Ex Parte Lin et al

Patent Trial and Appeal Board

May 17, 2016

12318806 (P.T.A.B. May. 17, 2016)

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.
12/318,806 01/08/2009 Shi-Lung Lin 5199/0253PUS1 2058
60601 7590 05/17/2016
Muncy, Geissler, Olds & Lowe, P.C.
4000 Legato Road
Suite 310
FAIRFAX, VA 22033
EXAMINER
SCHULTZ, JAMES
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
05/17/2016 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 SHI-LUNG LIN and DAVID TS WU1
________________

Appeal 2014-003499
Application 12/318,806
Technology Center 1600
________________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and JOHN G. NEW,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1Appellants state the real parties-in-interest are the inventors named above.
App. Br. 2.
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SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1–12, 14–15, 17–18, 20, 22, 25–28,
30–36, 38–39 and 43–45. Specifically, claims 1–3, 5–10, 12, 14–15, 17–21,
26–29, 35–36, 39 and 42 as unpatentable under 35 U.S.C. §103(a) as being
obvious over the combination of Kim (WO 2005/056797 A1, December 15,
2004) (“Kim”), Shi-Lung Lin et al., MicroRNA miR-302 Inhibits the
Tumorigenecity of Human Pluripotent Stem Cells by Coordinate
Suppression of the CDK2 and CDK4/6 Cell Cycle Pathways, 70 (22)
CANCER RES., 9473–82 (2010) (“Lin A”), Rezania (US 7,939,322 B2, May
10, 2011) (“Rezania”) and Shao-Yao Ying et al., Intron-derived microRNAs-
fine tuning of gene functions, 342 GENE 25-28 (2004) (“Ying”).2
Claims 1–12, 14–15, 17–18, 20, 22, 25–28, 30–36, 38–39 and 43–45
also stand rejected as unpatentable under the nonstatutory doctrine of
obviousness-type double patenting.
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellants’ invention is directed to a method for developing,
generating, and selecting tumor-free embryonic stem (ES)-like pluripotent
cells using electroporation delivery of an inducible tumor suppressor mir-
302 agent into mammalian cells. Specifically, the present invention relates
to a method and composition for generating a Tet-On/Off recombinant

2 Referred to in Appellants’ Brief as “Lin B.”
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transgene capable of expressing a manually re-designed mir-302 microRNA
(miRNA)/shRNA agent under the control of doxycyclin (Dox) in human
somatic/cancer cells and thus inducing certain specific gene silencing effects
on the differentiation-associated genes and oncogenes of the cells, resulting
in reprogramming the cells into an ES-like pluripotent state. Abstract.

REPRESENTATIVE CLAIM

Appellants argue the claims together. App. Br. 8–11. Claim 1 is
representative and recites:
1. A method for preventing stem cell tumorigenecity, said
method comprising these steps of:

(a) providing at least a cell substrate expressing a
plurality of CDK2 and the associated cell-cycle-
related genes targeted by mir-302;

(b) providing at least a recombinant nucleic acid
composition capable of being delivered and
processed into at least an intronic microRNA-like
gene silencing effector targeting said CDK2 and the
associated cell-cycle-related genes in said cell
substrate, wherein said intronic microRNA contains
at least a nucleic acid sequence homologous to
SEQ.ID.N0.3; and

(c) treating said cell substrate with said recombinant
nucleic acid composition under a condition that the
concentration of said intronic microRNA-like gene
silencing effector is sufficient to suppress said
CDK2 and the associated cell-cycle-related genes,
wherein said concentration is similar to or higher
than the mir-302 level found in human embryonic
stem cells.
App. Br. 15.
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ISSUES AND ANALYSES
We agree with, and adopt, the Examiner’s findings and conclusion
that the appealed claims are prima facie obvious over the cited prior art
references. We address the arguments raised by Appellants on appeal
below.

A. Denial of Priority to Appellants ’262 Application
Issue
Appellant argues the Examiner improperly denied priority to U.S.
Patent Application Serial No. 10/439,262 filed on May 15, 2003 (the “’262
application”) was improper. App. Br. 6.

