Cyanotech Corporationv.The Board of Trustees of the University of Illinois

Patent Trials and Appeals Board

Dec 12, 2014

08330194 - (D) (P.T.A.B. Dec. 12, 2014)

Trials@uspto.gov Paper 16
Tel: 571-272-7822 Entered: December 12, 2014

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 IPR2013-00401
1

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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I. INTRODUCTION
Cyanotech Corporation (“Cyanotech”) filed corrected petitions in
IPR2013-00401 (Paper 9, “Pet. ’401”) and IPR2013-00404 (IPR2013-
00404, Paper 8, “Pet. ’404”) requesting inter partes review of claims 1–27
of U.S. Patent No. 5,527,533 (“the ’533 patent”). The Board consolidated
IPR2013-00401 and IPR2013-00404 and instituted trial for the challenged
claims on the following grounds of unpatentability asserted by Cyanotech:
Reference(s) Basis Claims challenged
Grangaud
2
§ 102 1, 3, 8–15, 21, 22, and 26
Grangaud and Dowling
3
§ 103 1–15, 21, 22, and 26
Decision to Institute, 19 (Paper 17 (“Dec.”)).
After institution and consolidation of both trials, the Board of Trustees
of the University of Illinois (“the University”), filed its Patent Owner’s
Response (“Resp.”). Paper 32.
4
Cyanotech filed a Reply (Paper 43,
“Reply.”). The University did not file a motion to amend claims.
Cyanotech relies upon declarations of Florian J. Schweigert
(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FACTOR (1951) (unpublished doctorate dissertation, University of Lyon)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.
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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
Cyanotech filed a Reply (Paper 54).
Oral argument was conducted on July 16, 2014. A transcript is
entered as Paper 64 (“Tr.”).
This Final Written Decision addresses challenges to the patentability
of claims 1–15, 21, 22, and 26.
Cyanotech has proved by a preponderance of the evidence that claims
1–14 and 26 of the ’533 patent are unpatentable. Cyanotech has failed to
prove the unpatentability of claims 15, 21, and 22.
A. The ’533 Patent (Ex. 1001)
The retina of the eye, a component of the central nervous system, is
important for sight. Ex. 1001, 1:49–52; see also, Ex. 1045, 6–12. Retinal
structures important to vision include: a ganglion cell layer, which connects
the retina to the brain; an inner nuclear layer containing neurons, such as
bipolar cells; and an outer nuclear or photoreceptor cell layer. Ex. 1045, 6–
12. Photoreceptor cells convert light into signals that are transmitted to the
other neurons. Ex. 1001 at 1:57–60. The loss of a significant number of
photoreceptor cells adversely affects visual function. Id. at 3:6–13.
The ’533 patent discloses that eye diseases or injuries that can cause
damage to the retinal tissue and neurons include age-related macular
degeneration, photic injury, photoreceptor cell damage, ganglion cell
damage, traumatic injury, ischemic insult-related diseases, and inflammatory
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diseases. Id. at 1:9–14. Regarding photic injury, the ’533 patent discloses
that excessive light energy reaching the retina can overwhelm the metabolic
systems of photoreceptor cells causing damage to these neurons, either
directly or indirectly. Id. at 1:65–67. The ’533 patent further discloses that
free radical species can be generated by enzymatic processes or from the
combination or continuous or excessive exposure to light and the relatively
high concentration of oxygen in the eye. Id. at 2:1–5. The ’533 patent
discloses that the free radical species lead to functional impairment of cell
membranes and may cause temporary or permanent damage to retinal tissue.
Ex. 1001, 2:13–21. According to the ’533 patent, however, the presence of
antioxidant compounds counteracts the free radical species generated by
light to protect the retina from damage. Id. at 2:29–32.
The ’533 patent relates to methods of treating diseases and injuries to
the central nervous system, especially the eyes, comprising administering a
therapeutically-effective amount of astaxanthin. Ex. 1001, 1:9–19 and 6:54–
62. The ’533 patent discloses that astaxanthin is a highly-effective
antioxidant and ameliorates free radical-induced eye damage. Id. at 15:56–
60. Astaxanthin is disclosed as particularly suited for treatment of the eye
because, unlike other carotenoids such as β-carotene, astaxanthin can cross
the blood-retinal brain barrier readily. Id. at 10:18–22. According to the
’533 patent, comparative studies with β-carotene demonstrate that
astaxanthin is more effective than β-carotene at protecting rats from photic
injury. Id. at 13:60 to 14:50.
