Ex Parte Furcht et al

Patent Trial and Appeal Board

Dec 14, 2017

12416627 (P.T.A.B. Dec. 14, 2017)

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.
12/416,627 04/01/2009 Leo T. Furcht 890003-2000.1.1 4770
26294 7590 12/18/2017
TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P.
1300 EAST NINTH STREET, SUITE 1700
CLEVELAND, OH 44114
EXAMINER
BERKE-SCHLESSEL, DAVID W
ART UNIT PAPER NUMBER
1651
NOTIFICATION DATE DELIVERY MODE
12/18/2017 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):
rkline @ tarolli. com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte LEO T. FURCHT, CATHERINE M. VERFAILLIE, and MORAYMA
REYES
Appeal 2017-0043491
Application 12/416,627
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
RYAN H. FLAX, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to a cell culture comprising isolated
expanded human non-embryonic, non-germ cells. The Examiner rejected the
claims under 35 U.S.C. § 101 as directed to a judicial exception to patent
eligibility. We have jurisdiction under 35 U.S.C. § 6(b). The § 101 rejection is
reversed.
1 The Appeal Brief (“Appeal Br.”) 3 lists ABT Holding Company as the real-party-
in-interest.
Appeal 2017-004349
Application 12/416,627
STATEMENT OF THE CASE
Claims 64—69 and 81 stand rejected by the Examiner under 35U.S.C. § 101
as directed to subject matter that is ineligible for a patent because the claims are
drawn to a product of nature. Ans. 2.
Claim 64, the only independent claim on appeal, is reproduced below:
64. A cell culture comprising isolated expanded human nonembryonic,
non-germ cells, the cells having undergone at least 10-40 cell doublings
in culture, wherein the cells express oxt4 and have a normal karyotype.
There are three related appeals, all of which have been concurrently decided
with this one. The related appeals are:
Appeal 2017-004122 (Application 12/416,672); Appeal 2017-004123
(Application 12/416,700); Appeal 2017-004124 (Application 12/416,715.
REJECTION UNDER SECTION 101
The claims are directed to a cell culture comprising isolated expanded
human non-embryonic, non-germ cells which have undergone 10-40 cell doublings
in culture and which express oxt4.2 The Examiner rejected the claims under 35
2 The original claims were directed to isolated multipotent stem cells. See claims
entered Apr. 1, 2009. An amendment to the claims was entered January 7, 2010
cancelling all claims and adding claims drawn to a “cell culture comprising
isolated expanded human non-embryonic, non-germ cells” and, inter alia, where
the cells express oct4; the term “multipotent stem” was omitted from all the claims.
Despite the absence of this phrase from the claims, Appellants refer to the claimed
cells in their Briefs as “multipotent adult stem cells” (“MASCs”) (Appeal Br. 20)
and “stem cell lines” (Reply Br. 3, 4:1—3, 5). Furthermore, Dr. Robert J. Deans in
his declaration (Deans Decl. (2015)) discusses multipotent adult stem cells with
respect to the Section 101 rejection. Deans Decl. (2015) 2—6. We note that the
“Summary of the Invention” principally describes multipotent stem cells (e.g.,
Spec. 8:23; 9:14, 23—24; 10:15—16) capable of differentiating into other cell types
{id. at 9:4—10). The “Summary of the Invention” also describes cells expressing
high levels of telomerase {id. at 10:10—13), but the pending claims do not require
2
Appeal 2017-004349
Application 12/416,627
U.S.C. § 101 as being drawn to a product of nature. Final Act. 5. The Examiner
found that because “the cells have not undergone any transformations, and have
been extracted from a human, these cells fit under a judicial exception for patent
eligible claims” and “do not differ significantly from those found in nature.” Id.
Appellants contend the Examiner erred. Appellants contend that they have
provided
extensive evidence showing that epigenetic changes and changes in
cellular phenotype occur when cells, such as those claimed, are isolated
and expanded and have undergone at least 10-40 cell doublings in
culture, and that these changes are sufficient to demonstrate that the
claimed cells have markedly different characteristics from their closest
naturally-occurring counterpart.
Appeal Br. 8.
The evidence provided by Appellants includes: (1) a declaration by Robert J.
Deans, Ph.D. (Deans Decl. (2015) executed July 15, 2015) and (2) post-filing
publications said to show that cultured multipotent cells differ from the cells
originally isolated from the host animal. Dr. Dean stated that he is an expert in
adult stem cell biology and provided evidence of his experience in this field,
including publications and scientific leadership in stem cell research. Deans Decl.
