throbber
AMD. Ud, 1). Again, my cpinion in this regard is, in fact, confirmed by other
`
`confemporancous 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”:
`
`
`t
`
`
`4. Regeneron Pharmaceuticals
`Inc, Baver HealthCare AG.
`
`
`Regeneron and Bayer HealthCare Announce Encouraging
`
`
`32-Week Follow-Up Results frora a Phasco 2 Stady of VEGF
`Trap--Eye in Age-Related Macular Degeneration.:Media Re:
`
`
`tease! 2S Apr 20Us
`URL: http-//www.tegener-
`
`
`an.cont
`
`
`SR]
`
`
`
`Indeed, press releases such as Regeneron
`(Ex.1007, Adis, 268 (emphasis added)}.
`
`(28-September-2008) were well-known—and widely available—to the community
`
`interested in the subject matter of the 069 patent.
`
`(See, e.g, id, 262-63, 268-69),
`
`59.
`
`fa my opinion (and as confirmedby, 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 wouldhaveatleast led the person ofordinary
`
`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 electroniccopy.
`
`" See, ¢.g., Ex.1056, Regeneron (28-September-2008), 1.
`
`Qe ho
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 34
`
`Celltrion Exhibit 1014
`Page 457
`
`Celltrion Exhibit 1014
`Page 457
`
`

`

`60.
`
`For at
`
`least
`
`these reasons,
`
`it
`
`is my opinion that Regeneron (28-
`
`September-2008) was a well-known, printed publication that was publicly accessible
`
`to persons interested and ordinaniy skilled in the subject matter or art of the “069
`
`patent, exercising reasonable diligence, before 2011.
`
`3.
`
`April 2008 Press Release.
`
`61.
`
`Regeneron issued a press release dated April 30, 2009 (Ex.1028,
`
`Regeneron (30-April-2009)), which described the extension of Regeneron’s gicbal
`
`development program for VEGF Trap-Eye to include Central Retinal Vein
`
`Occlusion (“CRVO”), Ud. 1).
`
`62.
`
`Specifically, Regeneron (G0-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).” (ed. 1).
`
`63.
`
`A person of ordinary skill in the art would have understood that the
`
`dosing regimens disclosed in Regeneron (30-Apr-2009) included the experimental
`
`group that received 6 monthlyintravitreal injections of VEGF Trap-Hye at a dose of
`
`2 milligrams. (/d., 1).
`
`64. A person of ordinaryskili in the art would have been mterested i, and
`
`sought out,
`
`the information disclosed in Regeneron (30-April-2009) because it
`
`pertains to ongoing product development within the industry, meluding dosing
`
`regimens of a known therapy (VEGF Trap-Hye or afltbercept) in patients with
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 35
`
`Celltrion Exhibit 1014
`Page 458
`
`Celltrion Exhibit 1014
`Page 458
`
`

`

`CRVO. Ud, 1). Again, my opinion in this regardis, in fact, confirmed by other
`
`contemporancous prior art
`
`to the °G69 patent
`
`that expressly refer to similar
`
`Regeneron and Bayer press releases. For example, Adis provides the following
`
`among twenty separate references to onlme “Media Releases”
`
`t
`
`
`
`
`4. Regeneron Pharmaceuticals
`Inc, Baver HealthCare AG.
`
`
`Regeneron and Bayer HealthCare Announce Encouraging
`
`
`32-Week Follow-Up Results frora a Phasco 2 Stady of VEGF
`Trap--Eye in Age-Related Macular Degeneration.:Media Re:
`
`
`tease! 2S Apr 20Us
`URL: http-//www.tegener-
`
`
`an.cont
`
`
`SR]
`
`
`
`(Ex.1007, Adis, 268 (emphasis added)}.
`
`Indeed, press releases such as Regeneron
`
`(30-April-2009) were well-known—and widely available—to the community
`
`interested in the subject matter of the 069 patent.
`
`(See, e.g, id, 262-63, 268-69),
`
`65.
`
`fa 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-Aprii-2009)
`
`exercising reasonable diligence, which wouldhaveat least led the person ofordinary
`
`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 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 36
`
`Celltrion Exhibit 1014
`Page 459
`
`Celltrion Exhibit 1014
`Page 459
`
`

