Ex parte Berg

Board of Patent Appeals and Interferences

Jan 15, 1998

07825465 (B.P.A.I. Jan. 15, 1998)

Application for patent filed January 24, 1992. 1
According to applicant, this application is a continuation
of Application 07/534,894, filed June 7, 1990, abandoned.
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THIS OPINION WAS NOT WRITTEN FOR PUBLICATION
The opinion in support of the decision being entered today
(1) was not written for publication in a law journal and
(2) is not binding precedent of the Board.
Paper No. 18
UNITED STATES PATENT AND TRADEMARK OFFICE
____________
BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________
Ex parte JOHN N. BERG
____________
Appeal No. 93-3114
Application 07/825,4651
____________
ON BRIEF
____________
Before GRON, Administrative Patent Judge,
McKELVEY, Senior Administrative Patent Judge, and
WEIMAR, Administrative Patent Judge.
GRON, Administrative Patent Judge.
DECISION ON APPEAL UNDER 35 U.S.C. § 134
Appeal No. 93-3114
Application 07/825,465
Appellant does not contest the examiner’s holding 2
that Maas is prior art under 35 U.S.C. § 102(b).
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This is an appeal from an examiner’s rejections of
Claims 1-8, all claims pending in this application. Claims 1-
8 stand finally rejected under 35 U.S.C. § 102(b) as drawn to
a process which purportedly is described by Maas, Synthea
(Maas), “The Immune Responses of Mice and Cattle to
Fusobacterium Necrophorum,” A Dissertation Presented to the
Faculty of the Graduate School, University of Missouri-
Columbia, Berg, John N, Dissertation Supervisor, pages 1-215,
August 1986. Claims 1-8 stand finally rejected under 352
U.S.C. § 102(f) as drawn to a process which John N. Berg did
not himself invent. Claims 1-8 also stand finally rejected
under 35 U.S.C. § 103 as unpatentable over the combined
teachings of Abe et al. (Abe), “Immunization
of Mice Against Fusobacterium necrophorum Infection by
Parenteral or Oral Administration of Vaccine,” American
Journal of Veterinary Research, Vol. 39, No. 1, pp. 115-118
(January 1978); Nelson, U.S. 4,789,544, patented December 6,
1988; and Adam,
U.S. 4,061,751, patented December 6, 1977.
All claims stand or fall together (Appeal Brief, p. 4;
Appeal No. 93-3114
Application 07/825,465
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Examiner’s Answer, p.3). Representative Claim 1 reads:
1. A method for treating cattle and sheep
to prevent foot rot or liver necrosis comprising
administering a Fusobacterium necrophorum bacterin,
which is a B-propiolactone inactivated Fusobacterium
necrophorum isolate, to the animal being treated.
1. Rejections based on Maas
Claim 1 stands rejected under 35 U.S.C. § 102(b) because
Maas purportedly describes the claimed process, and under
35 U.S.C. § 102(f) because applicant signed a statement that
he actually examined the Maas dissertation prior to the June
7, 1990, the filing date of applicant’s parent application.
A. Maas’ disclosure
In Chapter III, “The Immune Responses of Mice and Cattle
to Fusobacterium Necrophorum,” at pages 101-102, bridging
paragraph, Maas describes the preparation of vaccines
(emphasis added):
Three whole-cell monovalent F. necrophorum
vaccines (FN 2101, FN 2382, and FN 3080) were
prepared. The bacteria were removed from the
surface of plate cultures (BHIBA) with a sterile
loop and suspended in sterile 0.1 M PBS at pH 7.1
to a turbidity comparable to a No. 5 tube of a
McFarland nephelometer set. Beta-propiolactone
(BPL) . . . was added (0.1% v/v). The resulting
mixtures were incubated for 4 days at 4 C to kill
the bacteria. . . . [T]he vaccines were then warmed
at 37 C for 4 hours to eliminate the concentration
of (BPL)(Staples, 1981). A low viscosity aluminum
hydroxide gel (10% v/v) . . . was added as an
Appeal No. 93-3114
Application 07/825,465
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adjuvant and gentamicin (30 ug/ml) . . . was added
as a preservative (Oden et al, 1974).
In Chapter IV, “The Immune Response of Cattle to Fusobacterium
Necrophorum,” at page 148, first full paragraph, Maas states:
The purpose of the present study was i) to determine
if leukotoxin neutralizing activity was present in bovine
sera after immunization with 2 F. necrophorum vaccine
preparations or experimental F. necrophorum
infection
and ii) to evaluate the effect of these vaccines or
infection on the peripheral blood lymphocyte
response.
