Ex Parte Pavlakis et al

Patent Trial and Appeal Board

Feb 15, 2017

13190969 (P.T.A.B. Feb. 15, 2017)

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.
13/190,969 07/26/2011 George N. Pavlakis 77867-816671 (262300US) 3204
45115 7590 02/17/2017
KILPATRICK TOWNSEND & STOCKTON LLP
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
EXAMINER
KINSEY WHITE, NICOLE ERIN
ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
02/17/2017 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):
ipefiling@kilpatricktownsend.com
jlhice@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GEORGE N. PAVLAKIS, ALEXANDER GRAGEROV,
and BARBARA K. FELBER1
Appeal 2015-006651
Application 13/190,969
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN G. NEW,
and TIMOTHY G. MAJORS, Administrative Patent Judges.
MAJORS, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims that have
been rejected as obvious and for nonstatutory obviousness-type double
patenting. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as The Government of the
United States, as represented by the Secretary of the Department of Health
and Human Services. (Br. 3.)
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Application 13/190,969
STATEMENT OF THE CASE
According to the Specification, “HIV-1 Gag is one of the most
conserved viral proteins . . . and the development of a safe and effective
HIV-1 vaccine may depend on the induction of effective CTL [cytotoxic T-
lymphocyte] and/or T-helper responses against conserved HIV-1 proteins
such as Gag.” (Spec. 2.)
Claims 1, 2, 5-8, and 16 are on appeal. Claim 1 is illustrative:
1. A method of stimulating an immune response against gag
in a mammal, the method comprising administering to the
mammal a nucleic acid construct encoding a fusion protein
comprising a [3-catenin 19-44 destabilizing amino acid sequence
covalently linked to a gag polypeptide; and a nucleic acid
construct encoding a secreted fusion protein comprising a MCP3
secretory amino acid sequence covalently attached to the gag
polypeptide, wherein the amount is effective to induce cytotoxic
and/or helper-induce[d] T lymphocytes and antibodies in said
mammal.
(Br. 15 (Claims App’x).)
The claims stand rejected by the Examiner as follows:
Claims 1, 5-8, and 16 under 35 U.S.C. § 103(a) over Sykes2 and
Kwak3 (“Rejection I”).
Claim 2 under 35 U.S.C. § 103(a) over Sykes and Kirkley4
(“Rejection II”).
2 Sykes et al., Genetic Live Vaccines Mimic the Antigenicity But Not
Pathogenicity of Live Viruses, 18:7 DNA and Cell Biol. 521-31 (1999).
3 Kwak et al., WO 99/46392 Al, published Sept. 16, 1999.
4 Kirkley et al., Adjuvant Properties ofMontanide CSA 720 with a
Recombinant HIV PI 7 gag Protein and Synthetic Peptide Antigens, 43
Scand. J. Immunol. 431-38 (1996).
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Claims 1, 2, 5-8, and 16 under 35 U.S.C. § 103(a) over Kipps,5
Applicants’ admission,6 Tobery,7 Widera,8 Qui I,9 Qui II,10 and Kwak
(“Rejection III”).
Claims 1, 2, and 5-8 for nonstatutory obviousness-type double
patenting over claim 1 of US 8,586,055 (“Rejection IV”).
REJECTION I
Issue
Has the Examiner established by a preponderance of the evidence that
claims 1, 5-8, and 16 would have been obvious under 35 U.S.C. § 103(a)
over Sykes and Kwak?
5 Kipps et al., US 6,287,569 Bl, issued Sept. 11, 2001.
6 Examiner cites Appellants’ disclosure that “a literature search for
characterized sequences able to target proteins to the ubiquitin-proteosome
degradation pathway gave the following, not necessarily representative, list:
. . . P-Catenin (aal9-44).” (Ans. 13 (quoting Spec. 25).)
7 Tobery et al., Targeting of HIV-1 Antigens for Rapid Intracellular
Degradation Enhances Cytotoxic TLymphocyte (CTL) Recognition and the
Induction of De Novo CTL Responses In Vivo After Immunization, 185:5 J.
Exp. Med. 909-20 (1997).
8 Widera et al., Increased DNA Vaccine Delivery and Immunogenicity by
Electroporation In Vivo, 164 The Journal of Immunology 463 5 40
(2000).
9 Qui et al., Evaluation of Novel Human Immunodeficiency Virus Type 1
Gag DNA Vaccines for Protein Expression in Mammalian Cells and
Induction of Immune Responses, 73:11 J. of Virology 9145-52 (1999).
