ABOCA S.P.A. SOCIET¿ AGRICOLA

Patent Trials and Appeals Board

Feb 19, 2020

14396202 - (D) (P.T.A.B. Feb. 19, 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.
14/396,202 10/22/2014 Valentino Mercati 4286.0060001 3225
26111 7590 02/19/2020
STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C.
1100 NEW YORK AVENUE, N.W.
WASHINGTON, DC 20005
EXAMINER
FIEBIG, RUSSELL G
ART UNIT PAPER NUMBER
1655
NOTIFICATION DATE DELIVERY MODE
02/19/2020 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):
e-office@sternekessler.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte VALENTINO MERCATI and ANNA MAIDECCHI
__________

Appeal 2019-003063
Application 14/396,2021
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, CHRISTOPHER G. PAULRAJ, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
pharmaceutical composition, which have been rejected under 35 U.S.C.
§ 101 as being directed to patent-ineligible subject matter and under 35
U.S.C. § 103 as being obvious. Oral argument was heard on January 27,
2020. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse the rejection under 35 U.S.C. § 101 but affirm the
rejection under 35 U.S.C. §103.

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 ABOCA
S.P.A. SOCIETÀ AGRICOLA. (Appeal Br. 3.)
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STATEMENT OF THE CASE
One of the secondary negative effects of diabetes is chronic foot
ulcers. (Spec. 1.) These ulcers are “often infected by bacteria and other
opportunistic infections.” (Id.) Moreover, “chronic wounds (ulcers) are
characterized by a very high recurrence rate.” (Id. at 2.) Appellant’s
invention is a composition for topical application for treating or preventing
the onset or aggravation of diabetic foot ulcers. (Id.) According to
Appellant’s Specification, the claimed combination of ingredients results in
a composition that exhibits a “barrier effect enabling to preserve the integrity
of the skin hydrolipid film.” (Id. at 3.)
Claims 1, 3–11, 13, and 15–24 are on appeal. Claim 1 is
representative and reads as follows:
1. A pharmaceutical composition for topical application, the
composition comprising
beeswax at a concentration of 0.1%–3% by weight,
an extract of Hypericum at a concentration of 3%–10%
by weight,
an extract of red grape vine at a concentration of 0.05%-
4% by weight,
an extract of horse chestnut at a concentration of 0.01%-
10% by weight,
an extract of Centella at a concentration of 0.01%-2% by
weight,
an extract of butcher’s broom at a concentration of
0.01%-5% by weight, and
an extract of Aloe at a concentration of 0.01%-3% by
weight.
(Appeal Br. 28; indentation and paragraphing added.)

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The prior art relied upon by the Examiner is:
Name Reference Date
Gupta US 2011/0124573 A1 May 26, 2011
El Mogy US 6,846,499 B2 Jan. 25, 2005
Shufa Li et al., Prospective randomized controlled study of a Chinese
herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic
foot ulcers: A preliminary report, 133 J Ethnopharmacology, 543–550,
2011
Kavitha K. Reddy et al., Common complementary and alternative
therapies with potential use in dermatologic surgery: Risks and benefits, J
Am. Acad. Dermatol., e1–e92, 2011

The following grounds of rejection by the Examiner are before us on
review:
Claims 1, 3–11, 13, 15, and 22 under 35 U.S.C. § 101 as being
directed to patent-ineligible subject matter.3
Claims 1, 3–11, 13, and 15–24 under 35 U.S.C. § 103 as being
unpatentable over Li, Gupta, Reddy, and El Mogy.4
DISCUSSION
I. Patent Eligible Subject Matter
The Dispute
The Examiner finds that the claimed composition is a combination of
nature-based components and thus “is a group of judicial exceptions unless
they have markedly different characteristics as compared to their closest

