Mipsalus ApS

Patent Trials and Appeals Board

Aug 19, 2021

2020005050 (P.T.A.B. Aug. 19, 2021)

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.
14/848,990 09/09/2015 Nicolas Otto Krogh 059551/467965 2117
826 7590 08/19/2021
ALSTON & BIRD LLP
ONE SOUTH AT THE PLAZA
101 SOUTH TRYON STREET
SUITE 4000
CHARLOTTE, NC 28280-4000
EXAMINER
YAKOVLEVA, GALINA M
ART UNIT PAPER NUMBER
1641
NOTIFICATION DATE DELIVERY MODE
08/19/2021 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):
usptomail@alston.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte NICOLAS OTTO KROGH and KLAUS GREGORIUS1
____________

Appeal 2020-005050
Application 14/848,990
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, ULRIKE W. JENKS, and
JOHN G. NEW, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies Mipsalus ApS as the real party-in-
interest. App. Br. 2.

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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 3–12 as unpatentable under 35 U.S.C.
§ 112(a) as lacking written descriptive support.
Claims 3–12 also stand rejected as unpatentable under 35 U.S.C.
§ 103 as being obvious over the combination of Levy, Phenylketonuria: Old
disease, new approach to treatment, 96 P.N.A.S. 1811–1813 (1999)
(“Levy”) in view of Ross et al. (US 2005/0276781 A1, December 15, 2005)
(“Ross”), Piletsky et al., On the Role of Electrostatic Interactions in the
Enantioselective Recognition of Phenylalanine in Molecularly Imprinted
Polymers Incorporating β–Cyclodextrin, 37 POLYMER J. 793–96 (2005)
(“Piletsky”), and Kristensen et al. (WO 2007/095949 A2, August 30, 2007)
(“Kristensen”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to methods of treatment of a
number of metabolic disorders where biomolecules derived from an ordinary
diet provoke disease symptoms in patients by administering to the
gastrointestinal tract of a patient in need thereof an effective amount of
molecular imprinted polymers (MIPs). Spec. 3, 12–13.

REPRESENTATIVE CLAIM
Claim 3 is representative of the claims on appeal and recites:
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3. A method for treatment, amelioration or
prophylaxis of a disease selected from the group consisting of
hyperphenylalaninemia (HPA), alcaptonuria (black urine
disease), tyrosinemia, hypertyrosinemia, myasthenia gravis,
histidinemia, urocanic aciduria, maple syrup urine disease
(MSUD), isovaleric academia (isovaleryl–CoA dehydrogenase
deficiency), homocystinuria, propionic academia,
methylmalonic academia, glutaric aciduria Type 1 (GA–1), and
galactosemia comprising administering to the gastrointestinal
tract of a patient in need thereof an effective amount of a
composition of molecular imprinted polymers (MIPs), said
composition being capable of binding a symptom provoking
agent of said disease.

App. Br. 19.

ISSUES AND ANALYSIS
We adopt the Examiner’s findings, reasoning, and conclusion that the
claims on appeal lack written descriptive support and are prima facie
obvious over the combined cited prior art. We address below the arguments
raised by Appellant.

A. Rejection of claims 3–12 for lack of written description

Issue 1
Appellant argues that the Examiner erred because the Examiner
improperly requires a working example in order to satisfy the written
description requirement. App. Br. 5, 13–14.

