Ex Parte Garrity-Park et al

Patent Trial and Appeal Board

Jan 5, 2018

13272044 (P.T.A.B. Jan. 5, 2018)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/272,044 10/12/2011 Megan Garrity-Park 07039-1022001 6290
26191 7590 01/09/2018
FISH & RICHARDSON P.C. (TC)
PO BOX 1022
MINNEAPOLIS, MN 55440-1022
EXAMINER
HAMMELL, NEIL P
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
01/09/2018 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MEGAN GARRITY-PARK, THOMAS C. SMYRK,
EDWARD V. LOFTUS JR., and WILLIAM J. SANDBORN
Appeal 2017-001396
Application 13/272,044
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to a method
for conducting a beneficial colonoscopy and biopsy surveillance regimen on
a human diagnosed with inflammatory bowel disease. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
Statement of the Case
Background
“Inflammatory bowel disease (IBD) refers to chronic diseases that
cause inflammation in the intestine. The major types of IBD are Crohn’s
1 Appellants identify the Real Party in Interest as the Mayo Foundation for
Medical Education and Research (see App. Br. 2).
Appeal 2017-001396
Application 13/272,044
disease and ulcerative colitis (UC)” (Spec. 1:17—19). “Patients with
longstanding and extensive IBD are at increased risk to develop colorectal
cancer (CRC). Because of this, patients with IBD are advised to undergo
surveillance colonoscopy and biopsy, every one to two years” {id. at 1:24—
26).
“[MJarkers (e.g., nucleic acid markers, polypeptide markers,
epigenetic markers, or combinations thereof) can be used to screen UC
patients to determine risk for developing CRC. Detection of such markers
may allow a physician to more closely monitor those patients deemed to be
at a higher risk of developing CRC” (Spec. 1:34 to 2:4).
The Claims
Claims 1 and 3 are on appeal and read as follows:
1. A method for conducting a beneficial colonoscopy and
biopsy surveillance regimen on a human diagnosed with
inflammatory bowel disease, wherein said method comprises:
(a) detecting the presence of an adenosine at the
polymorphic position of rsl 800629 in a TNF alpha nucleic acid
of said human,
(b) detecting the presence of a thymine at the
polymorphic position of rsl 143627 in an IL-1 beta nucleic acid
of said human,
(c) detecting the presence of hypermethylated RUNX3
nucleic acid by performing a methylation specific polymerase
chain reaction, using nucleic acid obtained from a colon sample
of said human and treated with bisulfite,
(d) detecting the presence of hypermethylated MINT1
nucleic acid by performing a methylation specific polymerase
chain reaction, using nucleic acid obtained from a colon sample
of said human and treated with bisulfite,
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(e) detecting the presence of hypomethylated COX-2
nucleic acid by performing a methylation specific polymerase
chain reaction, using nucleic acid obtained from a colon sample
of said human and treated with bisulfite, and
(f) conducting more frequent colonoscopy and biopsy
surveillance on said human than surveillance colonoscopy and
biopsy every year based at least in part on said presence of said
rs 1800629 polymorphism, said presence of said rsl 143627
polymorphism, said presence of said hypermethylated RUNX3
nucleic acid, said presence of said hypermethylated MINT1
nucleic acid, and said presence of said hypomethylated COX-2
nucleic acid.
3. The method of claim 1, wherein said inflammatory bowel
disease is ulcerative colitis.
The Issue
The Examiner rejected claims 1 and 3 under 35 U.S.C. § 103(a) as
obvious over Vogel,2 Xu,3 Garrity-Park,4 Imamura,5 Cleveland Clinic,6
Pepe,7 and Maxwell8 (Final Act. 2—6).
2 Vogel et al., Prospective study of interaction between alcohol, NSAID use
and polymorphisms in genes involved in the inflammatory response in
relation to risk of colorectal cancer, 624 Mutation Res. 88—100 (2007).
3 Xu et al., Methylation profde of the promoter CpG islands of 31 genes that
may contribute to colorectal carcinogenesis, 10 World J. Gastroenterology
3441^154 (2004).
4 Garrity-Park et al., Tumor Necrosis Factor-Alpha Polymorphisms in
Ulcerative Colitis-Associated Colorectal Cancer, 103 American J.
Gastroenterology 407—15 (2008).
5 Imamura et al., RUNX3 Promoter Region is Specifically Methylated in
Poorly-differentiated Colorectal Cancer, 25 Anticancer Res. 2621—30
(2005).
