Ex Parte Hone et al

Patent Trial and Appeal Board

Aug 11, 2016

09950335 (P.T.A.B. Aug. 11, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
09/950,335 09/10/2001
24239 7590 08/15/2016
MOORE & VAN ALLEN PLLC
P.O. BOX 13706
3015 Carrington Mill Boulevard, Suite 400
Research Triangle Park, NC 27709
FIRST NAMED INVENTOR
David Hone
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.
035413-41.00-010 1941
EXAMINER
HIRIY ANNA, KELAGINAMANE T
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
08/15/2016 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):
iplaw@mvalaw.com
usptomail@mvalaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DAVID HONE, GEORGE LEWIS,
TIMOTHY FOUTS, KEN BAGLEY, MICHAEL BOYSON,
CHRISTINE OBRIECHT, M.T. SHATA, and SIMON AGWALE
Appeal2014-007081
Application 09/950,335
Technology Center 1600
Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a
composition comprising a DNA plasmid construct. The Examiner rejected
the claims as anticipated and as obvious. We have jurisdiction under
35 U.S.C. § 6(b). We affirm.
1 Appellants identify the Real Party in Interest as the University of
Maryland, Baltimore (see App. Br. 3).
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Application 09/950,335
Statement of the Case
Background
"Although conventional DNA vaccines induce immune responses
against a diverse array of antigens, the magnitudes of the immune responses
have not always been sufficient to engender protective immunity" (Spec.
4:8-10). "The immunogenicity of conventional DNA vaccines is modified
by mixing the conventional DNA vaccine with an adjuvant or a second
plasmid encoding an immunoregulatory protein" (Spec. 8:25-27).
"However, heretofore, there has been no demonstration that DNA
vaccines that co-express an antigen in combination with adjuvants,
immunoregulatory agents, antisense RNAs, and catalytic RNAs are more
effective than a mixture of a conventional DNA vaccine and a plasmid that
encodes an immunoregulatory protein" (Spec. 9: 1--4).
The Claims
Claims 1, 3-11, 13, 14, 26-29, 49, and 51-55 are on appeal. Claim 1
is representative and reads as follows:
1. A composition comprising a DNA plasmid construct
wherein the DNA plasmid construct comprises:
an inserted exogenous antigen-encoding region encoding
a pathogenic antigen peptide component; and
a biologically active component-encoding region
encoding at least one immunoregulatory peptide, wherein the
immunoregulatory peptide consists of the A subunit of cholera
toxin or fragment thereof, wherein the A subunit and the
fragment thereof retain ADP-ribosylating activity of the cholera
toxin.
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The issues
A. The Examiner rejected claims 1, 3, 4, 8, 26, and 49 under 35 U.S.C.
§ 102(b) as anticipated by Choi2 (Ans. 5---6).
B. The Examiner rejected claims 1, 3-11, 13, 14, 26-29, 49, and 51-55
under 35 U.S.C. § 103(a) as obvious over Burton, 3 Choi, Agren (1997), 4
Agren (1999), 5 Sanchez, 6 and Barouch7 (Ans. 6-9).
A. 35 US.C. § 102(b) over Choi
The Examiner finds that:
Choi teaches a gene/nucleic acid construct or DNA plasmid
construct of a rotavirus fusion protein wherein, said gene
encodes a rota virus (pathogenic) subunit protein or a an
immunogenic fragment thereof and a fusion protein partner and
an adjuvant (immune-modulator protein) such as Al subunit of
cholera toxin (CTX-Al). The cholera toxin construct (CTAI-
2 Choi et al., US 6,589,529B1, issued July 8, 2003 ("Choi").
3 Burton et al., US 5,416,017, issued May 16, 1995 ("Burton").
4 Agren et al., Genetically Engineered Nontoxic Vaccine Adjuvant
That Combines B Cell Targeting with lmmunomodulation by
Cholera Toxin Al Subunit, 158 J. IMMUNOLOGY 3936-3946 (1997)
("Agren (1997)").
5 Agren et al., Adjuvanticity of the Cholera Toxin Al -Based Gene
Fusion Protein, CTAJ-DD, Is Critically Dependent on the ADP-
Ribosyltransferase and Jg-Binding Activity, 162 J. Immunology
2432-2440 (1999) ("Agren (1999)").
