Ex Parte Ishikawa et al

Board of Patent Appeals and Interferences

Aug 16, 2012

11895989 (B.P.A.I. Aug. 16, 2012)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
11/895,989 08/27/2007 Muriel Y. Ishikawa 1003-002-002F-RDIV01 3431
44765 7590 08/16/2012
THE INVENTION SCIENCE FUND
CLARENCE T. TEGREENE
11235 SE 6TH STREET
SUITE 200
BELLEVUE, WA 98004
EXAMINER
RIGGS II, LARRY D
ART UNIT PAPER NUMBER
1631
MAIL DATE DELIVERY MODE
08/16/2012 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 MURIEL Y. ISHIKAWA, EDWARD K.Y. JUNG,
NATHAN P. MYHRVOLD,
RICHA WILSON, and LOWELL L. WOOD, JR.
__________

Appeal 2011-013261
Application 11/895,989
Technology Center 1600
__________

Before DONALD E. ADAMS, LORA M. GREEN, and
STEPHEN WALSH, Administrative Patent Judges.

GREEN, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134 from the
Examiner’s rejection of claims 1, 5, 6, 12, 22, 23, 27-31, 33, 35, 41, 43, 46,
47, 51, 54, 55, 57, 58, 70, and 80. We have jurisdiction under 35 U.S.C.
§ 6(b).
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STATEMENT OF THE CASE
Claim 1 is the only independent claim on appeal, and reads as follows:
1. A computer-implemented method, comprising:
presenting one or more computable epitopes of at least one agent;
predicting, in a computing device, one or more pattern changes in the one
or more computable epitopes of the at least one agent, wherein the pattern
changes are determined by analysis of past evolutionary progressions in the
one or more computable epitopes of the at least one agent;
designating at least one immune response component operable for
modulating (a) at least one of the one or more computable epitopes of the at
least one agent or (b) at least one pattern-changed computable epitope; and
communicating, to at least one user, the designated at least one immune
response component.

The following grounds of rejection are before us for review:1
I. Claims 1, 5, 6, 12, 22, 23, 27-31, 33, 35, 41, 43, 46, 47, 51, 54, 55,
57, 58, 70, and 80 stand rejected under 35 U.S.C. § 102(b) as being
anticipated by Chirino2 (Ans. 4).
II. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 9 of USSN 10/925,905 (Ans. 9-10).
III. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 81 of USSN 11/900,442 (Ans. 10-11).

1 The obviousness-type double patenting rejections over USSNs 10/925,904
(Ans. 9), 11/044,656 (Ans. 12), 11/724,580 (Ans. 14), 11/891,871 (Ans. 20-
21), 11/897,574 (Ans. 23), are moot in view of the abandonment of those
applications.
2 Chirino et al., US 2003/0022285 A1, published Jan. 30, 2003.
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IV. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 29 of USSN 11/004,446 (Ans. 11-12).
V. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claims 51 and 56 of USSN 11/046,658 (Ans.
13).
VI. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 12 of USSN 11/724,593 (Ans. 14-15).
VII. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 15 of USSN 11/729,958 (Ans. 16-17).
VIII. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claims 25 and 50 of USSN 11/731,001 (Ans.
17).
IX. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 34 of USSN 11/807,335 (Ans. 17-18).
X. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 37 of USSN 11/807,336 (Ans. 18-19).
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XI. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 25 of USSN 11/807,337 (Ans. 19).
XII. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 17 of USSN 11/891,331 (Ans. 19-20).
XIII. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 9 of USSN 11/893,554 (Ans. 21-22).
XIV. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claims 1, 79, and 85 of USSN 11/895,341 (Ans.
22).
XV. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 1 of USSN 11/213,325 (Ans. 24).
XVI. Claim 1 stands provisionally rejected on the ground of
nonstatutory obviousness-type double patenting as being
unpatentable over claim 7 of USSN 11/904,636 (Ans. 24-25).

We affirm rejections I-XVI.

ISSUE
Has the Examiner established by a preponderance of the evidence that
Chirino anticipates the claimed methods?
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FINDINGS OF FACT
FF1. The Specification teaches that the “application relates, in general, to
detection and/or treatment” (Spec. 3).
FF2. As to “systems” for performing the method, the Specification teaches:
In one or more various aspects, related systems include
but are not limited to circuitry and/or programming for
effecting the herein-referenced method aspects; the circuitry
and/or programming can be virtually any combination of
hardware, software, and/or firmware configured to effect the
herein- referenced method aspects depending upon the design
choices of the system designer.

