`UNITED STATES PATENT AND TRADEMARK OFFICE
`
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`
`
`MYLAN PHARMACEUTICALS INC., CELLTRION, INC., and
`APOTEX, INC.
`Petitioners
`
`v.
`REGENERON PHARMACEUTICALS, INC.,
`Patent Owner
`
`
`Inter Partes Review No.: IPR2021-008811
`U.S. Patent No. 9,254,338 B2
`
`
`
`
`EXPERT DECLARATION OF DR. THOMAS A. ALBINI
`IN SUPPORT OF PETITIONER REPLY
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`
`
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`1 IPR2022-00258 and IPR2022-00298 have been joined with this proceeding.
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`Mylan Exhibit 1114
`Mylan v. Regeneron, IPR2021-00881
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`TABLE OF CONTENTS
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`Page
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`I.
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`QUALIFICATIONS AND BACKGROUND. ................................................ 1
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`A.
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`B.
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`C.
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`EDUCATION AND EXPERIENCE. ............................................................... 1
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`BASES FOR OPINIONS AND MATERIALS CONSIDERED. ............................ 1
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`SCOPE OF WORK. .................................................................................... 1
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`II.
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`LEGAL STANDARDS. .................................................................................. 2
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`III.
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`PERSON OF ORDINARY SKILL IN THE ART. ......................................... 2
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`IV. MISREPRESENTATIONS OF MY OPENING DECLARATION
`OPINIONS AND DEPOSITION TESTIMONY. ........................................... 3
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`V.
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`CLAIM CONSTRUCTION. ........................................................................... 3
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`A.
`
`PREAMBLE: “A METHOD FOR TREATING AN ANGIOGENIC EYE
`DISORDER IN A PATIENT.” ....................................................................... 3
`
`1.
`
`2.
`
`The Board correctly found that the preamble, although
`limiting, does not require any particular level of efficacy. ......... 3
`
`Dr. Do’s proposed construction for the “method for
`treating” preamble contradicts how a POSA would
`understand the claim language within the context of the
`intrinsic evidence. ....................................................................... 4
`
`a.
`
`b.
`
`Dr. Do’s proposed “high level of efficacy that is
`non-inferior to the standard of care” added
`limitation is not consistent with the intrinsic
`record. ............................................................................... 6
`
`Dr. Do’s proposed construction admittedly varies
`with respect to each of the “angiogenic eye
`disorders” covered by the claimed “method for
`treating.” ........................................................................17
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`TABLE OF CONTENTS
`(continued)
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`Page
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`3.
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`4.
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`Dr. Do’s Proposed Construction Adds Substantial
`Ambiguity To The Claims. .......................................................20
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`Regeneron’s Proposed Construction Relies Entirely on
`Extrinsic Evidence. ...................................................................29
`
`B.
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`“TERTIARY DOSE.” ................................................................................31
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`1.
`
`2.
`
`The Board correctly found that “the Specification
`expressly defines the terms ‘initial dose,’ ‘secondary
`doses,’ and ‘tertiary doses.’” .....................................................31
`
`PO and Dr. Do’s proposed construction for “tertiary
`dose(s)” is unsupported by the intrinsic evidence. ...................32
`
`C.
`
`“VEGF Trap-Eye.” ..............................................................................37
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`VI. GROUND 6: THE CHALLENGED CLAIMS ARE OBVIOUS
`BASED ON DIXON......................................................................................42
`
`A.
`
`B.
`
`C.
