Hans M. Albertsen

Patent Trials and Appeals Board

Jul 30, 2019

15168033 - (D) (P.T.A.B. Jul. 30, 2019)

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.
15/168,033 05/28/2016 Hans M. Albertsen HMA-003U 2044
52966 7590 07/30/2019
Schramm-Personal-ACT
Michael R. Schramm
350 West
2000 South
Perry, UT 84302
EXAMINER
BARSKY, JARED
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
07/30/2019 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):
mike@schrammpatent.com
mikeschramm@besstek.net
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HANS M. ALBERTSEN1
__________

Appeal 2019-002191
Application 15/168,033
Technology Center 1600
__________

Before ERIC B. GRIMES, FRANCISCO C. PRATS, and
DEBORAH KATZ, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of treating or preventing periodontal disease, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
“The present invention relates to methods for preventing or treating
periodontal disease (PD).” Spec. ¶ 2. “PD shall be understood to mean at
least one of gingivitis (GV) and periodontitis (PS).” Id. ¶ 3.

1 Appellant identifies the Real Party in Interest as Hans M. Albertsen.
Appeal Br. 2.
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The Specification states that
[e]pithelial repair (wound-healing) involves the trans-
differentiation of epithelial cells into motile mesenchymal cells
in a process known as epithelial-mesenchymal transition
(EMT). . . . During this process the epithelial barrier integrity is
temporarily lost. . . . [P]athogenic microbes can take advantage
of this temporary vulnerability to infect subjacent tissues.
Id. ¶ 6.
The Specification discloses “a method of treating PD . . . by
administering an EMT altering composition (EAC).” Id. ¶ 7. “Specific
exemplary EACs include, Sorafenib, Metacycline, Diphenyl difluoroketone,
Resveratrol, Curcumin, Emodin, and others.” Id. ¶ 10.
The Specification states that expression of E-cadherin (CDH2) is
characteristic of the epithelial state, while expression of N-cadherin (CDH1)
is characteristic of the mesenchymal state. Id. ¶ 9. “The ratio of expression
between, for example, CDH1 and CDH2 can therefore be used to assess the
cellular state of an epithelial tissue sample as epithelial or mesenchymal.” Id.
Claims 1–20 are on appeal. Claims 1, 8, 15, and 16 are illustrative and
read as follows:
1. A method of treating PD in a subject comprising
administering an EAC to said subject such that EMT of said
subject is altered.

8. A method of preventing PD in a PD asymptomatic
subject by maintaining epithelial barrier integrity comprising
administering an EAC to said subject such that EMT of said
subject is altered.

15. A method of treating PD in a PD asymptomatic
subject known to have at least one PD increased risk associated
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biomarker in said subject comprising administering an EAC to
said subject such that EMT of said subject is altered.

16. The method of claim 15, wherein said at least one
PD increased risk associated biomarker defines a CDH1/CDH2
expression ration [sic, ratio] of less than 1.0.

App. Br. 17, 18 (Claims Appendix).

The claims stand rejected as follows:
Claims 1–15 and 17–20 under 35 U.S.C. § 103(a) as obvious based on
Bartos2 and AlMoharib3 (Ans. 3) and
Claims 1–20 under 35 U.S.C. § 103(a) based on Bartos, AlMoharib,
and Heymann4 (Ans. 5).
I
The Examiner has rejected claims 1–15 and 17–20 under 35 U.S.C.
§ 103(a) as obvious based on Bartos and AlMoharib. The Examiner finds
that “Bartos teaches a pharmaceutical composition comprising curcumin to
treat and prevent inflammation, wherein a condition to be treated and
prevented is periodontitis. See par. 56.” Ans. 3 (emphasis omitted). The
Examiner finds that “AlMoharib teaches [that] several sensitive salivary
indicators of periodontitis are available to detect the presence, severity, and
response to treatment.” Id. at 4 (emphasis omitted). “Further, ‘Most