Analysis
Appellants argue their ’262 application teaches a method for
expressing intronic microRNA and contend mir-302, as disclosed in their
Specification in the instant appeal, is a bona fide natural intronic microRNA
expressed in humans. App. Br. 6. Appellants assert that it would have been
reasonable for a person of ordinary skill in the art to use the method of
the’262 application for expressing mir-302. Id.
Appellants contend that, as of 2004, 90 intronic microRNAs in
Humans were known in the art, and that mir-302 was one of these. App. Br.
6 (citing A. Rodriguez et al., Identification of Mammalian microRNA Host
Genes and Transcription Units, 14 GENOME RESEARCH 1902–1910 (2004)
(“Rodriguez”)Tables 1and 4). Appellants point to Table 4 of Rodriguez,
which explicitly lists mir-302 as one of the 26 intronic microRNAs as “Non-
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coding Transcription Units.” Id. Appellants argue Rodriguez further
suggests that the mechanisms of biogenesis for exonic and introic
microRNA expression may be different. Id. (citing Rodriguez, Abstract).
Appellants contend testing 26 microRNAs would not require unreasonable
effort for any person of ordinary skill in the art at the time of the ’262
application. Id. Appellants further argue that, since the transcription unit of
mir-302 does not encode any protein, a person of ordinary skill in the art
would be strongly motivated to use the method disclosed in the ’262
application for expressing mir-302 in human cells and studying its function
and mechanism as research in this area has been important since at least
2000. Id. Consequently, Appellants argue, a person of ordinary skill in the
art would have been strongly motivated to, and capable of, enabling the
method taught by the ’262 application for expressing mir-302. Id. at 7.
Appellants also argue that it would not have required undue
experimentation for a person of ordinary skill to achieve expression of mir-
302 by following the method disclosed in the ’262 application. App. Br. 7.
Appellants point to Examples 2 and 3 of the ’262 application and Examples
1–3 of Appellants’ instant Specification, which, Appellants argue, disclose
the required experimental steps comprising: (1) synthesizing the mir-302
DNA templates; (2) matching the DNA ends; (3) ligating the mir-302 into
the insertion site of a SpRNAi-RGFP gene expression vector; and (4)
delivering the vector into a cell for expression. Id. Appellants assert these
four steps were reasonably well-known DNA recombination technics to a
person of ordinary skill in the art and all materials were commercially
available at the time of the ’262 application. Id. Appellants assert that both
the ’262 application and the present invention use the same SpRNAi-RGFP
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gene to carry the intronic microRNA inserts for expression, indicating that
the methodology and design of these two inventions are actually
continuously connected to each other. Id.
Appellants argue further that the method of the ’262 application has
been tested in stem cells as shown in paragraphs [0024], [0025], [0038],
[0040], and [0105] as well as Figures 5 and 6 of the ’262 application. App.
Br. 7. The Appellants assert the Examiner has contended that preventing
stem cell tumorigenicity flows naturally from mir-302 expression and argue,
therefore, that a person of ordinary skill in the art, using the ’262 application
for expressing mir-302, would have naturally led to the invention now
claimed by Appellants. Id.
Finally, Appellants point to H.B. Houbaviy et al., Embryonic Stem
Cell-Specific MicroRNAs, 5 DEVELOPMENTAL CELL 351–358 (2003)
(“Houbaviy”). According to Appellants, Houbaviy teaches that mir-302 is
an embryonic stem cell-specific microRNA. Id. (citing Houbaviy Table 1).
Appellants therefore reason that a person of ordinary skill, having compared
the teachings of Rodriguez and Houbaviy, would realize that mir-302,
mir-15, mir-16, mir-30, mir-31, mir-93, mir-106, mir-141, and let-7d are the
nine intronic microRNAs expressed in embryonic stem cells. Id. Therefore,
argue Appellants, a person of ordinary skill in the art would have been
strongly motivated to test the over-expression effects of these nine intronic
microRNAs using the method of the ’262 application in embryonic stem
cells, which would then have led to the invention claimed in the instant ’806
application.
The Examiner responds that 35 U.S.C. § 120 requires that, in order to
receive the benefit of a priority claim, support for all aspects of the claimed
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invention must be evident in the manner required by 35 U.S.C. § 112, first
paragraph in the document to which the priority claim has been made.
Ans. 7. The Examiner denied priority to the ’262 application, as well as
U.S. Application Serial Nos. 11/278,143 and 12/149,7253 because
Appellants’ claimed invention requires mir-302 and no mention of mir-302
can be found in any of these earlier applications. Id. Furthermore, the
Examiner also finds no earlier application making any reference to CDK2,
whose downregulation is explicitly required in the instant invention. Id.
Finally, the Examiner finds, the 61/011,333 priority document (the “’333
priority document”), filed 1/16/2008, also lacks any teaching of preventing
stem cell tumorigenicity, because no reference to such mir-302-based
prevention of tumorigenicity is to be found in the document. Id. at 7–8.
The Examiner finds none of the deficient earlier applications provide
written description support for the presently claimed invention in the manner
required by 35 U.S.C. § 112, first paragraph, because the claimed invention
requires the use of a sequence-specific microRNA family, mir-302, and none
of the deficient earlier applications disclose anything about mir-302 or
related sequences. Ans. 9. The Examiner therefore finds there is no
evidence that Appellants were in possession of mir-302 at the time the ’262
application was filed on May 15, 2003. Id.
The Examiner further finds Appellants’ claimed method cannot be
practiced without mir-302; therefore, the Examiner finds, mir-302 is a
critical element of the claimed invention which cannot be excluded from the
claims or the Specification of the ’262 application and yet be considered to

