Ex Parte Quirk et al

Board of Patent Appeals and Interferences

Apr 2, 2010

10026393 (B.P.A.I. Apr. 2, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte STEPHEN QUIRK and DAVID JOHN TYRRELL
__________

Appeal 2009-013418
Application 10/026,393
Technology Center 1600
__________

Decided: April 5, 2010
__________

Before DONALD E. ADAMS, LORA M. GREEN, 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 metalloproteinases in a chronic wound. We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.

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Statement of the Case
Background
“Chronic wounds that do not heal well are characterized by an
increase in the activity of proteinase enzymes including, but not limited to,
matrix metalloproteinases (MMPs)” (Spec. 2, ll. 1-3). According to the
Specification “[s]ince the level of these enzymes is constantly in flux within
a chronic wound, it is therapeutically important to specifically identify
which proteinase, whether an enzyme or proenzyme, is at high levels” (Spec.
2, ll. 32-34).
The Claims
Claims 82-96 are on appeal. Claims 82 and 90 are representative and
read as follows:
82. A method for simultaneously detecting the presence
of at least two different metalloproteinases in a chronic
wound of a human or an animal, the method comprising:
a) collecting a sample of fluid from the chronic
wound, the sample comprising at least two different
metalloproteinases;
b) exposing the sample to a plurality of target
antibodies, wherein a first target antibody is configured to
bind with a first metalloproteinase to form a first target
antibody/metalloproteinase complex, and a second target
antibody is configured to bind with a second
metalloproteinase to form a second target
antibody/metalloproteinase complex; and
c) simultaneously identifying the first
metalloproteinase and the second metalloproteinase by
determining the presence or absence of a detectable or
measurable manifestation of a first signal element bound to
the first target antibody and a second signal element bound
to the second target antibody.

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90. The method of claim 82, wherein the first signal
element and the second signal element are the same.

The prior art
The prior art relied upon by the Examiner is found at pages 2-4 of the
Examiner’s Answer.

The issues
A. The Examiner rejected claims 82-96 under 35 U.S.C. § 103(a) as
being obvious over Sorsa, Rowe, and Sodek (Ans. 4-6).
B. The Examiner rejected claim 90 under 35 U.S.C. § 112, first
paragraph as not being enabled for identifying two or more
metalloproteinases in a mixed sample using a single signal element wherein
the metalloproteinases are not initially separated (Ans. 6-8).
C. The Examiner rejected claim 90 under 35 U.S.C. § 112, first
paragraph as not describing a method for identifying two or more
metalloproteinases in a mixed sample using a single signal element wherein
the metalloproteinases are not initially separated (Ans. 6-8).
A. 35 U.S.C. § 103(a) over Sorsa, Rowe, and Sodek
The Examiner concludes that it would have been obvious to the
ordinary artisan to “incorporate the array approach of Rowe et al into the
methods of Sorsa et al. In such a combined method, a sample of gingival
crevicular fluid from a patient with periodontal disease, comprising a
plurality of metalloproteases, would be reacted with particle-bound labeled
antibodies specific for each protease” (Ans. 6). The Examiner concludes
that “[m]otivation to thus combine the methods of Sorsa et al and Rowe et al
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is derived from the fact that metalloproteases, including MMP-8 and MMP-
9, are involved in periodontal disease” (Ans. 6)
Appellants argue that the prior art does not teach detection of MMPs
in chronic wounds, specifically that “whether considering the accepted
clinical definition of a chronic wound, as mentioned above, or combining the
standard definition of ‘chronic’ with that of ‘wound’, a periodontitis lesion,
as defined and used by Sorsa, et al., is not synonymous with the term
‘chronic wound’” (App. Br. 14).
Appellants argue that “it is respectfully submitted that no proper
motivation exists to combine the teachings of Sorsa, et al. with those of
Rowe, et al. and any such modification of the cited references relies on the
impermissible use of hindsight” (App. Br. 7). Appellants argue that
“[n]either Rowe, et al. nor Sodek, et al. provide a motivation for ignoring the
aspects of Sorsa, et al. that teach a method for detecting periodontal disease
through detection of only MMP-8, and the exclusion of other MMPs” (App.
Br. 10).
In view of these conflicting positions, we frame the obviousness issue
before us as follows:
Does the evidence of record support the Examiner’s conclusion that
one of skill in the art would have been motivated to combine the cited
references, and that doing so would lead a skilled worker to a method
meeting the limitations of claim 82?
Findings of Fact
1. The Specification does not define the term “chronic wounds”
but teaches that “[o]pen cutaneous wounds represent one major category of
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chronic wounds, which also include burn wounds, neuropathic ulcers,
pressure sores, venous stasis ulcers, and diabetic ulcers” (Spec. 1, ll. 17-19).
2. Sorsa teaches that:
Periodontal disease comprises a group of inflammatory
disorders originating from infections affecting the gingiva
(gum) and the alveolar (jaw) bone structures supporting the
teeth. The primary cause of periodontal diseases is bacterial
plaque attached to the teeth. This causes inflammation of the
gum which may result in destruction of the actual tooth-
supporting structure and bone. In periodontal disease, there
is usually a large accumulation of bacteria in plaque, both
above (supragingival) and below (subgingival) the gum line.
The plaque can calcify and form calculus deposits. The
calculus deposit and associated plaque can create a “pocket”
between the teeth and the gingiva which is characteristic of
the periodontal disease.

(Sorsa, col. 1, ll. 21-34).
3. Sorsa teaches that the prior art found “elevated collagenase
activity (MMP-1 and MMP-8) and gelatinases (MMP-2 and MMP-9) in
extracts of inflamed gingival tissues, gingival crevicular fluid and
salivary/mouthrinse-samples of periodontitis patients (Sorsa, T., et al., Ann.
N.Y. Acad. Sci., 732: 112-131, 1994)” (Sorsa, col. 6, ll. 2-7).
4. Sorsa teaches that the “activities of these proteinases have been
found to be positively correlated with the severity of periodontal
inflammation and pocket depth at the periodontitis lesion sites donating
these proteinases to gingival extracellular matrix and adjacent gingiva”
(Sorsa, col. 6, ll. 8-12).
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5. Sorsa teaches that “a method specific for MMP-8 in
periodontitis gingival crevicular fluid would be optimal in addressing the
course of tissue destruction events in periodontitis” (Sorsa, col. 8, ll. 1-3).
6. Sorsa teaches that “[g]ingival crevicular fluid sample is
collected with a sampling device. . . . The sample is then contacted with at
least one monoclonal antibody, which is already attached to the sampling or
test device or can be added to the combined sampling and test device”
(Sorsa, col. 15, ll. 39-46).
7. Sorsa teaches that “[w]estern blot analysis using both anti-
human MMP-8 and anti-human MMP-1 from the sample material given in
Table 1 show that MMP-8 existed in 70-75 kD inactive or latent and 65 kD
active forms, and MMP-1 was not detected” (Sorsa, col. 17, ll. 45-48).
8. Sorsa teaches that in making antibodies to proMM-8 for use in
the assay, the “clones are also tested for their cross-reaction to enzymes
structurally and immunologically related to MMP-8 which may be present in
gingival crevicular fluid samples (e.g., PMN-gelatinase [MMP-9], fibroblast
type collagenase [MMP-1] and stromelysin-1 [MMP-3])” (Sorsa, col. 20, l.
64 to col. 21, l. 2).
9. Rowe teaches the “array biosensor is designed to test multiple
samples for the presence of any of several analytes” (Rowe 3846, col. 2).
10. Rowe teaches that the “array biosensor demonstrated the
capability of performing simultaneous assays for very different types of
analytes on a single substrate” (Rowe 3851, col. 2).
11. Rowe teaches that the “array biosensor utilizes evanescent wave
excitation to interrogate patterns of fluoroimmunoassays immobilized on the
planar waveguide. This system detects and measures analytes in buffer and
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in a number of physiological fluids and is relatively unaffected by
nonspecifically bound components from complex samples” (Rowe 3847,
col. 1).
12. Sodek teaches that in “patients with either adult periodontitis or
with localized juvenile periodontitis the levels of active collagenase were
>15-fold higher than in control groups where active collagenase levels were
generally low. However, total collagenase was not significantly different
between the groups because of the presence of latent collagenase in control
group samples” (Sodek 355, col. 1).
13. Sodek teaches that “[a]nalysis of gelatinase activity also
showed significantly higher levels of the enzyme in the periodontitis groups”
(Sodek 355, col. 1).
Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
The Supreme Court has emphasized that “the [obviousness] analysis need
not seek out precise teachings directed to the specific subject matter of the
challenged claim, for a court can take account of the inferences and creative
steps that a person of ordinary skill in the art would employ.” KSR Int’l v.
Teleflex Inc., 550 U.S. 398, 418 (2007). As noted by the Court in KSR, “[a]
person of ordinary skill is also a person of ordinary creativity, not an
automaton.” 550 U.S. at 421.
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Claim terms are interpreted using the broadest reasonable
interpretation in light of the Specification. See, e.g., In re Hyatt, 211 F.3d
1367, 1372 (Fed. Cir. 2000) (“[D]uring examination proceedings, claims are
given their broadest reasonable interpretation consistent with the
specification.”). Also see In re Morris, 127 F.3d 1048, 1054-56 (Fed. Cir.
1997). (“Absent an express definition in their specification, the fact that
appellants can point to definitions or usages that conform to their
interpretation does not make the PTO's definition unreasonable when the
PTO can point to other sources that support its interpretation.”)
Analysis
Claim Interpretation
Claim interpretation is at the heart of patent examination because
before a claim is properly interpreted, its scope can not be compared to the
prior art. In this case, Appellants challenge the Examiner’s interpretation of
the phrase “chronic wound” as recited in Claim 82, arguing that “whether
considering the accepted clinical definition of a chronic wound, as
mentioned above, or combining the standard definition of ‘chronic’ with that
of ‘wound’, a periodontitis lesion, as defined and used by Sorsa, et al., is not
synonymous with the term ‘chronic wound’” (App. Br. 14). Appellants
argue that a periodontitis pocket “is not an injury or damage caused by
physical means persisting over a long period of time, it is not an injury in
which the skin or other external organic surface is torn, pierced, cut or
otherwise broken . . . and it is not produced by trauma or pathologic insult”
(App. Br. 14).
During prosecution, claim terms are given their broadest reasonable
interpretation as they would be understood by persons of ordinary skill in the
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art in the light of the Specification. Therefore, we first turn to the
Specification to determine whether the meaning of the phrase “chronic
wound” can be discerned.
The Specification teaches that “[o]pen cutaneous wounds represent
one major category of chronic wounds, which also include burn wounds,
neuropathic ulcers, pressure sores, venous stasis ulcers, and diabetic ulcers”
(Spec. 1, ll. 17-19; FF 1).
Appellants do not identify any portion of the Specification which
specifically defines the term “chronic wound”, but instead relies upon
dictionary definitions of the terms “chronic” and “wound” (see App. Br. 13-
14).
The Examiner finds that “the skilled artisan would, more likely than
not, interpret periodontitis as involving chronic wounds” (Ans. 18).
We find that the Examiner has the better position here. There is no
dispute that periodontal disease may be “chronic”, only that it is not a type
of “wound.” Appellants’ Specification contradicts Appellants’ argument to
limit wounds to injuries caused by physical means or to breaking or tearing
of skin or external surfaces (see App. Br. 14). The Specification expressly
recognizes that “diabetic ulcers” are a type of chronic wound, and diabetic
ulcers are not necessarily caused by physical means or tearing of the skin
(FF 1).
Therefore, we find that the term “chronic wound” in Claim 82
reasonably encompasses the periodontitis of Sorsa and Sodek, a chronic
condition which results in “inflammation of the gum which may result in
destruction of the actual tooth-supporting structure and bone” (Sorsa, col. 1,
ll. 25-27; FF 2).
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Obviousness
Sorsa teaches a method in which MMPs in crevicular fluid from the
periodontitis patient is collected and assayed for matrix metalloproteinases
using antibody binding (FF 3-6). Sorsa expressly teaches attempts at
detection of two different MMPs, MMP-1 and MMP-8, by Western blotting,
an antibody based detection technique (FF 7). Sorsa teaches that other
MMPs may be present in gingival crevicular samples including MMP-8,
MMP-9, MMP-1, and MMP-3 (FF 8).
Rowe is simply relied upon to demonstrate that the state of the art
permits the use of protein arrays for detection of proteins of interest with
antibody assays (FF 9-11).
Sodek is relied upon to further evidence that multiple MMPs are
found in gingival crevicular samples and are of interest in periodontitis (FF
12-13).
Appellants argue that “it is respectfully submitted that no proper
motivation exists to combine the teachings of Sorsa, et al. with those of
Rowe, et al. and any such modification of the cited references relies on the
impermissible use of hindsight” (App. Br. 7).
We are not persuaded. While we are fully aware that hindsight bias
often plagues determinations of obviousness, Graham v. John Deere Co.,
383 U.S. 1, 36 (1966), we are also mindful that the Supreme Court has
clearly stated that the “combination of familiar elements according to known
methods is likely to be obvious when it does no more than yield predictable
results,” KSR, 550 U.S. at 401.
This reasoning is applicable here. We find that applying the method
of Sorsa to detect all of the MMPs suspected of being present in gingival
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crevicular samples as taught by Sorsa and Sodek would have yielded the
predictable result of a more “efficient determination of which proteases are
present in patient samples for research analysis and/or clinical treatment”
(Ans. 6).
Appellants argue that “[n]either Rowe, et al. nor Sodek, et al. provide
a motivation for ignoring the aspects of Sorsa, et al. that teach a method for
detecting periodontal disease through detection of only MMP-8, and the
exclusion of other MMPs” (App. Br. 10).
We are not persuaded. Sorsa, while focused on the detection of
MMP-8 (FF 5), teaches that other MMPs may be found in periodontitis (FF
8). Further, Sodek clearly teaches that multiple MMPs are found in
periodontitis (FF 12-13). Like our appellate reviewing court, “[w]e will not
read into a reference a teaching away from a process where no such
language exists.” DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H.
Patrick Co., 464 F.3d 1356, 1364 (Fed.Cir. 2006).
Appellants argue that “none of the cited references disclose or suggest
the step of ‘collecting a sample from the fluid of a chronic wound’, and then
simultaneously identifying at least two different metalloproteinases in such a
fluid” (App. Br. 12).
We are not persuaded. First, as we have already noted, Sorsa
performs a Western blot on crevicular fluid from periodontitis patients
which simultaneously detected the presence or absence of MMP-1 and
MMP-8 (FF 7). Further, the entire reason that Rowe is present in the
rejection is to demonstrate that the ordinary artisan can routinely apply
protein arrays for the simultaneous detection of multiple proteins of interest
(FF 9-11).
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Conclusion of Law
The evidence of record supports the Examiner’s conclusion that one
of skill in the art would have been motivated to combine the cited
references, and that doing so would lead a skilled worker to a method
meeting the limitations of claim 82.
B. 35 U.S.C. § 112, first paragraph rejections
The Examiner finds that “the specification does not reasonably
provide enablement for identifying two or more metalloproteases in a mixed
sample using a single signal element wherein the metalloproteases are not
initially separated” (Ans. 7). The Examiner also finds that the “specification
fails to describe how, if both metalloproteases are in the same physical
location and identified with the same label, the artisan would know whether
the mixed sample comprised the first metalloprotease, the second
metalloprotease, or both metalloproteases” (Ans. 8).
Appellants argue that “the specification, in combination with what is
generally known to one of ordinary skill in the art, fully enables claim 90”
(App. Br. 19). Appellants argue that “there is no element of claim 90 that is
not adequately supported by the written description of the application as
filed” (App. Br. 24).
In view of these conflicting positions, we frame the enablement and
description issues before us as follows:
(i) Does the evidence of record support the Examiner’s conclusion
that the specification does not reasonably provide enablement for identifying
two or more metalloproteases in a mixed sample using a single signal
element wherein the metalloproteases are not initially separated?
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(ii) Does the evidence of record support the Examiner’s conclusion
that the specification fails to provide descriptive support for claim 90?
Findings of Fact
14. The Specification teaches that “[s]ensors of the present
invention can comprise a plurality of reaction sites for simultaneous
detection of more than one proteinase enzyme” (Spec. 7, ll. 3-4).
15. The Specification teaches that “signal element can be any
composition containing any indicator known in the art that provides a
detectable and/or measurable manifestation, without a chemical reaction,
when the signal element is concentrated in one location” (Spec. 8, ll. 30-33).
16. The Specification teaches that “[s]ignal elements can include,
but are not limited to, colorimetric compounds, fluorophores, chemo-
illuminescent compounds, magnetic compounds, radioactive compounds,
compounds that can be detected potentiometrically, light diffraction
elements, or combinations thereof” (Spec. 8, ll. 33-36).
17. In Example 6, the Specification teaches an ELISA assay in
which MMPs 1, 8, and 9 were detected (see, e.g., Spec. 17, ll. 27-32 and Fig.
6) The Specification teaches that the “assay was performed the same as in
Example 5” (Spec. 17, ll. 29-30).
18. In Example 5, the Specification teaches that the single signal
element was the label Pacific Blue, and that “a goat anti-mouse secondary
antibody, conjugated to Pacific Blue . . . was utilized for the detection phase
of the ELISA assay” (Spec. 17, ll. 13-15).