(Id. at 4-5.)
FF3. As to “immune response component,” the Specification teaches that it
may include, but is not limited to, at least a part of a
macrophage, a neutrophil, a cytotoxic cell, a lymphocyte, a T-
lymphocyte, a killer T-lymphocyte, an immune response
modulator, a helper T-lymphocyte, an antigen receptor, an
antigen presenting cell, a dendritic cell, a cytotoxic T-
lymphocyte, a T-8 lymphocyte, a CD1 molecule, a B
lymphocyte, an antibody, a recombinant antibody, a genetically
engineered antibody, a chimeric antibody, a monospecific
antibody, a bispecific antibody, a multispecific antibody, a
diabody, a chimeric antibody, a humanized antibody, a human
antibody, a heteroantibody, a monoclonal antibody, a
polyclonal antibody, a camelized antibody, a deimmunized
antibody, an anti-idiotypic antibody, an antibody fragment,
and/or a synthetic antibody and/or any component of the
immune system that may bind to an antigen and/or an epitope
thereof in a specific and/or a useful manner.

(Id. at 17-18.)

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FF4. As to “agent,” the Specification teaches:
The term “agent”, as used herein, . . . may include, for example,
but is not limited to, an organism, a virus, a dependent virus, an
associated virus, a bacterium, a yeast, a mold, a fungus, a
protoctist, an archaea, a mycoplasma, a phage, a
mycobacterium, an ureaplasma, a chlamydia, a rickettsia, a
nanobacterium, a prion, an agent responsible for a transmissible
spongiform encephalopathy (TSE), a multicellular parasite, a
protein, an infectious protein, a polypeptide, a
polyribonucleotide, a polydeoxyribonucleotide, a
polyglycopeptide, a polysaccharide, a nucleic acid, an
infectious nucleic acid, a polymeric nucleic acid, a metabolic
byproduct, a cellular byproduct, and/or a toxin. The term
“agent” . . . may include, but is not limited to, a putative
causative agent of a disease or disorder, or a cell or component
thereof that is deemed, for example, a target for therapy, a
target for neutralization, and/or or a cell whose apoptosis,
phagocytic envelopment, removal, lysis or functional
degradation may prove beneficial to the host. The term “agent”
. . . may also include, but is not limited to, a byproduct or
output of a cell that may be neutralized and/or whose removal
or functional neutralization may prove beneficial to the host.
Furthermore, the term “agent”. . . may include an agent
belonging to the same family or group as the agent of primary
interest, or an agent exhibiting a common and/or a biological
function relative to the agent of primary interest.

(Id. at 18.)
FF5. The Specification teaches further:
The term “epitope” . . ., as used herein, may include, but is not
limited to, a sequence of at least 3 amino acids, a sequence of at
least nine nucleotides, an amino acid, a nucleotide, a
carbohydrate, a protein, a lipid, a capsid protein, a coat protein,
a polysaccharide, a sugar, a lipopolysaccharide, a glycolipid, a
glycoprotein, and/or at least a part of a cell. As used herein, the
term “epitope”. . . may, if appropriate to context, be used
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interchangeably with antigen, paratope binding site, antigenic
determinant, and/or determinant. As used herein, the term
“determinant” can include an influencing element, determining
element, and/or factor, unless context indicates otherwise. In
one aspect, the term “epitope” . . . includes, but is not limited
to, a peptide-binding site. As used herein, the term “epitope”
. . . may include structural and/or functionally similar sequences
found in the agent . . . . The term “epitope”. . . includes, but is
not limited to, similar sequences observed in orthologs,
paralogs, homologs, isofunctional homologs, heterofunctional
homologs, heterospecific homologs, and/or pseudogenes of the
agent. . . . The epitope. . . may include any portion of the agent.
In one aspect, the epitope. . . may include at least a portion of a
gene or gene-expression product. In another aspect, the epitope
may include at least a part of a non-coding region.

