Nolan Zebulon. Frantz

Patent Trials and Appeals Board

Sep 4, 2019

13642576 - (D) (P.T.A.B. Sep. 4, 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.
13/642,576 10/22/2012 Nolan Zebulon Frantz 8968-00-US-01-HL 1036
23909 7590 09/04/2019
COLGATE-PALMOLIVE COMPANY
909 RIVER ROAD
PISCATAWAY, NJ 08855
EXAMINER
RODRIGUEZ, RAYNA B
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
09/04/2019 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):
Patent_Mail@colpal.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte NOLAN ZEBULON FRANTZ

Appeal 2019-002120
Application 13/642,576
Technology Center 1600
____________

Before ULRIKE W. JENKS, JOHN G. NEW, and JOHN E. SCHNEIDER,
Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b).
We REVERSE.

STATEMENT OF THE CASE
Claims 1, 2, 6, 7, 9–12, and 14 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief.

1 Appellant identifies the real party in interest as Hill’s Pet Nutrition, Inc.
Appeal Br. 2.
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Claim 1, is representative of the claims on appeal, and reads as
follows:
1. A method of treating or controlling osteoarthritis in a canine,
the method comprising:
detecting the osteoarthritis in the canine, wherein
detecting the osteoarthritis in the canine comprises measuring
decreased levels of one or more osteoarthritis biomarkers and
increased levels of ANXA1 (Annexin A1) in blood of the canine
as compared to healthy canines, and wherein the decreased
levels of the one or more osteoarthritis biomarkers and the
increased levels of ANXA1 (Annexin A1) in the blood indicate
the presence of the osteoarthritis in tissue of the canine; and
administering to the canine in need thereof a diet
comprising, on a dry weight basis:
protein: 18-22%;
fat: 14.4-17.6%;
carbohydrates: 45.9-56.1 %;
crude fiber: 8.1-9.9%;
DHA: 0.27-0.33%;
EPA: 0.45-0.55%;
Vitamin C: 202.5-247.5 ppm;
Vitamin E: 526.5-643.5 ppm; and
L-carnitine: 315.9-386.1 mg/kg,
wherein the one or more osteoarthritis biomarkers to be
measured are one or more of: interleukin 6 (IL-6), a disintegrin
and metallopeptidase with thrombospondin type 1 motif 4
(ADAMTS-4), interferon gamma (IFNG), hyaluronic acid
synthase 2 (HAS2), biglycan (BGN), sex determining region Y-
box 9 (SOX-9), a disintegrin and metallopeptidase with
thrombospondin type 1 motif 5 (ADAMTS-5), matrix
metalloproteinase 3 (MMP3), acid phosphastase 5 (ACP5),
interleukin 1A (ILIA), tenasin C (TNC), hyaluronic acid
synthase 3 (HAS3), cartilage oligomeric matrix protein
(COMP), insulin-like growth factor 1 (IGF-1), ghrelin (GHR),
X-prolyl dipeptidyl aminopeptidase (Xaa-Pro Peptidase),
receptor activator of NF-Kappa B ligand (RANKL), mothers
against decapentaplegic, drosophila, homolog of SMAD family
member 7 (SMAD7), prostaglandin E2 (PGE2), toll-like
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receptor 9 (TLR9), plasminogen (PLOD I), and SCL2A9
glucose transporter (SCL2A9).
Appeal Br. 15–16 (Claims Appendix) (emphasis added). The only other
independent claim, claim 12, is directed to a “method for treating an
inflammatory condition in a canine.” Id. at. 18.
The claims stand rejected as follows:
Claims
Rejected
Basis 
1, 2, 6, 7, 9–12,
and 14
pre-AIA 35 U.S.C. § 103(a) over Yamka,2 Toll,3
Waldron,4 Shields,5 Tagoe,6 and Kevorkian7

Examiner finds that Yamka teaches the claimed nutritional
composition for administration to canines, specifically, for the purpose of
treating animals suffering from an inflammatory condition. Ans. 5.
Examiner acknowledges that Yamka does not teach that the inflammatory
condition is osteoarthritis. Id. at 6. Examiner acknowledges that Yamka
does not teach the claimed carbohydrate, fiber, DHA, and EPA
concentrations, but relies on the teachings of Toll, Waldron, and Shields for
these limitations. See id. at 5–10. Examiner also relies on Toll and Waldron

