Bruno Colin et al.

Patent Trials and Appeals Board

Mar 18, 2021

2020004646 (P.T.A.B. Mar. 18, 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.
12/918,159 08/18/2010 Bruno Colin 146497 6449
25944 7590 03/18/2021
OLIFF PLC
P.O. BOX 320850
ALEXANDRIA, VA 22320-4850
EXAMINER
PYLA, PAUL D
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
03/18/2021 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):
OfficeAction25944@oliff.com
jarmstrong@oliff.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte BRUNO COLIN, DAVID MOSTICONE,
JEAN-CLAUDE RAYMOND,
THIERRY SOFIA, and ANTOINE VIMONT
____________

Appeal 2020-004646
Application 12/918,159
Technology Center 1600
____________

Before DONALD E. ADAMS, RYAN H. FLAX, and JAMIE T. WISZ,
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 59–87 (see Ans.2 3). We have jurisdiction under
35 U.S.C. § 6(b).
We REVERSE.

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
“bioMérieux” (Appellant’s December 5, 2019, Appeal Brief (Appeal Br.) 1).
2 Examiner’s April 2, 2020, Answer.
Appeal 2020-004646
Application 12/918,159

2
STATEMENT OF THE CASE
Appellant’s disclosure relates to “method for identifying one or more
microorganisms by means of an agglutination reaction carried out
simultaneously with the enrichment of the sample in microorganisms”
(Spec.3 1). Appellant’s independent claims 59, 77, and 82 are reproduced
below:
59. A method for detecting whether at least one
microorganism is present in a sample, comprising:
subjecting a mixture including the sample, a
sensitized solid support, and a culture medium in a container to
culturing conditions for 4 to 96 hours so as to culture the
microorganism when present in the sample such that the
microorganism is multiplied; and
measuring in real time an amount of binding of the
microorganism to the sensitized solid support at a plurality of
time points during the 4 to 96 hours of culturing;
wherein:
the microorganism is a unicellular organism;
the sensitized solid support includes (i) a solid
support, and (ii) an antigen, antibody, phage, phage protein,
antiligand, or ligand that enables binding between the
microorganism and the sensitized solid support;
binding of the microorganism to the sensitized
solid support indicates that the microorganism is present in the
sample; and
the binding of the microorganism to the sensitized
solid support takes place simultaneously with the multiplication
of the microorganism when present in the sample.
(Appeal Brief A-1 (emphasis added).)

3 Appellant’s August 18, 2010, Specification.
Appeal 2020-004646
Application 12/918,159

3
77. A method for detecting whether at least one
microorganism is present in a sample, comprising:
subjecting a mixture including the sample, a
sensitized solid support, and a culture medium in a container to
culturing conditions for 4 to 96 hours so as to culture the
microorganism when present in the sample such that the
microorganism is multiplied; and
periodically measuring in real time an amount of
binding of the microorganism to the sensitized solid support
during culturing;
wherein:
the microorganism is a unicellular organism;
the sensitized solid support includes (i) a solid
support, and (ii) an antigen, antibody, phage, phage protein,
antiligand, or ligand that enables direct binding between the
microorganism and the sensitized solid support;
binding of the microorganism to the sensitized
solid support indicates that the microorganism is present in the
sample; and
the binding of the microorganism to the sensitized
solid support takes place simultaneously with the multiplication
of the microorganism when present in the sample.
(Appeal Brief A-3–A-4 (emphasis added).)
82. A method for detecting whether at least one
microorganism is present in a sample, comprising:
subjecting a mixture including the sample, a
sensitized solid support, and a culture medium in a container to
culturing conditions for 4 to 96 hours so as to culture the
microorganism when present in the sample such that the
microorganism is multiplied; and
periodically measuring in real time an amount of
binding of the microorganism to the sensitized solid support
during culturing;
wherein:
Appeal 2020-004646
Application 12/918,159

4
the microorganism comprises a species of Listeria;
the sensitized solid support includes (i) a solid
support, and (ii) an antibody that enables direct binding
between the microorganism and the sensitized solid support;
binding of the microorganism to the sensitized
solid support indicates that the microorganism is present in the
sample; and
the binding of the microorganism to the sensitized
solid support takes place simultaneously with the multiplication
of the microorganism when present in the sample.
(Appeal Br. A-4–A-5 (emphasis added).)