`
`The POSA Would Have Had a Reasonable Expectation of
`Success That Q8 Dosing Regimen Would Be Effective. ....................42
`
`The Fact That Regeneron Initiated Phase 3 Testing Would Have
`Provided the POSA with a Reasonable Expectation of Success. ........43
`
`The Results of CLEAR-IT-2 Would Have Provided the POSA
`With a Reasonable Expectation of Success. .......................................49
`
`D. Dixon Would Have Provided the POSA With a Reasonable
`Expectation of Success in Achieving the Extended Dosing
`Regimen. ..............................................................................................52
`
`VII. NEITHER THE EYLEA LABEL NOR PHYSICIAN’S
`ADMINISTRATION OF EYLEA PRACTICE THE CHALLENGED
`CLAIMS. .......................................................................................................53
`
`VIII. SECONDARY CONSIDERATIONS. ..........................................................54
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`TABLE OF CONTENTS
`(continued)
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`IX. CERTAIN REGENERON PATENTS WOULD HAVE
`DISCOURAGED AND DISINCENTIVIZED OTHERS FROM
`DEVELOPING THE ’338 PATENT CLAIMED SUBJECT
`MATTER. ......................................................................................................59
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`Page
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`X. OPHTHALMOLOGISTS CHOOSE EYLEA BASED ON ITS
`PHARMACOKINETIC PROPERTIES. .......................................................63
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`1. My name is Dr. Thomas A. Albini and I have been retained by counsel
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`for Mylan Pharmaceuticals, Inc. (“Mylan” or “Petitioner”), to provide my opinions
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`in support of Petitioners Reply. I am the same Dr. Albini who wrote declarations in
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`support of Mylan’s Petition for Inter Partes Review of U.S. Patent Nos. 9,669,069
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`B2 (“the ’069 patent”) and 9,254,338 B2 (“the ’338 patent”), instituted as IPR2021-
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`00880 and IPR2021-00881, respectively. I also have been asked to reply to the
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`opinions and views of Patent Owner’s (“PO”) declarants, Diana V. Do, M.D., David
`
`M. Brown, M.D., and Lucian V. Del Priore, M.D., Ph.D.
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`I.
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`QUALIFICATIONS AND BACKGROUND.
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`A. EDUCATION AND EXPERIENCE.
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`2. My qualifications, education, and experience are set forth in my
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`previous report, Exhibit 1002, and my curriculum vitae is attached as Exhibit 1038.
`
`B.
`
`3.
`
`BASES FOR OPINIONS AND MATERIALS CONSIDERED.
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`In addition to my education, knowledge of the relevant published art,
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`training, and experience, in forming the opinions I provide in this declaration, I have
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`also considered the exhibits cited herein.
`
`C.
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`4.
`
`SCOPE OF WORK.
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`I have been retained by Petitioner as an expert in this matter to provide
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`various opinions regarding the ’338 patent. I receive $500 per hour for my services.
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`1
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`No part of my compensation is dependent upon my opinions given or the outcome
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`of this case. I do not have any current or past affiliation with Regeneron, or any of
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`the named inventors on the ’338 patent.
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`II. LEGAL STANDARDS.
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`5.
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`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
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`about various legal principles that govern my analysis. I have used my
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`understanding of those principles in forming my opinions. I summarized my
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`understanding of those legal principles in my previous declaration, Exhibit 1002,
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`and I incorporate that understanding as if set forth herein
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`III. PERSON OF ORDINARY SKILL IN THE ART.
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`6.
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`I presented my opinion regarding the knowledge and skill of a person
`
`of ordinary skill in the art (“POSA”) for the ’338 patent and ’069 patent in my
`
`opening declaration. (Ex.1002, Albini, ¶¶26-28). I understand the Board adopted
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`my definition in its Institution Decision as “reasonable and consistent with the ’338
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`patent.” (Paper 21, Institution Decision, 16).
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`7.
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`I understand that PO and Dr. Do have applied a different definition. PO
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`and Dr. Do contend that the POSA of the ’338 patent must be a licensed physician
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`2
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`(ophthalmologist) with “firsthand experience of diagnosing and treating angiogenic
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`eye disorders to which the patent is plainly directed.” (Ex.2051, Do Decl., ¶28).
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`8.
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`Although I disagree with PO and Dr. Do’s definition, and find it
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`significantly different than my own, I considered it when forming my opinions and
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`have confirmed that my opinions set forth herein, as well as in my opening
`
`declaration (Ex.1002), remain the same under either PO’s or Petitioner’s definition.
`
`IV. MISREPRESENTATIONS OF MY OPENING DECLARATION
`OPINIONS AND DEPOSITION TESTIMONY.
`
`9.
`
`I have reviewed PO’s Response (“POR”). I was surprised (and
`
`concerned) by how frequently PO misrepresented my deposition testimony. I felt
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`compelled to correct the record here. Accordingly, I prepared Appendix A attached
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`hereto which presents a side-by-side comparison of PO’s arguments that they
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`purportedly cite me as support against my actual opinions and testimony.
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`V. CLAIM CONSTRUCTION.
`PREAMBLE: “A METHOD FOR TREATING AN ANGIOGENIC EYE
`A.
`DISORDER IN A PATIENT.”
`
`1.
`
`The Board correctly found that the preamble, although
`limiting, does not require any particular level of efficacy.