2 Although this article was published in the print journal in 2013 (volume 68
number 4 (e127–e135)), the Examiner relied on the on-line publication, as
do we.
3 See Ans. 12.
4 Id.
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naturally-occurring counterpart (beeswax in a bee hive, or the compounds
that make up each extract found in the corresponding non-extracted plant).”
(Ans. 13; see also Final Action 2–4.) The Examiner finds that “there is no
evidence of record to indicate that the claimed product is markedly different,
structurally, chemically, functionally, than its naturally occurring
counterpart.” (Final Action 4.) The Examiner states that “[a] change in the
ratio or amount of extract does not transform the claims into an exemption of
the ‘judicial exception’ because amounts/ratios/percentages do not set forth a
‘markedly different’ structure as compared to the naturally-occurring
product” and “[c]ombining naturally-derived ingredients does not amount to
a claim which surmounts the judicial exception (Funk Brothers Seed Co. v.
Kalo Inoculant Co. – 333 U.S. 127 (1948)).” (Id.) Thus, the Examiner
concludes that “the claimed product is not eligible subject matter” under 35
U.S.C. § 101. (Id.)
Appellant argues that the claims are not directed to patent-ineligible
subject matter because the “[c]omponents of the claimed composition such
as beeswax and the plant extracts do not exist in nature . . . their existence
requires human manipulation to provide them in a form suitable to be
combined as a pharmaceutical composition.” (Appeal Br. 12–13.)
Appellant alternatively argues that the “claimed invention amounts to
significantly more than a judicial exception.” (Id. at 13.) Appellant
explains, in this regard, that the claimed invention requires a combination of
components to be present together at specific concentrations and that the
composition “possesses a therapeutic activity – treating a diabetic patient
with a foot ulcer – that is not possessed by the individual active
ingredient[s].” (Id. at 13.) Appellant contends that the “examples [in the
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Specification] demonstrate the improved activities of the claimed products
as compared to the crude extract.” (Id. at 14.)
There is no question that Appellant’s claimed composition includes
products derived from nature. (See Appeal Br. 13.) The question is whether
Appellant’s claim is directed to a judicial exception.
Analysis
35 U.S.C. § 101 defines patent-eligible subject matter. An invention
is patent-eligible if it claims a “new and useful process, machine,
manufacture, or composition of matter.” 35 U.S.C. § 101. The Supreme
Court, however, has carved out exceptions to what would otherwise appear
to be within the literal scope of § 101, e.g., “[l]aws of nature [and] natural
phenomena” such as products of nature that are considered “buildin[g]
block[s] of human ingenuity.” Alice Corp. v. CLS Bank Int’l, 573 U.S. 208,
216 (2014) (citing Ass’n for Molecular Pathology v. Myriad, 569 U.S. 576
(2013) and Mayo Collaborative Servs. v. Prometheus Labs, Inc., 566 U.S.
66, 89 (2012)). “The ‘manifestations of laws of nature’ are ‘part of the
storehouse of knowledge,’ ‘free to all men and reserved exclusively to
none.’” Manual of Patent Examiner Procedure (“MPEP”) § 2106.04 (b)
(quoting Funk, 33 U.S. at 130). “When a law of nature or natural
phenomenon is claimed as a physical product, the courts have often referred
to the exception as a ‘product of nature.’” MPEP § 2106.04(b)(II).
The Supreme Court has established a two-step framework for
“distinguishing patents that claim laws of nature, natural phenomena, and
abstract ideas from those that claim patent-eligible applications of those
concepts.” Alice, 573 U.S. at 216. “First, we determine whether the claims
at issue are directed to” a patent-ineligible concept. Id. If so, “we consider
the elements of each claim both individually and ‘as an ordered
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combination’ to determine whether the additional elements ‘transform the
nature of the claim’ into a patent-eligible application.” Id. (quoting Mayo,
566 U.S. at 78–79).
The United States Patent and Trademark Office (“PTO”) issued the
2019 Revised Patent Subject Matter Eligibility Guidance (“Guidance”),
indicating how the PTO would analyze patent eligibility under the Supreme
Court’s two-step framework. 84 Fed. Reg. 50–57 (January 7, 2019).
Under the Guidance, in determining what concept the claim is
“directed to,” we first look to whether the claim recites any judicial
exceptions, including laws of nature, natural phenomena, and/or abstract
ideas. (Guidance, 84 Fed. Reg. at 53–54.) (“Step 2A, Prong One”). If it
does, then we look to whether the claim recites additional elements that
integrate the recited judicial exception into a practical application. (Id. at
54–55 (citing MPEP § 2106.05(a)–(c), (e)–(h)).) (“Step 2A, Prong Two”).
Only if a claim (1) recites a judicial exception and (2) does not
integrate that exception into a practical application, i.e., it is found to be
“directed to” a judicial exception, do we then look to whether the claim
contains an “‘inventive concept’ sufficient to ‘transform’” the claimed
judicial exception into a patent-eligible application of the judicial exception.
Guidance, 84 Fed. Reg. at 56; see also Alice, 573 U.S. at 221 (quoting Mayo,
566 U.S. at 82).
Claims alleged to be patent-ineligible because they recite products of
nature are properly analyzed under the framework of the Guidance. See
Guidance, 84 Fed. Reg. at 54 n.20 (“This notice does not change the type of
claim limitations that are considered to recite a law of nature or natural
phenomenon. For more information about laws of nature and natural
phenomena, including products of nature, see MPEP 2106.04(b) and (c).”).
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Applying the Guidance, we disagree with the Examiner’s conclusion
