PTOVAIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respond to a collection of information unlessit contains a valid OMB control number.
`
`. Attorney Docket Number|PAT903988-US-CNT.
`
`
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`Title of Invention|HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`
`
`
`The application data sheetis part of the provisional or nonprovisional application for whichit is being submitted. The following form contains the
`bibliographic data arrangedin a format specified by the United States Patent and Trademark Office as outlined in 37 CFR 1.76.
`This document may be completed electronically and submitted to the Office in electronic format using the Electronic Filing System (EFS) or the
`document may be printed and included in a paperfiled application.
`
`
`Secrecy Order 37 CFR 5.2
`
`
`
`
`
`37 CFR 5.2 (Paper filers only. Applications that fall under Secrecy Order may notbefiled electronically.}
`
`Portionsorall ofthe application associated with this Application Data Sheet mayfall under a Secrecy Order pursuantto
`
`|
`
`
`
`
`Inventor Information:
`
`
`Inventor
`1
`Legal Name
`Prefix; Given Name Family Name Middle Name
`
`
`Daniel
`A.
`Gamache
`
`ResidenceInformation (Select One) () US Residency
`
`(©) NonUS Residency
`
`() Active US Military Service
`
`
`
`
`
`
`Mailing Addressof Inventor:
`
`
`
` Address1 5610 Hunterwood Lane
`
`
`
`Address 2
`
`
` City Arlington | State/Province | TX
`
`
`
`Postal Code 76017 | Country i US
`
`
`
`
`
`Inventor
`2
`
`Legal Name
`
`
`
`Family Name
`Prefix) Given Name
`Laman
`Alani
`
`Residence Information (Select One)
`(@) US Residency
`©) NonUS Residency
`() Active US Military Service
`
`
`
`
`
`
`City|Fort Worth State/Province|TX Country of Residence i|US
`
`
`Middle Name
`
`Mailing Address of Inventor:
`Address1
`6809 Shadow Creek Court
`
`Address 2
`
`City
`
`Fort Worth
`
`State/Province
`
`
`
`
`Inventor
`3
`Legal Name
`
`Prefix) Given Name
`Malay
`
`Middle Name
`
`Family Name
`Ghosh
`
`ResidenceInformation (Select One)
`
`(e) US Residency
`
`©) NonUS Residency
`
`() Active US Military Service
`
`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 1
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 1
`
`

`

`4
`Inventor
`Legal Name
` Prefix! Given Name Middle Name
`Family Name
`Francisco
`Javier
`Galan
`
`
`
`
`
`
`
`
`
`@) Non US Residency
`Residence Information (Select One) () US Residency
`Country of Residencei
`
`(©) Active US Military Service
`
`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`PAT903988-US-CNT
`
`oo
`Attorney Docket Number
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`
`
`
`
`
`Fort Worth USCity State/Province|TX Country of Residence|
`
`
`
` Mailing Addressof Inventor:
` 4221 Kirkland Court
`Address 1
`Address 2
`
`Fort Worth
`
`City
`Postal Code
`
`State/Province
`
`TX
`
`Remove
`
`EFS Web2.2.11
`
`Mailing Addressof Inventor:
`
`Address1
`c/dels Pins, 19
`
`Address 2
`
`
`City
`Postal Code
`
`Teia
`
`State/Province
`
`5
`
`Remove
`
`Inventor
`Legal Name
`
`Family Name
`Nuria
`Carreras
`
` Prefix Given Name Middle Name
`
` Barcelona
`
`
`
`Residence Information (Select One) () US Residency
`@) NonUS Residency
`() Active US Military Service
` City
` Country of Residencei | ES
`
`
`Perdiguer
`
`Mailing Addressof Inventor:
`Address 1
`
`c/Armadeu, 6
`Caldes de Montbui
`
`Address 2
`
`City
`
`Inventor
`
`6
`
` Barcelona
`| State/Province Postal Code
`| Country i
`
`
`
`08140
`
`ES
`
`Remove
`
`Legal Name
` Prefix} Given Name
`Middle Name
`Family Name
` Onkar
`N.
`Singh
`
`
`
`
`
`
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 2
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 2
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`Residence Information (Select One) () US Residency
`(©) NonUS Residency
`() Active US Military Service
`
`
`
`Mailing Addressof Inventor:
`Address1
`5606 Rachel Court
`
`Address 2
`
`
`TX
`State/Province
`Arlington
`City
`Postal Code
`
`
`generatedwithin this form by selecting the Add button.
