Federal Circuit disposition — 20-1956

NOTE: This disposition is nonprecedential.
United States Court of Appeals
for the Federal Circuit
______________________
IN RE: RAGHAVAN RAJAGOPALAN,
Appellant
______________________
2020-1956
______________________
Appeal from the United States Patent and Trademark
Office, Patent Trial and Appeal Board in No. 14/499,191.
______________________
Decided: May 18, 2021
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ROBERT F RITZ G REEN , Green, Griffith & Borg-Breen
LLP, Chicago, IL, argued for appellant Raghavan Ra-
jagopalan.
ROBERT M C BRIDE , Office of the Solicitor, United States
Patent and Trademark Office, Alexandria, VA, argued for
appellee Andrew Hirshfeld. Also represented by KAKOLI
CAPRIHAN , THOMAS W. K RAUSE , AMY J. N ELSON , FARHEENA
Y ASMEEN RASHEED .
______________________
Before TARANTO , BRYSON , and CHEN , Circuit Judges.
TARANTO , Circuit Judge.
Raghavan Rajagopalan is the named inventor on U.S.
Patent Application No. 14/499,191, entitled “Prevention of
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IN RE: RAJAGOPALAN 2
Illicit Methamphetamine Manufacture from Pseudoephed-
rine Using Food Flavor Excipients.” The Patent and Trade-
mark Office’s Patent Trial and Appeal Board rejected
claims 1–3 and 10 for obviousness based on two prior-art
references and rejected claims 12 and 13 for obviousness
based on those references together with a third. We affirm
the Board.
I
A
The ’191 application describes a composition that “pre-
vent[s] [the] illicit manufacture of methamphetamine”
from pseudoephedrine, a common pharmaceutical ingredi-
ent in over-the-counter allergy medication. J.A. 22. The
application explains the basic two steps in the manufacture
of methamphetamine from such available medications.
The first step is isolation, or extraction, of the
pseudoephedrine from the available medications, which
contain other components. The second step is a chemical
“reduction” reaction, involving reducing agents that donate
electrons to the pseudoephedrine to produce methamphet-
amine. J.A. 23.
The application discloses a pseudoephedrine composi-
tion that impedes the second (reduction) step of that con-
version process. Specifically, it discloses a combination of
pseudoephedrine with a food-flavoring excipient (an addi-
tive), J.A. 23, in which the “excipient may capture the elec-
trons from the reducing agent . . . at a much higher rate
than pseudoephedrine . . . thereby blocking the formation
of methamphetamine,” J.A. 25. These food-flavoring excip-
ients are referred to in the ’191 application as “organoleptic
agents.” J.A. 23.
Independent claim 1 is representative and recites:
1. A pharmaceutically acceptable composition for
deterring illicit manufacture of methamphetamine,
said composition comprising:
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IN RE: RAJAGOPALAN 3
(a) an active pharmaceutical ingredient, wherein
the active pharmaceutical ingredient is ephedrine
or pseudoephedrine; and
(b) an effective amount of an organoleptic excipi-
ent, wherein the organoleptic excipient is selected
from the group consisting of pyrazines, pyrim-
idines, thiazolines, thiazolidines, and thiazoles;
wherein said organoleptic excipient inhibits the
chemical reduction of said active pharmaceutical
ingredient to methamphetamine with reducing
agents; and wherein said reducing agents comprise
alkali metals, zinc, or phosphorous.
J.A. 455; see also Ex parte Rajagopalan, No. 2018-007283,
2020 WL 2126720, at *4 (P.T.A.B. Apr. 29, 2020) (Board
finding claim 1 representative).
B
The examiner and the Board relied on three prior-art
references—Giamalva, Adams, and Takakura—for reject-
ing claims 1–3, 10, 12, and 13 of the ’191 application, in-
voking the first two references for all claims and adding
Takakura for claims 12 and 13.
