Ex Parte Missiakas et al

Patent Trial and Appeal Board

Nov 29, 2017

12161315 (P.T.A.B. Nov. 29, 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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/161,315 02/19/2009 Dominique Missiakas ARCD:430US/10808297 1298
32425 7590 12/01/2017
NORTON ROSE FULBRIGHT US LLP
98 SAN JACINTO BOULEVARD
SUITE 1100
AUSTIN, TX 78701-4255
EXAMINER
LYONS, MARY M
ART UNIT PAPER NUMBER
1645
NOTIFICATION DATE DELIVERY MODE
12/01/2017 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):
aoipdocket @ nortonrosefulbright .com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte DOMINIQUE MISSIAKAS, YUKIKO STRANGER-JONES,
MONICA BURTS, and OLAF SCHNEEWIND1
Appeal 2016-003278
Application 12/161,315
Technology Center 1600
Before ERIC B. GRIMES, RICHARD J. SMITH, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
of eliciting an immune response, which have been rejected for lack of
enablement and lack of adequate written description. We have jurisdiction
under 35 U.S.C. § 6(b).
We affirm.
1 Appellants identify the Real Party in Interest as The University of Chicago.
(Appeal Br. 3.)
Appeal 2016-003278
Application 12/161,315
STATEMENT OF THE CASE
The Specification states that “[t]he Staphylococcus aureus pathogen is
the most common food-bome infection and it is responsible for causing a
number of other infections, including infections of open wounds and toxic
shock syndrome.” (Spec. 3:23—25.) The Specification states that “[t]he
invention is based on data that an immune response can be generated against
one or more extracellular proteins in bacteria, which includes secreted
virulence factors.” {Id. at 3:30 to 4:2.) “In certain embodiments a secreted
virulence factor is an Esx protein, for instance, all or part of an EsxA or
EsxB protein.” {Id. at 4:21—22.)
Claims 1—10, 14, 17, 18, 36, and 134—138 are on appeal. Claim 1 is
illustrative and reads as follows:
1. A method for eliciting a protective immune response against a
Staphylococcus aureus bacterium in a subject comprising providing to the
subject an effective amount of an isolated EsxA and EsxB protein that
provides resistance to infection, wherein the isolated protein comprises:
(1) an EsxA sequence at least 90% identical to SEQ ID NO:2; and
(2) an EsxB sequence at least 95% identical to SEQ ID NO:4.
The claims stand rejected as follows:
Claims 1-10, 14, 17, 18, 36, and 13^138 under 35 U.S.C. § 112, first
paragraph, for lack of adequate written descriptive support (Ans. 2) and
Claims 1-10, 14, 17, 18, 36, and 13^138 under 35 U.S.C. § 112, first
paragraph, for lack of enablement (Ans. 7).
I
The Examiner has rejected all of the claims on appeal for lacking
adequate written description. The Examiner finds that “the specification
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does not describe any structures (i.e. any protein or nucleotide sequences),
other than SEQ ID NOs 2 and 4, that possess at least 90-95% similarity to
SEQ ID NOs 2 or 4 and also retain the functional properties of eliciting a
protective immune response and providing resistance to infection.” (Ans. 3.)
The Examiner also finds that the Specification “fails to provide a
sufficient correlation between the claimed functional characteristics (i.e.
eliciting a protective immune response and providing resistance to a S.
aureus infection) and the necessary structural components (i.e. critical
domains within the sequences responsible for the claimed functional
property).” (Id. at 4.) Finally, the Examiner finds that the Specification
“adequately describes two complete chemical structures possessing the
claimed functions identified as SEQ ID NO: 2 (EsxA) and SEQ ID NO: 4
(EsxB; therefore, discloses only 1 representative species for each
subgenus).” (Id. at 5.) The Examiner concludes that
one of skill in the art would not accept the disclosure of SEQ ID
NO: 2 as representative of all other proteins with 90% identity to
SEQ ID NO: 2 and having that claimed activity and would not
accept the disclosure of SEQ ID NO: 4 as representative of all
other proteins with 95% identity to SEQ ID NO: 2 and having
that claimed activity.
(Id. at 6.)
We agree with the Examiner that the Specification does not describe
that claimed genus of proteins in a manner that shows that Appellants were
in possession of the full scope of the claimed invention at the time the
application was filed. A “sufficient description of a genus . . . requires the
disclosure of either a representative number of species falling within the
scope of the genus or structural features common to the members of the
genus so that one of skill in the art can ‘visualize or recognize’ the members
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of the genus.” Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1350
(Fed. Cir. 2010). “[T]he test for sufficiency is whether the disclosure of the
application relied upon reasonably conveys to those skilled in the art that the
inventor had possession of the claimed subject matter as of the filing date.”
Id. at 1351. “[T]he specification must describe an invention understandable
to that skilled artisan and show that the inventor actually invented the
invention claimed.” Id.
