Ex Parte Gewirtz

Board of Patent Appeals and Interferences

Feb 24, 2010

09993183 (B.P.A.I. Feb. 24, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ALAN GEWIRTZ
__________

Appeal 2009-006223
Application 09/993,183
Technology Center 1600
__________

Decided: February 24, 2010
__________

Before TONI R. SCHEINER, DEMETRA J. MILLS, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for anticipation and obviousness. We have jurisdiction under 35
U.S.C. § 6(b).

Appeal 2009-006223
Application 09/993,183

STATEMENT OF CASE
The following claims are representative.
1. A method for disrupting expression of a mammalian target gene at the
mRNA level in a human cell, wherein the method comprises initiating RNA
interference (RNAi) in vitro by exposing the human cell to a double-
stranded RNA (dsRNA) homologous to the target gene, wherein the dsRNA
consists essentially of two complementary linearized strands of RNA, the
transcription of each is independently controlled to generate paired RNAs of
defined length.

22. A method for disrupting expression of a mammalian target gene in vitro
in a human cell, wherein the method comprises providing an RNA sequence
homologous to a portion of a target gene, said RNA capable of inducing
RNAi of the target gene.

23. The method of claim 22, wherein the target gene is c-kit and the RNA is
KdsRNA in an amount effective to induce RNA interference, thereby
disrupting expression of-the target gene.

Cited References
Fire et al. (Fire ‘559) US 6,506,559 B1 Jan. 14, 2003
Gewirtz et al. WO 92/19252 Nov. 12, 1992
Kreutzer et al. WO 00/44895 Aug. 3, 2000

Phillip A. Sharp, RNAi and double-strand RNA, 13 GENES & DEVELOPMENT
139-141 (1999).

Appellant relied on the following references:
Kreutzer et al. US 2004/0175703 A1 Sept. 9, 2004
Andrew Fire (II), RNA-triggered gene silencing, 15 TRENDS IN GENETICS
358-363 (1999).

Mary K. Montgomery and Andrew Fire, Double-stranded RNA as a
mediator in sequence-specific genetic silencing and co-suppression, 14
TRENDS IN GENETICS 255-258 (1998).

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Florence Wianny and Magdalena Zernicka-Goetz, Specific interference with
gene function by double-stranded RNA in early mouse development, 2 NAT.
CELL BIOL. 70-75 (2000).

Paddison et al., Stable suppression of gene expression by RNAi in
mammalian cells, 99 PROC. NAT’L ACAD. SCI. 1443-1448 (2002).

Svoboda et al, Selective reduction of dormant maternal mRNAs in mouse
oocytes by RNA interference, 127 DEVELOPMENT 4147-4156 (2000).

Declaration of Dr. Alan M. Gewirtz, submitted September 14, 2005.

Declaration of Dr. Alan M. Gewirtz for Earlier Date of Invention, submitted
April 28, 2006.

Grounds of Rejection
1. Claims 1, 2, 5, 7-9, 11, 21,22, and 24-27 are rejected under 35 U.S.C. §
102(e) as being anticipated by Fire ‘559.
2. Claims 1, 2, 5, 7-9, 11, and 21-38 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Fire ‘559 as applied to claims 1, 2, 5, 7-9, 11, 21,
22, and 24-27 in the §102(e) rejection, Gewirtz (WO 92/19252) and Sharp.

FINDINGS OF FACT
The findings of fact below are applicable to the rejections of record.
1. The Examiner finds that, Fire ‘559 discloses “a method for inhibiting
expression of a target gene using double stranded RNA to induce RNAi in a
cell in vitro (Column 26, claim 1) wherein the cell is from an animal
(Column 26, claim 6).” (Ans. 4.)
2. The Examiner finds that:
Fire [‘559] disclose that the cell with the target gene may be
derived from or contained in any organism (column 8, line 13-
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14) and that examples of vertebrate animals include mammals
and human (column 8, lines 35-37) and that the cell having the
target gene may be “immortalized or transformed, or the like”
(column 8, lines 52-55) and that “the present invention could be
used for treatment or development of treatments for cancers of
any type, including solid tumors and leukemias. . .” (Column
10, lines 26-28).
(Id.)
3. The Examiner finds that:
Fire [‘559] disclose that lipid mediated carrier transport can be
used to introduce nucleic acids to cells (Column 9, lines 55-60).
Fire [‘559] also disclose that inhibition of gene expression
refers to the absence (or observable decrease) in the level of
protein and/or mRNA product from a target gene (Column 6,
lines 55-57), thereby indicating disruption of gene function
(which is to produce protein).

