Ex Parte Harris

Patent Trial and Appeal Board

Mar 22, 2019

11496063 (P.T.A.B. Mar. 22, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
11/496,063 07/28/2006
103479 7590 03/26/2019
Kilpatrick Townsend & Stockton LLP
Fluidigm Corporation
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
FIRST NAMED INVENTOR
Timothy Harris
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.
085665-0895780
(E047.0l.U
CONFIRMATION NO.
3139
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
03/26/2019 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):
ipefiling@kilpatricktownsend.com
pair_fluidigm@firsttofile.com
KTSDocketing2@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte TIMOTHY HARRIS
Appeal 2017-008991 1
Application 11/496,063
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREYN. FREDMAN, and
RYAN H. FLAX, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to methods of
sequencing nucleic acids. The Examiner rejected the claims for
indefiniteness, as lacking enablement, as failing to comply with the written
description requirement, as being directed to subject matter ineligible for
patenting, for obviousness, and for obviousness-type double patenting.
We have jurisdiction under 35 U.S.C. § 6(b)(l).
We reverse the indefiniteness rejection as to all but two claims.
We reverse the enablement and written description rejections.
1 As to the real party in interest, Appellant identifies "Fluidigm, a
corporation with head offices located in South San Francisco, California,
being the successor in interest to Helicos Biosciences Corporation, to which
this application was originally assigned by the inventors." Br. 2.
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We reverse the patent ineligibility rejection.
We affirm the obviousness and obviousness-type double patenting
rejections.
STATEMENT OF THE CASE
The following rejections are before us for review:
(1) Claims 1-8, 13-16, and 50-65, under 35 U.S.C. § 112, second
paragraph, as being indefinite (Ans. 2--4);
(2) Claims 1-8, 13, and 50-65, under 35 U.S.C. § 112, first paragraph,
as failing to comply with the enablement requirement (id. at 4--13);
(3) Claims 1-8, 13-16, and 50-65, under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement (id.
at 13-19);
(4) Claims 1-8, 13-16, and 50-65, 2 under 35 U.S.C. § 101, because
the claimed invention is not directed to patent eligible subject matter (id. at
19-27);
(5) Claims 1-8, 13-16, and 50-65, under 35 U.S.C. § I03(a) as being
unpatentable over Williams, 3 Sklar, 4 Fleming, 5 and admitted prior art (id. at
28-38);
(6) Claims 1-8, 13-16, and 50-65, on the ground of nonstatutory
double patenting over claims 1 and 8-20 of U.S. Patent No. 7,897,345 B2
2 The Examiner's inclusion of claim "665" among the claims subject to this
rejection is clearly a typographical error. See Ans. 27 (summarizing
rejection as being directed to "claims 1-8, 13-16, and 50-65").
3 US 6,255,083 Bl (issued July 3, 2001).
4 US 2003/0232365 Al (published Dec. 18, 2003).
5 US 6,090,593 (issued July 18, 2000)
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(issued Mar. 1, 2011; "the '345 patent") in view of Williams, Sklar, and
Fleming (id. at 38--41 ); and
(7) Claims 1-8, 13-16, and 50-53, on the ground of nonstatutory
double patenting over claims 1, 11-13, and 15-17 of U.S. Patent No.
7,491,498 B2 (issued Feb. 17, 2009; "the '498 patent") in view of Williams,
Sklar, and Fleming (id. at 41 ). 6
Claim 1 is representative and reads as follows:
1. A method for single molecule nucleic acid sequencing,
the method comprising:
(a) providing a plurality of duplexes, each
comprising a nucleic acid template containing a known
nucleotide sequence, a primer hybridized thereto, and a
first label, wherein the duplexes are bonded to a surface
so as to be optically resolvable;
(b) determining locations on the surface of the
duplexes by detecting the first label;
( c) extending the primers by at least three
consecutive nucleotides by a process that comprises
multiple iterations of the following steps:
(i) contacting the duplex with a labeled
nucleotide and a polymerase so as to extend the primers
by adding the nucleotide if the labeled nucleotide is
complementary to the next nucleotide on the template,
wherein the labeled nucleotide contains a label that is
different from the first label;
(ii) washing the duplexes to remove
unincorporated nucleotides,
(iii) determining locations on the surface of
6 Although the Examiner included claim 9 among the claims subject to this
ground of rejection (Ans. 41), claim 9 has been canceled. See Response to
Notice ofNon-Compliant Appeal Brief 13 (entered Aug. 29, 2016) (Claims
App'x).
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primers that were extended in step (i) by detecting the
labeled nucleotides that were added;
(iv) comparing the locations of labeled
nucleotides determined in step (iii) with the locations of
the duplexes to determine which of the primers have been
extended; and
( v) removing the label from the labeled
nucleotides added to the primers in step (i) before the
next iteration.
Response to Notice of Non-Compliant Appeal Brief 12 ("Claims App'x").
STANDARD OF REVIEW
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
primafacie case ofunpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
INDEFINITENESS
The Examiner's Prima Facie Case
In rejecting claims 1-8, 13-16, and 50-65 for indefiniteness, the
Examiner advance three rationales: (1) that the pending independent claims
omit essential steps (Ans. 2-3); (2) that the scope of the recitation "using an
alignment algorithm" in claims 55 and 65 is unclear (id. at 3); and (3) that
the scope of the term "about" in claims 59 and 65 is unclear (id. at 3--4).
