Ex Parte West et al

Patent Trial and Appeal Board

Jan 25, 2017

13279123 (P.T.A.B. Jan. 25, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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P.O.Box 1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/279,123 10/21/2011 Michael D. West BIOT-030 7454
105032 7590 01/25/2017 EXAMINER
Kin l ime Ine
c/o Jennifer Fleischer ARON, KIMBERLY A
1010 Atlantic Avenue, Suite 102
Alameda, CA 94501 ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
01/25/2017 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 MICHAEL D. WEST and KAREN B. CHAPMAN.1
Appeal 2016-000906
Application 13/279,123
Technology Center 1600
Before RICHARD J SMITH, JOHN E. SCHNEIDER, and
RACHEL H TOWNSEND, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to cell
lines expressing certain transcription factors which have been rejected as
anticipated and as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
The present invention is directed to progenitor cell lines having
unique gene expression and developmental capabilities including expression
1 Appellants identify the Real Party in Interest as BioTime, Inc. Appeal Br.
3.
Appeal 2016-000906
Application 13/279,123
of one or more transcriptional regulators. Spec. 9. The transcriptional
regulators include OCT4 and LHX3.
Claims 18—22 are on appeal. Claims 18, 20, and 21 are the sole
independent claims and read as follows:
18. An isolated progenitor cell line, wherein said isolated
progenitor cell line constitutively expresses OCT 4 and a
transcription factor selected from the group consisting of SIX1,
FOXA1, SOX17, SIX2, SOX21, PAX6, MYOD1, MYOG,
NEUROG1, NKX2.5, and combinations thereof, wherein the
expression level of OCT4 is greater than the expression level of
OCT4 in an iPS cell.
20. An isolated progenitor cell line, wherein said progenitor cell
line expresses the genes RESP18 and LHX3 simultaneously
and is the in vitro progeny of a pluripotent stem cell.
21. An isolated progenitor cell line, wherein said progenitor
cell line expresses a transcription factor and is a differentiated
cell line differentiated in vitro from a pluripotent stem cell.
The claims have been rejected as follows:
Claim 21 stands rejected under 35 U.S.C. § 102(b) as anticipated by
Oh.2
Claim 18 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Wolffe.3
Claims 18 and 19 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Wolffe in view of Jessell.4
2 Oh, US 7,510870 B2, issued Mar. 31, 2009 (“Oh”).
3 Wolffe et al., US 2006/0251642 Al, published Nov. 9, 2006 (“Wolffe”).
4 Jessell et al., US 2004/0014210 Al, published Jan. 2, 2004 (“Jessell”).
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Application 13/279,123
Claim 20 stands rejected under 35 U.S.C. § 103(a) as unpatentable
over Sang5 in view of Kubo.6
Claims 20 and 22 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Sang in view of Kubo and Gonzales.7
THE REJECTION BASED ON OH
Issue
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claim 21 is anticipated
by Oh under 35 U.S.C. § 102(b).
The Examiner finds that Oh discloses the generation of isolated
modified progenitor cells with the expression of an activated form of
STAT3. Final Act. 4. The Examiner finds that the constitutive expression
of STAT3 is capable of maintaining self-renewal and proliferation of the
progenitor cell and reducing the differentiation of the cells. Id. The
Examiner finds that the cells of Oh meet the limitations of claim 21. Id.
Appellants contend that Oh does not meet all the limitations of claim
21 in that the cells are not differentiated cells. Appeal Br. 11. Appellants
also contend that Oh does not anticipate in that it is not enabling. Appeal Br.
12. Appellants argue that Oh does not teach producing differentiated cells in
vivo from a pluripotent stem cell. Id.
