Ex Parte Kawaoka et al

Patent Trial and Appeal Board

Aug 1, 2016

11654863 (P.T.A.B. Aug. 1, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111654,863 01/18/2007
81244 7590 08/03/2016
Schwegman Lundberg & Woessner/WARF
P.O. Box 2938
Minneapolis, MN 55402
FIRST NAMED INVENTOR
Y oshihiro Kawaoka
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
800.032US2 8253
EXAMINER
CHEN, STACY BROWN
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
08/03/2016 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
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YOSHIHIRO KAW AOKA,
LUKE D. JASENOSKY, and GABRIELE NEUMANN
Appeal2014-008986
Application 11/654,863
Technology Center 1600
Before DONALD E. ADAMS, ULRIKE W. JENKS, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
ADAMS, Administrative Patent Judge.
DECISION ON APPEAL 1
This appeal under 35 U.S.C. § 134(a) involves claims 1---6, 8-18, and
21 (see App. Br. 1). Examiner entered a rejection under 35 U.S.C. § 103(a).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Appellants disclose "methods to prepare filovirus, e.g., Marburg virus
and Ebola virus, from cloned DNA and compositions useful therefore"
1 Appellants identify the Real Party in Interest as "Wisconsin Alumni
Research Foundation" (App. Br. 2).
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Application 11/654,863
(Spec. 4: 9-10). Claim 10 is representative and reproduced in the Claims
Appendix of Appellants' Brief.
Claims 1---6, 8-18, and 21 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over the combination of Miihlberger2 and Kawaoka. 3
ISSUE
Does the preponderance of evidence relied upon by Examiner support
a conclusion of obviousness?
FACTUAL FINDINGS (FF)
FF 1. Appellants disclose that Filoviridae represent a family of
"enveloped, nonsegmented negative-strand RNA virus" (Spec. 1: 16-17).
FF 2. Miihlberger discloses:
Marburg virus and Ebola virus ... are the only members of the
family filoviridae . ... Both possess a nonsegmented negative-
strand RNA genome ca. 19 kb in length with a coding capacity
for seven structural proteins. The genes are flanked by highly
conserved transcriptional start and stop signals[]. N oncoding
sequences containing the signals for replication and
encapsidation are located at the 2' and 5' ends of the genomes.
(Miihlberger 2333: col. 1, first paragraph; see Ans. 7 ("Miihlberger's
teachings are more than adequate to show that full-length genomes of
filoviruses were known"); Ans. 3; Ans. 7 (Appellants are "not claiming a
particular genome, [therefore,] the generic description of a filovirus genome
is sufficient to meet the limitations of [Appellants'] claims"); see also
Kawaoka Dec.4 i-f 5 ("[t]he Ebola virus genome is about 19 kb in length").)
2 Elke Miihlberger, et al., Comparison of the Transcription and Replication
Strategies of Marburg Virus and Ebola Virus by Using Artificial Replication
Systems, 73 J. Virology 2333-2342 (1999).
3 Kawaoka, et al., WO 00/60050, published Oct. 12, 2000.
4 Kawaoka Declaration, executed April 18, 2012.
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FF 3. Miihlberger discloses an isolated eukaryotic cell comprising the
following five vectors: (1) pTMl comprising the Ebola virus NP gene, (2)
pTMl comprising the Ebola virus VP35 gene, (3) pTMl comprising the
Ebola virus VP30 gene, ( 4) pTMl comprising the Ebola virus L gene, and
(5) an artificial minigene "[p]lasmid 215 containing the CAT gene flanked
by the leader and trailer regions of the [Marburg virus] genome"
(Miihlberger 2334: col. 1: first paragraph- col. 2: first paragraph; see Ans.
2-3).
FF 4. Examiner finds that Miihlberger fails to suggest: "the use of the
RNA polymerase II promoter in the vectors encoding the nucleocapsid
proteins" or "transcription termination sequences [in] each of the plasmid
vectors" and relies on Kawaoka to make up for these deficiencies in
Miihlberger (Ans. 3--4).
FF 5. Kawaoka discloses that a number of obstacles relating to the
generation of "infectious [negative-strand] RNA virus[] from cloned DNA"
have been overcome by "reverse genetics methods ... established to
produce nonsegmented negative-sense RNA viruses," such as "Filoviridae"
(Kawaoka 1: 11-22 and 7: 9-11; see generally id. at 6: 25 - 7: 11; see Ans.
4).
FF 6. Kawaoka discloses a composition
comprising a vector comprising a promoter linked to 5'
orthomyxovirus non-coding sequences linked to a desired
[sequence] linked to 3' orthomyxovirus non-coding sequences
linked to transcription termination sequences. The introduction
of such a composition to a host cell permissive for
orthomyxovirus replication results in recombinant virus
comprising vRNA corresponding to sequences of the vector
comprising 5' orthomyxovirus noncoding sequences linked to a
cDNA linked to 3' orthomyxovirus non-coding sequences.