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B. Exemplary Claims
Independent claims 1, 13, 14, 21, and 26 are illustrative of the claims
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
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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Office Patent Trial Practice Guide, 77 Fed. Reg. 48,756, 48,766 (Aug. 14,
2012). Claim terms are given their ordinary and customary meaning, as
would be understood by one of ordinary skill in the art in the context of the
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
Paulsen, 30 F.3d 1475, 1480 (Fed. Cir. 1994).
We expressly interpret below only those claim terms that require
analysis to resolve arguments related to the patentability of the challenged
claims.
1. Construction of the phrase “retinal damage or retinal disease”
We construed the phrase “retinal damage or retinal disease” recited in
claims 1–12 in the alternative to refer to two classes of conditions: retinal
damage and retinal disease. Dec. 9. The University argues for the
construction of the terms “retinal damage” and “retinal disease” as a single
concept such that both “retinal damage” and “retinal disease” refer to an
identical class of medical conditions. Resp. 15–16. Specifically, the
University contends that the specification confirms that free radical damage
is associated with both injuries and disease. Id. (citing Ex. 1001, 15:23–27
(“The administration of astaxanthin to an individual suffering from an eye
injury or disease, such as free radical induced injury, beneficiates the vision
of the individual by rescuing further photoreceptor cells from damage
destruction.”); 15:57–60 (“the administration of astaxanthin also provides a
method of treating free radical induced disease or injury to the central
nervous system in general”)).
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As stated by the University, the specification discloses methods of
treating damage caused by injury or disease (Resp. 14–15), however, the
specification does not contain any indication that the patentee intended to act
as his own lexicographer clearly defining “disease” and “damage” in the
same manner. For example, the specification does not clearly convey the
patentee’s intent to appoint a special meaning to the phrase “retinal damage
or retinal disease.”
We must determine, therefore, the ordinary meaning of “disease” and
“damage” as used in these claims to one of skill in the art in light of the
specification and prosecution history. In re Paulsen, 30 F.3d at 1480. In
this regard, the term “damage,” as used in the specification, refers to damage
resulting from injury or disease. Ex. 1001, 1:14–19. The specification does
not equate damage and disease, but provides that damage may be caused by
disease. Id. The meaning of the term disease, however, refers to conditions
that may cause damage (such as degenerative eye disease), and are treatable
themselves. Id. at 15:36–40. That is, the underlying cause of the damage is
treatable, not just the damage alone. The University does not direct our
attention to anything in the specification or prosecution that would clearly
alter the ordinary meaning of “disease” and “damage.” Resp. 14–16.
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
our Decision to Institute, we adopted the dictionary definition of “disease”
and construed the term as “[a] morbid entity ordinarily characterized by two
or more of the following criteria: recognized etiologic agent(s), identifiable
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group of signs and symptoms, or consistent anatomic alterations.” Dec. 8–9;
see, Pet. ’401 (citing Ex. 1040). We adopted the dictionary definition of
“damage” and construed the term as “[h]arm, diminution, or destruction of
an organ, body part, system, or function.” Id. We maintain these
constructions for “disease” and “damage” as they are consistent with the use
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
“retinal damage or retinal disease” refers to either retinal damage or retinal
disease.
We also maintain our constructions of “disease” and “damage” with
respect to claims 8–12, which recite particular types of retinal damage, and
thus, further limit “retinal damage” recited in claim 1. Claims 8–12,
however, do not limit further “retinal disease,” as recited in claim 1. Thus,
for example, claim 12 encompasses a method of treating an individual
suffering from damage caused by age-related macular degeneration or
suffering from any retinal disease.
B. The Prior Art
1. Summary of Grangaud
Grangaud discloses the results of experiments conducted on rats fed a
vitamin A-deficient diet. Ex. 1002, 43. The animals developed
complications of vitamin A deficiency that included xerophthalmia (“dry
eye”) and death. Visible signs of xerophthalmia were described as ocular
lesions. See e.g., id. at 44, 49. The restoration of vitamin A or astaxanthin
to the vitamin A-deficient diet was sufficient to heal the ocular lesions. Id.
Grangaud concluded that astaxanthin has vitamin A activity. Id. at 56.
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Grangaud further noted that the antioxidant strength of astaxanthin is
comparable to that of vitamin A, and that astaxanthin shares the
antixerophthalmic activity of vitamin A. Id.
Grangaud is silent as to the mechanism of the disease pathogenesis for
vitamin A deficiency. Grangaud provides no evidence tending to establish
that the vitamin A-deficient rats exhibited retinal damage.
