ophthalmic solutions. See, forexample, Kumar.
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`Kumarteaches that citrate isa commonly used buffer in the context of ophthalmic solutions
`
`(pg. 5, third paragraph). And while Kumar teaches that citrate would be undesirable in a
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`formulation intended to be at a pH of about 7.4, due to poor buffering capacity at this pH, citrate
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`would be highly effective within the pH rangerecited in claim 31, as citrate has pKa’s of across
`
`this range.
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`It thus would have been obvious to replace the phosphate buffer of Akorn with the
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`commonly usedcitrate buffer as taught by Kumar.
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`Conclusion
`
`Any inquiry concerning this communication or earlier communications from the examiner
`
`should be directed to ALEXANDER K SHOWALTER whosetelephone numberis (571)270-
`
`0610. The examiner can normally be reached M-F 9:00 am to 5:00 pm,eastern time.
`
`Examinerinterviews 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
`
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`
`

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`Application/Control Number: 16/08 ,426
`Art Unit: 1629
`
`Page 8
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`If attempts to reach the examinerby telephone areunsuccessful, the examiner’s supervisor,
`
`Jeffrey S Lundgren can be reached on (571) 272-5541. The fax phone numberfor the organization
`
`wherethis application or proceedingis assigned is 571-273-8300.
`
`Information regarding the status of published or unpublished applications may be obtained
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`from Patent Center. Unpublished application information in Patent Centeris available to registered
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`(IN USA OR CANADA)or 571-272-1000.
`
`/ALEXANDER K. SHOWALTER/
`
`Examiner, Art Unit 1629
`
`/JEFFREY S LUNDGREN/
`Supervisory Patent Examiner, Art Unit 1629
`
`