Ex Parte Leonard et al

Board of Patent Appeals and Interferences

Sep 22, 2010

09708352 (B.P.A.I. Sep. 22, 2010)

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.
09/708,352 11/08/2000 Joan D. Leonard 02108.0001U2 1597
7590 09/22/2010
KENYON & KENYON
ONE BROADWAY
NEW YORK, NY 10004
EXAMINER
FORD, VANESSA L
ART UNIT PAPER NUMBER
1645
MAIL DATE DELIVERY MODE
09/22/2010 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte JOAN D. LEONARD and ROBERT W. TULLY
__________

Appeal 2009-0138641
Application 09/708,352
Technology Center 1600
__________

Before ERIC GRIMES, FRANCISCO C. PRATS, and
JEFFREY N. FREDMAN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL2
This appeal under 35 U.S.C. § 134 involves claims to vaccines that
protect against diseases caused by Mycoplasma bovis. The Examiner
rejected the claims as anticipated and obvious.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

1 Oral argument was heard in this appeal on September 14, 2010.
2 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF THE CASE
“Clinical disease and losses associated with infections caused by
Mycoplasma bovis in beef and dairy cattle include: contagious mastitis,
respiratory pneumonia, joint infections (arthritic conditions),
keratoconjunctivitis, and middle ear infections” (Spec. 1).
Claims 1, 3-12, and 29-56 are pending and on appeal (App. Br. 5).3
Claims 1, 5, 8, and 29 illustrate the appealed subject matter and read as
follows:
1. A vaccine which is protective against Mycoplasma bovis
clinical disease in a bovine species comprising at least one
inactivated or attenuated Mycoplasma bovis biotype, an
adjuvant, and a pharmaceutically acceptable excipient, and
wherein the adjuvant does not include saponin and the clinical
disease includes respiratory pneumonia.

5. A vaccine which is protective against Mycoplasma bovis
clinical disease in a bovine species comprising at least one
inactivated or attenuated Mycoplasma bovis biotype, an
adjuvant, and a pharmaceutically acceptable excipient, wherein
at least one of the inactivated or attenuated Mycoplasma bovis
biotypes is selected from the group consisting of biotype A,
biotype B and Biotype C, and wherein the adjuvant does not
include saponin.

8. A vaccine which is protective against Mycoplasma bovis
clinical disease in a bovine species comprising at least two
inactivated or attenuated Mycoplasma bovis biotypes and a
pharmaceutically acceptable excipient.

29. A vaccine which is protective against Mycoplasma bovis
mastitis in a bovine species comprising at least one inactivated

3 Amended Appeal Brief filed March 7, 2008.
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or attenuated Mycoplasma bovis biotype and a
pharmaceutically acceptable excipient.

The Examiner cites the following documents as evidence of
unpatentability:
John Thayer Boothby, Immunologic Responses to Mycoplasma bovis
(1982) (Ph.D. dissertation on file with University Microfilms International)
(“Boothby I”).

F. Poumarat et al., Genomic, protein and antigenic variability of
mycoplasma bovis, 40 VETERINARY MICROBIOLOGY 305-321 (1994).

C.J. Thorns and E. Boughton, Effect of serial passages through liquid
medium on the virulence of Mycoplasma bovis for the mouse mammary
gland, 29 RESEARCH IN VETERINARY SCIENCE 328-332 (1980).

