Ex Parte Singh et al

Patent Trial and Appeal Board

Aug 31, 2017

13322495 (P.T.A.B. Aug. 31, 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.
13/322,495 11/25/2011 Shalini Singh 7668-83214-10 2904
69371 7590 09/05/2017
KLARQUIST SPARKMAN, LLP
121 S.W. SALMON STREET
SUITE 1600
PORTLAND, OR 97204
EXAMINER
BHAT, NARAYAN KAMESHWAR
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
09/05/2017 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):
docketing @klarquist.com
AS CChair @klarquist. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHALINI SINGH, FABIEN GAIRE, and
JAMES RANGER-MOORE
Appeal 2016-002399
Application 13/322,4951
Technology Center 1600
Before TAWEN CHANG, RACHEL H. TOWNSEND, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to methods of
scoring gene copy number in a sample from a subject. The Examiner
entered final rejections for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse the
Examiner’s obviousness rejection. Pursuant to 37 C.F.R. § 41.50(b),
however, we enter a new ground of rejection under 35 U.S.C. § 101.
1 Appellants identify the Real Party in Interest as Ventana Medical Systems,
Inc. App. Br. 2.
Appeal 2016-002399
Application 13/322,495
STATEMENT OF THE CASE
Background
The Specification discloses:
methods of scoring copy number of a gene of interest in a
biological sample, such as gene copy number detected by an in
situ hybridization assay. The method includes identifying
individual cells in the sample having highest number of signals
for the gene of interest detected by in situ hybridization, such that
individual copies of the gene are distinguishable in cells in the
sample. The number of signals for the gene is then counted in
the identified individual cells and an average number of signals
per cell is determined.
Spec. 2:20—26. The Specification discloses that the claimed methods of
scoring gene copy number can be used to predict a patient’s prognosis in the
case of neoplastic disease such as non-small lung cell carcinoma. Id. at 2:3—
6.
The Claims
Claims 1—16 and 18 are on appeal. Claim 1, the sole independent
claim, is illustrative and reads as follows:
1. A method of scoring copy number of a gene of
interest in a biological sample from a subject, comprising:
scanning the biological sample;
identifying at least three regions in the sample that have
highest concentration of cells having amplification of gene
signal;
identifying individual cells in each of the at least three
regions of the sample which have highest number of signals for
the gene detected by in situ hybridization, wherein individual
copies of the gene are distinguishable in cells in the sample;
counting a number of signals for the gene in each of the
identified cells; and
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determining an average number of signals per cell in the
identified cells, thereby scoring the gene copy number.
App. Br. 14 (Claims Appendix).
Appellants seek our review of the Examiner’s rejection of claims 1—16
and 18 under pre-AIA 35 U.S.C. § 103(a) as unpatentable over Pauletti2 in
view of Bartlett.3 We select claim 1 as representative of the claims subject
to this ground of rejection. 37 C.F.R. § 41.37(c)(l)(iv).
The Examiner finds that Pauletti teaches a
method of scoring copy number of a HER-2 gene of interest in a
biological sample from a subject, comprising . . . scanning of the
breast adenocarcinoma sample . . . [and that] at least 3 cells in
the breast adenocarcinoma sample have measurable amplified
HER-2 gene signals (i.e., the highest concentration) in at least
three neighboring cells and each of the 3 cells have at least three
distinct measurable signal (Fig. 1).
Final Act. 8.4 The Examiner finds Pauletti discloses that “amplified HER-2
gene signals in 3 neighboring cells and 3 distinct amplified HER-2 gene
signals in each of the said cells meets the limitation of identifying individual
cells having highest concentration of HER-2 gene signal.” Id. The
Examiner further finds Pauletti teaches “detecting 10 to 15 HER-2
signals/cell in the first group, which encompasses counting a number of
signals for the [HER-2] gene in each of the identified cells” and
2 Giovanni Pauletti et al, Assessment of Methods for Tissue-Based Detection
of the HER-2/now Alteration in Human Breast Cancer: A Direct
Comparison of Fluorescence in Situ Hybridization and
Immunohistochemistry, 18 J. Clin. Onc. 3651—3664 (2000).
3 John Bartlett & Amanda Forsyth, Detection o/HER2 Gene Amplification
by Fluorescence In Situ Hybridization in Breast Cancer, 120: Meth. Mol.
Med. 309-322 (2006).
4 Examiner’s Final Action, mailed Jan. 13, 2015.
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“determining the average number of signals per cell in the identified cells
and determining (i.e., scoring) the HER-2 gene copy number.” Id. at 9
(citations omitted).
The Examiner finds Pauletti does not disclose identifying at least three
regions in the sample that have highest concentration of cells having
amplification of gene signal, and looks to Bartlett for this limitation. Id. at
8—9. The Examiner finds Bartlett teaches “a FISH method for detecting
HER-2 gene amplification either by manual or by automatic method [that]
comprises hybridizing the HER-2/Chromosome 17 probe mixture from
Vysis (as also used by Pauletti) on the slide comprising a breast tissue
section and detecting the amplified HER-2 signals from the tumor cells.” Id.
at 9—10. The Examiner finds Bartlett teaches counting FISH signals “in 60
nonoverlapping tumor cell nuclei in the control and carcinoma sections and
recording the individual results for at least three different areas of the slide
comprising the tissue sample and scoring/counting signals from at least 20
nuclei each from separate tumor areas within the slide.” Id. at 10. The
Examiner further finds Bartlett’s protocol includes “identifying the cells
with highest HER-2 signals, counting the number of signals for the HER-2
signals and determining the average number of signals per cell in the
identified cells thereby scoring the HER-2 gene signal.” Id. (citation
omitted).
The Examiner concludes that the skilled artisan would recognize
“detecting the highest HER-2 signals from the tumor cells in different areas
relative to chromosome 17 probe of Bartlett. . . meets the limitation of the
step of identifying at least three regions in the sample that have highest
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concentration of cells having amplification of gene signal.” Id. The
Examiner finds that performing this identification step
provides rigorous quality control for the detection of HER-2 gene
amplification by FISH in breast cancer, thus providing
motivation to include the step of identifying the amplification of
gene signal from at least three different regions of Bartlett for
determining the gene copy number by FISH of Pauletti.
Final Act. 11 (citation omitted).
The Examiner further concludes the ordinarily skilled artisan would
have found it obvious to “include the step of identifying the amplification of
gene signal from at least three different regions of Bartlett for determining
the gene copy number by FISH of Pauletti.” Id. The Examiner cites “the
expected benefit of having the rigorous quality control for the detection of
HER-2 gene amplification as taught by Bartlett” as motivation for the
combination and predicts a reasonable expectation of success because
counting FISH signals is routinely practiced in the art. Id.
ISSUE
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that Pauletti and Bartlett
suggest the claimed subject matter.
ANALYSIS
Appellants argue the
claimed methods are doubly biased in that they include a directed
(non-random) identification of at least three regions of a sample
that have “highest concentration of cells having amplification of
gene signal” and also directed (nonrandom) identification of
individual cells “which have highest number of signals for the
gene” in each of the selected regions. The number of signals is
then counted in each of the identified individual cells and an
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average number of signals per cell in the identified cells is
determined.
App. Br. 4.
Appellants argue that Pauletti describes
identifying samples (slides) with high or strong gene signal and
selecting 10—20 nuclei from those samples for counting signal
number to enumerate the gene copy number. It does not state
that the selected nuclei were those that had the highest number
of signals for HER-2/neu, or even those with 10—15 scattered
signals/cell, but merely that the nuclei were in a sample having
“consistent presence of signal cluster(s) or more than 10 to 15
scattered signals/cell.” Pauletti et al. do not describe how the
individual cells were selected from within the samples, and
certainly does not disclose “identifying individual cells ... which
have highest number of signals for the gene ...; [and] counting a
number of signals for the gene in each of the identified cells ...”
as in Applicants’ claim 1.
Id. at 7 (alterations in original) (citation omitted).
Appellants argue that the method taught by Bartlett
merely indicates the importance of internal and external quality
controls in performing diagnostic FISH assays . . . addresses
general characteristics that the nuclei selected for counting
should have, and does not provide any description of selecting
regions for analysis that have “highest concentration of cells
having amplification of signal” or “identifying individual cells ...
which have highest number of signals for the gene ...”
Id. at 8—9 (second and third alterations in original). Rather, Appellants
argue, “the methods described by Bartlett et al. require counting of 20 cells
in three random areas of the slide, in order to capture possible heterogeneity
in the sample.” Id. at 9.
Appellants further argue that the combined teachings of Pauletti and
Bartlett do not establish prima facie obviousness because “Pauletti et al. do
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not describe selecting any particular region of the sample from which to
identify individual cells, let alone identifying any regions of the sample with
‘highest concentration of cells having amplification of gene signal...’” and
that Bartlett “does not remedy the deficiency of Pauletti et al., at least with
respect to ‘identifying at least three regions in the sample that have highest
concentration of cells having amplification of gene signal...’ as recited in
Applicants’ claim 1 (emphasis added).” Reply Br. 6 (alterations in original).
We agree with Appellants that the evidence does not support the
Examiner’s finding that Pauletti and Bartlett suggest all of the limitations of
claim 1.
An invention
composed of several elements is not proved obvious merely by
demonstrating that each of its elements was, independently,
known in the prior art. Although common sense directs one to
look with care at a patent application that claims as innovation
the combination of two known devices according to their
established functions, it can be important to identify 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.
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Pauletti’s disclosed method of detecting the number of gene signals by
FISH is described as being performed in “samples in which obvious HER-
2/neu gene amplification was present, ie, consistent presence of signal
cluster(s) or more than 10 to 15 scattered signals/cell. In this group, 10 to 20
nuclei were selected for signal enumeration from those that displayed the
highest number of HER-2/hew signals.” Pauletti 3652. However, Pauletti
does not teach focusing identification on areas of the cell with the highest
concentration of signals; rather, Pauletti teaches selection of samples from
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the array of all prepared samples that have the most consistently detectable
number of gene signals, e.g., the best samples for viewing hybridization. Id.
Furthermore, Bartlett teaches counting of more than three cells within a
signal area, but advocates scoring of “cells from three separate areas of the
tumor markedly increases the likelihood that [heterogeneity of
amplification] will be correctly observed.” Bartlett 318 § 4, Note 25. We
find that the Examiner has not sufficiently established why the skilled artisan
would have been motivated to use the counting technique disclosed by
Bartlett in — and only in — the regions of highest concentration of cell
staining (locations of highest gene signal), as required by claim 1. Because
the Examiner has not provided evidence sufficient to support a prima facie
case of obviousness, we reverse the rejection of claims 1—16 and 18 as
obvious based on Pauletti and Bartlett.
NEW GROUND OF REJECTION
Under the provisions of 37 C.F.R. § 41.50(b), we enter the following
new ground of rejection: Claim 1 is rejected under 35 U.S.C. § 101 as being
directed to non-statutory subject matter.
Overview
“Whoever invents or discovers any new and useful process, machine,
manufacture, or composition of matter, or any new and useful improvement
thereof, may obtain a patent therefor, subject to the conditions and
requirements of this title.” 35 U.S.C. § 101. Supreme Court precedents,
however, provide three specific exceptions to the broad categories of § 101:
laws of nature, natural phenomena, and abstract ideas. Bilski v. Kappos, 561
U.S. 593, 625 (2010). In Mayo, the claim at issue was directed to
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A method of optimizing therapeutic efficacy for treatment
of an immune-mediated gastrointestinal disorder, comprising:
(a) administering a drug providing 6-thioguanine to a
subject having said immune-mediated gastrointestinal disorder;
and
(b) determining the level of 6-thioguanine in said subject
having said immune-mediated gastrointestinal disorder,
wherein the level of 6-thioguanine less than about 230
pmol per 8x108 red blood cells indicates a need to increase the
amount of said drug subsequently administered to said subject
and
wherein the level of 6-thioguanine greater than about 400
pmol per 8x108 red blood cells indicates a need to decrease the
amount of said drug subsequently administered to said subject.
Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1295
(2012) (internal quotations omitted). The Supreme Court held that this
claim was directed to patent-ineligible subject matter because it sought to
claim a law of nature. Id. at 1305. The Court reasoned “[i]f a law of nature
is not patentable, then neither is a process reciting a law of nature, unless
that process has additional features that provide practical assurance that the
process is more than a drafting effort designed to monopolize the law of
nature itself.” Id. at 1297.
In Alice, the Supreme Court referred to the two-step analysis set forth
in Mayo, as providing “a framework for distinguishing patents that claim
laws of nature, natural phenomena, and abstract ideas from those that claim
patent-eligible applications of those concepts.” Alice Corp. Pty. Ltd. v. CLS
BankInt’l, 134 S. Ct. at 2355 (citingMayo, 132 S. Ct. at 1289). Under
Mayo, “[w]e must first determine whether the claims at issue are directed to
a patent-ineligible concept.” Id. Next, “we consider the elements of each
claim both individually and ‘as an ordered combination’ to determine
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whether the additional elements ‘transform the nature of the claim’ into a
patent-eligible application.” Id. (citing Mayo, 132 S. Ct. at 1298, 1297).
Under Mayo, to be patentable, a claim must do more than simply state
the law of nature or abstract idea and add the words “apply it.” Mayo, 132
S. Ct. at 1294; Gottschalkv. Benson, 409 U.S. 63, 67 (1972). A challenged
patent claim, properly construed, must incorporate enough meaningful
limitations to ensure that it claims more than just an abstract idea and not
just a mere “drafting effort designed to monopolize the [abstract idea].”
Alice, 134 S. Ct. at 2357 (alteration in original) (quoting Mayo, 132 S. Ct. at
1297). “Simply appending conventional steps, specified at a high level of
generality,” is not uenough'” for patent eligibility. Id. (quoting Mayo, 132 S.
Ct. at 1300, 1297). We use the foregoing framework to analyze the instantly
pending claim 1 to determine whether it embodies a patent-eligible
application of a law of nature or merely the law of nature itself.
Determination of whether independent claim 1 is directed to a patent-
ineligible concept.
Our initial question with regard to the method of claim 1 is whether it
is directed to a patent-ineligible concept. Claim 1 is directed to a method for
counting the number of copies of a gene signal in a biological sample, the
signal reflecting the “copy number,” which the Specification defines as:
Copy number: The number of copies of a nucleic acid
molecule in a cell. The copy number includes the number of
copies of one or more genes or portions thereof in genomic
(chromosomal) DNA of a cell. In a normal cell (such as a non­
tumor cell), the copy number of a gene (or any genomic DNA) is
usually about two (one copy on each member of a chromosome
pair). In some examples, the copy number of a gene or nucleic
acid molecule includes an average copy number taken from a
population of cells.
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Spec. 5:29—6:4. Thus, the Specification discloses that the gene copy number
of a cell is the number of copies of a nucleic acid in a cell, expressed in
some instances as an average population. Id. In light of this definition, we
find that the claimed method is directed to identifying a natural
phenomenon: the amount of a gene of interest that is naturally present in a
biological sample.
Moreover, to practice the claimed method, the user inspects a
biological sample of interest that has been treated such that the gene copies
per cell can be counted due to an emitted signal, counts the signal, and
subsequently “scores” the gene copy number by determining an average
number of signals per cell. Our reviewing Court has held “information as
such is an intangible” and thus, has “treated collecting information,
including when limited to particular content (which does not change its
character as information), as within the realm of abstract ideas.” Elec.
Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016)
(collecting cases). Likewise it has “treated analyzing information by steps
people go through in their minds, or by mathematical algorithms, without
more, as essentially mental processes within the abstract-idea category.” Id.
at 1354 (collecting cases).
In light of the foregoing, we find the method simply discloses the
abstract idea of counting and recording a natural phenomenon (gene copy),
which is a patent-ineligible concept.
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Determination of whether elements of independent claim 1 transform
the nature of the claim into a patent-eligible application.
Regarding the second prong of the test articulated by the Supreme
Court in Alice, we further consider the elements of claim 1 (the steps of the
claimed method) “both individually and ‘as an ordered combination’ to
determine whether the additional elements ‘transform the nature of the
claim’ into a patent-eligible application.” Alice, 134 S. Ct. at 2355 (quoting
Mayo, 132 S. Ct. at 1298, 1297). In this case, the recited steps of the
method, and the particular order of the steps, i.e., scanning a biological
sample that has been prepared by in situ hybridization for gene signals
reflecting the presence of copies of a gene, and counting the gene copies to
determine an average copy number, are all conventional steps in the art. As
recognized by the Examiner, identification of “regions in [a] sample that
have highest concentration of cells having amplification of gene signal is [a]
routine, well-established and conventional step for the use of FISH for
scoring HER-2 gene amplification in breast cancer.” Final Act. 10.
At the Oral Hearing on August 15, 2017, Appellants argued that the
claimed method of counting the gene signals to score the gene copy number
transformed the nature of the claim into a patent-eligible application:
JUDGE TOWNSEND: Okay. So my next question has
to do with the claim invention as a whole in that it appears to be
taking information that’s alreadyy in the tumor sample and
collecting information about it and making a determination
about that information that’s simply a count. How is that —
how does that overcome the case law as it stands now on 101?
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MS. GRAF: So I would say that this claim as a whole
adds something significantly more to any natural principle or
however you want to phrase the 101 issue. You know, as a
whole when you take the claim as a whole they’re adding this
bias to the counting, both the selecting of the regions and the
selecting of the cells in which they’re making this count, and
that’s something that was not routinely done in the art.
It is mentioned in the declaration from Dr. Ranger-
Moore. These kinds of reading methods are held to be biased
and in the field that you would typically want to avoid bias,
whereas in this case they're doing something that’s not routine
in the field and, you know, as demonstrated by the data
presented with the declaration this does provide something
more than what the standard methods in the art previously were
able to produce.
(Hearing transcript 14:7—15:7).
MS. GRAF: We’re talking about a method, and the
thing that’s significantly more that applicants claim it has is this
doubly biased method where you’re selecting regions that have
the highest concentration of cells with amplification, and then
out of those regions you’re selecting individual cells with the
highest number of signals to count.
So that is something that’s significantly more than what’s
previously been done in the art and it provides an advancement
in that it provides a better result that can be used, for example,
in the clinical arena.
(Id at 19:11-20).
We note Appellants argued these same points of novelty with respect
to the non-obviousness of their claims, that the method is “biased” or “non-
random” in its approach to identifying the cells in which to count gene copy
and then determining the average signal per cell from that count, thereby
scoring the gene copy, which is not taught or suggested by the prior art.
(E.g., Reply Br. 4.) We do not disagree with respect to non-obviousness.
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(See, supra, reversing the Examiner’s rejection of claim 1 for obviousness.)
A finding of novelty or non-obviousness, however, does not necessarily lead
to the conclusion that subject matter is patentable eligible.
“Groundbreaking, innovative, or even brilliant discovery does not by
itself satisfy the § 101 inquiry.” Ass ’n for Molecular Pathology v. Myriad
Genetics, Inc., 133 S. Ct. 2107, 2117 (2013)). As the Examiner noted, in
FISH, identifying regions in a sample that have highest concentration of
cells having amplification of gene signal is routine and conventional for
scoring gene amplification. We find nothing transformative in using such a
conventional step to identify three or more such regions and cells in those
regions with the highest number of signals so as to bias the counting, i.e., a
collection of conventional steps into an ordered combination to score gene
copy number. Merely selecting information for collection and analysis
“does nothing significant to differentiate a process from ordinary mental
processes, whose implicit exclusion from § 101 undergirds the information-
based category of abstract ideas.” Elec. Power Grp., 830 F.3d at 1355. We
therefore do not find the recited method steps transform the nature of claim 1
into a patent-eligible application.
We also find our reviewing Court’s decision in Ariosa Diagnostics,
Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015) informative. In that
case, the Court found patent ineligible a claim directed to “[a] method for
performing a prenatal diagnosis” that included obtaining a certain fraction
from a blood sample, amplifying certain nucleic acid from the fraction and
performing analysis on it to detect paternally inherited fetal nucleic acid.
788 F.3d 1371, 1374, 1376—78. According to the Court, that claim was
generally “directed to detecting the presence of a naturally occurring thing or
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a natural phenomenon,” i.e., paternally inherited cffDNA. Id. at 1376. The
Court explained that the “method steps were well-understood, conventional
and routine” and that “[t]he only subject matter new and useful as of the date
of the application was the discovery of the presence of cffDNA in maternal
plasma or serum.” Id. at 1377.
In this case, well-understood, conventional and routine steps are
applied to identify the number of copies of a gene, which are naturally
present in the cells of the biological sample being examined, and the
resulting copy number is not tied to any further step.
Furthermore, Appellants have not demonstrated that the gene copy
scored using the method reflects anything other than the accurate average
number of gene signals present per cell in the identified cells, a clear natural
phenomenon. Thus, we find that claim 1 is directed to an unpatentable law
of nature. We, therefore, enter this new ground of rejection of claim 1 under
§ 101, for lack of statutory subject matter pursuant to 37 C.F.R. § 41.50(b).
We have not reviewed the dependent claims to determine whether they are
likewise unpatentable under § 101, and leave them for the Examiner’s
consideration in any further prosecution.
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SUMMARY
For the reasons discussed, we reverse the Examiner’s obviousness
rejection and enter a new ground of rejection under 35U.S.C. § 101.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to
37 C.F.R. § 41.50(b) (effective Sept. 13, 2004; revised, 76 FR 72270, Nov.
22, 2011, effective Jan. 23, 2012). 37 C.F.R. § 41.50(b) provides “[a] new
ground of rejection pursuant to this paragraph shall not be considered final
for judicial review.
37 C.F.R. § 41.50(b) also provides that the appellant, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding
will be remanded to the examiner ....
(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record ....
REVERSED. 37 C.F.R, $ 41,501b)
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