Ex Parte Xu et al

Patent Trials and Appeals Board

Feb 27, 2019

12131610 - (D) (P.T.A.B. Feb. 27, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/131,610 06/02/2008
27114 7590 03/01/2019
W ARF/MKE/QUARLES & BRADY LLP
Attn: IP Docket
411 E. WISCONSIN A VENUE
SUITE 2350
MILWAUKEE, WI 53202-4426
FIRST NAMED INVENTOR
Ren-He Xu
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.
961081.00020 6155
EXAMINER
MONTANARI, DAVID A
ART UNIT PAPER NUMBER
1632
NOTIFICATION DATE DELIVERY MODE
03/01/2019 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):
pat-dept@quarles.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte REN-HE XU and JAMES A. THOMSON
Appeal2017-003146
Application 12/131, 610 1
Technology Center 1600
Before DEBORAH KATZ, JOHN E. SCHNEIDER, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an in
vitro culture comprising a substantially pure, replenishable population of
synchronous primate trophoblast cells, which have been rejected as being
directed to patent-ineligible subject matter. We have jurisdiction under 35
U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
"A trophoblast is a cell which is a precursor of the cells which
participate in the formation of the human placenta." (Spec. ,r 5.) "When an
1 Appellants identify the real party in interest as Wisconsin Alumni
Research Foundation. (Appeal Br. 3.)
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Application 12/131,610
embryo begins differentiation, at the stage of a blastocyst, the cells in the
inner cell mass are committed to form the cells which will become the
embryo, while the outer cells of the blastocyst become committed to
participate in the development of the placenta." (Id.)
"Stem cells are undifferentiated or only partially differentiated cells
that have the capability to differentiate into a number of progenitor and
mature cell lineages and types." (Id. ,r 3.) "Primate embryonic stem cells
are stem cultures created from embryos that survive indefinitely in culture
and demonstrate the ability to differentiate into the major tissue types of the
primate body." (Id. ,r 4.) The present invention is directed to a culture of
trophoblast cells derived from primate embryonic stem cells.
Claims 18 and 19 are on appeal. Claim 18 is representative and reads
as follows:
18. An in vitro culture comprising a substantially pure,
replenishable population of synchronous primate trophoblast
cells, wherein the synchronous primate trophoblast cells
express chorionic gonadotropin, are predominantly chorionic
gonadotropin-beta (CG-B) positive, and are derived directly in
vitro from undifferentiated primate embryonic stem cells
exposed to a trophoblast inducing factor selected from the
group consisting of bone morphogenetic protein 4 (BMP4 ),
bone morphogenetic protein 2 (BMP2), bone morphogenetic
protein 7 (BMP7), and growth and differentiation factor 5
(GDF5) without passing through an embryoid body stage.
(Appeal Br. 9.)
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The following ground of rejection by the Examiner is before us on
review:
Claims 18 and 19 under 35 U.S.C. § 101 as being directed to patent-
ineligible subject matter.
DISCUSSION
The Examiner finds that claims 18 and 19 are not directed to patent
eligible subject matter because they recite natural products, e.g., trophoblast
cells and primate embryonic stem cells. (Ans. 2-3.) According to the
Examiner, "the cells of the claimed invention are naturally occurring and
derived." (Id. at 3.) The Examiner finds further "there is no difference
between the primate trophoblast cells used in the claimed in vitro culture and
naturally occurring cells, the primate trophoblast cells do not have markedly
different characteristics, and thus are a 'product of nature' exception. (Id.;
see also id. at 5 ("The population of primate trophoblast cells as claimed is
indistinguishable from those that exist in nature.").)
The Examiner contends "[t]he only factors which can be examined
under 101 in the claimed in vitro culture are those that are recited in the
claim i.e. primate trophoblast cells. How the cells were obtained and the
knowledge of culturing of them are not considered with respect to a
composition." (Id. at 5.) The Examiner concludes that "[t]here are no other
additional elements recited in the claims that would amount to significantly
more than the judicial exceptions." (Id. at 4.),
We disagree with the Examiner's findings and conclusion that the
claims are directed to patent-ineligible subject matter.