6 Sanchez et al., Engineering of cholera toxin A-subunit for
carriage of epitopes at its amino end, 401 FEBS Letters 95-97
( 1997) ("Sanchez").
7 Barouch et al., Augmentation and Suppression of Immune
Responses to an HIV-I DNA Vaccine by Plasmid Cytokine/Ig
Administration, 161 J. Immunology 187 5-1882 (1998)
("Barouch").
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DD) is a nucleic acid construct that has nucleic acid sequences
coding for CTX-Al genetically associated with a segment of
Staphylococcal aureus (a pathogenic bacteria) protein A, an
antigenic protein, fragment (DD) fused to cholera toxin
(CT Al).
(Ans. 5).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Choi anticipates claim 1?
Findings of Fact
1. The Specification teaches that "[ t ]wo preferred configurations
are provided as exemplary of the CED vaccines of the present invention. The
first preferred configuration expresses a dicistronic mRNA .... In the
second configuration, the CED vaccine expresses at least two products from
distinct promoters" (Spec. 12 :25 to 13: 6).
2. Choi teaches that "a composition comprising a rotavirus protein
or an immunogenic portion thereof is genetically associated with a fusion
protein partner, and an adjuvant such as the Al subunit, the B subunit of
cholera toxin or E. coli heat-labile toxin present in a pharmaceutically
acceptable carrier" (Choi 6: 15-20).
3. Choi specifically teaches that the "rota virus fusion proteins
contemplated by the present invention are composed of a suitable fusion
protein partner in genetic association with a rotavirus protein or
immunogenic fragment thereof' (Choi 6:62---65).
4. Choi teaches that the "term in genetic association refers to a
contiguous sequence of amino acids produced from a mRNA produced from
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a gene containing codons for the amino acids of the rota virus protein and the
fusion protein partner" (Choi 6:65 to 7:2).
5. Choi teaches that:
A representative list of suitable fusion protein partners includes
maltose binding protein, poly-histidine segments capable of
binding metal ions, inteine, antigens to which antibodies bind,
S-Tag, glutathione-S-transferase, thioredoxin, ~-galactosidase,
nonapeptide epitope tag from influenza hemagglutinin, a 11-
amino acid epitope tag from vesicular stomatitis virus, a 12-
amino acid epitope from the heavy chain of human Protein C,
green fluorescent protein, cholera bolo toxin or its B subunit,
E. coli heat-labile holotoxin or its B subunit, CTAl-DD,
streptavidin and dihydrofolate reductase.
(Choi 7: 14--25; emphasis added).
6. Figure 1 of Choi is reproduced below:
l'ig111-., 1. Plasmid map of p.MAL-c2 used fm· oxpressfon of chim<>ri< MB!' protein•
gen ,)f\1116. v:J4- 1.)t intlli::;ii.l!-d VJ•/, .md
hlClN Xa c-:eavaw. site
"Recombinant plasmids ... were constructed using pMAL-c2 ... by
insertion of cDNAs encoding full length VP4 or VP6, or a truncated form of
VP7 (TrVP7) of rotavirus strain EDIM (FIG. 1)" (Choi 9:49--54).
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7. Agren ( 1997) teaches that "we consistently found that CT A 1-
D D exhibited at most 25% of the ADP-ribosylating activity of the intact
holotoxin .... Nevertheless, these results clearly demonstrated that despite
the incorporation of CT A 1 into a new structural environment it still had
retained significant enzymatic activity in the fusion protein" (Agren (1997)
3939, col. 2).
8. Figure 1 of Agren (1997) is reproduced below:
pCTAt-DD
J!:Wbp
foiclHl
"11IGU1lli 1. Schematic drawing of the pCTAI-uu plasmid. The pCTAl-
DD plasmid contains the CTAl gene (amino acids 1-194) cloned at Hindlll-
BamHI and two D fragments from the SpA gene under the control of the trp
promotor" (Agren (1997) 3939, col. 1).
9. Agren (1997) teaches:
Our goal was to construct a compound that would functionally
mimic the adjuvant effect of CT without being toxic to the host.
The CTAl-DD fusion protein fulfilled these requirements; its
augmenting effect was comparable in both magnitude and
quality to that of CT on systemic as well as mucosal immune
responses and, in contrast to CT, it did not cause intestinal fluid
secretion, GM1 receptor-dependent cAMP increases, or footpad
edema.
