Ex Parte Dixit

Patent Trials and Appeals Board

Apr 3, 2019

14421490 - (D) (P.T.A.B. Apr. 3, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/421,490 02/13/2015
43850 7590 04/05/2019
Morgan, Lewis & Bockius LLP (SF)
One Market, Spear Street Tower, Suite 2800
San Francisco, CA 94105
FIRST NAMED INVENTOR
Surjit Bhimarao Dixit
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. CONFIRMATION NO.
069480-5004-us 8063
EXAMINER
BORIN, MICHAEL L
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
04/05/2019 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):
sfipdocketing@morganlewis.com
donald.mixon@morganlewis.com
PTOL-90A (Rev. 04/07)
UNITED ST ATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SURJIT BHIMARAO DIXIT 1
Appeal2019-001877
Application 14/421,490
Technology Center 1600
Before FRANCISCO C. PRATS, T AWEN CHANG, and
JOHN E. SCHNEIDER,Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method of sampling and analysis of protein conformational dynamics, which
have been rejected as directed to a judicial exception to patent-eligible
subject matter without significantly more. We have jurisdiction under 3 5
U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
"Polymers are highly dynamic molecules and many of their
functionally important characteristics, such as affinity for substrates and
stability of active form, depend on an ensemble of the structures comprising
1 Appellant identifies the Real Party in Interest as Zymeworks Inc. (Appeal
Br. 3.)
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multiple conformational substates, their probabilities and transition rates,
and characteristics of the intrinsic free energy surface." (Spec. ,r 3.)
"[B]inding of a protein to particular targets is often associated with a
preferential selection of one or more of these conformations." (Id. ,r 4.)
The Specification states that traditional approaches for sampling the
conformations of polymer structures is carried out using deterministic or
stochastic simulation approaches. (Id. ,r 6.)
A deterministic approach, such as molecular dynamics simulation,
uses Newtonian mechanics to "calculate the trajectory of all the particles in
the system as a result of the interaction forces acting between them," with
atomic displacements estimated at very short time-steps and integrated in an
iterative computation to predict system dynamics over time. (Id. ,r 7.)
According to the Specification, this approach is "computationally intense,
making [it] impractical for studying slow conformational changes of larger
polymers, such as large proteins." (Id.)
A stochastic approach, such as the Metropolis 2 Monte Carlo method,
randomly selects and perturbs a number of variables in the system to
generate new configurations of the system. (Id. ,r 8.) "[A] new
configuration is accepted or rejected on the basis of an energetic criterion at
the temperature of interest, leading to a ... weighted ensemble of
thermodynamically relevant configurations." (Id.) A stochastic approach
"can result in significantly more efficient jumps between relevant
conformational states" as compared to a deterministic approach; however,
2 "The Metropolis criterion in a Monte Carlo simulation introduces a
temperature dependent energy function conditional that follows detailed
balance to achieve equilibrium sampling of states." (Spec. ,r 99.)
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pure stochastic approaches "tend to yield limited acceptance ratios resulting
in inefficient simulation." (Id.)
The Specification states that the claimed invention combines
[ d]eterministic and stochastic search methods ... in
(Id. ,r 12.)
a way that offers improved conformational
sampling of polymers compared to the use of either
of these two techniques by themselves. The
disclosed systems and methods incorporate the
strength of coarse grain models and heuristic
knowledge of polymers to predict hinge locations
on a polymer, Monte Carlo moves to introduce
large-scale conformational changes and combines
them with the strength of a Molecular Dynamics
simulation to provide detailed information on the
conformational flexibility around a structural
substrate. The disclosed systems and methods
provide for fmding diverse polymer conformations
and their relative populations concurrently, leading
to surprising speed and practicality of modeling in
light of previous methods and solutions.
Claims 1--4, 6-8, 11, 12, 19-21, 24--28, 30-38, 40--42, 44, 48, and49
are on appeal. 3 Claim 1 is illustrative and reproduced below:
1. A method of sampling and analysis of protein
conformational dynamics by searching the
conformation space of a protein to determine
whether a three-dimensional conformation of the
protein can co-engage each antigen in a plurality of
3 Claims 23, 39, 43, 45, and 46 have been cancelled. The Examiner did not
include claim 30 in the sole rejection (under 35 U.S.C. §101). (Final Act. 3.)
