Ex Parte Cain

Patent Trials and Appeals Board

Jun 14, 2019

13570303 - (D) (P.T.A.B. Jun. 14, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
13/570,303 08/09/2012 Kenneth D. Cain
29085 7590 06/17/2019
HOW ARD EISENBERG, ESQ.
200 Price A venue
Elm#4
Narberth, PA 19072
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.
814.0051 8445
EXAMINER
ZEMAN, ROBERT A
ART UNIT PAPER NUMBER
1645
MAIL DATE DELIVERY MODE
06/17/2019 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte KENNETH D. CAIN 1
Appeal2018-008253
Application 13/570,303 2
Technology Center 1600
Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and
ELIZBETH A. LA VIER, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This Appeal involves claims directed to a fish vaccine that contains a
live attenuated and avirulent derivative strain of a bacterium. The Examiner
rejected the claims as unpatentable under obviousness-type double-
patenting, as obvious under 35 U.S.C. § 103, and lacking a written
description under 35 U.S.C. § 112. Pursuant to 35 U.S.C. § 134, Appellant
appeals the Examiner's determination that the claims are unpatentable. We
have jurisdiction for the appeal under 35 U.S.C. § 6(b ).
The Examiner's decision is affirmed.
1 The Appeal Brief(" Appeal Br." entered March 6, 2018) lists The Board of
Regents of the University of Idaho as the real party in interest. Appeal Br. 3.
2 Referred to herein as "the '303 Application", "the Specification", or
"Spec.").
Appeal2018-008253
Application 13/570,303
STATEMENT OF THE CASE
The claims stand rejected by the Examiner as follows:
1. Claims 4---6, 10, and 11 on the ground of non-statutory
obviousness-type double patenting as unpatentable over claims 7-9 of U.S.
Patent No. 7,740,864 B2 (issued June 22, 2010) ("Cain '864") in view of
LaFrentz et al. (B. R. LaFrentz, Proteomic analysis of Flavobacterium
psychrophilum cultured in vivo and in iron-limited media, 87 DISEASES OF
AQUATIC ORGANISMS 171-82 (2009)) ("LaFrentz"). Ans. 3.
2. Claims 4---6, 10, and 11 under pre-AIA 35 U.S.C. § 103(a) as
obvious over Cain '864 and LaFrentz. Id. at 7.
3. Claims 4, 5, 10, and 11 under 35 U.S.C. § 112(a) or 35 U.S.C.
§ 112 (pre-AIA), first paragraph, as failing to comply with the written
description requirement. Id. at 4.
Claim 4 is illustrative of the claimed subject matter and reads as
follows (indents added for clarity):
4. A method for reducing morbidity and/or mortality of fish
due to disease caused by a bacterium comprising
administering to the fish a vaccine that contains a live
attenuated and a virulent derivative strain of the bacterium that
is effective to reduce morbidity and/or mortality of the fish due
to the disease caused by a live non-attenuated pathogenic strain
of the same bacterium and
which effective live attenuated and avirulent derivative
strain that is administered has been grown, prior to the
administering, in or on a medium that is iron-limited
from a live attenuated and avirulent primary strain which
had been grown in or on a medium that is not iron-limited, and
which attenuated and avirulent primary strain is effective in
reducing morbidity and/or mortality due to disease caused by
exposure of the fish to a live non-attenuated pathogenic strain
of the bacterium.
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Application 13/570,303
DOUBLE PATENTING REJECTION
The Examiner found that Cain '864 discloses methods of protecting
fish against diseases caused by Flavobacterium psychrophilum using a
Flavobacterium psychrophilum designated 259-93.B.17 which is deposited
with the ATCC under the accession number PTA-9205). Ans. 3. Claim 7 of
Cain '864 (14:40-45) is reproduced below:
7. A method of protecting non-wounded fish against disease
caused by non-attenuated Flavobacterium psychrophilum
comprising administering to the fish by mass immersion an
amount of an isolated, live attenuated, rifampicin-resistant
Flavobacterium psychrophilum sufficient to provide protection
to the non-wounded fish against the disease.
The Examiner found that Cain '864 differs from the rejected claims in
that it does not explicitly disclose the recited step of claim 4 in which the
strain "that is administered has been grown, prior to the administering, in or
on a medium that is iron-limited." Appeal Br. 29, 30 (Claims Appendix)
( claim 4, claim 11) ("which derivative strain that is administered has been
grown, prior to the administering, in or on an iron-limited medium.").
