Ex Parte Rasochova et al

Board of Patent Appeals and Interferences

Sep 14, 2010

11069601 (B.P.A.I. Sep. 14, 2010)

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.
11/069,601 02/28/2005 Lada Rasochova 38194-721.201 1713
21971 7590 09/14/2010
WILSON, SONSINI, GOODRICH & ROSATI
650 PAGE MILL ROAD
PALO ALTO, CA 94304-1050
EXAMINER
WORLEY, CATHY KINGDON
ART UNIT PAPER NUMBER
1638
MAIL DATE DELIVERY MODE
09/14/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte LADA RASOCHOVA and PHILIP PHUOC DAO
__________

Appeal 2010-000616
Application 11/069,601
Technology Center 1600
__________

Before ERIC GRIMES, CAROL A. SPIEGEL, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a plant
cell. The Examiner has rejected the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We reverse.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
Appeal 2010-000616
Application 11/069,601

2
STATEMENT OF THE CASE
Claims 20, 22, 25-27, 29, and 36-39 are on appeal (App. Br. 1).2 We
will focus on claim 20, the only independent claim on appeal, which reads as
follows:
20. An isolated plant cell comprising a non-infectious nucleic acid
comprising a nucleic acid sequence encoding a fusion peptide, wherein the
fusion peptide is comprised of at least one heterologous peptide of interest
and at least one viral capsid protein, wherein the heterologous peptide is
inserted into at least one surface loop of the viral capsid protein, and wherein
the nucleic acid is integrated into the genome of the plant cell.
Claims 20, 22, 25, 36, and 39 stand rejected under 35 U.S.C. § 103(a)
as obvious over Sojikul3 in view of Makowski4 (Ans.5 3).
Claim 26 stands rejected under 35 U.S.C. § 103(a) as obvious over
Sojikul in view of Makowski and Stöger6 (Ans. 5).
Claims 27, 29, 37, and 38 stand rejected under 35 U.S.C. § 103(a) as
obvious over Sojikul in view of Makowski and Lomonossoff7 (Ans. 6).

2 Claims 1-19, 23, 24, and 32-35 are also pending (App. Br. 2). Claims 1-
19, 23, and 32-35 have been withdrawn from consideration by the Examiner
and claim 24 has been indicated to be allowable (Final Rej. 2 & 8).
3 Punchapat Sojikul et al., A plant signal peptide-hepatitis B surface antigen
fusion protein with enhanced stability and immunogenicity expressed in
plant cells, 100 PNAS 2209-2214 (2003).
4 Lee Makowski, Structural constraints on the display of foreign peptides on
filamentous bacteriophages, 128 GENE 5-11 (1993).
5 “Ans.” refers to the supplemental Examiner’s Answer mailed June 3, 2009.
6 Eva Stöger et al., Cereal crops as viable production and storage systems
for pharmaceutical scFv antibodies, 42 PLANT MOLECULAR BIOLOGY 583-
590 (2000).
7 Lomonossoff, US 5,958,422, Sep. 28, 1999.
Appeal 2010-000616
Application 11/069,601

