Escape Therapeutics, Inc.

Patent Trials and Appeals Board

Dec 30, 2021

2021002116 (P.T.A.B. Dec. 30, 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.
15/941,753 03/30/2018 Basil M. Hantash ELIXP004 5045
51111 7590 12/30/2021
AKA CHAN LLP
Melvin Chan
900 LAFAYETTE STREET
SUITE 710
SANTA CLARA, CA 95050
EXAMINER
D' AMBROSIO, THEA
ART UNIT PAPER NUMBER
1654
NOTIFICATION DATE DELIVERY MODE
12/30/2021 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):
PTO-INBOX@AKACHANLAW.COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BASIL M. HANTASH and ANAN ABU UBEID
Appeal 2021-002116
Application 15/941,753
Technology Center 1600
BEFORE DONALD E. ADAMS, ERIC B. GRIMES, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL

Appeal 2021-002116
Application 15/941,753
2
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 20, 21, and 28–34.2 We have
jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
CLAIMED SUBJECT MATTER
“[S]irtuins are a class of proteins that possesses mainly NAD+-
dependent lysine deacetylase activity. Sirtuins are broadly recognized as
critical regulators of multiple metabolic pathways, sensors of energy and
redox status in cells, and modulators of oxidative stress.” Spec. ¶ 35. Sirtuins
are believed to play a role in repressing premature skin aging. Id. ¶ 34. The
invention is direct to the use of sirtuin modulation to improve skin
appearance. Id. ¶¶ 36–47. Claim 20, reproduced below, is illustrative of the
claimed subject matter:
20. A method of activating expression of a sirtuin gene in a skin
cell, the method comprising administering to a subject in need
thereof a composition comprising an effective amount of one or
more peptides, wherein the one or more peptides consist of SEQ
ID NO: 9, and the composition further comprises oxyresveratrol.

1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R.
§ 1.42(a). Appellant identifies the real party in interest as Escape
Therapeutics, Inc. Appeal Br. 2.
2 The Final Action mailed April 22, 2020, listed claims 11–15 and 18–27 as
pending in the application. Final Act. 1. Appellant, in an Amendment After
Final filed September 4, 2020, amended claims 20 and 21, cancelled claims
1–19 and 22–27 and entered new claims 28–34. The Examiner entered the
amendment in an Advisory Action mailed September 11, 2020.
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REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Hantash US 8,193,154 B2 June 5, 2012
Lavker and Sun, Epidermal stem cells: Properties, markers, and location,
97 Proc. Nat. Acad. Sci. USA 13473 (2000)
Blander et al., SIRT1 Promotes Differentiation of Normal Human
Keratinocytes, 129 J. Invest. Dermatol. 41 (2009)
Liu et al., A tale of terminal differentiation: IKKα, the master keratinocyte
regulator, 8 Cell Cycle 527 (2009)
Becatti et al., SIRT1 regulates MAPK pathways in vitiligo skin: insight
into the molecular pathways of cell survival, 18 J. Cell. Mol. Med. 514
(2014)
Xu et al., Advances in the Study of Oxyresveratrol, 10 Int. J. Pharmacol.
44 (2014)
European Nucleotide Archive (“ENA”), Coding ABB72675.1, https:/
/www.ebi.ac.uk/ena/data/view/ ABB72675
REJECTIONS
The Examiner has rejected the claims as follows:
Claims 20, 21, and 32–34 have been rejected under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, and ENA.
Claims 20, 28, and 29 have been rejected under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, ENA, and
Lavker.
Claims 20, 30, and 31 have been rejected under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, ENA, and Liu.
OPINION
Obviousness Based on Hantash Combined with Blander, Becatti, Xu and
ENA

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The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the subject matter of
claims 20, 21, and 32–34 would have been obvious to one of ordinary skill
in the art at the time the invention was made over Hantash combined with
Blander, Becatti, Xu and ENA.
The Examiner finds Hantash teaches administering a topical
preparation containing the peptide of SEQ ID NO: 9.3 Ans. 4. The Examiner
finds Hantash teaches a method of treating the skin using the topical
preparation including “freckles reduction, reduction of yellow mass-tone on
Asian skins and inhibition of skin[] dyschromia related to the aging process
as well as a reduction in redness linked to venous disorders and a reduction
in UV-induced pigmentation.” Id.
The Examiner find Becatti teaches “a subject in need of skin
whitening and/or inhibiting pigmentation of the skin associated with aging in
a skin cell would encompass a subject in need of activation of SIRT1.” Id. at
5.
The Examiner finds Blander teaches “that a skin cell, i.e., a
keratinocyte, necessarily contains a sirtuin gene, i.e., SIRT1, and evidence
that SIRT1 overexpression correlates to keratinocyte differentiation.” Id. at
5–6.
The Examiner finds:
[A]lthough Hantash does not expressly teach activating a
sirtuin gene (i.e., SIRT1) in a skin cell in a subject in need
thereof, given that Hantash teaches administering a topical