To address this deficiency, the Examiner cited the LaFrentz
publication. The Examiner found that LaFrentz discloses:
that the development of whole cell Flavobacterium
psychrophilum vaccines that can be administered using mass
delivery methods has not been successful since in vitro culture
conditions do not represent in vivo conditions and that iron,
which is readily available in culture media, is limited in vivo
due to host production of iron-binding proteins.
Ans. 3. The Examiner further that LaFrentz discloses that protein expression
differs between bacteria grown in iron-limited media and in media that is not
iron limited. Id. at 3--4. LaFrentz specifically identified proteins up-
regulated during culture of bacteria under in vivo and iron-limited media
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Application 13/570,303
conditions, and suggested "a role ofupregulated proteins in the pathogenesis
of F. psychrophilum" and that "these [proteins] may represent potential
vaccine candidate antigens." LaFrentz 171 (Abstract).
The Examiner determined it would have been obvious to one of
ordinary skill in the art to culture the Flavobacterium psychrophilum of Cain
'864 in iron-limited media prior to administration as required by the rejected
claims "to obtain a vaccine that is more immunologically identical to
bacterium found in nature (and therefore likely to be more effective) and
[that] could be administered via mass-delivery methods." Ans. 4. The
Examiner also found that one of ordinary skill in the art would be motivated
to do so "given the need for safer and more immunogenic vaccines." Id.
Appellant argues that LaFrentz is not pertinent because it "does not
pertain to using whole bacterial organisms as vaccine[s], but rather pertains
to using isolated proteins as vaccines." Appeal Br. 14.
This argument does not demonstrate persuasive error in the
Examiner's rejection. LaFrentz was not relied by the Examiner as the basis
for the vaccine. Rather, the Examiner cited Cain '864, whose claims are
directed to administering "isolated, live attenuated, rifampicin-resistant
Flavobacterium psychrophilum", for disclosing whole bacterial organisms as
a vaccine. Appellant did not establish that one of ordinary skill in the art
would not have looked to LaFrentz for guidance in making whole cell
attenuated vaccines. LaFrentz describes in its introduction the "need for an
effective vaccine," without limiting the vaccine to one involving only
isolated proteins. LaFrentz 171. LaFrentz also expressly mentions
"vaccines based on killed whole-cell preparations." Id. at 172. Thus, we are
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Application 13/570,303
not persuaded that the skilled worker seeking to improve vaccination would
not have considered the teachings in LaFrentz pertinent to this endeavor.
Appellant also disparages LaFrentz because it "pertains solely to the
growth of virulent, wild-type bacteria on iron-limited medium" and there is
no suggestion in it "that the effectiveness of an attenuated avirulent
bacterium grown on iron-rich medium would be increased if an attenuated
a virulent bacterium were grown in or on iron-limited medium." Appeal Br.
14. Appellant contends that the skilled worker would be "unable to predict
what differences in gene expression, if any, would occur in attenuated non-
virulent bacteria compared to wild-type" because of the changes to bacterial
genes that occur during attenuation. Id. Furthermore, Appellant that there is
"there is no indication in LaFrentz" that the up-regulation of proteins
observed in the iron-limited media would occur "if an attenuated bacteria
were to be grown on iron limited medium." Id. at 15.
Appellant has not provided adequate objective evidence that
attenuated bacteria, as claimed, would behave differently in iron-limited
media as compared to unattenuated bacteria, as described in LaFrentz.
While the Specification discloses that attenuation involves genetic changes,
e.g., in "genes involved in metabolic pathways and/or pathogenesis" (Spec.
2: 19-3: 1 ), Appellant did not provide evidence that such changes would
affect gene expression on an iron-limited media. An argument made by
counsel in a brief does not substitute for evidence lacking in the record.
Estee Lauder Inc. v. L 'Orea!, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997).
Appellant also argues that proteins up-regulated in iron-limited media
are not necessarily viable vaccine candidates. Appeal Br. 15. As evidence
of this, Appellant cited the Plant publication (Plant et al., FEMS Micro biol.
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Lett, 214, 358: 14--26) which Appellant states shows that GldN, a protein
up-regulated in LaFrentz when bacteria were cultured in iron-limited media,
was not a viable vaccine candidate. Id.
Plant was published in 2014. The priority date for the '303
Application is August 25, 2011. Obviousness is determined at the time of
the invention. 35 U.S.C. § 103(a) (pre-AIA) ("[T]he subject matter as a
whole would have been obvious at the time the invention was made to a
person having ordinary skill in the art to which said subject matter
pertains."). Plant, therefore, does not provide evidence of what one of
ordinary skill in the art would have reasonably expected "at the time the
invention was made."
Appellant also argues that the Examiner's logic that it would have
been obvious to culture the bacteria in iron-poor media is incorrect. Appeal
Br. 15-16. Appellant contends it "should make little or no difference"
whether the bacteria were cultured in iron-limited media prior to
administration because "after being administered, the bacteria would
necessarily grow in an iron-limited medium, and therefore, after growing for
a time within the iron-poor environment within the fish, they would produce
a similar protein expression pattern as would bacteria that were grown in
iron-limited media before administration to a fish." Id. at 16. Appellant
argues that, in contrast, the '303 Application discloses "the unexpected
discovery" that the attenuated bacteria grown in iron-limited media
enhanced vaccine effectiveness as compared to a vaccine already shown to
be effective. Id.
With respect to the argument that culturing bacteria in iron-limited
media "should make little or no difference", the Examiner responded that the
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bacteria comprising the vaccine "would not be present within the fish long
enough for an adaptation to a new environment (i.e. to shift their
phenotypes)" because they would be cleared by the immune system before
the transition can occur. Ans. 12. Appellant did not dispute the Examiner's
scientific reasoning, but rather argued that "a great difference" was
demonstrated in the '303 Application itself. Reply Br. 6-7.
However, as found by the Examiner, LaFrentz provides an
expectation that culture in iron-limiting conditions could provide better
targets for vaccination. LaFrentz discloses the inadequacy of whole-cell
vaccmes:
A possible explanation for the lack of protection foHowing
immunization with killed whole-cell F'lmiobacterium
p.\ychrophi!um preparations is that impmiant virulence
determinants and/or protective components of the bacterium are
not produced during in vitro culture in standard bacteriological
rnedia.
LaFrentz 172. Thus, LaFrentz discusses the deficiencies of in vitro culture.
To address this problem; LaFrentz cites scientific literature suggesting
the study of proteins expressed under in vivo conditions.
Id.
Brown et aL (1988) suggested that bacteria grown in vivo
should be analvzed in studies ahned at identifving virulence
J w ~
factors and vaccine candidate antigens, because expression of
these factors rnav be altered in the in vitro environment.
J
LaFrentz's study was undertaken to compare proteins expressed under
in vivo and iron-limited conditions:
Flavobacteriwn psychrophilum is the etiologic agent of
bacterial coldwater disease1 but the pathogenic mechanisms of
this important fish pathogen are not fully understood.
Identifying bacterial genes of F. psychrophilum differentially
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Application 13/570,303
expressed in vivo may lead to a better understanding of
pathogenesis and provide targets for vaccine development
LaFrentz 171 ( Abstract).
LaFrentz identified up-regulated proteins in its experiments can-ied
out in culture conditions. id. Based on these results, LaFrentz concluded:
It is likely that at least some of these proteins are involved in
the pathogenesis of this fish pathogen. Future research should
be aimed at determining the precise roles of these proteins in
the pathogenesis of F. psychrophilum and evaluating their
potential to provide protection against C\VD when used in
irnmunization trials.
Id. at 180.
Appellant has not provide adequate evidence, in view of this
disclosure of proteins up-regulated during in vitro culture under iron Hmiting
conditions and "Hkely ... involved in the pathogenesis," that little or no
difference in vaccine performance would be expected when the bacteria cells
were grown in iron-limiting conditions prior to administration.
As discussed above, Appellant did not establish by objective evidence
that attenuation would affect the pattern of expression in iron lirnited media.
vVhile LaFrentz discussed individual antigens1 Cain '864 provides the reason
to have used whole attenuated bacterial cells as the vehicle to deliver the
antigens for vaccination purposes.
Accordingly, the preponderance of the evidence supports the
Examiner's finding that one of ordinary skill in the art would have had
reason to grow that attenuated bacteria in the iron-limited media prior to
administration to the fish to provide the opportunity for the bacteria to
express the up-regulated proteins (LaFrentz 171 (Abstract)).
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Unexpected results
Appellant contend that the '303 Application discloses the "unexpected
discovery that, by taking an attenuated bacterial vaccine, one that had
already been shown to be effective as a vaccine, and then growing that same
attenuated bacteria in or on iron-limited media, and then administering this
vaccine to a fish, the effectiveness of the vaccine is greatly enhanced."
Appeal Br. 16.
