Ex Parte Wang

Board of Patent Appeals and Interferences

Jan 7, 2011

10280915 (B.P.A.I. Jan. 7, 2011)

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.
10/280,915 10/24/2002 Danher Wang D6578CIP/C 5121
7590 01/07/2011
DR. BENJAMIN ADLER
ADLER & ASSOCIATES
8011 CANDLE LANE
HOUSTON, TX 77071
EXAMINER
LI, BAO Q
ART UNIT PAPER NUMBER
1648
MAIL DATE DELIVERY MODE
01/07/2011 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 DANHER WANG,

Appellant.
_________________

Appeal 2010-004919
Application 10/280,915
Technology Center 1600
_________________

Before RICHARD TORCZON, SALLY GARDNER LANE, and SALLY C.
MEDLEY, Administrative Patent Judges.

LANE, Administrative Patent Judge.

DECISION ON APPEAL1
I. STATEMENT OF THE CASE
The appeal, under 35 U.S.C. § 134, is from a Final Rejection of claims
1, 3, 4, 8-13, 15-16, 44-46, 48-50, and 68-70.2 Appellant canceled claims 2,

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.
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5-7, 14, 17, 24-27, 47, 51-53, and 66-67, and withdrew claims 18-23, 28-43,
and 54-65. (See Response and Amendment under 37 C.F.R. § 1.111 filed in
Application 10/280,915 on March 3, 2008, pp. 2-10.3) We have jurisdiction
under 35 U.S.C. § 6(b). We affirm.
Appellant’s specification provides for recombinant viral vaccines
(Spec. 1).
The Examiner relied on the following international applications:
WO 96/112794 April 18, 1996 “Rosenberg”
WO 97/39771 October 30, 1997 “Chamberlain”
The Examiner also relied on the following research publications:
Ye et al., “Co-expression of hepatitis B virus antigens by a non-
defective adenovirus vaccine vector,” 118 Archives Virology 11-27 (1991)
(“Ye”).
He et al., “Construction of adenoviral and retroviral vectors
coexpressing the genes encoding the hepatitis B surface antigen and B7-1
protein.” 175 Gene 121-25 (1996) (“He”).

2 The Examiner’s Answer recites claims 1, 3-16, 44-46, 48-50, and 68-70 in
the rejection under 35 U.S.C. § 103 currently appealed. (Ans. 3). Claims 5-7
and 14, though, had been canceled before the Final Office Action. See
Response and Amendment under 37 C.F.R. § 1.111 filed in Application
10/280,915 on March 3, 2008, pp. 3-4.
3 The claims Appellant recites in the “Summary of Claims” and “Status of
Amendments” do not correspond to each other or to those recited in the
Claims Appendix to the Appeal Brief. We rely on the claims listing in the
Amendment of March 3, 2008, which corresponds to the Claims Appendix.
4 The Examiner listed WO 96/11278B in the “Evidence Relied Upon”
section of the Answer. (Ans. 2). The correct reference is WO 96/11279B1,
according to the Final Rejection (see Final Rejection mailed May 23, 2008,
p. 2) and the Appeal Brief (see App. Br. 5).
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Gao et al., “Biology of Adenovirus Vectors with E1 and E4 Deletions
for Liver-Directed Gene Therapy,” 70 J. Virology 8934-43 (1996) (“Gao”).
Sullivan et al., “Development of a preventive vaccine for Ebola virus
infection in primates,” 408 Nature 605-09 (2000) (“Sullivan”).
Appellant appeals the rejection of claims 1, 3-4, 8-13, 15-16, 44-46,
48-50, and 68-70 under 35 U.S.C. § 103(a) over Chamberlain or Rosenberg
along with He, Ye, Gao, and Sullivan.
Appellant discusses groups of dependent claims, including 3, 4, 9 and
10, 11-13, 44, 45 and 46, 48 and 49, 68 and 69, and 70, separately, but does
not raise any arguments about the elements of these claims that were not
raised against the rejection of claim 1. Accordingly we focus on claim 1 in
our review. See 37 C.F.R. § 41.37(c)(vii).
II. FINDINGS OF FACT
1. Appellant’s claim 1 recites:
A replication incompetent recombinant adenovirus,
comprising:
a first antigen sequence that is heterologous to the native
progenitor of the recombinant adenovirus and encodes a first
Ebola viral antigen from a first Ebola virus, expression of
which is under the transcriptional control of a first promoter;
a second antigen sequence that is heterologous to the
native progenitor of the recombinant adenovirus and encodes a
second Ebola viral antigen from a second Ebola virus,
expression of which is under the transcriptional control of a
second promoter, and
an immunostimulator sequence encoding an
immunostimulator, expression of which is under the
transcriptional control of the first or the second promoter,
wherein one or more of the first antigen sequence, the
second antigen sequence or the immunostimulator sequence
replaces substantially all of one or more of an El region, an E3
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region or an E4 region of the adenovirus, whereby expression
of the first and second antigen sequences and the
immunostimulator sequence elicit an immune response directed
against the first and second Ebola viral antigens upon infection
of a host by the replication incompetent recombinant
adenovirus.

