Ex Parte Kreutzer et al

Patent Trial and Appeal Board

Nov 29, 2016

13656540 (P.T.A.B. Nov. 29, 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.
13/656,540 10/19/2012 Roland Kreutzer 26421-21964 US 6558
77328 7590 12/01/2016
ALNYL AM/FENWICK
SILICON VALLEY CENTER
801 CALIFORNIA STREET
MOUNTAIN VIEW, CA 94041
EXAMINER
VIVLEMORE, TRACY ANN
ART UNIT PAPER NUMBER
1674
NOTIFICATION DATE DELIVERY MODE
12/01/2016 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):
ptoc @ fenwick.com
shubl @ fen wick, com
nmorad @ fen wick, com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ROLAND KREUTZER and STEFAN LIMMER1
Appeal 2015-004586
Application 13/656,540
Technology Center 1600
Before FRANCISCO C. PRATS, RICHARD J. SMITH, and TAWEN
CHANG, Administrative Patent Judges.
SMITH, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
isolated double stranded RNA (dsRNA). We have jurisdiction under 35
U.S.C. § 6(b).
We affirm.
1 According to Appellants, the real party in interest is Alnylam
Pharmaceuticals, Inc. (Appeal Br. 2.)
Appeal 2015-004586
Application 13/656,540
STATEMENT OF THE CASE
Claims on Appeal
Claims 1—7, 9—13, and 27—35 are on appeal.2 (Claims Appendix,
Appeal Br. 22—24.) Claim 1 is illustrative and reads as follows (emphasis
added):
1. An isolated double stranded RNA (dsRNA) comprising two
complementary oligoribonucleotide strands wherein the dsRNA is 15 to 49
base pairs in length, wherein one strand of the dsRNA is complementary to
an RNA transcript of at least part of a mammalian target gene and the other
strand of the dsRNA is complementary to the first strand, wherein the
dsRNA is enclosed by a micellar structure, and wherein said dsRNA is
capable of specifically inhibiting the expression of the mammalian target
gene.
Examiner’s Rejections
1. Claims 1—7, 9—13, and 27—35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 1 and 2 of U.S.
Patent No. 7,196,184,3 in view of Crooke4 and Wengel.5 (Ans. 2—3.)
2 Claim 35 was not specifically addressed in the Final Action dated May 12,
2014, and the rejection under 35 U.S.C. § 112, 4th paragraph contained a
typographical error in that it referred to claim 34 rather than claim 35. (Ans.
10.) The rejection of claim 34 under § 112 is thus withdrawn and a new
ground under § 112 entered as to claim 35. (Id. at 13—14.) Claim 35 was
also inadvertently left out of the double patenting and obviousness
rejections, and the Examiner entered new grounds of rejection in the Answer
as to claim 35 and those rejections. (Id. at 10-14.) Because Appellants filed
a Reply Brief responding to the rejections of claim 35, rather than reopening
prosecution as to the new grounds of rejection, we treat claim 35 as on
appeal, as subject to the new grounds rejection, and as included in the double
patenting and obviousness rejections.
3 Heidenreich et al., US 7,196,184 B2, issued Mar. 27, 2007.
4 Crooke, US 6,107,094, issued Aug. 22, 2000 (“Crooke”).
5 Wengel, US 2003/0134808 Al, published July 17, 2003 (“Wengel”).
2
Appeal 2015-004586
Application 13/656,540
2. Claims 1, 7, 9, 11, 12, and 30-35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 11 and 26 of
U.S. Patent No. 7,745,418.6 {Id. at 3.)
3. Claims 1, 7, 9, 11, 12, and 30-35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 1, 6—8, 13, 22,
29, and 30 of U.S. Patent No. 7,994,309.7 {Id. at 3-4.)
4. Claims 1—7, 9—13, and 27—35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 1—22 of U.S.
Patent No. 8,114,981.8 (Mat 4.)
5. Claims 1—7, 9—13, and 27—35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 1—6 and 9—16 of
U.S. Patent No. 8,183,362.9 {Id.)
