Khallar Alikhanov et al.

Patent Trials and Appeals Board

Dec 18, 2020

2020001916 (P.T.A.B. Dec. 18, 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.
12/798,027 03/29/2010 Khallar Abdumuslimovich Alikhanov 22754-042 4604
7590 12/18/2020
PATEL & ALUMIT, P.C.
16830 Ventura Boulevard, Suite 360
Encino, CA 91364
EXAMINER
BUNNER, BRIDGET E
ART UNIT PAPER NUMBER
1647
MAIL DATE DELIVERY MODE
12/18/2020 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KHALLAR ABDUMUSLIMOVICH ALIKHANOV,
LEONID YAZONOVICH KACHARAVA,
BAGODADI ASUMUSUMOVICH ALIKHANOV, and
PETER GEORGIEVICH PROKOPENKO
Appeal 2020-001916
Application 12/798,027
Technology Center 1600
Before JEFFEREY N. FREDMAN, TAWEN CHANG, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1–4 and 10–12. 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 the inventors
Khallar Abdumuslimovich Alikhanov, Leonid Yazonovich Kacharava,
Bagdadi Abumuslimovich Alikhanov, Peter Georgievich Prokopenko, and
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STATEMENT OF THE CASE
The Specification states that “[i]mmunoglobulins for . . . treatment of
autoimmune diseases are known” but that “the known agent is not intended
for use at the acute stage of an autoimmune disease” and, “to achieve
clinical performance, it is necessary to infuse large doses of immunoglobulin
continuously for several years.” Spec. ¶ 2.
The Specification similarly states that, while the art teaches
“trophoblastic ß-1-glycoprotein (TBG) with immunoregulatory properties[]
intended for treatment of various autoimmune diseases,” “when used at the
acute stage of an autoimmune disease, the effect of the known agent can
only occur 4–5 days after its introduction into the patient’s body.” Spec. ¶¶
3–4.
According to the Specification, “[t]he object of the invention is to
develop an agent with immunoregulatory properties and to accelerate the
clinical effect at the acute stage, mainly when treating autoimmune
diseases.” Spec. ¶ 5. Further according to the Specification, “[t]he essence
of the invention is that the claimed agent that comprises TBG and Ig has the
property to suppress the proliferative activity of mononuclear cells, and to
induce the suppressor activity and secretion of cytokines TFR-V1, IL-10, IL-
6.” Id. ¶ 9.

Alexandr Alexandrovich Terentiev. Appeal Br. 3. We note that, although
Appellant identifies five inventors in the Appeal Brief, we were unable to
locate an oath or declaration filed by Mr. Terentiev in the record.
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CLAIMED SUBJECT MATTER
The claims are directed to compositions consisting essentially of
trophoblastic ß-1-glycoprotein (TBG) and an immunoglobulin (Ig). Claims
1 and 11 are illustrative:
1. An agent with the property to induce suppressor activity
and cytokine secretion of mononuclear cells that consists
essentially of trophoblastic ß-1-glycoprotein (TBG), and
immunoglobulin (Ig).
11. A composition consisting essentially of trophoblastic ß-1-
glycoprotein (TBG) and an immunoglobulin, wherein the TBG and
the immunoglobulin are present in the composition in respective
amounts effective to enable the composition to suppress proliferative
activity of mononuclear cells of peripheral blood at least twice as
strongly as the TBG alone.
Appeal Br. 18 (Claims App.).

REJECTION
Claims 1–4 and 10–12 are rejected under 35 U.S.C. § 101 as being
directed to a judicial exception (i.e., a product of nature or a natural
phenomenon) to patent-eligible subject matter, without significantly more.
Ans. 3.

OPINION
A. Issue
The Examiner explains that the claims recite TBG and an
immunoglobulin, which are each a natural phenomenon (i.e., product of
nature). Ans. 4. The Examiner finds that “TBG is found in the serum of
pregnant women and has been isolated in pure form” and finds that “[i]t is
also well known in the relevant art that humans express five . . . antibody
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classes, called immunoglobulin[s].” Id. The Examiner further finds that
Briese2 teaches that “venous samples and retroplacental blood samples taken
after vaginal deliveries comprise [TBG] and immunoglobulins G, M, and
A.” Id. at 4–5.
The Examiner finds that the claims “recite a TBG and an
immunoglobulin . . . that are not markedly different in structure or function
from naturally occurring TBG or immunoglobulin,” and “also do not recite
any additional elements that integrate the judicial exception [(i.e., the
naturally occurring molecules)] into a practical application.” Ans. 5. The
Examiner finds that, likewise, “the overall combination of TBG and an
immunoglobulin in the claimed agent and composition does not render the
resulting agent/composition different from each of the components alone.”
Ans. 5. Accordingly, the Examiner concludes that “the claims as a whole do
not amount to significantly more than each ‘product of nature’ by itself.” Id.
Appellant contends that “the closest naturally occurring counterpart to
the claimed composition” is the “venous or retro-placental blood samples
comprising TBG and immunoglobulins G, M and A along with other
components” that are described in Briese. Appeal Br. 9. Appellant
contends that “the evidence of record shows that the claimed product has a
number of characteristics/properties that are markedly different than the
natural product as represented by the venous and retroplacental blood
samples taken after vaginal deliveries.” Id. at 11–16. Appellant contends
that claim 11 further “requires a level of suppressive activity that the