5 Sang et al., US 2005/0074880 Al, published Apr. 7, 2005 (’’Sang”).
6 Kubo et al., US 2009/0280096 Al, published Nov. 12, 2009 (“Kubo”).
7 Gonzales et al., Distribution Patterns of Estrogen Receptor a and ft in the
Human Cortes and Hippocampus During Development and Adulthood, 503
J. Comp. Neur. 790 (2007) (“Gonzales”).
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Application 13/279,123
Findings of Fact
We adopt as our own the Examiner’s findings and analysis. The
following findings are included for emphasis and reference convenience.
FF1. The Specification teaches that “[t]he term ‘differentiated cells’
when used in reference to cells made by methods of this invention from
pluripotent stem cells refer to cells having reduced potential to differentiate
when compared to the parent pluripotent stem cells. The differentiated cells
of this invention comprise cells that could differentiate further (i.e., they
may not be terminally differentiated).” Spec 5.
FF2. Oh discloses “[s]tem cells modified to express activated form of
STAT3 by genetic modification or protein delivery, and stem cells co­
cultured with cells expressing activated form of STAT3 exhibit increased
ex-vivo expansion and enhanced in-vivo regeneration accompanied by net
increase in stem cell self-renewal as compared to control group.” Oh
Abstract.
FF3. Oh teaches that the modified stem cell may have increased in-
vitro proliferative activity while maintaining multipotent characteristics of
unmodified parental cell.” Oh col. 3,11. 48—50.
Principles of Law
“Under 35 U.S.C. § 102, every limitation of a claim must identically
appear in a single prior art reference for it to anticipate the claim.” Gechter
v. Davidson, 116 F.3d 1454, 1457 (Fed. Cir. 1997).
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Application 13/279,123
Analysis
We believe Appellants have the better position. Oh clearly teaches
that the modified stem cells retain the multipotent capabilities of the parent
cells. FF3. Thus they are not differentiated cells as defined in the present
specification and as used in claim 21. FF1.
The Examiner contends that the claims do not provide a comparative
basis for the relative term “reduced potential” (see FF1) nor does the claim
identify the parent cells. Ans. 12. The Examiner argues that the claims only
require that there be some diminished capacity of the differentiated cells
relative to the parent cells to meet the definition of a differentiated cell.
Ans. 11—12. While this may be so, Oh teaches that the modified stem cell
line maintains the multipotent activity of the parent cell line. FF3. Thus, the
ability of the modified cells to differentiate is the same as the parent cells.
The modified stem cells of Oh do not meet the definition of a differentiated
cell line as the term is used in claim 21.
Conclusion of Law
We conclude that the Examiner has not established by a
preponderance of the evidence that claim 21 is anticipated by Oh.
THE REJECTION BASED ON WOLFFE
Issue
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claim 18 is unpatentable
over Wolffe under 35 U.S.C. § 103(a).
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Application 13/279,123
The Examiner finds that Wolffe discloses the use of zinc finger
nucleases to control cell differentiation and self-renewal. Final Act. 6. The
Examiner finds that the zinc finger nucleases can be targeted to one or more
promoter regions to turn on or off expression including the region for
expression of OCT4. Final Act. 6—7. The Examiner finds that Wolffe
discloses that OCT4 and Pax6 are known markers for pluripotent stem cells.
Final Act. 7. The Examiner concludes that
[a] person of ordinary skill in the art would have had a
reasonable expectation of success in targeting both Oct4 and
Pax6 with zinc finger nucleases to result in constitutive
expression of Oct4 and Pax 6, in isolated pluripotent stem cells
because Wolffe explicitly suggests Oct4 and Pax6 are known
targets for pluripotent stem cells (Table 1), and zinc finger
nucleases can target genes to provide constitutive expression.
The skilled artisan would have been motivated to utilize the
zinc finger technology of Wolffe in order to provide a high
degree of specificity in determining cell fate, and overcoming
known problems associated with propagating and maintaining
pluripotent cells in culture, as taught by Wolffe.
Final Act. 7.
Appellants contend that Wolfe does not teach all the limitations of
claim 18 in that Wolffe does not teach a cell line where the expression level
of OCT4 is greater than that for an iPS cell. Appeal Br. 16—18. Appellants
also argue that Wolffe does not teach or suggest a cell line wherein the line
constitutively expresses both OCT4 and Pax6. Appeal Br. 19. Appellants
also argue that one skilled in the art would not have a reasonable expectation
of success in that Wolffe teaches that OCT4 is expressed in undifferentiated
cells or by endoderm cells whereas Pax6 is expressed in cells differentiated
into neuroepithelium cells and ectoderm cells. Appeal Br. 19-20, Wolffe,
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Application 13/279,123
Table 1. Appellants argue that Wolffe teaches the down regulation of OCT4
which would lead one skilled in the art from expressing OCT4 in a
progenitor cell. Appeal Br. 21.
We believe Appellants have the better position. Wolffe teaches that
OCT4 and Pax6 are expressed by different cell types and at different stages
of development. OCT4 is expressed to establish and maintain
undifferentiated cells, whereas Pax6 is expressed during differentiation of
cells into neuroepithelium cells. Wolffe Table 1. The Examiner has offered
no credible explanation as to why one skilled in the art would seek to
express both markers at the same time. “[Rejections on obviousness
grounds cannot be sustained by mere conclusory statements; instead, there
must be some articulated reasoning with some rational underpinning to
support the legal conclusion of obviousness.” KSR Int’l Co. v. Teleflex Inc.,
550 U.S. 398, 418 (2007) {quoting In re Kahn, 441 F.3d 977, 988 (Fed. Cir.
2006).
The Examiner contends that Wolffe teaches that OCT4 and Pax6 are
markers commonly used to identify and characterize differentiated cells and
that zinc finger technology can be used to target more than one gene to
provide expression. Ans. 16—17. While this may be true, we agree with
Appellants that the Examiner has not pointed to anything in Wolffe which
would lead one skilled in the art to develop a cell line that constitutively
expressed both OCT4 and Pax6. Reply Br. 6.
We conclude that the Examiner has failed to establish by a
preponderance of the evidence that claim 18 would have been obvious over
Wolffe.
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THE REJECTION BASED ON WOLFFE AND JESSELL
Issue
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claims 18 and 19 would
have been obvious over Wolffe combined with Jessell.
The Examiner reiterates the findings with respect to Wolffe discussed
above. Final Act. 11. The Examiner finds that Jessell teaches that LHX3 is
a known marker for motor neuron differentiation and that Pax6 is an
upstream regulator of LHX3. Id. The Examiner conclude that
[i]t would have been obvious to the skilled artisan to combine
the teachings of Wolffe on a pluripotent cell line which
expresses OCT 4 and a transcription factor which indicates
differentiation (including partial differentiation) such as PAX6
further with the teachings of Jessell, as Jessell discloses that
LHX3 is a known marker for motor neuron differentiation, and
is regulated by PAX6. A skilled artisan would have been
motivated to combine Wolffe further with Jessell, because
Jessell discloses PAX6 is an upstream regulator of LHX3 in
neuronal differentiation. A skilled artisan would have had a
reasonable expectation of success as the utilizing of P AX6 or
LHX3 to identify differentiation of pluripotent cells was known
at the time of the invention.
Final Act. 11—12.
Appellants reiterate their contentions with respect to Wolffe and
further argue that Jessell does not cure the defects of Wolffe. Appeal Br. 22.
Appellants also argue that the Examiner has not articulated a rationale why
one skilled in the art would combine the references. Appeal Br. 23.
We believe Appellants have the better position. As discussed above,
the Examiner has not given a reasonable explanation as to why one skilled in
the art would develop a cell line where both OCT4 and Pax6 are expressed
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Application 13/279,123
constitutively. In addition, the Examiner in this rejection has not stated a
reasonable explanation why one skilled in the art would develop a cell line
that also expresses LHX3. The Examiner’s statement that LHX is a known
marker for neuron differentiation and is regulated by Pax6, Ans. 18, does not
explain why one skilled in the art would develop a cell line expressing all
three factors, especially given that OCT4 is expressed by undifferentiated
cells. We conclude that the Examiner has failed to establish by a
preponderance of the evidence that claims 18 and 19 would have been
obvious over Wolffe combined with Jessell under 35 U.S.C. § 103(a).
THE REJECTION BASED ON SANG AND KUBO
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claim 20 would have
been obvious over Sang combined with Kubo under 35 U.S.C. § 103(a).
The Examiner finds that Sang discloses progenitor cells which can
express neuronal marker or the endocrine marker LHX3, which is indicative
of pituitary differentiation. Final Act. 13. The Examiner finds that Kubo
discloses that embryoid cells can express RESP18. Final Act. 14. The
Examiner concludes that “[a] person of ordinary skill in the art would have
had a reasonable expectation of success in identifying progenitor cells with
the capability to become endocrine cells, as taught by Sang, to have
expression of both LHX3 and RESP 18 markers. The skilled artisan would
have been motivated to test for RESP 18 in addition to LHX3 because Kubo
discloses that RESP 18 is known to be expressed both in stem cells.” Id.
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Appellants contend that the references do not teach all of the
limitations of the claim. Appeal Br. 24. Appellants also contend that the
Examiner has not articulated a rationale why the teachings of the two
references should be combined nor would one skilled in the art have a
reasonable expectation of success. Appeal Br. 25—26.
We believe that Appellants have the better position. As the
Appellants point out, Kubo teaches that the expression of RESP18 is related
to pancreatic islet development. Appeal Br. 25, Kubo Table 1. Sang
discloses that LHX3 is associated with pituitary development. Appeal Br.
25, Sang || 13, 36, and 108. The Examiner has offered no credible rationale
why one skilled in the art would combine the teachings related to pancreatic
cells with the teachings of a reference related to pituitary cells to create a
cell line which expresses both RESP18 and LHX3.
We conclude that the Examiner has failed to establish by a
preponderance of the evidence that claim 20 would have been obvious over
Sang combined with Kubo under 35 U.S.C. § 103(a).
THE REJECTION BASED ON SANG COMBINED WITH KUBO AND
GONZALES
The issue with respect to this rejection is whether the Examiner has
established by a preponderance of the evidence that claims 20 and 22 would
have been obvious over Sang combined with Kubo and Gonzales under 35
U.S.C. § 103(a).
The Examiner reiterates the findings with respect to Sang and Kubo
discussed above. Final Act. 16. The Examiner finds that Gonzales discloses
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that the estrogen receptor 2 (ErP) is detected in a variety of gestational
neurons. Id. The Examiner concludes that
[a] person of ordinary skill in the art would have had a
reasonable expectation of success in identifying progenitor cells
with the capability to become neuronal or endocrine cells and
express LHX3 and RESP18, as taught by Sang and Kubo, to
have expression of LHX3, RESP18 and ESR2 markers. The
skilled artisan would have been motivated to test for ESR2 in
addition to LHX3 and RESP18 because Gonzales discloses that
ESR2 is known to be expressed both in neuronal tissues
throughout development and adulthood.
Id.
Appellants contend that a skilled artisan would not have a reasonable
expectation of success in combining the references in that each reference
describes a distinct type of cell. Appeal Br. 27. Appellants also argue that
the Examiner has not provided a rationale for combining the references.
Appeal Br. 28.
Once again we believe that Appellants have the better position. Each
of the references relates to a different type of cell. Sang is directed to
pituitary development, Sang || 13, 36, and 108. Kubo is directed to
pancreatic development, Kubo Table 1, and Gonzales is directed to neuronal
and glial cells, Gonzales Abstract. The Examiner has not articulated a
credible rationale for why one skilled in the art would combine the teachings
of the references to create a cell line expressing all three transcription
factors.
SUMMARY
We reverse the rejection under 35 U.S.C. § 102(b).
We reverse the rejections under 35 U.S.C. § 103(a).
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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).
REVERSED
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