Ex Parte Huber-Haag et al

Patent Trial and Appeal Board

Dec 2, 2016

12593462 (P.T.A.B. Dec. 2, 2016)

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.
12/593,462 09/28/2009 Karl-Josef Huber-Haag 3712036-1002 5913
29157 7590 12/06/2016
K&T Oates T T .P-Phiraan
EXAMINER
P.O. Box 1135
CHICAGO, IL 60690
PYLA, PAUL D
ART UNIT PAPER NUMBER
1653
NOTIFICATION DATE DELIVERY MODE
12/06/2016 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):
USpatentmail@klgates.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KARL-JOSEF HUBER-HAAG, MARIE-CLAIRE FICHOT,
FLORENCE ROCHAT, and NORBERT SPRENGER1
Appeal 2014-005255
Application 12/593,462
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, 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
administering to an infant delivered by caesarean section a probiotic and
prebiotic composition for promoting the development of an early bifidogenic
intestinal microbiota, which have been rejected as obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as Nestec S.A. (Appeal Br.
2.)
Appeal 2014-005255
Application 12/593,462
STATEMENT OF THE CASE
During the normal process of vaginal birth, the gastrointestinal tract of
a baby encounters bacteria from the digestive tract, skin, and environment of
the mother and starts to become colonized, whereas immediately before
birth, the gastrointestinal tract is thought to be sterile. (Spec. 1.) It has been
determined that “the rates of colonisation by Bifidobacteria ... in [infants
bom by] caesarean [section]. . . reached the rates of colonisation in the
vaginally delivered group only after one month.” (Id.)
“[I]t has recently been demonstrated that human milk contains not
only oligosaccharides but also Bifidobacteria.” (Spec. 3.) “Mother’s milk is
recommended for all infants. However, in some cases breast feeding is
inadequate or unsuccessful for medical reasons or the mother chooses not to
breast feed.” (Spec. 2.)
“[M]ore and more evidence is emerging which suggests that the
establishment of an appropriate intestinal microbiota early in life may be . . .
significant in subsequent healthy development.” (Spec. 3.) Appellants’
invention is directed to promoting the “establishment of an appropriate
intestinal microbiota in infants where this does not occur naturally.” (Id.)
Claims 1, 7-9, and 11-15 are on appeal.2 Claim 1 is representative
and reads as follows:
1. A method for promoting the development of an early
bifidogenic intestinal microbiota in infants delivered by
caesarean section comprising the step of administering to an
infant delivered by caesarean section a composition comprising
2 Claims 2, 3, 10, and 16-39 are also pending, but stand withdrawn from
consideration. (Ans. 2.)
2
Appeal 2014-005255
Application 12/593,462
Bifidobacterium lactis CNCM1-3446 and an oligosaccharide
mixture which comprises 5-20 wt% of at least one N-acetylated
oligosaccharide selected from the group consisting of
GalNAca 1,3Gaip 1,4Glc and Gaip l,6GalNAca 1,3 Gaip l,4Glc,
60-90 wt% of at least one neutral oligosaccharide selected from
the group consisting of Gaipi,6Gal, Gaipi,6Gaipi,4Glc
Gaip 1,6Gaip 1,6Glc, Gaipi,3Gaipi,3Glc, Gaipi,3Gaipi,4Glc,
Gaip 1,6Gaip 1,6Gaip 1,4Glc,Gaip 1,6Gaip 1,3Gaip 1,4Glc
Gaipi,3Gaipi,6Gaipi,4Glc and Gaipi,3Gaipi,3Gaipi,4Glc
and 5-30 wt% of at least one sialylated oligosaccharide selected
from the group consisting of NeuAca2,3Gaipi,4Glc and
NeuAca2,6Gaipi,4Glc.
(Appeal Br. 13.)
The following ground of rejection by the Examiner is before us on
review3:
Claims 1, 7-9, and 11-15 under 35 U.S.C. § 103(a) as unpatentable
over Boehm4, Donnet-Hughes,5 Sprenger,6 Isolauri,7 and Masco.8
3 The provisional obviousness-type double patenting rejections that were
pending as of the Final Office Action have been withdrawn in light of the
abandonment of the copending applications over which the rejections were
made. (Ans. 3.)