(Agren (1997) 3942, col. 2).
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Principles of Law
A "reference can anticipate a claim even if it 'd[ oes] not expressly
spell out' all the limitations arranged or combined as in the claim, if a person
of skill in the art, reading the reference, would 'at once envisage' the
claimed arrangement or combination." Kennametal, Inc. v. Ingersoll Cutting
Tool Co., 780 F.3d 1376, 1381 (Fed. Cir. 2015) (quoting In re Petering, 49
CCPA 993, 301F.2d676, 681 (1962)). Moreover, "a reference may still
anticipate if that reference teaches that the disclosed components or
functionalities may be combined and one of skill in the art would be able to
implement the combination." Blue Calypso, LLC v. Groupon, Inc., 815 F.3d
1331, 1344 (Fed. Cir. 2016).
Analysis
We begin with claim interpretation because before a claim is properly
interpreted, its scope cannot be compared to the prior art. In this case, claim
1 recites a "DNA plasmid construct" that comprises two components, "an
inserted exogenous antigen-encoding region encoding a pathogenic antigen
peptide component" and a region encoding "the A subunit of cholera toxin
or fragment thereof' and further requires that the cholera toxin region retain
ADP-ribosylating activity.
Claim 1 does not, however, provide any specific limitations on how
the plasmid is constructed. That is, while the Specification discloses
preferred configurations including a dicistronic mRNA that expresses both
components on a single mRNA with a single promoter or the use of two
distinct mRNAs expressed from separate promoters (FF 1 ), claim 1 does not
exclude a DNA plasmid construct in which the two components are
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expressed on a single mRNA from one promoter in the form of a fusion
protein.
Thus, claim 1 is reasonably interpreted as encompassing a DNA
plasmid construct that expresses a fusion protein comprising both a
"pathogenic antigen peptide component" and an "A subunit of cholera
toxin" component so long as the cholera toxin component retains ADP-
ribosylating activity.
Applying this interpretation to Choi, Choi teaches fusion proteins that
comprise rotavirus sequences as the "pathogenic antigen peptide
component" (FF 2--4) and provides a list of fusion partners including CTAl-
DD which comprises the A subunit of cholera toxin (FF 5). Agren
evidences that CTAl-DD retains ADP-ribosylating activity (FF 7). Choi
lists sixteen suitable fusion partners, with CTAl-DD as a specific
representative on that list, such that a person of ordinary skill in this art
would have "at once envisaged" CTAl-DD as a fusion protein partner with
the rotavirus protein of Choi (Kennametal, 780 F.3d at 1381; (FF 5)). Choi
exemplifies a fusion protein between maltose binding protein and rotavirus
proteins (FF 6).
Appellants contend that the "fusion protein of Choi comprises a ( 1)
rotavirus subunit protein and (2) protein partner in genetic association with
the recombinant rotavirus subunit. The adjuvant is added to a
pharmaceutical carrier along with the fusion proteins. The Al subunit of
cholera toxin can be used as an adjuvant" (App. Br. 11 ).
We find this argument unpersuasive because Choi teaches two
different embodiments, a first embodiment identified by Appellants in
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column 6 where cholera toxin is added as an adjuvant and a second
embodiment relied upon by the Examiner in column 7 where CTAl-DD or
cholera holo toxin are identified as "suitable fusion protein partners" with
rota virus proteins (FF 5). Therefore, Appellants' argument fails to address
the embodiment actually relied upon by the Examiner.
Appellants contend that
Importantly, Agren teaches that CTAl is toxic (as shown on
page 3936, right column first paragraph of Agren), and thus, the
fusion of the CT Al region to the staphylococcal protein A
(SpA) protein is essential (see abstract) to overcome the toxicity
while providing the binding ability. Clearly, using the CTAl-
DD fusion protein of Agren it not the same as using the isolated
CT Al of the present invention.
(App. Br. 12).
We find this argument unpersuasive because the DNA construct of
claim 1 "comprises" the two components. Thus, the DNA construct of claim
1 is open to the inclusion of other components including the Staphylococcal
protein A of Agren (FF 8). See In re Crish, 393 F.3d 1253, 1257 (Fed. Cir.