`
`All
`
`Inventors Must Be Listed - Additional
`
`Inventor Information blocks may be
`
`CorrespondenceInformation:
`
`Enter either Customer Number or complete the CorrespondenceInformation section below.
`
`For further information see 37 CFR 1.33(a).
`
`[_] An Addressis being provided for the correspondenceInformation of this application.
`Customer Number
`26356
`
`
`Email Address
`patent.docketing@alcon.com
`
`Application Information:
`Title of the Invention
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`Attorney Docket Number| PAT903988-US-CNT
`Small Entity Status Claimed
`[_]
`Application Type
`Nonprovisional
`
`Subject Matter
`
`Utility
`
`
`
`
`
`Total Number of Drawing Sheets(if any) Suggested Figure for Publication {if any)|15
`
`
`
`
`Filing By Reference:
`Only complete this section whenfiling an application by reference under 35 U.S.C. 111(c) and 37 CFR 1.57(a). Do not complete this section if
`application papers including a specification and any drawingsare being filed. Any domestic benefit or foreign priority information must be
`provided in the appropriate section(s) below(i.e., “Domestic Benefit/National Stage Information” and “Foreign Priority Information’).
`
`For the purposesofa filing date under 37 CFR 1.53(b), the description and any drawingsof the present application are replaced by this
`reference to the previouslyfiled application, subject to conditions and requirements of 37 CFR 1.57(a).
`
`
`
`filed application
`
`Application numberof the previously
`
`Filing date (YYYY-MM-DD)
`
`Intellectual Property Authority or Country i
`
`
`
`EFS Web2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 3
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 3
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Number
`Title of Invention
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`Application Data Sheet 37 CFR 1.76
`
`
`
`Publication Information:
`
`
`
` Request Early Publication (Fee required at time of Request 37 CFR 1.219)
`
`[]
`
`Request Not to Publish. | hereby request that the attached application not be published under
`35 U.S.C. 122(b) and certify that the invention disclosed in the attached application has not and will not be the
`subject of an application filed in another country, or under a multilateral international agreement, that requires
`publication at eighteen monthsafterfiling.
`
`
`Representative Information:
`
`
`Representative information should be provided for all practitioners having a power of attorney in the application. Providing
`this information in the Application Data Sheet does not constitute a powerof attorney in the application (see 37 CFR 1.32).
`Either enter Customer Number or complete the Representative Name section below.If both sections are completed the customer
`Numberwill be used for the Representative Information during processing.
`
`
`
`Please Select One: ©) Limited Recognition (37 CFR 11.9) (®) Customer Number ©) US PatentPractitioner
`
`
`
`Customer Number
`26356
`
`
`Domestic Benefit/National Stage Information:
`
`This section allows for the applicant to either claim benefit under 35 U.S.C. 119(e), 120, 121, or 365(c) or indicate National Stage
`entry from a PCT application. Providing this information in the application data sheet constitutes the specific reference required
`by 35 U.S.C. 119(e) or 120, and 37 CFR 1.78.
`When referring to the current application, please leave the application number blank.
`
`Prior Application Status|Pending
`
`Application Number
`Continuity Type
`Prior Application Number
`Filing Date (YYYY-MM-DD}
`
`Continuation of
`13475607
`2012-05-18
`
`Prior Application Status|Expired
`
`Application Number
`Continuity Type
`Prior Application Number
`Filing Date (YYYY-MM-DD)
`
`
`
`
`
`13475607
`
`Claims benefit of provisional
`
`61548957
`
`2011-10-19
`
`Prior Application Status|Expired
`
`Application Number
`Continuity Type
`Prior Application Number
`Filing Date (YYYY-MM-DD})
`
`13475607
`Claims benefit of provisional
`61487789
`2011-05-19
`
`Additional Domestic Benefit/National Stage Data may be generated within this form
`by selecting the Add button.
`
`
`Foreign Priority Information:
`
`EFS Web2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 4
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 4
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Data Sheet 37 CFR 1.76
`Application Number
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`
`
`
`This section allows for the applicant to claim priority to a foreign application. Providing this information in the application data sheet
`constitutes the claim for priority as required by 35 U.S.C. 119(b) and 37 CFR 1.55{d). When priority is claimed to a foreign application
`that is eligible for retrieval under the priority document exchange program (PDX) ithe information will be used by the Office to
`automatically attempt retrieval pursuant to 37 CFR 1.55(h)\(1) and (2). Under the PDX program, applicant bears the ultimate
`responsibility for ensuring that a copy of the foreign application is received by the Office from the participating foreign intellectual
`property office, or a certified copy of the foreign priority application is filed, within the time period specified in 37 CFR 1.55(g)(1).
