`Tel: 571-272-7822
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`Paper 65
`Entered: December 12, 2014
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`UNITED STATES PATENT AND TRADEMARK OFFICE
`_______________
`
`BEFORE THE PATENT TRIAL AND APPEAL BOARD
`____________
`
`CYANOTECH CORPORATION,
`Petitioner,
`
`v.
`
`THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS,
`Patent Owner.
`____________
`
`Case IPR2013-004011
`Patent 5,527,533
`____________
`
`Before SCOTT E. KAMHOLZ, SHERIDAN K. SNEDDEN, and
`GEORGIANNA W. BRADEN, Administrative Patent Judges.
`
`
`SNEDDEN, Administrative Patent Judge.
`
`
`FINAL WRITTEN DECISION
`35 U.S.C. § 318(a) and 37 C.F.R. § 42.73
`
`
`1 Consolidated with Case IPR2013-00404
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`
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`
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`IPR2013-00401 and IPR2013-00404
`Patent 5,527,533
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`I. INTRODUCTION
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`Cyanotech Corporation (“Cyanotech”) filed corrected petitions in
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`IPR2013-00401 (Paper 9, “Pet. ’401”) and IPR2013-00404 (IPR2013-
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`00404, Paper 8, “Pet. ’404”) requesting inter partes review of claims 1–27
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`of U.S. Patent No. 5,527,533 (“the ’533 patent”). The Board consolidated
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`IPR2013-00401 and IPR2013-00404 and instituted trial for the challenged
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`claims on the following grounds of unpatentability asserted by Cyanotech:
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`Reference(s)
`Grangaud2
`Grangaud and Dowling3
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`Basis Claims challenged
`§ 102
`1, 3, 8–15, 21, 22, and 26
`§ 103
`1–15, 21, 22, and 26
`
`Decision to Institute, 19 (Paper 17 (“Dec.”)).
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`After institution and consolidation of both trials, the Board of Trustees
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`of the University of Illinois (“the University”), filed its Patent Owner’s
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`Response (“Resp.”). Paper 32.4 Cyanotech filed a Reply (Paper 43,
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`“Reply.”). The University did not file a motion to amend claims.
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`Cyanotech relies upon declarations of Florian J. Schweigert
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`(Ex. 1033) and C. Kathleen Dorey, Ph.D. (Ex. 1045) in support of its
`
`
`2 RENÉ GRANGAUD, RESEARCH ON ASTAXANTHIN, A NEW VITAMIN A
`FACTOR (1951) (unpublished doctorate dissertation, University of Lyon)
`(Ex. 1003, the English translation of which is Ex. 1002).
`3 J.E. Dowling & I.R. Gibbons, The Effect of Vitamin A Deficiency on the
`Fine Structure of the Retina, in THE STRUCTURE OF THE EYE 85-99 (1961)
`(Ex. 1026).
`4 This reference to “Paper” and all other references to “Paper” from this
`point forward in this Final Written Decision of consolidated proceedings
`IPR2013-00401 and IPR2013-00404 refer to paper numbers on record in
`IPR2013-00401.
`
`2
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`IPR2013-00401 and IPR2013-00404
`Patent 5,527,533
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`Petition. The University relies upon a declaration of Shalesh Kaushal M.D.,
`
`Ph.D. (Ex. 2015) in support of its Response.
`
`Cyanotech filed a Motion to Exclude certain of the University’s
`
`evidence. Paper 47. The University filed an Opposition (Paper 51), and
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`Cyanotech filed a Reply (Paper 54).
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`Oral argument was conducted on July 16, 2014. A transcript is
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`entered as Paper 64 (“Tr.”).
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`This Final Written Decision addresses challenges to the patentability
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`of claims 1–15, 21, 22, and 26.
`
`Cyanotech has proved by a preponderance of the evidence that claims
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`1–14 and 26 of the ’533 patent are unpatentable. Cyanotech has failed to
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`prove the unpatentability of claims 15, 21, and 22.
