Ex Parte Harkins

Patent Trial and Appeal Board

Dec 30, 2015

11810349 (P.T.A.B. Dec. 30, 2015)

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.
11/810,349 06/05/2007 Lualhati E. Harkins N333.12-0001 2298
54704 7590 12/30/2015
LAW OFFICE OF PHILLIP F. FOX
10985 40TH PLACE NORTH
PLYMOUTH, MN 55441
EXAMINER
SCHUBERG, LAURA J
ART UNIT PAPER NUMBER
1657
MAIL DATE DELIVERY MODE
12/30/2015 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 PATENT TRIAL AND APPEAL BOARD
____________

Ex parte LUALHATI E. HARKINS1
____________

Appeal 2013-006245
Application 11/810,349
Technology Center 1600
____________

Before ULRIKE W. JENKS, JOHN G. NEW, and
JACQUELINE T. HARLOW, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims directed
to a composition for fixing biological samples. The Examiner rejects the
claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 According to Appellant, the Real Party in Interest is Newcomer Supply,
Inc. (App. Br. 2.)
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Application 11/810,349

2
STATEMENT OF THE CASE
Claims 1–31, 36, and 37 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief. Claim 1 is illustrative of the claims
on appeal, and reads as follows:
1. A composition, the composition comprising:
an aldehyde;
alcohol; and
a ketone; the volumetric ratio of the alcohol to the ketone
in the composition ranging from as low as about 0.8: 1 to as
high as about 4.5: 1 and the volumetric ratio of the alcohol to
the aldehyde in the composition ranging from as low as about
41.5: 1 to as high as about 450: 1.
Appellant seeks review of the Examiner’s rejection of claims 1–31,
36, and 37 under 35 U.S.C. § 103(a) as unpatentable over Bresser.2
The issue is: Does the preponderance of evidence of record support
the Examiner’s conclusion that based on the teachings of Bresser the
ordinary artisan would have been motivated to adjust the aldehyde levels of
the typical fixative solution as disclosed in Bresser?
Findings of Fact
FF1. Bresser discloses a typical fixative containing “20%-30% ethanol,
5% formalin and 5% acetone.” (Bresser col. 8, ll. 65–68; Ans. 4.)
FF2. Bresser discloses that fixatives generally “include 10-40% ethanol,
methanol, acetone or combinations thereof. These fixatives provide
good preservation of cellular morphology and preservation and
accessibility of antigens, and high hybridization efficiency.” (Bresser
col. 8, ll. 44–48; see Ans. 4.)

2 Bresser et al., US 5,225,326, issued July 6, 1993.
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Application 11/810,349

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FF3. Bresser discloses that
[T]he “fixative” component of the solution may contain a
compound which fixes the cellular components by cross-linking
these materials together, [such as] for example, . . .
formaldehyde. While this cross-linking agent must meet all of
the requirements above for the precipitating agent, it is
generally more “sticky” and causes the cells and membrane
components to be secured or sealed, thus, maintaining the
characteristics described above. The cross linking agents when
used are preferably less than 10% (v/v).
(Bresser col. 8, ll. 49–60; see Ans. 5, 8–9.)
FF4. Bresser discloses a fixation/hybridization cocktail in the form of a kit
that “contains 15-40% ethanol, 25-40 % formamide, 0-10%
formaldehyde, 0.1-1.5 M LiCl, 0.5-0.15M Tris-acetate (pH78),
0.05%-0.15% Triton-X 100, 20 μg/ml-200 μg/ml non-specific nucleic
acid.” (Bresser, col. 15, ll. 38–41 (emphasis added).)
FF5. Bresser discloses that specimens such as “cells, either as single cell
suspensions or as tissue slices may be deposited on solid supports
such as glass slides . . . [and] are fixed by choosing a fixative which
provides the best spatial resolution of the cells and the optimal
hybridization efficiency.” (Bresser, col. 2, l. 67 to col. 3, l. 5.)
“Specimens constitute any material which is composed of or contains
cells or portions of cells. The cells may be living or dead, so long as
the target biopolymer (DNA, RNA or protein) is unaltered and
undamaged and capable of detection.” (Bresser, col. 7, ll. 37–41.)
Principles of Law
“In cases involving overlapping ranges . . . even a slight overlap in
range establishes a prima facie case of obviousness.” In re Peterson, 315
F.3d 1325, 1329 (Fed. Cir. 2003). “[T]he existence of overlapping or
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Application 11/810,349

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encompassing ranges shifts the burden to the applicant to show that his
invention would not have been obvious.” Id. at 1330.
Analysis
Claim 1
Appellant contends that the Examiner failed to articulate a rationale
for finding obviousness. (App. Br. 12; see also Reply Br. 8.)
We are not persuaded that the Examiner has failed to articulate a
sufficient rationale for adjusting the aldehyde levels with respect to the
fixative formulation. Bresser discloses a fixative containing ethanol,
formalin,3 and acetone (FF1). The Examiner finds that Bresser recognizes
“that the choice of fixative and fixative procedures can affect cellular
constituents and cellular morphology and that one would select ingredients
based on which ones afford the highest hybridization efficiency with good
preservation of morphology.” (Ans. 6; see also FF2.) The Examiner finds
that Bresser disclosed a typical fixative formulation containing “20-30 %
ethanol, 5 % formalin and 5% acetone.” (Ans. 4; FF1) The Examiner finds
that the alcohol to aldehyde ratio in this typical formulation is “4:1 to 6:1
alcohol:ketone - which meets the claimed range, and 4:1 to 6:1
alcohol:aldehyde” (Ans. 4; FF1). The Examiner recognizes that Bresser
does not explicitly provide a formulation “containing the exact same
concentration ratio for alcohol:aldehyde as claimed” (Ans. 4). However, the
Examiner finds that Bresser discloses a range for the formaldehyde fixative
component that overlaps the claimed ratio. Specifically, “Bresser teaches

3 Formalin: An aqueous solution of formaldehyde that is 37 percent by
weight, usually also containing 10 to 15 percent methanol to prevent
polymerization of the formaldehyde. The Free Dictionary
http://www.thefreedictionary.com/formalin (last accessed Dec. 21, 2015).
Appeal 2013-006245
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[that] the fixative component of the solution may contain a compound such
as formaldehyde (aldehyde) in a concentration less than 10% (v/v)” (Ans. 5
(emphasis removed)). The Examiner interprets that less than 10% is a range
from 0-10%. We agree with this interpretation, and this interpretation is
further buttressed by Bresser’s disclosure itself, which recites a
fixation/hybridization cocktail containing formaldehyde in the range of
0-10% formaldehyde (FF4).
The Examiner concludes that Bresser provides a starting point and
[f]ixative concentrations are well known in the art to be
optimizable as they provide a recognized result on the cells that
are treated as evidenced by the Bresser patent which states that
the choice of fixative and fixative procedures can affect cellular
constituents and cellular morphology and that one would select
ingredients based on which ones afford the highest
hybridization efficiency with good preservation of morphology.
(Ans. 6–7; see also FF2 and FF3.) We find no error with the Examiner’s
rationale that based on Bresser’s disclosure it would have been obvious to
optimize the formaldehyde concentration in the fixative solution in order to
preserve cellular morphology.
Appellant contends that optimization per In re Aller, 220 F.2d 454,
456, (CCPA 1955), relied on by the Examiner does not work because “that
particular parameter must first be recognized as a result-effective variable,
i.e., a particular variable which achieves a recognized result, before the
determination of the optimum or workable ranges of said variable might be
characterized as routine experimentation.” (App. Br. 23; see also Reply
Br. 14.)
We are not persuaded by Appellant’s argument that the Examiner
failed to establish that changing the aldehyde concentration is recognized by
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Bresser as being a result-effective variable. The Examiner finds that Bresser
teaches formaldehyde as a fixative component that can range from 0–10%
formaldehyde in the solution. (See Ans. 5; see also 6, 8–9 (“this
concentration range would include very small amounts close to zero which
would allow for a high alcohol to aldehyde ratio such as that claimed by
Appellant”).) We find no error with the Examiner’s interpretation that the
formaldehyde (a.k.a. aldehyde) concentration in the fixative solution is
reasonably interpreted to range from 0–10% formaldehyde, an interpretation
buttressed by Bresser’s disclosure itself that contemplates a formaldehyde
concentration range from 0–10% in a fixation/hybridization solution (FF4).
The Examiner finds that Bresser provides the motivation to adjust the
components because the “patent states that the choice of fixative and fixative
procedures can affect cellular constituents and cellular morphology and that
one would select ingredients based on which ones afford the highest
hybridization efficiency with good preservation of morphology . . .
(therefore result effective variables).” (Ans. 10.) We agree with the
Examiner’s finding that adjusting the level of a cross linking agent, such as
formaldehyde, in the typical fixative solution would be recognized by the
ordinary artisan to be a result effective variable based on achieving the
desired stickiness needed to secure or seal the membrane components (FF4).
See In re Applied Materials, Inc., 692 F.3d 1289, 1295 (Fed. Cir. 2012)
(overlap of prior art range with claimed range “provides sufficient
motivation to optimize the ranges”); In re Boesch, 617 F.2d 272, 276 (CCPA
1980) (“discovery of an optimum value of a result effective variable in a
known process is ordinarily within the skill of the art”). Accordingly, the
ordinary artisan would recognize, based on Bresser’s teaching, that adjusting
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the cross-linking agent would affect how the membrane components are
secured or sealed in the procedure and that Bresser thus provides sufficient
motivation to adjust the concentration of that component (FF4). The law
does not require that the teachings of the reference be combined for the
reason or advantage contemplated by the inventor, as long as some
suggestion to combine the elements is provided by the prior art as a whole.
In re Beattie, 974 F.2d 1309, 1312 (Fed. Cir. 1992); In re Kronig, 539 F.2d
1300, 1304 (CCPA 1976).
On the record before us, we conclude the Examiner did not err in
rejecting claim 1 under 35 U.S.C. § 103(a) as being unpatentable over
Bresser.
Claim 10
With respect to the rejection of claim 10, Appellant relies on the same
arguments relied upon with respect to claim 1, discussed above. (App. Br.
17–18; see also Reply Br. 9–10.) For the reasons discussed above, we find
that the Examiner has established a prima facie showing of obviousness with
respect to claim 10, which Appellant has failed to rebut. Accordingly, we
affirm the rejection of claim 10 for the reasons set out by the Examiner in
the Answer (Ans. 2–11).
Claim 20
Claim 20 is directed to a frozen biological sample in contact with a
solution containing ketone, alcohol, water, and aldehyde. Claim 20 does not
contain a requirement for particular ratios of ketone, alcohol, and aldehyde.
With respect to the rejection of claim 20, Appellant contends that
“Example 6 is the only portion of the Bresser patent concerning fixation of a
frozen biological sample . . . [and] employs ethanol and formamide, and not
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any aldehyde or ketone (as required by claim 20), in the course of fixing the
frozen sample.” (App. Br. 20; see also Reply Br. 9.)
We are not persuaded. “[I]n a section 103 inquiry, ‘the fact that a
specific [embodiment] is taught to be preferred is not controlling, since all
disclosures of the prior art, including unpreferred embodiments, must be
considered.’” Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804,
807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA
1976).) It is well settled that disclosed examples and preferred embodiments
do not constitute a teaching away from a broader disclosure or even non-
preferred embodiments. See In re Susi, 440 F.2d 442, 446 n.3 (CCPA 1971).
Bresser teaches that cells may be living or dead as long as they
contain target DNA or protein to be detected (FF5). Bresser teaches that
cells or tissue slices are fixed and the choice of fixation buffer depends on
the particular resolution to be achieved (FF5). Bresser teaches a typical
fixation buffer containing 20%-30% ethanol, 5% formalin and 5% acetone
(FF1). Furthermore, formalin is known to be a mixture of formaldehyde and
water. Thus, Bresser discloses a composition containing ketone, alcohol,
water, and aldehyde.
We agree with the Examiner that Appellant’s argument is not
persuasive because example 6 of Bresser “is merely an illustration of one
possible embodiment and Bresser clearly suggests that any of the fixative
combinations disclosed could be reasonable expected to be used in such a
manner” (Ans. 11, citing Bresser col. 16, ll. 4–9 (“[t]he following examples
are offered by way of illustration and are not intended to limit the
invention)). There is nothing Bresser’s example 6 that would indicate that
the application of any of Bresser’s other disclosed fixation buffers such as
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Application 11/810,349

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the one containing 20%-30% ethanol, 5% formalin and 5% acetone (FF1)
would in any way be detrimental to the fixation of a frozen tissue sample, a
specimen expected to contain DNA and proteins. We agree with the
Examiner’s conclusion that based on the teachings of Bresser it would have
been obvious to treat tissue specimens, including frozen specimens, with a
fixation buffer containing ethanol, formaldehyde and acetone (see
FF1,FF3,FF5).
On the record before us, we conclude the Examiner did not err in
rejecting claim 20 under 35 U.S.C. § 103(a) as being unpatentable over
Bresser.
Claim 28
With respect to the rejection of claim 28, Appellant relies on the same
arguments relied upon with respect to claim 1, discussed above. (App. Br.
18–19; see also Reply Br. 12–13.) Thus, for the reasons discussed above,
we find that the Examiner has established a prima facie showing of
obviousness with respect to claim 28, which Appellant has failed to rebut.
Accordingly, we affirm the rejection of claim 28 for the reasons set out by
the Examiner in the Answer (Ans. 2–11).
Claims 2–9, 11–19, 21–27, 36, and 37
With respect to dependent claims 2–9, 11–19, 21–27, 36, and 37,
Appellant contends that these claims are allowable for the reasons discussed
for independent claims 1, 10, 20, and 28. (App. Br. 29.) Because Appellant
does not argue the claims separately, claims 2–9, 11–19, 21–27, 36, and 37
fall with their respective independent claims 1, 10, 20, and 28 for the reasons
discussed above. 37 C.F.R. § 41.37 (c)(1)(iv).
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SUMMARY
We affirm the rejection of claims 1, 10, 20, and 28 under 35 U.S.C.
§ 103(a) over Bresser. Claims 2–9, 11–19, 21–27, 36, and 37 we not
separately argued and fall with their respective independent claims.
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

tc
Formalin - definition of formalin by The Free Dictionary
http://www.thefreedictionary.com/formalin
Thesaurus ≠ Antonyms↔ Related Words≡ SynonymsLegend:
formalin
Also found in: Thesaurus, Medical, Financial, Encyclopedia, Wikipedia.
for·ma·lin (fôr′mə-lĭn)
n.
An aqueous solution of formaldehyde that is 37 percent by weight, usually also containing 10 to 15 percent
methanol to prevent polymerization of the formaldehyde.
[Originally a trademark.]
American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2011 by Houghton Mifflin Harcourt Publishing
Company. Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved.
formalin (ˈfɔːməlɪn) or formol
n
1. (Chemistry) a 40 per cent solution of formaldehyde in water, used as a disinfectant, preservative for
biological specimens, etc
Collins English Dictionary – Complete and Unabridged © HarperCollins Publishers 1991, 1994, 1998, 2000, 2003
for•ma•lin (ˈfɔr mə lɪn)
n.
a clear, colorless, aqueous solution of 40 percent formaldehyde.
[1893; formal(dehyde) + -in1]
Random House Kernerman Webster's College Dictionary, © 2010 K Dictionaries Ltd. Copyright 2005, 1997, 1991 by Random House,
Inc. All rights reserved.
Noun 1. formalin - a 10% solution of formaldehyde in water; used as a disinfectant or to preserve biological
specimens
≡ formol
↔ solution - a homogeneous mixture of two or more substances; frequently (but not necessarily) a
liquid solution; "he used a solution of peroxide and water"
Based on WordNet 3.0, Farlex clipart collection. © 2003-2012 Princeton University, Farlex Inc.
Page 1 of 2Formalin - definition of formalin by The Free Dictionary
12/21/2015http://www.thefreedictionary.com/formalin
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formalin formaline [ˈfɔːməlɪn] N → formalina f
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Page 2 of 2Formalin - definition of formalin by The Free Dictionary
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