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Analysis
In response to a restriction requirement made by the Examiner (filed
June 14, 2017, at 3), Appellant selected hyperphenylalanemia (“HPA”) as
the disease, L–phenylalanine as the symptom provoking agent, and method
i–(a–c) where a mimic of phenylalanine is elected as the template molecule
and L–phenylalanine is elected as the capture agent (filed August 11, 2017,
at 3) as the elected species for the claims presently on appeal.
The Examiner finds that claims 3–12 each contain subject matter that
was not described in Appellant’s Specification in such a way as to
reasonably convey to one skilled in the relevant art that the inventor had
possession of the claimed invention at the time the application was filed.
Final Act. 14. The Examiner finds that because the Specification fails to
describe a MIP having any of the functions recited in the claims, it
necessarily fails to describe a representative number of species within the
claimed genus. Ans. 19. The Examiner further finds that the Specification
fails to describe structural features common to members of the genus that
would allow a skilled artisan to distinguish MIPs encompassed by the claim
language from other MIPs. Id. The Examiner also finds that the
Specification fails to disclose any correlation between the structure and
function of the MIPs encompassed by the claim language. Id.
Specifically, the Examiner finds that Appellant attempts to claim the
broad genus of MIPs by functional characteristics in the absence of any
single example. Final Act. 19–20. The Examiner further finds that
Appellant does not disclose any relevant, identifying characteristics, i.e.,
structure or other physical characteristics and/or other chemical properties,
by functional characteristics coupled with a known or disclosed correlation
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between function and structure, or by a combination of such identifying
characteristics, sufficient to show Appellant was in possession of the
claimed genus of MIPs. Id. at 20.
Appellant argues that the Examiner’s reliance on the presence of a
workable example in the Specification is misplaced. “[T]he written
description requirement does not demand either examples or an actual
reduction to practice.” App. Br. 13 (citing Ariad Pharm., Inc. v. Eli Lilly &
Co., 598 F.3d 1336, 1352 (Fed. Cir. 2010)). Appellant asserts that what
must be provided by the inventors is a description of the invention that
convinces a skilled person that the inventors indeed had made the claimed
invention at the date of filing. App. Br. 13.
Appellant argues that, according to the principle of the claimed
treatment, if an agent (i.e., the MIP) is capable of selectively preventing the
disease–causing molecule from entering the patient’s blood circulation, the
result will be exactly the same as if the disease–causing molecule did not
initially appear in the diet. App. Br. 14. Appellant therefore asserts that this
principle of treatment does not depend on the exact molecule that is bound
by the MIPs, but rather on the efficacy of binding between the MIPs and the
disease–causing molecule since it is known that MIPs can be prepared
against virtually any molecule. Id. Therefore, Appellant argues, there is a
“descriptive link”, as stated in Ariad, between the formation of compositions
of purified MIPs and the diseases treated by the compositions. Id.
Appellant next points to the Declarations of Dr. Thomas Vorup–
Jensen (the “2018” and “2019 Vorup-Jensen Declarations,” filed June 22,
2018 and July 10, 2019, respectively) and the Specification as demonstrating
that the inventors were in possession of the relevant MIP production and
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purification technologies and the results obtainable from them. App. Br. 14.
The Specification and claims also make clear the link between the targeted
amino acids and the recited diseases. Id. Therefore, Appellant asserts, a
person of ordinary skill in the art would have understood the inventors to be
in possession of the invention, regardless of the lack of a specific working
example. Id.
We are not persuaded by Appellant’s argument. The written
description requirement of Section 112(a) requires that the Specification
must “clearly allow persons of ordinary skill in the art to recognize that [the
inventor] invented what is claimed.” Ariad at 1351 (alteration in original)
(quoting Vas–Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991)).
The test for the sufficiency of the description is “whether the disclosure of
the application relied upon reasonably conveys to those skilled in the art that
the inventor had possession of the claimed subject matter as of the filing
date.” Id. Specifically, the Specification “must describe an invention
understandable to that skilled artisan and show that the inventor actually
invented the invention claimed.” Id.
We agree with Appellant that neither examples nor an actual reduction
to practice of a claimed invention is required to satisfy the written
description requirement. Ariad at 1352; See also: Falko–Gunter Falkner v.
Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006). However, the claimed
invention itself must be adequately described in the written disclosure and/or
the drawings. Amgen v. Sanofi, 872 F.3d 1367, 1378 (Fed. Cir. 2017). For
example, disclosure of an antigen fully characterized by its structure,
formula, chemical name, physical properties, or deposit in a public
depository does not, without more, provide an adequate written description
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of an antibody claimed by its binding affinity to that antigen, even when
preparation of such an antibody is routine and conventional. Id. Similarly:
[T]he written description requirement for a claimed genus may
be satisfied through sufficient description of a representative
number of species by actual reduction to practice, reduction to
drawings, or by disclosure of relevant, identifying
characteristics, i.e., structure or other physical and/or chemical
properties, by functional characteristics coupled with a known or
disclosed correlation between function and structure, or by a
combination of such identifying characteristics, sufficient to
show the applicant was in possession of the claimed genus.

Regents of the Univ. of Cal. v. Eli Lilly, 119 F.3d 1559, 1568 (Fed. Cir.
1997). A “representative number of species” means that the species, which
are adequately described, are representative of the entire genus. AbbVie
Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 1300
(2014). When there is substantial variation within the genus, one must
describe a sufficient variety of species to reflect the variation within the
genus. Id.
Appellant’s Specification discloses two general examples of MIPs that
would be capable of binding to phenylalanine as a symptom provoking
agent. Spec. 10–11. The Specification discloses in one example that:
The purification of a population of MIPs that is polymerized with
phenylalanine as the target; for example, the phenylalanine MIPs
made by Piletsky. The phenylalanine MIPs made by Piletsky
have three potential target specific points of interaction with
phenylalanine: the phenyl ring, the amino group and the
carboxylic group. In particular, MIPs can contain binding
cavities that interact with one, two or all three specific target
points by utilizing chromatography methods.