2 US 2013/0296440 A1, published November 7, 2013.
3 Oral Fluid Based Biomarkers in Periodontal Disease: Part I. Saliva, 6(4)
J. INTL. ORAL HEALTH 95–103 (2014).
4 E- and N-Cadherin Distribution In Developing and Functional Human
Teeth under Normal and Pathological Conditions, 160(6) AM. J. PATHOL.
2123–33 (2002).
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biomarkers in . . . saliva are indicators of inflammatory events that precede
the destruction of the alveolar bone.’” Id. (emphasis omitted).
The Examiner concludes that it would have been obvious “to combine
the teachings of Bartos and AlMoharib . . . because curcumin is known to be
administered to treat and prevent periodontal disease by mitigating a
subject’s inflammatory response.” Id. The Examiner also concludes that
there are known techniques to predict the progression of
periodontal disease and it is known that inflammatory events
usually precede the destruction of the alveolar bone. Thus, a
trend in measured biomarkers for inflammation associated with
a development of periodontal disease would provide a subject
the ability to treat and prevent the same by administering
curcumin as taught by Bartos.
Id.
We agree with the Examiner that the methods of claims 1, 8, and 15
would have been obvious to a person of ordinary skill in the art based on
Bartos and AlMoharib. Bartos discloses “a method of treating an individual
for an inflammatory disorder” by administering “a pharmaceutical
composition comprising . . . pterostilbene, . . . curcumin, and a
pharmaceutically acceptable carrier.” Bartos ¶ 22. Curcumin is an EAC.
Spec. ¶ 10.
Bartos states that
[t]he pterostilbene/curcumin combinations are useful for
preventing, alleviating, or treating inflammatory or digestive
disorders such as, but not limited to, inflammatory bowel
disease, gastric esophageal reflux disease (GERD), and
ulcerative colitis. Other inflammatory conditions susceptible to
such treatment include: Crohn’s disease, laminitis, arthritis,
sarcoidosis, acne, periodontitis, atherosclerosis, and the like.
Bartos ¶ 56 (emphasis added).
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Thus, Bartos discloses preventing or treating periodontitis in a subject
by administering curcumin. Although Bartos does not state that the subject
of its method of “preventing” is asymptomatic, as recited in claim 8, that
requirement is inherent in Bartos’ method; a subject who does not have PD
is necessarily asymptomatic for PD.5 The methods made obvious by Bartos
meet the active step limitations of claims 1 and 8 and, for the reasons
discussed below, it is reasonable to conclude that they meet the functional
limitation of those claims as well.
As relevant to claim 15, AlMoharib states that “[p]eriodontitis is a
multifactorial chronic non-reversible inflammatory disease.” AlMoharib 95,
right col. AlMoharib discloses “biochemical markers in saliva that appear to
be promising in the future for periodontal diagnosis.” Id. AlMoharib states
that “[w]ith the advent of highly sensitive techniques, traces of markers can
be accurately established in saliva. . . . Most biomarkers in . . . saliva are
indicators of inflammatory events that precede the destruction of the alveolar
bone.” Id. at 99, left col. AlMoharib also states that “[w]ith the advantages
of an easy, safe, cost-effective, and noninvasive diagnostic approach, saliva
shows a high potential for monitoring periodontal disease.” Id.
In view of these teachings, it would have been obvious to treat PD in a
subject who was asymptomatic for PD but who had one of the biomarkers of
PD that are disclosed by AlMoharib, and specifically to treat such a subject
using Bartos’ method of administering curcumin in combination with
pterostilbene. Motivation to do so is provided by AlMoharib’s disclosure