2 Yamka et al., US 2009/0111877 A1, published Apr. 30, 2009 (“Yamka”).
3 Toll, Nutritional Management: Optimal Osteoarthritis Diet, SUPPLEMENT
TO NAVC CLINICIAN’S BRIEF 6 (2005) (“Toll”).
4 Waldron et al., WO 2006/002976 A2, published Jan. 12, 2006
(“Waldron”).
5 Shields, Jr. et al., US 6,156,355, issued Dec. 5, 2000 (“Shields”).
6 Clement E. Tagoe et al., Annexin-1 Mediates TNF -a-Stimulated Matrix
Metalloproteinase Secretion from Rheumatoid Arthritis Synovial
Fibroblasts, 181 J. IMMUNOL. 2813–20 (2008) (“Tagoe”).
7 Kevorkian et al., Expression Profiling of Metalloproteinases and Their
Inhibitors in Cartilage, 50 ARTHRITIS & RHEUMATISM 131–41 (2004)
(“Kevorkian”).
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for teaching using dietary supplements to treat canines with osteoarthritis.
Id. at 5–8. Examiner’s position is that the combination of Yamka, Toll,
Waldron, and Shields renders obvious a conclusion that osteoarthritis can be
treated using diet. See Ans. 5–10.
The present claims require two steps. Step one detects the
inflammatory condition, such as osteoarthritis. Step two instructs the
administration of a dietary supplement to a canine identified as suffering
from an inflammatory condition in step one. 8 Examiner acknowledges that
Yamka does not teach that the inflammatory condition is osteoarthritis. Ans.
6. “Yamka [also] does not explicitly teach the biomarker is ANXA1 or that
levels [of] ANXA1 are increased and one or more of the listed biomarkers
are decreased.” Id. at 10. Examiner relies on the teachings of Tagoe and
Kevorkian for the differential biomarker expression limitation as recited in
step one of the claims. Specifically Examiner finds that Tagoe “teach[es]
that annexin-1 is secreted by rheumatoid arthritis synovial fibroblasts in
response to TNFa and stimulates MMP-1 secretion (abstract). Moreover,
Kevorkian teaches ADAMTS5 (a disintegrin and metalloproteinase domain
with thrombospondin motif-5) expression is decreased in osteoarthritis
(abstract).” Id. at 11. Examiner concludes that it would have of been
obvious to treat osteoarthritis in an animal based on a decreased expression
of an osteoarthritis biomarker and an increased expression of ANXA1
(Annexin A1). Id.