Spec. 10. The Specification also discloses in a second example that:
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[P]henylalanine MIP particles are grinded to a size where they
become soluble. These phenylalanine MIP particles will have
fewer binding cavities compared to larger MIP particles and the
chance that a given particle has predominantly one type of
binding cavity. Similar as in the first example, these
phenylalanine MIP particles are purified by utilizing
chromatography methods.

Id.
However, as pointed out by the Examiner supra, the Specification
fails to describe structural features common to members of the genus that
would allow a skilled artisan to distinguish MIPs encompassed by the claim
language from other MIPs. Ans. 19. Rather, the Specification describes the
claimed MIPs by disclosing the structure of the intended target, e.g.,
phenylalanine, and relying on the binding affinity of potential MIPs to the
intended target. We find that the facts of this case are therefore similar to
those in Amgen in that Appellant is relying upon the structure of the intended
target and the binding affinity of the MIP to the intended target to establish
possession of the claimed MIPs, without also providing a sufficient
structural-functional description of the MIPs themselves. See Amgen, 872
F.3d at 1378.
We conclude that the disclosure of the nature of the intended target
does not, therefore, provide an adequate written description of the claimed
MIPs by its binding affinity to that intended target, even when preparation of
such MIPs is routine and conventional. We therefore agree with the
Examiner that Appellant’s Specification does not provide the written
descriptive support for the claims required by § 112(a).

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Issue 2
Appellant argues that the Examiner improperly conflates the standards
for written description and obviousness. App. Br. 15.

Analysis
The Examiner finds the Vorup-Jensen Declarations are not persuasive
in overcoming the 112(a) rejection because a factually unsupported expert
opinion that an application meets the requirements of 35 U.S.C. § 112 is not
entitled to any weight. Ans. 20 (citing MPEP §716.01(c)). Relying upon
our reviewing court’s decision in Amgen, the Examiner concludes that it is
not enough for the Specification to show how to make and use the invention,
i.e., to enable it, as asserted by the Vorup-Jensen Declarations, in light of the
inventors’ accessibility to compositions of MIPs capable of binding amino
acids with high affinity and capacity. Id. at 22.
The Examiner further finds that a description that merely renders the
invention obvious does not satisfy the written description requirement. Ans.
22–23 (citing Lockwood v. Am. Airlines, 107 F.3d 1565, 1571–72 (Fed. Cir.
1997)). The Examiner points to the Dr. Vorup-Jensen’s statement that the
technology apparently fulfills the purpose of providing MIPs with the
necessary binding properties in light of the references cited in the application
for preparing MIPs that exhibit high affinity and capacity (i.e., Kristensen),
the application itself, and the state of the art demonstrating that MIPs
binding phenylalanine could be prepared (i.e., Piletsky). Id. at 22. The
Examiner, therefore, finds that the Declarant’s presumption that the relevant
MIPS could be prepared, based upon the technology in the Specification and
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the prior art at the time of invention does not satisfy the written description
requirement. Id. at 22–23.
The Examiner also finds that Dr. Vorup-Jensen’s reliance on
Kristensen and Piletsky in supporting the written description requirement is
undermined by the Declarations of Dr. Thomas G. Jensen (the “2018” and
“”2019 Jensen Declarations,” filed June 22, 2018 and July 10, 2019). Ans.
23. Dr. Jensen states that Kristensen does not provide any information
concerning the level of affinity and capacity for target molecules of the
MIPs prepared. Id. (citing 2019 Jensen Decl. ¶¶ 7–8). The Examiner finds
that Dr. Jensen declares that Kristensen does not provide a reasonable
certainty that inborn errors of metabolism such as PKU could be treated with
MIPs. Id. (citing 2019 Jensen Decl. ¶ 7). Similarly, the Examiner notes that
Dr. Jensen states that the MIPs taught by Piletsky exhibit optimum binding
when the MIPs are suspended in increasing amounts of organic solvent, e.g.,
acetonitrile. Id. (citing 2019 Jensen Decl. ¶ 8). Dr. Jensen states that
Piletsky does not provide a reasonable expectation of success that inborn
errors of metabolism such as PKU could be treated with MIPs because an
organic solvent such as acetonitrile is not present in the gastrointestinal tract
in a patient. Id. (citing 2019 Jensen Decl. ¶ 8). The Examiner, therefore,
concludes that the testimony in the Vorup-Jensen Declarations are
undermined by those in the Jensen Declarations. Id.
Appellant argues that the Examiner’s reliance on the Jensen
Declarations as contradicting the Vorup-Jensen Declarations is improper
because it does not take into consideration the additional knowledge the
inventors had access to, which were not identified in the prior art. App. Br.
15. Appellant notes that the Examiner has not indicated that any of the
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pending claims are not enabled. Id. Moreover, Appellant asserts that the
Vorup-Jensen Declarations seek to assess the inventors’ knowledge whereas
the Jensen Declarations seek to provide information available to a person of
ordinary skill in the art. Id. Appellant asserts that it is clearly indicated in
Appellant’s Specification that the invention relates to the administration of
MIPs in order to treat phenylketonuria (PKU) and similar inborn errors of
metabolism, and specific references to the technology needed to obtain MIPs
effective for this purpose are made. Id.
Appellant further argues that the Vorup-Jensen Declarations address
whether a person of ordinary skill in the art, reading the application as filed,
would understand that the inventors had access to the claimed invention on
the date of filing. App. Br. 16. This determination is based on two facts: (1)
MIPs targeting virtually any molecule – including any amino acid – can be
routinely prepared, and (2) the inventors have demonstrated in later
publications that MIPs with surprisingly good binding properties are readily
produced by the technology disclosed in the present application and in
Kristensen. Id.
We are not persuaded by Appellant’s argument. We agree with
Appellant that the preparation of MIPs in general was well known in the art,
as taught by Piletsky and Kristensen. However, it is not enough for the
Specification to show how to make and use the invention, i.e., to enable it.
Amgen at 1377 (citing Ariad at 1345–46, 1347–48); see also: In re
Armbruster, 512 F.2d 676, 677 (C.C.P.A. 1975)). It is well settled that the
written description requirement is separate and distinct from the enablement
requirement. Ariad at 1341.