`

`66.
`
`Forat least these reasons, it is my opinion that Regencron (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 VINCFtrial. (/d., 1; see
`
`also Ex.1066, Bayer (18-February-2010), 1).
`
`68.
`
`The patients in the study were randomized into five groups: four
`
`experimental groups and one control group.
`
`(Ex.1057, Regeneron (18-February-
`
`2010), 1). One of the experimental groups 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... every 8-week dosing” while another experimental group recetved “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.” (ad).
`
`69. A person of ordinary skill im the art would have understood that the
`
`dosing regimens disclosed in Regeneron (18-February-2010) included the two
`
`experimental groups that received 2 mg intravitreal VEGF Trap-Eye either (1) every
`
`35
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 37
`
`Celltrion Exhibit 1014
`Page 460
`
`Celltrion Exhibit 1014
`Page 460
`
`

`

`other month following three initial monthly injections, or (2) as needed (PRN}
`
`following three initial monthly injections. Cal, 1).
`
`70. Aperson of ordinary skill in the art would have been interested in, and
`
`sought out, the information disclosed in Regeneron (18-Febrnary-2010) becauseit
`
`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). Agam, my opinion in 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”
`
`URL: bttp:/Avww.regener-
`
`Inc, Bayer HealthCare AG,
`{4. Regeneron Pharmaceuticals
`Regeneron und Bayer HealthCare Announce Encouraging
`32-Week Follow-Up Results from a Phase 2 Snidy of VEGF
`Si
`‘Trap-Eye in Age-Related Macular Degencration. Stodin Re
`Isase, 29 Ape200
`on.com
`
`(Ex.1007, Adis, 268 (emphasis added}).
`
`Indeed, press releases such as Regeneron
`
`(18-February-2010) were well-known-—-and widely available-—to the community
`
`interested im the subject matter ofthe °069 patent.
`
`(See, e.g., id, 262-63, 268-69).
`
`71.
`
`In my oprnion (and as confirmed by, e.g., Adis), a person of ordinary
`
`slall in the art would have also been able to locate Regeneron (18-February-2010}
`
`exercising reasonable diligence, which would haveat least led the person of ordinary
`
`skill in the art to Regeneron’s website where the document was easily accessible,
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 38
`
`Celltrion Exhibit 1014
`Page 461
`
`Celltrion Exhibit 1014
`Page 461
`
`

`

`and recognize and comprehend therefrom the essentials of the subject matter
`
`contained therem without further research or experimentation.” Thus, a person of
`
`ordinary skill in the art could have casily accessed Regeneron (18-February-2010)
`
`via Regeneron’s website and easily downloaded an electronic copy.
`
`72.
`
`For at
`
`jeast
`
`these reasons,
`
`if
`
`is my opmion that Regeneron (18-
`
`February-2010) was a well-known, printed publication that was publicly accessible
`
`io persons interested and ordinaniy skilled in the subject matter or art of the 069
`
`patent, exercising reasonable diligence, before 2011.
`
`5.
`
`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 their 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}hwo
`
`groups received either 0.5 or 2.0 mg of VEGF Trap-Eve administered every four
`
`weeks, and three groups receiveda single dose of 0.5, 2.0, or 4.0 mg of VEGFTrap-
`
`Eye.” Ud, 1). Furthermore, the President of Regeneron Research Laboratories was
`
`* £x.1057, Regeneron (18-February-2010), 1.
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 39
`
`Celltrion Exhibit 1014
`Page 462
`
`Celltrion Exhibit 1014
`Page 462
`
`