4 Boehm et al., WO 2007/045502 Al, published Apr. 26, 2007, and filed
Oct. 20, 2006.
5 Donnet-Hughes et al., WO 2006/108824 Al, published Oct. 19, 2006.
6 Sprenger et al., WO 2007/101675 Al, published Sept. 13, 2007, and filed
Mar. 7, 2007.
7 E. Isolauri et al., Probiotics: a role in the treatment of intestinal infection
and inflammation? 50 (Suppl. Ill) Gut, iii54-iii59 (2002).
8 Liesbeth Masco et al., Polyphasic taxonomic analysis of Bifidobacterium
animalis and Bifidobacterium lactis reveals relatedness at the subspecies
level: reclassification of Bifidobacterium animalis as Bifidobacterium
animalis subsp. animalis subsp. nov. and Bifidobacterium lactis as
3
Appeal 2014-005255
Application 12/593,462
DISCUSSION
The Examiner finds that Boehm teaches infants delivered by
caesarean section have a different intestinal flora compared with infants bom
vaginally. (Ans. 5.) Boehm also teaches that a healthy intestinal flora
reduces incidence of infections and provides for a strengthened immune
system and it is of “utmost importance to stimulate the healthy development
of the intestinal flora of infants born via cesarean section.” (Final Action 3-
4; Ans. 5.) According to the Examiner, Boehm teaches that breast milk is
“the gold standard” for developing nutrition for infants in order “to mimic
the compositional features and physiological effects of human breast milk”
and that human breast milk contains prebiotic fiber that stimulates the
development of a healthy intestinal flora. {Id.) The Examiner finds that
Boehm teaches a method for stimulating the development of a healthy
intestinal flora in an infant delivered by c-section comprising administering
a composition that includes at least one microorganism that may be
Bifidobacterium bifidum (now known as Bifidobacterium lactis (as indicated
by Isolauri), which is a subspecies of Bifidobacterium animalis (as indicated
by Masco)) and at least one indigestible oligosaccharide. (Final Action 4-5;
Ans. 5-6.) The indigestible oligosaccharide benefits the host “by selectively
stimulating the growth and/or activity of one or a limited number of bacterial
species in the colon.” (Id.) Boehm also teaches that “the composition can
be admixed with breast milk[,] which will contain additional
oligosaccharides.” (Id.) The Examiner acknowledges that Boehm does not
Bifidobacterium animalis subsp. lactis subsp. nov., 54 Int. J. Syst. Evol.
Microbiol., 1137^13 (2004).
4
Appeal 2014-005255
Application 12/593,462
teach the specifically claimed strain of B. lactis or the specific
oligosaccharide mixture claimed. (Final Action 6; Ans. 7.) However, the
Examiner finds that Donnet-Hughes and Sprenger suggest these specific
elements in a nutritional formula for infants.
In particular, the Examiner finds that, like Boehm, Donnet-Hughes is
concerned with promoting the development of a beneficial intestinal
microbiota in infants. (Ans. 9; Final Action 6.) Where Boehm is concerned
specifically with infants delivered by c-section, Donnet-Hughes is concerned
with neonates generally, which the Examiner notes includes infants
delivered via c-section. (Ans. 7.) In Donnet-Hughes, the neonate is
provided with a probiotic bacteria, such as B. lactis CNCM1-3446, and the
formulation provided to the neonate can also include carbohydrates and
fibers. (Final Action 6; Ans. 7.) Moreover, the Examiner finds that Donnet-
Hughes teaches that adding the foregoing to the neonate diet stimulates
beneficial intestinal microbiota, and promotes the maturation of the immune
system of the neonatal infant, just as Boehm teaches is the case with c-
section babies provided with probiotic Bifidobacterium and a prebiotic
combination. (Ans. 8-9; Final Action 6.) The Examiner finds that Sprenger
teaches an infant formula composition that comprises probiotic bacteria and
the prebiotic oligosaccharides recited in claim 1. (Final Action 6; Ans. 7.)