`
`
`Application Number
`Country |
`Filing Date (YYYY-MM-DD)
`Access Codel(if applicable)
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`
`Statement under 37 CFR 1.55 or 1.78 for AIA (First Inventor to File) Transition
`Applications
`
`
`This application (1} claims priority to or the benefit of an application filed before March 16, 2013 and (2) also
`contains, or contained at any time, a claim to a claimed invention that has an effective filing date on or after March
`16, 2013.
`NOTE: Byproviding this statement under 37 CFR 1.55 or 1.78, this application, with a filing date on or after March
`
`16, 2013, will be examined underthe first inventor to file provisions of the AIA.
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`Authorization to Permit Access:
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`Authorization to Permit Access to the Instant Application by the Participating Offices
`
`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 5
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 5
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`If checked, the undersigned hereby grants the USPTO authority to provide the European Patent Office (EPO),
`the Japan Patent Office (JPO), the KoreanIntellectual Property Office (KIPO), the World Intellectual Property Office (WIPO),
`and any other intellectual property offices in which a foreign application claiming priority to the instant patent application
`is filed access to the instant patent application. See 37 CFR 1.14(c) and (h). This box should not be checkedif the applicant
`does not wish the EPO, JPO, KIPO, WIPO,or otherintellectual property office in which a foreign application claimingpriority
`to the instant patent applicationis filed to have accessto the instant patent application.
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`In accordance with 37 CFR 1.14(h)(3), access will be provided to a copyof the instant patent application with respect
`to: 1) the instant patent application-as-filed; 2) any foreign application to which the instant patent application
`claims priority under 35 U.S.C. 119({a)-(d) if a copy of the foreign application that satisfies the certified copy requirement of
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`Providing assignmentinformation in this section does not substitute for compliance with any requirementof part 3 of Title 37 of CFR
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`If the applicant is the inventor (or the remaining joint inventor or inventors under 37 CFR 1.45), this section should not be completed.
`The information to be provided in this section is the name and addressof the legal representative whois the applicant under 37 CFR
`1.43; or the name and addressof the assignee, person to whom the inventoris under an obligation to assign the invention, or person
`who otherwise shows sufficient proprietary interest in the matter who is the applicant under 37 CFR 1.46.If the applicant is an
`applicant under 37 CFR 1.46 (assignee, person to whomthe inventoris obligated to assign, or person who otherwise showssufficient
`proprietary interest) together with one or more joint inventors, then the joint inventor or inventors whoare also the applicant should be
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`oO
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`Nameof the Deceased or Legally Incapacitated Inventor:
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`
`If the Applicant is an Organization check here.
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`
`Organization Name
`Alcon Research, Ltd.
`
`x
`
`Address 1
`
`6201 South Freeway
`
`Address 2
`IP Legal
`
`City
`Fort Worth
`State/Province
`TX
`
`
`Country || Us
`Postal Code
`76134-2099
`Phone Number
`(817) 551-8793
`Fax Number
`
`
`
`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 6
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 6
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`Email Address
`
`patent.docketing@alcon.com
`
`Add
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`
`1
`
`Complete this section if assignee information, including non-applicant assignee information, is desired to be included on the patent
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`publication as an applicant. For an assignee-applicant, complete this section only if identification as an assigneeis also desired on the
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`
`Remove
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`
`If the Assignee or Non-Applicant Assignee is an Organization check here. L]
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`:
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`selecting the Add button.
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`Signature:
`
`NOTE: This form must be signed in accordance with 37 CFR 1.33. See 37 CFR 1.4 for signature requirements and
`certifications
`
`
`Signature
`
`|/Scott A. Chapple, 46,287/
`
`Date (YYYY-MM-DD)|
`
`2014-06-13
`
`
`
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`Additional Signature may be generated within this form by selecting the Add button.
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`EFS Web2.2.11
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`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 7
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 7
`
`

`

`PTO/AIA/14 (12-13)
`Approvedfor use through 01/31/2014. OMB 0651-0032
`U.S. Patent and Trademark Office; U.S. DEPARTMENT OF COMMERCE
`Under the Paperwork Reduction Act of 1995, no persons are required to respondto a collection of information unless it contains a valid OMB control number.
