Susan Kircher et al.

Patent Trials and Appeals Board

Jan 23, 2020

11958827 - (D) (P.T.A.B. Jan. 23, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/958,827 12/18/2007 Susan Kircher BECTON 3.0-012 1771
147462 7590 01/23/2020
Botos Churchill IP Law LLP
430 Mountain Avenue
Suite 401
New Providence, NJ 07974
EXAMINER
GOUGH, TIFFANY MAUREEN
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
01/23/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte SUSAN KIRCHER, JON E. SALOMON, and
SHERYL DOUGLAS-MCKAY
__________

Appeal 2018-002838
Application 11/958,8271
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

TOWNSEND, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a medium
for detecting and differentiating species of enterococci, which have been
rejected as indefinite and/or obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We affirm the indefiniteness rejection and reverse the obviousness
rejection.

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 Becton,
Dickinson & Co. (Appeal Br. 1.)
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STATEMENT OF THE CASE
Enterococci are bacteria that “are normal inhabitants of the
gastrointestinal (GI) tract of humans and most animal.” (Spec. ¶ 3.)
However, “[c]olonization with these organisms often precedes infection,
including infection of the urinary tract, intra-abdominal cavity, and the
lining of the heart (i.e., endocarditis).” (Id.) Unfortunately, strains of
Enterococci that have been associated with increased mortality are resistant
to vancomycin,2 which is the current antibiotic treatment of choice for multi-
drug resistant organisms. (Id. ¶ 4.) Appellant’s invention is directed to a
medium for use in the detection of vancomycin-resistant enterococci. (Id. ¶
2.)
Claims 8, 11, 12, 23, 25–36, 38, and 51 are on appeal. Claim 25 is
representative and reads as follows:
25. A medium for detecting and differentiating species
of enterococci comprising:
a first substrate conjugated to a first imaging moiety,
wherein the first substrate preferentially interacts with a first
enzyme that is produced by a first species of enterococci
compared to a second enzyme that is produced by a second
species of enterococci; and
a second substrate conjugated to a second imaging
moiety, wherein the second substrate preferentially interacts
with the second enzyme that is produced by the second species
of enterococci compared to the first enzyme that is produced by
the first species of enterococci;
an inhibitor of non-vancomycin resistant enterococci
comprising vancomycin;

2 Such vancomycin resistant enterococcus species are referred to in the prior
art as VRE. (See, e.g., Hanson Abs.)
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a third substrate;
and cefoxitin;
wherein the third substrate, but not the first and second
substrates, induces the production of the first enzyme by at least
a third species of enterococci that produces the second enzyme
without inducement;
wherein the first imaging moiety images a first indicator
when the first substrate interacts with the first enzyme and the
second imaging moiety images a second indicator when the
second substrate interacts with the second enzyme;
and the combined presence of the first imaging moiety
and second imaging moiety image a third indicator in the
combined presence of the first enzyme and the second enzyme
produced by the third species of enterococci,
wherein, the first second and third indicators are
perceptually different from each other;
and wherein the cefoxitin in combination with
vancomycin either inhibits the growth of the third species of
enterococci but not the growth of the first or second species of
enterococci or the third species of enterococci overcomes the
inhibition wherein the third indicator indicates that the third
species overcame the inhibition.
(Appeal Br. 20–21.)

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The prior art relied upon by the Examiner is:
Name Reference Date
Chen WO 98/04674 Feb. 5, 1998
Chen US2002/0132285 A1 Sept. 19, 2002
Chen US6355449 B1 Mar. 12, 2002
Orenga US 2008/0145879 A1 June 19, 2008
Badal WO 92/12257 July 23, 1992
Hanson et al., Comparison of Simple and Rapid Methods for Identifying
Enterococci Intrinsically Resistant to Vancomycin, 37(3) J. Clin.
Microbiol., 815–17 (1999)
S. Vincent et al., Vancomycin resistance in Enterococcus gamnarum,
36(7) Antimicrob. Agents Chemother., 1392–99 (1992)

