AMD.
`
`(Ued., 1}. Agam, my opimion im this regard is, in fact, confirmed by other
`
`contemporaneous prior art
`
`to the °069 patent
`
`that expressly refer to similar
`
`Regeneron and Bayer press releases. For example, Adis provides the following
`
`among twenty separate references to online “Media Releases”:
`
`
`SLWWWWWDDDW yD radIdQEKM
`
`
`
`
`
`i4. Regeneron Pharmaceuticals
`[Inc, Bayer HealthCare AG.
`Regeneron and Bayer HealthCare Announce Encouraging
`
`
`32-Week Follow-Up Results from a Phase 2 Study of VEGF
`
`
`Trap-Eye in Age-Related Macular
`Degeneration. Media Re:
`
`
`
`
`
`tease: 20.406 200)
`JRL: hitpe//wwwregener-
`
`
`
`(Ex.1007, Adis, 268 (emphasis added)).
`
`Indeed, press releases such as Regeneron
`
`(28-September-2008) were well-known—and widely available—to the community
`
`interested in the subject matter of the "069 patent.
`
`(See, e.g., i, 262-63, 268-69).
`
`59.
`
`In my opinion (and as confirmed by, e.g., Adis), a person of ordinary
`
`skill in the art would have also been able to locate Regeneron (28-September-2008}
`
`exercising reasonable diligence, which would haveatleast led the person of ordinary
`
`skill in the art to Regeneron’s website where the document was easily accessible,
`
`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therein without further research or experimentation.’ Thus, a person of
`
`ordinary skill in the art could have easily accessed Regeneron (28-September-2008)
`
`via Regeneron’s website and easily downloaded an electronic copy.
`
`f
`is
`’ See, e.g, Ex.1056, Regeneron (28-September-2008), 1.
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 34
`
`Samsung Bioepis Exhibit 1014
`Page 457
`
`Samsung Bioepis Exhibit 1014
`Page 457
`
`
`
`(Ued., 1}. Agam, my opimion im this regard is, in fact, confirmed by other
`
`contemporaneous prior art
`
`to the °069 patent
`
`that expressly refer to similar
`
`Regeneron and Bayer press releases. For example, Adis provides the following
`
`among twenty separate references to online “Media Releases”:
`
`
`SLWWWWWDDDW yD radIdQEKM
`
`
`
`
`
`i4. Regeneron Pharmaceuticals
`[Inc, Bayer HealthCare AG.
`Regeneron and Bayer HealthCare Announce Encouraging
`
`
`32-Week Follow-Up Results from a Phase 2 Study of VEGF
`
`
`Trap-Eye in Age-Related Macular
`Degeneration. Media Re:
`
`
`
`
`
`tease: 20.406 200)
`JRL: hitpe//wwwregener-
`
`
`
`(Ex.1007, Adis, 268 (emphasis added)).
`
`Indeed, press releases such as Regeneron
`
`(28-September-2008) were well-known—and widely available—to the community
`
`interested in the subject matter of the "069 patent.
`
`(See, e.g., i, 262-63, 268-69).
`
`59.
`
`In my opinion (and as confirmed by, e.g., Adis), a person of ordinary
`
`skill in the art would have also been able to locate Regeneron (28-September-2008}
`
`exercising reasonable diligence, which would haveatleast led the person of ordinary
`
`skill in the art to Regeneron’s website where the document was easily accessible,
`
`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therein without further research or experimentation.’ Thus, a person of
`
`ordinary skill in the art could have easily accessed Regeneron (28-September-2008)
`
`via Regeneron’s website and easily downloaded an electronic copy.
`
`f
`is
`’ See, e.g, Ex.1056, Regeneron (28-September-2008), 1.
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 34
`
`Samsung Bioepis Exhibit 1014
`Page 457
`
`Samsung Bioepis Exhibit 1014
`Page 457
`
`
`
`60.
`
`For at
`
`least these reasons, 1 is my opinion that Regeneron (28-
`
`September-2008) was a well-known, printed publication that was publicly accessible
`
`io persons interested and ordinarily skilled in the subject matter or art of the “069
`
`patent, exercising reasonable dilipence, before 2011.
`
`3
`
`April 2009 Press Release,
`
`61.
`
`Regeneron issued a press release dated April 30, 2009 CEx.1028,
`
`Regeneron (30-Aprii-2009)), which described the extension of Regeneron’s global
`
`development program for VEGF Trap-Eye to include Central Retinal Vein
`
`OcchisionO(CRVO"). id, 1).
`
`62.
`
`Specifically, Regeneron (30-April-2009) stated that in the Phase 3
`
`CRVO program, GALILEO, patients would “receive 6 monthly intravitreal
`
`injections of |] VEGF Trap-Eye at a dose of 2 milligrams (mg).” Ua, 1).
`
`63.
`
`A person of ordinary shall in the art would have understood that the
`
`dosing regimens disclosed in Regeneron (30-April-2009) included the experimental
`
`group that received 6 monthlyintravitreal injections of VEGF Trap-Eye at a dose of
`
`2 milligrams. (fd, 1).
`
`64.