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The Examiner finds Vogel teaches assaying risk of colorectal cancer
by “detecting the presence of a thymine at the polymorphic position of
rsl 143627 in an IL-1 beta nucleic acid” but does not teach other elements of
claim 1 (Final Act. 3—6). T
The Examiner finds Garrity-Park teaches “patients with ulcerative
colitis (UC) inflammatory bowel disease are at an increased risk of
developing colorectal cancer” and that the “the presence of the adenosine at
the polymorphic position rsl 800629 is indicative of an increased risk of
developing colorectal cancer” (Final Act 3). The Examiner finds Imamura
teaches applying methylation specific PCR to RUNX3 because “increased
RUNX3 methylation is associated with CRC” (id. at 4). The Examiner finds
Xu teaches applying methylation specific PCR to MESTTl and COX2
because “hypermethylation of MINT 1 and hypomethylation of COX2 is
indicative of an increased risk of developing colorectal cancer” (id. at 4).
The Examiner finds Pepe teaches “combining diagnostic test results to
optimize diagnostic accuracy” (Final Act. 5). The Examiner finds Cleveland
Clinic teaches “patients with an inherited predisposition to colorectal cancer
6 Cleveland Clinic, How to Prevent Colorectal Cancer,
http://web.archive.Org/web/20090105202118/http://my.clevelandclinic.org/d
isorders/Colorectal_Cancer/hic_How_to_Prevent_Colorectal_Cancer.aspx
(available Jan 5, 2009, accessed Aug. 13, 2013).
7 Pepe et al., Combining diagnostic test results to increase accuracy, 1
Biostatistics 123—40 (2000).
8 Maxwell et al., Association of the tumour necrosis factor-308
variant with differential response to anti-TNF agents in the treatment of
rheumatoid arthritis, 17 Human Molecular Genetics 3532—8 (2008).
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are at a high risk for colorectal cancer. ... For such patients . . . the
Cleveland Clinic recommends colonoscopy every 6—12 months” (id.).
The Examiner finds
one of ordinary skill in the art would have concluded that the
human as a whole would have been at a very high risk of
developing colorectal cancer “based on” the totality of these
risk factors. Consequently, one would have been motivated to
have performed colonoscopy and biopsy surveillance more
frequent than every year in such a human because one of
ordinary skill would have considered that such a human would
have been at a very high risk of developing colorectal cancer.
(Final Act. 6).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that the prior art renders claim 1
obvious?
Findings of Fact
1. Garrity-Park teaches “UC [ulcerative colitis] patients are, in
general, at an increased risk for developing colorectal cancer (CRC)”
(Garrity-Park 407, col. 1)
2. Garrity-Park teaches “there remains a need to identify
additional screening tools that can pinpoint those UC patients at greatest risk
for developing CRC. Genomic DNA screening tools such as single
nucleotide polymorphism (SNP) analysis are particularly useful in
inflammatory disease settings like UC” (id. at 407, col. 2).
3. Garrity-Park teaches “a novel association between the —
308(G—>A) SNP in the TNF-a gene promoter and the development of UC-
CRC. We found that the prevalence of this SNP was significantly higher
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among the UC-CRC case group compared to the UC-no CRC control group”
(id. at 412, col. 1).
4. Maxwell evidences that the —308(G—>A) SNP is the
RSI800629 polymorphic position (see Maxwell, abstract).
5. Vogel teaches genotyping ofIL1 {3T-31C (rsl 143627) (Vogel
90, col 2) finding “[t]wo studies found no association to risk of colorectal
cancer for //.//?T-31C ... in agreement with our findings” (id. at 94, col. 2).
6. Vogel teaches “our results do not suggest that inborn variations
in the inflammatory response play any major role in risk of colorectal
cancer. However, our results may suggest that the PPAR/2 Pro12Ala
influence alcohol-induced colorectal cancer” (id. at 98, col. 1).
7. Xu teaches that the “COX2 . . . [and] MINT1 . . . genes have
also been studied in colon cancer, the methylation pattern of which was
found altered in CRC” (Xu 3444, col. 2).
8. Xu teaches “MINT1 . . . [was] identified as [a] CRC associated
hypomethylated gene[]” (id. at 3452, col. 1).
9. Xu teaches methylation specific PCR with bisulfite treatment
(id. at 3444, col. 1).
10. Imamura teaches “we investigated the methylation status of
RUNX3 in colorectal cancers and found that most (71 %) poorly-
differentiated colorectal cancers presented RUNX3 methylation, while only
31 % of other differentiated colorectal cancers did” (Imamura 2629, col. 1).
