Ex Parte West

Patent Trial and Appeal Board

Jan 10, 2018

13384302 (P.T.A.B. Jan. 10, 2018)

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.
13/384,302 03/12/2012 John Stephen West 531.05040101/IP-0504-US 6510
143934 7590 01/12/2018
MRG/Illumina
c/o Mueting, Raasch & Gebhardt, P.A.
P.O. Box 581336
Minneapolis, MN 55458-1336
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
01/12/2018 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
ptodocketing @ mrgs .com
illuminadocket@illumina.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN STEPHEN WEST1
Appeal 2018-000508
Application 13/384,302
Technology Center 1600
Before DEMETRA J. MILLS, FRANCISCO C. PRATS, 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
preparing libraries of nucleic acid sequence fragments for sequence analysis.
The Examiner rejected the claims as lacking utility, lacking enablement, and
for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.
1 Appellant identifies Illumina, Inc., as the real party in interest. App. Br. 3.
Appeal 2018-000508
Application 13/384,302
STATEMENT OF THE CASE
The following rejections are before us for review:2
(1) Claims 1, 2, 13, 14, 17, 20, 22, and 26-33, under 35 U.S.C. § 101,
as not supported by either a specific, substantial, and credible asserted utility
or a well-established utility (Ans. 2—6);
(2) Claims 1,2, 13, 14, 17,20, 22, and 26-33, under 35 U.S.C. § 112,
first paragraph, as failing to comply with the enablement requirement (id. at
6); and
(3) Claims 1, 2, 13, 14, 17, 20, 22, and 26—33, under 35 U.S.C.
§ 103(a), as being unpatentable over Appellant’s admitted prior art and
Koster3 (id. at 6—15).
Claim 1 is illustrative and reads as follows (Appeal Br., Claims
App’x):
1. A method of preparing a library of nucleic acid
fragments for sequence analysis, comprising:
(a) cleaving a target nucleic acid to produce a plurality of
double-stranded cleavage products, wherein the target nucleic
acid comprises human genomic DNA;
(b) ligating a first universal adapter to the double-
stranded cleavage products to form a plurality of double-
stranded templates having known ends, wherein the first
universal adapter comprises a region of double-stranded
sequence for ligation to the double-stranded cleavage products,
and a first universal adapter sequence;
(c) denaturing the double-stranded templates to produce a
plurality of single-stranded templates comprising the first
universal adapter sequence;
2 Although the Examiner’s restatement of the utility and enablement
rejections includes claim 25 (see Ans. 2, 6), claim 25 has been canceled (see
Appeal Br., Claims App’x).
3 US 7,198,893 B1 (issued Apr. 3, 2007).
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Application 13/384,302
(d) annealing the single-stranded templates to a
population of complementary primer nucleic acids attached to a
solid support;
(e) performing a defined number of at least 50
incremental extension cycles, each extension cycle comprising:
(i) extending each of the primer nucleic acids by
incorporating an unlabeled nucleotide complementary to
the annealed template and comprising a reversible
blocking moiety; and
(ii) contacting the incorporated nucleotide with a
deblocking agent to remove the blocking moiety;
thereby producing a population of extended primers
comprising different portions of the target nucleic acid, wherein
the individual extended primers in the population comprise a
defined length that is correlated with the number of incremental
extension cycles;
(f) subjecting the annealed templates to denaturing
conditions to remove the templates from the solid support; and
(g) ligating a second universal adapter sequence to the 3'
ends of the extended primers to produce a population of
immobilized nucleic acid fragments having universal adapter
sequences at both ends;
thereby preparing a library of nucleic acid fragments for
sequence analysis.
UTILITY/ENABLEMENT
The Examiner’s Prima Facie Case
In rejecting claims 1, 2, 13, 14, 17, 20, 22, and 25—33 for lack of
utility, the Examiner states as follows:
As a result of amendment, “the target nucleic acid [in the
claimed processes] comprises human genomic DNA.” It is
noted with particularity that the DNA sequence can be any
sequence found in any “human genomic DNA.” The claimed
method does not require that the “human genomic DNA” be
associated with any particular gene, much less any disease, but
rather, the sequence can be that found in any part of any human
genomic DNA. Given such breadth, the claimed method is not
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considered to satisfy the specific utility requirements of MPEP
2107.01 A.
The case at hand is deemed to be analogous to that of
MPEP 2107 (B) (D): “A method of making a material that itself
has no specific, substantial, and credible utility” is not
considered to satisfy the substantial utility requirement.