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Therefore, although Piletsky and Kristensen disclose methods of
making MIPs capable of binding a symptom provoking agent, we conclude
that Appellant’s access to these methods does not necessarily demonstrate
possession of the claimed MIPs, Dr. Vorup-Jensen’s opinion to the contrary
notwithstanding.
Furthermore, despite Dr. Vorup-Jensen’s opinion, the methods of
Piletsky and Kristensen do not disclose a necessary core structure for a MIP
that correlates to the desired function, i.e., binding to phenylalanine as a
symptom provoking agent in order to treat HPA. Notably, the Vorup-Jensen
Declarations do not point out specific structural characteristics taught by
Piletsky and/or Kristensen that would correspond to one or more structural
features common to the members of the claimed genus. The Federal Circuit
stated:
We have held that a sufficient description of a genus . . . requires
the disclosure of either a representative number of species falling
within the scope of the genus or structural features common to
the members of the genus so that one of skill in the art can
‘visualize or recognize’ the members of the genus.

AbbVie at 1350 (quoting Eli Lilly at 1568–69).
The disclosure must therefore adequately reflect the structural
diversity of the claimed genus, either through the disclosure of sufficient
species that are “representative of the full variety or scope of the genus,” or
by the establishment of “a reasonable structure–function correlation.” See
MPEP §2163(II)(A)(3)(a)(ii). Such correlations may be established “by the
inventor as described in the Specification,” or they may be “known in the art
at the time of the filing date.” Id.
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As discussed supra for Issue 1, the Specification fails to disclose
sufficient species that are representative of the full variety or scope of the
claimed genus. Further, neither Appellant’s Specification, the Vorup-Jensen
Declarations, nor the art at the time of the filing date, as exemplified by
Piletsky and Kristensen, establish a reasonable structure–function correlation
between the claimed MIPs and the molecules to which they bind. We
therefore conclude that the Specification fails to describe the claimed
invention in sufficient detail that one skilled in the art can reasonable
conclude that the inventors had possession of the claimed invention.

Issue 3
Appellant argues that the Examiner erred in relying upon Lockwood v.
Am. Airlines, 107 F.3d 1565, 1571–72 (Fed. Cir. 1997) in concluding that
the claims lack sufficient written descriptive support in the Specification.
App. Br. 16.

Analysis
The Examiner finds that a description that merely renders the
invention obvious does not satisfy the written description requirement. Final
Act. at 22–23. The Examiner points to Lockwood as holding that “while the
description requirement does not demand any particular form of disclosure
... or that the Specification recite the claimed invention in haec verba, a
description that merely renders the invention obvious does not satisfy the
requirement.” Lockwood, 107 F.3d at 1571–72 (as quoted in Ariad, 598
F.3d at 1352).
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Appellant argues that the Examiner’s reliance on Lockwood in making
the 112(a) rejection is misplaced. App. Br. 16. Rather, Appellant asserts
that our reviewing court’s decision in CenTrak, Inc. v. Sonitor Techs., Inc.,
915 F.3d 1360, 1367 (Fed. Cir. 2019) is distinguishable from Lockwood, and
should be controlling in the instant application. Id. Appellant points to the
holding in Centocor that:
In Lockwood, we affirmed a summary judgment ruling that a
patent was not entitled to an earlier priority date because its
parent applications did not make any reference to an “individual
merchandising apparatus that contained video disk players or
other equivalent storage means,” which was a claimed
limitation.… Here, in contrast, the specification at least mentions
base stations and receivers that use ultrasound, which makes this
case distinguishable from Lockwood.