The Specification states that Staphylococcal antigens include EsxA
and EsxB, and that “[tjhese proteins may be modified by deletion, insertion,
and/or substitution. In particular embodiments, modifications of these
proteins are capable of eliciting an immune response in a subject.” (Spec.
23:20—27.) The Specification states that “[i]n certain embodiments, the
EsxA sequence is . . . (SEQ ID NO:2). ... In other embodiments, the EsxB
sequence is . . . (SEQ ID NO:4).” {Id. at 23:31 to 24:5.)
The Specification defines “protective immunity” as follows:
“Protective immunity refers to a body’s ability to mount a specific immune
response that protects the subject from developing a particular disease or
condition that involves the agent against which there is an immune response.
An immunogenically effective amount is capable of conferring protective
immunity to the subject.” {Id. at 68:7—11.)
In a working example, the Specification states that “[ejfficacy of
purified EsxA antigen in raising protective immunity was studied in a sub-
lethal bacterial mouse challenge model. . . . The experiment suggests that
immunization with purified EsxA antigen confers partial protection against
S. aureus disease.” {Id. at 87:17—26.) The Specification also includes a
prophetic example that states, “[sjince animals acutely infected with S.
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aureus mount an immune response to EsxA and EsxB as judged by our
ELISA experiment. . . , the efficacy of purified antigens of raising
protective immunity will be tested in sub-lethal bacterial mouse challenge
models.” {Id. at 89:2—5.)
Thus, the Specification describes EsxA and EsxB and “confer[ring]
partial protection against S. aureus disease” (Spec. 87:26 (EsxA)) or “an
immune response” (Spec. 89:3 (both EsxA and EsxB)). The Specification
does not, however, describe which parts of each protein are responsible for
causing an immune response, nor does it describe a representative number of
species within the claimed genera that would show possession to a person of
ordinary skill in the art. In addition, the Specification does not describe
either EsxA or EsxB, or both of them together, as providing a protective
immune response, as required by claim 1, and defined in the Specification as
“a specific immune response that protects the subject from developing a
particular disease or condition that involves the agent against which there is
an immune response.” {Id. at 68:8—10.) We therefore agree with the
Examiner that the Specification’s description does not show that Appellants
were in possession of the claimed invention as of the filing date of the
application.
Appellants argue that “it is not necessary to disclose multiple
sequence variants having the claimed activity when sequence variants are
known to exist with the same activity as the disclosed sequence and there is
information known in the art correlating structure to function.” (Appeal Br.
8.) Appellants argue that
[t]he attached sequence alignments in Exhibits A and B show an
alignment of SEQ ID NO: 2 (EsxA) and four EsxA homologs (as
identified in Burts et al., “EsxA and EsxB are secreted by an
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ESAT-6-like system that is required for the pathogenesis of
Staphylococcus aureus infections,” PNAS, vol. 102 (4), 2005),
that were known in the art at the time of filing (Exhibit A) and
an alignment of SEQ ID NO: 4 (EsxB) and four EsxB variants
known in the art at the time of filing (Exhibit B).
(Id.) Appellants argue that “[b]y definition, as EsxA homologs and EsxB
variants, these sequences maintain the biological activity of EsxA and
EsxB.” (Id.)
This argument is unpersuasive. First, Exhibit A includes an alignment
of EsxA with four proteins, designated Lmo0056, SAG1039, CAC3713, and
BS—yukE. (Appeal Br., Ex. A.) Burts, the reference cited by Appellants as
showing that the sequences of the genes encoding these proteins were known
in the art, includes a figure showing the organization of genetic loci that
include the L. monocytogenes lmo0056 gene and the B. subtilis yukE gene,
but does not include anything that appears to correspond with genes
encoding either the SAG 1039 or CAC3713 sequences included in
Appellants’ Exhibit A. (See Burts 1170, Fig. IB.) More importantly, Burts
does not disclose sequence information for any of these genes, but simply
the organization of their genetic loci. Burts therefore does not support
Appellants’ position that the sequences of these genes were known in the art
at the time the application was filed. And Appellants point to no evidence to
support their position that the EsxB sequences shown in the Appeal Briefs
Exhibit B were known in the art.
Even if such sequences were known in the art, however, and were
likely to share the same function, that would not show possession of the
genus of proteins recited in the claims. The function of EsxA and EsxB is
that of secreted virulence factors of S. aureus (see Spec. 4:21—22), whereas
the function recited in the claims is that of eliciting a protective immune
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response. Thus, even if the other proteins shown in Appellants’ Exhibits A
and B would have been expected to share the function of EsxA and EsxB,
that is not evidence that such proteins would also share the function of
eliciting a protective immune response against S. aureus. Appellants’
evidence therefore does not show that those skilled in the art would have
recognized that Appellants were in possession of the claimed genera based
on their sequence similarity to other proteins.