that the claims are directed to patent-ineligible subject matter. We address
independent claim 1 as the representative claim for our analysis. There is no
dispute that claim 1 recites a “composition” and, thus, falls squarely within
the “composition of matter” statutory category. Consequently, we proceed
to the next steps of the analysis.
STEP 2A, Prong One:
In Step 2A, Prong One of the Guidance, we evaluate whether claim 1
recites a judicial exception, i.e., whether it sets forth or describes a product
of nature in accordance with the guidance in MPEP 2106.04 (b) and (c).
Guidance, 84 Fed. Reg. at 54; October 2019 Patent Eligibility Guidance
Update (“October 2019 Guidance Update”), available at
https://www.uspto.gov/PatentEligibility.
a. Product of Nature Analysis
There is no question that Appellant’s claimed composition includes
products derived from nature. (See Appeal Br. 13 (acknowledging that the
claimed beeswax and plant extracts “are derived from natural products”);
Final Action 2.) Indeed, the claim requires seven such nature-based
components.
Appellant argues that the existence of each of the claimed components
“requires human manipulation to provide them in a form suitable to be
combined as a pharmaceutical composition,” and, thus, each component as
used in the claimed composition “do[es] not exist in nature.” (Appeal
Br. 12–13.) That argument fails to distinguish the claimed components from
nature-based products. As the Supreme Court noted in Myriad, claiming a
natural product that is merely separated from elements found in its natural
environment, where the structure of the natural product is not otherwise
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altered, does not support a conclusion that the isolated product is patent
eligible. Myriad, 596 U.S. at 593–95 (contrasting cDNA, which is an exons-
only molecule that is not naturally occurring, from isolated DNA segments
because the isolated DNA segments do not contain altered genetic
information compared to the gene from which it was isolated,
notwithstanding that the isolated DNA segment had to be obtained from the
gene by breaking chemical bonds); see also In re BRCA-1 & BRCA2-Based
Hereditary Cancer Test Patent Litig., 774 F.3d 755, 761 (Fed. Cir. 2014)
(“A DNA structure with a function similar to that found in nature can only
be patent eligible as a composition of matter if it has a unique structure,
different from anything found in nature. . . Primers do not have such a
different structure and are patent ineligible”).
Nevertheless, the mere fact that “the components of the claimed
composition are all nature-based” (Ans. 13) does not end the inquiry as to
whether the claimed composition recites a judicial exception. As noted
above, claim 1 recites a combination of nature-based products. Such
combinations, even when they combine nature-based products that are not
grouped together in nature, have been held patent ineligible as a judicial
exception. Funk Bros., 333 U.S. at 130 (claims to bacterial mixtures held
ineligible as “manifestations of laws of nature” and “phenomena of nature”).
In Funk Bros., the Court explained that leguminous plants were
known to be able to fix nitrogen from the air in the plant with the aid of
Rhizobium bacteria. Id. It was known that no single species of the
Rhizobium bacteria was effective for all leguminous plants, single species
inoculants were sold in the prior art, and farmers would generally purchase
different inoculants to use in combination. Id. at 129. Although some
mixed culture products were known, they had “proved generally
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unsatisfactory because the different species of the Rhizobia bacteria
produced an inhibitory effect on each other when mixed in a common base.”
Id. The claimed composition was a mixture of strains of different species of
Rhizobium bacteria that were found not to be inhibitive of one another. Id.
at 130. The Supreme Court, however, found that the quality of non-
inhibition of these bacteria was a discovery of a “hitherto unknown
phenomenon of nature,” and although “[t]he aggregation of select strains of
the several species into one product is an application of that newly-
discovered natural principle,” each of the species that was packaged together
still only “infects the same group of leguminous plants which it always
infected,” “[e]ach species has the same effect it always had,” and there is no
change in the species of bacteria. Id. at 130–31. The Court further
explained that “[t]heir use in combination does not improve in any way their
natural functioning. They serve the ends nature originally provided and act
quite independently of any effort of the patentee.” Id. at 131.
With the foregoing in mind, we must consider whether the non-
naturally occurring combination of nature-based products recited by claim 1
has any characteristics that are markedly different from the naturally-
occurring products individually. See MPEP § 2106.04(c)(II)(A).
b. Markedly Different Characteristics Analysis
Appellant argues that the claimed composition that includes the seven
compounds derived from natural products at specific concentration ranges
“is significantly improved in functional properties as compared to . . . each
ingredient in the composition.” (Appeal Br. 13.) According to Appellant,
the examples in the Specification demonstrate the claimed composition
treats a diabetic patient with a foot ulcer, which is a functional activity not
possessed by the individual ingredients. (Id.)
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In particular, Appellant contends that “the claimed composition
clearly possesses therapeutic properties that are markedly different from the
individual beeswax and plant extracts because the latter are not effective in
treating diabetic foot ulcers or preventing their aggravation” (id. at 14) as
demonstrated by the examples in the Specification. (See also Reply Br. 3.)