915 F.3d at 1367
Appellant argues that the Specification more than “mentions” the
embodiment described in claim 3; the language of claim 3 is taken nearly in
haec verba from the Specification, e.g., page 3, lines 24–33. Id. at 17.
Appellant therefore asserts that the facts in Lockwood are distinguishable
from the facts present in this application. Id.
We are not persuaded by Appellant’s argument. Appellant’s
argument is not dispositive as to whether the claimed invention is described
in sufficient detail that one skilled in the art can reasonable conclude that the
inventors had possession of the claimed invention. Nothing in either
Lockwood or CenTrak, suggests that claim language taken nearly in haec
verba from the Specification necessarily constitutes the description of the
claimed invention in sufficient detail that that one skilled in the art can
reasonable conclude that the inventors had possession of the claimed
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invention. For the reasons stated above for Issues 1 and 2, the Specification
fails to describe the claimed invention in sufficient detail that one skilled in
the art can reasonable conclude that the inventors had possession of the
claimed invention. Consequently, we affirm the Examiner’s rejection of
claims 3–12 as lacking written descriptive support.

B. Rejection of claims 3–12 under 35 U.S.C. § 103
Issue 1
Appellant argues that the Examiner improperly conflates the standards
for Written Description and Obviousness. App. Br. 5–8.

Analysis
The Examiner finds that the facts presented in the Declarations are not
germane to the rejection at issue and showing is not commensurate in scope
with the claims. Ans. 28. The Examiner further finds that the statements
made in the Jensen Declarations clearly contradict the statements made in
the Vorup-Jensen Declarations. Id. at 31. In particular, Vorup-Jensen
opined that the inventors had access to the technology referenced in
Kristensen for preparing MIPs that exhibit high affinity and capacity, and
MIPs that bind phenylalanine are well established as evidenced by Piletsky.
Id. (citing 2019 Vorup-Jensen Decl., 7), whereas Jensen opined that the
cited prior art provides no information that amino acid binding MIPs would
or could exhibit a sufficiently high capacity and affinity so as to meeting the
phenylalanine binding requirements specified by the Levy reference. Id. at
28 (citing Jensen Decl., June 8, 2018, 6). The Examiner also finds that the
data provided in the Declaration of Dr. Klaus Gregorius (the “Gregorius
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Declaration”) does not show that the objective evidence of the alleged
nonobviousness is commensurate in scope with the claims, which are drawn
to the treatment, amelioration, or prophylaxis of a range of diseases, not all
of which are associated with phenylalanine. Id. at 32–33.
Appellant argues that the Examiner’s reliance on the Vorup-Jensen
Declarations to dismiss the Jensen Declarations is improper because the
standard for a rejection under 35 U.S.C. 103 is not based on what the
inventors knew, but what a person of ordinary skill in the art would have
known and expected. App. Br. 7.
Appellant further asserts that the statements made in the Vorup-Jensen
Declarations regarding what the present inventors understood cannot be
taken to indicate what a person of ordinary skill in the art would have
known, or to mean that the person of ordinary skill in the art would have had
a reasonable expectation of success in reaching the presently recited claims.
Id. Rather, Appellant argues that the Examiner fails to indicate from where
in the cited references a person of ordinary skill in the art would have
obtained knowledge that would render effective oral MIP treatment of PKU
obvious. Id. 7–8. Thus, Appellant asserts that the Examiner’s invocation of
what the inventors knew, as a means of dismissing arguments relating to
what a person of ordinary skill in the art knew, is clear error. Id. at 8.
We are not persuaded by Appellant’s argument. We acknowledge the
Declarants’ opinions. However, while an opinion as to a legal conclusion is
not entitled to any weight, the underlying basis for the opinion may be
persuasive. In re Chilowsky, 306 F.2d 908 (C.C.P.A. 1962). The Federal
Circuit held that:
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[i]n assessing the probative value of an expert opinion, the
examiner must consider the nature of the matter sought to be
established, the strength of any opposing evidence, the interest
of the expert in the outcome of the case, and the presence or
absence of factual support for the expert’s opinion.

Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 294
(Fed. Cir. 1985), cert. denied, 475 U.S. 1017 (1986). In the Jensen
Declarations, the Declarant opines that Kristensen failed to teach and/or
suggest a quantification of the improved binding capacity of the MIP
compositions and does not provide any quantitative measure of affinity
improvements in the MIP compositions. See 2018 Jensen Decl., 6.
However, the scope of the claimed methods does not require any specific
quantitative level/amount of binding capacity of the MIPs to phenylalanine.
We therefore find that the features upon which the Declarant relies (i.e.,
specific quantitative binding capacity of MIPs to be relevant for treatment of
HPA) are not recited in the rejected claims. Dr. Jensen further opines on
deficiencies found in Piletsky and Ross, which we address infra in Issues 3
and 4, respectively.
Regarding Appellant’s assertion that the Gregorious Declaration
demonstrates unexpected results, any differences between the claimed
invention and the prior art may be expected to result in some differences in
properties. In re Merck & Co., 800 F.2d 1091, 1099 (Fed. Cir. 1986). The
issue is whether the properties differ to such an extent that the difference is
really unexpected. Id. The evidence relied upon should establish “that the
differences in results are in fact unexpected and unobvious and of both
statistical and practical significance.” Ex parte Gelles, 22 USPQ2d 1318,
1319 (B.P.A.I. 1992). Further, MPEP §716.02(d) states that the objective
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evidence of nonobviousness must be commensurate in scope with the claims
which the evidence is offered to support. In other words, the showing of
unexpected results must be reviewed to see if the results occur over the
entire claimed range. In re Clemens, 622 F.2d 1029, 1036 (CCPA 1980).
For claims 3–9, we find that the claimed invention is not
commensurate in scope with the claims which the evidence is offered to
support because: (1) the scope of the claimed disorders/conditions to be
treated encompasses disorders/conditions that would not benefit from the
reduction of phenylalanine, e.g., myasthenia gravis; (2) the amount of the
blood phenylalanine concentration reduced by the MIPs resulting in the
treatment and/or amelioration of HPA is not claimed; and (3) the effective
amount of MIPs needed to achieve the high reduction of blood
phenylalanine concentration is limited to a single exemplary embodiment,
which is not claimed. As will be discussed below with respect to Issue 2, the
scope of the claimed methods do not require a specific reduced amount of
the symptom provoking agent, and thus, encompass any reduced amount of
the symptom provoking agent in the blood. Similarly, the scope of the
claimed methods do not require a specific effective amount of the
composition to achieve the desired result of treatment. Because the
Specification does not define what constitutes an “effective amount” or
provide any examples of amounts that would be effective for the treatment
of one or more of the claimed disorders/conditions, Appellant has not
demonstrated that the alleged unexpected results would occur over the entire
claimed range.
For claims 10–12, we similarly find that the claimed invention is not
commensurate in scope with the claims, which the evidence is offered to
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support for reasons (2) and (3) discussed supra. We, therefore, agree with
the Examiner that the data provided in the Gregorious Declaration is not
commensurate in scope with the claims.

Issue 2
Appellant argues that the Examiner fails to make a prima facie case of
obviousness. App. Br. 8–9.