(2015) 1—2, Curriculum Vitae 2.
it. The claims require oct4 expression. The Specification teaches that studies
“have shown that oct-4 is required for maintaining the undifferentiated phenotype
of ES cells.” Id. at 3:29—30. The Specification also teaches that its multipotent
stem cells express oct4. Id., 8:31—9:1. The examples in the Specification are of
MASCs expressing oct4 (id., 24:3—8, 26:15—16, 27:20—22, 30—32, 45:28, 74:22).
To the extent that the claim could be interpreted to be broader than multipotent
stem cells, it would be necessary to consider enablement and written description
under Section 112 for the full scope of the claim.
3
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Application 12/416,627
Findings of Fact (“FF”)
As evidence that stem cells, when expanded in culture, experience a change
in phenotype and genotype from the original isolate and, contrary to the findings of
the Examiner, are no longer a product of nature, Appellants cited the following
publications (Appeal Br. 10-12, 15):
Jennifer J. Bara, et al., Concise Review: Bone Marrow-Derived
Mesenchymal Stem Cells Change Phenotype following In Vitro Culture:
Implications for Basic Research and the Clinic, 32 Stem Cells 1713—23 (2014)
(“Bara”),
Andrew C. Boquest, et al., Isolation and Transcription Profiling of Purified
Uncultured Human Stromal Stem Cells: Alteration of Gene Expression after In
Vitro Cell Culture, 16 Molecular Biology of the Cell 1131^41 (2005)
(“Boquest”),
Ofer Shoshani, et al., Cell Isolation Induces Fate Changes of Bone Marrow
Mesenchymal Cells Leading to Loss or Alternatively to Acquisition of New
Differentiation Potentials, 32 Stem Cells 2008—20 (2014) (“Shoshani”),
Cheng Cheng Zhang and Harvey F. Lodish, Murine Hematopoietic Stem
Cells Change Their Surface Phenotype During Ex Vivo Expansion, 105 Blood
4314—20 (2005) (“Zhang and Lodish”), and
Kirsten R. McEwen, et al., The Impact of Culture on Epigenetic Properties
of Pluripotent Stem Cells and Pre-Implantation Embryos, 41 Biochem. Soc.
Trans. 711-19 (2013) (“McEwen”).
4
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The following findings of fact are pertinent:
Bara (2014)
FF1.
Mesenchymal stem cells (MSCs) are increasingly being used in tissue
engineering and cell-based therapies in all fields ranging from
orthopedic to cardiovascular medicine .... The majority of approaches
rely on an in vitro cell expansion phase in monolayer to produce large
cell numbers prior to implantation. It is clear from the literature that this
in vitro expansion phase causes dramatic changes in MSC phenotype
which has very significant implications for the development of
effective therapies.
Bara 1713.
FF2.
It is becoming increasingly apparent that cell surface marker expression
profiles of in vitro expanded MSCs differ compared to both freshly
isolated cells and those residing in their bone marrow niche
environment.
Id. at 1717 (col. 1).
FF3.
Boquest (2005)
Stromal stem cells proliferate in vitro and may be differentiated along
several lineages .... Compared with CD31+ cells, CD31 [stromal
stem] cells overexpressed transcripts associated with cell cycle
quiescence and sternness, and transcripts involved in the biology of
cartilage, bone, fat, muscle, and neural tissues . . . Clones of CD31
cells could be expanded in vitro and differentiated into cells with
characteristics of bone, fat, and neural-like tissue. On culture,
transcripts associated with cell cycle quiescence, sternness, certain
cytokines and organ specific genes were down-regulated, whereas
transcripts associated with signal transduction, cell adhesion, and
cytoskeletal components were up-regulated. CD31+ cells did not
proliferate in vitro. CD45 CD34+ CD105+ CD31 cells from human
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adipose tissue have stromal stem cell properties which may make them
useful for tissue engineering.
Boquest (2005) 1131 (Abstract).
FF4.
Expression of surface markers did not differ greatly between uncultured
and cultured CD31 cells (Table 1; Supplementary Table SI). The most
obvious differences were found within the group of integrins and
adhesion molecules, where expression of several molecules was up-
regulated in culture. Other key observations were increased expression
of the MSC-related marker CD 105 and loss of expression of the HSC
marker CD34. Comparison of the transcriptomes of the cultured cells
with those of the uncultured predecessors showed that the gene
expression profile was largely similar (Supplementary Figure 2, A-C).
