Ex Parte Browning et al

Patent Trial and Appeal Board

Apr 10, 2017

13202534 (P.T.A.B. Apr. 10, 2017)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/202,534 11/02/2011 Glenn Francis Browning 91965-818251 (002100US) 9244
20350 7590 04/12/2017
KILPATRICK TOWNSEND & STOCKTON LLP
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
EXAMINER
BASKAR, PADMAVATHI
ART UNIT PAPER NUMBER
1645
NOTIFICATION DATE DELIVERY MODE
04/12/2017 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):
ipefiling@kilpatricktownsend.com
jlhice@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GLENN FRANCIS BROWNING,
PHILIP FRANCIS MARKHAM, and CHI-WEN TSENG
Appeal 2016-004149
Application 13/202,5341
Technology Center 1600
Before FRANCISCO C. PRATS, RYAN H. FLAX and DAVID COTTA,
Administrative Patent Judges.
COTTA, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to a vaccine
composition. The Examiner rejected the claims on appeal under 35 U.S.C.
§ 103(a) as obvious.
We affirm.
1 According to Appellants, the real party in interest is Australian Poultry
CRC Pty Limited. App. Br. 3.
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Application 13/202,534
STATEMENT OF THE CASE
The Specification states that it was “known that vaccine compositions
comprising attenuated pathogenic microorganisms such as bacteria or
viruses are effective in producing a protective immune response in
vaccinated animals and humans.” Spec., p. 1,11. 23—25. Typically,
“attenuation of pathogenic organisms for use in a vaccine is achieved by
complete or partial removal of one or more virulence factors such that the
organism is no longer pathogenic.” Id. atp. 1,11. 30-32. The Specification
asserts that virulence factors like toxins are obvious targets for attenuation,
but factors that were not known to be “virulence factors” are “not obvious
targets for attenuation.” Id. at p. 2,11. 9-10.
The Specification explains that ATP binding cassette (“ABC”)
transporters — “membrane proteins that function to translocate substrates
across extra- and intra-cellular membranes” — “are not commonly thought of
as virulence factors.” Id. at p. 2,11. 12—15. The Specification then asserts
that “the present invention is predicated on the surprising finding that a loss
of function mutation of an ABC-transporter gene in pathogenic organisms
attenuated the pathogenic organisms although the attenuated organisms
remained immunogenic and persisted in the subject as assessed in a host-
disease model system.” Id., at p. 2,11. 19-24.
Claims 24, 40-43, and 45—50 are on appeal.2 Claim 24 is illustrative
and reads as follows:
2 In the Examiner’s Answer, the Examiner withdrew the pending rejection of
claim 44 under 35 U.S.C. § 103(a). Ans. 2. The patentability of claim 44 is,
thus, no longer a part of this appeal.
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Application 13/202,534
24. A vaccine composition comprising an
immunogenically effective amount of attenuated bacteria and a
pharmaceutically acceptable carrier, wherein:
the attenuated bacteria are attenuated by a mutation in an
Oligopeptide Transport ATP-Binding Protein OppD (OppD)
gene,
the mutation renders the OppD protein encoded by the
OppD gene non-functional, and
the attenuated bacteria can persist in a subject to which
the vaccine is administered.
The Examiner rejected claims 40-43, and 45—50 under 35 U.S.C.
§ 103(a) as obvious over the combination of Green,3 Podbielski,4 Hogarth5
and Garmory.6
FINDINGS OF FACT
1. Garmory discloses:
The purpose of this review is to demonstrate the
possibility of targeting ABC transporters for the
development of antibacterial vaccines and therapies.
Traditionally, bacterial ABC transporters have been
considered to play roles in nutrient uptake and drug
resistance. However, there is increasing evidence that
3 Green et al., A Peptide Permease Mutant of Mycobacterium bovis BCG
Resistant to the Toxic Peptides Glutathione and S-Nitrosoglutathione, 68(2)
Infection and Immunity 429-36 (2000) (“Green”).
4 Podbielski et al., Molecular Characterization of Group A Streptococcal
(GAS) Oligopeptide Permease (Opp) and its Effect on Cystein Protease
Production, 21(5) Molecular Microbiology 1087-99 (1996)
(“Podbielski”).
5 Hogarth et al., Genetic Organization of the Oligopeptide Permease (opp)
Locus of Salmonella Typhimurium and Escherichia Coli, 153(3) J.
Bacteriol. 1548-51 (1983) (“Hogarth”).
6 Garmory et al., ATP-Binding Cassette Transporters Are Targets for the
Development of Antibacterial Vaccines and Therapies, 72(12) Infection
and Immunity 6757-63 (2004) (“Garmory”).
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Application 13/202,534
these transport systems play either direct or indirect roles
in the virulence of bacteria.
Garmory 6758.
2. Garmory discloses: “the studies described in this review
indicate that ABC transporter proteins may be suitable targets for the
development of antibacterial vaccines, either through the development of
live attenuated bacteria or through the development of protein- and DNA-
based subunit vaccines.” Id. at 6762.
3. Garmory discloses:
The roles of ABC transporters in virulence of pathogenic
bacteria have been attributed to the requirement for uptake of
various nutrients. Several examples have been identified by
using signature-tagged mutagenesis (STM), a technique
designed to enable large-scale screening of bacterial mutants for
organisms that have an attenuated phenotype. . . . Multiple
animal infection models have also been used for STM to
identify genetic loci that may be universally important for
bacterial survival in vivo. When this approach was used with a
number of Staphylococcus aureus models of infection, the
largest gene class identified included genes encoding amino
acid or oligopeptide transporters. For example, an oppC
mutant was attenuated in multiple animal models. The oppC
gene encodes a permease component of an oligopeptide
transport system, Opp. In a separate study, STM was used to
identify clones of S. aureus with mutations in genes with
homology to oppD and oppF, which are genes that encode the
ABC-containing proteins of the same oligopeptide ABC
transport system.
Id. at 6758 (emphasis added).
4. Green discloses: “Using sequences from the available genome
database for Mycobacterium tuberculosis H37Rv, the oligopeptide permease
operon (oppBCDA) of Mycobacterium bovis BCG was cloned from a cosmid
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Application 13/202,534
library. An opp mutant strain was constructed by homologous
recombination with an allele of oppD interrupted by kanamycin and
streptomycin resistance markers.” Green Abstract.
5. Podbielski discloses: “To study the molecular and biological
functions of the GAS [Group A Streptococcal] opp operon, the Opp-
associated ATPase function was disrupted. . . . Insertional mutagenesis
utilizing the vector pSF152 was performed which resulted in a truncated
oppD gene and eliminated oppF expression.” Podbielski 1091.
6. Hogarth discloses complementation experiments using
bacteria with mutations to opp genes, including oppD. Hogarth 1548.
ANALYSIS
Appellants argue claims 24, 40-43, and 45—50 together as a group.
We designate claim 24 as representative of the group.
OppD is a gene encoding an ABC transporter protein. T he Examiner
found that Green, Podbielski and Hogarth each disclosed a strain of bacteria
with an oppD mutation. Ans. 2—3. The Examiner thus concluded that
Green, Podbielski, and ITogarth met all of the limitations of claim 24 with
the exception of a “pharmaceutical carrier.” Id. at 3.
The Examiner found that Garmory disclosed that “ABC transporter
proteins may be suitable targets for the development of antibacterial
vaccines, either through the development of live attenuated bacteria (see
page 6762, left column) or through the development of protein and DNA
based subunit vaccines (see page 6760, right column).” Id. Garmory further
disclosed that “mice immunized with a Brucella abortus mutant having a
deletion in a virulence gene encoding that ABC-containing protein ExsA
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Application 13/202,534
exhibited superior protective immunity against virulent B. abortus
challenge.” Id.
Based on the combined teachings of Garmory, Green, Podbielsld, and
Hogarth, the Examiner concluded:
it would have been obvious to one of skill in the art, at
the time of invention, to use the composition comprising
oppD mutants as taught by Green et al 2000 or
Podbielski et al or Hogarth et al in an immunogenic
composition comprising pharmaceutical carrier because
Garmory et al suggests ABC transporter proteins may be
suitable targets for the development of antibacterial
vaccines, either through the development of live
attenuated bacteria (see page 6762, left column) or
through the development of protein- and DNA-based
subunit vaccines (see page 6760, right column).
Id. We agree with the Examiner that the claimed composition would have
been obvious over the combination of Garmory, Green, Podbielski, and
Hogarth and address Appellants’ arguments below.