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`A. The ’533 Patent (Ex. 1001)
`
`The retina of the eye, a component of the central nervous system, is
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`important for sight. Ex. 1001, 1:49–52; see also, Ex. 1045, 6–12. Retinal
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`structures important to vision include: a ganglion cell layer, which connects
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`the retina to the brain; an inner nuclear layer containing neurons, such as
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`bipolar cells; and an outer nuclear or photoreceptor cell layer. Ex. 1045, 6–
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`12. Photoreceptor cells convert light into signals that are transmitted to the
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`other neurons. Ex. 1001 at 1:57–60. The loss of a significant number of
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`photoreceptor cells adversely affects visual function. Id. at 3:6–13.
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`The ’533 patent discloses that eye diseases or injuries that can cause
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`damage to the retinal tissue and neurons include age-related macular
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`degeneration, photic injury, photoreceptor cell damage, ganglion cell
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`damage, traumatic injury, ischemic insult-related diseases, and inflammatory
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`3
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`diseases. Id. at 1:9–14. Regarding photic injury, the ’533 patent discloses
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`that excessive light energy reaching the retina can overwhelm the metabolic
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`systems of photoreceptor cells causing damage to these neurons, either
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`directly or indirectly. Id. at 1:65–67. The ’533 patent further discloses that
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`free radical species can be generated by enzymatic processes or from the
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`combination or continuous or excessive exposure to light and the relatively
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`high concentration of oxygen in the eye. Id. at 2:1–5. The ’533 patent
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`discloses that the free radical species lead to functional impairment of cell
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`membranes and may cause temporary or permanent damage to retinal tissue.
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`Ex. 1001, 2:13–21. According to the ’533 patent, however, the presence of
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`antioxidant compounds counteracts the free radical species generated by
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`light to protect the retina from damage. Id. at 2:29–32.
`
`The ’533 patent relates to methods of treating diseases and injuries to
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`the central nervous system, especially the eyes, comprising administering a
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`therapeutically-effective amount of astaxanthin. Ex. 1001, 1:9–19 and 6:54–
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`62. The ’533 patent discloses that astaxanthin is a highly-effective
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`antioxidant and ameliorates free radical-induced eye damage. Id. at 15:56–
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`60. Astaxanthin is disclosed as particularly suited for treatment of the eye
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`because, unlike other carotenoids such as β-carotene, astaxanthin can cross
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`the blood-retinal brain barrier readily. Id. at 10:18–22. According to the
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`’533 patent, comparative studies with β-carotene demonstrate that
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`astaxanthin is more effective than β-carotene at protecting rats from photic
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`injury. Id. at 13:60 to 14:50.
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`4
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`IPR2013-00401 and IPR2013-00404
`Patent 5,527,533
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`B. Exemplary Claims
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`Independent claims 1, 13, 14, 21, and 26 are illustrative of the claims
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`at issue in this inter partes review and recite as follows:
`
`1. A method of treating an individual suffering from
`retinal damage or retinal disease, said method comprising
`administering a therapeutically effective amount of
`astaxanthin to the individual to improve the vision of the
`individual.
`
`13. A method of treating an individual comprising
`administering a therapeutically effective amount of
`astaxanthin to the individual to protect neurons in a retina
`of the individual from free-radical induced retinal injury.
`
`14. A method of treating an individual suffering from
`neuronal damage to a retina comprising administering a
`therapeutically-effective amount of astaxanthin to the
`individual to improve the condition of the retina.
`
`21. A method of treating an individual suffering from a
`free radical-induced injury to a central nervous system,
`said method comprising administering a therapeutically-
`effective amount of astaxanthin to the individual to
`improve the condition of the central nervous system.
`
`26. A method of treating an individual suffering from a
`degenerative retinal disease, said method comprising
`administering a therapeutically effective amount of
`astaxanthin to the individual to retard the progress of the
`disease.