2004) ("The reasonable interpretation of the claims containing both of the
terms 'comprising' and 'consists' is that the term 'consists' limits the 'said
portion' language to the subsequently recited numbered nucleotides, but the
earlier term 'comprising' means that the claim can include that portion plus
other nucleotides. Read in context, the claims thus do not preclude a DNA
sequence having additional nucleotides.")
Therefore, Choi anticipates claim 1 by reasonably teaching a fusion
protein composed of a rotavirus protein fused to CTAl-DD where CTAl
constitutes the A subunit of cholera toxin (FF 2-5); where CTAl-DD
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Application 09/950,335
inherently retains ADP-ribosylating activity (FF 7); and where claim 1 is
open to the inclusion of additional sequences such as the Staphylococcal
protein A in CTAl-DD.
Appellants contend that "it should be noted Choi does not disclose a
DNA construct including nucleotide sequences for expressing a pathogenic
antigen and the A subunit of cholera toxin" (Reply Br. 2).
We find this argument unpersuasive because Choi expressly relies
upon Agren (1999) for the CTAl-DD fusion protein (see Choi 38:64---65),
and Agren (1999) relies upon Agren (1997) for CTAl-DD expression, where
Agren (1997) evidences the plasmid that expresses the CTAl-DD fusion
protein was known (FF 8). See Continental Can Co. USA, Inc. v. Monsanto
Co., 948 F.2d 1264, 1268 (Fed. Cir. 1991) ("To serve as an anticipation
when the reference is silent about the asserted inherent characteristic, such
gap in the reference may be filled with recourse to extrinsic evidence.")
Conclusion of Law
The evidence of record supports the Examiner's conclusion that Choi
anticipates claim 1.
B. 35 USC§ 103(a) over Burton, Choi, Agren (1997), Agren (1999),
Sanchez, and Barouch
The Examiner finds that
Burton teaches a gene construct in plasmid and viral vectors
expressing cholera toxin with its activity intact and consisted of
Cholera toxin A subunit .... Further Burtons constructs made
in various viral vectors also contained viral immunogen
sequences ofHSV, AAV or adenovirus .... Burton reference
also teach using several plasmid vectors that are cloned with
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and express CT A and along with an antigenic protein and the
plasmid vectors.
(Ans. 7). The Examiner finds that Choi teaches a "DNA plasmid construct
of a rotavirus fusion protein" (id.). The Examiner finds that Agren (1997)
teaches "cholera toxin A (CTA) subunit as a potent andjuvant [sic] and the
CTAI, which exhibit ADP-ribosyl[t]ransferase-activity is a strong systemic
and mucosal adjuvant" (Ans. 8). The Examiner finds that Agren (1997)
teaches "cloning and expression of a non-toxic enzymatically active CTAI
fusion protein (CTAI-DD) to be used as a vaccine adjuvant" (id.). The
Examiner finds that Agren ( 1999) teaches a "recombinant method of making
CT A fusion protein with an antigen and its ability to cause greatly enhanced
immune response" (id.). The Examiner finds that Sanchez teaches
"plasmids or nucleic acid-constructs in which is genetically engineered DNA
plasmid carrying a CT A encoding region and fused to a region encoding a
antigenic peptide" (id.). The Examiner finds that "Barouch teaches a DNA
vaccine construct comprising coding sequences of HIV viral antigen gp120
fused with immune-regulatory peptide IL-2 coding sequences" (id.).
The Examiner finds it obvious
to incorporate into viral or plasmid DNA constructs of Burton
that encodes CTAI having the ADP-r[i]bosylating activity or
Choi's plasmid constructs encoding an a fusion gene encoding
Choletoxin Al and a Staphylococcal aureus protein A
(pathogenic antigen) DD-segment (CTAI-DD) and a viral
antigen, an additional or a substitute nucleic acid sequence that
encodes an HIV antigen (e.g., gp120) and generate a genetic
construct presumably for enhancing an immune response
towards HIV infection
(Ans. 9).
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The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the prior art renders claim 1
obvious?
Findings of Fact
10. Burton teaches
a recombinant nucleic acid molecule of the present invention
comprises a tissue specific promoter controlling the expression
of a non-lethal cholera toxin gene and a cholera toxin gene
located 3' of the tissue specific promoter. . . . The present
invention also contemplates a segment of the cholera toxin Al
gene that encode a polypeptide that is an enzyme that is capable
of catalyzing the ADP-ribosylation and activation of Gs, the
GTP-binding regulatory component that stimulates the
adenylate cyclase complex.
