Johnpro Biotech Inc.

Patent Trials and Appeals Board

Jul 30, 2020

2019006078 (P.T.A.B. Jul. 30, 2020)

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.
15/519,559 04/17/2017 Pei-Ru LIAO AJ7028CN_P2836-1-US 6936
108266 7590 07/30/2020
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EXAMINER
MATOS NEGRON, TAINA DEL MAR
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
07/30/2020 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):
ahuang@pypat.com
bonnielee@pypat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte PEI-RU LIAO and KWAN-HWA CHI
__________

Appeal 2019-006078
Application 15/519,559
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
CHRISTOPHER G. PAULRAJ, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a
method of reducing irinotecan hydrochloride induced gastrointestinal
toxicity. The Examiner rejected the claims as obvious. 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 Johnpro
Biotech Inc. (see App. Br. 3).
2 We have considered and refer to the Specification of Apr. 17, 2017
(“Spec.”); Final Action of Sept. 13, 2018 (“Final Act.”); Appeal Brief of
Nov. 21, 2018 (“Appeal Br.”); and Examiner’s Answer of Feb. 25, 2019
(“Ans.”).
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Statement of the Case
Background
“Irinotecan hydrochloride or camptothecin (CPT)-11 is one of the few
anti-cancer drugs that has been approved for the treatment of colorectal and
other gastrointestinal cancers, small cell and non-small cell lung cancer and
other malignancies” (Spec. ¶ 4). “However, the use of irinotecan is often
limited by its poor oral bioavailability and frequent gastrointestinal (GI)
toxicity, particularly severe diarrhea generally occurred more than 24 hrs
after the administration of irinotecan” (id.). The Specification teaches
“administering 1-50 mg/Kg of silychristin3 to the subject, so as to ameliorate
or alleviate symptoms of CPT-11 induced GI toxicity” (id. ¶ 45).
The Claims
Claims 1–9 are on appeal. Claim 1 is representative and reads as
follows:
1. A method of reducing irinotecan hydrochloride induced
gastrointestinal (GI) toxicity in a subject who underwent an
irinotecan hydrochloride treatment, comprising,
orally administering 1–50 mg/Kg of silychristin to the
subject so as to ameliorate or alleviate symptoms of the
irinotecan hydrochloride induced GI toxicity.

The Issues
A. The Examiner rejected claims 1, 2, and 8 under 35 U.S.C. § 103(a) as
obvious over Pauletti4 (Final Act. 3–5).

3 We spell the term “silychristin” or “silichristin” consistent with how it is
spelled in the source reference.
4 Pauletti et al., US 2007/0036834 A1, published Feb. 15, 2007.
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B. The Examiner rejected claims 3–6 and 9 under 35 U.S.C. § 103(a) as
obvious over Pauletti and Hecht5 (Final Act. 5–8).
C. The Examiner rejected claim 7 under 35 U.S.C. § 103(a) as obvious
over Pauletti and Fuchs6 (Final Act. 8–9).

A. 35 U.S.C. § 103(a) over Pauletti
The Examiner finds Pauletti teaches cancer treatment with “one anti-
cancer agent in combination with a botanical bioavailability modulator,
wherein said anti-cancer drug is selected from the group consisting of
compound listed in tables 8 and 9” and where botanical bioavailability
modulator may comprise silichristin (Final Act. 3). The Examiner finds
Pauletti teaches an overlapping range of silichristin amounts from 0.01 to
750 mg (see id.). The Examiner acknowledges that Pauletti “does not
explicitly teach silychristin ameliorates or alleviates symptoms of CPT 11
induced GI toxicity” or the amounts recited in claims 1 and 2 (Final Act. 4).
The Examiner finds the claims obvious because Pauletti teaches the
combination of an anti-cancer drug and a botanical “enhances the
therapeutic benefit to the patient” (Final Act. 4). The Examiner finds “the
amounts disclosed by Pauletti et al. overlap with the instantly claimed dose
range and the amount of botanical bioavailability modulator are used to
enhance intraepithelial and systemic delivery” (id. at 5).
The issue with respect to this rejection is: Does a preponderance of

