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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 151
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 152
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 153
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 154
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 155
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 156
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`
`
`Title of Invention:
`
`USE OF A VEGF ANTAGONIST TO TREAT ANGIOGENIC EYE DISORDERS
`
`section
`
`
`
`First Named Inventor/Applicant Name:
`
`George D. Yancopoulos
`
`neni
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`Paymentinformation:
`
`The Director of the USPTO is hereby authorized to charge indicated fees and credit any overpaymentas follows:
`
`[pepestaccount
`
`Page 157
`Exhibit2053
`Regeneron Pharmaceuticals, Inc.
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.
`IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 158
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 159
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 160
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
`
`
`
`
`Application Number
`Application/Control No.
`Applicant(s)/Patent under
`
`* 16/159,282 *
`
`Examiner
`
`Yancopoulos, George D.
`Art Unit
`
`LOCKARD, JON MCCLELLAND | 1647
`
`a 16/159,282
`
`Document Code - DISQ
`
`Internal Document - DO NOT MAIL
`
`Telephone:
`
`TERMINAL
`DISCLAIMER
`
`APPROVED
`
`O DISAPPROVED
`
`Date Filed:
`
`28 June 2019
`
`This patent is subject
`to a Terminal
`Disclaimer
`
`Approved/Disapproved by:
`
`ICRYSTAL QUEEN/
`
`Technology Center: PLRC
`
`S.P.
`Ti
`k
`Offi
`TSSewate Magemark Office
`
`.
`.
`+
`TerminalDisclaimer
`
`Part of Paper No. 20190707
`
`Page 161
`Exhibit2053
`Regeneron Pharmaceuticals, Inc.
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.
`IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 162
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 163
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 164
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 165
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 166
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 167
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`
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`Atty Dkt. No.: REGN-008CIPCON4
`USSN: 16/159,282
`showing of improved unexpected results. Thus, while the rejection is citing case law (In re Aller) which
`
`supports the position that where the general conditions of a claim are disclosed within the priorart, it is
`
`not inventive to discover optimal ranges, the Examineris aware that this case law is not applicable to
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`situations where improved unexpected results are shown (MPEP 2145). Such results have been obtained
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`and are described in the working examplesofthe present application and in the attached publication,
`
`portions of whichare referred to below.
`
`Applicants do not acquiesce to the prima facie obviousness of the claimed invention over the
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`invention claimed within the cited patents. This is because there are virtually an infinite number of
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`different possible treatment protocols. However, notwithstanding any prima facie case of obviousness,
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`applicants have demonstrated improved and unexpected results, and based on such, the rejections should
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`be reconsidered and withdrawn.
`
`The attached Heieret al. paper published in December of 2012, and as such is not prior art with
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`respect to the present application claiming priority to November 21, 2011.
`
`The Heieret al. paper showsresults of a protocol of the type claimed on over 2,400patients.
`
`The protocols summarized in the Heieret al. paper correspond to those in Example 4 of the present
`
`application which involve the use of the VEGFreceptor-based chimeric molecule knownasaflibercept
`or "VEGFTrap."! The Heieretal. results suggest that by administering the VEGF antagonistin
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`accordance with a dosage regimen as claimed in independent claims 21 and 32,it is possible to treat
`
`angiogenic eye disorders such as AMD while administering doses on a less frequent basis than
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`previously thought possible. This provides enormous benefits to patients, reduces health care cost,
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`reduces the pain and suffering of the patient, as well as the inconvenienceto the patient and their family,
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`and as such provides a major step forward in the treatmentof patients suffering from angiogenic eye
`
`disorders, which is worthy of patent protection.
`
`The attached Heier et al. article is a peer reviewed article published in “Ophthalmology” which
`
`describes the aforementioned clinical trial as follows:
`
`“Patients were randomized in a 1:1:1:1 ratio to the following regimens: 0.5 mg
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`aflibercept every 4 weeks (0.5q4); 2 mg aflibercept every 4 weeks (2q4); 2mg
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`aflibercept every 8 weeks (2q8) after 3 injections at week 0, 4 and 8 (to maintain
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`masking, sham injections were given at the interim 4-week visits after week 8); or
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`' Aflibercept is a VEGF receptor-based chimeric molecule as defined in claim 33.
`
`Page 168
`Exhibit2053
`Regeneron Pharmaceuticals, Inc.
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.
`IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 169
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 170
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 171
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 172
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 173
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 174
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 175
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 176
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 177
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 178
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 179
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 180
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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`
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`Atty Dkt. No.: REGN-008CIPCON4
`USSN: 16/159,282
`supports the position that where the general conditions of a claim are disclosed within the priorart, it is
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`not inventive to discover optimal ranges, the Examineris aware that this case law is not applicable to
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`situations where improved unexpected results are shown (MPEP 2145). Such results have been obtained
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`and are described in the working examplesofthe present application and in the attached publication,
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`portions of whichare referred to below.
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`Applicants do not acquiesce to the prima facie obviousness of the claimed invention over the
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`invention claimed within the cited patents. This is because there are virtually an infinite number of
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`different possible treatment protocols. However, notwithstanding any prima facie case of obviousness,
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`applicants have demonstrated improved and unexpected results, and based on such, the rejections should
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`be reconsidered and withdrawn.
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`The attached Heieret al. paper published in December of 2012, and as such is not prior art with
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`respect to the present application claiming priority to November21, 2011.
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`The Heieret al. paper shows results of a protocol of the type claimed on over 2,400 patients.
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`The protocols summarized in the Heieret al. paper correspond to those in Example 4 of the present
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`application which involve the use of the VEGF receptor-based chimeric molecule knownasaflibercept
`or "VEGFTrap."! The Heieret al. results suggest that by administering the VEGF antagonistin
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`accordance with a dosage regimen as claimed in independent claims 21 and 32,it is possible to treat
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`angiogenic eye disorders such as AMD while administering doses on a less frequent basis than
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`previously thought possible. This provides enormous benefits to patients, reduces health care cost,
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`reduces the pain and suffering of the patient, as well as the inconvenienceto the patient and their family,
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`and as such provides a major step forward in the treatment of patients suffering from angiogenic eye
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`disorders, which is worthy of patent protection.
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`The attached Heieret al. article is a peer reviewedarticle published in “Ophthalmology” which
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`describes the aforementioned clinical trial as follows:
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`“Patients were randomized in a 1:1:1:1 ratio to the following regimens: 0.5 mg
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`aflibercept every 4 weeks (0.5q4); 2 mg aflibercept every 4 weeks (2q4); 2mg
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`aflibercept every 8 weeks (2q8) after 3 injections at week 0, 4 and 8 (to maintain
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`masking, sham injections were given at the interim 4-week visits after week 8); or
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`0.5mg ranibizumab every 4 weeks (Rq4). Consecutively enrolled patients were
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`' Aflibercept is a VEGFreceptor-based chimeric molecule as definedin claim 33.
`
`Page 181
`Exhibit2053
`Regeneron Pharmaceuticals, Inc.
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc.
`IPR2023-00884
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`Regeneron Pharmaceuticals, Inc. Exhibit 2053 Page 182
`Samsung Bioepis Co., Ltd. v. Regeneron Pharmaceuticals, Inc. IPR2023-00884
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