Ex Parte Roemisch et al

Board of Patent Appeals and Interferences

Apr 19, 2010

10359704 (B.P.A.I. Apr. 19, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JUERGEN ROEMISCH, WIEGAND LANG,
ANNETTE FEUSSNER, GUDRUN MUTH-NAUMANN,
HANS-ARNOLD STOEHR, CHRISTIAN KANNEMAIER,
KLAUS PREISSNER, and FUMIE NAKAZAWA
__________

Appeal 2009-007937
Application 10/359,704
Technology Center 1600
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Decided: April 19, 2010
__________

Before CAROL A. SPIEGEL, LORA M. GREEN, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
monoclonal antibody or fragment thereof. The Examiner has rejected claims
as lacking adequate written description and being indefinite. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse the written description
rejection, but affirm the indefiniteness rejection.
Appeal 2009-007937
Application 10/359,704

STATEMENT OF THE CASE
Claims 1, 3, 5, 15, and 21-25 are on appeal (App. Br. 1).1 We will
focus on claim 1, the only independent claim on appeal, which reads as
follows:
1. An isolated monoclonal antibody or fragment thereof that
significantly inhibits at least one of blood clotting factor VII-activating
protease (FSAP) or a FSAP proenzyme at equimolar concentrations.
Claims 1, 3, 5, 15, and 21-25 stand rejected under 35 U.S.C. § 112,
first paragraph, as failing to comply with the written description requirement
(Ans. 4).
Claims 1, 3, 5, 15, and 21-25 stand rejected under 35 U.S.C. § 112,
second paragraph, as being indefinite (Ans. 6).
WRITTEN DESCRIPTION
The Examiner finds that it introduced new matter to amend “claim 1
to recite that the isolated antibody ‘significantly’ inhibits FSAP when
present at ‘equimolar concentrations’” (Ans. 4).
Appellants argue:
[T]he present application expressly supports independent
claim 1, and very nearly provides in haec verba support for a
“monoclonal antibody . . . that significantly inhibits the
proteolytic activity of [FSAP] at equimolar concentrations,” by
disclosing[, at page 8, lines 17-19, of the Specification,] “a
monoclonal antibody for inhibiting scFSAP activation. Even
amounts equimolar to FSAP significantly reduced activation[.]”
(App. Br. 10.)