2 Von V. Briese et al., Zur Konzentration einiger Serum-, Schwangerschafts-
und Immunglobuline sowie Östriol im Retroplazentarblut, 105
ZENTRALBLATT GYNÄKOLOGIE 845 (1983).
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evidence of record shows is not present in the natural product such that the
product defined in claim 11 is markedly different from the natural product.”
Id. at 16.
Except for claims 1 and 11, Appellant does not separately argue the
claims. We therefore focus our analysis on claims 1 and 11 as
representative. The issue with respect to this rejection is whether the
claimed subject matter is markedly different from products of nature.
B. Analysis
Unless otherwise noted, we adopt the Examiner’s findings of fact and
reasoning regarding the patent eligibility of claims 1 and 11 (July 30, 2018
Office Act. 3–15; Ans. 3–20) and agree that claims 1 and 11 are directed to
products of nature without significantly more. Only those arguments made
by Appellant in the briefs have been considered; arguments not presented in
the briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv). We highlight certain
points below for emphasis.
An invention is patent-eligible if it claims a “new and useful process,
machine, manufacture, or composition of matter.” 35 U.S.C. § 101.
However, courts have carved out certain exceptions from subject matter that
would otherwise appear to be within the literal scope of § 101. These
include, for example, laws of nature and natural phenomena, which are often
referred to as “products of nature” when claimed as a physical
product. Alice Corp. v. CLS Bank Int’l, 573 U.S. 208, 216 (2014); MPEP §
2106.04(b)(II).
We analyze this case under the framework set forth by the Supreme
Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566
U.S. 66 (2012), and applied by our reviewing court in Ariosa Diagnostics,
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Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). As the Ariosa court
explained:
In Mayo . . . , the Supreme Court set forth a framework
for distinguishing patents that claim laws of nature,
natural phenomena, and abstract ideas from those that
claim patent-eligible applications of those concepts.
First, we determine whether the claims at issue are
directed to a patent-ineligible concept. . . . If the answer
is yes, then we next consider the elements of each claim
both individually and “as an ordered combination” to
determine whether additional elements “transform the
nature of the claim” into a patent-eligible application.
. . . The Supreme Court has described the second step of
this analysis as a search for an “inventive concept”—i.e.,
an element or combination of elements that is “sufficient
to ensure that the patent in practice amounts to
significantly more than a patent upon the [ineligible
concept] itself.”
Id. at 1375.

Whether Claims Are Directed to a Product of Nature
We begin with the first step of the Mayo test, namely whether a claim
is “directed to” a patent-ineligible concept. On January 7, 2019, the Director
of the USPTO issued the “2019 Revised Patent Subject Matter Eligibility
Guidance” (“Revised Guidance”), which provides further details regarding
how the Patent Office analyzes patent-eligibility questions under 35 U.S.C. §
101. 84 Fed. Reg. 50–57 (Jan. 7, 2019). Under the Revised Guidance, the
first step of the Mayo test (i.e., Step 2A of the Revised Guidance) is “a two-
pronged inquiry.” Id. at 54. In prong one, we evaluate whether the claim
recites a judicial exception, such as laws of nature, natural phenomena, or
abstract ideas. Id. If the claim recites a judicial exception, the claim is
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further analyzed under prong two, which requires “evaluat[ion of] whether
the claim recites additional elements that integrate the exception into a
practical application of that exception.” Id. The Revised Guidance explains
that, “[i]f the recited exception is integrated into a practical application of
the exception, then the claim is eligible at Prong Two of . . . Step 2A [of the
Revised Guidance].” Id.