3 “Hantash teaches administering a topical preparation to the skin containing
a peptide essentially identical to [its] SEQ ID NOs: 1 or 2,” where Hantash’s
SEQ ID NO: 2 is identical with “instantly claimed SEQ ID NO: 9.” Ans. 4,
7.
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preparation or composition comprising instantly claimed SEQ
ID NO: 9 to a subject in order to whiten skin, or inhibit skin[]
dyschromia related to the aging process as well as reduce UV-
induced pigmentation where the topical preparation or
composition is applied to the surface of the keratinous tissue
thereby necessarily containing keratinocytes, it would
necessarily follow that the keratinocytes in the keratinous tissue
contain SIRT1 as taught by Blander et al. Similarly, it would
necessarily follow that a subject in need of SIRT1 activation in
a skin cell is a subject in need of whitening of the skin or in
need of inhibiting . . . skin[] dyschromia related to the aging
process as well as reduce UV-induced pigmentation because
SIRT1 activation protects perilesional vitiligo as taught by
Becatti et al. As such, the activation of SIRT1 expression in the
keratinocyte skin cells in order to whiten skin and/or inhibit
skin[]dyschromia related to the aging process as well as reduce
UV-induced pigmentation would necessarily occur. In other
words, the instantly claimed method is directed to the biological
mechanism by which instant SEQ ID NO: 9 whitens skin and/or
inhibits skin[] dyschromia related to the aging process as well
as reduce UV-induced pigmentation.

Id. at 6.
With respect to the inclusion of oxyresveratrol, the Examiner finds
Hantash teaches that the composition may contain other ingredients useful in
skin whitening. Id. at 8. The Examiner finds Blander teaches resveratrol is a
known SIRT1 activator. Id. The Examiner finds Xu teaches oxyresveratrol is
a natural derivative of revesatrol and exhibits a skin-whitening effect. Id.
The Examiner finds Xu teaches that oxyresveratrol increases levels of
SIRT1. Id.
The Examiner concludes:
it would have been prima facie obvious to one of ordinary skill
in the art at the time the invention was made to modify the
teachings of Hantash and administer a composition comprising
an effective amount of SEQ ID NO: 9 and an additional skin
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whitening agent such as oxyresveratrol in order to
lighten/whiten skin and/or inhibit skin[] dyschromia related to
the aging process as well as reduce UV-induced pigmentation
by activating expression of SIRT1 in a skin keratinocyte. One
of ordinary skill in the art at the time the invention was made
would have been motivated to do so because administering a
composition comprising SEQ ID NO: 9 in combination with a
skin whitening agent was known to lighten/whiten skin and/or
inhibit skin[] dyschromia related to the aging process as well as
reduce UV-induced pigmentation by activating expression of
SIRT1 in a skin keratinocyte as taught by Hantash and as
evidenced by Becatti et al. and Blander et al.; and because
administering oxyresveratrol, a natural derivative of
resveratrol[,] to the skin was known to function as a whitening
agent and known to exhibit neuroprotective effects by
activating SIRT1 expression as taught by Xu et al.

Id. at 9. The Examiner goes on to find:
Additionally and/or alternatively, “[i]t is prima facie
obvious to combine two compositions each of which is taught
by the prior art to be useful for the same purpose, in order to
form a third composition to be used for the very same purpose
.... [T]he idea of combining them flows logically from their
having been individually taught in the prior art.” In re
Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA
1980). . . . Thus, since the references teach agents that are
effective in lightening/whitening skin and/or inhibiting skin[]
dyschromia related to the aging process as well as reducing
UV-induced pigmentation, it would have been obvious to
combine the two agents with the expectation that such a
combination would be effective in lightening/whitening skin
and/or inhibiting skin[] dyschromia related to the aging process
as well as reducing UV-induced pigmentation. Thus, combining
them flows logically from their having been individually taught
in the prior art by constituting the combination of prior art
elements according to known methods to yield predictable
results pursuant under KSR.