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Preferably, ... the promoter is a RNA polymerase l[,RNA
polymerase II, or RNA polymerase III,] promoter, a T7
promoter, and a T3 promoter. It is also preferred that the
transcription termination sequence is a RNA polymerase
I[,RNA polymerase II, or RNA polymerase III,] transcription
termination sequence, or a ribozyme. For example, the cDNA
may encode an immunogenic epitope, such as an epitope useful
in a cancer therapy or vaccine.
(Kawaoka 5: 32 - 6: 14; see id. at 3: 10 ("orthomyxoviruses such as
influenza A virus[]"); Ans. 4.)
FF 7. Kawaoka discloses
A method to prepare influenza virus ... compris[ing]
contacting a cell with a plurality of the vectors [set forth in
Kawaoka's disclosure] in an amount effective to yield
infectious influenza virus ... and isolating virus from a cell
contacted with the [vector] composition. Thus, [Kawaoka]
provides isolated virus, as well as a host cell contacted with the
composition or isolated virus.
(Kawaoka 6: 18-24; see id. at 7: 9-11 ("the same approach may be
employed for other virus[] to generate nonsegmented negative strand RNA
viruses (i.e., ... Filoviridae)"; id. at Abstract ("[t]he invention provides a
composition useful to prepare influenza A virus[], e.g., in the absence of
helper virus"); Ans. 4 and 6.)
ANALYSIS
Based on the combination of Miihlberger and Kawaoka, Examiner
concludes that, at the time Appellants' invention was made, it would have
been prima facie obvious to substitute a filovirus genomic cDNA operably
linked to a transcription termination sequence, for Miihlberger' s artificial
minigene "in order to produce infections particles" as suggested by
Kawaoka (Ans. 3-5; FF 2-7). In this regard, Examiner finds that a person of
ordinary skill in this art would have recognized that Miihlberger' s genes
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could have been operatively linked to any of a number of promoters, such as
RNA polymerase II promoters and transcription termination sequences as
suggested by Kawaoka (Ans. 4; FF 6).
We recognize, but are not persuaded by, Appellants' contention that
"there is no mention in [Miihlberger] of a report of an infections filovirus
cDNA clone and [Miihlberger] does not describe or provide the sequence of
an infectious filovirus cDNA clone" (App. Br. 13; cf FF 2).
We recognize, but are not persuaded by, Appellants' contention that
"the first apparent scientific literature report of a full-length infectious
filovirus clone was in Volchkov5" (App. Br. 13; see Reply Br. 2-3).
Appellants' contention fails to explain why, when a specific sequence is not
required by Appellants' claimed invention, a person of ordinary skill in this
art could not have obtained an infectious filovirus genomic cDNA in view of
the combination of Miihlberger and Kawaoka (FF 2-7). The obviousness
inquiry "not only permits, but requires, consideration of common knowledge
and common sense." DyStar Textilfarben GmbH & Co. v. C.H. Patrick Co.,
464 F.3d 1356, 1367 (Fed. Cir. 2006); see KSR Int'! Co. v. Teleflex Inc., 550
U.S. 398, 421 (2007). For the foregoing reasons we are not persuaded by
Appellants' contentions regarding the hypothetical assembly of a "'full-
length' [filovirus] sequence ... from various virus subsequences (App. Br.
13-14). Appellants' contention fails to explain why a person of ordinary
skill in this art would have performed such a hypothetical experiment (cf FF
2).
5 Volchkov et al. Recovery of Infectious Ebola Virus from Complementary
DNA: RNA Editing of the GP Gene and Viral Cytotoxicity, 291 Science
1965-1969 (2001).
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We recognize, but are not persuaded by, Kawaoka's declaration that
"[i]t is well known that the propagation of larger plasmids (e.g., those over
about 15 kbp) in bacteria quite often leads to deletions of portions of the
plasmid" (Kawaoka Dec. i-f 6 (emphasis added); see Reply Br. 3 and 4). The
Kawaoka Dec. fails to provide persuasive evidence or testimony that a
person of ordinary skill in this art would have reasonably expected that all
plasmids over about 15 kbp that may be propagated through bacteria, prior
to insertion into eukaryotic cells, would have deletions and that, if not, a
person of ordinary skill in this art would not have understood how to screen
for those eukaryotic cells that did not contain deletions. In the alternative,
the Kawaoka Dec. fails to provide persuasive evidence or testimony as to
why a person of ordinary skill in this art would have utilized prokaryotic
cells instead of eukaryotic cells to propagate the plasmids. In sum, the
Kawaoka Dec. fails to overcome the weight of evidence on this record,
which suggests that the methodology utilized by Kawaoka can be used "to
generate nonsegmented negative strand RNA viruses (i.e., ... Filoviridae )"
(FF 7).