3 The present application is a continuation-in-part of the ’262 application and
U.S. Application Serial Nos. 11/278,143 and 12/149,725.
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adequately supported under 35 U.S.C. § 112, first paragraph. App. Br. 9.
The Examiner is not persuaded by Appellants’ argument that the ’262
application teaches methods of using miRNA generally, and that mir-302 is
typical of the miRNA species allegedly within the scope of the ’262
application, because Appellants have not demonstrated possession of mir-
302 within the disclosures of the 262 application. Id. at 10. Furthermore,
the Examiner finds that, although Appellants argue that mir-302 was known
in the art as early as the teachings of Rodriguez and Houbaviy, the Examiner
finds the ’262 application was filed prior to these earliest mir-302
disclosures.4 Id. The Examiner therefore finds that, although Appellants
argue that they should receive the priority benefit of something that (1) they
did not disclose, and (2) is not in the prior art at the time of the ’262
application’s filing, Appellants have nevertheless failed to demonstrate
possession of the essential mir-302 as required by 35 U.S.C. § 112, first
paragraph. Id.
We agree with the Examiner. 35 U.S.C. § 120 recites:
An application for patent for an invention disclosed in the
manner provided by section 112(a) (other than the requirement
to disclose the best mode) in an application previously filed in
the United States, or as provided by section 363, which is filed
by an inventor or inventors named in the previously filed
application shall have the same effect, as to such invention, as
though filed on the date of the prior application, if filed before
the patenting or abandonment of or termination of proceedings
on the first application or on an application similarly entitled to
the benefit of the filing date of the first application and if it
contains or is amended to contain a specific reference to the
earlier filed application….

4 Houbaviy and Rodriguez were published in August 2003 and 2004,
respectively.
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We agree with the Examiner that § 120 requires that, for a later application
to claim the benefit of a prior application, that prior application must meet
the requirements of written description support established under 35 U.S.C.
§112, first paragraph.
The first paragraph of 35 U.S.C. § 112 recites:
The specification shall contain a written description of the
invention, and of the manner and process of making and using it,
in such full, clear, concise, and exact terms as to enable any
person skilled in the art to which it pertains, or with which it is
most nearly connected, to make and use the same, and shall set
forth the best mode contemplated by the inventor of carrying out
his invention.