According to the Examiner, the foregoing facts would have suggested
to the person of ordinary skill in the art to substitute B. lactis CNCM 1-3446
in the Boehm formulation for the “predictable result of successfully
stimulating the development of a healthy intestinal flora in an infant
(delivered by caesarean section).” (Ans. 8-9; Final Action 7.) The
5
Appeal 2014-005255
Application 12/593,462
Examiner further finds that one of ordinary skill in the art would have
further been motivated to include the oligosaccharide mixture of Sprenger so
that the infant formula composition would more closely resemble breast
milk and stimulate the healthy development of the intestinal flora of infants.
(Ans. 7-9; Final Action 8-9.)
We agree with the Examiner’s factual findings and conclusion that
Boehm, Donnet-Hughes, and Sprenger make obvious the claimed method of
promoting the development of an early bifidogenic intestinal microbiota in
infants delivered by c-section using the recited composition.
Appellants argue that the references fail to suggest administering to an
infant delivered by c-section the specifically claimed B. lactis strain (Appeal
Br. 6-8). In particular, Appellants contend that “the teachings of Donnet-
Hughes regarding neonatal infants generally are not necessarily applicable to
infants bom by caesarean delivery” because “[t]he overall pattern of
combination of risks in infants bom by caesarean delivery is fundamentally
different from the risk of the general infant population” and “Donnet-
Hughes is entirely directed to development of intestinal microbiota in
formula-fed infants in order to more closely conform the intestinal
microbiota to that of breast fed babies” and is “completely silent regarding
infants bom by caesarean delivery.” (Appeal Br. 7.) Further, according to
Appellants, “Boehm itself demonstrates that the teachings of Donnet-Hughes
regarding neonatal infants generally are not necessarily applicable to infants
bom by caesarean delivery by disclosing that, for infants delivered by
caesarean section, ‘their intestinal flora at birth is completely different from
the intestinal [flora of] infants bom via the vaginal route.’” (Appeal Br. 7-
6
Appeal 2014-005255
Application 12/593,462
8.) Appellants further contend that prior art demonstrates that health
benefits conferred by a specific bacterial strain to a host are strain specific
and are not predictable. (Appeal Br. 7 (citing Senok9); Reply Br. 3—4.) We
do not find these arguments persuasive.
In particular, whether the overall risk pattern may be different
between infants delivered via c-section and infants generally, Donnet-
Hughes is concerned with neonates as a class; as the Examiner noted (Ans.
11), the neonate class of Donnet-Hughes does not exclude infants delivered
by c-section. Moreover, whether Donnet-Hughes is concerned with
mimicking the intestinal microbiota of breast fed babies, it, nevertheless,
teaches the use of B. lactis CNCM1-3446 for the purpose of promoting the
development of a beneficial intestinal microbiota and to promote the
maturation of the immune system of a neonatal infant “in need thereof.”
(Donnet-Hughes 3 and Abstr.) Donnet-Hughes explains that in some
situations infants are not breast fed for a variety of reasons, and regardless of
reason, the gut microbiota of non-breast fed infants is different from that of
breast fed infants including with respect to the population of Bifidobacteria.
(Donnet-Hughes 1.) Similar to the difference in gut bacteria noted by
Donnet-Hughes, Boehm teaches that infants delivered by c-section lack
several species of Bifidobacteria, as compared to those bom vaginally,
including B. lactis. (Boehm 14-16 (Tables 1 and 2).) Boehm further
teaches that “biodiversity [of the intestinal flora] is of great importance for
achieving the desired physiological effects and optimally stimulate the
9 A. C. Senok et al., Probiotics: facts and myths, 11(12) Clin. Microbial.
Infect., 958-66 (2005).
7
Appeal 2014-005255
Application 12/593,462
health of the infant” and thus indicates that, among other probiotics, B. lactis
would be a beneficial probiotic to administer to infants (Boehm 2—4, 18
(Example 4), 7.) Consequently, Boehm teaches that infants bom via c-
section would be “in need” of promoting maturation of the immune system
just like neonates who are not breast fed and that B. lactis would be one of
the beneficial species to provide.