Revised Guidance Step 2A, Prong 1
With respect to the first prong of Step 2A of the Revised Guidance,
we agree with the Examiner that claims 1 and 11 recite patent-ineligible
products of nature. Ans. 4.
The Supreme Court has explained that a claimed composition
becomes more than a product of nature where it is “a product of human
ingenuity” that is “new ‘with markedly different characteristics from any
found in nature.’” Ass’n Molecular Pathology v. Myriad Genetics, Inc., 569
U.S. 576, 590–591 (2013) (quoting Diamond v. Chakrabarty, 447 U.S. 303,
319–310 (1980)). In this case, both independent claims 1 and 11 recite
trophoblastic ß-1-glycoprotein (TBG) and an immunoglobulin. The
Examiner found, and Appellant has not disputed, that these are proteins that
occur naturally in the human body. Id. at 4; see also, e.g., Briese Abstract
(stating that pregnancy specific beta1-glycoprotein (SP1)3 and
immunoglobulins G, M, and A are found in venous and retroplacental blood
samples after vaginal delivery). Appellant has not argued that the TBG and

3 The Examiner notes, and Appellant does not dispute, that pregnancy
specific beta1-glycoprotein (SP1) is also known as trophoblastic ß-1-
glycoprotein (TBG). Ans. 4–5.
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immunoglobulin recited in the claims are themselves different from such
naturally occurring molecules, nor, as further discussed below, has
Appellant pointed to persuasive evidence that the combination of the
proteins results in “a product of human ingenuity” that is “new ‘with
markedly different characteristics from any found in nature.’” Myriad, 569
U.S. at 590–591. Accordingly, we agree with the Examiner that the
evidence of record supports a finding that the claims 1 and 11 recite products
of nature.
Appellant contends that “the markedly different characteristics
analysis with respect to the claimed combination of components requires a
comparison between the combination of components and its naturally
occurring counterpart combination,” which Appellant contends to be the
“venous or retro-placental blood samples comprising TBG and
immunoglobulins G, M and A along with other components.” Appeal Br. 9;
see also Reply Br. 4–5. Appellant contends that “the claimed product has a
number of characteristics/properties that are markedly different” than this
naturally occurring counterpart combination, including non-toxicity,
“counter-suppressor activity,” and enhanced suppressor activity. Appeal Br.
11–16.
We are not persuaded. Independent claims 1 and 11 recite an agent or
a composition that “consists essentially of” TBG and immunoglobulin.
Appellant does not persuasively explain why venous or retroplacental blood
samples taken after vaginal deliveries, which comprises a large number of
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other biological molecules, would be a closer naturally occurring counterpart
than naturally occurring TBG and immunoglobulin molecules.4
Appellant cites to MPEP § 2106.04(c) in support of its position,
arguing that where the claims are directed to a combination of components,
“the markedly different characteristics analysis should be performed with
respect to the combination, not separately with respect to the component
parts.” Appeal Br. 9; Reply Br. 4. In particular, Appellant cites to the
MPEP example in which “a claim to ‘a probiotic composition comprising a
mixture of Lactobacillus and milk’” is analyzed for markedly different
characteristics with respect to the mixture of Lactobacillus and milk rather
than to the Lactobacillus separately and the milk separately. Id.; MPEP
§ 2106.04(c)(I)(A).
We agree that “[w]here the claim is to a nature-based product
produced by combining multiple components . . . , the markedly different

4 We recognize that Dr. Khallar Abdumuslimovich Alikhanov states in his
declaration that “[t]he closest naturally occurring counterpart” to the claimed
agent is “venous or retroplacental blood samples comprising TBG and
immunoglobulins G, M and A along with other components.” Appeal Br. 9;
Reply Br. 4; K. Alikhanov Decl. ¶ 2. However, Dr. Alikhanov provides no
persuasive reasoning for this conclusory statement, and we decline to accord
the statement significant weight. See Velander v. Garner, 348 F.3d 1359,
1371 (Fed. Cir. 2003) (“[A]ccord[ing] little weight to broad conclusory
statements [in expert testimony before the Board] that it determined were
unsupported by corroborating references” was “within the discretion of the
trier of fact to give each item of evidence such weight as it feels
appropriate.”). Appellant also points to declarations submitted by Leonid
Yazonovich Kacharava and Bagdadi Abdumuslimovich Alikhanov to
support its position. Appeal Br. 9. However, as Appellant acknowledges,
“the evidence presented in each of the declarations is substantially the
same,” id. at 10, and we find them equally lacking.
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characteristics analysis should be applied to the resultant nature-based
combination, rather than its component parts.” MPEP § 2106.04(c)(I)(A).
That is, the analysis compares the claimed mixture of nature based products
to the appropriate counterpart. The appropriate counterpart may be the
individual nature-based components of the combination. MPEP §
§ 2106.04(c)(II)(A). Thus, the example in the MPEP cited by Appellant is
inapposite. Indeed, the MPEP makes clear that, although the natural
counterpart selected for markedly different analysis should be in its natural
state, care should be taken “not to confuse the counterpart with other
material that may occur naturally with, or adjacent to, the counterpart.”
MPEP § 2106.04(c)(II)(A).
We further note that the implication of Appellant’s argument is that
simply isolating components from a product of nature may be sufficient to
render those components individually or in combination patent-eligible.
However, this position has been rejected by the Supreme Court in Myriad,
which held that simply “separating [an important and useful] gene from its
surrounding genetic material is not an act of invention.” 569 U.S. at 591.
We conclude that isolating two naturally occurring molecules from their
surrounding biological material and putting them together is likewise not an
act of invention.
Instead, we agree with the Examiner that the rationale articulated by
the Supreme Court in Funk Brothers Seed Co. v. Kalo Inoculant Co., 333
U.S. 127 (1948), is applicable to this case and shows that the claimed agent
and composition are not markedly different from products of nature. Ans. 5.
In Funk Brothers, the Supreme Court held that a mixed culture of Rhizobia
bacteria “capable of inoculating the seeds of plants belonging to several
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cross-inoculation groups” without inhibiting each other to be patent-
ineligible. As the court explained,
[t]he qualities of these bacteria, like the heat of the sun, electricity, or
the qualities of metals, are part of the storehouse of knowledge of all
men. They are manifestations of laws of nature, free to all men and
reserved exclusively to none. He who discovers a hitherto unknown
phenomenon of nature has no claim to a monopoly of it which the law
recognizes. If there is to be invention from such a discovery, it must
come from the application of the law of nature to a new and useful
end.
Funk Brothers, 333 U.S. at 130. Similarly, in this case, the combination of
TBG and immunoglobulin proteins is not patent-eligible: Appellant has
provided no persuasive evidence that the combination produces a new
molecule, a change in either TBG or the immunoglobulins, or an
“enlargement of the range of their utility.”5 Id. at 131.
Appellant contends that Funk Brothers is inapposite because in that
case “there is nothing . . . to suggest the existence of a natural counterpart
comprising a mixture of the bacterial strains.” Reply Br. 4–5. We do not

