Ex Parte Eldridge et al

Patent Trial and Appeal Board

Dec 9, 2016

13454884 (P.T.A.B. Dec. 9, 2016)

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.
13/454,884 04/24/2012 John Eldridge PC64516B 2018
25291
Pfizer Tne
7590 12/13/2016 EXAMINER
Attn:Legal Patent Department, Chief IP Counsel HIRIYANNA, KELAGINAMANE T
235 East 42nd Street
NEW YORK, NY 10017 ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
12/13/2016 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):
-IPGSMadisonDocketing @pfizer. com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN ELDRIDGE, ZIMRA R. ISRAEL,
MICHAEL A. EGAN, and STEPHEN A. UDEM1
Appeal 2014-009780
Application 13/454,884
Technology Center 1600
Before FRANCISCO C. PRATS, JOHN G. NEW, and RYAN H. FLAX,
Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to compositions
and methods of inducing an antigen-specific immune response in
mammalian subjects. The Examiner rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner’s rejection of
claims 1—5, 16—18, 20—25, 32—37, and 40-42 under 35 U.S.C. § 103(a) for
1 Appellants state that the “real parties in interest are the assignee of the
present application, Wyeth LLC, which is a subsidiary of Pfizer Inc., and
Profectus BioSciences, Inc., which licenses the present application from
Wyeth LLC.” App. Br. 1.
Appeal 2014-009780
Application 13/454,884
obviousness over Schnell,2 Gherardi,3 Rose,4 Ramshaw,5 Rovinski,6 Ertl,7
andHaglund.8 Ans. 4—8.
We initially address a number of procedural issues. First, as
Appellants note (Reply Br. 1) the rejection entered by the Examiner in the
Final Office Action did not include the Schnell reference, in contrast to the
rejection advanced on pages 4—8 of the Examiner’s Answer. Although
reliance on a new reference in the Examiner’s Answer constitutes a new
ground of rejection (see 37 C.F.R. § 41.39(a)(2)),9 Appellants have
expressly requested that the appeal be maintained. Reply Br. 1.
2 US 2003/0124146 A1 (published July 3, 2003).
3 M. Magdalena Gherardi et al., Interleukin-12 (IL-12) Enhancement of the
Cellular Immune Response against Human Immunodeficiency Virus Type 1
Env Antigen in a DNA Prime/Vaccinia Virus Boost Vaccine Regimen Is Time
and Dose Dependent: Suppressive Effects of IL-12 Boost Are Mediated by
Nitric Oxide, 74 J. Virol. 6278—86 (2000).
4 Nina F. Rose et al., An Effective AIDS Vaccine Based on Live Attenuated
Vesicular Stomatitis Virus Recombinants, 106 Cell 539-49 (2001).
5 Ian A. Ramshaw and Alistair J. Ramsay, The prime-boost strategy:
exciting prospects for improved vaccination, 21 Immunology Today 163—
65 (2000).
6 US 2002/0051770 Al (published May 2, 2002).
7 US Patent No. 6,210,663 B1 (issued Apr. 3, 2001).
8 Karl Haglund et al., Robust Recall and Long-Term Memory T-cell
Responses Induced by Prime-Boost Regimens with Heterologous Live Viral
Vectors Expressing Human Immunodeficiency Virus Type 1 Gag and Env
Proteins, 76 J. Virol. 7506—17 (2002).
9 The Advisory Action entered January 3, 2014, purports to present a
modified obviousness rejection, citing Schnell, the modified rejection being
advanced in view of the entry of the amendment addressed therein.
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Second, as Appellants contend (Reply Br. 1), claims 19 and 26—31
have been canceled and should not have been included in the Examiner’s
statement of the rejection. See Response 7 (Response under 37 C.F.R.
§ 1.116, filed September 19, 2013 (canceling claims 19 and 26—31)); see
also Advisory Action 1 (Advisory Action entered November 6, 2013)
(entering amendment filed September 19, 2013)).