It is well-established, however, that “[t]he purpose of the ‘written
description’ requirement is broader than to merely explain how to ‘make and
use’; the applicant must also convey with reasonable clarity to those skilled
in the art that, as of the filing date sought, he or she was in possession of the
invention.” Vas-Cath Inc. v. Mahurkar, 935 F.2d 1559, 1563–64 (Fed. Cir.
1991) (emphasis added). Although possession alone is not sufficient to
satisfy the written description requirement of § 112’s first paragraph, it is
essential to the purpose of the statute. See Enzo Biochem, Inc. v. Gen-Probe
Inc., 323 F.3d 956, 969 (Fed. Cir. 2002). Consequently, Appellants must
demonstrate that they were in possession of mir-302 in the ’262 application.
This they have not done. Appellants point to no disclosure in the ’262
application that indicates that they were in possession of mir-302 at the time
of filing. Nor do they point to any prior art published prior to the filing date
of the ’262 application that teaches or suggests mir-302. Appellants’
argument that it would not have required undue experimentation for a person
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of ordinary skill to have arrived at mir-302 is inapposite: the first paragraph
of § 112 requires a demonstration of possession of the invention.
Moreover, Appellants adduce no affidavits or declarations by the
inventors, supported by evidence of record, indicating that they were in
possession of mir-302 in May, 2003, when the ’262 application was filed.
Nor are we persuaded by Appellants’ argument that, because 90
intronic microRNAs in humans were known generally in the art, mir-302
was somehow also known and therefore falls within the scope of the ’262
application. We agree with the Examiner that mir-302 is essential and
central to Appellants’ claimed invention, and therefore requires Appellants
to demonstrate passion of mir-302 at the time the ’262 application was filed.
Consequently we agree with the Examiner’s conclusion that
Appellants’ application on appeal cannot claim priority benefit of the ’262
application and that the references cited by the Examiner are valid prior art
to Appellants’ instant application.

B. Rejection of the claims under 35 U.S.C. § 103(a)
Issue
Appellants argue the Examiner erred in finding the claims on appeal
are obvious over the combined cited prior art. App. Br. 8.

Analysis
Appellants argue Kim neither teaches nor suggests “preventing stem
cell tumorigenicity” as recited in claim 1. App. Br. 8. Appellants argue that,
despite the Examiner’s finding Kim “teaches treating cancer,” stem cells are
not cancer cells, and teaching treating cancer cells is not the same as
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teaching preventing stem cell tumorigenicity. Id. (citing Advisory Act. 9–10
March 15, 2013). Appellants argue that stem cells, by definition, are
pluripotent, whereas cancer cells are not, and that stem cells normally do not
possess genetic mutations, whereas cancer cells do. Id. at 9. Appellants
maintain that despite the Examiner’s finding “[i]n treating the process of
cancer as disclosed by Kim, the miR-302 constructs would naturally prevent
stem cell tumorigenicity,” the Examiner misapprehended the fact that
cancer formation is due to an accumulative of mutations rather than stem
cell tumorigenicity. Id. Furthermore, contend Appellants, the Examiner
may not argue that “preventing stem cell tumorigenicity” flows naturally
from mir-302 expression while denying Appellants’ priority claim to the
’262 Application because, if so, the ’262 application enables the invention of
the '806 application. Id.
Appellants argue further that Kim does not teach mir-302 can silence
CDK2 to inhibit stem cell tumorigenicity, as required by claim 1. App.
Br. 10. Appellants content that although the prior art teach mir-302 is
present in embryonic stem cells, FIG. 8C of Appellants’ Specification
discloses that the natural expression level of mir-302 in human embryonic
stem cells (“hESCs”) is not sufficient to effectively silence CDK2. Id.
Appellants assert their Specification discloses that, to effectively silence
CDK2, mir-302 must be expressed at a higher level beyond that found
normally in hESCs. Appellants point to Kim’s teaching: “[s]pecially, of
miRNAs provided in the present invention, miR-200c, miR-368, miR-154*,
miR-302b*-302b-302c*-302c-302a*- 302a-302d-367 cluster on
chromosome 4 and miR-371-372-373*-373 cluster on chromosome 19 are
expressed specifically in undifferentiated human embryonic stem cells.” Id.
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(quoting Kim 24, ll. 1–4). Appellants contend Kim thus teaches there should
be no other differentiated human cells expressing mir-302 and, hence, the
expression level of mir-302 in undifferentiated hESCs should be not only the
highest but also the only observed level in humans. Id. Therefore this
teaching of Kim can only be interpreted to show that a mir-302 level higher
than that of hESCs cannot be naturally found in humans. Id. Appellants
argue that the remaining cited prior art references do not cure the alleged
deficiencies of Kim.
The Examiner responds that Kim teaches treating cancer, which
involves the treatment of tumors. Ans. 13. The Examiner finds that,
because tumors are well-known in the art to comprise cancer stem cells, it
necessarily follows that a practitioner treating cancer according to the
method of Kim will naturally inhibit the tumorigenicity of stem cells. Id.
citing, e.g., S. Gidekel et al., Oct-3/4 is a Dose-dependent Oncogenic Fate
Determinant, 4(5) CANCER CELL, 5, 361-370 (2003) (cited in Applicants’
IDS)). Furthermore, finds the Examiner, even if, arguendo, Appellants are
correct that treating cancer cells is not the same as preventing stem cell
tumorigenicity, any systemic administration of a mir-302-expressing vector
in a human will result in that vector reaching at least some of the
endogenous stem cells that humans necessarily possess. Ans. 13. The
Examiner finds such a process would inhibit or prevent such stem cells from
becoming tumorigenic, thereby satisfying the claim limitation. Id. Finally,
the Examiner finds the limitation relating to “preventing stem cell
tumorigenicity” occurs in the preamble, and finds the language therefore
does not breathe life and meaning to the claim as a whole. Id. The
Examiner finds this is because stem cells are ubiquitous in mammals and are
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not normally tumorigenic. Id. The Examiner therefore places no weight on
the language of the preamble requiring that a certain type of cell avoid doing
what the cell would not normally do. (i.e., become tumorigenic ). Id.
With respect to Appellants’ argument that Kim does not teach mir-302
can silence CDK2 to inhibit stem cell tumorigenicity, the Examiner finds
CDK2 inhibition by mir-302 is a function that naturally occurs in response
to mir-302 administration to a cell, which is the method taught by Kim.
Ans. 15. The Examiner finds there is no manipulative or structural
difference between the method taught by Kim in combination with the cited
art and those of the presently claimed invention. Id. Therefore, the
Examiner finds, Kim need not expressly teach this latent property (CDK2
inhibition) of mir-302 administration to a cell in order for the claim to be
obvious over Kim. Id. (citing M.P.E.P. § 2112.02; In re Hack, 245 F.2d
246, 248 (C.C.P.A. 1957); In re May, 574 F.2d 1082, 1090 (C.C.P.A. 1978).
The Examiner finds the inhibition of CDK2 by mir-302 may be
likened to a “wherein” or “whereby” clause, since its recitation in claim 1
amounts to nothing more than an intended use or purpose. App. Br. 15. The
Examiner quotes M.P.E.P. § 2111.04:
In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329 (Fed.
Cir. 2005), the court held that when a “‘whereby’ clause states a
condition that is material to patentability, it cannot be ignored in
order to change the substance of the invention.” Id. However,
the court noted (quoting Minton v. Nat’l Ass’n of Securities
Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003)) that a
“whereby clause in a method claim is not given weight when it
simply expresses the intended result of a process step positively
recited.”