8 In a prior decision we affirmed claims directed at treating or controlling
inflammatory conditions by administering a dietary supplement to a canine.
See Board Decision mailed March 30, 2017 (“Decision”).
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Examiner finds that “Tagoe teaches annexin-1 mediates TNFa
stimulated matrix metalloproteinase secretion from rheumatoid arthritis
synovial fibroblasts.” Ans. 10. Examiner finds that Kevorkian “Kevorkian
teaches ADAMTS5 (a disintegrin and metalloproteinase domain with
thrombospondin motif-5) expression is decreased in osteoarthritis.” Id. at
13. Examiner finds that “[t]he motivation [for the combination] would have
been the establishment by Tagoe that RA SF secrete ANXA1 and the
establishment by Kevorkian that ADAMTS5 expression is decreased in
osteoarthritis.” Id. at 11.
The Examiner acknowledges that the cited references do
not explicitly teach the inverse correlation between the specific
inflammatory biomarkers in blood cited in the claims and
ANXA1. As set forth above, Yamka teaches cartilage
protection can be measured by various means, including an
analysis of arthritis biomarkers and potential arthritis
biomarkers such as TI collagen synthesis, matrix
metalloproteinase (MPP), osteocalcin, alkaline phosphatase
activity, COMP, and fragments of cartilage damage [0037]. . . .
The motivation would have been the establishment by Tagoe
that RA SF secrete ANXA1 and the establishment by
Kevorkian that ADAMTSS expression is decreased in
osteoarthritis.
Id. at 17–18.
The issue is whether the preponderance of evidence of record supports
Examiner’s conclusion that the method of controlling or treating
osteoarthritis (or an inflammatory condition) by administering a nutritional
supplement after identifying the animal in need of treatment by measuring
differential expression of biomarkers is obvious?
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A. Findings of Fact (FF)
FF1. Tagoe teaches that “[a]nnexins are highly conserved calcium- and
phospholipidbinding proteins that share common structures but exert
diverse functions.” Tagoe 2813. “Annexin-1 (previously lipocortin-
1) is a potent inhibitor of inflammation both in vitro and in vivo.” Id.
Annexin-1 has also been shown to be secreted and thereby provides
additional anti-inflammatory effects. Id.
In contrast to the anti-inflammatory effects of annexin-1,
we observed that annexin-1 mediates TNF-α-stimulated
secretion of MMP-1 from RA SF [(rheumatoid arthritis
(RA) synovial fibroblasts (SF))]. Specifically, annexin-1
is rapidly secreted from preformed intracellular pools in
response to TNF-α stimulation, and autoengages FPRL-1
to stimulate Erk, Jnk, and NF-KB activation, resulting in
MMP-1 secretion.
Id. at 2814.
FF2. Tagoe “also observed increases in MMP-3 but not MMP-13 secretion
in response to Ac2-26 [(annexin-1 N-terminal peptide)], alone or in
combination with TNF-α (data not shown), suggesting that secreted
annexin-1 may specifically regulate the secretion of multiple
proteolytic enzymes.” Id. at 2819.
FF3. Kevorkian shows the expression of MMP genes in cartilage from
osteoarthritis patients (OA) in comparison to normal cartilage. “The
most significant increases in expression of MMPs in cartilage from
OA patients compared with normal were for MMP13 and MMP28 (P
< 0.001), while the most significant decreases were for MMP1 and
MMP3 (P < 0.001).” Kevorkian 135.
FF4. Kevorkian also teaches that “the expressed aggrecanases, ADAMTS1,
ADAMTS5, ADAMTS9, and ADAMTS15 were all significantly
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decreased in cartilage from OA patients compared with normal
cartilage.” Id.
B. Principle of Law
“[E]xaminer bears the initial burden, on review of the prior art or on
any other ground, of presenting a prima facie case of unpatentability.” In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
C. Analysis
Appellant contends that Tagoe does not “teach or suggest that blood
from canines suffering from osteoarthritis or inflammation exhibits
increased expression of ANXA1 without the external stimulation of TNF-α.”
Br. 9 (emphasis omitted). At best, Tagoe teaches a need for TNF-α
stimulation for annexin-1 secretion. Id. Because “Tagoe explicitly discloses
that both normal and rheumatoid arthritic patients exhibit expression of
annexin-1; and thus, teaches that annexin-1 is not reliable as a biomarker to
distinguish between normal and rheumatoid arthritic patients.” Id. at 11
(emphasis omitted).
Appellant also contends that “Kevorkian does not even discuss
biomarker ANXA1.” Id. at 10. “[A]t best, [Kevorkian] discloses measuring
expression levels of biomarkers in human tissue. Nowhere, however, does
Kevorkian teach or suggest measuring one or more osteoarthritic biomarkers
in blood of canines, much less, measuring a decrease in the expression of
ADAMTS5 in the blood of canines.” Id. (emphasis omitted).
After considering the art and arguments presented, we find that the
preponderance of the evidence does not support Examiner’s conclusion that
the claims are rendered obvious. A prima facie case for obviousness
“requires a suggestion of all limitations in a claim,” CFMT, Inc. v. Yieldup
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Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003) and “a reason that would
have prompted a person of ordinary skill in the relevant field to combine the