5 As Appellant has pointed out, “it is inherently impossible to prevent PD in
a subject that already has PD.” Appeal Br. 8.
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that using biomarkers found in saliva provides “the advantages of an easy,
safe, cost-effective, and noninvasive diagnostic approach.” AlMoharib 99,
left col.
Appellant argues that the references do not teach that an EAC is
administered “such that EMT of said subject is altered,” as required by the
claims. Appeal Br. 2–3. Appellant argues that
administration of curcumin does not necessarily cause the
alteration of EMT in a patient. For instance, curcumin may be
over administered (overdose), under administered (under-dose),
or administered in combination with another counteracting
composition (e.g. chlorhexidine, which is commonly used to
treat PD can be a counteracting agent to curcumin with respect
to altering EMT) and by so doing may not cause the claimed
alteration of EMT in a patient.
Id. at 3. Appellant argues that, “as claimed, the administration of curcumin
must be ‘such that EMT of said subject is altered’ (i.e. an effective amount
and method of administering of curcumin to cause alteration of EMT).” Id.
This argument is unpersuasive because the prior art suggests a method
that includes the active step required by each of claims 1, 8, and 15:
administering curcumin to a subject having certain characteristics. Since the
obvious method administers the same compound to the same patient as
recited in the claims, it is reasonable to conclude that that method would also
meet the claims’ functional limitation: altering the EMT of the subject.
The burden thus shifts to Appellant to show that the method made
obvious by the prior art does not meet the limitations of the claims. See In re
Best, 562 F.2d 1252, 1254–55 (CCPA 1977):
[W]here the Patent Office has reason to believe that a functional
limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent
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characteristic of the prior art, it possesses the authority to
require the applicant to prove that the subject matter shown to
be in the prior art does not possess the characteristic relied on.
See also id. at 1255: “Whether the rejection is based on ‘inherency’ under 35
U.S.C. § 102, on ‘prima facie obviousness’ under 35 U.S.C. § 103, jointly or
alternatively, the burden of proof is the same, and its fairness is evidenced
by the PTO’s inability to manufacture products or to obtain and compare
prior art products.” (footnote omitted).
Here, Appellant speculates that the method made obvious by Bartos
(or Bartos and AlMoharib) might not have the effect recited in the claims if
too little curcumin, or too much, was administered. Appeal Br. 3. However,
Appellant does not specify what dosages of curcumin would be too low or
too high to cause the recited effect, and Appellant’s Specification provides
no guidance on this issue. Appellant also does not address the dosage range
of 50–2000 mg/day that is expressly disclosed by Bartos. See Bartos ¶ 51.
Appellant also speculates that the recited effect might not be achieved
if curcumin was administered along with something like chlorhexidine,
which would counteract curcumin’s effect. Appeal Br. 3. Bartos, however,
discloses administering curcumin in combination with pterostilbene, not
chlorhexidine. Appellant has not pointed to evidence showing that
pterostilbene would counteract the EMT-altering effect of curcumin.
With respect to claim 15, Appellant argues that “the AlMoharib
biomarkers are not ‘PD asymptomatic’ biomarkers.” Appeal Br. 4.
This argument is also unpersuasive, because claim 15 requires a “PD
increased risk associated biomarker,” not a PD asymptomatic biomarker. If
Appellant intends to argue that AlMoharib’s markers are not found in
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asymptomatic patients, the evidence does not support that position.
AlMoharib discloses that “highly sensitive techniques” allow “traces of
markers [to] be accurately established in saliva,” and that most saliva
biomarkers “are indicators of inflammatory events that precede the
destruction of the alveolar bone.” AlMoharib 99, left col. Thus, AlMoharib
discloses that its markers can be detected in a subject before alveolar bone
loss occurs, which reasonably appears to describe a subject who is
asymptomatic for PD.