At page 151, last paragraph, Maas states (emphasis added):
A whole-cell (FN 3080 WC) and a RRE (FN 3080
RRE) vaccine were prepared for immunization of calves.
The whole-cell vaccine was prepared as described in
Chapter III.
See Group III of Table 1. Experimental design of bovine F.
necrophorum immunological study, page 153. “An experimental
infection with F. necrophorum isolate FN 3080 was induced in
the group II, III, and IV calves 7 days after the last
immunization (Table 1)” (pages 152 & 154, bridging sentence).
The experiments were designed (page 170, last full sentence):
. . . to determine if, after specific immunization
or infection, leukotoxin neutralizing activity and
transformed lymphocytes were present which may
contribute to effective antitoxic and cellular
immunity to F. necrophorum infections in cattle.
Appeal No. 93-3114
Application 07/825,465
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Maas analyzed the results as follows (page 170, last two
lines, through page 171, first full paragraph; emphasis
added):
Leukotoxin neutralizing activity in specific
bovine antiserum to the leukotoxic substances of
F. necrophorum has not been previously reported.
In this study, an increased macrophage viability
was demonstrated when 2 leukotoxin types were
incubated with sera from calves that had been
immunized or infected with FN 3080 preparations
(Tables 3 and 4). This viability was significantly
greater than that observed with serum from calves
that had received only PBS injections.
These data indicate the presence of a specific
leukotoxin neutralizing component in the bovine sera.
The sera . . . from F. necrophorum-immunized and
-infected calves (no. 74, 78 and 76; Table 2) used in
this leukotoxin neutralization assay were positive for
anti-F. necrophorum antibody with the ELISA screen. The
detection of specific antibody and specific leukotoxin
neutralizing activity in the same serum samples from
calves immunized or infected with F. necrophorum but
not in the control serum suggests that specific
antitoxin may be generated in the bovine using
F. necrophorum vaccines and may, therefore, be an
important aspect of protection in vivo.
However, Maas also found that (pages 180-181, bridging
paragraph):
Peripheral blood lymphocytes from F. necrophorum-
immunized and -experimentally infected calves did
not demonstrate uniform specific stimulation when
cultured with a ribosome-rich antigen prepared from
F. necrophorum. However, these calves did produce
anti-F. necrophorum antibody as assessed by the enzyme-
Appeal No. 93-3114
Application 07/825,465
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linked immunosorbent assay. The response observed
with the lymphocyte transformation is not at clinical
variance with the pathological events noted in
necrobacillosis infections of the bovine.
B. Applicant’s disclosure
Applicant’s specification teaches (Spec., p. 3, lines 5-
32):
The present invention relates to a process for
bacterin preparation in which B-propiolactone (BPL)
is used to inactivate virulent F. necrophorum isolates.
Residual BPL may be hydrolyzed and an adjuvant may then
be added. The bacterin prepared by this process is
useful in the prevention and control of F. necrophorum
in ruminant animals such as sheep, goats and cattle
under normal field conditions.
The present invention also relates to a
B-propiolactone (BPL) killed bacterin prepared from
virulent isolates of Fusobacterium necrophorum which
is useful as an aid in protecting against diseases
caused by F. necrophorum in cloven hoofed animals (i.e.
cattle, sheep, goats, etc.). Examples of such diseases
include Footrot, Liver Abscess, Calf Diphtheria,
Interdigital Dermatitis, etc. Previous attempts at
preparing efficacious bacterins using Fusobacterium
necrophorum have been unsuccessful, probably due to
the fact that critical antigens necessary for induction
of immunity were not preserved by use of inactivation
processes which involved heat or formaldehyde. Applicant
has found, however, through challenge studies conducted
in mice that BPL inactivated, adjuvanted cultures can
protect mice against experimental challenge with
heterologous isolates of F. necrophorum. Field
challenge trials conducted in pregnant sheep and
feedlot cattle have also shown that the BPL inactivated
bacterin of the present invention is effective in
reducing both incidence and severity of ovine and bovine
Footrot.
The present invention can be practiced with any
virulent isolate of F. necrophorum. . . .