`

`quoted as stating “[olur Phase 3 program is being designed to test this possibility
`
`and further evaluate the safety and efficacy of various doses and dosing intervals of
`
`the VEGF Trap-Eye.” 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 Qvet AMD).”
`
`(Ud, 1).
`
`Specifically, Regeneron (2-August-2007)
`
`described “VEGF Trap-Eye ... doses... 2.0 mg at an eight-week dosing interval.”
`
`(id),
`
`76.
`
`Regeneron and Bayer HealthCare AGissued a press release dated April
`
`28, 2008 (Ex.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-relatedMacular Degeneration
`
`(wet AMD)”treated with VEGF Trap-Eye. Ud, 1: see also Ex.1067, Bayer (28-
`
`April-2008), 1).°°
`
`discussed herein is essentially the same as the information disclosed withmthe
`
`corresponding Bayer Press Releases.
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`
`Celltrion Exhibit 1014
`
`Celltrion Exhibit 1014
`Page 463
`
`

`

`77,
`
`The patients m the study were “randomized to five dose groups” as
`
`follows:
`
`()
`
`monthly dose of 0.5 milligrams (ng) 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-Evyefor twelve weeks followed
`
`by therapy at the same dose on a PRNdosing schedule;
`
`quarterly dose of 0.5 mg of VEGF Trap-Eve (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 bytherapyat the same dose on a PRN dosing schedule; or
`
`quarterly dose of 4.0 me of VEGE Trap-Eye (at baseline and week 12)
`
`followed by therapyat the same dose on a PRN dosing schedule.
`
`(Ex.1012, Regeneron (28-April-2008), 1).
`
`78.
`
`Regeneron (28-Apml-2008) added that VEGF Trap-Eye was being
`
`evaluated “using a monthly loading dose of... 2.0 mg for 12 weeks, followed by a
`
`nine-month fixed-dosing regimen of ... 2.0 mg every eight weeks” or “monthly
`
`doses of 0.5 or 2.0 milligrams (mg} of VEGF Trap-Eye for 12 weeks” followed by
`
`1 “PRN?”(or pro re hata) is commonlyunderstood as “as needed” dosing.
`
`39
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 41
`
`Celltrion Exhibit 1014
`Page 464
`
`Celltrion Exhibit 1014
`Page 464
`
`

`

`“therapy at the same dese on a PRN dosing schedule based upon the physician
`
`assessment of the need for re-treatment.” CEx.1012, Regeneron (28-April-2008), 1-
`
`DVea}.
`
`79,
`
`Regeneron issued a press release dated September 14, 2009 (Ex. 1068,
`
`Regeneron (14-September-2009)) which deseribed two “Phase 3 clinical
`
`trials
`
`evaluating VEGF Trap-Eye in the treatment of the neovascular form of age-related
`
`macular degeneration (wetAMD).” and a phase 2 trial “forthe treatment of Diabetic
`
`Macular Edema (DME).” Ud, 1). Speerfically, Regeneron (14-September-2009)
`
`described “VEGF Trap-Eye... dosed... 2.0 mg every eight weeks (ollowing 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. (/d.).
`
`80.
`
`Aperson of ordinary skill in the art would have understood that the
`
`dosing regimens disclosed m 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.” (/d., 1).
`
`81. A person of ordinary skill imthe art would have been interested in, and
`
`sought out, the information disclosed in the above Press Releases because they
`
`pertain to ongoing product development within the industry, includme dosing
`
`repimens of a known therapy (VEGFTrap-Eye or aflibercept) in patients with wet
`
`AQ
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 42
`
`Celltrion Exhibit 1014
`Page 465
`
`Celltrion Exhibit 1014
`Page 465
`
`