Giamalva is a published patent application, U.S. Pa-
tent Application Publication No. 2007/0243140, entitled
“Pharmaceutical Composition Containing Sympathomi-
metic Amine Salt and Co-Distillable Additive.” Giamalva
recognizes that over-the-counter medications containing
pseudoephedrine (which is a sympathomimetic amine) may
be used to illicitly manufacture methamphetamine. See
Giamalva ¶¶ 3–4. And Giamalva notes that
[i]t has thus been found desirable to formulate
sympathomimetic amine-containing products in or-
der to render isolation of the sympathomimetic
amine more difficult or otherwise interfere with ef-
forts to produce illegal drugs from common [over-
the-counter] medications, e.g., by altering reactants
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IN RE: RAJAGOPALAN 4
used to convert sympathomimetic amine to meth-
amphetamine.
Id. ¶ 5 (emphases added).
The reference teaches including an additive in the com-
pound to “inhibit[] reduction of the sympathomimetic
amine and/or its derivatives.” Id. ¶ 17. The additive,
Giamalva teaches, should have properties sufficiently sim-
ilar to the pseudoephedrine to prevent separation of the
two when distillation is used to isolate pseudoephedrine be-
fore chemical reduction to methamphetamine. See id. ¶ 43.
The additive may be an odorant, i.e., a compound that “ex-
hibit[s] a characteristic odor, and in some cases, a charac-
teristic flavor as well, particularly during purification
and/or conversion of sympathomimetic amines in illegal
drug synthesis, or in the product of the illegal synthesis it-
self.” Id. ¶ 47. The odor can be unpleasant and, if released
during preparation, “render such preparation distasteful
and/or serve as a recognizable signal to law enforcement.”
Id. ¶ 48. Critically, inclusion of the additive can also “in-
terfere[] with the reduction to methamphetamine by com-
peting with pseudoephedrine for the reducing agent.” Id.
¶ 46.
Giamalva elaborates on the odorant’s role at each of the
two steps involved in the process of manufacturing meth-
amphetamine. At the first step of the methamphetamine-
production process, where the pseudoephedrine is isolated,
“an odorant can deter misuse of commercially available
sympathomimetic amines by imparting a very strong odor
to a material, even after multiple attempts to isolate” it.
Id. ¶ 52. At the second step of the production process,
where the pseudoephedrine is chemically converted into
methamphetamine, “specific odorants” that are “present at
sufficiently high levels” (higher than those required to
simply create the odor) “can inhibit one or more of the re-
actions, e.g., reduction, used to convert the sympathomi-
metic amine to an illegal drug.” Id. (emphasis added).
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IN RE: RAJAGOPALAN 5
Giamalva further explains that a “specific odorant” may be
a “standard flavorant.” Id. And it adds that embodiments
include odorants that “contain nitrogen, e.g., as a volatile
amine.” Id. ¶ 53.
Adams is a journal article: T.B. Adams et al., The
FEMA GRAS Assessment of Pyrazine Derivatives Used as
Flavor Ingredients, 40 Food and Chemical Toxicology 429
(2002). It teaches that pyrazines are nitrogen-containing
compounds that are used as flavoring agents in foods. Id.
at 430. It explains that acetylpyrazine is the most com-
monly used pyrazine flavoring ingredient in the United
States, and it discloses the structure of acetylpyrazine. Id.
at 430, 434.
Takakura is a published patent application, U.S. Pa-
tent Application Publication No. 2012/0052177, entitled
“Flavoring Material.” Takakura teaches that thiazoles are
known organoleptic compounds. See Takakura ¶¶ 26, 30,
45–48. Takakura further teaches that 5-acetyl-2,4-dime-
thylthiazole “impart[s] a particularly favorable livestock
meat stock flavor.” Id. ¶ 48.