11. Cleveland Clinic recommends that “people with an inherited
disposition to colorectal cancer” should be tested with “[flexible
sigmoidoscopy or colonoscopy every 6—12 months” (Cleveland Clinic 3).
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12. Pepe teaches “[w]hen multiple diagnostic tests are performed
on an individual or multiple disease markers are available it may be possible
to combine the information to diagnose disease” (Pepe 123, abstract).
Principles of Law
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was
taken by the applicant. The degree of teaching away will of
course depend on the particular facts; in general, a reference
will teach away if it suggests that the line of development
flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
Analysis
Appellants contend:
The Vogel et al. reference clearly discourages a person having
ordinary skill in the art from detecting a thymine at the
polymorphic position of rsl 143627 in an IL-I beta nucleic acid
and using that detected thymine to determine that a human
diagnosed with inflammatory bowel disease is in need of
colonoscopy and biopsy surveillance more frequently than
every year, because the Vogel et al. reference unambiguously
discloses that the presence of the rsl 143627 polymorphism as
presently claimed is “unlikely to be productive” in determining
the risk of developing colorectal cancer.
(App. Br. 16).
The Examiner finds this argument “not persuasive because Vogel is
neutral regarding the relationship between the presence of a thymine at the
polymorphic position of rsl 143627 and the risk of developing colorectal
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cancer because Vogel’s result simply did not rise to the level of statistical
significance” (Ans. 11). The Examiner finds
In view of Vogel, one of ordinary skill in the art would
admittedly not be able to determine whether a patient was at an
increased or decreased risk of developing colorectal cancer
based solely on the detection of the presence of a thymine at
rsl 143627 only. However, the claims are not solely directed to
a method for detecting the presence of a thymine at rsl 143627
only. Rather, the claims recite numerous other items in steps
(a) and (c)-(e) that the prior art clearly teaches are associated
with the presence of colorectal cancer.
(Id. at 11—12).
We find that Appellants have the better position. Claim 1 requires,
among other steps, a step of “(b) detecting the presence of a thymine at the
polymorphic position of rsl 143627 in an IL-1 beta nucleic acid of said
human” and a step “(f) conducting more frequent colonoscopy and biopsy
surveillance on said human than surveillance colonoscopy and biopsy every
year based at least in part on . . . said presence of said rsl 143627
polymorphism.” Thus, claim 1 connects detection of the polymorphism of
step (b) to a specific action by a physician or patient of performing more
frequent surveillance than would otherwise be performed.
Vogel, however, teaches that after genotyping of //.//? T-31C
(rsl 143627) “[t]wo studies found no association to risk of colorectal cancer
for /L//?T-31C ... in agreement with our findings” (FF 5). Vogel therefore
specifically teaches that a thymine at position rsl 143627 has no association
with colorectal cancer (FF 5). Vogel’s disclosure that rsl 143627 is not
associated with colorectal cancer, would have discouraged an ordinary
artisan from including this assay in a multiplex inflammatory bowel disease
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diagnosis assay, because Vogel teaches the assay would provide no
additional useful information. Moreover, “[a] reference teaches away when
it suggests that the line of development flowing from the reference’s
disclosure is unlikely to be productive of the result sought by the applicant.”
Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012).
That is precisely the situation here, where Vogel suggests that testing for the
presence of thymine at position rsl 143627 is unlikely to assist in
determining a surveillance regimen for inflammatory bowel disease (see FF
5).
We note the Examiner’s citation of the other steps in the method (see
Ans. 12) is entirely irrelevant to the question of whether step (b) as related to
step (f) would have been obvious or taught away. “A claimed invention may
be obvious even when the prior art does not teach each claim limitation, so
long as the record contains some reason why one of skill in the art would
modify the prior art to obtain the claimed invention.” Nike, Inc. v. Adidas
Ag, 812 F.3d 1326, 1335 (fed. Cir. 2016). However, some cognizable reason
is required and no such reason is present to include the thymine at position
rsl 143627 assay of Vogel with the other cited prior art.
Conclusion of Law
The evidence of record does not support the Examiner’s conclusion
that the prior art renders claim 1 obvious.
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SUMMARY
In summary, we reverse the rejection of claims 1 and 3 under 35
U.S.C. § 103(a) as obvious over Vogel, Xu, Garrity-Park, Imamura,
Cleveland Clinic, Pepe, and Maxwell.
REVERSED
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