Id. at 1135 (col. 2).
FF5.
Nevertheless, we found that the cultured cells differ from their
uncultured counterparts. Whether these changes interfere with the
sternness of these cells, or just represent the consequence of in vitro
culture adherent to plastic surfaces, remains to be investigated.
Id. at 1140 (col. 2).
Shoshani (2014)
FF6.
Here, we show that mesenchymal cells, a priori exhibiting a limited
differentiation potential, may gain new capacities and become
multipotent following single-cell isolation. These fate changes were
accompanied by upregulation of differentiation promoting genes, many
of which also became H4K20mel methylated. Early events in the
process included TGFp and Wnt modulation, and downregulation of
hypoxia signaling. Indeed, hypoxic conditions inhibited the observed
cell changes. Overall, cell isolation from neighboring partners caused
major molecular changes and particularly, a newly established
epigenetic state, ultimately leading to the acquisition of new
differentiation potentials and an altered cell fate.
Shoshani (2014) 2008 (Abstract).
6
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FF7.
We found that sparse culture conditions experienced by MSCs in the
process of cloning causes changes in gene expression, epigenetic
profile, and signaling pathways, which ultimately lead to acquisition of
new differentiation potentials.
Id. at 2009 (col. 1).
FF8.
The results demonstrated that MSCs with a limited differentiation
potential are able to undergo cell fate changes when cultured in sparse
conditions. This leads to loss of potentials in some instances, and
surprisingly also to gain of potentials up to the point of acquisition of
multipotency. Also, single-cell cloning is sufficient to completely alter
the nature of the cell which becomes divergent from the parental
population.
Id. at 2019 (col. 2).
Zhang and Lodish (2005)
FF9.
We have developed a simple culture system that supports extensive
expansion of LT-HSCs [long-term hematopoietic stem cells].
Importantly, the expansion of LT-HSCs exceeded that of the more
differentiated cells. Our most striking result is that the surface proteins
on cultured HSCs differ significantly from those on freshly isolated
HSCs. This suggests that HSCs possess a certain level of plasticity in
surface protein expression that does not appear to alter significantly
their functions as stem cells.
Zhang and Lodish (2005) 4318-4319.
McEwen (2013)
FF10.
Recent studies have, however, found that the choice of culture
condition has a significant impact on epigenetic profiles of cultured
pluripotent cells. Mouse and human ESCs (embryonic stem cells) show
substantial epigenetic differences that are dependent on the culture
condition, including global changes to DNA methylation and histone
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modifications and, in female human ESCs, to the epigenetic process of
X chromosome inactivation.
McEwen (2013) 711 (Abstract).
FF11.
However, several recent reports . . . have documented that the culture
conditions in which pluripotent stem cells are grown have a major effect
on the epigenetic state of the cells. Pronounced changes in both global
levels and genomic localization of epigenetic marks have been reported
in mouse and human pluripotent stem cells grown using different
culture systems.
Id. at 712 (col. 1).
Deans Declaration (2015)
FF12. Dr. Deans stated in his declaration, citing the Jones publication:
There were a series of genes, reflecting important biological functions,
that changed as a consequence of ex vivo isolation [of mesenchymal
stem cells (MSC)]. Those changes included important changes in
extracellular matrix proteins. There were also changes in many of the
early receptors, such as, STR0-1, which could be used to purify the
progenitor cells but which is rapidly lost on ex vivo expansion.
Deans Decl. (2015) 3.
FF13. Dr. Deans also stated:
we had obtained similar analytical data for MAPCs. We had performed
purification and enrichment of the cells from bone marrow aspirate and
identified gene cascades before and after plating. We observed a strong
change in important pathways ... a comparison was made with respect
to the specific genes and the gene cascades that differentially express
in the in vivo-isolated compared to the ex vivo-isolated and expanded
cell population. We found significant changes in cell surface marker
expression, including, class II HLA being present on the precursor but
being absent on the expanded cell product. That is a change in an
important biological parameter that regulates the ability of the cells to
immune-sensitize or stimulate an immune response.
Id. at 3^4.
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Application 12/416,627
FF14. Dr. Deans also stated in his declaration that cells after ex vivo culture
had not been observed to engraft which he interpreted to mean that the cells “had
been modified significantly in terms of extracellular matrix proteins and
responsiveness to migratory proteins so they were no longer able to home to their
normal niche and integrate and actively participate as a natural cell should be able
to do.” Id. at 4—5. Dr. Deans cited published studies consistent with his
statements. Id. at 5.