C
On September 29, 2017, the examiner issued a final re-
jection of independent claim 1 and dependent claims 2, 3,
10, 12, and 13 of the ’191 application. J.A. 403–28 (Final
Rejection). On April 29, 2020, the Board affirmed the ex-
aminer’s rejections of the claims as obvious in light of
Giamalva combined with Adams or with Adams and
Takakura. Rajagopalan, 2020 WL 2126720, at *4–7. Be-
cause Mr. Rajagopalan has not argued that the Board
adopted new grounds of rejection and denied him a re-
quired opportunity to respond, we limit our description to
the Board’s decision.
The Board set forth the findings of fact that were key
to its decision. It found that “Giamalva teaches the prepa-
ration of a pharmaceutical composition comprising
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IN RE: RAJAGOPALAN 6
pseudoephedrine and a volatile amine odorant.” Id. at *3
(citing Giamalva Abstract). It found, too, that Giamalva
teaches what Giamalva paragraph 5 expressly states—the
desirability of formulating a product containing a sympa-
thomimetic amine such as pseudoephedrine so as to “‘inter-
fere with efforts to produce illegal drugs from common
[over-the-counter] medications, e.g., by altering reactants
used to convert sympathomimetic amine to methampheta-
mine.’” Id. (quoting Giamalva ¶ 5). The Board further
found that Giamalva teaches what Giamalva paragraph 47
states—use of odorants as codistillable additives “‘that in-
terfere with subsequent chemical reactions for converting
sympathomimetic amine compounds to illegal drugs.’” Id.
(quoting Giamalva ¶ 47). The Board added that Adams
teaches aroma-producing pyrazine-based flavoring ingredi-
ents, including acetylpyrazine, which is among the struc-
tures covered by claim 1, as made explicit in Formula I of
the ’191 application’s specification. Id. at *3 (citing Adams
429–30).
The Board also “adopt[ed] the [e]xaminer’s findings as
[its] own, including with regard to the scope and content of,
and motivation to modify or combine, the prior art.” Id. at
*3. One of the examiner’s findings was that “‘[i]t would
have been obvious to one of ordinary skill in the art to com-
bine the teachings of Giamalva . . . with the organoleptic
agents disclosed by Adams’” and that, with that combina-
tion, “‘conversion of any pure pseudoephedrine to metham-
phetamine [would be] hindered with a reasonable
expectation of success.’” Id. at *2 (quoting J.A. 420–21).
That finding, as the examiner made explicit to the Board,
is a finding of “motivation to combine . . . with a reasonable
expectation of success.” J.A. 497 (examiner’s answer).
The Board summarized: “Giamalva teaches a composi-
tion comprising pseudoephedrine and an amine[-]based
odorant which interferes with the conversion of
pseudoephedrine. Adams teaches that pyrazines[,] includ-
ing those having a chemical structure meeting the
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IN RE: RAJAGOPALAN 7
requirements of [F]ormula I in the Specification, exhibit
aromas. We agree with the [e]xaminer that it would have
been obvious to substitute the pyrazines of Adams for the
odorants of Giamalva.” Rajagopalan, 2020 WL 2126720, at
*5 (citations omitted).
The Board considered and rejected Mr. Rajagopalan’s
arguments against the examiner’s obviousness rejections.
Id. at *4–7. The Board first rejected the contention that
the invention claimed in the ’191 application satisfies a
long-felt need—a contention, the Board concluded, that
was only attorney argument, unsupported by any “objec-
tive evidence . . . that there was a long-felt need and that
the present invention satisfied that need.” Id. at *4. The
Board next rejected Mr. Rajagopalan’s argument that the
prior art taught away from the combination that the Board
found the art actually taught. Id. Mr. Rajagopalan also
contended that the cited prior art “does not enable the
claimed composition” because “the compositions taught by
Giamalva do not inhibit the chemical conversion of
pseudoephedrine to methamphetamine,” id. at *5, but the
Board concluded otherwise. The Board reasoned that be-
cause “the composition resulting from the combination of
Giamalva and Adams matches the claimed composition,”
Mr. Rajagopalan had the burden to show that the
Giamalva-Adams combination composition “would not pos-
sess the same property” as the claimed composition, but
Mr. Rajagopalan had “not offered any persuasive evidence”
to make that showing. Id. Similarly, the Board concluded,
Mr. Rajagopalan had “not offered any evidence of unex-
pected results.” Id. at *6.