Id. at 10.
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Appellant contends that Hantash does not teach or suggest the use of
oxyresveratrol. Appeal Br. 5. Appellant also contends that Hantash relates to
the inhibition of an enzyme and not activation of the sirtuin gene. Id.
Appellant contends that Hantash is concerned with skin appearance
whereas Becatti and Blander focus on skin health. Id. at 6.
Appellant contends that neither Blander nor Becatti teach the use of
oxyresveratrol. Id. Appellant contends that while Becatti and Blander teach
the use of resveratrol, resveratrol is different than oxyresveratrol. Id.
Appellant contends that Xu shows there are significant differences between
resveratrol and oxyresveratrol including differences in bioavailability,
stability, cytotoxicity and radical scavenging ability. Id. at 6–7.
Appellant contends that Xu only discusses oxyresveratrol’s ability to
increase SIRT1 levels in connection with neuroprotective effects and that
that teaching is speculative. Id. at 8.
We adopt the Examiner’s findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established a
prima facie showing that the subject matter of the claims would have been
obvious over Hantash combined with Blander, Becatti, Xu and ENA to a
person of ordinary skill in the art at the time the invention was made.
Appellant has not produced evidence showing, or persuasively argued, that
the Examiner’s determinations on obviousness are incorrect. Only those
arguments made by Appellant in the Briefs have been considered in this
Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R.
§ 41.37(c)(1)(iv) (2015). We have identified claim 20 as representative;
therefore, all claims fall with claim 20. We address Appellant’s arguments
below.
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Appellant contends Hantash does not disclose the use of oxyrevesatrol
nor does it discuss the activation of a sirtuin gene. Appeal Br. 5. We are not
persuaded by this argument.
Appellant’s argument is an attack on the teaching of the individual
reference, not on the combined teachings of the references. “Non-
obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references. . . . [The reference] must be read, not in isolation, but for what it
fairly teaches in combination with the prior art as a whole.” In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
Hantash teaches the topical application of a peptide matching SEQ ID
NO. 9 and teaches that other skin whitening agents may be included in the
composition. Hantash, col. 5, ll. 42–52; col. 16, ll. 44–61. Xu teaches that
oxyrevesatrol is a skin whitening agent and increases SIRT1 levels. Xu, 4–5.
With respect to SIRT1 activation, we agree with the Examiner that:
Hantash teaches administering a topical composition
comprising an effective amount of SEQ ID NO: 9 in
combination with a skin whitening agent to a subject in order to
whiten skin, or inhibit skin[] dyschromia related to the aging
process as well as reduce UV-induced pigmentation where the
topical preparation or composition is applied to the surface of
the keratinous tissue thereby necessarily containing
keratinocytes. Becatti teaches that a subject in need of skin
whitening and/or inhibiting pigmentation of the skin associated
with aging in a skin cell would encompass a subject in need of
activation of SIRT1. Blander teaches that keratinocytes
necessarily contain a sirtuin gene, i.e., SIRT1. Thus, the
combined teachings of Hantash, Becatti, and Blander suggest
the instantly claimed patient population, i.e., a subject in need
of activating SIRT1 expression in a skin cell where the
activation of SIRT1 expression in the keratinocyte skin cells in
order to whiten skin and/or inhibit skin[] dyschromia related to
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the aging process as well as reduce UV-induced pigmentation
would necessarily occur.
Therefore, the instantly claimed method is directed to a
biological mechanism by which instant SEQ ID NO: 9 whitens
skin and/or inhibits skin[] dyschromia related to the aging
process as well as reduce UV-induced pigmentation. The
claiming of a new use, new function or unknown property
which is necessarily present in the prior art does not necessarily
make the claim patentable.