Third, as Appellants point out (Reply Br. 1), review of the electronic
application file suggests that the Schnell reference cited by the Examiner,
U.S. Patent Application Publication No. 2003/0124146 A1 (published July
3, 2003), is not cited in any of the information disclosure statements filed by
Appellants, or the lists of references cited by the Examiner. Based on their
citation to specific pages and disclosures therein, however, it appears that
both the Examiner and Appellants have a copy of the reference. See Ans. 5—
6 (citing and characterizing || 32, 59, 90, 109-112, and 151 of Schnell); see
also Reply Br. 2 (citing and characterizing || 56, 90, and 151 of Schnell).
Fourth, like the Schnell reference, review of the electronic application
file suggests that the Rose reference cited by the Examiner, volume 106,
pages 539-549, of the journal Cell, published in 2001, is not cited in any of
the information disclosure statements filed by Appellants, or the lists of
references cited by the Examiner. Based on their citation to specific pages
and disclosures therein, however, it appears that both the Examiner and
Appellants have a copy of the reference. See Ans. 6, 10 (citing and
characterizing pages 540 and 546—547 of Rose); see also App. Br. 15 (citing
and characterizing page 546 of Rose); Reply Br. 6—7 (citing and
characterizing page 539 of Rose).
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Turning to the merits, claim 1 is representative of the appealed subject
matter, and reads as follows (App. Br. 24):
1. A method of inducing an antigen-specific immune
response in a mammalian subject, said method comprising the
steps of:
(a) administering to said subject an effective amount of a
priming composition, which comprises a first DNA plasmid
comprising a DNA sequence encoding an antigen under the
control of regulatory sequences directing expression thereof by
said first DNA plasmid, and a second DNA plasmid comprising
a DNA sequence encoding an interleukin-12 cytokine under the
control of regulatory sequences directing expression thereof by
said second DNA plasmid, wherein said first DNA plasmid and
said second DNA plasmid are co-administered; and
(b) administering to said subject an effective amount of a
boosting composition, which comprises a recombinant vesicular
stomatitis virus (VSV) comprising a nucleic acid sequence
encoding said antigen under the control of regulatory sequences
directing expression thereof by said recombinant VSV,
wherein an immune response specific to the antigen is
induced in the subject.
OBVIOUSNESS
The Examiner’s Position
The Examiner cited Schnell as disclosing a method of inducing an
immune response to HIV antigens, the process using recombinant VSV
(rVSV), as recited in Appellants’ representative claim 1, “as efficient
booster vectors for enhancing immune responses induced in the host by the
same antigen administered in a DNA-based (plasmid) vector vaccine
(prime),” as also recited in representative claim 1. Ans. 5—6. The Examiner
found that Schnell differed from Appellants’ claim 1 in that Schnell did not
administer an IL-12 plasmid as part of the priming composition. Id. at 6.
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To address that deficiency, the Examiner cited Gherardi as disclosing
a method of inducing an immune response to an HIV antigen in which the
priming composition, as recited in claim 1, included a plasmid encoding the
antigen for which the immune response was sought, and also a plasmid
encoding IL-12. Ans. 6. The Examiner found that Gherardi differed from
Appellants’ claim 1 in that, in the boosting composition, Gherardi used
recombinant vaccinia and pox viruses rather the rVSV required by claim 1.
Id.
To address that deficiency, the Examiner cited Rose as disclosing “the
advantages using VSV vectors for developing an [effective AIDs (HIV)
vaccine,” and noted in particular Rose’s teaching of “boosting the prime-
vector induced immune response in a host with distinct strains of VSV
vectors that carry[] the same antigen as the priming vector.” Id. The
Examiner also noted Rose’s teaching that “the immune response elicited
using a VSV vector was far superior, about as high as six to eight fold higher
than that could be obtained using a vaccinia virus (VV) vector boost.” Id.
(citing Rose 546).
The Examiner cited Ramshaw as evidence that the immunization
strategy recited in Appellants’ claim 1, of using a priming composition
composed of a plasmid encoding the antigen for which an immune response
was desired, followed by viral vectors encoding that antigen, was known to
be an “exciting prospect for improved vaccination.” Id. at 6—7 (quoting
Ramshaw 163 (Title)).
