Ex Parte Degelaen et al

Board of Patent Appeals and Interferences

Feb 25, 2009

10702507 (B.P.A.I. Feb. 25, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JACQUES DEGELAEN, JEAN-MARIE FRERE,
BENOIT GRANIER, and BERNARD JORIS
__________

Appeal 2008-5883
Application 10/702,507
Technology Center 1600
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Decided:1February 25, 2009
__________

Before ERIC GRIMES, LORA M. GREEN,
and JEFFREY N. FREDMAN, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s final rejection of claims 24, 26-32, and 34-40. We have
jurisdiction under 35 U.S.C. § 6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2008-5883
Application 10/702,507

STATEMENT OF THE CASE
The claims are directed to an assay kit for detecting one or more
antibiotics having a β-lactam ring. Claim 24 is representative of the claims
on appeal, and reads as follows:
24. An assay kit for detecting one or more antibiotics containing a β-
lactam ring in a liquid dairy product, said assay kit comprising:
(a) an assay device comprising a solid support, said solid support
comprising (a) a first and second end, and (b) the following membranes (i)-
(iii), fixed in succession starting from the first end,
(i) a purification membrane which retains interfering
substance(s) and allows antibiotics and detection reagents in the liquid dairy
product to migrate by tangential capillary migration from the first end
towards the second end of the solid support, while preserving the activity of
the antibiotics and detection reagents during said migration, said interfering
substance(s) being substances which prevent such migration, said
purification membrane being made from non-woven polyester fibers which
is capable of retaining leukocytes in the milk,
(ii) an immobilization membrane comprising first and second
capture substances, said first capture substance being one or more antibiotics
containing a β-lactam ring which specifically bind to a receptor, which is a
BlaR and BlaR-CTD protein obtained from Bacillus lichenformis, said
second capture substance being a substance which binds to an independent
reference substance, and
(iii)2 an absorbent membrane,
(b) a detection reagent in the test kit comprising the receptor which is
the BlaR and BlaR-CTD protein obtained from Bacillus lichenformis which
specifically binds to antibiotics containing a β-lactam ring in the dairy
product, and
(c) the independent reference substance.

The Examiner relies on the following evidence:
Markovsky US 6,319,466 Nov. 20, 2001
Pall US 6,074,869 Jun. 13, 2000

2 The reference to (iv) in the claims on appeal attached to the Appeal Brief
appears to be in error. (See Amendement dated April 18, 2007.)
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Litman EP 0 093 613 Sep. 11, 1983

B. Joris et al., Expression in Escherichia coli of the carboxy terminal
domain of the BLAR sensory-transducer protein of Bacillus licheniformis as
a water-soluble Mr 26 000 penicillin-binding protein, 70 FEMS
MICROBIOLOGY LETTERS, 107-114 (1990).

We affirm.

ISSUE (Obviousness)
The Examiner concludes that claims 24, 26-32, and 36-40 are
rendered obvious by the combination of Markovsky, Joris, and Litman, and
that claims 34 and 35 are rendered obvious by the combination of
Markovsky, Joris, and Litman, as further combined with Pall.
Appellants contend that the combination is based on an “obvious to
try” rationale, and that the Examiner engaged in hindsight reasoning.
Thus, the issue on Appeal is: Have Appellants demonstrated that the
Examiner erred in combining the references to arrive at the claimed
invention?

FINDINGS OF FACT
FF1 The Examiner rejects claims 24, 26-32, and 36-40 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Markovsky, Joris, and
Litman (Ans.3 4). As Appellants do not argue the claims separately, we

3 All references to the Answer (Ans.) are to the Examiner’s Answer dated
December 17, 2007. We note that a Supplemental Examiner’s Answer was
sent out on May 15, 2008, but that Answer merely corrected minor
informalities in the headings.
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focus our analysis on claim 24, and claims 26-32 and 36-40 stand or fall
with that claim. 37 C.F.R. § 41.37(c)(1)(vii).
FF2 The Examiner cites Markovsky for teaching all of the elements of
claim 24 (Ans. 4-5), except for teaching the use of receptors obtained from
Bacillus lichenformis as the labeled reagent or the use of a reference that is
independent of the analyte (id. at 5).
FF3 The Examiner notes, however, that Markovsky teaches that “the
receptor may bind a family of analytes which have similar structural binding
sites,” and also teaches that “test kits for detecting beta-lactams in biological
fluids are well known in the art.” (Id.)
FF4 The Examiner finds further that Markovsky teaches a lateral flow
assay device for detecting β-lactam antibiotics, and the use of receptors that
are specific to the analyte, thus it would be “entirely within the skills of the
ordinary artisan to choose a receptor that is specific for the analyte.” (Id. at
9.)
FF5 Specifically, Markovsky teaches the use of a labeled receptor that
reacts with the analyte to form a receptor-analyte complex (Markovsky, col.
1, ll. 53-55), wherein the receptor may bind a family of analytes that have
similar structural binding sites (id. at col. 2, ll. 11-13).
FF6 Markovsky specifically teaches an assay test strip for beta-lactam
antibiotics in milk (id. at col. 8, ll. 13-15).
FF7 Markovsky also exemplifies the use of a beta-lactam receptor from
Bacillus stearothermophilus (id. at col. 12, ll. 35-39).
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FF8 The Examiner cites Joris for teaching that BLAR and BLAR-CTD are
involved in the induction of β-lactamase in Bacillus lichenformis (Ans. 5
(see Joris Abstract)).
FF9 Joris teaches that BLAR-CTD, the carboxy-terminal domain of
BLAR, is a water-soluble, penicillin binding protein (Joris Abstract).
FF10 The Examiner cites Litman for teaching “a method and device for
detecting an analyte comprising a measurement surface and a calibration
surface binding to a reagent independent from the analyte.” (Ans. 6 (citing
Litman 4, ll. 24-37).)
FF11 The Examiner concludes that it would have been obvious to the
ordinary artisan to use the BLAR and BLAR-CTD receptors as taught by
Joris in the device of Markovsky because Joris discloses that the BLAR and
BLAR-CTD receptors are readily available and are known in the art as
having β-lactamase activity, and thus the ordinary artisan “would have a
reasonable expectation of success in using receptors BlaR and BlaR-CTD to
detect beta-lactams antibiotics such as penicillin as taught by Markovsky.”
(Ans. 6.)
FF12 The Examiner concludes further that the use of an independent
reference or calibration agent is well known in the art, and thus it would
have been obvious to the ordinary artisan to use the calibration reagents and
the method of Litman in the device of Markovsky because “Litman teaches
that it is advantageous to use a reagent that is independent from the analyte
to provide a calibration or reference signal such that a standard for
evaluation of the analyte at the detection zone can be obtained.” (Id. at 7.)
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FF13 The Examiner also rejects claims 34 and 35 under 35 U.S.C. § 103(a)
as being obvious over the combination of Markovsky, Joris, and Litman, as
further combined with Pall (Ans. 7).
FF14 The combination of Markovsky, Joris, and Litman are relied upon as
above (id.).
FF15 The Examiner notes that the combination fails to specifically disclose
the pore size of the purification membrane (id.).
FF16 The Examiner cites Pall for teaching membranes for filtering
biological samples, such as leukocytes and milk, wherein the membrane is a
non-woven web (polyethylene) having an average pore size of 3 to 8 μm (id.
(citing Pall, col. 8, ll. 54-60)).
FF17 The Examiner concludes that
it would have been obvious to one of ordinary skill in the art at
the time the invention was made to use the purification
membrane taught by Pall in the device of Markovsky as
modified by Joris because such a membrane is well known in
the art and provides the advantage of a substantially uniform
porous medium that can separate large somatic cells from a
biological sample.

(Ans. 8.)

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).
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The Supreme Court has recently 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, ___, 127 S. Ct. 1727, 1741 (2007). “The
combination of familiar elements according to known methods is likely to be
obvious when it does no more than yield predictable results.” Id. at 1739.
An “[e]xpress suggestion to substitute one equivalent for another need not be
present to render such substitution obvious.” In re Fout, 675 F.2d 297, 301
(CCPA 1982). As noted by the Supreme Court,
If a person of ordinary skill can implement a predictable
variation, § 103 likely bars its patentability. For the same
reason, if a technique has been used to improve one device, and
a person of ordinary skill in the art would recognize that it
would improve similar devices in the same way, using the
technique is obvious unless its actual application is beyond his
or her skill.

KSR, 127 S.Ct. at 1740.
Moreover, “[w]hen there is a design need or market pressure to solve
a problem and there are a finite number of identified, predictable solutions, a
person of ordinary skill has good reason to pursue the known options within
his or her technical grasp. If this leads to the anticipated technical success, it
is likely the product not of innovation but of ordinary skill and common
sense.” Id. at 1742.

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ANALYSIS
Appellants argue that Markovsky teaches the use of a beta-lactam
receptor from Bacillus stearothermophilus (BST), which was well known as
a receptor, and that there is no description of another specific bacterial
protein that may be used in the assay (App. Br.4 9). Given the large number
of bacteria, Appellants argue that the ordinary artisan would not select the
membrane receptor of claim 24 based on the teachings of Markovsky (Reply
Br. 2).
Appellants assert that while Joris describes BLAR proteins that bind
beta-lactam antibiotics, there is no discussion of their use in a lateral flow
assay, and thus there is no way to determine from the reference that the
proteins would be effective in determining beta-lactam antibiotics in such as
an assay, or that they even would be able to flow in the assay (App. Br. 9-
10).5 According to Appellants, the Examiner’s rejection is based on an
“obvious to try” premise, but “[i]n a complex lateral flow assay as claimed,
there would be no assurance that the BlaR or BlaR-CTD proteins would
function in such an assay, since the complex with the antibiotic is subjected
to lateral flow.” (Id. at 10). Appellants argue further that the combination

4 All references to the Appeal Brief (App. Br.) are to the Supplemental
Appeal Brief dated September 19, 2007.
5 In the Reply Brief, Appellants raise the argument (which was not raised in
the Appeal Brief) that Joris does not discuss that the receptor functions for a
large number of antibiotics (Reply Br. 2). Claim 32, however, is drawn to
an assay kit, and thus the recitation of which antibiotic is being tested for is a
statement of intended use. In addition, as the combination uses the same
labeled receptor as used by Appellants, the ability of that receptor to bind to
the claimed Markush group of antibiotics would be an inherent property of
that receptor.
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“could not lead one skilled in the art to [the] claimed invention without
hindsight.” (Reply Br. 3-4).
We have considered Appellants’ arguments, but do not find them to
be convincing. Markovsky teaches a lateral flow assay for detecting β-
lactam antibiotics in milk (FF4, FF6). Markovsky teaches the use of a
labeled receptor that specifically binds the antibiotic in the test strip (FF3-
FF5), and specifically exemplifies the use of a beta-lactam receptor from
BST (FF7). We agree with the Examiner, however, that the ordinary artisan
would understand that other receptors which specifically bind the analyte of
interest would be useful in the assay and the device (see FF4). Joris teaches
that the Bacillus lichenformis protein BLAR and BLAR-CTD (the carboxy-
terminal domain of BLAR) specifically bind to penicillin (FF8, FF9). Thus,
it would have been well within the level of skill in the art to substitute the
BLAR or BLAR-CTD receptor of Bacillus lichenformis for the beta-lactam
receptor from BST as exemplified by Joris, because each specifically
recognizes a beta-lactam antibiotic.
We recognize that there are a large number of bacteria from which
beta-lactam receptors may be obtained, but just because the group of
obvious variants may be large does not make the use of any specific-binding
protein for a beta-lactam antibiotic any less obvious. In addition, while
Appellants argue that there is no assurance that the BLAR or BLAR-CTD-
beta-lactam antibiotic will flow in the assay, Appellants have not provided
any scientific reasoning or evidence that the ordinary artisan would not
expect the complex to flow, especially given the different assays exemplified
by Markovsky. Note that arguments of counsel cannot take the place of
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evidence in the record. In re Scarbrough, 500 F.2d 560, 566 (CCPA 1974).
Moreover, while there may not be one-hundred percent assurance that the
assay will work with a different specific binding protein, that is not the
standard by which obviousness is measured: All that is required is a
reasonable expectation of success, not absolute predictability of success. In
re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988).
Appellants argue further that while Litman teaches the use of a
calibration surface that binds to a reagent that it is independent from the
analyte, and while the use of such calibration is known, its use is not known
in the claimed assay (App. Br. 10).
Appellants’ arguments are again not found to be convincing. As
found by the Examiner, the use of an independent reference or calibration
agent is well known in the assay art, and Litman provides a reason for
adding an independent reference or calibration agent by teaching that it is
advantageous to use a reagent that is independent from the analyte to
provide a calibration or reference signal such that a standard for evaluation
of the analyte at the detection zone can be obtained (FF12). Moreover,
Appellants have not provided any evidence or scientific reasoning as to why
it would have been beyond the level of ordinary skill in the art to use a
calibration surface that binds to a reagent that it is independent from the
analyte as taught by Litman in the assay of Markovsky.
As to the rejection of claims 34 and 35 over the combination of
Markovsky, Joris, and Litman, as further combined with Pall, Appellants
reiterate their arguments as to the combination of Markovsky, Joris, and
Litman (App. Br. 11-12). Appellants argue further that claims 34 and 35
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require an 8 μm pore size, which is small, and contend that there is no
suggestion in Pall that the BlaR or BlaR-CTD bound with antibiotics would
pass through the web of Pall (id.).
We point Appellants’ attention to the response to arguments set forth
above. In addition, Markovsky teaches a use of membranes in the assay
device for beta-lactam devices (see, e.g., FF2), thus the ordinary artisan
would have a reasonable expectation of success of using the membrane of
Pall in the device of Markovsky (see, e.g., Ans. 11).

CONCLUSIONS OF LAW
We conclude that Appellants have not demonstrated that the Examiner
erred in combining the references to arrive at the claimed invention.
We thus affirm the rejection of claims 24, 26-32, and 36-40 under 35
U.S.C. § 103(a) as being obvious over the combination of Markovsky, Joris,
and Litman, as well as the rejection of claims 34 and 35 under 35 U.S.C.
§ 103(a) as being obvious over the combination of Markovsky, Joris, and
Litman, as further combined with Pall.

TIME LIMITS
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

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LP
IAN C. McLEOD, P.C.
2190 COMMONS PARKWAY
OKEMOS MI 48864

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