Appellants’ argument that Donnet-Hughes “fails to suggest that B.
lactis CNCM1-3446 can be used to treat any of the specific health
conditions of the caesarean-section infants that the claimed invention targets
and solves” (Appeal Br. 7; Reply Br. 2) is also unavailing.
In determining whether the subject matter of a patent claim is
obvious, neither the particular motivation nor the avowed
purpose of the patentee controls. . . . [A]ny need or problem
known in the field of endeavor at the time of invention and
addressed by the patent can provide a reason for combining the
elements in the manner claimed.
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 419-20 (2007). As discussed,
Donnet-Hughes teaches that B. lactis CNCM 1-3446 promotes the
development of a beneficial intestinal microbiota and the maturation of the
immune system of a neonatal infant “in need thereof,” such as those that are
not breast fed and thus have a less appreciable population of Bifidobacteria
than those that are breast fed. (Donnet-Hughes 1.) And Boehm teaches that
infants delivered via c-section, like those who are not breast fed, have a less
appreciable population of Bifidobacteria than infants who are bom
vaginally. Thus, regardless of the fact that Donnet-Hughes may not identify
that B. lactis CNCM 1-3446 “can be used to treat any of the specific health
conditions of the caesarean-section infants that the claimed invention targets
8
Appeal 2014-005255
Application 12/593,462
and solves” (Appeal Br. 7; Reply Br. 2) it, nevertheless, provides incentive
for one of ordinary skill in the art to select that strain of B. lactis to use in the
Boehm method of increasing the species of beneficial intestinal flora in
infants delivered by c-section.
We disagree with Appellants that Boehm or Senok support finding it
unpredictable as to whether c-section infants would similarly benefit if the
B. lactis provided was B. lactis CNCM 1-3446. That the intestinal flora is
different between infants delivered vaginally and by c-section does not
suggest that addition of B. lactis CNCM 1-3446 to the diet of these infants
would not promote the maturation of the immune system of c-section infants
just as Boehm indicates B. lactis generally would. Moreover, while Senok
indicates generally that “[cjurrent evidence indicates that probiotic effects
are strain-specific” (Senok 959), the Examiner has provided prima facie
evidence that B. lactis CNCM 1-3446 administered to infants regardless of
the method of delivery of the infant would be expected to promote the
maturation of the immune system. As already noted, the neonate population
of Donnet-Hughes does not differentiate between infants delivered vaginally
or by c-section, noting simply the importance of promoting development of
the beneficial intestinal microbiota in neonatal infants and accomplishing
this goal with provision of B. lactis CNCM 1-3446. Sprenger notes, like
Boehm, that “immediately before birth, the gastrointestinal tract of a baby is
thought to be sterile” and that during the process of birth, the gastrointestinal
tract of a baby “encounters bacteria from the digestive tract and skin of the
mother and starts to become colonised.” (Sprenger 2.) Sprenger further
notes, like Donnet-Hughes, that “[ljarge differences exist with respect to the
9
Appeal 2014-005255
Application 12/593,462
composition of the gut microbiota in response to the infant’s feeding” and
that breast fed babies include “appreciable populations of bifidobacteria.”
{Id.) Similarly to Donnet-Hughes, Sprenger teaches that B. lactis CNCM I-
344610 in combination with prebiotics “promote[s] the establishment of a
bifidogenic intestinal microbiota in infants” (Sprenger 14 and 18 (Example
5, and Figures 3-5)) regardless of whether these infants are neonates, bom
by c-section or bom vaginally, and that adding this to the infant diet
“encourage[s] gut colonization to take place and . . . promote[s] colonization
with the ‘good’ bacteria,” including bifidobacteria, “rather than the harmful
bacteria - pathogens such as Clostridia, etc.” which are “usually present” in
formula fed infants (Sprenger 2-3, 14.) Thus, regardless of Senok’s general
statement concerning strain specificity of probiotics, one of ordinary skill in
the art would reasonably expect B. lactis CNCM 1-3446 to promote a
beneficial intestinal microbiota in infants delivered by c-section or vaginally,
and whether neonate or not, in light of the prior art cited by the Examiner.
