BIOMERIEUX et al.

Patent Trials and Appeals Board

Aug 19, 2021

2021001845 (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.
14/701,002 04/30/2015 Yasemin ATAMAN-ONAL 143869.02 1246
25944 7590 08/19/2021
OLIFF PLC
P.O. BOX 320850
ALEXANDRIA, VA 22320-4850
EXAMINER
GODDARD, LAURA B
ART UNIT PAPER NUMBER
1642
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):
OfficeAction25944@oliff.com
jarmstrong@oliff.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte YASEMIN ATAMAN-ONAL,
SANDRINE BUSSERET, JEAN-PHILIPPE CHARRIER, and
GENEVIEVE CHOQUET-KASTYLEVSKY1
________________

Appeal 2021-001845
Application 14/701,002
Technology Center 1600
________________

Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
JOHN G. NEW, Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies bioMerieux, Centre National de la
Recherche Scientifique, and Institut Curie as the real parties-in-interest.
App. Br. 1.
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SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Non-Final Rejection of claims 11–14 and 18–27 as unpatentable
under 35 U.S.C. § 112(a) as failing to comply with the written description
requirement.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to a method for the in vitro
diagnosis of colorectal cancer by determining the presence of the Ezrin
tumor marker in a biological sample, and using at least one anti-Ezrin
monoclonal antibody directed against an Ezrin epitope. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claim 11 is representative of the claims on appeal and
recites:
11. An assay system comprising:

a first non-human monoclonal antibody directed against
the epitope of SEQ ID No.1; and

a second non-human monoclonal antibody directed
against an epitope selected from the group consisting of SEQ ID
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No.2, SEQ ID No.4+SEQ ID No.52, and SEQ ID No.6+SEQ ID
No.7.

App. Br. Claims App’x A-1.

ISSUE AND ANALYSIS
We agree with and adopt the Examiner’s findings, reasoning, and
conclusion that the claims lack the requisite written descriptive support in
Appellant’s Specification. We address below the arguments raised by
Appellant.

Issue
Appellant argues that the Examiner erred because a person of ordinary
skill in the art would understand from Appellant’s Specification that
Appellant was in possession of the claimed invention at the time the
invention was filed. App. Br. 4.

Analysis
The Examiner finds that the claims are drawn to an assay or kit
comprising or using a first non-human monoclonal antibody directed against
the epitope of SEQ ID NO:1; and a second nonhuman monoclonal antibody

2 The expression “epitope of sequence SEQ ID No.X+SEQ ID No.Y” is
intended to mean an epitope constituted of two distinct parts of the protein
from which the epitope is derived, the antibody which recognizes this
epitope having to recognize these two parts. This recognition is very
probably linked to the sequences being in proximity in the three-
dimensional structure of the protein. Spec. 6.
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directed against an epitope selected from the group consisting of SEQ ID
NO:2, SEQ ID NO:4+5, and SEQ ID NO:6+7. Non-Final Act. 3. The
Examiner therefore finds that the claims broadly encompass all non-human
monoclonal antibodies binding to the claimed sequences of the Ezrin target
protein.3 Id.
The Examiner finds that the Appellant’s Specification, by providing
isolated hybridomas, describes eight monoclonal anti-Ezrin antibodies: two
exemplary antibodies that bind SEQ ID NO:1; two exemplary antibodies
that bind SEQ ID NO:2, one that binds either SEQ ID NO:4 or 5; and one
that binds either SEQ ID NO:6 or 7. Non-Final Act. 4. The Examiner finds
that the Specification does not disclose the structural sequence of the
monoclonal antibodies, i.e., the structural sequence required of an antibody
to possess the function of binding to the specific Ezrin sequence epitopes
recited in the claims. Therefore, the Examiner finds, the Specification does
not provide sufficient representative examples or adequate description for
the entire genus of non-human monoclonal antibodies binding to SEQ ID
NOs:1, 2, 3+4, and 6+7.
The Examiner notes that, to provide adequate written description and
evidence of possession of the claimed antibody genus, Appellant’s
Specification can: (1) structurally describe representative anti-Ezrin
antibodies that function to specifically bind the epitopes of SEQ ID NO:1, 2,