Ans. 5.
Although the Examiner concedes that Appellant’s claims encompass
the preparation of libraries of nucleic acid fragments that would be useful
sequencing targets, the Examiner contends that the rejection is nonetheless
proper, because the claims are not limited to the preparation of such
libraries. Id. at 6 (“While nucleic acids, which satisfy the utility
requirements of 35 USC [§] 101, were known at the time of filing, such
narrowing limitations have not been read into the claims.'1'’) (emphasis
added).
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability. . . .
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.
We agree with Appellant that a preponderance of the evidence does
not support the Examiner’s prima facie case of lack of utility.
As Appellant argues, the Specification discloses that the claimed
methods, which generate libraries of nucleic acids useful in paired-end
sequencing processes, have an established utility that is both specific and
substantial:
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The technique of “paired-end” or “pairwise” sequencing
is generally known in the art of molecular biology, particularly
in the context of whole-genomic shotgun sequencing. Many
applications in DNA sequencing use paired-end methods to
obtain sequence information on a length scale longer than an
individual read. Paired-end sequencing allows the
determination of two “reads” of sequence from two places on a
single polynucleotide duplex. The advantage of the paired-end
approach is that there is significantly more information to be
gained from sequencing two stretches each of “n” bases from a
single template than from sequencing “n” bases from each of
two independent templates in a random fashion.
Spec. 3.
Indeed, as noted above, the Examiner concedes that the claims
encompass subject matter having utility. See Ans. 6 (“While nucleic acids,
which satisfy the utility requirements of 35 USC [§] 101, were known at the
time of filing, such narrowing limitations have not been read into the
claims.'’'’) (emphasis added).
The Examiner contends, nonetheless, that the claims must be amended
to encompass only subject matter having utility under § 101. See id.
(“Applicant is urged to consider amending the claims such that the claims
are drawn to those nucleic acids that unquestionably do have utility under 35
USC [§] 101 and which are adequately supported by the original
disclosure.”); see also id. at 17 (contending that rejected claims encompass
preparing libraries of nucleic acids that are not diagnostic of a specific
disease).
We are not persuaded. It might be true that the claims encompass
conceivable embodiments for which no useful application is known. That
fact, however, does not demonstrate that the claimed process lacks utility
under § 101. See Stiftung v. Renishaw PLC, 945 F.2d 1173, 1180 (Fed. Cir.
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1991) (“[T]he fact that an invention has only limited utility and is only
operable in certain applications is not grounds for finding lack of utility.”)
(quoting Envirotech Corp. v. Al George, Inc., 730 F.2d 753, 762 (Fed. Cir.
1984) (bracketing in original)). Here, the claimed processes yield libraries
of nucleic acid fragments undisputedly useful in the process of paired-end
sequencing, a process undisputedly “known in the art of molecular biology,
particularly in the context of whole-genomic shotgun sequencing.” Spec. 3;
see also App. Br. 16.
Accordingly, because a preponderance of the evidence does not
support the Examiner’s prima facie case of lack of utility, we reverse the
Examiner’s rejection on that ground. Because the Examiner’s enablement
rejection is grounded entirely in the utility rejection (see Ans. 6), we reverse
the enablement rejection as well.
OBVIOUSNESS
The Examiner’s Prima Facie Case
In rejecting claims 1, 2, 13, 14, 17, 20, 22, and 26—33 over
“applicant’s admissions” and Koster (Ans. 6), the Examiner cites
Appellant’s Specification, and the documents incorporated by reference
therein, as evidence that the techniques employed in each of the steps of the
processes recited in independent claims 1 and 26 were known in the art (see
id. at 10-13).4
4 The Examiner cited Koster as evidence that steps recited in dependent
claims 14 and 30 were known in the art. Ans. 14. Because our decision as it
relates to independent claims 1 and 26 is dispositive as to this rejection, we
do not discuss Koster further.
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In particular, the Examiner cites page 25 of the Specification, and the
Gormley5 reference cited therein, as evidence that it was known in the art to
create a library of template nucleic acids with primer-extendable universal
adapters at the ends of the nucleic acid molecules, and that the primer
extension products were amenable to amplification by PCR. Ans. 10—11
(citing Spec. 25; Gormley H 14—17, 73, 74, 79, and 81).
The Examiner cites page 28 of the Specification as evidence that
methods for attaching nucleic acids to a solid support were known in the art.