`
`10.
`
`I reviewed the Board’s institution decision. (Paper 21). I understand
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`that the Board has found that the phrase “a method for treating an angiogenic eye
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`disorder in a patient” is a limitation of the claim. (Paper 21, Institution Decision,
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`3
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`19). I further understand that the Board found that the “method for treating”
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`preambles “do not require the recited method steps to provide an effective treatment.”
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`(Paper 21, Institution Decision, 21). To that end, I also understand that the Board
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`concluded that “the disclosure [in the specification] that such [beneficial therapeutic]
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`effects ‘can be achieved’” does not “demonstrate[] adequately that the claims
`
`require any particular level of efficacy.” (Id.). I agree with the Board that the term
`
`“method for treating an angiogenic eye disorder in a patient,” although limiting, does
`
`not require any particular level of efficacy.
`
`2.
`
`Dr. Do’s proposed construction for the “method for treating”
`preamble contradicts how a POSA would understand the
`claim language within the context of the intrinsic evidence.
`
`11.
`
`I have reviewed Dr. Do’s declaration (Ex.2051) and her deposition
`
`testimony (Ex.1109). I understand that Dr. Do believes the “method for treating an
`
`angiogenic eye disorder in a patient” preamble term must be construed as follows:
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`(Ex.1138, Do Dep. Ex. 4, ’338 patent claim 1; Ex.2051, Do Decl., ¶84). I also
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`understand that PO’s other experts, Dr. Brown and Dr. Del Priore, did not provide
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`4
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`their own opinions regarding claim construction, but instead, adopted Dr. Do’s
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`opinion and proposed claim construction. 2 (Ex.2050, Brown Decl., ¶¶99-100;
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`Ex.1110, Brown Tr., 16:25-17:4; Ex.2048, Del Priore Decl., ¶¶36-37). For the
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`reasons I provide below, I disagree with Dr. Do’s proposed construction for the
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`“method of treating” preamble claim term.3
`
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`2 Dr. Brown also confirmed that he did not review the ’338 patent prosecution
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`history, which, I understand, is part of the intrinsic record that must be considered
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`when forming an opinion regarding claim construction. (Ex.1110, Brown Tr., 69:15-
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`20; 102:22-23).
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`3 Instead, in my opinion, the plain language of the claims (when read in light of the
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`specification which discloses multiple methods that do not achieve a so-called
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`“high level of efficacy”) suggests that no particular level of efficacy is required by
`
`any of the covered methods for treating.
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`
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`5
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`a.
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`Dr. Do’s proposed “high level of efficacy that is non-
`inferior to the standard of care” added limitation is not
`consistent with the intrinsic record.4
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`12. The Claims. As I outlined in my opening declaration (Ex.1002, Albini,
`
`¶43), there are no parameters set forth in claims 1, 3-11, 13-14, 16-24, 26 of the ’338
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`patent (“the Challenged Claims”) or any guidance from the claims themselves that,
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`in my opinion, would inform a POSA as to some specialized meaning for the
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`“method for treating” preamble claim term. Consequently, in my opinion, a POSA
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`would (as I did) apply a plain and customary meaning to this term, which would
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`include administering a therapeutic agent to a patient and would not require any
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`particular level of efficacy.
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`13.
`
`I also do not find support in the claims for Dr. Do’s “high level of
`
`efficacy” or “standard of care” limitations. As Dr. Do testified, the Challenged
`
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`4 I have been informed that the “intrinsic record” is the primary source for
`
`determining claim meaning and includes the claims, the specification, and the
`
`prosecution history. I have also been informed that claims are to be construed with
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`a presumption that the language in the claim carries its ordinary and customary
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`meaning amongst persons of ordinary skill in the relevant art at the time of the
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`invention.
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`
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`6
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`Claims are completely silent with respect to any “efficacy” limitation.5 (Ex.1109,
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`Do Tr., 88:11-20 (“‘[E]fficacy’ is not literally written in Claim 1 . . . .”). Similarly,
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`the claims make no mention of the claimed method being “non-inferior” to the then-
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`existing “standard of care.” Instead, in my opinion, a POSA interpreting the claims
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`in light of specification, e.g., Examples 1-6, would conclude that the claims are
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`directed to methods that do not require any particular level of efficacy. (See, e.g.,
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`Ex.1110, Brown Tr., 23:16-24:3 (explaining that the data presented in Example 4
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`for the 2Q8 arm are consistent with what was previously seen with Macugen).