The Examiner cited Rovinski and Ertl as also disclosing methods for
generating an immune response to HIV, wherein the priming composition
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used a plasmid encoding the target antigen, and the boosting composition
included viral vectors also encoding the target antigen. Ans. 7.
While the Examiner found that Gherardi, Ramshaw, Rovinski, and
Ertl did not teach using VSV as a vector in their boosting compositions, the
Examiner cited Haglund as teaching that “the immune response elicited
using VSV as vector was as high as six to eight fold higher than that could
be obtained using a vaccinia virus vector and further boosting with VV
containing same antigen increased the efficacy.” Id. The Examiner found,
therefore, that at the time of Appellants’ invention Haglund, “clearly
established] VS Vs as the more efficient vectors than VVs [vaccinia
viruses,] and safer[,] and Haglund clearly had established efficacy of VSVs
for both priming and boosting.” Id.
Based on the references’ combined teachings, the Examiner
concluded:
[I]t would have been obvious for one of ordinary skill in the art
to incorporate into Schnell[’]s method of making and using
HIV vaccines using plasmid DNA vectors and/or a rhabdoviral
vector (VSV) a prime boost strategy of efficiently inducing an
antigen-specific immune response to an antigen comprising
steps of administering first a priming composition comprising a
DNA plasmid encoding a desired antigen (HIV protein or HCV
protein) and then providing a boosting composition of a
rhabdo viral vector (rVSV or rRabies virus) encoding the same
antigen and expressed under the control of a promoter to further
enhance the antigen specific immune response and further
provide the priming composition with an additional plasmid
expressing interleukin-12 (cytokine) as taught by Gehrardi [sic]
and further following the teachings of Rose and Haglund for the
advantages of using a VSV-vector boost in place of the more
commonly used vaccinia virus based boost. One of ordinary
skill in the art would have been motivated to make and use said
prime-boost strategy for providing vaccine for an efficacious
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immune response in order prophylactically and/or
therapeutically treat a pathogenic or an allergenic disease. One
of ordinary skill in the art would have a reasonable expectation
of success for making [and] using said compositions because of
[sic] the prior art clearly teaches prime boost strategy for an
improved vaccination and prior art further clearly teaches
improved prime boost and safety of using VSV over VV and
still further teaches enhancing the immune response by
including a plasmid encoded cytokine IL-[1]2 in the
administered prime compositions of the vaccine. Thus, the
claimed invention was prima facie obvious.
Ans. 7—8.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
We have carefully considered Appellants’ arguments and the evidence
advanced in support those arguments. Appellants’ arguments do not
persuade us, however, that a preponderance of the evidence fails to support
the Examiner’s prima facie case of obviousness as to representative claim 1.
Claim 1 is directed to a method of inducing an antigen-specific
immune response in a mammalian subject. App. Br. 24. Claim 1 requires,
in step (a) of the method, co-administering to the subject a priming
composition that includes (1) a plasmid encoding a target antigen under the
control of regulatory sequences directing expression of the antigen, and (2) a
plasmid encoding interleukin-12 (IL-12) under the control of regulatory
sequences directing expression of IL-12. Id. Claim 1 requires, in step (b),
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administering to the subject a boosting composition composed of a
recombinant vesicular stomatitis virus (rVSV) nucleic acid sequence that
encodes the target antigen under the control of regulatory sequences
directing expression the antigen. App. Br. 24.
Gherardi discloses methods of inducing an immune response to the
HIV “Env” antigen in mammalian subjects, mice. Gherardi 6278 (abstract).
As required by step (a) of claim 1, Gherardi discloses administering a
priming composition that includes (1) a plasmid encoding a target antigen,
the HIV Env target antigen, and (2) a plasmid encoding IL-12, the priming
composition being followed by administration of a viral vector boosting
composition. See id. (“The delivery of IL-12 and Env product during
priming with a DNA vector, followed by a booster with VV [vaccinia virus]
expressing the Env gene (rVVenv), was found to trigger the optimal CMI
[cell-mediated immune] response compared with other immunization
schedules studied.”); see also id. at 6280 (“Groups of mice were immunized
with DNA plasmids expressing HIV-1 Env (penv) or in combination with
DNA plasmids expressing IL-12 (penv + pIL-12) and, when required,
boosted 14 days later with penv ... or with rVV expressing gpl60 . . . .”).
