`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`MYLAN PHARMACEUTICALS INC.,
`Petitioner
`
`v.
`
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`
`Inter Partes Review No.: IPR2021-00881
`
`
`U.S. Patent No. 9,254,338 B2
`Filed: July 12, 2013
`Issued: February 9, 2016
`Inventor: George D. Yancopoulos
`
`Title: USE OF A VEGF ANTAGONIST TO TREAT
`ANGIOGENIC EYE DISORDERS
`
`
`EXPERT DECLARATION OF DR. THOMAS A. ALBINI
`IN SUPPORT OF PETITION FOR INTER PARTES REVIEW OF
`U.S. PATENT NO. 9,254,338 B2
`
`
`
`
`
`
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 1
`
`Joining Petitioner: Apotex
`
`

`

`
`
`
`I.
`
`TABLE OF CONTENTS
`
`Page
`
`QUALIFICATIONS AND BACKGROUND. ................................................ 1
`
`A.
`
`Education and Experience. .................................................................... 1
`
`B.
`
`Bases for Opinions and Materials Considered. ..................................... 4
`
`C.
`
`Scope of Work. ...................................................................................... 4
`
`II.
`
`LEGAL STANDARDS. .................................................................................. 4
`
`III.
`
`PERSON OF ORDINARY SKILL IN THE ART. ......................................... 9
`
`IV. SUMMARY OF OPINIONS. ........................................................................ 10
`
`V.
`
`THE ’338 PATENT (Ex.1001). ..................................................................... 12
`
`A.
`
`Claim Construction. ............................................................................ 14
`
`VI. BACKGROUND. .......................................................................................... 19
`
`A. Vitreoretinal Disorders. ....................................................................... 19
`
`1.
`
`2.
`
`3.
`
`Age-related macular degeneration (AMD). .............................. 20
`
`Diabetic retinopathy (DR). ........................................................ 22
`
`Diabetic macular edema (DME). .............................................. 22
`
`B.
`
`Angiogenesis and Vascular Endothelial Growth Factor (VEGF). ...... 22
`
`C.
`
`VEGF Antagonists. ............................................................................. 23
`
`D. VEGF Trap-Eye/Aflibercept. .............................................................. 27
`
`E.
`
`Regeneron’s Press Releases and Clinical Trials. ................................ 29
`
`VII. SCOPE AND CONTENT OF THE PRIOR ART REFERENCES. ............. 35
`
`A. Dixon (Ex.1006). ................................................................................. 35
`
`i
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`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 2
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`Joining Petitioner: Apotex
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`

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`TABLE OF CONTENTS
`(continued)
`
`
`
`B.
`
`Adis (Ex.1007). ................................................................................... 40
`
`Page
`
`C.
`
`Regeneron (8-May-2008) (Ex.1013). .................................................. 43
`
`D. NCT-795 (Ex.1014). ........................................................................... 45
`
`1.
`
`2.
`
`ClinicalTrials.gov. ..................................................................... 45
`
`NCT-795 discloses the VIEW1 regimen. ................................. 48
`
`E.
`
`F.
`
`NCT-377 (Ex.1015). ........................................................................... 50
`
`’664 Patent (Ex.1009). ........................................................................ 53
`
`G.