(Ans. 4-5.)
4. The Examiner finds that “the limitation ‘selecting a human cell
expressing the target gene’ is not defined in the specification, so for prior art
purposes, this recitation is being interpreted to mean a cell line that contains
a target gene and is capable of being treating with a dsRNA” (id. at 5-6).
5. “Fire [‘559] teach target genes that are oncogenes (col. 11).” (Ans. 6.)
6. The Examiner finds that:
Fire [‘559] also teach that inhibition of gene expression refers
to the absence (or observable decrease) in the level of protein
and/or mRNA product from a target gene as determined by
measurement of the target gene or expression from said target
gene (Column 6, lines 55-57), thereby indicating disruption of
gene function (which is to produce protein).

(Id.)
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7. The Examiner finds that:
Fire [‘559] teach that using the methods of their invention, gene
disruptions may be used to discover the function of a target
gene and to produce disease models in which the target gene is
involved in causing or preventing a pathological condition (col.
5, lines 30-37). Fire [‘559] disclose that relative to antisense
approaches, their invention has advantages in the stability of the
material to be delivered (col. 3, line 20).

(Id.)
8. “Fire [‘559] do not teach the nucleotide sequence of the oncogene c-Kit.”
(Id.)
9. “Gewirtz et al. teach the antisense inhibition of c-Kit proto-oncogene
expression in human cells and that c-kit antisense oligonucleotides are
particularly useful against leukemia and melanoma (see page 15, lines 6-
25).” (Id.)
10. “Gewirtz et al. disclose that the c-Kit cDNA sequence was known in
1987 and cite Yarden et al. Gewirtz et al. do not specifically teach inhibition
in HL-60 cell lines or CHP 100 cell lines.” (Ans. 6.)
11. “Sharp is added as a general reference supporting the idea that RNAi is a
general mechanism that is likely to be a general mechanism for gene
regulation and may be critical for many developmental and antiviral
processes.” (Id. at 7.)
12. The Examiner concludes that:
It would have been prima facie obvious to one of
ordinary skill in the art, at the time the instant invention was
made, to substitute an dsRNA oligonucleotide in place of the
antisense oligonucleotide in a method of inhibiting the
expression of the oncogene c-Kit in vitro using an antisense
inhibitor in human leukemia cells (as taught by Gewirtz et al.),
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wherein the dsRNA was comprised in pharmaceutical
composition (as taught by Fire [‘599]) because antisense
inhibition of c-Kit was taught in the prior art as inhibiting the
expression of KitR in human leukemia cells (as taught by
Gewirtz et al.), because dsRNA can be used to initiate RNA
interference in vitro by targeting oncogenes in human cells
including leukemia (as taught by Fire [‘599]) and because
relative to antisense approaches, dsRNA used to inhibit gene
expression has advantages in the stability of the material to be
delivered (as taught by Fire [‘599]).

(Id.)
13. The Examiner concludes that:
[I]t would have been further obvious to use a HL-60 cell
line for the study of leukemia in vitro and further obvious to use
CHP 100 to study the cellular events associated with
neuroblastoma. Fire [‘559] does not specifically disclose the
optimal time of incubation of said dsRNA with a cell or the
optimal concentration of dsRNA used but it would have been
obvious to one of skill in the art and a matter of routine
optimization to determine the amount of time to expose the
dsRNA to the cell to achieve the most efficient gene
interference and to determine the optimal workable ranges of a
dsRNA that most efficiently caused gene interference in a cell.
MPEP 2144.05 states in part “where the general conditions of a
claim are disclosed in the prior art, it is not inventive to
discover the optimum or workable ranges by routine
experimentation.”

(Ans. 7-8.)
14. The Examiner concludes that:
One of ordinary skill in the art would have been
motivated to practice a method of inhibiting the expression of
the oncogene c-Kit in vitro in human leukemia cells or
melanoma cells (as taught by Gewirtz et al.) using a dsRNA to
initiate RNA interference wherein the dsRNA was comprised in
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pharmaceutical composition (as taught by Fire [‘559]) because
antisense inhibition of c-Kit was taught in the prior art as
inhibiting the expression of KitR in human leukemia cells (as
taught by Gewirtz et al.) and because relative to antisense
approaches, dsRNA used to inhibit gene expression has
advantages in the stability of the material to be delivered and
has advantages of sequence specificity (as taught by Fire
[‘559]).

