Ex Parte Bastian et al

Patent Trial and Appeal Board

Jun 19, 2017

13151935 (P.T.A.B. Jun. 19, 2017)

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.
13/151,935 06/02/2011 Boris Bastian ABOTP009D1 5834
22434 7590 06/21/2017
Weaver Austin Villeneuve & Sampson LLP
P.O. BOX 70250
OAKLAND, CA 94612-0250
EXAMINER
SALMON, KATHERINE D
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
06/21/2017 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):
USPTO@wavsip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte BORIS BASTIAN,
LARRY E. MORRISON, and SUSAN JEWELL
Appeal 2016-002925
Application 13/151,935
Technology Center 1600
Before JEFFREY N. FREDMAN, ROBERT A. POLLOCK, and
RICHARD J. SMITH, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving a combination of
in situ hybridization probes. The Examiner rejected the claims as obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“Diagnostic ambiguity has significant adverse consequences for
patients. Misclassifying a melanoma as benign may be fatal, and diagnosing
a benign lesion as malignant may result in significant morbidity” (Spec. 13).
“Comparative genomic hybridization (CGH) of primary melanomas has
1 Appellants identify the Real Parties in Interest as Abbott Laboratories and
The Regents of the University of California (see App. Br. 1).
Appeal 2016-002925
Application 13/151,935
identified losses at 6q, 8p, 9p, and lOq and gains at lq, 6p, chromosome 7,
8q, 17q, and 20q to be the most common DNA copy number changes in
melanoma” (Spec. 14).
“The present invention is based on an assessment of the ability of
combinations of probes using a multi-color fluorescent in situ hybridization
(FISH) test to detect copy number changes of chromosomal regions
commonly found to be aberrant in melanoma” (Spec. 14).
The Claims
Claims 18 and 28 are on appeal. Claim 18 is representative and reads
as follows:
18. A combination of in situ hybridization probes that
consists of not more than three probes, wherein a first probe
selectively hybridizes to chromosome subregion 6p25, a second
probe selectively hybridizes to chromosome subregion 6q23,
and a third probe selectively hybridizes to chromosome
subregion llql3, wherein each probe comprises a detection
moiety.
The Issues
The Examiner rejected claims 18 and 28 under 35 U.S.C. § 103(a) as
obvious over Namiki,2 Bastian,3 Hughes,4 and Milliken5 (Final Act. 3—5).
2 Namiki et al., Genomic alterations in primary cutaneous melanomas
detected by metaphase comparative genomic hybridization with laser
capture or manual microdissection: 6p gains may predict poor outcome, 157
Cancer Genetics Cytogenetics 1-11 (2005).
3 Bastian et al., Gene Amplifications Characterize Acral Melanoma and
Permit the Detection of Occult Tumor Cells in the Surrounding Skin, 60
Cancer Research 1968-73 (2000).
4 Hughes et al., Microarray comparative genomic hybridisation analysis of
intraocular uveal melanomas identifies distinctive imbalances associated
with loss of chromosome 3, 93 British J. Cancer 1191—96 (2005).
2
Appeal 2016-002925
Application 13/151,935
The Examiner finds Namiki teaches chromosomal regions “6q23,
6p25 and 1 lql3 can be detected [in] melanoma sample[s] and that these
regions were associated with gains or losses in tumors” but “does not teach
probes to the specific regions” (Ans. 3).
The Examiner finds Bastian teaches “designing probes labeled with
Cy3 or digoxigenin (e.g. detection moiety)” and “that these probes were
used to hybridize to 1 lql3” (Id.). The Examiner also finds Bastian teaches
“a probe to 6p25” (Id.). The Examiner finds Hughes teaches “a gain in 6p25
and that this gain was detecting using probes in samples from melanoma
patients” (Id.). The Examiner finds Millikin teaches “a probe to detect the
region of Myb (6q22-23)” and “that this region is associated with
melanoma” (Ans. 4).
The Examiner finds it obvious “to design any number of combinations
of probe sets for detecting associations with melanoma including the claims
probe set” and “combine any known probes associated with melanoma from
a finite number of probes with the intended result of screening tumor
samples” (Ans. 4).
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner’s conclusion
that the probe sets of claims 18 or 28 would have been obvious?
(ii) If so, have Appellants presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
5 Millikin et al., Loss of Heterozygosity for Loci on the Long Arm of
Chromosome 6 in Human Malignant Melanoma, 51 Cancer Research
5449-53 (1991).
