PCT/US2020/037042 16.10.2020
`
`PATENT COOPERATION TREATY
`
`PCT
`INTERNATIONAL SEARCH REPORT
`
`(PCT Article 18 and Rules 43 and 44)
`
`FOR FURTHER ACTION
`' see Form PCT/ISA/220 as well as, where applicable, item 5 below.
`Internationalfiling date (day/month/year)
`(Earliest) Priority Date (day/month/year)
`10 June 2020
`10 June 2019
`
`VIiSUS THERAPEUTICS,INC.
`
`Applicant’s or agent’s file reference
`VISU-8PCT
`
`International application No.
`PCT/US2020/037042
`
`Applicant
`
`This international search report has been prepared bythis International Searching Authority and is transmitted to the applicant according
`to Article 18. A copy is being transmitted to the International Bureau.
`This international search report consists ofa total of
`G
`sheets.
`C] It is also accompanied by a copyof each prior art documentcited in this report.
`
`
`1. Basis of the report
`a. With regard to the language, the international search was carried out on the basisof:
`x] the international application in the language in whichit wasfiled.
`which is the language of
`LJ a translation of the international application into
`a translation furnished for the purposes of international search (Rules 12.3(a) and 23.1(b)).
`b L] This international search report has been established taking into account the rectification of an obvious mistake authorized
`by or notified to this Authority under Rule 91 (Rule 43.65is(a)).
`G ] With regard to any nucleotide and/or amino acid sequence disclosed in the international application, see Box No.1.
`
`2. ] Certain claims were found unsearchable (see Box No. JI).
`
`3.
`
`x] Unity of invention is tacking (see Box No. 1D.
`
`4. With regardto thetitle,
`x] the text is approved as submitted by the applicant.
`L_]
`the text has been established by this Authority to read as follows:
`
`5. With regard to the abstract,
`
`the text is approved as submitted by the applicant.
`the text has been established, according to Rule 38.2, by this Authority as it appears in Box No. IV. The applicant may,
`within one month from the date of mailing of this international search report, submit comments to this Authority.
`
`6. With regard to the drawings,
`a.
`the figure of the drawings to be published with the abstract is Figure No.
`Xx]
`as suggested by the applicant.
`[J as selected by this Authority, because the applicant failed to suggest a figure.
`LJ as selected by this Authority, because this figure better characterizes the invention.
`b. L] noneof the figures is to be published with the abstract.
`
`22
`
`Fonn PCT/ISA/2 10 (first sheet) July 2019)
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`

`

`PCT/US2020/037042 16.10.2020
`
`INTERNATIONAL SEARCH REPORT
`
`
`
` Box No. Il
`Observations where certain claims were found unsearchable (Continuation of item 2 of first sheet)
`
`International application No.
`PCT/US 2020/037042
`
`This international search report has not been established in respect of certain claims under Article 17(2)(a) for the following reasons:
`I. [] Claims Nos:.:
`because they relate to subject matter not required to be searched by this Authority, namely:
`
`2. [| Claims Nos.:
`because theyrelate to parts of the international application that do not comply with the prescribed requirements to such an
`extent that no meaningful international search can be carried out, specifically:
`
`3. [] Claims Nos.:
`because they are dependent claims andare not drafted in accordance with the second andthird sentences of Rule 6.4(a).
`
`Box No. III
`
`Observations where unity of invention is lacking (Continuation of item 3 of first sheet)
`
`This Intemational Searching Authority found multiple inventions in this intemational application, as follows:
`See extra sheet(s).
`
`i. [| Asall required additional search fees were timely paid by the applicant, this international search report covers all searchable
`claims.
`
`2. [] Asall searchable claims could be searched withouteffort justifying additional fees, this Authority did not invite payment of
`additional fees.
`
`3. [] Asonly someofthe required additional search fees were timely paid by the applicant, this international search report covers
`only those claims for which fees were paid, specifically claims Nos.:
`
`4. SJ No required additional search fees were timely paid by the applicant. Consequently,this international search report is restricted
`to the invention first mentioned in the claims;
`it is covered by claims Nos.:
`1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, 69
`
`
`
`
`
`
`Remark on Protest
`
`L] The additional search fees were accompanied by the applicant’s protest and, where applicable, the
`paymentof a protestfee.
`[] The additional search fees were accompanied by the applicant’s protest but the applicable protest
`fee was not paid within the time limit specified in the invitation.