FF15. Dr. Deans also stated, in response to the Examiner’s inquiry about a
permanent epigenetic fingerprint:
Our group has performed experiments in which a common donor bone
marrow has been used to establish both MAPC and MSC cultures in
parallel. Following 7—10 days in initial culture the established MAPC
cultures are switched to MSC culture conditions and vice versa.
Switching the culture to MSC conditions does not induce the MAPC to
become MSC. Nor does exposing MSCs to MAPC culture conditions
result in inducing the MSCs to adopt a MAPC phenotype. The assay
employed in this analysis is an epigenetic miRNA fingerprinting
analysis.
Id. at 5—6.
Roobrouck (2011)-
Roobrouck’s results are not entirely consistent with Dr. Deans’ statements
(FF15) because Roobrouck describes experiments in which the developmental
potential of different stem cells are affected by the culture conditions:
FF16.
hMAPCs [human multipotent adult progenitor cells] cultured under
MSC [human mesenchymal cell] conditions lost their endothelial
3 Valerie D. Roobrouck et al., Differentiation Potential of Human Postnatal
Mesenchymal Stem Cells, Mesoangioblasts, and Multipotent Adult Progenitor
Cells Reflected in Their Transcriptome and Partially Influenced by the Culture
Conditions, 29 Stem Cells 871—82 (2011) (“Roobrouck”).
9
Appeal 2017-004349
Application 12/416,627
differentiation capacity, whereas this was retained when cultured under
Mab [conditions, however, myogenic capacity was not gained under
Mab conditions. These studies demonstrate that hMSCs, hMab [human
mesoangioblasts], and hMAPCs have different properties that are
partially mediated by the culture conditions.
Roobrouck 871 (Abstract).
FF17.
The proliferative potential of the cells was affected by the secondary
culture conditions. MAPC_to_MSC [hMAPCs cultured under MSC
conditions] and MAPC_to_Mab cultures [hMAPCs under Mab
conditions] could only be expanded for 10—15 additional PD and did
not reach 60—70 PD.
Id. at 877 (col. 2).
FF18.
There were also phenotypic changes induced by plating the cells under
different culture conditions. MAPC_to_MSC became CD140alow,
CD140b+, and MHC class I+ . . . Likewise, MAPC_to_Mab became
CD 140alow,CD 140blow and MHC class 1+ . . . NG2 and MHC class II
expression was . . . acquired on MAPC_to_Mab, although expression
of MHC class II was very low on MAPCs cultured under Mab
conditions.
Id.
FF19.
Likewise, when hMAPCs were switched to either MSC or Mab culture
conditions, their expressed gene profile moved away from that of
hMAPCs and became more similar to that of hMSCs or hMab,
respectively (Fig. 7A, 7B). As expected from the global analysis of
gene expression, the lists of differentially expressed genes between the
original culture and the switched condition revealed that genes
determined as “characteristic” for each cell type (Fig. 4C) became
upregulated or downregulated under the switched condition (Fig. 7C,
7D).
Id. at 878 (col. 1).
10
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Application 12/416,627
FF20. However, Roobrouck also noted that culture conditions did not
reverse all changes in MAPC:
Furthermore, analysis of MAPC„to„Mab versus liMAPCs
demonstrated that the former did not acquire expression of skeletal
genes MYF5 or MLK2, in line with the observation that they did not
form skeletal myofibers in functional assays. The observation that not
all genes were reversed in MAPC__to„Mab is also reflected by the
differences observed in PC2 between hMab and MAPC...to...Mab
conditions (Fig. 7B),
Id. at 878 (col. 1-2).
FF21. Thus, based on their experiments (see, e.g., FF20), Roobrouck
concluded “this study also demonstrates that the phenotypic and functional
properties, as well as the expressed gene profile are partially influenced by changes
in the culture conditions.” Id. at 881 (col. 1).
Examiner’s Position
The Examiner determined that “Applicant has provided no evidence,
whatsoever, that there was any ‘markedly different characteristics’ imparted to the
cells by serially culturing the cells in conventional medium and on conventionally
used culture surfaces.” Ans. 4. The Examiner further stated that the Specification
“has made no suggestion, whatsoever, that the serial expansion of these cells
imparts any changes, it appears that the limitation requiring expansion is nothing
more than a manner of isolating and expanding populations that are large enough
to be usable by the artisan.” Id. at 8.
