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`Title of Invention
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`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`The application data sheet is part of the provisional or nonprovisional application for which it is being submitted. The following form contains the
`bibliographic data arranged in a format specified by the United States Patent and Trademark Office as outlined in 37 CFR 1.76.
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`Secrecy Order 37 CFR 5.2
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`Inventor Information:
`
`
`Inventor
`1
`Legal Name
`
`Prefix Given Name Family Name Middle Name
`
`
`Daniel
`A.
`Gamache
`
`
`
`Residence Information (Select One) ® US Residency 0 Non US Residency 0 Active US Military Service
`
`
`
`
`Mailing Address of Inventor:
`
`Address 1
`5610 Huntenyood Lane
`
`Address 2
`
` City Arlington I StatelProvince I TX
`
`
`
`
`
`Postal Code 76017 I Country i US
`
`
`
`
`Inventor
`2
`
`Prefix Given Name
`Laman
`
`Legal Name
`
`
`
`
`Residence Information (Select One) © US Residency 0 Non US Residency 0 Active US Military Service
`
`
`
`
`US
`Country of Residence I
`TX
`State/Province
`Fort Worth
`City
`
`
`Middle Name
`
`Family Name
`Alani
`
`Mailing Address of Inventor:
`
`——
`Tx
`
`us
`
`Family Name Malay
`
`
`Inventor
`3
`Legal Name
`
`Prefix Given Name
`
`Middle Name
`
`Ghosh
`Residence Information (Select One) (9 US Residency 0 Non US Residency 0 Active US Military Service
`
`
`
`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 1
`
` _
`
`_
`Application Data Sheet 37 CFR 1.76
`
`
`Attorney Docket Number
`PAT903988—US—CNT
`
`Application Number
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 1
`
`
`
`PTO/AIN14 (12-13)
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`PAT903988-U S—CNT
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`Attorney Docket Number
`
` _
`
`_
`Application Data Sheet 37 CFR 1.76
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`US
`TX
`State/ProvinceFort WorthCity Country of Residence i
`
`
`
`
`
`
`
`
`Mailing Address of Inventor:
`
`Address 1
`4221 Kirkland Court
`
`Address 2
`
`Fort Worth
`StatelP rovi nce
`TX
`City
`Postal Code
`
`Country i
`
`Remove
`
`4
`Inventor
`Legal Name
`
`Prefix Given Name
`Middle Name
`Family Name
`Galan
`Javier
`Francisco
`
`Residence Information (Select One) 0 US Residency
`Country of Residence i
`
`(9 Non US Residency 0 Active US Military Service
`
`
`
`
`
`
`
`Mailing Address of Inventor:
`
`Address 1
`c/dels Pins, 19
`
`Address 2
`
`Teia
`City
`
`I StatelProvince
`Postal Code
`Country i
`
`5
`
`
`
`
`
`Inventor
`Legal Name
`
`Prefix Given Name
`Middle Name
`Family Name
`
`
`
`Nuria
`
`Carreras
`
`
`
`Perdiguer
`
`
`
`Residence Information (Select One) 0 US Residency 6) Non US Residency 0 Active US Military Service
`
`City
`Barcelona
`Country of Residence i
` IE5
`
`
`Mailing Address of Inventor:
`Address 1
`c/Armadeu, 6
`
`Caldes de Montbui
`Address 2
`
`Barcelona
`City
` I StatelProvince
`
`08140
`ES
`Postal Code
` I Country i
`
`
`Inventor
`6
`
`Legal Name
`
`Prefix Given Name
`
`Middle Name Family Name
`N.
`Onkar
`Singh
`EFS Web 2.2.11
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`
`
`
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`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 2
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 2
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`
`PTO/AlA/14 (12-13)
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`Application Data Sheet 37 CFR 1.76
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`Attorney Docket Number
`PAT903988-US-CNT
`
`Application Number
`
`
`
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`Residence Information (Select One) @ US Residency 0 Non US Residency 0 Active US Military Service
`
`
`Mailing Address of Inventor:
`Address 1
`5606 Rachel Court
`
`Address 2
`
`
`City
`
`Arlington
`
`StatelP rovince
`
`TX
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`
`Postal Code
`Country i
`
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`patent.docketing@alcon.com
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`Application Information:
`Title of the Invention
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`Attorney Docket Number PAT903988—US-CNT
`Small Entity Status Claimed
`|:|
`Application Type
`Nonprovisional
`
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`
`Subject Matter
`Utility
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`Total Number of Drawing Sheets (if any)
`5
`Suggested Figure for Publication (if any)
`1
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`Novartis AG Exhibit 2001
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`IPR2020-00295
`
`Page 3
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 3
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`PTO/AlA/14 (12-13)
`Approved for use through 01/31/2014. OMB 0651-0032
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`Title of Invention
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`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`Attorney Docket Number PAT903 988-US-CNT
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`Application Data Sheet 37 CFR 1.76
`Application Number
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`Publication Information:
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` Request Early Publication (Fee required at time of Request 37 CFR 1.219)
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`I hereby request that the attached application not be published under
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`35 U.S.C. 122(b) and certify that the invention disclosed in the attached application has not and will not be the
`:I
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`Prior Application Status
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`Application Number
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`Continuation of
`13475607
`2012—05—1 8
`
`
`
`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
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`
`
`
`
`Application Number
`
`Continuity Type
`
`Prior Application Number
`
`Filing Date (YYYY-MM-DD)
`
`13475607
`
`Claims benefit of provisional
`
`61487789
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`2011-05-19
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`Novartis AG Exhibit 2001
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`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
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`PTO/AlA/14 (12-13)
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`Application Data Sheet 37 CFR 1.76
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`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
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`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
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`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
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`Novartis AG Exhibit 2001
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`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
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`If checked, the undersigned hereby grants the USPTO authority to provide the European Patent Office (EPO),
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`organization Name
`Alcon Research, Ltd.