(Id. at 8.)
15. The Examiner finds that:
One of ordinary skill in the art would have expected
success in practicing a method of inhibiting the expression of
the oncogene c-Kit in vitro in human leukemia cells (as taught
by Gewirtz et al.) using a dsRNA to initiate RNA interference
wherein the dsRNA was comprised in pharmaceutical
composition (as taught by Fire [‘559]) because antisense
inhibition of c-Kit was taught in the prior art as inhibiting the
expression of KitR in human leukemia cells (as taught by
Gewirtz et al.), because Fire [‘559] teach that dsRNA can be
used to initiate RNA interference in human cells and because
relative to antisense approaches, dsRNA used to inhibit gene
expression has advantages in the stability of the material to be
delivered (as taught by Fire [‘559]).

(Ans. 8-9.)
16. The Examiner finds that “it is not disputed that Fire [‘559] et al. did not
exemplify his invention in human cells, but just because Fire [‘559] did not
reduce to practice his invention does not mean the invention was not
enabled.” (Id. at 10.)
17. The Examiner finds that:
Since the issuance of the Fire [‘559]. . ., which is presumed to
be enabled, thousands of post-filing art references have
repeatedly shown that the methods of Fire et al. [‘559] work in
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human cells. In fact, Fire et al. won a Nobel Prize for their
discovery, largely based upon the implications of its use in
humans, and the discovery that the process underlies an entire
RNA-dependent system of gene regulation that is conserved at
some level across virtually every multi-cellular organism (see
Zamore, Nat. Struct. Biol. From the IDS for review).

(Ans. 10.)

18. Fire II, Trends in Genetics 1999 (Exhibit I, Evidence Appendix), states
that, with regard to medical applications involving targeted silencing of
renegade genes, that “[a]lthough this hope is not ruled out by any current
data, the simple protocols used for invertebrate and plant systems are
unlikely to be effective. Mammals have a vehement response to dsRNA, the
best-characterized component of which is protein kinase (PKR) that
responds to dsRNA by phosphorylating (and inactivating) translation factor
EIF2a …” (Page 363.)
19. The Examiner finds that the “paragraph cited by Appellant is not
evidence that Fire felt his invention was limited to invertebrate animals and
his thoughts on whether this would work was mere speculation and was not
an admission by Fire as alleged by Appellant.” (Ans. 10-11.)
20. The Examiner finds that, to the contrary, “this mere speculation has
proved to be unfounded given the voluminous amount of post-filing art that
has shown the methods of Fire [‘559] work in human cells.” (Id. at 11.)
21. Wianny shows that dsRNA can be used as a specific inhibitor of gene
activity in mouse oocyte and preimplantation embryo. (Wianny, 73, right
col.)
22. Wianny disclosed that concerns in Fire II, Trends Genetic 1999 that
RNAi might not work in the mouse may have been raised prematurely. (Id.)
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23. Wianny discloses that dsRNA is specific to the corresponding gene and
it does not cause a general translation arrest, because embryos continue to
develop without signs of cell death. (Wianny, 73, right col.)
24. Wianny states that “natural” dsRNA may be less effective at inducing
PKR, and the degree of induction could vary between cell types, in which
case RNAi would be effective. (Id.)
25. Wianny states that they anticipate that dsRNA mediated inhibition of
gene expression should be equally effective in other mammals, including
both domestic animals and humans. (Wianny, 74, left col.)
26. Svoboda confirmed the results in Wianny and demonstrated that RNAi is
an effective and efficient method to inhibit the translation of maternal
messenger RNAs that are recruited in oocyte maturation in the mouse.
(Svoboda, 4153, right col.)
27. Paddison acknowledged the early successful results of Wianny and
Svoboda in injection dsRNA into early stage mouse embryos and the
achievement of DNA silencing. (Paddison, 1445, left col.).

Discussion
1. Claims 1, 2, 5, 7-9, 11, 21, 22, and 24-27 are rejected under 35 U.S.C. §
102(e) as being anticipated by Fire [‘559].

