Ex Parte KIY et al

Board of Patent Appeals and Interferences

Jan 30, 2003

08676971 (B.P.A.I. Jan. 30, 2003)

The opinion in support of the decision being entered today was not written
for publication and is not binding precedent of the Board.

Paper No. 31

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte THOMAS KIY, and
RUDIGER MARQUART
__________

Appeal No. 2001-0380
Application No. 08/676,971
__________

ON BRIEF
__________

Before ADAMS, MILLS and GREEN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL

This is a decision on the appeal under 35 U.S.C. § 134 from the examiner’s final
rejection of claims 1-14, which are all the claims pending in the application.
Claim 1 is illustrative of the subject matter on appeal and is reproduced
below:
1. A method for culturing ciliates, comprising the steps of:
placing ciliates and medium therefor in a culture flask;
providing said culture flask with a stirrer having a magnetic core,
wherein said stirrer is suspended in the top part of the culture flask
such that the stirrer does not touch the flask bottom, and wherein the
motion of said stirrer is driven by means of a magnetic field; and
stirring said ciliates in said culture medium.

The references relied upon by the examiner are:
Appeal No. 2001-0380 Page 2
Application No. 08/676,971

Wergeland et al. (Wergeland) 5,008,197 Apr. 16, 1991
Hofmann et al. (Hofmann), “External Factors Limiting the Multiplication Potential
of Tetrahymena,” J. Cell Sci., Vol. 50, p. 407-418 (1981)

Griffiths, “Scaling-up of Animal Cell Cultures” Animal Cell Culture: a practical
approach, Chp. 3, pp. 33-39 (1987)

Lognay et al. (Lognay), “Improvement of Fed Batch Mass Culture for γ Linolenic
Biosynthesis by Tetrahymena Rostrata,” Biotechnology Letters, Vol. 11, No. 6,
pp. 423-426 (1989)
GROUNDS OF REJECTION
Claims 1, 2 and 5-9 stand rejected under 35 U.S.C. § 103 as obvious over
Hofmann in view of Wergeland and Griffiths.
Claims 1, 3, 4 and 10-14 stand rejected under 35 U.S.C. § 103 as obvious
over Hofmann in view of Wergeland, Gosselin and Griffiths.
We reverse.

DISCUSSION
Claims 1, 2 and 5-9:
According to the examiner (Answer, page 4), Hofmann “teach a method
for culturing the ciliates, Tetrahymena, which belong to the group Holotrichia,
comprising the steps of placing ciliates in an Erlenmeyer flask containing media
and shaking the flask at a low speed to avoid generation of foam….” The
examiner recognizes, however, that Hofmann “do not teach stirring the ciliates
with a magnetic stirrer at a particular speed, nor … a membrane aeration stirrer
or stirring by a reciprocating mixing technique.” Id. To make up for these
deficiencies in Hofmann, the examiner relies on Wergeland and Griffiths.
The examiner relies on Wergeland (id.) to “teach a method and device for
improving oxygenation of fragile cells in culture … wherein mammalian cells in
Appeal No. 2001-0380 Page 3
Application No. 08/676,971

medium are stirred with a suspended aeration membrane stirrer driven by a
magnetic field….” With regard to Griffiths, the examiner finds (id.) Griffiths
“teaches that magnetic drive stirrers provide a more homogeneous liquid/cell
suspension via axial and radial flow as well as laminar and turbulent mixing….”
In response, appellants argue (Brief, page 7), the art relied up by the
examiner discusses mammalian cells, and does not suggest the use of “stirrer
technology for culturing ciliates … [which] are sensitive to shear forces and were
not though to be amenable to techniques that involve a high degree of physical
disruption.” Appellants refer to the Kiy Declaration to support this position.
According to Kiy (Declaration, paragraph 4), “[c]iliates belong to the most
sensitive of all cells to shear forces and that mammalian cells, on the other hand,
are either adapted to with stand shear force or are treated in such a way as to
lessen the negative effect of shear force.” Therefore appellants argue (Brief,
page 7), “the skilled artisan would not reasonably expect to use stirring with
ciliates, since such a technique would be expected to break these fragile cells.”
Upon review of the references, we note that Wergeland disclose (Column
1, lines 12-16), “the invention is concerned with the oxygenation of biological
cultures using so-called microcarrier techniques, wherein e.g., tissue cells or
mammalian cells are grown on a solid surface in the form of small carrier
beads.”1 Example 7 of Wergeland as relied upon by the examiner (Answer,
page 4, “column 7, lines 31-36”), requires the use of “cells cultivated on
microcarriers (see column 7, line 6). We also note that as relied upon by the

1 We note that there is no evidence on this record that ciliates are grown on microcarriers.
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Application No. 08/676,971

examiner (Answer, page 4) Griffiths (page 55, Figure 8, examples D-F), discuss
the “[t]ypes of impellers for growing suspension and microcarrier cells.” As the
examiner explains (Answer, page 4), “magnetic drive stirrers provide a more
homogeneous liquid/cell suspension via axial and radial flow as well as laminar
and turbulent mixing.” However, Griffiths teaches (page 62), “[t]he energy
generated at the tip of the stirrer blade is a limiting factor as it gives rise to a
damaging shear force. Shear forces are created by fluctuating liquid velocities in
turbulent areas.” According to Griffiths (page 63), “[t]he greater the turbulence
the more efficient the mixing, but a compromise has to be reached so that cells
are not damaged.” As Griffiths point out (id.), “[i]f the cells are too fragile for
stirring, or if sufficient mixing cannot be obtained without causing unacceptable
shear rates then an alternative mixing system may have to be used.”
In response, the examiner maintains (Answer, page 14):
one of ordinary skill in the art would have had a high
expectation of successfully maintaining high growth levels
and minimizing cell damage, i.e., foaming, of the fragile
ciliates by modifying the culture method of Hofmann et al. to
gently mix the cells and medium with overhead magnetic
stirring, and to renew nutrients by batch-fed or cyclic
medium exchange methods.

The examiner, however, identifies no evidence to support this conclusion. In this
regard, we remind the examiner that “[t]he consistent criterion for determination
of obviousness is whether the prior art would have suggested to one of ordinary
skill in the art that this process should be carried out and would have a
reasonable likelihood of success, viewed in the light of the prior art.” In re Dow
Chemical Co. 837 F.2d 469, 473, 5 USPQ2d 1529, 1531 (Fed. Cir. 1988).
Appeal No. 2001-0380 Page 5
Application No. 08/676,971

Furthermore, as set forth in In re Kotzab, 217 F.3d 1365, 1369-70, 55
USPQ2d 1313, 1316 (Fed. Cir. 2000):
A critical step in analyzing the patentability of claims pursuant to
section 103(a) is casting the mind back to the time of invention, to
consider the thinking of one of ordinary skill in the art, guided only
by the prior art references and the then-accepted wisdom in the
field. … Close adherence to this methodology is especially
important in cases where the very ease with which the invention
can be understood may prompt one “to fall victim to the insidious
effect of a hindsight syndrome wherein that which only the
invention taught is used against its teacher.”
…
Most if not all inventions arise from a combination of old elements.
… Thus, every element of a claimed invention may often be found
in the prior art. … However, identification in the prior art of each
individual part claimed is insufficient to defeat patentability of the
whole claimed invention. … Rather, to establish obviousness
based on a combination of the elements disclosed in the prior art,
there must be some motivation, suggestion or teaching of the
desirability of making the specific combination that was made by
the applicant. [Citations omitted].

On this record, we agree with appellants that the examiner failed to identify
where the prior art of record provides the requisite suggestion to make the
specific combination leading to appellants’ claimed invention. In our opinion, the
statement of the rejection, at best, establishes that individual parts of the claimed
invention were known in the prior art. The statement of the rejection, however,
fails to establish that a person of ordinary skill in the art would have a reasonable
expectation of success in combining the elements disclosed in the prior art in the
manner necessary to arrive at appellants’ claimed invention. Therefore, it is our
Appeal No. 2001-0380 Page 6
Application No. 08/676,971

opinion that the examiner failed to meet her burden2 of establishing a prima facie
case of obviousness.
Accordingly we reverse the rejection of claims 1, 2 and 5-9 under 35
U.S.C. § 103 as obvious over Hofmann in view of Wergeland and Griffiths.
Claims 1, 3, 4 and 10-14:
The examiner relies on Hofmann, Wergeland and Griffiths as above in
addition to noting that Griffiths also teaches (Answer, page 6) “a cyclic medium
exchange method of culturing cells comprising the intermittent replacement of a
constant fraction of the culture with an equal volume of medium.” In addition, the
examiner finds that Gosselin (id.), “teach a method of culturing Tetrahymena by
a batch-fed culture system which results in a doubling of cell growth compared to
a simple batch culturing technique….”
Gosselin’s batch culture techniques, however, fail to make up for the
deficiencies, see supra, in the combination of Hofmann, Wergeland and Griffiths.

2 The initial burden of presenting a prima facie case of obviousness rests on the examiner. In re
Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443, 1444 (Fed. Cir. 1992).
Appeal No. 2001-0380 Page 7
Application No. 08/676,971

Accordingly, we reverse the rejection of claims 1, 3, 4 and 10-14 under 35 U.S.C.
§ 103 as obvious over Hofmann in view of Wergeland, Gosselin and Griffiths.
REVERSED

)
Donald E. Adams )
Administrative Patent Judge )
)
)
) BOARD OF PATENT
Demetra J. Mills )
Administrative Patent Judge ) APPEALS AND
)
) INTERFERENCES
)
Lora M. Green )
Administrative Patent Judge )

Appeal No. 2001-0380 Page 8
Application No. 08/676,971

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