With respect to the evidence provided by Appellants, the Examiner found
that the “evidence is drawn to other cell-types, and not the instantly claimed cell-
types.” Id. at 5. Furthermore, the Examiner noted that Appellants had provided
evidence that its pluripotent cells differ from other stem cell types, including the
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mesenchymal stem cells described in the evidence provided by Appellants. Id.
The Examiner therefore concluded:
Since the evidence does not directly apply to the instantly claimed cell-
type, and the fact that the Appellant has gone through significant efforts
to show that the cells of the art are, in fact, different than the instantly
claimed cells, it is unclear how the Appellant can argue that these
changes would necessarily apply to this cell-type.
Id.
The Examiner did not find persuasive Dr. Deans’ statement that cells after ex
vivo expansion were different from the cells after immediate isolation, and
indicated:
In addition to only suggesting that one marker may have “significant
changes,” the Appellant has not provided the laboratory data for these
results (graphs, charts or other numerical data), preventing the Office
from making an objective assessment of the alleged changes, and if they
are considered to be significant changes. The Appellant further states
that the cells of the instant invention were unable to engraft, following
ex vivo/in vitro culture; however, this suggests that the cells may
possesses a lack of utility.
Id. at 6; see also id. at 10 (noting “the lack of data of data presented by the
Appellant”).
Discussion
The principal issue regarding the Section 101 rejection on appeal is whether
the claimed cells which have undergone 10-40 cell doublings in culture and which
express oct4 are different from the progenitor cell type that exists in vivo in a
human before culture because of undergoing changes during their growth and cell
division.
To begin, we must address what is meant by the claimed cells being
“different” from the cells that occur naturally in a human. While cells may express
different genes and proteins at different times during cell culture, the difference
12
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must be relatively permanent (e.g., a modification to the DNA) (see Deans Decl.
(2015) 8, 14, 15), and not just a transient and reversible change to the cell, but one
that results in a structural difference between the cultured cell and the cell
originally isolated from the human. Thus, while the reported changes in gene
expression (e.g., FF2) might reflect structural changes to the DNA structure,
Appellants did not provide evidence that they necessarily do. Indeed, Roobrouck
showed some of the gene expression changes in a stem cell could be reversed by a
change in culture medium (FF16—FF19).
The Examiner initially found that the claimed cells were the same as those
found in nature, shifting the burden to Appellants to prove otherwise. In response,
Appellants provided evidence from a number of publications, as summarized in the
Findings of Fact, supra, that expression profiles changed during cell culture of
stem cells (see, e.g., FF2, FF4, FF6, and FF18). The publications disclosures
involved mesenchymal, stromal, and hematopoietic stem cells (FF1, FF3, FF6, and
FF9), but not the claimed cell type.4
Appellants cited experiments disclosed in Boquest, which led its authors to
conclude that cultured stromal and mesenchymal cells are “differing from” the
same cell type obtained from the original mammalian source prior to culture (FF5).
Appellants also cited a second publication which concluded that “single-cell
cloning [of mesenchymal cells] is sufficient to completely alter the nature of the
cell which becomes divergent from the parental population” (FF8).
4 The Examiner and Appellants appear to agree that the cells described in the
publications are not the same as those which are claimed, despite the absence of
the explicit terms in the claim that the cells are adult multipotent stem cells.
13
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Application 12/416,627
Importantly, Appellants also provided evidence that epigenetic5 structural
changes to the genome had occurred in mesenchymal and embryonic stem cells,
namely in methylation and histone modification (FF6, FF7, F10, and FF11). Dr.
Deans also summarized experiments, although no data was shown, that MAPC
cells had undergone epigenetic changes (FF15).
The Examiner did not find the evidence persuasive because it was “drawn to
other cell-types, and not the instantly claimed cell-types” and because the
Specification did not characterize the differences that occur to the claimed cell
during the cell culture doublings. Ans. 4, 5, and 8. However, the Examiner did
not address Dr. Deans’ reasoning that the results for mesenchymal and embryonic
stem cells are relevant to the claimed cells because “cells must adapt in order to
grow in a two-dimensional plate culture or in suspension culture where they are not
in contact with other cells in their in vivo niche.” Deans Decl. (2015) 3. In other
words, Appellants’ evidence supports that if changes to the genome, including
methylation and histone modification, occurred in other types of stem cells during
cell culture adaptation, it is scientifically logical that the changes also occurred to
the claimed cell line when it was cultured. As noted by Dr. Deans “cell culture is
non-physiological” and artificial (id.) and thus does not represent changes that
would occur naturally.
