Ex Parte Sutter et al

Board of Patent Appeals and Interferences

Nov 8, 2010

10488301 (B.P.A.I. Nov. 8, 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.
10/488,301 08/30/2004 Gerd Sutter 1406/185 3902
25297 7590 11/09/2010
JENKINS, WILSON, TAYLOR & HUNT, P. A.
3100 Tower Blvd.
Suite 1200
DURHAM, NC 27707
EXAMINER
LUCAS, ZACHARIAH
ART UNIT PAPER NUMBER
1648
MAIL DATE DELIVERY MODE
11/09/2010 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 GERD SUTTER, VOLKER ERFLE, YUAN WANG,
GUANGDI LI, LI-XIN ZHU and CAROLINE STAIB
__________

Appeal 2010-005288
Application 10/488,301
Technology Center 1600
__________

Before ERIC GRIMES, LORA M. GREEN, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a
recombinant vaccinia virus. The Examiner has rejected the claims as

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 2010-005288
Application 10/488,301

2
nonenabled and obvious. We have jurisdiction under 35 U.S.C. § 6(b). We
reverse the nonenablement rejection but affirm the obviousness rejections.
STATEMENT OF THE CASE
Claims 1, 3-5, 7-15, 21, 22, 25, and 26 are on appeal. Claims 1 and
12 are representative and read as follows:
1. A recombinant modified vaccinia virus Ankara (MVA), wherein
the recombinant MVA comprises DNA sequences encoding structural
antigens selected from among an HCV envelope glycoprotein E1
polypeptide, and an HCV envelope glycoprotein E2 polypeptide, epitopes
thereof, and combinations thereof.

12. A pharmaceutical composition comprising at least one
recombinant MVA of claim 1 and pharmaceutically acceptable carriers or
adjuvants.

The claims stand rejected as follows:2
• Claims 12 and 13 under 35 U.S.C. § 112, first paragraph, for lack of
enablement (Answer 4-5);
• Claims 1, 3-5, 7-10, 12-15, 21, 22, and 25 under 35 U.S.C. § 103(a)
as obvious based on Sutter,3 Selby,4 and Staib5 (Answer 7);

2 In addition to the rejections summarized above, the Examiner has rejected
the claims for obviousness-type double patenting and provisional
obviousness-type double patenting (Answer 12-18). Appellants have agreed
to file terminal disclaimers, when appropriate, to obviate each of the double
patenting rejections (Appeal Br. 20-23). Since Appellants are not appealing
the double patenting rejections, we will not address them.
3 Sutter et al., Nonreplicating vaccinia vector efficiently expresses
recombinant genes, 89 PROC. NATL. ACAD. SCI. USA 10847-10851 (1992).
4 Selby et al., U.S. Patent 6,121,020, issued Sept. 19, 2000.
5 Staib et al., Transient host range selection for genetic engineering of
modified vaccinia virus Ankara, 28 BIOTECHNIQUES 1137-1148 (2000).
Appeal 2010-005288
Application 10/488,301

3
• Claims 1, 3-5, 7-10, 12-15, 22, 25, and 26 under 35 U.S.C. § 103(a)
as obvious based on Sutter, Jolly,6 and Staib (Answer 10); and
• Claim 11 under 35 U.S.C. § 103(a) as obvious based on Sutter,
Selby, Staib, and Op De Beeck7 (Answer 11).
I.
The Examiner has rejected claims 12 and 13 as nonenabled, on the
basis that the Specification “does not reasonably provide enablement for
vaccines or pharmaceutical compositions comprising” a recombinant MVA
virus encoding an HCV antigen (Answer 4-5).8 The Examiner reasons that
“the claim language reading on vaccines indicates that these claims are
requiring a protective effect, and the term ‘pharmaceutical’ in claim 12
indicates that the claim is requiring a therapeutic effect” (id. at 5).
The Examiner finds that “the application does not demonstrate that the
administration of such compositions would result in either a protective effect
or . . . a therapeutic effect” and “the art teaches that, as yet, no effective
HCV immune based therapy has been shown effective” (id. at 6). The
Examiner concludes that “the indicated claims are rejected for exceeding the
scope for which the application has enabled those in the art” (id.).
Appellants argue, among other things, that the Specification discloses
uses for the claimed composition other than producing a protective or