According to Appellant, the “examples demonstrate the improved activities
of the claimed products as compared to the crude extract.” (Appeal Br. at
14.)
Appellant’s Specification provides a comparison of 1) a composition
that includes all seven of the claimed ingredients (as well as including other
ingredients) against 2) a composition that contains extract of Hypericum,
jojoba oil, and foliar gel of Aloe vera. (Spec. 10–11 (comparing Example 1
described at Spec. 8–9 to a commercially available composition that includes
two of the seven claimed ingredients (extract of Hypericum and Aloe)).)
The reported results are an observed improvement in average condition
value of the foot in both cases, but composition 1 that included the seven
claimed ingredients plus additional ingredients had a more improved result.
(Id. at 11.) Such a comparison does not establish that the claimed
composition possesses a therapeutic activity “that is not possessed by the
individual active ingredient[s]” because a) the observed results show that at
least two of the ingredients result in similar therapeutic activity just not at
the same therapeutic benefit, and b) the comparison was not between the
therapeutic benefit of the claimed composition and that of an individual
component of the claimed composition.
Appellant’s Specification also provides a “comparative barrier effect
test” in which a composition that includes the seven claimed ingredients (as
well as a number of other ingredients) is compared to seven other
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compositions, each such composition being the same as the tested claimed
composition but excluding one of the claimed components. (Spec. 12–17,
see especially Tables 1 and 2.) According to the Specification the in vitro
test demonstrates, “[d]epending on the insulating abilities of the sample, a
decrease in the migration of the inflammatory agent from the top chamber
and, accordingly, a lesser stimulation of the cells to cytokines production.”
(Spec. 12.) According to the Specification, the “barrier effect enables to
preserve the integrity of the cutaneous hydrolipid film by exerting a
protective action, and enables also the other components of the composition
to remain adhered for a longer time into contact on the irritated skin,
preventing a quick washing off thereof . . . thereby enabling the composition
to carry on its effect for a longer time.” (Id. at 11–12.)
According to the Specification, the test
design exploits the principle due to which cells subjected to
contact with an inflammatory agent produce and secrete pro-
inflammatory mediators (cytokines) into the extracellular
environment in an amount correlated to the degree of
inflammation caused. The greater the amount of inflammatory
agent that reaches the cells, the greater the amount of cytokines
released.
(Id. at 12.) Based on the experimentation, Appellant’s Specification states
that
[t]he obtained data, reported in Table 2 . . . show how all
samples tested . . . prove to have more or less markedly a
barrier effect . . . [but] that the barrier effect by far most
effective (IL-6 cytokine release inhibition equal to 82%) is
observed with the composition of the invention, compared to all
other formulations [tested].
(Id. at 17.) Table 2 is provided below
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(Id. at 17.) We do not understand the in vitro test described above to
establish a therapeutic activity of the claimed invention in treating diabetic
ulcers. The activity measured is cytokine release inhibition, not treating
diabetic ulcers. Although there may be a correlation to treating a diabetic
ulcer, treatment itself is not demonstrated. Moreover, we do not find this
example, like the prior example discussed, to be a demonstration of
“improved activities of the claimed products as compared to the crude
extract” (Appeal Br. 14) as there is simply no comparison against any crude
extract.
On the other hand, as Appellant’s Specification states: “the barrier
effect enables to preserve the integrity of the cutaneous hydrolipid film by
exerting a protective action.” (Spec. 11–12.) Thus, we conclude that this
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latter example is relevant to a determination of whether the claimed
invention has an improved functional property in the markedly different
characteristic analysis.
Although the Examiner is correct that this was not a comparison of the
therapeutic benefit of the claimed composition to that of an individual
component of the claimed composition (Ans. 13), the collective data
demonstrates that the combination provides a barrier effect that is different
from a simple additive effect of each individual component. That is, if there
were a simple additive effect of the cytokine release inhibition, the sum of
each of the calculated difference between the measured inhibition of the
compositions lacking a single ingredient from the measured inhibition of the
composition including all claimed ingredients should add up to the observed
release inhibition for the composition including all claimed ingredients. It
does not.
Following the Attorney position (Appeal Br. 24–25) that “Inhibition
of IL-6 Release Due to Drug” can be calculated by subtracting the % IL-6
cytokine release inhibition in Table 2 of each composition A1–A7 from 82%
(the % IL-6 cytokine release inhibition for Composition A), one obtains the
following data.
Test Composition Inhibition of IL-6 Release Due to
Drug that is “lacking”
Composition A1 lacking organic
beeswax
82-46 = 36%
Composition A2 lacking Hypericum
oil
82-36 = 46%
Composition A3 lacking Red grape
vine LE
82-64 = 18%
Composition A4 lacking Horse
chestnut LE
82-33 = 49%
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Composition A5 lacking Centella
LE
82-65 = 19%
Composition A6 lacking butcher’s
broom LE
82-57 = 25%
Composition A7 lacking Aloe dry
extract
82-20 = 62%