We analyze this case under the two-step framework described by the
Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories,
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Application 12/131,610
Inc., 566 U.S. 60 (2012) and Alice Corp. v. CLS Bankint'l, 573 U.S. 208
(2014) taking into consideration the "2019 Revised Patent Subject Matter
Eligibility Guidance" ("Revised Guidance"), issued by the Director of the
USPTO on January 7, 2019, and which provides further details regarding
how the Patent Office is to analyze patent-eligibility questions under 35
U.S.C. § 101. 84 Fed. Reg. 50-57 (Jan. 7, 2019).
We first examine whether the composition of claim 18 is directed to a
law of nature. Not every claim that involves natural products is directed to
patent-ineligible subject matter. As the Supreme Court noted "[t]he rule
against patents on naturally occurring things is not without limits, ... for 'all
inventions at some level embody, use, reflect, rest upon, or apply laws of
nature, natural phenomena, or abstract ideas,' and 'too broad an
interpretation of this exclusionary principle could eviscerate patent law."'
Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576,
589 (2013) (quoting Mayo, 566 U.S. at 71). Thus, "[d]iscoveries that
possess 'markedly different characteristics from any found in nature' [] are
eligible for patent protection." In re Roslin Institute, 750 F.3d 1333, 1336
(Fed. Cir. 2014 (quoting Diamond v. Chakrabarty, 447 U.S. 303, 310
(1980)). As our reviewing Court noted in Roslin, the claim to "a live-born
clone of a pre-existing, non-embryonic, donor mammal, wherein the
mammal is selected from cattle, sheep, pigs, and goats" was patent-ineligible
because the clone "is an exact genetic replica ... and does not possess
'markedly different characteristics"' from the donor parent. Roslin, 750
F.3d at 1337 ("Dolly's genetic identity to her donor parent[,which parent is
acknowledged to be unpatentable,] renders her unpatentable."). The Court
explained that "the word 'cloned' in the pending claims connotes genetic
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Application 12/131,610
identity, and the claims say nothing about a phenotypic difference between
the claimed subject matter and the donor mammals." Id. at 1338. The Court
further noted that "[a]ny phenotypic differences between Roslin's donor
mammals and its claimed clones are the result of 'environmental factors,'
Appellant's Br. 21, uninfluenced by Roslin's efforts" and thus, the
phenotypic differences were nature's handiwork, not "any effort of the
patentee." Id.
Claim 18 requires that the in vitro culture comprises a substantially
pure, replenishable population of synchronous trophoblast cells that are
derived directly in vitro from undifferentiated primate embryonic stem cells
and do not pass through an embryoid body stage. In determining that this
culture is a patent-ineligible product of nature, the Examiner first contends
that because the trophoblast cells are derived from a living tissue, "the cells
of the claimed invention are naturally occurring and derived." (Ans. 3.) We
find the record evidence does not support the Examiner's finding as to either
points. That is, while it is true that trophoblasts are naturally occurring, the
claimed trophoblasts are not naturally occurring. Moreover, that the cells
are derived from embryonic stem cells that are natural products is
immaterial, as the claimed trophoblasts derived therefrom are not themselves
naturally occurring and possess markedly different characteristics than
naturally occurring trophoblasts that are not simply "nature's handiwork", as
will be explained.
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Trophoblasts are naturally established in mammalian embryogenesis
from the blastomere. (Ireland2 527.)3 The blastomere can also form cells of
the inner cells mass (ICM). (Id.; see also Spec. ,r 5.) Embryonic stem cells,
unlike trophoblasts, are derived naturally from the ICM. (Spagnoli4 1.)
Moreover, trophoblasts are not naturally produced by embryonic stem cells. 5
When cultured in vitro, primate embryonic stem cells can form an embryoid
body. (Spec. ,r 4.) An embryoid body comprises undifferentiated
pluripotent stem cells and differentiated cell types, which "spontaneously
give rise to a mixed population of differentiated cell types including
trophoblasts." ( Golos Dec. 6 ,r 9.) However, embryo id bodies are not
naturally occurring, they arise in culture. (Spagnoli 1-3; see also Golos
Dec. ,r 9.)
2 Ireland, Visualizing Human Biology, 3rd Ed. Wiley and Sons Inc. (2008).
This reference was cited by the Examiner during prosecution of the present
application on appeal in a Notice of References Cited dated October 7, 2014
and was referenced in the Non-Final Office Action accompanying that
Notice. (Non-Final Office Action dated Oct. 7, 2014, at 3).
