Ex Parte Nair et al

Board of Patent Appeals and Interferences

Jun 25, 2010

11264452 (B.P.A.I. Jun. 25, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/264,452 11/01/2005 Sankar Nair 60140.0004US01 4618
23552 7590 06/25/2010
MERCHANT & GOULD PC
P.O. BOX 2903
MINNEAPOLIS, MN 55402-0903
EXAMINER
SKOWRONEK, KARLHEINZ R
ART UNIT PAPER NUMBER
1631
MAIL DATE DELIVERY MODE
06/25/2010 PAPER
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.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte SANKAR NAIR, SOUMENDU BHATTACHARYA,
VISHWANATH NATARAJAN, and ABHIJIT CHATTERJEE
__________

Appeal 2009-014830
Application 11/264,452
Technology Center 1600
__________

Decided: June 25, 2010
__________

Before ERIC GRIMES, DONALD E. ADAMS, and DEMETRA J. MILLS,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a system
for determining the length of DNA molecules. The Examiner has rejected
some of the claims as directed to nonstatutory subject matter or including
new matter, and has rejected all of the claims for obviousness. We have
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jurisdiction under 35 U.S.C. § 6(b). We affirm the rejection for nonstatutory
subject matter but reverse the other rejections.
STATEMENT OF THE CASE
The Specification discloses determining the length of DNA molecules
based on the time it takes for an individual DNA molecule to pass through a
nanopore under the influence of an electric field (id. at 9, ¶ 30). The
Specification discloses that “[a]n initial DC stimulus produces a coarse size
distribution assay of the sample that can then be refined by an optimized AC
stimuli [sic] specific to each region of the size distribution produced by the
DC stimulus” (id. at 9, ¶ 29). That is, because of random forces acting on
the DNA molecules, two molecules of similar size might not be
distinguishable based on the DC stimulus alone (id. at 17, ¶ 50). However,
“if a sinusoidal [AC] signal with carefully adjusted frequency, amplitude,
and phase is added to the DC signal, the sensitivity for certain pairs of bases
can be enhanced significantly” (id. at 18, ¶ 51).
Claims 8-10, 12-16, 18-20, and 26-32 are on appeal. Claim 8 is
representative and reads as follows:
8. A system for evaluating the length of biopolymers in a sample, the
system comprising:
a memory storage for maintaining a database; and
a processing unit coupled to the memory storage, wherein the
processing unit is operative to:
use a direct current stimulus to determine a direct current base length
region corresponding to at least a portion of the sample, the direct current
base length region appearing to correspond to biopolymers of only one
length after the direct current stimulus is used;
determine an initial value for at least one alternating current stimulus
characteristic;
use a combination stimulus comprising a combination of the direct
current stimulus and an alternating current stimulus to determine that the
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Application 11/264,452

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direct current base length region corresponds to a first set of biopolymers
and a second set of biopolymers, the first set of biopolymers having a first
base length and the second set of biopolymers having a second base length,
wherein the processing unit being operative to use the combination stimulus
comprises the processing unit operative to iteratively optimize the at least
one alternating current stimulus characteristic, starting with the determined
initial value, to increase the sensitivity of the determined direct current base
length region wherein the processing unit being operative to iteratively
optimize comprises the processing unit being operative to iteratively adjust
the alternating current stimulus characteristic from the determined initial
value to increase a difference between a mean translocation time
corresponding to the first set of biopolymers and a mean translocation time
corresponding to the second set of biopolymers;
use the at least one optimized alternating current stimulus
characteristic value to determine a length of a biopolymer in the sample; and
output the determined length of the biopolymer.

The claims stand rejected as follows:
• Claims 14-16 and 18-20 under 35 U.S.C. § 101 as directed to
nonstatutory subject matter (Ans. 4);
• Claims 27 and 28 under 35 U.S.C. § 112, first paragraph, as
including new matter (Ans. 5);
• Claims 8-10, 12-16, and 18-20 under 35 U.S.C. § 103(a) as obvious
in view of Cao,1 Flory,2 and Demana3 (Ans. 6);
• Claims 8, 14, 26, and 30 under 35 U.S.C. § 103(a) as obvious in
view of Cao, Flory, Demana, and Sauer4 (Ans. 10);

1 Cao et al., US 2004-0033515 A1, published Feb. 19, 2004.
2 Flory, US 2004-0149580 A1, published Aug. 5, 2004.
3 Tshenge Demana et al., Improved Separation of Nucleic Acids with Analyte
Velocity Modulation Capillary Electrophoresis, 83 ANAL. CHEM. 2795-2797
(1991).
4 Sauer et al., US Patent 6,413,792 B1, issued July 2, 2002.
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• Claims 8, 27, and 28 under 35 U.S.C. § 103(a) as obvious in view of
Cao, Flory, Demana, and Chen5 (Ans. 11-12); and
• Claims 31 and 32 under 35 U.S.C. § 103(a) as obvious in view of
Schwartz,6 Chen, Sauer, Demana, and Walters7 (Ans. 13).
I.
The Examiner has rejected claims 14-16 and 18-20 under 35 U.S.C.
§ 101 as being directed to nonstatutory subject matter. The claims have not
been argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii). The rejected claims are directed to a “computer-readable
storage medium” that stores instructions for carrying out steps like those
performed by the processing unit of claim 8.
The Examiner finds that the Specification defines “computer-readable
medium” to include “a carrier wave from the Internet,” and therefore the
claims encompass non-statutory subject matter under In re Nuijten, 500 F.3d
1346 (Fed. Cir. 2008) (Ans. 4). We agree with the Examiner’s finding and
conclusion.
Appellants point out that the claims were “amended to recite ‘A
computer-readable storage medium’” and argue that “the reference in the
specification to a carrier wave validly implies accessing, via a network,
computer-readable instructions for executing the claimed method” (Reply
Br. 3).

5 C.-M. Chen et al., Nanopore sequencing of polynucleotides assisted by a
rotating electric field, 82 APPLIED PHYSICS LETTERS 1308-1310 (Feb. 24,
2003)
6 Schwartz et al., US Patent 6,221,592 B1, issued Apr. 24, 2001.
7 Walters et al., EP Patent Application 1 329 502 A2, published July 23,
2003.
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Appellants’ argument does not persuade us that the rejection is in
error. The Specification states that “although embodiments of the present
invention have been described as being associated with data stored in
memory and other storage mediums, aspects can also be stored on or read
from other types of computer-readable media, such as . . . a carrier wave
from the Internet” (Spec. 24, ¶ 66, emphases added).
Contrary to Appellants’ argument, the Specification does not state or
imply that a carrier wave is not a storage medium. The Specification’s
description is reasonably interpreted to mean that aspects of the invention
can be either stored on or read from any of the listed media, including a
carrier wave. Carrier waves are not patentable subject matter. Nuijten, 500
F.3d at 1357 (“A transitory, propagating signal . . . is not a ‘process,
machine, manufacture, or composition of matter’ . . . ; thus, such a signal
cannot be patentable subject matter.”). We affirm the rejection of claims 14-
16 and 18-20 under 35 U.S.C. § 101.
II.
The Examiner has rejected claims 27 and 28 under 35 U.S.C. § 112,
first paragraph, as including new matter (Ans. 5). Claims 27 and 28 depend
from claim 8 and add the limitation that the combination of the direct current
stimulus and alternating current stimulus is derived using a “realistic
physics-based model.”
The Examiner finds that the realistic physics-based model described
in the Specification “only takes into account the DC driving voltage and DC
sensitivity. . . . The specification does not disclose a physics-based[ ] model
that combines the effects of a combination AC and DC current.” (Ans. 6.)
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Appellants contend that the Specification describes the disputed
limitation because it “discloses that a physics model based on Newtonian
motion may be used to derive a characteristic for an alternating current
component of a combination stimulus” (Appeal Br. 8). Appellants point to
the physics-based model described on pages 16-17 of the Specification and
the description on page 21 of using the model to derive an initial alternating
current characteristic (Appeal Br. 7).
We agree with Appellants that the Examiner has not adequately
shown that a skilled worker would not recognize in the Specification a
description of the disputed limitation. The Examiner acknowledges that the
Specification describes a realistic physics-based model (Ans. 5). The
Specification describes simulating the behavior of DNA molecules based on
DC and AC stimuli:
For example, a solution with base lengths 1390, 1760, 2680,
and 2760 may be used. Sensing unit 105 output from this
solution may be simulated with a DC stimulus of 100 mV. . . .
Next each region shown in FIG. 11 was simulated with an AC
stimulus. The initial AC frequency choice for stimulus was
calculated from the inverse of the mean translocation time of
the region.
(Spec. 21, ¶¶ 58-59.)
The Examiner has not explained why a skilled worker would not
recognize in the passages cited by Appellants a description of deriving a
combination AC/DC stimulus using a realistic physics-based model. We
therefore reverse the new matter rejection.
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III.
Issue
The Examiner has rejected claims 8-10, 12-16, and 18-20 as obvious
in view of Cao, Flory, and Demana (Ans. 6); claims 8, 14, 26, and 30 as
obvious in view of Cao, Flory, Demana, and Sauer (Ans. 10); and claims 8,
27, and 28 as obvious in view of Cao, Flory, Demana, and Chen (Ans.
11-12). The same issue is dispositive for each of these rejections, so we will
consider them together.
The Examiner finds that Cao teaches “a system with memory storage
and a processing unit” that determines the length of macromolecules such as
DNA using “direct current, alternating current, and combinations thereof”
(Ans. 7). The Examiner finds that Flory teaches altering AC current
parameters to eliminate non-uniform translocation of biopolymers through
nanopores (id. at 7-8) and that Demana teaches iteratively optimizing AC
current parameters in a combination AC/DC field to increase the sensitivity
of separation of different-sized DNA fragments (id. at 8-9). The Examiner
concludes that it would have been obvious to modify the system taught by
Cao “with the apparatus and method of controlling the translocation of
biopolymers of Flory” (id. at 9) and “to modify the system of nanopore
electrophoresis of Cao et al. in view of Flory with the alteration in separation
resolution using a combination AC-DC field of Demana et al. because
Demana et al. shows that a combination AC-DC field will shorten nucleic
acid transit times and improve resolution” (id. at 10).
Appellants contend that “Cao, Flory and Demana, either individually
or in combination, at least do not disclose a ‘processing unit operative to
iteratively optimize the at least one alternating current stimulus
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characteristic, starting with the determined initial value, to increase the
sensitivity of the determined direct current base length region,’ as recited by
independent Claim 8” (Appeal Br. 11-12).
The issue with respect to this rejection is: Do the cited references
support the Examiner’s conclusion that it would have been obvious to
modify Cao’s system to include an iteratively optimized combination
AC/DC field?
Findings of Fact
1. Cao teaches that “[n]anofabrication of extremely small fluidic
structures, such as channels, can be used in bionanotechnology for the direct
manipulation and analysis of biomolecules, such as DNA, and proteins at
single molecule resolution” (Cao 1, ¶ 5).
2. Cao discloses that DNA “tends to form a disordered tangle of
compact random coils in free solution” (id. at 1, ¶ 6) and “[i]t is challenging
to efficiently move long DNA arranged as a blob into the small channels,
since it is energetically unfavorable for long biopolymers to spontaneously
elongate and enter nanochannels” (id. at 1, ¶ 7). Thus, “problems such as
DNA clogging at the junction of nano-and macro-environment have arisen”
(id.).
3. Cao addresses this problem by providing a “gradient interface area
. . . formed of lateral spatial gradient structures for narrowing the cross
section . . . from the micron to the nanometer length scale. . . . The gradient
structures can be used to squeeze and funnel biomolecules into a small
nanofluidic area.” (Id. at 1, ¶ 12.)
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4. Cao’s Figure 2 is reproduced below:

Figure 2 shows how “[g]radient interface area 12 is used to effectively
stretch and align biopolymers 22 before they approach nanofluidic area 16.
Biopolymers 22 can be preliminarily stretched between adjacent pairs of
microposts 18 before entering nanochannels 21.” (Id. at 3, ¶ 42.)
5. Cao discloses that “the distance D2 between gradient structures 23
is reduced in a range of about a radius of gyration of biopolymer 22 to
substantially a diameter of biopolymer 22” (id. at 3, ¶ 43).
6. Cao discloses that its apparatus can be used to analyze
macromolecules, “includ[ing] the sizing of one DNA macromolecule” (id. at
5, ¶ 71).
7. Cao discloses that “[t]he length of a single DNA can be
detected/reported and intensity profile can be plotted. In various
embodiments . . . , the method of analyzing a macromolecule includes
correlating the detected signal to at least one of the following properties:
length, conformation, and chemical composition.” (Id. at 5-6, ¶ 72.)
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8. The Examiner concludes that Demana would have made it obvious
to modify Cao’s system in a way that meets the requirement of claim 8 to
“iteratively optimize” an alternating current characteristic (Ans. 10).
9. Demana describes separation using polyacrylamide gel
electrophoresis of a mixture of DNA fragments ranging in size from 72 bp to
1353 bp (Demana 2795, right col. and 2796, Figure 1).
10. Demana discloses that “the three fragments larger than about 700
bp (872, 1078, and 1353 bp) are poorly resolved in our gel with a dc field
only” (id. at 2796, left col.).
11. Demana describes superimposing on the DC field an AC field at
frequencies of 52, 78, 98, and 107 Hz (id. at 2796, legend to Fig. 1).
12. Demana discloses that the larger “fragments are easily resolved
by the imposition of an ac field. The best resolution is observed at 78 Hz.
Above that frequency the peaks again move closer together” (id. at 2796, left
col.).
13. Demana concludes that “[s]uperimposition of an ac field causes a
decrease in migration time and an improvement in resolution” (id. at 2795,
right col.).
Analysis
Cao discloses a device that moves a mixture of DNA molecules
through a “gradient interface area” that stretches the individual DNA
molecules from their tangled, random-coil conformation to a stretched,
elongated conformation that can more easily enter a nanochannel. Cao
discloses that the distance between the structures in the gradient interface
area is reduced to substantially the diameter of the biopolymer (DNA) and
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that the device can be used to analyze single DNA molecules, confirming
that each nanochannel in its device analyzes an individual DNA molecule.
Demana discloses that when a mixture of DNA fragments was moved
through a polyacrylamide gel using a DC field only, the fragments having
the three largest sizes all moved at about the same rate, resulting in detection
of a single peak. Demana discloses that superimposing an AC field on the
DC field allowed resolution of the three largest fragments, with the best
resolution resulting from a 78-Hz AC field.
The Examiner has not adequately explained why a person of ordinary
skill in the art would have found it obvious to combine Demana’s
combination AC/DC field with Cao’s device. Demana’s technique
addresses the problem of multiple DNA fragments moving through a
substrate at similar rates, so that they are not distinguished as different DNA
molecules. But Cao’s device separates each individual DNA molecule in a
sample, from all the other DNA molecules in the sample, before the DNA
molecule enters a nanochannel for analysis. Thus, in Cao’s system, there is
no possibility that multiple DNA molecules would be detected as a single
molecule. Since Demana’s technique is directed to a problem that would not
exist in Cao’s system, the Examiner has not adequately explained why a
person of ordinary skill in the art would have combined the two.
Conclusion of Law
The cited references do not support the Examiner’s conclusion that it
would have been obvious to modify Cao’s system to include an iteratively
optimized combination AC/DC field.
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IV.
Issue
The Examiner has rejected claims 31 and 32 as obvious in view of
Schwartz, Chen, Sauer, Demana, and Walters (Ans. 13). The Examiner
finds that “Schwartz et al. shows using direct current to determine DNA
lengths” (Ans. 14) and concludes that it would have been obvious to modify
Schwartz’s system by, among other things, including “the alteration in
separation resolution using a combination AC-DC field of Demana et al.
because Demana et al. shows that a combination AC-DC field will shorten
nucleic acid transit times and improve resolution” (id. at 17).
Appellants contend that the Examiner has acknowledged that
“Schwartz, even in combination with Chen and Sauer, does not disclose
either applying a combination of AC and DC currents or analyzing
molecules that correspond to different lengths under DC and combination
stimuli” (Appeal Br. 15) and the other cited references do not make up for
this deficiency (id. at 15-16).
The issue with respect to this rejection is: Do the cited references
support the Examiner’s conclusion that it would have been obvious to
modify Schwartz’s system to include an iteratively optimized combination
AC/DC field?
Additional Findings of Fact
14. Schwartz discloses “methods and systems for determining the
nucleotide sequence of individual double stranded nucleic acid molecules
elongated and fixed to a solid-surface by nicking the nucleic acid molecule,
enzymatically adding labeled nucleotides and imaging the labeled
nucleotides” (Schwartz, abstract).
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15. The only part of Schwartz cited by the Examiner in the rejection
is Figure 11 (Ans. 14).
16. Schwartz’s Figure 11 shows a standard computer system, with
keyboard, display, CPU, RAM, and software (Schwartz, Fig. 11 and col. 58,
ll. 1-23).
Analysis
The Examiner finds that “Schwartz et al. shows using direct current to
determine DNA lengths” (Ans. 1 4) but does not cite any specific passage in
Schwartz to support this finding. We do not find any disclosure in Schwartz
of using direct current to determine DNA length. On the contrary, Schwartz
describes a method of sequencing DNA in which the DNA molecules are
fixed to a surface.
By contrast, Demana separates DNA fragments by moving them
through a substrate using a combination of AC and DC fields. The
Examiner has not adequately explained why a person of ordinary skill in the
art would have found it obvious to combine Demana’s combination AC/DC
field with Schwartz’s system, when the purpose of Demana’s AC/DC field is
to move DNA molecules through a substrate and Schwartz’s DNA
molecules are fixed to a substrate and unable to move regardless of whether
an electric field is imposed.
Conclusion of Law
The cited references do not support the Examiner’s conclusion that it
would have been obvious to modify Schwartz’s system to include an
iteratively optimized combination AC/DC field.
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SUMMARY
We affirm the rejection of claims 14-16 and 18-20 under 35 U.S.C.
§ 101. We reverse the new matter and obviousness rejections.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

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MERCHANT & GOULD PC
P.O. BOX 2903
MINNEAPOLIS MN 55402-0903