Appeal No. 93-3114
Application 07/825,465
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Applicant prepared his test vaccines in a manner which
appears to be identical or substantially the same as the
vaccine preparation method described at pages 101-102 of Maas;
i.e. the fermented cultures are cooled to a temperature of
about 4 to 7 C (Spec., p. 5, lines 3-6), the cooled culturesO
are inactivated with BPL (0.11% v/v)(Spec. p. 5, lines 6-9),
the culture is maintained at about 4 to 7 C during theO
inactivation stage (Spec., p. 5, lines 13-15), the BPL-
containing culture is heated to about 36 to 38 C for 3 to 5O
hours to remove or inactivate BPL (Spec., p. 5, lines 15-22),
preservatives such as gentamicin (30 micrograms/ml) are
preferably added (Spec., p. 5, lines 23-28), and adjuvants
such as 10% aluminum hydroxide gel are particularly preferred
(Spec., p. 5, lines 29-34). While Maas vaccinated test
calves, applicant vaccinated adult cattle.
In Example 1 (Spec., pp. 6-9), applicant reports that
3.3% of control cattle developed cases of acute foot rot when
challenged. However, 1.4% of the vaccinated cattle developed
cases of acute foot rot (Spec., p. 8, lines 11-19). According
to applicant, “[a] 64.1% reduction in clinical index was
observed among vaccinated cattle” (Spec., p. 8, lines 24-25).
Example 1 is the only reported example of immunization trials
Appeal No. 93-3114
Application 07/825,465
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on cattle. On that basis, applicant found that (Spec., p. 8,
lines 26-31):
. . . vaccination resulted in a statistically
significant reduction in incidence of acute foot
rot in feedlot cattle and also showed signs of
reducing severity of disease. Results show that
the BPL inactivated F. necrophorum bacterin is
efficacious against foot rot in cattle under normal
field conditions.
C. Claim interpretation
Consistent with the specification and its exemplified
success, we hold that applicant's claimed “method for treating
cattle . . . to prevent foot rot or liver necrosis comprising
administering . . . a B-propiolactone inactivated
Fusobacterium necrophorum isolate” broadly reads on
vaccinating cattle with a B-propiolactone inactivated
Fusobacterium necrophorum isolate, with or without adjuvant,
to significantly reduce the incidence of and control foot rot
or liver necrosis in cattle. Claim language is to be given
its broadest reasonable interpretation consistent with the
description of the invention in the specification. In re
Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir.
1989).
D. Findings
Appeal No. 93-3114
Application 07/825,465
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We find that Maas reasonably appears to describe the
process applicant claims. Accordingly, we affirm the
examiner’s rejections of Claims 1-8 under 35 U.S.C. § 102(b)
over Maas and under 35 U.S.C. § 102(f) because applicant
indicated by his signing of the Maas dissertation that he had
“examined a dissertation entitled THE IMMUNE RESPONSES OF MICE
AND CATTLE TO FUSOBACTERIUM NECROPHORUM presented by Synthea
Maas” prior to the June 7, 1990 filing date of his parent
application and that “it is worthy of acceptance” (Maas, the
signature and acceptance page). While applicant appears to
believe that Maas’ dissertation describes subject matter
outside the scope of the process presently being claimed on
appeal, we surmise that he is reading limitations of the
specification into the claims, which is improper. In re
Prater, 415 F.2d 1393, 1404, 162 USPQ 541, 550 (CCPA 1969).
2. Rejection in view of Abe, Nelson, and Adam
Claims 1-8 stand rejected under 35 U.S.C. § 103 as
unpatentable in view of the teachings of Abe, Nelson and Adam.
We affirm.
Appeal No. 93-3114
Application 07/825,465
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Abe describes methods for immunizing mice against
Fusobacterium necrophorum. In one method affording protection
against the bacterium to a degree of 54.1 to 77.5%, a vaccine
formulated from formaldehyde (0.4%)-inactivated Fusobacterium
necrophorum cells and an aluminum hydroxide adjuvant was
administered to mice by intraperitoneal (IP) injection (Abe,
p. 115, Summary (col. 1) and Materials and Methods, Vaccine
Preparation (col. 2); and pp. 116-117, bridging paragraph).
Abe found that vaccine toxicity is a major factor in preparing
Fusobacterium necrophorum vaccines (Abe, pp. 117-118,
Discussion) and proffered an improvement on procedures which
had previously utilized alum-precipitated toxoids of F.
necrophorum to reduce the incidence of hepatic abscesses in
cattle in light of this major factor (Abe, p. 115, col. 1,
last full sentence).