We are not persuaded by Appellants' reliance on the Kawaoka Dec. to
support their contention that differences between the influenza A virus and
Ebola virus genome differ, therefore, "observations or findings obtained for
one virus family do not necessarily apply to members of another virus
family," which is contrary to Kawaoka's disclosure (see Kawaoka Dec. i-f 5
(emphasis added); cf FF 5-7). See generally, KSR Int'! Co. v. Teleflex Inc.,
550 U.S. 398, 421 (2007):
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
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the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that is was obvious under § 103.
We recognize, but are not persuaded by, Appellants' contention that
Miihlberger fails to "provide[] for infectious filovirus in the absence of
helper virus," which fails to account for Kawaoka's contribution to the
combination of references relied upon by Examiner (App. Br. 13; FF 7). In
this regard, we recognize Appellants' contention that "a single infectious
[filovirus] clone encodes VP40 as well as all the other trans-acting filovirus
proteins and has cis-acting elements for transcription replication and
encapsidation" (App. Br. 13; see Reply Br. 3--4). Therefore, we are not
persuaded by Appellants' contention that the combination of Miihlberger
and Kawaoka fails to suggest an "infectious filovirus in the absence of
helper virus[; because,] VP40 was not provided in trans" (App. Br. 14--15).
As Examiner explains, "[b ]y providing the full genome, VP40 would have
been" present in the eukaryotic cell suggested by the combination of
Miihlberger and Kawaoka (Ans. 6).
For the foregoing reasons, we are not persuaded by Appellants'
contentions that the combination of Miihlberger and Kawaoka fails to
provide a person of ordinary skill in this art with a reasonable expectation of
success (App. Br. 15-18).
For the foregoing reasons, but are not persuaded by Appellants'
contention that Examiner failed to "give proper weight, to Appellant's [sic]
evidence submitted in support of patentability as a whole," specifically, the
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Kawaoka Dec., Le,6 Zhang,7 and Via8 (App. Br. 18-21). In this regard,
Appellants' reliance on Via to suggest that "large plasmids have a tendency
to be lost" fair' s no better than the same statement made in the Kawaoka
Dec. discussed above (see App. Br. 19; cf Kawaoka Dec. i-f 6). The Zhang
abstract relates to a method that "simplifies the cloning of randomly
mutagenized genes or gene fragments for constructing high titer random
mutant libraries" (Zhang, Abstract; cf App. Br. 19). Appellants provide no
persuasive argument or evidence to support a conclusion that the
combination of Miihlberger and Kawaoka, or Appellants' claim 10, relates
to random mutant libraries. Appellants rely upon Le to suggest that "cloning
can be difficult if the cloning vector lacks unique restriction[] sites" (App.
Br. 19 (emphasis added)). Appellants, however, fail to establish an
evidentiary basis on this record to support a conclusion that the vector
suggested by the combination of Miihlberger and Kawaoka lacks unique
restriction sites, or even if it did, that a person of ordinary skill in this art, at
the time of Appellants' claimed invention, would not understand how to
introduce unique restriction sites into a cloning vector. At best, Appellants'
contentions relate to the possibility that some disadvantageous event might
occur to some, not all, nucleic acid that may be introduced into some, not all,
eukaryotic cells following the methodology set forth by the combination of
Miihlberger and Kawaoka. Appellants have not, however, explained why a
6 Le et al., CaSpeR5, a family of Drosophila transgenesis and shuttle vectors
with improved multiple cloning sites, 42 BioTechniques 164--166 (2007).
7 Zhang et al., Easy two-step method for randomizing and cloning gene
fragments," 634 Methods Mol. Biol. 399--407 (2010) (Abstract only).
8 Via et al., Isolation of restriction fragments from large plasmids recovered
from bacteria with multiple plasmids," 11Biotechniques442 (1991)
(Abstract only).
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person of ordinary skill in this art would not have had a reasonable
expectation of successfully obtaining, and expanding, a second population of
eukaryotic cells comprising all of the intact, unadulterated, nucleic acid
introduced into a first population of eukaryotic cells as suggested by the
combination of Miihlberger and Kawaoka. As Examiner explains, the
evidence relied upon by Appellants identify potential "difficulties as well as
solutions, which show that while the cloning process requires routine
experimentation, it is possible" (Ans. 8). In re 0 'Farrell, 853 F.2d 894, 903
(Fed. Cir. 1988). ("Obviousness does not require absolute predictability of
success ... all that is required is a reasonable expectation of success").
Therefore, notwithstanding Appellants' contentions to the contrary,
Appellants' supplemental evidence was considered and found to be
insufficient to outweigh the preponderance of evidence, on this record, in
support of Examiner's rejection.
For the foregoing reasons, we recognize, but are not persuaded by,
Appellants' contentions regarding a "full [ filovirus] genome" that comprises
mutations rendering it non-infectious (Reply Br. 2).
CONCLUSION OF LAW
The preponderance of evidence relied upon by Examiner supports a
conclusion of obviousness. The rejection of claim 10 under 35 U.S.C.
§ 103(a) as unpatentable over the combination of Miihlberger and Kawaoka
is affirmed. Claims 2-6, 8-18, and 21 are not separately argued and fall
with claim 10.
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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
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