`
`II. DISCUSSION
`
`A. Claim Interpretation
`
`In an inter partes review, claim terms in an unexpired patent are
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`interpreted according to their broadest reasonable construction in light of the
`
`specification of the patent in which they appear. 37 C.F.R. § 42.100(b);
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`5
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`IPR2013-00401 and IPR2013-00404
`Patent 5,527,533
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`Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,
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`2012). Claim terms are given their ordinary and customary meaning, as
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`would be understood by one of ordinary skill in the art in the context of the
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`entire disclosure. In re Translogic Tech., Inc., 504 F.3d 1249, 1257 (Fed.
`
`Cir. 2007). Any special definition for a claim term must be set forth in the
`
`specification with reasonable clarity, deliberateness, and precision. In re
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`Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
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`We expressly interpret below only those claim terms that require
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`analysis to resolve arguments related to the patentability of the challenged
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`claims.
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`1. Construction of the phrase “retinal damage or retinal disease”
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`We construed the phrase “retinal damage or retinal disease” recited in
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`claims 1–12 in the alternative to refer to two classes of conditions: retinal
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`damage and retinal disease. Dec. 9. The University argues for the
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`construction of the terms “retinal damage” and “retinal disease” as a single
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`concept such that both “retinal damage” and “retinal disease” refer to an
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`identical class of medical conditions. Resp. 15–16. Specifically, the
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`University contends that the specification confirms that free radical damage
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`is associated with both injuries and disease. Id. (citing Ex. 1001, 15:23–27
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`(“The administration of astaxanthin to an individual suffering from an eye
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`injury or disease, such as free radical induced injury, beneficiates the vision
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`of the individual by rescuing further photoreceptor cells from damage
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`destruction.”); 15:57–60 (“the administration of astaxanthin also provides a
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`method of treating free radical induced disease or injury to the central
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`nervous system in general”)).
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`6
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`As stated by the University, the specification discloses methods of
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`treating damage caused by injury or disease (Resp. 14–15), however, the
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`specification does not contain any indication that the patentee intended to act
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`as his own lexicographer clearly defining “disease” and “damage” in the
`
`same manner. For example, the specification does not clearly convey the
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`patentee’s intent to appoint a special meaning to the phrase “retinal damage
`
`or retinal disease.”
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`We must determine, therefore, the ordinary meaning of “disease” and
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`“damage” as used in these claims to one of skill in the art in light of the
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`specification and prosecution history. In re Paulsen, 30 F.3d at 1480. In
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`this regard, the term “damage,” as used in the specification, refers to damage
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`resulting from injury or disease. Ex. 1001, 1:14–19. The specification does
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`not equate damage and disease, but provides that damage may be caused by
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`disease. Id. The meaning of the term disease, however, refers to conditions
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`that may cause damage (such as degenerative eye disease), and are treatable
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`themselves. Id. at 15:36–40. That is, the underlying cause of the damage is
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`treatable, not just the damage alone. The University does not direct our
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`attention to anything in the specification or prosecution that would clearly
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`alter the ordinary meaning of “disease” and “damage.” Resp. 14–16.
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`In view of the above, we do not construe “retinal damage” and
`
`“retinal disease” as a single concept. The evidence of record does not
`
`support a finding that the patentee acted as his own lexicographer by clearly
`
`defining the claim terms “damage” and “disease” in the same manner. In
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`our Decision to Institute, we adopted the dictionary definition of “disease”
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`and construed the term as “[a] morbid entity ordinarily characterized by two
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`or more of the following criteria: recognized etiologic agent(s), identifiable
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`7
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`group of signs and symptoms, or consistent anatomic alterations.” Dec. 8–9;
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`see, Pet. ’401 (citing Ex. 1040). We adopted the dictionary definition of
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`“damage” and construed the term as “[h]arm, diminution, or destruction of
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`an organ, body part, system, or function.” Id. We maintain these
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`constructions for “disease” and “damage” as they are consistent with the use
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`of these terms in the Specification. “Retinal damage” refers to damage to
`
`the retina and “retinal disease” refers to disease of the retina. The phrase
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`“retinal damage or retinal disease” refers to either retinal damage or retinal
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`disease.
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`We also maintain our constructions of “disease” and “damage” with
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`respect to claims 8–12, which recite particular types of retinal damage, and
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`thus, further limit “retinal damage” recited in claim 1. Claims 8–12,
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`however, do not limit further “retinal disease,” as recited in claim 1. Thus,
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`for example, claim 12 encompasses a method of treating an individual
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`suffering from damage caused by age-related macular degeneration or
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`suffering from any retinal disease.
`
`B. The Prior Art
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`1. Summary of Grangaud
`
`Grangaud discloses the results of experiments conducted on rats fed a
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`vitamin A-deficient diet. Ex. 1002, 43. The animals developed
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`complications of vitamin A deficiency that included xerophthalmia (“dry
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`eye”) and death. Visible signs of xerophthalmia were described as ocular
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`lesions. See e.g., id. at 44, 49. The restoration of vitamin A or astaxanthin
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`to the vitamin A-deficient diet was sufficient to heal the ocular lesions. Id.
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`Grangaud concluded that astaxanthin has vitamin A activity. Id. at 56.
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`8
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`Grangaud further noted that the antioxidant strength of astaxanthin is
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`comparable to that of vitamin A, and that astaxanthin shares the
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`antixerophthalmic activity of vitamin A. Id.
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`Grangaud is silent as to the mechanism of the disease pathogenesis for
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`vitamin A deficiency. Grangaud provides no evidence tending to establish
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`that the vitamin A-deficient rats exhibited retinal damage.
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`2. Summary of Dowling
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`Dowling discloses the results of a study showing the effect of vitamin
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`A deficiency on the fine structure of the retina. Ex 1026. Dowling used an
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`albino rat model kept on a vitamin A-free diet, supplemented with vitamin A
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`acid. Id. at 85. The vitamin A acid kept the rats healthy and growing, but
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`did not support the visual cycle and thus the rats gradually become night-
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`blind. Id. Dowling discloses that the visual cells (photoreceptor cells) of
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`animals fed such a diet degenerated after 2 months on the diet. Id. at 87–88.
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`Other retinal cells, such as bipolar and ganglion cells, however, appeared
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`normal, even after 6 months on the diet. Id. Dowling also discloses that the
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`damage to the retinal cells is reversible by giving vitamin A to the deficient
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`animals. Id. at 94.
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`C. Patentability of Original Claims
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`To prevail in its challenges to the patentability of claims, the
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`petitioner must establish facts supporting its challenges by a preponderance
`
`of the evidence. 35 U.S.C. § 316(e); 37 C.F.R. § 42.1(d).
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`9
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`1. Anticipation of Claims 1, 3, 8–15, 21, 22, and 26 by Grangaud
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`The Court of Appeals for the Federal Circuit summarized the
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`analytical framework for determining whether prior art anticipates a claim as
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`follows:
`
`in a printed
`invention was “described
`the claimed
`If
`publication” either before the date of invention, 35 U.S.C.
`§ 102(a), or more than one year before the U.S. patent
`application was filed, 35 U.S.C. § 102(b), then that prior art
`anticipates the patent. Although § 102 refers to “the invention”
`generally, the anticipation inquiry proceeds on a claim-by-claim
`basis. See Hakim v. Cannon Avent Group, PLC, 479 F.3d 1313,
`1319 (Fed. Cir. 2007). To anticipate a claim, a single prior art
`reference must expressly or inherently disclose each claim
`limitation. Celeritas Techs., Ltd. v. Rockwell Int’l Corp., 150
`F.3d 1354, 1361 (Fed. Cir. 1998). But disclosure of each
`element is not quite enough—this court has long held that
`“[a]nticipation requires the presence in a single prior art
`disclosure of all elements of a claimed invention arranged as in
`the claim.” Connell v. Sears, Roebuck & Co., 722 F.2d 1542,
`1548 (Fed. Cir. 1983) (citing Soundscriber Corp. v. United
`States, [] 360 F.2d 954, 960 (1966) (emphasis added)).
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`Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1334–35 (Fed. Cir.
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`2008). We must analyze prior art references as a skilled artisan would. See
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`Scripps Clinic & Res. Found. v. Genentech, Inc., 927 F.2d 1565, 1576 (Fed.