3 Trophoblasts are the outer cells of the blastocyst and participate in the
development of the placenta. (Spec. ,r 5.)
4 Spagnoli et al., Guiding embryonic stem cells towards differentiation:
lessons from molecular embryology, 16 Current Opinion in Genetics &
Development 1-7 (2006). Spagnoli was cited by Appellants during
prosecution of the application on appeal and relied on in the After Final
Response filed March 27, 2014. (After Final Response at 4.)
5 Thus, the claimed trophoblasts are not "naturally derived" from embryonic
stem cells, i.e., they are induced to form in in vitro culture.
6 Declaration of Thaddeus G. Golos, dated April 6, 2015. The Golos
Declaration was submitted by Appellants during prosecution with the
response filed April 7, 2015. (See Response to Non-Final Office Action at
3.)
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The Examiner next contends that the "nature-based products, i.e., a
population of primate trophoblast cells" of the in vitro culture have the same
genotype and phenotype and structure as naturally occurring cells and
"[h ]ow the cells were obtained" is not considered with respect to such
product claims. (Ans. 3, 5.) It is true that "[t]he patentability of a product
does not depend on its method of production" in the context of determining
patentability over the prior art. In re Thorpe, 777 F.2d 695, 698 (Fed. Cir.
1985). 7 However, as discussed above, if the product made by the recited
process is established to result in a product that has markedly different
characteristics from any found in nature, then it is patent-eligible,
notwithstanding further evaluation for patentability over prior art. Thus, the
relevant question, with respect to the § 101 issue here, is whether the
claimed in vitro culture of primate trophoblast cells that are required to be a
substantially pure, replenishable population of synchronous trophoblast cells
that are derived directly in vitro from undifferentiated primate embryonic
stem cells and do not pass through an embryoid body stage are markedly
different from naturally occurring trophoblast cells, i.e., trophoblast cells
from a blastomere. See Roslin, 750 F.3d 1339 (concluding "[t]here is
nothing in the claims, or even in the specification, that suggests that the
clones are distinct in any relevant way from the donor animals of which they
are copies."). As Appellants point out Dr. Golos's testimony supports a
conclusion that "it was well understood in the field that human placenta-
7 However, to the extent that certain structure is implied by the process
steps, that must be considered, In re Garnero, 412 F.2d 276,279 (CCPA
1979), as should any evidence of unexpected properties compared to the
prior art product, see, e.g., In re Marosi, 710 F.2d 798, 802 (Fed. Cir. 1983).
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derived trophoblasts do not proliferate in vitro[, rather such] in vivo-derived
trophoblasts form a non-replenishable, terminally differentiated trophoblast
population." (Appeal Br. 7 (citing Golos Dec. ,r,r 7, 9).) Golos explains that
placenta derived trophoblasts "do not proliferate ... when cultured in vitro."
(Golos Dec. ,r 7 .) Rather, such cells "terminally differentiate" when cultured
in vitro. (Id.) Golos explains that cells that are "incapable of replication" in
vitro are not "replenishable" in vitro. (Id.)
Golos also explains that while there where methods known for
synchronizing cells in culture, synchronized cells are "artificially induced."
(Golos Dec. ,r 8 (citing Jackman8.) Golos also states: "No isolated
substantially pure population of synchronized, replenishable human
trophoblasts exists in nature." (Golos Dec. ,r 9.)
In short, we find the foregoing evidences that trophoblast cells from
nature when cultured in vitro are not replenishable, and synchronicity of
cells in culture is artificially induced, i.e., not natural. As a consequence, we
conclude that the claimed in vitro culture of replenishable, synchronous
primate trophoblast cells derived from undifferentiated primate embryonic
stem cells without passing through an embryoid body stage are markedly
different from naturally occurring trophoblast cells.
Therefore, we reverse the Examiner's rejection of claims 18 and 19 as
being directed to patent-ineligible subject matter.
8 Jackman, Cell Cycle Analysis: Methods for Synchronizing Cells at
Specific Stages of the Cell Cycle, in Current Protocols in Cell Biology,
8.3.1-8.3.20 (1998).
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SUMMARY
We reverse the rejection of claims 18 and 19 under 35 U.S.C. § 101 as
being directed to patent-ineligible subject matter.
REVERSED
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