`
`’758 Patent (Ex.1010). ........................................................................ 54
`
`H. Dix (Ex.1033). ..................................................................................... 55
`
`VIII. UNPATENTABILITY OF THE ’338 PATENT. ......................................... 56
`
`A.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Anticipated by Dixon (Ex.1006). ........................................................ 56
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Claim 1 of the ’338 patent is anticipated by Dixon. ................. 61
`
`Dependent claims 3 and 4 are anticipated by Dixon. ............... 64
`
`Dependent claim 5 is anticipated by Dixon. ............................. 65
`
`Dependent claims 6 and 7 are anticipated by Dixon. ............... 66
`
`Dependent claims 8-10 are anticipated by Dixon. .................... 67
`
`Dependent claims 11 and 13 are anticipated by Dixon. ........... 68
`
`Independent claim 14 is anticipated by Dixon. ........................ 69
`
`Dependent claims 16 and 17 are anticipated by Dixon. ........... 70
`
`Dependent claims 18 and 20 are anticipated by Dixon. ........... 71
`
`ii
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 3
`
`Joining Petitioner: Apotex
`
`

`

`TABLE OF CONTENTS
`(continued)
`
`Page
`
`
`
`10. Dependent claim 19 is anticipated by Dixon. ........................... 72
`
`11. Dependent claims 21-23 are anticipated by Dixon. .................. 73
`
`12. Dependent claims 24 and 26 are anticipated by Dixon. ........... 74
`
`B.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Anticipated by Adis (Ex.1007)............................................................ 75
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Claim 1 of the ’338 patent is anticipated by Adis. ................... 75
`
`Dependent claims 3 and 4 are anticipated by Adis. .................. 78
`
`Dependent claim 5 is anticipated by Adis. ............................... 79
`
`Dependent claims 6 and 7 are anticipated by Adis. .................. 81
`
`Dependent claims 8-10 are anticipated by Adis. ...................... 82
`
`Dependent claims 11 and 13 are anticipated by Adis. .............. 82
`
`Independent claim 14 is anticipated by Adis. ........................... 83
`
`Dependent claims 16 and 17 are anticipated by Adis. .............. 84
`
`Dependent claims 18 and 20 are anticipated by Adis. .............. 85
`
`10. Dependent claim 19 is anticipated by Adis. ............................. 86
`
`11. Dependent claims 21-23 are anticipated by Adis. .................... 87
`
`12. Dependent claims 24 and 26 are anticipated by Adis. .............. 87
`
`C.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Anticipated by the Regeneron Press Release Dated May 8, 2008
`(Regeneron (8-May-2008) (Ex.1013). ................................................ 88
`
`1.
`
`Independent claim 1 of the ’338 patent is anticipated by
`Regeneron (8-May-2008). ......................................................... 88
`
`iii
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 4
`
`Joining Petitioner: Apotex
`
`

`

`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Dependent claims 3 and 4 are anticipated by Regeneron
`(8-May-2008). ........................................................................... 91
`
`Dependent claim 5 is anticipated by Regeneron (8-May-
`2008). ........................................................................................ 92
`
`Dependent claims 6 and 7 are anticipated by Regeneron
`(8-May-2008). ........................................................................... 94
`
`Dependent claims 8-10 are anticipated by Regeneron (8-
`May-2008). ................................................................................ 94
`
`Dependent claims 11 and 13 are anticipated by
`Regeneron (8-May-2008). ......................................................... 95
`
`Independent claim 14 is anticipated by Regeneron (8-
`May-2008). ................................................................................ 96
`
`Dependent claims 16 and 17 are anticipated by
`Regeneron (8-May-2008). ......................................................... 97
`
`Dependent claims 18 and 20 are anticipated by
`Regeneron (8-May-2008). ......................................................... 98
`
`10. Dependent claim 19 is anticipated by Regeneron (8-May-
`2008). ........................................................................................ 99
`
`11. Dependent claims 21-23 are anticipated by Regeneron (8-
`May-2008). ..............................................................................100
`
`12. Dependent claims 24 and 26 are anticipated by
`Regeneron (8-May-2008). .......................................................101
`
`D.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Anticipated by NCT00509795 (NCT-795) (Ex.1014). ..................... 101
`
`1.
`
`Independent claim 1 of the ’338 patent is anticipated by
`NCT-795. ................................................................................101
`
`2.