5 We are cognizant that “the examiner bears the initial burden, on review of
the prior art or on any other ground, of presenting a prima facie case of
unpatentability.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
However, we find that the Examiner has established a prima facie case in
this instance by showing that the claimed agent/composition recite only
molecules that are naturally occurring and that these naturally occurring
molecules have the properties recited in the claims. “[T]he prima facie case,
[is] an evidentiary burden-shifting device available to the examiner in the
initial stage of examination. . . . An examiner can find a prima facie case of
unpatentability upon initial review of the prior art or on any other statutory
condition of patentability. . . . If the examiner establishes a prima facie case,
the burden shifts to the applicant to come forward with rebuttal evidence or
argument.” In re Brandt, 886 F.3d 1171, 1176 (Fed. Cir. 2018) (internal
citations omitted).
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find this argument to be persuasive, because the claim at issue is not directed
to the venous or retroplacental blood of a pregnant woman and does not
recite all of the components therein and, as the Examiner points out, there is
likewise no evidence of a natural counterpart of an agent that “consists
essentially of” TBG and Ig. Ans. 10. Appellant further contends that,
“assuming arguendo that there were no natural counterpart comprising
multiple components as claimed, . . . the claimed product would have to be
compared to each of the natural products individually, not in combination.”
Reply Br. 5. To the extent Appellant is arguing that the characteristics (e.g.,
suppressive effect) of the claimed agent/composition should be compared to
TBG and immunoglobulin separately, without considering the characteristics
of the other claimed naturally occurring compound in the agent/composition,
we are not persuaded. This argument would be contra to, e.g., Funk
Brothers, in which a mixed culture of Rhizobia bacteria was found to be
patent-ineligible even though the mixture was capable of inoculating the
seeds of plants belonging to several cross-inoculation groups whereas
individual species of bacteria in the mixture could be used successfully only
in plants of the particular cross-inoculation group corresponding to the
species. 333 U.S. at 129–132.
Appellant contends that by withdrawing the anticipation rejection over
Briese the Examiner “implicit[ly] acknowledge[d] that Briese does not show
or suggest [the] basic and novel properties” of the claimed agent, namely
“induce[ment of] accelerated suppressor activity and cytokine secretion of
mononuclear cells without toxicity such that the agent is effective for
clinical use in treating autoimmune diseases.” Appeal Br. 9; see also id. at 8
(contending that the PTO has “implicitly acknowledged that the claims of
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record are novel and nonobvious over Briese and all other prior art
reference” because “[t]here are presently no prior art rejections being
applied against the claims”).
We are not persuaded by Appellant’s apparent argument that the
claimed agent and composition on appeal are patent-eligible because they
are novel. “The ‘novelty’ of any element or steps in a process, or even of
the process itself, is of no relevance in determining whether the subject
matter of a claim falls within the § 101 categories of possibly patentable
subject matter.” Diamond v. Diehr, 450 U.S. 175, 188-89, (1981). Likewise,
the novelty of a claimed composition is not determinative of whether they
fall within the product of nature judicial exception. See, e.g., Funk Brothers,
333 U.S. at 130–131 (finding claims to composition of non-inhibitive strains
of bacteria to be patent-ineligible despite the fact that the composition is
“new and different,” because mere “aggregation of species fell short of
invention within the meaning of the patent statutes”). To the extent
Appellant is arguing that the lack of an anticipation rejection over Briese
suggests that the claimed agent or composition is “markedly different” from
a product found in nature, we are not persuaded because, as discussed above,
we agree with the Examiner that the proper comparison of the claimed
agent/composition is to naturally occurring TBG and immunoglobulin
proteins, rather than to the post-vaginal delivery venous or retroplacental
blood samples of Briese.
Having determined that the proper comparison of the claimed
agent/composition is to naturally occurring TBG and immunoglobulin
proteins, we turn next to Appellant’s contention that the claimed
agent/composition has “markedly different” characteristics than products of
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nature, including non-toxicity, “counter-suppressor activity,” and enhanced
suppressor activity. Appeal Br. 11–16.
We first note that, as discussed above, Appellant’s arguments
improperly compared the claimed agent/composition to venous and
retroplacental blood samples rather than the proteins themselves as they
occur in nature. Appeal Br. 11–16. Thus, Appellant’s arguments are not
persuasive. Indeed, as the Examiner points out, the evidence of record
shows that neither TBG nor immunoglobulin is toxic. Ans. 12; see also,
e.g., Chan6 20:30–48 (teaching that SP1 protein (i.e., TBG) has “growth
promoting activities”), 21:15–22:4 (suggesting administration of
pregnancy/placenta specific proteins as pharmaceutical agents);
Golovistikov ’3267 Abstract (teaching a method of treating autoimmune
disease by administering TBG); 1:49–64 (teaching that use of TBG achieves
the objective of “treatment of autoimmune disease by administering a
preparation which shows an immune correcting activity and does not cause
side effects”), 2:18–48 (teaching that “[p]referably TBG should be
administered parenterally or intravenously after preculturing TBG . . . with
auto-MNC from peripheral blood”), 4:14–21 (Example 3, describing patient
receiving TBG injections (0.5 ml having concentration of 60 µg/ml) into the
joints); Sewell8 387, left column (teaching that “[i]ntravenous
immunoglobulin (IVIg) . . . is the treatment of choice for patients with