Analysis
The Examiner finds that the combination of references renders the
claimed invention obvious. Ans. 31. The Examiner finds that Kristensen
teaches a method for treating, ameliorating or reducing the risk of a disease
by administering to the gastrointestinal tract of a patient MIPs having high
binding capacity and specificity for binding target molecules found in the
patient’s gastrointestinal tract. Id. These compositions are free from MIPs,
which do not bind the target molecules. Id.
The Examiner finds, however, that Kristensen does not teach
administering MIPs that specifically bind phenylalanine in order to treat
PHA in a patient. To cure these deficiencies, the Examiner relies on
combining Kristensen with Piletsky, Levy, and Ross. Piletsky teaches MIPs
that specifically bind to phenylalanine. Final Act. 24. Levy teaches that
phenylketonuria (“PKU”), with its associated HPA and mental retardation, is
a classic genetic disease where successful treatment of HPA requires control
of ingested phenylalanine, and suggests that patients with PKU would
welcome any method to alleviate the strain and biochemical abnormalities
imposed by diet. Id. at 21–22, 26. Ross teaches methods for synthesizing
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MIPs having an affinity for dietary phosphates and their use for treatment of
hyperphosphatemia thereby constituting the oral administration of MIPs that
can be used to decrease the serum level of dietary molecules in patients with
metabolic disorders by binding the dietary molecules in the patient’s
gastrointestinal tract and excreting them in the patient’s feces thereby
preventing their uptake in the patient’s blood. Id. at 22–23, 26.
Therefore, the Examiner concludes, it would have been obvious to a
skilled artisan to make and use phenylalanine MIPs for the treatment,
amelioration, or prophylaxis of HPA. Final Act. 26. A person of ordinary
skill in the art would have been motivated to combine the references,
because there was great interest and need in developing dietary substitutes to
alleviate the strain and biochemical abnormalities experienced by patients
with HPA. Id. The Examiner further concludes that, because the use of
orally administered MIP composition for decreasing the serum level of
dietary molecules in patients with metabolic disorders by binding the dietary
molecules in the patient’s gastrointestinal tract and excreting them in the
patient’s feces are known in the art. Id.
Appellant argues that the Examiner has not established a prima facie
case of obviousness because a person of ordinary skill in the art would not
have had a reasonable expectation of success in achieving the claimed
invention. App. Br. 8. Appellant asserts that while the inventors of the
claims on appeal found that the method disclosed in Kristensen can provide
for MIPs of sufficiently strong binding, a person of ordinary skill in the art
would know from the prior art only that (1) MIPs against phenylalanine can
be prepared, and (2) that such MIPs can be “improved” by the Kristensen
technology. Id. However, Appellant argues that there is nothing in the prior
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art to suggest to a skilled person that the MIPs purified according to
Kristensen would have the necessary binding properties to be relevant for
the treatment of the diseases claimed. Id.
Appellant also argues that a person of ordinary skill in the art would
not have a reasonable expectation of success because: (1) Ross provides
MIPs that are less effective than the existing therapeutic agents; (2) Piletsky
provides MIPs that are only good binders when suspended in organic
solvents; (3) Kristensen is silent on any quantitative improvements in
binding properties provided by the process disclosed therein; (4) diseases
such as PKU have only been treated by strict dietary measures; and (5) Levy
suggests substituting the missing enzymatic activity, which would not be an
effect obtainable by using MIPs. Final Act. 8–9.
We are not persuaded by Appellant’s argument. We acknowledge
Appellants’ arguments regarding the defects in each cited reference.
However, “[t]he test for obviousness is not whether … the claimed invention
must be expressly suggested in any one or all of the references. Rather, the
test is what the combined teachings of the references would have suggested
to those of ordinary skill in the art.” In re Keller, 642 F.2d 413, 425
(C.C.P.A. 1981) (emphasis added). Furthermore, one cannot show
nonobviousness by attacking references individually where the rejections are
based on combinations of references. Keller, 642 F.2d at 426; In re Merck
& Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
In the appeal presently before us, the Examiner relies on Kristensen
for teaching a method of treating, ameliorating, or reducing the risk of a
disease by administering to the gastrointestinal tract of a patient MIPs
having high binding capacity and specificity for binding target molecules
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found in the patient’s gastrointestinal tract, but also upon Piletsky for
teaching MIPs that specifically bind phenylalanine, Levy for establishing
that there is a great interest and need in approaches substituting for diet in
order to alleviate the strain and biochemical abnormalities imposed by the
diet in patients with HPA, and Ross for teaching the use of orally
administered MIP composition for decreasing the serum level of dietary
molecules in patients with metabolic disorders by binding the dietary
molecules in the patient’s gastrointestinal tract and excreting them in the
patient’s feces.
We agree with the Examiner that a person of ordinary skill in the art
would conclude that the claims are obvious over the teachings of the
combined references. Appellant finds fault with the references individually,
but does not engage with the Examiner’s finding the combined teachings of
the references. That is not sufficient to overcome the Examiner’s prima
facie conclusion of obviousness.

Issue 3
Appellant argues that the Examiner erred in dismissing the
Appellants’ arguments regarding Piletsky as irrelevant. App. Br. 9–10.