6. Claims 1, 7, 9—12, and 30-35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 1, 6, 7, 14, 19,
30, and 31 of U.S. Patent No. 8,273,870.10 {Id. at 4-5.)
7. Claims 1, 7, 9, 11, 12, and 30-35 stand rejected on the ground of
nonstatutory obviousness-type double patenting over claims 9 and 22 of U.S.
Patent No. 8,273,868.* 11 {Id. at 5.)
8. Claim 30 stands rejected under 35 U.S.C. § 112(d) or 35 U.S.C. § 112
(pre-AIA), 4th paragraph, as being of improper dependent form. {Id.)
6 John et al., US 7,745,418 B2, issued June 29, 2010.
7 Kreutzer et al., US 7,994,309 B2, issued Aug. 9, 2011.
8 Kreutzer et al., US 8,114,981 B2, issued Feb. 14, 2012.
9 Kreutzer et al., US 8,183,362 B2, issued May 22, 2012.
10 Kreutzer et al., US 8,273,870 B2, issued Sept. 25, 2012
11 John et al., US 8,273,868 B2, issued Sept. 25, 2012.
3
Appeal 2015-004586
Application 13/656,540
9. Claim 32 stands rejected under 35 U.S.C. § 112(b) or 35 U.S.C. § 112
(pre-AIA), second paragraph, as indefinite. {Id. at 6.)
10. Claim 35 stands rejected under 35 U.S.C. § 112(d) or 35 U.S.C. § 112
(pre-AIA), 4th paragraph, as being of improper dependent form. {Id. at 13.)
11. Claims 1—7, 9—13, and 27—35 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over Crooke, Sridhar,12 and Wengel. {Id. at 6—8.)
12. Claims 1—7, 9—13, and 27—35 stand rejected under 35 U.S.C. § 103(a)
as unpatentable over Fire,13 George,14 Wengel, and Sridhar. {Id. at 8—10.)
FINDINGS OF FACT
We adopt as our own the Examiner’s findings and analysis concerning
the scope and content of the prior art. The following findings are included
for emphasis and reference convenience.
FF 1. The Examiner finds that Crooke teaches “oligomeric
compounds that bind to a target RNA strand and are substrates for dsRNase
enzymes,” and that the “oligomeric compounds include oligoribonucleotides
and other oligomeric compounds having a linear sequence of linked
ribonucleoside subunits incorporated therein.” (Ans. 6, citing Crooke col.
12.)
FF 2. Crooke teaches oligoribonucleotides used for experiments “to
determine if mammalian cells . . . contain double-strand RNase activity.”
(Crooke col. 50,11. 36-AO.)
FF 3. Crooke teaches that “[i]t is more preferred that the
oligoribonucleotides and oligoribonucleosides of the present invention
12 Sridhar et al., US 5,739,271, issued Apr. 14, 1998 (“Sridhar”).
13 Fire et al., US 6,506,559 Bl, issued Jan. 14, 2003 (“Fire”).
14 George et al., US 5,683,873, issued Nov. 4, 1997 (“George”).
4
Appeal 2015-004586
Application 13/656,540
comprise from about 15 to about 25 nucleoside subunits.” (Crooke col. 14,
11. 13-16.)
FF 4. The Examiner finds that “use of liposomes as a vehicle for
delivering nucleic acids to cells was well known at the time the invention
was made” and that “liposomes are useful for intracellular delivery of
oligonucleotides for diagnostic purposes.” (Ans. 8, citing Sridhar Abstract;
col. 1,1. 53—col. 2,1. 13.)
FF 5. Fire teaches a process for inhibiting expression of a target gene
in a cell in which “RNA containing [] nucleotide sequences identical to a
portion of the target gene are preferred for inhibition.” (Fire col. 7,11. 53—
54.)
FF 6. Fire teaches that “[t]he length of the identical nucleotide
sequences may be at least 25, 50, 100, 200, 300 or 400 bases.” (Fire col. 8,
11. 5-6.)