The Examiner also did not address the disclosure in Roobrouck (2011)
stating that the properties of multipotent adult stem cells are only partially
mediated by culture conditions (FF16, FF20, FF21), which is consistent with
5 “The set of heritable chemical changes to an organism's genome, such as DNA
methylation or histone modification, that modify gene expression but do not
change the DNA sequence itself.” https://www.thefreedictionary.com/epigenome
(accessed Dec. 1, 2017).
14
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Dr. Deans summary about epigenetic changes to the adult stem cells (FF15) and
that observed in other stem cell lines (FF6, FF7, FF10, and FF11). In other words,
there is evidence, which was not refuted by the Examiner, that some of the changes
to the claimed cells are not reversible by altering cell culture conditions, but
instead represent structural and non-reversible changes to the cells, e.g., changes to
the histone structure and DNA methylation (“epigenetic”) of the cell’s genome.
Dr. Deans also described expression and behavioral differences between the
cells after isolation and after the ex vivo expansion (FF13—FF14). While this data
does not necessarily prove that the two cell populations are structurally different
from each other, the expression data is of the same type observed with
mesenchymal cells which were characterized as being different (FF5, FF7)) and
which were also accompanied by structural DNA methylation changes to the cells
(FF6). Consistently, changes in gene expression, epigenetic profile, and signaling
pathways were characterized by Shoshani as “completely altering] the nature of
the cell which becomes divergent from the parental population” (FF8).
The Examiner did not find Dr. Deans’ summary of the experiments
sufficient because the underlying data was not provided. Ans. 6, 10 (see above).
However, the Examiner did not give a reason to doubt Dr. Deans’ credibility,
particularly, when the changes reported were consistent with those described by
mesenchymal cell lines. Moreover, Dr. Deans’ statements about the loss of
engrafting is supported by published reports (FF14).6 While the Examiner is
correct that such distinguishing data and information is not the Specification and
would have been useful here, we have not been pointed to legal authority that
would require it.
6 Such published study also establishes the utility of the claimed cells (FF14),
rebutting the Examiner’s concern about a lack of utility (Ans. 6).
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In our opinion, as with utility rejections under Section 101, the PTO has the
initial burden of establishing that the claimed subject matter is a judicial exception
to patentability. See In re Swartz, 232 F.3d 862, 864 (Fed. Cir. 2000) (utility under
35 U.S.C. 101). Once this burden was met, as it was here, “the burden shifts to the
applicant to submit evidence sufficient to convince” the ordinary skilled worker
(id.) that the claimed subject matter is not directed to a judicial exception,
specifically in this case, to a product of nature. Appellants provided rebuttal
evidence, as discussed above, that the claimed cells are structurally different from
those cells found occurring naturally in a human body. The Examiner did not
persuasively identify a defect in Appellant’ evidence, particularly in Dr. Deans’
scientific logic about the pertinence of data from other pluripotent stem cell lines to
the claimed cells because of their adaptation to cell culture, as well as the
consistency between Dr. Deans’ statements about the properties of the claimed
cells with those of other stem cells as summarized in the Findings of Fact.
SUMMARY
The rejection of claims 64—69 and 81 under 35 U.S.C. § 101 is reversed.
REVERSED
16
Notice of References Cited
Application/Control No.
12/416,627
Applicant(s)/Patent Under
Reexamination
Examiner
David W. Berke-Schlessel
Art Unit
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Dates in MM-YYYY format are publication dates. Classifications may be US or foreign.
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PTO-892 (Rev. 01-2001) Notice of References Cited Part of Paper No.
12/13/2017 Epigenome - definition of epigenome by The Free Dictionary
Epigenome » definition of epigenome by The Free Dictionary
https:ZAvww.th efreediciionary.com/epigenome
w' quickbooks
Also found in: Medical, Encyclopedia, Wskipedsa.
ep-i-ge-nome ^ (epi-jemom)
n.
The set of heritable chemical changes to an organism's genome, such as DNA methylation or histone modification, that
modify gene expression but do not change the DNA sequence itself.
epl-geno'rrtic (-je-no'mfk) adj.
American Heritage® Dictionary of the English Language, Fifth Edition. Copyright © 2016 by Houghton Mifflin Harcourt Publishing Company.
Published by Houghton Mifflin Harcourt Publishing Company. All rights reserved.
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