`
`Dependent claims 3 and 4 are anticipated by NCT-795. ........104
`
`iv
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 5
`
`Joining Petitioner: Apotex
`
`

`

`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Dependent claim 5 is anticipated by NCT-795. ......................105
`
`Dependent claims 6 and 7 are anticipated by NCT-795. ........106
`
`Dependent claims 8-10 are anticipated by NCT-795. ............107
`
`Dependent claims 11 and 13 are anticipated by NCT-795. ....108
`
`Independent claim 14 is anticipated by NCT-795. .................108
`
`Dependent claims 16 and 17 are anticipated by NCT-795. ....110
`
`Dependent claims 18 and 20 are anticipated by NCT-795. ....110
`
`10. Dependent claim 19 is anticipated by NCT-795. ....................111
`
`11. Dependent claims 21-23 are anticipated by NCT-795. ..........112
`
`12. Dependent claims 24 and 26 are anticipated by NCT-795. ....113
`
`E.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Anticipated by NCT00637377 (NCT-377) (Ex.1015). ..................... 113
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`Independent claim 1 of the ’338 patent is anticipated by
`NCT-377. ................................................................................113
`
`Dependent claims 3 and 4 are anticipated by NCT-377. ........116
`
`Dependent claim 5 is anticipated by NCT-377. ......................117
`
`Dependent claims 6 and 7 are anticipated by NCT-377. ........118
`
`Dependent claims 8-10 are anticipated by NCT-377. ............119
`
`Dependent claims 11 and 13 are anticipated by NCT-377. ....120
`
`Independent claim 14 is anticipated by NCT-377. .................120
`
`Dependent claims 16 and 17 are anticipated by NCT-377. ....122
`
`v
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 6
`
`Joining Petitioner: Apotex
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`

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`
`
`TABLE OF CONTENTS
`(continued)
`
`Page
`
`9.
`
`Dependent claims 18 and 20 are anticipated by NCT-377. ....123
`
`10. Dependent claim 19 is anticipated by NCT-377. ....................123
`
`11. Dependent claims 21-23 are anticipated by NCT-377. ..........124
`
`12. Dependent claims 24 and 26 are anticipated by NCT-377. ....125
`
`F.
`
`Claims 1, 3-11, 13, 14, 16-24, and 26 of the ’338 Patent Are
`Obvious in View of Dixon, Either Alone or in Combination
`with the ’758 Patent or Dix. .............................................................. 126
`
`1.
`
`2.
`
`3.
`
`4.
`
`5.
`
`6.
`
`7.
`
`8.
`
`9.
`
`Independent claim 1. ...............................................................126
`
`Dependent claims 3 and 4. ......................................................129
`
`Dependent claim 5. .................................................................130
`
`Dependent claims 6 and 7. ......................................................131
`
`Dependent claims 8-10. ..........................................................132
`
`Dependent claims 11 and 13. ..................................................133
`
`Independent claim 14. .............................................................133
`
`Dependent claims 16 and 17. ..................................................135
`
`Dependent claims 18 and 20. ..................................................135
`
`10. Dependent claim 19. ...............................................................136
`
`11. Dependent claims 21-23. ........................................................137
`
`12. Dependent claims 24 and 26. ..................................................137
`
`IX. SECONDARY CONSIDERATIONS. ........................................................ 138
`
`vi
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 7
`
`Joining Petitioner: Apotex
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`

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`
`1. My name is Dr. Thomas A. Albini. I have been retained by counsel for
`
`Mylan Pharmaceuticals Inc. (“Mylan” or “Petitioner”) to provide my opinion
`
`regarding U.S. Patent No. 9,254,338 (Ex.1001, the “’338 patent”), which I
`
`understand is assigned to Regeneron Pharmaceuticals, Inc. (“Regeneron”). I
`
`understand that Petitioner intends to petition for inter partes review of the ’338
`
`patent, and will request that the United States Patent and Trademark Office cancel
`
`certain claims of the ’338 patent as unpatentable. My opinions in this expert
`
`declaration support Petitioner’s request for inter partes review of the ’338 patent and
`
`the cancellation of claims 1, 3-11, 13-14, 16-24, and 26 (the “challenged claims”).
`
`I.
`
`QUALIFICATIONS AND BACKGROUND.
`
`A. Education and Experience.
`
`2.
`
` I received a Bachelor of Arts degree, Magna Cum Laude, from
`
`Princeton University in 1994. I obtained my M.D. from Johns Hopkins University
`
`School of Medicine in 1999. I completed an internal medicine internship at Jackson
`
`Memorial Hospital in Miami, Florida, and an ophthalmology residency at the
`
`Doheny Eye Institute of the University of Southern California.
`
`3.
`
`After my residency, I completed a uveitis and ocular pathology clinical
`
`and research fellowship at the Doheny Eye Institute followed by a vitreoretinal
`
`surgery fellowship at the Cullen Eye Institute of the Baylor College of Medicine.
`
`1
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`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 8
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`Joining Petitioner: Apotex
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`4.