ISSUE
The Examiner argues that Fire ‘559 teaches each element of the
claimed method, including practice of the method in vitro and in vivo, and
describes its applicability to transformation of human cells. The Examiner
argues that Fire ‘559 is presumed to be enabled.
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Appellant contends that Fire ‘559 is a non-enabled anticipatory
reference with respect to the human cells claimed.
The issue is: Has Appellant demonstrated error in the Examiner’s
anticipation rejection and has Appellant rebutted the presumption that Fire
‘559 is an enabling anticipatory reference by a preponderance of the
sufficient evidence?
PRINCIPLES OF LAW
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. See In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Anticipation does not require the actual creation or reduction to
practice of the prior art subject matter; anticipation requires only an enabling
disclosure. In re Donohue, 766 F.2d 531, 533 (Fed. Cir. 1985).
In patent prosecution the Examiner is entitled to reject application
claims as anticipated by a prior art patent without conducting an inquiry into
whether or not that patent is enabled or whether or not it is the claimed
material (as opposed to the unclaimed disclosures) in that patent that are at
issue. In re Sasse, 629 F.2d 675, 681 (CCPA 1980) (“[W]hen the PTO cited
a disclosure which expressly anticipated the present invention … the burden
was shifted to the applicant. He had to rebut the presumption of the
operability of [the prior art patent] by a preponderance of the evidence.”
[Emphasis added]. The applicant, however, can then overcome that
rejection by proving that the relevant disclosures of the prior art patent are
not enabled. Id. See also Amgen Inc. v. Hoescht Marion Roussel, Inc., 314
F.3d 1313, 1355 (Fed. Cir. 2003). Thus, “a presumption arises that both the
claimed and unclaimed disclosures in a prior art patent are enabled,” which
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appellants “can then overcome [ ] by proving that the relevant disclosures of
the prior art patent are not enabled.” Id.
In the infringement setting,
Like the applicant in ex parte prosecution, … the patentee may
argue that the relevant claimed or unclaimed disclosures of a
prior art patent are not enabled and therefore are not pertinent
prior art. If a patentee presents evidence of nonenablement that
a trial court finds persuasive, the trial court must then exclude
that particular prior art patent in any anticipation inquiry, for
then the presumption has been overcome.
Id.
Prior art is not enabling so as to be anticipating if it does not enable a
person of ordinary skill in the art to carry out the invention. See Elan
Pharms., Inc. v. Mayo Found. For Medical Educ. And Research, 346 F.3d
1051, 1057 (Fed. Cir. 2003).
Appellant can carry its burden of lack of enablement only by showing
that all of the disclosed alternative modes are insufficient to enable the
claims, because “‘[t]he enablement requirement is met if the description
enables any mode of making and using the invention.’” Johns Hopkins Univ.
v. CellPro, Inc., 152 F.3d 1342, 1361 (Fed. Cir. 1998) (quoting Engel Indus.,
Inc. v. Lockformer Co., 946 F.2d 1528, 1533 (Fed. Cir. 1991)).
A patent claim “cannot be anticipated by a prior art reference if the
allegedly anticipatory disclosures cited as prior art are not enabled.” Elan
Pharms., Inc., 346 F.3d at 1054. “The standard for what constitutes proper
enablement of a prior art reference for purposes of anticipation under section
102, however, differs from the enablement standard under section 112. In re
Hafner, . . . 410 F.2d 1403 (Cust. & Pat.App.1969).” Rasmusson v.
SmithKline Beecham Corp., 413 F.3d 1318, 1325 (Fed. Cir. 2005).
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“[S]ection 112 ‘provides that the specification must enable one skilled in the
art to ‘use’ the invention whereas [section] 102 makes no such requirement
as to an anticipatory disclosure.' Hafner, 410 F.2d at 1405.” Id. Thus,
“proof of efficacy is not required for a prior art reference to be enabling for
purposes of anticipation. . . . [T]he proper issue is whether the [prior art] is
enabling in the sense that it describes the claimed invention sufficiently to
enable a person of ordinary skill in the art to carry out the invention.” Impax
Labs., Inc. v. Aventis Pharms. Inc., 468 F.3d 1366, 1383 (Fed. Cir. 2006)
(emphasis added). A prior art reference is anticipatory under 35 U.S.C.
§102(b) if it discloses each and every element of the claimed invention,
either explicitly or inherently, and if it enables person of ordinary skill in art
to make the invention without undue experimentation. In re Gleave, 560
F.3d 1331, 1337-8 (Fed. Cir. 2009).
The state of the art existing at the filing date of the application is used
to determine whether a particular disclosure is enabling as of the filing date.
Chiron Corp. v. Genentech, Inc., 363 F.3d 1247, 1254 (Fed. Cir. 2004) (“a
patent document cannot enable technology that arises after the date of
application”).
Publications dated after the filing date providing information publicly
first disclosed after the filing date generally cannot be used to show what
was known at the time of filing. In re Gunn, 537 F.2d 1123, 1128 (CCPA
1976); In re Budnick, 537 F.2d 535, 538 (CCPA 1976) (In general, if an
applicant seeks to use a patent to prove the state of the art for the purpose of
the enablement requirement, the patent must have an issue date earlier than
the effective filing date of the application.). While a later dated publication
cannot supplement an insufficient disclosure in a prior dated application to
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make it enabling, applicant can offer the testimony of an expert based on the
publication as evidence of the level of skill in the art at the time the
application was filed. Gould v. Quigg, 822 F.2d 1074, 1078 (Fed. Cir. 1987).
The examiner should not use post-filing date references to
demonstrate that the patent is non-enabling. Exceptions to this rule could
occur if a later-dated reference provides evidence of what one skilled in the
art would have known on or before the effective filing date of the patent
application. In re Hogan, 559 F.2d 595, 605 (CCPA 1977).
If individuals of skill in the art state that a particular invention is not
possible years after the filing date, that would be evidence that the disclosed
invention was not possible at the time of filing and should be considered. In
In re Wright, 999 F.2d 1557, 1562 (Fed. Cir. 1993) an article published 5
years after the filing date of the application adequately supported the
examiner’s position that the physiological activity of certain viruses was
sufficiently unpredictable so that a person skilled in the art would not have
believed that the success with one virus and one animal could be
extrapolated successfully to all viruses with all living organisms.