The following rejections are before us for review:
(1) Claims 1, 3, 5, 6, 29, 30, 40-44, and 52-55, rejected under 35
U.S.C. § 102(b) as anticipated by Boothby I (Ans. 3-5);
(2) Claims 1, 3-12, and 29-56, rejected under 35 U.S.C. § 103(a) as
obvious over Boothby I, Poumarat, and Thorns (Ans. 5-9).
ANTICIPATION
ISSUE
The Examiner cites Boothby I as disclosing vaccine compositions that
contain killed M. bovis (Ans. 4). The Examiner also notes Boothby I’s
disclosure that, once vaccinated with the composition, “there was no sign of
respiratory illness in any calves used in the study (page 136). Therefore, the
vaccines were protective against respiratory infection caused by M. bovis”
(id. at 5).
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Appellants argue the claims subject to this rejection separately (see
App. Br. 11-14). Specifically, with respect to all of the rejected claims,
Appellants contend that the absence of unfavorable reactions resulting from
the claimed vaccine, contrasted with the unfavorable delayed
hypersensitivity caused by Boothby I’s vaccine, “is a real difference between
the Appellants’ vaccine and Boothby I” (id. at 11).
Regarding claims 5, 6, and 54, Appellants argue that Boothby I does
not disclose that the vaccine contains at least one of M. bovis biotypes A, B,
or C, as those claims require (id. at 12). Regarding claims 29, 30, and 40-44,
Appellants argue that the evidence of record does not support a finding that
Boothby I’s vaccine is protective against mastitis (id. at 12-14; see also
Reply Br. 6-11).
We select claims 1, 5, and 29 as representative of the rejected claims.
See 37 C.F.R. § 41.37(c)(1)(vii).
Thus, in view of the positions advanced by Appellants and the
Examiner, the issue with respect to this rejection is whether the evidence of
record supports the Examiner’s position that Boothby I describes an M.
bovis vaccine that has all of the features required by claims 1, 5, and 29.
FINDINGS OF FACT (“FF”)
Specification
1. The Specification discloses using PCR fingerprinting to differentiate
field isolates and strains of M. bovis into various biotypes designated as A,
B, and C (Spec. 12-13).
2. Thus, M. bovis DNA is isolated and amplified using primers with the
sequences in SEQ ID NO: 1 and SEQ ID NO: 2, and is then electrophoresed
on an agarose gel, the gel showing different banding patterns characteristic
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of the three biotypes, A, B, and C, identified by Appellants (id.; see also
Figures 1 and 2 (showing characteristic bands of biotypes A, B, and C on
agarose gels)).
3. The Specification does not disclose that the M. bovis strain California
201 was among the strains tested for biotype (see id. at 13).
4. The Specification states that the “term ‘biotype’ means a variant of a
species, i.e. a strain, that can be distinguished by one or more characteristics,
such as ribosomal RNA sequence variation, DNA polymorphisms,
serological typing, or toxin production” (id. at 5).

Boothby I
5. Boothby I studied “the effect of systemic and respiratory
administration of killed M bovis antigen in combination with various
adjuvants on the immune responses of calves to vaccination, and to
experimental challenge exposure with live M bovis in the nares and
bronchio-alveolar region (BAR)” (Boothby I 129-130).
6. In the study, Boothby I vaccinated 15 calves with various preparations
of the M. bovis strain California 201 (id. at 131): “[t]hree animals were
vaccinated with killed M bovis in phosphate buffered saline solution
(PBSS), and the remaining 12 were vaccinated with the same antigen in
combination with one of 4 adjuvant preparations (3 calves per experimental
group)” (id. at 130).
7. Boothby I’s vaccine compositions contained formalin-killed M. bovis
cells as the antigen in the following formulations:
Preparations for systemic immunization consisted of 0.5
ml antigen, 1.0 ml Freunds Incomplete Adjuvant and 0.5 ml of
one of the following in aqueous solution: 10.0 mg N-
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acetylmuramyl-L-alanyl-D-isoglutamine (MDP), 5.0 mg
Amphotericin B (Am-B), 500 mg of combined magnesium/
aluminum hydroxide with 2 x 1010 killed Bordetella pertussis
(Bp). The other experimental groups received the same antigen
in Freunds incomplete adjuvant alone (FIA) or in PBSS without
adjuvant. Vaccine preparations for intranasal and intratracheal
immunization were the same as those used for systemic
immunization except that the oil phase (FIA) and
magnesium/aluminum hydroxide were omitted, and the total
volume was adjusted to 15 mls with PBSS.

(Id. at 131 (citations omitted).)
8. Boothby I summarizes its results as follows:
The adjuvant preparations elicited strong systemic antibody
responses compared to those measured in calves not given
adjuvant. Most calves given adjuvants responded to
vaccination in the respiratory tract with a strong IgA response,
but these responses were not above those of calves given M
bovis antigen without adjuvant. Calves given some adjuvants
developed strong delayed-type hypersensitivity responses
compared to calves given M bovis without adjuvant as
measured by skin test, but none of the calves developed a
strong cellular response as measured by lymphocyte
stimulation.