`[J Noprotest accompanied the payment of additional search fees.
`
`Form PCT/ISA/2 10 (continuation offirst sheet(2)) (July 2019)
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`

`

`PCT/US2020/037042 16.10.2020
`
`INTERNATIONAL SEARCH REPORT
`
`}
`
`
`International application No.
`PCT/US2020/037042
`
`
` A. CLASSIFICATION OF SUBJECT MATTER
`
`IPC(8) - A61K 31/498; A61K 9/00; A61K 31/27; A61P 27/10 (2020.01)
`CPC - A61K 31/498; A61K 9/0048; A61K 31/27; A61P 27/10 (2020.08)
`
`
`
`
`
`According to International Patent Classification (IPC) or to both nationalclassification and IPC
`B.
`FIELDS SEARCHED
`
`
` Minimum documentation searched (classification system followed by classification symbols)
`
`see Search History document
`
`! Documentation searched other than minimum documentation to the extent that such documents are included in the fields searched
`
`US 2011/0152274 A1 (KAUFMAN) 23 June 2011 (23.06.2011) entire document
`
`1-6, 11-20, 25-32, 48, 49,
`
`Relevant to claim No.
`
`
`see Search History document
`
`
`
`Electronic data base consulted during the international search (name of data base and, where practicable, search terms used)
`
`see Search History document
`C. DOCUMENTS CONSIDERED TO BE RELEVANT
`
`
`54-59, 63-67, 69
`
` 1-6, 11-20, 25-32, 48, 49,
`US 2003/0036535 A1 (NOLAN) 20 February 2003 (20.02.2003) entire document
`
`54-59, 63-67, 69
`
`
`WO 2016/172712 A2 (SYONEXIS INC) 27 October 2016 (27.10.2016) entire document
`
`14, 28
`
`
`
`US 2016/0250225 A1 (ALLERGANINC) 01 September 2016 (01.09.2016) entire document
`
`
`
`48, 49, 56-59, 67
`
`
`
`
`
`
`
`[| Further documents are listed in the continuation of Box C.
`[] See patent family annex.
`
`.
`Special categories of cited documents:
`later documentpublishedafter the internationalfiling date
`or
`ty
`date and not in conflict with the application but cited to understand
`“A” documentdefining the general state of the art whichis not considered
`to be of particular relevance
`the principle or theory underlying the invention
`“BD” document cited by the applicant in the international application
`“x” document of particular relevance; the claimed invention cannot be
`“E”
`earlier application or patent but published onorafter the international
`considered novelor cannot be considered to involve an inventivestep
`filing date
`whenthe documentis taken alone
`“1.” document which may throw doubts on priority claim(s) or which
`“Y” document of particular relevance; the claimed invention cannot
`is cited to establish € publication date of anothercitation or other
`be considered to involve an inventive step when the documentis
`special reason (as specified)
`combined with one or more other such documents, such combination
`“OQ” documentreferring toan oral disclosure,use, exhibition or other means
`being obviousto a person skilled in the art
`“p’?
`documentpublished prior to the international filing date but laterthan "&” document memberof the same patent family
`the priority date claimed
`Date ofthe actual completion of the international search
`
`“T"
`
`
`30 September 2020
`1 6 0 C T 20 20
`
` Authorized officer
`
`
`Nameand mailing address of the ISA/US
`Blaine R. Copenheaver
`Mail Stop PCT, Attn: ISA/US, Cornmissioner for Patents
`
`
`P.O. Box 1450, Alexandria, VA 22313-1450
`
`
`Facsimile No. 571-273-8300
`
`
`Form PCT/ISA/2 10 (second sheet) (July 2019)
`
`Telephone No. PCT Helpdesk: 571-272-4300
`
`Date of mailing of the international search report
`
`

`

`INTERNATIONAL SEARCH REPORT
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`PCT/US2020/037042 16.10.2020
`
`International application No.
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`PCT/US2020/037042
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`Continued from Box No.Il| Observations where unity of invention is lacking
`
`Claims 1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, and 69 have been analyzed subjectto the restriction that the claims read on a method
`for treating and ameliorating or reducing at least one refractive error of a pseudophakic patient selected from the group consisting of
`myopia, hyperopia, and astigmatism, comprising: administering to at least one eye of the patient an ophthalmic preparation comprising: a
`therapeutically effective amount of one parasympathomimetic drug, wherein the parasympathomimetic drug is carbachol, or
`pharmaceutically acceptable salts thereof; and a therapeutically effective amount of an alpha agonist or an alpha antagonist, wherein the
`an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically acceptable salts thereof; methods of treating at jeast one
`refractive error in a patient that has had ocular surgery thereof; and methods for treating and ameliorating or reducing at least one
`refractive error of a pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism thereof.