10 Qui et al., Enhancement of Primary and Secondary Cellular Immune
Responses against Human Immunodeficiency Virus Type 1 Gag by Using
DNA Expression Vectors That Target Gag Antigen to the Secretory
Pathway, 74:13 J. of Virology 5997-6005 (2000).
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Findings of Fact (FF)
FF 1. The Examiner’s findings of fact and statement of Rejection I
may be found at pages 3-8 and 19-25 of the Examiner’s Answer. (See also
Final Act. 3-8.) We adopt the Examiner’s findings and provide the
following for emphasis.
FF 2. Sykes relates to HIV vaccines and teaches “[ijnitial vaccine
efforts focused on raising antibodies to the HIV envelope gpl20 protein. . . .
Poor antibody persistence and lack of cross-isolate reactivity have made it
clear that an effective vaccine will need to generate a robust immune
response with a strong cellular component.” (Sykes 521.)
FF 3. Sykes teaches
constructing] libraries by cloning overlapping fragments of the
proviral genome into mammalian expression plasmids . . . [and]
inserting library fragments into a vector downstream of a
secretory gene sequence led to augmented antibody responses,
and insertion downstream of a ubiquitin sequence enhanced
cytotoxic lymphocyte responses. Also fragmentation of gag into
subgenes broadened T-cell epitope recognition.
{Id. at Abstract; see also id. at 524 and Fig. 1 (describing three vectors —
HIV insert-encoded antigens fused to a secretory protein; antigens expressed
as ubiquinated fusions; and antigen expression with no fusion to permit
natural localization).)
FF 4. Sykes “demonstrate[s] that fusion of library encoded antigens
with either ubiquitin or a secretory protein can enhance cytotoxic
lymphocyte or antibody levels, respectively.” {Id. at 522.) Sykes teaches
“ELISA analysis of sera showed that the library of fusions to secreted hGH
generated the highest anti-Gag-specific antibody levels . . . [and] the
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ubiquitin fusion library (UB) maximized cytolysis.” (Id. at 525; see also id.
at Figs. 3A & 3B.)
FF 5. Kwak teaches “a fusion polypeptide comprising a chemokine
and ... a viral antigen which is administered as either a protein or nucleic
acid vaccine to elicit an immune response . . . effective in treating or
preventing HIV infection.” (Kwak Abstract; see also id. at 2:8
(“Chemokines are a group of usually small secreted proteins”).) Kwak
teaches “a fusion polypeptide comprising a human chemokine and a human
immunodeficiency virus (HIV) antigen, wherein the chemokine can be IP-
10, MCP-1, MCP-2, MCP-3 . . . and/or MDC.” (Kwak 3:9-12; see also id.
at 8:22-9:11 (disclosing, for example, “SEQ ID NO:56 (human MCP-3
fused with HIV gpl20)”).)
FF 6. Appellants’ Specification discloses “to design ‘Gag-
destabilized’ constructs, a literature search for characterized sequences able
to target proteins to the ubiquitin-proteosome degradation pathway gave the
following, not necessarily representative, list: c-Myc . . . [and] b-Catenin
aal9-441' (Spec. 25 (emphasis added).)
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 Inti Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
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ordinary skill can implement a predictable variation [of a known work],
§103 likely bars its patentability.” Id. at 417.
Analysis
Appellants argue the patentability of claims 1, 5-8, and 16 as a group.
We select claim 1 as representative. 37 C.F.R. § 41.37(c)(l)(iv).
According to the Examiner, “it is known in the art that the human
immune system comprises two distinct branches that respond to pathogens
or foreign antigens differently: humoral immune responses (antibodies) and
cellular immune responses (T-cells such as cytotoxic T cells (CTLs)).”
(Ans. 3.) The Examiner finds that Sykes teaches “HIV antigens targeted to
the secretion pathway had very high antibody responses and HIV antigens
targeted to the degradation pathway had maximized cytolytic activity from
CTLs.” {Id. at 4.) Thus, according to the Examiner, Sykes observations
“solve the two problems initially discussed by Sykes et al. [regarding
development of HIV vaccines]: poor antibody persistence and the need of a
strong cellular component.” {Id. (emphasis removed).)