FF 7. Fire teaches that “[t]he cell with the target gene may be derived
from or contained in any organism . . . [t]he organism may [be an] . . .
animal. . . the animal may be a vertebrate . . . [e]xamples of vertebrate
animals include . . . mammal.” (Fire col. 8,11. 12—36; see also Appeal Br.
15.)
DISCUSSION
We adopt and agree with the Examiner’s findings, analysis, and
conclusions set forth in the Final Action (Final Act. 2—11), as clarified by the
Answer, and Examiner’s Answer (Ans. 2—25). The rejections are affirmed,
and Appellants’ arguments are addressed below.
5
Appeal 2015-004586
Application 13/656,540
Rejection Nos. 1—7
Appellants do not contest the rejections for obviousness-type double
patenting (Nos. 1—7). Accordingly, those rejections are affirmed. See 37
C.F.R. § 41.37(c)(l)(iv); Hyatt v. Dudas, 551 F.3d 1307, 1314 (Fed. Cir.
2008).
Rejection Nos. 8—10: Section 112
Issue
Whether a preponderance of the evidence of record supports the
Examiner’s conclusion that claims 30, 32, and 35 fail to comply with 35
U.S.C. § 112.
Analysis
Claim 30
The Examiner rejects claim 30 “as being of improper dependent form
for failing to further limit the subject matter of the claim upon which it
depends, or for failing to include all the limitations of the claim upon which
it depends.” (Ans. 5.) In particular, the Examiner asserts that “claim 1 is
directed to a dsRNA and [claim 30] now recites a third strand which does
not further define the claimed invention, which is the dsRNA, not the RNA
transcript.” (Id. at 25.)
Appellants argue that claim 30 does not broaden the scope of claim 1,
but rather “narrows the scope of claim 1 by clarifying the nature of the RNA
transcript.” (Appeal Br. 18.) Appellants argue further that “claim 30
provides structural limitations to the claim by clarifying that the RNA
transcript cannot be a part of the dsRNA, which provides a structural
limitation that further limits the dsRNA of claim 1.” (Reply Br. 10.)
6
Appeal 2015-004586
Application 13/656,540
We find that the Examiner has the better position. Claim 1 defines the
claimed invention as the dsRNA, not the RNA transcript. (Appeal Br. 22.)
Thus, the recitation of claim 30 does not further define the claimed
invention. Moreover, Appellants argument that claim 30 clarifies that “the
RNA transcript cannot be a part of the dsRNA” is not persuasive because,
according to claim 1, the RNA transcript is not part of the claimed dsRNA.
Claim 32
The Examiner found that claim 32 was indefinite because “the
limitation of this claim [] relate [s] to how the compound will be used for one
possible intended use. The amount to be used is a relative quantity . . .
which is not related to the claimed dsRNA itself, but is based on the cell in
which the dsRNA is to be used.” (Ans. 6.)
Appellants argue that claim 32 “does not recite an intended use of the
dsRNA, but an amount of dsRNA” (Appeal Br. 19) and that “an amount of
dsRNA relative to an amount of RNA transcript is a structural limitation of
the dsRNA” (Reply Br. 10).
We find that the Examiner has the better position. While Appellants
argue that “[t]he acceptability of relative terminology in claim language
‘depends on whether one of ordinary skill in the art would understand what
is claimed, in light of the specification’” (Appeal Br. 20, citing MPEP
2173.05(b)), Appellants do not point us to any part of the Specification or
otherwise make of record what they believe one skilled in the art would
understand by the terminology in claim 32. Moreover, attorney argument
cannot take the place of record evidence. Estee Lauder Inc. v. L ’Oreal, S.A.,
129 F.3d 588, 595 (Fed. Cir. 1997). The phrase “at an amount” as
7
Appeal 2015-004586
Application 13/656,540
determined by “an amount” of RNA transcript (which is not claimed) is thus
indefinite.