`
`I was an instructor in ocular inflammation, uveitis, and ophthalmic
`
`pathology at the Doheny Eye institute from 2003-2004. I joined the faculty at the
`
`Bascom Palmer Eye Institute of the University of Miami Miller School of Medicine
`
`as an Assistant Professor of Clinical Ophthalmology in 2006. I held the position of
`
`Associate Professor of Clinical Ophthalmology at the Bascom Palmer Eye Institute
`
`from 2012 to June 2018. Since July 2016, I have served as co-director of the
`
`vitreoretinal surgery fellowship. Since June 2018, I have been a Professor of Clinical
`
`Ophthalmology. In my current and prior positions, I have been involved in the
`
`teaching and training of medical students, fellows, and residents in the area of
`
`ophthalmological surgical techniques, specifically, injection protocols for the
`
`administration of therapeutics for the treatment of age-related macular degeneration
`
`(AMD) and other vitreoretinal eye disorders. Further, in 2006, I began my current
`
`roles as a staff ophthalmologist at both the Anne Bates Leach Eye Hospital of the
`
`Bascom Palmer Eye Institute as well as the Jackson Memorial Hospital.
`
`5.
`
`I was awarded the American Academy of Ophthalmology Achievement
`
`Award in 2011 and Senior Achievement Award in 2019. In 2012, I received the
`
`Service Award from the American Society of Retina Specialists for outstanding
`
`service to the Society’s scientific and educational programs. I also received the
`
`Senior Honor Award from the American Society of Retina Specialists in 2012.
`
`2
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 9
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`Joining Petitioner: Apotex
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`6.
`
`I have served as an editor, co-editor, or on the editorial board of several
`
`publications, including Retina Today, the website for the American Society of
`
`Retina Specialists, New Retina MD, and the Journal of VitreoRetinal Diseases.
`
`7. My clinical practice is focused on the diagnosis and treatment of
`
`patients suffering from various macular diseases, such as macular degeneration,
`
`diabetic retinopathy and related disorders, as well as uveitis. I have experience with
`
`surgical interventions as well as the prescription and administration of various
`
`intravitreally-administered anti-angiogenesis agents.
`
`8.
`
`I was and currently am a member in several Professional and Academic
`
`Societies, including American Academy of Ophthalmology, Association for
`
`Research in Vision and Ophthalmology, American Society of Retina Specialists,
`
`Miami Ophthalmological Society, Vitrectomy Buckle Society, American Uveitis
`
`Society, The Macula Society, Pan American Association of Ophthalmology, and
`
`The Retina Society, among others.
`
`9.
`
`I have authored or co-authored over two hundred and fifty (250)
`
`publications, including book chapters, peer-reviewed scientific papers, abstracts,
`
`and other published works. Several of these publications pertain to AMD, retinal
`
`detachment, retinal and choroidal diseases, or diabetic macular edema (DME),
`
`among other disorders of the eye.
`
`3
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 10
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`Joining Petitioner: Apotex
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`10.
`
`In all, I have over fifteen (15) years of hands-on clinical and research
`
`experience specializing in treating vitreoretinal disorders and the prescription, and
`
`intravitreal administration, of VEGF antagonists. I have included a copy of my
`
`curriculum vitae in support of my opinions. (Ex.1038, Albini CV).
`
`B.
`
`Bases for Opinions and Materials Considered.
`
`11.
`
`In addition to my education, knowledge of the relevant published art,
`
`training, and experience, in forming the opinions I provide in this declaration, I have
`
`also considered the exhibits cited herein.
`
`C.
`
`Scope of Work.
`
`12.
`
`I have been retained by Petitioner as an expert in this matter to provide
`
`my various opinions regarding the ’338 patent. I receive $500 per hour for my
`
`services. No part of my compensation is dependent upon my opinions given or the
`
`outcome of this case. I do not have any current or past affiliation with Regeneron,
`
`or any of the named inventors on the ’338 patent.
`
`II. LEGAL STANDARDS.
`
`13. For my opinions in this declaration, I understand that it requires
`
`applying various legal principles. As I am not an attorney, I have been informed
`
`about various legal principles that govern my analysis. I have used my
`
`understanding of those principles in forming my opinions. I summarize my
`
`understanding of those legal principles as follows:
`
`4
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 11
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`Joining Petitioner: Apotex
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`14. Burden of Proof. I understand that Petitioner bears the burden of
`
`proving unpatentability in this proceeding by a preponderance of the evidence. I am
`
`informed that this preponderance of the evidence standard means that Petitioner
`
`must show that unpatentability is more probable than not.