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`14. The Specification. There is no definition for the “method for treating”
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`preamble term in the specification either. And, in my opinion, nothing in the
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`5 By comparison, U.S. Patent No. 10,888,601 (“the ’601 patent”), which I
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`understand is a child of the ’338 patent, claims priority to the same application and
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`shares the same specification as the Challenged Claims. However, the ’601 patent
`
`recites claims that expressly include efficacy-related limitations. (See, e.g., Ex.1134,
`
`’601 patent, claims 3-6). No such language exists in the Challenged Claims, which,
`
`in my opinion, suggests that the inventor never intended, and a POSA would never
`
`conclude, that the claimed “method for treating” requires any particular level of
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`efficacy.
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`7
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`specification would require the claimed method to have any particular level of
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`efficacy. In my opinion, a POSA would rely on the specification’s disclosure that
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`“beneficial therapeutic effects can be achieved in patients suffering from angiogenic
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`eye disorders by administering a VEGF antagonist”—not that such effects must be
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`achieved. (Ex.1001, ’338 patent, 2:3-10; Paper 21, Institution Decision, 21). As the
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`Board noted, according to the patent disclosure, a “VEGF antagonist administered
`
`to the patient in each dose is, in most cases [i.e., not all], a therapeutically effective
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`amount.” (Paper 21, Institution Decision, 20; Ex.1001, ’338 patent, 2:3-10, 6:48-
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`50). Combined with the Examples, which demonstrate a large variety of effective
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`(and ineffective) treatments, I believe a POSA would conclude that the Challenged
`
`Claims do not require any particular level of efficacy.
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`15. The term “standard of care” is also not defined—and, based on my
`
`review—does not appear anywhere in the ’338 patent specification. (Ex.1109, Do
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`Tr., 150:2-20 (“I don’t recall the words ‘standard of care’ was used in the ’338
`
`patent . . . .”), 89:2-5). And, in my opinion, nothing in the specification would inform
`
`a POSA that non-inferiority to the so-called “standard of care” was a prerequisite to
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`8
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`the claimed method.6 Instead, the patent Examples include several regimens that
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`meet the dosing schedule of the Challenged Claims but where no information is
`
`provided about whether or not they are “non-inferior” to the existing standard of care.
`
`(Ex.1001, 5:11-29, 13:50-14:34 (Example 5), 15:16-16:67 (Example 7)). In my
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`opinion, a POSA would nonetheless accept those regimens as “method[s] for treating”
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`within the scope of the Challenged Claims. Accordingly, I see no basis in the ’338
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`patent specification for reading-into the Challenged Claims that the “method for
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`treating” must be “non-inferior to the standard of care” for each and every
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`angiogenic eye disorder covered.
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`16. The term “high level of efficacy” does appear once in the patent
`
`specification; however, in my opinion, this is not a definition and I disagree with PO
`
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`6 I find it important to point out that “non-inferior[ity] to the [existing] standard of
`
`care” is a very subjective term that is not only prone to multiple interpretations based
`
`on, at least, the particular angiogenic disorder being treated, the treatment being
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`administered, and what point in time (e.g., in relation to FDA approval) the treatment
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`occurs. Moreover, a POSA would not be able to determine whether a “method of
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`treating” is non-inferior to the existing standard of care for months, if not years, after
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`implementing the accused dosing regimen.
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`9
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`(and Dr. Do) that a POSA would read this language as a limitation on the Challenged
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`Claims.
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`17. Specifically, the specification provides the following:
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`
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`(Ex.1001, ’338 patent, 1:53-59). I have reviewed PO’s and Dr. Do’s descriptions of
`
`this passage and their arguments relying on it to limit the Challenged Claims. (Paper
`
`38, 6-7; Ex.2051, Do Decl., ¶¶46-53, 90-91). PO and Dr. Do seem to focus their
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`arguments and opinions on only the last half of the last sentence of this paragraph—
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`specifically, that “there remains a need in the art for new administration regimens
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`for angiogenic eye disorders, especially those which allow for less frequent dosing
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`while maintaining a high level of efficacy.” (Ex.1001, ’338 patent, 1:53-59
`
`(Background)). I disagree with their narrow reading. In my opinion, a POSA would
`
`read this statement within the context of the complete paragraph and not in isolation.