We agree with Appellant that there is a “large disparity in activity
when individual components are removed from the [claimed] composition.”
(Reply Br. 3.) Furthermore, the evidence in this case indicates that there is
some interaction between the components when they are present together
such that it cannot be said that “[e]ach species has the same effect it always
had.” Funk Bros., 333 U.S. at 130–31. For example, a composition that
included beeswax and Red grape vine LE but not Centella LE exhibited 65%
IL-6 release, whereas a composition that included beeswax and Centella LE
but not Red grape vine LE exhibited 64% IL-6 release inhibition. (Spec. 17,
Table 2.) On the other hand, a composition that included Red grape vine
LE, Centella LE, and beeswax but not Horse chestnut LE exhibited 33% IL-
6 release inhibition, whereas a composition that included Red grape vine LE,
Centella LE, beeswax and Horse chestnut LE but not Hypericum oil
exhibited 36% IL-6 release inhibition. (Id.) Unlike the case in Funk
Brothers, we cannot conclude from the evidence that each component has
the “same effect” when put together in the combination that it always had
individually. Funk Bros., 333 U.S. at 131.
The Examiner discounts the evidence altogether because “it is not
evidence of any new characteristic or any unexpectedly higher activity,” and
“[f]or synergy to be demonstrated, the activity of the combined composition
must be higher than the additive effects of the individual ingredients,” and
“[t]his requires a careful analysis of the activity at different dosages for the
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individual ingredients compared to the activity at different dosages of the
combined composition.” (Ans. 13.) As will be discussed in the obviousness
section below, we agree with the Examiner that there is insufficient evidence
that the combination results in a combined effect that is synergistic, i.e.,
greater than the sum of the separate effects of the individual ingredients.
However, evidence establishing that components in combination do not have
the same effect as they do individually is sufficient to establish patent-
eligibility of a combination of nature-based products. See Funk Bros., 333
U.S. at 131.
Although Appellant only exemplifies IL-6 release inhibition for a
specific dosage of each ingredient, Appellant’s Specification indicates that
the composition of the present invention “exerts . . . a barrier effect” (Spec.
3), which can be measured as “percent of IL-6 release reduction” (id. at 13),
and provides for ranges of each of the claimed ingredients to be included in
such a composition (id. at 4–6, 8–9). Those ranges are recited in claim 1.
Furthermore, the Examiner has not provided a reason or evidentiary basis to
doubt that the same barrier effect would be achieved throughout the claimed
ranges of the ingredients used in combination. Cf. In re Wright, 999 F.2d
1557, 1561–62 (Fed. Cir. 1993) (explaining that the Office bears the initial
burden of providing a reasonable explanation why it believes the scope of a
claim is not adequately enabled); In re Brana, 51 F.3d 1560, 1566 (Fed. Cir.
1995) (explaining that the Office bears the initial burden of presenting
evidence showing that one of ordinary skill in the art would reasonably
doubt the asserted utility).
Appellant’s disclosure is similar to that found sufficient to support
that the mixture of nature-based products in the dosage unit of claim 4 of
Example 44 of the October 2019 Guidance Update had a changed functional
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property compared to the components individually. See October 2019
Guidance Update, Appendix 1 at 11, 16–17 available at
https://www.uspto.gov/PatentEligibility. Claim 4 of Example 44, like claim
1 at issue here, includes a range of ingredients. In particular, claim 4 of
Example 44 recites: a dosage unit of denveric acid where “the protamine
that is mixed with the denveric acid in a container [is] in an amount of 0.75
to 1.5 mg of protamine to every mg of denveric acid.” Id. at 11. In the
Example, it is noted that the disclosure provides “that a mixture of denveric
acid with protamine . . . in a particular amount (0.75 mg to 1.5 mg of
protamine per every mg of denveric acid) changes the glycemic control
characteristics to be long-acting.” Id. It is explained in the October 2019
Guidance Update that such disclosure (1) supports an interpretation of the
claim, under the broadest reasonable interpretation, that the claimed mixture
has the disclosed “particular glycemic control characteristics,” id. at 16, and
(2) supports the finding that the “mixture claimed” “when combined in the
claimed ratio” “has a different effect (the changed glycemic control
characteristics) than its natural counterparts” and the conclusion that the
claimed mixture “has markedly different characteristics” than its natural
counterparts, id. at 17.
Although claim 1, at issue here, does not explicitly recite the cytokine
release inhibition characteristic of the claimed composition, we determine
such a characteristic is an appropriate analytic to determine a marked
difference so long as the characteristic is possessed by the composition
under the broadest reasonable interpretation of the claim. See id. (“It is not
necessary for the claim to explicitly recite a characteristic that is markedly
different, so long as the broadest reasonable interpretation of the claim
reflects that the claimed product possesses at least one appropriate
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characteristic that is markedly different.”) As we noted above, one of
ordinary skill in the art would recognize that the barrier effect is an inherent
property of the claimed mixture in light of the Specification’s disclosure that
such an effect is possessed by a composition having the combination of
recited ingredients within the ranges claimed.
Moreover, we conclude that there is sufficient evidence that
establishes the claimed composition including the mixture of beeswax,
extract of Hypericum, extract of red grape vine, extract of horse chestnut,
extract of Centella, extract of butcher’s broom, and extract of Aloe, each
present in particular concentrations by weight, has a different effect in
combination than the effect of each individual natural component.5 This
combined effect, regardless of whether it is synergistic, changes the overall
characteristic of the claimed composition such that we find that claim 1 does
not recite a product of nature, and therefore is not directed to a judicial
exception. Because we reach our conclusion under Step 2A, Prong One of
the Guidance, we do not proceed to the other steps under the Guidance.

