Ex Parte Lizzi

Patent Trial and Appeal Board

Sep 25, 2012

11832508 (P.T.A.B. Sep. 25, 2012)

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.
11/832,508 08/01/2007 Tiffiny Marie LIZZI BECTON 3.0-064 6196
63863 7590 09/25/2012
David W. Highet, VP & Chief IP Counsel
Becton, Dickinson and Company
(Lerner David Littenberg)
1 Becton Drive , MC 110
Franklin Lakes, NJ 07417-1880
EXAMINER
CHUNDURU, SURYAPRABHA
ART UNIT PAPER NUMBER
1637
MAIL DATE DELIVERY MODE
09/25/2012 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 TIFFINY MARIE LIZZI
__________

Appeal 2011-012625
Application 11/832,508
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a method
for extracting nucleic acids from a biological sample. The Examiner
rejected the claims as anticipated. We have jurisdiction under 35 U.S.C.
§ 6(b). We affirm-in-part and enter a new ground of rejection.

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Application 11/832,508

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Statement of the Case
Background
“The pretreatment of samples with an agent that can aid in the cell
lysis can reduce or eliminate the need for a heat lysis step and thus
significantly decrease the time required to perform such assays” (Spec. 1).
The Claims
Claims 1, 3-12, 14-16, and 19-21 are on appeal. Claims 1, 3, and 11
are representative and read as follows:
1. A method for obtaining or preserving nucleic acids
from a biological sample comprising:
combining bromelain with a biological sample; and
extracting nucleic acids from the sample,
wherein the sample contains a bacterial cell or a virus.

3. The method of claim 1, wherein the amount of
bromelain used is between 0.01 U/mL and 100 U/mL.

11. A method for extracting nucleic acids from a
biological sample to be used in a nucleic acid-based
diagnostic assay comprising:
combining the sample with bromelain at room
temperature;
extracting nucleic acid from the sample; and
subjecting the sample to a nucleic acid-based diagnostic
assay.

The issue

The Examiner rejected claims 1, 3-12, 14-16, and 19-21 under 35
U.S.C. § 102(b) as anticipated by Zielenski
1
(Ans. 4-5).