Appellants’ reliance on Orthokinetics, Inc. v. Safety Travel Charts,
Inc., 806 F.2d 1565 (Fed. Cir. 1986), is misplaced. That decision is based on
patent validity in a district court, rather than a decision in an ex parte appeal
within the USPTO. Our reviewing court has noted “that indefmiteness
rejections by the USPTO arise in a different posture from that of
indefmiteness challenges to an issued patent.” In re Packard, 751 F.3d
1307, 1312 (Fed. Cir. 2014). Furthermore, our reviewing court stated:
during patent prosecution [ ] claims can be amended, ambiguities
should be recognized, scope and breadth of language explored,
and clarification imposed. ... An essential purpose of patent
examination is to fashion claims that are precise, clear, correct,
and unambiguous. Only in this way can uncertainties of claim
scope be removed, as much as possible, during the administrative
process.
In re Zletz, 893 F.2d 319, 321—322 (Fed. Cir. 1989). Accordingly,
Appellants failed to meet their burden before the USPTO of “precisely
defm[ing] the invention.” See In re Morris, 127 F.3d 1048, 1056 (Fed. Cir.
1997).
Claim 35
The Examiner rejects claim 35 “as being of improper dependent form
for failing to further limit the subject matter of the claim upon which it
depends, or for failing to include all the limitations of the claim upon which
it depends.” (Ans. 13.) In particular, the Examiner finds that
The statement in claim 1 that the dsRNA is capable of inhibiting
expression is a mere recitation of a characteristic of the dsRNA,
but does not impart a structural limitation itself; any dsRNA
satisfying the structural requirements of claim 1 would be
expected to have the recited function. Claim 35 does not limit
8
Appeal 2015-004586
Application 13/656,540
claim 1 because it recites a limitation that does not further define
the structure, but instead states only how the compound of claim
1 would function if used for one possible intended use.
{Id.)
Appellants argue that claim 35 limits the final wherein clause of claim
1 (italicized above) by stating that “the inhibition occurs upon introduction
of the dsRNA into a mammalian cell.” (Reply Br. 4—5 and 9—10.)
We find that the Examiner has the better position. Claim 1 is directed
to a composition of matter (dsRNA). The “wherein” clause of claim 1
merely recites a use of the claimed dsRNA, not a structure of the dsRNA,
and thus adds nothing to the patentability of the claim. See Catalina Mktg.
Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002).
Claim 35 also recites a use (not structure) and cannot further limit a wherein
clause that is not itself a limitation of claim 1.
Conclusion
A preponderance of evidence of record supports the Examiner’s
conclusion that claims 30, 32, and 35 fail to comply with 35 U.S.C. § 112.
Rejection Nos. 11—12: Obviousness
Issue
Whether a preponderance of evidence of record supports the
Examiner’s conclusion of obviousness under 35 U.S.C. § 103(a).
9
Appeal 2015-004586
Application 13/656,540
Rejection No. 11
Analysis
Appellants contest the obviousness rejections of claims 1, 9, and 30-
35 based on Crooke, Sridhar, and Wengel. (Appeal Br. 3—11; Reply Br. 2—
5.) We address the arguments as to those claims below.
Claim 1
Appellants argue that “the RNA duplexes of Crooke are produced to
test whether the duplexes would be cleaved in the presence of rat liver
extracts in vitro.” (Appeal Br. 4.) Thus, according to Appellants, “one of
ordinary skill would not put Crooke’s RNA duplexes into micellar structures
for intracellular delivery since there was no motivation to deliver Crooke’s
RNA duplexes into cells.” {Id.) Moreover, according to Appellants, “[a]
skilled artisan would have understood from Crooke as a whole that the
oligomeric compounds were intended to be introduced to a cell for binding
with a target RNA to then form a double-stranded structure within the cell
that could then be cleaved by dsRNAse.” (Id. at 5.) Thus, according to
Appellants, motivation to combine Crooke and Sridhar “is plainly lacking
without impermissible hindsight.” (Reply Br. 3.)