`
`
`Attorney Docket Number|PAT903988-US-CNT
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
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`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`This collection of information is required by 37 CFR 1.76. The information is required to obtain or retain a benefit by the public which
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`EFS Web2.2.11
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`Novartis AG Exhibit 2001
`
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`
`Page 8
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 8
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`

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`CFR 1.14, as a routine use, to the public if the record wasfiled in an application which became abandonedor in which the proceedings were)
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`USPTO becomesaware of a violation or potential viclation of law or regulation.
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`EFS Web 2.2.11
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`Novartis AG Exhibit 2001
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`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
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`Atty. Docket No.: PAT903988-US-CNT
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`HIGH CONCENTRATION OLOPATADINE
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`OPHTHALMIC COMPOSITION
`
`Cross-Reference to Related Application
`
`This application is a continuation application of U.S. Utility Patent
`Application No. 13/475,607 filed May 18, 2012 (nowallowed), which claims
`priority based on U.S. Provisional Patent Application Scrial No. 61/487,789 filed
`May 19, 2011 and U.S. Provisional Patent Application Serial No. 61/548,957 filed
`October 19, 2011.
`
`Technical Field of the Invention
`
`invention relates to an ophthalmic composition containing a
`The present
`relatively high concentration of olopatadine. More particularly,
`the present
`invention relates to an ophthalmic aqueous solution containing a relatively high
`concentration of solubilized olopatadine wherein the solution is capable of
`providing enhanced relief from symptoms of ocular allergic disorders (e.g.,
`conjunctivitis) in the early phase, the late phase or preferably both phases.
`
`Background of the Invention
`
`Individuals suffering from allergic conjunctivitis experience symptoms such
`as ocular irritation, itchiness, redness and the like.
`It has been found that these
`symptomsare significantly reduced using topical ophthalmic solutions containing
`olopatadine.
`Such solutions are sold under the tradenames PATANOL® and
`PATADAY®, which are both commercially available from Alcon Laboratories,
`Inc., Fort Worth, TX.
`
`These marketed solutions were generally believed to be the most efficacious
`products known for addressing symptomsof allergic conjunctivitis. Surprisingly,
`and as discussed further below,
`it has been discovered that relatively high
`concentration solutions of olopatadine provide significantly improved reduction of
`late phase ocular allergic conjunctivitis symptoms in addition to relief from early
`phase symptoms. Even more surprising,
`it has been discovered that such high
`concentrations of olopatadine also provide significantly improved reduction of
`redness in the early phase. Further,
`it has been discovered that enhanced relief
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`Atty. Docket No.: PAT903988-US-CNT
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`from these carly and late phasc symptoms can be achicved through once a day
`dosing of relatively high concentration olopatadine solution as opposed to greater
`dosing frequencics.
`
`The discovery of improved reduction of early and late phase symptoms is
`quite significant and desirable for individuals suffering from allergic conjunctivitis.
`Generally, these discoveries can provide patients greater relief from itching and
`provide better aesthetic appearance to the eye. Further, avoiding more frequent
`dosing is more convenient for patients and helps assure better compliance. Further
`yet, improved early prevention and/or reduction of redness is particularly desirable
`since patients generally have a desire to keep as muchredness out of their eyes as
`possible.
`
`The discovery that relatively high concentration solutions of olopatadine can
`relicve late phasc ocular allergic conjunctivitis symptoms provides hope to
`sufferers of ocular allergic conjunctivitis that a single dose of olopatadine per day
`could provide a substantial degree of full day rclicf from their symptoms.
`However, the development of a multi-dose ophthalmic solution that includes high
`concentrations of olopatadine necessary to achicve desired levels of cfficacy is
`extremely difficult and complex.
`
`Solubilizing high concentrations of olopatadine in a stable manner has
`provendifficult by itsclf. Olopatadine, by itsclf, is only soluble in water (pH about
`7.0) at room temperature up to a concentration of about 0.18 w/v%. However,it is
`desirable to achicve solubilization of much higher concentrations of olopatadine in
`an effort to treat late phase allergic conjunctivitis.
`
`Solubilizing such higher concentrations of olopatadine has proven difficult.
`As one cxample, excipicnts
`such as polycthylene glycol
`(PEG) 400 and
`polyvinylpyrrolidone (PVP), when used at reasonably desirable concentrations,
`have proven incapable,
`alone or
`in combination, of solubizing sufficient
`concentrations of olopatadine in compositions having approximately neutral pH.
`Thus, innovation is required to solubilize a sufficient concentration of olopatadine.