2. Summary of Dowling
Dowling discloses the results of a study showing the effect of vitamin
A deficiency on the fine structure of the retina. Ex 1026. Dowling used an
albino rat model kept on a vitamin A-free diet, supplemented with vitamin A
acid. Id. at 85. The vitamin A acid kept the rats healthy and growing, but
did not support the visual cycle and thus the rats gradually become night-
blind. Id. Dowling discloses that the visual cells (photoreceptor cells) of
animals fed such a diet degenerated after 2 months on the diet. Id. at 87–88.
Other retinal cells, such as bipolar and ganglion cells, however, appeared
normal, even after 6 months on the diet. Id. Dowling also discloses that the
damage to the retinal cells is reversible by giving vitamin A to the deficient
animals. Id. at 94.
C. Patentability of Original Claims
To prevail in its challenges to the patentability of claims, the
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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1. Anticipation of Claims 1, 3, 8–15, 21, 22, and 26 by Grangaud
The Court of Appeals for the Federal Circuit summarized the
analytical framework for determining whether prior art anticipates a claim as
follows:
If the claimed invention was “described in a printed
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)).
Finisar Corp. v. DirecTV Grp., Inc., 523 F.3d 1323, 1334–35 (Fed. Cir.
2008). We must analyze prior art references as a skilled artisan would. See
Scripps Clinic & Res. Found. v. Genentech, Inc., 927 F.2d 1565, 1576 (Fed.
Cir. 1991) (to anticipate, “[t]here must be no difference between the claimed
invention and the reference disclosure, as viewed by a person of ordinary
skill in the field of the invention”).
To establish inherent disclosure, the evidence must show that a feature
necessarily is described in the reference, and that it would be recognized by
persons of ordinary skill. In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999); cf. EMI Grp. N. Am., Inc. v. Cypress Semiconductor Corp., 268 F.3d
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1342, 1351 (Fed. Cir. 2001) (“Theoretical mechanisms or rules of natural
law that are recited in a claim, that themselves are not patentable, however,
do not need to be recognized by one of ordinary skill in the art for a finding
of inherency.”). The mere fact that a certain thing may result from a given
set of circumstances is not sufficient to establish inherency. In re Rijckaert,
9 F.3d 1531, 1534 (Fed. Cir. 1993). Inherency may not be established by
probabilities or possibilities. In re Oelrich, 666 F.2d 578, 581 (CCPA
1981).
Cyanotech contends that Grangaud’s disclosure of the administration
of dietary astaxanthin to cure xerophthalmia (“dry eye”) in vitamin A-
deficient rats anticipates claims 1, 3, 8–15, 21, 22, and 26, which are
directed to a method of administering a therapeutically effective amount of
astaxanthin to improve the vision of an individual suffering from retinal
damage or retinal disease. Pet. 15–17. For the reasons expressed below, we
conclude that Cyanotech has demonstrated by a preponderance of evidence
that Grangaud anticipates claims 1, 3, 8–14 and 26. Cyanotech has failed to
establish by a preponderance of evidence that Grangaud anticipates claims
15, 21, and 22.
a. Claims 1, 3, and 10
Claim 1 encompasses a method of treating an individual suffering
from retinal damage with the administration of astaxanthin in an amount
sufficient to improve the vision of the individual. Claims 3 and 10 depend
directly from claim 1. Claim 3 requires astaxanthin to be administered
orally. Claim 10 specifies that the retinal damage may be photoreceptor cell
retinal damage.
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Although Grangaud discloses the administration of astaxanthin to cure
ocular lesions (Ex. 1002, 43, 44, 49), Cyanotech concedes that Grangaud
does not discuss whether or not vitamin A-deficient rats exhibit retinal
damage. Pet. 18–19. Cyanotech contends, however, that animals
developing xerophthalmia due to vitamin A-deficiency inherently suffer
retinal damage. Id. For support of this assertion, Cyanotech relies on the
Declaration of Florian J. Schweigert (“Schweigert declaration”) (Ex. 1033)
to establish that vitamin A-deficient rats exhibiting dry eye necessarily have
retinal damage and, more specifically, photoreceptor cell retinal damage.
