Ex Parte Langland et al

Patent Trial and Appeal Board

Oct 28, 2016

13015374 (P.T.A.B. Oct. 28, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/015,374 01127/2011 Rachel Langland
22829 7590 11/01/2016
Roche Molecular Systems, Inc,
4300 Hacienda Drive
Pleasanton, CA 94588
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
24003-US3 2502
EXAMINER
HANEY, AMANDA MARIE
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
11/01/2016 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):
misty.prasad@roche.com
pair_roche@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RACHEL LANGLAND, LIN WU, THAD SHARP, and
STEPHEN WILL 1
Appeal2015-004842
Application 13/015,374
Technology Center 1600
Before ERIC B. GRIMES, RICHARD J. SMITH, and RY ANH. FLAX,
Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
of determining sensitivity of cancer cells to a BRAF kinase inhibitor. We
have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
1 According to Appellants, the real party in interest is ROCHE
MOLECULAR SYSTEMS, INC. (Br. 5.)
Appeal2015-004842
Application 13/015,374
STATEMENT OF THE CASE
Background
"The invention provides a diagnostic assay to detect a mutation at
position 600 of the BRAF gene for use in selecting cancer patients ... who
are candidates for treatment with a B-Raf inhibitor." (Spec. i-f 31.)
Claims on Appeal
Claims 1 and 5-24 are on appeal.2 (Appendix, Br. 23-26.) Claim 1,
the only independent claim, is illustrative and reads as follows:
1. A method of determining sensitivity of cancer cells to a BRAF kinase
inhibitor, the method comprising: providing a nucleic acid sample from
cancer cells from a patient that has a cancer; amplifying a target
polynucleotide sequence in the nucleic acid sample using a primer pair that
amplifies the target polynucleotide sequence, wherein the target
polynucleotide sequence comprises codon 600 in BRAF and amplification is
performed in the presence of a labeled oligonucleotide probe that consists of
SEQ ID NO: 1 and detects the presence of a mutated sequence at the codon
600 in BRAF consisting of the mutations V600E, V600D and V600K; and
detecting the presence or absence of a mutation V600E, V600D or V600K in
BRAF; determining that the cancer is sensitive to the BRAF inhibitor if the
mutation V600E, V600D or V600K in BRAF is present.
(Br. 23.)
Examiner's Rejections
1. Claims 1, 5-14, 17-19, and 21 stand rejected under 35 U.S.C.
2 Claims 25-32 are withdrawn from further consideration as being drawn to
a nonelected invention. (Final Act. dated May 29, 2014, at 2.)
2
Appeal2015-004842
Application 13/015,374
§ 103(a) as unpatentable over Mitsiades,3 Benlloch,4 Kinoshita, 5 Spittle,6 and
GenBank.7 (Final Act. 10.)
Claims 1, 5-14, 17-19, and 21 were not argued separately, and we
therefore limit our consideration to claim 1.
2. Claim 15 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, and Syvanen. 8 (Id.
19.)
3. Claim 16 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, and Bustin. 9 (Id. 20-
21.)
4. Claim 20 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, and Chen. 10 (Id. 21.)
3 Mitsiades et al., Targeting BRAFv6ooE in thyroid carcinoma: therapeutic
implications, MOL. CANCER THER. 6(3), 1070-78 (2007) ("Mitsiades") .
.dT""t. 11 1 '1 T"'\., ,• f'T\T'\,T""""TTT/r\r\T"l"J.f, ,• • /""'f 7 , 7/""'f
~ tlenuocn et ai., uerecnon OJ 15JUir v ouur, 1viuranon zn cotorecrat cancer
Comparison of Automatic Sequencing and Real-Time Chemistry
Methodology, 8 J. MOL. DIAGN. 5, 540-43 (2006) ("Benlloch").
5 Kinoshita et al., Application of probes having 2 '-deoxyinosine for typing of
single nucleotide polymorphisms (SNPs) using DNA microarray,
ANAL YTICA CHIMICA. ACTA. 561, 25-31 (2006) ("Kinoshita").
