PTO/AlA/14 (12-13)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
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`
`
`
`
`Title of Invention
`
`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.
`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 paper filed application.
`
`
`Secrecy Order 37 CFR 5.2
`
`Portions or all of the application associated with this Application Data Sheet may fall under a Secrecy Order pursuant to
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`
`
`37 CFR 5.2 (Paper filers only. Applications that fall under Secrecy Order may not be filed electronically.)
`
`
`
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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)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
`PAT903988-U S—CNT
`
`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
`
`
`
`
`
`
`
`
`
`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
`
`

`

`PTO/AlA/14 (12-13)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
`
`
`Application Data Sheet 37 CFR 1.76
`
`
`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
`
`
`Postal Code
`Country i
`
`generated within this form by selecting the Add button.
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`All
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`Inventors Must Be Listed - Additional
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`Correspondence Information:
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`Enter either Customer Number or complete the Correspondence Information section below.
`For further information see 37 CFR 1.33(a).
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`
`D An Address is being provided for the correspondence Information of this application.
`Customer Number
`26356
`
`
`
`patent.docketing@alcon.com
`
`Email Address
`
`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)
`5
`Suggested Figure for Publication (if any)
`1
`Filing By Reference:
`Only complete this section when filing an application by reference under 35 U.S.C. 111(c) and 37 CFR l.57(a). Do not complete this section if
`application papers including a specification and any drawings are 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 purposes of a filing date under 37 CFR I.53(b), the description and any drawings of the present application are replaced by this
`reference to the previously filed application, subject to conditions and requirements of 37 CFR I .57(a).
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`Intellectual Property Authority or Country i
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`Application number of the previously
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`Filing date (YYYY—MM—DD)
`
`filed application
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`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 3
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 3
`
`

`

`PTO/AlA/14 (12-13)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`Attorney Docket Number PAT903 988-US-CNT
`
`
`Application Data Sheet 37 CFR 1.76
`Application Number
`
`Publication Information:
`
`
` Request Early Publication (Fee required at time of Request 37 CFR 1.219)
`
`I hereby request that the attached application not be published under
`Request Not to PUbIlSh.
`35 U.S.C. 122(b) and certify that the invention disclosed in the attached application has not and will not be the
`:I
`subject of an application filed in another country, or under a multilateral international agreement, that requires
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`publication at eighteen months after filing.
`
`
`
`Representative Information:
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`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 power of attorney in the application (see 37 CFR 1.32).
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`Please Select One: 0 US Patent Practitioner 0 Limited Recognition (37 CFR 11.9) (9 Customer Number
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`Customer Number 26356
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`Domestic Benefithational Stage Information:
`This section allows for the applicant to either claim benefit under 35 U.S.C. 119(e), 120, IZI, 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. l 19(e) or 120, and 37 CFR 1.78.
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`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—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
`
`
`
`
`
`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 Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 4
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 4
`
`

`

`PTO/AlA/14 (12-13)
`Approved for 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 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 PBX 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 ofthe foreign priority application is filed, within the time period specified in 37 CFR 1.55(g)(1).
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`
`Application Number
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`Statement under 37 CFR 1.55 or 1.78 for AIA (First Inventor to File) Transition
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`Applications
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`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
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`16, 2013.
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`NOTE: By providing 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 under the 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
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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
`
`Page 5
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 5
`
`

`

`PTO/AIN14 (12-13)
`Approved for 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 unless it contains a valid OMB control number.
`
`Application Data Sheet 37 CFR 1.76
`
`
`Attorney Docket Number
`PAT903988-US-CNT
`
`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 Korean Intellectual 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 checked if the applicant
`does not wish the EPO, JPO, KIPO, WIPO, or other intellectual property office in which a foreign application claiming priority
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`In accordance with 37 CFR 1.14(h)(3), access will be provided to a copy of 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
`37 CFR 1.55 has been filed in the instant patent application; and 3) any U.S. application—as—filed from which benefit is
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`In accordance with 37 CFR 1.14(c), access may be provided to information concerning the date of filing this Authorization.
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`Applicant Information:
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`Providing assignment information in this section does not substitute for compliance with any requirement of part 3 of Title 37 of CFR
`to have an assignment recorded by the Office.
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`Applicant
`1
`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 address of the legal representative who is the applicant under 37 CFR
`1.43; or the name and address of the assignee, person to whom the inventor is 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 whom the inventor is obligated to assign, or person who otherwise shows sufficient
`proprietary interest) together with one or more joint inventors, then the joint inventor or inventors who are also the applicant should be
`identified in this section.
`
`
`
`@ Assignee
`0 Legal Representative under 35 U.S.C. 117
`0 Joint Inventor
`
`0 Person to whom the inventor is obligated to assign.
`0 Person who shows sufficient proprietary interest
`If applicant is the legal representative, indicate the authority to file the patent application, the inventor is:
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`Mailing Address Information:
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`
`
`X
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`Name of the Deceased or Legally Incapacitated Inventor :
`
`
`If the Applicant is an Organization check here.
`
`
`organization Name
`Alcon Research, Ltd.
`
`Address 1
`
`6201 South Freeway
`
`
`Address 2
`IP Legal
`
`
`City
`Fort Worth
`StateIProvince
`TX
`
`Country i us
`Postal Code
`76134-2099
`Phone Number
`(817) 551—8793
`Fax Number
`
`
`
`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 6
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 6
`
`

`

`PTO/AlA/14 (12-13)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
`
`Attorney Docket Number PAT903988-US-CNT
`
`Application Number
`
`
`Application Data Sheet 37 CFR 1.76
`
`
`Title of Invention
`
`HIGH CONCENTRATION OLOPATADINE OPHTHALMIC COMPOSITION
`
`
`Email Address
`patent.docketing@alcon.com
`
`Add
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`Assignee
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`1
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`Complete this section if assignee information, including non-applicant assignee information, is desired to be included on the patent
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`
`If the Assignee or Non-Applicant Assignee is an Organization check here.
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`
`Middle Name
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`Given Name
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`Fax Number
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`Mailing Address Information For Assignee including Non-Applicant Assignee:
`
`Address 1
`
`
`Address 2
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`City
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`Additional Assignee or Non-Applicant Assignee Data may be generated within this form by
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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
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`certifications
`
`Signature
`lScottA. Chapple 46 287]
`Date (YYYY-MM-DD)
`2014—06—13
`
`Additional Signature may be generated within this form by selecting the Add button.
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`EFS Web 2.2.11
`
`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC V. Novartis AG
`IPR2020-00295
`
`Page 7
`
`Novartis AG Exhibit 2001
`Ayla Pharma LLC v. Novartis AG
`IPR2020-00295
`Page 7
`
`

`

`PTO/AlA/14 (12—13)
`Approved for use through 01/31/2014. OMB 0651-0032
`US. 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 unless it contains a valid OMB control number.
`
`_
`_
`Application Data Sheet 37 CFR 1.76
`
`
`Attorney Docket Number
`PAT903988-US-CNT
`
`Application Number
`
`
`
`
`
`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 Web 2.2.11
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`Novartis AG Exhibit 2001
`
`Ayla Phat-ma LDC 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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`CFR 1.14, as a routine use, to the public if the record was filed in an application which became abandoned or in which the proceedings were
`terminated and which application is referenced by either a published application, an application open to public inspections or an issued
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`
`A record from this system of records may be disclosed, as a routine use, to a Federal, State, or local law enforcement agency, if the
`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
`
`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
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`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
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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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`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