Ex Parte Olson et al

Board of Patent Appeals and Interferences

Jun 1, 2010

11471694 (B.P.A.I. Jun. 1, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte KEITH R. OLSON, PETER A. FUNG,
and RICHARD M. EGLEN
__________

Appeal 2010-000026
Application 11/471,694
Technology Center 1600
__________

Decided: June 2, 2010
__________

Before ERIC GRIMES, TONI R. SCHEINER, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134 involving claims to methods
of detecting mitosis. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.

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Statement of the Case
Background
The invention relates to methods for detecting mitosis by using
enzyme fragmentation complementation (EFC) pairs. “[T]he members of
the pair are referred to as an enzyme donor (‘ED’), which is arbitrarily the
smaller member, and an enzyme acceptor (‘EA’)” (Spec. 3 ¶ 0011). The
Specification teaches that “[c]ells here will comprise one member of the pair
of the EFC in the nucleus and the other member of the EFC pair in the
cytosol.” (Spec. 3 ¶ 0111). According to the Specification, after “mitosis,
the two members (EA and ED) of the EFC pair come into complex
formation. In the presence of a substrate that provides a detectable product
the mitotic event can be determined” (Spec. 3 ¶ 0111).
The Claims
Claims 1 and 3-7 are on appeal.1 Claim 1 is representative and reads
as follows:
1. A method for detecting mitosis employing
members of enzyme fragmentation complex pairs capable of
complexing to form an active β-galactosidase enzyme, said
members being an enzyme donor and an enzyme acceptor,
wherein one of said members is in the cytosol and the other
of said members is in the nucleus of a cell, said method
comprising:
growing said cells in a medium for mitosis to occur;
and
measuring enzyme activity with a detectable
substrate;
wherein a level of enzyme activity is a measure of the
amount of mitosis.

1 Claim 8 was withdrawn without traverse (Resp. Elec. 9/04/2007).
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The prior art

The Examiner relies on the following prior art references:
Blau et al. US 2005/0287522 A1 Dec. 29, 2005
Naqvi et al. US 7,135,325 B2 Nov. 14, 2006

The issues2
A. The Examiner rejected claims 1, 3-5, and 7 under 35 U.S.C. § 102(e)
as anticipated by Blau (Ans. 3-5).
B. The Examiner rejected claims 1 and 3-7 under 35 U.S.C. § 103(a) as
obvious over Blau and Naqvi (Ans. 5-6).
We consider these rejections together, since they both turn on whether
Blau inherently anticipates Claim 1 (see App. Br. 8).
The Examiner finds that Blau teaches a “method for detecting nuclear
translocation employing members of enzyme fragmentation complex pairs
capable of complexing to form an active β-galactosidase, the members being
an enzyme donor (substantially smaller α-fragment fused to a cytosolic
protein of interest) and an enzyme acceptor (ω-fragment fused to a nuclear
localization signal (NLS)” (Ans. 3). The Examiner finds that “[i]t is
inherent in the method of Blau et al. that the measurement of enzyme
activity would also be a measurement of mitosis as Blau et al. incubates the
cells for times of up to 4 hours with assays of enzyme activity every hour”
(Ans. 4).
Appellants argue that “[c]rucial to the success of the Blau invention is
that during the assay the nucleus retains an intact envelope. Otherwise, the

2 The double patenting rejection was withdrawn in view of a
Terminal Disclaimer (see Misc. Comm. 9/11/09).
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two fragments would be able to complex in the absence of translocation. A
corollary of this is that mitosis will give a false positive” (App. Br. 3).
Appellants argue that “[i]t clearly follows that there can be no anticipation,
when the purpose of the two inventions is different, the reagents employed
in the two inventions are different, mitosis in the Blau invention is
specifically precluded and there is neither a site of interest or a compound of
interest in the subject invention” (App. Br. 4).
In view of these conflicting positions, we frame the issue before us as
follows:
Does the evidence of record support the Examiner’s conclusion that
Blau inherently teaches the limitations of Claim 1?
Findings of Fact (FF)
1. Figure 2A of Blau is reproduced below:

“FIG. 2A is a schematic showing the design of the nuclear translocation
assay. In the left panel, the ω fragment is localized to the nucleus with a
nuclear localization signal (NLS) and the cytosolic protein of interest is
fused to the minimal α peptide. Upon stimulation the α fusion moves to the
nucleus and complements the ω, increasing β-galactosidase activity” (Blau
16 ¶ 0153).
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2. Figures 3A and 3B of Blau are reproduced below:

“FIG. 3A shows a time course of cells expressing the GR-α fusion and
either the ω-NLS (Left) or tEGFR-ω (right) and assayed for β-galactosidase
activity after treatment with 1 μM dexamethasone for the indicated times.
FIG. 3B shows dose versus time. Cell lines shown in FIG. 3A [sic, 3B]
were treated with varying concentrations of dexamethasone and assayed
over time” (Blau 16 ¶ 0159).
3. Blau teaches that “the presence or absence of detectable signal
is determined from the translocation of the reporter components into the
same subcellular compartment” (Blau 14 ¶ 0133).
4. Blau teaches that the “signal may be subjectively evaluated by
comparing the signal to a set of control signals” (Blau 14 ¶ 0134).
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5. Blau teaches that “[a]ddition of 1 µM dexamethasone for 3
hours to the gain of signal assay resulted in a 3.5 fold induction of ß-
galactosidase activity, while the loss of signal assay showed a slightly better
signal to noise ratio of approximately 5-fold (FIG. 3A)” (Blau 17 ¶ 0160).
Principles of Law
“It is well settled that a prior art reference may anticipate when the
claim limitations not expressly found in that reference are nonetheless
inherent in it.” In re Cruciferous Sprout Litigation, 301 F.3d 1343, 1349
(Fed. Cir. 2002). “It matters not that those of ordinary skill heretofore may
not have recognized these inherent characteristics.” Id. at 1350. See, e.g.,
MEHL/Biophile Int'l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999) (“Under the principles of inherency, if the prior art necessarily
functions in accordance with, or includes, the claimed limitations, it
anticipates.”)
“A ‘whereby’ clause that merely states the result of the limitations in
the claim adds nothing to the patentability or substance of the claim.” Texas
Instruments Inc. v. U.S. Int’l. Trade Comm’n, 988 F.2d 1165, 1172 (Fed.
Cir. 1993).
Analysis
Blau teaches a series of manipulative steps in which there are two
fragments of an enzyme fragmentation complex which can form an active
β-galactosidase enzyme, where “the ω fragment is localized to the nucleus
with a nuclear localization signal (NLS) and the cytosolic protein of interest
is fused to the minimal α peptide” (Blau 16 ¶ 0153; FF 1).
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Blau teaches steps including growing the cells containing these
fragments in medium and measuring enzyme activity with a detectable
substrate (FF 2-5)
The Examiner does not dispute that Blau does not teach the preamble
requirement of “detecting mitosis” but rather contends that it “is inherent in
the method of Blau et al. that the measurement of enzyme activity would
also be a measurement of mitosis” (Ans. 4).
Appellants respond that “there can be no anticipation, when the
purpose of the two inventions is different, the reagents employed in the two
inventions are different, mitosis in the Blau invention is specifically
precluded and there is neither a site of interest or a compound of interest in
the subject invention” (App. Br. 4).
While we agree with Appellants that the preamble breathes life and
meaning into this claim, so that the purpose of the claimed invention differs
from the purpose of Blau’s assay, this does not necessarily defeat inherent
anticipation. See, e.g., MEHL/Biophile Int'l Corp. v. Milgraum, 192 F.3d
1362, 1365 (Fed. Cir. 1999). We agree with the Examiner that Blau
inherently satisfies the requirements of claim 1.
Specifically, we are referring to the control measurements taught and
exemplified by Blau (FF 4-5). Blau teaches that “[a]ddition of 1 µM
dexamethasone for 3 hours to the gain of signal assay resulted in a 3.5 fold
induction of β-galactosidase activity, while the loss of signal assay showed a
slightly better signal to noise ratio of approximately 5-fold (FIG. 3A)” (Blau
17 ¶ 0160; FF 5).
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When Blau finds a 3.5 fold induction, that induction is reasonably
