AVEDRO, INC.

Patent Trials and Appeals Board

May 19, 2021

2020005719 (P.T.A.B. May. 19, 2021)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
14/281,638 05/19/2014 Pavel Kamaev (2330) 14-1498-US 4801
20306 7590 05/19/2021
MCDONNELL BOEHNEN HULBERT & BERGHOFF LLP
300 S. WACKER DRIVE
32ND FLOOR
CHICAGO, IL 60606
EXAMINER
DICKINSON, PAUL W
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
05/19/2021 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
docketing@mbhb.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte PAVEL KAMAEV, MARC D. FRIEDMAN,
EVAN SHERR, and DAVID MULLER
____________

Appeal 2020-005719
Application 14/281,638
Technology Center 1600
____________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 1, 4, 22, and 24 (Final Act.2 1).3 We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as “Glaukos
Corporation” (Appellant’s December 30, 2019, Appeal Brief (Appeal Br.)
3).
2 Examiner’s December 6, 2018 Final Office Action.
3 Appellant’s pending claims 7, 10, 13–15, 27, and 29 stand withdrawn from
consideration (Final Act. 1).
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2
STATEMENT OF THE CASE
Appellant’s disclosure “relates generally to treatment of eye disorders,
and more particularly, to systems, methods, and compositions that generate
cross-linking activity for treatment of eye disorders” (Spec. 2). Claims 1,
22, and 24 are reproduced below:
1. A composition for applying therapy to a cornea of an eye,
comprising:
a cross-linking agent including a concentration of at least
1 mg/ml of riboflavin, the cross-linking agent configured to
generate cross-linking activity in the cornea in response to
exposure to a photo-activating light; and
at least one additive different from the cross-linking
agent and including a concentration of at least 0.1 mM of iron
additive that enhances the cross-linking activity generated by
the riboflavin by accelerating decomposition of hydrogen
peroxide during photo-activation of the riboflavin to increase a
concentration of hydroxyl radicals.
22. The composition of claim 1, wherein the cross-linking
agent includes a concentration of between I mg/ml and 5 mg/ml
riboflavin.
24. The composition of claim 1, wherein the composition
includes a concentration of 0.5 mM of the iron additive.
(see Appellant’s February 12, 2020, Response to Notification of Non-
Compliant Appeal Brief.)
Claims 1, 4, 22, and 24 stand rejected under 35 U.S.C. § 103 as
unpatentable over Karageozian.4
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?

4 Karageozian et al., US 6,537,545 B1, issued Mar. 25, 2003.
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FACTUAL FINDINGS (FF)
FF 1. Karageozian “relates to methods for accelerating non-surgical
corneal reshaping involving the release of corneal hardening agents which
facilitate reshaping of the cornea to correct refractive errors of the eye”
(Karageozian 1:20–24; see also id. at Abstract (Karageozian discloses “[a]n
Enzyme Orthokeratology method . . . for correcting refractive errors in the
eyes of a subject mammal”); see Ans.5 3, 5).
FF 2. Examiner finds that “Karageozian teaches a composition comprising
corneal hardening agents for reshaping the cornea and correcting refractive
errors of the eye, such as keratoconus” (Ans. 5 (citing Karageozian,
Abstract; 1:21–24; 4:34); see also Ans. 3, 5).
FF 3. Karageozian discloses the use of oxidative hardening agents, such as
“copper sulfate (CuSO4) and iron sulfate (FeSO4), [a]scorbic acid and
CuSO4 or Fe2(SO4)3 and other complexes of copper and iron as oxidative
crosslinking agents,” in Enzyme Orthokeratology (Karageozian 10:9–12; see
id. at 10:5–8 (Karageozian discloses that these “reagents act by producing
oxygen free radicals,” which “interact with labile sites in the cornea
resulting in the induction of inter- and intramolecular chemical bonds.”); see
also Ans. 5).
FF 4. Karageozian discloses “[t]he use of ultraviolet light (UV) . . . to
induce oxidative cross-links,” wherein “[t]he judicious use of UV alone or in
combination with various photosensitizersis contemplated for use to induce
oxidative cross-links. Examples of photosensitizers include riboflavin. . . .”
(Karageozian 10:19–23; see Ans. 3, 5).

