Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`REMARKS
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`Status of the Claims
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`Claims 31-35, 37, 39-45, and 49-53 are currently pending. The following remarksare in
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`response to the Examiner's Office Action mailed on March 28, 2023. Claims 34 and 35 are
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`amended. Reconsideration is respectfully requested in light of the following remarks.
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`Upon entry of the proposed amendments, claims 31-35, 37, 39-45, and 49-53 will be
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`under examination.
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`Decision of PTAB in Related US Patents
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`Applicant notes that the PTABrendered their decision in three related US patents under
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`Inter Partes Review in US10,888,557, US10,842,787, and US10,940,145. A copy of the decision
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`has been submitted in the Information Disclosure Statement filed with this response. Although
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`Applicant disagrees with the decision of the Board, Applicant subrnits that the amendedclaims
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`submitted herein address the concerns of the PTAB.
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`Claims Reiections Under 35 U.S.C.
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`S103
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`Claims 31-45 and 49-53 were rejected as allegedly obvious over US 4,952,536
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`(“Morris”) and in view of US 5,716,952 (WoldeMussie’}. Applicant respectfully disagrees.
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`Morris Cannot Be Properly Modified to Include the pif Range of WoldeMussie
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`MPEP 2143.01 VI states that, “{i]fa proposed modification would renderthe priorart
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`invention being modified unsatisfactory for its intended purpose, then there is no suggestion or
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`motivation to make the proposed modification.” /n re Gordon, 733 F.2d 900, 221 USPQ 1125
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`(Fed. Cir. 1984).
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`Morris discloses an aqueous solution of edrophoniumand atropine to antagonize
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`nondepolarizing blockade during medical treatment. Morris at Abstract.
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`In some embodiments,
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`Morris discloses an aqueous solution where atropine or atropine sulfate is present at 4
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`concentration of about 0.01 to about 0.Smg/g.” See Morris at Col. 3, 27-31. WoldeMussie
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`discloses the use of some muscarinic antagonists in an ophthalmic composition for treating
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`Atty. Docket No.: 46682-701.317
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`

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`Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`glaucomaand intraocular hypertension, however WoldeMussie does not disclose the use of
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`atropine.
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`As acknowledged bythe office, Morris does not disclose pH of about 4.8 to about 6.4 as
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`recited by the present claims. The office relies on table 1 of WoldeMussie to correct this
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`deficiency of Morris. However, the proposed modification would render Morris unsatisfactory
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`for its purpose.
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`A POSITA would not expect the pH range offered by WoldeMussie of 4.5 to 7.5 to be an
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`acceptable pH range to formulate a stabilized composition of atropine. Kondritzer et al, Journal
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`of pharmaceutical sciences, 46(9), pp. 331-535 (1957) CKondritzer”) stated that “[t]he pH of
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`minimum hydrolysis [of atropine] has been calculated and found to vary with temperature from
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`pH 4.11 at 0° to pH 3.24at 100°” See D2 at p 335. Kondritzer further claims that “[s}tabilityis
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`claimed for 0.1%sterilized atropine sulfate solution in storage if the pHis kept in the range 2.8-
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`6.0, distinct deterioration on storage occurring ifthe pH is kept at 7 or higher.” See Kondritzer
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`at p/ 332, emphasis added. However, this is for 0.1%atropine sulfate, rather than the claimed
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`0.001 wt%o to 0.05 wt, and which has different requirements for stability (See instant
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`application at [0072], “some muscarinic antagonist (e.g. atropine) liquid compositions
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`formulated at lower concentrations (e.g. 0.001%to 0.08%) present stability challenges that are
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`less 0 in higher concentrations (e.g. 0.1-1%).”} Further, Lund et al (The kinetics of atropine
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`and apoatropine in aqueous solutions”) states that Kondritzer “investigated the alkaline and acid
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`hydrolysis of atropine” but that these studies failed to take apoatropine formation into account
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`and concludes the stable pH range for maximum stability of atropine is a pH range of 2.0-4.0.
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`See Lund, page f and Table 6. Therefore, a POSTTA would not expect a reasonable expectation
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`of success in formulating an atropine composition at a pH greater than 4.0 suchas the range of
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`45 to 7.5 offered by WoldeMuisse for its non-atropine formulation.