With reference to Dowling (Ex. 1026), Dr. Schweigert testifies that
severe vitamin A deficiency causes degeneration in the retina that precedes
dry eye. Ex. 1033 ¶¶ 27, 36, and 39–43. Dowling reported that albino rats
experienced degeneration of visual cells (photoreceptor cells) after about 2
months of vitamin A deficiency. Ex. 1026, 87-88. Such retinal damage
could be reversed upon restoring vitamin A to rats’ diets. Id. at 94. The
other retinal cells (bipolar and ganglion cells), however, appeared normal
with vitamin A deficiency. Id. at 87-88. According to Schweigert, the
astaxanthin administration by Grangaud necessarily treats retinal damage,
because astaxanthin is converted in rat retina into vitamin A, which is then
used to reconstruct the retina. Ex. 1033 ¶¶ 23 and 43; see Ex. 1045, 59, 60,
and 160.
The University argues that at the time of invention it was accepted
scientific fact that astaxanthin did not have any Vitamin A activity. Resp.
30–31 and 35–36 (citing Ex. 2015 ¶¶ 97–102; Ex. 2010, 2483). The
University adds that the work of Grangaud was rejected as unreliable to
establish that astaxanthin exhibited Vitamin A activity. Id. at 30–31. These
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arguments are unpersuasive to controvert the evidence presented by
Cyanotech that, during Vitamin A deficiency, astaxanthin is converted to
Vitamin A by the rat. Ex. 1002, 44; Ex. 1033 ¶¶ 42–43 and 51; Ex. 1045,
59–60, 73, 160, 163–164. That is, while astaxanthin itself is without
Vitamin A-like activity, a biological pathway exist in rats that is capable of
metabolically converting astaxanthin to Vitamin A, whereby Vitamin A may
present its own activity.
In view of the above, we conclude that the preponderance of the
evidence presented by Cyanotech demonstrates that retinal damage is
inherent to the condition of vitamin A deficiency-induced xerophthalmia.
Grangaud’s animals were kept on a vitamin A-deficient diet for about 2
months (Ex. 1002, 43), and Dowling supports a conclusion that animals kept
on such a diet would have suffered retinal damage. Ex. 1026, 88–89.
Dowling also supports a finding that restoration of vitamin A to the diet
could reverse the damage caused by a vitamin A deficiency. Id. at 94–96.
Grangaud did not administer vitamin A itself, but rather administered
astaxanthin. Astaxanthin, however, is capable of being converted to vitamin
A in rats, which then would be available to correct the retinal damage caused
by a vitamin A-deficient diet, as well as treat ocular lesions resulting from
xerophthalmia, thereby improving the vision of the rats. Pet., 14-16; Ex.
1002, 44; Ex. 1033 ¶¶ 42–43 and 51; Ex. 1045, 60 and 160. As such, the
inherent action of astaxanthin would have resulted in improved vision in
Grangaud’s animal model.
The University argues that it is unclear whether Grangaud isolated
astaxanthin. Id. at 27–31. The University contends that Grangaud’s
spectrographic analysis of the Aristoeomorpha foliacea (krill) oil
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administered to the xeropthalmic rats was insufficient to identify the active
compound in the oil as astaxanthin because the peaks observed by Grangaud
were “broad” and different from the peak for free astaxanthin referenced in
the literature (492 nm). Resp. 28 (citing Ex. 2015 at ¶¶ 86–90). That is, the
University argues that it is unclear whether Grangaud isolated astaxanthin or
whether Grangaud correctly identified astaxanthin as the compound that
gave rise to the observed vitamin A activity. Id. at 27–31.
We are not persuaded by the University’s argument. Even if we were
to agree with the University that Grangaud’s krill oil contained other
carotenoids, the University does not dispute that Grangaud’s krill oil
contained astaxanthin, which, upon administration to vitamin A-deficient
rats, is converted to vitamin A for use in the retina. Ex. 1002, 50:31–51:20;
Ex. 1033 ¶¶ 23, 42, 43, 51.
The University’s also argues that neither Grangaud nor Dowling
suggests that vitamin A deficiency (to which each is directed) is related, in
any way, to either free radical damage to a retina or central nervous system,
or to any of the disorders or diseases to which the claims are directed. This
argument is unpersuasive as the evidence shows that astaxanthin is
converted in vivo to vitamin A, which is then available to treat vitamin A
deficiency-induced xerophthalmia. Ex. 1002, 50:31–51:20; Ex. 1033 ¶¶ 23,
42, 43, 51
In view of the above, we find that Grangaud’s disclosure of a method
of feeding astaxanthin to rats suffering vitamin A deficiency-induced
xerophthalmia meets all elements of the methods recited in claims 1, 3, and
10. Accordingly, we conclude that Grangaud anticipates claims 1, 3, and 10.
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b. Claims 8–9 and 11–12
Claims 8–9 and 11–12 depend directly from claim 1 and further limit
the retinal damage element of claim 1. Claim 8 requires the retinal damage
to include free radical-induced retinal damage. Claim 9 requires the retinal
damage to include light-induced retinal damage. Claim 10 requires the
retinal damage to include ganglion cell retinal damage. Claim 11 requires
the retinal damage to include age-related macular degeneration.