1 Claims 6, 8, 12-14, 16-18, and 26-30 are also pending but have been
withdrawn from consideration by the Examiner. Claims 2 and 4 have been
indicated to be allowable. (App. Br. 1.)
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Issue
Did the Examiner err in concluding that amending claim 1 to recite an
antibody or fragment thereof that “significantly inhibits” FSAP or a FSAP
proenzyme “at equimolar concentrations” introduced new matter into the
claims?
Findings of Fact
FF1. The Specification states that the invention “relates to a monoclonal
antibody which inhibits the blood clotting factor VII-activating protease
[FSAP] or its proenzyme. Particularly suitable for this purpose is the
monoclonal antibody produced by hybridoma cell line DSM ACC 2533.”
(Spec. 3.)
FF2. In Example 1, the Specification discloses “the effect of the
monoclonal antibody from DSM ACC 2533 on (auto)activation of scFSAP”
(single-chain FSAP), which is the proenzyme (id. at 2 & 7 (emphasis
omitted)).
FF3. The Specification discloses:
[The monoclonal antibody from DSM ACC 2533] is a highly
potent, monoclonal antibody for inhibiting scFSAP activation.
Even amounts equimolar to FSAP significantly reduce
activation, and this renders this inhibitory, monoclonal antibody
a very valuable diagnostic and preparative excipient. The high
effectivity at relatively low concentration makes a potential use
of this monoclonal antibody for administration in humans
attractive.
(Id. at 8.)
Principles of Law
“In order to satisfy the written description requirement, the disclosure
as originally filed does not have to provide in haec verba support for the
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claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding Inc., 230
F.3d 1320, 1323 (Fed. Cir. 2000). Nonetheless, the disclosure must convey
with reasonable clarity to those skilled in the art that the inventor was in
possession of the invention. See id.
“A specification may, within the meaning of 35 U.S.C. § 112, ¶ 1,
contain a written description of a broadly claimed invention without
describing all species that claim encompasses.” Utter v. Hiraga, 845 F.2d
993, 998 (Fed. Cir. 1988). “In the absence of . . . blazemarks, simply
describing a large genus of compounds is not sufficient to satisfy the written
description requirement as to particular species or sub-genuses.” Fujikawa
v. Wattanasin, 93 F.3d 1559, 1571 (Fed. Cir. 1996). However,
[t]he notion that one who fully discloses, and teaches those
skilled in the art how to make and use, a genus and numerous
species therewithin, has somehow failed to disclose, and teach
those skilled in the art how to make and use, that genus minus
two of those species, and has thus failed to satisfy the
requirements of § 112, first paragraph, appears to result from a
hypertechnical application of legalistic prose relating to that
provision of the statute.
In re Johnson, 558 F.2d 1008, 1019 (CCPA 1977).
Analysis
The Specification states that the invention “relates to a monoclonal
antibody which inhibits . . . [FSAP] or its proenzyme” (FF1). The Examiner
does not allege that the Specification does not provide adequate written
description to support the genus of monoclonal antibodies that inhibit FSAP
or its proenzyme (Ans. 4-5).
Within this genus, the Specification discloses that the monoclonal
antibody produced by hybridoma cell line DSM ACC 2533 is a
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“[p]articularly suitable” species (FF1). The Specification states that this
species “is a highly potent, monoclonal antibody for inhibiting scFSAP
activation” and that “[e]ven amounts equimolar to FSAP significantly reduce
activation” (FF3). The Specification also states that “this renders this
inhibitory, monoclonal antibody a very valuable diagnostic and preparative
excipient” and that the “high effectivity at relatively low concentration
makes a potential use of this monoclonal antibody for administration in
humans attractive” (FF3). Based on these disclosures, we agree with
Appellants that their Specification clearly conveys that they were interested
in those monoclonal antibodies within the broader genus that significantly
reduce activation even at equimolar amounts. Thus, we agree with
Appellants that it did not introduce new matter to amend the claims to
exclude those monoclonal antibodies that do not significantly inhibit FSAP
or a FSAP proenzyme at equimolar concentrations.
Conclusion
The Examiner erred in concluding that amending claim 1 to recite an
antibody or fragment thereof that “significantly inhibits” FSAP or a FSAP
proenzyme “at equimolar concentrations” introduced new matter into the
claims. We therefore reverse the written description rejection.
INDEFINTENESS
The Examiner argues that “it unclear what level of inhibition is to be
considered significant” (Ans. 6).
Appellants argue that “[t]hose of ordinary skill in this art understand
that ‘significant inhibition,’ as opposed to mere ‘inhibition’ means inhibition
that has statistical significance” (App. Br. 16).
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Issue
Did the Examiner err in concluding that the term “significantly”
renders claim 1 indefinite?
Findings of Fact
FF4. A dictionary defines the term “significant” as:
1. Having or expressing a meaning; meaningful.
2. Having or expressing a covert meaning; suggestive . . .
3. Having or likely to have a major effect; important . . .
4. Fairly large in amount or quantity . . .
5. Statistics Of or relating to observations or occurrences that
are too closely correlated to be attributed to chance and
therefore indicate a systematic relationship.
THE AMERICAN HERITAGE® DICTIONARY OF THE ENGLISH LANGUAGE (2007),
http://www.credoreference.com/entry/hmdictenglang/significant (accessed
April 08, 2010).
FF5. Appellants rely on the following three Rule 132 Declarations: the
Declaration of Dr. Jochen Mueller-Cohrs (Exhibit 1); the Declaration of
Han-Arnold Stöhr (Exhibit 10); and the Declaration of Dr. Thomas Weimer
(Exhibit 11) (App. Br. 16 & Appendix B).
FF6. The Stöhr Declaration states that he tested the effect of four mouse
monoclonal antibodies, AC4, AD1, CE9, and FA3, discussed in Choi-
Miura2 “on the pro-urokinase activating activity of two-chain factor VII-
activating protease (tc-FSAP) and compared the effect to that of an antibody
according to the present invention, called 1102/570” (Stöhr Dec. ¶¶ 3 & 5).

