Pachmann, Ulrich et al.

Patent Trials and Appeals Board

Nov 6, 2020

2020002647 (P.T.A.B. Nov. 6, 2020)

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.
14/419,149 05/29/2015 Ulrich PACHMANN 6460-0113PUS1 1940
2292 7590 11/06/2020
BIRCH STEWART KOLASCH & BIRCH, LLP
8110 Gatehouse Road
Suite 100 East
Falls Church, VA 22042-1248
EXAMINER
KIM, TAEYOON
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
11/06/2020 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte ULRICH PACHMANN and KATHARINA PACHMANN
__________

Appeal 2020-002647
Application 14/419,149
Technology Center 1600
__________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and
MICHAEL A. VALEK, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a
method of testing sensitivity of tumor cells or a therapeutic measure for
treating a tumor disease. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We reverse.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as the
Applicant, Ulrich Pachmann and Katharina Pachmann (see Appeal Br. 1).
2 We have considered the Specification of May 29, 2015 (“Spec.”); Final
Office Action of Jan. 8, 2019 (“Final Act.”); Appeal Brief of Oct. 3, 2019
(“Appeal Br.”); and Examiner’s Answer of Dec. 16, 2019 (“Ans.”).
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Statement of the Case
Background
“The invention provides a method for culturing a subpopulation of
circulating epithelial tumor cells from a body fluid from a human or animal,
more particularly a mammal, affected by an epithelial tumor” (Spec. 3:8–
11). “The response of the circulating tumor cells to a therapy correlates
strongly with a relapse-free survival” (id. at 5:10–12).
The Claims
Claims 8–12 and 19 are on appeal. Claim 8 is the sole independent
claim, is representative and reads as follows:
8. A method of testing sensitivity of tumor cells with
respect to a medicament or a therapeutic measure for treating a
tumor disease underlying the occurrence of circulating
epithelial tumor cells in a human or animal, comprising:
(i) separating cells present in a body fluid from the
human or the animal and containing at least one nucleus
in each case from the body fluid without selection of
certain of these cells;
(ii) transferring said separated cells to a cell culture
medium;
(iii) culturing said transferred separated cells under
cell culture conditions in said cell culture medium
containing at least an animal serum, a growth stimulator
and one growth factor, wherein the growth stimulator is
insulin and hydrocortisone and wherein the growth factor
is Epidermal growth factor, and wherein the cells are
cultured for at least 24 hours in suspension at least until a
subpopulation of tumor cells, which does not require
adherence to a surface for proliferation, has formed
spheroids by proliferation, and wherein tumor cells
which have formed the spheroids during culturing are
separated from the cultured tumor cells, by separating the
spheroids formed during culture; and
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(iv) testing of sensitivity of tumor cells in the
spheroids obtained in step (iii) with respect to the
medicament or the therapeutic measure by exposing the
spheroids obtained in step (iii) to the medicament or the
therapeutic measure and analyzing the effect of the
exposure.

The Rejection3
The Examiner rejected claims 8–12 and 19 under U.S.C. § 103(a) as
obvious over Goodman,4 Kawabe,5 Friedrich,6 Vinci,7 Marrinucci,8 and Wu9
(Final Act. 3–7).
The Examiner finds Goodman teaches screening CTCs (circulating
tumor cells) for drug sensitivity (Final Act. 5) by obtaining cells without
separation, and growing the cells in a culture medium for at least 24 hours to
form spheroids (id. at 3–4). The Examiner finds Goodman teaches both
serum free and serum containing media (id. at 3). The Examiner finds
Marrinucci evidences that CTCs can originate from non-small lung cancer

3 We note that the Examiner has acknowledged that Marchetti et al., US
2014/0322356 A1, published Oct. 30, 2014, is not prior art to the instant
application (see, e.g., Ans. 3).
4 Goodman et al., US 2013/0078667 A1, published Mar. 28, 2013.
5 Kawabe et al., US 2006/0014157 A1, published Jan. 19, 2006.
6 Friedrich et al., Spheroid-based drug screen: considerations and practical
approach, 4 Nature Protocols 309–24 (2009).
7 Vinci et al., Advances in establishment and analysis of three-dimensional
tumor spheroid-based functional assays for target validation and drug
evaluation, 2012 BMC Biology 10–29 (2012).
8 Marrinuchi et al., Circulating Tumor Cells From Well-Differentiated Lung
Adenocarcinoma Retain Cytomorphologic Features of Primary Tumor Type,
133 Arch Pathol Lab Med 1468–71 (2009).
9 Wu, R., Growth of Human Lung Tumor Cells in Culture, in Culture of
Human Tumor Cells 1–21 (Pfragner and Freshney, Eds., Wiley-Liss, Inc.)
(2004).
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(id. at 4).
The Examiner acknowledges that Goodman does not suggest the use
of hydrocortisone and insulin in the growth media for CTCs (see Final Act.
4).
The Examiner finds that “Wu teaches that insulin, hydrocortisone and
EGF are principal supplements in the medium for culturing lung cancer
cells” (Final Act. 4). The Examiner finds it obvious that “one skilled in the
art would consider insulin, hydrocortisone and EGF as supplements for the
culture medium for non-small cell lung cancer cells, and would utilize them
for CTCs of NSCLC origin” (id.). The Examiner relies upon Kawabe,
Friedrich, and Vinci to show that spheroids may be used for drug screening
and for elements of the dependent claims (see, e.g., id. at 5–6).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that Wu does not
teach away from the use of serum containing medium?
Findings of Fact
1. Goodman teaches, regarding the preamble and step (iv), that
“applications for using the isolated and expanded CTCs include . . . drug
sensitivity testing . . . and treatment response assessment” (Goodman ¶ 60).
2. Goodman teaches, regarding step (i), that “the sample can be
processed to remove or reduce the number of non-CTC in the sample (i.e., to
enrich for CTC) and the resulting cell population that contains CTC can be
cultured in accordance with the methods described herein. Alternatively, the
sample can be cultured without further processing” (Goodman ¶ 28).
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3. Goodman teaches, regarding step (ii), that:
Many suitable media formulations are well known and
conventional in the art, such as RPMI media, Knockout serum
replacement media, F12K, and DMEM. The culture media is
preferably supplemented with a low concentration of serum,
plasma or growth factors (i.e. 5% or less (v/v) serum or plasma)
or is serum or plasma free.
(Goodman ¶ 33).
4. Goodman teaches, regarding step (iii), an example of culturing
to form spheroids:
Culturing of the CTCs in spheroid forming culture media: Once
the buffy coat cells containing the CTCs were ready the media
was freshly reconstituted by mixing 0.5 μ1 human EGF (200
μg/ml), 100 μl of knockout serum and 5 ml of DMEM/F12
working media. The working media contained DMEM/F 12
media base with 5 ml non essential amino acid, and 0.5 ml
BME (100 μM stock in PBS) and 5 ml of penicillin/
streptomycin. . . . The growth of the CTCs was monitored for
14 days before they were passaged to fresh media.
(Goodman ¶ 70).
5. Wu teaches “We, as well as other researchers, initially used a
serum-supplemented medium to establish primary cultures of normal
specimens and lung tumor specimens. These attempts have proven to be
unsuccessful” (Wu 3).
6. Wu teaches their laboratory was
The first to develop a serum-free, hormone-supplemented
medium for primary human airway epithelial cell growth and
long-term maintenance in culture. The principal supplements in
this medium are insulin, transferrin, hydrocortisone, epidermal
growth factor (EGF), retinoid, and a supplement essential for
cyclic adenosine monophosphate (cAMP) generation.
(Wu 3).
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7. Wu teaches, regarding non-small cell lung cancer (“NSCLC”)
cell culturing, that “phenotypic differences among different tumor cells
required different culture media and growth supplements” (Wu 4).
8. Wu teaches, in Protocol 1.4, that to obtain floating aggregates,
use a “serum-free, HITES-based medium” (Wu 13).
Principles of Law
“A reference may be said to teach away when a person of ordinary
skill, upon reading the reference, would be discouraged from following the
path set out in the reference, or would be led in a direction divergent from
the path that was taken by the applicant.” In re Gurley, 27 F.3d 551, 553
(Fed. Cir. 1994).
Analysis
Appellant contends “Wu teaches away from initially using a medium
containing an animal serum in conjunction with insulin, hydrocortisone and
EGF for the culture of floating cells, which do not require adherence to a
surface for proliferation and for initiating formation of spheroids” (Appeal
Br. 7). Appellant contends that Wu teaches
According to Protocol 1.4, step (b), the cells are cultured
without serum for 1 to 2 weeks. Under these conditions most
SCLC cells grow as floating aggregates, whereas normal cells
will attach to the dish to proliferate. Thus, it is easy to
recognize that the primary culture has SCLC cells. According
to Protocol 1.5, Adenocarcinoma and Large Cell Carcinoma
Cells (which are equivalent to NSCLCs, see Wu, page 2, next
to last sentence of next to last paragraph) adhere to the surface
of the flask during culturing.
(Appeal Br. 7).
The Examiner acknowledges that “it is understood that the steps (a)-
(d) of Wu in p. 13 are carried out in the absence of serum for establishing
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primary lung cancer cell culture (SCLC)” (Ans. 8). The Examiner contends
that “Goodman teaches the use of serum for suspension culture of CTCs (see
paras. 33-34)” (id.). “Thus, it is the Examiner’s position that teachings of
Marchetti and/or Wu are not sufficient to be considered as evidence teaching
away the use of serum for CTC suspension culture, when Wu as well as
Goodman teaches that serum can be used for CTC suspension culture” (id.).
We find that Appellant has the better position. Whether Wu or
Goodman generally teach that serum has been used for culturing CTC cells
does not address the specific teaching by Wu that “[w]e, as well as other
researchers, initially used a serum-supplemented medium to establish
primary cultures of normal specimens and lung tumor specimens. These
attempts have proven to be unsuccessful” (FF 5). Wu teaches, instead, the
use of serum-free media (FF 6). Wu teaches that different cells require
different media (FF 7) and teaches to use serum-free media to get floating
aggregates such as spheroids (FF 8). Thus, we agree with Appellant that Wu
would discourage the use of medium containing serum for growth of this
cell population into spheroids and therefore teaches away from the recitation
in claim 1 to use a “cell culture medium containing at least an animal
serum.”
The Examiner’s reliance on Goodman does not persuade us
differently. Goodman only generically teaches serum or serum free media
(FF 3), but in Goodman’s only example of growing spheroid cells, Goodman
uses serum-free medium (FF 4). Thus, Goodman does not address or cure
Wu’s teaching away. Marchetti is not prior art, so the Examiner’s continued
reliance on this reference does not properly address the rejection. The other
cited references also do not address this issue.
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Conclusion of Law
A preponderance of the evidence of record does not support the
Examiner’s conclusion of obviousness.
SUMMARY
In summary:
Claims
Rejected
35 U.S.C. §  Reference(s)/Basis Affirmed Reversed
8–12, 19 103 Goodman, Kawabe,
Friedrich, Vinci,
Marrinucci, Wu
8–12, 19

REVERSED