3
Appeal 2016-002925
Application 13/151,935
Findings of Fact
1. Namiki teaches: “We performed metaphase CGH analysis on
20 primary cutaneous melanomas . . . Comparison between genomic
alterations in primary tumors and cell lines suggested some chromosomal
regions were associated with tumor progression in vivo” (Namiki 1, col. 2).
2. Namiki teaches, in Table I, patients whose comparative
genomic hybridization shows gains in 6p25 and 1 lql3, losses in 6q23, as
well as amplified 11 ql3 levels (see Namiki 3, Table 1, patients 1, 2, 6, 8,
and 12).
3. Bastian teaches the “most frequently amplified regions in AMs
[acral melanomas] occurred at 1 lql3” (Bastian abstract).
4. Bastian teaches “we studied five biopsies of AM in situ using
FISH with markers for the two regions (1 lql3 and 22ql2) that were most
commonly amplified in the invasive AMs” (Bastian 1970, col. 1).
5. Bastian teaches: “Probes mapping to amplified regions and
reference probes for regions that were unchanged by CGH analysis were
selected from the laboratories resource. Probes were labeled with Cy3 ... or
with digoxigenin” (Bastian 1968, col. 2 to 1969, col. 1).
6. Bastian teaches a FISH [fluorescent in situ hybridization]
probe, RMC06B005, that is specific for the chromosomal region 6p25-pter
(see Bastian 1971, table 2).
7. Hughes teaches the “genomic DNA arrays used in these
experiments were obtained from the Cancer Research UK DNA Microarray
Facility and consist of 3421 BAC and PAC clones, which provide an
average genomic resolution of 1 Mb” (Hughes 1192, col. 1).
4
Appeal 2016-002925
Application 13/151,935
8. Hughes teaches detection of gains in 6p25 (see Hughes 1195,
table 3).
9. Milliken teaches: “Malignant melanoma bas been documented
to display recurring abnormalities of chromosome 6, particularly the long
arm (6q)” (Milliken 5449, abstract).
10. Milliken teaches the probe pHM2.6 at the c-MYB locus that
localizes to 6q23 (see Milliken 5451, table 1).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Mat417.
“That the [prior art] patent discloses a multitude of effective
combinations does not render any particular formulation less obvious.”
Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir.
1989).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 3—5; FF 1—10) and agree that
the claims are obvious over Namiki, Bastian, Hughes, and Milliken. We
address Appellants’ arguments below.
Prima Facie Obviousness
Appellants contend “[w]ith respect to 6p25 and 6q23, contrary to the
Examiner’s statement above, Namiki’s results do not pinpoint these specific
chromosome subregions, but instead relate to broader regions” (App. Br. 5).
5
Appeal 2016-002925
Application 13/151,935
Appellants contend “Namiki teaches that there would be no benefit to
probing an 1 lq region in combination with the 6q and 6p regions disclosed
in Namiki” because “adding an 1 lq probe to a 6p and 6q probe combination
would not result in the identification of any additional tumor” (Id.).
Therefore, Appellants contend that “one of skill in the art would not, based
on Namiki, combine an 1 lq probe with a 6p and a 6q probe because there
would be no benefit to justify the increased expense. Namiki thus actually
teaches away from the combination of a probe targeting 1 lql3 with probes
targeting 6p25 and 6q23” (Id.; cf. Reply Br. 7).
We do not find these arguments persuasive. While Namiki teaches,
for example, gains in patient 6 at positions 6p25-p22 (FF 2; Namiki Table
1), that teaching of the 6p25-p22 region suggests detection of the entire
region, including 6p25, to the ordinary artisan. Therefore, a probe to 6p25
would function to detect a region identified by Namiki as being of interest.
Similarly, Namiki teaches that regions 1 lql3 and 6q23 are also of interest
(FF 2).
We also find the teaching away argument unpersuasive. A teaching
away requires a reference to actually criticize, discredit, or otherwise
discourage the claimed solution. See In re Fulton, 391 F.3d 1195, 1201
(Fed. Cir. 2004) (“The prior art’s mere disclosure of more than one
alternative does not constitute a teaching away from any of these alternatives
because such disclosure does not criticize, discredit, or otherwise discourage
the solution claimed”).
Namiki’s teaching of chromosomal regions that show gains or losses
in melanoma does not criticize, discredit, or discourage the use of any
particular region, and 11 q 13 in particular, but simply suggests reasonable
6
Appeal 2016-002925
Application 13/151,935
regions for analysis in melanoma patients. Just as some ordinary artisans
might perform a cost benefit analysis as proposed by Appellants’ counsel
without supporting evidence other than “common sense”, other ordinary
artisans interested in redundancy might select 1 lql3 for a variety of other
reasons. Attorney’s arguments in a brief cannot take the place of evidence.