`
`15. Claim Construction. I have also been told that when I review and
`
`consider the claims, the claim term(s) should be analyzed under their ordinary and
`
`customary meaning as understood from the perspective of one of ordinary skill in
`
`the art, taking into account the claim language itself, specification, and prosecution
`
`history pertaining to the patent, as well as relevant extrinsic evidence. I have applied
`
`this standard in formulating my opinions, and set forth my understanding of the
`
`scope of particular claim terms discussed below.
`
`16. Anticipation. I have been asked to consider the question of
`
`anticipation, namely, whether the claims cover something that is new, or novel. I
`
`am told that the concept of anticipation requires that each and every element of a
`
`challenged claim is present in or otherwise taught by a single reference. I also
`
`understand that an anticipatory reference does not need to explicitly describe each
`
`element because anticipation can occur when a claimed limitation is necessarily
`
`inherent or otherwise implicit in the relevant reference.
`
`17. Obviousness. I have been asked to consider the question of
`
`obviousness/non-obviousness. Again, I am told that this analysis must be from the
`
`5
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`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 12
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`Joining Petitioner: Apotex
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`perspective of the person of ordinary skill in the art, and whether such person would
`
`consider any differences between the prior art and what is claimed to have been
`
`obvious. To make this assessment, I have been informed that the concept of patent
`
`obviousness involves four factual inquiries:
`
`•
`
`the scope and content of the prior art;
`
`•
`
`the differences between the claimed invention and the prior art;
`
`•
`
`the level of ordinary skill in the art; and
`
`• so-called secondary considerations of non-obviousness.
`
`18.
`
`I have further been instructed that one cannot use the challenged patent
`
`itself (here, the ’338 patent) as a guide from which to select prior art elements, or
`
`otherwise engage in hindsight. Rather, the better approach is to consider what the
`
`person of ordinary skill in the art knew, and what the art taught; suggested; or
`
`motivated the person of ordinary skill in the art to further pursue; and to differentiate
`
`between steps that were routinely done (such as in response to known problems,
`
`steps, or obstacles), and those which, for example, may have represented a different
`
`way of solving existing or known problems.
`
`19.
`
`I am also informed that when there is some recognized reason to solve
`
`a problem, and there are a finite number of identified, predictable, and known
`
`solutions, a person of ordinary skill in the art has good reason to pursue the known
`
`options within his or her technical grasp. If such an approach leads to the expected
`
`6
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`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 13
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`Joining Petitioner: Apotex
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`success, it is likely not the product of innovation but of ordinary skill and common
`
`sense. In addition, when a patent simply arranges old elements with each performing
`
`its known function and yields no more than what one would expect from such an
`
`arrangement, the combination is obvious.
`
`20.
`
`I understand that before reaching any final conclusion on obviousness,
`
`the obviousness analysis requires consideration of objective indicia of non-
`
`obviousness, if offered. These must be considered to ensure that, for example, there
`
`were not some unanticipated problems, obstacles, or hurdles that may seem easy to
`
`overcome in hindsight, but which were not readily overcome prior to the relevant
`
`invention date of the patents/claims at issue here. I understand that these objective
`
`indicia are also known as “secondary considerations of non-obviousness,” and may
`
`include long-felt but unmet need and unexpected results, among others. I also
`
`understand, however, that any offered evidence of secondary considerations of non-
`
`obviousness must be comparable with the scope of the challenged claims. This
`
`means that for any offered evidence of secondary considerations of non-obviousness
`
`to be given substantial weight, I understand the proponent of that evidence must
`
`establish a “nexus” or a sufficient connection or tie between that evidence and the
`
`merits of the claimed invention, which I understand specifically incorporates any
`
`novel element(s) of the claimed invention. If the secondary considerations evidence
`
`offered actually results from something other than the merits of the claim, then I
`
`7
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`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
`Page 14
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`Joining Petitioner: Apotex
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`understand that there is no nexus or tie to the claimed invention. I also understand
`
`it is the patentee that has the burden of proving that a nexus exists.