5 Examiner’s June 2, 2020, Answer.
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FF 5. Karageozian discloses that its
oxidative cross-linking methods can be used alone to induce
cross-links in a subject, or may be use[d] in combination with
the aldehyde or enzymatic cross-linking methods when
compatible. For example, UV and ascorbic acid may be used in
conjunction to induce cross-linking. Conversly, CuSO4 and
lysyl oxidase may not be used simultaneously since, as is well
known in the art, [CuSO4] inhibits lysyl oxidase activity.
(Karageozian 10:25–32.)
FF 6. Karageozian discloses that “[t]he corneal hardening chemicals, such
as various agents and enzymes, used in [Karageozian’s] methods . . ., in
addition to the proper dosages of such agents and enzymes, can be
determined by one of skill in the art through routine experimentation”
(Karageozian 10:35–39; see Ans. 6).
FF 7. Examiner finds:
Karageozian fails to teach a concentration of at least 1 mg/ml of
riboflavin and at least 0.1 mM of iron additive (claim 1), and
further fails to teach a concentration of between 1 mg/ml and 5
mg/ml riboflavin (claim 22), and further fails to teach a
concentration of 0.5 mM of iron additive (claim 24).
(Ans. 3)
ANALYSIS
Based on Karageozian, Examiner concludes that, at the time
Appellant’s invention was made, it would have been prima facie obvious to
utilize a combination of oxidative cross-linking methods, such as an iron
additive (FeSO4) and UV in combination with a riboflavin photosensitizer
(see FF 3–5; see generally Ans. 3, 5). Karageozian further makes obvious
the use of “routine experimentation” to determine the appropriate
concentrations of each reagent (see FF 6; see also Ans. 3, 5). See In re
Aller, 220 F.2d 454, 456 (CCPA 1955) (“[W]here the general conditions of a
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claim are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation.”).
Examiner further reasons that although Karageozian does not
discloses “that FeSO4 accelerates decomposition of hydrogen peroxide
during photo-activation of the riboflavin to increase a concentration of
hydroxyl radicals,” “the composition rendered obvious by Karageozian
would exhibit the claimed property, that is, the FeSO4 would be an iron
additive that enhances the cross-linking generated by the riboflavin by
accelerating decomposition of hydrogen peroxide during photo-activation of
the riboflavin to increase a concentration of hydroxyl radicals” (Ans. 4).
See In re Swinehart, 439 F.2d 210, 212–13 (CCPA 1971) (“[I]t is elementary
that the mere recitation of a newly discovered function or property,
inherently possessed by things in the prior art, does not cause a claim drawn
to those things to distinguish over the prior art.”); see also Atlas Powder Co.
v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999) (“[T]he discovery of a
previously unappreciated property of a prior art composition, or of a
scientific explanation for the prior art's functioning, does not render the old
composition patentably new to the discoverer”).