`
`Form PCT/ISA/210 (extra sheet) (July 2019)
`
`

`

`INTERNATIONAL SEARCH REPORT
`
`PCT/US2020/037042 16.10.2020
`
`International application No.
`
`PCT/US2020/037042
`
`This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive
`concept under PCT Rule 13.1. In order for all inventions to be examined, the appropriate additional examination fees need to be paid.
`
`Group I+: claims 1-32, 48, 49, 54-59, and 63-69 are drawn to methodsfor treating and ameliorating or reducing at least one refractive
`error of a pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism, and methodsoftreating at
`least one refractive error in a patient that has had ocular surgery.
`
`Group Il: claims 33-47, 50-53, and 60-62 are drawn to methods of creating multifocality in a pseudophakic patient, reducing symptoms of
`presbyopiain a patient having an eye or both eyes.
`
`Group III: claims 70-72 are drawn to methods for preventing a parasympathomimetic induced myopic shift in a pseudophakic patient
`receiving parasympathomimetic drugs or pharmaceutically acceptable salts thereof.
`
`Thefirst invention of Group I+ is restricted to a method for treating and ameliorating or reducing at least one refractive error of a
`pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism, comprising: administering to at least
`one eye of the patient an ophthalmic preparation comprising: a therapeutically effective amount of one parasympathomimetic drug,
`wherein the parasympathomimetic drug is carbachol, or pharmaceutically acceptable salts thereof; and a therapeutically effective
`amountof an alpha agonist or an alpha antagonist, wherein the an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically
`acceptable salts thereof; methodsof treating at least one refractive error in a patient that has had ocular surgery thereof; and methods
`for treating and ameliorating or reducing at least one refractive error of a pseudophakic patient selected from the group consisting of
`myopia, hyperopia, and astigmatism thereof. It is believed that claims 1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, and 69 read onthisfirst
`namedinvention and thus these claims will be searched withoutfee to the extent that they read on the above embodiment.
`
`Applicantis invited to elect additional formula(e) for each additional species to be searched in a specific combination by paying an
`additional fee for each set of election. Each additional elected formula(e) requires the selection of a single definition for each compound
`variable. An exemplary election would be a methodfor treating and ameliorating or reducing at least one refractive error of a
`pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism, comprising: administering to at least
`one eye of the patient an ophthalmic preparation comprising: a therapeutically effective amount of one parasympathomimetic drug,
`wherein the parasympathomimetic drug is pilocarpine, or pharmaceutically acceptable salts thereof; and a therapeutically effective
`amountof an alpha agonist or an alpha antagonist, wherein the an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically
`acceptable salts thereof; methods oftreating at least one refractive error in a patient that has had ocular surgery thereof; and methods
`for treating and ameliorating or reducing at least one refractive error of a pseudophakic patient selected from the group consisting of
`myopia, hyperopia, and astigmatism thereof. Additional formula(e) will be searched upon the payment of additional fees. Applicants must
`specify the claims that read on any additional elected inventions. Applicants must further indicate, if applicable, the claims which read on
`the first namedinventionif different than what was indicated abovefor this group. Failure to clearly identify how any paid additional
`invention fees are to be applied to the “+” group(s) will result in only the first claimed invention to be searched/examined.
`
`The inventions listed in GroupsI+, tl, and III do not relate to a single general inventive concept under PCT Rule 13.1, because under
`PCT Rule 13.2 they lack the same or corresponding special technical features for the following reasons:
`
`The special technical features of Group I+, methods for treating and ameliorating or reducing at least one refractive error of a
`pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism, and methods oftreating at least one
`refractive error in a patient that has had ocular surgery, are not present in GroupsIl and I!I; the special technical features of GroupII,
`methods of creating multifocality in a pseudophakic patient, reducing symptomsof presbyopia in a patient having an eye or both eyes,
`are not presentin Groups !+ and Ill; and the special technical features of Group III, methods for preventing a parasympathomimetic
`induced myopic shift in a pseudophakic patient receiving parasympathomimetic drugs or pharmaceutically acceptable salts thereof, are
`not present in Groups I+ and Il.