Analysis
A claim does not comply with 35 U.S.C. § 112, second paragraph,
"when it contains words or phrases whose meaning is unclear." In re
Packard, 751 F.3d at 1310, 1314 (Fed. Cir. 2014) (approving, for pre-
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issuance claims, the standard from MPEP § 2173.05(e)); see also Ex parte
McAward, Appeal 2015-006416, 2017 WL 3669566, at *5 (PTAB Aug. 25,
2017) (precedential) (adopting the approach for assessing indefiniteness
approved by the Federal Circuit in Packard).
That is, "claims are required to be cast in clear-as opposed to
ambiguous, vague, indefinite-terms." Packard, 751 F.3d at 1313.
Lacking Essential Steps
We reverse the Examiner's indefiniteness rejection of independent
claims 1, 63, and 65 alleging the absence of essential steps in the claims.
While the Examiner alleges that claims 1, 63, and 65 lack a number of
essential steps (see Ans. 2-3, 47--48), the Examiner identifies no unclear,
ambiguous, or vague language in the claims. As Appellant contends,
moreover, the Examiner does not advance any evidence suggesting that a
skilled artisan would fail to understand what steps are encompassed by the
nucleic acid sequencing processes recited in claims 1, 63, and 65.
Rather, the Examiner's position, as we understand it, is that the
alleged lack of detail as to the specific steps encompassed by claims 1, 63,
and 65 renders them overly broad. It is well settled, however, that that
"breadth is not to be equated with indefiniteness." In re Miller, 441 F.2d
689, 693 (CCPA 1971).
Because the Examiner does not persuade us that a skilled artisan
would consider the processes recited in claims 1, 63, and 65 to be unclear,
ambiguous, or vague because the scope of the claimed processes is
uncertain, we reverse the Examiner's rejection of claims 1, 63, and 65 for
indefiniteness.
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Using an Alignment Algorithm
We reverse the Examiner's indefiniteness rejection of claims 55 and
65 based on their recitation of using an alignment algorithm.
The Examiner rejected claims 55 and 65 as indefinite, based on the
assertion that it is unclear what alignment algorithms are encompassed by
the claims, and also based on the assertion that it is unclear what it means to
use an alignment algorithm. Ans. 3. In rejecting the claims, however, the
Examiner provided no clear explanation why a skilled artisan would consider
the claim language at issue unclear, ambiguous, or vague. See id. Nor did
the Examiner advance any evidence suggesting that a skilled artisan would
fail to understand what an alignment algorithm is, or what it means to use an
alignment algorithm.
Indeed, consistent with Appellant's contentions that a skilled artisan
would understand what it means to use an alignment algorithm, and directly
contrary to the Examiner's own conclusion of indefiniteness, the Examiner
cited prior art disclosing the use of an alignment algorithm to compare
sequences, when rejecting the claims for obviousness. See id. at 33-34
( citing Fleming 12:21-27); see also Fleming 12:21-27 ("Sequencing was
done by an automated unit and the obtained sequences were compared with
Genbank archives using the BLAST algorithm .. .. Prior to computer
analysis the automated readout was visually inspected for deletions. Both
the BLASTN and BLASTX functions were used." (emphasis added; citation
omitted)).
That the rejected claims do not recite a particular alignment algorithm
(see Ans. 49), establishes, at best, that the claims might be considered
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relatively broad in that respect. Again, however, "breadth is not to be
equated with indefiniteness." In re Miller, 441 F.2d at 693.
In sum, because preponderant evidence does not support the
Examiner's conclusion that a skilled artisan would consider the processes
recited in claims 55 and 65 to be unclear, ambiguous, or vague, to the extent
that the scope of the claimed processes is uncertain, we reverse the
Examiner's rejection of claims 55 and 65 for indefiniteness.
"About"
The Examiner rejected claims 59 and 65 as indefinite because "[t]he
term 'about' is not defined by the claim(s), the specification does not
provide a standard for ascertaining the requisite degree, and one of ordinary
skill in the art would not be reasonably apprised of the scope of the
invention." Ans. 3.
As the Examiner points out (Ans. 50), Appellant advanced no
argument explaining why the Examiner erred in determining that the use of
the term "about" renders claims 59 and 65 indefinite. See Br., generally.
We, therefore, summarily affirm the Examiner's rejection of claims
59 and 65 for indefiniteness, based on the use of the term "about" in those
claims. See MPEP § 1205.02 ("If a ground of rejection stated by the
examiner is not addressed in the appellant's brief, appellant has waived any
challenge to that ground of rejection and the Board may summarily sustain
it, unless the examiner subsequently withdrew the rejection in the
examiner's answer.").
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ENABLEMENT
The Examiner's Prima Facie Case
In rejecting claims 1-8, 13, and 60-65 as failing to comply with the
enablement requirement, the Examiner determined that practicing the full
scope of the claimed invention would require undue experimentation, based
on the breadth of the claims, the alleged unpredictability in the art, and the
alleged large quantity of experimentation required to practice the full scope
of the claimed subject matter. Ans. 5-13. Although not presented in a
particularly straightforward manner, as we understand it, the Examiner's
rejection is based on the determination that the claims encompass using any
prior-art-known or future-known nucleic acid sequence in a process of
determining the sequences of any and all target nucleic acids, from any and
all types of organisms. See id. at 9-12.
Therefore, the Examiner reasons, practicing the full scope of the
claimed methods would take a significant amount of time and effort. See id.
at 13 ("[T]he aspect of having to work for many tens of years just to provide
the starting materials for [a] minute fraction of the scope of the claimed
invention is deemed to constitute both an unreasonable length of time and
undue experimentation.").