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Id. at 15–16. Consequently, the Examiner finds, the limitation of claim 1
reciting “treating said cell substrate with said recombinant nucleic acid
composition under a condition that the concentration of said intronic
microRNA-like gene silencing effector is sufficient to suppress said CDK2
and the associated cell-cycle-related genes” should not be given patentable
weight.
Finally, with respect to the amount of mir-302 required to be
administered to be effective, the Examiner finds the optimization of the
method taught by Kim for using mir-302 for treating cancer via a vector
would establish the concentration that would result in expression sufficient
to inhibit CDK2, because CDK2 is known to be fundamentally involved in
cell replication. App. Br. 16. The Examiner finds that a person of ordinary
skill in the art, seeking to treat cancer using mir-302 following the method of
Kim, would find a level of expression of mir-302 sufficient to stop cell
replication, and by extension, sufficiently suppress CDK2. Id.
We agree with the Examiner. The language of claim 1 reciting “A
method for preventing stem cell tumorigenicity,” is in the preamble of the
claim. Our reviewing court has held:
In general, a preamble limits the invention if it recites essential
structure or steps, or if it is “necessary to give life, meaning, and
vitality” to the claim. Conversely, a preamble is not limiting
“where a patentee defines a structurally complete invention in the
claim body and uses the preamble only to state a purpose or
intended use for the invention.