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`Cir. 1991) (to anticipate, “[t]here must be no difference between the claimed
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`invention and the reference disclosure, as viewed by a person of ordinary
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`skill in the field of the invention”).
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`To establish inherent disclosure, the evidence must show that a feature
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`necessarily is described in the reference, and that it would be recognized by
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`persons of ordinary skill. In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
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`1999); cf. EMI Grp. N. Am., Inc. v. Cypress Semiconductor Corp., 268 F.3d
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`10
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`1342, 1351 (Fed. Cir. 2001) (“Theoretical mechanisms or rules of natural
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`law that are recited in a claim, that themselves are not patentable, however,
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`do not need to be recognized by one of ordinary skill in the art for a finding
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`of inherency.”). The mere fact that a certain thing may result from a given
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`set of circumstances is not sufficient to establish inherency. In re Rijckaert,
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`9 F.3d 1531, 1534 (Fed. Cir. 1993). Inherency may not be established by
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`probabilities or possibilities. In re Oelrich, 666 F.2d 578, 581 (CCPA
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`1981).
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`Cyanotech contends that Grangaud’s disclosure of the administration
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`of dietary astaxanthin to cure xerophthalmia (“dry eye”) in vitamin A-
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`deficient rats anticipates claims 1, 3, 8–15, 21, 22, and 26, which are
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`directed to a method of administering a therapeutically effective amount of
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`astaxanthin to improve the vision of an individual suffering from retinal
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`damage or retinal disease. Pet. 15–17. For the reasons expressed below, we
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`conclude that Cyanotech has demonstrated by a preponderance of evidence
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`that Grangaud anticipates claims 1, 3, 8–14 and 26. Cyanotech has failed to
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`establish by a preponderance of evidence that Grangaud anticipates claims
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`15, 21, and 22.
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`a. Claims 1, 3, and 10
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`Claim 1 encompasses a method of treating an individual suffering
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`from retinal damage with the administration of astaxanthin in an amount
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`sufficient to improve the vision of the individual. Claims 3 and 10 depend
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`directly from claim 1. Claim 3 requires astaxanthin to be administered
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`orally. Claim 10 specifies that the retinal damage may be photoreceptor cell
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`retinal damage.
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`11
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`Although Grangaud discloses the administration of astaxanthin to cure
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`ocular lesions (Ex. 1002, 43, 44, 49), Cyanotech concedes that Grangaud
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`does not discuss whether or not vitamin A-deficient rats exhibit retinal
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`damage. Pet. 18–19. Cyanotech contends, however, that animals
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`developing xerophthalmia due to vitamin A-deficiency inherently suffer
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`retinal damage. Id. For support of this assertion, Cyanotech relies on the
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`Declaration of Florian J. Schweigert (“Schweigert declaration”) (Ex. 1033)
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`to establish that vitamin A-deficient rats exhibiting dry eye necessarily have
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`retinal damage and, more specifically, photoreceptor cell retinal damage.
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`With reference to Dowling (Ex. 1026), Dr. Schweigert testifies that
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`severe vitamin A deficiency causes degeneration in the retina that precedes
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`dry eye. Ex. 1033 ¶¶ 27, 36, and 39–43. Dowling reported that albino rats
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`experienced degeneration of visual cells (photoreceptor cells) after about 2
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`months of vitamin A deficiency. Ex. 1026, 87-88. Such retinal damage
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`could be reversed upon restoring vitamin A to rats’ diets. Id. at 94. The
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`other retinal cells (bipolar and ganglion cells), however, appeared normal
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`with vitamin A deficiency. Id. at 87-88. According to Schweigert, the
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`astaxanthin administration by Grangaud necessarily treats retinal damage,
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`because astaxanthin is converted in rat retina into vitamin A, which is then
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`used to reconstruct the retina. Ex. 1033 ¶¶ 23 and 43; see Ex. 1045, 59, 60,
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`and 160.
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`The University argues that at the time of invention it was accepted
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`scientific fact that astaxanthin did not have any Vitamin A activity. Resp.