6 Jolly et al., U.S. Patent 6,297,048, issued Oct. 2, 2001.
7 Op De Beeck et al., The transmembrane domains of hepatitis C virus
envelope glycoproteins E1 and E2 play a major role in heterodimerization,
275 JOURNAL OF BIOL. CHEM. 31428-31437 (2000).
8 Claim 13 is directed to “[t]he pharmaceutical composition of claim 12, in
the form of a vaccine.”
Appeal 2010-005288
Application 10/488,301

4
therapeutic effect in humans and therefore adequately teaches how to use the
claimed compositions (Appeal Br. 6-7).
We agree with Appellants that the Examiner has not shown that undue
experimentation would be required to make the claimed compositions.
“[D]uring examination proceedings, claims are given their broadest
reasonable interpretation consistent with the specification.” In re Hyatt, 211
F.3d 1367, 1372 (Fed. Cir. 2000). The broadest reasonable interpretation of
claims 12 and 13 is that they encompass any composition comprising the
recited components that is suitable for use as a pharmaceutical or as a
vaccine, respectively. The Examiner has not shown that making the claimed
compositions or using them in, for example, research involving vaccination
of mice (Spec. 22-23) would require undue experimentation. We therefore
reverse the rejection of claims 12 and 13 under 35 U.S.C. § 112, first
paragraph.
II.
Issue
The Examiner has rejected claims 1, 3-5, 7-10, 12-15, 21, 22, and 25
as obvious based on Sutter, Selby, and Staib (Answer 7) and claim 11 as
obvious based on Sutter, Selby, Staib, and Op De Beeck (Answer 11). The
Examiner has also rejected claims 1, 3-5, 7-10, 12-15, 22, 25, and 26 as
obvious based on Sutter, Jolly, and Staib (Answer 10). Since Appellants
rely on the same arguments with respect to each of the rejections, we will
address them together.
The Examiner finds that Sutter and Staib both disclose MVA vectors
for use in vaccines (Answer 7-8). The Examiner also finds that Selby and
Appeal 2010-005288
Application 10/488,301

5
Jolly teach immunogenic compositions comprising vectors containing
nucleic acids encoding the HCV E1 or E2 protein (id. at 8, 10). The
Examiner concludes that it would have been obvious to combine the MVA
vaccine vector taught by Sutter and Staib with the HCV E1- or E2-encoding
nucleic acid taught by Selby or Jolly, because Sutter and Staib teach that
MVA has advantages over other vaccinia vectors in vaccine compositions
(id. at 9, 11). The Examiner also concludes that Op De Beeck would have
made obvious the additional limitation of dependent claim 11 (id. at 11-12).
Appellants contend that the Examiner’s combination of references
would not have been obvious because “Sutter and Staib describe in at best a
very general way the potential feasibility of MVA for expressing
recombinant genes” and “Selby’s examples only provide immuno-
precipitation data” (Appeal Br. 9). Appellants also contend that “for both the
delivery system (MVA) as well as the expressed epitope (E1 or E2), many
alternatives existed, which is evidence that the specific combination is
nonobvious” (id. at 10).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s conclusion that a person of ordinary skill in
the art would have considered it obvious to combine an MVA vector with a
nucleic acid encoding the E1 or E2 glycoprotein from HCV?
Findings of Fact
1. Sutter discloses that “[m]odified vaccinia Ankara (MVA) [is] a
highly attenuated vaccinia virus strain that has been safely tested in humans”
(Sutter, abstract)
Appeal 2010-005288
Application 10/488,301

6
2. Sutter discloses that “there is clinical experience using MVA for
primary vaccination of over 120,000 humans against smallpox. During
extensive field studies, including high risk patients, no side effects were
associated with the use of the MVA vaccine.” (Id. at 10847, left col.)
3. Sutter discloses that “for use as a gene expression vector, no other
characterized naturally derived or genetically engineered strain of poxvirus
is known to have a similar combination of desirable properties and to have
been so extensively tested in humans as MVA” (id. at 10851, left col.).
4. Staib discloses that “[r]ecombinant MVA has been successfully
evaluated for vaccination against a variety of infectious diseases or cancer in
animal models, and the first MVA vectors have now entered clinical
investigation” (Staib 1137, right col.).
5. Selby discloses that the “viral genomic sequence of HCV is
known” and “there are three putative structural proteins, consisting of the N-
terminal nucleocapsid protein (termed ‘core’) and two envelope
glycoproteins, ‘E1’ (also known as E) and ‘E2’ (also known as E2/NS1)”
(Selby, col. 1, ll. 23, 38-41).
6. Selby discloses that the “HCV E1 and E2 glycoproteins are of
considerable interest because they have been shown to be protective in
primate studies” (id. at col. 1, ll. 53-55).
7. Selby discloses truncated E1 and E2 glycoproteins that lack their
membrane-spanning domain, and are secreted rather than retained in the
endoplasmic reticulum membrane (id. at col. 2, ll. 21-52).
8. Selby discloses that “vaccines containing polynucletides [sic]
encoding for the truncated, secreted proteins can be used for nucleic acid
Appeal 2010-005288
Application 10/488,301