(Id. at 128.)
9. Boothby I notes that, “[s]ince none of the calves in the present study
showed any signs of respiratory illness although a wide range of immune
responses were observed, there must be a wide range of acceptable
responses to M bovis infection as previously observed” (id. at 136).
10. Boothby I also notes that “[a]ll groups receiving adjuvant preparations
developed delayed-type hypersensitivity at 14 weeks as determined by
increase in skinfold thickness at 72 hours” (id.).

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Poumarat
11. The Examiner cites Poumarat as evidence that the M. bovis in
Boothby I’s vaccines is necessarily one of the claimed biotypes, A, B, or C
(Ans. 13).
12. Poumarat describes a study that investigated “the genomic, protein
and antigenic variability of M. bovis” (Poumarat 306).
13. “Restriction endonuclease analysis (REA) with three enzymes SmaI,
PstI, BamHI . . . identif[ied] 13 different genomic groups among 37
Mycoplasma bovis strains. One genomic group was comprised of 14
strains” (id. at 305 (abstract)).
14. Poumarat investigated strains from each of the genomic groups for
antigen variability using polyclonal and monoclonal antibodies, and found
that the strains’ antigenic profiles “differed markedly one from the other, the
heterogeneity being equally great among the strains belonging to the same
genomic group as those coming from different groups” (id.).
Thus, Poumarat concluded, “[t]here appeared to be no relation
between the genomic variability of M. bovis and the antigenic variability”
(id. at 318).
15. Poumarat concluded that “[t]wo highly-variable antigenic systems
have been identified so far for M. bovis, but their in vivo function is not
known. It is evident that this antigenic variability must be taken into
account in developing diagnostic and vaccination strategies” (id. at 319).

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Boothby II 4
16. Appellants cite Boothby II as evidence that Boothby I’s vaccines were
not protective against mastitis (App. Br. 21-22; Reply Br. 6-9); and the
Examiner disputes Appellants’ characterization of the reference (Ans. 20).
17. Boothby II investigated the “effect of vaccination on milk production .
. . in vaccinated and control cows experimentally challenged in two of four
quarters [of their udders] with live Mycoplasma bovis” (Boothby II 200
(abstract)).
18. Boothby II’s vaccine contained formalin-killed M. bovis strain
California 201 in Freund’s Complete Adjuvant (id. at 202).
19. Boothby II discloses that “[a]ll challenged quarters became infected,
had strong California Mastitis Test reactions, and had a drastic (> 85%) loss
in milk production” (id. at 200 (abstract)).
20. Regarding unvaccinated cows, Boothby II discloses that “four of eight
challenged quarters on control cows remained infected, had mostly positive
California Mastitis Test scores, produced mostly normal-appearing milk, and
recovered some productive capabilities” (id.).
21. Regarding vaccinated cows, Boothby II discloses that, “[b]y the end
of the study no M. bovis could be recovered from challenged quarters on
vaccinated cows and the milk appeared mostly normal. The California
Mastitis Test scores on these quarters, however, remained elevated” (id.).
22. Boothby II further notes:

4 J.T. Boothby et al., Experimental Intramammary Inoculation with
Mycoplasma bovis in Vaccinated and Unvaccinated Cows: Effect on Milk
Production and Milk Quality, 50 CAN. J. VET. RES. 200-204 (1986).

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All challenged quarters on vaccinated cows remained CMT-
positive for the duration of the study while some challenged
quarters on control cows became CMT-negative. Among
unchallenged quarters, four of eight quarters on vaccinated
cows and three of eight quarters on control cows developed
CMT reactivity, but most became CMT-negative by the end of
the study.

(Id. at 202-203.)
PRINCIPLES OF LAW
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.

“To anticipate a claim, a prior art reference must disclose every
limitation of the claimed invention, either explicitly or inherently.” In re
Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
As stated in In re Best, 562 F.2d 1252, 1254-1255 (CCPA 1977)
(quoting In re Swinehart, 439 F.2d 210, 212-13 (CCPA 1971)):
[W]here the Patent Office has reason to believe that a functional
limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent
characteristic of the prior art, it possesses the authority to
require the applicant to prove that the subject matter shown to
be in the prior art does not possess the characteristic relied on.