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`30–31 and 35–36 (citing Ex. 2015 ¶¶ 97–102; Ex. 2010, 2483). The
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`University adds that the work of Grangaud was rejected as unreliable to
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`establish that astaxanthin exhibited Vitamin A activity. Id. at 30–31. These
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`12
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`arguments are unpersuasive to controvert the evidence presented by
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`Cyanotech that, during Vitamin A deficiency, astaxanthin is converted to
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`Vitamin A by the rat. Ex. 1002, 44; Ex. 1033 ¶¶ 42–43 and 51; Ex. 1045,
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`59–60, 73, 160, 163–164. That is, while astaxanthin itself is without
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`Vitamin A-like activity, a biological pathway exist in rats that is capable of
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`metabolically converting astaxanthin to Vitamin A, whereby Vitamin A may
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`present its own activity.
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`In view of the above, we conclude that the preponderance of the
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`evidence presented by Cyanotech demonstrates that retinal damage is
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`inherent to the condition of vitamin A deficiency-induced xerophthalmia.
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`Grangaud’s animals were kept on a vitamin A-deficient diet for about 2
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`months (Ex. 1002, 43), and Dowling supports a conclusion that animals kept
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`on such a diet would have suffered retinal damage. Ex. 1026, 88–89.
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`Dowling also supports a finding that restoration of vitamin A to the diet
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`could reverse the damage caused by a vitamin A deficiency. Id. at 94–96.
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`Grangaud did not administer vitamin A itself, but rather administered
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`astaxanthin. Astaxanthin, however, is capable of being converted to vitamin
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`A in rats, which then would be available to correct the retinal damage caused
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`by a vitamin A-deficient diet, as well as treat ocular lesions resulting from
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`xerophthalmia, thereby improving the vision of the rats. Pet., 14-16; Ex.
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`1002, 44; Ex. 1033 ¶¶ 42–43 and 51; Ex. 1045, 60 and 160. As such, the
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`inherent action of astaxanthin would have resulted in improved vision in
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`Grangaud’s animal model.
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`The University argues that it is unclear whether Grangaud isolated
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`astaxanthin. Id. at 27–31. The University contends that Grangaud’s
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`spectrographic analysis of the Aristoeomorpha foliacea (krill) oil
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`13
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`administered to the xeropthalmic rats was insufficient to identify the active
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`compound in the oil as astaxanthin because the peaks observed by Grangaud
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`were “broad” and different from the peak for free astaxanthin referenced in
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`the literature (492 nm). Resp. 28 (citing Ex. 2015 at ¶¶ 86–90). That is, the
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`University argues that it is unclear whether Grangaud isolated astaxanthin or
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`whether Grangaud correctly identified astaxanthin as the compound that
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`gave rise to the observed vitamin A activity. Id. at 27–31.
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`We are not persuaded by the University’s argument. Even if we were
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`to agree with the University that Grangaud’s krill oil contained other
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`carotenoids, the University does not dispute that Grangaud’s krill oil
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`contained astaxanthin, which, upon administration to vitamin A-deficient
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`rats, is converted to vitamin A for use in the retina. Ex. 1002, 50:31–51:20;
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`Ex. 1033 ¶¶ 23, 42, 43, 51.
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`The University’s also argues that neither Grangaud nor Dowling
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`suggests that vitamin A deficiency (to which each is directed) is related, in
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`any way, to either free radical damage to a retina or central nervous system,
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`or to any of the disorders or diseases to which the claims are directed. This
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`argument is unpersuasive as the evidence shows that astaxanthin is
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`converted in vivo to vitamin A, which is then available to treat vitamin A
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`deficiency-induced xerophthalmia. Ex. 1002, 50:31–51:20; Ex. 1033 ¶¶ 23,
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`42, 43, 51
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`In view of the above, we find that Grangaud’s disclosure of a method
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`of feeding astaxanthin to rats suffering vitamin A deficiency-induced
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`xerophthalmia meets all elements of the methods recited in claims 1, 3, and
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`10. Accordingly, we conclude that Grangaud anticipates claims 1, 3, and 10.
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`14
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`b. Claims 8–9 and 11–12
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`Claims 8–9 and 11–12 depend directly from claim 1 and further limit
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`the retinal damage element of claim 1. Claim 8 requires the retinal damage
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`to include free radical-induced retinal damage. Claim 9 requires the retinal
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`damage to include light-induced retinal damage. Claim 10 requires the
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`retinal damage to include ganglion cell retinal damage. Claim 11 requires
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`the retinal damage to include age-related macular degeneration.
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`The evidence of record shows that vitamin A functions as a precursor
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`to the structural protein rhodopsin, found in the retina. Ex. 2105 ¶ 84.
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`Dowling discloses that the loss of this structural protein in vitamin-A
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`deficiency causes photoreceptor cell loss and night-blindness, which may be
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`corrected by adding vitamin A back to the diet. Ex. 1026; see Ex. 1045, 29–
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`30 and Ex. 2015 ¶ 46. In view of the above, we find that the preponderance
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`of the evidence presented by Cyanotech supports a finding that Grangaud’s
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`animals were suffering from vitamin A deficiency that necessarily resulted
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`in retinal damage.
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`The preponderance of the evidence presented by Cyanotech, however,
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`fails to demonstrate that Grangaud’s animals were suffering necessarily from
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`free radical-induced retinal damage (claim 8) or light-induced retinal
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`damage5 (claim 9). Certain forms of vitamin A may have antioxidant
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`properties, and thus, be capable of protecting the retina from free radical-
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`induced retinal damage (Ex. 1033 ¶ 37), however, vitamin A is not the only
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`antioxidant that plays a role in the retina—at least both vitamin C and E also
`
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`5 Light generates free radicals in the retina, and thus, light-induced retinal
`damage is a specific form of free radical-induced retinal damage. Ex. 2015,
`¶ 60; see Ex. 1001, 2:1-4.
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`15
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`play an antioxidant role in the retina. Ex. 1029 and Ex. 1045, 18–19.
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`Grangaud’s animals were suffering from vitamin A deficiency, but the
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`retinal damage seen with this condition may be explained by the lack of
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`rhodopsin. Ex. 2015 ¶ 50 and Ex. 1045, 86–88. There is insufficient
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`evidence on this record to conclude that the absence of vitamin A alone
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`would create conditions that resulted necessarily in free radical-induced
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`retinal damage. Accordingly, we are not able to conclude that Grangaud’s
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`animals were suffering necessarily from free radical-induced retinal damage,
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`as required by claims 8 and 9.
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`Regarding claim 11, Dowling teaches that animals suffering from
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`vitamin A deficiency have normal ganglion cells. Ex. 1026, 88. Thus, the
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`evidence does not support a finding that Grangaud’s animals were
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`experiencing ganglion cell retinal damage. Ex. 1026. Regarding claim 12,
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`Grangaud does not disclose the treatment of an animal suffering from age-
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`related macular degeneration. Accordingly, we are not able to conclude that
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`Grangaud’s animals were necessarily suffering from the conditions required
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`by claims 11 and 12.
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`However, as discussed previously, we do not construe the phrase
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`“retinal damage or retinal disease” as a single concept. As such, claims 8–9
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`and 11–12 do not limit further the concept of disease in the preamble of
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`claim 1, from which claims 8–9 and 11–12 depend. We also construed the
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`term “disease” to refer to conditions in which the underlying cause of
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`damage is treatable. In this regard, Grangaud discloses a method of treating
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`an individual suffering from retinal disease—that is, xerophthalmia.
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`Xerophthalmia is a nutritional disorder that may be treated by replacement
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`of vitamin A, and thus, meets the element of retinal disease recited in the
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`16
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`claims. Ex. 2015 ¶ 56. Accordingly, we conclude that Grangaud anticipates
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`claims 8–9 and 11–12.
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`c. Claim 13
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`Claim 13 recites a method comprising administering a therapeutically-
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`effective amount of astaxanthin to protect neurons in a retina from free-
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`radical induced retinal injury. Cyanotech presents evidence that astaxanthin
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`is an antioxidant that is capable of being transported into the retina, and
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`argues that the biological role of astaxanthin obtained from the diet
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`inherently involves protecting neurons in a retina from free-radical induced
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`retinal injury. Pet. 14–15, 22 and 59 (citing Ex. 1002 and Ex. 1033 ¶¶ 24–25
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`and 43–45).