Analysis
We agree with Appellant that preponderant evidence does not support
the Examiner's conclusion of non-enablement.
As our reviewing court has explained, the Examiner "bears an initial
burden of setting forth a reasonable explanation as to why [he or she]
believes that the scope of protection provided by that claim is not adequately
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enabled by the description of the invention provided in the specification of
the application." In re Wright, 999 F.2d 1557, 1561---62 (Fed. Cir. 1993).
"The scope of enablement ... is that which is disclosed in the
specification plus the scope of what would be known to one of ordinary skill
in the art without undue experimentation." National Recovery Technols. Inc.
v. Magnetic Separation Sys., Inc., 166 F.3d 1190, 1196 (Fed. Cir. 1999).
Although the Specification must enable the skilled artisan to practice
the full scope of the claimed subject matter, "[i]t is well settled that patent
applicants are not required to disclose every species encompassed by their
claims, even in an unpredictable art." In re Vaeck, 947 F.2d 488, 496 (Fed.
Cir. 1991 ). Moreover, a claim does not lack enablement merely because it
encompasses inoperative embodiments. Atlas Powder Co. v. E.I. du Pont
De Nemours & Co., 750 F.2d 1569, 1576 (Fed. Cir. 1984).
Rather, as our reviewing court has noted:
[T]here must be sufficient disclosure, either through illustrative
examples or terminology, to teach those of ordinary skill [in the
art] how to make and how to use the invention as broadly as it
is claimed. This means that the disclosure must adequately
guide the art worker to determine, without undue
experimentation, which species among all those encompassed
by the claimed genus possess the disclosed utility.
Vaeck, 947 F.2d at 496 (footnote omitted).
In the present case, each of Appellant's independent claims is directed
to a process of sequencing a single nucleic acid molecule. Claims App'x 12,
15, and 16. Each of the independent claims requires providing a plurality of
labeled duplexes, the duplexes being bonded to a surface. Id.
Each surface-bonded duplex is composed of a template nucleic acid to
be sequenced, and a primer hybridized thereto. Id. As noted by the
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Examiner, in addition to the target nucleic acid molecule to be sequenced,
the template component of the duplex includes a molecule having "a known
nucleotide sequence" attached to it. Id.
As explained in the Specification, the known sequence attached to the
template may be a poly( dA) tail, with the primer hybridized thereto being a
poly(dT) oligonucleotide. See Spec. ,r 35; see also id. ,r,r 60-63 (working
example describing polyadenylation of digested sample DNA to be
sequenced and hybridization of a polydT(50) primer to the polyadenylated
sample DNA).
As recited in claims 1, 63, and 65, the locations of the surface-bound
duplexes are determined by detecting the label attached to the duplexes.
Claims App'x 12, 15, 16. Claims 1, 63, and 65 then recite extending the
hybridized primers by contacting the surface-bonded duplexes with a
polymerase and a nucleotide having a second label, followed by washing,
and if the labeled nucleotide is incorporated into the complement to the
template, the label is detected. Id. Each of claims 1, 63, and 65 recites
extending the primers by at least three consecutive nucleotides. Id.
As explained in the Specification, fluorescent labeling may be used,
and detection of the location of the surface-bound duplexes, as well as the
location of labeled nucleotides incorporated into the duplexes, may be
performed by microscopy using an imaging system depicted in Figure 3.
See, e.g., Spec. ,r,r 14, 45, and 52; see also Fig. 3 (showing imaging system);
Fig. 2 (showing stack of images obtained after each successive labeled
nucleotide incorporation event).
Thus, as is evident, by knowing the identity of each nucleotide
consecutively added to the template, and the location of each nucleotide
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added to the template, the sequence of each of the surface-bound templates
may be determined. See Spec. ,r,r 60-69 (working example showing
sequencing of bacteriophage M13mp18 at about 99% accuracy).
Therefore, as Appellant contends, the Specification not only describes
how to perform the claimed process, but also provides a working example.
We agree with the Examiner that, given their broadest reasonable
interpretation consistent with the Specification, Appellant's independent
claims 1, 63, and 65 encompass sequencing numerous target nucleic acids in
addition to the sequence exemplified in the Specification, using any known
sequence and hybridizing complement that allows primer extension. The
Examiner does not, however, advance specific persuasive evidence
demonstrating that an ordinary artisan would have needed to experiment
unduly to determine suitable primer and complementary sequences for
practicing the claimed invention, particularly given the poly( dA) and
poly( dT) sequences described in the Specification. And the existence of
numerous as yet undiscovered and un-sequenced potential target sequences
does not persuade us that a skilled artisan only would have been able to
practice the methods as claimed and described by experimenting unduly.
We do not agree, moreover, with the Examiner's implication that
Appellant must draft the claims in a manner that excludes application of the
claimed process to as yet undiscovered target sequences. See Ans. 6 ("[T]he
claimed methods have been construed as encompassing that which will
become 'known' at some point in the future.").
As explained by our reviewing court's predecessor, "[i]t is always
possible to put something into a combination to render it inoperative. It is
not the function of the claims to exclude all such matters but to point out
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what the combination is." In re Anderson, 471 F.2d 1237, 1242 (CCPA
1973). In the present case, the claims are not directed to methods of
sequencing every known organism. Rather, the claims are simply directed to
methods of single molecule nucleic acid sequencing by a primer extension
that incorporates labeled nucleotides. As noted above, Appellant's
Specification describes how to perform the claimed process, and provides a
working example.