The examiner cannot, however, establish inherency merely by
demonstrating that the asserted limitation is probable or possible. In re
Oelrich, 666 F.2d 578, 581 (CCPA 1981). Nonetheless, if “the disclosure is
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sufficient to show that the natural result flowing from the operation as taught
would result in the performance of the questioned function, it seems to be
well settled that the disclosure should be regarded as sufficient.” Id.
(quoting Hansgirg v. Kemmer, 102 F.2d 212, 214 (CCPA 1939)).
ANALYSIS
A preponderance of the evidence supports the Examiner’s finding that
Boothby I anticipates claim 1. Claim 1 recites a vaccine which is protective
against Mycoplasma bovis respiratory pneumonia in a bovine species. The
vaccine must contain at least one inactivated or attenuated M. bovis biotype,
an adjuvant that does not contain saponin, and a pharmaceutically acceptable
excipient.
As the Examiner points out, Boothby I discloses vaccines that contain
formalin-killed M. bovis, combined with any one of several adjuvants which
Appellants do not dispute lack saponin, and the pharmaceutically acceptable
excipient water (FF 7). As the Examiner also points out, the vaccines
elicited strong antibody responses, and none of the vaccinated calves in the
study showed any signs of respiratory illness, despite having been
experimentally challenged in the nares and bronchio-alveolar regions with
live M. bovis (FF 5, 8, 9).
Thus, the Examiner has provided evidence that Boothby I’s vaccine
not only contains the ingredients required by claim 1, but also meets claim
1’s functional limitation requiring protection against respiratory pneumonia.
In contrast, while Appellants urge that the Examiner has failed to adequately
explain why Boothby I meets the functional limitation in claim 1 (see Reply
Br. 2-6), Appellants provide no specific reasoning or evidence that
undermines the reasonableness of the Examiner’s fact-based finding.
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Rather, Appellants argue only that the hypersensitivity resulting from
Boothby I’s vaccine (FF 10) demonstrates that Boothby I’s vaccine is
different than the vaccine recited in claim 1 (App. Br. 11). Claim 1 does not,
however, recite any limitation that excludes vaccines which result in
hypersensitivity. Thus, as Appellants’ argument is not directed to a
limitation present in claim 1, Appellants’ argument is not persuasive of that
claim’s patentability.
In sum, a preponderance of the evidence supports the Examiner’s
finding that Boothby I anticipates claim 1. We therefore affirm the
Examiner’s anticipation rejection of that claim over Boothby I, as well as
claims 3, 52, 53, and 55, which were not argued separately. See 37 C.F.R.
§ 41.37(c)(1)(vii).
We agree with Appellants, however, that the Examiner has not shown
that Boothby I’s vaccine inherently contains at least one inactivated M. bovis
biotype selected from biotypes A, B, and C, as recited in claim 5. As noted
above, biotypes A, B, and C are identified by a specific PCR fingerprinting
method prescribed in the Specification (FF 1, 2).
As also noted above, no evidence is presented by the Examiner that
any of the strains identified as having biotypes A, B, or C was the California
201 strain used in Boothby I’s vaccine (FF 3). As further noted above,
Poumarat discloses that restriction endonuclease analysis of M. bovis DNA
identified 13 different genomic groups among 37 M. bovis strains (FF 13).
The Examiner urges that Poumarat demonstrates that Boothby I’s
strain is one of the biotypes recited in claim 5 (Ans. 13). However, given
the potential number of M. bovis genomic groups to which Boothby I’s
strain might belong (at least 13), and given that California 201 is not among
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the strains of record that fall within the claimed biotypes, we are not
persuaded that an ordinary artisan would have concluded that Boothby I’s
M. bovis strain necessarily falls within biotypes A, B, or C.
In sum, because the preponderance of the evidence does not support
the Examiner’s finding that Boothby I’s vaccine necessarily contains one of
the biotypes recited in claim 5, we reverse the Examiner’s anticipation
rejection of that claim, and its dependent claims 6 and 54, over Boothby I.
We also agree with Appellants that a preponderance of the evidence
does not support the Examiner’s finding that Boothby I’s vaccine is
inherently protective against M. bovis mastitis in a bovine species, as recited
in claim 29. We note, as the Examiner argues, that Boothby II discloses that
a vaccine containing formalin-killed California 201, the same M. bovis strain
used in Boothby I, resulted in no M. bovis being recoverable from quarters
challenged with live M. bovis (see FF 21).
However, as Appellants point out, the California Mastitis Test (CMT)
scores on all vaccinated quarters remained elevated throughout the duration
of Boothby II’s study (id.). In contrast, as noted above, some challenged