6 Chan, US 5,169,835, issued Dec. 8, 1992.
7 Golovistikov et al., US 6,150,326, issued Nov. 21, 2000.
8 W. A. C. Sewell & S. Jolles, Immunomodulatory Action of Intravenous
Immunoglobulin, 107 IMMUNOLOGY 387 (2002).
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antibody deficiencies” and is also “used as an ‘immunomodulatory’ agent in
an increasing number of immune and inflammatory disorders”).
Likewise, the evidence of record shows that both TBG and
immunoglobulin have suppressive effects at the concentrations exemplified
in the Specification and/or in Exhibit D of the K. Alikhanov Declaration.
Chan teaches, for example, that TBG (or SP1 protein) “at a concentration of
as low as 10 µg/ml inhibits lymphocyte proliferation significantly (50%) in a
mixed lymphocyte assay” and that “[i]nhibition is 85% at 30 µg/ml and
100% at 100 µg/ml.”9 Chan 20:10–27 (Example 9); see also Golovistikov

9 The amounts of TBG used in the examples in the Specification range from
0.5 mcg/ml to 480 mcg/ml when used in combination with immunoglobulin,
and 1 mcg/ml to 960 mcg/ml when used alone, wherein TBG amounts of 0.5
mcg/ml and 480 mcg/ml when used with immunoglobulin, and 1 mcg/ml
and 960 mcg/ml when used alone, resulted in 0% inhibition index. Spec. ¶¶
23 (Table 1), 33 (Table 2), 64 (Table 3), 66 (Table 4), 68 (Table 5), 70
(Table 6), 72 (Table 7), 74 (Table 8), 75 (Table 9), 78 (Table 10). The doses
used in Exhibit D of the K. Alikhanov Declaration are “TBG with
immunoglobulin in the amount of 30 mkg/ml, with a ratio of 1:1[, 1:99, and
1:19] with immunoglobulin” in, respectively, Examples 14, 15, and 16. We
note that it is unclear whether 30 mkg/ml refers to 30 mg/ml or 30 mcg/ml
(µg/ml). On the one hand, it is stated in the declaration that the doses
administered do not exceed tens of milligrams/ml, suggesting that 30
mkg/ml refers to 30 mg/ml. K. Alikhanov Decl. ¶ 6a (emphasis added). On
the other hand, the declaration states that, “[b]y the 36th week of pregnancy,
the concentration of TBG [in the blood of a pregnant woman] reaches a
maximum of approximately 330-400 µg/ml,” id. ¶ 6b, and refers to this
concentration as “about 10 times greater” than the doses administered in the
examples of Exhibit D, suggesting that 30 mkg/ml refers to 30 µg/ml. See
also Appeal Br. 14 (stating that “the Declaration at paragraph 6a and Exhibit
D . . . shows that the administration of the claimed product to patients in
very small concentrations not exceeding tens of micrograms/ml have
significant suppressive effects”) (emphasis added).
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’326 2:18–20, 2:37–47. With respect to immunoglobulin, Sewell teaches
that “IVIg has been shown to have a considerable inhibitory effect on
mitogen-induced T-cell proliferation in vitro.” Sewell 387, left column.
More specifically, Sewell teaches that “[b]oth antigen-dependent and
antigen-independent responses are inhibited by IVIg in a dose-dependent
manner” and that “T-cell proliferation in response to anti-CD3 or tetanus
toxoid was shown to be inhibited by IVIg in a dose-dependent manner over a
range of IgG concentrations (0–10 mg/ml).10 Id. at 387, right column.
Given that both TBG and immunoglobulins have suppressive effects,
we agree with the Examiner that Appellant’s evidence, which allegedly
shows that the claimed agent/composition demonstrates enhanced
suppressive effects when compared to use of TBG alone, does not
persuasively show that the claimed agent/composition is markedly different
from products of nature. Ans. 17–19.
Appellant contends that “the issue at hand is not ‘synergy’, but
whether the claimed product has a ‘markedly different characteristic’ from
the natural product” and further contends that, “[w]here, as here, the Office
has already decided that the claimed product is novel and nonobvious over
the natural product, as described in Briese, there is no reason to consider the
issue of synergy.” Appeal Br. 15. We are not persuaded because, as