7
immunization. . . . Generally, the polynucleotide is administered as a vector”
(id. at col. 13, ll. 43-62).
9. Selby discloses that the “E1 and E2 polypeptides and
polynucleotides encoding the polypeptides can be used in vaccine
compositions, individually or in combination” (id. at col. 11, ll. 59-62).
10. Jolly discloses “methods of treating hepatitis C infections . . .
comprising the step of administering to a warm-blooded animal a vector
construct which directs the expression of at least one immunogenic portion
of a hepatitis C antigen. . . . [T]he vector construct may express the core
antigen C, antigen E1, [or] antigen E2/NS2.” (Jolly, col. 3, ll. 50-58.)
11. Jolly discloses that “[v]ector constructs of the present invention
may be delivered by a variety of methods, including for example by . . . a
recombinant virus selected from the group consisting of poliovirus,
rhinovirus, pox virus (e.g., the canary pox virus or the vaccinia virus)” etc.
(id. at col. 4, ll. 29-33).
Analysis
Claim 1 is directed to a recombinant MVA vector comprising DNA
encoding an HCV E1 or E2 glycoprotein.
Sutter discloses that MVA has been used to vaccinate human patients
against smallpox (FF 2) and that no other strain of poxvirus has MVA’s
combination of desirable properties and extensive human testing (FF 3).
Staib discloses that recombinant MVA vectors had been used for vaccinating
animal models against a variety of infectious diseases and were in clinical
investigation at the time Appellants made the claimed invention (FF 4).
Appeal 2010-005288
Application 10/488,301

8
Selby discloses vaccines containing vectors comprising
polynucleotides encoding the E1 or E2 glycoprotein of HCV or truncated
versions of them (FF 8, 9). Jolly discloses treating hepatitis C infection by
administering, for example by a recombinant vaccinia virus, vector
constructs that express an immunogenic HCV antigen such as the E1 or E2
antigen (FFs 10, 11). We agree with the Examiner’s conclusion that it
would have been obvious to use the MVA vector taught by Sutter and Staib
as the vector in the compositions disclosed by Selby and Jolly, because
Sutter and Staib disclose that MVA had desirable properties for use in
vaccines and was well-known for use in humans.
Appellants argue Sutter and Staib do not suggest using MVA for
expression of HCV antigens such as the E1 or E2 glycoproteins, and that
Selby’s examples only show immunoprecipitation, which is “remote from
therapeutic data and provides no motivation to combine E2 and E1 with an
MVA” (Appeal Br. 9). Appellants also argue that Jolly does not mention
MVA and “[t]hus, Jolly provides no motivation to combine E2 and E1 with
an MVA” (id. at 14).
These arguments are unpersuasive because they do not take into
account the full disclosure of the cited prior art references. Whether a
claimed invention would have been obvious is based on the disclosure of the
prior art as a whole. See In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991)
(The test of obviousness is “whether the teachings of the prior art, taken as a
whole, would have made obvious the claimed invention.”); In re Young, 927
F.2d 588, 591 (Fed. Cir. 1991) (“Patents are part of the literature of the art
and are relevant for all they contain.”). Here, we agree with the Examiner
Appeal 2010-005288
Application 10/488,301

9
that the product of claim 1 would have been obvious based on the full
disclosures of the cited references.
Appellants also argue that “for both the delivery system (MVA) as
well as the expressed epitope (E1 or E2), many alternatives existed, which is
evidence that the specific combination is nonobvious” (Appeal Br. 10, 14).
This argument is also unpersuasive. The claimed combination is no
less obvious simply because the cited references would also have made it
obvious to combine nucleic acids encoding immunogenic polypeptides other
than E1 or E2 with an MVA vector, or to combine non-MVA vectors with
nucleic acids encoding E1 or E2. See Merck & Co. v. Biocraft Labs. Inc.,
874 F.2d 804, 807 (Fed. Cir. 1989) (“That the ‘813 patent discloses a
multitude of effective combinations does not render any particular
formulation less obvious. This is especially true because the claimed
composition is used for the identical purpose taught by the prior art.”); KSR
Int’l Co. v. Teleflex Inc., 550 U.S. 398, 419 (2007) (“What matters is the
objective reach of the claim. If the claim extends to what is obvious, it is
invalid under § 103.”).
With regard to claim 12, Appellants argue that the Examiner’s
rejection for nonenablement is based on the unpredictability of the effect of
the claimed pharmaceutical composition, and “[i]f the subject matter is
unpredictable, the fact that the immune response can be generated at all is
believed to represent an unexpected result” (Appeal Br. 12, 15).
This argument is unpersuasive because, as discussed above in the
context of enablement, claim 12 is properly interpreted as directed to a
composition that is suitable for pharmaceutical administration, not one that
Appeal 2010-005288
Application 10/488,301

