Ex Parte Shchepinov

Patent Trial and Appeal Board

Mar 22, 2018

12922449 (P.T.A.B. Mar. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/922,449 12/07/2010
20995 7590 03/26/2018
KNOBBE MARTENS OLSON & BEAR LLP
2040 MAIN STREET
FOURTEENTH FLOOR
IRVINE, CA 92614
FIRST NAMED INVENTOR
Mikhail S. Shchepinov
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
RETOP.002NP 1461
EXAMINER
CARTER, KENDRA D
ART UNIT PAPER NUMBER
1627
NOTIFICATION DATE DELIVERY MODE
03/26/2018 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):
j ayna.cartee@knobbe.com
efiling@knobbe.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MIKHAIL S. SHCHEPINOV 1
Appeal2016-004912
Application 12/922,449
Technology Center 1600
Before JOHN G. NEW, RICHARD J. SMITH, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for treating breast cancer. A hearing was held on March 8, 2018. We have
jurisdiction under 35 U.S.C. § 6(b). 2
We reverse.
1 According to Appellant, the real party in interest is Retrotope Inc. (Appeal
Br. 4.)
2 As discussed below, our jurisdiction does not extend to the Examiner's
withdrawal of claim 70.
Appeal 2016-004912
Application 12/922,449
STATEMENT OF THE CASE
Claims on Appeal
Claims 47-51, 53, 54, 59, and 61---69 are on appeal. 3 (Claims
Appendix, Br. 29-31.) Claim 47 is illustrative and reads as follows:
4 7. A method, comprising:
selecting a human patient in need of treatment for a
condition associated with degradation of lysine-containing
moieties, wherein the condition is breast cancer or fibrosis;
repeatedly delivering to the patient an effective lysine-
oxidation-inhibiting material consisting essentially of a
compound of Formula (I), Formula (II), or Formula (III)
Formula (I)
wherein D is deuterium;
o po~9J H,~~~ I l,.OH
D DD MHz
FORMULA III
wherein a carbon in Formula (I), (II), or (III) is optionally
carbon-13; and
wherein the carbon-13, deuterium or both are enriched at
least 20% more individually or collectively in comparison to
naturally occurring carbon-13, deuterium or both at the same
positions in the compound; and
thereby treating the condition by affecting an alteration of
the isotopic composition of lysine-containing moieties in the
3 Appellant elected the compound of Formula II and breast cancer. (See
Final Action dated April 1, 2015, at 2.) Claims 52, 55-58, 60, and 70 are
withdrawn because they are drawn to a non-elected species. (Id.)
2
Appeal 2016-004912
Application 12/922,449
body of the patient to effectively reduce the extent of degradation
of lysine-containing moieties in vivo in the patient.
Examiner's Rejection
Claims 47-51, 53, 54, 59, and 61---69 stand rejected under 35 U.S.C.
§ 103 (a) as unpatentable over Roomi, 4 Oba, 5 Raap, 6 Ando,7 Foster, 8 Gant, 9
Tonn, 10 Haskins, 11 Wolen, 12 Browne, 13 Baillie, 14 & Gouyette. 15 (Ans. 2-
4 Roomi et al., In Vitro and In Vivo Antitumorigenic Activity of a Mixture of
Lysine, Praline, Ascorbic Acid, and Green Tea Extract on Human Breast
Cancer Lines MDA-MB-231 and MCF-7, 22 Medical Oncology, 129-38
(2005) ("Roomi").
5 Oba et al., A Simple Route to L-[5,5,6,6-D4] Lysine Starting/ram L-
pyroglutamic acid, 12 Jpn. J. Deuterium Sci., 1-5 (2006).
66 Raap et al., Enantioselective synthesis of isotopically labelled a-amino
acids. Preparation of (c:-13 C)-L-a-aminoadipic acid and five isotopomers of
L-lysine with 13C, 15N and 2H in the J- and c:-positions, Reel. Trav. Chim.
Pays-Bas 109, 277-86 (1990).
7 Ando et al., US 6,603,008 Bl, issued Aug. 5, 2003.
8 Foster, US 6,221,335 Bl, issued April 24, 2001.
9 Gant et al., US 2007/0082929 Al, pub. April 12, 2007.
10 Tonn et al., Simultaneous Analysis of Diphenhydramine and a Stable
Isotope Analog (2 H10) Diphenhydramine Using Capillary Gas
Chromatography with Mass Selective Detection in Biological Fluids from
Chronically Instrumented Pregnant Ewes, 22 Biological Mass Spectrometry,
633--42 (1993).