`

`AMD. (See TY 42-43, 50, 58, 64, 70, above}. Again, my opmion in this regard is, in
`
`fact, confirmed by other contemporaneous prior art to the “069 patent that expressly
`
`refer to sunilar Regeneron and Bayerpress releases. For example, Adis provides the
`
`following among twenty separate references to online “Media Releases”:
`
`EE
`
`
`
`Inc, Bayer HealthCare AG.
`Regeneron and Baver HealthCare Announce Encouraging
`32-Week Follow-Up Results trom a Phase 2 Study of VEGF
`Trap-Eye in Age-Related Macular Degeneration. Median Re-
`
`teaser 29 Apr 2008,
`URL: http://www. regener-
`om.corn
`IMOSJ]HNed
`
`
`
` id. Regeneron Pharmaceuticals
`
`(Ex. 1007, Adis, 268 (emphasis added)). Indeed, press releases such as Regeneron’s
`
`Press Releases were well-known-—and widely available-—-to the community
`
`miterested tn the subject matter of the ‘069 patent.
`
`(See, e.g., id, 262-63, 268-69).
`
`82.
`
`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 these Regeneron Press Releases
`
`exercising reasonable diligence, which would haveat least led the person ofordinary
`
`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, Regeneron (27-March-2007), 1, Ex.1054, Regeneron (2-August-2007),
`
`i; Ex.1012, Regeneron (28-April-2008), 1, Ex.1068, Regeneron (14-September-
`
`2009), 1,
`
`Ay
`
`Mylan Exhibit 1903
`Mylan v. Regeneron, IPFR2021-00880
`Page 43
`
`Celltrion Exhibit 1014
`Page 466
`
`Celltrion Exhibit 1014
`Page 466
`
`

`

`ordinary skill
`
`im the art could have easily accessed these Press Releases via
`
`Regeneron’s website and casily downloaded an electronic copy.
`
`83.
`
`For at least these reasons,
`
`it is my opinion that Regeneron’s Press
`
`Releases outlined above were well-known, printed publications that were publicly
`
`accessible fo persons interested and ordinarily skilled in the subject matter or art of
`
`the °069 patent, exercising reasonable diligence, before 2011.
`
`C.
`
`CLINiCALTRIALS.GOV,
`
`84.
`
`ChnicalTrials.gov is an electronic registry and results database of
`
`clinical studies supported by the U.S. 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 information
`
`on publicly and privately supported clinical studies on a wide range of diseases and
`
`conditions.’ Each study record includes a summary of the study protocol.
`
`ChnicalTrials. gov includes records for several clinical studies involving aflibercept,
`
`including:
`
`e
`
`VIEW! (ClinicalTrials govidentifier NCT00509795) (Ex. 1014, NCT-
`
`795);
`
`'S Bx.1069, Background-ClinicalTrials.gov, 1-3.
`
`42
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 44
`
`Celltrion Exhibit 1014
`Page 467
`
`Celltrion Exhibit 1014
`Page 467
`
`

`

`®
`
`®
`
`VIEW? (ClinicalTrials.govidentifier NCT00637377) (Ex.1015, NCT-
`
`377), and
`
`GALILEO (ClinicalTrials.gov identifier NCTOI012973)
`NCT-973).
`
`(Ex.1029,
`
`85. NCT-973 (GALILEO) was first available as of at least July 22, 2010
`
`and describes a clinical study titled “A Randomized, Doubie-masked, Sham-
`
`controlled Phase 3 Study of the Efficacy, Safety and Tolerability of Repeated
`
`Intravitreal Administration of VEGF Trap-Eye in Subjects With Macular Edema
`
`Secondary to Central Retinal Vein Occlusion (CRVO).” CEx.1029, NCT-9753, 5;
`
`Ex.1070, Wayback-Affidavit-069 (Wayback Machine records showing public
`
`availability of NCT-973 priorto Jan. 13, 2011); Ex.1071, Holz, 278 (GALILEOis
`
`a phase IT, randomised, double-masked, multi-centre clinical study.. . registered as
`
`NCTO1012973 on clinicaltrials.gov”).4 NCT-973 lists the following experimental
`
`“arms” ofthe study:
`
`4SeealsoEx.1014,NCT-795, 3; Ex.1070, Wayback Affidavit-069 (Wayback
`
`Machine records showing public availability of NCT-795, describing a clinical study
`
`titled “A Randomized, Double Masked, Active Controlled Phase U1 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,
`
`(a2
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 45
`
`Celltrion Exhibit 1014
`Page 468
`
`Celltrion Exhibit 1014
`Page 468
`
`