3 The Ezrin marker (Swiss Prot No. P15311, also known as p81, Cytovillin
or Villin-2) is a protein which provides binding between the cell membrane
and actin filaments of the cytoskeleton of the cell, and has been described
as a diagnostic marker for certain cancers, such as colon cancer. Spec. 3–
4.
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4+5, and 6+7; or (2) describe structural features common to the members of
the genus, which features constitute a substantial portion of the genus. Non-
Final Act. 4–5. Alternatively, the Examiner finds, the Specification can
show that the claimed invention is complete by disclosure of sufficiently
detailed, relevant identifying characteristics, functional characteristics when
coupled with a known or disclosed correlation between function and
structure, or some combination of such characteristics. Id. at 5 (citing
University of California v. Eli Lilly and Co., 119 F.3d 1559 (Fed. Cir.
1997)). The Examiner further reasons that a disclosure that does not
adequately describe a product itself logically cannot adequately describe a
method of using that product. Id.
The Examiner finds, in the appeal presently before us, that the only
factor present in the claims is a recitation of the antibody function: “directed
against the epitope of SEQ ID NO:#.” Non-Final Act. 5. The Examiner
finds that Appellant’s Specification fails to describe structural features
common to the members of the genus, because the Specification fails to
disclose a single exemplary antibody sequence that functions as claimed. Id.
at 5–6. The Examiner finds that a functional definition of an antibody does
not suffice to define the genus, because it is only an indication of what the
antibody does, rather than what it is. Id. at 6. The Examiner finds that
Appellant’s Specification fails to provide any structural features coupled to
the claimed functional characteristics, other than for the few named
antibodies. Id. The Examiner also finds that the Specification fails to
describe a sufficient representative number of antibody sequences for the
potentially vast genus of antibodies that function as claimed. Id.
Accordingly, the Examiner concludes, in the absence of sufficient recitation
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of distinguishing identifying characteristics, Appellant’s Specification does
not provide adequate written description of the claimed genus. Id.
Appellant argues that the Examiner acknowledges that the
Specification discloses methods for producing non-human monoclonal
antibodies (and particularly mouse antibodies), and also describes the recited
epitopes (which define binding domains). App. Br. 5 (citing Non-Final Act.
4). Appellant asserts that the epitopes are defined by sequence (SEQ ID
No.1 and SEQ ID No.2, SEQ ID No.4+SEQ ID No.5, and SEQ ID
No.6+SEQ ID No.7), which are set forth in Table 6 of the Specification, as
well as in the sequence listing. Id. Appellant contends that, in view of the
routine, art-recognized method of making antigen-specific antibodies, one of
ordinary skill in the art would have recognized that Appellant’s disclosure of
SEQ ID No.1, SEQ ID No.2, SEQ ID No.4+SEQ ID No.5, and SEQ ID
No.6+SEQ ID No.7 put Appellant in possession of non-human monoclonal
antibodies that bind to the recited epitopes. Id.

Appellant argues further that the Examiner has misapplied the law of
§ 112(a). App. Br. 5. Appellant contends that the Examiner’s reliance upon
University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916 (Fed. Cir.
2004) and AbbVie Deutsch/and Gmbh v. Janssen Biotech, Inc., 759 F.3d
1285 (Fed. Cir. 2014) as supporting the position that the Specification does
not support the full scope of the claimed antibodies is misplaced. Id. (citing
Non-Final Act. 5–7). Specifically, Appellant argues that the appeal before
us can be distinguished from those cases. Id.
Appellant first argues that, to the extent that the cited cases do not
relate to assay system, kit, or method claims, they are not pertinent to the
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instant claims. App. Br. 5. Furthermore, argues Appellant, the claims at
issue in those cases all recited a particular therapeutic effect; that is, the
recited compounds or antibodies were defined by their therapeutic function.
Id. Appellant points to the claims in Rochester as reciting a non-steroidal
compound “that selectively inhibits activity of the PGHS-2 gene product in a
human host in need of such treatment.” Id. at 5–6 (quoting Rochester, 358
F.3d at 918). Appellant argues that our reviewing court characterized the
inhibitory function as a “critical aspect” of the claimed method, and noted
that this aspect of the invention was “hypothetical” because the inventors
never had actual knowledge of such inhibiting compounds. Id. at 6 (citing
Rochester, 358 F.3d at 926–27).
Appellant notes that the court found that, because the specification
“did not provide any guidance that would steer the skilled practitioner
toward [the recited] compound … and has not provided evidence that any
such compounds were otherwise within the knowledge of a person of
ordinary skill in the art,” it concluded that the specification did not set forth
enough detail to allow a person of ordinary skill in the art to recognize that
the inventors invented what was claimed. Id. (quoting Rochester, 358 F.3d
at 929).
Appellant also argues that the instant claims can be distinguished from
the claims at issue in AbbVie. According to Appellant, the claims in AbbVie
were directed to fully human antibodies useful for treating diseases. App.
Br. 6 (citing AbbVie, 759 F.3d at 1290–91). Appellant contends that the
claims defined the antibodies by their ability to neutralize interleukin 12
activity. Id. (citing AbbVie, 759 F.3d at 1299). According to Appellant, the
court emphasized the challenges in developing fully human antibodies, and
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held that the specification (which only described a small number of human
antibodies) did not support a claim to every fully human antibody that would
achieve the recited neutralizing activity. Id. (citing AbbVie, 759 F.3d at
1301) (citing Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341,
1352 (2011)).
Appellant points to the Examiner’s citation to AbbVie as holding that
“if the disclosed species only abide in a corner of the genus, one has not
described the genus sufficiently to show that the inventor invented, or had
possession of, the genus.” App. Br. 6 (citing Non-Final Act. 6 (quoting
AbbVie, 759 F.3d at 1300)). However, argues Appellant, the Examiner
quotes this single statement from AbbVie without any consideration of the
particular issues that the court was addressing. Id. Appellant points to the
court’s discussion in the very next paragraph, which warned that the analysis
should not be taken “too far” in the analysis of written description issues,
“because, even if one builds a house only in one corner of the plot, one may
still own the whole plot.” Id. (quoting AbbVie, 759 F.3d at 1300).
Pertinently, Appellant argues, the Examiner did not address the court’s focus
on the fact that the antibodies in AbbVie were human antibodies that were
difficult to develop, and imparted a particular therapeutic effect. Id. at 6–7.
Appellant also points to our reviewing court’s decisions Fiers v.
Revel, 984 F.2d 1164 (Fed. Cir. 1993), University of California v. Eli
Lilly & Co., 119 F.3d 1559 (Fed. Cir. 1997), and Enzo Biochem, Inc. v. Gen-
Probe Inc., 323 F.3d 956 (Fed. Cir. 2002), cited by the Examiner. App. Br.
7 (citing Non-Final Act. 5). Appellant contends that the facts in these cases
can also be distinguished from those in the appeal presently before us. Id.
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In Fiers, for example, the claims at issue were directed to DNA, and
the specification did not disclose any methods for producing the claimed
DNA. The court held that a “bare reference” to the DNA did not indicate
that the inventors were in possession of the DNA. App. Br. 7 (citing Fiers,
984 F.2d at 1166, 1171). In contrast, Appellant argues, the Specification
sets forth a detailed description for producing the recited antibodies
according to conventional techniques and based on disclosed epitope
sequences. Id. (citing Spec., 20, 38–40).
Appellant argues that the claims in Eli Lilly related to recombinant
plasmids and microorganisms that produce human insulin, and the
Specification provided only a general method by way of a constructive
example, which the court held did not sufficiently describe the invention.
App. Br. 7 (citing Eli Lilly, 119 F.3d at 1562, 1567). However, Appellant
contends, the court did not “speculate” about scenarios in which non-genetic
material is properly described. Id.
According to Appellant, the claims in Enzo Biochem were directed to
nucleic acid probes defined by their ability to hybridize to deposited strains
of N. gonorrhoeae. App. Br. 7 (citing Enzo Biochem, 323 F.3d at 960).
Appellant points to the court’s statement that “[i]t is not correct … that all
functional descriptions of genetic material fail to meet the written
description requirement.” Id. at 8 (citing Enzo Biochem, 323 F.3d at 964).