(Burton 8:54---67).
11. Agren (1999) teaches that:
i\Jthough CTi\.1-DD adjuvant \Vas shov,rn to act through i\DP-
ribosylation of target proteins in the cell-free NAD-agmatine
system ... we did not know whether the fusion protein indeed
also could act on intact cells ... [the] results unequivocally
demonstrated that the CTAI-DD fusion protein acts on intact B
cells by exerting ADP-ribosyltransferase activity.
(Agren (1999) 2437, col. 1-2).
12. Sanchez teaches that "engineering at the amino end of CT A
lead to the successful carriage of a 16 amino acid heterologous peptide
which included the enterotoxin analogue CAELCCNP AC" (Sanchez 97, col.
1 ).
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13. Barouch teaches that:
Studies were initiated to explore the use of plasmid-expressed
cytokines as a strategy for amplifying immune responses
elicited by plasmid DNA vaccines. pVIJ-gp120, a DNA
vaccine encoding HXBc2 gp120 IIIB, has previously been
shown to elicit potent humoral and cellular immune responses
in mice and nonhuman primates. This vaccine is derived from
p UC 19 with a kanamycin resistance gene; a CMV IE 1
enhancer, promoter, and intron A; the gene encoding gp120;
and a bovine growth hormone polyadenylation sequence.
(Barouch 1877, col. 1; references omitted).
Principles of Law
"The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results."
KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). "If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability." Id. at 417. i\.s noted by the Supreme Court in KSR, "[a]
person of ordinary skill is also a person of ordinary creativity, not an
automaton." Id. at 421.
Analysis
We adopt the Examiner's findings regarding the scope and content of
the prior art (Ans. 6-9; FF 2-13) and agree that the claimed method would
have been obvious over the teachings of Burton, Choi, Agren ( 1997), Agren
(1999), Sanchez, and Barouch. We address Appellants' arguments below.
Appellants contend that "Burton never considers adding an antigen
peptide that may initiate an immune response"; that "the Choi reference like
the Burton reference does not in any way teach or suggest a plasmid
containing DNA that expresses a pathogenic antigen and the Al subunit of
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cholera toxin"; that "the statement by Agren [(1997)] that the CTAI subunit
is considered toxic would discourage anyone from using the CT Al without
the DD region of the SpA"; that Agren (1999) provides "no teaching or
incentive to isolate the Al subunit from the IgG binding moiety such as in
the present invention because of the discussed toxicity"; that the "Sanchez
reference merely reiterates the importance of combining cholera toxin A-
subunit (CTA) with cholera toxin B-subunit (CTB) to reduce toxicity"; and
that the Barouch reference "also must include the immunoregulatory peptide
IL-2 which is one more component that must be introduced into the
proposed mixture of references" (see App. Br. 15-21 ).
We do not find these arguments persuasive. "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., 800 F.2d 1091, 1097 (Fed. Cir. 1986). A reference "must be read, not
in isolation, but for what it fairly teaches in combination with the prior art as
a whole." Id.
As already discussed, Choi' s fusion protein construct comprising a
rotavirus protein fused to CTAI-DD alone anticipates claim 1 (FF 2---6),
thereby rendering claim 1 obvious. Indeed, under the broadest reasonable
interpretation of claim I, the pCTAl-DD plasmid encoding the CTAI-DD
fusion protein of Agren (1997) also teaches each of the limitations of claim 1
(FF 8). Specifically, the pCTAl-DD plasmid comprises an inserted
exogenous antigen encoding region, D domains of the Staphylococcal
protein A, that is reasonably interpreted as antigen peptide component from
a pathogenic organism, a Staphlococcus sp., as well as the A subunit of
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cholera toxin that retains ADP-ribosylating activity while remaining
nontoxic (FF 7-9).
Sanchez provides an additional example of an A subunit of cholera
toxin fused to a pathogenic antigen peptide component, the enterotoxin
sequence (FF 12). Barouch is relied upon to address dependent claims that
require HIV gp120 as the antigen, and Barouch demonstrates gp120 vaccine
plasmids (FF 13).