`

`
`
`.
`Experimental: Arm 1
`
`VEGP Trap-Eye Intravitreal
`
`Injection
`
`intravitreal injection. Weeks 0 to 20
`
`injection of VEGF Trap-Eye every4
`
`weeks; weeks 24 to 48 every 4 weeks
`
`re-assessment and either (PRN}
`
`injection of VEGF Trap-Eve or sham
`
`injection; weeks 52 to 100safety
`
`
`
`
`follow-up.
`
`
`Sham Comparator: Ann 2
`
`Sham treatment. Weeks 0 to 20 sham
`
`Shamtreatment
`a1
`
`treatment every 4weeks; weeks 24 to
`
`2011); Ex.1G18, Heter-2012, 2539
`
`(‘Patients
`
`im VIEW 1
`
`(registered at
`
`www.clinicaltriais. gov on July 31, 2007... °)); Ex. 1015, NCT-377, 3-4: Ex.1070,
`
`Wayback- Affidavit (Wayback Machine records showing public availability of NCT-
`ope
`if377, describing a clinical study titled “A Randomized, Double Masked, Active
`
`Controlled, Phase 3 Study of the Efficacy, Safety, and Tolerability of Repeated
`
`Doses of Intravitreal VEGYTrap in Subjects With Neovascular Age-related Macular
`
`Degeneration (AMD),” prior
`
`to Jan. 13, 2011); Ex.1018, Heter-2012, 2539
`
`(“Patients m VIEW 2
`
`(registered at www.clinicalinals. gov on March 12,
`
`2008 ...”))).
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 46
`
`Celltrion Exhibit 1014
`Page 469
`
`Celltrion Exhibit 1014
`Page 469
`
`

`

`
`
`
`
`| follow-up.
`
`i 48 every 4 weeks re-assessment and
`
`|| shaminjection; weeks 52 to 100 safety
`
`(Ex.1029, NCT-973, 3).)° The experimental anns above included the group which
`
`required participants to receive “[wleeks 0 to 20 injection of VEGF Trap-Eye every
`
`4 weeks; weeks 24 to 48 every 4 weeks re-assessment and either PRN) injection of
`
`VEGF Trap-Eye or sham injection; weeks 52 to 100 safety follow-up.” (/a.).'°
`
`86.
`
`A person of ordinary skill m the art would have understood that the
`
`dosing regimens disclosed in NCT-973 included the experimental group 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.1014, NCT-795, 8 (experimental arms included the group which
`
`required participants to receive “2.0 mg VEGF Trap-Eye administered every 8
`
`weeks Gnecluding one additional 2.0 mg dose at week 4) during the first year’);
`
`Ex.1015, NCT-377, 6 (expermmental arms included the group which required
`
`participants to recetve “2.0 mg VEGF Trap-Eye administered every 8 weeks
`
`(including one additional 2,0 mg dose at Week 4} during the first year’).
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 47
`
`Celltrion Exhibit 1014
`Page 470
`
`Celltrion Exhibit 1014
`Page 470
`
`

`

`received VEGF Trap-Eve every four weeks for twenty weeks followed by “(PRN)}
`
`injection of VEGF Trap-Eye.” (Ex.1029, NCT-973, 5).7
`
`87.
`
`Aperson of ordinary skill in the art would have been interested in and
`
`easily accessed and sought out the information disclosed on the ClinicalTrials,gov
`
`website regarding NCT-795, NCT-377, and NCT-973 because they each pertain to
`
`ongoing product development within the industry, including dosing regimens ofa
`
`known therapy (VEGF Trap-Pye or aflibercept) m 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 disseminated or otherwise made available to the extent that persons
`
`interested and ordinarily skilled in the subject matter or art of the "069 patent,
`
`exercising reasonable diligence, could locate them.
`
`88. My opmion in
`
`this
`
`regard is,
`
`in
`
`fact,
`
`confirmed by other
`
`contemporaneous prior art to the °069 patent that expressly cited to clinical trial
`
`’ See also Ex.i014, NCT-795, 8 (including 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 (included the experimental group that received
`
`VEGFTrap-Eye 2.0 mg every two months “including one additional 2,0 mg dose at
`
`Week 47).
`
`46
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`
`Celltrion Exhibit 1014
`
`Celltrion Exhibit 1014
`Page 471
`
`

`

`records from Clinical Trials gov, including NCT-795, NCT-377, and NCT-973. For
`
`example, Reichert (Ex.1072, Reichert)'* provides the following disclosures of NCT-
`
`795, NCT-377, and NCT-973:
`
`In the 4 arm
`(Lucentis®, Genentech}.
`VIEW 1 study [NOTOOSQ9795]. adult
`patients (50 years and older) in arms |
`and 2 are administered either 0.5 or 2.0
`mg aflibercept every four weeks for 1 year,
`then the same dose ts administered as fre-
`quently as every four weeks but no less
`
`frequently than evety 12 weeks. Patients
`pletion date isAugust 2011.
`
`(/d., 94 Cemphasis added)}:
`
`is September 2013. The on-going VIEW
`2 [NCTQ0637377) has the same designas
`VIEW1, but is being conducted at sites
`in Europe, Asia Pacific, Japan and Latin
`America by Bayer. A total of1,21] patients
`were recruited: the estitmared.study com-.
`
`Ud, 935 (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).
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 49
`
`Celltrion Exhibit 1014
`Page 472
`
`Celltrion Exhibit 1014
`Page 472
`
`

`

`
`
`
`
`
`SSSRSSSRSG
`In the placebo-controlled GALILEOS
`study [NOL01012973], patients in the
`experimental
`arm receive
`intravitreal’
`‘injections of aflibercept every tour weeks
`during weeks 0-20, every four weeks
`
`‘during weeks 24 to 52 plus additional\:
`SS
`
`injections of either aflibercept or placebo
`on week 60 and 68 at
`re-assessment.S
`sonweekOUand06atfe-assessment.<o
`
`(d., 95 (emphasis added)}. Moreover, Reichert makes multiple, express references
`
`to obtaining information online directly from ClinicalTrials. gov. Ud, 79 (Table 7
`
`(listed on chmicaltrials.gov’)); id. , 99 (Ref. No. 69 (citing ClinicalTrials. gov record
`
`and corresponding internet address})).
`
`89. Similarly, Anderson (Ex.1073, Anderson)!’ provides the following
`
`disclosures of NCT-795 and NCT-377 online reports:
`
`
`
`
` ie
`‘Two phase HI! clinical tdals are underway (VIEW-1 in the USA
`and Canada and VIEW-2 in Durope, AsiaVacific, Japan and Latin
`America). These non-inferiority studies aim to compare efficacy of
`VEGF Trap against ranibizimab. Study completion is expected in
`
`2012 and 2011
`
`&
`
` act of VEGE
`
` Ex.1073, Anderson, 272 (Anderson is a printed publication that was publicly
`
`available prior to January 13, 2011, and would be considered pricrart to the “069
`
`patent).
`
`AS
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 50
`
`Celltrion Exhibit 1014
`Page 473
`
`Celltrion Exhibit 1014
`Page 473
`
`