Principles of Law for remaining obviousness rejections
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness. Only if that
burden is met, does the burden of coming forward with evidence or
argument shift to the applicant.” In re Rijckaert, 9 F.3d 1531, 1532 (Fed.
Cir. 1993) (citations omitted). In order to determine whether a prima facie
case of obviousness has been established, we considered the factors set forth
in Graham v. John Deere Co., 383 U.S. 1, 17 (1966); (1) the scope and
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content of the prior art; (2) the differences between the prior art and the
claims at issue; (3) the level of ordinary skill in the relevant art; and (4)
objective evidence of nonobviousness, if present.
“[O]bviousness requires a suggestion of all limitations in a claim.”
CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, 1342 (Fed. Cir. 2003)
(citing In re Royka, 490 F.2d 981, 985 (CCPA 1974)).

ANALYSIS
Appellant contends that Fire ‘559 is a non enabled reference with
respect to the claimed method in human cells. (App. Br. 4.) Appellant
contends that the Declaration evidence and other evidence of record supports
that Fire ‘559 is not enabled for transformation of human cells with dsRNA.
(App. Br. 12-14.) Appellant argues that Fire II summarizes the state of the
art at that time of the Fire ‘559 application for patent and teaches that if
RNAi existed in cells, “it would probably be necessary either to induce a
transient lapse in PKR response, or to use a dose incapable of activating the
PKR response to practice RNAi methods in mammalian cells. Yet Fire
[‘559] provides no guidance on any methods or means of inducing a lapse in
the PKR response, nor were any methods predictable at the time of
Appellant’s filing.” (App. Br. 11 (emphasis omitted).)
We have carefully considered all enablement related evidence of
record, including Declaration evidence, and conclude that the Appellant has
failed to rebut the presumption that the disclosure of the Fire ‘559 is enabled
for transformation of human cells with dsRNA by a preponderance of the
evidence.
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In particular, the pending claims are limited to “initiating RNA
interference in vitro by exposing the human cell to a double-stranded RNA
… .” (Claim 1).
We find that while Fire II, Trends in Genetics (1999) may have
speculated about the PKR response potentially interfering with in vivo
medical applications using “simple protocols,” Appellant has provided no
evidence that one of ordinary skill in the art at the time of Fire ‘559’s
application filing would have believed that Fire ‘559 would not work in less
complex in vitro applications using human cells, an application
encompassed by claim 1. Appellant provides no evidence that one of
ordinary skill in the art, following the method set forth in Fire ‘559, would
be unsuccessful at modifying human cells in vitro. Fire II says nothing
about concerns related to in vitro applications of the method of Fire ‘559 in
human cells.
If individuals of skill in the art state that a particular invention is not
possible years after the filing date, that would be evidence that the disclosed
invention was not possible at the time of filing and should be considered. In
In re Wright, 999 F.2d at 1562. However, in this case, we conclude that the
speculative statements in Fire II do constitute evidence that the procedures
outlined in the Fire ‘559 patent would not work. The statements made in
Fire II were not based on any evidentiary data convincing to one of ordinary
skill in the art and thus are not conclusive, but merely speculative
statements. Later publications, such as Wianny, Svoboda and Paddison
confirmed that the procedures outlined in Fire ‘559 would work in
mammalian cells, and Wianny particularly stated regarding dsRNA-
mediated inhibition of gene expression in the mouse, that “[w]e anticipate