Appellant directs us to Example 4 of the '303 Application as evidence
of unexpected results. Appeal Br. 16. Example 4a discloses the results for
the fish vaccinated by injection as described in Example 2a. Spec. 13.
Example 4b describes the results for fish vaccinated by immersion as
described in Example 2b. Spec. 14--15. The fish used in the examples were
Coho salmon ( Oncorhynchus kisutch ). Spec. 11: 8-9. The strain of bacteria
was CSF259-93 .B 17, the same strain disclosed and claimed ( claim 9) in
Cain '864. Spec. 11:14--15.
In Example 4a, as shown in Table 1 of the '303 Application, the
unvaccinated control fish, had a mortality rate of 65.3%. Spec. 13. In
contrast, fish vaccinated with CSF259-93.Bl 7 had a mortality rate of only
6. 7% and a relative survival rate of 90% as compared to the unvaccinated
control. Fish vaccinated with CSF259-93 .B 17 grown in iron-limited media
prior to administration, as required by the rejected claims, had a mortality
rate of 1.3% and a relative survival rate of 98% as compared to the control.
Appellant calculates this difference to be an 80% increase in survival rate by
using CSF259-93 .B 1 7 grown in iron-limited media. Appeal Br. 9.
In Example 4b, as shown in Table 2 of the '303 Application,
unvaccinated fish had a mortality rate of 54 %, while fish vaccinated with
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CSF259-93.Bl 7 had a mortality rate of 29.3% and a relative survival rate of
46% as compared to the unvaccinated control. Spec. 15. Fish vaccinated
with CSF259-93 .B 17 grown in iron-limited media prior to administration, as
required by the rejected claims, had a mortality rate of 14. 7% and a relative
survival rate of 73% as compared to the control. Appellant calculates this
difference to be a 49% increase in survival rate by using CSF259-93.Bl 7
grown in iron-limited media. Appeal Br. 9.
A showing of "unexpected results" can be used to demonstrate the
non-obviousness of a claimed invention. In re Soni, 54 F.3d 746, 750 (Fed.
Cir. 1995) ("One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of 'unexpected results,' i.e., to show that
the claimed invention exhibits some superior property or advantage that a
person of ordinary skill in the relevant art would have found surprising or
unexpected."). Those results must be "surprising or unexpected" to one of
ordinary skill in the art when considered in the context of the closest prior
art. Id. "Mere improvement in properties does not always suffice to show
unexpected results .... [H]owever, when an applicant demonstrates
substantially improved results, ... and states that the results were
unexpected, this should suffice to establish unexpected results in the absence
of evidence to the contrary." Id. at 7 51.
It is stated in the '303 Application that "enhanced protection obtained
by vaccination with a bacterial strain that has been grown in or on an iron-
limited medium is surprising because iron is an essential element for
bacterial growth and, therefore, media on which bacteria are grown
generally include iron-containing ingredients." Spec. 5:20-6: 1. While the
Specification contains a statement that the results are "surprising" as
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required under Soni, it explains that this is because iron is considered an
essential element for growth. However, LaFrentz describes culturing cells
under iron-limited conditions. LaFrentz used the iron chelator DPD to
chelate and limit iron in the media. LaFrentz 172-173. LaFrentz reported
that DPD inhibited bacterial growth, but used a reduced concentration of
DPD "for the subsequent growth of F. psychrophilum in iron-limited
conditions to identify proteins with different spot intensities." Id. at 174
("Growth in iron-limited media"). Thus, the Specification's explanation as
to why for the enhanced protection is "surprising" appears to have
undermined by LaFrentz, who teaches growing bacteria under iron-limiting
conditions. Appellant did not provide adequate objective evidence that the
results described in the Specification would have been obvious to one of
ordinary skill in that art in view of the cited LaFrentz publication.
Even if the data disclosed in the '303 Application are considered to be
unexpected in view of Cain '864 and LaFrentz, however, these data are not
commensurate with the full scope of the claims. Unexpected results must be
"commensurate in scope with the degree of protection sought by the claimed
subject matter." In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005). The
results in Example 4 are for a single attenuated strain of bacteria,
Flavobacterium p,~ychrophilum CSF259-93.Bl 7, in a single fish species,
Coho salmon ( Oncorhynchus kisutch ). Claim 4, however, is not limited to a
specific fish or attenuated bacterial strain. Claim 11 is also not limited to
specific fish or to a specific attenuated Flavobacteriurn psychrophilum.
Appellant has not provided an explanation as to why this single example in
the Specification, using one attenuated strain and one fish species,
establishes that any disease causing bacteria in any fish species, would show
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the amount of enhancement in survival asserted to be unexpected for
Flavobacterium psychrophilum CSF259-93 .B 17 in Coho salmon.
Summary
For the foregoing reasons and those of the Examiner, the obviousness-
type double-patenting rejection of claim 4 is affirmed. Claims 5, 6, 10, and
11 were not argued separately and fall with claim 4. 37 C.F.R.
§ 4I.37(c)(l)(iv).
OBVIOUSNESS BASED ON CAIN '864 AND LAFRENTZ
Appellant's arguments for the rejection under 35 U.S.C. § 103 based
on Cain '864 and LaFrentz are the same as those the obviousness-type
double-patenting. Appeal Br. 24--28. For the foregoing reasons and those of
the Examiner, the obviousness-type double-patenting rejection of claim 4 is
affirmed. Claims 5, 6, 10, and 11 were not argued separately and fall with
claim 4. 37 C.F.R. § 4I.37(c)(l)(iv).
WRITTEN DESCRIPTION REJECTION
To satisfy the written description requirement of 35 U.S.C. § 112, the
inventor must "convey with reasonable clarity to those skilled in the art that,
as of the filing date sought, he or she was in possession of the invention."
Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563---64 (Fed. Cir. 1991)
(emphasis omitted). "One shows that one is 'in possession' of the invention
by describing the invention, with all its claimed limitations .... " Lockwood
v. Am. Airlines, Inc., 107 F.3d 1565, 1572 (Fed. Cir. 1997) (emphasis
omitted).
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The Examiner stated that the claim lacked a written description
because the Specification "is silent as to what 'phenotype' is required for a
given bacteria to an effective vaccine against a given bacterial fish pathogen
or whether there is a correlation between phenotype and efficacy as a
vaccine." Ans. 5. The Examiner also stated:
Id.
the [S]pecification does not disclose distinguishing and
identifying features of a representative number of members of
the genus of vaccines to which the claims are drawn, such as a
correlation between the structure of the bacteria (phenotype)
and its recited function (to elicit the recited immune response),
so that the skilled artisan could immediately envision, or
recognize at least a substantial number of members of the
claimed genus of vaccines.
We are not persuaded by the Examiner's analysis that the claims do
not comply with the written description requirement of 35 U.S.C. § 112.
The "phenotype" of the claimed avirulent strains is that it is "attenuated" and
"effective to reduce morbidity and/or mortality of the fish due to the disease
caused by a live non-attenuated pathogenic strain of the same bacterium."
The Specification describes attenuation:
Direct and random approaches can be used to induce mutations
into bacterial pathogens to achieve attenuation. Direct
approaches include mutation or deletion of genes involved in
metabolic pathways and/or pathogenesis, while random
approaches include genetic methods such as transposon
mutagenesis or the use of chemicals such as antibiotics.
Spec. 2:20-3:1. From this description, it appears that attenuation can be
achieved in different ways and accomplished by different mutations ( e.g., in
genes involved metabolic pathways and/or pathogenesis). The Examiner's
requirement that attenuated strains have a specific "structure" did not take
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into account this explicit disclosure in the Specification that different
structural genomic changes can be responsible for the same attenuated
phenotype.
The Examiner also requires that there be a substantial number of
members of the claimed genus of vaccines to envision the genus. However,
the Specification discloses that attenuated live bacterial vaccines affecting
fish were known in the art and cites five examples. Spec. 3:5-15. The
Examiner did not explain why these disclosed examples were insufficient to
establish that the inventor had possession of the claimed genus of attenuated,
avirulent bacteria.
In our view, the disclosure of the five examples of attenuated strains,
the description of attenuation, and the working examples of an attenuated,
a virulent species within the scope of the claim (Example 4 ), establishes that
the inventor had possession of the claimed invention with all its limitations.
The written description rejection of claims 4, 5, 10, and 11 is reversed.
DECISION
Claims 4---6, 10, and 11 on the ground of non-statutory double
patenting over claims 7-9 of Cain '864 in view ofLaFrentz is affirmed.
Claims 4---6, 10, and 11 under pre-AIA 35 U.S.C. § 103(a) as obvious
over Cain '864 and LaFrentz is affirmed.
Claims 4, 5, 10, and 11 under 35 U.S.C. § 112(a) or 35 U.S.C.
§ 112 (pre-AIA), first paragraph, as failing to comply with the written
description requirement is reversed.
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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)(l)(iv).
AFFIRMED
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