5 Appellant also argues that it was not known that each of the individual
ingredients was useful to treat diabetic foot ulcers. (See, e.g., Reply Br. 3.)
We do not find this argument persuasive to establish the claimed
composition possesses a markedly different characteristic. To the extent the
barrier effect can be interpreted to be useful to treat diabetic foot ulcers
because it inhibits IL-6 cytokine release, Appellant’s evidence appears to
establish that each claimed component provides some barrier effect in the
cytokine release inhibition test. As the Supreme Court explained in Funk
Brothers, “we cannot so hold [that the combination is invention] without
allowing a patent to issue on one of the ancient secrets of nature now
disclosed.” Funk Bros., 333 U.S. at 132. These components each of which
has a barrier effect “act [to effect that barrier effect] quite independently of
any effort of the patentee.” Id.
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Dependent claims 3–11, 13, and 22 recite additional components
and/or further specify the components of the composition of claim 1.
Dependent claim 15 recites a medical device according to the composition of
claim 1. Neither Appellant nor the Examiner has presented separate
arguments for these claims. We observe, however, that insofar as these
other claims include the composition of claim 1, the analysis and reasoning
set forth above would also apply to these claims.
In view of the foregoing, we reverse the Examiner’s rejection of
claims 1, 3–11, 13, 15, and 22 under 35 U.S.C. § 101 as being directed to
patent-ineligible subject matter.
II. Obviousness
We address the Examiner’s rejection as it relates to claim 1 because
claims 3–11, 13, and 15–24 have not been argued separately, and therefore
fall with claim 1 for the reasons set forth below. 37 C.F.R. § 41.37(c)(1)(iv).
The Examiner finds that Li discloses a topical composition for treating
diabetic foot ulcers that includes various extracts and beeswax as a base.
(Final Action 5.) The Examiner finds that Gupta teaches the use of aloesin
extracted from aloe can be used to treat disorders of the skin related to
diabetes, and that the extract can be used in combination with antioxidants
such as hypericum and micro-circulation improvement ingredients such as
extracts from horse chestnut, butcher’s broom, Centella, or red vine. (Id. at
6.) The Examiner finds that Reddy teaches “the beneficial effect” of many
of the aforementioned ingredients of Gupta on wound healing. The
Examiner concludes that it would have been obvious to one of ordinary skill
in the art “to combine the recited extracts as taught by Gupta and Reddy [for
their known benefits in wound healing] . . . into a composition comprising
beeswax as taught by Li . . . for wound healing” “since each is well known
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in the art for the same purpose and . . . it would have been logical to
combine then for that same purpose. “ (Final Action 6.)6
The Examiner recognizes that “[t]he cited references do not
specifically teach using the extract in the amounts claimed . . .,” but explains
that “[t]he amount of a specific ingredient in a composition is clearly a
result-effective parameter that a person of ordinary skill in the art would
routinely optimize.” (Id. at 7–8.)
Appellant first argues that the Examiner’s rejection is in error because
the Examiner did not provide evidence that the concentrations of each
ingredient present in the composition are result-effective variables. (Appeal
Br. 19.)7 Appellant further argues, in the alternative, that the invention