6 Spittle et al., Application of a BRAF Pyrosequencing Assay for Mutation
Detection and Copy Number Analysis in Malignant Melanoma, 9 J. MOL.
DIAGN. 4, 464--71 (2007) ("Spittle").
7 GenBank Accession NM_004333.3 GI: 90265828 (Aug. 20, 2006)
("GenBank").
8 Syvanen, Accessing Genetic Variation: Genotyping Single Nucleotide
Polymorphisms, 2 NATURE REV. 930-42 (2001) ("Syvanen").
9 Bustin, Absolute quantification of mRNA using real-time reverse
transcription polymerase chain reaction assays, 25 J. MOLECULAR
ENDOCRINOLOGY, 169-93 (2000) ("Bustin").
1° Chen et al., US 2002/0150925 Al, published Oct. 17, 2002 ("Chen").
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Appeal2015-004842
Application 13/015,374
5. Claim 22 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, and Tsai. 11 (Id. 22-
23.)
6. Claim 23 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, and Sidransky. 12 (Id.
23-24.)
7. Claim 24 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Mitsiades, Benlloch, Kinoshita, Spittle, GenBank, Sidransky, and Tsai.
(Id. 25.)
ISSUE
Whether a preponderance of the evidence of record supports the
Examiner's conclusions of obviousness under 35 U.S.C. § 103(a).
Rejection No. 1
Analysis
The Examiner concludes that, based on the cited art, claim 1 would
have been obvious to one of ordinary skill in the art at the time of the
invention. (Final Act. 10-19.) Appellants' rebuttal focuses on objective
evidence of nonobviousness, and includes the Cheng Declaration 13 and
Sharma Affidavit. 14 (Br. 15-22.)
11 Tsai et al., Development of a novel inhibitor of cogenic b-raf, 47 Proc.
Amer. Assoc. Cancer Res., Abstract (2006) ("Tsai").
12 Sidransky et al., US 2005/0048533 Al, published Mar. 3, 2005
(''S idransky").
13 Declaration under 37 CPR 1.132 Submitted with Response to an Office
Action, by Suzanne Cheng, dated Feb. 11, 2014 ("Cheng Declaration" or
"Dec 1. ").
14 Affidavit under 37 CPR 1.132 Submitted with Response to an Office
Action, by Ashish Sharma, dated Oct. 18, 2012 ("Sharma Affidavit" or
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Application 13/015,374
We adopt the Examiner's findings and analysis as set forth in the
Final Action (Final Act. 10-35) and Answer (Ans. 2-11). Moreover, for the
reasons set forth therein, and for the reasons set forth below, we conclude
that the Examiner has established a prima facie case of obviousness and that
Appellants' arguments and evidence do not overcome or rebut that prima
facie case.
Unexpected Results
Appellants state that "[t]he method utilizes a probe (SEQ ID NO: 1)
that was designed to detect the most common mutation V 600E.
Unexpectedly, the probe was also able to detect rare mutations V600D and
V600K." 15 (Br. 11.) Appellants point to the Cheng Declaration, that quotes
an article by Anderson, 16 to argue that "Dr. Cheng explains why detection of
the V600K mutation was considered unexpected." (Id. at 17, citing Cheng
Deel. f 5.) Appellants also point to the Cheng Declaration, and an article by
Chapman, 17 to argue that "finding that V600K tumors also respond to the
"Aff."). The Sharma Affidavit generally relates to sales of the co bas® kit
which "enables a user to practice the method described in claim 1 of the
patent application." (Aff. f 4.)
15 We note that claim 1 recites that SEQ ID NO: 1 "detects the presence of a
mutated sequence at the codon 600 in BRAF consisting of the mutations
V600E, V600D and V600K." (Br. 23, emphasis added.)
16 Anderson et al., Multisite Analytic Performance Studies of a Real-Time
Polymerase Chain Reaction Assay for the Detection of BRAF V600E
Mutations in Formalin-Fixed Paraffin-Embedded Tissue Specimens of
Malignant Melanoma, 136 ARCH. PATROL. LAB. MED. 1-7 (2012)
("Anderson").