Ans. 18.
Appellant contends that Hantash is directed to skin appearance
whereas Blander and Becatti relate to skin health. Appeal Br. 5–6. We are
not persuaded by this argument.
Hantash teaches that the disclosed compositions can be used to treat
UV-induced pigmentation. Hantash col. 19, ll. 34–40. Becatti teaches “[t]wo
key mediators of skin damage, UV radiation and H2O2, down-regulate
SIRT1 expression in cultured skin keratinocytes.” Becatti, 515. We agree
with the Examiner that this demonstrates that Hantash does relate to skin
health, not just skin appearance. See Ans. 19–20.
Appellant contends that Blander and Becatti do not teach the use of
oxyresveratrol but rather resveratrol which is a different compound. Appeal
Br. 6.
Appellant is again attacking the teachings of the individual references
and not the combination of references. The Examiner cited Blander and
Becatti for their teaching of the role of SIRT1 in skin cells and its
relationship to skin whitening or inhibiting pigmentation. Ans. 21. Xu is
cited for teaching the role of oxyresveratrol in skin whitening and as a
SIRT1 activator. Id.
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Appellant contends that Xu teaches that oxyresveratrol has significant
differences in chemical and biological activity when compared to
resveratrol. Appeal Br. 7–8. Again we find this argument unpersuasive.
The fact that oxyresveratrol may be inferior to resveratrol in some
aspect does not render the use of the compound non-obvious. “[J]ust because
better alternatives exist in the prior art does not mean that an inferior
combination is inapt for obviousness purposes.” In re Mouttet, 686 F.3d
1322, 1334 (Fed. Cir. 2012).
Moreover, as the Examiner points out, Xu teaches how to address the
alleged shortcomings of oxyresveratrol. Ans. 22–25.
Finally, Appellant contends that Xu only discusses oxyresveratrol’s
effect on SIRT1 with respect to neurological disorders and not skin care.
Appeal Br. 8. Appellant contends that this would not lead one skilled in the
art to substitute oxyresveratrol for resveratrol as taught by Blander and
Becatti. Id.
We are not persuaded by this argument. While we agree with
Appellant that Xu discusses oxyresveratrol’s effect on SIRT1 expression in a
neurological context, as the Examiner points out, Xu teaches that
“oxyresveratrol has an obvious whitening effect in guinea pigs and humans.”
Ans. 25. The Examiner goes on to point out:
oxyresveratrol had better performance in inhibiting UVB
irradiation-induced melanogenesis in brown guinea pig skin
compared with Mulberroside A and showed stronger tyrosinase
inhibitory activity compared to dioscin and Mulberroside A
(See Xu reference, pg. 5, 1st paragraph). Thus, Xu teaches that
oxyresveratrol is a good natural tyrosinase inhibitor with a great
potential and that can be used in cosmetics as a skin whitening
agent.

Id.
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Given that Hantash teaches “the tyrosinase inhibitor peptides and
formulation of the present invention can also be optionally mixed with each
other and with other skin whitening agents for purposes of treatment, i.e.,
skin lightening or whitening,” Hantash col. 16, ll. 44–48, we agree with the
Examiner that one skilled in the art would have been:
motivated with a reasonable expectation of success to utilize
oxyresveratrol as an additional skin whitening agent in
combination with SEQ ID NO: 9 in order to treat a subject
suffering from UV-induced pigmentation. Therefore, the fact
that Xu does not expressly teach that oxyresveratrol increases
SIRT1 expression in an epidermal context does not preclude a
finding of obviousness.

Id.; see KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007)(“In
determining whether the subject matter of a patent claim is obvious, neither
the particular motivation nor the avowed purpose of the patentee controls.
What matters is the objective reach of the claim. If the claim extends to what
is obvious, it is invalid under § 103.”).
Based on the foregoing we conclude that a preponderance of the
evidence supports the Examiner’s conclusion that the subject matter of
claims 20, 21, and 32–34 would have been obvious to one of ordinary skill
in the art at the time the invention was made over Hantash combined with
Blander, Becatti, Xu and ENA.

Obviousness Based on Hantash Combined with Blander, Becatti, Xu, ENA,
and Lavker

Appellant’s sole argument with respect to this rejection is that ENA
and Lavker do not “provide the missing link with oxyresveratrol” discussed
in response to the first rejection. Appeal Br. 9. As discussed above, we do
Appeal 2021-002116
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not find the teachings of the references to be deficient with respect to the use
of oxyresveratrol. Therefore, we affirm this rejection.

Obviousness Based on Hantash Combined with Blander, Becatti, Xu, ENA,
and Liu

Appellant’s sole argument with respect to this rejection is that Liu
does not “provide the missing link with oxyresveratrol” discussed in
response to the first rejection. Appeal Br. 9–10. As discussed above, we do
not find the teachings of the references to be deficient with respect to the use
of oxyresveratrol. Therefore, we affirm this rejection.
CONCLUSION
The Examiner’s rejections are affirmed.
More specifically,
The rejection of claims 20, 21, and 32–34 under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, and ENA is
affirmed.
The rejection of claims 20, 28, and 29 under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, ENA, and
Lavker is affirmed.
The rejection of claims 20, 30, and 31 under 35 U.S.C. § 103 as
unpatentable over Hantash in view of Blander, Becatti, Xu, ENA, and Liu is
affirmed.

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
20, 21, 32–
34
103 Hantash, Blander,
Becatti, Xu, ENA
20, 21, 32–
34

20, 28, 29 103 Hantash, Blander,
Becatti, Xu, ENA,
Lavker
20, 28, 29
20, 30, 31 103 Hantash, Blander,
Becatti, Xu, ENA,
Liu
20, 30, 31
Overall
Outcome
20, 21, 28–
34

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). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED