Cornelis Hack et al.

Patent Trials and Appeals Board

Dec 24, 2021

2021001235 (P.T.A.B. Dec. 24, 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.
14/240,903 06/09/2014 Cornelis Erik Hack P6041926PCT/US 2225
132452 7590 12/24/2021
N.V. Nederlandsch Octrooibureau
New Babylon City Offices
Anna van Buerenplein 21a
The Hague, 2595 DA
NETHERLANDS
EXAMINER
DILLAHUNT, SANDRA E
ART UNIT PAPER NUMBER
1646
NOTIFICATION DATE DELIVERY MODE
12/24/2021 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):
USPTO@nlo.eu
shultz@nlo.eu
uspractice@nlo.eu
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte CORNELIS ERIK HACK and CAFER YILDIZ
____________

Appeal 2021-001235
Application 14/240,903
Technology Center 1600
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
ULRIKE W. JENKS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s
decision to reject claims 16, 18, 20, 21, 25, and 27 (Appeal Br. 2). 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 “UMC
Utrecht Holding B. V.” (Appellant’s November 5, 2020, Appeal Brief
(Appeal Br.) 2).
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STATEMENT OF THE CASE
Appellant’s disclosure relates to “a method . . . to boost thrombin
activity to stimulate blood clotting” (Spec.2 1). Claim 16 is reproduced
below:
16. A method for treating or reducing the risk of bleeding in a
human hemophilia patient comprising administering to the
patient an effective amount of an inhibitor of antithrombin III
that is an antibody or antibody fragment that specifically binds
to antithrombin III,
wherein, activity of the antibody or antibody fragment inhibitor
is characterized as follows:
(a) when the antibody inhibitor is added to pooled plasma from
a healthy subject and mixed with thrombin or factor Xa to form
a mixture, the mixture prevents, by more than 20%, a reduction
in activity of the thrombin and factor Xa by the plasma in an in
vitro assay of thrombin activity and factor Xa-activity,
compared to the reduction in the activity of the thrombin or the
factor Xa in a mixture containing the same pooled plasma but in
the absence of the added inhibitor; and
(b) the activity described in (a) is correlated with the ability of
the antibody or fragment, when administered to said patient, to
bind to antithrombin III and to treat or reduce the risk of
bleeding in said patient.
(Appeal Br. 11.)

Claims 16, 18, 20, 21, 25, and 27 stand rejected under the written
description provision of 35 U.S.C. § 112, first paragraph.

2 Appellant’s February 25, 2014, Specification.
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ISSUE
Does the preponderance of evidence on this record support
Examiner’s finding that Appellant’s Specification fails to provide written
descriptive support for the claimed invention?
ANALYSIS
The method of Appellant’s claim 16, reproduced above, comprises,
inter alia, the administration of an effective amount of an antibody or
antibody fragment that specifically binds to and is an inhibitor of
antithrombin III. In addition, Appellant’s claim 16 requires that:
(a) when the antibody inhibitor is added to pooled plasma from
a healthy subject and mixed with thrombin or factor Xa to form
a mixture, the mixture prevents, by more than 20%, a reduction
in activity of the thrombin and factor Xa by the plasma in an in
vitro assay of thrombin activity and factor Xa-activity,
compared to the reduction in the activity of the thrombin or the
factor Xa in a mixture containing the same pooled plasma but in
the absence of the added inhibitor; and
(b) the activity described in (a) is correlated with the ability of
the antibody or fragment, when administered to said patient, to
bind to antithrombin III and to treat or reduce the risk of
bleeding in said patient.
(see generally Ans.3 4 (Examiner finds that Appellant’s claim 16 “broadly
encompass[es] a genus of antibodies described solely by their function of
binding to antithrombin III and preventing, by more than 20%, a reduction in
activity of the thrombin and factor Xaa when added to pooled plasma, as
measured by an in vitro assay of thrombin or Xaa activity”).)
Examiner finds that Appellant’s Specification “discloses two anti-
antithrombin III polyclonal antibodies; however, no antibody is described by

3 Examiner’s September 3, 2020, Answer.
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CDRs or other sequences” (id. at 5–6). Appellant’s antibodies, and
fragments thereof, are instead described only by their function (id. at 6).
Examiner finds that “functional characteristics of antibodies (including
binding specificity and affinity) are dictated on their structure” and that
“[a]mino acid sequence and conformation of each of the heavy and light
chain CDRs are critical in maintaining the antigen binding specificity and
affinity which is characteristic of the parent immunoglobulin” (id. at 6
(citing Vajdos4)). Examiner finds that amino acid modification of “any
given CDR” has unpredictable effects on antibody binding (Ans. 6 (citing
Brown5)).
Examiner further finds that Appellant’s Specification
provides no description of how binding of an antibody in any
specific region of antithrombin III would lead to inhibition or
blocking of its activity. It is possible that binding to
antithrombin III at some antigen sequences will not result in
inhibited activity, as they may not affect conformation, protein
binding or other aspects of antithrombin III activity. Without
demonstration that any antibody that binds antithrombin III
would result in neutralization of antithrombin III activity, one
of ordinary skill in the art could not predict the potential
neutralizing capability of any given antibody. Antibodies are
capable of binding to any number of possible epitopes on a

4 Vajdos et al., Comprehensive Functional Maps of the Antigen-binding Site
of an Anti-ErbB2 Antibody Obtained with Shotgun Scanning Mutagenesis,
320 J. Mol. Biol. 415–428 (2002).
5 Brown et al., Tolerance to Single, but Not Multiple, Amino Acid
Replacements in Antibody VH CDR2: A Means of Minimizing B Cell
Wastage from Somatic Hypermutation?, 156 J. Immunol. 3285–3291 (1996).
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given protein, and not all of those interactions will result in lost
activity for the antigen protein.
(Ans. 6–7 (citing Knoller6).)
In sum, Examiner finds, “with the exception of two polyclonal
antibodies,” Appellant’s Specification “does not disclose any antibody
having the claimed functions” and, thus, Appellant’s claim 16
“encompass[es] a vast genus of antibodies that have no correlation between
their structure and function” (id. at 4). Examiner, therefore, finds that
Appellant’s Specification fails to provide written descriptive support for the
entire genus encompassed by Appellant’s claim 16 (id.).
“[T]he test for sufficiency [of the written 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.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351
(Fed. Cir. 2010) (en banc). To be complete, we note that the written
description standard set out in Ariad applies to antibodies. See
Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1376–79 (Fed. Cir. 2017) (applying
the Ariad standard to antibodies claimed based on their binding and blocking
activities); see also AbbVie Deutschland GmbH & Co. v. Janssen Biotech,
Inc., 759 F.3d 1285, 1298–1300 (Fed. Cir. 2014) (same).
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.”

6 Knoller et al., Monoclonal Antibodies Against Antithrombin III:
Identification of Their Epitopes and Effects on Antithrombin III Activities,
180 Eur. J. Biochem. 319–326 (1989).
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Ariad, 598 F.3d at 1350. “[A]n adequate written description requires a
precise definition, such as by structure, formula, chemical name, physical
properties, or other properties, of species falling within the genus sufficient
to distinguish the genus from other materials.” Id. Although “functional
claim language can meet the written description requirement when the art
has established a correlation between structure and function,” “merely
drawing a fence around the outer limits of a purported genus is not an
adequate substitute for describing a variety of materials constituting the
genus and showing that one has invented a genus and not just a species.” Id.
In addition, although Appellant's claim 16 is directed to a method rather than
a product, we note that the same standard applies with regard to the written
description requirement. As the Rochester Court made clear:
Regardless whether a compound is claimed per se or a method
is claimed that entails the use of the compound, the inventor
cannot lay claim to that subject matter unless he can provide a
description of the compound sufficient to distinguish infringing
compounds from non-infringing compounds, or infringing
methods from non-infringing methods.
Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir.
2004).
For the foregoing reasons, we agree with Examiner’s finding the
Appellant’s Specification fails to provide written descriptive support for the
genus of antibodies, and fragments thereof, that fall within the scope of
Appellant’s claim 16.
“One shows that one is ‘in possession’ of the invention by describing
the invention, with all its claimed limitations, not that which makes it
obvious. . . . One does that by such descriptive means as words, structures,
figures, diagrams, formulas, etc., that fully set forth the claimed invention.”
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Lockwood v. Am. Airlines Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997)
(emphasis omitted); see also Ariad, 598 F.3d at 1352 (Although those of
ordinary skill in this art may understand how to prepare antibodies, “it is the
specification itself that must demonstrate possession. And 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.”). Therefore, we are not persuaded by Appellant’s
contentions that the disclosed methods of making and screening antibodies
provide a description of the claimed antibodies (see Appeal Br. 6–10).
We acknowledge Appellant’s contention that antibodies that bind
antithrombin III were known in the art (see Appeal Br. 7–8). For example,
Appellant contends that “Knoller describes two antibodies, A36 and B108,
that interfere with antithrombin III inhibition of thrombin” (Appeal Br. 7
(citing Knoller 323–324)). We note, however, that, in contrast to
Appellant’s contention to the contrary, Knoller supports Examiner’s
findings. In particular, Knoller discloses that although “A36 could prevent
heparin-enhanced AT activity only if it was reacted with AT prior to the
addition of heparin;” “B108 enhanced AT activity in the absence or in the
presence of heparin” and a third antibody, A10, “had no effect” (Knoller
324). Appellant fails to direct attention to a disclosure in its Specification,
or in Knoller, that describes the structural differences between these three
antibodies that result in each antibody’s functional differences.
As discussed above, regardless of whether a claim is directed to a
method or product, the same standard applies with regard to the written
description requirement. See Rochester, 358 F.3d at 926. Therefore, we are
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not persuaded by Appellant’s contention that its claim 16 is directed to a
method not an antibody or genus of antibodies (Appeal Br. 7).
CONCLUSION
The preponderance of evidence on this record supports Examiner’s
finding that Appellant’s Specification fails to provide written descriptive
support for the claimed invention. The rejection of claim 16 under the
written description provision of 35 U.S.C. § 112, first paragraph, is affirmed.
Claims 18, 20, 21, 25, and 27 are not separately argued and fall with claim
16.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
16, 18, 20,
21, 25, 27
112, first
paragraph
Written
Description
16, 18, 20,
21, 25, 27

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) (2019).

AFFIRMED