interpreted as an induction relative to a control or background signal, that is,
a comparison to the signal produced by cells which were grown for 3 hours
without the addition of the dexamethasone (see FF 4-5). These control cells
were grown in medium in which mitosis can occur at some level, and the
enzyme activity of the β-galactosidase fragments was measured with a
detectable substrate.
That measured background level of enzyme activity is inherently at
least a partial measure of the amount of mitosis. That is, the level of enzyme
activity inherently includes the enzyme activity attributable to mitosis, as
well as any enzyme activity attributable to other causes. This is reasonably
interpreted as satisfying the claim clause that “wherein a level of enzyme
activity is a measure of the amount of mitosis.” “A ‘whereby’ clause that
merely states the result of the limitations in the claim adds nothing to the
patentability or substance of the claim.” Texas Instruments Inc. v. U.S. Int’l.
Trade Com’n, 988 F.2d 1165, 1172 (Fed. Cir. 1993).
Appellants argue that “there can be no anticipation, when the purpose
of the two inventions is different” (App. Br. 4). This is not a correct
statement of the law. “It matters not that those of ordinary skill heretofore
may not have recognized these inherent characteristics.” In re Cruciferous
Sprout Litigation, 301 F.3d 1343, 1350 (Fed. Cir. 2002). The question is
whether the prior art inherently taught and performed the method, not
whether the prior art recognized that performance. In this case, in measuring
the control levels of activity, Blau clearly performs the claimed method,
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even though Blau equally clearly does not recognize that performance (FF 1-
5).
Appellants argue that Blau does not inherently anticipate because “[i]t
is apparent from Blau’s results that there is little, if any, mitosis over a 4-
hour period. Therefore, Blau does not observe the results of mitosis except
as background with all of the other factors associated with background and
cannot be found to teach a method for determining mitotic index” (App. Br.
5).
We are not persuaded because Appellants’ claim 1 does not require
determining a mitotic index, but rather requires detecting mitosis “wherein a
level of enzyme activity is a measure of the amount of mitosis” (Claim 1).
We can accept Appellants’ factual argument that mitosis may not occur, or
may occur minimally, during the 4-hour period measured by Blau, and still
find that Blau measures the level of enzyme activity, and that Blau’s
measurement inherently measures the amount of mitosis. The amount of
mitosis may be zero, or a low amount in Blau, but that still reasonably
satisfies the claim requirement, since the claim does not require that mitosis
occur, only that the level of enzyme activity measure the amount of mitosis
(see Claim 1). If there is no mitosis, and Blau measures a consequent low
level of enzyme activity due to other background causes, Blau inherently
obtains a measure of the amount of mitosis. See, e.g., MEHL/Biophile Int'l
Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999) (“Under the
principles of inherency, if the prior art necessarily functions in accordance
with, or includes, the claimed limitations, it anticipates.”)
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Appellants argue that “[w]hile the readout may be [the] same, having
β-galactosidase turnover, mitosis is interfering with Blau’s determination”
(App. Br. 8). This argument essentially concedes the point regarding
inherency, in light of Mehl and Cruciferous. Blau and the claimed invention
yield the same readout, but interpret that readout differently based upon the
intended process being performed. Thus Blau is reasonably interpreted as
inherently performing the claimed method, and simply not appreciating the
inherent result regarding mitosis.
Conclusion of Law
The evidence of record supports the Examiner’s finding that Blau
inherently teaches the limitations of Claim 1.

SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C. §
102(e) as anticipated by Blau and, for the same reason, under 35 U.S.C.
§ 103(a) as obvious in view of Blau. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 3-7 as these
claims were not argued separately.
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)(iv)(2006).

AFFIRMED

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