2 N.-H. Choi-Miura et al., Proteolytic Activation and Inactivation of the
Serine Protease Activity of Plasma Hyaluronan Binding Protein, 24 BIOL.
PHARM. BULL. 448-52 (2001).
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FF7. The Stöhr Declaration also states that the assay was controlled in two
ways: (1) “a buffer control, without antibody, was incubated at both 4 °C
and at the experimental temperature of 37 °C”; and (2) “a negative control
antibody [373-1-213] specific for Factor VIII was used to control for non-
specific binding” (id. at ¶ 9-10).
FF8. In addition, the Stöhr Declaration states that “the tests with AC4,
AD1, CE9, and FA3 [hereinafter, “the Choi-Miura antibodies”] show that
these antibodies do not significantly inhibit FSAP activity” (id. at ¶ 11).
FF9. Relying on experiments conducted by Mr. Stöhr, the Weimer
Declaration states that the “Choi-Miura antibodies bind to FSAP but do not
significantly inhibit FSAP activity” (Weimer Dec. ¶¶ 6-8).
FF10. The Mueller-Cohrs Declaration states that the data presented in the
Stöhr and Weimer Declarations was analyzed “with established statistical
methods in order to determine whether the inhibition rate of any of these
antibodies was statistically significant” (Mueller-Cohrs Dec. ¶ 2).
FF11. The Mueller-Cohrs Declaration also states:
The inhibitory effect of antibody 1102/570 [of the present
invention] on FSAP was significantly higher than the inhibitory
effects of the four antibodies AC4, CE9, AD1, and FA3. The
statistically significant difference between the inhibitory effects
of antibody 1102/570 and the other antibodies holds for the
concentration-effect relationship as a whole and particularly for
the effect at a concentration equimolar to the FSAP
concentration.
(Id. at ¶ 4.)
FF12. Attached to the Mueller-Cohrs Declaration is a document entitled
“Statistical analysis of experimental data comparing the effects of five
monoclonal antibodies on the pro-urokinase activating activity of two-chain
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factor VII activating protease.” This document indicates that, in addition to
comparing an antibody of the present invention, 1102/570, to the Choi-
Miura antibodies, antibody 1102/570 and the Choi-Miura antibodies were
statistically compared to negative control antibody 373-1-213. In particular,
this document states, at page 4, that “[a]ny observed effect of a monoclonal
antibody at a particular concentration can . . . be compared with the values of
the negative control antibody by a statistical test to assess whether the effect
of the monoclonal antibody at that concentration differs significantly from
the effect of the negative control antibody.” In addition, this document
states, at page 5, that, “[a]t a concentration of 1.25 µg/ml, which was
approximately equimolar to the FSAP concentration (0.5 µg/ml), the
inhibitory effect of antibody 1102/570 was highly significant whereas the
inhibitory effect of the four antibodies AC4, CE9, AD1 and FA3 was not
significant,” as compared to the negative control antibody.
Principles of Law
“It is axiomatic that, in proceedings before the PTO, claims in an
application are to be given their broadest reasonable interpretation consistent
with the specification.” In re Sneed, 710 F.2d 1544, 1548 (Fed. Cir. 1983).
“A claim is indefinite if its legal scope is not clear enough that a
person of ordinary skill in the art could determine whether a particular
composition infringes or not.” Geneva Pharms., Inc. v. GlaxoSmithKline
PLC, 349 F.3d 1373, 1384 (Fed. Cir. 2003). “The test for definiteness is
whether one skilled in the art would understand the bounds of the claim
when read in light of the specification.” Miles Labs., Inc. v. Shandon Inc.,
997 F.2d 870, 875 (Fed. Cir. 1993).
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“[I]f a claim is amenable to two or more plausible claim constructions,
the USPTO is justified in requiring the applicant to more precisely define the
metes and bounds of the claimed invention by holding the claim
unpatentable under 35 U.S.C. § 112, second paragraph, as indefinite.” Ex
parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008) (precedential).
Analysis
The term “significant” can be defined in different ways (FF4). In the
field of statistics, the term “significant” is defined as “[o]f or relating to
observations or occurrences that are too closely correlated to be attributed to
chance and therefore indicate a systematic relationship” (FF4). However,
when the term “significantly” is read in context in the Specification (see
FF3), we do not agree that the Specification indicates that the term
“significant” is being used in the context of statistics, nor do we agree that
the Declarations relied upon by Appellants demonstrate that one of ordinary
skill in the art would understand that to be the case.
Moreover, even if we were to accept Appellants’ argument that the
term “significant” refers to “statistically significant,” this definition raises
the question of what the antibody should be statistically compared to.
Appellants argue that the Mueller-Cohrs Declaration “defines ‘significant
inhibition’ as FSAP inhibition by an inhibitory antibody, compared to a
negative control antibody, which reached statistical significance” (App.
Br. 16). We do not agree.
First, a Declaration cannot be used to retroactively define a claim
term. Thus, the issue is not whether the Mueller-Cohrs Declaration defines
the term “significantly,” but whether the Declaration provides sufficient
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evidence of how the term would have been understood by one of ordinary
skill in the art at the time of filing of the instant disclosure.
An attachment to the Mueller-Cohrs Declaration describes statistically
assessing whether the effect of a monoclonal antibody differs significantly
from the effect of a negative control antibody (FF12). However, we do not
agree that the Mueller-Cohrs Declaration is sufficient to demonstrate that, in
view of the Specification, one of ordinary skill in the art would have
understood the term “significant inhibition” to mean statistically significant
inhibition, as compared to a negative control antibody.
Conclusion
The Examiner did not err in concluding that the term “significantly”
renders claim 1 indefinite. We therefore affirm the indefiniteness rejection
of claim 1. Claims 3, 5, 15, and 21-25 have not been argued separately and
therefore fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

cdc

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