We are not persuaded. As the Examiner explains, Crooke’s disclosure
is not limited to single stranded oligonucleotides that act via the antisense
mechanism. (Ans. 15.) In this regard, it is well settled that a prior art
reference may be read for all that it teaches, including uses beyond its
primary purpose. In re Mouttet, 686 F.3d 1322, 1331 (Fed. Cir. 2012). As
further explained by the Examiner, “Crooke also produces and uses double
stranded oligonucleotides as ‘artificial substrates’ which satisfy the
structural limitations of the claims” and are “used for experiments
10
Appeal 2015-004586
Application 13/656,540
‘determining] if mammalian cells . . . contain double-strand RNase
activity.’” (Ans. 15; FF 2.) Moreover, as stated by the Examiner, “there is a
reason for the person of ordinary skill to perform further experiments within
these cells. The person of ordinary skill recognizes that if one wishes to
study dsRNAses in cells, then intracellular delivery would be necessary.”
(Ans. 15-16.)
Claim 1 recites a double stranded RNA (dsRNA) that is “enclosed by
a micellar structure.” (Appeal Br. 22.) According to Appellants, based on
Crooke’s teachings “as a whole,” motivation to combine Crooke and Sridhar
is lacking because “there was no motivation to deliver Crooke’s RNA
duplexes into cells.” (Appeal Br. 4—5; Reply Br. 2—3.) However, “[i]n
determining whether the subject matter of a patent claim is obvious, neither
the particular motivation nor the avowed purpose of the patentee controls,”
KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007), and “[o]ne of
ordinary skill in the art need not see the identical problem addressed in a
prior art reference to be motivated to apply its teachings” Cross Med.
Prods., Inc. v. Medtronic Sofamor Danek, Inc. 424 F.3d 1293, 1323 (Fed.
Cir. 2005). Moreover, evaluating suggestion or motivation in an
obviousness analysis “not only permits, but requires, consideration of
common knowledge.” DyStar Textilfarben GmbH & Co. Deutschland KG v.
C.H. Patrick Co., 464 F.3d 1356, 1367 (Fed. Cir. 2006).
Here, the Examiner makes clear that “[t]he person of ordinary skill
recognizes that if one wishes to study dsRNAses in cells, then intracellular
delivery would be necessary” (Ans. 16), and that the use of liposomes (a
micellular structure) for intracellular delivery of oligonucleotides “was well
known at the time the invention was made” (Ans. 8; FF 4). Thus, the
11
Appeal 2015-004586
Application 13/656,540
Examiner concluded, and we agree, that the enclosure of Appellants’ recited
dsRNA in a micellular structure would have been obvious.
We find Appellants’ argument regarding “impermissible hindsight”
similarly unpersuasive. (See Appeal Br. 5 and Reply Br. 3.) Appellants
adduce no evidence that the Examiner’s findings were beyond the level of
ordinary skill in the art at the time of invention, nor do they point to any of
the Examiner’s findings that could have been taken only from Appellants’
Specification. See In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971).
Claim 9
Appellants rely on the same arguments set forth above in connection
with claim 1 (Appeal Br. 6), and they are unpersuasive as to claim 9 for the
reasons set forth above.
Claim 30
Appellants argue that “Crooke does not disclose a third strand at all”
and rely on the same arguments advanced above in connection with claim 1.
(Appeal Br. 7—8.) However, as discussed above, claim 30 does not further
limit claim 1 and is obvious for the reasons set forth in connection with
claim 1. (See Ans. 16.)
Claim 31
Appellants rely on the same motivation arguments as set forth above
in connection with claim 1, and those arguments are unpersuasive as to
claim 31 for the reasons set forth above. (See Appeal Br. 8; Ans. 16—17.)
Claim 32
Appellants argue that the cited art “does not teach or suggest a dsRNA
at an amount, wherein the amount of dsRNA introduced into a mammalian
cell is less than an amount of RNA transcript of the mammalian target gene
12
Appeal 2015-004586
Application 13/656,540
in the mammalian cell.” (Appeal Br. 8.) However, “the patentability of
apparatus or composition claims depends on the claimed structure, not on
the use or purpose of that structure.” Catalina Mktg., 289 F.3d at 809. Here,
as the Examiner explains, the claims are directed to the dsRNA while the
amount recited in claim 32 “is a relative amount that is related to the cell in
which the dsRNA is to be used.”15 (Ans. 17.)
Claim 33
Appellants rely on the same arguments set forth above (Appeal Br.