discussed above, the proper comparison is between the claimed composition

10 As the Examiner points out, the Specification indicates the amounts of
immunoglobulin used only as a ratio to the TBG amounts. Ans. 19.
However, the examples have TBG:immunoglobulin ratios ranging from 1:1
to 1:99. Spec. ¶¶ 64–79. For TBG concentrations of 0.5 to 480 µg/ml, see
supra note 8, this would indicate immunoglobulin concentration ranges of
0.5 µg/ml to 47.5 mg/ml.
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and the naturally occurring TBG and immunoglobulin. To the extent the
allegedly enhanced activity of the claimed composition is merely the result
of the combined activity of the naturally occurring TBG and
immunoglobulin proteins, the claimed composition is not markedly different
from naturally occurring products.11
Finally, we are also unpersuaded by Appellant’s contention that the
alleged “counter-suppressor” activity of the claimed agent/composition
renders the claimed agent/composition markedly different from products of
nature. Appellant contends that the claimed product “[i]nduces stimulation
(counter-suppressor) activity of the peripheral blood lymphocytes of patients
suffering from autoimmune disease in remission stage in approximately 60%
of cases” and that, “[i]n contrast, counter-suppressor activity could not be

11 Although it is not necessary to our affirmance, we also agree with the
Examiner that, even if Appellant’s evidence suffices to show synergy at
some ratios of TBG and immunoglobulin, such evidence is not
commensurate with the scope of claims 1 and 11, because these claims do
not recite any specific concentrations of TBG and/or immunoglobulin, and
“Appellant has not established synergy at [all ratios of
TBG/immunoglobulin encompassed by the claims], or by the mere presence
of trace amounts of TBG or immunoglobulin.” Ans. 6–7. Appellant argues
that “claim 1 requires the agent to have ‘the property to induce suppressor
activity and cytokine secretion of mononuclear cells,’” and a skilled artisan
“would understand that this precludes the TBG and immunoglobulin from
being present in trace amounts.” Appeal Br. 15. Assuming for argument’s
sake that the preamble in claim 1 is limiting, the claim at most requires the
agent consisting essentially of TBG and immunoglobulin to have the recited
suppressive effect. As discussed above, both TBG and immunoglobulin
individually provide such suppressive effect at a range of concentrations;
thus, the preamble of claim 1, even if limiting, does not require each of TBG
and immunoglobulin to be present in an amount Appellant alleges to result
in “markedly different” suppressive activity of the combination.
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present in retroplacental blood samples from the body of a pregnant woman”
since “[t]he function of TBG is to form tolerance in a mother’s immune
system against the fetus.” Appeal Br. 13 (citing K. Alikhanov Decl. ¶ 5, Ex.
C).
Putting aside the fact that Appellant has not argued that the alleged
counter-suppressor activity renders the claimed agent/composition markedly
different from natural TBG or immunoglobulin proteins (as opposed to
retroplacental blood samples), we note that Appellant alleges that the
claimed agent/composition induces stimulation activity of the peripheral
blood lymphocytes only in a subset of the population (i.e., 60% of cases in
patients suffering from autoimmune disease in remission stage). Appeal Br.
13. In other words, the claimed composition exhibits that activity in only
certain environments. Thus, even assuming that counter-suppressive activity
of the combination of TBG and immunoglobulin would establish the
claimed agent is “markedly different” from the proteins individually,
Appellant has not shown that the combination of TBG and immunoglobulin
as claimed does not encompass products of nature (e.g., in the cases where
the claimed agent/composition does not exhibit counter-suppressor
activity).12