The following grounds of rejection by the Examiner are before us on
review:
Claims 8, 11, 12, 23, 25–36, 38, and 51 under 35 U.S.C. § 103(a) as
unpatentable over Chen (any one of ’674, ’285 and ’449), Orenga, Badal,
Hanson, and Vincent.
Claim 38 under 35 U.S.C. § 112, second paragraph as being indefinite
for being dependent from cancelled claim 37.3
DISCUSSION
The Examiner finds that each of the Chen references teach a medium
for detecting E. faecalis, E. faecium, E. casseliflavus, and E. gallinarum,
which are vancomycin resistant Enterococci, that comprises a first and

3 In its Reply Brief, Appellant concedes that claim 38 on appeal does
depend from claim 37 (Reply Br. 1–2), a concession with which we agree, as
reflected in the Amended Appeal Brief Claims Appendix filed August 30,
2017. Because Appellant does not contest the section 112 rejection as
applied to claim 38, that rejection is summarily affirmed.
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second substrate of which is conjugate to an image moiety and where the
substrates “are selected to interact with a first and second enzyme produced
by different species of microorganism.” (Final Action 4.) The Examiner
further finds that the medium also includes vancomycin and cephalosporins,
such as cefoxamine, as well as other inhibitors. (Id.)
The Examiner finds Orenga teaches a medium for distinguishing
species of a microorganism that includes two substrates selected to interact
with different enzymes produced by different microorganism species and
which are conjugated to chromophores. (Id.) The Examiner also finds that,
like Chen, Orenga teaches including vancomycin and cephalosporins and
other inhibitors in the medium. (Id. at 5.) Orenga specifically indicates the
use of vancomycin and cephalosporins for distinguishing Enterococci. (Id.)
The Examiner further finds that Orenga teaches using “the substrates alpha-
D-glucopyranoside, beta-D-galactopyranosidase and methyl-alpha-D-
glucopyranosidase (0370-0378, Ex. 4) to identify E. faecalis, E. faecium and
E. casseliflavus and E. gallinarum.” (Id.) The Examiner further finds that
Orenga teaches the use of a combination of antimicrobials to distinguish
between three different species of microorganisms, as well as using a third
substrate. (Id.)
The Examiner finds that Vincent teaches that it was known that E.
gallinarum expresses low-level resistance to glycopeptide antibiotics, e.g.,
vancomycin, and that this resistance is overcome with cephalosporins.
(Final Action 6.) The Examiner also finds that Vincent teaches “there is a
synergistic effect of the combination on vancomycin resistance in E.
gallinarum (a VanC phenotype) which differs from both E. faecalis, E.
faecium (vanA and VanB phenotypes).” (Id.)
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The Examiner further finds that Hanson teaches that (1) E. faecalis
and E. faecium have a high-level vancomycin resistance while E. gallinarum
and E. casseliflavus express low-level resistance and, in fact, “will grow
in/on vancomycin containing media” and (2) the substrate methyl-α-D-
glucopyranoside (MGP) can be used to determine whether E. gallinarum and
E. casseliflavus are present in a sample as compared to E. faecalis and E.
faecium because E. faecalis and E. faecium are negative in an MGP analysis
whereas E. gallinarum and E. casseliflavus are positive. (Final Action 6.)
In light of the foregoing teachings, the Examiner determines that the
prior art “clearly teach a first, second and third claimed substrate for
distinction among Enterococci species” (id. at 5) and that Vincent would
have motivated the use of vancomycin and a cephalosporin for use in