Finally, Appellant points to the Federal Circuit’s decision in Amgen
Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). App. Br. 8. Appellant points
out that the court’s decision in that case “follows the Federal Circuit’s
pattern of finding claims directed to human or humanized antibodies invalid
for lack of adequate written description.” Id. (emphases in original).
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Appellant contends that the claims at issue in Amgen all recited a
particular therapeutic effect: blocking binding of PCSK9 to LDL-R. App.
Br. 8 (citing Amgen, 872 F.3d at 1372). Appellant relates that the Federal
Circuit noted the “trial-and-error process” that the inventors used to generate
human monoclonal antibodies that were effective as PCSK9 inhibitors for
treatment of high levels of LDL cholesterol in the bloodstream. Id. (citing
Amgen, 872 F.3d at 1371–72). The court rejected the district court’s jury
instructions, which stated that a correlation between structure and function
could be satisfied for any antibody by the disclosure of a fully characterized
antigen if the level of skill and knowledge in the art was such that
production of antibodies against the antigen was conventional or routine. Id.
(citing Amgen, 872 F.3d at 1376–79. Appellant notes that, although the
court acknowledged that “as long as an applicant has disclosed a ‘fully
characterized antigen,’ … the applicant can then claim an antibody by its
binding affinity to that described antigen,” (Amgen, 872 F.3d at 1377
(quoting Noelle v. Lederman, 355 F.3d 1343, 1349 (Fed. Cir. 2004)).
Appellant also contends that the court also emphasized that “each case
involving the issue of written description[] ‘must be decided on its own
facts’” (Amgen, 872 F.3d at 1377 (quoting Vas-Cath Inc. v. Mahurkar, 935
F.2d 1555, 1562 (Fed. Cir. 1991)).
Appellant acknowledges that the Amgen court held that the disclosure
of a fully characterized antigen is likely not sufficient to satisfy the written
description for all antibodies against the antigen, it did not indicate that such
disclosure would never be sufficient to satisfy the written description for a
claimed antibody against the antigen. App. Br. 9. Instead, Appellant argues,
it emphasized that the issue of whether the claims are adequately supported
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by the written description is a fact-based inquiry, and that the “newly
characterized antigen” test “flouts basic legal principles of the written
description requirement” to the extent that it is applied as a per se rule. Id.
(quoting Amgen, 872 F.3d at 1377).
Appellant argues that because the claims at issue in Amgen were
directed to human antibodies that exhibited a particular therapeutic effect,
disclosing the structure of the antigen was not enough to satisfy the written-
description requirement. App. Br. 9. Appellant asserts that such is not the
case with the instant claims, which are not directed to antibodies (human or
otherwise) having any particular therapeutic effect. Id. Rather, argues
Appellant, the claims are drawn not to an antibody, but are drawn to an
assay system, kit, or method. Id. Therefore, Appellant contends, the Amgen
does not change the fact that the instant claims are supported by the written
description. Id.
We are not persuaded by Appellant’s arguments. As an initial matter,
we agree with Appellant that the claims on appeal are severally directed to
either a system (independent claim 11), a kit (independent claim 13), or a
method (independent claim 25). Nevertheless, each of the claims comprise
primarily a “non-human monoclonal antibody directed against the epitope of
SEQ ID No.1” and a “non-human monoclonal antibody directed against an
epitope selected from the group consisting of SEQ ID No.2, SEQ ID
No.4+SEQ ID No.5, and SEQ ID No.6+SEQ ID No.7” or a minor variation
thereof. The question before us, then, is whether the Specification provides
adequate written descriptive support for the non-human monoclonal
antibodies recited in the claims. The written description requirement with
respect to particularly claimed subject matter is met if the specification
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shows that the inventors had in fact invented what is claimed, and that they
had possession of it. Vas–Cath, 935 F.2d at 1563–64. Possession is shown
by disclosure in the patent. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d
1336, 1351 (Fed. Cir. 2010) (en banc). Specifically, to satisfy the written
description requirement for a claimed genus, a patentee may either disclose a
representative number of species falling within the scope of the genus, or
disclose 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.
Amgen, 872 F.3d at 1375–76.
Appellant has elected to claim functionally the genera of antibodies in
question, i.e., the antibodies are claimed by what they do, viz., bind to
epitopes of certain SEQ ID Nos, and not by their structure. Indeed,
Appellant points to no single disclosure of the claimed antibody structure in
the Specification.
We are not persuaded by Appellant’s characterization of the various
Federal Circuit cases presented in its brief. In AbbVie, for example, the
claims functionally characterized human antibodies or antibody fragments
that bind to human IL-2 by the measure of their koff rate (the first-order rate
constant for the dissociation of the protein-ligand complex). According to
our reviewing court:
The koff rate is merely a desired result, rather than the actual
means for achieving that result. The asserted claims are directed
to new compositions, i.e., fully human antibodies having desired
IL–12 binding characteristics. It is undisputed that the structure
of the antibody determines its antigen binding characteristic. In
order to demonstrate that it has invented what is claimed,
AbbVie’s patents must adequately describe representative
antibodies to reflect the structural diversity of the claimed genus.