17 Chapman et al., Improved Survival with Vemurafenib in Melanoma with
BRAF V600E Mutation, 364 N. ENGL. J. MED. 2507-2516 (2011)
("Chapman").
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Appeal2015-004842
Application 13/015,374
BRAF V 600E-specific inhibitor venmrafenib was an unexpected result with
a significant practical advantage." (Id. at 17-18, citing Cheng Deel. f 6.)
Based on these arguments, Appellants contend that the Examiner erred in
relying on Kinoshita (n.5 supra) to conclude that "the ability of SEQ ID
NO:l to bind all three of the mutations V600E, V600D and V600K ... is
not unexpected," because "Kinoshita offers no more than general guidance
on using inosine in probes." (Id. at 18-19.)
Unexpected results require a showing that a person of ordinary skill in
the art would have found the results (i.e., detecting V600D and V600K
mutations) unexpected. See Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371
(Fed. Cir. 2007). Moreover, for the reasons set forth in the Answer and as
discussed below, we agree with the Examiner that the results proffered by
Appellants are not shown to be unexpected, and find no error in the
Examiner's reliance on Kinoshita.
The Cheng Declaration quotes Anderson as stating:
The cobas test while not specifically designed for the detection
of non-V600E mutations, demonstrated substantial cross-
reactivity with some non-V600E mutations and this detected
70% of V600K mutations and the only V600D-mutantion [sic]
in this cohort. (p. 5, right col., 1st par., emphasis added.)
(Deel. f 5.)
The complete quote, with deleted wording included in italics, reads as
follows:
The cobas test, while not specifically designed for the detection
of non-V600E mutations or being able to discriminate between
codon 600 mutations, demonstrated substantial cross-reactivity
with some non-V600E mutations, and thus detected 70% of the
V600K mutations and the only V600D-mutation in this cohort.
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Application 13/015,374
(Anderson 5, rt. col., 11. 6-11, emphasis added.)
We are not persuaded that the above quote shows that a person of
ordinary skill in the art would have found the detection of mutations at
codon 600 other than V600E mutations by Appellants' probe to be
unexpected. Moreover, we do not find any reason to conclude that the
detection ofV600D and V600K mutations would have been unexpected,
based on an accurate quote of Anderson, because Appellants' test was not
specifically designed for being able to discriminate between codon 600
mutations. (Id.) That is, it appears that the complete statement from
Anderson reflects that, while Appellants' test was "not specifically designed
for the detection ofnon-V600E mutations," it was understood that non-
V600E mutations would be detected, albeit without discriminating between
the particular mutations at codon 600. The complete statement thus suggests
that it was not unexpected that Appellants' probe would detect mutations
other than V600E, such as V600K or V600D. Moreover, Appellants'
argument regarding Chapman and the "practical advantage" of detecting
V600K mutations is similarly unpersuasive of unexpected results.
State of Prior Art
Appellants refer to the Cheng Declaration, and its citation to
Chapman, to argue that "the art did not recognize the need to test for the
V600K mutation as it was not known that the V600E-specific drug could
benefit those patients as well." (Br. 19-20, citing Cheng Deel. f 6.)
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Appellants also refer to the Cheng Declaration to argue the "inability of
prior art to solve the problem." (Id. at 20-21, citing Cheng Deel. ff 8-11.) 18
The Examiner explains that the prior art of Spittle (n.6 supra) teaches
"that [it] is important to use an assay that identifies the common V600E as
well as variant BRAF mutations" and that Spittle discloses "a pyro
sequencing assay that was able to detect the V600E, V600K, V600D, and
V600R mutations." (Ans. 8.) We are thus not persuaded that the prior art
did not (1) recognize the need to test for the V600K mutation, or (2) solve
the alleged problem of detecting the V600K mutation.
Praise by Others
Appellants point to the Cheng Declaration and several articles cited
therein as allegedly "praising the unique ability of the method to detect
additional mutations, especially V600K." (Br. 20, citing Cheng Deel. f 7.)