quarters on control, i.e. unvaccinated, cows became CMT-negative (FF 22).
Thus, even if we assume that the Examiner has made a prima facie
case of anticipation by showing that Boothby I’s vaccine contains the same
species of organism, Boothby II shows that essentially the same vaccine as
in Boothby I did not protect cows against mastitis as measured by the CMT
test, and as compared to controls.
As noted above, inherency cannot be established by probability or
possibility. In re Oelrich, 666 F.2d at 581. Given the results presented in
Boothby II, we agree with Appellants that a preponderance of the evidence
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does not show that the vaccine in Boothby I inherently protects against M.
bovis mastitis in a bovine species, as required by claim 29. Accordingly, we
reverse the Examiner’s rejection of that claim, and its dependent claims 30
and 40-44, as anticipated by Boothby I.
OBVIOUSNESS
ISSUE
Claims 1, 3-12, and 29-56 stand rejected under 35 U.S.C. § 103(a) as
obvious over Boothby I, Poumarat, and Thorns (Ans. 5-9). The Examiner
cites Boothby I for its disclosure of a vaccine containing inactivated M.
bovis, but concedes that Boothby I does not include more than one biotype
in its vaccine (Ans. 7-8).
The Examiner reasons that an ordinary artisan would nonetheless have
considered it obvious to include more than one biotype in Boothby I’s
vaccine in view of Poumarat’s teaching of a “marked intraspecies genomic
heterogeneity among isolates of Mycoplasma bovis collected from different
geographic origins and that antigenic variability must be taken into account
in developing diagnostic and vaccination strategies” (id. at 9).
The Examiner further reasons that an ordinary artisan would have
considered it obvious to use attenuated M. bovis biotypes in Boothby I’s
vaccine in view of Thorns’ teaching that “high passaged M. bovis strains
were less virulent and produced only minor histopathological changes in
vaccinated animals and do not cause systematic changes in inoculated
animals” (id.).
Appellants argue the claims subject to this rejection separately (see
App. Br. 18-22). Specifically, with respect to all of the rejected claims,
Appellants contend that the absence of unfavorable reactions resulting from
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the claimed vaccine, contrasted with the unfavorable delayed
hypersensitivity caused by Boothby I’s vaccine, and the undesirable
histopathological changes caused by Thorns’ preparation, demonstrates that
the cited references do not support a prima facie case of obviousness (id. at
18).
Regarding claims 8-12, 31-39, and 46-51, Appellants argue that the
cited references do not suggest including more than one biotype in an M.
bovis vaccine because Poumarat teaches that the same degree of variability
exists within genomic groups as across them (id. at 19). Thus, Appellants
urge, because “Poumarat teaches that there would be no gain in antigenic
variability from including more than one type of Mycoplasma bovis in a
vaccine . . . there would be no point in having more than one type of
Mycoplasma bovis in a vaccine” (id.). Appellants urge that Poumarat
therefore “teaches away from the invention defined by claims 8-12, 31-39,
and 46-51” (id.).
Regarding claims 29, 30, and 40-45, Appellants argue that none of the
cited references teach or suggest preparing a vaccine that is protective
against M. bovis mastitis (id. at 20-21). Specifically, Appellants argue, the
evidence of record shows that there was a long-felt need for a vaccine
against bovine M. bovis mastitis, which others had tried and failed to fulfill
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(id. at 21-22 (citing Hanson I,5 Hanson II,6 and Boothby II); see also Reply
Br. 10-11 (citing Heller7)).
Regarding claims 34-39 and 46-51, Appellants note that these claims
“require that the at least two biotypes be genetically different, as judged by
analysis of DNA or RNA” (App. Br. 20). Given Poumarat’s express
teaching that genetic differences are irrelevant with respect to antigenicity,
Appellants argue, an ordinary artisan “would clearly interpret this
conclusion as a teaching that nothing is to be gained from including biotypes
that are genetically different in a vaccine, and thus would be discouraged
from the invention of claims 34-39 and 46-51” (id.).
Regarding claim 56, Appellants argue that, “although Thorns does
disclose attenuated strains of Mycoplasma bovis, Thorns states that these
strains are not vaccines, but might provide ‘further insight’ which could
‘perhaps’ lead to the development of a vaccine” (id. at 22 (citing Thorns
332)). Thus, Appellants conclude, given the absence of “disclosure of an
attenuated vaccine that is protective against respiratory pneumonia in any of
Boothby I, Thorns, or Poumarat, and the lack of any suggestion as to how
such a vaccine could be produced in those references, it cannot properly be
said that those references make obvious claim 56” (id.).

5 Maureen Hanson, Mycoplasma mastitis: It’s everyone’s problem, BOVINE
VETERINARIAN 4-8 (September 2001).
6 Maureen Hanson, Mycoplasma mastitis: Prevention and control, BOVINE
VETERINARIAN 12-20 (October 2001).
7 Martin Heller et al., Antigen capture ELISA using a monoclonal antibody
for the detection of Mycoplasma bovis in milk, 37 VETERINARY
MICROBIOLOGY 127-133 (1993).
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We select claims 1, 8, 29, 34, and 56 as representative of the rejected
claims. See 37 C.F.R. § 41.37(c)(1)(vii).
Thus, in view of the positions advanced by Appellants and the
Examiner, the issue with respect to this rejection is whether the evidence of
record supports the Examiner’s position that an ordinary artisan would have
found claims 1, 8, 29, 34, and 56 prima facie obvious in view of Boothby I,
Poumarat, and Thorns.
FINDINGS OF FACT
23. Thorns discloses a study in which the “mouse mastitis model was
used to examine strains of Mycoplasma bovis. Strains that had been
passaged in liquid medium more than 60 times were markedly less virulent
than the same or different strains with fewer passages” (Thorns 328
(abstract)).
24. “Whereas the low passage strains produced a systemic response in
some mice and severe pathological and histopathological changes in the
mammary glands of all, the high passage strains produced only minor
histopathological changes” (id.).
25. Based on its results, Thorns concludes that “[w]hatever mechanisms
the virulent strains have lost or modified, they should provide further insight
into the pathogenesis of M bovis mastitis which could perhaps lead to a
stable vaccine for this disease” (id. at 332).
PRINCIPLES OF LAW
As the Supreme Court pointed out in KSR Int'l Co. v. Teleflex
Inc., 550 U.S. 398 (2007), when determining whether the prior art supplied a
reason for practicing the claimed subject matter, the analysis “need not seek
out precise teachings directed to the specific subject matter of the challenged
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claim, for a court can take account of the inferences and creative steps that a
person of ordinary skill in the art would employ.” Id. at 418; see also id. at
421 (“A person of ordinary skill is . . . a person of ordinary creativity, not an
automaton.”).
The Court also reaffirmed that prima facie obviousness requires a
reasonable expectation of success:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.