Grounds of rejection before this Panel for review:
I. Claims 59, 60, and 62–87 stand rejected under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Burns,4
Manafi,5 Atrache,6 and Hansen.7
II. Claims 59, 71, and 77 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over the combination of Burns, Manafi,
Atrache, Hansen, and Sun.8

4 Burns et al., US 2006/0246535 A1, published Nov. 2, 2006.
5 Manafi et al., Fluorogenic and Chromogenic Substrates Used in Bacterial
Diagnostics, 55 MICROBIOLOGICAL REVIEWS 335–48 (1991).
6 Atrache et al., US 5,415,997, issued May 16, 1995.
7 Hansen, US 5,286,452, issued Feb. 15, 1994.
8 Sun et al., FOOD-BORNE PATHOGENS, Use of bioluminescent
Salmonella for assessing the efficiency of constructed phage-based
biosorbent, 27 JIMB 126–28 (2001).
Appeal 2020-004646
Application 12/918,159

5
III. Claim 61 stands rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Burns, Manafi, Atrache,
Hansen, and McCoy.9

ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Burns discloses “agglutination methods for detecting
microorganisms in solutions or suspensions,” which are “based in part on the
discovery that agglutination methods utilizing the selectivity of antigen
binding sites of antibodies are sensitive enough to selectively detect
microorganism contaminants, without first culturing the microorganisms”
(Burns ¶¶ 3 and 26 (emphasis added)).
FF 2. Burns discloses:
[M]ethods of detecting a microorganism . . . in an aqueous
solution or suspension where the aqueous solution or
suspension does not comprise precultured microorganisms.
The methods first comprise mixing the solution or suspension
with microspheres coated with antibodies or antibody fragments
comprising an antigen binding site selective for the
microorganism. This creates a microsphere-
solution/suspension mixture. The method then comprises
evaluating the microsphere-solution/suspension mixture for
agglutination. In these methods, the presence of agglutination

9 McCoy, US 2007/0218522 A1, published Sept. 20, 2007.
Appeal 2020-004646
Application 12/918,159

6
indicates that the solution or suspension contains the
microorganism.
(Burns ¶ 37 (emphasis added); see also id. ¶ 60 (emphasis added) (Burns
discloses that “it is within the scope of the invention that these multiple
antibody/antibody fragment microbeads could be used with a bacteria that
has been precultured from the substrate where contamination is
suspected.”).)
FF 3. Burns discloses that “nonlimiting examples” of aqueous solution or
suspension within the scope of its invention:
[I]nclude environmental sources such as sewage, streams,
rivers, lakes, ground water, irrigation water, municipal water
supplies, tap water, and wells; food or animal feed including
extracts of solid food or feed; medical products including liquid
medicines and solutions and suspensions or extracts of solid
medicines; and vertebrate (including mammalian, e.g., human)
body fluids and products such as urine, bile, stool, peritoneal
washings, sputum, bronchial aspirate, cerebrospinal fluid, pus,
blood, and extracts of those fluids; and blood products such as
plasma, serum, and blood products that are substantially
purified from other blood products, such as red blood cells,
platelets, factor IX, factor VII, albumin, and antibodies. Blood
products, particularly blood cells and platelets, are preferred,
since there is an acute need for rapid tests for detecting
contaminating microorganisms in these products.
(Burns ¶ 38.)
FF 4. Burns uses the term “microorganism” to mean “a microscopic
prokaryotic, archeal, or eukaryotic organism that is suspected of
contaminating the aqueous solution or suspension, including bacteria, fungi
and parasitic species that are capable of infecting vertebrates,” wherein the
term “‘[m]icroorganism’ does not include viruses” (Burns ¶ 39).
Appeal 2020-004646
Application 12/918,159

7
FF 5. Burns discloses that the term “‘selective’ means the ability of the
antibody or antigen binding site to noncovalently bind to the microorganism
but not other related microorganisms” (Burns ¶ 39; see id. ¶ 40 (Burns
discloses that “[i]t is understood that antibodies selective for any particular
species of bacteria could be produced without undue experimentation.
Preferred are bacteria that are known pathogenic contaminants. Non-
limiting examples include . . . Listeria spp.”)).
FF 6. Burns discloses that its “methods are useful with any type of
microsphere known in the art, for example red blood cells
(‘hemagglutination’). Preferably, the microspheres are latex microspheres,
since these are widely used in agglutination methods and techniques to bind
antibodies to latex microspheres, either covalently or noncovalently, are well
developed” (Burns ¶ 44).
FF 7. Burns discloses that its “methods can be used with any agglutination
format, for example a hanging drop slide . . ., or in wells of multiwell plates,
such as a typical 96-well microtiter plate,” wherein “agglutination of the
microspheres can be assessed visually with the naked eye or through a
microscope . . . or using an instrument that measures light scattering” (Burns
¶¶ 48–49).
FF 8. Burns discloses that its methods are “not narrowly limited to any
particular type of antibody or antibody fragment comprising an antigen
binding site. Thus any type of antibody or fragment known in the art . . . can
be used,” wherein “[t]he antibodies can also comprise a detectible label,
such as a radioactive, fluorescent, hapten (e.g., digoxigenin), or ligand (e.g.,
biotin) labels, which could aid in detecting agglutination” (Burns ¶ 51).
Appeal 2020-004646
Application 12/918,159

8
FF 9. Examiner finds that Burns fails to disclose “the measuring in real-
time an amount of binding of the microorganism to the support at a plurality
of time points during the 4-96 hour (4-16 hours for claim 75) of culture
time” (Ans. 11).
FF 10. Atrache “relates to methods for detecting low levels of a particular
microorganism, or microorganisms from a mixed culture or sample using
antibodies and solid immunosorbent supports without the need for a
preliminary or further growth step in selective media” (Atrache 1:12–17
(emphasis added)).
FF 11. Atrache discloses:
[A] method for detecting low levels of a particular
microorganism . . . in a sample which method comprises:
exposing the sample to a solid support to which are adsorbed
antibodies specific for the microorganism or microorganisms
being detected, said antibodies being capable of selective
capture and immobilisation of the microorganism or
microorganisms without compromising the ability of the
microorganism or microorganisms to replicate; washing the
support to remove unbound materials; adding sterile nutrient
broth to the support; incubating the support in the nutrient
broth at a temperature and for a time relative to the generation
time of the microorganism or microorganisms sufficient to
allow the microorganism or microorganisms to reach a
detectable level; washing the support and then performing an
immunoassay on the support using an immunoreagent specific
for the microorganism or microorganisms being detected.
(Atrache 3:57–4:7)
FF 12. Atrache discloses microorganisms, within the scope of its disclosure,
include Listeria species” (Atrache 4:18–18).
FF 13. Atrache discloses:
The exposure of the sample to the antibody-coated support is
generally for 1 hour or less. The wash steps are preferably
Appeal 2020-004646
Application 12/918,159

9
performed using sterile saline buffer, more preferably Tris-
saline buffer. Virtually any nutrient broth may be used in the
method, however, preferred broths are tryptone soya broth and
M broth. The incubation in nutrient medium may be overnight
and is usually at 37° C.
(Atrache 4:19–26.)
FF 14. Manafi discloses techniques “for detection and differentiation of
bacteria,” “based on the utilization of chromogenic and fluorogenic
substrates for detection of activities of specific enzymes. These sensitive
methods have led to improved accuracy and faster detection and may be
performed by using the primary isolation media, thus bypassing the need for
time-consuming isolation procedures prior to identification” (Manafi 335;
see id. (Manafi reviews “recent publications, with particular emphasis on
methods for specific detection of Escherichia coli”)).
FF 15. Hansen “relates to optical analytical methods based on rates of
particle agglutination” (Hansen 1:8–12).
FF 16. Hansen discloses that “[a]n important aspect of particle
agglutination . . . is that scattered light intensity measured as a function of
time can be the basis for a very sensitive kinetic immunoassay” (Hansen
2:54–58).
FF 17. Hansen discloses:
[A] quantitative, kinetic, particle agglutination method for
simultaneously measuring the concentrations of several
analytes in a single fluid sample. The method entails the use of
a novel high resolution optical flow particle analyzer instrument
wherein detection by a single light detector of unidirectional
low angle forward light scatter from differently sized and/or
refractive indexed coated monomeric particles and their
multimeric aggregates, is the basis of a stable kinetic method
designed for simultaneous assays of multiple analytes in a
single sample. The expressions “particles”, “spheres”,
Appeal 2020-004646
Application 12/918,159

10
“microspheres” and “beads” are used interchangeably herein
and are intended to refer to polymeric (e.g., latex, polystyrene)
spherical particles of generally uniform diameter and refractive
index relative to the surrounding medium.
(Hansen 8:8–23; see id. at 12:45–49 (Hansen’s “procedure involves
suspending in an assay reagent solution appropriate to the particular analytes
being estimated antibody-coated monomeric spheres of different diameter or
refractive index.”).)
FF 18. Hansen discloses that its method “may be used to measure either
agglutination or inhibition of agglutination of coated particle,” wherein
“[c]omponents of the reaction mixture may be added concurrently or
sequentially” (Hansen 13:22–26).
FF 19. Examiner finds that “if Burns, Manafi, Atrache and Hansen do not
teach that the agglutination detectable signal reaction implements a phage-
bacterial protein reaction,” Sun makes up for this deficiency (see Ans. 22;
see also 22–24).
FF 20. Examiner finds that the combination of “Burns, Manafi, Atrache and
Hansen do not explicitly teach that the microorganisms are counted
according to the most probable number method” and relies on McCoy to
make up for this deficiency (see Ans. 24; see also 24–26).
ANALYSIS
I
Based on the combination of Burns, Manafi, Atrache, and Hansen,
Examiner concludes that, at the time Appellant’s invention was made, it
would have been prima facie obvious to use Atrache’s “incubation times and
temperatures,” in the method of Burns, Manafi, Atrache, and Hansen, to
“provide an improved assay where slow growing or hard to detect
Appeal 2020-004646
Application 12/918,159

11
microorganisms (e.g., Listeria monocytogenes) can be tested which expands
the range of the assay to such microorgamsms” (Ans. 20; see FF 1–18).
Examiner further concludes that, at the time Appellant’s invention was
made, it would have been prima facie obvious “to add the culture medium a
chromogenic or fluorescent enzymatic substrate that directly detects an
enzymatic activity of the microorganism (when present in the sample)
independent of agglutination so as to provide a robust assay that can detect
microorganisms based direct contact of produced enzymes” and “replace the
kinetic assay of Hansen for the endpoint assay in Burns . . . [to] provide an
improved assay where slow growing or hard to detect microorganisms can
be tested and analyzed real-time with multiple data points during the
analysis” (Ans. 20–21.) We are not persuaded
Burns discloses methods of detecting a microorganism in an aqueous
solution or suspension that has, or has not, been precultured (FF 2 (emphasis
added)).
Atrache discloses a method, wherein at least one microorganism, in a
sample, is captured with a solid support comprising adsorbed antibodies
specific for the microorganism being detected to form a microorganism-solid
support complex, washing the complex to remove unbound materials,
incubating the complex in a nutrient broth, at a temperature and for a time
relative to the generation time of the microorganism or microorganisms
sufficient to allow the microorganism or microorganisms to reach a
detectable level, washing the complex, and then performing an immunoassay
on the complex using an immunoreagent specific for the microorganism or
microorganisms being detected (FF 11; see also FF 10 (Altrache discloses
“methods for detecting low levels of a particular microorganism, or
Appeal 2020-004646
Application 12/918,159

12
microorganisms from a mixed culture or sample using antibodies and solid
immunosorbent supports without the need for a preliminary or further
growth step in selective media”) (emphasis added)). Thus, Atrache, like
Burns, discloses the detection of microorganisms that have either been
precultured or not cultured.
Examiner relies on Manafi and Hansen to disclose techniques for
detecting a microorganism by either agglutination or the detection of
specific enzymes produced by the microorganism (see FF 14–18). Examiner
does not, however, identify a teaching in either reference to support a
conclusion that the detection of the microorganism would be
contemporaneous with the culturing of the microorganism as required by
Appellant’s claimed invention.
Thus, the combination of Burns, Manafi, Atrache, and Hansen
suggests, at best, a method of preculturing a microorganism obtained from a
sample prior to identifying the microorganism (see FF 1–18). This is,
however, not what Appellant claimed. To the contrary, Appellant’s claimed
invention requires, inter alia, “subjecting a mixture including the sample, a
sensitized solid support, and a culture medium in a container to culturing
conditions for 4 to 96 hours so as to culture the microorganism when present
in the sample such that the microorganism is multiplied,” wherein “the
binding of the microorganism to the sensitized solid support takes place
simultaneously with the multiplication of the microorganism when present in
the sample” and “binding of the microorganism to the sensitized solid
support indicates that the microorganism is present in the sample,” wherein
binding of the microorganism to the sensitized solid support is measured in
Appeal 2020-004646
Application 12/918,159

13
real time during culturing (see Claim 59: Appeal Br. A-1; see also Claim
77: Appeal Br. A-3–A-4; Claim 82: Appeal Br. A-4–A-5).
We acknowledge Examiner’s assertion that a microorganism may
grow in the sample itself (i.e. blood, plasma, serum, environmental sources
such as sewage, streams, rivers, lakes, ground water, irrigation water,
municipal water supplies, etc.) (Ans. 28). According to Examiner, because
“bacteria can grow in stored blood products, such blood products are
representative of a culture media where bacteria are . . . cultured at any time
prior to testing” and, thus, “Burns teaches methods for testing samples that
are precultured or cultured prior to testing” (id.). Examiner’s assertion,
however, conflates the sample with the culture medium and, thus, fails to
account for the requirement of Appellant’s claimed invention that the sample
is mixed with, inter alia, culture medium (see, e.g., Claim 59: Appeal Br.
A-1; see also Claim 77: Appeal Br. A-3–A-4; Claim 82: Appeal Br. A-4–
A-5). See CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir.
2003) (citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)) (“[O]bviousness
requires a suggestion of all limitations in a claim.”).
Therefore, we agree with Appellant’s contention that the combination
of “Burns, Atrache, Hansen, and Manafi do not teach or suggest subjecting a
mixture containing a sample . . . and a culture medium to culturing
conditions for 4 to 96 hours so as to multiple the microorganism, or
measuring binding of the microorganism to the solid support during
culturing, as recited by claims 59, 77, and 82” (Appeal Br. 18; see also
Reply Br.10 2 (“Burns does not teach or suggest measuring an amount of

10 Appellant’s June 2, 2020 Reply Brief.
Appeal 2020-004646
Application 12/918,159

14
binding of the microorganism to a sensitized solid support during culturing
of a mixture including a sample, a culture medium, and the solid support.”);
see generally Reply Br. 2–14).
II
Based on the combination of Burns, Manafi, Atrache, Hansen, and
Sun, Examiner concludes that, at the time Appellant’s invention was made,
it would have been prima facie obvious “to substitute the microspheres of
Burns, Manafi, Atrache and Hansen for the microspheres in Sun since Sun
provides an alternative capturing ligand that would improve and expand the
testing techniques discussed in Burns, Manafi, Atrache and Hansen” (Ans.
23; see FF 1–19).
As Appellant explains, however, “Sun, which is only applied as
allegedly teaching magnetic beads coated with a biotinylated
bacteriophage . . . do[es] not cure the above-deficiencies of Burns, Manafi,
Atrache, and Hansen with respect to independent claims 59, 77, and 82”
(Appeal Br. 31). We agree.
III
Based on the combination of Burns, Manafi, Atrache, Hansen, and
McCoy, Examiner concludes that, at the time Appellant’s invention was
made, it would have been prima facie obvious “to add the McCoy MPN
technique to Burns, Manafi, Atrache and Hansen since McCoy provides an
alternative analytical method that would improve and to provide accurate
results of the testing techniques discussed in the Burns, Manafi, Atrache and
Hansen references” (Ans. 26; see also FF 1–18 and 20).
As Appellant explains, however, “McCoy, which is only applied as
allegedly teaching the additional feature recited by dependent claim 61,
Appeal 2020-004646
Application 12/918,159

15
do[es] not cure the above-deficiencies of Burns, Manafi, Atrache, and
Hansen with respect to independent claims 59, 77, and 82” (Appeal Br. 31).
We agree.
CONCLUSION
The preponderance of evidence relied upon by Examiner fails to
support a conclusion of obviousness.
Rejection I: The rejection of claims 59, 60, and 62–87 under
35 U.S.C. § 103(a) as unpatentable over the combination of Burns, Manafi,
Atrache, and Hansen is reversed.
Rejection II: The rejection of claims 59, 71, and 77 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Burns, Manafi, Atrache,
Hansen, and Sun is reversed.
Rejection III: The rejection of claim 61 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Burns, Manafi, Atrache, Hansen, and
McCoy is reversed.
DECISION SUMMARY
In summary:
Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
59, 60,
62–87
103 Burns, Manafi,
Atrache, Hansen
59, 60,
62–87
59, 71, 77 103 Burns, Manafi,
Atrache, Hansen,
Sun
59, 71, 77
61 103 Burns, Manafi,
Atrache, Hansen,
McCoy
61
Overall
Outcome
59–87

REVERSED