Claim 1:
Appellant contends that “[b]ecause Karageozian considers FeSO4 to
be an oxidative cross-linking agent on its own, it fails to contemplate the
effect of iron as an enhancing additive on the reactions associated with the
photoactivation of riboflavin as disclosed by the present invention” (Appeal
Br. 10; see also id. at 12–13; Reply Br. 2–3). Appellant further contends
that “[w]ithout the understanding of the effect of iron as an enhancing
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additive on the photoactivation of riboflavin, one of ordinary skill in the art
would not have been able to determine the specific concentrations recited by
claim 1” (Appeal Br. 10; see also Reply Br. 5, 7–8). We are not persuaded.
As discussed above, Karageozian makes obvious the combination of
oxidative cross-linking methods, such as an iron additive (FeSO4) and UV in
combination with a riboflavin photosensitizer (see FF 3–5). Karageozian
further discloses that oxidative cross-linkers, such as FeSO4, act by
producing oxygen free radicals (FF 3). Thus, a person of ordinary skill in
this art would have appreciated that in the combined method made obvious
by Karageozian, FeSO4 will necessarily enhance the cross-linking activity
generated by the riboflavin by accelerating decomposition of hydrogen
peroxide during photo-activation of the riboflavin to increase a concentration
of hydroxyl radicals (see FF 3–5). All that remains, is determining the
optimum concentration of reagents, which Karageozian discloses is routine
by those of ordinary skill in this art (FF 6). Appellant failed to provide an
evidentiary basis on this record to support a conclusion that, in contrast to
Karageozian’s disclosure, those of ordinary skill in this art would not have
arrived at Appellant’s claimed concentration of riboflavin and FeSO4,
through routine experimentation.
Karageozian discloses that oxidative cross-linking methods can be
used in combination and exemplifies the use of UV in combination with the
oxidative crosslinking agent, ascorbic acid (FF 5). Thus, we are not
persuaded by Appellant’s contention that “Karageozian does not suggest
combining two oxidative cross-linking agents” (Appeal Br. 12; see also
Reply Br. 5).
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For the foregoing reasons, we are not persuaded by Appellant’s
contention that Examiner relied on improper hindsight.
We are also not persuaded by Appellant’s contention that
“Karageozian warns that simultaneously using an oxidative cross-linking
agent with another element can be ineffective and produce undesired
results,” and, therefore, “Karageozian’s warning would place any
expectation of success for such combination in doubt” (Reply Br. 5–6). We
recognize that Karageozian discloses that “oxidative cross-linking methods
can be used alone to induce cross-links in a subject, or may be use[d] in
combination with the aldehyde or enzymatic cross-linking methods when
compatible” and exemplifies compatible and non-compatible combinations
(FF 5). Appellant, however, failed to establish an evidentiary basis on this
record to support a conclusion that those of ordinary skill in this art would
have reasonably expected that the combination of oxidative cross-linking
methods comprising FeSO4 and riboflavin to represent a non-compatible
combination. See In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)
(“Obviousness does not require absolute predictability of success . . . all that
is required is a reasonable expectation of success.”).
Karageozian expressly discloses that “[t]he corneal hardening
chemicals, such as various agents and enzymes, used in [Karageozian’s]
methods . . ., in addition to the proper dosages of such agents and enzymes,
can be determined by one of skill in the art through routine experimentation”
(FF 6). Therefore, we are not persuaded by Appellant’s contention that
“[w]hen considered in total, the various concentrations of enzymes and
agents suggested by Karageozian present a very broad range of possibilities
that does not invite routine optimization” (Reply Br. 8).
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Claims 22 and 24:
As discussed above, Karageozian makes obvious the combination of
oxidative cross-linking methods, such as an iron additive (FeSO4) and UV in
combination with a riboflavin photosensitizer (see FF 3–5). Karageozian
further makes obvious the use of “routine experimentation” to determination
the appropriate concentrations of each reagent (see FF 6). Thus, we find no
error in Examiner’s prima facie case of obviousness (cf. Appeal Br. 13
(Appellant contends that “the Office acknowledges that
Karageozian . . . fails to teach a concentration of between 1 mg/ml and 5
mg/ml riboflavin as recited by claim 22, and also fails to teach a
concentration of 0.5 mM of iron additive as recited by claim 24”)).
CONCLUSION
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claims 1, 22, and 24 under 35
U.S.C. § 103(a) as unpatentable over Karageozian is affirmed. Claim 4 is
not separately argued and falls with claim 1.

DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4, 22, 24 103 Karageozian 1, 4, 22, 24
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv).

AFFIRMED