`
`The GroupsI+, II, and Ill formulae do not share a significant structural element requiring the selection of alternatives for the one or more
`parasympathomimetic drug and the alpha agonist or alpha antagonist and accordingly these groupslack unity a priori.
`
`Additionally, even if Groupst+, ll, and III were considered to share the technical features of a method for treating and ameliorating or
`reducing at least one refractive error of a pseudophakic patient selected from the group consisting of myopia, hyperopia, and
`astigmatism, and a methodfor treating and ameliorating or reducing at least one refractive error of a pseudophakic patient that has had
`ocular surgery comprising: administering to an eye or both eyes of the patient an ophthalmic preparation comprising: a therapeutically
`effective amount of one or more parasympathomimetic drugs, or pharmaceutically acceptable salts thereof; and a therapeutically
`effective amount of an alpha agonist or an alpha antagonist, or pharmaceutically acceptable salts thereof, and a permeation enhancer:
`wherein at least intermediate vision of the pseudophakic patient is improved from administration of the ophthalmic preparation to the eye
`or both eyes of the patient, these shared technical features do not represent a contribution over the prior art as disclosed by US
`2011/0152274 A1 to Kaufman and US 2003/0036535 A1 to Nolan.
`
`US 2011/0152274 A1 to Kaufman teaches a methodfor treating and ameliorating or reducing at least one refractive error of a patient
`(Para. [0017], method for temporarily treating, ameliorating, or reducing presbyopia; Para. [0011], method for ameliorating or reducing
`presbyopia of a patient having an eye), comprising: administering to an eye or both eyes of the patient an ophthalmic preparation
`comprising: a therapeutically effective amount of one or more parasympathomimetic drugs, or pharmaceutically acceptable salts thereof;
`and a therapeutically effective amount of an alpha agonist or an alpha antagonist, or pharmaceutically acceptable salts thereof (Para.
`[0011], administering to the eye a therapeutically effective amount of an ophthalmic preparation comprising one or more
`parasympathomimetic drugs or one or more cholinesterase inhibitors, or their pharmaceutically acceptable salts, and one or more alpha
`agonists or antagonists, or their pharmaceutically acceptable salts; Para. [0020], applying to the one or both eyes of the patient a
`therapeutically effective amount of carbachol, or pharmaceutically acceptable salts thereof, and an effective amount of brimonidine).
`
`Additionally, US 2003/0036535 A1 to Nolan teaches a pseudophakic patient that has had ocular surgery (Para. [0045], the method of
`this invention can be successfully used to treat diminished visual acuity in phakic as well as pseudophakic patients ... this method can
`
`Form PCT/ISA/2 10 (extra sheet) (July 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`PCT/US2020/037042
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`INTERNATIONAL SEARCH REPORT
`
`International application No.
`
`be successfully used to treat patients with artificial and rigid intraocular lenses (IOL's). |OL's are inserted at the time of cataract surgery);
`selected from the group consisting of myopia, hyperopia, and astigmatism (Para. [0032], treatment for myopia); and a permeation
`enhancer(Para. [0043], other pharmaceutically acceptable carriers or excipients that are known to enhance membrane permeability and
`cellular uptake of the drug can be used as diluents with or without modification for application to the eye); wherein at least intermediate
`vision of the pseudophakic patient is improved from administration of the ophthalmic preparation to the eye or both eyes ofthe patient
`(Para. [0044], A single topical application of a given AChE inhibitor at bedtime can enhance visual acuity in the phakic emmetropic
`patients as well as in pseudophakic patients for a few days. For example, application of one to two drops of phospholine iodide of a
`selected concentration at bedtime canalleviate the diminished vision of the patients for at least five days).
`
`The inventionslisted in GroupsI+, Il, and III therefore lack unity under Rule 13 because they do not share a same or corresponding
`special technical feature.
`
`Form PCT/ISA/210 (extra sheet) (July 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`PATENT COOPERATION TREATY
`
`From the
`INTERNATIONAL SEARCHING AUTHORITY
`
`To: LYNDA M. WOOD
`
`BROWN & MICHAELS PC
`118 NORTH TIOGA STREET
`SUITE 400
`ITHACA, NY 14850
`
`!