`
`21. With respect to long-felt need, I understand that the evidence must
`
`show that a particular problem existed for a long period of time. More specifically,
`
`I understand that for a “need” to be long-felt and unmet, (i) the need must be
`
`persistent and recognized by those of ordinary skill in the art; (ii) the need must not
`
`be satisfied by another before the alleged invention; and (iii) the claimed invention
`
`itself must satisfy the alleged need. I also understand that long-felt need is analyzed
`
`as of the date that the problem is identified. Furthermore, I understand that long-felt
`
`need should be based upon alleged inadequacies in the technical knowledge of those
`
`skilled in the art, not due to business-driven market forces.
`
`22.
`
`I further understand that, absent a showing of a long-felt, unmet need,
`
`the mere passage of time without the claimed invention is not evidence of non-
`
`obviousness.
`
`23. With respect to unexpected results, I understand that any results upon
`
`which a patentee wishes to rely as an indicator of non-obviousness must be based on
`
`a comparison of the purported inventions with the closest prior art.
`
`24. However, I understand that secondary considerations will not overcome
`
`a strong showing of obviousness.
`
`8
`
`Mylan Exhibit 1002
`Mylan v. Regeneron, IPR2021-00881
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`25. Public Availability. I have also been asked to consider whether there
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`is a reasonable likelihood that some of the references discussed herein would have
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`been publicly accessible before the priority date of the ’338 patent. I have been
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`informed that a reference is “publicly accessible” if the document has been
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`disseminated or otherwise made available to the extent that persons interested and
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`ordinarily skilled in the subject matter or art exercising reasonable diligence, can
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`locate it.
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`III. PERSON OF ORDINARY SKILL IN THE ART.
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`26. As I mentioned above, I have been informed by counsel that my
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`analysis is to be conducted from the perspective of a person of ordinary skill in the
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`art at the time of the invention. I also understand that the person of ordinary skill in
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`the art is assumed to know, understand, and be familiar with all of the relevant prior
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`art, and that such person is not an automaton, but rather a person of ordinary
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`creativity.
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`27.
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`I have also been informed by counsel that in defining a person of
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`ordinary skill in the art, the following factors may be considered: (1) the educational
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`level of the inventor; (2) the type of problems encountered in the art; (3) prior art
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`solutions to those problems; (4) rapidity with which innovations are made; and (5)
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`sophistication of the technology and educational level of active workers in the field.
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`28. After considering the above-mentioned factors, it is my opinion that a
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`person of ordinary skill in the art would have: (1) knowledge regarding the diagnosis
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`and treatment of angiogenic eye disorders, including the administration of therapies
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`to treat said disorders; and (2) the ability to understand results and findings presented
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`or published by others in the field, including the publications discussed herein.
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`Typically, such a person would have an advanced degree, such as an M.D. or Ph.D.
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`(or equivalent, or less education but considerable professional experience in the
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`medical, biotechnological, or pharmaceutical field), with practical academic or
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`medical experience in: (i) developing treatments for angiogenic eye disorders, such
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`as AMD, including through the use of VEGF antagonists, or (ii) treating of same,
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`including through the use of VEGF antagonists.
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`IV. SUMMARY OF OPINIONS.
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`29.
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`It is my opinion that Dixon anticipates the challenged claims of the ’338
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`patent through Dixon’s disclosure of the dosing regimen used by Regeneron in their
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`Phase 3 VIEW1 and VIEW2 AMD trials (3 monthly doses of 2 mg, followed by 2
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`mg every eight weeks).
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`30.
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`It is my opinion that Adis anticipates the challenged claims of the ’338
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`patent through Adis’ disclosure of the dosing regimen used by Regeneron in their
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`Phase 3 VIEW1 and VIEW2 AMD trials (3 monthly doses of 2 mg, followed by 2
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`mg every eight weeks).
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`31.
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`It is my opinion that Regeneron’s May 2008 Press Release (“Regeneron
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`(8-May-2008)”) anticipates the challenged claims of the ’338 patent through the
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`disclosure of the dosing regimen used by Regeneron in their Phase 3 VIEW2 AMD
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`trial (3 monthly doses of 2 mg, followed by 2 mg every eight weeks).