12 As discussed above, Appellant has argued that the preamble of claim 1,
which recites “[a]n agent with the property to induce suppressor activity . . .
of mononuclear cells,” should be considered limiting. Appeal Br. 15, 18
(Claims App.) (emphasis added). Similarly, claim 11 recites a composition
wherein “the TBG and the immunoglobulin are present in the composition in
respective amounts effective to enable the composition to suppress
proliferative activity of mononuclear cells of peripheral blood at least twice
as strongly as the TBG alone.” Appeal Br. 18 (Claims App.) (emphasis
added). We note that Appellant’s argument above that the claims only
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Although we need not rely on the following to affirm the Examiner’s
rejection, we also note that Golovistikov ’326 appears to teach that TBG
alone possesses the alleged counter-suppressor/stimulatory activity. See,
e.g., Golovistikov ’326 2:54–58 (stating that “FIG. 1 discloses stipulatory
[sic] (countersuppressor) and suppressor activity as percentage of TBG-
induced lymphocytes in peripheral blood of the patients suffering
disseminated sclerosis at the acute stage (1), at the initial stage of remission
(2), and at the remission stage (3)”), Fig. 1 (showing stimulatory activity at
the initial stage of remission), 3:32–40 (Example 1, stating that
“immunological study carried out [in a patient] during the remission stage
[showed] that stimulatory (countersuppressor) activity T-lymphocytes in
peripheral blood was 28%” and that “[a]t the present stage the treatment
with TBG should be avoided”), 4:28–31 (stating that “[t]he normal value . . .
at the initial stage of remission . . . is 66.6%±16.1 (stimulatory activity)”).
Thus, “counter-suppressive” activity in the claimed agent/composition does
not render it “markedly different” from product(s) of nature (i.e., the
naturally-occurring TBG molecule).
Relying on Sewell, Appellant contends that, to the extent the
markedly different analysis is to be conducted with respect to TBG and
immunoglobulins individually, the claimed agent is nevertheless markedly
different than products of nature, because, “at the concentrations used with
TBG as exemplified in the present specification, immunoglobulins do not

encompass agents/compositions having suppressive effect appears
contradictory to Appellant’s argument here that the claimed
agent/composition is markedly different from product(s) of nature because it
possesses counter-suppressive properties.
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reveal any suppressive effect.” Appeal Br. 10. Instead, Appellant contends,
“immunoglobulins reveal a suppressive effect in vitro only at concentrations
that are tens and hundreds of times greater and in vivo only at concentrations
that are hundreds and thousands of times greater.” Id.
We are not persuaded. As an initial matter and as the Examiner notes,
the claims do not recite specific concentrations of immunoglobulin. Ans.
17. See In re Self, 671 F.2d 1344, 1348 (CCPA 1982) (“[A]ppellant’s
arguments fail from the outset because . . . they are not based on limitations
appearing in the claims.”).
However, even assuming for argument’s sake that immunoglobulins
do not have a suppressive effect at concentrations used in the examples of
the Specification, and that the allegedly enhanced suppressive effect of the
agents/compositions in these examples as compared to TBG renders them
“markedly different” from a product of nature as a result of “human
ingenuity,” there is no persuasive evidence of such enhanced suppressive
effect commensurate with the scope of the claims (e.g., at higher
immunoglobulin concentrations than those used in the examples).
Moreover, Appellant does not point to a specific portion of Sewell
that suggests immunoglobulins do not have any suppressive effect at the
concentration exemplified in the Specification. Appeal Br. 10. As the
Examiner points out and as discussed above, Sewell in fact teaches that “T-
cell proliferation in response to anti-CD3 or tetanus toxoid was shown to be
inhibited by IVIg [(intravenous immunoglobulin)] in a dose-dependent
manner over a range of IgG concentrations (0–10mg/ml).” Sewell 387, right
column; Ans. 17. Thus, as the Examiner explains, Sewell suggests that
immunoglobulins do have suppressive effect at concentrations that overlap
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the range of concentrations exemplified in the Specification. Ans. 17.
Appellant has not pointed to any error in the Examiner’s reasoning in this
regard in the Reply Brief.
Appellant contends that, with respect to claim 11,
[t]he characteristics of [the claim] are additionally
different insofar as claim 11 requires that the recited
TBG and immunoglobulin are present in the claimed
composition in respective amounts effective to enable the
composition to suppress proliferative activity of
mononuclear cells of peripheral blood at least twice as
strongly as TBG alone. Claim 11 thus requires a level of
suppressive activity that the evidence of record shows is
not present in the natural product such that the product
defined in claim 11 is markedly different from the natural
product for this reason as well.
Appeal Br. 16. In the Reply Brief, Appellant further contends that, with
particular respect to claim 11, the Examiner erred in relying on “prior art
describ[ing] specific amounts of [TBG and immunoglobulin] individually,”
because the references individually cannot show the recited characteristic of
the claimed combination and because “the Examiner has provided no basis
for performing the ‘markedly different characteristic’ analysis with a
combination of references.” Reply Br. 5–6.
We are not persuaded for the reasons already discussed. That is,
given that evidence shows that the immunoglobulin molecule that occurs in
nature also has the effect of suppressing the proliferative activity of
mononuclear cells, and given that claim 11 does not recite any particular
concentration ranges of TBG or immunoglobulin, a preponderance of
evidence supports a finding that the limitations of claim 11 can be met by
adjusting the relative concentrations of naturally occurring TBG and
immunoglobulin molecules. As also discussed above, Appellant has not
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provided persuasive evidence that combining TBG and immunoglobulin
results in a composition that is “markedly different” from naturally
occurring product(s). Accordingly, we agree with the Examiner claim 11
encompasses products of nature and is thus patent-ineligible.
Finally, Appellant contends that the Examiner improperly failed to
consider evidence other than the Specification in determining whether the
claimed product is markedly different from products of nature. Reply Br. 1–
3. We are not persuaded because the Examiner explicitly took into account,
for example, the K. Alikhanov Declaration and its exhibits. See, e.g., Ans.
17–18.