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Principles of Law
When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth
a reasonable explanation as to why it believes that the scope
of protection provided by that claim is not adequately
enabled by the description of the invention provided in the
specification of the application.

In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993). “[T]he question of
undue experimentation is a matter of degree. The fact that some
experimentation is necessary does not preclude enablement; what is required
is that the amount of experimentation ‘must not be unduly extensive.”’ PPG
Indus., Inc. v. Guardian Indus. Corp., 75 F.3d 1558, 1564 (Fed. Cir. 1996).
“In order to satisfy the written description requirement, the disclosure
as originally filed does not have to provide in haec verba support for the
claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding Inc., 230
F.3d 1320, 1323 (Fed. Cir. 2000). A disclosure provides adequate written
description if it conveys with reasonable clarity to those skilled in the art that
the inventor was in possession of the invention. See id.
Analysis
We again begin with claim interpretation. Claim 90 requires that “the
first signal element and the second signal element are the same”. We
interpret “signal element” consistent with the Specification as “any indicator
known in the art that provides a detectable and/or measurable manifestation”
(Spec. 8, ll. 30-32; FF 15). Therefore, Claim 90 requires the use of the
identical indicator in the detection method.
The Specification not only teaches, but actually exemplifies, a well
known and standard assay for simultaneously identifying proteins using a
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single signal element which detects two different target antibodies.
Specifically, in Example 6, the Specification teaches an ELISA assay in
which MMPs 1, 8, and 9 were detected (see, e.g., Spec. 17, ll. 27-32 and Fig.
6) The Specification teaches that the “assay was performed the same as in
Example 5” (Spec. 17, ll. 29-30; FF 17). In Example 5, the Specification
teaches that the single signal element was the label Pacific Blue, and that “a
goat anti-mouse secondary antibody, conjugated to Pacific Blue . . . was
utilized for the detection phase of the ELISA assay” (Spec. 17, ll. 13-15; FF
18).
Therefore, the Specification exemplifies detection of multiple MMPs
where the first and second signal elements are the same (FF 17-18).
We are not persuaded by the Examiner’s argument that the
“specification fails to describe how, if both metalloproteases are in the same
physical location and identified with the same label, the artisan would know
whether the mixed sample comprised the first metalloprotease, the second
metalloprotease, or both metalloproteases” (Ans. 8).
This argument misreads Claims 82 and 90 to require that the MMPs
are in the same physical location. There is no requirement in either Claim
82 or Claim 90 for the MMP antibodies to be in the same physical location.
The requirements in the claims are that the MMPs are simultaneously
detected and Claim 90 further requires that the same signal element is used
for detection of both target antibodies (see Claims 82 and 90). The use of
ELISA assays for such detection with the same “signal element” is both
remarkably well known and is exemplified in the Specification (FF 17-18).

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Conclusions of Law
(i) The evidence of record does not support the Examiner’s
conclusion that the specification does not reasonably provide enablement for
identifying two or more metalloproteases in a mixed sample using a single
signal element wherein the metalloproteases are not initially separated.
(ii) The evidence of record does not support the Examiner’s
conclusion that the specification fails to provide descriptive support for
claim 90.
SUMMARY
In summary, we affirm the rejection of claim 82 under 35 U.S.C. §
103(a) as obvious over Sorsa, Rowe, and Sodek. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 83-96 as these
claims were not argued separately.
We reverse the rejections of claim 90 under 35 U.S.C. § 112, first
paragraph enablement and written description.
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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