Mr. Rajagopalan did not make separate arguments as
to the examiner’s rejection of claims 12 and 13 for obvious-
ness based on the combination of Giamalva, Adams, and
Takakura, so the Board likewise affirmed that rejection.
See id. at *4, *7.
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IN RE: RAJAGOPALAN 8
Mr. Rajagopalan timely appealed under 35 U.S.C.
§ 141(a). We have jurisdiction. See 28 U.S.C. § 1295(a)(4).
II
Obviousness is a question of law that we review de
novo, with underlying factual determinations reviewed for
substantial evidence. PersonalWeb Techs., LLC v. Apple,
Inc., 917 F.3d 1376, 1381 (Fed. Cir. 2019). Factual findings
include “the scope and content of the prior art, the differ-
ences between the prior art and the claimed invention, the
level of ordinary skill in the art, the presence or absence of
a motivation to combine or modify with a reasonable expec-
tation of success, and objective indicia of non-obviousness.”
Ariosa Diagnostics v. Verinata Health, Inc., 805 F.3d 1359,
1364 (Fed. Cir. 2015). On substantial-evidence review, we
ask “‘whether a reasonable fact finder could have arrived
at the agency’s decision’ and require[] examination of the
‘record as a whole, taking into account evidence that both
justifies and detracts from an agency’s decision.’” Intelli-
gent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821
F.3d 1359, 1366 (Fed. Cir. 2016) (quoting In re Gartside,
203 F.3d 1305, 1312 (Fed. Cir. 2000)).
In this case, obviousness follows readily from the
Board’s key factual findings if those findings are supported
by substantial evidence. As described above, the Board, in
its expressly stated findings and in its adoption of the ex-
aminer’s findings, found that Giamalva teaches using an
amine-based odorant to interfere with the chemical conver-
sion of pseudoephedrine to methamphetamine; that Adams
discloses particular odorants, namely, pyrazines, which
come within claim 1 of the ’191 application and its specifi-
cation; and that a relevant artisan had a motivation to use
the Adams-disclosed compositions as odorants in the
Giamalva composition with a reasonable expectation of
success of hindering the chemical conversion. Those find-
ings are supported by substantial evidence.
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IN RE: RAJAGOPALAN 9
Some of the support is found in evidence the Board ex-
pressly quoted or cited. See, e.g., Giamalva ¶ 5 (“It has thus
been found desirable to formulate sympathomimetic
amine-containing products [like pseudoephedrine] in order
to render isolation of the sympathomimetic amine more dif-
ficult or otherwise interfere with efforts to produce illegal
drugs from common [over-the-counter] medications . . . .”),
¶ 47 (teaching codistillable additives “that interfere with
subsequent chemical reactions for converting sympathomi-
metic amine compounds to illegal drugs”); see also Adams
429–30. Additional supporting evidence is found on the
face of Giamalva at paragraphs 17, 43, 46, 48, 52, and 53
(all quoted above). Those paragraphs, among other things,
disclose the motive to inhibit the reduction reaction, the
use of odorants to achieve that inhibition, the inclusion of
“standard flavorants” among the “specific odorants” de-
scribed as inhibiting reduction, and the use of nitrogen-con-
taining odorants like volatile amines. See id. Adams, for
its part, adds that pyrazines are commonly used amine (ni-
trogen-containing) odorants and that one type of pyrazine
(acetylpyrazine) is the most commonly used pyrazine fla-
vorant in the United States. Adams 430. The ’191 appli-
cation itself makes clear that acetylpyrazine falls within
the group of amine odorants recited in the claims because
acetylpyrazine has the structure of Formula I set forth in
the application. Compare J.A. 20 (Formula I), with Adams
434 (acetylpyrazine).