10), and those arguments are unpersuasive as to claim 33 for the reasons set
forth above.
Claim 34
Appellants rely on the same arguments set forth above; namely, that
“none of the references alone or in combination teach a dsRNA enclosed by
a micellar structure at all.” (Appeal Br. 11.) That argument is unpersuasive
as to claim 34 for the reasons set forth above.
Claim 35
Appellants argue that “[c]laim 35 is patentable for at least the same
reasons that claim 1 is patentable” and that “claim 35 does limit claim 1, as
it recites that ‘the inhibition occurs upon introduction of the dsRNA into a
mammalian cell.”’ (Reply Br. 4.) We are unpersuaded, for the reasons set
15 We do not agree with Appellants’ contention, based on In re Lemin, 326
F.2d 437 (CCPA 1964), that an amount recited in a composition claim is
necessarily a “physical limitation.” (Reply Br. 4.) See, e.g., Syntex (U.S.A.)
LLC v. Apotex, Inc., 407 F.3d 1371, 1378 (Fed. Cir. 2005) (construing the
term “in a stabilizing amount” in a drug formulation claim as not a
limitation).
13
Appeal 2015-004586
Application 13/656,540
forth above in connection with claim 1 and because claim 35 is a non­
limiting statement of a use of the claimed dsRNA, as also set forth above.
Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
conclusion that claims 1, 9, and 30-35 are obvious under 35 U.S.C. § 103(a).
Claims 2—7, 10—13, and 27—29 were not argued separately and fall with
claim 1.
Rejection No. 12
Analysis
Appellants contest the obviousness rejections of claims 1 and 35 by
advancing arguments regarding the disclosure of Fire (relating to dsRNAs)
and secondary considerations. (Appeal Br. 11—18; Reply Br. 5—10.)
Claim 1
Length of dsRNA
Appellants argue that “one of ordinary skill would not find it obvious
to make a dsRNA of 15 to 49 base pairs based on the disclosure of Fire.”
(Appeal Br. 12.) In particular, Appellants argue that Fire’s reference to
identical nucleotide sequences of at least 25 bases “means that the dsRNA
itself could be hundreds of base pairs long, as long as 25 bases of the dsRNA
are identical to a portion of the target gene,” and support this argument by
reference to certain RNA constructs disclosed in Fire. (Id. at 12—13.)
Appellants also take issue with the Examiner’s reference to claim 15 of Fire
as support for the position that Fire discloses a dsRNA of 25 base pairs in
14
Appeal 2015-004586
Application 13/656,540
length, based on the contention that claim 15 was not present at the time the
Fire patent application was filed.16 (Appeal Br. 15; Reply Br. 7.)
Appellants also point to two articles for the proposition that “[t]he
state of the art at the time [Fire was filed] also lends evidence that one of
ordinary skill would not find it obvious to make dsRNAs of 15 to 49 base
pairs in length based on the teachings of the Fire patent.” (Appeal Br. 13.)
Appellants cite to Ngo17 for the proposition that “it was understood in the
field that dsRNAs had to be . . . over 150 base pairs [] to be effective, and
really much longer than that for robust inhibition,” and a Fire Article18 that
Appellants argue discloses dsRNAs “between 299-1033 kilobases in length,
but no dsRNAs that were 25 base pairs long.” {Id. at 14.) Thus, according
to Appellants, “[o]ne of ordinary skill would be led away from believing that
dsRNAs of 15 to 49 base pairs were effective.” {Id. at 14—15.)
We are not persuaded. As explained by the Examiner, Fire teaches
“that the dsRNAs can be as short as 25 nucleotides” and the teachings of
Fire are not limited to its working examples.19 (Ans. 18.) See Mouttet, 686
16 Claim 15 of Fire recites “said double-stranded ribonucleic acid structure is
at least 25 bases in length.” (Fire cols. 27.)
17 Ngo et al., Double-stranded RNA induces mRNA degradation in
Trypanosoma brucei, Proc. Natl. Acad. Sci. USA 95, 14687—92 (1998)
(“Ngo”).
18 Fire et al., Potent and specific genetic interference by double-stranded
RNA in Caenorhabditis elegans, Nature 391, 806—11 (1998) (“Fire Article”).
19 We acknowledge, but are unpersuaded by, Appellants’ argument that at
least two of Fire’s RNA constructs contain introns and that, “since mRNAs
do not contain any intron sequences,” Fire’s constructs are longer than any
regions thereof that are identical to a target RNA sequence. (Appeal Br. 12—
13.) As the Examiner explains, “primary mRNAs transcripts do contain
intron sequences,” whereas “mature mRNA” is apparently what Appellants
are referring to by “mRNAs” that do not contain introns, and Fire uses the
15
Appeal 2015-004586
Application 13/656,540
F.3d at 1331. And while Fire claim 15 may not have been present at the
time Fire was filed, its presence in Fire as issued supports the Examiner’s
position that the specification of Fire as filed disclosed dsRNAs as short as
25 nucleotides. Moreover, as the Examiner also explains, “there is no basis
to conclude that the RNA of Fire would be hundreds of nucleotides long
with only a 25 nucleotide portion identical or complementary to the target.”
(Id. at 19.) Accordingly, we discern no error in the Examiner’s finding that
Fire teaches and suggests a dsRNA as recited in claim 1. See In re Baird, 16
F.3d 380, 383 (Fed. Cir. 1994) (“a reference must be considered not only for
what it expressly teaches, but also for what it fairly suggests.”) (quoting In
re Burckel, 592 F.2d 1175, 1179 (CCPA 1979)).20
We are similarly unpersuaded by Appellants’ arguments regarding the
Ngo article and Fire Article, and how those articles purportedly led away
from dsRNAs of 15 to 49 base pairs. Fire teaches and suggests the dsRNA
as recited in claim 1, and Appellants’ arguments do not persuade us that Ngo
or the Fire Article criticize, discredit, or otherwise discourage the claimed
invention. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Mammalian Target Genes
Appellants argue that, while Fire discloses that the cell with the target
gene may be derived from a mammal, Fire “does not teach that one strand of
term “target gene” and does not equate that term with the term “mature
mRNA.” (Ans. 20.)
20 We also acknowledge, but are unpersuaded by, Appellants argument that
the sentence in Fire stating “[t]he length of the identical nucleotide
sequences may be. . .” (FF 6) applies only to the immediately preceding
sentence regarding an alternative functional definition. (Reply Br. 6.) (See
Fire col. 7,1. 53—col. 8,1. 6.)
16
Appeal 2015-004586
Application 13/656,540
the dsRNA is complementary to an RNA transcript of at least part of a
mammalian target gene.” (Appeal Br. 15.) Appellants also cite to Fire and
“the general understanding in the field” for the proposition that one of
ordinary skill would not have been motivated to make (and would have been
led away from making) “a dsRNA having one strand that is complementary
to an RNA transcript of at least part of a mammalian target gene.” {Id. at
16.)
We are not persuaded by Appellants’ arguments. Fire teaches the
application of its dsRNA to a mammalian gene. (FF 7.) Appellants rely on
the Fire Article as “strongly suggesting] that dsRNAs were not functional in
mammals” based on the protein kinase response (PKR). (Appeal Br. 16.)
Appellants rely on the Sen21 article for the elicitation of an interferon
response by the introduction of long dsRNA into mammalian cells. {Id. at
16—17.) However, as explained by the Examiner, Fire “recognized the PKR
issue” and cites to Proud22 (which cites to Manche23) as informing “one of
ordinary skill that introducing dsRNA of less than about 33bp in length
would avoid entirely the activation of the PKR protein, thus avoiding
entirely the interferon response.”24 (Ans. 21—23.) Appellants also point to a
21 Sen et al., A brief history of RNAi: the silence of the genes, FASEB J. 20,
1293-99 (2006) (“Sen”).
22 Proud, PKR: a new name and new roles, TIBS 20, 241—46 (1995)
(“Proud”).