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PRINCIPLES OF LAW
A claim “composed of several elements is not proved obvious merely
by demonstrating that each of its elements was, independently, known in the
prior art.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Where claimed subject matter has been rejected as obvious in
view of a combination of prior art references, a proper analysis
under § 103 requires, inter alia, consideration of two factors:
(1) whether the prior art would have suggested to those of
ordinary skill in the art that they should make the claimed
composition or device, or carry out the claimed process; and
(2) whether the prior art would also have revealed that in so
making or carrying out, those of ordinary skill would have a
reasonable expectation of success.
In re Vaeck, 947 F.2d 488, 493 (Fed. Cir. 1991). See also KSR Int’l Co. v.
Teleflex Inc., 550 U.S. at 416 (“The combination of familiar elements
according to known methods is likely to be obvious when it does no more
than yield predictable results.”).
I
The Examiner relies on Sojikul for teaching “a Nicotiana tabacum
plant transformed with a nucleic acid encoding the hepatitis B surface
antigen (HBsAg) in fusion with an N-terminal extension of a VSPαS or
VSPαL peptide” (Ans. 4). The Examiner finds that “HBsAg is a ‘virus
capsid protein’ because it is a surface protein from a virus and is able [to]
self-assemble to form virus-like particles” (id.). The Examiner also finds
that Sojikul teaches “that the transformed cells were grown in liquid
suspension cultures” (id.).
The Examiner relies on Makowski for teaching “the insertion of
peptides of interest into the surface loop of a coat protein” (id.). The
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Examiner concludes that it would have been obvious “to modify the viral
particles taught by Sojikul et al to include an insertion into a surface loop
protein as taught by Makowski” (id. at 5). The Examiner finds:
Common sense dictates that one would want the peptide of
interest to be displayed on the surface of the virus particle,
rather than folded inside the virus particle where it would be
inaccessible. Furthermore, one would have been motivated to
utilize a surface loop because Makowski teaches that a
nonhelical loop at the surface is an attractive insertion site for
displaying the peptide of interest.
(Id.)
In rejecting claim 26, the Examiner additionally relies on Stöger for
teaching a transgenic rice plant (id. at 6).
Appellants argue, however, that, because of the fundamental
differences between enveloped HBsAg virus-like particles (VLP) and non-
enveloped filamentous bacteriophage virus particles, “there can be no
reason, teaching, or suggestion to a skilled artisan to combine the Sojikul
and Makowski references” (Reply Br. 4-5). In particular, Appellants argue
that “the teachings of Makowski do not apply to all viral particles because of
differences in particle structure and mechanism of particle formation” (id. at
7). In addition, Appellants argue that because “Sojikul’s enveloped VLPs
are so fundamentally different from non-enveloped . . . filamentous viruses
in terms of particle structure, symmetry and formation, there is no
motivation or suggestion for a skilled artisan to apply Sojikul’s teaching to
the completely unrelated and fundamentally different Makowski’s
bacteriophages with any reasonable expectation of success” (id. at 6).
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Appellants also argue that Stöger does not overcome the deficiencies of
Sojikul and Makowski (id. at 8).
Issue
Has the Examiner set forth a prima facie case that it would have been
obvious to combine Sojikul with Makowski in the manner claimed with a
reasonable expectation of success?
Findings of Fact
1. Sojikul relates to the “use of transgenic plants to express orally
immunogenic protein antigens” (Sojikul 2209).
2. “HBsAg is a transmembrane protein with uncleaved internal
signal sequences that facilitate cotranslational translocation and integration
of HBsAg into the endoplasmic reticulum (ER) membrane” (id.).
3. Sojikul discloses “a recombinant HBsAg modified to contain a
plant signal peptide fused to its amino terminus. The signal peptide from
soybean vegetative storage protein vspA (VSPαS) directed endoplasmic
reticulum targeting of HBsAg in plant cells, but was not cleaved and resulted
in enhanced VSPαS-HBsAg fusion accumulation.” (Id.)
4. Makowski discloses “[p]otential sites for the insertion of
foreign peptides into the major coat protein, gp8, of M13,” a filamentous
bacteriophage (Makowski 5).
5. Makowski also discloses the “structure of the coat protein of
another filamentous phage, Pseudomonas phage Pf1. . . . Because it contains
a 7-aa surface loop in the major coat protein, the Pf1 coat protein may have
significant advantages over gp8 of M13 as a vehicle for phage display.”
(Id.)
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6. In addition, Makowski discloses that the “nonhelical loop in the
Pf1 coat protein represents the kind of structure that could be viable when
inserted into the M13 coat protein” (id. at 8).
7. In particular, Makowski discloses:
Examination of the structure of the coat protein of Pf1 suggests
that a nonhelical surface loop can be inserted into the
continuous α-helical structure of M13 without causing a fatal
loss of virion stability. . . . Once a nonhelical loop is inserted
successfully into the coat protein helix, a site within that loop
may represent a more attractive insertion site.
(Id. at 9.)
Analysis
The Examiner does not find that HBsAg was known to have a
nonhelical surface loop. In addition, the Examiner does not provide
sufficient basis to reasonably conclude that, based on Makowski’s teaching
to insert the nonhelical surface loop of the coat protein of filamentous phage
Pf1 into M13, another filamentous phage, it would have been obvious to
insert the same surface loop into a transmembrane protein, such as HBsAg,
with a reasonable expectation of achieving a similar result. Thus, we agree
with Appellants that the Examiner has not set forth a prima facie case that it
would have been obvious to combine Sojikul with Makowski in the manner
claimed with a reasonable expectation of success. We therefore reverse the
obviousness rejections of claim 20 and claims 22, 25, 26, 36, and 39, which
depend therefrom.
II
In rejecting claims 27, 29, 37, and 38, which also depend from
claim 20, the Examiner relies on Sojikul and Makowski as discussed above
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Application 11/069,601

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(Ans. 7). In addition, the Examiner relies on Lomonossoff for teaching
“vectors comprising the complete viral genome of the cowpea mosaic virus
(CPMV)” (id.). The Examiner concludes that it would have been obvious
“to modify the plants generated by Sojikul et al to use the nucleic acids
taught by Lomonossoff . . . because Lomonossoff teaches that vaccines for
many important diseases (ie. Foot and mouth disease (FMDV), human
rhinovirus (HRV), polio, hepatitis A, and human immune deficiency virus
(HIV)[)] can be raised using these constructs” (id.).
Appellants argue, however, that “Lomonossoff teaches infectious
vectors comprising the complete viral genome of the CPMV for use in
infecting the virus’ native host” (App. Br. 6). Appellants also argue:
“Lomonossoff’s and Makowski’s teachings are not compatible with the
intended purpose of Sojikul because the latter teaches a cell containing a
non-infectious nucleic acid. There can be no suggestion or motivation to
combine Sojikul and Lomonossoff/Makowski because of the incompatibility
of the two references.” (Id. at 7.) In addition, Appellants argue
“Lomonossoff teaches away from an element of all the claims, namely that
the nucleic acid is non-infectious” (id.).
Issue
Has the Examiner set forth a prima facie case that it would have been
obvious to combine Sojikul with Lomonossoff to provide a plant cell
comprising a non-infectious nucleic acid?
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Findings of Fact
8. Lomonossoff “relates to the use of viruses as carriers (vectors)
for the production or presentation of foreign peptides” (Lomonossoff, col. 1,
ll. 4-6).
9. Lomonossoff discloses “assembled particles of a plant virus
containing a foreign peptide in which the corresponding foreign nucleic acid
has been inserted into the plant virus genome” (id. at col. 2, ll. 37-40).
10. In particular, Lomonossoff discloses that “the plant virus is
cowpea mosaic virus (CPMV) and the foreign insert is made immediately
preceding the proline 23 . . . residue in the βB-βC loop of the small capsid
protein” (id. at col. 2, ll. 43-46).
11. Lomonossoff also discloses that “cDNA clones of CPMV
RNAs M and B have been constructed, in which the cDNA clone of the
M RNA contains an inserted oligonucleotide sequence encoding a foreign
peptide, which makes use of the cauliflower mosaic virus (CaMV) 35S
promoter sequence . . . to generate infectious transcripts in the plant” (id. at
col. 3, ll. 30-36).
12. In addition, Lomonossoff discloses that “[i]nfection of cowpea
protoplasts . . . leads to multiplication and assembly of modified virus
particles” (id. at col. 5, ll. 27-31).
Analysis
Lomonossoff discloses CPMV cDNA clones containing an inserted
oligonucleotide sequence encoding a foreign peptide, which makes use of a
promoter sequence to generate infectious transcripts in plants (FF 11). The
Examiner finds that it would have been obvious “to modify the plants
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Application 11/069,601

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generated by Sojikul et al to use the nucleic acids taught by Lomonossoff”
(Ans. 7). However, we agree with Appellants that the evidence supports the
conclusion that this combination would result in a plant cell comprising an
infectious nucleic acid, not a non-infectious nucleic acid as recited in
claim 20.
The Examiner argues, however, that there are benefits to having a
stably transformed plant. Thus, “one of ordinary skill in the art would have
appreciated that an infectious viral expression system was not the only
design choice available for the expression of a polypeptide of interest.”
(Ans. 13-14.) However, the Examiner has not presented sufficient evidence
supporting this position. Thus, we agree with Appellants that the Examiner
has not set forth a prima facie case that it would have been obvious to
modify Sojikul to use Lomonossoff’s nucleic acid modified to provide a
non-infectious nucleic acid. We therefore reverse the obviousness rejection
of claims 27, 29, 37, and 38.

REVERSED

alw

WILSON, SONSINI, GOODRICH & ROSATI
650 PAGE MILL ROAD
PALO ALTO, CA 94304-1050