Given these disclosures, we agree with the Examiner (Ans. 9—10) that
Gherardi describes a process that differs from the process recited in
Appellants’ claim 1 only in that Gherardi uses vaccinia virus in its boosting
composition, rather than the rVSV recited in step (b) of claim 1.
As the Examiner notes, however {id. at 10), Rose discloses using
rVSV in the boosting composition, as well as the priming composition, of a
prime-boost regimen for inducing an immune response to HIV:
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We developed an AIDS vaccine based on attenuated
VSV vectors expressing env and gag genes and tested it in
rhesus monkeys. Boosting was accomplished using vectors
with glycoproteins from different VSV serotypes. . . . VSV
vectors are promising candidates for human AIDS vaccine trials
because they propagate to high titers and can be delivered
without injection.
Rose 539 (abstract).
In particular, as the Examiner found (Ans. 10), Rose discloses that
VSV is significantly better than the vaccinia virus used in Gherardi at
inducing immune responses to the HIV Env antigen. Id. at 546 (“In direct
vector comparisons in mice, we find that the humoral and cellular immune
response to HIV Env expressed by VSV are 6—10 fold great than those
generated by vaccinia virus expressing the same HIV Env.” (citation
omitted)).
As the Examiner found, moreover (Ans. 10), beyond the significant
improvement over the vaccinia virus used in Gherardi, Rose discloses that
VSV provides a number of advantages as an immunizing vector, including
“the ease with which they can be grown.” Rose 546. Rose describes the
following additional advantages to VSV as an immunizing vector:
[I]n the VSV-HA mouse model, as few as ten infectious virus
particles given intranasally induce immune responses
equivalent to those generated with 105 infectious particles
because the vector replicates. If the results from mice apply to
primates, it might be possible to produce sufficient AIDS
vaccine for more than one billion people starting from one liter
of supernatant from VSV vector-infected cells.
... In addition, the ability to exchange the VSV envelope
G proteins and escape the neutralizing antibody to the vector
allows major boosting of immune responses. Another major
advantage of VSV vectors is that they are replication competent
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and carry out limited replication and spread until they are
eliminated by nonadaptive and adaptive immune responses.
Because the virus replicates entirely in the cytoplasm from only
RNA intermediates, there are no concerns about persistence
through integration [into] host DNA or damage of host DNA.
Rose 546 (citations omitted, emphasis added).
Accordingly, in view of Rose’s disclosure that using VSV as an
immunizing vector produces immune responses six- to ten-fold greater than
Gherardi’s vaccinia virus, and further in view of the various advantages
taught by Rose of using VSV as an immunizing vector, including the
advantage of allowing “major boosting” {id.), the Examiner persuades us
that an ordinary artisan practicing Gherardi’s method had good reasons for,
and a reasonable expectation of success in, substituting the VSV immunizing
vectors taught in Rose for the vaccinia virus vectors used in Gherardi’s
boosting composition. The Examiner, therefore, also persuades us that the
process recited in Appellants’ representative claim 1 would have been prima
facie obvious to an ordinary artisan.
Appellants’ arguments do not persuade us to the contrary.
Appellants contend that the Examiner failed to consider the full scope
of the prior art, and ignored the fact that numerous primer-booster
combinations were known in the art to be useful for generating immune
responses. App. Br. 3—11; Reply Br. 3^4. In particular, Appellants cite a
number of references to show that, in addition to the DNA-based primer
composition/rVSV-based booster composition regimen recited in
Appellants’ claim 1, it was known in the art that a variety of antigen delivery
techniques were useful for generating immune responses, including
protein/polypeptide antigens, adenovirus delivery, adenovirus-associated
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delivery, alphavirus, flaviviras, Herpes Simplex Vims, Lactobacillus,
Paramyxovirus, Poliovims, Poxvims, Proviral DNA, and Salmonella. App.
Br. 4—7. Appellants cite additional references to show that the numerous
potential antigen delivery techniques known in the art were known to be
combined in a number of different ways to yield a large number of different
primer/booster regimens. Id. at 7—11.