Appellants’ argument that any prima facie case of obviousness has
been overcome with evidence of unexpected results (Appeal Br. 9-10) is
also unpersuasive. “To be particularly probative, evidence of unexpected
results must establish that there is a difference between the results obtained
and those of the closest prior art, and that the difference would not have been
expected by one of ordinary skill in the art at the time of the invention.”
10 Appellants contend that “Sprenger does not teach B. lactis CNCM I-
3446.” (Appeal Br. 8.) We disagree. Sprenger specifically identifies this
strain which it also calls “NCC 2818” as the one that was tested in in vivo
experiments and for which “results are shown in Figures 3, 4 and 5.”
(Sprenger 18 (Example 5).)
10
Appeal 2014-005255
Application 12/593,462
Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977
(Fed. Cir. 2014). Appellants’ evidence is deficient on both accounts.
As the Examiner notes, Appellants’ evidence is not a comparison to
the closest prior art. (Ans. 12-15.) Boehm teaches a composition
comprising B. lactis among other Bifidobacterium and at least one
indigestible oligosaccharide for administration to infants delivered by c-
section. (Boehm 18 (Ex. 4).) Boehm’s Example 4 thus differs from the
method of claim 1 in the strain of B. lactis and the specific oligosaccharides
recited. Sprenger’s Example 5 describes administration of B. lactis CNCM
1-3446 and an oligosaccharide mixture that comprised “about 30 wt%
GalNAca 1,3Gaip 1,4Glc and Gaipi,6GalNAcal,3Gaipi,4Glc, 50 wt% of
Gaip 1,6Gaip 1,4Glc and Gaipi,3Gaipi,4Glc and 20 wt% of
NeuAca2,3Gaipi,4Glc and NeuAca2,6Gaipi,4Glc.” (Sprenger 15:7-9,
18:5-26.) Sprenger’s Example 5 thus differs from the method of claim 1
only in the amounts of the recited oligosaccharides and the subjects to whom
it was administered (a mouse “model of human infant microbiota” in
Sprenger {id. at 18:12) versus infants delivered by c-section in claim 1).
Appellants’ comparison, while being in a mouse model of c-section delivery,
did not compare against a mouse model that was provided with a B. lactis
strain and a galactooligosaccharide taught by Boehm, nor was it a
comparison between the composition of Sprenger provided in mouse models
reflective of a “model of human infant microbiota” as compared to a mouse
model of infants delivered by c-section. Instead, Appellants’ comparison is
between a group who was initially provided with B. longum and given B.
11
Appeal 2014-005255
Application 12/593,462
lactis CNCM1-3446 and CMOS-GOS11 against a control group that was
provided with additional B. longum. (Appeal Br. 9-10; Ans. 14.)
Appellants’ evidence, therefore, does not show a comparison to the closest
prior art.
Moreover, based on the teachings of Boehm, the use of any B. lactis
strain would have been expected to stimulate the development of a healthy
intestinal flora in an infant delivered by c-section, and as discussed above
the teaching of Donnet-Hughes and Sprenger would teach one of ordinary
skill in the art that B. lactis CNCM 1-3446 in particular would achieve those
results.
Claims 7-9 and 11-15 have not been argued separately and, therefore,
fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
For the reasons discussed above, we affirm the rejection of claims 1,
7-9, and 11-15 under 35 U.S.C. § 103(a) as unpatentable over Boehm,
Donnet-Hughes, Sprenger, Isolauri, and Masco.
11 CMOS-GOS is an oligosaccharide mixture including N-acetylated
oligosaccharides, neutral oligosaccharides and sialylated oligosaccharides.
(Spec. 16.) The CMOS-GOS used in the examples contains about 9 wt %
N-acetylated oligosaccharides, about 82 wt % neutral
oligosaccharides and about 9 wt % sialylated oligosaccharides. (Spec. 18.)
12
Appeal 2014-005255
Application 12/593,462
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
13