11 Haskins, The Application of Stable Isotopes in Biomedical Research, 9
Biological Mass Spectrometry, 269-77 (1982).
12 Wolen, The Application of Stable Isotopes to Studies of Drug
Bioavailability and Bioequivalence, 26 J. Clin. Pharmacol., 419-24 (1986).
13 Browne, Stable Isotope Techniques in Early Drug Development: An
Economic Evaluation, 38 J. Clin. Pharmacol., 213-20 (1998).
14 Baillie, The Use of Stable Isotopes in Pharmacological Research, 33
Pharmacological Reviews, 81-132 (1981).
15 Gouyett, Synthesis of Deuterium-labelled Elliptinium and its Use in
Metabolic Studies, 15 Biomedical and Environmental Mass Spectrometry,
243--47 (1988).
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Application 12/922,449
12.)
DISCUSSION
Issue
Whether a preponderance of evidence of record supports the
Examiner's rejection under 35 U.S.C. § 103(a).
Analysis
Claim 4 7, the only independent claim on appeal, is directed to a
method for treating breast cancer that includes the delivery to the patient of
"an effective lysine-oxidation-inhibiting material consisting essentially of' a
deuterated lysine compound. (Appeal Br. 29.) Use of the phrase "consisting
essentially of' limits the delivery of an effective lysine-oxidation-inhibiting
material to the delivery of the claimed deuterated lysine compound "and
those [ingredients] that do not materially affect the basic and novel
characteristic(s)" of the claimed invention. In re Herz, 537 F.2d 549, 551-
52 (CCPA 1976).
In rejecting claim 4 7, the Examiner acknowledges that Roomi does
not teach the deuterated lysine compound (Formula II), or that the patient is
human, or "treating the condition by affecting an alteration of the isotopic
composition of lysine-containing moieties in the body of the patient to
effectively reduce the extent of degradation of lysine-containing moieties in
vivo in the patient." (Ans. 3.) With regard to the phrase "consisting
essentially of," the Examiner states that Roomi "teaches the treatment of
breast cancer with a nutriment containing lysine, proline, arginine, ascorbic
acid and epigallocatechin gallate." (Id. at 4.) The Examiner further points
to two sentences in Roomi that read "[t]hese nutrients [lysine, ascorbic acid,
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Application 12/922,449
proline, and epigallocatechin gallate (EGCG)] manifested markedly higher
anti-proliferative and anti-invasive [effects] when used synergistically than
individually. Our results also showed that the nutrient mixture suppressed
the growth of these tumors, without any adverse effects, in nude mice."
(Roomi 130, left col., last two sentences of 3rd par. (cited at Ans. 4).) The
Examiner concludes from these two sentences that "the individual nutrients
are also effective in treating breast cancer." (Ans. 4.) The Examiner relies
on the additional cited references to conclude that it is obvious to make
deuterated analogs of known drugs (e.g., lysine) "to obtain better
pharmaceutical properties and to obtain valuable information about how the
un-deuterated ... drug or closely related drugs act in the body." (Id.)
Appellant contests the rejection by arguing, in part, that the Examiner
"incorrectly characterized Roomi as teaching using lysine alone to treat
cancer," and that "[n]othing in Roomi or any of the other cited references
would motivate a person of ordinary skill in the art to select lysine from the
nutrient mixture (let alone isotopically modify it as presently claimed)."
(See Appeal Br. 11-17.)
We find that Appellant has the better position. A determination of
obviousness includes an objective analysis of the "scope and content of the
prior art." See KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007)
(quoting Graham v. John Deere Co. of Kansas City, 383 U.S. 1, 17-18
(1966)). According to the Examiner, in the two sentence quoted from
Roomi above, "the key word is 'higher."' (Ans. 15.) That is, according to
the Examiner, "Roomi clearly teaches that the combination and the
individual[] administration of the components treat breast cancer. Therefore,
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Application 12/922,449
although the combination of the four components are better, they all work
individually." (Id.)