`

`Ud., 275 (emphasis added}). Anderson made additional references to obtaining
`
`information from ClinicalTrials. gov. Ud, 272-77, 280; see also id., 373 (Figure |
`
`(Graph displaying
`
`the mumber of
`
`clinical
`
`trials
`
`registered with
`
`the
`
`ClinicalTrials. gov registry (http://clmicaltrials. gov) each year between 2001 and
`
`2009."))).
`
`90. Another example, Cinlla (Ex.1074, Ciulla),”’ provides the following:
`
`igaS
`
`<\&\\\\
`
`52 (P<0.0001 for both from baseline). Currently, 6
`randomized, international phase PLL studies (VIIEW-1 and
`
`
`
`VIEW-2) (bup:/Avww.clinicaliials.gov
`fe
`©
`
`) are comparing intravitreal VEF
`a} trap
`
`
`‘ with ranibizgumah:
`
`Ud., 162 (emphasis added)}. Cilla also made numerous other references to
`
`ChnnicalTrials.gov and obtaining information from that database. (fa, 162-63).
`
`91.
`
`Ni (Ex.1075, Nij}*' provided the following:
`
`** Ex .1074, Ciulia, 158 (Ciulla is a printed publication that was publicly available
`
`prior to January 13, 2011, and would be considered prior art to the °069 patent).
`
`“| Ex. 1075, Ni, 401 (Ni is a printed publication that was publicly available prior to
`
`January 13,2011, and would be considered prior art to the ’069 patent).
`
`AQ
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 51
`
`Celltrion Exhibit 1014
`Page 474
`
`Celltrion Exhibit 1014
`Page 474
`
`

`

`
` ofIVTEGEF Trap--Eye|inSubjects withWet
`AMD (VIEW 1). hipsi
`
`
`\28 Vascular Endothelial Growth Factor (VEGF)
`\_Trap-Eye: Investigation of Efficacy and Sate-
`
`ty in Wet Age-Related Macular Degenera-
`A
`
`tion ne (VIEW 2). hitp/fclinicaltrial
`
`
`
`ViNC1003/7377tomers
`
`Ss
`
`\
`
`%Ya
`A7 Z.
`
`(id., 409 (emphasis added}). Additionally, Ni references numerous clinical trials
`
`with citations to ClinicalTrials.govas the source of the information.
`
`(See, e.g., id,
`
`408-10).
`
`92. Another example, Zarbin (Ex.1076, Zarbin)** provided thefollowing:
`
`
`SSSAswoR}.SSS
`
`
`Phase
`|
`feab
`tral’ VEGF Trap-by
`in
`a
`hupuiichnicalalseeovettshow/kTUOSO079SMern=
`
`
`S
`VEGE+Trup-Evedcrank=14) is formulated for intravitreal
`
`
`©
`inyection, appears to be effective in a Phase 2 trial
`Gwe. bmctodaynet/retinatoday/2009/1 O/article asp lf=
`
`(oes)8.pep and iS how being compare With ©
`
`
`
`
`22 Ex.1076, Zarbin, 1350 (Zarbin is a printed publicationthat was publicly available
`
`prior to January 13, 2011, and would be considered prior art to the °069 patent).
`
`50
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 52
`
`Celltrion Exhibit 1014
`Page 475
`
`Celltrion Exhibit 1014
`Page 475
`
`

`

`(fd, 1360 (emphasis added)}. Additionally, Zarbin also references numerous
`
`clinical trials with citations to ClinicalTrials.gov as the source of the information.
`
`(See id., 1351-52, 1356-62).
`
`93. Dixon (Ex.1006, Dixon}? provides the following citations, further
`
`confirming that both NCT-795 and NCT-377,
`
`inchading the dosing regimens
`
`disclosed therein, were publicly available as ofat least Septernber 28, 2008:
`
`
`
`
`Double-Masked Study of Efficacy and
`
`Safety ofYT VEGF Trap-Eyve in Subjects
`With WerAMID (VIEW 2B [CinicalTrials.
`
`
`
`gov identifiers N
`a
`
`ClinicalTrials. gov fonline]
`
`heep//clinicalerials. gov/cr2/show
`
`NCTOOS89795
`VEGF Thap-Eve: Investigation of Efficacy
`
`andSafety in Wet AMID (VIEW2),
`[Clinical Trials. vov identifier:
`
`clinicalPrials.gov
`NUPQUGS
`TA
`
`
`? hetp//elinicalerials.
`fonline]
`255
`
`cowlct2/sh
`
`
`
`
`
`
`(d@.,
`
`1579 (emphasis added)).
`
`Accordingly,
`
`it
`
`is my firm opinion that
`
`ClinicalTrials.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 January 13, 2011, and wouldbe considered priorart to the “069 patent).
`
`5]
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 53
`
`Celltrion Exhibit 1014
`Page 476
`
`Celltrion Exhibit 1014
`Page 476
`
`