Analysis
The Examiner finds that the optimization of the mobile phase for
HPLC studies of hydrophobic and electrostatic interactions involved in
ligand recognition by MIPs taught by Piletsky is clearly irrelevant to the
issue whether MIPs are suitable for treatment of PKU. Ans. 31.
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Appellant argues that the Jensen Declarations demonstrate that a
person of ordinary skill in the art would not have a reasonable expectation of
success in light of the teachings of Piletsky. App. Br. 9–10 (citing 2019
Jensen Decl., 3). Jensen states that the MIPs of Piletsky exhibit optimum
binding when the MIPs are suspended in increasing amounts of organic
solvent and there are no organic solvents present in any significant amounts
in the gastrointestinal tract. Id. As such, Jensen opined that a person of
ordinary skill in the art would not have a reasonable expectation of success
because there is no expectation that the same optimum binding of the MIPs
in the presence of an organic solvent would occur in the gastrointestinal tract
lacking the organic solvent. Id.
We are not persuaded by Appellant’s argument. We acknowledge
that Piletsky teaches that MIPs capable of binding phenylalanine exhibit
optimum binding when suspended in increasing amounts of organic solvent.
We also acknowledge that the same organic solvents tested are not present in
any significant amounts in the gastrointestinal tract, and acknowledge that
the Jensen Declaration states that a person of ordinary skill in the art would
not have a reasonable expectation of success in light of the evidence taught
by Piletsky. See 2019 Jensen Decl. 3. However, as we have explained
supra, the teachings of Piletsky are combined with those of Kristensen,
Ross, and Levy. Kristensen expressly teaches a method for improved
preparation of MIPs that are enriched for those MIP particles that bind to
particular target molecules. Final Act. 24 (citing Kristensen Abstr.). Neither
Appellant nor the Jensen Declarations address the combined teachings of the
references to establish that the MIPs suggested by the combination of
references would not reasonably be expected to bind phenylalanine in the
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gastrointestinal tract of a patient. We therefore find that Appellant fails to
provide evidence showing that a person of ordinary ski in the art could have
had no reasonable expectation of success.
Additionally, obviousness does not require absolute predictability,
however, at least some degree of predictability is required. Evidence
showing there was no reasonable expectation of success may support a
conclusion of nonobviousness. In re Rinehart, 531 F.2d 1048, 1052 (CCPA
1976). Piletsky does not teach or suggest that the MIPs exhibiting optimum
binding in the presence of an organic solvent cannot be administered in vivo,
or that the MIPs would exhibit no binding in the absence of an organic
solvent. As we have explained, the scope of the claimed methods
encompass any amount of treatment and/or amelioration resulting from any
amount of binding. As such, the same optimum binding of the MIPs in the
presence of an organic solvent is not necessary to read on the scope of the
claimed methods.
Furthermore, Appellant has not provided any data to suggest that the
MIPs taught by Piletsky would not exhibit any binding to phenylalanine in
the gastrointestinal tract. The Jensen Declarations do not provide any
factual support that the MIPs taught by Piletsky would not exhibit any
binding to phenylalanine in the gastrointestinal tract.
We consequently conclude that the combined teachings of Piletsky
and Kristensen, which teach methods of preparing MIPs to exhibit improved
binding to a target molecule, outweighs the testimony of the Jensen
Declaration opinion. See Ashland Oil at 294. We therefore conclude that
the totality of the rebuttal evidence of nonobviousness fails to outweigh the
evidence of obviousness.
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Issue 4
Appellant argues that the Examiner erred by dismissing the
Appellant’s arguments with respect to the teachings of Ross. App. Br. 10–
11.

Analysis
The Examiner finds that Dr. Jensen’s opinions with respect to
inoperability of Ross is not supported by any factual data. Ans. 33. The
Examiner emphasized that Ross teaches methods for synthesizing MIPs
having an affinity for dietary phosphates and their use for treatment of
hyperphosphatemia. Id. The Examiner further relies on the combination of
Ross with Kristensen, which teaches preferred methods of preparing
insoluble MIPs as indicated by the Specification. Id. Therefore, the
Examiner concludes that when all of the evidence is considered, the totality
of the rebuttal evidence of nonobviousness fails to outweigh the evidence of
obviousness. Id.
Appellant argues the Examiner has misunderstood the argument
regarding Ross. App. Br. 10. Contrary to the Examiner’s understanding, the
Appellant is not asserting that Ross is inoperable. Id. Rather, Appellant
argues that the Jensen Declarations demonstrate that the MIPs used in Ross
are less effective than the known means for reducing phosphate levels, and
that Phe–binding MIPs having comparable binding properties as those
provided in Ross would not motivate a skilled person to utilize such Phe–
binding MIPs in treatment of the diseases claimed because an effective
phenylalanine–binding MIP composition would need to be administered in a
prohibitively high amount (at least 81 grams) per day. Id. Appellant further
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argues that the Examiner has not provided any explanation as to why the
conclusions regarding Ross made by Jensen are erroneous. Id.
We are not persuaded by Appellant’s argument. As we have
explained supra, the claimed methods are rejected based on a combination
of references and not on Ross alone. Kristensen expressly teaches a method
for treating, ameliorating or reducing the risk of a disease by administering
an effective amount of a composition comprising MIPs that exhibit improved
binding to a target molecule in the gastrointestinal tract of a patient in need
of such treatment. Final Act. 24–25 (citing Kristensen, abst.; 5:25–31; 7:1–
6; 23:23–25; 24:21–28) (emphasis added). As discussed supra, the claimed
effective amount is not limited. Thus, the Jensen Declaration’s discussion of
Ross does not take into account that Ross is combined with additional
references. We, therefore, agree with the Examiner’s conclusion that when
all of the evidence is considered, the totality of the rebuttal evidence of
nonobviousness fails to outweigh the evidence of obviousness.
Accordingly, we affirm the Examiner’s rejection of these claims.

CONCLUSION
The rejection of claims 3–12 as failing the written description
requirement under 35 U.S.C. § 112(a) is affirmed.
The rejection of claims 3–12 as unpatentable under 35 U.S.C. § 103(a)
is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(1)(iv).

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AFFIRMED

Claims
Rejected
35 U.S.C. §  Reference(s)/Basis Affirmed Reversed
3–12 112(a) Written Description 3–12
3–12 103(a) Levy, Piletsky, Ross,
Kristensen
3–12
Overall
Outcome
3–12