The Examiner acknowledges Sykes “does not teach administering the
two constructs together” nor that “the secretory sequence is MCP3 or that
the degradation sequence is [3-catenin 19-44 as claimed.” (Ans. 4-5.) The
Examiner concludes, however, that these would have been obvious
modifications and that, in administering the modified constructs, the skilled
person would have reasonably expected to stimulate an immune response by
inducing CTLs and antibodies as reported in Sykes. {Id. at 4-5, 21-23.)
The Examiner reasons the skilled artisan would have been motivated
to administer both constructs “given the fact that it is desirable to elicit
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broader protection by inducing an immune response comprising both a
strong humoral (antibody) and a strong cellular (CTL) immune response . . .
and given a desire to overcome the problem with HIV vaccines” reported in
Sykes. {Id. at 4-5.) The Examiner further reasons that “because the key to
the enhanced humoral and cellular immune responses is the secretion and
degradation of the antigen, it would be obvious ... to select any known
degradation and secretory sequences in the art to fuse to the HIV protein
(e.g., gag or gpl20).” {Id. at 5.) The Examiner thus concludes it would have
been obvious to “replace the degradation and secretory sequences of Sykes
et al. with other known degradation and secretory sequences from proteins
such as [3-catenin and MCP-3 . . ., which are disclosed in the art for targeting
proteins to the degradation/proteasome and secretory pathways.”11 {Id. at 6.)
We agree with the Examiner’s fact-finding, reasoning, and conclusion
that claim 1 would have been obvious over Sykes and Kwak. Sykes teaches
that constructs comprising a destabilizing ubiquitin gene sequence and a
secretory gene sequence linked to library-encoded antigens made from the
HIV genome led to augmented CTL and antibody responses respectively.
(FF 3—4.) It would have been obvious to use other secreted gene sequences,
such as MCP-3 in view of Kwak’s teachings of fusion polypeptides
comprising MCP-3 and HIV antigen for treatment of HIV infection. (FF 5.)
With respect to the fusion protein comprising [3-catenin and gag, Appellants
11 As evidence that skilled persons were aware of the claimed degradation
sequence (]3-catenin 19-44) and secretory sequence (MCP3) at the time of
invention, the Examiner cites an undisputed admission in Appellants’
Specification and the teachings of Kwak. (Ans. 5-6 and 20.)
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do not dispute that [3-catenin was a known sequence targeting the ubiquitin-
proteosome degradation pathway. (FF 6.) Sykes teaches ubiquinated,
proteasome-targeting vectors as enhancing the immune response (FF 3) and
it would have been obvious to substitute the [3-catenin sequence — as an art-
recognized alternative — in Sykes’ constructs. KSR, 550 U.S. at 416.
Although Sykes does not expressly disclose administering both
constructs to a single subject, such an administration scheme would have
been obvious to elicit broader protection and induce a CTL and antibody
response. (Ans. 19-21.) Indeed, in identifying poor antibody persistence as
a problem with existing HIV vaccines, and the prevailing need for a “robust
immune response with a strong cellular component,” Sykes suggests the
desirability of a treatment that includes both a humoral and cellular response
— addressing both branches of the immune system (id. at 4). Accordingly,
the skilled artisan would have predictably administered both constructs and,
in view of Sykes, would have reasonably expected to induce antibody and
CTL immune responses in the subject. (FF 2—4.)
Appellants argue Sykes “does not lead one of ordinary skill to
Applicants’ invention, either alone or in combination with Kwak.” (Br. 5.)
More specifically, Appellants contend the Examiner has not provided
sufficient reasoning or evidence to show (1) why Sykes is
predictive of the results obtained here when the experimental
results in Sykes show a different pattern of immune response,
and (2) that one of skill could have otherwise predicted the
enhanced immune response achieved in accordance with the
present invention.
(Id. at 6.)
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In support, Appellants cite Sykes’ data and contrast it with data in
Appellants’ Specification. Appellants assert that inoculation with Sykes’
secretory sequence construct (GHLIB) resulted in low peptide specific lysis
(CTL response). {Id.) Also, Appellants assert, Sykes’ degradation sequence
construct (UBLIB) provided a “fairly low” antibody response. {Id.)
Appellants thus contend Sykes’ data differs from Appellants’ testing of
“MCP-3 modified [secretion] and CATE-modified [[3-catenin degradation]
constructs individually,” which “showed that both constructs demonstrated
proliferative responses (a measure of cellular immune response) that were
greater than that obtained with unmodified gag.” {Id. at 6-7.)