For the reasons discussed above, we affirm the rejection of claims 1,
8, and 15 under 35 U.S.C. § 103(a) based on Bartos and AlMoharib. Claims
2–7, 9–14, and 17–20 were not argued separately and therefore fall with
claims 1, 8, and 15. 37 C.F.R. § 41.37(c)(1)(iv).
II
The Examiner has rejected all of the claims on appeal as obvious
based on Bartos, AlMoharib, and Heymann. With regard to claims 1–15 and
17–20, the positions of the Examiner and Appellant are the same as
discussed above. Ans. 5–8; Appeal Br. 9–16. We affirm the rejection of
claims 1–15 and 17–20 under 35 U.S.C. § 103(a) based on Bartos,
AlMoharib, and Heymann for the reasons discussed above.
With respect to claim 16, the Examiner finds that “Bartos and
AlMoharib do not teach a ratio of E-cadherin to N-cadherin.” Ans. 6. The
Examiner finds, however, that Heymann teaches that E-cadherin and
N-cadherin are expressed in developing teeth, and “[b]oth are downregulated
in adult teeth, but N-cadherin was re-expressed in the dental pulp of carious
and injured teeth.” Id. The Examiner finds that Heymann discloses that
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N-cadherin’s pattern of expression in carious lesions “indicat[es] a
correlation between upregulation of N-cadherin and inflammatory events.”
Id. (emphasis omitted).
The Examiner reasons that, because both E- and N-cadherin are
down-regulated in (healthy) adult teeth, and N-cadherin is re-expressed and
upregulated in carious and injured teeth, one “would expect a ratio in an
inflammatory condition, such as periodontitis or periodontal disease, to
upregulated N-cadherin (i.e., the denominator), thereby rendering a ratio that
is less than 1.” Id. Thus, it would have been obvious to use Bartos’ method
to treat a subject having greater expression of N-cadherin than of E-cadherin
(i.e., a CDH1/CDH2 ratio of less than 1.0) because one “would expect that
the expression of N-cadherin would be greater than E-cadherin in subjects
with dental inflammation.” Id. at 7.
We agree with, and adopt, the Examiner’s reasoning and conclusion.
With respect to claim 16, Appellant argues that the Specification
“does not teach CDH1/CDH2 ratio changes per se, nor does it teach that the
CDH1/CDH2 ratio is reflective of epithelial homeostasis and mesenchymal
repair.” Appeal Br. 11. Rather, Appellant argues, the Specification teaches
that individuals genetically predisposed to enter the
mesenchymal repair state more readily that [sic] other people
(in other words: their natural homeostatic CDH1/CDH2 ration
[sic] is lower than the general population) are at elevated risk
for periodontal disease because the mesenchymal state is
vulnerable to bacterial infections, and thus would benefit
shifting their homeostatic balance towards the epithelial state
by administering an EMT altering compound (EAC) that shifts
the balance towards the epithelial state.
Id.
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This argument is unpersuasive. First, claim 16 recites a CDH1/CDH2
ratio of less than 1.0, not “lower than [that of] the general population,” and
the Examiner has persuasively explained why the recited limitation would
have been obvious to a skilled artisan based on the cited references.
In addition, Appellant’s argument is unsupported by Appellant’s
Specification, which states that
[t]he ratio of expression between, for example, CDH1 and
CDH2 can therefore be used to assess the cellular state of an
epithelial tissue sample as epithelial or mesenchymal. For
instance, if the ratio of CDH1/CDH2, such as observed in a
periodontal pocket biopsy sample of a PD asymptomatic
patient, is less than 1.0, the ratio is considered to be a marker
associated with a majority mesenchymal state and an increased
risk of PD.
Spec. ¶ 9. Thus, the Specification states that the CDH1/CDH2 ratio indicates
whether a tissue sample is in the epithelial state or mesenchymal state, not
whether individuals are more readily predisposed to enter the mesenchymal
repair state.
In sum, the Examiner has shown that the prior art would have made
obvious the CDH1/CDH2 limitation of claim 16, and we affirm the rejection
of claim 16 under 35 U.S.C. § 103(a) based on Bartos, AlMoharib, and
Heymann.
SUMMARY
We affirm both of the rejections on appeal.
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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