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`18. The first sentence in this paragraph reads: “Methods for treating eye
`
`disorders using VEGF antagonists are mentioned in, e.g., U.S. Pat. Nos. 7,303,746;
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`7,306,799; 7,300,563; 7,303,748; and US 2007/0190058.” (Ex.1001, ’338 patent,
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`10
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`1:53-59 (Background)). In my opinion, a POSA would read this statement as PO’s
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`description of the state of the art that the claimed method seeks to improve. I have
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`reviewed U.S. Pat. Nos. 7,303,746; 7,306,799; 7,300,563; 7,303,748; and US
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`2007/0190058 for disclosures of “[m]ethods for treating eye disorders using VEGF
`
`antagonists.” To the extent any of these patents disclose a method for treating, as I
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`explain in the following paragraphs, none of those disclosed methods require any
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`particular level of efficacy.
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`19. U.S. Pat. No. 7,303,746 (“the ’746 patent”) (Ex.1016), titled “Methods
`
`of treating eye disorders with modified chimeric polypeptides,” consists of claims
`
`directed toward “[a] method of treating retinal neovascularization,” for example,
`
`independent claim 1 reads:
`
`
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`(Ex.1016, ’746 patent, 69:50-54). As seen here, the claims do not require any
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`particular level of efficacy. The ’746 patent specification is also completely silent
`
`as to any efficacy requirements for the claimed method of treating. Rather, the
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`disclosure describes
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`the production, purification, characterization, binding,
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`pharmacokinetic analysis, and administration of fusion polypeptides.
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`11
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`20. U.S. Pat. No. 7,306,799 (“the ’799 patent”) (Ex.1016), titled “Use of
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`VEGF inhibitors for treatment of eye disorders,” consists of claims directed toward
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`“A therapeutic method for treating or ameliorating an eye disorder” (claims 1-3) and
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`“A method for the treatment of a human subject diagnosed with age-related macular
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`degeneration” (claims 4-11). Even though the claims of the ’799 patent call for an
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`“effective amount of a vascular endothelial growth factor (VEGF) inhibitor,” the
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`claims are silent as to any particular level of efficacy required for the claimed method.
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`Likewise, the specification makes no mention of any efficacy requirements.
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`21. U.S. Pat. No. 7,300,563 (“the ’563 patent”) (Ex.1144), titled “Use of
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`N-alllyl substituted amines and their salts as brightening agents in nickel plating
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`baths,” is directed to brightening agents in nickel plating baths. The ’563 patent
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`claims and specification have nothing to do with “[m]ethods for treating eye
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`disorders using VEGF antagonists.”7
`
`
`7 Assuming PO’s reference to the ’563 patent was a typo, I reviewed U.S. Pat. No.
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`7,300,653 (“the ’653 patent”) (Ex.1145), titled “Method of treating corneal
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`transplant rejection,” and assigned to Regeneron. Like the other patents cited in
`
`the ’338 patent specification, the ’653 patent does not disclose methods for treating
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`22. U.S. Pat. No. 7,303,748 (“the ’748 patent”) (Ex.1148), titled “Method
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`of treating eye injury with local administration of a VEGF inhibitor,” consists of
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`claims directed to methods of treating an eye injury with an “effective amount of an
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`agent capable of blocking or inhibiting vascular endothelial growth factor (VEGF)-
`
`mediated activity . . . such that the eye injury is ameliorated or improved.” (See, e.g.,
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`Ex.1148, ’748 patent, 15:57-65). The claims do not require any particular level of
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`efficacy. The specification defines the phrase “therapeutically effective dose” as “a
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`dose that produces the desired effect for which it is administered.” (Ex.1148, ’748
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`patent, 4:22-24). Further, the specification describes studies in rats where the results
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`showed “inhibition of neovascular proliferation” or “decrease in corneal neovascular
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`area.” (See, e.g., ’748 patent, Examples 2-3). However, like the claims, the
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`specification does not describe any level of efficacy that is required for the claimed
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`methods of treating an eye injury.
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`that require any particular level of efficacy. The claims are directed toward methods
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`for “improving [corneal] transplant survival” (claims 1-4), “reducing the incidence
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`of corneal transplant rejection” (claim 5), and “treating corneal transplant rejection”
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`(claims 6-8). The claims do not require any particular level of efficacy. Likewise,
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`the specification does not limit the claims to any particular level of efficacy.