Revised Guidance Step 2A, Prong 2
The second prong of Step 2A asks whether the claims as a whole
integrate the judicial exception into a practical application of the
exception. Revised Guidance, 84 Fed. Reg. at 54. In order to answer this
question, we first “[i]dentify[] whether there are any additional elements
recited in the claim beyond the judicial exception(s)” and, if so, “evaluat[e]
those additional elements individually and in combination to determine
whether they integrate the exception into a practical application.” Id. at 54-
55. As explained earlier, although Appellant’s claims recite a product of
nature, they would still be patent-eligible if the answer to the above question
is affirmative.
We find that claims 1 and 11 do not recite additional elements that
integrate the recited product of nature into a practical application of the idea.
In particular, as discussed above, the agent and composition recited in claims
1 and 11, respectively – i.e., “an agent with the property to induce
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suppressor activity and cytokine secretion of mononuclear cells that consists
essentially of trophoblastic ß-1-glycoprotein (TBG), and immunoglobulin
(Ig)” and “[a] composition consisting essentially of trophoblastic ß-1-
glycoprotein (TBG) and an immunoglobulin,” where the TBG and
immunoglobulin are present in amounts so as to “enable the composition to
suppress proliferative activity of mononuclear cells of peripheral blood at
least twice as strongly as the TBG alone – fall within the product of nature
exception to patent-eligibility. Accordingly, there are no additional elements
recited in the claims beyond the judicial exception, and the claims are
directed to products of nature.

Mayo Step Two: Whether Claim 1 Amounts to “Significantly More”
Finally, as to the second step of the Mayo test, the Revised Guidance
directs us to consider whether claim 1 includes “additional elements . . .
[that] provide[] ‘significantly more’ than the recited judicial exception.” 84
Fed. Reg. at 56. The Revised Guidance states that an additional element that
“simply appends well-understood, routine, conventional activities previously
known in the industry, specified at a high level of generality, to the judicial
exception, . . . is indicative that an inventive concept may not be
present.” Id.
As discussed above, here the claims only recite the products of nature,
without more. That is, other than the naturally occurring molecules
themselves, claims 1 and 11 only require that the molecules be isolated
and/or combined such that the claimed agent and/or composition “consist
essentially” of TBG and immunoglobulin and recite certain properties of the
agent and/or composition. As discussed above with respect to Prong 1 of
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Step 2A of the Revised Guidance, however, isolating and/or combining the
natural molecules in question does not result in a product of “human
ingenuity” that is “markedly different” from products of nature. Funk
Brothers, 333 U.S. at 130–131; Myriad, 569 U.S. at 591 (holding that simply
“separating [an important and useful] gene from its surrounding genetic
material is not an act of invention”).
Accordingly, we affirm the Examiner’s rejection of claims 1 and 11 as
directed to patent-ineligible judicial exceptions, without significantly more.

CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/
Basis
Affirmed Reversed
1–4, 10–12 101 Eligibility 1–4, 10–12

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