`
`PCT
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`(PCT Rule 43dis. 1)
`
`
`Date ofmailing
`1 6
`CT
`
`
`(day/month/year)
`0
`7020
`
`
`
`
`
`Applicant’s or agent’s file reference
`FOR FURTHER ACTION
`
`
`VISU-8PCT
`See paragraph 2 below
`
`
`
`
`
`Priority date (day/month/year)
`International filing date (day/month/year)
`International application No.
`
`
`PCT/US2020/037042
`10 June 2020
`10 June 2019
`
`
`International Patent Classification (IPC) or both national classification and IPC
`
`IPC(8) - A61K 31/498; A61K 9/00; A61K 31/27; A61P 27/10 (2020.01)
`
`CPC - A61K 31/498; A61K 9/0048; A61K 31/27; A61P 27/10 (2020.08)
`
`
`
`Applicant’ WiSUS THERAPEUTICS, INC.
`
`1. This opinion contains indications relating to the following items:
`x] Box No.
`|
`Basis of the opinion
`[| Box No.
`Priority
`Box No.
`Non-establishment of cpinion with regard to novelty, inventive step and industrial applicability
`
`Box No.
`
`Box No.
`
`Box No. VI
`
`Lack ofunity of invention
`
`Reasoned statement under Rule 43 dis. 1(a)(i) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`Certain documentscited
`
`MOUXX Box No. VIII Certain observations on the international application
`
`For further options, see Form PCT/ISA/220.
`
`Box No. VII Certain defects in the international application
`
`FURTHER ACTION
`
`If a demandfor international preliminary examination is made, this opinion will be considered to be a written opinion ofthe
`International Preliminary Examining Authority (‘‘IPEA’’) except that this does not apply where the applicant chooses an Authority
`other than this one to be the IPEA and the chosen IPEAhasnotified the International Bureau under Rule 66.1 4is(b) that written
`opinions of this International Searching Authority will not be so considered.
`If this opinionis, as provided above, considered to be a written opinion of the IPEA, the applicantis invited to submit to the IPEA
`a written reply together, where appropriate, with amendments, before the expiration of 3 months from the date of mailing of Form
`PCT/SA/220 or before the expiration of 22 months from the priority date, whichever expires later.
`
`| Name and mailing address of the ISA/US|Date of completion of this opinion Authorized officer
`
`Mait Stop PCT, Attn: ISA/US
`Blaine R. Copenheaver
`Commissioner for Patents
`]
`P.O. Box 1450, Alexandria, VA 22313-1450
`3 PCT Helpdesk: 571-272-4300
`| Facsimile No. 571-273-8300
`i Telephone No. 571-272-4300
`Form PCT/ISA/237 (cover sheet) (revised January 2019)
`
`30 September 2020
`
`
`
`

`

`PCT/US2020/037042 16.10.2020
`
`INTERNATIONAL SEARCHING AUTHORITY
`
`Box No. I
`
`Basis of this opinion
`
`1. With regard to the language, this opinion has been established on the basis of:
`
`International application No. WRITTEN OPINION OF THE
` PCT/US2020/037042
`
`
`
`
`
`the international application in the language in which it wasfiled.
`
`
`
`whichis the language ofa translation
`a translation of the international application into
`
`
`furnished for the purposesof international search (Rules 12.3(a) and 23.1(b)).
`
`
`
` This opinion has been established taking into accountthe rectification of an obvious mistake authorized by or notified to
`this Authority under Rule 91 (Rule 437s. 1(b)).
`
`
`
` 3. [] With regard to any nucleotide and/or amino acid sequence disclosed in the international application, this opinion has been
`established on the basis of a sequencelisting:
`
`
`a. [| forming part of the international applicationasfiled:
`C] in the form of an Annex C/ST.25 textfile.
`
`
`CL] on paperorin the form of an imagefile.
`
`
`furnished together with the international application under PCT Rule 13¢er.1(a) for the purposesof international!
`
`
`search only in the form of an Annex C/ST.25 textfile.
`
`
`
`
`c. [| furnished subsequentto the international filing date for the purposes of international search only:
`[__]
`in the form of an Annex C/ST.25text file (Rule 13ser.1(a)).
`
`
` [] on paperorin the formof an imagefile (Rule 13/er.1(b) and Administrative Instructions, Section 713).
` 4, [] In addition, in the case that more than one version or copy of a sequencelisting has been filed or furnished, the required
`~~
`statements that the information in the subsequent or additional copies is identical to that forming part of the application as
`
`filed or does not go beyond the applicationas filed, as appropriate, were furnished.