10
necessarily provides a therapeutic effect when administered. Appellants
have pointed to no evidence that combining a pharmaceutical carrier with an
MVA vector encoding an HCV E1 or E2 glycoprotein would have involved
any unpredictability.
With regard to claim 26, Appellants assert that Large9 teaches that
HCV core proteins are immunosuppressive and argue that it was unexpected
that an MVA construct encoding an HCV core protein induced an immune
response (Appeal Br. 17-18). In response, the Examiner points to Liu,10 and
finds that its teachings “suggest that the immunosuppressive effects were
limited to core protein of HCV 1a genotypes, and specifically indicate that
they were not present with respect to HCV 1b genotypes” (Answer 30).
Appellants “submit that one of ordinary skill in the art would not take
alleged suggestions from Liu that it is possible that not all core proteins are
immunosuppressive and/or rather that maybe it is the vector or some other
factor causing the immunosuppression” (Appeal Br. 18).
We agree with the Examiner that Appellants have not shown that the
Examiner’s rejection of claim 26 is in error. Jolly discloses vector
constructs comprising an HCV antigen, including the core protein (FF 10)
and, as discussed above, Sutter and Staib would have made it obvious to use
an MVA vector in Jolly’s vector construct.

9 Large et al., Suppression of Host Immune Response by the Core Protein of
Hepatitis C Virus: Possible Implications for Hepatitis C Virus Persistence,
162 JOURNAL OF IMMUNOLOGY, 931-938 (1999).
10 Liu et al., Hepatitis C Virus Genotype 1b Core Protein Does Not Exert
Immunomodulatory Effects of Virus-Induced Cellular Immunity, 76 JOURNAL
OF VIROLOGY NO. 3, 990-997 (2002)
Appeal 2010-005288
Application 10/488,301

11
It is true that Large discloses that, in mice infected with vaccinia/HCV
recombinant viruses, “the HCV core protein was sufficient for
immunosuppression, prolonged viremia, and increased mortality. These
results suggest that the HCV core protein plays an important role in the
establishment and maintenance of HCV infection by suppressing host
immune responses.” (Large, abstract.) However, as the Examiner pointed
out, Liu discloses that “the HCV core protein, of genotype 1b, has no
modulatory effects on induction of virus-specific immune responses and
may therefore be a suitable component of an HCV vaccine” (Liu 990, right
col.).
Both Large and Liu were published before the effective filing date of
the claims on appeal. Therefore, a person of ordinary skill in the art would
have been aware that core-induced immunosuppression could be avoided by
using an HCV 1b genotype when carrying out Jolly’s suggestion to make a
vector encoding an HCV core antigen. Appellants have not provided an
adequate basis for their assertion (Appeal Br. 18) that a skilled worker would
not have credited Liu’s statement that the HCV 1b core protein does not
cause immunosuppression. Appellants’ argument that Large teaches away
from the claimed product (Appeal Br. 18) and that the lack of
immunosuppression was unexpected (id. at 17) are therefore unpersuasive.
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that a
person of ordinary skill in the art would have considered it obvious to
combine an MVA vector with a nucleic acid encoding the E1 or E2
glycoprotein from HCV.
Appeal 2010-005288
Application 10/488,301

12
SUMMARY
We reverse the rejection of claims 12 and 13 for lack of enablement.
We affirm the rejection of claims 1, 3-5, 7-10, 12-15, 21, 22, and 25 as
obvious based on Sutter, Selby, and Staib; the rejection of claims 1, 3-5,
7-10, 12-15, 22, 25, and 26 as obvious based on Sutter, Jolly, and Staib; and
the rejection of claim 11 as obvious based on Sutter, Selby, Staib, and Op De
Beeck.
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

lp

JENKINS, WILSON, TAYLOR & HUNT, P. A.
3100 TOWER BLVD.
SUITE 1200
DURHAM NC 27707