determining the presence of E. gallinarum and Hanson would have
motivated one having ordinary skill in the art to include MGP as a third
substrate to detect a third Enterococci species since the MGP substrate can
differentiate vanC Enterococci species, which include E. gallinarum, from
E. faecalis and E. faecium (id. at 6–7).
We agree with the Examiner that the combination of references
suggests a medium for differentiating three different species of Enterococcus
that includes vancomycin and cephalosporin and three substrates that are
species specific. But we do not agree that the Examiner has established the
claimed medium is prima facie obvious.
Orenga teaches different medium for detecting at least three different
microorganisms in a sample (Orenga ¶ 109) where the different
microorganisms can be different species within the same genus (Orenga
¶ 257 (“This third embodiment of the invention makes is possible to
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distinguish, in the same sample, a first and a second group comprising the
same species of microorganisms”), ¶ 282 (the “third embodiment of the
invention is not limited to distinguishing 3 groups of microorganisms, but
may make it possible to distinguish 4, 5 or even more groups of
microorganisms.”).) Orenga teaches that markers for differentiating
microorganism groups means the use of a “specific substrate” “which does
not have the same properties on a first and on a second group.” (Orenga
¶¶ 40–41.) While not exemplified, Orenga suggests use of three different
substrates for detecting three different species particularly because it
describes using as many substrates in the context of identifying three
different genera of microorganisms. (Id. ¶¶ 283–293).
In other words, one of ordinary skill in the art would have reasonably
understood from Orenga’s teaching that three different substrates could be
used in a medium for distinguishing species of microorganisms just as it
could be used to distinguish between genera of microorganism. In re GPAC
Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (“In determining whether
obviousness is established by combining the teachings of the prior art, the
test is what the combined teachings of the references would have suggested
to those of ordinary skill in the art.”) (Internal quotations omitted.) Thus,
we disagree with Appellant that Orenga “does not disclose or suggest a
medium that is even capable of delivering a perceptual differen[ce] among
three VRE species.” (Appeal Br. 11.) While Orenga exemplifies only the
use of 2 different substrates conjugated to a chromogen for differentiating
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Enterococcus species that are species specific (Orenga Example 4), it
nevertheless suggests the use of a third substrate.4
Additionally, contrary to Appellant’s argument (e.g., Reply Br. 8), we
agree with the Examiner that the references together suggest a medium that
includes vancomycin and a cephalosporin when detecting vancomycin-
resistant Enterococci species. Chen teaches including both vancomycin and
a cephalosporin (cefotaxime) in the same medium when using the medium
for assessing the presence of Enterococci species. (See Chen ’6745 at 35/2
Component II, and 17–18.) We also agree with the Examiner that Orenga
teaches a medium that includes vancomycin and an additional inhibitor, such
as cefotaxime. (Orenga ¶¶ 49, 57, 211–14, 220–226.)
Vincent teaches that E. gallinarum is weakly vancomycin resistant
and that the resistance can be overcome with a cephalosporin, such as
cefoxitin and cefotaxime. (Vincent 1394 (Table 3), 1397.) Vincent also
teaches that vanA and vanB resistant Enterococci have a different

