Ex Parte Ueda et al

Patent Trial and Appeal Board

May 23, 2018

13637107 (P.T.A.B. May. 23, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/637,107 12/13/2012 Minoru Ueda
22910 7590 05/25/2018
BANNER & WITCOFF, LTD.
28 STATE STREET
SUITE 1800
BOSTON, MA 02109-1701
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
007801.00003 1085
EXAMINER
CORDAS, EMILY ANN
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
05/25/2018 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):
PT0-2291 O@bannerwitcoff.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MINORU UEDA, YOICHI YAMADA, KATSUMI EBISA WA,
AKIHITO YAMAMOTO, KIYOSHI SAKAI, KOHKI MATSUBARA,
HISASHI HATTORI, MASAHIKO SUGIYAMA, and
TAKANORI INOUE 1
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Application 13/637, 107
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a
composition for repairing damaged tissue, which have been rejected as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
"Stem cells from human exfoliated deciduous teeth (SHED) and
permanent teeth dental pulp stem cells (DPSCs) derived from wisdom tooth,
1 Appellants identify the Real Party in Interest as NATIONAL
UNIVERSITY CORPORATION NAGOYA UNIVERSITY. Br. 2.
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which are medical wastes, were identified as novel stem cell groups having
self-renewal capacity and pluripotency similar to those of BMSCs [bone
marrow stem cells]." Spec. i-f 6.
Claims 1, 2, 9, 10, and 24 are on appeal. Claim 1 is illustrative and
reads as follows:
1. A damaged part treatment composition for repairing a
damaged part of a target tissue, the composition comprising a
dental pulp stem cell-conditioned medium which does not
comprise any serum, wherein the medium comprises vascular
endothelial growth factor (VEGF), hepatocyte growth factor
(HGF), insulin-like growth factor (IGF), platelet-derived
growth factor (PDGF) and transforming growth factor B
(TGF-B), and wherein the medium further comprises a neurite
outgrowth activity in the presence of a nerve regeneration
inhibitory substance or an apoptosis inhibitory activity toward
neuronal cells.
DISCUSSION
The Examiner has rejected claims 1, 2, 9, 10, and 24 under 35 U.S.C.
§ 103(a) as obvious based on Iohara, 2 Gandia, 3 Tran-Hung, 4 Nakashima, 5
2 Iohara et al., A Novel Stem Cell Source for Vasculogenesis in Ischemia:
Sub fraction of Side Population Cells from Dental Pulp, 26 STEM CELLS
2408 (2008).
3 Gandia et al., Human Dental Pulp Stem Cells Improve Left Ventricular
Function, Induce Angiogenesis, and Reduce Infarct Size in Rats with Acute
Myocardial Infarction, 26 STEM CELLS 638 (2008).
4 Tran-Hung et al., Quantification of angiogenic growth factors released by
human dental cells after injury, 53 ARCHIVES OF ORAL BIOLOGY 9 (2008).
5 Nakashima et al., US 2011/0177041 Al, published July 21, 2011.
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Sakai, 6 and Lim. 7 Ans. 3. The Examiner finds that "Iohara teaches a
composition comprising of cell-free conditioned medium from stem cells or
side population cells from dental pulp (dental pulp stem cells)." Id. at 4.
The Examiner finds that "Iohara teaches that the cells express cytokines,
including VEGF and HGF, and, therefore, the conditioned medium would
inherently contain VEGF and HGF." Id.
The Examiner finds that "Gandia reports that dental pulp stem cells
express VEGF and IGF," that "Tran-Hung reports dental pulp stem cells
express VEGF and PDGF," and that "Nakashima reports dental pulp stem
cells express TGF-B." Id. The Examiner also finds that "Sakai teaches
dental pulp stem cell (DPSC) conditioned medium restored neurite extension
activity of cerebral granular neurons ... and that neurite extension through
the inhibition of multiple axon growth inhibitors (AG Is) is a unique
characteristic of the DPSCs." Id. at 4--5.
The Examiner finds that Iohara' s conditioned medium is not free of
serum, as recited in claim 1, but "Lim teaches a composition comprising
conditioned cell culture medium from mesenchymal stem cells which does
not include serum" and "teaches that there are advantages to using serum-
free medium." Id. at 5. The Examiner concludes that it would have been
obvious "to use serum-free medium in the composition of Iohara for the
6 Sakai et al., Human dental pulp-derived stem cells promote locomotor
recovery after complete transection of the rat spinal cord by multiple neuro-
regenerative mechanisms, 122 J. CLIN. INVEST. 80 (2012).
7 Lim et al., WO 2008/020815 Al, published Feb. 21, 2008.
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benefits of improved reproducibility of the composition and to decrease the
possibility of contamination by adventitious agents," as taught by Lim. Id.
We agree with the Examiner that the composition of claim 1 would
have been obvious to a person of ordinary skill in the art based on the cited
references. Iohara discloses "a highly vasculogenic subfraction of side
population (SP) cells ... from dental pulp. The CD3I-;CD146- SP cells,
demonstrating CD34+ and vascular endothelial growth factor-2
(VEGFR2)/Flkl +,were similar to EPCs [endothelial progenitor cells]."
Iohara 2408, Abstract.
Iohara reports that these cells showed "multilineage differentiation
potential" and "expressed several proangiogenic factors, such as VEGF-A."
Id. Iohara also reports that "[t]he expression of angiogenic (VEGF-A,
HGF)" cytokines "was stronger in CD3 I-;CD146- SP cells compared with
CD3l+;CD146- SP cells." Id. at 2413. Iohara states that "[c]onditioned
medium from this [CD3 I-;CD146-J subfraction showed the mitogenic and
antiapoptotic activity on human umbilical vein endothelial cells. In
conclusion, subfraction of SP cells from dental pulp is a new stem cell
source." Id. at 2408, Abstract.
Gandia discloses that "[ d]ental pulp stem cells (DPSC) ... are able to
secrete vascular endothelial growth factor (VEGF), insulin-like growth
factor-I (IGF-1) and -2 (IGF-2)." Gandia 638. Tran-Hung discloses that
human dental pulp cells "secreted significant levels of PDGF-AB, VEGF
and FGF-2." Tran-Hung 9, Abstract. Nakashima discloses that "dental pulp
stem cells ... express larger amounts of neural factors such as BDNF, NPY,
TGFB 1, and TGFB3 than those of, for example, bone marrow stem cells and
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adipose stem cells." Nakashima i-f 87. Sakai discloses that human dental
pulp stem cells "inhibited the SCI-induced apoptosis of neurons" and
"promoted the regeneration of transected axons by directly inhibiting
multiple axon growth inhibitors." Sakai 80, Abstract.
Lim discloses a method of preparing a conditioned cell medium by
culturing mesenchymal stem cells (MS Cs) and isolating the cell culture
medium. Lim, Abstract. "In particular, MSCs may be made by propagating
a cell obtained by dispersing a embryonic stem (ES) cell colony, or a
descendent thereof, in the absence of co-culture in a serum free medium
comprising FGF2." Id. at 12.
The serum-free media may comprise chemically-defined media
in which all components have a known chemical structure.
Chemically-defined serum-free media is advantageous as it
provides a completely defined system which eliminates
variability[,] allows for improved reproducibility and more
consistent performance, and decreases [the] possibility of
contamination by adventitious agents.
Id. at 17.
Thus, it would have been obvious to a person of ordinary skill in the
art to modify Iohara's method of producing a conditioned medium from
dental pulp stem cells by using a serum-free medium, because Lim teaches
that using a (chemically-defined) serum-free medium eliminates variability,
allows for more consistent performance, and decreases the possibility of
contamination. We therefore agree with the Examiner that the composition
of claim 1 would have been obvious based on the cited references.
Appellants do not dispute the Examiner's findings that, as evidenced
by Iohara, Gandia, Tran-Hung, and Nakashima, dental pulp stem cells
produce VEGF, HGF, IGF, PDGF, and TGF-B, and therefore conditioned
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medium from such cells would contain these factors. See Br. 6, 9.
Appellants also do not dispute that, as evidenced by Sakai, dental pulp stem
cell-conditioned medium comprises neurite extension activity in the
presence of axon growth inhibitors (i.e., "nerve regeneration inhibitory
substance[ s ]," as recited in claim 1 ). See id. at 9.