We, therefore, agree with the Examiner's finding that it would have
been obvious to make "a construct encoding a pathogenic antigen[] (e.g.,
HIV antigen gp120 or other viral antigens) and encoding the adjuvant
cholera toxin (CTAl) because [the] prior art clearly recognized []CTAl as a
potent adjuvant in the induction of immunity or immune response towards a
relevant pathogen and thus prophylactically or therapeutically treat a
disease" (Ans. 9).
We recognize, but find unpersuasive, Appellants' argument that "one
skilled in the art after reading this Agren [sic] reference, which uses the
CTAl-DD protein construct, would not consider using only the A subunit of
cholera toxin alone or in combination with an antigen because of the toxicity
issue" (App. Br. 17). As already discussed, to the extent that toxicity is an
issue, the presence of the Staphylococcal protein A D domains resolves the
toxicity and the claims do not exclude these D domains from the plasmid.
We also do not agree with Appellants that the Examiner "ignore[d]
this negative effect by focusing on only certain portions of the Agren
references" (App. Br. 19). As discussed above, the DNA construct of claim
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1 is open to the inclusion of other components including the Staphylococcal
protein A of Agren (1997). In re Crish, 393 F.3d at 1257.
Appellants contend that "conspicuously missing from this record is
any evidence, other than the Examiner's speculation that one of ordinary
skill in the art would have been motivated to make the modifications of the
prior art to arrive at the present invention" (App. Br. 21 ). Appellants also
contend that "with the lack of clues pointing to the most promising
combination, an artisan could spend years experimenting with different
combinations without success" (Reply Br. 6).
We do not find these arguments persuasive because Choi teaches
fusion proteins for vaccine purposes (FF 2) and Agren (1997) specifically
teaches that the CTAI-DD fusion protein "mimic[s] the adjuvant effect of
CT without being toxic to the host" (FF 9), thereby providing a reason to
include this fusion protein in the vaccine of Choi. Barouch further provides
reasons to use gp120 in functional DNA vaccines (FF 13). These are
specific reasons that would motivate the ordinary artisan to combine the
teachings of the references as suggested by the Examiner.
Appellants further contend that "effectiveness of pathogenic antigen/
Al subunit of cholera in a single plasmid is surprisingly unexpected. For
example, a review of the results of Example 7 and Figure 9 of the instant
application shows an increase of serum IgG response against gp 120" (App.
Br. 23).
We do not find the unexpected arguments evidence persuasive for
several reasons. First, even accepting that the specific plasmid encoding
gp120 and a particular fragment of the cholera toxin A provides IO-fold or
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1000-fold better results, this evidence is not commensurate in scope with
claim 1 which is drawn to any plasmid construct with any pathogenic
antigen peptide and any fragment of cholera toxin A that retains ADP-
ribosylating activity. See In re Tiffin, 448 F.2d 791, 792 (CCPA 1971)
("[O]bjective evidence of non-obviousness must be commensurate in scope
with the claims which the evidence is offered to support").
In addition, the results were not compared with the closest prior art of
either Choi or Agren ( 1997), to demonstrate that the 10-fold or 1000-fold
improvements were unexpectedly better than the results obtained by Choi,
Agren (1997), Agren (1999), or Sanchez. See In re Baxter Travenol Labs.,
952 F.2d 388, 392 (Fed. Cir. 1991) ("[W]hen unexpected results are used as
evidence of nonobviousness, the results must be shown to be unexpected
compared with the closest prior art.").
Finally, Appellants contend that "the use by the Examiner of a
multiplicity of references in an effort to show obviousness is in itself
persuasive of the futility of attempting to establish a prima facie case of
obviousness" (App. Br. 27).
We are not persuaded. It has been recognized that reliance on a "large
number of references" does not, without more, weigh against the
obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 986
(Fed. Cir. 1991) ("The criterion, however, is not the number of references,
but what they would have meant to a person of ordinary skill in the field of
the invention.").
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Conclusion of Law
The evidence of record supports the Examiner's conclusion that the
prior art renders claim 1 obvious.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 102(b) as anticipated by Choi. Claims 3, 4, 8, 26, and 49 fall with claim 1.
37 C.F.R. § 41.37(c)(l)(iv).
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Burton, Choi, Agren (1997), Agren (1999), Sanchez, and
Barouch. Claims 3-11, 13, 14, 26-29, 49, and 51-55 fall with claim 1.
37 C.F.R. § 41.37(c)(l)(iv).
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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