The evidence of record shows that vitamin A functions as a precursor
to the structural protein rhodopsin, found in the retina. Ex. 2105 ¶ 84.
Dowling discloses that the loss of this structural protein in vitamin-A
deficiency causes photoreceptor cell loss and night-blindness, which may be
corrected by adding vitamin A back to the diet. Ex. 1026; see Ex. 1045, 29–
30 and Ex. 2015 ¶ 46. In view of the above, we find that the preponderance
of the evidence presented by Cyanotech supports a finding that Grangaud’s
animals were suffering from vitamin A deficiency that necessarily resulted
in retinal damage.
The preponderance of the evidence presented by Cyanotech, however,
fails to demonstrate that Grangaud’s animals were suffering necessarily from
free radical-induced retinal damage (claim 8) or light-induced retinal
damage
5
(claim 9). Certain forms of vitamin A may have antioxidant
properties, and thus, be capable of protecting the retina from free radical-
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

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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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 on this record 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 able to conclude that Grangaud’s
animals were suffering necessarily from free radical-induced retinal damage,
as required by claims 8 and 9.
Regarding claim 11, Dowling teaches that animals suffering from
vitamin A deficiency have normal ganglion cells. Ex. 1026, 88. Thus, the
evidence does not support a finding that Grangaud’s animals were
experiencing ganglion cell retinal damage. Ex. 1026. Regarding claim 12,
Grangaud does not disclose the treatment of an animal suffering from age-
related macular degeneration. Accordingly, we are not able to conclude that
Grangaud’s animals were necessarily suffering from the conditions required
by claims 11 and 12.
However, as discussed previously, we do not construe the phrase
“retinal damage or retinal disease” as a single concept. As such, claims 8–9
and 11–12 do not limit further the concept of disease in the preamble of
claim 1, from which claims 8–9 and 11–12 depend. We also construed the
term “disease” to refer to conditions in which the underlying cause of
damage is treatable. In this regard, Grangaud discloses a method of treating
an individual suffering from retinal disease—that is, xerophthalmia.
Xerophthalmia is a nutritional disorder that may be treated by replacement
of vitamin A, and thus, meets the element of retinal disease recited in the
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claims. Ex. 2015 ¶ 56. Accordingly, we conclude that Grangaud anticipates
claims 8–9 and 11–12.
c. Claim 13
Claim 13 recites a method comprising administering a therapeutically-
effective amount of astaxanthin to protect neurons in a retina from free-
radical induced retinal injury. Cyanotech presents evidence that astaxanthin
is an antioxidant that is capable of being transported into the retina, and
argues that the biological role of astaxanthin obtained from the diet
inherently involves protecting neurons in a retina from free-radical induced
retinal injury. Pet. 14–15, 22 and 59 (citing Ex. 1002 and Ex. 1033 ¶¶ 24–25
and 43–45).
As discussed above, Grangaud discloses the results of experiments
conducted on albino rats fed a vitamin A-deficient diet. Ex. 1002, 43. The
University does not dispute that astaxanthin obtained from the diet is capable
of crossing the blood-retinal barrier to protect neurons in a retina from free-
radical induced damage. Resp. 4–8. Rather, the University argues that
evidence of record does not demonstrate that vitamin A protects the retina
from free-radical attack and that the vitamin A-deficient rats in Grangaud do
not suffer retinal damage from free radicals necessarily. Id. at 12 and 19–24.
The language of claim 13, however, does not require the
administration of vitamin A nor does it require an individual to suffer from
free-radical damage. Claim 13 requires the administration of astaxanthin to
an individual and, as summarized above, both parties agree that
astaxanthin’s biological role involves antioxidant activities in the retina.
Paper 64, 18:10–13; Resp. 5. Thus, the necessary result of such
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administration would be protection of neurons in a retina from free-radical
induced retinal injury. Accordingly, we conclude that Grangaud anticipates
claim 13.
d. Claim 14
Claim 14 recites 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. As discussed above with regard to claims 1 and 10, the
preponderance of evidence of record demonstrates that neuronal damage to a
retina is inherent to the condition of vitamin A deficiency-induced
xerophthalmia. Furthermore, as discussed above, the inherent action of
astaxanthin involves conversion to vitamin A, which is then available to
repair the retina, thereby improving vision in Grangaud’s animal model.