This is sufficient evidence of a motivation to use the
Adams pyrazine, a standard flavorant amine, as an odor-
ant in the Giamalva formulation, creating a composition
that, as a prima facie matter, Giamalva indicates would be
reasonably expected to have the claimed inhibition-of-re-
duction property. In this circumstance, “the burden shifts
to the patentee to provide evidence” to rebut the examiner’s
prima facie case—here, specifically, to show that the
claimed inhibition of reduction would not result. See In re
Brandt, 886 F.3d 1171, 1176 (Fed. Cir. 2018); ACCO
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IN RE: RAJAGOPALAN 10
Brands Corp. v. Fellowes, Inc., 813 F.3d 1361, 1365–66
(Fed. Cir. 2016); In re Best, 562 F.2d 1252, 1255 (CCPA
1977). Mr. Rajagopalan has not undermined the Board’s
determination that he did not rebut the prima facie case.
Mr. Rajagopalan argues that the prior-art references
do not teach using the organoleptic excipient in an “effec-
tive amount,” which the ’191 application defines as an
amount that sufficiently inhibits the formation of metham-
phetamine to be “less than about 25%” of the formed com-
position. J.A. 26; Rajagopalan Opening Br. at 11–12, 32.
But the Board adopted the examiner’s findings, which in-
clude a finding that the claimed “effective amount” in the
’191 application is taught in Giamalva’s disclosure of the
most preferred amount of odorant to add. See J.A. 410.
Giamalva supports that finding. It teaches that the ratio
of additive to pseudoephedrine should “preferably” be
“from about 10:1 to about 1:10,” “[m]ore preferably” “from
about 3:1 to about 1:3,” and “[m]ost preferably” “from about
2:1 to about 1:2.” Giamalva ¶ 56. The ’191 application
teaches that if the ratio of the excipient Formula I to
pseudoephedrine is roughly 1:1, which is within the range
of Giamalva’s most preferred ratios, then the amount will
be effective, in that methamphetamine will be no more
than 6% of the product of the reduction process. See J.A.
30–31.
With respect to claims 12 and 13, which depend on
claim 1 but specify particular excipients, Mr. Rajagopalan
made no separate arguments before the Board that the
combination of Giamalva, Adams, and Takakura failed to
establish that the claims are unpatentable for obviousness.
See J.A. 433–62 (Rajagopalan Appeal Brief), 516–27 (Ra-
jagopalan Reply Brief). Such arguments have accordingly
been forfeited. See In re Google Tech. Holdings LLC, 980
F.3d 858, 863 (Fed. Cir. 2020). In any event, we note that
Takakura discloses 5-acetyl-2,4-dimethylthiazole, which,
as Mr. Rajagopalan does not dispute, is a thiazole described
by the structure of Formula III recited in claims 12 and 13.
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IN RE: RAJAGOPALAN 11
Compare J.A. 20 (Formula III), with Takakura ¶¶ 47–48;
see also Rajagopalan Opening Br. at 28–30. Takakura fur-
ther discloses that 5-acetyl-2,4-dimethylthiazole is a fla-
vorant that “impart[s] a particularly favorable livestock
meat stock flavor.” Takakura ¶ 48; see also J.A. 424 (Final
Office Action). Thus, for reasons similar to those stated
above, substantial evidence supports the finding that a rel-
evant artisan would have been motivated to substitute the
flavorant from Takakura for the odorants in Giamalva’s
teachings. See J.A. 424; cf. Rajagopalan, 2020 WL
2126720, at *4–5 (explaining why a relevant artisan would
combine Giamalva and Adams).
III
We have considered Mr. Rajagopalan’s remaining ar-
guments and find them unpersuasive. For the foregoing
reasons, we affirm the Board’s determination that claims
1–3, 10, 12, and 13 of the ’191 application are unpatentable
for obviousness.
The parties shall bear their own costs.
AFFIRMED
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