Appellants’ argument is unpersuasive. Appellants contend the skilled
person needed to predict Appellants’ testing data, but the expectation of
success required to demonstrate obviousness corresponds to the scope of the
claims. Intelligent Bio-Systems, Inc. v. Illumina Cambridge Ltd., 821 F.3d
1359, 1367 (Fed. Cir. 2016) (“The reasonable expectation of success
requirement refers to the likelihood of success in combining references to
meet the limitations of the claimed invention.”). Claim 1 does not require
the construct comprising the secretory sequence enhance a cellular response
versus unmodified gag, as allegedly shown in Appellants’ data. Neither
does claim 1 require the construct comprising the destabilizing sequence
enhance antibodies. Claim 1 is to a method of stimulating an immune
response that “is effective to induce” CTFs and antibodies in a mammal.
And claim 1 encompasses a method where one construct induces CTFs, and
the other induces antibodies. With this claim scope in mind, the skilled
artisan would have reasonably expected that administering an MCP3
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secretory construct would augment antibodies and administering a [3-catenin
destabilizing construct would augment a CTL response in a subject —
consistent with Sykes’ teachings. (Ans. 22; FF 2^4.)
Appellants argue Sykes does not lead one of ordinary skill in the art to
expect an enhanced immune response using a combination of vectors. (Br.
7.) Appellants again cite data in the Specification and contend it shows “the
combination of MCP3-gag and CATE-gag provided a proliferative response
that was even better than that obtained with CATE-gag alone.” (Id.)
Inasmuch as Appellants’ argument suggests an expectation of success
was required that is not consistent with the scope of claim 1, we are
unpersuaded for the reasons discussed above. The claims require inducing a
humoral and cellular (e.g., CTL) response — not that any particular immune
response be “enhanced” by co-administration of vectors compared to an
unclaimed threshold.
Appellants do not expressly argue that they have provided evidence of
secondary considerations. We nevertheless consider Appellants’ argument
and data to determine whether it provides objective evidence sufficient to
show nonobviousness and overcome the Examiner’s case. We are not
persuaded that it does. First, the data in the Specification relates to a
specific administration scheme that is not required by claim 1, and we are
not persuaded the data is commensurate with claim l’s broad scope. In re
Lindner, 457 F.2d 506, 508 (CCPA 1972) (“It is well established that the
objective evidence of nonobviousness must be commensurate in scope with
the claims.”). For example, claim 1 does not require the constructs be
administered at the same time and it does not specify the number of
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administrations. But Appellants’ data shows the constructs were
concurrently administered at least three times at discrete intervals (i.e., 0, 14,
28 days) over the course of weeks before immune response was tested.
(Spec. 28.) Second, as noted by Examiner, Appellants have not shown that
their results are not due to variables like route of administration
(intramuscular versus the ear in Sykes) or amount of the construct delivered
(lOOug versus lOug in Sykes), which differ between Appellants’ data and
the prior art. (Ans. 23.) Third, Appellants have not persuasively shown
their results are surprising or unexpected compared to the additive response
that would have been expected with combined administrations of DNA
constructs reasonably suggested by Sykes. (See Final Act. 23-25; FF 2^1.)
We also recognize, but find unpersuasive, Appellants’ contention that
antibody and cellular immune responses are in competition and thus the
skilled person would have predicted one type of response diminishes the
other. (Br. 8.) Again, the claims encompass constructs that merely induce
an antibody and CTF response, and even assuming competition between
immune responses occurs, that does not mean that one type of response is
eliminated. Appellants’ evidence is not to the contrary. The textbook
excerpt cited by Appellants, after generally mentioning ways in which T cell
subsets can regulate each other, states that “certain responses are dominated
by either humoral (Th2) or cell-mediated (ThI) immunity. However, under
many circumstances in vivo, there is a mixed ThI and Th2 response.”12 That
12 See Br. 8 (identifying “Appendix A, from a 2001 textbook at the
website://www.ncbi.nlm.nih.gov/books/NBK27125, provided with
Applicants’ response filed December 26, 2013.”)