`

`and widely available—to the community interested in the subject matter of the °069
`
`patent.
`
`94.
`
`Prior to 2011, a person of ordinary skill in the 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 ordinary skill
`
`in the art
`
`to the
`
`ClinicalTrials. 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 ofordinary
`
`skill ia the art could have easily accessed NCT-795, NCT-377, and NCT-973 via
`
`ClinicalTrials.gov and easily downloaded an electronic copyof cach.
`
`95.
`
`For the reasons outlined above, a person of ordinary skill in the art
`
`would have considered the pasting dates cited at ClmicalTrials.govto be trustworthy
`
`and authoritative and itis 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
`
`reasonablediligence, before 2011.
`
`4 See Ex. 1014, NCT-795, 1, Ex.1015, NCT-377, 1, Ex.1029, NCT-973, 1.
`
`nn NO
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 54
`
`Celltrion Exhibit 1014
`Page 477
`
`Celltrion Exhibit 1014
`Page 477
`
`

`

`D.
`
`SEC FILINGS,
`
`96. As 1 note above (see 4] 41-44), company press releases were well-
`
`known, and widely available,
`
`to persons of ordinary skill
`
`in the art. This was
`
`especiallytrue ofpersons of ordinaryskill in the art of the °069 patent, who expressly
`
`cited Bayer and Regeneron press releases. GSee, e.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 in the pharmaceutical
`
`industry and academia. A company’s SECtilings provide “reliable information
`
`about [the company] that allows a person mthe 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 also Ex.1078, Schneider, 258 (noting that “SEC
`
`filmgs ... have been considered fo be among the most accurate and reliable...
`
`sources of information available”), Ex.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 (CEDGAR”) or a
`
`company’s website.
`
`(See, e.g., Ex.1080, Zucchi), SEC filings provide, infer alia,
`
`information regardmg the company’s finances as well as recent business activity.
`
`(See id, Ex.1081, Hayes, 3-4, 8-10).
`
`a CAF
`
`Mylan Exhibit 1003
`Mylan v. Regeneron, IPFR2021-00880
`Page 55
`
`Celltrion Exhibit 1014
`Page 478
`
`Celltrion Exhibit 1014
`Page 478
`
`

`

`99,
`
`in my experience in the industry, SEC filings for pharmaceutical or
`
`biotechnology companies included information regarding ongoing development of
`
`different products, including ongoing clinical trials and the results of completed
`
`clinical trials. Thus, a person of ordinaryskill in the art would utilize the information
`
`contamed therein, amongst other references, to keep up te 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 imsuch
`
`“Financial and Operating Results” as confirmed bythe prior art:
`
`
`
`
`8. Regeneron Pharmaceuticals Inc. Regeneron Reports Second
`
`Quarter Figsaciabaad Operating Reailiss BLA Filing for Auto-
`Inflammatory Diseases Planned for Early 2007: Two Antibody
`
`Candidates from Veloclmmune(R} Program to Enter Clinical
`
`
`
`Trials Each Year Beginning in 2007. Media Release: 3 Aug
`
`2006.
`URL: http:/Ayww.regeneron.cem
`
`
`
`
`
`(Ex.1007, Adis, 268 (emphasis added), see also id. (Ref. Nos. 6, 18)).
`
`101. Second, in my opinion, a person of ordinaryskill in the art would have
`
`been aware of such company filings, such as Regeneron’s September 30, 2009 10-
`
`Q 2009 10-0") CEx,. 1021, 2009 10-Q), and would routinely look to 10-Q filings to
`
`determine what drugs and treatments pharmaceutical companies were working on,
`
`Here, Regeneron disclosed information regarding, among other things, its ongoing
`
`development of the VEGF Trap-Eye program—specif

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