Ex Parte Weise et al

Patent Trial and Appeal Board

Jan 10, 2018

13995688 (P.T.A.B. Jan. 10, 2018)

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.
13/995,688 06/19/2013 Dale Wade Weise X19557 8088
25885 7590 01/12/2018
FT T T TT T Y fr TOMPANY
EXAMINER
PATENT DIVISION HORNING, MICHELLE S
P.O. BOX 6288
INDIANAPOLIS, IN 46206-6288 ART UNIT PAPER NUMBER
1648
NOTIFICATION DATE DELIVERY MODE
01/12/2018 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):
patents @ lilly.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DALE WADE WEISE and JAMES ROBERT HARRIS
Appeal 2017-001422
Application 13/995,688
Technology Center 1600
Before JEFFREY N. FREDMAN, TAWEN CHANG, and
RYAN H. FLAX, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal1 under 35U.S.C. § 134 involving claims to an
immunogenic composition comprising: a modified, live bovine viral diarrhea
virus type lb. The Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We affirm.
Statement of the Case
Background
“BVDV [bovine viral diarrhea virus] is now recognized as an
important etiologic agent in the Bovine Respiratory Disease Complex
(BRDC)” (Spec. 2:11-12). “The disease, which infects cattle of all ages
(including nursing calves), is characterized by rapid breathing, coughing,
1 Appellants identify the Real Party in Interest as Eli Lilly and Company (see
App. Br. 2).
Appeal 2017-001422
Application 13/995,688
depression, loss of appetite, ocular and nasal discharge, and elevated
temperatures” (Spec. 2:12—15). “BVDV-lb is the predominate subtype of PI
[persistently infected] cattle entering domestic feedlots, there are currently
no USDA-licensed vaccines that are specific for BVDV-lb infection” (Spec.
3:2-4).
“Because of the potential for great economic loss in unvaccinated
herds, there is a need for cost-effective (and preferably, single-dose)
vaccines containing modified, live BVDV-lb viruses that induce
prophylaxis against BVDV infections in mammalian livestock populations”
(Spec. 3:8-11).
The Claims
Claims 1—3, 6, 8, and 12 are on appeal. Independent claim 1 is
representative and reads as follows:
1. An immunogenic composition comprising: a modified,
live bovine viral diarrhea virus type lb (BVDV-lb), a
veterinary-acceptable carrier, and optionally an adjuvant;
wherein the modified, live BVDV-lb is a TGAC strain of
BVDV-lb altered by passaging in tissue culture cells.
The Issue
The Examiner rejected claims 1—3, 6, 8, and 12 under 35 U.S.C.
§ 103(a) as obvious over Meyers,2 Littledike,3 and Kumar4 (Final Act. 2-4).
2 Meyers et al., WO 2007/117303 A2, published Oct. 18, 2007.
3 Littledike et al., Consequences of Antigenic Diversity of Bovine Viral
Diarrhea Virus, Roman L. Hruska U.S. Meat Animal Research Center, 339,
pp. 180—182 (1993) (http://digitalcommons.unl.edu/hruskareports/339).
4 Kumar et al., US 2007/0031450 Al, published Feb. 8, 2007.
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Application 13/995,688
The Examiner finds Meyers teaches “a composition comprising a
modified, live [virus of] BVDV1, a veterinary-acceptable carrier, and [] an
adjuvant” (Final Act. 3). The Examiner finds Meyers teaches “the
production of attenuated viruses via repeated passage in bovine or porcine
cells are widely known and commonly used in the art” (id.).
The Examiner notes Meyers “does not explicitly describe that the
BVDV-lb is a TGAC strain that has been passaged in cells” (Final Act. 3).
The Examiner finds Littledike teaches “viral BVDV isolates, TGAC
and Singer” (Final Act. 3). The Examiner finds Kumar “teaches that both
BDV Type I and II can be passaged in tissue culture cells in order to
attenuate [their] ability to cause disease but maintain[] [their] ability to
protect against disease or infection when administered to animals” (id. at 4).
The Examiner finds it obvious to include “BVDV isolates that have
been attenuated via cell passaging, including TGAC and Singer, into the
composition taught by [Meyers]. One would have been motivated to do so
in order to induce immune responses in an animal in need thereof without
causing disease” (Final Act. 4).
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner’s conclusion
that Meyers, Littledike, and Kumar render claim 1 obvious?
(ii) If so, have Appellants presented evidence of secondary
considerations that, when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness?
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Findings of Fact
1. Meyers teaches a “vaccine for the treatment and/or prophylaxis
of microbiological infection in cattle, that comprises a live attenuated BVDV
as described herein and at least one further immunological active component
for treating or preventing diseases or disorders in cattle caused by an
infectious agents other than BVDV” (Meyers 27:30—33).
2. Meyers teaches:
The term “BVDV” as used herein refers to all viruses belonging
to species bovine viral diarrhea virus (BVDV) type 1 (BVDV-
1) and BVDV type 2 (BVDV-2), including any sub-species
such as la, lb, 2a, 2,b, and the like in the genus Pestivirus
within the family Flaviviridae .... The more classical BVDV
type 1 strains and the more recently recognized BVDV type 2
strains display some limited but distinctive differences in
nucleotide and amino acid sequences.
(Meyers 22:24—28).
3. Meyers teaches that “the immunogenic and vaccine
compositions of [its] invention can include one or more veterinary-
acceptable carriers. As used [in Meyers], ‘a veterinary-acceptable carrier’
includes any and all solvents, dispersion media, coatings, adjuvants”
(Meyers 98:21—24).
4. Meyers teaches:
Currently, licensed BVDV MLV vaccines are produced using
attenuated viruses obtained via repeated passage in bovine or
porcine cells ... A single dose of MLV vaccine is sufficient
for immunization, and duration of the immunity can last for
years in vaccinated cattle. However, as these vaccines have
been developed using type I BVDV virus strains, the protection
is against type I virus only. Moreover, these vaccines, although
attenuated, are most often associated with safety problems. The
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vaccine viruses may cross the placenta of pregnant animals, e.g.
cows and lead to clinical manifestations in the fetus and/or the
induction of persistently infected calves. Therefore, they
cannot be applied to breeding herds that contain pregnant cows.
Pregnant cows have to be kept separate from vaccinated cattle
to protect fetuses and must not be vaccinated themselves.
(Meyers 2:19—30).
5. Littledike teaches the “purpose of [its] study was to identify
cattle in MARC’s herd that were persistently infected with BVDV and test
the isolates of BVDV from the MARC herd to determine if these natural
field viruses could be neutralized by serum obtained from MARC cows
vaccinated with killed BVDV” (Littledike 180, col. 1).
6. Littledike teaches that “[s]era were tested for neutralizing
antibodies against one or more of the following viruses: cytopathic viral
isolates BVD-TGAC and BVD-Singer” (Littledike 180, col. 2).
7. Littledike teaches that, “[although the herd surveyed in [its]
study had been on a killed BVDV vaccination program for 7 yr, two
persistently infected cows were identified” (Littledike 181 col. 1). In
particular, Littledike teaches:
Virus was isolated from 3 of 448 samples of serum that
had neutralized antibody titers of 64 or less against BVD-
TGAC virus (Table 1). In those three samples of serum, the
neutralizing antibody titers against BVD-TGAC virus were less
than 2, 2, and 32. The corresponding neutralizing antibody
titers against BVD-Singer virus were 32, 64, and 256.
Persistent infection was subsequently confirmed in two cows.
(Littledike 180, col. 2).
8. Kumar teaches:
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An attenuated vims is a vims that has been altered, typically by
passaging in tissue culture cells, to attenuate its ability to cause
disease, but which maintains its ability to protect against
disease or infection when administered to animals. . . .
Illustrative immunogens include, but are not limited to . . .
bovine viral disease Type I and Type II (BVD Type I and Type
II).
(Kumar | 17).
Principles of Law
The Examiner has the initial burden of establishing a prima facie case
obviousness under 35 U.S.C. § 103. In re Oetiker, 977 F.2d 1443, 1445
(Fed. Cir. 1992). “The combination of familiar elements according to
known methods is likely to be obvious when it does no more than yield
predictable results.” KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416
(2007).
Prima facie obviousness can be rebutted by presenting evidence of
secondary considerations and when such evidence is submitted, all of the
evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472—
1473 (Fed. Cir. 1984).
Analysis
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 2-4; FF 1—8) and agree that the
claims are obvious over Meyers, Fittledike, and Kumar. We address
Appellants arguments below.
Prima Facie obviousness
Appellants contend “Meyers does not disclose a modified, live
BVDV-lb altered by passaging in tissue culture cells” (App. Br. 6).
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We find this argument unpersuasive because the claims are rejected as
obvious, not anticipated by Meyers. Meyers teaches attenuated BVDV lb
vaccines (FF 1—2) that may include veterinary acceptable carriers and
adjuvants (FF 3). Meyers teaches that one known mode of attenuation is by
repeated passage in tissue culture cells (FF 4). Kumar also teaches that
BVDV 1 may be an attenuated virus passaged in tissue culture cells (FF 8).
As the Examiner notes, neither Meyers nor Kumar teaches the strain TGAC
(Final Act. 3), but Littledike teaches the TGAC strain of BVDV (FF 5—6).
Littledike teaches that this strain may cause persistent infection in cows
(FF 7), providing a reason for the ordinary artisan to choose this strain for
attenuation as taught by Meyers and Kumar in order to develop a vaccine to
eliminate this persistent infection.
Appellants contend:
Meyers teaches away from creating modified, live BVDV
viruses by repeated passaging in tissue culture cells, as such
modified, live viruses would present a safety risk and would
thus be inappropriate for use in immunogenic compositions.
Meyers, p. 2, lines 19 — 30. Instead, Meyers teaches that using
molecular techniques to introduce specific deletions into the
viral genome results in modified, live BVDV viruses useful in
safe and effective immunogenic compositions.
(App. Br. 6).
We find the teaching away argument unpersuasive. In Medichem, the
court explained that “[wjhere the prior art contains ‘apparently conflicting’
teachings (i.e., where some references teach the combination and others
teach away from it) each reference must be considered ‘for its power to
suggest solutions to an artisan of ordinary skill. . . considering] the degree
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to which one reference might accurately discredit another.’” Medichem, S.A.
v. Rolabo, S.L., 437 F.3d 1157, 1165 (Fed. Cir. 2006) {quoting In re Young,
927 F.2d 588, 591 (Fed. Cir. 1991)).
Meyers teaches the use of BVDV viruses attenuated by cell culture
passage as licensed vaccines while also teaching that these vaccines have
certain disadvantages including limited protection and safety concerns for
pregnant cows (FF 4). Kumar evidences that vaccines are routinely
generated by attenuating virus by passage in tissue culture cells for viruses
such as BVDV 1 (FF 8). Thus, as we balance the teachings to generate
BVDV 1 vaccines by attenuation with the disadvantage that the virus may be
less desirable for herds of cattle with pregnant females, we agree with the
Examiner that to the extent there is a teaching away, it is “directed to a
specific population comprising pregnant cows” (Ans. 6). There is no
teaching away from the broader embodiment of a tissue culture attenuated
BVDV 1 virus vaccine for cattle that are not pregnant (or bulls that are
incapable of becoming pregnant).
Moreover, that Meyers teaches the prior art had “licensed vaccines”
generated by tissue culture attenuation demonstrates that the ordinary artisan
and the regulatory bodies that license vaccines recognize the utility of
BVDV vaccines generated by attenuating the virus in tissue culture (FF 4).
To the extent that Meyers prefers attenuation by mutation, rather than
attenuation in tissue culture, those disclosed examples and preferred
embodiments do not constitute a teaching away from a broader disclosure or
non-preferred embodiments. In re Susi, 440 F.2d 442, 446 n.3 (CCPA
1971).
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Appellants contend:
The fact that the TGAC strain exists does not indicate there a
reasonable expectation of success in altering any BVDV-lb
strain by passaging in tissue culture cells. Indeed, a central
point of Littledike is that significant variability exists among
BVDV strains. Applicant would argue there is no reasonable
chance of success in altering the TGAC strain by passaging in
tissues, because of the variability between BVDV-la and
BVDV-lb strains (See Littledike), and because at least some
attempts at altering BVDV-la strains by passaging in tissue
culture cells have failed. (See Meyers, p. 2, lines 19 — 30).
(App. Br. 6). Appellants further contend that “Kumar does not correct the
deficiencies of Meyers and Littledike . . . Kumar was merely referring to live
BVDV-la, not live-attenuated BVDV-lb” (id. at 7). Appellants contend
“Kumar does not unambiguously refute the disclosure of Meyers that at least
some attempts at altering BVDV-la strains by passaging in tissue culture
cells have failed” (id. at 7).
We find the expectation of success argument unpersuasive because
the portion of Meyers cited by Appellants at page 2, lines 19—30 does not
teach any failure or inability to alter a BVDV-la strain by tissue culture
passage (FF 4). Indeed, Appellants point to no specific evidence of any
unpredictability or difficulties in generating an attenuated BVDV-1 or 2
vaccine by tissue culture, only that the attenuated virus may be undesirable
in pregnant cows. By contrast, Meyers teaches that tissue culture is a
process by which currently licensed attenuated BVDV vaccines are
produced (FF 4) and Kumar teaches that this is the ordinary process for
obtaining a viral immunogen for a vaccine, generally referring to viruses
including BVDV subtypes (FF 8). Lastly, Littledike evidences that out of
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448 samples of cows infected with BVD-TGAC, only three had low levels
of neutralizing antibody and 445 therefore had sufficient levels (FF 7). This
reasonably supports the Examiner’s position that an attenuated BVD-TGAC
virus would be capable of generating neutralizing antibodies (see Ans. 6).
“Obviousness does not require absolute predictability of success ... all that
is required is a reasonable expectation of success.'1'’ In re Kubin, 561 F.3d
1351, 1360 (Fed. Cir. 2009).
Appellants contend: “Because the prior art references were not
properly considered as a whole, and because the references do not teach the
claim elements as alleged by the Examiner, a prima facie case of
obviousness has not been established by the Examiner” (App. Br. 9).
Appellants reiterate the argument regarding Meyer’s teaching that the
attenuated virus was unsafe and that “Meyers specifically excludes use of
viruses altered by passage in tissue culture cells from the disclosed
invention” (id.). Appellants also reiterate the argument that “Kumar does
not clearly and unambiguously disclose a modified, live BVDV-lb altered
by passaging in tissue culture cells” (id.).
We remain unpersuaded by this argument because Meyers and Kumar
establish that the ordinary artisan routinely obtained attenuated BVDV
viruses for use in vaccine compositions (FF 1, 4, 8). Moreover, Meyers and
Kumar teach the ordinary artisan routinely used tissue culture passaging to
generate attenuated BVDV virus strains (FF 4, 8). Finally, Meyers teaches
that BVDV strains may include all viruses “including any sub-species such
as la, lb . . . and the like” (FF 2) while Kumar generally teaches all “BVD
Type I and Type II” (FF 8), and Littledike teaches BVD-TGAC was a
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known BVDV vims strain (FF 6). Consequently, the prior art as a whole
reasonably renders obvious a BVD-TGAC vaccine compositions generated
by the prior art technique of tissue culture passaging because tissue culture
passaging was a known, recognized technique for producing licensed
vaccines to BVDV strains (FF 4).
Appellants contend:
The Examiner provides no rationale or support for substituting
the modified, live BVDV of Meyers having deletions in the Ems
and/or Npro genes with the BVDV-lb of the instant application,
which is altered by passaging in tissue culture cells. The
Examiner has not cited any reference or provided any common
sense reasoning to explain why such a substitution should be
made, and, as addressed herein, Meyers expressly teaches
against such a substitution.
(App. Br. 10).
We find this argument unpersuasive because the Examiner provides a
reason to incorporate an attenuated TGAC strain of BVDV into an animal
vaccine, specifically “in order to induce immune responses in an animal in
need thereof without causing disease” (Final Act. 4). This reason is
consistent with the motivation of Meyers to create a “combination vaccine
. . . that comprises a live attenuated BVDV” (FF 1) that includes “all vimses
belong to species bovine viral diarrhea vims (BVDV) type 1 (BVDV-1) and
BVDV type 2 (BVDV-2), including any sub-species” (FF 2). We agree with
the Examiner that the ordinary artisan, informed by Littledike that the
TGAC strain of BVDV persistently infected cattle (FF 6—7), would have had
reason to attenuate the TGAC BVDV strain by tissue culture methods well
known in the prior art as evidenced by Meyers and Kumar (FF 4, 8) and
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incorporate that attenuated virus into vaccine compositions to prevent
infection in naive animals.
Secondary Considerations
Appellants contend:
Littledike and Bolin disclosed in 1991 that vaccines containing
inactivated BVDV-la were not sufficient to confer protection
against all BVDV infections. In 2002, Fulton reported vaccines
containing modified, live BVDV-la or inactivated BVDV-la
and BVDV-lb were still not entirely effective at preventing
disease caused by BVDV. Appellant argues these references,
cited by the Examiner, provide evidence of a long-felt but
unsolved need, that of protecting cattle from bovine respiratory
disease caused by BVDV infections.
(App. Br. 11).
We are not persuaded. To establish a long-felt need, three elements
must be proven. First, the need must have been a persistent one that was
recognized by ordinarily skilled artisans. In re Gershon, 372 F.2d 535, 538
(CCPA 1967). Second, the long-felt need must not have been satisfied by
another before Appellants’ invention. See Newell Companies, Inc. v.
Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988) (“[OJnce another
supplied the key element, there was no long-felt need or, indeed, a problem
to be solved . . . .”). Third, the invention must, in fact, satisfy the long-felt
need. In re Cavanagh, 436 F.2d 491, 496 (CCPA 1971).
In this case, Appellants have provided no evidence supporting the first
two of these three elements. While a general desire for vaccines to BVDV is
clearly evident in the cited prior art, Appellants do not provide evidence of
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an art-recognized need for the specific vaccine of claim 1. While Fulton5
recognizes infections by the “BVDVlb TGAC strain,” Fulton notes that
animals vaccinated with prior art BVDV vaccines “were tested for
antibodies in the [virus neutralization test] with the CP BVDVla NADL
strain, the CP BVDVlb TGAC strain, or the CP BVDV2 125-C strain.
Cross-reactive and type-specific antibodies to all 3 viruses were found in the
individual animals” (Fulton 188, col. 2). Thus, Fulton evidences that the
current vaccines were capable of neutralizing the TGAC strain of BVDV
(see Fulton 188, col. 2). Indeed, Fulton concludes the “implications for
effective vaccination against BVDVlb are obvious: (1) there must be
demonstration of the efficacy of current BVDVla vaccines against
BVDVlb; (2) new BVDVlb components to add to current BVDVla
vaccines should be developed; or (3) current BVDVlb vaccine should be
used” (Fulton 189, col. 1). Thus, Fulton recognizes that there is no clear
evidence of need because the then current BVDV 1 a vaccines may be
effective and the then current BVDVlb vaccines were expected to be
effective (see Fulton 188, col. 2).
As to the second element, while Littledike teaches that the killed
BVDV vaccine was not fully effective against the TGAC strain of BVDV
(FF 7), Appellants provide no evidence that the licensed attenuated virus
BVDV strains taught by Meyers (FF 4) failed to satisfy the need. Moreover,
as noted above, Fulton suggests that one option for BVDVlb is that the
5 Fulton et al., Bovine viral diarrhea virus (BVDV) lb: predominant BVDV
subtype in calves with respiratory disease, 66 Canadian J. Veterinary
Res. 181-90 (2002).
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“current BVDVlb vaccine should be used” (Fulton 189, col. 1). Fulton, also
prior art to Appellants’ filing date, therefore evidences that any need for a
BVDVlb vaccine is satisfied by the then available “current BVDVlb
vaccine” (id).
Appellants contend “the same references also provide evidence of the
failure of others. In particular, Appellant draws emphasis to Table I of
Fulton which describes the number of vaccines against BVDV which have
been produced” (App. Br. 11—12). Appellants contend “nearly 20 years
passed before the instant application demonstrated success in producing a
modified, live BVDV-altered by passaging in tissue culture cells. Appellant
argues this long period of time is significant evidence that it was not obvious
to produce a modified, live BVDV-altered by passaging in tissue culture
cells” (App. Br. 12).
We are not persuaded. “The mere age of the references is not
persuasive of the unobviousness of the combination of their teachings,
absent evidence that, notwithstanding knowledge of the references, the art
tried and failed to solve the problem.” In re Wright, 569 F.2d 1124, 1127
(CCPA 1977). Appellants have not provided evidence addressing this point.
See In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995) (“It is well settled that
unexpected results must be established by factual evidence. Mere argument
or conclusory statements . . . [do] not suffice.”).
In particular, Appellants provide no evidence of attempts to generate
an attenuated vaccine against the TGAC strain of BVDV that failed. Table I
of Fulton, cited by Appellants, identifies virus strains in commercially
available vaccines, but provides no evidence of any failures to generate an
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attenuated vaccine of any type (see Fulton 183, col. 2). Indeed, because
Fulton teaches the availability of a “current BVDVlb vaccine” (Fulton 189,
col. 1), Fulton suggests the success of others, rather than their failure.
Conclusion of Law
(i) The evidence of record supports the Examiner’s conclusion that
Meyers, Littledike, and Kumar render claim 1 obvious.
(ii) Appellants have not presented evidence of secondary
considerations, that when weighed with the evidence of obviousness, is
sufficient to support a conclusion of non-obviousness.
SUMMARY
In summary, we affirm the rejection of claim 1 under 35 U.S.C.
§ 103(a) as obvious over Meyers, Littledike, and Kumar. Claims 2, 3, 6, 8,
and 12 fall with claim 1.
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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