We are not persuaded that the Examiner failed to consider the full
scope of the prior art. Nor are we persuaded that the Examiner employed
improper hindsight in making the conclusion of obviousness, as Appellants
contend. See id. at 15—16, 18; see also Reply Br. 6—7.
That numerous antigen delivery techniques and numerous prime/boost
regimens were known in the art does not negate Gherardi’s disclosure, noted
above and cited by the Examiner, of a regimen useful for generating an
immune response to the HIV Env antigen. Gherardi 6278 (“The delivery of
IL-12 and Env product during priming with a DNA vector, followed by a
booster with VV [vaccinia vims] expressing the Env gene (rVVenv), was
found to trigger the optimal CMI [cell-mediated immune] response
compared with other immunization schedules studied.”).
Thus, given Gherardi’s disclosure of the usefulness of its process in
generating an immune response to the HIV Env antigen, an ordinary artisan
had a reason, based on the prior art rather than on improper hindsight, to use
Gherardi’s process when generating an immune response to that antigen. As
noted above, moreover, Rose teaches that using VSV as an immunizing
vector for the same antigen, including in the boost composition, provides a
number of desirable advantages, among them a many-fold improvement in
the level of immune response generated, as compared to the specific virus
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used in Gherardi’s process. Rose 546. Again, therefore, rather than
improper hindsight, the prior art cited by the Examiner provides ample
reason for substituting Rose’s VSV for Gherardi’s vaccinia virus in
Gherardi’s process.
We are not persuaded, moreover, that because numerous useful
options existed in the prior art, selection of any one particular suitable option
would necessarily be unobvious, based solely on the presence of a large
number of options, as Appellants seem to suggest. See App. Br. 17—18.
Taken to its logical extension, the selection of any known and useful
solution in a crowded art, or in any technological pursuit (as here) for which
numerous suitable options have been advanced, would necessarily be
unobvious, based solely on the fact that numerous viable options were
available. In that regard, to the extent Appellants suggest that motivation
exists for only the most desirable option available, our reviewing court has
squarely rejected that proposition:
[0]ur case law does not require that a particular combination
must be the preferred, or the most desirable, combination
described in the prior art in order to provide motivation for the
current invention. “[T]he question is whether there is
something in the prior art as a whole to suggest the desirability,
and thus the obviousness, of making the combination,” not
whether there is something in the prior art as a whole to suggest
that the combination is the most desirable combination
available. See In re Beattie, 91A F.2d [1309,] 1311 (internal
quotation omitted; emphasis added). . . . [A] finding that the
prior art as a whole suggests the desirability of a particular
combination need not be supported by a finding that the prior
art suggests that the combination claimed by the patent
applicant is the preferred, or most desirable, combination.
In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004).
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While we acknowledge the asserted differences between
representative claim 1 and Schnell, Ramshaw, Haglund, Rovinski, Ertl,
Gherardi, and Rose (see App. Br. 11—15; Reply Br. 1—2), we are not
persuaded that the Examiner failed to ascertain the differences between the
claimed invention and the prior art, as Appellants argue (see App. Br. 11—
15). As noted above, the Examiner found, and we agree, that Gherardi
describes a process, useful for generating an immune response to the HIV
Env antigen, that differs from the process recited in Appellants’ claim 1 only
in that Gherardi uses a vaccinia virus in its booster composition, rather than
the rVSV recited in claim 1. See Ans. 9—10. Because the Examiner
identified a reference describing a process distinguishable from the claimed
process only as to that single difference, Appellants do not persuade us the
Examiner failed to the make the required fact finding of ascertaining the
differences between the claimed invention and the most relevant prior art.
Appellants argue, under KSR Int 7 Co. v. Teleflex Inc., 550 U.S. 398
(2007), Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358
(Fed. Cir. 2008), Abbott Labs. v. Sandoz, Inc., 544 F.3d 1341 (Fed Cir
2008), and Eisai Co. Ltd. v. Dr. Reddy's Laboratories, Ltd., 533 F.3d 1353
(Fed. Cir. 2008), that “[a]n invention is not obvious if the following factors
are present:
• The number of possible alternatives is not small,
• The results obtainable from each alternative, alone or in
combination, are not predictable, and
• The claimed invention is identified through the use of
hindsight.”