Catalina Marketing International, Inc. v. Coolsavings.com, Inc., 289 F.3d
801, 808 (Fed. Cir. 2002) (internal citations omitted). The Federal Circuit
has since enlarged upon this subject:
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Whether to treat a preamble term as a claim limitation is
“determined on the facts of each case in light of the claim as a
whole and the invention described in the patent.” While there is
no simple test for determining when a preamble limits claim
scope, we have set forth some general principles to guide that
inquiry. “Generally,” we have said, “the preamble does not limit
the claims.” Nonetheless, the preamble may be construed as
limiting “if it recites essential structure or steps, or if it is
‘necessary to give life, meaning, and vitality’ to the claim.” A
preamble is not regarded as limiting, however, “when the claim
body describes a structurally complete invention such that
deletion of the preamble phrase does not affect the structure or
steps of the claimed invention.

American Medical Systems, Inc. v. Biolitec, Inc., 618 F.3d 1354, 1358–1359
(Fed. Cir. 2010) (internal citations omitted).
In the appeal presently before us, we agree with the Examiner that the
language of the preamble does not limit the claim. The language preamble
states the overall purpose of the method of the claim, viz., “preventing stem
cell tumorigenicity,” but we find that that all of the steps of that method
could be practiced, when viewed in light of the Specification, by following
the subsequent steps recited in the body of the claim without reference to the
preamble. We therefore find that the preamble does not limit the claim and
we uphold the Examiner’s finding on this ground.
Furthermore, we agree with the Examiner that the method of Kim,
which teaches treating cancer cells with mir-302, inherently teaches
suppression of CDK2, because treatment of the cells with a sufficiently high
expression of mir-302 to stop cell proliferation necessarily would result in
the suppression of CDK2. To establish inherency, “the limitation at issue
necessarily must be present, or the natural result of the combination of
elements explicitly disclosed by the prior art.” Par Pharmaceutical, Inc.,
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and Alkermes Pharma Ireland Limited, v. Twi Pharmaceuticals, Inc., 773
F.3d 1186, 1195-96 (Fed. Cir. 2014). We agree with the Examiner that Kim
teaches suppression of cancer cell proliferation via treatment with mir-302,
and that CDK2 was known in the art to be fundamentally involved in cell
proliferation. Moreover, we agree that suppression of CDK2 is the natural
result of the treatment of cancer cells with mir-302, as taught by Kim.
Furthermore, we agree with the Examiner that a person of ordinary
skill in the art, upon learning the teachings of Kim, would be motivated to
optimize the expression of mir-302 in the treatment of cancer cells to
suppress cancer cell proliferation. And because it was well-known in the art
that CDK2 is fundamental to cell proliferation, we further agree with the
Examiner that a person of skill in the art would optimize the “concentration
of said intronic microRNA-like gene silencing effector is sufficient to
suppress said CDK2 and the associated cell-cycle-related genes, wherein
said concentration is similar to or higher than the mir-302 level found in
human embryonic stem cells,” as required by claim 1. We consequently
affirm the Examiner’s rejection of claims 1–12, 14–15, 17–18, 20, 22, 25–
28, 30–36, 38–39 and 43–45.

C. Rejection under the Nonstatutory Doctrine of Obviousness-Type Double
Patenting

Issue
Appellants argue the Examiner erred in finding claims 1–12, 14–15,
17–18, 20, 22, 25–28, 30–36, 38–39 and 43–45 are unpatentable
unpatentable under the nonstatutory doctrine of obviousness-type double
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patenting over the combination of Appellants’ US Application Serial No.
12/149,725 (the “’725 application”) and Kim.

Analysis
Appellants point to claim 1 of the ’725 application, which recites:
A method for reprogramming mammalian cells to pluripotent
stem cells, comprising the steps of:

(a) constructing a recombinant nucleic acid composition that
contains at least an intron encoding a mir-302-like
microRNA effector;

(b) introducing said recombinant nucleic acid composition
into a plurality of mammalian cells, wherein said plurality
of mammalian cells generate a plurality of mir-302-like
microRNA effectors derived from said intron to a level
that is sufficient to induce DNA demethylation of Oct3/4
promoter and activate Oct3/4 expression, which
consequently results in reprogramming the cells to a
plurality of stem cell-like pluripotent cells.