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AbbVie, 759 F.3d at 1301 (citing Eli Lilly, 119 F.3d at 1568; Fiers, 984 F.2d
at 1171).
In so holding, the court noted that:
Functionally defined genus claims can be inherently vulnerable
to invalidity challenge for lack of written description support,
especially in technology fields that are highly unpredictable,
where it is difficult to establish a correlation between structure
and function for the whole genus or to predict what would be
covered by the functionally claimed genus.… It is true that
functionally defined claims can meet the written description
requirement if a reasonable structure-function correlation is
established, whether by the inventor as described in the
specification or known in the art at the time of the filing date.

Id. (citations omitted). In this case, as in AbbVie, the record here does not
indicate such an established correlation.
Similarly, in Amgen, the claims at issue covered the entire genus of
antibodies that bind to specific amino acid residues on PCSK9 and block
PCSK9 from binding to LDL-Rs:
An isolated monoclonal antibody, wherein, when bound to
PCSK9, the monoclonal antibody binds to at least one of the
following residues: S153, I154, P155, R194, D238, A239, I369,
S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID
NO:3, and wherein the monoclonal antibody blocks binding of
PCSK9 to LDL[-]R.

Amgen, 872 F.3d at 1372 (quoting US 8,829,165 col. 427 ll. 47–53). The
Amgen claims closely mirror the claims presently on appeal.
In Amgen, the court held that:
An adequate written description must contain enough
information about the actual makeup of the claimed products—
“a precise definition, such as by structure, formula, chemical
name, physical properties, or other properties, of species falling
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within the genus sufficient to distinguish the genus from other
materials,” which may be present in “functional” terminology
“when the art has established a correlation between structure and
function.”

Id. at 1378 (quoting Ariad, 598 F.3d at 1350). The court expressly rejected
the jury instructions given by the district court below, which stated:
In the case of a claim to antibodies, the correlation between
structure and function may also be satisfied by the disclosure of
a newly characterized antigen by its structure, formula, chemical
name, or physical properties if you find that the level of skill and
knowledge in the art of antibodies at the time of filing was such
that production of antibodies against such an antigen was
conventional or routine.

Amgen, 872 F.3d at 1376. In rejecting these instructions, the Federal Circuit
held that:
We cannot say that this particular context, involving a “newly
characterized antigen” and a functional genus claim to
corresponding antibodies, is one in which the underlying science
establishes that a finding of “make and use” (routine or
conventional production) actually does equate to the required
description of the claimed products. For us to draw such a
conclusion, and transform a factual issue into a legally required
inference, we would have to declare a contested scientific
proposition to be so settled as to be entitled to judicial notice.
That we cannot do.

Id. at 1378. The court further held that:
[T]he “newly characterized antigen” test flouts basic legal
principles of the written description requirement. Section 112
requires a “written description of the invention.” But this test
allows patentees to claim antibodies by describing something
that is not the invention, i.e., the antigen. The test thus contradicts
the statutory “quid pro quo” of the patent system where “one
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describes an invention, and, if the law’s other requirements are
met, one obtains a patent.”

Id. at 1378–79 (quoting Ariad, 598 F.3d at 1345).
Furthermore, the fact that Appellant’s claims are directed to a kit,
assay, or method comprising “non-human monoclonal antibodies” directed
against the recited epitopes only expands the scope of the genus in question.
The claimed genus could conceivably derive monoclonal antibodies from
rhesus monkey, rat, mouse4, or bottle-nosed dolphin that are directed against
the various epitopes. However, only a single example of the claimed genus
have been disclosed in the Specification. It is self-evident that the structure
of the antibodies contained in such a capacious genus could vary widely.
Appellant has not provided any evidence of a clearly understood structure:
function correlation in the art, or a representative number of species with the
claimed genus such that a person of ordinary skill in the art would
understand that Appellant was in possession of the invention at the time of
filing. We consequently affirm the Examiner’s rejection of the claims.

CONCLUSION
The rejection of claims 11–14 and 18–27 as unpatentable under 35
U.S.C. § 112(a) is affirmed.

AFFIRMED

4 The sole example in the Specification describing production of monoclonal
antibodies discloses monoclonal antibodies produced by mouse
splenocytes fused with Sp2/0-Ag14 myeloma cells. Spec. 39.
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Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
11–14, 18–27 112 Written description 11–14, 18–27