1
Zielenski et al., US 2005/0214926 A1, published Sep. 29, 2005.
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The Examiner finds that Zielenski teaches the steps of “combining
bromelain (lysis buffer comprising protease) with a biological sample that
contains one or more nucleases at room temperature . . . extracting nucleic
acids from the sample . . . wherein the biological sample contains a bacterial
cell or virus . . . and subjecting the sample to a nucleic acid-based diagnostic
assay” (Ans. 4). The Examiner finds regarding claim 3 that “Zielenski et al.
teach that protease (bromelain equivalent) is used in a concentration ranging
from 0.1 to 10u/ml” (Ans. 4). The Examiner finds regarding claim 11 that
“Zielenski et al. teach that the sample is incubated with the enzyme at room
temperature or between 20- 75° C” (Ans. 5).
Appellant “submit[s] . . . that Zielenski does not teach a lysis buffer in
which bromelain is the required constituent for extracting nucleic acid from
bacteria cells or a virus (claim 1) or inhibiting the activity of nuclease (claim
7), but merely contemplates bromelain as a potential, less preferred, and
optional constituent for lysis” (App. Br. 9).
Appellant contends that “one skilled in the art would not substitute
bromelain for proteinase K with any reasonable expectation of success
because Zielenski does not suggest to the skilled person that bromelain, in
and of itself, is a suitable lysis buffer constituent” (App. Br. 10).
Appellant contends, regarding claim 3, that “Zielenski never indicates
a concentration of proteolytic enzyme that could be used for either of these
purposes.” (App. Br. 17). Appellant contends, regarding claim 11, that
“there is no disclosure in Zielenski of combining any specific enzyme with a
sample at room temperature to extract nucleic acid” (App. Br. 23).
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The issue with respect to this rejection is: Does the evidence of record
support the Examiner‟s conclusion that Zielenski anticipates claims 1, 3, and
11?
Findings of Fact
1. The Specification teaches that the “term „combining‟ bromelain
with a sample as used herein encompasses both adding bromelain to a
sample, and adding a sample to bromelain. Combining also includes actively
mixing, but combining also includes incubating without an active mixing
step” (Spec. 2).
2. The Specification teaches that the “samples that are treated by
the present methods can generally include any biological samples that
contain proteins, including gelatin, or nucleic acid of human or animal
origin. The biological samples typically contain one or more prokaryotic
cells, eukaryotic cells, or viruses and also include yeast” (Spec. 8).
3. Zielenski teaches a method “comprising the steps of (a)
providing an aequous lysis buffer that contains a chaotropic agent; (b)
mixing the lysis buffer with the biological sample . . . and incubating the
mixture; . . . contacting the mixture . . . with the solid phase, thereby
adsorbing the nucleic acid from the mixture to the solid phase” (Zielenski 4
¶ 0029).
4. Zielenski teaches that “it is preferred that the lysis buffer of step
(a) contains an enzyme with proteolytic activity. . . . It is even more
preferred that the enzyme with proteolytic activity is selected from the group
consisting of . . . Bromelain” (Zielenski 5 ¶ 0039).
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5. Zielenski teaches that the “invention also encompasses
biological samples, from which nucleic acids are purified, comprising
viruses or bacterial cells, as well as isolated cells from multicellular
organisms as e.g. human and animal cells” (Zielenski 8 ¶ 0063).
6. Zielenski teaches that “the skilled artisan will test for
proteolytic activity of a selected protease in a buffer containing a chaotropic
agent at different concentrations. A protease active under the chaotropic
conditions of a mixture according to step (b) is preferably selected”
(Zielenski 5 ¶ 0039).
7. Zielenski teaches “[o]ptimization of the duration of the
incubation with the protease as well as the optimization of the incubation
temperature can be performed by the expert” (Zielenski 5 ¶ 0039).
8. Zielenski teaches that “[p]referably, the activity of proteinase K
in the mixture of step (b) is between 0.1 U/ml and 10 U/ml” (Zielenski 5 ¶
0040).
9. Zielenski teaches that it “is further preferred that the mixture of
step (b) including a protease is incubated for a certain amount of time and at
ambient conditions that allow proteolytic activity. It is preferred that the
mixture of step (b) is incubated for 10 min to 30 min at a temperature
between 20° C. and 75° C.” (Zielenski 7 ¶ 0054).
Principles of Law
For a prior art reference to anticipate a claim, it must disclose all of
the limitations of the claim, “arranged or combined in the same way as in the
claim.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370
(Fed.Cir.2008).
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Analysis
Claim 1
Zielenski teaches a method in which a lysis buffer is combined with a
biological sample followed by the extraction of the nucleic acid onto a solid
phase (FF 3). Zielenski teaches that the lysis buffer preferably contains a
protease, where a preferred protease is Bromelain (FF 4). Zielenski teaches
that the biological sample may contain a bacterial cell or virus (FF 5).
Appellant “submit[s] . . . that Zielenski does not teach a lysis buffer in
which bromelain is the required constituent for extracting nucleic acid from
bacteria cells or a virus (claim 1) or inhibiting the activity of nuclease (claim
7), but merely contemplates bromelain as a potential, less preferred, and
optional constituent for lysis” (App. Br. 9).
We are not persuaded. The instant situation is similar to that in
Wrigley, where the Court finds that:
This is not a case in which the prior art reference merely
discloses a genus and the claim at issue recites a species of
that genus. . . . Shahidi specifically discloses WS–23 as a
coolant and menthol as a flavoring agent. The question for
purposes of anticipation is therefore whether the number of
categories and components in Shahidi was so large that the
combination of WS–23 and menthol would not be
immediately apparent to one of ordinary skill in the art.