App. Br. 13. Appellants contend that the differences between claim 1 of the
’725 application and claim 1 of the instant appeal render the subject matter
claimed in each claim patentably distinct. Id. at 12. Specifically, Appellants
argue: (1) claim 1 of the current application is a method for “preventing stem
cell tumorigenicity,” whereas claim 1 of the ’725 application is a method for
“reprogramming mammalian cells to pluripotent stem cells”5; (2) claim 1 of

5 Appellants state claim 1 of the ’725 application is a method for: “inducing
intronic mir-302-mediated gene silencing effects in mammalian cells.” We
find no such language in claim 1 of the ’725 application, but we find this
language of the preamble to be equivalent.
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the current application has a step requiring “expressing a plurality of
CDK2,” whereas claim 1 of the ’725 application contains no such limitation;
(3) claim 1 of the current application also has a step requiring “an intronic
microRNA-like gene silencing effector targeting said CDK2,” whereas claim
1 of the ’725 application) contains no such limitation; and (4) claim 1 of the
current application has a further step requiring “a condition that the
concentration of said intronic microRNA-like gene silencing effector is
sufficient to suppress said CDK2” while the claim 1 of the ’725 application
contains no such specification. App. Br. 18. Appellants contend that, for
these reasons, the differences in the language of the claims render the
methods claimed in each patentably distinct. Id.
The Examiner finds that, although the conflicting claims are not
identical, they are not patentably distinct, because the claims of the both
applications teach methods of expressing gene silencing elements
comprising the use of an intron-encoded gene silencing effector. Non-Final
Act. 14.6 The Examiner finds that, whereas the competing claims do not
teach the expression of mir-302, nor the production of stem cells that result
from the use of mir-302, the use of mir-302 in such a method is obvious over
Kim. Id. The Examiner finds Kim teaches expressing mir-302 from
expression vectors and, for the reasons cited supra, in the Examiner’s §103
analysis, it would have been obvious to one of ordinary skill in the art to
substitute mir-302 in place of the gene silencing elements of claim 1 of the
’725 application, because Kim teaches expressing such elements would

6 The Examiner relies upon these findings in the Answer. See Ans. 17.
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Application 12/318,806

19
allow for greater study of how stem cells maintain pluripotency, and that
such elements may be useful in treating cancer. Id.
We agree with the Examiner. As an initial matter, Appellants
compare claim 1 of the current application with claim 1 of the ’725
application without reference to the teachings of Kim. “[O]ne cannot show
non-obviousness by attacking references individually where … the
rejections are based on combinations of references.” In re Keller, 642 F.2d
413, 426 (C.C.P.A. 1981).
With respect to Appellants’ argument (1) we have already found that
the claim language “preventing stem cell tumorigenicity” in the current
claim 1 is preamble language which does not limit the claim. The language
of claim 1 of the ’725 application recites “reprogramming mammalian cells
to pluripotent stem cells,” which, for similar reasons, is not limiting on that
claim.
With respect to (2) we agree with the Examiner’s conclusion that the
teachings of Kim, when combined with those of the ’725 application would
render claim 1 of the current application obvious based upon the fact that
Kim teaches using mir-302 in the treatment of proliferating cancer cells and
CDK2 is essential to the regulation of the cell cycle and proliferation.
With respect to (3) and (4), we have related supra the reasons why we
agree with the Examiner that these limitations flow naturally from the
teachings of Kim. Therefore, despite Appellants’ argument that certain
limitations present in the current claim 1 are absent from claim 1 of the ’725
application, we agree with the Examiner’s conclusion that the claim 1 of the
current application is obvious over the combination of claim 1 of the ’725
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Application 12/318,806

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application and Kim. We consequently affirm the Examiner’s rejection of
claims 1–12, 14–15, 17–18, 20, 22, 25–28, 30–36, 38–39 and 43–45.

CONCLUSION
We agree with the Examiner’s findings and conclusions establishing a
prima facie case of obviousness and we do not find Appellant’s arguments
to the contrary persuasive. We consequently affirm the Examiner’s rejection
of the claims.

DECISION
The Examiner’s rejection of claims 1–3, 5–10, 12, 14–15, 17–21, 26–
29, 35–36, 39 and 42 as unpatentable under 35 U.S.C. § 103(a) is affirmed.
The Examiner’s rejection of 1–12, 14–15, 17–18, 20, 22, 25–28, 30–
36, 38–39 and 43–45 as unpatentable under the nonstatutory doctrine of
obviousness-type double patenting is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1). See 37 C.F.R.
§ 1.136(a)(1)(iv).

AFFIRMED