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`13
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`23. U.S. Publication No. 2007/0190058 (“the ’058 publication) (Ex.1135),
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`titled “Method for treating intraocular neovascular diseases,” consists of claims
`
`directed to a method for treating wAMD and intraocular neovascular disease
`
`comprising “first individual doses” and “second individual doses” of a VEGF
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`antagonist. (See, e.g., Ex.1135, ’058 publication at claim 1). The claims do not
`
`describe any level of efficacy that is required for the claimed methods of treating.
`
`Nor does the specification. The specification defines the “term ‘effective amount’
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`or ‘therapeutically effective amount’ [as] refer[ring] to an amount of a drug effective
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`to treat a disease or disorder in a mammal. In the case of age-related macular
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`degeneration (AMD), the effective amount of the drug can reduce or prevent vision
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`loss.” (Ex.1135, ’058 publication, [0072]). Paragraph [0072] further discloses how
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`to measure the efficacy of the treatment but does not describe any level of efficacy
`
`that is required for the claimed methods. Example 1 describes that “[e]fficacy is
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`assessed by changes in preventing vision loss, e.g., measured by the mean change in
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`best correction visual acuity (BCVA) from baseline to 12 months or 24 months,” but
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`again does not describe any level of efficacy that was achieved or required. (See
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`Ex.1135, ’058 publication, [0137]).
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`24.
`
`In sum, none of the patents listed in the ’338 patent specification as the
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`“Background” of “[m]ethods for treating eye disorders using VEGF antagonists”
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`(Ex.1001, ’338 patent, 1:53-55) disclose methods requiring any particular level of
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`efficacy. In my opinion, the ’338 patent inventor emphasized the regimens of the
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`prior art, not any particular level of efficacy, to purportedly differentiate the current
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`method: “[n]onetheless, there remains a need in the art for new administration
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`regimens for angiogenic eye disorders.” (Ex.1001, ’338 patent, 1:55-57 (emphasis
`
`added)). After drawing this distinction, the ’338 patent inventor highlighted, as a
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`particularly preferred embodiment of such “new administration regimens,” “those
`
`which allow for less frequent dosing while maintaining a high level of efficacy.” (Id.,
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`1:57-59). In my opinion, a POSA would not read this identification of preferred
`
`embodiments as a limitation on the Challenged Claims.
`
`25. That being said, the ’338 patent does define the term “efficacy.” While
`
`it continues to be my opinion that the Challenged Claims do not require any
`
`particular level of efficacy, if one were to assume that they do, then, in my opinion,
`
`a POSA would apply the definition of “efficacy” expressly provided in the ’338
`
`patent specification (which is consistent with a POSA’s knowledge, skill and
`
`experience):
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`15
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`(Ex.1001, ’338 patent, 7:15-32). Accordingly, in my opinion, a POSA would
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`logically conclude that if one were to equate the claimed “method for treating” with
`
`a particular efficacy, the requisite level would be consistent with this express
`
`definition—i.e., efficacy within 104 weeks from initiation, and that the patients
`
`exhibit a loss of 15 or fewer letters on the ETDRS visual acuity chart. (Ex.1002,
`
`Albini, ¶43). PO and Dr. Do, however, disagree with this express definition and do
`
`not use it in their construction of the “method for treating” claim term—presumably
`
`because this definition does not constitute a “high level” of efficacy. (Paper 38, POR,
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`20-22; Ex.1109, Do Tr., 91:12-93:12).
`
`16
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` Neither PO nor Dr. Do provide an explanation for why they do not
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`26.
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`apply the patent’s express definition of “efficacy.”
`
`b.
`
`Dr. Do’s proposed construction admittedly varies with
`respect to each of the “angiogenic eye disorders”
`covered by the claimed “method for treating.”
`
`27.