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that it should be equally effective in other mammals, including both
domestic animals and humans.” (Wianny, 74, left col.)
We have further reviewed the credentialed Declaration of Alan
Gewirtz dated September 14, 2005, which provides a review of the evidence
of record. The Declaration fails to account, however, for the legal
presumption in this case and Appellant’s burden to rebut the presumption of
the Fire ‘559 patent’s enablement. Furthermore, an anticipatory disclosure
does not have to be reduced to practice, so the fact that data was never
presented in Fire ‘559 showing the effect of dsRNA in vertebrate and human
cells, as alleged by the Declarant, is not controlling. What is controlling is
whether Fire ‘559 discloses each and every element of the claimed
invention, which Appellant acknowledges in the Appeal Brief at page 7, and
whether it enables person of ordinary skill in art to make the invention
without undue experimentation. In re Gleave, 560 F.3d 1331, 1337-8 (Fed.
Cir. 2009). Appellant has presented no evidence that one of ordinary skill in
the art following the method set forth in Fire ‘559 would not have been able
to transform human cells in vitro, and later publications, such as Wianny,
Svoboda and Paddison, reasonably appear to confirm that the procedures
outlined in Fire ‘559 would work in mammalian cells.

CONCLUSION OF LAW
We conclude that Appellant has failed to rebut the presumption that
Fire’559 was enabled by a preponderance of evidence. Thus we conclude
that a preponderance of the evidence supports that Fire ‘559 method was
enabled for transformation of human cells in vitro, at the time of its filing.
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2. Claims 1, 2, 5, 7-9, 11, and 21-38 are rejected under 35 U.S.C. § 103(a)
as being unpatentable over Fire ‘559 as applied to claims 1, 2, 5, 7-9, 11, 21-
22 and 24-27 in the 102(e), Gewirtz (WO 92/19252) and Sharp.

ISSUE
Appellant contends that there would have been no expectation of
success of practicing a method for inhibiting the expression of the oncogene
c-kit in vitro in human leukemia cells (Reply Br. 18) and that the cited
references do not teach each element claimed because Fire ‘559 does not
teach transformation of human cells (Reply Br. 19). Appellant argues that
there would have been no motivation to combine the cited references.
(Reply Br. 22.)
We are not persuaded. For the reasons discussed herein with respect
to Fire’s [‘559] disclosure of disclosure of the transformation of human
cells, we conclude that Appellant has not provided sufficient evidence of
lack of an enabling disclosure.
With respect to Appellant’s argument concerning motivation to
combine the cited references or resolve the issues in Fire ‘559 regarding
RNAi in mammalian systems (App. Br. 23), the Examiner found that
One of ordinary skill in the art would have expected
success in practicing a method of inhibiting the expression of
the oncogene c-Kit in vitro in human leukemia cells (as taught
by Gewirtz et al.) using a dsRNA to initiate RNA interference
wherein the dsRNA was comprised in pharmaceutical
composition (as taught by Fire [‘559]) because antisense
inhibition of c-Kit was taught in the prior art as inhibiting the
expression of KitR in human leukemia cells (as taught by
Gewirtz et al.), because Fire [‘559] teach that dsRNA can be
used to initiate RNA interference in human cells and because
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relative to antisense approaches, dsRNA used to inhibit gene
expression has advantages in the stability of the material to be
delivered (as taught by Fire [‘559]).

(Ans. 8-9.)
We conclude that the Examiner has provided a rationale as to why one
of ordinary skill in the art would have combined the cited references and that
Appellant has not rebutted or countered this rationale by a preponderance of
evidence.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED

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