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`in contrast to the cited references, the present application includes detailed description of
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`the stability and degradation problems in Table 24A showing that as atropine is forrnulated at a
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`higher pH, its stability deteriorates. Table 24A shows specifically that a pH above 6.4 shows
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`worse stability characteristics than formulations with pH within the claimed range of about 4.8 to
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`about 6.4. Therefore, modifying the solution of Morris with the pH of WoldeMussie would not
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`Atty. Docket No.: 46682-701.317
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`Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`resultin the claimed composition. Instead, the pH range taught in WoldeMussie for the different
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`and distinct active ingredient would not actually provide the stability found by the Applicantat
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`the presently claimed formulation and pH. For these reasons, the combination of Morris and
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`WoldeMussie is improper and would not provide a person of skill in the art with any expectation
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`of success, much less a reasonable expectation of success formulating atropine at the pH range
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`of WoldeMussie.
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`Forat least these reasons, the present claims are not obvious in viewof the cited
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`references. Applicant respectfully requests withdrawal ofthe rejection under § 103.
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`Double Patenting
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`Nonstatutory double patenting
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`Claims 31-45 and 49-53 were rejected as allegedly patentably indistinct over claims 1-23
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`of US 10,940,145 (the °145 patent”). Applicant respectfully disagrees.
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`Without conceding in the basis of the rejection, and solely to expedite prosecution of this
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`application, Applicant submits herewith this application a terminal disclaimer over the “145
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`patent.
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`Claims 31-45 and 49-53 were rejected as allegedly patentably indistinct over claims 1-15
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`of US 11,520,095 (Miura’). (Applicant belteves the Office is referring to US 11,052,095, the
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`“OOS patent’) and claims 1-23 of US 11,052,094 “(the °094 patent”).
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`As described above, claim 1 recites:
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`{a] kit comprising: 4. a container comprising a monotherapeutic pharmaceutical
`composition, the monotherapeutic pharmaceutical composition comprising:
`i. a sole ophthalmic agent, wherein the sole ophthalmic agent is atropine or atropine
`sulfate, ancl wherein the atropine or atropine sulfate is provided at about 0.01 mg/g to
`about 0.5 ma/g:
`ik. water;
`iti. a buffer to provide a pH from about 4.8 to about 6.4;
`iv. a tonicity adjusting agent; and
`v. a viscosity agent; and
`b. instructions for use.
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`Applicant submits the claims are patently distinct from claims of the ‘094 patentfor at
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`loast the following reasons. Claim 1 of the ‘094 patent recites “Lajn ophthalmic composition
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`comprising from about 0.001 wt %to about 1 wt %of an ophthalmic agent and denterated
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`-7-
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`Atty. Docket No.: 46682-701.317
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`Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`water ... wherein the ophthalmic agent comprises pilocarpime.” Emphasis added. Claim 1 of the
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`‘095 patent contains similar features. Claim | of the instant application does not recite these
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`features. Further, neither the “094 patent nor the “O95 patent recites an ophthalmic composition
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`comprising atropine, as recited in claim | of the instant application.
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`Claims 31-45 and 49-53 were rejected as allegedly patentably indistinct over claims 1-23
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`of US 11,596,625 (the °625 patent”). Applicant respectfully disagrees.
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`Applicant submits the claims are patentably distinct from the claims of the ‘625 patent for
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`at least the following reasons. Claim 1 of the “625 patent recites “[ain ophthalmic composition,
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`comprising from about 0.005 wt% to about 0.03 wt% of a muscarinic antagonist and deuterated
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`water...” Emphasis added. Claim 1 of the present application does not recite this feature.
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`Claims 31-45 and 49-53 were rejected as allegedly patentably indistinct over claims 1-23
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`of US 11,464,769 (Puri “769") and claims 1-20 of US 10,251,875 (Puri °8757). Applicant
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`respectfully disagrees.