App. Br. 17—18; see also Reply Br. 4—5.
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We are not persuaded, however, that the present facts meet the
criteria Appellants advance.
As an initial matter, Appellants do not persuade us that KSR stands for
the requirement implied by Appellants, that obviousness can be shown only
when the prior art presents a small number of options. To the contrary, the
Supreme Court reaffirmed, without condition on the number of prior art
options, that “when a patent ‘simply arranges old elements with each
performing the same function it had been known to perform’ and yields no
more than one would expect from such an arrangement, the combination is
obvious.” KSR, 550 U.S. at 417 (quoting Sakraida v. AgPro, Inc., 425 U.S.
273, 282 (1976)).
Moreover, rather than presenting innumerable options as to antigen
presentation techniques, Appellants identify only fourteen options, “a”
though “n.” App. Br. 4—7. Thus, on the current record, an ordinary artisan
seeking to induce an immune response using a prime-boost technique was
not faced with an insurmountably vast universe of possible options. Rather,
the evidence shows that the artisan had at hand a finite number antigen
presentation techniques which could be used in the priming composition,
and the same finite number antigen presentation techniques which could be
used in the boosting composition.
For the reasons discussed above, moreover, Appellants do not
persuade us that selecting Gherardi’s prime-boost regimen would have been
based on hindsight. Nor are we persuaded, for the reasons discussed above,
that substituting Rose’s VSV for the vaccinia virus boost composition in
Gherardi’s process would only have been done through hindsight.
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Appellants also do not persuade us that they have advanced evidence
of unpredictability sufficient to undercut the Examiner’s prima facie case.
We acknowledge Ramshaw’s disclosure that, in experiments involving a
malaria vaccine, a DNA prime/vaccinia virus (VV) boost regimen was
rendered inoperative merely by changing the order of prime versus boost, or
changing the strain of virus in the boosting composition. Ramshaw 164
(“Either reversing the order of immunization or changing the strain of VV
from MVA [modified vaccinia virus Ankara strain] or the closely related
NYVAC strain to the WR strain (which replicates extensively in mice),
resulted in a failure of protection.”).
We acknowledge also the disclosures in Allen,10 Horton,11 and
Woodberry,12 that using a DNA prime/MVA boost regimen failed to induce
fully protective immune responses. See Allen 4108 (abstract); Horton 7187
(abstract); Woodberry 2599 (abstract).
The prime-boost regimen in Ramshaw, however, relates to a different
antigen (malaria) than the HIV Env antigen described in Gherardi and Rose.
See Ramshaw 164. Moreover, each of Ramshaw, Allen, Horton, and
10 Todd M. Allen et al., Tat-VaccinatedMacaques Do Not Control Simian
Immunodeficiency Virus SIVmac239 Replication, 76 J. Virol. 4108—12
(2002).
11 Helen Horton et al., Immunization of Rhesus Macaques with a DNA
Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad
Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and
Reduces Initial Viral Replication but Does Not Prevent Disease Progression
fallowing Challenge with Pathogenic SIVmac239, 76 J. Virol. 7187—202
(2002).
12 Tonia Woodberry et al., Prime Boost Vaccination Strategies: CD8 T Cell
Numbers, Protection, and Thl Bias, 170 J. Immunol. 2599-604 (2003).
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Woodberry uses a different boosting vector, modified vaccinia virus Ankara
strain (MVA), than the VSV vector taught in Rose as providing a six- to ten­
fold improvement over vaccinia virus when used to generate an immune
response to the HIV Env antigen. See Ramshaw 164; Allen 4108 (abstract);
Horton 7187 (abstract); Woodberry 2599 (abstract). Appellants do not
persuade us, therefore, that the disclosures of Ramshaw, Allen, Horton, and
Woodberry demonstrate that an ordinary artisan lacked a reasonable
expectation of success when substituting Rose’s VSV for the vaccinia virus
in Gherardi’s boost composition. Indeed, the alleged lack of ultimate
success in using the MVA booster described in Allen, Horton, and
Woodberry actually bolsters the Examiner’s position that an ordinary artisan
had good reason to substitute VSV for vaccinia virus in Gherardi’s booster
composition, particularly in light of Rose’s teaching, discussed above, that
VSV provided a six- to ten-fold improvement over vaccinia virus with
respect to generating an immune response.