Nelson teaches (Nelson, col. 2, lines 45-50; emphasis
added):
Gram-negative bacterial cells devoid of
o-carbohydrate side-chains can be inactivated by
boiling or treatment with anti-bacterial agents
such as formaldehyde (0.2 percent v/v), beta-
propriolactone [sic], or antibiotics. The preferred
method to inactivate the cells is with formaldehyde.
The record establishes and accordingly we find that
Appeal No. 93-3114
Application 07/825,465
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Fusobacterium necrophorum cells are gram-negative bacterial
cells (Spec., p. 1, lines 8-14; Maas, Chapter I, Introduction,
p. 2, first paragraph).
Adams teaches that Fusobacterium necrophorum is
responsible for foot rot and liver abscesses and other lesions
in ruminant animals (Adams, col. 1, lines 34-51). Adams
utilized mice as models for determining the activity of
compounds against Fusobacterium necrophorum infection in
ruminant animals (Adams, col. 8, Example 2).
We conclude that persons having ordinary skill in the
art in view of the combined prior art teachings reasonably
would have been led to expect success in treating cattle with
B-propiolactone-inactivated Fusobacterium necrophorum bacterin
to prevent or control foot rot or liver necrosis. We agree
with the examiner’s view that a reasonable expectation of
success is required and not absolute predictability to sustain
a rejection for unpatentability under 35 U.S.C. § 103.
Compare In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673,
1681 (Fed. Cir. 1988).
While appellant’s view that persons having ordinary skill
in the art would not have been led by the combined prior art
Appeal No. 93-3114
Application 07/825,465
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teaching to use B-propiolactone-inactivated Fusobacterium
necrophorum bacterin over the use of formaldehyde, heat, and
antibiotics deserves and has been granted considerable weight,
i.e., the prior art certainly prefers to use formaldehyde to
inactivate gram-negative bacteria, we find the evidence as a
whole insufficient to support patentability for the full scope
of the subject matter claimed.
Having carefully considered the decision rendered and
supporting opinion in In re Baird, 16 F.3d 951, 8 USPQ2d 1550
(Fed. Cir. 1994) in light of the evidence presented in that
case, it is our view that the evidence in this case warrants a
different result. Here, unlike the case in Baird, the prior
art expressly states that B-propiolactone may be used to
inactivate gram-negative bacteria and that Fusobacterium
necrophorum is a gram-negative bacterium. Thus, at the time
this application was filed, the claimed process would have
been prima facie obvious to persons having ordinary skill in
the art for the specific utility indicated in applicant’s
specification. Here, the prior art does not indicate why
formaldehyde was preferred. We will not hazard a guess.
Moreover, here applicant has not compared the activity of B-
Appeal No. 93-3114
Application 07/825,465
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propiolactone-inactivated F. necrophorum to formaldehyde-
inactivated F. necrophorum. Absent objective evidence of
record establishing that B-propiolactone-inactivated F.
necrophorum is unexpectedly superior to formaldehyde-
inactivated F. necrophorum “for treating cattle and sheep to
prevent foot rot or liver necrosis” (Claim 1), we are obliged
to affirm the examiner’s rejection of the claimed subject
matter under 35 U.S.C. § 103. Finally, we note the statement
on page 3, lines 23-26, of the specification that:
Applicant has found, however, through challenge
studies conducted in mice that BPL inactivated,
adjuvanted cultures can protect mice against
experimental challenge with heterologous isolates
of F. necrophorum.
With the above statement noted, we also note that the process
of Claim 1 on appeal does not require inclusion of an
adjuvant.
3. Conclusion
We affirm the examiner’s final rejection of Claims 1-8
under 35 U.S.C. § 102(b).
We affirm the examiner’s final rejection of Claims 1-8
under 35 U.S.C. § 102(f).
We affirm the examiner’s final rejection of Claims 1-8
under 35 U.S.C. § 103.
Appeal No. 93-3114
Application 07/825,465
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No time period for taking any subsequent action
in connection with this appeal may be extended under
37 CFR § 1.136(a).
AFFIRMED
Teddy S. Gron )
Administrative Patent Judge )
)
)
)
Fred E. McKelvey, Senior ) BOARD OF
PATENT
Administrative Patent Judge ) APPEALS AND
) INTERFERENCES
)
)
Elizabeth C. Weimar )
Administrative Patent Judge )

Appeal No. 93-3114
Application 07/825,465
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Patent Department
Miles Inc.
Mobay Road
Pittsburgh, PA 15205-9741