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“certain responses” may be dominated by one type of immunity does not
evidence that the skilled person would have expected the DNA constructs
here to diminish, much less eliminate, the antibody or CTL response,
especially since Appellants’ evidence recognizes that mixed humoral and
cell-mediated responses are common. In further support, Appellants cite
Kipps. But Kipps states “production of antibodies directed to [tumor-cell
presented] antigens have been hypothesized to inhibit cellular immune
responses to such antigens.” (Kipps 3:18-21 (emphasis added).) Kipps’
hypothesis and Appellants’ other citations, balanced against the full record,
would not have negated the skilled person’s reasonable expectation of
success in augmenting a cellular and antibody response with the modified
constructs of Sykes. Nor does Appellants’ evidence rise to the level of a
teaching away from the Examiner’s proposed modification of the art. In re
Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
Conclusion of Law
For the reasons above, we conclude the Examiner established by a
preponderance of the evidence that claim 1 would have been obvious over
Sykes and Kwak. Claims 5-8 and 16 have not been argued separately and
thus fall with claim 1.
REJECTION II
Claim 2 depends from claim 1 and adds “administering a nucleic acid
construct encoding the gag protein in a form that lacks a destabilizing
sequence and lacks a secretory sequence.” (Br. 15 (Claims App’x).)
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The Examiner finds that Kirkley “demonstrates that an HIV protein
antigen (gag) administered to a subject is [naturally] processed by the host
and induces a humoral (antibody) immune response.” (Ans. 8.)13 According
to the Examiner, “one would be motivated to administer the HIV protein
antigen . . . along with the two DNA constructs of Sykes et al. to ensure a
more thorough exposure of the subject’s immune system to the different
forms of the HIV antigen” — by using DNA constructs that target the
degradation and secretory pathways, and by using the natural processing
pathway for protein antigen. (Ans. 8-9 (citing In re Kerkhoven, 626 F.2d
846, 850 (CCPA 1980) (“It is prima facie obvious to combine two
compositions each of which is taught by the prior art to be useful for the
same purpose, in order to form a third composition which is to be used for
the very same purpose.”)).)
We agree with and adopt the Examiner’s fact-finding, reasoning, and
conclusion that claim 2 would have been obvious. (Ans. 8-9, 25-26.)
Appellants argue the Examiner “fails to provide any evidence or
reasoning to suggest that something is lacking in an immunogenic
composition comprising MCP3- and CATE-modified gag such that one of
skill would consider it desirable to also include a gag protein without the
modifications.” (Br. 10.) Appellants contend “Sykes observed only a
minimal response in T cell cytotoxicity when using the GHLIB libraries”
and “[tjhere is no evidence in the rejection that one of skill would consider it
13 Although not expressly identified by the Examiner (Ans. 8), we interpret
the rejection of claim 2 as also relying on Kwak’s teachings for the reasons
discussed concerning the rejection of claim 1, from which claim 2 depends.
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desirable to combine GHLIB with SSLIB and moreover, to also include the
UBLIB [unmodified construct]” of Sykes. {Id.) Appellants also contend
their testing data showed the combination of three vectors “together elicit an
even greater enhancement in the cellular immune response than is observed
with the combination of MCP3-gag and CATE-gag only.” (Id.)
We are not persuaded. As noted by the Examiner, the skilled person
would have had reason to predictably combine three vectors to ensure
processing of the antigen through multiple pathways with the reasonable
expectation that it would provide more thorough exposure and protection.
(Ans. 8-9, 25-26.) Appellants’ data is not persuasive for the reasons
discussed above concerning Rejection I. Further, we are not persuaded that
Appellants established that the combination of three vectors provides results
that are surprising or unexpected to a nonobvious extent compared to the
additive immune response that would have been reasonably expected from
Sykes. Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967,
977 (Fed. Cir. 2014) (differences in degree are not as persuasive in rebutting
obviousness as differences in kind).
REJECTION III
The Examiner rejected claims 1, 2, 5-8, and 16 over Kipps,
Applicants’ admissions, Tobery, Widera, Qui I, Qui II, and Kwak.
Appellants argue the patentability of the claims as a group and we
again select claim 1 as representative.
The Examiner finds that Kipps teaches “fusion protein comprising a
destabilizing amino acid sequence covalently attached to a heterologous
amino acid sequence of interest,” which increases a cellular immune
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response. (Ans. 10; see Kipps 2:44 47 and 63-66 (“vectors that encode for
chimeric immunogens which have enhanced rates of degradation via the
ubiquitin-proteosome pathway are able to generate an enhanced cellular
immune response”).) According to Examiner, Kipps teaches “viral antigens
are especially preferred targets.” (Ans. 10.) Examiner’s findings concerning
Kwak’s secretion constructs are discussed above. {Id. at 11.) Examiner
finds Appellants admitted [3-catenin was a known destabilizing sequence and
Examiner finds Widera, Qui I, and Qui II teach “use of HIV proteins, e.g.,
gag and env, as an immunogen in DNA vaccines.” {Id. at 13-14.) Examiner
finds Tobery “teaches that ‘targeting of viral antigens for rapid cytoplasmic
degradation represents a novel and highly effective vaccine strategy for the
induction of enhanced de novo CTL responses in vivo’ and that gag, pol, and
nef represent excellent [CTL] targets.” {Id. at 14 (quoting Tobery).)
