Ex Parte Terbrueggen

Patent Trial and Appeal Board

Aug 21, 2017

12798108 (P.T.A.B. Aug. 21, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O.Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/798,108 03/29/2010 Robert Terbrueggen 068433-5002-US 6073
67374 7590 08/23/2017
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
08/23/2017 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
SFIPDOCKETING@MORGANLEWIS .COM
DONALD.MIXON @MORGANLEWIS .COM
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROBERT TERBRUEGGEN1
Appeal 2016-005406
Application 12/798,108
Technology Center 1600
Before DEMETRA J. MILLS, DONALD E. ADAMS, and
RYAN H. FLAX, Administrative Patent Judges.
MILLS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134. The Examiner has rejected
the claims as directed to non-patent eligible subject matter. Claims 1—31
were cancelled. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 Appellant identifies the real party in interest as Dx Terity Diagnostics
Incorporated. (App. Br. 2).
Appeal 2016-005406
Application 12/798,108
STATEMENT OF CASE
According to the Specification, page 4, when using DNA microarrays
[t]he requirement of many upstream processing steps prior to
contacting the DNA array with the sample can significantly increase
the time and cost of detecting a nucleic acid target(s) by these
methods. It can also have significant implications on the quality of
the data obtained. For instance, some amplification procedures are
very sensitive to target degradation and perform poorly if the input
nucleic acid material is not well preserved .... Technologies that
can eliminate or reduce the number and/or complexity of the
upstream processing steps could significantly reduce the cost and
improve the quality of results obtained from a DNA array test. One
method for reducing upstream processing steps involves using
ligation reactions to increase signal strength and improve specificity.
. . . There remains a need for methods and compositions for
efficient and specific nucleic acid detection. Accordingly, the present
invention provides methods and compositions for nonenzymatic
chemical ligation reactions which provides very rapid target detection
and greatly simplified processes of detecting and measuring nucleic
acid targets.
The following claims are representative.
32. A method for detecting in a sample, comprising a plurality
of sample nucleic acids of different nucleic acid sequences, the
presence of at least one specific target nucleic acid sequence
comprising a first and a second target domain, the domains located
adjacent to one another, comprising the steps of:
(a) contacting the sample nucleic acids with a plurality of different
probes sets, each probe set comprising:
(i) a first ligation probe comprising:
(1) a first probe domain complementary to said first target
domain;
(2) a first non-complementary region being non­
complementary to the said target nucleic acid sequence; and
2
Appeal 2016-005406
Application 12/798,108
(3) a 5’-ligation moiety comprising a DABSYL moiety,
and
(ii) second ligation probe comprising:
(1) a second probe domain complementary to said second
target domain;
(2) a second non-complementary region, being non­
complementary to the said target nucleic acid sequence;
(3) a 3’ ligation moiety comprising a phosphorothioate
moiety;
(b) ligating said first and second ligation probes in the absence of a
ligase enzyme to form a ligation product; wherein at least one of said
ligation probes comprises a variable spacer nucleic acid sequence such
that each ligation product is a different length;
(c) amplifying said ligation product to form ligation amplicons under
conditions whereby a fluorescent label is incorporated into said
amplicons; and
(d) detecting the presence of said ligation amplicons by detecting the
presence of said fluorescent label. (Emphasis added.)
36. A method for detecting in a sample, comprising a plurality of
sample nucleic acids of different nucleic acid sequences, the presence of at
least one specific target nucleic acid sequence comprising a first and a second
target domain, the domains located adjacent to one
another, comprising the steps of:
(a) contacting the sample nucleic acids with a plurality of different
probes sets, each probe set comprising:
(i) a first ligation probe comprising:
(1) a first probe domain complementary to said first target
domain;
(2) a first non-complementary region being non-
complementary to the said target nucleic acid sequence; and
(3) a 5'-ligation moiety comprising a halogen leaving
group', and
3
Appeal 2016-005406
Application 12/798,108
(ii) second ligation probe comprising:
(1) a second probe domain complementary to said second
target
domain;
(2) a second non-complementary region, being non­
complementary to the said target nucleic acid sequence;
(3) a 3' ligation moiety comprising a phosphorothioate
moiety;
(b) ligating said first and second ligation probes in the absence of a
ligase enzyme to form a ligation product; wherein at least one of said
ligation probes comprises a variable spacer nucleic acid sequence such
that each ligation product is a different length;
(c) amplifying said ligation product to form ligation amplicons under
conditions whereby a fluorescent label is incorporated into said
amplicons; and
(d) detecting the presence of said ligation amplicons by detecting the
presence of said fluorescent label. (Emphasis added.)
Cited References
Barany et al. US 2006/0024731 Al Feb. 2, 2006
Kool et al. US 2006/0199192 Al Sept. 7, 2006
Thomas US 2007/0218477 Al Sept. 20, 2007
Grounds of Rejection
Claims 32-43 are rejected under 35 U.S.C. § 101, because the claimed
invention is not directed to patent eligible subject matter.
FINDINGS OF FACT
The Examiner’s findings of fact are set forth in the Final Action 6—10,
Examiner’s Answer 3—11.
4
Appeal 2016-005406
Application 12/798,108
PRINCIPLES OF LAW
In making our determination, we apply the preponderance of the
evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427
(Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings
before the Office).
§ 101- Patent Eligible Subject Matter
The Examiner finds that, based upon an analysis with respect to the
claim as a whole, claims 32—43 are directed to a law of nature/natural
principle, which the Examiner finds to be a judicial exception to patentable
subject matter eligibility. Final Act. 6. The Examiner then analyses whether
the claim as a whole recites something significantly more than the judicial
exception(s). Final Act. 7—8.
The Examiner determines, after reviewing whether the claims as a
whole recites something significantly different than the judicial exceptions,
that factors weight against patent eligibility and the claims do not recite
subject matter significantly different than the judicially excepted subject
matter. Final Act. 8. For example, the Examiner finds that the claims recite,
in addition to the judicial exception, merely steps that are well-understood,
purely conventional or routine in the relevant field. In support of this
position, the Examiner directs attention to US 2006/0199192 A1 (Kool et
al.). Kool et al., paragraph [0137], which teaches synthesis of
oligonucleotides that comprise DABSYL on the 5’ terminus (applicant’s
first probe domain). And in paragraph [0138], Kool et al., teach DABSYL-
mediated autoligation wherein the oligo with the DABSYL 5’-ligation
moiety autoligates with a second ligation probe that comprises a 3 ’ ligation
5
Appeal 2016-005406
Application 12/798,108
moiety comprising a phosphorothioate moiety wherein the first and second
ligation probes are annealed to a complementary nucleic acid. Id.
The Examiner analyzes the additional method steps and determines
that the additional steps constitute insignificant extra-solution activity, e.g.,
are merely appended to the judicial exception and recite elements/steps in
addition to the judicial exception(s) that amount to nothing more than a mere
field of use. Id. at 9-10. Thus, the Examiner concludes that claims 32-43
are directed to patent ineligible subject matter. Id at 10.
Appellant contends that the
Examiner uses the incorrect standard in analyzing whether the claims
are drawn to patent eligible subject matter. In particular, the
Examiner fails to analyze the claims a whole. Moreover, Appellant
submits that the claims, when analyzed under the proper standard, are
not wholly directed to a judicial exception and, therefore, quality as
patent eligible subject matter under 35 U.S.C. §101.
App. Br. 10.
Appellant argues that, “even assuming, arguendo, that the claims
include a ‘natural phenomenon, ’ the claims in no way preempt the use of
such natural phenomenon and thus represent patent eligible subject matter.”
Id. at 12. Appellant further argues that, “[t]he claims do include nucleic
acids, but they are not, in fact, naturally occurring, as they have been
chemically modified with synthetic moieties; the claims actually relate to the
detection of target nucleic acid sequences using specific non-naturally
occurring ligation probes.” Id. at 17. Appellant argues that the claims
include, “two ligation probes [that] are transformed into a single ligation
product with a number of different, synthetic components, which are further
transformed using amplification to form an additional synthetic component
6
Appeal 2016-005406
Application 12/798,108
(amplicons with fluorescent labels).” Id. at 20. Appellant argues that the
claims “include additional features that provide practical assurance that the
process is more than a drafting effort designed to monopolize the alleged
laws of nature.” Id. at 23.