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`32.
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`It is my opinion that Regeneron’s publicly accessible clinicaltrials.gov
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`submissions (NCT-795 and NCT-377) also anticipate the challenged claims of the
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`’338 patent through their disclosure of the dosing regimen used by Regeneron in
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`their Phase 3 VIEW1 and VIEW2 AMD trials (3 monthly doses of 2 mg, followed
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`by 2 mg every eight weeks).
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`33.
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`It is my opinion that the public disclosures of Regeneron’s
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`VIEW1/VIEW2 trials make the challenged claims obvious, because they disclose all
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`aspects of the claimed dosing regimen, and because combined with the skilled
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`person’s knowledge regarding the VEGF Trap-Eye/aflibercept sequence and
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`structure (as disclosed in the ’758 patent and Dix), as well as the motivation in the
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`art to reduce injection frequency, and the positive results observed in the Phase 2
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`CLEAR-IT clinical trials, persons of ordinary skill in the art would have had a
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`reasonable expectation of success in using the VIEW1/VIEW2 regimens.
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`34.
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`It is also my opinion that there are no “secondary considerations” that
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`would support the patentability of the claims of the ’338 patent. First, it is my
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`understanding that secondary considerations are not relevant in the context of
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`anticipation and it is my opinion that each of the VIEW1/VIEW2 disclosures
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`mentioned above anticipate the ’338 patent claims. Second, in the context of
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`obviousness, it is my opinion that the arguments presented by Regeneron to the U.S.
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`Patent and Trademark Office do not support a finding of surprising or unexpected
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`results, especially given the positive and promising results reported for the Phase 2
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`trial and public disclosure of the Phase 3 dosing regimen.
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`V. THE ’338 PATENT (Ex.1001).
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`35.
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`I have read the ’338 patent, which is titled “Use of a VEGF Antagonist
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`to Treat Angiogenic Eye Disorders,” as well as the issued claims. I am very familiar
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`with the state of the art at the time this patent was first filed, which I have been asked
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`to assume is January 13, 2011.1 The ’338 patent lists George D. Yancopoulos as the
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`sole inventor.
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`1 I understand the following from the cover page of the ’338 patent: (i) Application
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`No. 13/940,370 (“the ’370 application”) issued as the ’338 patent on or about
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`February 9, 2016; (ii) the ’370 application was filed July 12, 2013; (iii) as a
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`“continuation-in-part” of application No. PCT/US2012/020855, which was filed on
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`January 11, 2012; and (iv) the ’338 patent lists three “provisional” applications filed,
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`respectively, on (a) January 13, 2011; (b) January 21, 2011; and (c) November 21,
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`36.
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`Ihave reviewed the ’338 patent claims from the perspective of a person
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`of ordinary skill in the art and applied each claim’s ordinary and customary meaning
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`in light of the claims, the specification, and the prosecution history, as well as any
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`relevant extrinsic evidence. I understand that Petitioner is challenging claims1, 3-
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`11, 13-14, 16-24, and 26.
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`37.
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`Claims | and 14 are the only independentclaimsandreadas follows:
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`1. A method for treating an angiogenic eye disorder in a
`patient, said method comprising sequentially administering
`to the patient a single initial dose of a VEGF antagonist,
`followed by one or more secondary doses of the VEGF 5
`antagonist, followed by one or more tertiary doses of the
`VEGFantagonist;
`wherein each secondary dose is administered 2 to 4 weeks
`after the immediately preceding dose; and
`wherein eachtertiary dose is administered at least 8 weeks 1°
`after the immediately preceding dose;
`wherein the VEGF antagonist is a VEGF receptor-based
`chimeric molecule comprising (1) a VEGFR1 compo-
`nent comprising amino acids 27 to 129 of SEQ ID NO:2;
`(2)a VEGFR2 component comprising amino acids 130-
`231 of SEQ ID NO:2; and (3) a multimerization com-
`ponent comprising amino acids 232-457of SEQ ID
`NO:2.
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`2011, as “Related U.S. Application Data.” (See Ex.1001, ’338 patent at Cover).
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`I
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`have been asked to assumethat the priority date of the ’338 patent is January 13,
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`2011.
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`I have formed no opinion regarding the merit of