23 Manche et al., Interactions between Double-Stranded RNA Regulators and
the Protein Kinase DAI, 12 Mol. Cell. Biol. 11, 5238-48 (1992)
(“Manche”).
24 Appellants attempt to distinguish Proud and Manche from Fire based on
their publication dates, and state that “Proud and Manche may not represent
the state of the art at the time of the instant application.” (Reply Br. 8.) But
Proud (which cites to Manche) was incorporated by reference into Fire and
17
Appeal 2015-004586
Application 13/656,540
quote from Tuschl25 that reads (in pertinent part) “[i]f RNAi exists in
mammals ... it is likely obscured by the rapid induction of dsRNA of
nonspecific antiviral responses.” (Appeal Br. 16.) Such an equivocal
postulation about what is “likely” does not persuade us that a person of skill
in the art would be “led away from” a dsRNA strand complementary to an
RNA transcript of at least part of a mammalian target gene, particularly
given the express teachings of Fire.
Secondary Considerations
Appellants argue that “[t]he fact that a dsRNA of 15 to 49 base pairs
in length would be capable of specifically inhibiting expression of a
mammalian target gene was unexpected,” citing the Fire Article and Tuschl.
(Appeal Br. 17.) Appellants also refer to a statement from the Specification
to argue that “it was a surprising result that the shorter dsRNAs would
operate via dsRNA-mediated inhibition of gene expression in mammals.”
(Appeal Br. 17, citing Spec. 111.)
Based on Fire’s teachings, we are not persuaded that a person of
ordinary skill in the art would have found “that a dsRNA of 15 to 49 base
pairs in length would be capable of specifically inhibiting expression of a
mammalian target gene” to be unexpected. See Pfizer, Inc. v. Apotex, Inc.,
480 F.3d 1348, 1371 (Fed. Cir. 2007). Moreover, “[m]ere lawyer’s
arguments and conclusory statements in the specification, unsupported by
referred to as “indicative of the level of skill in the art.” (Fire col. 22,11. 5—
8, 20.) See Callaway Golf Co. v. Acushnet Co., 576 F.3d 1331, 1346 (Fed.
Cir. 2009) (discussing incorporation by reference).
25 Tuschl et al., Targeted mRNA degradation by double-stranded RNA in
vitro, Genes & Development 13, 3191-97 (1999) (“Tuschl”).
18
Appeal 2015-004586
Application 13/656,540
objective evidence, are insufficient to establish unexpected results.” In re
Wood, 582 F.2d 638, 642 (CCPA 1978).
We do not find that Appellants’ arguments regarding secondary
considerations are persuasive or otherwise sufficient to rebut the prima facie
case of obviousness. Moreover, the dsRNA of claim 1 is taught by Fire and
that dsRNA “enclosed by a micellar structure” would have been obvious
based on the combination of Fire and Sridhar for the reasons set forth above
in connection with the combination of Crooke and Sridhar in Rejection No.
11.
Claim 35
Appellants argue that claim 35 is patentable based on their arguments
regarding claim 1 and their arguments that claim 35 limits claim 1. (Reply
Br. 9.) Appellants also argue that the references do not teach that “the
dsRNA is capable of inhibiting expression of the mammalian target gene
upon introduction of the dsRNA into a mammalian cell.” (Id.) Appellants
argue further that there is no motivation to “to encapsulate a dsRNA of 15 to
49 base pairs in length in a micellar structure.” (Id. at 9—10.)
We are not persuaded. Claim 1 is unpatentable for the reasons set
forth above and claim 35 does not further limit claim 1 for the reasons set
forth above. Moreover, we find Appellants’ argument regarding lack of
motivation to encapsulate the dsRNA based on Fire alone or in combination
with other references similarly unpersuasive for the reasons set forth above.
Conclusion of Law
A preponderance of evidence of record supports the Examiner’s
conclusion that claims 1 and 35 are obvious under 35 U.S.C. § 103(a).
19
Appeal 2015-004586
Application 13/656,540
Claims 2—7, 9—13, and 27—34 were not argued separately and fall with claim
1.
SUMMARY
We affirm all rejections of all claims on appeal.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
AFFIRMED
20