5 Hecht, J., Gastrointestinal Toxicity of Irinotecan, 12 Oncology
72–8 (1998)
6 Fuchs et al., Irinotecan in the treatment of colorectal cancer, 32:
Cancer Treatment Reviews 491–503 (2006).
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the evidence of record support the Examiner’s conclusion that Pauletti
suggests the limitations of claims 1, 2, and 8?
Findings of Fact
1. Pauletti teaches
a method for augmenting drug delivery of anti-viral and/or anti-
cancer drugs into epithelial cells and/or into the systemic
circulation by delivering such drugs to a subject in need thereof
vaginally or buccally in an especially formulated composition
increasing their therapeutic efficacy by providing means for
increasing the drug solubility and permeability.
(Pauletti ¶ 20).
2. Pauletti teaches, as to the anti-cancer agents, that “Table 8
summarizes information of currently FDA-approved anti-cancer agents that
are clinically used in the treatment of various cancers taking advantage of
various modes of action” and Table 8 specifically recites irinotecan (Pauletti
¶ 87).
3. Pauletti teaches that the table 8 anti-cancer agents having
“bioavailability problems may be advantageously administered by the
vaginal or buccal mucosal compositions and devices using a method of the
invention” (Pauletti ¶ 90).
4. Pauletti teaches, as to the botanicals component:
To enhance intraepithelial or systemic delivery of anti-cancer
and anti-viral agents following vaginal/buccal administration,
functional activity of membrane efflux systems or drug-
metabolizing cytochrome P450 enzymes may be inhibited by
inclusion of from about 0.001 to about 10% by weight of non-
toxic, purified or unpurified extracted natural products
originating from plant, microorganism, or animal sources.
(Pauletti ¶ 65).
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5. Pauletti teaches that “preferred purified constituents isolated
from the botanical bioavailability modulator sources that are incorporated
into vaginal or buccal compositions between about 0.01 and about 750 mg
are . . . silichristin” (Pauletti ¶ 66).
6. Pauletti teaches the “dose of each agent is chosen to achieve
pharmacologically effective drug concentrations. The specific transmucosal
formulations have been found to permit the high bioavailability of a number
of pharmacologic agents” (Pauletti ¶ 69).
7. Pauletti teaches
By advantageously combining all three above described
features in the transmucosal compositions and/or devices for
vaginal or buccal delivery of anti-viral or anticancer drugs, this
invention achieves greater concentrations of these drugs in the
desired target tissue or the blood circulation system. Such
higher systemic concentration of the drug ultimately enhances
the therapeutic benefit to the patient at a decreased risk for
undesired gastrointestinal toxic side effects.
(Pauletti ¶ 73).
8. The Examiner finds “70 mg of silychristin for a 70kg [person]
would have yield 1 mg/kg, thus the dose range disclosed by Pauletti et al.
overlaps from 1 mg/kg to 10.71 mg/kg” (Final Act. 5).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
Prima facie obviousness
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We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Ans. 3–5; FF 1–8) and agree that Pauletti
renders the claims obvious. We address Appellant’s arguments below.
Appellant contends
the anti-cancer composition of Pauletti et al. comprises at least
one anti-cancer agent, and a non-ionizable glycol ether or a
botanical bioavailability modulator, in which the anti-cancer
drugs is selected from the compounds respectively listed in
Tables 8 and 9, which include more than 50 compounds.
Pauletti et al. teach more than 30 preferred non-ionizable glycol
ethers as listed in Table 1 and paragraph [0149], and more than
100 preferred botanical bioavailability modulators as listed in
claim 5 and paragraphs [0065]-[0066], [0151]-[0152].
Accordingly, more than 6,500 ((50 compounds x 30 non-
ionizable glycol ethers) + (50 compounds x 100 modulators)) of
possible combination may be derived from Pauletti et al.