Id. at 421 (emphasis added).
ANALYSIS
Appellants’ arguments do not persuade us that the Examiner failed to
make a prima facie case of obviousness with respect to claim 1.
As discussed above, claim 1 does not contain any language that
excludes vaccines that might have undesired side effects, such as the
hypersensitivity or minor histopathological changes exhibited, respectively,
by the preparations described in Boothby I and Thorns (FF 10, 24). Thus,
because Appellants’ argument is not directed to a limitation present in the
claim, the argument is not persuasive of the claim’s patentability.
As also discussed above, Boothby I’s vaccines elicited strong
antibody responses, and none of the vaccinated calves in Boothby I’s study
showed any signs of respiratory illness, despite having been experimentally
challenged in the nares and bronchio-alveolar regions with live M. bovis (FF
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5, 8, 9), thus providing evidence that Boothby I’s vaccine not only contains
the ingredients required by claim 1, but also meets claim 1’s functional
limitation requiring protection against respiratory pneumonia.
As Appellants point to no clear or direct evidence controverting the
reasonableness of the Examiner’s conclusion of obviousness with respect to
claim 1, we affirm the Examiner’s obviousness rejection of that claim over
Boothby I, Poumarat, and Thorns. As they were not argued separately,
claims 3-7 and 52-55 fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii).
Claim 8 recites a vaccine which is protective against any Mycoplasma
bovis clinical disease in a bovine species. The vaccine must contain at least
two inactivated or attenuated M. bovis biotypes and a pharmaceutically
acceptable excipient.
As noted above, the Specification defines biotype as “a variant of a
species, i.e. a strain, that can be distinguished by one or more characteristics,
such a ribosomal RNA sequence variation, DNA polymorphisms,
serological typing, or toxin production” (Spec. 5 (FF 4)).
Thus, because biotypes can be differentiated by serological typing,
claim 8 encompasses a vaccine that contains at least two strains of M. bovis
that have different antigens as determined through immunological testing.
As noted above, Poumarat found through immunological testing that M.
bovis has “[t]wo highly-variable antigenic systems. . . . It is evident that this
antigenic variability must be taken into account in developing diagnostic and
vaccination strategies” (Poumarat 319 (FF 15)).
Given the high degree of antigenic variability in M. bovis, and
Poumarat’s express teaching that this variability must be taken into account
when developing vaccination strategies, we agree with the Examiner that an
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ordinary artisan would have been prompted by Poumarat to include more
than one M. bovis biotype in Boothby I’s vaccine, so as to ensure protection
against more than just one strain.
We acknowledge Poumarat’s disclosure that the antigenic variability
in M. bovis detected in its investigation was not linked to the genomic
groups the study identified (FF 14). As discussed above, however, claim 8
encompasses compositions in which the two biotypes are distinguishable by
serological testing. Given the teachings in Poumarat, discussed above, we
are not persuaded that an ordinary artisan lacked impetus for combining two
serologically different biotypes in an M. bovis vaccine.
As Appellants’ arguments do not persuade us that the Examiner failed
to make a prima facie case of obviousness with respect to claim 8, we affirm
the Examiner’s rejection of that claim over Boothby I, Poumarat, and
Thorns, as well as claims 9-12, 31, and 32, which were argued in the same
group as claim 8, and which were not argued separately elsewhere. See 37
C.F.R. § 41.37(c)(1)(vii).
Claim 34 recites “[t]he vaccine of claim 8 wherein the at least two
inactivated or attenuated Mycoplasma bovis biotypes are genetically
different as determined by an analysis of DNA or RNA from the biotypes.”
We again acknowledge Poumarat’s disclosure that the antigenic
variability in M. bovis detected in its investigation was not directly linked to
the genomic groups it identified (FF 14). We are not persuaded, however,
that an ordinary artisan would have reasonably inferred from this teaching
that nothing would be gained from including genetically different strains in
an M. bovis vaccine, as Appellants argue (App. Br. 20).
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Rather, in our view, an ordinary artisan would have reasonably
expected that differences in antigens between M. bovis strains would
ultimately be reflected in the strains’ genetic makeup. Thus, while it might
be true that the methods used by Poumarat did not uncover any specific link
between the particular genomic groups identified in the study and antigenic
variability, given that an ordinary artisan would have expected strains with
different antigens to be genetically different, we agree with the Examiner