We do not find the Examiner's position to be a proper objective
analysis of Roomi as a whole. As Appellant argues, "Roomi emphasizes the
synergistic anticancer effect of the mixture [ascorbic acid, pro line, lysine,
and green tea extract (EGCG)] and focuses on the use of the whole mixture
instead of any specific component for inhibiting the growth of breast cancer
cell lines." (Appeal Br. 11.) Moreover, Appellant argues that "[t]he
statement that ' [ t ]hese nutrients manifested markedly higher anti-
proliferative and anti-invasive [effects] when used synergistically than
individually' does not mean that the individual nutrients necessarily had
activity." (Id. at 12.) Furthermore, according to Appellant, "there is no
experimental or even anecdotal evidence in [Roomi] that lysine alone is
effective to treat breast cancer." (Id.)
We find Appellant's analysis of Roomi persuasive. While a reference
may be read for all that it teaches, In re Mouttet, 686 F.3d 1322, 1331 (Fed.
Cir. 2012), we do not view the scope and content of Roomi as teaching that
lysine alone is effective to treat breast cancer. Notably, Roomi specifically
states that "[a]scorbic acid has been reported to have cytotoxic and
antimetastatic actions on malignant cell lines," and that "EGCG is a potent
anticancer agent." (Roomi 138, left col.) No similar reference to lysine
alone as an anticancer agent appears in Roomi. Moreover, the two sentences
from Roomi, relied on by the Examiner and quoted above, refer to "a
previous study" by Netke et al. 16 of lysine, ascorbic acid, proline, and
16 Netke et al., A Specific Combination of Ascorbic Acid, Lysine, Praline and
Epigallocatechin Gallate Inhibits Proliferation and Extracellular Matrix
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Application 12/922,449
EGCG. (Roomi 130, left col., sentence prior to the two quoted sentences.)
Although not cited in the rejection on appeal, Netke is of record and
indicates that it investigated the inhibitory effects of a combination of
ascorbic acid, proline, and lysine used separately (i.e., as a combination
without EGCG) and together with various concentrations ofEGCG, finding
that the combination of ascorbic acid, proline, and lysine "exerts a potent
antiproliferative and antimetastatic effect on several cancer cell lines," but
that there is "a synergy in the anticancer activities of the combination of
[ascorbic acid, proline, and lysine] and EGCG." (Netke 7, 11.) 17 Thus,
reading the quoted sentences relied upon by the Examiner in context, and
Roomi as a whole, we are persuaded by Appellant that "Roomi does not
teach or suggest that lysine alone would be effective in treating cancer."
(Appeal Br. 11.)
Based on the forgoing analysis, we are also persuaded by Appellant
that a person of ordinary skill in the art would not have been motivated to
select lysine and modify it with deuterium, and use such deuterated lysine
compound in the method as claimed. The Examiner's stated rationale for
selecting lysine from the mixture taught by Roomi is "because it is known to
treat cancer." (Ans. 15.) On this record, we do not find that lysine alone is
known to treat cancer, and thereby find no motivation for selecting lysine
and modifying it with deuterium.
Accordingly, for the reasons of record and as set forth above, we
reverse the rejection of claim 47 under 35 U.S.C. § 103(a). Claims 48-51,
Invasion of Various Human Cancer Cell Lines, Res. Commun. Pharmacol.
Toxicol. Emerging Drugs 2, 37-50 (2003) ("Netke").
17 Page citations are to Netke pages 1-12 of record.
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Application 12/922,449
53, 54, 59, and 61---69 depend, directly or indirectly, from claim 47, and
therefore stand with claim 4 7.
Claim 70
Appellant contends that "the Examiner erroneously marked Claim 70
as withdrawn," and that "Claim 70 was not drawn to a non-elected species."
(Appeal Br. 25.) The Examiner disagrees with Appellant. (Ans. 21-22.)
Claim 70 is not before us on appeal, and the issue of whether claim 70
was erroneously withdrawn by the Examiner is a matter for petition to the
Commissioner rather than appeal. See In re Hengehold, 440 F.2d 1395,
1398-1404(CCPA1971).
Conclusion of Law
A preponderance of evidence of record fails to support the Examiner's
rejection of claims 47-51, 53, 54, 59, and 61---69 under 35 U.S.C. § 103(a).
SUMMARY
We reverse the rejection of claims 47-51, 53, 54, 59, and 61---69 on
appeal.
REVERSED
8