`
`Address 1
`
`6201 South Freeway
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`Address 2
`IP Legal
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`
`City
`Fort Worth
`StateIProvince
`TX
`
`Country i us
`Postal Code
`76134-2099
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`(817) 551—8793
`Fax Number
`
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`2014—06—13
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`IPR2020-00295
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`terminated and which application is referenced by either a published application, an application open to public inspections or an issued
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`USPTO becomes aware of a violation or potential violation of law or regulation.
`
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`EFS Web 2.2.11
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`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
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`Page 9
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`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 9
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`
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`Atty. Docket N0.: PAT903988-US-CNT
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`HIGH CONCENTRATION OLOPATADINE
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`OPHTHALMIC COMPOSITION
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`Cross-Reference to Related Application
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`This application is a continuation application of US. Utility Patent
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`Application No. 13/475,607 filed May 18, 2012 (now allowed), which claims
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`priority based on US. Provisional Patent Application Serial No. 61/487,789 filed
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`May 19, 2011 and US. Provisional Patent Application Serial No. 61/548,957 filed
`October 19, 2011.
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`Technical Field of the Invention
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`The present
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`invention relates to an ophthalmic composition containing a
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`relatively high concentration of olopatadine. More particularly,
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`the present
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`invention relates to an ophthalmic aqueous solution containing a relatively high
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`concentration of solubilized olopatadine wherein the solution is capable of
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`providing enhanced relief from symptoms of ocular allergic disorders (e.g.,
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`conjunctivitis) in the early phase, the late phase or preferably both phases.
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`Background of the Invention
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`Individuals suffering from allergic conjunctivitis experience symptoms such
`as ocular irritation, itchiness, redness and the like.
`1t has been found that these
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`symptoms are significantly reduced using topical ophthalmic solutions containing
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`olopatadine.
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`Such solutions are sold under the tradenames PATANOL® and
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`PATADAY®, which are both commercially available from Alcon Laboratories,
`Inc, Fort Worth, TX.
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`These marketed solutions were generally believed to be the most efficacious
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`products known for addressing symptoms of allergic conjunctivitis. Surprisingly,
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`and as discussed further below,
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`it has been discovered that relatively high
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`concentration solutions of olopatadine provide significantly improved reduction of
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`late phase ocular allergic conjunctivitis symptoms in addition to relief from early
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`phase symptoms. Even more surprising,
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`it has been discovered that such high
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`concentrations of olopatadine also provide significantly improved reduction of
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`redness in the early phase. Further,
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`it has been discovered that enhanced relief
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`Novartis AG Exhibit 2001
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`Ayla Pharma LDC v. Novartis AG
`IPR2020-00295
`
`Page 10
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`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 10
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`
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`Atty. Docket N0.: PAT903988-US-CNT
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`from these early and late phase symptoms can be achieved through 011cc a day
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`dosing of relatively high concentration olopatadine solution as opposed to greater
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`dosing frequencies.
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`The discovery of improved reduction of early and late phase symptoms is
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`quite significant and desirable for individuals suffering from allergic conjunctivitis.
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`Generally, these discoveries can provide patients greater relief from itching and
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`provide better aesthetic appearance to the eye. Further. avoiding more frequent
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`dosing is more convenient for patients and helps assure better compliance. Further
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`yet, improved early prevention and/or reduction of redness is particularly desirable
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`since patients generally have a desire to keep as much redness out of their eyes as
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`possible.
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`The discovery that relatively high concentration solutions of olopatadine can
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`relieve late phase ocular allergic conjunctivitis symptoms provides hope to
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`sufferers of ocular allergic conjunctivitis that a single dose of olopatadine per day
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`could provide a substantial degree of full day relief from their symptoms.
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`However, the development of a multi-dose ophthalmic solution that includes high
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`concentrations of olopatadine necessary to achieve desired levels of efficacy is
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`extremely difficult and complex.
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`Solubilizing high concentrations of olopatadine in a stable manner has
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`proven difficult by itself. Olopatadine, by itself, is only soluble in water (pH about
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`7.0) at room temperature up to a concentration of about 0.18 w/v%. However, it is
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`desirable to achieve solubilization of much higher concentrations of olopatadine in
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`an effort to treat late phase allergic conjunctivitis.
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`Solubilizing such higher concentrations of olopatadine has proven difficult.
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`As one example, excipients
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`such as polyethylene glycol
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`(PEG) 400 and
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`polyvinylpyrrolidone (PVP), when used at reasonably desirable concentrations,
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`have proven incapable,
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`alone or
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`in combination, of solubizing sufficient
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`concentrations of olopatadine in compositions having approximately neutral pH.
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`Thus, innovation is required to solubilize a sufficient concentration of olopatadine.
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`In the process of such innovation,
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`is has been discovered that higher
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`molecular weight PEGs such as PEG 6000 can significantly enhance solubility of
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`olopatadine. However, such PEGs cause risk of discomfort when administered to
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`Ayla Pharma LDC V. Novartis AG
`IPR2020-00295
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`Page 11
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`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 11
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`Atty. Docket N0.: PAT903988-US-CNT
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`humans.
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`It has also been discovered that cyclodextrins, such as hydroxypropyl-y-
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`cyclodextrin, hydroxypropyl-B-cyclodextrin and sulfoalkyl ether-B-cyclodextrin,
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`have the ability to solubilize significantly higher concentrations of olopatadine.
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`However, use of undesirably high concentrations of cyclodextrins has been found
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`to reduce olopatadine efficacy and/or preservation efficacy of solutions. As such,
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`still further innovation was needed to create a desirable olopatadine formulation
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`that not only solubilized sufficient amounts of olopatadine, but also allowed the
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`formulation to achieve other desirable pharmaceutical characteristics.
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`Thus, the present invention is directed at an ophthalmic composition that can
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`provide high concentrations of olopatadine topically to the eye. Further, the present
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`invention is directed to such a composition wherein the olopatadine is solubilized in
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`solution in a stable manner, the composition exhibits consistent efficacy against late
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`phase symptoms of allergic conjunctivitis,
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`the composition exhibits sufficient
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`antimicrobial activity to provide desired levels of preservation efficacy or any
`combination thereof.
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`Summary of the Invention
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`The present invention is directed to an ophthalmic composition for treatment
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`of allergic conjunctivitis.
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`The composition will
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`include a relatively high
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`concentration of olopatadine, preferably at least 0.67 w/v % olopatadine, preferably
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`dissolved in solution. The composition Will typically include a cyclodextrin, and
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`more particularly. a y-cyclodextrin derivative and/or a B-cyclodextrin derivative to
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`aid in solubilizing the olopatadine.
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`The cyclodextrin derivative is preferably
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`hydroxypropyl-y-cyclodextrin (HP-y-CD), hydroxypropyl- B-cyclodextrin (HP- [3-
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`CD),
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`sulfoalkyl ether B-cyclodextrin (SAE- B-CD)(e.g.,
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`sulfobutyl ether
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`[3-
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`cyclodextrin (SBE-B-CD». or a combination thereof.
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`The composition will
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`typically include a lactam polymer (e.g., polyvinylpyrrolidone (PVP)) to aid in the
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`solubilization of the olopatadine. The composition will also typically include a
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`polyether (e.g., polyethylene glycol (PEG)) for enhancing solubility and/or aiding
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`in achieving the desired tonicity.
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`It is generally desirable for the composition to be
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`disposed in an eyedropper, have a pH of 5.5 to 8.0, to have an osmolality of 200 to
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`450,
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`to have a viscosity of 10 to 200 cps or any combination thereof. The
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`composition will also typically include a preservative to allow the composition to
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`achieve United States and/or European Pharmacopeia preservation standards.
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`Preferred preservatives include a polymeric quaternary ammonium compound, such
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`-3-
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`Novartis AG Exhibit 2001
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`Ayla Pharma LDC V. Novartis AG
`IPR2020-00295
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`Page 12
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`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 12
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`
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`Atty. Docket N0.: PAT903988-US-CNT
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`as polyquaternium-l, and benzalkonium chloride. The composition also typically
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`includes borate and/or polyol to aid in achieving desired preservation.
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`The present invention also contemplates a method of treating ocular allergy
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`symptoms. The method will include topically applying a composition having a
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`defined combination of the characteristics described above to an eye of a human.
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`This step of topically applying the composition preferably includes dispensing an
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`eyedrop from an eyedropper.
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`Brief Description of the Drawings
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`FIG. 1 is a graph of mean conjunctival redness determined by a conjunctival
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`allergen challenge (CAC) at 27 minutes.
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`FIG. 2 is a graph of mean conjunctival redness determined by a conjunctival
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`allcrgcn challcngc (CAC) at16 hours.
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`FIG. 3 is a graph of mean total rcdncss determined by a conjunctival
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`allergen challenge (CAC) at 24 hours.
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`FIG. 4 is a graph of mean ocular itching determined by a conjunctival
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`allcrgcn challcngc (CAC) at 24 hours.
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`FIG. 5 is a graph of mean conjunctival rcdncss dctcrminc by a conjunctival
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`allergen challenge (CAC) at 24 hours.
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`Detailed Description of the Invention
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`The present invention is predicated upon the provision of an ophthalmic
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`composition for treatment of allergic conjunctivitis. The ophthalmic composition is
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`preferably an aqueous solution. The ophthalmic composition includes a relatively
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`high conce