The omission appears to be inadvertent, and Appellant includes claim 30 in
the Appeal Brief as a claim rejected under 35 U.S.C. §101. Accordingly, for
purposes of this opinion, we treat claim 30 as rejected under 35 U.S.C. §101
as well.
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target antigens, the protein compnsmg a frrst
plurality of residues, the method comprising:
at a computer system having one or more
processors and memory storing one or more
programs to be executed by the one or more
processors:
(A) obtaining from the memory an initial set
of three-dimensional coordinates {xlA_init, ,
XNA_init, X 1 B-init, .. . , XMB_init, X 1 C_init, .. . ,
XPC_init, ... } for the protein, wherein
the polymer comprises a plurality of
domains,
each respective xlA in {xlA_init, ... ,
XNA_m1t, X 1 B-init, .. . ' XMB_init, X 1 c_init, .. . '
XPC_init, . . . } is a three dimensional coordinate for
an atom in a frrst domain in the plurality of domains,
each respective xlB in {xlA_init, ... ,
XNA_init, X 1 B-init, .. . , XMB_init, X 1 C_init, .. . ,
XPC_init, . . . } is a three dimensional coordinate for
an atom in a second domain in the plurality of
domains, and
each respective xlc in {xlA_init, ... ,
XNA_init, X 1 B-init, .. . , XMB_init, X 1 C_init, .. . ,
XPC_init, . . . } is a three dimensional coordinate for
an atom in a frrst hinge of the protein, wherein the
frrst hinge comprises a second plurality of residues
that is a subset of the frrst plurality of residues,
wherein the protein is characterized by an ability for
the frrst and second domain to pivot with respect to
each other about the frrst hinge;
(B) altering the initial set of three-
dimensional coordinates of the protein by pivoting
the frrst domain with respect to the second domain
about the frrst hinge thereby obtaining an altered set
of three-dimensional coordinates {xlA_alt, ... ,
XNA_alt, x 1 B-alt, ... , XMB_alt, x 1 c_alt, ... , XPC_alt,
... } for the protein, wherein
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all atoms within the frrst domain are
held fixed with respect to each other during the
altering, and
all atoms within the second domain are
held fixed with respect to each other during the
altering;
( C) scoring, using a scoring module, a
calculated potential energy of the altered set of
coordinates versus a calculated potential energy of
the initial three-dimensional coordinates for the
protein with a Metropolis criterion, wherein, when
the Metropolis criterion is satisfied, the altered set
of three-dimensional coordinates is accepted as the
initial set of three-dimensional coordinates;
(D) performing additional instances of the
altering (B) and the scoring ( C) until an energy of
the altered set of three-dimensional coordinates
{xlA_alt, ... ' XNA_alt, XlB-alt, ... ' XMB_alt,
xlc_alt, ... , XPC_alt, ... } satisfy the Metropolis
criterion; and
(E) evaluating whether the altered set of
three-dimensional coordinates {xlA_alt, ... ,
XNA_alt, x 1 B-alt, ... , XMB_alt, x 1 c_alt, ... , XPC_alt,
... } can co-engage each antigen in the plurality of
target antigens by docking the altered set three-
dimensional coordinates to a model of the plurality
of antigens.
(Appeal Br. 34--35 (Claims App'x).)
TheExaminerrejectsclaims 1--4,6-8, 11, 12, 19-21,24--28,30-38,
40--42, 44, 48, and 49 under 35 U.S. C. § 101 as being directed to a judicial
exception to patent-eligible subject matter without significantly more. (Final
Act. 3.)
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DISCUSSION
Issue
The Examiner concludes that the claims are directed to "a
computational method of searching conformation space of a polypeptide," or
"a computer system comprising a processor and memory storing instructions
to execute a method," wherein the method includes the steps of "obtaining
coordinates of polymer molecule, altering the coordinates by protein packing
algorithm, scoring the altered coordinates by energy function using
Metropolis criterion, [ and] matching protein and antigen coordinates."
(Final Act. 3, 5.) The Examiner concludes that, "[a]s such, the claims are
directed to collecting and manipulating information, organizing information
through mathematical concepts such as mathematical algorithms, and
comparing information to target data." (Id. at 3.) The Examiner further
concludes that such manipulation and comparison of data "can be performed
mentally and is an idea of itself." (Id.) Thus, the Examiner concludes that
"the claims are directed to an abstract idea which is a judicial exception."
(Id.)
The Examiner fmds that, analyzing the claims as a whole, the
additional limitations recited in the claims do not amount to significantly
more than an abstract idea, because "the claims as a whole do not provide
significantly more than a generic computer upon which the claimed
[ abstract] method steps are executed." (Id. at 4.)
Appellant contends that claim 1 is not directed to an abstract idea
because, among other things, it is "a specific implementation of a solution to
a problem in the molecular docking arts" and provides an improvement in
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computer functionality and/ or the technical fields of protein conformation
analysis and/or molecular docking. (Appeal Br. 19-20, 23, 25-28; Reply
Br. 2, 4---6, 13). Appellant further contends that, "even if claim 1 were
directed to a judicial exception ... the claimed method is still patent eligible
because it provides a specific solution that was not a well-understood,
routine, conventional activity previously engaged in by scientists in the
field." (See, e.g., Appeal Br. 20.)
The issue with respect to this rejection is whether the Examiner erred
in concluding that the claims are directed to an abstract idea without
significantly more.
Analysis
We analyze this case under the framework set forth by the Supren1e
Court in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66
(2012), and applied by our reviewing court in AriosaDiagnostics, Inc. v.
Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015). As theAriosa court
explained:
In Mayo . . . , the Supreme Court set forth a
framework for distinguishing patents that claim
laws of nature, natural phenomena, and abstract
ideas from those that claim patent-eligible
applications of those concepts. First, we determine
whether the claims at issue are directed to a patent-
ineligible concept. ... If the answer is yes, then we
next consider the elements of each claim both
individually and "as an ordered combination" to
determine whether additional elements "transform
the nature of the claim" into a patent-eligible
application. . . . The Supreme Court has described
the second step of this analysis as a search for an
"inventive concept"-i.e., an element or
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combination of elements that is "sufficient to ensure
that the patent in practice amounts to significantly
more than a patent upon the [ineligible concept]
itself."
Id. at 1375 (alteration in original).
A1ayo Step One: Whether Claim l ls Directed to Abstract Idea
We begin with the first step of the A1ayo test, namely whether a claim
is "directed to" a patent-ineligible concept. On January 7, 2019, the Director
of the USPTOissued the "2019 Revised Patent SubjectJvfatter Eligibility
Guidance" ("Revised Guidance"), which provides further details regarding
how the Patent Office analyzes patent-eligibility questions under 35 U.S.C.
§ 101. 84 Fed. Reg. 50-57 (Jan. 7, 2019). Under the Revised Guidance, the
first step of the 1i1ayo test (i.e., Step 2A of the Revised Guidance) is "a two-
pronged inquiry." Id. at 54. In prong one, we evaluate whether the claim
recites a judicial exception, such as laws of nature, natural phenomena, or
abstract ideas. Id. If the claim recites a judicial exception, the claim is
fmiher analyzed under prong two, which requires '"evaluat[ion ofj whether
the claim recites additional elements that integrate the exception into a
practical application of that exception." Id. The Revised Guidance explains
that, "[i]f the recited exception is integrated into a practical application of
the exception, then the claim is eligible at Prong Two of . .. Step 2A [ of the
Revised Guidance]." Id.
FirstProngofRevised Guidance Step 2A
We agree with the Examiner that claim 1 recites a judicial exception.
In particular, step (C) of claim 1 recites "scoring . .. a calculated potential
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energy of the altered set of coordinates versus a calculated potential energy
of the initial three-dimensional coordinates for the protein with a Metropolis
criterion, wherein, when the Metropolis criterion is satisfied, the altered set
of three-dimensional coordinates is accepted as the initial set of three
dimensional coordinates" for the protein. (Appeal Br. 34--35 (Claims
App 'x).) Step (D) of claim 1 further requires repeatedly "altering the initial
set of three-dimensional coordinates of the protein by pivoting the frrst
domain [ of the protein] with respect to the second domain about the frrst
hinge" while holding the atoms fixed with respect to other atoms within the
same domain and then performing the scoring step in ( C) "until an energy of
the altered set of three-dimensional coordinates ... satisfy the Metropolis
criterion." (Id. at 34--3 5 ( Claims App 'x).) As explained in the
Specification, "[t]he Metropolis criterion ... introduces a temperature
dependent energy function conditional that follows detailed balance to
achieve equilibrium sampling of states." (Spec. ,r 99.) Thus, we find that
claim 1 recites "mathematical concepts - mathematical relationships,
mathematical formulas or equations, mathematical calculations," which are
abstract ideas. Revised Guidance, 84 Fed. Reg. at 52.
Second Prong of Revised Gui dance Step 2A
The second prong of Step 2A asks whether the claims as a whole
integrate the judicial exception into a practical application of the exception,
frrst by "[i]dentifying whether there are any additional elements recited in
the claim beyond the judicial exception( s ), "then by "evaluating those
additional elements individually and in combination to determine whether
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they integrate the exception into a practical application." Revised Guidance,
84 Fed. Reg. at 54--55.
In this case, the elements recited in claim 1 beyond the mathematical
relationships, fon11ulas, or equations include "a computer system having one
or more processors and memory storing one or more programs to be
executed bythe one or more processors." (Appeal Br. 34 (Claims App'x).)
Claim l also includes steps (A), (B), and (E). Step (A) recites "obtaining ...
an initial set of three-dnnensional coordinates ... for [a] proten1 ...
compris[ing] a plurality of dmnains" and "characterized by an ability for [a]
first and second doman1 to pivot with respect to each other about [a] frrst
hinge." (J d.) Step (B) recites "altering the initial set of three-dnnensional
coordinates of the proten1 by pivoting the first domain with respect to the
second doman1 about the frrst hn1ge thereby obtaining an altered set of three
dnnensional coordinates ... for the protein," wherein "all atoms within the
frrst [ and second] don1ain are held f1xed with respect to each [ of the J other
[ atmns in the first and second domain] durn1g the altering. (Id.) Fn1ally,
step (E) recites "evaluating whether the altered set of three-dnnensional
coordinates ... can co-engage each antigen n1 the plurality of target antigens
by docking the altered set three-dimensional coordn1ates to a model of the
plurality of antigens." (Id. at 35.)
Evaluating these additional elen1ents in combination, we conclude
~ .
that clann l as a whole n1tegrates the mathematical concepts recited in steps
(C) and (D) into a practical application. In particular, the additional
elements in combination appear to provide an improvement to a technical
field or technical fields, nainely, the fields of computer-hnplemented protein
conformation analysis and molecular docking. Revised Guidance, 84 Fed.
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Reg. at 55 ( explaining that "[a]n additional element reflect[ing] ... an
improvementto [a] technology or technical field" may integrate the judicial
exception into a practical application); }vfcRO, Inc. v. Bandai Namco Garnes
Am. Inc., 837 F.3d 1299 (Fed. Cir. 2016).
For example, the Specification explains thatthe claimed systems and
methods combine "[d]eten11inistic and stochastic search methods ... in a
way that offers improved conformational sampling of polymers compared to
the use of either of these two techniques by themselves." (Spec. ,r 12.)
I\1ore specifically, the Specification explains that, in traditional ivionte Carlo
approach (a stochastic approach), "'perturbations are introduced anywhere
along the prnnmy sequence of the poly111er and are restricted to very small
magnitudes," because "[i]n these traditional methods, 111aking large moves
leads to, in most cases, a disturbance of inten1al domain structures and
unfavorable energetic states." (Id. ,r 100). In contrast, claim 1 provides a
method where the internal domain structures are held constant while the
domains are pivoted about a hinge. According to the Specification, such
methods, which "'utilize hinge parameter perturbations ... are more likely to
lead to energetically feasible states [that] will be accepted by the algorithm."
(Id.)
As in AfcRO, therefore, inclain1 1 "[i]t is the incorporation of the
claimed rules, not the use of the c0111puter, that 'in1proved [the J existmg
technological process' by allowing" the efficient generation and analysis of
polyn1er confon11ational states that are potentially nnportant ill interacting
with target molecules such as antigens. AfcRO, 837F.3dat 1314(second
alteration in original). Likewise, as in AfcRO, the claimed method "goes
beyond merely 'organizing [ existing] information into a new fonn,"'
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because "[t]he claimed process uses a combined order of specific rules that
renders infon11ation into a specific format that is then used and applied to
create desired results": a series of protein conformations in energetically
feasible states that may be able to bind to desired target molecules. Id. at
1315 (first alteration in original). \Vhile the results (i.e., desirable protein
confon11ations) may not be tangible, the A1cRO court has explained that
"there is nothing that requires a method 'be tied to a machine or transfon11
an article' to be patentable." Id.
The Examiner asserts that all of the steps in claim l "are drawn to
various 1nanipulations of data - collecting and manipulating infonnation,
organizing information through 1nathematical concepts such as mathe1natical
algorithms, and cmnparing inf onnation to target data." (Ans. 3.) Thus,
according to the Examiner, "other than addressing the method as con1puter-
nnplemented, i.e., which n1erely requfres generic cmnputer n11plementation,
there are no additional elen1ents in the clan11s that amount to significantly
more than the abstract idea." (Id. at 5.) Revised Guidance, 84 Fed. Reg. at
55 ( explainn1g that the judicial exception may be n1tegrated into a practical
application if"[ a]n additional element reflect ... an nnprovement to [a]
technolof,'Y or technical field").
\Ve acknowledge that our reviewing court has held the following
typically to be abstract: "collecting infon11ation, including when linlited to
particular content"; "analyzn1g n1f01mation by steps people go through in
thefr minds, or by n1athematical algorith1ns, without 1nore"; and "presenting
the results of abstract processes of collecting and analyzing information,
without more." Elec. Power Grp .. LLC v. Alstom S.A., 830 F.3d 1350,
1353-1354 (Fed. Cir. 2016). However, claim 1 is distinguishable from
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Electric Power Group, because in that case"[ t ]he advance [the claim]
purpmi[ s] to make is a process of gathering and analyzing information of a
specified content, then displaying the results, and not any particular
asse1iedly inventive technology for performing those functions." Id. at
1354. In contrast, as discussed above, claim 1 does not merely claim only a
result that purportedly improved a technical field; rather, it claims a specific
way of achieving such a result See SAP Am., Inc. v. InvestPic, LLC, 809
F. 3d 1161, 1167 (Fed. Cir. 2018) ( distinguishing AicRO because the claims
in A1cRO "had the specificity required to transfonn a clann from one
clanning only a result to one clanning a way of achieving it").
The Examn1er asserts that, unlike lvicRO, "the instant invention, even
though drawn to specific set of parameters and specific algorithm, does not
demonstrate an nnprovement in conventional n1dustry practice." ( Ans. 3.)
Sn11ilarly, the Exan1iner asserts that, "[i]n the instant case, unlike Enfish,
there is no de111onstrated specific improven1ent n1 computer capabilities
(such as the self-referential table for a computer database ... ); instead, the
clanns are drawn to ... a process that qualifies as an 'abstract idea' for
which computer are invoked merely as a tool." (Id. at 4.) The Examn1er
asserts that "changing the amount of computational steps performed by
processor does not den1onstrate nnprovement in computer functionality."
(Id.)
\Ve agree with the Examiner that the clan11 does not result an
nnprovement in computer capabilities in the 111anner of Enjish, LLC v.
lvficroscft Corp., 822 F.3d 1327 (Fed. Cir. 2016): Appellant has not shown
that claim l requires the computer to act in anything other than its "norrnal,
expected rnanner." Cf SRI Int 'l. Inc. v. Cisco 5'.ys., Inc., AppealNo. 2017-
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2223, 2019\VL 1271160 at *4 (Fed. Cir. Jvfar. 20, 2019) (finding claims not
directed to an abstract idea where they "prevent the nonnal, expected
operation of a conventional computer network"). Nevertheless, we are not
persuaded by the Examiner's response, because a claim may also be patent
eligible if it provides an improvement in another technology or technical
field, and the Examiner provides no explanation as to why claim 1, despite
the statements in the Specification and "even though drawn to specific set of
parameters and specific algorithm, does not demonstrate an improvement in
conventional industry practice" relating to computer-implemented protein
conformation sampling and analysis. (Ans. 3.) The Examiner has not
provided persuasive evidence, for instance, that the process previously used
in protein conformation sampling and analysis is the same as the process
required by clain1 1. See, e.g., 1VlcRO, 837 F.3d at 1314 (fmding claims
patent eligible in part because they were "unlike Flook, Bi !ski, and Alice,
where the clain1ed con1puter-automated process and the prior art process
were carried out in the same way").
Accordingly, we reverse the Examiner's rejection of claim 1 as
directed to patent-ineligible subjectmatterwithout significantly more. We
reverse the Examiner's rejection of claims 2--4, 6-8, 11, 12, 19-21, 24--28,
30-38, 40--42, 44, 48, and 49, which all depend directly or indirectly from
claim 1, for the same reasons.
SUMMARY
For the reasons above, we reverse the Examiner's decision rejecting
claims 1--4, 6-8, 11, 12, 19-21, 24--28, 30-38, 40--42, 44, 48, and 49.
REVERSED
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