In addition, although Ramshaw, Allen, Horton, and Woodberry might
suggest that an ordinary artisan would not have been able to predict with
absolute certainty whether Rose’s VSV would be useful in the boosting
composition in Gherardi’s process, a conclusion of prima facie obviousness
does not require that degree of predictability. See In re O ’Farrell, 853 F.2d
894, 903-04 (Fed. Cir. 1988) (“Obviousness does not require absolute
predictability of success. . . . For obviousness under § 103, all that is
required is a reasonable expectation of success.”); accord, In re Kubin, 561
F.3d 1351, 1359-61 (Fed. Cir. 2009).
Appellants’ arguments (App. Br. 21; Reply Br. 7—8), also do not
persuade us that the prior art teaches away from the process recited in
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representative claim 1. We again acknowledge Ramshaw’s disclosure that,
in experiments involving a malaria vaccine, a DNA prime/vaccinia virus
(VV) boost regimen was rendered inoperative merely by changing the order
of prime versus boost, or changing the strain of virus in the boosting
composition. Ramshaw 164. We acknowledge also Sutter’s13 disclosure
that VSV lacked certain attributes present in other viral vectors used for
inducing immune responses. Sutter S141 (Table 1).
As our reviewing court has explained, however, a reference “does not
teach away ... if it merely expresses a general preference for an alternative
invention but does not ‘criticize, discredit, or otherwise discourage’
investigation into the invention claimed.” DePuy Spine, Inc. v. Medtronic
Sofamor Danek, Inc., 567 F.3d 1314, 1327 (Fed. Cir. 2009) (citation
omitted).
In the present case, Appellants do not identify any discussion in
Ramshaw regarding VSV, nor do Appellants identity any disclosures in
either Ramshaw or Sutter criticizing, discrediting, or otherwise discouraging
investigation into the claimed invention. While Sutter might suggest that
VSV would not have been the preferred alternative, that suggestion does not
constitute a teaching away. See id. Sutter’s teachings, moreover, must also
be viewed in light of the disclosure in Rose, discussed above, that VSV
provided a six- to ten-fold improvement over vaccinia virus with respect to
generating an immune response, and also in light of the other advantages
Rose describes when using VSV.
13 Gerd Sutter and Jurgen Haas, Novel vaccine delivery systems: solutions to
HIV vaccine dilemmas?, 15 Aids S139—145 (2001).
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In sum, for the reasons discussed, Appellants do not persuade us that
the evidence of record fails to support the Examiner’s prima facie case of
obviousness as to representative claim 1. Appellants also do not persuade
us, for the reasons discussed below, that they have advanced secondary
evidence of obviousness sufficient to outweigh the evidence of prima facie
obviousness discussed above.
Appellants contend that, as compared to studies discussed in
Ramshaw, the results of the experiment described in Example 3 of the
Specification, shown in Appellants’ Figures 2—5 and Table 1, demonstrate
that the claimed invention demonstrates unexpected results. App. Br. 21—22.
We are not persuaded. It is well settled that that “when unexpected
results are used as evidence of nonobviousness, the results must be shown to
be unexpected compared with the closest prior art.” In re Baxter-Travenol
Labs., 952 F.2d 388, 392 (Fed. Cir. 1991).
In the instant case, we understand the closest prior art of record to be
Gherardi, which, as discussed, describes a method of generating an immune
response by co-administering a plasmid encoding the target antigen and a
plasmid encoding IF-12, as the priming composition, followed by a viral
vector boosting composition. Gherardi 6278 (abstract), 6280.
In contrast, the evidenced advanced by Appellants relates to a
comparison between multiple priming compositions only, and multiple
boosting compositions only. See Spec. 43 (“The results of these assays
demonstrate a surprising synergistic effect of a prime/boost regimen
according to this invention, when compared to the results of administering
multiple priming compositions only and multiple boosting compositions
only.” (emphasis added)).