Accordingly, for the reasons discussed, we agree with Appellant that a
preponderance of the evidence does not support the Examiner's conclusion
that Appellant's claims lack enablement. We, therefore, reverse the
Examiner's enablement rejection.
WRITTEN DESCRIPTION
The Examiner's Prima Facie Case
In rejecting claims 1-8, 13, and 60-65 as failing to comply with the
written description requirement, the Examiner applied a rationale similar to
that applied above in relation to enablement. Specifically, as with the
enablement rejection discussed above, the Examiner determined that the
claims "encompass[] the sequencing of any and all nucleic acids, regardless
of source" (Ans. 16), and also encompass using any and all primers capable
of hybridizing with a nucleic acid having a known sequence (see id. at 16-
17). As with the enablement rejection, the Examiner noted that the claims
therefore encompass sequencing nucleic acids obtained from billions of
organisms. Id. at 17.
Based on those determinations, the Examiner reasoned that the
claimed subject matter lacks sufficient written description support because
(1) the Specification does not describe sequencing a representative number
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of nucleic acids of those encompassed by the claims, and (2) the
Specification does not disclose common identifying properties allowing
sequencing of any and all nucleic acids. See id. at 19 ("[T]he disclosure has
not been found to satisfy either prong of the written description test .... ").
Analysis
For reasons similar to those discussed above as to the Examiner's
enablement rejection, we also reverse the Examiner's written description
rejection.
Our reviewing court has directed:
A claim will not be invalidated on section 112 grounds
simply because the embodiments of the specification do not
contain examples explicitly covering the full scope of the claim
language. That is because the patent specification is written for
a person of skill in the art, and such a person comes to the
patent with the knowledge of what has come before. Placed in
that context, it is unnecessary to spell out every detail of the
invention in the specification; only enough must be included to
convince a person of skill in the art that the inventor possessed
the invention and to enable such a person to make and use the
invention without undue experimentation.
Falkner v. Inglis, 448 F.3d 1357, 1366 (Fed. Cir. 2006) (quoting LizardTech,
Inc. v. Earth Resource Mapping, PTY, Inc., 424 F.3d 1336, 1345 (Fed. Cir.
2005)); see also Capon v. Eshhar, 418 F.3d 1349, 1359 (Fed. Cir. 2005)
("[T]he determination of what is needed to support generic claims to
biological subject matter depends on a variety of factors, such as the existing
knowledge in the particular field, the extent and content of the prior art, the
maturity of the science or technology, the predictability of the aspect at
issue.").
In the present case, as discussed above, contrary to the Examiner's
determination that the Specification fails to provide any examples of known
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sequences and primers complementary thereto, the Specification not only
describes how to perform the claimed process, but also provides a working
example. See Spec. ,r,r 60-69 (working example describing polyadenylation
of digested sample DNA to be sequenced, followed by hybridization of a
polydT(50) primer to the polyadenylated sample DNA, followed by
extension of primer with labeled oligonucleotides allowing sequence
determination of target DNA at about 99% accuracy).
The Specification also discloses that the described and claimed
sequencing processes may be applied to a variety of nucleic acids from a
number of different sources. Id. ,r 24.
We agree with the Examiner that the rejected claims are not limited to
a particular template targeted for sequencing. We also agree with the
Examiner that the claims are not limited to a particular known sequence as
the hybridizing partner for the extended primer.
The Examiner, however, fails to identify persuasive evidence
suggesting that it would be unpredictable whether the sequencing process as
disclosed and claimed would be applicable to nucleic acids other than those
exemplified and described in the Specification, to the extent that a skilled
artisan would question whether Appellant was in possession of the claimed
invention. Nor does the Examiner identify persuasive evidence suggesting
that it would be unpredictable for a skilled artisan to determine a suitable
known sequence and hybridizing partner for use in the process as disclosed
and claimed, such that Appellant's possession of the claimed invention
would be doubted by a skilled artisan.
Because we are not persuaded that preponderant evidence supports the
Examiner's determination that claims 1-8, 13, and 60-65 lack sufficient
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descriptive support, we reverse the Examiner's rejection of claims 1-8, 13,
and 60-65 as failing to comply with the written description requirement.
ELIGIBILITY FOR PA TENTING
The Examiner's Prima Facie Case
In rejecting claims 1-8, 13-16, and 50-65 as being directed to subject
matter not eligible for patenting, the Examiner stated that the claimed
"aspect of 'determining' and 'comparing' are deemed to be an abstract
idea." Ans. 19.
In particular, the Examiner concluded that the claimed determining
and comparing steps encompass mental processes, as do a number of other
steps recited in the claims. Id. at 19-22. The Examiner determined that the
remaining "active, physically-transforming steps are deemed to be well
understood and routine in the art and do not add significantly more than the
judicial exception (Question 2B of the Interim Guidelines)" (id. at 22).
The Examiner cited a number of paragraphs from the Specification, as
well as the Williams, Sklar, and Fleming references cited in the obviousness
rejection discussed below, as evidence that the non-mental steps recited in
the claims were well understood, routine, and conventional in the art. Id. at
22-27. The Examiner reasoned, therefore, that the non-mental steps recited
in the rejected claims "do not add significantly more than the judicial
exception." Id. at 27.
Analysis
An invention is patent-eligible if it claims a "new and useful process,
machine, manufacture, or composition of matter." 35 U.S.C. § 101. The
Supreme Court has long interpreted 35 U.S.C. § 101 to include implicit
exceptions, however: "[l]aws of nature, natural phenomena, and abstract
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ideas" are not patentable. Alice Corp. v. CLS Bank Int 'l, 573 U.S. 208, 216
(2014).