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`For this type [double patenting] of rejection to be appropriate, there must be either at least
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`one inventor in common, common applicant, or a common owner/assignee. See MPEP 1504.06
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`Applicant notes that netther the Puri ‘769 patent nor the Puri “875 patent does not haveat
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`least one commoninventor, common applicant, or common owner/assignee with the instant
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`application. Further, Applicant notes that claim 1 of Puri ‘769 recites “[a] storage stable liquid
`low-dose atropine ophthalmic formulation comprising:...(7} bypromelose 2910 iman amount
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`of 5.0m¢/ml of the ophthalmic formulation...” Emphasis added. Claim 1 of the present
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`application does not recite this feature. Claim 1 of Puri ‘875 recites “lal liquid storage-stable
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`low-dose ophthalmic atropine composition consisting essentially of: an aqueous solution
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`comprising a buffer, a tonicity agent, a chelator, a viscosity modifier, and atropimeor a
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`pharmaceutically acceptable salt thereof...” Emphasis added. Claim 1 of the present application
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`does not recite this feature.
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`As such, Applicant respectfully requests the withdrawal of the nonstatutory double
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`patenting rejections.
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`Provisional statutory double patenting
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`Atty. Docket No.: 46682-701.317
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`Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`Claims 31-45 and 49-33 were provisionally rejected over claims 1-99 of US 17/7384841
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`(Ostrow ‘841"). Applicant respectfully disagrees.
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`Claim 43 of Ostrow‘841 recites “[aln ophthalmic composition comprising from about
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`0.001 wt%s to about 0.5 wt% of a muscarinic antagonist, deuterated water at a pH of from about
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`4 2 to about 7.9, and 0.01 wt%to about 0.50 wi’ EDTA.” Emphasis added. Claim 1 of the
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`present application does not recite this feature.
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`Claims 31-45 and 49-53 as allegedly patentably indistinct over claims 1-19 of US
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`17/894882 COstrow 882”), claims 1-18 of US 17/894884 (“Ostrow‘884”), claims 1-19 of US
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`17/894885 (Ostrow °885”), claims 31-49 of US 17/681560 (Ostrow°560”), claims 31-48 of
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`US 17/721831 C Ostrow °831"), and clarms 31-49 of US 17/721838 (Ostrow °833°). Applicant
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`respectfully disagrees.
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`Without conceding in the basis of the rejection, and solely to expedite prosecution ofthis
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`application, Applicant will file a terminal disclaimer once allowable subject matter has been
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`identified and/or an application listed herein issues.
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`Claims 31-45 and 49-53 were rejected as allegedly patentably indistinct over claims 1-20
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`of US 18/055940 (Ostrow °940”), claims 1-20 of US 18/055945 (Ostrow °945”) and claims I-
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`20 of US 18/055949 (Ostrow °949"). Applicant respectfully disagrees.
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`Ostrow “940 recites “[a] stabilized ophthalmic composition for treating pre-myopia,
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`myopia, or progression of myopia, comprising from about 0.001 wi%to about 0.05 wtof
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`atropine or atropine sulfate and deuterated water...” Emphasis added. Claim | of Ostrow ‘945
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`aod Claim 1 of Ostrow “949 recite similar features. Claim | of the present application does not
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`recite this feature.
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`As such, Applicant respectfully requests the withdrawal of the provisional statutory
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`double patenting rejections.
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`a.
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`Atty. Docket No.: 46682-701.317
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`Application No. 16/908,426
`Response tc Non-Final Office Action Mailed March 28, 2023
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`CONCLUSION
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`In light of the remarks set forth above, Applicants believe that the pending claims are
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`under condition for alowance. Applicants respectfully solicit the Examiner to expedite the
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`prosecution of this patent application to issuance. Should the Examiner have any questions, the
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`Examiner is encouraged to telephonethe undersigned at (415) 947-2155.
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`The Commissioneris authorized to charge any underpayment or credit any overpayment
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`to Deposit account No. 23-2415 (Attorney Docket No, 46682-701.317).
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`Respectfully subrnitted,
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` /Tyler Bird/
`Tyler Bird
`Reg. No. 79,511
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`Date: September 27, 2023
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`By:
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`WILSON SONSINI GOODRICH & ROSATI
`650 Page Mill Road
`Palo Alto, CA 94304-1050
`Phone:
`(415) 947-2155
`Customer No. 21971
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`-10-
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`Atty. Docket No.: 46682-701.317
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