`
`b.
`
` 5. Additional comments:
`
`Form PCT/ISA/237 (Box No. 1) (revised January 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`Box No. IV
`
`Lackof unity of invention
`
`International application No.
`
`PCT/US2020/037042
`
`Y. x In responseto the invitation (Form PCT/ISA/206) to pay additional fees the applicant has, within the applicable time limit:
`[] paid additional fees.
`[] paid additional fees under protest and, where applicable, the protest fee.
`[] paid additional fees underprotest but the applicable protest fee was not paid.
`[x]
`not paid additional fees.
`2. [| This Authority found that the requirement of unity of invention is not complied with and chose notto invite the applicant to
`pay additionalfees.
`
`3. This Authority considers that the requirement of unity of invention in accordance with Rule 13.1, 13.2 and 13.3 is
`[| complied with.
`
`not complied with for the following reasons:
`
`<See Supplemental Box>
`
`4.
`
`Consequently, this opinion has been established in respect of the following parts of the international application:
`[| all parts.
`
`the parts relating to claims Nos. 1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, 69
`
`Form PCT/ISA/237 (Box No. IV)(revised January 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`International application No.
`PCT/US2020/037042
`
`Box No. V
`
`Reasoned statement under Rule 43is.1(a)(i) with regard to novelty, inventive step and industrial applicability;
`citations and explanations supporting such statement
`
`miosis (Kaufman Para. [0023]; Para. (0024); Para. [(0003)).
`
`| Regarding claim 1, Nolan discloses a method for treating and ameliorating or reducing at least one refractive error of a pseudophakic
`| patient selected from the group consisting of myopia, hyperopia, and astigmatism (Abstract, method for improving vision ... improve the
`visual acuity in the human patient ‘Para. [0032], treatment for myopia; Para. [0045], the method ofthis invention can be successfully used
`to treat diminished visual acuity in phakic as well as pseudophakic patients ... this method can be successfully used to treat patients with
`artificial and rigid intraocular lenses (IOL's). IOL's are inserted at the time of cataract surgery), comprising: administering to at least one
`eye of the patient an ophthalmic preparation (Para. [0020], topical application of an acetylcholine esterase (AChE)inhibitor to the patient
`Para. [0060], For the treatment and prevention congenital and acquired color vision blindness, treatment of ocular hypertension, glaucoma
`and progressive of myopia and potentiation of best visual acuity it can be applied in one or both eyes) comprising: a therapeutically
`effective amount of one drug (Para. [0019], topical administration of acetylcholine esterase inhibitors in a concentration effective to
`improve eye vision in humans); methods oftreating at least one refractive error in a patient that has had ocular surgery thereof (Para.
`[0045], the method ofthis invention can be successfully used to treat diminished visual acuity in phakic as well as pseudophakic patients
`... this method can be successfully used to treat patients with artificial and rigid intraocular lenses (IOL's). |OL’s are inserted at the time of
`cataract surgery); and methods for treating and ameliorating or reducing at least one refractive error of a pseudophakic patient selected
`from the group consisting of myopia, hyperopia, and astigmatism thereof (Para. [0032], treatment for myopia; Para. [0045], the method of
`this invention can be successfully used to treat diminished visual acuity in phakic as well as pseudophakic patients ... this method can be
`successfully usedto treat patients with artificial and rigid intraocular lenses (IOL's). |OL’s are inserted at the time of cataract surgery), but
`fails to explicitly disclose a therapeutically effective amount of one parasympathomimetic drug, wherein the parasympathomimetic drug is
`carbachol, or pharmaceutically acceptable salts thereof; and a therapeutically effective amount of an alpha agonist or an alpha antagonist,
`wherein the an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically acceptable salts thereof. However, Kaufmanis also
`in the field of methods for treating refractive errors in patients (Kaufman, Abstract; Claim 41) and teaches a therapeutically effective
`} amount of one parasympathomimetic drug, wherein the parasympathomimetic drug is carbachol, or pharmaceutically acceptable salts
`thereof (Kaufman Para. [0020], a therapeutically effective amount of an ophthalmic preparation comprising one or more
`Pparasympathomimetic drugs or cholinesterase inhibitors, or pharmaceutically acceptable salts thereof, and one or more alpha agonists or