In determining whether a claim falls within an excluded category, we
are guided by the Supreme Court's two-step framework, described in Mayo
Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012) and
Alice, 573 U.S. at 217-18 (citing Mayo, 566 U.S. at 75-77). In accordance
with that framework, we first determine what concept the claim is "directed
to." See Alice, 573 U.S. at 219 ("On their face, the claims before us are
drawn to the concept of intermediated settlement, i.e., the use of a third party
to mitigate settlement risk.").
Concepts determined to be abstract ideas, and thus patent ineligible,
include certain methods of organizing human activity, such as fundamental
economic practices (Alice, 573 U.S. at 219-20; Bilski v. Kappas, 561 U.S.
593, 611 (2010)); mathematical formulas (Parker v. Flook, 437 U.S. 584,
594--95 (1978)); and mental processes (Gottschalkv. Benson, 409 U.S. 63,
69 (1972)).
If the claim is "directed to" an abstract idea, we tum to the second
step of the Alice and Mayo framework, where "we must examine the
elements of the claim to determine whether it contains an 'inventive
concept' sufficient to 'transform' the claimed abstract idea into a patent-
eligible application." Alice, 573 U.S. at 221 ( quotation marks omitted).
The PTO recently published revised guidance on the application of
§ 101. USPTO, 2019 Revised Patent Subject Matter Eligibility Guidance,
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84 Fed. Reg. 50 (January 7, 2019) ("Memorandum" or "Office Guidance"). 7
Under that guidance, we first look to whether the claim recites the following:
(1) any judicial exceptions, including certain groupings of
abstract ideas (i.e., mathematical concepts, certain methods of
organizing human interactions such as a fundamental economic
practice, or mental processes); and
(2) additional elements that integrate the judicial exception into
a practical application (see MPEP § 2106.05(a}-(c), (e}-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that
exception into a practical application, do we then look to whether the claim:
(3) adds a specific limitation beyond the judicial exception that
are not "well-understood, routine, conventional" in the field
(see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional
activities previously known to the industry, specified at a high
level of generality, to the judicial exception.
See Memorandum.
In the present case, the Examiner does not persuade us that
Appellant's claims recite subject matter that is ineligible for patenting.
Appellant's independent claims 1, 63, and 65 are not directed to
mathematical concepts or methods of organizing human interactions. We
are not persuaded, moreover, that the Examiner has established that the
claimed steps of determining the locations of the labeled surface-bound
duplexes, and comparing the locations of the incorporated labeled
nucleotides to the original locations of the surface-bound duplexes, could
practicably be performed by the human mind alone, and, therefore, amount
to mental processes.
7 Available at https://www.govinfo.gov/content/pkg/FR-2019-01-
07/pdf/2018-28282.pdf.
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As discussed above, Appellant's Specification discloses the use of a
specific imaging system that involves the use of lasers and a microscope to
determine the locations of the fluorescently labeled surface-bound duplexes,
and the fluorescently labeled nucleotides added thereto. See, e.g., Spec.
,r,r 14, 45, and 52; see also Fig. 3 (showing imaging system); Fig. 2 (showing
stack of images obtained after each successive labeled nucleotide
incorporation event). The evidence of record, therefore, does not support the
Examiner's determination that is practicable to perform the claimed
determining and comparing steps solely by a mental process.
Even if it were practicable to perform the claimed determining and
comparing steps solely by mental processes (which, as noted above, the
evidence does not support), the claimed processes include critical steps
which are actual physical steps that involve the use of non-abstract tangible
components. Specifically, the claims all require preparing a product
composed of a labeled nucleic acid duplex bonded to a surface, contacting
that surface-bound duplex with labeled nucleotides and a polymerase,
washing the surface-bound duplex with its incorporated nucleotide to
remove unincorporated nucleotides, and removing the label from the
incorporated nucleotide. Claims App'x 12, 15, and 16.
Thus, even if the evidence were to support the premise that the
claimed determining and comparing steps could practicably be performed
solely by mental processes, the claimed determining and comparing steps are
nonetheless integrated into a practical application, demonstrated by the fact
that steps critical to the claimed processes are actual physical steps that
involve the use of non-abstract tangible components.
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The fact that the physical steps recited in the claims might be
described in the prior art does not persuade us that the claims are ineligible
for patenting. See Office Guidance, 84 Fed. Reg. at 54 ("[A] claim that
includes conventional elements may still integrate an exception into a
practical application, thereby satisfying the subject matter eligibility
requirement of Section 101.").
In sum, for the reasons discussed, the Examiner does not persuade us
that Appellant's claims are directed to subject matter that is ineligible for
patenting. We, therefore, reverse the Examiner's rejection of claims 1-8,
13-16, and 50-65 on that ground.
OBVIOUSNESS
The Examiner's Prima Facie Case
In rejecting claims 1-8, 13-16, and 50-65 over Williams, Sklar,
Fleming, and admitted prior art, the Examiner cited Williams as disclosing a
method of sequencing single nucleic acid molecules in which a polymerase
incorporates fluorescently labeled nucleotides into a surface-bound template.
Ans. 32-33.
The Examiner found that Williams' s process differs from the
processes recited in Appellant's claims in that, "[ w ]hile Williams has been
found to teach using fluorescent labels in a sequencing reaction, it has not
been found to teach using a primer that is labeled in combination with
labeled nucleotides." Id. at 33.
As evidence that a skilled artisan would have considered Appellant's
claimed processes obvious despite that difference, the Examiner cited Sklar
as disclosing that it was known in the art of nucleotide sequencing to label
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both the primer and added nucleotide as a FRET (fluorescent resonance
energy transfer) pair. Id. ( citing Sklar ,r 63).
The Examiner cited Fleming as evidence it would have been obvious
to use a sequence alignment algorithm in nucleic acid processes. Id. at 33-
34. The Examiner cited a number of paragraphs from Appellant's
Specification as admitted prior art evidence that the elements of the claimed
invention recited in the dependent claims would have been obvious features
of a nucleic acid sequencing process. See id. at 34--3 7.
Based on the combined teachings in the cited prior art, the Examiner
reasoned:
[I]t would have been obvious to one of ordinary skill in
the art at the time of the invention to have modified the method
of Williams with that of Sklar et al., therein allowing for the
determination of polymorphisms by use of FRET, and to have
further modified the methods of Williams and Sklar et al., with
that of Fleming et al., whereby sequence alignments are
performed either via automated means o[r] visually, wherein if
via automated means, known algorithms are used. It would
have also been obvious to said routineer in the art to have taken
advantage of known polymerases, known methods and means
of linking nucleic acids to supports, known blocking agents,
known labels that, along with detection means, are not only
known but commercially available.
Id. at 37-38.
Analysis
Having considered the arguments and evidence advanced by
Appellant and the Examiner, Appellant does not persuade us that the
Examiner's conclusion of obviousness is not supported by a preponderance
of the evidence.
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As the Supreme Court explained in KSR Int 'l Co. v. Teleflex Inc., 550
U.S. 398 (2007), "when a patent 'simply arranges old elements with each
performing the same function it had been known to perform' and yields no
more than one would expect from such an arrangement, the combination is
obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273
(1976)).
In the present case, as the Examiner found, and Appellant does not
dispute, Williams discloses a process of single molecule nucleic acid
sequencing that includes the steps, recited in Appellant's claim 1, of
providing a surface-bonded primer-template duplex, and using a polymerase
to extend the template-hybridized primer with labeled nucleotides:
This invention provides for a method of ... sequencing a
target nucleic acid [NA] comprising the steps of: i.
immobilizing ... the target nucleic acid onto a solid support in
a single molecule configuration; ii. contacting the solid support
with a solution containing: ... (a) ... a polymerase; (b) a
primer nucleic acid which complements a region of the target
nucleic acid downstream of the region to be sequenced; ( c) NTP
where each type of base is differently labeled on the phosphate
portion, where the labels provide a unique signal that is
selectively detectable upon incorporation ofNTP into the
polymerase extension product; iii. permitting the polymerase to
sequentially extend the primer incorporating the NTP creating a
complement to the target nucleic acid; and, iv. determining
extension of the primer by detecting the unique signal from the
labeled NTP to genotype or to sequence the target nucleic acid.
It is preferred that the NTPs are labeled on the gamma
phosphate with a fluorescent label that differentially fluoresces
when the gamma phosphate is cleaved away from the
nucleoside. The immobilized moieties can further comprise an
array of locations each bearing a single molecule of ... target
nucleic acid.
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Williams 2: 17--42.
As the Examiner found, and Appellant does not dispute, Williams' s
process differs from the process of Appellant's claim 1 only in that Williams
does not disclose that its surface-bound duplex includes a label. As the
Examiner found, however, and Appellant does not dispute, Sklar discloses
that when performing primer extension sequencing reactions, it was
desirable to include a label on the extended primer as one partner of a FRET
pair, such that incorporation a labeled nucleotide onto the extended primer
would result in detectable fluorescence identifying the added nucleotide:
The labeled primer is hybridized to the locus, and single base
extension of the labeled primer is performed with fluorescently
labeled dideoxyribonucleotides (ddNTPs) in dye-terminator
sequencing fashion, except that no deoxyribonucleotides are
present. An increase in fluorescence of the added ddNTP in
response to excitation at the wavelength of the labeled primer is
used to infer the identity of the added nucleotide.
Sklar ,r 63.
Appellant does not assert error in the Examiner's finding that the
combined teachings of Williams and Sklar would have suggested
configuring Williams' s process to include a labeled primer that, using the
FRET effect, would fluoresce upon incorporation of a labeled nucleotide
into the extended primer. Nor does Appellant contend that the claimed
process yields unexpected results.
Rather, Appellant contends that the Examiner erred by failing to
consider the claimed invention as a whole, because the cited prior art does
not teach or suggest:
• determining the positions of the duplexes on the surface
by way of locations on the surface of the duplexes by detecting
the first label - step (b) of claim l;
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• comparing the locations of labeled nucleotides
determined in step (iii) with the locations of the duplexes - step
(iv); or
• removing the label from the labeled nucleotides added
to the primers in step (i) before the next iteration - step (v).
Br. 10.
In response, the Examiner cited the Braslavsky reference8 ( cited in
Appellant's Specification (Spec. ,r 7)) as evidence that when performing
array-based sequencing reactions involving the extension of surface-bound
primer-template complexes as recited in Appellant's claim 1, it was well
known in the art to determine the initial location of the surface-bound
primer-template duplexes, and to determine location of the labeled
nucleotides incorporate into the duplexes, by comparing the location of the
incorporated nucleotides to the original location of the labeled primer-
template duplexes:
When as here one is trying to determine the nucleotide
sequence of a plurality of "DNA template oligonucleotides"
(appellant's "nucleic acid template"), and that these multiple
templates are bound to different positions on a common
support, it is essential that one be able to correlate a given
position with a nucleotide having been incorporated into the
elongating primer. To not be able to do so would not allow one
to determine the nucleotide sequence of such hybridized and
immobilized templates.
Ans. 61. Citing the Braslavsky reference as admitted prior art, the Examiner
responds also that "performing multiple wash steps was admittedly well
known in the art." Id.
8 Ido Braslavsky et al., Sequence information can be obtained from single
DNA molecules, 100 PNAS 3960-64 (2003).
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We find that the preponderance of the evidence supports the
Examiner's position. We first note that Appellant did not file a reply brief
alleging error in the Examiner's determination that the claimed steps of
determining the location of the surface-bound template-primer complex,
comparing that location to the location of the incorporated labeled
nucleotide, and removing the label from the labeled nucleotide after
incorporation, were well known in the art.
We note also Braslavsky's disclosure that its primer-extension
sequencing process involves determining the location of the surface-bound
template-primer complex and comparing that location to the location of the
incorporated labeled nucleotide:
DNA template oligonucleotides were hybridized to a
fluorescently labeled primer and bound to the surface via
streptavidin and biotin with a surface density low enough to
resolve single molecules. The primed templates were detected
through their fluorescent tags, their locations were recorded for
future reference, and the tags were photobleached. Labeled
nucleotide triphosphates and DNA polymerase enzyme were
then washed in and out of the flow cell while the known
locations of the DNA templates were monitored for the
appearance of fluorescence.
Braslavsky 3960.
As noted above, Williams discloses that its sequencing process can
involve the use of arrays. See Williams 2:40-42. Williams also discloses
the importance of knowing the locations of the extended molecules at each
array location. See id. at 3: 14--17 ("The array members are optionally
addressed so that the locations are defined and comparative information
between sites can be generated and recorded by the optical reader.").
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Given the disclosures in Williams of using arrays of nucleic acid
molecules of defined locations in its sequencing processes, we discern no
error in the Examiner's determination that it would have been obvious in
view of Williams to determine the location on the array of the initial
template-primer complex, as well as the location (by comparison) of the
incorporated labeled nucleotide, particularly in light of Braslavsky's
disclosure of the usefulness of those determinations.
Moreover, given Williams's disclosure of using a nucleotide label that
is liberated from the primer-template complex upon incorporation, we
discern no error in the Examiner's determination that it would have been
obvious to remove the label after nucleotide incorporation, particularly given
Braslavsky' s disclosure of photo bleaching the incorporated label.
In sum, for the reasons discussed, Appellant does not persuade us that
preponderant evidence fails to support the Examiner's conclusion of
obviousness as to claim 1. We, therefore, affirm the Examiner's rejection of
claim 1 over Williams, Sklar, Fleming, and admitted prior art. Because they
were not argued separately, claims 2-8, 13-16, and 50-65 fall with claim 1.
DOUBLE PATENTING
The Examiner's Prima Facie Case
The Examiner's rejection of claims 1-8, 13-16, and 50-65 for
obviousness-type double patenting over claims 1 and 8-20 of the '345 patent
in view of Williams, Sklar, and Fleming applies a rationale similar to the
rationale applied in the obviousness rejection, discussed above. See Ans.
39--41.
In particular, based on the teachings Williams, Sklar, and Fleming, the
Examiner reasoned that "the prior art of record fairly teaches a method of
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sequencing individual nucleic acid molecules which have been bound to a
surface and wherein the primer and the nucleotides being added are both
labeled." Id. at 40. In addition, the Examiner reasoned, "as shown above,
the aspect of aligning a determined sequence with that known, including the
use of algorithms, was also known in the art." Id. at 41.
In rejecting claims 1-8, 13-16, and 50-53 for obviousness-type
double patenting over claims 1, 11-13, and 15-17 of the '498 patent, the
Examiner applied essentially identical reasoning. See id.
Analysis
In evaluating obviousness-type double patenting, the Federal Circuit
has explicitly "endorsed an obviousness determination similar to, but not
necessarily the same as, that undertaken under 35 U.S.C. § 103 in
determining the propriety of a rejection for double patenting." In re Braat,
937 F.2d 589, 592-93 (Fed. Cir. 1991).
Thus, in making an obviousness-type double patenting rejection, the
Examiner must show that a claimed invention is "a mere variation of [the
patented invention] ... which would have been obvious to those of ordinary
skill in the relevant art ... [ and] there must be some clear evidence to
establish why the variation would have been obvious which can qualify as
'prior art."' In re Kaplan, 789 F.2d 1574, 1579-80 (Fed. Cir. 1986).
In the present case, as to the rejection based on the claims of the '345
patent, Appellant contends that the Examiner "does not explain with
particularity how these [ cited] references suggest the combination of all the
elements and steps of the claimed invention configured and utilized as stated
in the claims." Br. 10. Appellant does not, however, explain specifically
which elements of representative rejected claim 1 are not taught or suggested
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by the combination of claims 1 and 8-20 of the '345 patent, Williams, Sklar,
and Fleming. See id. We are not persuaded, moreover, that the teachings
cited by the Examiner fail to render obvious the process recited in rejected
representative claim 1.
Appellant's claim 1 recites a process of single molecule nucleic acid
sequencing that includes the steps of providing a plurality of surface-bonded
primer-template duplexes, and using a polymerase to extend the template-
hybridized primers by at least three consecutive nucleotides with labeled
nucleotides. Claims App'x 12.