4 We also agree with the Examiner that Chen, similar to Orenga, is
concerned with two or more nutrient indicators that yield distinctively
different detectable signals so as to distinguish between species of
microorganisms. (See, e.g., Chen ’674 at 6.) That Chen may use “sequential
detection” of the nutrient indicators so that there is no detectable signal
interference (Appeal Br. 9) is not relevant to whether or not the medium
claimed, which requires, inter alia, the presence of two different substrates,
is obvious over the cited prior art. That is because Chen’s method of
detection of the imaging moiety conjugated to the substrate is not necessary
to address whether the claimed first and second substrates of the medium are
present and are conjugated to an imaging moiety and that the moiety
“images” an indicator after the substrate interacts with an enzyme produced
from a species of Enterococci.
5 We only refer to Chen ’674, but understand the disclosures of each of the
Chen references cited by the Examiner to be substantially similar.
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phenotype, e.g., their vancomycin resistance is not overcome with
cephalosporins. (Vincent 1397.) Vincent further teaches that E. faecium is a
vanB bacteria and that E. faecalis is a vanA bacteria. (See id. at 1393 (Table
1.) Hanson teaches the importance of identifying VRE (Hanson 815). Thus,
one of ordinary skill in the art would have found it obvious to include a
substrate that would detect whether the weakly resistant E. gallinarum was
present in a sample should the resistance not be overcome with the
cephalosporin suggested for use in the medium by both Chen and Orenga.
Hanson teaches such a substrate is MGP because E. gallinarum (and E.
casseliflavus) can acidify MGP but E. faecalis and E. faecium cannot.
(Hanson 815 (a change in the color from red to yellow is indicative of a
positive result), 816 (Table 1).)
Nevertheless, despite the foregoing analysis, we do not agree with the
Examiner that the references relied upon render obvious a composition
where the first and second substrate are conjugated to first and second
imaging moieties, respectively, that in combination image a third indicator
indicative of the third species of Enterococcus. That is because we find
Orenga teaches that in assessing three or more different species of the same
group of microorganisms, one of those species is growth inhibited by the
antimicrobial and the remaining species are distinguished by markers that
are in the medium that are specific to each of the different species that will
grow in the medium. (See, e.g., Orenga ¶¶ 94–98, 257, 282, 368, 382, 384.)
Furthermore, Chen teaches independent detection of the different nutrient
indicators to determine the presence of a particular bacteria. (Chen ’674 at
6.) Chen indicates that the approach it takes by using a second nutrient
indicator that produces a colorless intermediate first before reacting it with a
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developing agent “prevents interference from the colored product of the first
nutrient indicator” in detecting a second bacteria. (Id. at 6–7.) Thus, we
agree with Appellant (although for a somewhat different reason) that Chen
teaches away from employing a mixture of chromogenic indicators to detect
one particular species.
We agree with the Examiner that by including MGP, as the third
substrate, which is reasonably suggested by Hanson as a specifies specific
substrate for E. gallinarum and not for E. faecalis and E. faecium (Hanson
816 Table 1), the repressed enzyme in E. gallinarum that is the same enzyme
that is produced by a first species of Enterococci, would inherently be
activated, provided that E. gallinarum broke through the vancomycin-
cephalosporin inhibition. (Ans. 10.) But that is not the same thing as
finding that the combined presence of the first imaging moiety and second
imaging moiety “image a third indicator in the combined presence of the
first enzyme and the second enzyme produced by the third species of
enterococci,” i.e., the combined presence of the first and second imaging
moiety indicate the third species of enterococci where Orenga suggests the
inclusion of a different colored marker specific to a species for all non-
growth inhibited microorganisms.
Orenga does not recognize the ability of a medium without a third
chromogenic imaging moiety to image a third species and Chen teaches
there can be a problem of interference from colored products masking one
another (Chen ’674 at 6.). “That which may be inherent is not necessarily
known. Obviousness cannot be predicated on what is unknown. Such a
retrospective view of inherency is not a substitute for some teaching or
suggestion supporting an obviousness rejection.” In re Rijckaert, 9 F.3d
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1531, 1534 (Fed. Cir. 1993) (internal citations and quotations omitted); see
also PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1195 (Fed. Cir.
2014) (distinguishing a prior case finding obviousness based on inherency
because, in that case, “neither party disputed that the [claimed features] were
expected in light of the dosages disclosed in the prior art” (emphasis added))
Nor is there any evidence that Orenga actually generated a medium that
would anticipate the instant claims.
We conclude that it is only by hindsight that one would arrive at a
medium required by claim 25
wherein the first imaging moiety images a first indicator
when the first substrate interacts with the first enzyme and the
second imaging moiety images a second indicator when the
second substrate interacts with the second enzyme;
and the combined presence of the first imaging moiety
and second imaging moiety image a third indicator in the
combined presence of the first enzyme and the second enzyme
produced by the third species of enterococci.
Consequently, we reverse the Examiner’s rejection of claims 8, 11, 12, 23,
25–36, 38, and 51 under 35 U.S.C. § 103(a) as unpatentable over Chen (any
one of ’674, ’285 and ’449), Orenga, Badal, Hanson, and Vincent.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
38 112,
second
paragraph
38
8, 11, 12,
23, 25–36,
38, 51
103(a) Chen ’674, Chen
’285, Chen ’449,
8, 11, 12,
23, 25–36,
38, 51
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Orenga, Badal,
Hanson, Vincent
Overall
Outcome
38 8, 11, 12,
23, 25–36,
51

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-IN-PART