Accordingly, Grangaud’s method of feeding astaxanthin to rats suffering
vitamin A deficiency-induced xerophthalmia meets all elements of claim 14.
e. Claim 15
Claim 15 depends from claim 14 and specifies that the neuronal
damage may be caused by photic injury to the retina. Cyanotech contends
that damage resulting from photo injury is caused by free radicals created by
photic energy. Pet. 23.
As discussed above with regard to claim 8, the preponderance of
evidence of record does not support a conclusion that Grangaud’s animals
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-
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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
injury, as required by claim 15.
f. Claims 21 and 22
Claim 21 recites a method of treating an individual suffering from a
free radical-induced injury to a central nervous system. Claim 22 depends
from claim 22 and specifies that the central nervous system may be the
retina. As discussed above with regard to claim 15, the preponderance of
evidence of record does not support a conclusion that Grangaud’s animals
were necessarily suffering from free radical-induced retinal damage.
Accordingly, we are not able to conclude that the preponderance of evidence
shows that Grangaud’s animals were necessarily suffering from free radical-
induced injury as required by claims 21 and 22.
g. Claim 26
Claim 26 recites a method comprising administering a therapeutically
effective amount of astaxanthin to retard the progress of a degenerative
retinal disease. The specification identifies age-related macular
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degeneration as one such degenerative retinal disease. Ex. 1001, 15:36–40.
The specification also discloses that degenerative retinal diseases result in
injury to the photoreceptor cells. Id. at 7:50–59.
Grangaud discloses the administration of astaxanthin to rats suffering
from xerophthalmia due to being kept on a vitamin A-deficient diet. Ex.
1002, 43. Vitamin A deficiency inherently results in the loss of
photoreceptor cells. Ex. 1033 ¶¶ 27, 36, and 39–43; see Ex. 1026, 87–88.
Due to this loss of photoreceptor cells, we consider vitamin A deficiency a
degenerative retinal disease encompassed by claim 26. Grangaud’s
administration of astaxanthin to vitamin A deficient rats necessarily retarded
the progress of retinal damage caused by vitamin A deficiency—astaxanthin
is converted in rat retina into vitamin A, which then is used to reconstruct
the retina. Ex. 1033 ¶¶ 23 and 43; see Ex. 1045, 59, 60, and 160.
Accordingly, Grangaud’s method of feeding astaxanthin to rats suffering
vitamin A deficiency-induced xerophthalmia meets all elements of the
method recited in claim 26. We conclude that Grangaud anticipates claim
26.
2. Obviousness
“Section 103 [of 35 U.S.C.] forbids issuance of a patent when ‘the
differences between the subject matter sought to be patented and the prior art
are such that the subject matter as a whole would have been obvious at the
time the invention was made to a person having ordinary skill in the art to
which said subject matter pertains.’” KSR Int’l Co. v. Teleflex Inc., 550 U.S.
398, 406 (2007)(quoting 35 U.S.C. §103). To establish obviousness of a
claimed invention, all the claim limitations must be taught or suggested by
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the prior art. See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342
(Fed. Cir. 2003).
To establish inherent disclosure, the evidence must show that a feature
is necessarily described in the reference, and that it would be so recognized
by persons of ordinary skill. In re Robertson, 169 F.3d 743, 745 (Fed. Cir.
1999).
Cyanotech contends that the combination of Grangaud and Dowling
renders claims 1–15, 21, 22, and 26 obvious. For the reasons expressed
below, we conclude that Cyanotech has demonstrated by a preponderance of
evidence that the combination of Grangaud and Dowling would have
rendered claims 1–14 and 26 obvious. Cyanotech has failed, however, to
establish by a preponderance of evidence that claims 15, 21, and 22 would
have been obvious.
a. Obviousness of Claims 1–15, 21, 22, and 26 over Grangaud
and Dowling
(1) Claims 1–14 and 26
Cyanotech challenges claims 1–14 and 26 as obvious over Grangaud
and Dowling. Cyanotech presents substantially the same evidence for both
their anticipation and obviousness challenges of claims 1, 3, 8–14, and 26.
