Ex Parte Ma

Board of Patent Appeals and Interferences

Apr 24, 2009

10911766 (B.P.A.I. Apr. 24, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte WU MA
__________

Appeal 2008-5773
Application 10/911,766
Technology Center 1600
__________

Decided:1 April 24, 2009
__________

Before ERIC GRIMES, RICHARD M. LEBOVITZ, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a cell
culturing method. The Examiner has rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).
Appeal 2008-5773
Application 10/911,766

STATEMENT OF THE CASE
Claims 2-22 are pending and on appeal. We will focus on claims 2, 7,
11, and 17, which read as follows:
2. A method comprising the steps of:
providing primary mammalian neural stem cells and progenitor cells;
placing the stem cells and the progenitor cells in an extracellular
matrix; and
maintaining the matrix in a culture medium and a microgravity
environment.
7. The method of claim 2, wherein the culture medium comprises basic
fibroblast growth factor and brain derived neurotrophic factor.
11. The method of claim 2, wherein the microgravity environment is
created in a bioreactor rotating vertically at 10-15 RPM.
17. The method of claim 2;
wherein the extracellular matrix comprises type I collagen;
wherein the culture medium comprises basic fibroblast growth factor
and brain derived neurotrophic factor; and
wherein the microgravity environment is created in a bioreactor
rotating vertically at 10-15 RPM.
The Examiner relies on the following references:
Madry et al. US 2002/0177224 A1 Nov. 28, 2002;
Stephen M. O’Connor et al., Primary neural precursor cell expansion,
differentiation and cytosolic Ca2+ response in three-dimensional collagen
gel, 102 JOURNAL OF NEUROSCIENCE METHODS 187-195 (2000);
Hoi Pang Low et al., NEURAL PRECURSOR CELLS FORM
RUDIMENTARY TISSUE-LIKE STRUCTURES IN A ROTATING-WALL
VESSEL BIOREACTOR, 37 IN VITRO CELL. DEV. BIOL. 141-147 (2001);
Melissa K. Carpenter et al., In Vitro Expansion of a Multipotent
Population of Human Neural Progenitor Cells, 158 EXPERIMENTAL
NEUROLOGY 265-278 (1999);
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Christine E. Schmidt and Jennie Baier Leach, Neural Tissue
Engineering: Strategies for Repair and Regeneration, 5 ANNU. REV.
BIOMED. ENG. 293-347 (2003); and
Gordana Vunjak-Novakovic et al., Microgravity Studies of Cells and
Tissues, 974 ANN. N.Y. ACAD. SCI. 504-517 (2002).
Claims 2-5, 9, 11-16, and 22 stand rejected under 35 U.S.C. § 103(a)
as obvious over O’Connor in view of Low (Ans. 4).
Claims 2-6, 8, 9, 11-16, and 22 stand rejected under 35 U.S.C.
§ 103(a) as obvious over O’Connor in view of Low and Carpenter (Ans. 6).
Claims 2-9 and 11-22 stand rejected under 35 U.S.C. § 103(a) as
obvious over O’Connor in view of Low, Carpenter, and Schmidt (Ans. 7).
Claims 2-5, 9-16, and 22 stand rejected under 35 U.S.C. § 103(a) as
obvious over O’Connor in view of Low and Madry (Ans. 8).
PRINCIPLES OF LAW
“In determining whether obviousness is established by combining the
teachings of the prior art, the test is what the combined teachings of the
references would have suggested to those of ordinary skill in the art.” In re
GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal quotations
omitted). “[A]ny need or problem known in the field of endeavor at the time
of invention and addressed by the patent can provide a reason for combining
the elements in the manner claimed.” KSR Int’l v. Teleflex Inc., 550 U.S.
398, 420 (2007).
“[W]hen unexpected results are used as evidence of nonobviousness,
the results must be shown to be unexpected compared with the closest prior
art.” In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
“Mere recognition of latent properties in the prior art does not render
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nonobvious an otherwise known invention.” Id. In addition, “it is well
settled that unexpected results must be established by factual evidence.
‘Mere argument or conclusory statements in the specification does not
suffice.’” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997) (quoting In re
De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)). In addition, “[a]ttorney’s
argument in a brief cannot take the place of evidence.” In re Pearson, 494
F.2d 1399, 1405 (CCPA 1974).
O’CONNOR AND LOW
The Examiner relies on O’Connor for disclosing “the culturing of
primary neural precursor cells (a term which includes both neural stem and
progenitor cells . . . ) in a three-dimensional collagen gel” (Ans. 4).
The Examiner relies on Low for disclosing “the culturing of
embryonic murine neural precursors in a type of rotating wall vessel (RWV)
bioreactor, termed a high-aspect ratio vessel, or HARV” (id.).
The Examiner concludes that the “ordinary skilled artisan, seeking a
method to differentiate and culture neural precursor cells, would have been
motivated to use the HARV bioreactor of Low et al with the methods of
O’Connor et al because Low et al teach[es] ‘HARV culturing does appear to
favor the differentiation of neural precursors’” (id. at 5 (quoting Low 147,
first column, first full ¶)).
Issues
Did the Examiner set forth a prima facie case that it would have been
obvious to modify O’Connor’s method to use the HARV bioreactor
disclosed in Low?
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If so, did Appellant rebut the prima facie case of obviousness with an
adequate showing of unexpected results?
With regard to claim 11, did the Examiner set forth a prima facie case
that it would have been obvious to create the microgravity environment in a
bioreactor rotating vertically?
Findings of Fact
1. O’Connor discloses “cultur[ing] neural precursor cells [NPC] in
a three-dimensional (3D) collagen gel” (O’Connor, Abstract).
2. In particular, O’Connor discloses that “neuroepithelial cells . . .
from embryonic day 13 rat cortex [were] dispersed within type I collagen
and maintained for up to 30 days in vitro” (id.).
3. O’Connor states that the “findings suggest the suitability of the
3D culture system for the proliferation and differentiation of neural
precursor cells” (id.).
4. O’Connor also states that “[w]e are interested in the NPC
cultures because of their potential as a renewable cell source for tissue-based
biosensor applications where whole cells are incorporated as the sensing
element” (id. at 188).
5. In addition, O’Connor discloses that the cells were
“resuspended in a serum-free medium . . . containing . . . recombinant
human basic fibroblast growth factor” (id. at 189).
6. Low discloses that, “[o]rdinarily, cells are grown as liquid
cultures in a flask, but a novel, alternative system makes use of the rotating-
wall vessel (RWV) bioreactor” (Low 141).
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7. Low discloses that “[r]otational speed is adjusted so that the
cells or cellular aggregates remain suspended in synchronous rotation with
the vessel. These cultures in ‘free fall’ are characterized by low shear stress
and randomized gravitational vectors, simulating microgravity.” (Id.)
8. In particular, Low discloses “experiments that compare the
properties of neural precursors grown conventionally in stationary flasks
with those cultured in RWV bioreactors known as high-aspect ratio vessels
(HARVs)” (id. at 143).
9. With regard to cells grown in HARVs, Low discloses that the
HARVs were rotated horizontally (id. at 144).
10. Low also discloses that neural precursor cells cultured in
rotating HARVs formed large 1-2 mm long objects within 3 days, but that
these structures “were never observed in the corresponding stationary-flask
cultures [or] if the HARV was rotated in the vertical plane” (id. at 145-146).
11. In addition, Low discloses that “HARV cultures of EGF-
responsive neural precursor cells lead to the formation of a few (1-10) large
structures rather than the numerous (1000-10.000) small neurospheres
characteristic of conventional flask cultures” (id. at 146).
12. Low concludes:
[T]he growth rate of cells in HARVs . . . may approach an order
of magnitude less than that of cells in flasks after 3 d of culture.
Part of this decreased growth presumably reflects increased cell
death. . . . In any case, our results suggest that the HARV
bioreactor is not a useful technology for the purpose of
expanding cell numbers in vitro prior to neurotransplantation.
(Id. at 147.)
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13. Low also concludes, however, that “HARV culturing does
appear to favor the differentiation of neural precursors, with the generation
of unique, three-dimensional neural tissues consisting of primitive
proliferating cells on the outside and cells immunoreactive for neuronal and
glial markers on the inside” (id.).
14. The Specification discloses that “[n]eural stem and progenitor
cells immobilized in collagen gels can be cultured in vitro in a RWV
bioreactor for up to 10 weeks. The collagen-entrapped cells both proliferate
and differentiate, and form multi-layered tissues that resemble developing
neural tissue.” (Spec. ¶ [0014].)
15. The Specification also discloses that “the functional engineered
tissue-like constructs can be maintained in vitro for up to 10 weeks. This
method demonstrates the promise of utility of tissue-engineered constructs
not only for in vitro studies of neural stem cell biology, but also for a tissue
replacement strategy with new functional brain-like tissues.” (Id. at
¶ [0016].)
16. In the Example, the Specification discloses that cell-collagen
constructs were prepared as described in O’Connor (id. at [0019]).
The primary neural stem and progenitor cells were [then]
cultured in the cell-collagen-bioreactor system for up to
10 weeks in a serum-free medium containing [basic fibroblast
growth factor (bFGF)] and together with [brain derived
neurotrophic factor (BDNF)]. The collagen-entrapped neural
stem and progenitor cells actively proliferated and
differentiated into the major neural phenotypes composing the
central nervous system, including neurons, astrocytes, and
oligodendrocytes. The cell-collagen constructs cultured in
RWV bioreactors gradually compacted 3-4 fold and became
elliptically shaped, tissue-like structures (Figs. 1 and 2)
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averaging 5 mm in diameter. The compact size of the tissue
contrasts with the progressive expansion of neuroepithelial
cells, which were cultured under static conditions (without
rotation). . . . The multiple layers of different phenotypes
composing the RWV-generated tissue are reminiscent of the
developing rat cerebral cortex (Fig. 5). . . .
[T]he two cell layers composing the engineered tissue exhibit
properties similar to those developing in vivo.
(Id. at [0020]-[0021].)
17. The Declaration of Wu Ma, who is the inventor of the present
application, states:
The claimed process produced unexpected results. As detailed
in the specification in paragraphs 0020-0021 (incorporated
herein), a complex three-layered architecture was formed that
emulated the cerebral cortex of embryonic brain. There is no
disclosure in the O’Conner [sic2] or Low references that would
lead one skilled in the art to conclude that such a structure
would result from the presently claimed methods.
(July 12, 2006, Wu Ma Declaration, ¶ 6.)
18. A portion of Table 1 of Vunjak-Novakovic is reproduced
below:

This Figure depicts a rotating wall vessel with arrows showing vertical
rotation (Vunjak-Novakovic 506).

2 In the Wu Ma Declaration and the Appeal Brief, Appellant refers to
O’Connor as “O’Conner.”
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Analysis
O’Connor discloses “cultur[ing] neural precursor cells in a three-
dimensional (3D) collagen gel” (Finding of Fact (FF) 1). Low discloses
culturing neural precursor cells in a HARV bioreactor and that “HARV
culturing does appear to favor the differentiation of neural precursors” (FF 8
& 13). We agree that the Examiner has set forth a prima facie case that it
would have been obvious to modify O’Connor’s culturing method to use a
HARV bioreactor, as described in Low, in an effort to favor differentiation
(Ans. 5).
Appellant argues, however, that there would have been no reason to
combine Low with O’Connor (App. Br. 4). In particular, Appellant argues:
Low concludes that the HARV bioreactor is not a useful
technology for expanding cell numbers. . . . The growth rate of
cells in HARVs approached an order of magnitude less than
that of cells in flasks because of increased cell death. . . . While
Low may have succeeded at differentiation . . . , attempts at
expansion were not successful versus flask culturing.
(Id. at 5.) In addition, Appellant argues that “O’Conner already
demonstrated cell differentiation using a stationary collagen matrix” (id.).
Thus, Appellant concludes:
A person of ordinary skill in the art would not look to the
HARV of Low to improve the culture of O’Conner. Given that
differentiation is already present in O’Conner, Low would teach
that stationary culturing is better than the HARV for
O’Conner’s method, as the HARV causes cell death. The lack
of a reason to combine is further reinforced by the fact that
O’Conner is concerned with finding a renewable cell source for
tissue-based biosensor applications requiring an unlimited
source of cells. . . . Using the cell culture methods of O’Conner
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in the bioreactor of Low would not be expected to cause the cell
proliferation needed in O’Conner.
(Id.)
We are not persuaded. O’Connor discloses that the “findings suggest
the suitability of the 3D culture system for the proliferation and
differentiation of neural precursor cells” (FF 3). In addition, Low discloses
that neural precursor cells cultured in rotating HARVs formed large objects
within 3 days, but that these structures “were never observed in the
corresponding stationary-flask cultures,” and that “HARV culturing does
appear to favor the differentiation of neural precursors” (FF 10 & 13). Thus,
although O’Connor discloses that differentiation can be obtained using its
method, we agree that one of ordinary skill in the art would have been
motivated to use the HARV bioreactor in O’Connor’s method in an effort to
enhance differentiation.
As noted by Appellant, Low discloses that, presumably due in part to
cell death, “the growth rate of cells in HARVs . . . may approach an order of
magnitude less than that of cells in flasks after 3 d of culture” and that their
“results suggest that the HARV bioreactor is not a useful technology for the
purpose of expanding cell numbers in vitro prior to neurotransplantation”
(FF 12). However, we agree with the Examiner that in order to favor
differentiation, rather than expanding cell numbers, it would have been
obvious to use HARV culturing, as described in Low. We recognize that
O’Connor states that they were “interested in the NPC cultures because of
their potential as a renewable cell source for tissue-based biosensor
applications where whole cells are incorporated as the sensing element”
(FF 4). However, we agree that one of ordinary skill in the art reading
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O’Connor would understand that its disclosure is not limited by this goal and
instead provides a method that can be used to differentiate neural precursor
cells and that this method could be further enhanced by using HARV
culturing, as described in Low.
Appellant also argues:
[T]he references use cells from different species, from different
regions, and from embryos of different ages and used different
growth factors. O’Conner used embryonic day 13 rat cortical
neuroepithelial cells . . . and basic fibroblast growth factor
(bFGF). . . . Low used embryonic day 16 mouse
stratium/subventricular zone cells . . . and epidermal growth
factor. . . . There is no expectation of success from combining
such divergent methods.
(App. Br. 5.)
We are not persuaded. As noted by the Examiner (Ans. 11), both
O’Connor and Low disclose culturing neural precursor cells (FF 1 & 8).
Appellant has not provided an adequate explanation as to why there would
not have been a reasonable expectation of success in using O’Connor’s
collagen gel and Low’s HARV bioreactor on neural precursor cells and with
culturing mediums different from the ones specifically used in each of these
references.
In addition, Appellant argues that the “presently claimed method
produced unexpected results” (App. Br. 6). In particular, Appellant argues:
The specification describes a complex three-layered
architecture that emulated the cerebral cortex of embryonic
brain (0020-0021). As stated in paragraph 6 of the Declaration
Under 37 C.F.R. § 1.131 of Wu Ma, there is no indication in the
references that such a structure would be expected.
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The claimed method is able to sustain the culture for 10 weeks.
. . . This is significantly longer than what was shown in either
O’Conner (30 days) or Low (3 days).
The claimed method is able to produce a tissue with evidence of
neural function (0021, line 1; 0016, lines 12-16). O’Conner’s
method [provides a] cluster of differentiated cells (p. 191,
col. 1, lines 48-51), but no neural function is disclosed. Low
produced only a “proto-tissue” (p. 146, col. 2, line 1), but there
is no evidence of any neural function. There is no disclosure of
a structure resembling a cerebral cortex.
Further, Fig. 1 of the present application shows that the rotary
collagen matrix produced a smaller structure than the static
collagen matrix. This is the opposite of what was seen in Low,
where rotation produced larger structures.
(Id.)
We are not persuaded. First, with regard to Specification Figure 1, it
is not clear from the Specification that the rotary collagen matrix produced a
smaller structure that the static collagen matrix. In particular, it is not clear
that Figure 1 depicts, for the static culture, a single large structure rather than
numerous smaller structures. Thus, we do not agree that Appellant has
shown that Figure 1 of the present application is opposite to the teachings of
Low.
With regard to the Declaration of Wu Ma, it states that the “claimed
process produced unexpected results,” in particular that there is no
disclosure in O’Connor or Low that would lead one skilled in the art to
conclude that the presently claimed methods would result in “a complex
three-layered architecture . . . that emulated the cerebral cortex of embryonic
brain” (FF 17). However, the Declaration and the Specification paragraphs
incorporated therein do not provide sufficient factual evidence that the
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claimed method would result in a more complex three-layered architecture
that emulated the cerebral cortex of embryonic brain as compared to the
methods disclosed in O’Connor and Low.
The Specification does discloses that, in contrast with the progressive
expansion of neuroepithelial cells cultured under static conditions, the “cell-
collagen constructs cultured in RWV bioreactors [for up to 10 weeks]
gradually compacted 3-4 fold and became elliptically shaped, tissue-like
structures (Figs. 1 and 2) averaging 5 mm in diameter” (FF 16). However,
the Declaration does not explain why this would have been unexpected in
view of the disclosure in Low that, within only 3 days, neural precursor cells
cultured in rotating HARVs formed large 1-2 mm long objects (FF 10).
Therefore, we do not find Wu Ma’s conclusory statement that the “claimed
process produced unexpected results” persuasive.
With regard to the arguments that the “claimed method is able to
sustain the culture for . . . significantly longer” and that the “claimed method
is able to produce a tissue with evidence of neural function,” Appellant has
not provided sufficient factual evidence that the claimed method provides a
superior result or that any superior result would have been unexpected.
“Attorney’s argument in a brief cannot take the place of evidence.” In re
Pearson, 494 F.2d at 1405.
With regard to claim 11, Appellant argues that “Low teaches that
larger, differentiated structures were never observed if the HARV was
rotated in the vertical plane. . . . Thus, Low teaches even more strongly
against vertical rotation than it does for horizontal rotation.” (App. Br. 5.)
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We agree with Appellant that the Examiner has not set forth a prima
facie case that claim 11 would have been obvious. Low discloses that the
HARV bioreactors were rotated horizontally (FF 9). The Examiner has not
adequately explained why vertical rotation would have been obvious.
The Examiner argues:
“[R]otating vertically” is interpreted broadly to encompass
either readily obvious orientation of the HARV because both
can be interpreted to be “rotated vertically”: 1) if the HARV is
situated on its side, i.e. as depicted in Table 1 (page 506) of
Vunjak-Novakovic et al, the rotation includes a vertical aspect,
(see the circular arrows surrounding the rotating vessel
illustrations in Table 1 of Vunjak-Novakovic); and, 2) the
HARV is situated on one of its ends, i.e. situated 45° relative to
the diagram from Table 1 above. It is likely the first situation
detailed above (i.e. as depicted in Table 1 of Vunjak-Novakovic
et al) is the situation taught by Low et al, and therefore is
considered to anticipate the limitation “rotating vertically.”
(Ans. 12.)
We agree with the Examiner that Vunjak-Novakovic depicts a rotating
wall vessel with arrows showing vertical rotation (FF 18). However, we
agree with Appellant that the Examiner has not adequately explained why
rotating this vessel so that it is situated on one of its ends would provide
vertical rotation (Reply Br. 3).
Conclusion
The Examiner set forth a prima facie case that it would have been
obvious to modify O’Connor’s method to use the HARV bioreactor
disclosed in Low, and Appellant did not rebut this prima facie case of
obviousness with an adequate showing of unexpected results. Therefore, we
affirm the obviousness rejection of claim 2 over O’Connor in view of Low.
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Claims 3-5, 9, 12-16, and 22 have not been argued separately and therefore
fall with claim 2. 37 C.F.R. § 41.37(c)(1)(vii).
However, the Examiner did not set forth a prima facie case that it
would have been obvious to create the microgravity environment in a
bioreactor rotating vertically. Therefore, we reverse the obviousness
rejection of claim 11 over O’Connor in view of Low.
O’CONNOR AND LOW IN VIEW OF CARPENTER OR MADRY
Claim 2 is also rejected over O’Connor and Low in view of Carpenter.
Since we have affirmed the rejection of this claim over O’Connor and Low,
we also affirm the rejection of this claim over O’Connor and Low in view of
Carpenter. Claims 3-6, 8, 9, 12-16, and 22 have not been argued separately
and therefore fall with claim 2.
Claim 2 is also rejected over O’Connor and Low in view of Madry.
Since we have affirmed the rejection of this claim over O’Connor and Low,
we also affirm the rejection of this claim over O’Connor and Low in view of
Madry. Claims 3-5, 9, 10, 12-16, and 22 have not been argued separately
and therefore fall with claim 2.
Claim 11 is also rejected over O’Connor and Low in view of
Carpenter or Madry. We have reversed the rejection of claim 11 over
O’Connor in view of Low. In addition, the Examiner has not pointed to any
disclosure in either Carpenter or Madry that would make up for the
deficiency discussed above (Ans. 6 & 8). Thus, we conclude that the
Examiner has not set forth a prima facie case that claim 11 would have been
obvious over O’Connor and Low in view of Carpenter or Madry. We
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therefore reverse the obviousness rejections of claim 11 over these
references.
O’CONNOR, LOW, CARPENTER AND SCHMIDT
The Examiner relies on O’Connor and Low as discussed above
(Ans. 7). The Examiner also relies on O’Connor for teaching “that the
neural stem and progenitor cells are grown in the presence of bFGF” (id.).
The Examiner relies on Schmidt for teaching “that BDNF can be used
to aid in the differentiation of neural cells” (id.). In particular, the Examiner
argues that Schmidt discloses that “‘BDNF supports motor neuron survival
and promotes the axonal growth of motor and sensory neurons’” (id.).
The Examiner concludes that “[o]ne would have been motivated to
include BDNF in the combined culture system of O’Connor and Low
because BDNF was a know[n] factor capable of aiding in neuronal
differentiation, one of the very purposes of both O’Connor and Low” (id.).
Issues
Did the Examiner set forth a prima facie case that it would have been
obvious to include BDNF, as disclosed in Schmidt, in the culture medium of
the method of O’Connor as combined with Low?
With regard to claims 11 and 17, did the Examiner set forth a prima
facie case that it would have been obvious to create the microgravity
environment in a bioreactor rotating vertically?
Findings of Fact
19. Schmidt discloses that the “role of neurotrophic factors in
neural regeneration has been the focus of extensive research” (Schmidt 309).
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20. In particular, Schmidt discloses that “[o]ne family of
neurotrophic factors, the neurotrophins, has been heavily investigated in
nerve regeneration studies” (id.).
21. Schmidt also discloses that the “neurotrophins include . . .
brain-derived neurotrophic factor (BDNF)” (id.).
22. Specifically, Schmidt discloses that “BDNF supports motor
neuron survival . . . and promotes the axonal growth of motor . . . and
sensory . . . neurons” (id. at 310).
23. In addition, Schmidt discloses that, “[o]utside the neurotrophin
family, other factors of importance [include] . . . basic fibroblast growth
factor” (id. at 309).
24. Specifically, Schmidt discloses that basic fibroblast growth
factor (bFGF) has “been associated with enhanced regeneration following
injuries in the peripheral nerve . . . and spinal cord. . . . Like other
neurotrophins . . . , bFGF has been associated with increased outgrowth of
sensory neurons from the dorsal root ganglia, thorough the PNS-CNS
transition zone, and into the spinal cord.” (Id. at 311.)
Analysis
As discussed above, O’Connor discloses “cultur[ing] neural precursor
cells in a three-dimensional (3D) collagen gel” (FF 1). As the culture
medium, O’Connor discloses a serum-free medium containing basic
fibroblast growth factor (FF 5). For the reasons discussed above, we agree
with the Examiner that it would have been obvious to modify O’Connor’s
culturing method to use a HARV bioreactor, as disclosed in Low.
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Schmidt discloses that “BDNF supports motor neuron survival . . . and
promotes the axonal growth of motor . . . and sensory . . . neurons” (FF 22).
Thus, we agree with the Examiner that it would have been obvious to
additionally include BDNF in the culture medium (Ans. 7 & 13-14).
Appellant argues, however, that in Schmidt BDNF “is disclosed in the
context of biomolecular therapy for regeneration after injury. . . . There is no
disclosure that BDNF would be useful in in vitro cell culture or in
combination with bFGF.” (App. Br. 7.)
We are not persuaded. Instead, we agree with the Examiner that it
would have been obvious to use BDNF in in vitro cell culture. As noted by
the Examiner:
[O]ne of skill in the art . . . would understand that such growth
factors are extremely useful, even necessary, for the culture and
differentiation of neural cells in vitro. Considering that the
neural precursor cells of the prior art are taken directly from
neural tissue, where the art of record indicates BDNF is active,
it would be surprising if BDNF did not function in vitro on such
cells.
(Ans. 14.)
In addition, based on the disclosure in Schmidt that BDNF and bFGF
are both neurotrophic factors with different activities (FF 19-24), as well as
the specific teaching in O’Connor of including bFGF in its culture medium
(FF 5), we agree with the Examiner that it would have been obvious to
include BDNF in combination with bFGF.
However, as discussed above, we do not agree that it would have been
obvious based on the disclosures in O’Connor and Low for the microgravity
environment to be created in a bioreactor rotating vertically. In addition, the
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Examiner does not rely on Carpenter or Schmidt to overcome this deficiency
(Ans. 7).
Conclusion
The Examiner has set forth a prima facie case that it would have been
obvious to include BDNF, as disclosed in Schmidt, in the culture medium of
the method of O’Connor as combined with Low. We therefore affirm the
obviousness rejection of claim 7 over O’Connor, Low, Carpenter, and
Schmidt. Claims 2-6, 8, 9, 12-16, and 22 have not been argued separately
and therefore fall with claim 7.
However, the Examiner has not set forth a prima facie case that it
would have been obvious to create the microgravity environment in a
bioreactor rotating vertically. Therefore, we reverse the obviousness
rejection over O’Connor, Low, Carpenter, and Schmidt of claims 11 and 17
and of claims 18-21, which depend from claim 17.
ORDER
We affirm the obviousness rejections of claims 2-10, 12-16, and 22.
However, we reverse the obviousness rejections of claims 11 and 17-21.
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-IN-PART

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ASSOCIATE COUNSEL (PATENTS)
CODE 1008.2
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