However, our review of the cited articles indicates that, at most, Appellants'
test was more (or less) sensitive compared to other similar tests, but that the
articles do not reflect any "unique" ability of the claimed method to detect
additional mutations. (See also Ans. 9.)
Commercial Success
Appellants point to the Sharma Affidavit to argue "successful sales of
the product incorporating the invention despite the availability of less
expensive similar tests." (Br. 21.) The Sharma Affidavit refers to a BRAF
Sell Sheet (Exhibit 1) and a Product Insert (Exhibit 2) as referring to the
18 The Cheng Declaration cites to articles and other documents. (Cheng
Deel. ff 8-11.)
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Application 13/015,374
sensitivity of the co bas® kit towards V 600 mutations other than V 600E.
(Aff. ff 5, 6.)
The Sharma Affidavit addresses sales of the co bas® kit by stating that
while "the use of the co bas® kit is not required to detect the BRAF
mutations," the cobas® kit "has been continuously displacing cheaper" lab
developed tests despite its higher cost. (Id. f 7.) This statement is supported
by a chart (Exhibit 3) identified as showing "the share of the testing market
in the U.S. for each test since the introduction of the cobas® kit." (Id.) The
Sharma Affidavit also states that "[i]n my opinion, the sales of the co bas® kit
have been excellent in the United States and good in the rest of the world,"
including a chart (Exhibit 4) listing numbers of sales by country. (Id. ff 8,
9.) Furthermore, according to the Sharma Affidavit, while "[m]any factors
may have contributed to excellent sales of the co bas® kit ... sensitivity,
specificity, and unique mutation detection profile ... are definitely among
the contributing factors." (Id. f 10.)
In the ex parte process of patent examination, the USPTO "must rely
upon the applicant to provide hard evidence of commercial success." In re
Huang, 100 F.3d 135, 139--40 (Fed. Cir. 1996) (noting that the USPTO
"lacks the means or resources to gather evidence which supports or refutes
the applicant's assertion that the sales constitute commercial success"). We
find such hard evidence lacking in the present case, and that Appellants have
failed to persuasively establish either commercial success or a nexus
between sales and the claimed method.
While Appellants provide data regarding the number of cobas® kits
sold, "evidence related solely to the number of units sold provides a very
weak showing of commercial success, if any." Huang, 100 F.3d at 140
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Application 13/015,374
(citing cases). In this case, Appellants' sales data "provides no indication of
whether this represents a substantial quantity in this market." Id. Thus,
Appellants have failed to provide sufficient information to determine
whether the co bas® kit has been commercially successful. See id.
Even if Appellants had established commercial success, that success
would only be relevant "if there is proof that the sales were a direct result of
the unique characteristics of the claimed invention-as opposed to other
economic and commercial factors unrelated to the quality of the patented
subject matter." Id. The Sharma Affidavit indicates that many factors may
have contributed to sales and that the "unique mutation detection profile" is
"definitely among the contributing factors." (Id. f 10.) Such conclusory
assertions do not establish the required nexus between the sales and claimed
invention, such as might be achieved by "an affidavit from the purchaser
explaining that the product was purchased due to the claimed features." See
Huang, 100 F.3d at 140.
Conclusion of Law
A preponderance of the evidence of record supports the Examiner's
conclusion that claim 1 is obvious under 35 U.S.C. § 103(a). Furthermore,
Appellants have not provided evidence of secondary considerations that,
when weighed with the evidence favoring obviousness, shows that claim 1
would have been nonobvious. Claims 5-14, 17-19, and 21 were not argued
separately and fall with claim 1.
Rejection Nos. 2-7
Appellants do not contest Rejections 2-7. Accordingly, the rejections
of claims 15, 16, 20, and 22-24 are affirmed. See 37 C.F .R. § 41.41 (b )(2);
Hyatt v. Dudas, 551F.3d1307, 1314 (Fed. Cir. 2008).
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SUMMARY
We affirm the rejections of all claims on appeal.
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
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