Ex Parte Gundling et al

Patent Trial and Appeal Board

Jan 24, 2018

13876144 (P.T.A.B. Jan. 24, 2018)

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.
13/876,144 08/16/2013 Gerard Gundling ISIS-31467/US-2/PCT 3237
58057 7590 01/26/2018
Pasimir Tones; P
EXAMINER
2275 Deming Way, Suite 310
Madison, WI 53562
GITOMER, RALPH J
ART UNIT PAPER NUMBER
1655
NOTIFICATION DATE DELIVERY MODE
01/26/2018 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):
docketing @ c asimirj ones .com
pto.correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GERARD GUNDLING, THOMAS LAFFLER,
CRISTINA A. IVY, and LENDELL CUMMINS
Appeal 2016-006029
Application 13/876,1441
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN G. NEW, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to methods of
extracting fungal nucleic acid. The Examiner entered final rejections for
obviousness.2
We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.
1 Appellants identify the real party in interest as Ibis Biosciences, Inc. App.
Br. 3.
2 The Examiner withdrew the rejection of claim 12 under 35 U.S.C. § 112,
first paragraph. Ans. 2.
Appeal 2016-006029
Application 13/876,144
STATEMENT OF THE CASE
Background
The Specification discloses:
methods for extraction of fungal (e.g., yeast spp., filamentous
fungal spp.) nucleic acid (e.g., DNA). In some embodiments,
the present invention provides enhanced nucleic acid extraction
from samples comprising fungal cell(s) wherein enzymatic
(e.g., lysostaphin treatment, lyticase treatment) sample
treatment is performed in combination with mechanical (e.g.,
bead beating) sample treatment.
Spec. 1:6-10.
Claims 1, 4—14, 21 are pending and on appeal. Sole independent
claim 1 is illustrative and reads as follows:
1. A method of extracting fungal nucleic acid from a
sample, comprising:
a) treating said sample with enzymatic treatment wherein
said enzymatic treatment comprises treatment with lysostaphin
and lyticase in a reaction mixture;
b) treating said reaction mixture with mechanical
treatment^] and
c) extracting said nucleic acid from said reaction mixture
wherein a combination of said enzymatic treatment comprising
said lysostaphin and said lyticase with said mechanical
treatment results in an increased yield of said extracted nucleic
acid compared to enzymatic treatment or mechanical treatment
performed separately.
App. Br. 24 (Claims Appendix).
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Appellants seek our review of the rejection of claims 1, 4—14,
and 21 under pre-AIA 35 U.S.C. § 103(a) as obvious over Fong3 in
view of each of Einsele4 and Karakousis.5 Final Act. 4—6.6
OBVIOUSNESS-CLAIMS 1-20
In rejecting claims 1, 4—14, and 21 over Fong, Einsele, and
Karakousis, the Examiner cited Fong as teaching that protocols for
preparation of nucleic acids from microbial samples “need to be adapted for
each microbe type, a lysis protocol for fungi may not be suitable for bacteria
or parasites.” Final Act. 4. The Examiner finds Fong teaches an extraction
method that uses the enzymes lysostaphin and lyticase and is “suitable for
the simultaneous enzymatic disruption of both bacterial and yeast cells [and]
allow[s] for the release of nucleic acid from both cell types in a single
reaction.” Id. The Examiner finds Fong also discloses that the enzymes
have lytic activities and can be used in “various combinations.” Id.
In reiterating the rejection in the Examiner’s Answer, the Examiner
additionally finds Fong discloses physical methods of lysing cells to release
nucleic acids that retain their integrity along with “chemical methods
including osmosis . . . and enzymatic attack,” along with disclosing “15
various combinations of enzymes.” Ans. 3. The Examiner additionally
finds that Fong discloses that “the appropriate enzyme concentrations are
3 US 2008/0193912 Al, pub. Aug. 14, 2008 (“Fong”).
4 US 2004/0002592 Al, pub. Jan. 1, 2004 (“Einsele”).
5 A. Karakousis et al., An assessment of the efficiency offungal DNA
extraction methods for maximizing the detection of medically important
fungi using PCR, 65 J. Microbiol. Meth. 38-48 (2006) (“Karakousis”).