`antagonists, or pharmaceutically acceptable salts thereof ... applying to the one or both eyes of the patient a therapeutically effective
`amount of carbachol, or pharmaceutically acceptable salts thereof; Para. (0012), the one or more parasympathomimetic drugsis
`pilocarpine, or carbachol, or their pharmaceutically acceptable salts); and a therapeutically effective amount of an alpha agonist or an
`alpha antagonist, wherein the an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically acceptable salts thereof (Kaufman
`Para, [0020], a therapeutically effective amount of an ophthalmic preparation comprising one or more parasympathomimetic drugs or
`cholinesterase inhibitors, or pharmaceutically acceptable salts thereof, and one or more alpha agonists or antagonists, or pharmaceutically
`acceptable salts thereof ... applying to the one or both eyes of the patient ... an effective amount of brimonidine; Para. [0012], the one or
`more alpha agonistsis brimonidine, or a pharmaceutically acceptable salt thereof). It would have been obvious to one of ordinary skill in
`the art at the time of the invention to modify Nolan with the teachings of Kaufman. The motivation for doing so would have beento
`incorporate an acetylcholine receptor agonist and an alpha androgenic agonist and thereby, in combination, create optically beneficial
`
`Statement
`
`Novelty (N)
`
`Inventive step (IS)
`
`Industrial applicability (IA)
`
`Claims
`Claims
`
`1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, 69
`None
`
`Claims
`Claims
`
`Claims
`Claims
`
`None
`1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, 69
`
`1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, 69
`None
`
`Citations and explanations:
`2.
`Claims 1-6, 11-20, 25-32, 48, 49, 54-59, 63-67, and 69 have been analyzed subjectto the restriction that the claims read on a method for
`treating and ameliorating or reducing at least one refractive error of a pseudophakic patient selected from the group consisting of myopia,
`hyperopia, and astigmatism, comprising: administering to at least one eye of the patient an ophthalmic preparation comprising: a
`therapeutically effective amount of one parasympathomimetic drug, wherein the parasympathomimetic drug is carbachol, or
`pharmaceutically acceptable salts thereof; and a therapeutically effective amount of an alpha agonist or an alpha antagonist, wherein the
`an alpha agonist or an alpha antagonist brimonidine, or pharmaceutically acceptable salts thereof; methods of treating at least one
`refractive error in a patient that has had ocular surgery thereof; and methods for treating and ameliorating or reducing at least one
`refractive error of a pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism thereof.
`
`Claims 1-6, 11-13, 15-20, 25-27, 29-32, 54, 55, 63-66, and 69 lack an inventive step under PCT Article 33(3) as being obvious over Nolan
`in view of Kaufman.
`
`Form PCT/ISA/237 (Box No. V) (revised January 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`WRITTEN OPINION OF THE
`INTERNATIONAL SEARCHING AUTHORITY
`
`Box No. VIII Certain observations on the international application
`
`International application No.
`
`PCT/US2020/037042
`
`The following observations on the clarity of the claims, description, and drawings or on the question whether the claims are fully
`supported by the description, are made:
`
`Claim 41 is objected to under PCT Rule 66.2(a)(v) as lacking clarity under PCT Article 6 becauseclaim 41 is indefinite for the following
`reason(s):
`
`Regarding claim 41, the claim depends from claim 78, which does not exist. Herein, claim 41 has been analyzed as dependentfrom claim
`40 to provide sufficient antecedent basis for "phentolamine", as best interpreted.
`
`Form PCT/ISA/237 (Box No.VIII) (revisedJanuary 2019)
`
`

`

`PCT/US2020/037042 16.10.2020
`
`WRITTEN OPINION OF THE
`
`INTERNATIONAL SEARCHING AUTHORITY PCT/US2020/037042
`
`International application No.
`
`Supplemental Box
`
`In case the space in any of the preceding boxesis not sufficient.
`Continuationof:
`
`<Box No. IV Lack of unity of invention>
`
`This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive
`concept under PCT Rule 13.1. In orderfor all inventions to be examined, the appropriate additional examination fees need to be paid.
`
`Group I+: claims 1-32, 48, 49, 54-59, and 63-69 are drawn to methods for treating and ameliorating or reducing at least one refractive error
`of a pseudophakic patient selected from the group consisting of myopia, hyperopia, and astigmatism, and methods oftreating at least one
`refractive error in a patient that has had ocular surgery.
`
`Group II: claims 33-47, 50-53, and 60-62 are drawn to methods of crea