Pet. 29–44. With regard to claims 2 and 4–7, we determined in our Decision
to Institute that the evidence presented Cyanotech’s Petition reasonably
supported a finding that the administration routes and dosages encompassed
by claims 2 and 4–7 would have been a predictable variation of the teachings
of Grangaud that could have been implemented by one of ordinary skill in
the art. Dec. 15–16, (citing KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 417
(2007) (“If a person of ordinary skill can implement a predictable variation,
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§ 103 likely bars its patentability.”)).
In its Response, the University argues separately for the
nonobviousness of claims 8, 9 and 11–13. Resp. 33–40. The University
further argues that several lines of objective evidence (or “secondary
considerations”) demonstrate the non-obviousness of claims 1–14 and 26.
Id. at 45–51. In particular, the University argues praise (id. at 46–48),
commercial success (id. at 49), commercial acquiescence (id.), copying (id.
at 50), unexpected results (id. at 50–51), and long-felt but unmet need (id. at
51). The University does not argue separately for the nonobviousness of the
elements recited in claims 1–7, 10, 14 and 26.
In making our decision on the obviousness of the University’s claims
over prior art, the entirety of the evidence submitted, including the evidence
based on the applied prior art and the evidence of nonobviousness based on
secondary consideration factors, has been considered as a whole.
Regarding the University’s arguments addressing the specific
elements of claims 8, 9, 11, and 12, we agree that Grangaud fails to disclose
retinal damage comprising free radical-induced retinal damage (claim 8),
light-induced retinal damage (claim 9), ganglion cell retinal damage (claim
11), and age-related macular degeneration (claim 12). We do not find
claims 8, 9, 11, and 12 to be so limited, however, due to the recitation of
“retinal disease” in independent claim 1. None of dependent claims 8, 9, 11,
or 12 further limits the “retinal disease” recited in claim 1. Rather, we find
that Grangaud discloses the treatment of xerophthalmia, which is a
nutritional disorder that may be treated by replacement of vitamin A, and
thus meets the element of retinal disease recited in these claims. Ex. 2015 ¶
56.
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As to secondary considerations, we note that factual inquiries for an
obviousness determination include secondary considerations based on
evaluation and crediting of objective evidence of nonobviousness. Graham
v. John Deere Co., 383 U.S. 1, 17 (1966). Notwithstanding what the
teachings of the prior art would have suggested to one with ordinary skill in
the art at the time of the University’s invention, the totality of the evidence
submitted, including objective evidence of nonobviousness, may lead to a
conclusion that the claimed invention would not have been obvious to one
with ordinary skill in the art. In re Piasecki, 745 F.2d 1468, 1471-1472
(Fed. Cir. 1984). However, such a conclusion requires the finding of a
nexus to establish that the evidence relied upon traces its basis to a novel
element in the claim and not to something in the prior art. Institut Pasteur &
Universite Pierre Et Marie Curie v. Focarino, 738 F.3d 1337, 1347 (Fed.
Cir. 2013). All types of objective evidence of nonobviousness must be
shown to have nexus. In re GPAC Inc., 57 F.3d at 1580 (nexus generally); In
re Huang, 100 F.3d 135, 140 (Fed. Cir. 1996) (commercial success); In re
Antor Media Corp., 689 F.3d 1282, 1293 (Fed. Cir. 2012) (licensing); Wm.
Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1364 (Fed.
Cir. 2012) (copying); Rambus Inc. v. Rea, 731 F.3d 1248, 1256 (Fed. Cir.
2013) (long-felt need); and In re Kao, 639 F.3d 1057, 1069 (Fed. Cir. 2011)
(unexpected results).
As discussed above, we conclude that claims 1, 3, and 8–12 are
anticipated by Grangaud, as evidenced by Dowling. Because anticipation is
the epitome of obviousness, a disclosure that anticipates under 35 U.S.C.
§ 102 also renders the claim unpatentable under 35 U.S.C. § 103. See In re
Fracalossi, 681 F.2d 792, 794 (CCPA 1982) (“[E]vidence establishing lack
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of all novelty in the claimed invention necessarily evidences obviousness.”);
In re Meyer, 599 F.2d 1026, 1031 (CCPA 1979); In re Pearson, 494 F.2d
1399, 1402 (CCPA 1974). Here, Cyanotech presents substantially the same
evidence for both their anticipation and obviousness challenges of claims 1,
3, 8–14, and 26. As such, and for the same reasons set forth in our
anticipation analysis above, we hold that claims 1, 3, 8–14, and 26 are
rendered obvious by Grangaud, alone or in combination with Dowling.
