Ex Parte Brillowska-Dabrowska

Patent Trial and Appeal Board

Aug 24, 2016

14175853 (P.T.A.B. Aug. 24, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/175,853 02/07/2014 Anna H. Brillowska-Dabrowska
270 7590 08/26/2016
HOWSON & HOWSON LLP
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Building 620, Suite 210
Blue Bell, PA 19422
UNITED STATES DEPARTMENT OF COMMERCE
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ATTORNEY DOCKET NO. CONFIRMATION NO.
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EXAMINER
PANDE, SUCHIRA
ART UNIT PAPER NUMBER
1637
NOTIFICATION DATE DELIVERY MODE
08/26/2016 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANNA H. BRILLOWSKA-DABROWSKA
Appeal2016-006485
Application 14/175,853 1
Technology Center 1600
Before ULRIKE W. JENKS, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
FLAX, Administrative Patent Judge.
DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a method of extracting nucleic acid from fungi. Claims 1,
2, 6-9, and 16 are on appeal as rejected under 35 U.S.C. § 103(a). We have
jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 The Real Party in Interest is Statens Serum Institut. Br. 4.
Appeal2016-006485
Application 14/175,853
STATEMENT OF THE CASE
The Specification describes, "[t]he current diagnosis of dennatophytes
[a fungal skin infection] is based on microscopic identification of spores and
hyphae in clinical specimens followed by in vitro culture and morphological
identification of the fungus," and that this technique has too low sensitivity,
shows false negative results too often, and may take several weeks for
results. Spec. 2, 19-26. As an improved diagnosis technique, the
Specification describes, "a three step[] procedure [for] the extraction of
DNA from e.g. nail samples and enables the diagnosis of infections caused
by any of the dermatophytes (pan-dermatophyte)," e.g., "Trichophyton
rubrum, Microsprorum canis, Trichophyton mentagrophytes-Trichophyton
tonsurans complex and Epidermophytonjloccosum infection." Spec. 3, 1. 33
to 4, 1. 4. The Specification describes an embodiment, as follows:
a method of extracting nucleic acid from fungi comprising the
steps of heating the sample in a lysis buffer and subsequent
mixing the solution with a neutralizing buffer, where the lysis
buffer consists of a reducer, a salt and a buffering compound in
an aqueous solution and the neutralizing buffer is a 0,5 [sic] -
3 % w/v, preferably a 2 % w/v protein solution. The target fungi
belong to the group of yeasts (e.g. Candida albicans, Candida
glabrata, Pichia pastoris, Sacharomyces cerevisiae) and molds,
especially keratinophylic fungi, dermatophytes, which are
species belonging to the genera Trichophyton, Epidermophyton
or Microsporum. The reducer in the lysis buff er is chosen from
sodium carbonate, sodium sulfite, beta-mercaptoethanol,
dithiotreitol, sodium sulfide, sodium chlorate, sodium iodate and
sodium bicarbonate, the salt is chosen from potassium chloride
and ammonium persulfate and where the buffering compound is
chosen from sodium salt of 3-(Cyclohexylamino )-2-hydroxy-
lpropanesulfonic acid, TRIS, HEPES, phosphate buffer. A
preferred lysis buffer consists of potassium chloride (KCl),
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Application 14/175,853
sodium bicarbonate (NaHC03) and tris(hydroxymethyl)
aminomethane (TRIS). The sample in lysis buffer is heated to
between 80 and 100°C, preferably 95°C for app. 10 minutes. The
protein in the neutralizing buff er can be chosen from bovine
serum albumin (BSA), ovalbumin or other suitable protein.
Spec. 4, 1. 26 to 5, 1. 6.
The appealed claims can be found in the Claims Appendix of the
Appeal Brief. Claim 1 is the sole independent claim and reads as follows:
1. A method of extracting nucleic acid from fungi comprising
the following steps:
(a) heating a patient sample containing the fungi in a lysis buffer
to between 80 and 100°C for a period not to exceed 10 minutes,
said patient sample selected from the group consisting of hair,
skin, and nail; and
(b) mixing the solution with a neutralizing buffer;
wherein said lysis buffer consists of, in aqueous solution: (i) a
reducer selected from the group consisting of sodium carbonate,
sodium sulfate, betamercaptoethanol, dithiothreitol, sodium
sulfide, sodium chloride, sodium chlorite, sodium iodate, and
sodium bicarbonate; (ii) a salt selected from the group consisting
of potassium chloride and ammonium persulfate; and (iii) a
buffering compound selected from the group consisting of
CAPSO, TRIS, HEPES, and phosphate buffer;
wherein said neutralizing buffer is an aqueous 0.5 - 3% w/v
protein solution; and
wherein the cell wall of said fungi is not disrupted prior to step
(a).
Br. 18 (Claims App'x).
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Appeal2016-006485
Application 14/175,853
The following rejections are on appeal:
Claims 1, 2, 6, 7, 9, and 16 rejected under 35 U.S.C. § 103(a) over
Liu,2 Machouart,3 Bair,4 Sreenivasaprasad,5 Wang,6 and Al-Soud.7 Final
Action 7.
Claim 8 rejected under 35 U.S.C. § 103(a) over Liu, Machouart, Bair,
Sreenivasaprasad, Wang, Al-Soud, and Ronaghi. 8 Final Action 22.
DISCUSSION
We address both obviousness rejections together because the same
determinative facts and arguments apply to each.
The Examiner determined that Liu combined with Machouart, Bair,
Screenivasaprasad, Wang, and Al-Soud disclosed a method rendering the
2 Don Liu et al., Rapid Mini-Preparation of Fungal DNA for PCR, 38 J.
CLTI-HCAL l\1ICROBIOLOGY 471 (2000) (hereinafter "Liu").
3 Marie Machouart-Dubach et al., Rapid Discrimination among
Dermatophytes, Scytalidium spp., and Other Fungi with a PCR-Restriction
Fragment Length Polymorphism Ribotyping Method, 39 J. CLINICAL
MICROBIOLOGY 685-90 (2001) (hereinafter "Machouart").
4 U.S. Patent Application Pub. No. US 2007/0043216 Al (published Feb. 22,
2007) (hereinafter "Bair").
5 Surapareddy Sreenivasaprasad, Isolation of Fungal Nucleic Acids, Chapter
8 in THE NUCLEIC ACID PROTOCOLS HANDBOOK 37--45 (2000)
(hereinafter "Sreenivasaprasad").
6 Danhui Wang et al., A High-Throughput System for the Rapid Extraction of
Plant Genomic DNA for Genome Mapping and Marker-Assisted Breeding
Studies, 10 JALA 242--45 (2005) (hereinafter "Wang").
7 Waleed Abu Al-Soud and Peter Radstrom, Effects of Amplification
Facilitators on Diagnostic PCR in the Presence of Blood, Feces, and Meat,
38 J. CLINICAL MICROBIOLOGY 4463-70 (2000) (hereinafter "Al-Soud").
8 Mostafa Ronaghi, Pyrosequencing Sheds Light on DNA Sequencing, 11
GENOME RES. 3-11 (2001) (hereinafter "Ronaghi").
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Appeal2016-006485
Application 14/175,853
claimed subject matter obvious thereover. The Examiner has combined
several references and cited discrete portions thereof aimed at identifying
each individual element of the appealed claims. While there is no error in
the combining of a plurality prior art where there is motivation to do so, the
question here is whether this combination presents a prima facie case for
obviousness and includes the necessary motivation-to-combine to hold it
together. We find that the final rejection fails.
Appellants contend there is insufficient explanation in the rejections
as to how the prior art references would be combined to yield predictable
results with an expectation of success and that there was no motivation to
make the combination. Br. 11. We find the preponderance of the evidence
of records supports Appellants' contentions. Absent the use of
impermissible hindsight using the present claims as a roadmap, we fail to see
how and why the Examiner's combination would have been made.
Liu disclosed a straight-forward, "rapid, low-cost, and reliable DNA
extraction procedure for fungi" where a solution of Tris lysis buffer, NaCl,
sodium dodecyl sulfate, and EDTA are used to extract DNA from a lump of
mycelia fungi tissue. Liu 4 71. This is left at room temperature and
potassium acetate is added to neutralize the solution. Id. This method is
described by Liu as taking only an hour and as "optimized." Id.
The Examiner cites Machouart as supporting the determination that
the fungi of Liu could be obtained from samples of hair/skin/nail and also
determined that one of ordinary skill in the art would have been motivated to
combine Machouart with Liu because patients may be suspected to have
dermatitis. Final Action 10-11. This is not an unreasonable determination.
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The Examiner cites Bair for the purpose of replacing Liu's NaCl salt
with KCl (an RNA-complexing salt in lysis solution) and as confirmation
that Tris may be used as a buffer. Final Action 12-16. Bair does indicate
NaCl and KCl are likely interchangeable alternatives, but it is unclear why a
skilled artisan would replace Liu's salt with the alternative of Bair.
The Examiner also cites Bair for disclosure of B-mercaptoethanol as a
reducer to replace Liu's EDTA. Final Action 14, 18. While Bair does
disclose combining either TCEP or B-ME with EDTA "to reduce the
disulfide bonds in RN ases ... necessary ... for high RN ase-containing
tissues, for example, spleen and pancreas," (Bair ,-i 67), it is unclear why
such a replacement with or even mere addition of B-ME would be useful in
Liu' s process. We are not persuaded by the Examiner's determination.
The Examiner also determined that Bair taught or suggested adding
heat to increase the solubility of KCl and ammonium chloride used as a salt
(inserted in Liu's process), but also expressed that Liu's detergent (sodium
dodecyl sulfate) would be removed because its presence reduces the
solubility of ammonium chloride. Final Action 15-16. Exactly where the
motivation would come from to make these changes to the "optimized"
process of Liu is not clear and we are not persuaded it existed.
Following from the determination that the room temperature process
of Liu needs added heat to increase salt solubility, the Examiner cites
Sreenivasaprasad for a disclosure of heating a sample to 100°C (for 11 min)
during its process. Final Action 16. The primary motivation for this change,
besides the Examiner's perceived need to change Liu' s disclosed salt to
similar salts with solubility difficulties in the presence of detergent, which
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Application 14/175,853
the Examiner determined is present in, but should be removed from Liu, is
that such heating would "not destroy nucleic acids and [is] routinely used."
Id. We are again unpersuaded there would have been motivation to make
such a change to Liu' s process.
Similarly, the Examiner cites Wang because it disclosed heating a
sample to 85°C for 10 min. The Examiner has not sufficiently articulated
why the person of ordinary skill in the art would have looked to Wang to
improve Liu's method and it appears that the Examiner has improperly used
hindsight to find references that bookmark the recited process's heating
limitation (and other limitations).
Because none of the aforementioned references disclosed adding
protein, the Examiner cites Al-Soud for the use of BSA at 0.6% w/v. Final
Action 20-21. Al-Soud disclosed the use of this protein to enhance
amplification when substances such as meat/blood/feces are present. See Al-
Soud 4463. It is unclear why adding this protein to the process of Liu,
which does not mention fungal proximity to meat or blood or feces, would
be particularly useful.
"Obviousness requires more than a mere showing that the prior art
includes separate references covering each separate limitation in a claim
under examination." Unigene Labs., Inc. v. Apotex, Inc., 655 F.3d 1352,
1360 (Fed. Cir. 2011). "Rather, obviousness requires the additional showing
that a person of ordinary skill at the time of the invention would have
selected and combined those prior art elements in the normal course of
research and development to yield the claimed invention." Id. Moreover,
while it is well-established that any obviousness analysis must, on some
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level, rely on hindsight, it is impermissible to engage in a hindsight
reconstruction of the claimed invention, using the applicant's invention as a
template and selecting elements from references to fill the gaps.
Interconnect Planning Corp. v. Feil, 774 F.2d 1132, 1143 (Fed. Cir. 1985).
Here, the obviousness rejections of the claims fails under these tests. The
Examiner has not explained why, based on the cited combination, the skilled
artisan would have increased the temperature in Liu' s lysis process, added
additional salts to the lysis buffer, replaced Liu's reducer, removed its
detergent, and then neutralized with a buffer containing protein.
For the above reasons, we find the preponderance of evidence of
record does not support the Examiner's determination that the claims would
have been obvious over the cited prior art combinations. Therefore, we
reverse the rejections.
S Ul\11\.1,,L\ .. R Y
The rejection of claims 1, 2, 6, 7, 9, and 16 under 35 U.S.C. § 103(a)
over Liu, Machouart, Bair, Sreenivasaprasad, Wang, and Al-Soud is
reversed.
The rejection of claim 8 under 35 U.S.C. § 103(a) over Liu,
Machouart, Bair, Sreenivasaprasad, Wang, Al-Soud, and Ronaghi is
reversed.
REVERSED
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