The Examiner finds that Kipps and Kwak do not specifically disclose
administering both types of fusion proteins. {Id. at 11.) The Examiner
concludes, however, that it would have been obvious to combine fusion
proteins of Kipps and Kwak. {Id.) The Examiner reasons “both types of
fusion proteins are known in the art for improving the immune response
(either antibody response or CTL response) of the attached antigen” and the
skilled person would have been “motivated to administer the claimed
composition to indue[e] both humoral and cellular immune responses . . .
resulting in a broader immune response against the antigen.” {Id. at 12.)
We agree with and adopt the Examiner’s fact-finding, reasoning, and
conclusion that claim 1 would have been obvious over Kipps, Applicants’
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admission, Tobery, Widera, Qui I, Qui II, and Kwak. (Ans. 9-16 and 27-
30.)
Appellants argue “the rejection fails to provide any evidence or
reasoning as to why one of skill would have expected the claimed
combination of gag vectors to provide a robust cellular immune response.”
(Br. 11.) This argument is unpersuasive for reasons similar to those
provided above regarding Rejection I. As noted by the Examiner, the skilled
artisan would have been motivated to administer two constructs to a subject
to “solve the problems of poor antibody persistence and the need of a strong
cellular component and to induce a broader immune response.” (Ans. 30.)
Examiner finds “[ejach construct of Kipps et al. and Kwak et al. targets one
of the[ known] branches of the immune system” — antibodies and cellular
immune response — and Kipps and Kwak “observed enhanced cellular and
humoral immune responses, respectively.” {Id. at 27 (emphasis omitted).)
Based on these and the other teachings of the cited art, the skilled artisan
would have had a reasonable expectation of success in administering both
constructs to induce CTL and antibody response in the subject. {Id.)
Appellants contend Kipps “response is limited to the cellular branch
of the immune system and does not include the production of antibodies to
the immunogen.” (Br. 11-12.) The Examiner, however, relies on Kwak for
teaching a MCP3 secretion construct that would be expected to induce
antibodies in the subject. Nonobviousness cannot be established by
attacking the references individually. In re Merck & Co., 800 F.2d 1091,
1097 (Fed. Cir. 1986). Insofar as Appellants contend Kipps teaches away
from the present invention, we are unpersuaded for the reasons discussed
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above; Kipps’ reference to a hypothesis that antibodies may inhibit a cellular
immune response to antigens presented by tumor cells does not criticize or
discredit a therapy aimed at inducing humoral and cellular immunity.
Appellants’ remaining arguments and citation of data are essentially
reprisals of the positions raised concerning Rejections I and II. These
arguments and data are not persuasive for the reasons stated by the Examiner
(Ans. 27-30) and those discussed above.
We conclude the Examiner established by a preponderance of the
evidence that claim 1 would have been obvious over Kipps, Applicants’
admission, Tobery, Widera, Qui I, Qui II, and Kwak. Claims 2, 5-8, and 16
were not argued separately and thus fall with claim 1.
REJECTION IV
Examiner rejected claims 1,2, and 5-8 for nonstatutory obviousness-
type double patenting over claim 1 of US 8,586,055. (Ans. 16-19.)
Appellants assert that “[tjhis rejection is not appealed.” (Br. 4.) The
double patenting rejection is thus summarily affirmed.
SUMMARY
We affirm the rejection of claims 1, 5-8, and 16 under 35 U.S.C.
§ 103(a) over Sykes and Kwak.
We affirm the rejection of claim 2 under 35 U.S.C. § 103(a) over
Sykes and Kirkley.
We affirm the rejection of claims 1, 2, 5-8, and 16 under 35 U.S.C.
§ 103(a) over Kipps, Applicants’ admission, Tobery, Widera, Qui I, Qui II,
and Kwak.
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We affirm the nonstatutory obviousness-type double patenting
rejection of claims 1, 2, and 5-8 over claim 1 of US 8,586,055.
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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