6 The Examiner relies on El Mogy to address the inclusion of jojoba oil in
the claimed composition, which is a component not required by claim 1.
Appellant does not argue the dependent claims separately (see, e.g., Appeal
Br. 26), and thus, we need not address this reference.
7 In the Reply Brief, Appellant argues for the first time that the Examiner’s
combination to arrive at the claimed composition “picks and chooses from
the prior art teaching” where the prior art does not teach or suggest
combining the components at the claimed concentrations and is thus based
on an improper obvious to try analysis. (Reply Br. 4.) In the Appeal Brief,
obvious to try was only raised in conjunction with the concentrations of each
of the components. (Appeal Br. 19.) “[T]he reply brief [is not] an
opportunity to make arguments that could have been made in the principal
brief on appeal to rebut the Examiner’s rejections, but were not.” Ex parte
Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative). As stated in Ex
parte Borden, consideration by the Board of new arguments presented for
the first time in the Reply Brief that could have been presented earlier would
“vitiate the force of the requirement in Board Rule 37(c)(1)(vii) that ‘[a]ny
arguments or authorities not included in the brief . . . will be refused
consideration by the Board, unless good cause is shown’.” Id. Appellant
has not demonstrated any specific Examiner findings presented for the first
time in the Answer that necessitated this specific new argument in rebuttal in
the Reply Brief. Nor do we find any substantial differences in the
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“provides unexpected results.” (Id.; see also id. at 24–25 (based on the data
in Table 2, “[t]herefore, the combination of active ingredients in Appellant’s
claimed composition is clearly synergistic”).) We do not find Appellant’s
arguments persuasive.
As to Appellant’s first argument, it is true that a change to a parameter
may be patentable if the parameter was not recognized as “result-effective.”
In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012) (citing
In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). However, the situation
where a “parameter optimized was not recognized to be a result-effective
variable” is only a “narrow” exception to the general principle of In re Aller,
220 F.2d 454 (CCPA 1955) that “the discovery of an optimum value of a
variable in a known process is normally obvious.” E.I. DuPont de Nemours
& Co. v. Synvina C.V., 904 F.3d 996, 1009 (Fed. Cir. 2018) (citing In re
Applied Materials, 692 F.3d at 1297).
It cannot be disputed that the concentration of an active ingredient in a
therapeutic composition would be recognized by one of ordinary skill in the
art as a result effective variable, even where that ingredient is a naturally