Appellants argue, however, that
Ioh[ a ]ra is merely concerned with a subfraction of side
population (SP) cells based on CD31 and CD 146. This is in
stark contrast to the claimed composition which is directed to
dental pulp stem cells that are not disclosed to be fractionated.
Therefore, the cell source that generated the conditioned
medium in Ioh[a]ra is different from that as presently claimed.
. . . [T]he compositions of conditioned media vary depending
on the source cells.
Id. at 6.
This argument is unpersuasive, because Iohara expressly states that its
CD31-, CD 146- "subfraction of SP cells from dental pulp is a new stem cell
source." Iohara 2408, Abstract (emphases added). Thus, Iohara's disclosure
supports the Examiner's finding that Iohara discloses stem cells from dental
pulp, and medium conditioned by such cells. As the Examiner pointed out,
"the claim language includes conditioned medium from all types of dental
pulp stem cells" and "does not exclude subpopulations of dental pulp stem
cells." Ans. 7. As the Examiner also pointed out, id., Appellants have not
pointed to evidence showing that Iohara' s dental pulp stem cells produce a
conditioned medium that differs from that defined by claim 1.
Appellants also argue that "the conditioned media of Ioh[ a ]ra is
further different from the claimed composition because it is not serum free.
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... [C]onditioned media containing residual serum is unsuitable for
administration." Br. 6-7.
As we understand it, Appellants' argument is that Iohara's
conditioned medium is not a "damaged part treatment composition," as
recited in claim 1, because it is unsuitable for administration. However, as
the Examiner pointed out, Ans. 8, the rejection is based on a combination of
Iohara's teaching of dental pulp stem cells and Lim's teaching of the
advantages of using serum-free media for stem cells. Thus, the composition
made obvious by the combined teachings of the references is a serum-free
conditioned medium from dental pulp stem cells. Whether Iohara's
composition itself would be considered a "damaged part treatment
composition" is not germane to the basis of the rejection.
Appellants also argue that "the cell source that generated the
conditioned medium in Lim is different from that as presently claimed. In
other words, Lim does not teach a composition comprising a dental pulp stem
cell-conditioned medium as presently claimed since it merely teaches
conditioned media from mesenchymal stem cells." Br. 7. Again, however,
the rejection is based on the combined teachings of the cited references, and
the composition made obvious by those teachings is a serum-free conditioned
medium from dental pulp stem cells.
Appellants argue that "Lim only teaches a serum-free medium at the
initial stage of differentiating embryonic stem (ES) cells into mesenchymal
stem cells. In later stages, the mesenchymal stem cells were cultured in
media in the presence of serum." Id. Similarly, Appellants argue that "Lim
merely discloses use of a serum free medium comprising FGF2 when
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obtaining MSCs by culturing ES cells ... , and Lim does not provide a
motivation to use a serum free medium for preparing a conditioned
medium." Id. at 8-9.
This argument is also unpersuasive. Lim states that "[ m ]edia for
isolating and propagating pluripotent stem cells can have any of several
different formulas." Lim 43 (emphasis added). Lim provides exemplary
serum-containing and serum-free media. Id. at 43--44. As the Examiner
pointed out, Ans. 12, Lim provides examples that describe culturing stem
cells (embryonic stem cell-derived mesenchymal stem cells, or ESC-MSCs)
in serum-free media:
Examples 7 to 15 describe experiments to analyse the
proteome of human ESC-derived MSCs (hESC-MSCs). In
these experiments, a chemically defined serum-free culture
media is conditioned by human ESC-derived MSCs (hESC-
MSCs) [and] analysed using a clinically compliant protocol.
Lim 60.
Appellants have not pointed to evidence showing that a person of
ordinary skill in the art would not have expected Iohara's dental pulp stem
cells to likewise be amenable to culturing in serum-free media.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a). Claims
2, 9, 10, and 24 have not been argued separately and therefore fall with
claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm the rejection of claims 1, 2, 9, 10, and 24 under 35 U.S.C.
§ 103(a) based on Iohara, Gandia, Tran-Hung, Nakashima, Sakai, and Lim.
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TIME PERIOD FOR RESPONSE
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
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