(Appeal Br. 9–10). Appellant states “[s]ince Pauletti et al. fail to teach or
suggest the specified sub-combination of anti-cancer agent, and a non-
ionizable glycol ether or a botanical bioavailability modulator, one skilled
artisan would NOT be motivated to arrive at the present combination” (id. at
10).
Appellant asserts, relying on MPEP § 2144.08, that “[s]ince Pauletti et
al. fail to disclose a small recognizable class of candidate members (i.e.,
anti-cancer drugs, ionizable glycol ethers and botanical bioavailability
modulators), the ‘size of the genus’ factor tends toward a finding of non-
obviousness” (Appeal Br. 11).
We find this argument unpersuasive because “picking and choosing
may be entirely proper in the making of a 103, obviousness rejection.” In re
Arkley, 455 F.2d 586, 587 (CCPA 1972). Pauletti teaches, and actually
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claims, picking and choosing an anti-cancer agent such as irinotecan and a
botanical such as silichristin (FF 2, 5; claims 1, 3, 6 of Pauletti).
As to the argument regarding thousands of possible combinations, the
court in Merck found that prior art disclosing 1200 “effective combinations
does not render any particular formulation less obvious.” Merck & Co., Inc.
v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). Similarly, in
Corkill, an obviousness rejection was affirmed in light of prior art teachings
that “hydrated zeolites will work” in detergent formulations, even though
“the inventors selected the zeolites of the claims from among ‘thousands’ of
compounds.” In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985). We
therefore find that the number of other possible combinations encompassed
by Pauletti does not negate the obviousness of the particular formulation of
irinotecan and silichristin.
As to the genus/species argument relying upon MPEP § 2144.08 and
In re Baird, 16 F.3d 380, 382 (Fed. Cir. 1994), we note that section of the
MPEP and Baird do not refer to situations involving a specific disclosure in
a list, but rather a generic chemical formula. Perricone distinguishes this
situation, noting a “specific disclosure, even in a list, makes this case
different from cases involving disclosure of a broad genus without reference
to the potentially anticipating species.” Perricone v. Medicis Pharm. Corp.,
432 F.3d 1368, 1377 (Fed. Cir. 2005). Appellant’s claim 1 “recites a
combination of elements that were all known in the prior art, and all that was
required to obtain that combination was to substitute one well-known . . .
agent for another.” Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683
F.3d 1356, 1364 (Fed. Cir. 2012). We therefore find the Examiner’s
selection of irinotecan and silichristin from two different lists in the same
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reference is distinguishable from the genus/species situation argued by
Appellant.
We note Appellant provides no evidence that the selection of a
combination of irinotecan and silichristin results in any unexpected result or
that other botanicals would not have operated with irinotecan in a way that
“enhances the therapeutic benefit to the patient at a decreased risk for
undesired gastrointestinal toxic side effects” as taught by Pauletti (FF 7) and
also recited in claim 1.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that Pauletti suggests the limitations of claims 1, 2, and 8.
B. and C. 35 U.S.C. § 103(a) over Pauletti and Hecht or Fuchs
Appellant does not separately argue either of these obviousness
rejection, and instead relies upon its arguments concerning Pauletti (see
App. Br. 12; “neither Hecht et al. nor Fuchs et al. cured the deficiency of
Pauletti et al.”). Having found no deficiency in Pauletti, we are not
persuaded by Appellant’s contention to the contrary regarding the
obviousness of claims 3–7 and 9 over Pauletti and either Hecht or Fuchs.
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 8 103 Pauletti 1, 2, 8
3–6, 9 103 Pauletti, Hecht 3–6, 9
7 103 Pauletti, Fuchs 7
Overall
Outcome
1–9
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED