Ex Parte Densham

Patent Trial and Appeal Board

Mar 30, 2016

10478036 (P.T.A.B. Mar. 30, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
10/478,036 11/17/2003
21365 7590 04/01/2016
GEN PROBE INCORPORATED
10210 GENETIC CENTER DRIVE
Mail Stop #1 I Patent Dept.
SAN DIEGO, CA 92121
FIRST NAMED INVENTOR
Daniel Henry Densham
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.
GP247-0l.UT 6371
EXAMINER
POHNERT, STEVEN C
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
04/01/2016 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):
patentdept@hologic.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DANIEL HENRY DENSHAM1
Appeal2013-005462
Application 10/478,036
Technology Center 1600
Before LORA M. GREEN, MELANIE L. McCOLLUM, and ANNETTE R.
REIMERS, Administrative Patent Judges.
McCOLLUM, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
polynucleotide sequence determining method. The Examiner has rejected
the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse.
STATEMENT OF THE CASE
Claims 1, 9, 10, 14, 17, 18, 21, 30, 31, 36-40, and44-46 are on
appeal (App. Br. 7). Claim 1 is representative and reads as follows:
1 Appellant identifies the real party in interest as Gen-Probe Incorporated
(App. Br. 6).
Appeal2013-005462
Application 10/478,036
1. A method for determining the sequence of a
polynucleotide, consisting essentially of the sequential steps of:
(i) contacting a polynucleotide processive enzyme
immobilised in a fixed position having a metal nanoparticle
positioned on or proximal to the enzyme with a target
polynucleotide to form a complex;
(ii) contacting the complex with one or more nucleoside
triphosphates selected from the group consisting of dA TP,
dTTP, dGTP, and dCTP, under conditions sufficient to induce
polynucleotide processive enzyme activity;
(iii) generating a non-linear optical signal in the area
encompassing at least a portion of the immobilized enzyme;
and
(iv) detecting an effect as the complex interacts with the
one or more nucleoside triphosphates, by measurement of the
non-linear optical signal, wherein the non-linear optical signal
measurement consists of measuring the second or third
harmonic signals, thereby determining the sequence of the
polynucleotide.
Claim 38 is also independent and recites the same sequential steps (i) and (ii)
as claim 1 .
2
Appeal2013-005462
Application 10/478,036
Claims 1, 9, 14, 17, 18, 21, 30, 31, 36-40, and 44--46 stand rejected
under 35 U.S.C. § 103(a) as obvious over Stemple2 in view ofGrow,3 West,4
Vo-Dinh,5 Haller,6 Peleg,7 and Lewis8 (Ans. 4). 9
Claim 10 stands rejected under 35 U.S.C. § 103(a) as obvious over
Stemple in view of Grow, West, Vo-Dinh, Haller, Peleg, Lewis, and
Densham10 (Ans. 13). 11
2 Stemple et al., WO 00/53805 Al, Sept. 14, 2000.
3 Grow, US 5,866,430, Feb. 2, 1999.
4 West et al., WO 01/06257 Al, Jan. 25, 2001.
5 Tuan Vo-Dinh, Surface-Enhanced Raman Spectroscopy Using Metallic
1\fanostructures, 17 TRENDS II'-~ 1A..NALYTICAL CHE1\1ISTRY 557-82 (1998).
6 Kurt L. Haller et al., Spatially Resolved Surface Enhanced Second
Harmonic Generation: Theoretical and Experimental Evidence for
Electromagnetic Enhancement in the Near Infrared on a Laser
Microfabricated Pt Surface, 90 J. CHEM. PHYS. 1237-52 (1989).
7 Gadi Peleg et al., Nonlinear Optical Measurement of Membrane Potential
around Single Molecules at Selected Cellular Sites, 96 PROCEEDINGS
NATIONAL ACADEMY OF SCIENCES 6700--04 (1999).
8 Aaron Lewis et al., Second-Harmonic Generation of Biological Interfaces:
Probing the Membrane Protein Bacteriorhodopsin and Imaging Membrane
Potential around GFP Molecules at Specific Sites in Neuronal Cells of
c. elegans, 245 CHEMICAL PHYSICS 133--44 (1999).
9 The Examiner's Answer also lists claim 15 as rejected on this basis
(Ans. 4). However, claim 15 was canceled (App. Br. 7).
10 Densham, WO 00/60114 A2, Oct. 12, 2000.
11 Claims 1, 9, 10, 14, 17, 18, 21, 30, 31, 36-40, and 44--46 are also objected
to by the Examiner (Ans. 3). However, this issue is not appealable and is,
therefore, not discussed further herein.