Wm. Wrigley Jr. Co. v. Cadbury Adams USA LLC, 683 F.3d 1356, 1361
(Fed. Cir. 2012). In the instant case, we find that the selection of Bromelain,
a protease which was specifically identified and listed as a preferred protease
for use in the lysis buffer (FF 4), from a moderately extensive list, would
have been immediately apparent as useful to one of ordinary skill in the art.
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Appellant contends that “one skilled in the art would not substitute
bromelain for proteinase K with any reasonable expectation of success
because Zielenski does not suggest to the skilled person that bromelain, in
and of itself, is a suitable lysis buffer constituent” (App. Br. 10).
We are not persuaded. The rejection at issue is for anticipation, and
Appellant has not advanced evidence that suggests, with any specificity, that
an ordinary artisan would have considered Zielinski‟s disclosure non-
enabling as to the use of Bromelain in the disclosed process, nor has
Appellant provided any clear or specific evidence suggesting that Bromelain
would not work in Zielinski‟s process. Here, given the explicit teaching in
Zielenski that Bromelain is a preferred enzyme for the lysis buffer (FF 4),
we conclude that Zielenski is an enabling reference, i.e., that there is a
reasonable expectation of success in selecting Bromelain. Appellant
provides no clear or specific evidence to rebut this teaching of Zielenski and
support the assertion that Bromelain would not be expected to succeed.
Claim 3
The Examiner finds that “Zielenski et al. teach that protease
(bromelain equivalent) is used in a concentration ranging from 0.1 to
10u/ml” (Ans. 4).
Appellant contends, regarding claim 3, that “Zielenski never indicates
a concentration of proteolytic enzyme that could be used for either of these
purposes” (App. Br. 17). Appellant also argues that “there is no indication
that the concentrations of proteinase K were applicable to the other types
and classes of proteolytic enzymes recited by Zielenski” (id.).
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We find that Appellant has the better position. While Zielenski
teaches the use of Bromelain (FF 4), and suggests testing the protease
selected for activity (FF 6), Zielenski does not teach any specific details
regarding the units of Bromelain necessary for the lysis buffer of Zielenski,
but instead teaches only units for proteinase K (FF 8). See In re Arkley, 455
F.2d 586, 587 (CCPA 1972) (“[C]ombining various disclosures not directly
related to each other by the teachings of the cited reference … may be
entirely proper in the making of a 103, obviousness rejection … but it has no
place in the making of a 102, anticipation rejection.”)
Claim 11
The Examiner finds Zielenski teaches “that the sample is incubated
with the enzyme at room temperature or between 20- 75° C” (Ans. 5).
Appellant contends, regarding claim 11, that “there is no disclosure in
Zielenski of combining any specific enzyme with a sample at room
temperature to extract nucleic acid” (App. Br. 23).
We find that Appellant has the better position. There is no single
example or teaching of incubating bromelain at room temperature, so as to
fall within the scope of claim 11. Instead, a list of desired proteases is
provided (FF 4) and a list of desirable temperatures is provided (FF 9). A
claim is not anticipated by a reference when such independent picking and
choosing is required to arrive at the claimed invention. See In re Arkley, 455
F.2d 586, 587 (CCPA 1972).
Conclusion of Law
The evidence of record supports the Examiner‟s conclusion that
Zielenski anticipates claim 1.
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The evidence of record does not support the Examiner‟s conclusion
that Zielenski anticipates claims 3 and 11.

New Ground of Rejection
Under the provisions of 37 C.F.R. § 41.50(b), we enter the following
new ground of rejection.
Claims 3-6, 8-12, 14-16, and 19-21 are rejected under 35 U.S.C. §
103(a) as obvious over Zielenski.
Additional Findings of Fact
10. Zielenski teaches that the sample may contain “hepatitis B virus
(HBV), hepatitis C virus (HCV), the human immunodeficiency virus (HIV)”
(Zielenski 8 ¶ 0064).
11. Zielenski teaches that “the target nucleic acid component is
further manipulated and detected, i.e. it is amplified with the polymerase
chain reaction which specifically amplifies target sequences to detectable
amounts . . . Other possible amplification reactions are . . . NASBA . . .
strand displacement amplification (SDA)” (Zielenski 8 ¶ 0065).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
Analysis
As discussed above, Zielenski teaches a method in which a lysis
buffer is combined with a biological sample followed by the extraction of
the nucleic acid onto a solid phase (FF 3). Zielenski teaches that the lysis
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buffer preferably contains a protease, where a preferred protease is
Bromelain (FF 4). Zielenski teaches that the biological sample may contain
a bacterial cell or virus (FF 5).
With regard to claims 11 and 14, Zielenski teaches subjecting the
extracted nucleic acid to a nucleic acid based diagnostic assay after
extraction including isothermal amplification assays such as SDA and
NASBA (FF 11).
With regard to claim 12, Zielenski teaches samples comprising HIV
and Hepatitis B virus (FF 10).
With regard to claims 3, 4, 8, 9, 20, and 21, Zielenski does not teach
specific amounts of Bromelain for use in the lysis buffer.
However, Zielenski does teach that protease amounts are subject to
routine optimization, specifically teaching that “the skilled artisan will test
for proteolytic activity of a selected protease in a buffer containing a
chaotropic agent at different concentrations” (Zielenski 5 ¶ 0039; FF 6).
Zielenski also teaches that ranges for a different protease than Bromelain,
proteinase K, fall in a range of 0.1 U/ml to 10 U/ml (FF 8). The discovery of
an optimum value of a results-effective variable in a known process is
normally obvious. In re Antonie, 559 F.2d 618, 620 (CCPA 1977); In re
Aller, 220 F.2d 454, 456 (CCPA 1955).
We therefore find the specific concentrations claimed, which overlap
Zielenski‟s range of concentrations of proteinase K, would have been prima
facie obvious as known results-effective variables in the absence of any
evidence of secondary considerations (FF 6, 8).
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With regard to claims 5, 6, 10, 11, 12, 14-16, and 19-21, Zielenski
does not teach specific temperatures for Bromelain incubation.
However, Zielenski does teach that temperature of incubation is
subject to routine optimization, specifically teaching that “optimization of
the incubation temperature can be performed by the expert” (Zielenski 5 ¶
0039; FF 7). The discovery of an optimum value of a results-effective
variable in a known process is normally obvious. In re Antonie, 559 F.2d at
620.
In addition, Zielenski teaches an overlapping range of temperatures,
specifically that it “is preferred that the mixture of step (b) is incubated for
10 min to 30 min at a temperature between 20° C. and 75° C.” (Zielenski 7 ¶
0054; FF 9). As our reviewing court stated in Peterson:
In cases involving overlapping ranges, we and our
predecessor court have consistently held that even a slight
overlap in range establishes a prima facie case of
obviousness …. We have also held that a prima facie case of
obviousness exists when the claimed range and the prior art
range do not overlap but are close enough such that one
skilled in the art would have expected them to have the same
properties. Titanium Metals Corp. v. Banner, 778 F.2d 775,
783 (Fed. Cir. 1985).

In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003).
We therefore find the specific temperatures claimed, which overlap
the range of incubation temperatures disclosed in Zielenski, would have
been prima facie obvious as known results-effective variables and as
overlapping ranges in the absence of any evidence of secondary
considerations (FF 7, 9).
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Conclusion of Law
The evidence of record supports the conclusion that Zielenski renders
claims 3-6, 8-12, 14-16, and 19-21 obvious.

SUMMARY
In summary, we affirm the rejection of claims 1 and 7 under 35
U.S.C. § 102(b) as anticipated by Zielenski.
We reverse the rejection of claims 3-6, 8-12, 14-16, and 19-21 under
35 U.S.C. § 102(b) as anticipated by Zielenski.
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12,
2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 C.F.R. §
41.50(b) provides “[a] new ground of rejection pursuant to this paragraph
shall not be considered final for judicial review.”
We reject claims 3-6, 8-12, 14-16, and 19-21 under 35 U.S.C. §
103(a) as obvious over Zielenski.
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment
of the claims so rejected or new evidence relating to the
claims so rejected, or both, and have the matter reconsidered
by the Examiner, in which event the proceeding will be
remanded to the Examiner. . . .
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(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record. . .

AFFIRMED-IN-PART, 37 C.F.R. § 41.50(b)

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