In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). We also agree with the
Examiner’s position that “this appears to be arguing intended use and not the
structure of the composition” (Ans. 3).
Appellants contend that “Bastian does not teach a probe that
‘selectively hybridizes to chromosome subregion 6p25,’ as required by the
claims. Instead, Bastian teaches a probe to the much larger subregion of
6p25-pter” (App. Br. 6). Appellants contend the “Examiner makes an error
similar to that in Buszard by turning the concept of selectivity on its head in
reading ‘selectively hybridizes to 6p25’ as encompassing hybridization to
one or both flanking regions of any size” (Reply Br. 4).
We find this argument unpersuasive because the claim does not
exclude probes that selectively hybridize to the entire 6p25-pter subregion
because these probes also selectively hybridize to 6p25 as well as additional
portions of chromosome 6. That is, a probe to the entirety of chromosome 6
will hybridize selectively to both chromosome 6 and to 6p25, satisfying the
claim requirement (see, e.g., Ans. 4 “The claims rather encompass structures
that hybridize to regions that include these recite chromosomal regions”).
Unlike In re Buszard, 504 F.3d 1364 (Fed. Cir. 2007) where the
interpretation was inconsistent with the Specification, the Examiner’s
interpretation of “selectively hybridizes” is fully consistent with the
definition in the Specification which states:
7
Appeal 2016-002925
Application 13/151,935
“[Selectively hybridize to,” as used herein refer to the binding,
duplexing, or hybridizing of a nucleic acid molecule
preferentially to a particular nucleotide sequence under
stringent conditions. The term “stringent conditions” refers to
conditions under which a probe will hybridize preferentially to
its target subsequence, and to a lesser extent to, or not at all to,
other sequences.
(Spec. 18). Thus, any probe that binds to 6p25 under stringent conditions
reasonably satisfies the requirements of claim 18 when read in light of the
Specification, and Bastian suggests probes that will specifically bind to 6p25
and additional regions (FF 6). Appellants provide no evidence that the probe
RMC06B005 will not bind to 6p25 and provide no evidentiary support for
their argument that: “Probes that include more than just the 6p25 subregion
simply cannot function as required for the selectively hybridizing probes to
6p25, 6q23, and 1 lql3 described in Appellants’ specification” (Reply Br. 6).
Appellants contend
one of skill in the art seeking to use probes to the regions
identified by Namiki to further explore associations with
melanoma would not limit their efforts to the claimed three-
and four-probe combinations, but would instead presumably
use a much larger panel of probes to explore associations with
melanoma in a comprehensive manner.
(App. Br. 6).
We do not find this argument persuasive because the combination of
familiar elements according to known methods is likely to be obvious. See
KSR, 550 U.S. at 416. Here, the prior art recognizes that labeled probes to
chromosomal regions are well known to the person of ordinary skill and
Hughes even evidences that arrays of 3421 different probes were well
known to the ordinary artisan (FF 7). Selection of a particular subset from
8
Appeal 2016-002925
Application 13/151,935
these sets, particularly when combined with the disclosure in Namiki that
these three regions are associated with melanoma, reasonably represents a
combination of familiar elements. Just as a selection of three different size
screws from the display of hundreds of fasteners at Home Depot represents a
combination of known elements, so too, selection of three different probes to
known chromosomal regions also represents a combination of known
elements. “That the [prior art] discloses a multitude of effective
combinations does not render any particular formulation less obvious.” In re
Corkill, 111 F.2d 1496, 1500 (Fed. Cir. 1985).
Appellants respond that
this position requires one to accept that the selection of
individual species from the very large genus disclosed in the
references (or worse, undisclosed smaller subregions of these
species) cannot be inventive and, further, that the combination
of the selected species into three-probe or four-probe sets
cannot be inventive. This position clearly runs afoul of the rule
articulated above in Ortho-McNeil.
(App. Br. 9).
We find this argument unpersuasive because the instant facts are
unlike the situation in Ortho-McNeil in which the inhibitor was unknown,
the starting materials were unknown, and therefore selection of the inhibitor
did “not present a finite (and small in the context of the art) number of
options.” Ortho-McNeil Pharmaceutical, Inc. v. Mylan Laboratories, Inc.,
520 F.3d 1358, 1364 (Fed. Cir. 2008). Here, Namiki provides a limited list
of CGH regions from which the ordinary artisan may select probes (FF 2,
see Namiki Table 1), while probes to chromosomal regions in general, and
even to some of these regions were routinely generated, well known, and
sometimes even commercially available (see Spec. 159).