3
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Application 10/478,036
I
The Examiner relies on Stemple for teaching "the use of a polymerase
molecule immobilized on a solid support ... to determine nucleotide
sequences" (Ans. 5). The Examiner finds:
Stemple teaches contact of an immobilized polynucleotide
processive enzyme (polymerase) with a polynucleotide to
determine the sequence. . . . Stemple teaches incorporation of
labeled nucleotides into polynucleotides . . . . Stemple teaches
the use of caged nucleotide triphosphates . . . . Stemple teaches
photolysis of linker to remove linker . . . . Stemple thus teaches
the use of unblocked nucleoside triphosphates. Stemple teaches
polymerase molecules immobilized on a solid support . . . . The
polymerase taught by Stemple is an enzyme. Stemple teaches,
"Raman scattering may be used to detect PRPs" . . . . Stemple
teaches that plasmon-resonant particles (PRP) are colloidal silver
nanoparticles . . . . Stemple clearly envisions the use of other
methods of detection including ... plasmon resonance, FRET,
TIRFM, confocal microscopy, etc. Further Stemple specifically
suggests substitutions and equivalents.
(Id. at 5-7.)
The Examiner relies on West for teaching "the use of nanoshells for in
vivo and in vitro detection of biological analytes by surface enhanced
Raman Light scattering" (id. at 7). The Examiner finds:
West teaches the metal nanoparticle can be attached to
biomolecules including oligonucleotides, proteins and enzymes .
. . . West teaches the non-linear optical properties of metal
nanoshells can be enhanced by placement of the plasmon
resonance at or near the optical wavelengths of interest .... West
teaches the use of a glucose oxidase-nanoshell conjugate ....
The glucose oxidase-nanoshell conjugate is an enzyme-
nanoparticle conjugate in which the metal nanoparticle is
position[ ed] on the enzyme. West teaches that the glucose
oxidase-nanoshell conjugate allows for detection of
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Application 10/478,036
conformational changes due to the binding of glucose or its
products to the enzyme . . . . West teaches ... one can readily
appreciate that other chemicals or analytes may be monitored
similarly and other proteins or biomolecules may be similarly
adsorbed to other nanoshells.
(Id. at 7-9.)
The Examiner relies on Grow for teaching "a method for detecting
and monitoring chemical analytes by Raman spectroscopy including enzyme
substrate binding" (id. at 9). The Examiner finds that Grow "teaches his
method allows detection of a biological component (enzyme) and its reactive
capacity" and "the use of his method to detect nucleic acids by
hybridization" (id.). The Examiner also finds that "Grow teaches surface
enhanced Raman spectroscopy ... using a roughened silver layer ...
increases the normal Raman scattering as much as 109 times" (id.).
The Examiner concludes:
[I]t would have been prima facie obvious to one of skill in the art
at the time the invention was made to use the surface enhanced
Raman spectroscopy method of Grow and West as well as the
nanoparticles of West attached to nucleotides, the DNA
processive enzyme or the polynucleotide to improve Stemple's
method of DNA sequencing. The artisan would be motivated
because Grow teaches surface enhanced Raman spectroscopy
improves detection of molecular structure and movement and the
roughened silver surface increases Raman scattering and West
teaches the use of nanoparticles attached allows for detection
with little purification. Further West teaches methods of
attaching nanoparticles to enzymes and oligonucleotides were
known and suggest their use in monitoring enzyme activity or
activity.
(Id. at 10.)
5
Appeal2013-005462
Application 10/478,036
The Examiner relies on Vo-Dinh for teaching "that SERS [surface-
enhanced Raman scattering] has been extended to include surface enhanced
second harmonic generation as demonstrated by Haller" (id. at 11 ). The
Examiner relies on Haller for teaching "that as they did not have the
requisite detectors they use SHG [second harmonic generation] instead of
Raman spectroscopy" and that the SHG signal intensity "is not only
sensitive to enhancement of the SERS surface, but can detect adsorbate
coverage, elucidate orientation and track molecular resonances" (id. at 11-
12). The Examiner relies on Peleg for teaching "that second harmonic
generation with single molecule sensitivities uses old ideas similar to those
used [in] Raman Scattering" (id. at 12). The Examiner relies on Lewis for
teaching "second harmonic imaging of a bacterial rhodopsin a protein" (id.).
The Examiner concludes that it would have been obvious "to substitute
second harmonic imaging as taught Vo-Dinh, Peleg and Lewis in the method
of Stemple, Grow and West or use the second harmonic imaging method in
conjunction with the surface plasmon resonance taught by Stemple and
Grow" (id.).
Analysis
Stemple discloses:
[A] plurality of polymerase molecules is immobilized on a solid
support through a covalent or non-covalent interaction. A
nucleic acid sample and oligonucleotide primers are introduced
to the reaction chamber in a buffered solution containing all four
labeled-caged nucleoside triphosphate terminators. Template-
driven elongation of a nucleic acid is mediated by the attached
polymerases using the labeled-caged nucleoside triphosphate
terminators. Reaction centers are monitored by the microscope
system until a majority of sites contain immobilized polymerase
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Application 10/478,036
bound to a nucleic acid template with a single incorporated
labeled-caged nucleotide terminator. The reaction chamber is
then flushed with a wash buffer. Specific nucleotide
incorporation is then determined for each active reaction center.
