Ex Parte Terbrueggen et al

Patent Trial and Appeal Board

Feb 28, 2018

13474596 (P.T.A.B. Feb. 28, 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.
13/474,596 05/17/2012 Robert Terbrueggen 068433-5003-US 7402
67374 7590 03/02/2018
MORGAN, LEWIS & BOCKIUS LLP (SF)
ONE MARKET, SPEAR STREET TOWER, SUITE 2800
SAN FRANCISCO, CA 94105
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
03/02/2018 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROBERT TERBRUEGGEN, YENBOU LIU,
JOHN RAY CHILDERS JR., CHANG HEE KIM, and
MAJID R. ABEDI1
Appeal 2016-001717
Application 13/474,596
Technology Center 1600
Before RICHARD J. SMITH, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
methods of detecting a plurality of different target nucleic acids in a target
sample, which have been rejected as lacking enablement and as indefinite.
We have jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as DxTerity Diagnostics
Incorporated. (Appeal Br. 3.)
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STATEMENT OF THE CASE
“The detection of specific nucleic acids is an important tool for
diagnostic medicine and molecular biology research.” (Spec. 13.) “Ideally,
a gene probe assay should be sensitive, specific and easily automatable.”
{Id. 14.) According to the Specification, “the present invention provides
methods and compositions for non-enzymatic chemical ligation reactions
which provides rapid target detection and greatly simplified processes of
detecting and measuring target nucleic acids.” {Id. 110.) Further according
to the Specification,
[advantages of using non-enzymatic approaches for nucleic acid
target detection include lower sensitivity to non-natural DNA
analog structures, ability to use RNA target sequences and lower
cost and greater robustness under varied conditions. In
particular, the methods described herein do not require
significant sample preparation; that is, the ligation reactions can
be performed in the presence of contaminants and buffers that
would inhibit or inactivate enzymatic processes for detection.
... In addition, methods and compositions of the present
invention are useful in detection of nucleic acids from samples
that are degraded....
{Id. 1 62.)
Claims 26—30 and 33—44 are on appeal. Claim 26 is illustrative and
reproduced below:
26. A method of detecting a plurality of different target
nucleic acids in a target sample, wherein each target
nucleic acid comprises an adjacent first and a second
target domain, said method comprising:
a) providing a reaction mixture comprising said target
sample in lysis buffer comprising 2 to 6 molar
guanidinium salt
b) contacting said reaction mixture with a plurality of
different probes sets, each probe set comprising:
i) a first nucleic acid ligation probe comprising:
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1) a first probe domain complementary to a
first target domain of a target nucleic acid;
2) a first primer sequence; and
3) a 5’-ligation moiety; and
ii) a second nucleic acid ligation probe comprising:
1) a second probe domain complementary to a
second target domain of said one target
nucleic acid;
2) a second primer sequence; and
3) a 3’ ligation moiety;
wherein one of said first or second nucleic acid ligation
probes comprises a detectable label and the other
comprises one of a binding partner pair;
c) ligating said first and second ligation probes in the
absence of a ligase enzyme to form a plurality of
different ligation products;
d) contacting said ligation products with a solid support
comprising the other of said binding partner pair such
that said ligation products are captured on said solid
support;
e) washing said solid support;
f) amplifying said different ligation products; and
g) detecting the presence of said ligation products.
(Appeal Br. 29 (Claims App.).)
The Examiner rejects claims 26—30 and 33—44 under 35 U.S.C.
§ 112(a) or pre-AIA 35 U.S.C. § 112, first paragraph, as failing to comply
with the enablement requirement. (Ans. 2.)
The Examiner rejects claims 26—30 and 33—44 under 35 U.S.C.
§ 112(b) or pre-AIA 35 U.S.C. § 112, second paragraph, as being indefinite
for omitting essential elements. (Ans. 17.)
I.
Issue
The Examiner has rejected claims 26—30 and 33—44 as failing to
comply with the enablement requirement. The Examiner construes “target
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nucleic acids” as “encompassing any and all manner of genomic DNA as
found in any [life] form” and notes that “the claimed method does not
require . . . that the target nucleic acids be known at the time of filing, much
less require that any one of the target nucleic acids ... be that which had
utility under 35 [U.S.C. §] 101 at the time of filing.” (Ans. 7—8.) The
Examiner concludes that the claims are non-enabled because “[t]he state of
the art has advanced to the point that certain problems and/or difficulties are
known to exist” and because, in light of the breadth of the claims, “[t]he
quantity of experimentation necessary is great, on the order of many man-
years, and then with little if any reasonable expectation of successfully
enabling the full scope of the claims.” {Id. at 9—16.) The Examiner further
concludes that the claimed methods are either generally inoperable or
encompass inoperable embodiments. {Id. at 8—9.)
Appellants contend among other things that “the claims are not
directed to determining new target sequences” but rather “detection of target
sequences using novel methods.” (Appeal Br. 16—17.) Appellants contend
that practicing the claimed methods does not require undue experimentation,
because “[pjrobes are designed and made (usually by ordering them from a
plethora of available commercial outfits), the standard molecular biology
reactions are done, although using novel combinations of reagents, and
detection is achieved.” {Id. at 18—19.) Appellants further dispute the
Examiner’s contention that the appealed claims are generally inoperable and
contend that, to the extent the claims encompass inoperable embodiments, a
skilled artisan “could determine which embodiments encompassed by the
pending claims would be inoperative or operative with little effort than is
normally required in the art.” {Id. at 19—22.)
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The issue with respect to this rejection is whether the preponderance
of evidence of record support the Examiner’s conclusion that the
Specification does not enable the full scope of the claimed inventions.
Analysis
The examiner bears the initial burden of showing that a claimed
method is not enabled. See In re Wright, 999 F.2d 1557, 1561—62 (Fed. Cir.
1993) (“[T]he PTO bears an initial burden of setting forth a reasonable
explanation as to why it believes that the scope of protection provided by
that claim is not adequately enabled by the description of the invention
provided in the specification of the application.”). In this case, we find that
the Examiner has not established a prima facie case of lack of enablement.
Claim Breadth
The Examiner first contends that ‘“the target nucleic acids’ have been
construed as fairly encompassing any and all manner of genomic DNA as
found in any [life] form, e.g., any and all bacteria, virus, fungi, mammals,
etc.” and that this encompasses an enormous amount of DNA. (Ans. 6—8;
see also id. at 18—19.)
To the extent the Examiner is contending that breadth alone renders
the claim non-enabled, we are not persuaded. Although the breadth of the
claim is a factor we consider in determining whether a claim is enabled, In
re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988), “there is no magical relation
between the number of representative examples and the breadth of the
claims; the number and variety of examples are irrelevant if the disclosure is
‘enabling.’” In re Borkowski, 422 F.2d 904, 910 (CCPA 1970). The
Examiner has emphasized the large number of known virus types and
bacteria, fungi, plant, and mammal species (Ans. 7—8); however, the
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Examiner has neither provided evidence regarding the level of
unpredictability in the art relevant to the breadth of the claimed invention,2
nor, as we discuss below, persuasively explained how such breadth renders
the claims non-enabled.
The Examiner contends that the claimed method does not require the
target nucleic acids to be known or to have utility under 35 U.S.C. § 101 at
the time of the filing. (Ans. 6—8.) To the extent the Examiner contends that
enablement of the full scope of the claim requires all possible target nucleic
acids to be sequenced and their utility demonstrated, we are unpersuaded.
As Appellants point out, the claims are not directed to particular (or all
possible) target nucleic acids, but rather to a general method of detecting
whether a target nucleic acid is present in a sample. (Appeal Br. 16.) The
invention that must be enabled is the invention defined by the claims. See
CFMT, Inc. v. Yieldup Inti Corp., 349 F.3d 1333, 1338 (Fed. Cir. 2003)
(“Title 35 does not require that a patent disclosure enable one of ordinary
skill in the art to make and use a perfected, commercially viable embodiment
absent a claim limitation to that effect.”). Thus, when the claims are not
directed to identification of new or all possible target nucleic acids of
interest, achieving such a result is not required for the claims to be enabled.
Likewise, although we agree that the claimed methods must have a
specific and substantial utility in order for the claims to be enabled, In re
2 As discussed in more detail below, the Examiner cites two articles to show
that the art recognizes certain potential drawbacks to polymerase chain
reaction (“PCR”), a particular method of amplification. (Ans. 9-10.)
However, the Examiner does not explain how these potential drawbacks
render the results of the claimed method unpredictable based on the
particular types of target nucleic acids used.
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Fisher, 421 F.3d 1365, 1378 (Fed. Cir. 2005), we cannot agree with the
Examiner’s apparent position that this requires a showing of the utility of all
possible target nucleic acids. The Specification states that gene probe assays
are useful tools in diagnostic medicine and molecular biology research and
that the claimed methods provide some advantages over prior art enzymatic
approaches for nucleic acid target detection, flflf 3, 62.) A method that
provides advantages over prior art methods used in diagnostic medicine and
molecular biology research would seem to satisfy the utility requirement,
even if it does not allow immediate detection of, or identify a utility for, all
possible target nucleic acids. Put another way, unlike the claim at issue in
Fisher, which recites expressed sequence tags (ESTs) useful only for
conducting experiments on the genes of unknown function of which the
ESTs were a part, the claimed methods here are broadly useful for detecting
target nucleic acids having particular sequences.
Unpredictability of the Art
The Examiner next contends that “[t]he state of the art has advanced
to the point that certain problems and/or difficulties are known to exist.”
(Ans. 9.) The Examiner points to two references, Thrippleton3 and Von
Toeme,4 that discuss problems with polymerase chain reaction (PCR), a
method of amplifying genomic material such as DNA, presumably because
the claims include a step relating to amplification of ligation products. (Id.
at 5 (construing amplification step to encompass PCR), 9-10.)
As with the Examiner’s contention regarding claim breadth, we find
that the Examiner has not sufficiently tied the alleged unpredictability in the
3 Thrippleton et al., US 2013/0040847 Al, published Feb. 14, 2013.
4 Von Toeme, US 2013/0040843 Al, published Feb. 14, 2013.
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art to the claims at issue. For instance, Thrippleton teaches that “[intrinsic
problems of PCR lie in its sensitivity and proneness to inhibitors” and that
“[i]n PCRs on clinical samples the DNA/RNA is extracted from very crude
and extremely variable matrices that frequently harbour polymerase
inhibiting components,” which may “generate undesirable false negative
results.” (Ans. 10.) The Examiner does not explain, however, how PCR’s
sensitivity to inhibitors renders a skilled artisan unable to practice a claim in
which amplification is of ligation products bound to a solid support and
occurs after washing.
Likewise, Von Toeme teaches that problems with “conventional real­
time PCR specific target detection methods” include “[t]he influence of
reagent pipetting variations” and variation in quantity due to different
instruments or “non-optimal characteristics in the amplification/detection
method” such as, e.g., stray light, temperature differences, or differences in
the plastic materials holding the sample. {Id. (internal quotation marks
omitted).) The Examiner does not explain how these potential issues
relating to quantification of the target in the sample render a skilled artisan
unable to practice a claim that requires detection and not necessarily
quantification.
In short, we find that the Examiner has not shown by a preponderance
of evidence that the potential problems of PCR discussed in Thrippleton and
Von Toeme render a skilled artisan unable to perform the amplification step
recited in the claims.5
5 The Examiner also notes without further explanation that another “aspect
of unpredictability” is that “the length of the probe can and does affect the
specificity of the interaction of [the] probe with [the] target.” (Ans. 11.)
The Examiner points to statements in the Specification in support of this
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Quantity of Experimentation
The Examiner contends that “[t]he quantity of experimentation
necessary is great, on the order of many man-years, and then with little if
any reasonable expectation of successfully enabling the full scope of the
claims.” (Ans. 10; see also id. at 20.)
The Examiner first contends that, “[i]n order to practice the full scope
of the invention, one would have to first determine the nucleotide sequence
for each and every organism, much less any gene of interest, before one
would be able to select appropriate probe and/or primer sequences that are
essential to the claimed invention.” {Id. at 11.) As we have already
discussed above, the claims are not directed towards identification of new or
all possible target nucleic acids of interest but rather a general method of
whether any particular target nucleic acid is present in the sample. Thus, we
disagree with the Examiner that a skilled artisan would need to a priori
determine the nucleotide sequence for each and every organism or gene of
interest in order to practice the full scope of the invention.* * * * 6
statement. {Id.) The Examiner has cited no evidence or persuasively shown
that a skilled artisan would not be able to design a probe having a length that
ensures sufficient specificity in the probe/target interaction to practice the
claimed invention.
6 The Examiner cites as support for his position Wyeth and Cordis Corp. v.
Abbott Labs., 720 F.3d 1380 (Fed. Cir. 2013). (Ans. 13.) Although we
agree with the general statements of law from Wyeth cited by the Examiner,
the facts of Wyeth render it inapposite. The claim at issue in Wyeth recites
“a method of treating or preventing ‘restenosis in a mammal . . . which
comprises administering an antirestenosis effective amount of rapamycin to
said mammal.” Wyeth, 720 F.3d at 1382. The Wyeth Court found that
“there is no genuine dispute that practicing the full scope of the claims
would require synthesizing and screening each of at least tens of thousands
of compounds.” Id. at 1385. In this case, because the claim does not require
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The Examiner also contends that, “[a]s presently worded, the claimed
method fairly encompasses use of multiplex detection of short tandem repeat
(STR) loci at issue in Promega Corp. v. Life Techs Corp.,” 773 F.3d 1388
(Fed. Cir. 2014) (reversed and remanded by Life Tech Corp. v. Promega
Corp., 137 S.Ct. 734 (2017) on other grounds), which our reviewing court
found to be non-enabled. (Ans. 13; see also id. at 21.)
The claim at issue in Promega recites “[a] kit for simultaneously
analyzing short tandem repeat sequences in a set of short tandem repeat loci
from one or more DNA samples, comprising: A single container containing
oligonucleotide primers for each locus in a set of short tandem repeat loci
which can be co-amplified, comprising HUMCSF1PO, HUMTPOX, and
HUMTH01.” Id. at 1343. The Promega Court found that, “[i]n this field of
technology, introducing even a single [short tandem repeat (STR)] locus to
an existing loci multiplex significantly alters the chemistry of, and has an
the target nucleic acid to perform any particular function, and because the
Examiner has not persuasively shown that whether the claimed method
would work is dependent on the specific structure (i.e., sequence) of the
target nucleic acid, we do not agree that practicing the full scope of the
claims would require sequencing and testing all potential target nucleic
acids. In re Vaeck, 947 F.2d 488 (Fed. Cir. 1991), which is cited in the
portion of Wyeth relied upon by the Examiner, is inapposite for similar
reasons. Specifically, the claims at issue in Vaeck are directed towards a
chimeric gene capable of being expressed in Cyanobacterial cells. Id. at
490. In that case, however, it was found that the molecular biology of
Cyanobacteria had only recently become the subject of intensive
investigation, which is also limited to a few genera, and that the level of
unpredictability regarding heterologous gene expression in Cyanobacteria as
a group is thus high. Id. at 493. Here, again, the Examiner has failed to
show that the practice of the claimed method would unpredictably depend on
the particular type or sequence of the target nucleic acid.
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unpredictable effect on, whether the resulting multiplex will successfully co­
amplify.” Id. at 1346.
The Examiner contends that,
[w]hile the issue in Promega dealt with the enablement of the full
scope of primers to be used in amplification, the claimed method
presents issues of enablement directed at not only the primer, which is
a component of the ‘nucleic acid ligation probe[s]’, but also the means
used to effect ligation, for as required in Claim 26, step c), one is
required to effect ‘ligating said first and second ligation probes in the
absence of a ligase enzyme to form a plurality of different ligation
products’ (emphasis added). While the first and second ‘nucleic acid
ligation probes’ are to hybridize to a first and second target domain,
the ‘target domain[s]’ can be of any size. Further, there is no
requirement that the first and second ligation probes actually
hybridize immediately adjacent to one another such that ligation could
possibly occur.
(Ans. at 14—15.)
We are not persuaded that the Examiner has established that the same
enablement analysis applies to the claims at issue in Promega and the claims
on appeal. For instance, the unpredictability discussed in Promega relates to
co-amplification of multiple STR loci, whereas the amplification required in
the claims relates to amplification of ligation products. In any event,
assuming that the Examiner is correct that the claimed method encompasses
co-amplification of STRs as described in Promega, we are not persuaded
that the Examiner’s citation to Promega, without more, suffices to establish
a prima facie case of non-enablement. As Appellants point out, the priority
dates of Promega patents and the application on appeal differ, and the
Examiner has not cited evidence or argued that the state of the art has
remained the same. (Reply Br. 4.)
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As discussed above, the Examiner also contends that Appellants have
not enabled the full scope of‘“ligating said first and second ligation probes
in the absence of a ligase enzyme to form a plurality of different ligation
products.’” (Ans. 14—15 (internal quotation marks omitted).) In particular,
the Examiner contends that the Specification states that the identification of
litigation moieties recited in the claims “depends on the chemistry of the
ligation to be used” and that,
[a]s presently worded, the claimed method fairly encompasses
any future devised means that would allow for the requisite
ligation of the first and second nucleic acid ligation probes as the
claimed method is not limited to any particular “chemistry” and,
thus[], fairly “cover[s] potentially thousands of undisclosed
embodiments in an unpredictable field.”
(Id. at 15.) The Examiner further responds to Appellants’ argument as
follows:
[NJeither the disclosure nor the Brief has been found to teach in
detail how any and all manner of first and second probes in an
infinite number of “different probe sets” are to be ligated “in the
absence of a ligase enzyme.” While ligation between probes via
use of a ligase is well developed in the art, the aspect of ligating
probes “in the absence of a ligase enzyme” is highly
unpredictable.
(Id. at 21.)
Although we appreciate the Examiner’s position, we note that
negative limitations, such as a limitation excluding the use of ligation
enzyme, are not per se impermissible. Cf. Santarus, Inc. v. Par Pharm., Inc.,
694 F.3d 1344, 1351 (Fed. Cir. 2012) (stating that “[njegative claim
limitations are adequately supported when the specification describes a
reason to exclude the relevant limitation”). The Specification teaches
several “non-enzymatic or template mediated chemical ligation methods”
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that may be used in the claimed invention, including, e.g., use of nucleophile
ligation moieties. (See, e.g., Spec. Tflf 117, 146—148.) On the other hand, the
Examiner has not cited any reason or evidence to support his contention that,
“[wjhile ligation between probes via use of a ligase is well developed in the
art, the aspect of ligating probes ‘in the absence of a ligase enzyme’ is highly
unpredictable.” (Ans. 21.) In light of the lack of evidence regarding the
predictability of ligation in the absence of a ligase enzyme, we find that the
Examiner has not sufficiently established a prima facie case that the claims
are not enabled as to the limitation of “ligating said first and second ligation
probes in the absence of a ligase.”7 See Wright, 999 F.2d at 1561—62
(“When rejecting a claim under the enablement requirement of section 112,
the PTO bears an initial burden of setting forth a reasonable explanation as
to why it believes that the scope of protection provided by that claim is not
adequately enabled by the description of the invention provided in the
specification of the application; this includes, of course, providing sufficient
reasons for doubting any assertions in the specification as to the scope of
enablement. If the PTO meets this burden, the burden then shifts to the
applicant to provide suitable proofs indicating that the specification is indeed
enabling.”) (citation omitted).
7 Likewise, although the Examiner argues that the claims on appeal present
“issues of enablement directed at. . . the primer, which is a component of
the ‘nucleic acid ligation probe[s],” and emphasizes that “the ‘target
domain[s] ’ can be of any size,” the Examiner does not provide persuasive
evidence or arguments regarding how either inclusion of primers in the
ligation probes or the size of the target domains render the claims on appeal
non-enabled, other than by reference to Promega. (Ans. 14—15.) As already
discussed, we do not find the reference to Promega without more to
establish a prima facie case of non-enablement.
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Inoperable Embodiments
The Examiner also contends that the claims on appeal are not enabled
because they are inoperable and/or include inoperable embodiments.
The Examiner first contends that, although the claimed method
requires “the production of ‘a plurality of different ligation products,’” the
claim describes only “a first nucleic acid ligation probe” and “a second
nucleic acid ligation probe,” which can only form one ligation product.
(Ans. 8-9.)
We are not persuaded. The claims require “a plurality of different
probe sets,” with each probe set comprising a first and a second nucleic acid
ligation probe.” (Appeal Br. 29 (Claims App.).) The ligation of the first and
second ligation probes from the plurality of different probe sets would result
in a plurality of different ligation products.
In a similar vein, the Examiner contends that the claim requires
performing the “step of ‘detecting the presence of ligation products’”
without requiring that “the products have a size and[/]or label that is
distinguishable from any and all other ligated probes that are directed to any
other member of the ‘plurality of different target nucleic acids in a target
sample.’” (Ans. 15—16.) The Examiner contends that “[sjimply detecting
any ‘ligation products’ which is/are indistinguishable from that for any other
member of the ‘plurality of different target nucleic acids’ would not allow
one to determine whether or not one has actually detected ‘a plurality of
different target nucleic acids in a target sample’ or just one.” {Id. at 16; see
also id. at 19—20.)
We are not persuaded. The Specification teaches using “detectable
labels to aid in the identification ... of the ligated oligonucleotide product,
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including, for example,. . . optical[] and electrochemical labels [or] variable
spacer sequences or ‘size tags’ comprising nucleic acid sequences that are
sized to be specific for a particular target.” (Spec. 1 60.) The Examiner
does not explain why such disclosures in the Specification would not enable
a skilled artisan to select different detectable labels that allows identification
of a plurality of different target nucleic acids in a target sample.8
The Examiner contends that the claimed method is further inoperable
because “[t]he claim language does not preclude the first and second ligation
probes being parts of a common oligonucleotide that hybridizes to adjacent
target nucleic acid sequences therein allowing for ligation (circularization)
of the oligonucleotide.” (Ans. 6-7 (explaining that “Applicant. . . teaches
that the first and second probes may actually be opposite ends of but a single
oligonucleotide”), 9.) The Examiner contends that, “[accordingly, any and
all sequences present in a linear form would also be present in the ligated
form,” and “there [would be] no change in amount of detectable label[]
whether or not any hybridization ever occurred, much less any ligation.”
(Id.)
As we understand it, the Examiner’s contention is that, to the extent
the first and second ligation probes constitute two ends of a single
oligonucleotide, and where one probe comprises a detectable label and the
other comprises one of a binding partner pair, the oligonucleotide when
8 The Examiner appears to believe that enablement requires the claim to
contain all of the information necessary to make and use the claim. It is the
Specification, however, that must enable the claims. Wright, 999 F.2d at
1561 (“[T]o be enabling, the specification of a patent must teach those
skilled in the art how to make and use the full scope of the claimed invention
without ‘undue experimentation.’”) (citations omitted).
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contacted with “a solid support comprising the other of said binding partner
pair” will be captured on the solid support and be detected regardless of
whether hybridization or ligation has taken place. The Examiner also
appears to argue first and second litigation probes located on two ends of the
same oligonucleotide will necessarily be ligated and the oligonucleotide
circularized.
We are not persuaded that the Examiner has established a prima facie
case that the Specification does not enable a skilled artisan to practice the
claimed invention because the claims do not specifically exclude the first
and second probes from being on same oligonucleotide. For instance, the
Specification states:
It should be noted that the “upstream” and “downstream”
oligonucleotides can, optionally, constitute the two ends of a
single oligonucleotide, in which event ligation yields a circular
ligation product. The binding regions on the 5 ’ and 3 ’ ends of
the linear precursor oligonucleotide must be linked by a number
of intervening nucleotides sufficient to allow binding of the 5 ’
and 3 ’ binding regions to the polynucleotide target.
(Spec. 1129.) The Examiner provides no evidence or persuasive argument
that the 5 ’ and 3 ’ ends of the linear precursor comprising the upstream and
downstream oligonucleotides (i.e., the first and second ligation probes)
would automatically ligate to each other given the teaching that they must be
linked by a number of intervening nucleotides sufficient to allow binding to
the polynucleotide target and thus presumably not located in immediate
proximity to each other.
Likewise, the Examiner provides no evidence or persuasive argument
that a skilled artisan would not be able to choose (1) a form of the first and
second ligation probes and (2) a means of detection that would permit
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detection of the ligation probes only when hybridization to the
polynucleotide target has occurred.
The Examiner also contends that,
[a]s presently worded, there is no requirement that the probes
hybridize such that the 3 ’ and 5 ’ ligation moieties are adjacent to
one another such that ligation could occur. In support of this
interpretation, attention is directed to paragraph [0120], which
teaches that in addition to using two ligation probes, one may opt
to use “more than two ligation probes” when additional
specificity is desired. Absent means and proper orientation, it
stands to reason that ligation would not spontaneously occur. In
short, the method would be inoperable.
(Ans. 15.)
We are not persuaded. The Examiner once again appears to believe,
erroneously, that the claims themselves (rather than the Specification) must
set forth all the information that allows a skilled artisan to practice the
claimed invention. In this case, the Specification teaches that
[legation probes of the invention are designed such that when the
probes bind to a part of the target polynucleotide in close spatial
proximity, a chemical ligation reaction occurs between the
probes. In general, the probes comprise chemically reactive
moieties (herein generally referred to as “ligation moieties”) and
bind to the target polynucleotide in a particular orientation, such
that the chemically reactive moieties come into close spatial
proximity, thus resulting in a spontaneous ligation reaction that
can take place without the use of a ligase enzyme.
(Spec. 1109.) The Examiner has not explained or provided persuasive
evidence why, in light of such disclosure, a skilled artisan would not be able
to design ligation probes that would allow ligation to spontaneously occur
without undue experimentation. Cf. Atlas Powder Co. v. E.I. du Pont De
Nemours & Co., 750 F.2d 1569, 1576—77 (Fed. Cir. 1984) (explaining that
“it is not a function of the claims to specifically exclude . . . possible
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inoperative substances ...” and stating that claims are not necessarily
invalid for including inoperative embodiments absent a showing that such
inoperative embodiments “in effect forces one or ordinary skill in the art to
experiment unduly in order to practice the claimed invention”) (internal
quotation marks and citations omitted).
Finally, the Examiner discounts Appellants’ contention that a skilled
artisan “could determine which embodiments encompassed by the pending
claims would be inoperative or operative with little effort than is normally
required in the art,” finding the contention to be attorney argument rather
than evidence. (Ans. 20 (internal quotation marks omitted).) Although we
agree that attorney arguments are no substitute for evidence, Johnston v.
IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989), we are also cognizant
that the Examiner bears the initial burden of showing that a claimed method
is not enabled. Wright, 999 F.2d at 1561—62. As discussed above, we find
that the Examiner has not sufficiently articulated a reasonable explanation as
to why the claims on appeal are not adequately enabled by the Specification
and, thus, has not established a prima facie case of non-enablement.
Accordingly, we reverse the Examiner’s rejection of claims 26—30 and
33—44 as lacking enablement.
II.
Issue
The Examiner has rejected claims 26—30 and 33—44 as indefinite. The
Examiner finds that the claims are “incomplete for omitting [the] essential
elements” of “[mjeans of effecting the ligation” and “[m]eans for detecting
the ‘detectable label.’” (Ans. 17.) In response to the Appeal Brief, the
Examiner further clarifies that the metes and bounds of the claimed methods
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cannot be readily determined because (1) the Specification explains that “the
ligation moiety depends upon the chemistry to be used” but “[t]he claimed
method does not specify the chemistry used, much less specify if the ligation
is to be ‘spontaneous’ and/or whether any linker is to be used” and (2) “in
order to practice the claimed method, use of some means (elements) for
‘detecting the presence of said ligation products’ is both required and is not
recited.” {Id. at 22—23.)
Appellants contend that a skilled artisan “would recognize that
ligation spontaneously occurs between the 5’- and 3’- ligation moieties” and
further “would understand how to identify a detection method, depending on
the particular detectable label used,” including for instance the methods of
detecting a detectable label set forth in the Specification. (Appeal Br. 27;
see also Reply Br. 6—8.)
We find the Examiner has not established a prima facie case that the
claims are indefinite. “The definiteness inquiry focuses on whether those
skilled in the art would understand the scope of the claim when the claim is
read in light of the rest of the specification.” Union Pacific Resources Co. v.
Chesapeake Energy Corp., 236 F.3d 684, 692 (Fed. Cir. 2001). The
gravamen of the Examiner’s rejection, however, appears to be that the
claims are too broad. That is, the Examiner has not contended that a skilled
artisan would not understand what is meant by “ligating the first and second
ligation probes,” “a ligase enzyme,” or “detecting the presence of. . .
ligation products” in light of the Specification; rather, the Examiner’s
complaint is that the claims should have further specified particular means of
ligation and detection. However, “breadth is not to be equated with
indefmiteness.” In re Miller, 441 F.2d 689, 693 (CCPA 1971).
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Accordingly, we reverse the Examiner’s rejection of claims 26—30 and
33—44 as indefinite.
SUMMARY
For the reasons above, we reverse the Examiner’s decision rejecting
claims 26—30 and 33^44.
REVERSED
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