Appellants argue that while Green, Podbielski, and Hogarth “disclose
the generation and characterization of certain bacterial strains comprising
opp mutations[,]. . . bacteria having a mutation rendering a certain gene
product non-functional are not necessarily (attenuated. App. Br. 8.
Appellants contend that Garmory describes “a vaccine that is based on
bacteria with a non-functional ABC exopolvsaccharide transporter (exsA
protein),” and that “[t]his is an entirely different class of ABC transporter
than OppD, which is an ABC peptide transporter.” Id. at 10. Appellants
point to Garmory’s teaching that ABC transporters “comprise one of the
largest protein families” and that ABC transporters are “functionally diverse,
covering a variety of different biological roles such as membrane transport,
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RNA translation, and DNA repair and [are] involved in a very wide range of
substrates including nucleic acids, nucleotide triphosphates, sugars, lipids,
sterols, drugs, oligopeptides, ATP/GTP, and numerous other metabolic
products.” Id. Given the large and functionally diverse nature of the ABC
protein family, Appellants contend that the skilled artisan would not
reasonably have expected that “immunogenically effective amounts of
attenuated OyyD mutant bacteria could be generated and combined with a
pharmaceutically acceptable carrier in order to arrive at the claimed vaccine
composition.” Id. at 10—11.
We are not persuaded. Garmory teaches that ABC transporter
proteins play a role in the virulence of bacteria. FF1; see also Garmory
6758—59 (under section heading “ABC transporters have roles in bacterial
virulence”). Garmory further teaches that ABC transporter proteins may be
“suitable targets for the development of antibacterial vaccines . . . through
the development of live attenuated bacteria . . . .” FF2. While Garmony
does not disclose the use of oppD mutants as a vaccine, Garmory does
disclose that a mutation to the oppC gene attenuated Staphylococcus aureus
in multiple animal models. FF3. And Garmony further discloses that oppD
encodes proteins of the same transport system as oppC. Id. In view of these
teachings, we find that a skilled artisan would reasonably have expected that
a mutation to the oppD gene would attenuate bacteria. Given this
expectation, it would have been obvious to incorporate the oppD mutant
bacteria of Green, Podbielski, or Hogarth with a pharmaceutically acceptable
carrier in a vaccine. Appellants’ arguments regarding the size and diversity
of the genus of ABC transporter proteins and regarding Garmory’s teaching
of a vaccine from a different class of ABC transporter protein are not
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persuasive because, in view of the above discussed teachings of Garmory,
they would not have diminished the expectations of the skilled artisan with
respect to the attenuating effects of mutations of oppD.
Appellants argue that because “Green, Podbielski, and Hogarth fail to
teach about the immunogenic properties of the bacteria or about the capacity
of the bacteria to persist in a subject, there is no basis for the Examiner’s
assumption that the compositions allegedly taught by the cited references
comprise an immunogenically effective amount of attenuated bacteria.”
App. Br. 7. We find this argument unpersuasive because the Examiner relies
upon a combination of references — not Green, Podbielski, or Hogarth alone
— to render the claims obvious. See, In re Merck & Co., 800 F.2d 1091,
1097 (Fed. Cir. 1986) (“Non-obviousness cannot be established by attacking
references individually where the rejection is based upon the teachings of a
combination of references.”). As discussed above, Garmory suggests
incorporating oppD mutant bacteria, like that disclosed in Green, Podbielski,
and/or Hogarth, with a pharmaceutically acceptable carrier in a vaccine.
This suggestion encompasses an “immunogenically effective amount of
attenuated bacteria,” particularly given the breadth of the term
“immunogenically effective amount.” See, Spec. p. 17 (“The vaccine
composition may comprise any dose of bacteria, sufficient to evoke an
immune response” including specified amounts of 103 and 1019 attenuated
bacteria.).
Accordingly, we affirm the Examiner’s determination that claim 24 is
obvious under 35 U.S.C. § 103(a) over the combination of Green,
Podbielski, Hogarth, and Garmory. Because they were not argued
separately, claims 40-43, and 45—50 fall with claim 24.
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SUMMARY
For the reasons provided herein and those set forth in the Examiner’s
Answer and the Final Office Action, the rejection of claims 24, 40 43, and
43—50 under 35 U.S.C. § 103(a) as obvious over the combination of Green,
Podbielski, Hogarth, and Garmory is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1).
AFFIRMED
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