`
`is has been discovered that higher
`In the process of such innovation,
`molecular weight PEGs such as PEG 6000 can significantly enhance solubility of
`olopatadine. However, such PEGscause risk of discomfort when administered to
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`Atty. Docket No.: PAT903988-US-CNT
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`It has also been discovered that cyclodextrins, such as hydroxypropyl-y-
`humans.
`cyclodextrin, hydroxypropyl-B-cyclodextrin and sulfoalkyl ether-B-cyclodextrin,
`have the ability to solubilize significantly higher concentrations of olopatadinc.
`However, use of undesirably high concentrations of cyclodextrins has been found
`to reduce olopatadine efficacy and/or preservation efficacy of solutions. As such,
`still further innovation was needed to create a desirable olopatadine formulation
`that not only solubilized sufficient amounts of olopatadine, but also allowed the
`formulation to achieve other desirable pharmaceutical characteristics.
`
`Thus, the present invention is directed at an ophthalmic composition that can
`provide high concentrations of olopatadine topically to the eye. Further, the present
`invention is directed to such a composition wherein the olopatadineis solubilized in
`solution in a stable manner, the composition exhibits consistent efficacy against late
`phase symptoms of allergic conjunctivitis,
`the composition exhibits sufficient
`antimicrobial activity to provide desired levels of preservation cfficacy or any
`combination thereof.
`
`Summary of the Invention
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`The present invention is directed to an ophthalmic composition for treatment
`of allergic conjunctivitis.
`The composition will
`include a relatively high
`concentration of olopatadine, preferably at least 0.67 w/v % olopatadine, preferably
`dissolved in solution. The composition will typically include a cyclodextrin, and
`more particularly, a y-cyclodextrin derivative and/or a B-cyclodextrin derivative to
`aid in solubilizing the olopatadinc.
`The cyclodextrin derivative is preferably
`hydroxypropyl-y-cyclodextrin (HP-y-CD), hydroxypropyl- B-cyclodextrin (HP- B-
`CD),
`sulfoalkyl ether B-cyclodextrin (SAE- B-CD)(c.g.,
`sulfobutyl cther B-
`cyclodextrin (SBE-B-CD)), or a combination thereof.
`The composition will
`typically include a lactam polymer(c.g., polyvinylpyrrolidone (PVP)) to aid in the
`solubilization of the olopatadine. The composition will also typically include a
`polyether(e.g., polyethylene glycol (PEG)) for enhancing solubility and/or aiding
`in achieving the desired tonicity.
`It is generally desirable for the composition to be
`disposed in an eyedropper, have a pH of 5.5 to 8.0, to have an osmolality of 200 to
`450,
`to have a viscosity of 10 to 200 cps or any combination thereof. The
`composition will also typically include a preservative to allow the composition to
`achieve United States and/or European Pharmacopeia preservation standards.
`Preferred preservatives include a polymeric quaternary ammonium compound, such
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`Atty. Docket No.: PAT903988-US-CNT
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`as polyquaternitum-1, and benzalkonium chloride. The composition also typically
`includes borate and/or polyol to aid in achieving desired preservation.
`
`The present invention also contemplates a method of treating ocular allergy
`symptoms. The method will include topically applying a composition having a
`defined combination of the characteristics described above to an eye of a human.
`This step of topically applying the composition preferably includes dispensing an
`eyedrop from an eyedropper.
`
`Brief Description of the Drawings
`
`FIG. 1 is a graph of mean conjunctival redness determined by a conjunctival
`allergen challenge (CAC) at 27 minutes.
`
`FIG. 2 is a graph of mean conjunctival redness determined by a conjunctival
`allergen challenge (CAC) at16 hours.
`
`FIG. 3 is a graph of mean total redness determined by a conjunctival
`allergen challenge (CAC)at 24 hours.
`
`FIG. 4 is a graph of mean ocular itching determined by a conjunctival
`allergen challenge (CAC) at 24 hours.
`
`FIG. 5 is a graph of mean conjunctival redness determine by a conjunctival
`allergen challenge (CAC)at 24 hours.
`
`Detailed Description of the Invention
`
`The present invention is predicated upon the provision of an ophthalmic
`composition for treatment of allergic conjunctivitis. The ophthalmic composition is
`preferably an aqueous solution. The ophthalmic composition includes a relatively
`high concentration of olopatadine solubilized in aqueous solution. The ophthalmic
`composition also includes a unique set of excipients for solubilizing the ol