Id. at 12. The Examiner cites page 35 of the Specification as evidence that
methods were known in the art for ligating adapters to nucleic acid
fragments. Id. The Examiner cites pages 18, 19, and 44 of the Specification
as evidence that it was known in the art to incorporate nucleotides having a
reversible blocking group into a primer extension reaction. Id. at 12—13.
The Examiner concludes, based on the disclosures in the
Specification, that an ordinary artisan would have considered it obvious “to
have devised universal adapters and to have ligated same to double-stranded
fragments of a nucleic acid that is to undergo sequence analysis, and that the
primer extension reactions comprise the incorporation of nucleotides that
have reversible blocking moieties as well as the incorporation of a 3'
adapter.” Id. at 13.
The Examiner reasons that, “[b]y using nucleotides that have a
reversible blocking group, the researcher has direct control over just how
many nucleotides are being incorporated, therein providing a template for
5 US 2007/0128624 A1 (published June 7, 2007).
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sequencing that has a known length, which in turn provides for greater
consistency between sequencing reactions, when performed.” Id.
The Examiner notes in particular that, “[a]s evidenced above, the
reagents and underlying methods were all well known in the art. Further, the
claimed method simply combines known procedures with known reagents.”
Id.
Analysis
In KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), although the
Supreme Court emphasized “an expansive and flexible approach” to the
obviousness question {id. at 415), it also reaffirmed the importance of
determining “whether there was an apparent reason to combine the known
elements in the fashion claimed by the patent at issue.” Id. at 418 (emphasis
added).
We have noted that evidence of a suggestion, teaching, or
motivation to combine may flow from the prior art references
themselves, the knowledge of one of ordinary skill in the art, or,
in some cases, from the nature of the problem to be solved. . . .
The range of sources available, however, does not diminish the
requirement for actual evidence. That is, the showing must be
clear and particular. Broad conclusory statements regarding the
teaching of multiple references, standing alone, are not
“evidence.”
In re Dembiczak, 175 F.3d 994, 999 (Fed. Cir. 1999) (citations omitted).
Thus, even post-WST?, “[ojbviousness requires more than a mere showing
that the prior art includes separate references covering each separate
limitation in a claim under examination.” Unigene Laboratories, Inc. v.
Apotex, Inc., 655 F.3d 1352, 1360 (Fed. Cir. 2011).
In the present case, Appellant persuades us that a preponderance of
the evidence does not support the Examiner’s prima facie case of
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Application 13/384,302
obviousness. In particular, Appellant persuades us that the Examiner did not
“clearly articulate why a person having ordinary skill in the art would have
been motivated to select each of the claimed method steps from disparate
sequencing techniques[,]” nor did the Examiner articulate persuasively why
an ordinary artisan “would have been motivated to combine each of those
elements, once selected, to achieve the claimed methods.” Appeal Br. 22—
23.
As noted above, the Examiner cites page 28 of the Specification as
evidence that methods for attaching nucleic acids to a solid support were
known in the art (Ans. 12), and cites page 35 of the Specification as
evidence that methods were known in the art for ligating adapters to nucleic
acid fragments (id.). As Appellant contends, however, the Examiner did not
explain specifically how or why those techniques should be combined with
the sequencing techniques disclosed in the other portions Specification cited
by the Examiner, in particular the process taught in the cited portions of the
Gormley reference. See id. at 10—14 (setting forth Examiner’s obviousness
rationale).
Because the Examiner did not explain specifically how or why an
ordinary artisan would have combined the disparate techniques discussed in
the Specification at page 28 (attaching nucleic acids to a solid support), and
page 35 (ligating adapters to nucleic acid fragments), with the other prior art
processes discussed in the Specification, to arrive at the specific processes
recited in Appellant’s independent claims 1 and 27, Appellant persuades us
that a preponderance of the evidence does not support the Examiner’s prima
facie case of obviousness. See Unigene v. Apotex, 655 F.3d at 1360
(“Obviousness requires more than a mere showing that the prior art includes
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separate references covering each separate limitation in a claim under
examination.”).
It is well settled that, as a predicate to a conclusion of obviousness,
the “differences between the prior art and the claims at issue are to be
ascertained.” KSR, 550 U.S. at 406 (quoting Graham v. John Deere Co.,
383 U.S. 1, 17 (1966)). Our reviewing court has explained, in particular,
that “section 103 requires a fact-intensive comparison of the claimed process
with the prior art rather than the mechanical application of one or another
per senile.” In re Ochiai, 71 F.3d 1565, 1571 (Fed. Cir. 1995). In the
present case, the lack of an adequate explanation as to how or why the
disparate teachings in the prior art would have been combined to arrive at
the specific processes claimed is underscored by the fact that the Examiner
did not make express findings as to the differences between the prior art and
the claims at issue.
We acknowledge the Examiner’s contention that “[b]y using
nucleotides that have a reversible blocking group, the researcher has direct
control over just how many nucleotides are being incorporated, therein
providing a template for sequencing that has a known length, which in turn
provides for greater consistency between sequencing reactions, when
performed.” Ans. 13. We acknowledge also that step (e) of the processes
recited in both claim 1 and claim 27 requires the use of a reversibly blocked
nucleotide to incrementally extend the template annealed to the solid
support. Appeal Br., Claims App’x.
That using reversibly blocked nucleotides in a primer extension
reaction allegedly would have been expected to provide for greater
consistency between sequencing reactions does not remedy the lack of a
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specific explanation, discussed above, as to how or why an ordinary artisan
would have combined the disparate techniques discussed in the Specification
at page 28 (attaching nucleic acids to a solid support) and page 35 (ligating
adapters to nucleic acid fragments) with the other prior art processes
discussed in the Specification, to arrive at the specific processes recited in
Appellant’s independent claims 1 and 27.
Moreover, the Examiner does not identify any specific teachings in
the prior art (as opposed to Appellant’s Specification) suggesting or
implying that consistency was a difficulty in prior art processes similar to
those recited in claims 1 and 27, for example the processes disclosed in
Gormley, or that the problem would be addressed by using reversibly
blocked nucleotides. The Examiner’s failure to identify any specific prior
art disclosure, suggesting or implying that reversibly blocked nucleotides
would be desirable, or even useful, in processes such as that described in
Gormley, supports Appellant’s contentions that, on this record, using
reversibly blocked nucleotides in the manner recited in claims 1 and 27 only
would have been considered obvious through improper hindsight based on
Appellant’s Specification.
In response to Appellant’s arguments, the Examiner cites Barnes6 as
evidence that an ordinary artisan would have been motivated to use
reversibly blocked nucleotides in a primer extension process such as that
described in Gormley. See Ans. 20 (citing Barnes 10:56—65). The Examiner
also cites McKeman I7 and McKeman II8 as evidence of the desirability of
6 US 7,057,026 B2 (issued June 6, 2006).
7 US 2008/0003571 A1 (published Jan. 3, 2008).
8 WO 2006/084132 A2 (published Aug. 10, 2006).
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using unlabeled reversibly-blocked nucleotides in primer extension
reactions. Id. at 20—24 (citing McKeman 1110, 146, and 147; McKeman
II1120, 26, and 27).
We acknowledge McKeman I’s disclosure that, when performing the
specific sequencing by synthesis reactions described therein, the lengths of
the sequenced tags can vary, and the tags can be separated from other tags in
the target sequence by a consistent separation distance. McKeman IH 146,
147. We acknowledge McKeman II’s disclosure of using PCR amplification
to prepare, from a single nucleic acid fragment, populations of substantially
identical nucleic acids which can contain multiple primer binding regions.
McKeman II126, 27.
We also acknowledge Barnes’s disclosure that “[a]ny technique that
involves the interaction between a nucleotide and an enzyme may make use
of the molecules of the invention. For example, the molecule may be used as
a substrate for a reverse transcriptase or terminal transferase enzyme.”
Barnes 10:61—65 (emphasis added).
As Appellant points out, however, the molecules of Barnes’s
invention are “[njucleosides and nucleotides . . . that are linked to detectable
labels via a cleavable linker group.” Bames, Abstract (emphasis added).
Thus, even when viewed in light of the cited disclosures in McKeman
I and II, we are not persuaded that the Examiner has adequately explained
why Barnes’s general disclosure of using the labeled molecules of its
invention in enzyme-catalyzed reactions involving nucleotides provides
adequate motivation for using a reversibly blocked unlabeled nucleotide, as
required by Appellant’s independent claims 1 and 27, in the specific type of
process claimed, or in processes such as that described in Gormley.
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In sum, for the reasons discussed, Appellant persuades us that the
Examiner has not explained adequately why the specific processes recited in
independent claims 1 and 27 would have been obvious to an ordinary
artisan. Because we conclude, therefore, that a preponderance of the
evidence does not support the Examiner’s prima facie case of obviousness as
to claims 1 and 27, we reverse the Examiner’s rejection under § 103 of those
claims, as well as their dependent claims.
SUMMARY
For the reasons discussed, we reverse each of the Examiner’s
rejections.
REVERSED
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