ANALYSIS
We do not find that, on balance, the Examiner has provided sufficient
evidence to support a prima facie case of lack of patentable eligible subject
matter. It has been established that
“while a claim drawn to a fundamental principle”—i.e., a law
of nature, natural phenomenon, or abstract idea—“is unpatentable, ‘an
application of a law of nature or mathematical formula to a known
structure or process may well be deserving of patent protection.’”
Bilski, 545 F.3d at 953 (quoting Diehr, 450 U.S. at 187). The key
issue for patentability, then, at least on the present facts, is whether a
claim is drawn to a fundamental principle or an application of a
fundamental principle.
Prometheus Laboratories Inc. v. Mayo Collaborative Services, 581 F.3d
1336, 1242 (Fed. Cir. 2009). The Supreme Court has also made clear that
the patent eligibility of a claim as a whole should not be based on whether
selected limitations constitute patent-eligible subject matter. See Bilski v.
Kappos, 130 S.Ct. 3218, 3230 (2010), (citing Diamond v. Diehr, 450 U.S.
175, 185 (1981); Parker v. Flook, 437 U.S. 584, 594 (1978)).
In analyzing patent eligibility questions under 35 U.S.C. § 101, the
Supreme Court instructs us to “first determine whether the claims at issue
are directed to a patent-ineligible concept.” Alice Corp. Pty Ltd. v. CLS
Bank Int’l, 134 S. Ct. 2347, 2355 (2014). If this threshold is met, we move
to a second step of the inquiry and “consider the elements of each claim both
7
Appeal 2016-005406
Application 12/798,108
individually and ‘as an ordered combination ’ to determine whether the
additional elements ‘transform the nature of the claim’ into a patent-eligible
application.” Id. (quoting Mayo Collaborative Servs. v. Prometheus Labs.,
Inc., 132 S. Ct. 1289, 1297 (2012) (italicized emphasis added)); see also
“Guidance For Determining Subject Matter Eligibility Of Claims Reciting
Or Involving Laws of Nature, Natural Phenomena, & Natural Products,”
(Guidance) issued by the U.S. Patent and Trademark Office, March 2014.
Step One
Taking up the first step of the patent-eligibility analysis, we do not
find that claim 1 is has been established to be directed to a law of nature or
natural phenomenon. “At some level, ‘all inventions . . . embody, use,
reflect, rest upon, or apply laws of nature, natural phenomena, or abstract
ideas,’” and whether one takes a macroscopic or microscopic view of a
claim may be determinative on the issue. Alice, 134 S. Ct. at 2354 (quoting
Mayo, 132 S. Ct. at 1293); and see Amdocs (Israel) Ltd. v. Openet Telecom,
Inc., 841 F.3d 1288, 1299 (Fed. Cir. 2016).
Looking to the Specification to enlighten us as to the claimed
invention, as did the Federal Circuit in Enfish, LLC v. Microsoft Corp., 822
F.3d 1327 (Fed. Cir. 2016), we find that the Specification explains the
invention to be directed to “methods for detecting one or more nucleic acid
targets present in a sample . . . .” Spec. 11. The Examiner finds that the
claims focus on the natural phenomenon of autoligation of adjacent termini
of nucleic acids that are annealed to a complementary sequence. Final Act
6. The claims also are arguably focused on the natural phenomenon of
8
Appeal 2016-005406
Application 12/798,108
nucleic acids occurring as DNA and/or RNA, that they can be “amplified”
and also be separated and detected via capillary electrophoresis. Id.
While the method claims may, tangentially, broadly read on detection
of nucleic acids, we find that the method steps within the scope of the
claims, when read as a whole, ordered combination, are directed to patent
eligible subject matter. In particular, the objective of the claim 32 method of
detecting a target nucleic acid, using a non-naturally occurring ligation probe
having a 5’-ligation moiety comprising a DABSYL2 moiety, is to reduce
“upstream processing steps . . . using ligation reactions to increase signal
strength and improve specificity.” Spec. 4. We are persuaded by Appellants
that the method of “the claims include[s], ‘two ligation probes [that] are
transformed into a single ligation product with a number of different,
synthetic components, which are further transformed using amplification to
form an additional synthetic component (amplicons with fluorescent
labels).’” App. Br. 20.
The Examiner contends that the claimed process steps include the
natural phenomenon of “autoligation” without the use of ligase enzymes.
Ans. 4. Appellant responds, arguing that
Naturally occurring nucleic acids do not “autoligate;” it is only
in the presence of the synthetic ligation moieties that are spatially
2 4-(4-Dimethylaminophenylazo)benzenesulfonyl chloride (DABYSL).
DABYSL provides a synthetic or non-natural 5’ leaving group to the
upstream probe. Spec. 16. Thus, the first ligation probe has a 5’synthetic or
non-natural leaving group attached through a flexible linker and a
downstream oligonucleotide which has a 3’ thiophosphoryl group. This
configuration leads to a significant increase in the rate of reaction and results
in multiple copies of ligated product being produced for every target. Spec.
15.
9
Appeal 2016-005406
Application 12/798,108
adjacent does such ligation occur. Essentially, by providing particular
specific chemical moieties, a chemical reaction will occur when the
moieties are spatially adjacent.
App. Br. 17.
Thus, the issue is whether the claimed method for detecting nucleic
acids in a sample involves something other than conventional physical
implementation of a natural phenomenon. See Genetic Technologies v.
Menial LLC, 818 F.3d 1369, 1380 (Fed. Cir. 2016). We answer this question
in the affirmative. As argued by Appellants, we find that the ordered
combination of the limitations in the method for detection of claim 32
provides the requisite inventive concept. BASCOM Glob. Internet Servs.,
Inc. AT&T Mobility LLC, 827 F3d. 1341, 1349-52; Mayo Collaborative
Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289, 1298 (2012)( (“[A] new
combination of steps in a process may be patentable even though all the
constituents of the combination were well known and in common use before
the combination was made,” citing Diehr, 450 U. S. at 188). The claimed
method provides a “technology based solution” that improves performance
of the nucleic acid detection method by increasing signal strength and
improve reaction specificity. In other words, claim 32 is drawn to an
application of a method of detection of nucleic acids deserving of patent
protection.
Even if we were to agree that claim 32 is directed to an ineligible
natural phenomenon under Alice’s step one, the claim is eligible under
Alice’s step two because it contains a sufficient “inventive concept.” Alice,
134 S. Ct. at 2355. In other words, the claimed method provides “a
technological solution” to a technological problem in the DNA detection
10
Appeal 2016-005406
Application 12/798,108
method technology, providing a detection method with improved signal
strength and specificity. This provides the requisite something more than
the performance of‘“well-understood, routine, [and] conventional activities
previously known to the industry.’” See Content Extraction & Transmission
LLC v. Wells Fargo Bank, Nat’l Ass ’n, 776 F.3d 1343, 1347-48 (quoting
Alice, 134 S.Ct. at 2359) (alteration original).
The claims here are not simply directed to the ability of DNA and
RNA to be detected or the natural phenomenon of autoligation, instead the
claims are directed to a new and useful method of detection, which provides
improved performance of the detection method by increasing signal strength
and improve reaction specificity, using synthetic intermediates. Compare,
Rapid Litigation Management Ltd. v. CellzDirect, Inc., 827 F.3d 1042, 1048
(2016) (“The end result of the ’929 patent claims is not simply an
observation or detection of the ability of hepatocytes to survive multiple
freeze-thaw cycles. Rather, the claims are directed to a new and useful
method of preserving hepatocyte cells.”).
The Examiner finds that individual method steps of the claim 32
method are known in the art and that the claimed method employs known,
conventional and routine assay steps. Ans. 5. However, we agree with
Appellant that the Examiner has not reviewed the claimed method as an
ordered combination or as a whole, consistent with 2014 Interim Guidance
On Patent Subject Matter Eligibility, 70 Federal Register 74618 (December
16, 2014), at 74622. App. Br. 13. In fact, while not determinative under the
rejection at issue, it is also significant that the Examiner has presented no
prior art rejection of the detection methods of claims 32, 36 or 40, as an
11
Appeal 2016-005406
Application 12/798,108
ordered combination, or for the remaining pending claims.3 In particular,
the Examiner presents no element by element claim analysis, or reasoned
analysis for anticipation and/or obviousness with respect to patentability of
the pending claims in view of Kool or other cited prior art.
Appellant contends that Claim 36 is directed to a similar method,
although the “5 ’ ligation moiety is a halogen leaving group rather than
DABSYL. As is well known in the art, naturally occurring nucleic acids do
not comprise halogen leaving groups. Similarly, Claim 40 uses leaving
groups and nucleophilic groups as ligation moieties.” App. Br. 16. Again,
while the Examiner may have provided evidence that individual process
steps were conventional or known in the art, the Examiner has not provided
a reasoned analysis as to why the claims as a whole, or ordered combination
do not recite patent eligible subject matter.
Step Two
For the sake of completeness, turning to the second step under Alice,
we have determined that the claims recite the “something more” or
significantly different than the judicial exception, as required by the
Supreme Court to transform a law of nature or natural phenomenon into a
3 Under the principles of compact prosecution, regardless of whether a
rejection under 35 U.S.C. § 101 is made based on lack of subject matter
eligibility, a complete examination should be made for every claim under
each of the other patentability requirements: 35 U.S.C. §§ 102, 103, 112,
and 101 (utility, inventorship and double patenting) and non-statutory
double patenting. Thus, Office personnel should state all non-cumulative
reasons and bases for rejecting claims in the first Office action. MPEP
§2106 (III).
12
Appeal 2016-005406
Application 12/798,108
patent-eligible invention. See Alice, 134 S. Ct. at 2355 (citing Mayo, 132 S.
Ct. at 1303).
The Examiner finds that the
Use of these target sequences, probes, primers,
fluorescent labels, and polymerases, as well as any of the
requisite 5 ’ and 3 ligation moieties, and “uncharacterized“
means (e.g., “leaving group“ of claim 40) for performing
ligation without use of a ligase enzyme, amplification, and
detection- all of which are discovered by others in the future,
yet encompassed by, and when used to practice the claimed
invention, would constitute both certain practices of well
known, conventional and routine assaying steps and the lack of
substantive and significant claimed embodiments that reflect a
patent-eligible practical application of the judicial exception.
In contrast to appellant’s assertions, the reasons set forth
above clearly do teach that the claimed method would preempt
many aspects of the biotech industry.
Ans. 5. Thus, the Examiner concludes that the claims recite elements/steps
in addition to the judicial exception(s) that are well-understood, purely
conventional or routine in the relevant field. Final Act. 9 (factor j weighing
against eligibility). In sum, the Examiner finds that the claims are impacted
by guidance factors h—l4 weighing against patent eligibility. Id. at 8.
Appellant disagrees with the Examiner’s assertion that
the claims encompass “natural and spontaneous chemical
ligation reactions of naturally present target nucleic acid
domains.” For example, the ligating step of independent claim
32 occurs between a 5’ ligation moiety that includes a
DABSYL moiety and a 3’-ligation moiety that includes a
phosphorothioate moiety. The ligating step of independent
claim 36 occurs between a 5’-ligation moiety that includes a
halogen leaving group moiety and a 3 ’ -ligation moiety that
4 Guidance 4—5.
13
Appeal 2016-005406
Application 12/798,108
includes a phosphorothioate moiety. Appellant submits that
such DABSYL, halogen leaving groups and phosphorothioate
moieties are not “naturally present” in target nucleic acid. Such
moieties are attached to non-naturally occurring nucleic acid.
As such, the autoligation that occurs between such non-
naturally occurring molecules is not a natural phenomenon.
Reply Br. 11—12.
For the reasons discussed herein, we do not find that the Examiner has
established that the claims, when read in view of the Specification,
encompass merely naturally occurring autoligation reactions falling within
the judicial exception as directed to a natural phenomenon and are, thus, not
patent eligible. The Specification reasonably supports that the ligation steps
of the claims require non-naturally occurring ligation moieties. Spec. 13-18.
Furthermore, we find that the Examiner has not fully considerd the elements
of each claim both individually and “as an ordered combination” to
determine whether the additional elements “transform the nature of the
claim” into a patent-eligible application of a law of nature or natural
phenomenon. Compare, Mayo Collaborative Servs. v. Prometheus Labs.,
Inc., 132 S. Ct. 1289, 1298 (2012).
In view of our findings above, the claim rejection for lack of patent
eligible subject matter under 35U.S.C. § 101 is reversed.
CONCLUSION OF LAW
The rejection of the claims for lack of patent eligible subject matter
under 35 U.S.C. § 101 is reversed.
14
Appeal 2016-005406
Application 12/798,108
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
REVERSED
15