`
`A person of ordmary skill im the art would have been interested in, and
`
`sought out,
`
`the mformation disclosed in Regeneron (30-April-2009) because it
`
`pertains to ongomg product development within the industry, meluding dosing
`
`regimens of a known therapy (VEGF Trap-Eye or aflibercept) in patients with
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 35
`
`Samsung Bioepis Exhibit 1014
`Page 458
`
`Samsung Bioepis Exhibit 1014
`Page 458
`
`
`
`CRVO.
`
`(Ud,
`
`|). Again, my opinion in this regard is, in fact, confirmed by other
`
`contemporaneous prior art
`
`to the °069 patent
`
`that expressly refer to similar
`
`Regeneron and Bayer press releases. For example, Adis provides the following
`
`among twenty separate references to online “Media Releases”:
`
`
`SLWWWWWDDDW yD radIdQEKM
`
`
`
`i4. Regeneron Pharmaceuticals
`[Inc, Bayer HealthCare AG.
`Regeneron and Bayer HealthCare Announce Encouraging
`
`32-Week Follow-Up Results from a Phase 2 Study of VEGF
`
`Trap-Eye in Age-Related Macular
`Degeneration. Media Re:
`
`tease: 20.406 200)
`JRL: hitpe//wwwregener-
`
`
`
`
`
`
`
`
`
`(Ex.1007, Adis, 268 (emphasis added)).
`
`Indeed, press releases such as Regeneron
`
`(30-Apni-2009) were well-known—and widely available—to the community
`
`interested in the subject matter of the "069 patent.
`
`(See, e.g., i, 262-63, 268-69).
`
`65.
`
`In my opinion (and as confirmed by, e.g., Adis), a person of ordinary
`
`skill in the art would have also been able to locate Regeneron (30-April-2009)
`
`exercismg reasonable diligence, which would haveatleast led the person of ordinary
`
`skill in the art to Regeneron’s website where the document was easily accessible,
`
`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therein without further research or experimentation.» Thus, a person of
`
`ordinary skill in the art could have easily accessed Regeneron (30-April-2009) via
`
`Regeneron’s website and easily downloaded an electronic copy.
`
`* Ex 1028, Regeneron (30-April-2009), 1.
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 365
`
`Samsung Bioepis Exhibit 1014
`Page 459
`
`Samsung Bioepis Exhibit 1014
`Page 459
`
`
`
`66.
`
`For at least these reasons, it is my opinion that Regeneron (30-April-
`
`2009) was a well-known, printed publication that was publicly accessible to persons
`
`interested and ordinarily skilled in the subject matter or art of the “069 patent,
`
`exercising reasonable diligence, before 2011.
`
`4.
`
`February 2010 Press Release,
`
`67.
`
`Regeneron issued a press release dated February 18, 2010 (Ex.1057,
`
`Regeneron (18-February-2010)), which described the “DA VINCI” tal. Ua., 1: see
`
`aise Ex.1066, Bayer (18-February-2010), 1).
`
`68.
`
`The patients im the study were randomized into five groups:
`
`four
`
`experimental eroups and one control group.
`
`(Ex.1057, Regeneron (18-February-
`
`2010), 1}. One of the experimental proups received “three intial monthly doses of
`
`2.0 mg of VEGF Trap-Eye (at baseline and weeks 4 and 8), followed through week
`
`24 by... every &-week dosing” while another experimental group received “three
`
`initial monthly doses of 2.0 mg of VEGF Trap-Eye(at baseline and weeks 4 and 8),
`
`followed through week 24 by ... as needed (PRN) dosing with specific repeat dosing
`
`criteria.” (Ud. }.
`
`69.
`
`A person of ordinary skill m the art would have understood that the
`
`dosing regimens disclosed in Regeneron (18-February-2010) included the two
`
`experinental proups that received 2 mg mtravitreal VEGF Trap-Eye either (1) every
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPR2021-00650
`Page 37
`
`Samsung Bioepis Exhibit 1014
`Page 460
`
`Samsung Bioepis Exhibit 1014
`Page 460
`
`
`
`other month following three initial monthly injections, or (2) as needed (PRN}
`
`following three mitial monthly injections. Ua, 1}.
`
`70. Aperson of ordinary skill in the art would have been interested im, and
`
`sought out, the information disclosed in Regeneron (18-February-2010) because if
`
`pertains to ongoing product development within the industry, including dosing
`
`regimens of a known therapy (VEGF Trap-Eye or aflibercept) in patients with DME.
`
`Ud., 1). Again, my opinion im this regard is,
`
`in fact, confirmed by other
`
`contemporaneous prior art
`
`to the “069 patent
`
`that expressly refer to simular
`
`Regeneron and Bayer press releases. For example, Adis provides the following
`
`among twenty separate references to online “Media Releases”
`
`
`
`
`Grrr65HGOOWQWWAQJ;wwwwwwniss§vTIM|NMA”!D[AAAi
`Ww
`
`\ i4. Regeneron Pharmaceuticals
`Inc, Bayer HealthCare AG.
`\
`Regeneron and Bayer HealthCare Announce Encouraging
`32-Week Follow-Up Results from a Phase 2 Study of VEGF
`\
`
`Trap-Eye in Age-Related |
`uv Degeneration. Meda Re:
`.
`
`\
`Ieuses 29 AvrQ0gs8,
`URL; hitp:/Awww.regener-
`
`‘A YgZ
` on.com
`
`gy
`
`(Ex.1007, Adis, 268 (emphasis added)).
`
`Indeed, press releases such as Regeneron
`
`(18-February-2010) were well-known-——and widely available—to the community
`
`mterested in the subject matter of the “069 patent.
`
`(See, ¢.., id., 262-63, 268-69).
`
`71.
`
`In myopinion (and as confirmed by, e.g., Adis), a person of ordinary
`
`skill in the art would have also been able to locate Regeneron (1 8-February-2010)
`
`exercising reasonable diligence, which would haveat least led the person of ordinary
`
`skill m the art to Regeneron’s website where the document was easily accessible,
`
`36
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 35
`
`Samsung Bioepis Exhibit 1014
`Page 461
`
`Samsung Bioepis Exhibit 1014
`Page 461
`
`
`
`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therein without further research or experimentation.” Thus, a person of
`
`ordinary skill in the art could have easily accessed Regeneron (18-February-2010)
`
`via Regeneron’s website and casily downloaded an electronic copy.
`
`72.
`
`For at
`
`least these reasons,
`
`if 1s my opinion that Regeneron (18-
`
`February-2010) was a well-known, printed publication that was publicly accessible
`
`io persons interested and ordinanlyskilled in the subject matter or art of the “069
`
`patent, exercising reasonable diligence, before 2011.
`aw
`o.
`
`Additional Regeneron Press Releases.
`
`73.
`
`Regeneron and Bayer HealthCare AG issued a press release dated
`
`March 27, 2007 CEx.1053, Regeneron (27-March-2007)), which described the
`
`twelve-week data for a “Phase 2 randomized study of ther VEGF Trap-Eye in
`
`patients with the neovascular form of age-related macular degeneration (wet
`
`AMD)” Ud, 1).
`
`74,
`
`The patients in the study were “randomized to 5 groups” where “[t}wo
`
`groups received either 0.5 or 2.0 mg of VEGF Trap-Eye administered every four
`
`weeks, andthree groups receiveda single dose of 0.5, 2.0, or 4.0 mg of VEGFTrap-
`
`Eye.” Uad., 1). Furthermore, the President of Regeneron Research Laboratories was
`
`°Ex.1057, Regeneron (1 8-February-2010), 1.
`
`we ~~
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 39
`
`Samsung Bioepis Exhibit 1014
`Page 462
`
`Samsung Bioepis Exhibit 1014
`Page 462
`
`
`
`quoted as stating “[ojur Phase 3 program is being designedto test this possibility
`
`and further evaluate the safety and efficacy of various doses and dosing intervals of
`
`the VEGF Trap-Eve.” Ud).
`
`75.
`
`Regeneron and Bayer HealthCare AGissued a press release dated
`
`August 2, 2007 (Ex.1054, Regeneron (2-August-2007)) which described “a Phase 3
`
`study of the VEGF Trap-Eye in the neovascular form of age-related macular
`
`degeneration (wet AMD)” Ud, 1). Specifically, Regeneron (2-August-2007}
`
`described “VEGF Trap-Eye ... doses... 2.0 mg at an eight-week dosing interval.”
`
`(id),
`
`76.
`
` Regencron and Bayer HealthCare AGissued a press release dated April
`
`28, 2008 CEx.1012, Regeneron (28-April-2008)) which described the thirty-two-
`
`week results from a “double-masked, prospective, randomized, multi-center Phase
`
`2 trial” in patients with the “neovascular form of Age-related Macular Degeneration
`
`(wet AMD)” treated with VEGF Trap-Eye.
`
`(U/d., 1; see also Ex.1067, Bayer (28-
`
`April-2008), 1).'°
`
`© T note that
`
`the information disclosed within the Regeneron Press Releases
`
`discussed herem is essentially the same as the information disclosed within the
`
`corresponding Bayer Press Releases.
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 40
`
`Samsung Bioepis Exhibit 1014
`Page 463
`
`Samsung Bioepis Exhibit 1014
`Page 463
`
`
`
`77.
`
`The patients in the study were “randomized to five dose groups” as
`
`follows:
`
`CG)
`
`monthly dose of 0.5 milligrams (mg) of VEGF Trap-Eye for twelve
`
`weeks followed by therapy at
`
`the same dose on a PRN'! dosing
`
`schedule;
`
`monthly dose of 2.0 mg of VEGF Trap-Eye for twelve wecks followed
`
`by therapyat the same dose on a PRN dosing schedule;
`
`(3)
`
`quarterly dose of 0.5 mg of VEGF Trap-Eye (at baseline and week 12)
`
`followed by therapyat the same dose on a PRN dosing schedule;
`
`(4)
`
`quarterly dose of 2.0 mg of VEGF Trap-Eye (at baseline and week 12)
`
`followed by therapyat the same dose on a PRNdosing schedule; or
`
`anCay “New
`
`quarterly dose of 4.0 mg of VEGF Trap-Eye (at baseline and week 12}
`
`followed bytherapyat the same dose on a PRN dosing schedule.
`
`(Ex.1012, Regeneron (28-April-2008), 1).
`
`78.
`
`Regeneron (28-Apni-2008) added that VEGF Trap-Eye was being
`
`evaluated “using a monthly loading dose of... 2.0 mg for 12 weeks, followed bya
`
`nine-month fixed-dosing regimen of ... 2.0 mg every eight weeks” or “monthly
`
`doses of 0.5 or 2.0 milligrams Gng) of VEGF Trap-Eye for 12 weeks” followed by
`
`1 SDRN” (or pro re nata) is commonly understood as “as needed” dosing.
`
`39
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 41
`
`Samsung Bioepis Exhibit 1014
`Page 464
`
`Samsung Bioepis Exhibit 1014
`Page 464
`
`
`
`“therapy at the same dose on a PRN dosing schedule based upon the physician
`
`assessment of the need for re-treatment.” (Ex.1012, Regeneron (28-April-2008), 1-
`
`2).
`
`79.
`
`Regeneron issued a press release dated September 14, 2009 (Ex. 1068,
`
`Regeneron (1 4-September-2009)) which described two “Phase 3 clinical
`
`tnais
`
`evaluating VEGF Trap-Eye in the treatment of the neovascular form ofage-related
`
`macular degeneration (wet AMD),” and a phase 2 trial “for the treatment of Diabetic
`
`Macular Edema (DME).” Ud, 1). Specifically, Regeneron (14-September-2009)
`
`described “VEGF Trap-Eye...dosed...2.0 mg every cight weeks following three
`
`monthly doses)” in the phase 3 trials and dosing of “2 mg on an as-needed (PRN)
`
`basis after three monthly loading doses,” in the phase 2 trial. (ed).
`
`80.
`
`<Aperson of ordinary skill in the art would have understood that the
`
`dosing regimens disclosed in Regeneron (14-September-2009)
`
`included the
`
`experimental groups that were to receive VEGF Trap-Eye “2.0 mg every cight weeks
`
`(following three monthly doses),” or “2 mg on an as-needed (PRN) basis after three
`
`monthly loading doses.” (Ud, 1}.
`
`81. A person of ordmaryskill in the art would have been interested im, and
`
`sought out, the information disclosed in the above Press Releases because they
`
`pertain to ongoing product development within the industry,
`
`including dosing
`
`regimens of a knowntherapy (VEGF Trap-Eye or aflibercept) in patients with wet
`
`At}
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 42
`
`Samsung Bioepis Exhibit 1014
`Page 465
`
`Samsung Bioepis Exhibit 1014
`Page 465
`
`
`
`AMD. (See *© 42-43, 50, 58, 64, 70, above). Again, my opinion in this regard is, im
`
`fact, confirmed by other contemporaneous prior art to the “06% patent that expressly
`
`refer to sumilar Regeneron and Bayerpress releases. For example, Adis provides the
`
`following among twenty separate references to online “Media Releases”:
`
`
`
` Wee
`
`
`
`
`
`Inc, Bayer HealthCare AG.
`i4. Regeneron Pharmaceuticals
`Regeneron and Bayer HealthCare Announce Encouraging
`32-Week Fallow-Up Results from a Phase 2 Study ef VEGF
`
`Trap-Eye in Age-Related Macular Degeneration. Media Re-
`jease: 29 Ane 2008.
`URL: http://www.regener-
`on.com
`
`
`
`
`
`
`
`
`(Ex. 1007, Adis, 268 (emphasis added))}. Indeed, press releases such as Regeneron’s
`
`Press Releases were well-known---and widely available--to the community
`
`interested in the subject matter of the °069 patent.
`
`(See, ¢.g., iad, 262-63, 268-69).
`
`82.
`
`In my opinion (and as confirmed by, e.g., Adis}, a person of ordinary
`
`skill mthe art would have also been able to locate these Regeneron Press Releases
`
`exercising reasonable diligence, which would haveat least led the person of ordinary
`
`skill in the art to Regeneron’s website where these documents were easily accessible,
`
`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therein without further research or experimentation.’* Thus, a person of
`
`Ex 1053, Reveneron (27-March-2007), 1, Ex.1054, Regeneron (2-August-2007),
`
`i, Ex. 1012, Regeneron (28-Apnil-2008), 1, Ex 1068, Regeneron (14-September-
`
`2009),1.
`
`At
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 43
`
`Samsung Bioepis Exhibit 1014
`Page 466
`
`Samsung Bioepis Exhibit 1014
`Page 466
`
`
`
`ordimary skill
`
`im the art could have easily accessed these Press Releases via
`
`Regeneron’s website and easily downloaded an electronic copy.
`
`83.
`
`For at least these reasons, it is my opmion that Regeneron’s Press
`
`Releases outhned above were well-known, printed publications that were publicly
`
`accessible to persons interested and ordinarily skied in the subject matter or art of
`
`the °069 patent, exercising reasonable diligence, before 2011.
`
`C.
`
`CLINICAL TRIALS.GOV,
`
`84.
`
`ClinicalTrials. gov is an electronic registry and results database of
`
`clinical studies supported by the US. National Institutes of Health that is open and
`
`accessible to the public as a “resource that provides patients, their family members,
`
`health care professionals, researchers, and the public with easy access to mformation
`
`on publicly and privately supported clinical studies on a wide range ofdiseases and
`
`4
`conditions.’ Each study record includes a summary of the study protocal,
`
`Chical Triais.gov includes records for several clinical studies mvolving aflibercept,
`
`imcluding:
`
`e
`
`VIEW! (ClinicalTrials.gov identifier NCT00509795) (Ex.1014, NCT-
`
`795):
`
`SS Bx.1069, Back eground-Clinical Trials.gov, 1-3.
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 44
`
`Samsung Bioepis Exhibit 1014
`Page 467
`
`Samsung Bioepis Exhibit 1014
`Page 467
`
`
`
`®
`
`®
`
`VIEW2 (Clinical Trials.govidentifier NCT00637377) CEx.1015, NCT-
`
`377), aad
`
`GALILEO (ClinicalTriais.gov identifier NCTO1012973)
`NCT-973).
`
`(Ex.1029,
`
`85. NCT-973 (GALILEO) was first available as ofat least July 22, 2010
`
`and describes a clinical study titled “A Randomized, Double-masked, Sham-
`
`controlled Phase 3 Study of the Efficacy, Safety and Tolerability of Repeated
`
`Intravitreal Admmmistration of VEGF Trap-Eye im Subjects With Macular Edema
`
`Secondary to Central Retinal Vern Occlusion (CRVO).” CEx.1029, NCT-973, 5;
`
`Ex.1070, Wayback-Affidavit-O69 (Wayback Machine records showing public
`
`availability of NCT-973 prior to Jan. 13, 2011); Ex. 1071, Holz, 278 CGALILEOis
`
`a phase I, randomised, double-masked, multi-centre clinical study .. . registered as
`
`NCTOL012973 onclinicaltrials.gow’). NCT-973 lists the following experimental
`
`“arms” ofthe study:
`
`
`
`4 See also Ex.1014, NCT-795, 3; Ex.1070, Wayback Affidavit-069 (Wayback
`
`Machine records showing public availability ofNCT-795, describing a clinical study
`
`titled “A Randomized, Double Masked, Active Controlled Phase Il] Study of the
`
`Efficacy, Safety, and Tolerability of Repeated Doses of Intravitreal VEGF Trap in
`
`Subjects With Neovascular Age-Related Macular Degeneration,” prior to Jan. 13,
`
`> C2
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 45
`
`Samsung Bioepis Exhibit 1014
`Page 468
`
`Samsung Bioepis Exhibit 1014
`Page 468
`
`
`
`|
`| Expermmental: Arm |
`|
`| VEGF Trap-EyeIntravitreal
`
`Injection
`
`|
`
`intravitreal injection. Weeks 0 to 20
`
`injection of VEGF Trap-Eye every 4
`
`weeks, weeks 24 to 48 every 4 weeks
`
`re-assessment and either (PRN)
`
`myjection of VEGF Trap-Eye or sham
`
`| Shamtreatment
`
`myection; weeks 52 to 100 safety
`|
`follow-up.
`|
`
`
`| Sham Comparator: Arm 2
`
`Sham treatment. Weeks 0 to 20 sham
`
`treatment every 4weeks:; weeks 24 to
`
`2011); Ex.1018, Heter-2012, 2539 (‘Patients m VIEW 1
`
`(registered at
`
`www.clincaltnals.gov on July 31,2007... 9); Ex.1015, NCT-377, 3-4; Ex.1070,
`
`Wayback-Affidavit (Wayback Machine records showing public availability ofNCT-
`
`377, describing a clinical study titled “A Randomized, Double Masked, Active
`
`Controlied, Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated
`
`Doses of Intravitreal VEGF Trap in Subjects With Neovascular Age-related Macular
`
`Degeneration (AMD),” prior to Jan. 13, 2011); Ex.1018, Heier-2012, 2539
`
`(“Patients
`
`in VIEW2 (registered at www.clinicaltrials.gov on March 12,
`
`2008... ))Je
`
`Aa
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 45
`
`Samsung Bioepis Exhibit 1014
`Page 469
`
`Samsung Bioepis Exhibit 1014
`Page 469
`
`
`
`| 48 every 4 weeks re-assessment and
`
`| follow-up.
`
`shaminjection; weeks 52 to 100safety
`
`i |
`
`(Ex.1029, NCT-973, 5). The experimental arms above included the group which
`
`required participants to receive “Twleeks 0 to 20 mjection of VEGF Trap-Eye every
`
`4 weeks; weeks 24 to 48 every 4 weeks re-assessment and either (PRN) injection of
`
`VEGFTrap-Eye or sham injection; weeks 52 to 100 safety follow-up.” (/d.).'°
`
`86.
`
`<A person of ordinary skill m the art would have understood that the
`
`dosing regimens disclosed in NCT-973 included the experimental group
`gE
`£
`&
`
`that
`
`© See also Ex.1014, NCT-795, 6-8 (Experimental Arms 1-3); Ex.1015, NCT-377, 6
`
`(Experimental Arms 1-3).
`
`'® See also Ex.i014, NCT-795, 8 (experimental arms included the group which
`
`required participants to receive “2.0 mg VEGF Trap-Eye administered every 8&8
`
`weeks (including one additional 2.0 mg dose at weck 4) during the first year’),
`
`Ex.1015, NCT-377, 6 (experimental arms inchided the group which required
`
`participants to recetve “2.0 mg VEGF Trap-Eye administered every 8 weeks
`
`Gincliding one additional 2,0 mg dose at Week 4) during the first year’).
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 47
`
`Samsung Bioepis Exhibit 1014
`Page 470
`
`Samsung Bioepis Exhibit 1014
`Page 470
`
`
`
`received VEGF Trap-Eye every four weeks for twenty weeks followed by “(PRN)
`
`injection of VEGF Trap-Eye.” (Ex.1029, NCT-973, 5).
`
`87. A person of ordinary skill m the art would have been interested in and
`
`easily accessed and sought out the information disclosed on the ClinicalTnals,gov
`
`website regarding NCT-795, NCT-377, andNCT-973 because they each pertain to
`
`ongoing product development within the industry, including dosing regimens of a
`
`known therapy (VEGF Trap-Eve or aflibercept) in patients with wet AMD.
`
`(Ex. 1014, NCT-795, 3; Ex.1015, NCT-377, 3-4; Ex.1029, NCT-973, 3). Thus, in
`
`my opinion, NCT-795, NCT-377, and NCT-973 were all “publicly accessible” as
`
`they were dissemimated or otherwise made available to the extent that persons
`
`miterested and ordinarily skilled in the subject matter or art of the “069 patent,
`
`exercising reasonable diligence, could locate them.
`
`88. My opinion in this
`
`regard is,
`
`im fact,
`
`confirmed by other
`
`contemporaneous prior art to the °069 patent that expressly cited to clmical trial
`
`’ See also Ex.1014, NCT-795, 8 Gneluding the experimental group that received
`
`VEGF Trap-Eye 2.0 mg every two months “including one additional 2.0 mg dose at
`
`Week 4°); Ex.1015, NCT-377, 6 Gnchided the experimental group that received
`
`VEGFTrap-Eve 2.0 mg every two months “including one additional 2.0 mg doseat
`
`Week 4’).
`
`46
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 45
`
`Samsung Bioepis Exhibit 1014
`Page 471
`
`Samsung Bioepis Exhibit 1014
`Page 471
`
`
`
`records from Clinical Trials. gov, including NCT-795, NCT-377, and NCT-973. Por
`
`example, Reichert (Ex.1072, Reichert)!® provides the following disclosures of NCT-
`
`795, NCT-377, and NCT-973:
`
`
`
`\\\\~\\N
`
`e
`Ne
`
` (Lucentis™, Genentech)“in the 4 arm
`
`VIEW 1 study (NCTO0S09795], adult
`patients (50 years and older) in arms |
`and 2 are administered either 0.5 or 2.0
`mg aflibercept every four weeks for | year,
`then the same dose is administered as fre-
`quently as every four weeks but no less
`*
`frequently than every 12 weeks. Patients
`SAQAQAWWWWWaDvlb§hlll"
`
`\\\\\\..
`
`
`
`(/d., 94 (emphasis added)),
`
`
`is September 2013. The on-going VIEW
`2 [NCTQQ637377) has the same design as
`VIEW1, but is being conducted at sites
`in Europe, Asia Pacific, Japan and Latin
`America byBayer. A total oft21)patients
`
`were= recruited; the estimated.study com:
`
`
`
`(/d., 95 (emphasis added); see also id., 96); and
`
`8 Ex.1072, Reichert, 76; see also id, cover (Reichert is a printed publication that
`
`was publicly available prior to January 13,2011, and would be considered prior art
`
`to the “069 patent).
`
`fa ~~
`
`Miylan Exhibit 1003
`Mylan v. Regeneron, IPR2021-00650
`Page 49
`
`Samsung Bioepis Exhibit 1014
`Page 472
`
`Samsung Bioepis Exhibit 1014
`Page 472
`
`
`
`~Inthe“placebo-controlled‘GALILEO)
`study [N€}01012973],
`patients in the
`experimental
`arm receive
`intravitreal®
`injections ofaflibercept every four weeks
`=
`\
`\
`\during weeks 0-20, every four weeks|
`\
`.
`during weeks 24 to 52 plus additional
`XN
`&
`\injections ofeither aflibercept or placebo\
`\
`\
`\on week60 and|68_at_Fe-assessment.<
`
`Anos TURAN TURAN
`
`
`(Ud., 95 (emphasis added)). Moreover, Reichert makes multiple
`
`2 CXPress references
`
`to obtaining information online directly from Clinical Trials. gov.
`
`(/d., 79 (Table
`
`(“hsted on clinicaltrialsgov"); a, 99 (Ref. No. 69 (citing ClinicalTrials pov record
`
`and corresponding internet address)}).
`
`89. Similarly Anderson (Ex.1073, Anderson)’? provides the
`
`following
`
`disclosures of NCT-795 and NCT-377 online reports:
`
`
`
`&
`
`
`
`\
`
`
`
`‘Two phase HI clinical trials are underway (VIEW-1 in the USA
`and Canada and VIEW-2.in Burope, Asia-Pacific, Japan and Latin
`Ametica). These non-inferiority studies aim to compare efficacy of
`VEGF Trap against ranibizimab. Study completion is expected in
`
` Ex.1073, Anderson, 272 (Anderson is a printed publication that was publicly
`
`available prior to January 13, 2011, and would be considered prior art to the “069
`
`patent).
`
`Miylan Exhibit 1003
`Mylan v. Regeneron, IPR2021-00650
`Page 50
`
`Samsung Bioepis Exhibit 1014
`Page 473
`
`Samsung Bioepis Exhibit 1014
`Page 473
`
`
`
`(id, 275 (emphasis added)). Anderson made additional references to obtaming
`
`information from ChinicalTnals.gov. Ud, 272-77, 280: see also id, 373 (igure |
`
`(“Graph
`
`displaying
`
`the mumber of
`
`clinical
`
`tnais
`
`registered with
`
`the
`
`ClinicalTnals gov registry (http://clmucaltrialsgov) each year between 2001 and
`
`2009.79).
`
`90. Another example, Crulla (Ex.1074, Ciulla),” provides the following:
`
`. 52 (P<0.0001 for both from baseline). Currently,
`
`two
`
` < with ranibizumab.
`
`
`(id., 162 (emphasis added)). Cilla also made numerous other references to
`
`ClinicalTnials.gov and obtaining information from that database. (/d., 162-63).
`
`91.
`
`Ni (Ex.1075, Ni}?! provided the following:
`
`*° Py 1074, Crolla, 158 (Ciuila is a printed publication that was publicly available
`
`prior to January 13, 2011, and would be considered prior art ta the °069 patent).
`
`“1 Ex 1075, Ni, 401 €Ni
`
`is a printed publication that was publicly available priorto
`
`January 13, 2011, and would be considered prior art to the 069 patent).
`
`49
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 31
`
`Samsung Bioepis Exhibit 1014
`Page 474
`
`Samsung Bioepis Exhibit 1014
`Page 474
`
`
`
`
`
`BURGERPEEKCREPEEKCRECKseteiesSOY
`“Double-Masked-‘StudyofEfficacyrand$afety |
`
`
`of [VT VEGFTrap-Eyein Subjects with Wet
`AMD(VIEW 1). aS(hwww,es
`
`
`
`
` “ndothelial Growth Factor (VEGE)
`
`Trap-Eye: Investigation of Efficacy andSafe-
`
`
`ty in Wet Age-Related Macular Degenera-
`tion (AMD)(VIEW2).es :
`
`LOLLELULERYCOLELLO
`
`
`i
`
`*
`
`(id, 409 (emphasis added)). Additionally, Ni references numerous clinicaltrials
`
`with citations to ClicalTrials.gov as the source of the information.
`
`(See, e.g, a,
`
`408-10),
`
`92. Another example, Zarbin (Ex.1076, Zarbin)”’ provided the following:
`
`
`
`
`a Phase
`Vin
`| clinical“trial. VEGE Trap-Eye
`aipwchinicalaralscov/clg/showsNCTOOS00785Herm
`VEGE+Taupoe&rank=! 4) 4s formulated for intravitreal
`myection, appears to be eNective in a Phase 2 trial
`
`cwww.bmetodaynet/retinatoday/2009/] O/article.asp tb
`{O09O08 php) and is now beins compared with &
`
`ranibizumab in a Phase 3 clinical trial. AAV?2-sFLTOL
`
`S
`
`oe
`
`77 Ex.1076, Zarbin, 1350 (Zarbinis a printed publicationthat was publicly available
`
`prior to January 13, 2011, and would be considered priorart to the 069 patent).
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 52
`
`Samsung Bioepis Exhibit 1014
`Page 475
`
`Samsung Bioepis Exhibit 1014
`Page 475
`
`
`
`Ud, 1360 (emphasis added)). Additionally, Zarbin also references numerous
`
`clinical tals with citations to ClinicalTnals gov as the source of the information.
`
`(See ie, 1351-52, 1356-62).
`
`93. Dixon (Ex.1006, Dixon)? provides the following citations, further
`
`2
`confirming that both NCT-795 and NCT-377 including the dosing regimens
`
`3
`disclosed therein, were publicly available as of at least September 28, 2008:
`
`
`
`
`
`Double-Masked Study of Efficacy and
`Satery of IVT VEGF Trap-Eve in Subjects
`Wich Wer AMCD (VIEW1) [ClnicalTrials.
`
`\\\A
`
`NN\\AAAE
`
`gov identifier: IN Clinical Trials. gay [online].
`hrep/felinicalerials. gov/ce2/show/
`NCT00509795
`VEGF Trap-Eye: Investigation of Efficacy
`andSafety in Wer AMT) (VTEW2}.
`[Clinical Trials.govidentifer:
`
`NITO06
`
`fonlinel.!
`
`
`gov/ct2/shovw
`
`
`one
`
`gy
`
`hetp/fchnicaltrials.
`FATF
`
`N
`iN
`
`NAN\\\AS
`
`N\\A
`
`NN\\AAANi
`
`NNNN\\\AA.
`
`
`
`Ud.,
`
`1579 (emphasis added)}.
`
`Accordingly,
`
`it
`
`is my firm opinion that
`
`Clinical Trials.gov records,NCT-795, NCT-377, and NCT-973, were well-known-—
`
`3 Ex 1006, Dixon, 1573 (Dixon is a printed publication that was publicly available
`
`prior to Tanuary 13, 2011, and would be considered prior art to the “069 patent).
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPR2021-00650
`Page 53
`
`Samsung Bioepis Exhibit 1014
`Page 476
`
`Samsung Bioepis Exhibit 1014
`Page 476
`
`
`
`and widely available—to the community interested m the subject matter of the “069
`
`patent.
`
`94.
`
`Prior to 2011, a person of ordinary skill imthe art would have also been
`
`able to locate NCT-795, NCT-377, and NCT-973 exercising reasonable diligence,
`
`which would have at
`
`least
`
`led the person of ordimary skill
`
`in the art
`
`to the
`
`ClincalTrials. gov website where the documents were easily accessible, and
`
`recognize and comprehend therefrom the essentials of the subject matter contained
`
`therein without further research or experimentation.** Thus, a person of ordinary
`
`skill in the art could have easily accessed NCT-795, NCT-377, and NCT-973 wia
`
`ClinicalTrials.gov and easily downloaded an electronic copyof each.
`
`95.
`
`For the reasons outlined above, a person of ordinary skill in the art
`
`would have considered the posting dates cited at ClinicalTrials.govto be trustworthy
`
`and authoritative and it is my opinion that NCT-795, NCT-377, and NCT-973 were
`
`well-known, printed publications that were publicly accessible to persons interested
`
`and ordinarily skilled in the subject matter or art of the “069 patent, exercising
`
`reasonable diligence, before 2011.
`
`4 See Ex. 1014, NCT-795, 1, Ex.1015, NCT-377, 1, Ex.1029,NCT-973,1.
`“2
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 54
`
`Samsung Bioepis Exhibit 1014
`Page 477
`
`Samsung Bioepis Exhibit 1014
`Page 477
`
`
`
`D.
`
`SEC Fines.
`
`96. As I note above (see {] 41-44), company press releases were weill-
`
`known, and widely available,
`
`to persons of ordinary skill in the art. This was
`
`especially true of persons of ordmaryskill in the art of the °069 patent, who expressly
`
`cited Bayer and Regeneron press releases.
`
`(See, ¢.g., Ex.1007, Adis, 262-63, 268-
`
`69).
`
`97. Moreover, domestic publicly-traded companies are required to file
`
`certain forms with the SEC, and this is well-known bythose tn the pharmaceutical
`
`industry and academia. A company’s SECfilings provide “reliable information
`
`about [the company]? that allows a person in the art to ensure that they are well
`
`informed and up-to-date on all of the most important developments.
`
`(Ex.1077,
`
`Corporate Finance Institute, 1-3; see aise Ex. 1078, Schneider, 258 (noting that “SEC
`
`filmes ... have been considered to be among the most accurate and reliable...
`
`sources of information available”); kx.1079, Kuepper, 1-4).
`
`98.
`
`SEC filings, such as a company’s Form 10-Q, are easily accessible via
`
`the Electronic Data Gathermg, Analysis, and Retrieval system EDGAR”) or a
`
`company’s website.
`
`(See, ¢.g., Ex 1080, Zucchi}. SEC filings provide, infer alia,
`
`information regarding the company’s finances as well as recent business activity.
`
`(See id; Ex. 1081, Hayes, 3-4, 8-10).
`
`Css Mb
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPR2021-00650
`Page 55
`
`Samsung Bioepis Exhibit 1014
`Page 478
`
`Samsung Bioepis Exhibit 1014
`Page 478
`
`
`
`99.
`
`in my experience in the industry, SEC filmes for pharmaceutical or
`
`biotechnology companies included information regarding ongoing development of
`
`different products, including ongoimg clinical tnais and the results of completed
`
`clinical trials. Thus, a person of ordinary skallin the art would utthze the information
`
`contained therem, amongst other references, to keep up to date on the development
`
`in the field of interest, especially with direct competitors.
`
`100. First, a person of ordinary skill in the art would be interested in such
`
`“Financial and Operating Results” as confirmed bythe priorart:
`
`
` &. Regeneron Pharmacetiticals Inc. Regeneron Reports Second
`
`Quarter Pingaclal aad Opersine Rests: BLA Filing for Auto-
`Inflammatory Diseases Planned for Early 2007; Two Antibody
`Candidates from Veloclmmune(R) Progrem to Enter Clinical
`
`
`Trials
`inning in 2007. Media Release: 3 Aug
` MMOWMWAN
`
`EEURL: httipvAvww.regeneron.com
`2006.8
`Y
`
`
`(Ex.1007, Adis, 268 (emphasis added); see also iad. (Ref. Nos. 6, 18)).
`
`101. Second, in my opinion, a person of ordinary skill in the art would have
`
`been
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