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Patent Trials and Appeals Board

Nov 20, 2019

15581344 - (D) (P.T.A.B. Nov. 20, 2019)

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.
15/581,344 04/28/2017 Makiko Yoshimoto TORT-100US1 3873
23122 7590 11/20/2019
RATNERPRESTIA
2200 Renaissance Blvd
Suite 350
King of Prussia, PA 19406
EXAMINER
SISSON, BRADLEY L
ART UNIT PAPER NUMBER
1634
NOTIFICATION DATE DELIVERY MODE
11/20/2019 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):
PCorrespondence@ratnerprestia.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte MAKIKO YOSHIMOTO, HIDEO AKIYAMA,
and HITOSHI NOBUMASA
____________

Appeal 2019-004740
Application 15/581,344
Technology Center 1600
____________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and
MICHAEL A. VALEK, Administrative Patent Judges.

VALEK, Administrative Patent Judge.

DECISION ON APPEAL
Appellant1 submits this appeal under 35 U.S.C. § 134(a) involving
claims to a method for extracting RNA from a biological sample. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
STATEMENT OF THE CASE
Appellant’s Specification states that a method “for isolation of RNA
frequently employed [is] phenol extraction, precipitation from chaotropic
salt solutions and adsorption to silica membranes.” Spec. ¶ 2. The

1 We use the word “Appellant” to refer to “applicant” as defined in
37 C.F.R. § 1.42. Appellant identifies Toray Industries, Inc. as the real party
in interest.
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Specification refers to two prior art references describing solutions for such
methods––one disclosing “a solution for RNA extraction comprising 2 to 5
M guanidine and 40 to 60% phenol” and a second disclosing a solution
comprising “a 30 to 50% phenol solution containing 0.5 to 2 M guanidine.”
Id. ¶¶ 3–4. According to the Specification, “RNA isolated using the
solutions and methods described in [these references] still shows
contamination with (residual) genomic DNA in an amount which can be
detected by the reverse transcription-polymerase chain reaction assay (RT-
PCR), leading to problems such as loss of quantitativeness of RNA” and
thus an additional step, e.g., treatment with DNase, is required to remove the
DNA. Id. ¶¶ 6–8. “The present invention aims to solve these problems”
based on the “present inventors . . . discover[y] that the phenol concentration
has an especially strong relationship with the effect of prevention of
contamination with DNA.” Id. ¶¶ 10–11.
Claims 7, 8, and 11–17 are on appeal and can be found in the Claims
Appendix of the Appeal Brief. Claim 7 is representative of the claims on
appeal. It reads as follows:
7. A method for extracting RNA from a biological sample
containing RNA and at least DNA, said method comprising the
steps of:
homogenizing said biological sample together with a solution
comprising:
(a) phenol in an amount of not less than 53% by volume
based on the total amount of said solution, wherein the amount
of phenol does not exceed a percentage that excludes any of
components (b)-(e);
(b) an aliphatic alcohol having a plurality of hydroxyl
groups in an amount of 3 to 10% by volume based on the total
amount of said solution;
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(c) a guanidinium salt at a concentration of 0.5 to 2.0 M
based on the total amount of said solution;
(d) a thiocyanate at a concentration of 0.1 to 0.5 M based
on the total amount of said solution;
(e) a buffer for maintaining the pH of said solution at 4 to
6;
centrifuging the obtained mixture; and recovering an RNA-
containing aqueous layer produced by the centrifugation.
App. Br. 15.
Appellant seeks review of the following rejections:
I. Claims 7, 8, and 11–17 under 35 U.S.C. § 102 as
anticipated by Chomczynski;2 and
II. Claims 7, 8, and 11–17 under 35 U.S.C. § 103 as obvious
over Chomczynski.
App. Br. 5.
Analysis
I. Anticipation Rejection
The issue for this rejection is whether the preponderance of the
evidence supports Examiner’s finding that Chomczynski anticipates
Appellant’s claims.
Examiner finds that Chomczynski describes a method for isolating
substantially pure RNA suitable for PCR using a solution with the same
ingredients as in claim 7. See Final 5–7. The only difference is that
Chomczynski states that the amount of phenol in that solution ranges from
“about 30%-50% by volume,” whereas Appellant’s claims recite phenol in
“an amount of not less than 53% by volume.” Id. at 6 (quoting
Chomczynski 4:58). Notwithstanding the foregoing difference in phenol

2 US 5,346,994, issued Sept. 13, 1994 (“Chomczynski”).
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concentration, Examiner determines Chomczynski anticipates because “[t]he
use of the expression ‘about’ is recognized as encompassing values both
below and above the recited value.” Id.
Appellant contends Examiner erred in finding that Chomczynski
anticipates the claimed phenol range because the word “about” in
Chomczynski’s stated range of “about 30%-50%” modifies only the lower
boundary, i.e., 30%. Appeal Br. 6. Appellant further argues that even if
“about” is interpreted to apply to both the “floor and ceiling of the phenol
range disclosed by Chomczynski, there is no support in the record to suggest
that ‘about’ 50% would include the floor of Appellant’s range, i.e., 53%.”
Reply Br. 3.
We are persuaded by Appellant’s argument that Chomczynski does
not disclose the solution recited in Appellant’s claims. An amount that is
“not less than 53%,” as recited in claim 7, is not the same as Chomczynski’s
disclosure of solutions of “about 30%-50%” phenol. Even if “about”
modifies the upper limit of Chomczynski’s range, Examiner failed to
establish an evidentiary basis on this record to support a finding that about
50% reads on a solution comprising “not less than 53% phenol,” as claimed.
Therefore, Chomczynski does not anticipate. See Titanium Metals, 778 F.2d
at 783 (“[A]nticipation under § 102 can be found only when the reference
discloses exactly what is claimed.”).
The ’155 patent,3 which Chomczynski incorporates by reference, does
not support the anticipation rejection. See Ans. 12 (relying on the phenol
range taught in the ’155 patent). The ’155 patent discloses a different

3 US 4,843,155, issued June 27, 1989 (“’155 patent”).
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isolation method wherein a solution comprising “about 40% to about 60%
phenol” is used in combination with a higher amount of guanidinium (i.e., 2-
5 M). See ’155 patent, 2:44–46, 3:40. Chomczynski distinguishes the
method in the ’155 patent, stating it is not “capable” of achieving the results
of the method taught therein. Chomczynski, 2:48–55. Accordingly,
Chomczynski and the ’155 patent disclose two distinct methods. Examiner
cannot combine aspects of the ’155 patent’s method with Chomczynski’s
method to demonstrate anticipation of the present claims. See Sanofi-
Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1083 (Fed. Cir. 2008) (“To
anticipate, the reference must not only disclose all elements of the claim
within the four corners of the document, but must also disclose those
elements arranged as in the claim.”) (quotations omitted). Accordingly, we
reverse the rejection of claims 7, 8, and 11–17 as anticipated by
Chomczynski.
II. Obviousness Rejection
The issue for this rejection is whether the preponderance of the
evidence supports Examiner’s finding that Appellant’s claims are obvious
over Chomczynski.
Examiner determines that if Chomczynski does not anticipate,
Appellant’s claims are “still deemed to have been obvious” over that
reference. Final 7. In particular, Examiner determines it would be a matter
of routine and obvious optimization for a skilled artisan to “adjust[] the
concentrations of a known reactant [phenol] from 50% to 53%,” as claimed.
Id. at 8.
Appellant argues “even assuming Chomczynski presents a prima facie
case of obviousness” that case is rebutted by Appellant’s evidence of
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“secondary considerations of non-obviousness.” Appeal Br. 5. Specifically,
Appellant relies on the Declaration of Ms. Makiko Yoshimoto dated Sept. 5,
2015 (“Yoshimoto Decl.”), which it contends presents “unexpected and
surprising results” achieved by using a solution comprising 53% phenol as
compared to one with 50% phenol. Id. at 13.
Upon considering the record as a whole, we determine that the
preponderance of the evidence of record does not support Examiner’s
conclusion of obviousness. As discussed below, Appellant’s evidence of
unexpected results is sufficient to overcome Examiner’s prima facie
showing.
Appellant does not specifically dispute Examiner’s finding it would
be routine to adjust the concentration from 50% to 53%. See Appeal Br. 11–
13. Thus, we find no error in Examiner’s conclusion that Chomczynski
supports a prima facie showing of obviousness
What distinguishes Appellant’s claims, however, is the evidence of
unexpected results set forth in Appellant’s Specification and the Yoshimoto
Declaration.4 The Specification provides examples that allow for a

4 Examiner states that the Yoshimoto Declaration is not part of the record
because it was not “presented prior to the filing of the notice of appeal” on
September 30, 2018. Ans. 15. However, as Appellant points out, the
Yoshimoto Declaration, which was originally filed in support of the parent
application 13/816,792, was also presented in support of the present
application in Appellant’s responses filed September 12, 1017 and February
21, 2018. Reply Br. 1–2, n. 1. In each response, Appellant expressly relied
on the Yoshimoto Declaration to advance its unexpected results argument,
quoted the pertinent data from such, and identified where the declaration
appeared in file history for the ’792 application. 9/12/17 Resp. 7–8; 2/21/18
Resp. 8–9. In the first of these responses, Appellant also stated that a copy
of the Yoshimoto Declaration was supplied with the response “[f]or
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comparison of the solution of the claimed method (e.g., Examples 1–4) to
the closest prior art (i.e., a solution with 50% phenol as in Comparative
Example 1). See Spec. ¶¶ 39–79. The Specification also includes figures
showing electropherograms of RNA isolated in these examples. Id. at Figs.
1–4. According to the Specification, the solutions in Examples 1–4, which
comprise varying amounts of phenol ranging from 53% to 65%, but are
otherwise identical to the solution in Comparative Example 1, resulted in
RNA with “good” purity. Id. at 43, 45 (Tables 1 and 3). In contrast, the
purity obtained using the 50% phenol solution in Comparative Example 1
was “not good.” Id.
The Yoshimoto Declaration quantifies these results by calculating the
relative amounts of the RNA and DNA in each of these examples based on
their electropherograms. See Yoshimoto Decl. ¶¶ 8–11. According to the
Yoshimoto Declaration, the content of contaminating DNA in Comparative
Example 1 was 63% of the total nucleic acid isolated, whereas it was only 2-
8% in Examples 1–4. Id. at ¶ 11. The Specification explains these results
are significant because RNA obtained according to the prior art method in
Comparative Example 1 requires further purification before it can be
amplified via PCR, whereas the claimed method yields RNA that is

convenience.” 9/12/17 Resp. 7, n.1. But it appears that copy was not
included with that filing. Notwithstanding that oversight, we agree with
Appellant that the Yoshimoto Declaration was presented in support of the
present application prior to the date of the notice of appeal and is therefore
part of the record before us. In contrast, Appellant appears to concede that it
did not present the “Second Yoshimoto Declaration” prior to noticing this
appeal and we do not rely on it for our decision here. See Appeal Br. 4.
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sufficiently free of contaminating DNA to be amplified without additional
purification. See Spec. ¶¶ 6, 16.
We agree with Appellant that, on this record, the results evidenced by
the Specification and Yoshimoto Declaration are unexpected and probative
of non-obviousness. Considering “the entire merits of the matter” in light of
this evidence, we determine that the preponderance of the evidence does not
support the rejection. See In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir.
1986). Accordingly, we reverse.
CONCLUSION
The rejection of claims 7, 8, and 11–17 under 35 U.S.C. § 102 as
anticipated by Chomczynski is reversed. The rejection of claims 7, 8, and
11–17 under 35 U.S.C. § 103 as obvious over Chomczynski is reversed.
DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
7, 8, 11–17 102 Chomczynski 7, 8, 11–17
7, 8, 11–17 103 Chomczynski 7, 8, 11–17
Overall
Outcome
7, 8, 11–17

REVERSED