elements in the way the claimed new invention does.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007).
To begin with we note that rheumatoid arthritis and osteoarthritis are
distinct diseases with different etiologies. Although both describe
inflammation of the joints – rheumatoid arthritis is an autoimmune disorder
while osteoarthritis arthritis is a degenerative joint disorder, described as the
wearing down of the cartilage that leads to bones rubbing against each other.
See Spec. ¶¶ 2–3.
Here, the claims require a differential expression of ANXA1 (Annexin
A1) and an osteoarthritis biomarker, such as for example matrix
metalloproteinase 3 (MMP3) or a disintegrin and metallopeptidase with
thrombospondin type I motif 5 (ADAMTS-5) among others. We note that
Tagoe teaches that TNF-α stimulation of rheumatoid arthritis synovial
fibroblasts results in the secretion of not only ANXA1 but also an MMP-3.
FF1–FF2. Increased expression level in MMP3 is the exact opposite of what
is required by the claim. The claim requires detection of osteoarthritis based
on showing an increased level in blood of ANXA1 (Annexin A1) while the
concentration of the biomarker, such as an MMP-3, is decreased. Examiner
has not explained why one of skill in the art would look to rheumatoid
arthritis synovial fibroblasts for teaching a correlation with osteoarthritis in
the first place. In addition, Examiner has not explained why one would only
consider the ANXA1 teaching from Tagoe but then ignore the increased
levels of MMP3 secretion taught in that reference. In other words, why is
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the secretion of ANXA1 in a rheumatoid arthritis model system indicative of
osteoarthritis but the secretion of MMP3 is not indicative of osteoarthritis?
We agree with Appellant that Kevorkian does not make up for the
deficiency in Tagoe. Kevorkian looks at cartilage from human patients with
osteoarthritis and compares it normal cartilage. Kevorkian teaches that
MMP3 and ADAMTS5 gene expression is decreased in osteoarthritis
cartilage as compared to normal cartilage. FF3–FF4. We agree with
Appellant, however, that Kevorkian does not teach ANXA1 gene expression
or secretion into the blood in the osteoarthritis model. Thus, we know
nothing about the normal concentrations of ANXA1 in the blood in this
patient population. Additionally, Kevorkian’s experimental results are
derived from cartilage and not from blood samples as required by the claims.
We understand that a decrease in gene expression implies a reduction in the
protein encoded by the gene. However, a decrease in gene expression does
not tell one of ordinary skill in the art whether the gene product is normally
secreted and detectable in the blood. In order for the method to be able to
measure a decrease in a particular product would require a showing that the
product is ordinarily expressed and secreted in sufficient quantities to be
detectable by assay in the blood.
Examiner has not explained why based on the contradictory evidence,
disclosed from different disease models, one of ordinary skill in the art
would have reasonably selected parts from one reference while ignoring
those part of the references that that do not support Examiner’s conclusion.
Specifically, Tagoe’s observation of secretion MMP3 in conjunction with
ANXA1 (Annexin A1). FF1–FF2. Prior art should be read in its entirety,
and considered for all that it teaches and suggests to the skilled artisan.
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W.L. Gore & Assoc., Inc. v. Garlock, Inc., 721 F.2d 1540, 1547, 1554 (Fed.
Cir. 1983). Focusing on one biomarker ANXA1 (Annexin A1) while
ignoring the rest of the teaching in Tagoe violates the prohibition against
picking and choosing only those parts that are favorable while ignoring the
rest. In re Hedges, 783 F.2d 1038, 1041 (Fed. Cir. 1986)(“It is
impermissible within the framework of section 103 to pick and choose from
any one reference only so much of it as will support a given position, to the
exclusion of other parts necessary to the full appreciation of what such
reference fairly suggests to one of ordinary skill in the art.” (citation and
internal quotes omitted)). Here, Tagoe teaches that both ANXA1 (Annexin
A1) and MMP-3 are secreted from rheumatoid arthritis synovial fibroblasts.
Examiner bears the burden of explaining why the particular Tagoe teaching
of ANXA1 secretion from the rheumatoid arthritis synovial fibroblast are
particularly relevant for a diagnosis of osteoarthritis but Tagoe’s teaching of
secretion of MMP3 are not applicable for the diagnosis of osteoarthritis.
Because Examiner has not explained the contradictory evidence presented in
Tagoe and Kevorkian, we find that that Examiner has not established that the
cited art meets all the claim limitations.
Thus, considering the references as a whole, we cannot conclude that
the Examiner has shown obviousness by a preponderance of the evidence.
We therefore reverse the rejection of claims 1, 2, 6, 7, 9–12, and 14 as
obvious based on the combination of Yamka, Toll, Waldron, Shields, Tagoe,
and Kevorkian.

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SUMMARY
Claims
Rejected
Basis  Affirmed Reversed
1, 2, 6, 7, 9–12,
and 14
35 U.S.C. § 103(a)  1, 2, 6, 7, 9–
12, and 14
Outcome 1, 2, 6, 7, 9–
12, and 14

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

REVERSED