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`As discussed above, Grangaud discloses the results of experiments
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`conducted on albino rats fed a vitamin A-deficient diet. Ex. 1002, 43. The
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`University does not dispute that astaxanthin obtained from the diet is capable
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`of crossing the blood-retinal barrier to protect neurons in a retina from free-
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`radical induced damage. Resp. 4–8. Rather, the University argues that
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`evidence of record does not demonstrate that vitamin A protects the retina
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`from free-radical attack and that the vitamin A-deficient rats in Grangaud do
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`not suffer retinal damage from free radicals necessarily. Id. at 12 and 19–24.
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`The language of claim 13, however, does not require the
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`administration of vitamin A nor does it require an individual to suffer from
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`free-radical damage. Claim 13 requires the administration of astaxanthin to
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`an individual and, as summarized above, both parties agree that
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`astaxanthin’s biological role involves antioxidant activities in the retina.
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`Paper 64, 18:10–13; Resp. 5. Thus, the necessary result of such
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`17
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`Patent 5,527,533
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`administration would be protection of neurons in a retina from free-radical
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`induced retinal injury. Accordingly, we conclude that Grangaud anticipates
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`claim 13.
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`d. Claim 14
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`Claim 14 recites a method of treating an individual suffering from
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`neuronal damage to a retina comprising administering a therapeutically-
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`effective amount of astaxanthin to the individual to improve the condition of
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`the retina. As discussed above with regard to claims 1 and 10, the
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`preponderance of evidence of record demonstrates that neuronal damage to a
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`retina is inherent to the condition of vitamin A deficiency-induced
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`xerophthalmia. Furthermore, as discussed above, the inherent action of
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`astaxanthin involves conversion to vitamin A, which is then available to
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`repair the retina, thereby improving vision in Grangaud’s animal model.
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`Accordingly, Grangaud’s method of feeding astaxanthin to rats suffering
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`vitamin A deficiency-induced xerophthalmia meets all elements of claim 14.
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`e. Claim 15
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`Claim 15 depends from claim 14 and specifies that the neuronal
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`damage may be caused by photic injury to the retina. Cyanotech contends
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`that damage resulting from photo injury is caused by free radicals created by
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`photic energy. Pet. 23.
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`As discussed above with regard to claim 8, the preponderance of
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`evidence of record does not support a conclusion that Grangaud’s animals
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`were suffering necessarily from free radical-induced retinal damage caused
`
`by photic injury. Certain forms of vitamin A may have antioxidant
`
`properties, and thus, be capable of protecting the retina from free radical-
`
`18
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`
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`IPR2013-00401 and IPR2013-00404
`Patent 5,527,533
`
`
`induced retinal damage (Ex. 1033 ¶ 37), however, vitamin A is not the only
`
`antioxidant that plays a role in the retina—at least both vitamin C and E also
`
`play an antioxidant role in the retina. Ex. 1029 and Ex. 1045, 18–19.
`
`Grangaud’s animals were suffering from vitamin A deficiency, but the
`
`retinal damage seen with this condition may be explained by the lack of
`
`rhodopsin. Ex. 2015 ¶ 50 and Ex. 1045, 86–88. There is insufficient
`
`evidence to conclude that the absence of vitamin A alone would create
`
`conditions that resulted necessarily in free radical-induced retinal damage.
`
`Accordingly, we are not persuaded that the preponderance of evidence
`
`shows that Grangaud’s animals were necessarily suffering from photic
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`injury, as required by claim 15.
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`f. Claims 21 and 22
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`Claim 21 recites a method of treating an individual suffering from a
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`free radical-induced injury to a central nervous system. Claim 22 depends
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`from claim 22 and specifies that the central nervous system may be the
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`retina. As discussed above with regard to claim 15, the preponderance of
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`evidence