Following detection, the reaction chamber is irradiated to uncage
the incorporated nucleotide and flushed with wash buffer once
again. The presence of labeled-caged nucleotides is once again
monitored before fresh reagents are added to reinitiate synthesis,
to verify that reaction centers are successfully uncaged .... The
sequencing cycle outlined above is repeated until a large
proportion of reaction centers fail.
(Stemple 3.) Stemple also discloses that "each of the caged terminators is
labeled with a colloidal silver plasmon-resonant particle (PRP)," wherein
"PRPs are metallic nanoparticles" (id. at 15).
We understand the Examiner's position that "for the label caged
terminator nucleotides with silver nanoparticles to be incorporated into a
polynucleotide as taught by Stemple the label caged terminator nucleotides
with silver nanoparticles have to be in contact with the enzyme and thus the
nanoparticles are on or proximal to the polynucleotide processive enzyme"
(Ans. 17; see also id. at 25). However, the Examiner does not adequately
explain how Stemple teaches that a metal nanoparticle is on or proximal to
the enzyme at the time it is contacted with the target polynucleotide to form
a complex. Instead, the Examiner acknowledges that "Stemple does not
specifically teach the use of a metal particle positioned on or near a
polynucleotide processive enzyme prior to the complex being contacted with
nucleotide triphosphates" (id. at 7). Thus, we agree with Appellant that the
Examiner has not adequately shown that Stemple teaches or suggests:
the sequential steps of ... contacting a polynucleotide processive
enzyme immobilised in a fixed position having a metal
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Application 10/478,036
nanoparticle positioned on or proximal to the enzyme with a
target polynucleotide to form a complex; [and] ... contacting the
complex with one or more nucleoside triphosphates selected
from the group consisting of dATP, dTTP, dGTP, and dCTP,
under conditions sufficient to induce polynucleotide processive
enzyme activity,
as recited in claims 1 and 38 (App. Br. 17-18).
In addition, we conclude that the Examiner has not adequately
explained how the other references overcome this deficiency. The Examiner
finds that "West teaches [that its] metal nanoparticle can be attached to
biomolecules including oligonucleotides, proteins and enzymes" (Ans. 7; see
also id. at 16). In particular, the Examiner finds that West teaches a
"glucose oxidase-nanoshell conjugate [that] allows for detection of
conformational changes due to the binding of glucose or its products to the
enzyme" (id. at 9). The Examiner also finds that Peleg teaches "selectively
directing an antibody with a 1-nm gold label to a specific membrane
protein" and that "in figure 1 Peleg suggest[ s] detection of a multimeric
protein complex, as the antigen, primary antibody and secondary antibodies
are each proteins" (id. at 20). In addition, the Examiner finds that "the
teachings of Grow suggest the labeling of an enzyme" (id. at 28). However,
we conclude that the Examiner does not adequately explain why it would
have been obvious to label Stemple's polymerase enzyme.
The Examiner concludes that it would have been obvious "to use ...
the nanoparticles of West attached to nucleotides, the DNA processive
enzyme or the polynucleotide to improve Stemple's method of DNA
sequencing" (id. at 10). In particular, the Examiner states that the "artisan
would be motivated because ... West teaches the use of nanoparticles
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Application 10/478,036
attached allows for detection with little purification ... [and] methods of
attaching nanoparticles to enzymes and oligonucleotides were known and
[West] suggest[ s] their use in monitoring enzyme activity or activity" (id.).
We are not persuaded.
As noted by the Examiner (id. at 9), West discloses "metal nanoshells
[that] have been conjugated with the enzyme glucose oxidase" (West 17).
However, we agree with Appellant that the Examiner does not adequately
explain how West teaches or suggests "positioning a metal nanoparticle on
or proximal to a polynuc[le ]otide processive enzyme" (App. Br. 18). In
particular, we conclude that the fact that one of skill in the art could have
labeled a particular enzyme is insufficient to explain why one of skill in the
art would have labeled a particular enzyme.
Conclusion
The Examiner has not set forth a prima facie case that the applied
references suggest the methods of claims 1 and 38. We, therefore, reverse
the obviousness rejections of claims 1 and 3 8 and of claims 9, 14, 17, 18, 21,
30, 31, 36, 37, 39, 40, and 44--46, which depend directly or indirectly from
claims 1 or 3 8.
II
In rejecting claim 10, the Examiner relies on Stemple, Grow, West,
Vo-Dinh, Haller, Peleg, and Lewis as discussed above (Ans. 13). However,
the Examiner finds that "Stemple, Grow, West, Vo-Dinh, Haller, Peleg, and
Lewis do not teach the enzyme is a helicase or primase enzyme," as recited
in claim 10 (id.). Thus, the Examiner relies on Densham to overcome this
deficiency (id. at 13-14).
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Application 10/478,036
The Examiner does not adequately explain how Densham overcomes
the deficiency discussed above with regard to claim 1. Thus, we agree with
Appellant that the Examiner does not adequately explain how the applied
references suggest the method of claim 10, which depends from claim 1
(App. Br. 46). We, therefore, reverse the obviousness rejection of claim 10.
REVERSED
10