Ex Parte Wiedenheft et al

Patent Trial and Appeal Board

Mar 22, 2018

13039160 (P.T.A.B. Mar. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
13/039, 160 03/02/2011
84220 7590 03/26/2018
UC Berkeley - 01L
Bozicevic, Field & Francis LLP
201 REDWOOD SHORES PARKWAY
SUITE 200
REDWOOD CITY, CA 94065
FIRST NAMED INVENTOR
Blake Wiedenheft
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.
BERK-105 1276
EXAMINER
PROUTY, REBECCA E
ART UNIT PAPER NUMBER
1652
NOTIFICATION DATE DELIVERY MODE
03/26/2018 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):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte BLAKE WIEDENHEFT,
KAIHONG ZHOU, and JENNIFER A. DOUDNA
Appeal2017-004858 1
Application 13/039, 160
Technology Center 1600
Before FRANCISCO C. PRATS, DEBORAH KATZ, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to methods of
generating nucleic acid fragments. The Examiner rejected the claims for
obviousness.
We have jurisdiction under 35 U.S.C. § 6(b)(l). We reverse.
1 Appellants state that the "real party in interest in this appeal is The Regents
of the University of California." Br. 3.
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Application 13/039,160
STATEMENT OF THE CASE
Claims 12-15 and 20-27 are on appeal. The following rejections are
before us for review:
(1) Claims 12-15 and 20-27, under 35 U.S.C. § 103(a) as being
unpatentable over Tetz2 and Makarova3 (Ans. 2-3); and
(2) Claims 13, 15, 22, 23, and 26, under 35 U.S.C. § 103(a) as being
unpatentable over Tackett4 and Makarova (Ans. 3--4).
Claims 12 and 13 are the independent claims on appeal and read as
follows:
12. A method of generating nucleic acid fragments, the
method comprising:
contacting a DNA substrate with a polypeptide
comprising an amino acid sequence having at least about 90%
amino acid sequence identity to the amino acid sequence set
forth in any of SEQ ID NOs: 1-22, wherein said contacting
comprises contacting a surface comprising a biofilm, wherein
the DNA substrate is extracellular DNA from microorganisms
present in the biofilm, and wherein the contacting results in
generation of nucleic acid fragments.
13. A method of generating nucleic acid fragments, the
method comprising:
contacting a DNA substrate with a polypeptide
comprising an amino acid sequence having at least about 90%
amino acid sequence identity to the amino acid sequence set
2 George V. Tetz et al., Effect of DNase and Antibiotics on Biofilm
Characteristics, 53 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 1204--
1209 (2009).
3 Kira S. Makarova et al., A DNA repair system specific for thermophilic
Archaea and bacteria predicted by genomic context analysis, 30 NUCLEIC
ACIDS RES. 482--496 (2002).
4 US 6,524,578B1 (issued Feb. 25, 2003).
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forth in any of SEQ ID NOs: 1-22, wherein said contacting
comprises contacting an epithelial surface of an animal,
wherein the DNA substrate is extracellular DNA from
microorganisms present on the surface, and wherein the
contacting results in generation of nucleic acid fragments.
Br. 10.
OBVIOUSNESS-TETZ AND MAKAROV A
The Examiner's Prima Facie Case
In rejecting claims 12-15 and 20-27 over Tetz and Makarova, the
Examiner cited Tetz as describing "methods of degrading extracellular DNA
produced by microorganisms present in a biofilm comprising contacting the
surface comprising the biofilm with DNase I for 24 hours." Ans. 2.
The Examiner cited Marakova as describing "a group of homologous
proteins predicted to be a novel nuclease family (See figure 2, which
includes several of the proteins of SEQ ID NOS:[]l-22) and name this
family of proteins as cas 1." Id. The Examiner noted that Makarova "do [es]
not specifically show that these proteins have nuclease function but teach[ es]
that the family of proteins have structural features indicative of a nuclease
function (page 486)." Id.
Based on the references' combined teachings, the Examiner reasoned:
As [Makarova] et al. explicitly predict that these proteins have
nuclease function it would have been obvious to one of
ordinary skill in the art to substitute the DNase I of Tetz et al.
with the enzymes of [Makarova] with the expectation that they
would cleave the extracellular DNA of the biofilm in a similar
fashion as each have nuclease activity.
Id. at 2-3.
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Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
primafacie case ofunpatentability ....
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), although the
Supreme Court emphasized "an expansive and flexible approach" to the
obviousness question, id. at 415, it also reaffirmed the importance of
determining "whether there was an apparent reason to combine the known
elements in the fashion claimed by the patent at issue." Id. at 418 (emphasis
added).
Thus, as the Federal Circuit has since explained, "obviousness
concerns whether a skilled artisan not only could have made but would have
been motivated to make the combinations or modifications of prior art to
arrive at the claimed invention." Belden Inc. v. Berk-TekLLC, 805 F.3d
1064, 1073 (Fed. Cir. 2015)
Ultimately, therefore, "[i]n determining whether obviousness is
established by combining the teachings of the prior art, 'the test is what the
combined teachings of the references would have suggested to those of
ordinary skill in the art."' In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir.
1995) (citation omitted).
We agree with Appellants that a preponderance of the evidence does
not support the Examiner's conclusion of obviousness. In particular, we are
not persuaded that the cited references would have suggested using
Makarova's genetically predicted proteins in Tetz's processes.
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Turning to the art, Tetz describes a study in which it was discovered
that the "cleavage of extracellular DNA leads to the formation of an altered
biofilm that permits the increased penetration of antibiotics. Thus, the
addition of DNase enhances the effect of antibiotics, resulting in decreased
biofilm biomass and numbers of CPU." Tetz 1204 (abstract).
In particular, Tetz's data "indicate that the destruction of extracellular
DNA by DNase I leads to a decrease in the extracellular
matrix/[ extracellular polymeric matrix], and as a result, antibacterial agents
act more effectively to reduce the biofilm biomass and the numbers of
CPU." Id. at 1208.
To destroy the extracellular DNA, Tetz used "[b ]ovine pancreatic
DNase I (Sigma Chemical Co., St. Louis, MO) with a specific activity of
2,200 Kunitz units/mg." Id. at 1204.
Makarova discloses that, "[ d]uring a systematic analysis of conserved
gene context in prokaryotic genomes, a previously undetected, complex,
partially conserved neighborhood consisting of more than 20 genes was
discovered in most Archaea ... and some bacteria." Makarova 482
(abstract).
Makarova discloses that the "gene composition and gene order in this
neighborhood vary greatly between species, but all versions have a stable,
conserved core that consists of five genes. One of the core genes ...
encodes a RecB family exonuclease .... " Id.; see also id. at 486
(describing "predicted" function as "RecB-like nuclease" (Table 1) );
Makarova explains that "RecB protein, which is sporadically
distributed in bacteria, contains helicase and nuclease domains and is a
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subunit of the RecBCD recombinase complex, one of the major systems of
recombinational repair in E.coli." Id. at 486 (citations omitted).
Makarova discloses that another gene that belongs to the discovered
neighborhood of genes encodes "a predicted HD-superfamily hydrolase
(possibly a nuclease)." Id. at 482 (abstract); see also id. at 486 ("[W]e
consider it likely that this protein is a previously undetected nuclease that
functions within the putative novel DNA repair system.") and id. at 486,
Table 1 (describing "predicted" function as "[p ]utative novel nuclease").
Makarova discloses that the "functional features of the proteins
encoded in this neighborhood suggest that they comprise a previously
undetected DNA repair system, which, to our knowledge, is the first repair
system largely specific for thermophiles to be identified." Id. at 482
(abstract).
Makarova concludes that "[ e ]xperimental validation of the predictions
made here should include both demonstration of individual biochemical
activities, particularly those of the predicted novel polymerase and nuclease,
and of the RAMPs, and elucidation of the physiological role of the system as
a whole." Id. at 494.
As noted above, the Examiner's rationale for rejecting independent
claim 12 over Tetz and Makarova is that it would have been obvious to
"substitute" Makarova's nuclease for the DNase I used in Tetz's process
"with the expectation that they would cleave the extracellular DNA of the
biofilm in a similar fashion as each have nuclease activity." Ans. 3.
We first note, however, that the Examiner does not identify,
specifically, which ofMakarova's predicted nucleases is posited as having
DNA-degrading activity equivalent to Tetz's DNase I. In addition, as also
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seen above, rather than being nucleases that totally and indiscriminately
degrade DNA like Tetz's DNase I, Makarova's predicted nucleases are
posited as being part of a DNA repair system. Because neither Makarova's
predicted RecB-like nuclease, nor Makarova's predicted novel nuclease, has
even been predicted to have biochemical activities similar to those taught in
Tetz, we are not persuaded one of ordinary skill in the art would have
considered it obvious to substitute them for the enzymes taught in Tetz.
The Examiner does not persuade us that an ordinary artisan would
have considered a protein with predicted nuclease activity as a component of
a DNA repair system to be a substantial equivalent to a commercially
available, biochemically characterized DNase I, for use in destroying
extracellular DNA. The Examiner does not persuade us, therefore, that the
cited references would have suggested substituting Makarova's predicted
proteins for Tetz's DNase I. Accordingly, we reverse the Examiner's
rejection of claim 12, and its dependent claims, over Tetz and Makarova.
OBVIOUSNESS-TACKETT AND MAKAROV A
The Examiner's Prima Facie Case
In rejecting claims 13, 15, 22, 23, and 26 over Tackett and Makarova,
the Examiner cited Tackett as describing "methods of degrading
extracellular DNA on human skin comprising contacting the skin with one
or more nucleases so as to cleave the extracellular DNA into individual
nucleotides or into fragments too short to bind with substantial avidity to
chromosomal DNA (i.e., less than about 15 nucleotides in length)." Ans. 3.
The Examiner noted in particular that Tackett's Example 1 describes
"contacting the skin with the nuclease solution for 50 minutes." Id. at 3--4.
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The Examiner conceded, however, that Tackett does not "teach the
use of a nuclease of one of SEQ ID NO:[]l-22." Id. at 4.
Similar to the rejection discussed above, the Examiner cited Makarova
as describing several proteins with amino acid sequences encompassed by
the claims, and concluded that, because Makarova predicted that those
proteins likely have nuclease function, it would have been obvious "to use
one or more of the nucleases of Markova in the methods of Tackett with the
expectation that they would cleave the extracellular DNA of in a similar
fashion as each have nuclease activity." Id.
Analysis
We again agree with Appellants that a preponderance of the evidence
does not support the Examiner's conclusion of obviousness. In particular,
we are not persuaded that the cited references would have suggested using
Makarova's genetically predicted proteins in Tackett's processes.
Tackett discloses a "method of treating human skin with a solution
containing nuclease so that the treatment results in the reduction of
discoloration and wrinkles in human skin." Tackett 3: 13-16.
Tackett explains:
The nuclease in the nuclease solution will degrade extra-cellular
nucleic acids into nucleotides or oligonucleotides which are too
short to have substantial avidity for chromosomal DNA. This
in tum will prevent oligonucleotides and polynucleotides from
binding to the chromosome in human tissue cells, which
prevents the over-production of protein and improper
production of protein by individual cells. By altering the
production of protein, wrinkles are reduced.
Id. at 3:20-27.
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Tackett states:
As used herein, the term "nuclease" refers to an enzyme
or enzymes capable of degrading extra-cellular DNA and/or
RNA. An "exogenous" nuclease refers to a nuclease originally
produced by cells other than the cells being contacted, and to
nuclease produced by artificial means such as peptide synthesis
or chemical alteration of a different enzyme.
Id. at 8:20-25.
Tackett discloses that "[a]ny nuclease, that is capable of degrading
oligonucleotides and polynucleotides present in the cytoplasm of human skin
cells, may be used. It is desirable to use a combination of nucleases so that
both RNA and DNA oligonucleotides and polynucleotides present in the
cytoplasm and extra-cellular fluid will be digested." Id. at 5:34--39.
Tackett explains that "when choosing a nuclease it is important to use
a nuclease that not only sufficiently degrades or breaks up large fragments of
DNA and/or RNA, but also to choose a nuclease or combination of
nucleases that will break-up both DNA and RNA oligonucleotides and
polynucleotides." Id. at 5:50-55.
Tackett discloses that the "most preferred nuclease composition used
in the present method contains approximately 500 milliliters of water,
approximately 60 grams of co-factor, preferably magnesium sulfate, and
approximately 15,000 Kunitz units of DNase and 10,000 Kunitz units of
RNase." Id. at 4:44--48.
Tackett exemplifies using a combination of DNase I from Sigma
Chemical Company "having an activity of 1,500 K[ unitz] u[ nits ]/mg" and
Ribonuclease A also from Sigma Chemical "having an activity equal to
approximately 100 Ku/mg of protein." Id. at 9:5-15.
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As noted above, the Examiner's rationale for rejecting independent
claim 13 over Tackett and Makarova is that it would have been obvious to
use Makarova's nucleases in Tackett's process "with the expectation that
they would cleave the extracellular DNA of [sic] in a similar fashion as each
have nuclease activity." Ans. 4.
As with the rejection discussed above, however, the Examiner does
not identify, specifically, which of Makarova's predicted nucleases is
posited as having DNA-degrading or RNA-degrading activity similar to the
enzymes used by Tackett, such that Makarova's predicted proteins would be
useful in Tackett's process. As seen above, Tackett repeatedly states that the
nucleases useful in its process are those that substantially degrade DNA
and/or RNA, producing fragments small enough that they exhibit no binding
avidity to chromosomal DNA. Although we recognize that prior art is not
limited to preferred or exemplified embodiments, Tackett's preference for
DNase I and RNase with significant degradative activities illustrates the
degree to which essentially total DNA/RNA degradation is critical to the
disclosed process.
In contrast, as seen above, rather than being nucleases that degrade
DNA and RNA to the extent that no binding avidity remains, as Tackett
requires of its nucleases, Makarova's predicted nucleases are posited as
being part of a DNA repair system. In addition, as also seen above, neither
Makarova's predicted RecB-like nuclease, nor Makarova's predicted novel
nuclease was suggested to be similar to the enzymatic activities taught in
Tackett.
The Examiner does not persuade us that an ordinary artisan would
have considered a protein with a predicted nuclease activity as a component
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of a DNA repair system to be useful in Tackett's process, in which
essentially total DNA/RNA degradation is essential, and which, to that end,
uses DNase and RNase having significant degradative activities. The
Examiner does not persuade us, therefore, that the cited references would
have suggested using Makarova's predicted proteins in Tackett's process.
Accordingly, we reverse the Examiner's rejection of claim 13, and its
dependent claims, over Tackett and Makarova.
SUMMARY
For the reasons discussed, we reverse both of the Examiner's
obviousness rejections.
REVERSED
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