Appellant's claim 1 recites washing the duplexes to remove
unincorporated nucleotides, determining the locations on the surface of the
primers that were extended by detecting the labeled nucleotides that were
added, comparing the locations of labeled nucleotides with the locations of
the duplexes to determine which of the primers have been extended, and
removing the label from the labeled nucleotides added to the primers before
the next iteration of labeled nucleotide addition. Id.
Claims 1, 8, and 19 of the '345 patent, cited by the Examiner, read as
follows:
1. A method for sequencing a nucleic acid template, the
method comprising:
conducting a sequencing-by-synthesis reaction on a
template nucleic acid/primer duplex, wherein the reaction is
controlled such that on average no more than three nucleotides
are added to the primer per incorporation cycle; and
determining a sequence of the template based upon order
of incorporation of the nucleotides to the primer over multiple
incorporation cycles, wherein the nucleotides are not chain
terminating nucleotides, and wherein the template/primer
duplexes are individually optically resolvable.
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8. The method of claim 1, wherein the determining
comprises optically identifying the incorporated nucleotide(s).
19. The method according to claim 1, wherein the
duplexes are attached to a solid support.
The '345 patent, 22:59-24:18.
As is evident, claims 1, 8, and 19 of the '345 patent recite a similar
sequencing process to that recited in rejected claim 1, including rejected
claim 1 's step of providing a plurality of surface-bonded primer-template
duplexes, and using a polymerase to extend the template-hybridized primers
by at least three consecutive nucleotides with labeled nucleotides.
Moreover, as discussed above in relation to the Examiner's obviousness
rejection, Williams discloses using arrays of nucleic acid molecules of
defined locations in sequencing processes. See Williams 2:40-42, 3:14--17.
We, therefore, discern no error in the Examiner's determination that it would
have been obvious in view of Williams to use an array in a sequencing
process as recited in the claims of the '345 patent, and to determine the
location on the array of the initial template-primer complex, as well as the
location (by comparison) of the incorporated labeled nucleotide.
Further, as also discussed above in relation to the Examiner's
obviousness rejection, Williams discloses using a nucleotide label that is
liberated from the primer-template complex upon incorporation. See id. at
2:37--40. Accordingly, we discern no error in the Examiner's determination
that it would have been obvious in the process recited in the '345 patent
claims to remove the label after nucleotide incorporation. Lastly, because
the '345 patent claims recite the addition of up to three nucleotides to the
template-bound primer, we discern no error in the Examiner's determination
that the step of removing unincorporated nucleotides by washing recited in
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rejected claim 1 would have been an obvious step in the process recited in
the claims of the '345 patent.
In sum, for the reasons discussed, Appellant does not persuade us
preponderant evidence fails to support the Examiner's conclusion that the
process recited in representative rejected claim 1 would have been obvious
over claims 1 and 8-20 of the '345 patent in view of Williams, Sklar, and
Fleming. We, therefore, affirm the Examiner's rejection of claim 1 on that
ground. Because they were not argued separately, claims 2-8, 13-16, and
50-65 fall with claim 1.
As the Examiner points out (Ans. 63), Appellant advanced no
argument explaining why the Examiner erred in determining that the
processes recited in claims 1-8, 13-16, and 50-53 under consideration
herein would have been obvious over claims 1, 11-13, and 15-17 of the
'498 patent in view of Williams, Sklar, and Fleming. See Br., generally.
We, therefore, summarily affirm the Examiner's rejection of claims
1-8, 13-16, and 50-53 for obviousness-type double patenting over claims 1,
11-13, and 15-17 of the '498 patent in view of Williams, Sklar, and
Fleming. See MPEP § 1205.02.
SUMMARY
For the reasons discussed, we reverse the Examiner's rejection of
claims 1-8, 13-16, and 50-65, as being indefinite based on the absence of
essential steps in the claims.
For the reasons discussed, we reverse the Examiner's rejection of
claims 55 and 65, as being indefinite based on the language in those claims
reciting the use of and algorithm.
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For the reasons discussed, we affirm the Examiner's rejection of
claims 59 and 65, as being indefinite based on the presence of the term
"about" in those claims.
For the reasons discussed, we reverse the Examiner's rejection of
claims 1-8, 13, and 50-65, under 35 U.S.C. § 112, first paragraph, as failing
to comply with the enablement requirement.
For the reasons discussed, we reverse the Examiner's rejection of
claims 1-8, 13-16, and 50-65, under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement.
For the reasons discussed, we reverse the Examiner's rejection of
claims 1-8, 13-16, and 50-65, under 35 U.S.C. § 101, as not being directed
to patent eligible subject matter.
For the reasons discussed, we affirm the Examiner's rejection of
claims 1-8, 13-16, and 50-65, under 35 U.S.C. § 103(a) as being
unpatentable over Williams, Sklar, Fleming, and admitted prior art.
For the reasons discussed, we affirm the Examiner's rejection of
claims 1-8, 13-16, and 50-65, on the ground of nonstatutory double
patenting over claims 1 and 8-20 of the '345 patent in view of Williams,
Sklar, and Fleming.
For the reasons discussed, we affirm the Examiner's rejection of
claims 1-8, 13-16, and 50-53, on the ground of nonstatutory double
patenting over claims 1, 11-13, and 15-17 of the '498 patent in view of
Williams, Sklar, and Fleming.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l ). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
31