6 Examiner’s Final Action, mailed May 27, 2015.
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readily determined by one of ordinary skill in the art and typically will range
from 0.1 unit/ml. to 106 units/mL” as well as the use of standard buffers in
the lysing and purifying steps. Id. at 3^4.
The Examiner cited Einsele as teaching “extracting fungal DNA with
lyticase with mechanical treatment.” Id. at 5. In the Answer, the Examiner
revises this finding to state that “No mechanical treatment is taught by
Einsele but in paragraph 64 the cells are first lysed hypotonically followed
by enzymatic lysis with various buffers.” Ans. 4. The Examiner finds
Einsele teaches use of a buffer in the lysis, neutralization, and DNA
detection steps of the disclosed methods. Id.
The Examiner cited Karakousis as teaching lyticase digestion and
comparing “protonase K and lyticase . . . with other methods of lysis.” Id.
The Examiner finds that Karakousis discloses use of “proteinase K or
lyticase digestion prior to mechanical methods improves the efficiency of
extracting DNA from fungi.” Id.
In reiterating the rejection in the Examiner’s Answer, the Examiner
additionally finds Karakousis discloses “the physical characteristics of fungi
have prevented the development of a single universal fungal DNA extraction
method [and that many] fungal DNA isolation methods use a variety of
disruption methods including both digestion enzymes and mechanical
methods,” both types of which are disclosed. Ans. 3. The Examiner further
finds Karakousis discloses use of a mortar and pestle (mechanical)
extraction method followed by sodium hydroxide for alkali chemical (non­
mechanical) extraction “as well as in combination with lyticase and other
enzymes with buffers.” Id. at 3^4.
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The Examiner concludes that the skilled artisan would have found it
obvious
to pretreat microbes with both lysostaphin and lyticase as taught
by Fong and to also then employ mechanical treatment as
taught by each of Einsele and Kara[k]ousis because both
Einsele and Kara[k]ousis first pretreat with enzymes and then
follow with mechanical treatment. The selection of enzymes
for the pretreating depends upon which microbes are desired to
be lysed.
Id.
In reiterating the rejection in the Examiner’s Answer, the Examiner
additionally finds the skilled artisan would have understood from the
references that because “fungal cell walls are highly variable in different
species in size, chemically, and physically,” with most being “resistant to
lysis with detergents,” that obtaining “a high yield of extracted nucleic acid
may require more than one type of method because different types of cell
walls will be better lysed by certain methods than others” with some
methods negatively impacting the yield and/or requiring additional
purification steps. Ans. 4.
In addition to traversing the Examiner’s restated rationale (Reply Br.
4—5), Appellants contend, for a number of reasons, that the Examiner has not
established that Fong, Einsele, and Karakousis teach or suggest the claimed
methods. Appeal Br. 11—20; Reply Br. 5—7.
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a prima
facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
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record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
In the present case, Appellants do not persuade us that a
preponderance of the evidence fails to support the Examiner’s conclusion
that the nucleic acid purification method of claim 1 would have been
obvious to an ordinary artisan. Unless otherwise indicated herein, we adopt
the Examiner’s findings of fact, reasoning on scope and content of the
claims and prior art, and conclusions set out in the Final Action and
Answer.7 Only those arguments made by Appellants in the Appeal Brief
and properly presented in the Reply Brief have been considered in this
Decision. Arguments not so presented in the Briefs are waived. See 37
C.F.R. § 41.37(c)(l)(iv) (2015); see also Ex parte Borden, 2010 WL 191083
at *2 (BPAI 2010) (informative) (“Any bases for asserting error, whether
factual or legal, that are not raised in the principal brief are waived.”).
As required by claim 1, Fong discloses a method of extracting fungal
nucleic acid from a sample comprising treating the sample with the enzymes
lysostaphin and lyticase in a reaction mixture, prior to extracting the nucleic
acid. Fong || 4, 11, 15. Also as required by claim 1, Fong discloses
multiple known methods of mechanical treatment used to extract nucleic
acids. Id. at 13. While Fong discloses that its claimed method is suitable
for automation because it “can be used on a variety of types of
microorganisms, can be carried out in a single reaction vessel, and does not
require any mechanical or physical shearing methods,” {Id. at 19) Fong does
7 We note the Examiner’s concession at Ans. 4 that “[n]o mechanical
treatment is taught by Einsele,” and adopt the Examiner’s revised findings
regarding Einsele.
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not teach that mechanical methods cannot be used, only that methods
employing mechanical disruption “are not suitable for automation.” Id. at
1 5. The claimed method does not require automation.
A teaching away requires a reference to actually criticize, discredit, or
otherwise discourage the claimed solution. See In re Fulton, 391 F.3d 1195,
1201 (Fed. Cir. 2004) (“The prior art’s mere disclosure of more than one
alternative does not constitute a teaching away from any of these alternatives
because such disclosure does not criticize, discredit, or otherwise discourage
the solution claimed”). Appellants do not identify, and we do not find, any
teaching in any of the cited prior art that teaches criticizes, discredits, or
discourages the use of mechanical and enzymatic lytic methods together.
We are thus not persuaded by Appellants’ argument that Fong teaches away
from the claimed method. App. Br. 15, 17—18; Reply Br. 4—5.
We note, as Appellants contend, that none of the references describes
a specific embodiment having the particular combination of steps and
components recited in claim 1. See, e.g., App. Br. 15, 18, and 20, citing
Sanofi-Aventis Deutschland GmbH v. Glenmark Pharmaceuticals Inc., 748
F.3d 1354 (Fed. Cir. 2014) as teaching that “claims in the unpredictable
biomedical arts are not obvious when, as here,... a specific combination
has not been disclosed in the prior art.” App. Br. 20. We are not persuaded
that Appellants have accurately recited the holding of Sanofi or that its facts
are analogous to the facts of this case.
In Sanofi, the plaintiffs patent claimed a combination of two active
ingredients into a single dosage product used to treat hypertension: the
angiotensin converting enzyme (ACE) inhibitor trandolapril, and the calcium
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channel blocker/agonist verapamil hydrochloride. Id. at 1357. The
defendant appealed the jury’s finding of patent validity over a challenge of
obviousness. Id. at 1355. Defendant argued the jury’s verdict was against
the weight of evidence because previously known ACE inhibitors were
“single-ring” compounds, making it obvious to try substituting prior art
compounds with a “double-ring” ACE inhibitor to achieve the claimed
combination. Id. at 1359. Plaintiff argued that there was no prior
knowledge that the combination of a double-ring ACE inhibitor with
calcium antagonists, as patented, would be longer lasting than the
hypertension treatments at the time, and thus the verdict should be sustained.
Id. The court upheld the jury’s verdict that the patent was not invalid as
obvious, finding that substantial evidence supported the jury’s finding that
the skilled artisan would not have predicted the success of longer-lasting
hypertension control by pairing a “double-ring” ACE inhibitor with a
calcium agonist. Id. at 1360.
The facts of Sanofi are not analogous to those in this case. Here, Fong
discloses both mechanical and enzymatic methods are known in the art and
teaches the claimed combination of enzymes, as stated above. In addition,
Karakousis teaches that using enzymatic (lyticase or proteinase K digestion
in a sorbitol based buffer) and mechanical methods (grinding with mortar
and pestle) together resulted in “substantial improvements” in yield.
Karakousis 46-47. Therefore, unlike Sanofi in which there was no prior
teaching of making the claimed combination, here, mechanical and
enzymatic methods were previously taught to improve yield, and the claimed
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combination of lysostaphin and lyticase enzymes to extract nucleic acids
was known.
As the Supreme Court has explained, “when a patent ‘simply arranges
old elements with each performing the same function it had been known to
perform’ and yields no more than one would expect from such an
arrangement, the combination is obvious.” KSRInt’l Co. v. Teleflex Inc.,
550 U.S. 398, 417 (2007) (quoting Sakraida v. AgPro, Inc., 425 U.S. 273,
282 (1976)). In the present case, as noted above, Fong discloses both
mechanical and enzymatic methods are known in the art and teaches the
claimed combination of enzymes, as stated above. Karakousis teaches that
using enzymatic and mechanical methods together resulted in improved
yield. Accordingly, we are unpersuaded by Appellants’ argument that “the
Office does not indicate how methods designed to avoid mechanical
disruption may be combined with methods that rely on mechanical
disruption with an expectation of arriving at a working method.” App. Br.
17. As discussed above, Karakousis teaches that mechanical and enzymatic
methods when used together yield improved recovery as opposed to
individual use of each method. Karakousis 46-47.
In light of Karakousis’ teaching of the need to explore various
methods to identify optimal nucleoid acid extraction methods (e.g.,
Karakousis 39), we discern no error in the Examiner’s conclusion that it
would have been obvious to employ the pretreatment of microbes with
enzymes as taught by Fong, followed by mechanical treatment as taught by
Karakousis. Final Act. 5. Indeed, we find the subject matter of Appellants’
claim 1 prima facie obvious in view of Fong and Karakousis alone. The
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Board may rely upon fewer than all the references cited by the Examiner.
See In re May, 574 F.2d 1082, 1090 (CCPA 1978).
We acknowledge, but are unpersuaded by, Appellants’ contention
(App. Br. 19) that the claimed method produces unexpected results, given
that Karakousis teaches the combination of enzymatic and mechanical lysis
resulted in “substantial improvements.” Karakousis 46-47. Appellants fail
to adduce any persuasive evidence of record as to why a person of ordinary
skill in the art at the time of invention would have found Appellants’
invention to be unexpected or surprising when compared to the nearest prior
art, here, Karakousis’ “substantial improvements.” See In re Baxter
TravenolLabs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected
results are used as evidence of nonobviousness, the results must be shown to
be unexpected compared with the closest prior art”). See also Bristol-Myers
Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014)
(“To be particularly probative, evidence of unexpected results must establish
that there is a difference between the results obtained and those of the closest
prior art, and that the difference would not have been expected by one of
ordinary skill in the art at the time of the invention.”).
Although Appellants assert that the results shown on page 8 of the
Specification and in Table 1 and Figure 2 show unexpectedness, Appellants
produce no evidence comparing the results obtained to any prior art process,
as required. Indeed, the arguments advanced by Appellants point to
precisely the advantages that a person of ordinary skill would expect from
combining the references, as seen in Karakousis, and therefore speak
directly to why a person of ordinary skill in the art would be motivated to
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combine the references. In addition, the only assertion of record that the
results presented in the Specification were unexpected appears in
Appellants’ briefs. Appellants’ contentions, therefore, are unsupported
attorney argument, which is not sufficient to rebut the Examiner’s evidence-
supported prima facie case. See In re Geisler, 116 F.3d 1465, 1471 (Fed.
Cir. 1997). Consequently, we are not persuaded by Appellants’ arguments
as the results identified by Appellants as unexpected do not overcome the
strong case of obviousness based on the express teachings of Fong and
Karakousis. See Newell Co., Inc., (Fed. Cir. 1988), 864 F.2d at 768 (finding
alleged unexpectedly superior results were ultimately insufficient to
overcome the conclusion of obviousness based on findings of fact). Pfizer,
Inc. v. Apotex, Inc., 480 F.3d 1348, 1372 (Fed. Cir. 2007) (secondary
consideration of unexpected results “does not overcome the strong showing
of obviousness in this case”). To the extent that Appellants appear to argue
the alleged unexpected results are due to the absence of a chelating agent
(see App. Br. 19), we note that this argument relates only to claim 21,
discussed below, as claim 1 does not exclude use of a chelating agent.
We also acknowledge, but are unpersuaded by, Appellants’ contention
that the Examiner’s rejections are “based on a combination of references
made impermissibly in hindsight.” App. Br. 17. Appellants point to no
persuasive evidence that any of the Examiner’s findings were beyond the
level of ordinary skill at the time of the invention or could have been taken
only from Appellants’ Specification. See In re McLaughlin, 443 F.2d 1392,
1395 (CCPA1971).
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In sum, for the reasons discussed, Appellants do not persuade us that a
preponderance of the evidence fails to support the Examiner’s conclusion
that the nucleic acid purification method of claim 1 would have been prima
facie obvious to an ordinary artisan. We, therefore, affirm the Examiner’s
rejection of claim 1 over Fong and Karakousis. Because they were not
argued separately, claims 4—14 fall with claim l.8 37 C.F.R.
§ 41.37(c)(l)(iv).
OBVIOUSNESS - CLAIM 21
Appellants separately argue claim 21, which depends from claim 1
and further recites “wherein said reaction mixture does not comprise a
chelator.” App. Br. 24 (Claims Appendix). Appellants argue that Fong,
Einsele, and Karakousis each use a chelating agent in their respective lytic
8 Although Appellants’ Brief at 16 mentions method steps and components
recited in claims 8—12 that Appellants allege the Examiner has not
addressed, no mention is made of any component or step recited in claims 4—
7, 13, or 14. Moreover, separately arguing a claim requires “more
substantive arguments in an appeal brief than a mere recitation of the claim
elements and a naked assertion that the corresponding elements were not
found in the prior art.” In reLovin, 652 F.3d 1349, 1357 (Fed. Cir.
2011). As Appellants’ arguments for all but claim 21 are restricted in this
regard, we find Appellants waived arguments regarding these individual
claims. See Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir. 2008) (“In the
event of such a waiver, the PTO may affirm the rejection of the group of
claims that the examiner rejected on that ground without considering the
merits of those rejections.”). We note, moreover, that 37 C.F.R.
§ 41.37(c)(l)(iv) requires separate subheadings for separately argued claims,
and that claim 21 was the sole claim argued in the manner required by the
rule. See App. Br. 21.
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reactions, with Fong specifically teaching that its method ‘“utilizes a high
concentration of a chelating agent.” App. Br. 21. Appellants argue that the
Examiner’s Final Action “fails to indicate how a reaction mixture that
excludes a chelating agent is obvious over three references that alone, and in
combination, provide methods that use a chelating agent.” Id. at 22.
The Examiner responds that Fong teaches that “many of the listed
hydrolytic enzymes are shown to have optimal activity in the presence of
divalent metal ions, and it is the examiner’s position this would likely
preclude including chelating agents with those enzymes, (see claim 21).”
Ans. 3. The Examiner further states that no chelating agents are included in
the reactions discussed on page 47 column 1 “as well as in combination with
lyticase and other enzymes with buffers.” Id. at 3^4.
In reply, Appellants argue that the Examiner’s first responsive
statement is personal opinion and contrary to the teachings of Fong. Reply
Br. 1—2. Appellants further reply that the Examiner’s statement regarding
Karakousis’ lack of chelating agents is generic and without reference to
any specific experiment, and that the portion of Karakousis used by the
Examiner to reject the claims in fact teaches use of a chelating agent. Id. at
2-3.
We find Appellants have the better argument. Fong teaches that the
activity of divalent metal ions is enhanced by chelation:
It is also well documented that lyticase can effectively degrade
the yeast cell wall mainly via the P-l,3-glucanse activity. Many
of these hydrolytic enzymes are shown to have optimal activity
in the presence of divalent metal ions, such as Mg++, Ca++,
etc. It is well documented that lyticase activity requires a
reducing agent, such as P-mercaptoethanol or DTT, to
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effectively lyse the yeast cell wall. EDTA is a well known metal
chelator which is very effective in weakening the outer cell
membrane of bacteria by chelating the Mg++ and Ca++,
which are essential elements holding the membranes structure
by linking LPS (lipopolysaccharide) and proteins together.
Fong 14 (emphasis added). Furthermore, Karakousis teaches use of a
chelating agent in its lyticase digestion buffer, as stated by Appellants.
Reply Br. 3^4. Additional arguments taught by Karakousis on page 47,
which may have been the experiments referenced by the Examiner, teach use
of the sorbitol buffer (with a chelating agent) or a commercial “MO BIO
kit,” (see Karakousis 44, Figure 2 legend) which the Examiner has not
shown does not contain chelating agents.
“An examiner bears the initial burden of presenting a prima facie case
of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011). Because that burden has not been carried here, we reverse the
rejection of claim 21 under 35 U.S.C. § 103(a).
SUMMARY
For the reasons discussed, we affirm the rejection of claims 1
and 4—14 under pre-AIA 35 U.S.C. § 103(a) as obvious over Fong and
Karakousis, but reverse the rejection of claim 21 over these
references.
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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