Appellants also argue that
[a] person of skill in the art might not be able to predict with
perfect accuracy which of the species encompassed by the claims
would retain the function of eliciting a protective immune
response, but would expect that many EsxA and EsxB variants
having conservative substitutions, changes in non-conserved
residues, short deletions or insertions, and retaining 90% or
greater sequence identity to SEQ ID NO: 2 and 95% or greater
sequence identity to SEQ ID NO: 4 would retain the ability to
elicit a protective immune response
(Appeal Br. 10.)
This argument is unpersuasive, because Appellants have not pointed
to evidence that supports it. “Attorney’s argument in a brief cannot take the
place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
We conclude that the rejection of claim 1 for lack of adequate written
description is supported by a preponderance of the evidence of record.
Claims 2—10, 14, 17, 18, 36, and 134—138 have not been argued separately
and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
II
The Examiner has rejected all of the claims on appeal on the basis that
the Specification “does not reasonably provide enablement for a method for
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eliciting a protective immune response against a Staphylococcus aureus
bacterium in a subject comprising providing an effective amount of a
sequence at least 90% identical to SEQ ID NO: 2 and at least 95% identical
to SEQ ID NO: 4.” (Ans. 7.)
The Examiner finds that “the nature of the invention is a chemical
case, where there is natural unpredictability in performance of certain
species or subcombinations other than those specifically enumerated” {id. at
8); that the claims encompass a vast number of species {id. at 8—9); that the
Specification does not provide guidance regarding the required amount of
screening {id. at 9-10); and, although the level of skill in the art is high,
even one of skill in the art could not predictably extrapolate the
teachings in the specification, limited to only two actual
sequences: SEQ ID NO: 2 and SEQ ID NO: 4, to any and all
sequences at least 90% identical to SEQ ID NO: 2; and any and
all sequences at least 95% identical to SEQ ID NO: 4 (i.e.
trillions of sequences) wherein the sequences maintain the
claimed function of eliciting a protective immune response
against Staphylococcus aureus and providing resistance to
infection, as so broadly claimed.
{Id. at 12—13.) The Examiner concludes that “in view of the nature of the
invention, lack of guidance and direction provided by Applicant, the broad
and variable genus, the lack of predictability, and the lack of structure-
function correlation, there would be undue experimentation required to
practice the full scope of the methods as claimed.” {Id. at 13.)
We agree with the Examiner that the Specification does not provide
sufficient guidance to enable a person of ordinary skill in the art to practice
the full scope of claim 1 without undue experimentation. As discussed
above with respect to written description, the Specification provides no
guidance regarding the domains of either EsxA or EsxB that are important to
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the function of eliciting a protective immune response, nor does the
Specification provide any working examples other than SEQ ID NO: 2 and
SEQ ID NO: 4 for doing so, and even with respect to those specific
sequences, the Specification discloses only that “purified EsxA antigen
confers partial protection against S. aureus disease” (Spec. 87:25—26) and
that “the efficacy of [EsxA and EsxB] purified antigens of raising protective
immunity will be tested in sub-lethal bacterial mouse challenge models” {id.
at 89:4—5.)
Thus, the Specification does not provide guidance in determining
which EsxA sequences that are at least 90% identical to SEQ ID NO: 2, or
which EsxB sequences that are at least 95% identical to SEQ ID NO: 4,
would be most likely to have the function of eliciting a protective immune
response against S. aureus, particularly in light of the fact that the
Specification does not show that even SEQ ID NO: 2 or SEQ ID NO: 4
themselves have that function.
The Examiner calculates that claim 1 encompasses trillions of
different variants of SEQ ID NO: 2 and SEQ ID NO: 4. (Ans. 8—9.) In view
of the lack of guidance provided by the Specification as to which variants
would be likely to have a function that has not even been shown to be
possessed by SEQ ID NO: 2 or SEQ ID NO: 4 itself, we agree with the
Examiner that it would require undue experimentation to practice the full
scope of the claims based on the guidance provided by the Specification.
Appellants
point to EsxA homologs and EsxB variants, known at the time of
filing and shown in Exhibits A and B. These sequences maintain
the biological activity of EsxA and EsxB and alignment of the
same provides information correlating structure to function that
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demonstrates the variability in structure that is allowed while
maintaining function.
(Appeal Br. 12.)
As discussed above, however, Appellants’ evidence does not show
that the sequences that are shown in Exhibits A and B were known at the
time this application was filed, nor do they show that other known proteins
would have shared the function of eliciting a protective immune response
against S. aureus, as opposed to the function of being secreted virulence
factors. This argument is therefore unpersuasive.
Claims 2—10, 14, 17, 18, 36, and 134—138 have not been argued
separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
SUMMARY
We affirm both of the rejections on appeal.
TIME PERIOD FOR RESPONSE
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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