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Because the evidence of unexpected results advanced by Appellants
does not include a comparison to a method of generating an immune
response by co-administering a plasmid encoding the target antigen and a
plasmid encoding IL-12, as the priming composition, followed by a viral
vector boosting composition, as taught by the closest prior art (Gherardi),
Appellants do not persuade us that the evidence of unexpected results is
sufficient to outweigh the evidence, discussed above, of prima facie
obviousness.
It is also well settled that “objective evidence of nonobviousness must
be commensurate in scope with the claims.” In re Kulling, 897 F.2d 1147,
1149 (Fed. Cir. 1990) (citation omitted). In the instant case, the evidence of
unexpected results advanced by Appellants is limited to macaques (see Spec.
39-44 (Example 3)), whereas representative claim 1 encompasses any
mammalian subject.
In sum, for the reasons discussed, Appellants do not persuade us that
the evidence of record fails to support the Examiner’s prima facie case of
obviousness as to representative claim 1. Because, for the reasons
discussed, Appellants have not advanced secondary evidence of
nonobviousness sufficient to outweigh the evidence of prima facie
obviousness advanced by the Examiner, we affirm the Examiner’s rejection
of claim 1 over the cited references. Because they were not argued
separately, claims 3—5, 16—18, 20—25, 32—35, 40, and 42 fall with claim 1.
See 37 C.F.R. § 41.37(c)(l)(iv).
As to the remaining claims, Appellants contend that the cited
references fail to teach or suggest the invention recited in claims 2, 36, 37,
and 41. App. Br. 12; Reply Br. 8.
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Technically, to argue claims separately, “[u]nder each heading
identifying the ground of rejection being contested, any claim(s) argued
separately or as a subgroup shall be argued under a separate subheading that
identifies the claim(s) by number.” 37 C.F.R. § 41.37(c)(l)(iv). Appellants
have not presented argument as to separate claims by providing a separate
subheading, as required.
Nevertheless, each of claims 2, 36, and 41 is a dependent claim that
requires the virus used in the boosting composition to be a replication
competent virus. See App. Br. 24, 27. As noted above, Rose discloses that
one major advantage of using VSV as an antigen delivery vector is that it is
replication competent. Rose 546. Given this teaching, Appellants do not
persuade us that the cited references fail to suggest using a replication
competent VSV in Gherardi’s boosting composition. We, therefore, affirm
the Examiner’s rejection as to claims 2, 36, and 41 as well.
Claim 37, by contrast, requires the VSV to be replication incompetent.
App. Br. 27. As Appellants point out (see, e.g., App. Br. 12), Ramshaw
discloses that using replication incompetent viruses as vectors may also have
certain advantages. Ramshaw 163 (“[Rjecombinant viral vectors,
particularly those that are in some way, unable to replicate in mammalian
hosts . . . have significant advantages over alternative immunization
strategies. These constructs are replication deficient, non-integrating, stable
and are relatively easy to prepare.”).
Accordingly, Appellants do not persuade us that the cited references
fail to suggest the replication incompetent virus recited in Appellants’ claim
37. Although following Ramshaw’s teachings and using a replication
incompetent virus would negate one of the advantages described by Rose for
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using VSV, Rose, nonetheless describes a number of other advantages
attendant to using VSV viruses as immunizing vectors, including, among
others, a six- to ten-fold improvement in the immune response generated, as
compared to vaccinia viruses. Accordingly, because Appellants do not
persuade us that the cited prior art fails to suggest the use of a replication
incompetent VSV in a boosting composition, as recited in Appellants’ claim
37, we affirm the Examiner’s obviousness rejection as to that claim as well.
SUMMARY
For the reasons discussed, we affirm the Examiner’s rejection of
claims 1—5, 16—18, 20—25, 32—37, and 40-42 under 35 U.S.C. § 103(a) for
obviousness over Schnell, Gherardi, Rose, Ramshaw, Rovinski, Ertl, and
Haglund.
TIME PERIOD
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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