Because we have determined that claims 1, 3, and 8–12 lack a novel feature
with which to establish a nexus with secondary considerations, Cyanotech,
as a matter of law, cannot establish a nexus. In re Kao, 639 F.3d at 1068
(Objective evidence that results from something that is not “both claimed
and novel in the claim” lacks a nexus to the merits of the invention.).
As to claims 2 and 4–7, the University has not directed any arguments
to these claims specifically and has not made any attempts to establish a
nexus between the presented objective evidence of nonobviousness and
these claims. Thus, we maintain our unopposed determination that the
specific doses and routes of administration recited in these claims are
predictable variations within the technical grasp of a person of ordinary skill
in the art, and are not persuaded by the objective evidence that claims 2 and
4–7 are nonobvious.
In view of the above, we conclude that Cyanotech has demonstrated
the unpatentability of claims 1–14 and 26 by a preponderance of the
evidence.
(2) Claim 15
Claim 15 depends from claim 14. As discussed above, we conclude
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that the preponderance of evidence of record demonstrates that neuronal
damage to a retina is inherent to the condition of vitamin A deficiency-
induced xerophthalmia.
The question before us with regard to claim 15, however, is whether
such neuronal damage is due to photic injury, ischemic insult, or intraocular
pressure-related insult to the retina, each of which, as argued by Cyanotech,
causes damage via a release of free radicals. See Pet. 16. We find that the
preponderance of evidence of record does not support a finding that neuronal
damage to a retina observed in the condition of vitamin A deficiency-
induced xerophthalmia is necessarily caused by any of these insult
occurrences. Rather, the preponderance of evidence of record suggests that
the inherent contribution of astaxanthin to the effective treatment of vitamin
A deficiency-induced xerophthalmia involves the conversion of astaxanthin
to vitamin A, where vitamin A is then available to repair and improve the
condition of the retina. As such, the treatment of neuronal damage
comprising photic injury to the retina, ischemic insult to the retina, or
intraocular pressure-related insult to the retina is not suggested by the
combination of references cited by Cyanotech. In re Dillon, 919 F.2d 688,
718 (Fed. Cir. 1990) (“Arguments based on ‘inherent’ properties cannot
stand when there is no supporting teaching in the prior art. Inherency and
obviousness are distinct concepts.”)(citing In re Spormann, 363 F.2d 444,
448 (CCPA 1966)).
Accordingly, we conclude that Cyanotech has not met its burden to
prove claim 15 obvious by a preponderance of evidence.
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(3) Claim 21 and 22
Claim 21 recites a method of treating an individual suffering from a
free radical-induced injury to a central nervous system. Claim 22 depends
from claim 21 and specifies that the central nervous system may be the
retina. As discussed above with regard to claim 15, the preponderance of
evidence of record does not support a conclusion that the retinal damage
Grangaud’s animals necessarily were suffering was induced by free radicals.
Accordingly, we conclude that Cyanotech has not met its burden to prove
claims 21 and 22 obvious by a preponderance of evidence.
III. CYANOTECH’S MOTION TO EXCLUDE
Cyanotech seeks to exclude Exhibits 2033–2036. Paper 47, 1. As
discussed above, however, we have determined that Cyanotech, as a matter
of law, cannot establish a nexus because the challenged claims lack a novel
feature for with which to establish a nexus with secondary considerations.
Because we do not rely on any of exhibits 2033–2036 to reach the final
decision, we dismiss Cyanotech’s motion as moot.
IV. CONCLUSION
Cyanotech has shown, by a preponderance of the evidence, that claims
1–14 and 26 of the ’533 patent are unpatentable. Cyanotech, however, has
failed to meet its burden of proof regarding the unpatentability of claims 15,
21, and 22.

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V. ORDER
In consideration of the foregoing, it is hereby:
ORDERED that claims 1–14 and 26 of the ’533 patent are determined
to be unpatentable;
FURTHER ORDERED that Cyanotech’s request for cancellation of
claims 15, 21, and 22 is denied;
FURTHER ORDERED that Cyanotech’s Motion to Exclude is
dismissed as moot; and
FURTHER ORDERED that because this is a final written decision,
parties to the proceeding seeking judicial review of the decision must
comply with the notice and service requirements of 37 C.F.R. § 90.2.

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For PETITIONER:

Joseph A. Rhoa
NIXON & VANDERHYE P.C.

George E. Darby
PARADISE PATENT SERVICES, INC.

For PATENT OWNER:

Mark D. Schuman
Iain A. McIntyre
CARLSON CASPERS