9
Appeal 2016-002925
Application 13/151,935
Appellants contend
knowing that copy number gains in larger regions including
6p25 are associated melanoma does not teach or suggest that
those copy number gains are at 6p25. Bastians’ and Hughes’
data are consistent with copy number gains at 6p24, for instance
(explaining the negative result for Bastian’s 6p25-pter probe),
in which case a probe that was truly selective for 6p25 would
not detect the copy number gains disclosed by Hughes.
(App. Br. 7).
We find this argument, founded on speculation regarding the
teachings of the prior art, unpersuasive. That is, Appellants provide no
evidence that Bastian and Hughes teaching of 6p25 as showing gains in
melanoma is incorrect, but simply speculate that there may be some actual
adjacent region that has the gains. However, “attorney argument [is] not the
kind of factual evidence that is required to rebut a prima facie case of
obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997).
Moreover, if 6p25 is part of a larger region associated with chromosomal
gains in melanoma, then detection of 6p25 will provide some information
regarding melanoma and will therefore be a desirable probe, consistent with
the disclosure in Hughes for gains at 6p25.3 (FF 8; see Hughes 1195, table
3).
Unexpected Results
Appellants contend
Appellants’ specification demonstrates that an 1 lql3 probe
complements a 6p25 probe, as well as a 6q23 probe. This is
most easily seen by comparing the results observed for a three-
probe combination including probes targeting 6p25, 6q23, and
CEP6 (see page 17, Table 6, probe sets 21, 22, and 26
[numbered from the top]), showing sensitivities of 82%-85%
and specificities of 90%-93 %, with the result observed when
10
Appeal 2016-002925
Application 13/151,935
an 1 lql3 probe is added to this combination, which gives a
specificity of a sensitivity of 88% and a specificity of 97%.
Thus, whereas Namiki predicted the 1 lql3 addition would not
improve the results observed, in fact, this addition improved
sensitivity by at least 3% and specificity by at least 4%. As
noted above, these improvements are clinically significant, as
well as unexpected.
(App. Br. 10).
We do not find the evidence persuasive of unexpected results or other
secondary considerations. In particular, we note that the Specification itself
never identifies the result as unexpected, at best stating that “probe
combinations should desirably provide DFI < 0.2905 to be worth the added
expense” (Spec. 181). This is a statement suggesting that the ordinary
artisan balance costs with value received, not a statement supporting
unexpected results. See In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972)
(“[I]t is not enough to show that results are obtained which differ from those
obtained in the prior art: that difference must be shown to be an unexpected
difference”).
Because the Specification does not identity the results as unexpected,
Appellants must provide evidence explaining why the results are, in fact,
unexpected. Currently, Appellants only have attorney argument supporting
this point (App. Br. 10; cf. Reply Br. 9). See In re Soni, 54 F.3d 746, 750
(Fed. Cir. 1995) (“It is well settled that unexpected results must be
established by factual evidence. Mere argument or conclusory statements . .
. [do] not suffice.”). We also disagree with Appellants’ statement that
Namiki “predicted the 1 lql3 addition would not improve the results
observed” (App. Br. 10). Namiki teaches that 1 lql3 is associated with some
melanomas and the ordinary artisan would therefore have recognized
11
Appeal 2016-002925
Application 13/151,935
addition of this probe would allow for detection of melanomas where, due to
experimental error or other heterogeneity in the samples, 1 lql3 detection
occurs while detection of 6p25 or 6q23 do not.
As we evaluate the data identified by Appellants in Table 6, there is
no evidence that an improvement in sensitivity of 3% and specificity by 4%
by including the 1 lql3 probe would not have been expected by the ordinary
artisan, given the teachings in Namiki that 1 lql3 was associated with some
melanomas (FF 2), nor is there evidence that these results demonstrate “a
new and unexpected result which is different in kind and not merely in
degree from the results of the prior art.” In re Huang, 100 F.3d 135, 139
(Fed. Cir. 1996).
Conclusion of Law
(i) The evidence of record supports the Examiner’s conclusion that the
probe sets of claims 18 or 28 would have been obvious.
(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
SUMMARY
In summary, we affirm the rejection of claims 18 and 28 under 35
U.S.C. § 103(a) as obvious over Namiki, Bastian, Hughes, and Milliken
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
12