(App. Br. 18; Claims App’x).

2. Sullivan teaches that there is a need for vaccines against the
high mortality rate of Ebola virus infection. (Sullivan abstract and pp. 607-
08).
3. Sullivan teaches that plasmid DNA vaccines directed against
combinations of different Ebola virus antigens (including nucleoprotein and
glycoproteins of different Ebola subtypes) induce immune responses.
(Sullivan Table 1).
4. Sullivan teaches that a recombinant adenoviral vector vaccine
directing high levels of expression of the Ebola glycoprotein GP(Z) boosts
the immunity provided by DNA Ebola GP vaccines. (Sullivan, pp. 606-07).
5. Sullivan does not teach an Ebola vaccine from an adenoviral
vector expressing two different Ebola antigens and an immunostimulator.
6. Chamberlain teaches that vaccines may be made from
adenoviruses (Chamberlain, p. 9) and may include one or more antigens (id.,
p. 8) and genes encoding cytokines, such as interleukin-2 and interferon-γ
(id., p. 9), which are immunostimulators within the scope of Appellant’s
claim 1 (see dependent claims 48 and 49, App. Br. 20, Claims App’x).
7. Like Chamberlain, Rosenberg teaches vaccines that are made
from recombinant viruses and express one or more antigens of a disease
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causing agent, along with an immunostimulatory molecule. (Rosenberg, pp.
8-9).
8. Ye teaches adenoviruses that are replication incompetent and
have two hepatitis B virus antigens inserted into their E4 and E3 deleted
regions of their genomes. (Ye, Fig. 1).
9. Gao teaches that adenovirus vectors with deletions in E1 and
E4 have safety and efficacy advantages. (Gao, abstract and p. 8942).
10. He teaches an adenoviral vector that expresses two proteins: (1)
a Hepatitis B antigen, under the control of CMV promoter and (2) a protein
that costimulates T cell activation, under the control of an internal ribosomal
entry site (“IRES”). He teaches that the dicistronic (or bicistronic)5
expression cassette can be inserted into either the E1 or E3 region of a
replication incompetent adenovirus. (He, abstract, Fig. 2, and p. 124).
11. Appellant’s claim 13 recites:
The replication incompetent recombinant adenovirus of claim
12, wherein the first and the second antigen sequences are
expressed bicistronically via an internal ribosomal entry site or
via a splicing donor-acceptor mechanism.

(App. Br. 19, Claims App’x). Appellant’s claim 12 recites:
The replication incompetent recombinant adenovirus of claim
11, wherein the first and the second antigen sequences are
expressed bicistronically by the same promoter.

(App. Br. 19, Claims App’x). Appellant’s claim 11 recites:
The replication incompetent recombinant adenovirus of claim 1,
wherein the first and second promoters are the same promoter
positioned in the same region of the recombinant adenovirus.

5 Having or involving two cistrons, loci responsible for generating a protein.
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(App. Br. 19, Claims App’x).
III. ISSUE
Would those of skill in the art have had reason to make an adenovirus
expressing Ebola antigens and an immunostimulator with the claimed
features and have had a reasonable expectation of success from the prior art
cited?
IV. ANALYSIS
Sullivan teaches that there is a need for vaccines against Ebola virus,
which has a high mortality rate. (FF 2; Sullivan, abstract and pp. 607-08).
Sullivan also teaches that multicomponent vaccines expressing different
Ebola proteins, including vaccines based on adenoviral vectors, can be
effective in providing sterilizing immunity. (FFs 3 and 4; Sullivan, Table 1
and pp. 606-07). But, Sullivan fails to teach a recombinant adenovirus that
expresses two different Ebola antigens and an immunostimulator. (FF 5).
Given the design needs to produce vaccines that protect against the lethal
effects of Ebola virus, one of skill in the art would have had “good reason to
pursue 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.” KSR Int’l, Co. v. Teleflex, Inc., 550 U.S.
398, 421 (2007).
Chamberlain and Rosenberg teach that vaccines may be made from
adenoviruses and may include one or more antigens and genes encoding
cytokines, such as interleukins and interferons. (FFs 6 and 7; Chamberlain,
pp. 8-9; and Rosenberg, pp. 8-9). Ye teaches adenoviral vectors that are
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replication incompetent and have two hepatitis B virus antigens inserted into
the E3 and E4 regions of the viral genomes. (FF 8; Ye, Fig. 1.). Similarly,
Gao teaches that adenovirus vectors with deletions in E1 and E4 have safety
and efficacy advantages. (FF 9; Gao, abstract and p. 8942). He also teaches
expression of foreign genes in a replication incompetent E1 or E3 deleted
adenovirus, but by using one foreign promoter and an IRES for bicistronic
gene expression. (FF 10; He, abstract, Fig. 2, and p. 124). Those of skill in
the art would have considered it obvious to have combined these features
from the prior art in an adenovirus expressing Ebola antigens and
immunostimulators since adenoviral vectors had been shown to provide high
levels of expression and enhanced immune responses and can be modified to
express multiple proteins safely and effectively.6
Appellant argues that those of skill in the art would not have had a
reasonable expectation of success in expressing multiple antigens in an
adenovirus from Sullivan because the multivalent vaccine taught by Sullivan
is a plasmid DNA vaccine. (App. Br. 16.) “Non-obviousness cannot be
established by attacking references individually where the rejection is based
upon the teachings of a combination of references.” In re Merck & Co., Inc.,
800 F.2d 1091, 1097 (Fed. Cir. 1986). Chamberlain, Rosenberg, Gao, Ye,
and He each teach expression of foreign proteins from adenoviral vectors.

6 Appellant claims that the antigen and immunostimulator sequences replace
one or more of the E1, E3, or E4 regions of the adenovirus, but without
specific placement. Ye, Gao, and He each teach replacing the E1, E3, and/or
E4 regions of an adenovirus with foreign expression sequences. (FFs 8-10).
Thus, we are not persuaded that the prior art fails to teach the “exact
placement” of expression sequences claimed, as Appellant argues. (See
App. Br. 16-17).
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Appellant has not provided evidence that those of skill in the art would have
expected the Ebola antigen and immunostimulatory proteins of the claimed
adenovirus to require different expression conditions from the sequences
expressed in the adenoviral vectors of the cited references.
Appellant argues that those of skill in the art would have had neither
motivation nor a reasonable expectation of success in constructing the
adenoviral vectors of Chamberlain and Rosenberg with multiple Ebola
antigens because these references teach methods of “prime-boost
vaccination,” which Appellant asserts requires two different recombinant
vectors. (App. Br. 6 and 7-8). “Prime-boost vaccination” is a method of
using a vaccine (see Chamberlain, p. 4), whereas Appellant claims an
adenovirus, as taught in Chamberlain and Rosenberg. Appellant does not
provide sufficient evidence to show that those of skill in the art would not
have considered the adenovirus vectors of Chamberlain and Rosenberg in
constructing a vaccine against Ebola, regardless of how these references
teach using those vectors.
Appellant argues that those in the art would not have been motivated
to perform the E1 and E4 deletions taught in Gao with the “prime-boost
vaccines” of Chamberlain and Rosenberg to arrive at the claimed adenovirus
because Gao teaches only a method of “liver-directed gene delivery.” (App.
Br. 8). Gao, though, teaches that insertion of heterologous sequences into
deletions of a replication incompetent adenovirus provides for a safer vector
that exhibits prolonged expression of the heterologous sequences. (FF 9;
Gao, p. 8942). It is likely that safety and increased efficacy of Ebola
antigens and immunostimulants would be as important to designers of
vaccines against Ebola as it is to those designing gene delivery (gene
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therapy) vectors. Appellant has not directed us to evidence to show that
these characteristics would not have been important in vaccine design.
Appellant also argues that He teaches away from the claimed
adenovirus because it teaches that multiple recombinant genes with
individual promoters and poly(A) signals for each gene, as in the claimed
adenovirus, may be too big for the packaging capacity of the adenoviral
vector. (App. Br. 8). Appellant does not point to, and we do not find, a
teaching in He of a specific size above which adenoviral vectors are
inoperable. Thus, we are not persuaded that He teaches away from the size
of the claimed adenovirus inserts. Furthermore, He proposes the same
solution of using a bicistronic expression cassette that relies on a foreign
promoter and an IRES, as recited in Appellant’s dependent claims.
(Compare FFs 10 and 11).
V. CONCLUSION
Appellant has not persuaded us that the Examiner was incorrect in
finding that those of skill in the art would have had reason for, and a
reasonable expectation of success in, making an adenovirus expressing
Ebola antigens and an immunostimulator with the claimed features from the
prior art cited.
VI. ORDER
Upon consideration of the record and for the reasons given, the
rejection of claims 1, 3, 4, 8-13, 15-16, 44-46, 48-50, and 68-70 under 35
U.S.C. § 103(a) over Chamberlain or Rosenberg along with He, Ye, Gao,
and Sullivan is AFFIRMED.
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AFFIRMED

cc:
Dr. Benjamin Adler
Adler & Assoc.
8011 Candle Lane
Houston, TX 77071

KMF