that an ordinary artisan would have been prompted to include genetically
different strains, as identified by DNA or RNA analysis, in an M. bovis
vaccine.
Accordingly, as Appellants’ arguments do not persuade us that the
Examiner erred in concluding that claim 34 would have been prima facie
obvious to an ordinary artisan, we affirm the Examiner’s rejection of that
claim as obvious over Boothby I, Poumarat, and Thorns, as well as claims
35-39, and 46-51, which were argued with claim 34 (App. Br. 20).
Regarding claim 29, however, we conclude that a preponderance of
the evidence does not support the Examiner’s position that an ordinary
artisan following the teachings of Boothby I, Poumarat, and Thorns would
have had a reasonable expectation in producing a vaccine protective against
M. bovis mastitis in a bovine species. We again note, as the Examiner
argues, that Boothby II discloses that a vaccine containing formalin-killed
California 201, the same M. bovis strain used in Boothby I, resulted in no M.
bovis being recoverable from quarters challenged, i.e. experimentally
infected, with live M. bovis (see FF 21).
However, as noted above, the California Mastitis Test (CMT) scores
on all vaccinated quarters remained elevated throughout the duration of
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Boothby II’s study (id.). In contrast, as also noted above, some challenged
quarters on control, i.e. unvaccinated, cows became CMT-negative (FF 22).
Thus, Boothby II shows that essentially the same vaccine as in
Boothby I did not protect cows against mastitis as measured by the CMT
test, and as compared to controls. Given this disclosure, we are not
persuaded that an ordinary artisan following the teachings of Boothby I,
Poumarat, and Thorns would have had a reasonable expectation of
producing a vaccine capable of protecting against M. bovis bovine mastitis.
Accordingly, we find Appellants’ arguments persuasive that claims
29, 30, and 40-45 would not have been obvious over Boothby I, Poumarat,
and Thorns, and reverse the Examiner’s obviousness rejection of those
claims.
Claim 56 recites “[a] vaccine which is protective against Mycoplasma
bovis clinical disease in a bovine species comprising at least one attenuated
Mycoplasma bovis biotype and a pharmaceutically acceptable excipient,
wherein the clinical disease includes respiratory pneumonia.”
As discussed above, Boothby I discloses a vaccine containing
formalin-killed M. bovis, the vaccine being protective against respiratory
pneumonia. While Boothby I might not disclose the use of attenuated M.
bovis in its vaccine, Thorns, however, describes preparing attenuated M.
bovis strains which are of such low virulence that they only induce small
histopathological changes in the mouse mastitis model (FF 23, 24).
As noted above, Thorns expressly teaches that the avirulent strains
“should provide further insight into the pathogenesis of M bovis mastitis
which could perhaps lead to a stable vaccine for this disease” (Thorns 332
(FF 25)). Thus, given these teachings, we agree with the Examiner that an
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ordinary artisan preparing an M. bovis vaccine with killed cells according to
Boothby I would have reasoned that Thorns’ attenuated strains would be
effective in a similar fashion to the killed cells in a vaccine composition
targeting respiratory disease in cows.
We acknowledge, as Appellants argue, that an ordinary artisan might
have considered Thorns’ “perhaps” language (FF 25) as only a prophetic
suggestion of a mastitis vaccine. Claim 56, however, is directed to a vaccine
that is protective against respiratory pneumonia, not mastitis.
Given the positive results obtained by Boothby I against respiratory
symptoms when using killed M. bovis cells as a vaccine (FF 5, 8, 9), and the
absence of any clear or direct evidence from Appellants controverting the
adequacy of those findings, a preponderance of the evidence supports the
Examiner’s position that an ordinary artisan would have had a reasonable
expectation that Thorns’ live, but attenuated, M. bovis cells would also
function suitably in a vaccine protective against respiratory pneumonia.
Thus, as Appellants’ arguments do not persuade us that the Examiner failed
to make a prima facie case of obviousness with respect to claim 56, we
affirm the Examiner’s rejection of that claim over Boothby I, Poumarat, and
Thorns.

SUMMARY
We affirm the Examiner’s rejection of claims 1, 3, 52, 53, and 55 as
anticipated by Boothby I.
However, we reverse the Examiner’s rejection of claims 5, 6, 29, 30,
40-44, and 54 as anticipated by Boothby I.
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We also affirm the Examiner’s rejection of claims 1, 3-12, 31-39, and
46-56 as obvious over Boothby I, Poumarat, and Thorns.
However, we reverse the Examiner’s rejection of claims 29, 30, and
40-45 as obvious over Boothby I, Poumarat, and Thorns.

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-IN-PART

cdc

KENYON & KENYON
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