Examiner’s initial findings and the Examiner’s findings stated in the Answer
that would warrant the new arguments presented in the Reply Brief for the
first time. In any event, we agree with the Examiner (Final Action 4–7) that
the prior art teaches the claimed ingredients are useful for wound healing
and that it would have been prima facie obvious to combine them to achieve
the combined benefits with a reasonable expectation of success. “It 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 which is 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 (CCPA 1980).

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derived product. (See, e.g., Reddy e4 (“Zinc 15 to 30 mg daily is used to aid
in wound healing.”); e5 (“Grape seed extract is used for strengthening
vessels and preventing bruising. Common dosing is 50 to 300 mg daily
perioperatively.”); e6 (“Recommended dosing [of propolis] is 1 to 3 mL
topical tincture daily until healed.”).) (“A recognition in the prior art that a
property is affected by the variable is sufficient to find the variable result-
effective.” Applied Materials, 692 F.3d 1297. Thus, we find that one of
ordinary skill in the art would have understood that each ingredient taught to
be useful for wound healing (Reddy e6 (Table V)) would have an
effectiveness that is dependent upon its concentration, and we agree with the
Examiner that it would have been obvious to optimize the amount to achieve
the desired effectiveness. “[W]here the general conditions of a claim are
disclosed in the prior art, it is not inventive to discover the optimum or
workable ranges by routine experimentation.” Aller, 220 F.2d at 45.
“[B]y definition, any superior property must be unexpected to be
considered evidence of non-obviousness.” Pfizer, Inc. v. Apotex, Inc., 480
F.3d 1348, 1371 (Fed. Cir. 2007). In arguing that the claimed invention
possesses unexpected results, Appellant asserts that Example 2 at pages 10–
11 of the Specification demonstrates that those diabetic patients treated with
the claimed invention had an improvement three times greater than the
control group treated with a commercial composition that included extracts
of Hypericum and Aloe, two of the seven claimed ingredients. (Appeal Br.
21.) In Appellant’s example, cutaneous zones of the foot having ulcers were
observed and assigned a number depending on assessment of dryness and
fissures. (Spec. 10–11.) Neither Appellant’s description in the Specification
nor Appellant’s argument related to this example states that the observed
result after application with the claimed composition was unexpected. Nor
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do we find the evidence to be demonstrative of an unexpected result given
that the prior art teaches ingredients such as extract of vitis vinifera (grape
vine) decreases wound closure time and Centella increases re-epithelization
rate and wound contracture rate (Reddy Table V). In other words, one of
ordinary skill in the art would have expected the addition of these
ingredients to result in an improved condition of the skin as compared to use
of a composition that did not include them.
Regarding the second experiment (Example 3) described in the
Specification (pages 11–17), Appellant argues that the barrier effect (shown
by demonstration of the inhibition of IL-6 cytokine release) is synergistic for
the combination of ingredients. (Appeal Br. 23–25.) We do not agree that
the evidence demonstrates synergy. The “evidence” of synergism is based
on attorney calculations, not statements in the Specification or by a qualified
expert. “[A]ttorney argument [is] not the kind of factual evidence that is
required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d
1465, 1470 (Fed. Cir. 1997).
Also, as discussed above, following the Attorney position that
“Inhibition of IL-6 Release Due to Drug” can be calculated by subtracting
the % IL-6 cytokine release inhibition” in Table 2 of each composition A1–
A7 from 82% (the % IL-6 cytokine release inhibition” for Composition A)
one obtains the following data.
Test Composition Inhibition of IL-6 Release Due to
Drug that is “lacking”
Composition A1 lacking organic
beeswax
82-46 = 36%
Composition A2 lacking Hypericum
oil
82-36 = 46%
Composition A3 lacking Red grape
vine LE
82-64 = 18%
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Composition A4 lacking Horse
chestnut LE
82-33 = 49%
Composition A5 lacking Centella
LE
82-65 = 19%
Composition A6 lacking butcher’s
broom LE
82-57 = 25%
Composition A7 lacking Aloe dry
extract
82-20 = 62%

The foregoing calculations do not establish an effect of the ingredients in
combination that is greater than the sum of their separate effects, e.g., the
inhibition due to Aloe dry extract is 62%, the inhibition due to Horse
Chestnut LE is 49%, and the inhibition due to Hypericum oil is 46%, yet the
combination of these components and 4 more results in inhibition of 82%.
Rather, for the reasons discussed in detail in the patent-eligibility section
above, all that the data demonstrates is that the ingredients in combination
interact with each other in some manner. Indeed, it would appear from the
data that some of the interactions may even negatively affect the inhibition
of IL-6 when added to other ingredients
Thus, for the foregoing reasons we affirm the Examiner’s rejection of
claims 1, 3–11, 13, and 15–24 as being obvious over Li, Reddy, Gupta, and
El Mogy.

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CONCLUSION
In summary:

Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1, 3–11, 13,
15, 22
101 Eligibility 1, 3–11, 13,
15, 22
1, 3–11, 13,
15–24
103(a) Li, Reddy, Gupta,
El Mogy
1, 3–11, 13,
15–24

Overall
Outcome
1, 3–11, 13,
15–24

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).

AFFIRMED