`
`I read Dr. Do’s proposed construction as admittedly varying with
`
`respect to each of the different “angiogenic eye disorders” covered by the claimed
`
`“method for treating”: “[a] method for treating an angiogenic eye disorder in a
`
`patient [that achieves a high level of efficacy that is non-inferior to the standard of
`
`care, for that particular angiogenic eye disorder, at the time of patent filing].” (See
`
`Ex.1138, Do Dep. Ex. 4, ’338 patent claim 1; Ex.2051, Do Decl., ¶84). As a
`
`threshold matter, I must point out that the ’338 patent specification defines the term
`
`“angiogenic eye disorder” as “any disease of the eye which is caused by or associated
`
`with the growth or proliferation of blood vessels or by blood vessel leakage” and
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`provides a “non-limiting” list of nineteen (19) angiogenic eye disorders that are
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`treatable using “the methods of the present invention”:
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`17
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`(Ex.1001, ’338 patent, 5:11-29). I agree with Dr. Do’s and Dr. Brown’s conclusions
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`that the patent’s definition for “angiogenic eye disorder(s)” is “reasonable,” “logical”
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`and “inclusive.” (Ex.1109, Do Tr., 156:15-157:2; Ex.1110, Brown Tr., 108:19-25).
`
`28. Applying Dr. Do’s proposal, the claimed method must, in my opinion,
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`“achieve[] a high level of efficacy that is non-inferior to the standard of care, for
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`[each one of those 19] particular angiogenic eye disorder[s].” Indeed, Dr. Do
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`testified that “the standard of care is specific to the angiogenic eye disorder that is
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`being treated under this claimed method of treatment.” (Ex.1109, Do Tr., 162:9-12
`
`(emphasis added)).
`
` Dr. Do’s
`
`testimony here captures my fundamental
`
`disagreements with her proposed construction. Specifically, the so-called “standard
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`of care” for each angiogenic eye disorder covered by the Challenged Claims is (i)
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`undefined in the patent specification,8 (ii) subject to change with each disorder, and
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`(iii) entirely subjective to the ophthalmologist administering the treatment as well as
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`the patient being treated.9
`
`
`8 As I stated above, the claims and the specification are silent as to the so-called
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`“standard of care” for any of the nineteen (19) listed angiogenic eye disorders.
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`Moreover, in my opinion, the so-called “standard of care” in Dr. Do’s proposal
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`encompasses not only knowing the drug being administered, but also the dosing
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`regimen—which, according to PO, “[t]here are virtually an infinite number of
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`different treatment protocols that could be tested.” (Ex.1017, ’338 FH, 288). While
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`Drs. Do and Brown often referred to “Lucentis and Avastin off-label” as the standard
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`of care, they do not set forth an exact dosing regimen for either with respect to all of
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`the angiogenic eye disorders covered by the Challenged Claims.
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`9 For example, Dr. Brown testified that “the standard of care [before January 2011]
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`for diabetic macular edema really depended on what access the patients had,” i.e.,
`
`whether a POSA could get DME patients on a Lucentis trial which “is the standard
`
`of care, if you could get it,” or had to use off-label Avastin, “[but s]ome patients
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`couldn’t afford it because it wasn’t covered by their insurance.” (Ex.1110, Brown
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`19
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`29. Consequently, in my opinion, Dr. Do’s proposal introduces a large
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`amount of variety and uncertainty with respect to what treatment regimen satisfies
`
`the “method for treating” preamble (and when).
`
`3.
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`Dr. Do’s Proposed Construction Adds Substantial Ambiguity
`To The Claims.
`
`30.
`
`In addition to being unsupported by the intrinsic evidence, it is my
`
`opinion that Dr. Do’s proposed construction adds a substantial amount of ambiguity
`
`to the Challenged Claims.
`
`31. No Means or Parameters for Measuring a “High Level of Efficacy.”
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`In my opinion, under Dr. Do’s proposed construction, the POSA must be able to
`
`analyze whether a 2Q8 dosing regimen achieves a “high level of efficacy”—in other
`
`words, one needs to know what to measure, when to measure it, and how to perform
`
`that measurement. Based on my review, the ’338 patent provides no such guidance
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`and thus a POSA would be able to use any test he or she sees fit and/or is available.
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`This lack of guidance, in my opinion, adds a large amount of variety and ambiguity
`
`
`Tr., 110:2-22). Dr. Brown further explained that for some patients, who didn’t have
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`access to Lucentis or Avastin, focal laser was still the standard of care. (Id., 110:19-
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`22, 117:5-20; Ex.1068, Regeneron (14-September-2009) (describing “focal laser
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`treatment” as “the current standard of care in DME”)).
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`20
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`with respect to what falls within the claims (as construed by Dr. Do) and what does
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`not.
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`32. For example, there are several tests available to an ophthalmologist that
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`can be used to determine the efficacy of a treatment for an angiogenic eye disorder
`
`such as Best Corrected Visual Acuity (BCVA) using the Early
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