(Id. at 19).
FF6. As to the term “computable epitope,” the Specification teaches:
The term “computable epitope” as used herein, includes,
but is not limited to, an epitope . . . whose likely future mutable
forms may be predicted by using, for example, including, but
not limited to, practicable computer-based predictive
methodology and/or practicable evolutionary methods and/or
practicable probabilistic evolutionary models and/or practicable
probabilistic defect models and/or practicable probabilistic
mutation models.

(Id. at 21.)
FF7. The Examiner’s statement of the rejection may be found at pages 5-8
of the Answer. We also highlight the following facts from Chirino.
FF8. Chirino teaches that it relates
to the use of a variety of computational methods for modulating
the immunogenicity of proteins by identifying and then altering
potential amino acid sequences that elicit an immune response
in a host organism. In particular, proteins will be screened for
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MHC binding motifs [MHC], T cell receptor [TCR], and B cell
receptor [BCR] binding sequences.

(Chirino, p. 1, ¶2.)
FF9. Chirino teaches further:
[T]he present invention provides methods for generating
polypeptides exhibiting enhanced immunogenicity comprising
the steps of inputting a target protein backbone structure with
variable residue positions into a computer, applying at least one
computational immunogenicity filter to generate a set of
primary variant amino acid sequences, computationally
analyzing said set of primary variant amino acid sequences
using at least one protein design algorithm and identifying at
least one variant protein with enhanced immunogenicity. This
same method may be used to generate polypeptides exhibiting
reduced immunogenicity.

(Id. at p. 2, ¶18.)
FF10. According to Chirino, “the methods of the invention involve starting
with a target protein and using computational analysis to generate a set of
primary sequences” (id. at pp. 7-8, ¶69), and “sequence and/or structural
alignment programs can be used to generate primary libraries” (id. at p. 8,
¶76).
FF11. Chirino teaches that “sequence homology based alignment methods
can be used to create sequence alignments of proteins related to the target
structure,” which are “then examined to determine the observed sequence
variations,” which are tabulated to define a primary library (Id. at p. 8, ¶79.)
FF12. According to Chirino:
Sequence based alignments can be used in a variety of
ways. For example, a number of related proteins can be
aligned, as is known in the art, and the “variable” and
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“conserved” residues defined; that is, the residues that vary or
remain identical between the family members can be defined.
These results can be used to generate a probability table, as
outlined below. Similarly, these sequence variations can be
tabulated and a secondary library defined from them as defined
below. Alternatively, the allowed sequence variations can be
used to define the amino acids considered at each position
during the computational screening. Another variation is to
bias the score for amino acids that occur in the sequence
alignment, thereby increasing the likelihood that they are found
during computational screening but still allowing consideration
of other amino acids. This bias would result in a focused
primary library but would not eliminate from consideration
amino acids not found in the alignment. . . .

(Id. at p. 8, ¶80.)
FF13. Chirino teaches that the computational processing results in a set of
optimized variant candidate sequences, which are different from the target
protein sequence in regions critical for MHC, TCR, or BCR binding (id. at p.
14, ¶124.)
FF14. Chirino teaches further:
In an additional aspect, the present invention provides
methods for eliciting an enhanced immune response in a patient
comprising the steps of inputting a target protein backbone
structure with variable residue positions into a computer,
applying in any order at least one computational protein design
algorithm and at least one computational immunogenicity filter,
identifying at least one variant protein with enhanced
immunogenicity, and administering said variant protein to a
patient.

(Id. at p. 2, ¶21.)

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PRINCIPLES OF LAW
In order for a prior art reference to serve as an anticipatory reference,
it must disclose every limitation of the claimed invention, either explicitly or
inherently. In re Schreiber, 128 F.3d 1473, 1477 (Fed. Cir. 1997).
Moreover, our mandate is to give claims their broadest reasonable
interpretation. In re American Academy of Science Tech Center, 367 F.3d
1359, 1364, (Fed. Cir. 2004). “An essential purpose of patent examination is
to fashion claims that are precise, clear, correct, and unambiguous. Only in
this way can uncertainties of claim scope be removed, as much as possible,
during the administrative process.” In re Zletz, 893 F.2d 319, 322 (Fed. Cir.
1989).

ANALYSIS
Initially, we note that Appellants appear to argue claims 1, 30, 41, 43,
80 as a group (see, e.g., App. Br. 40). We thus choose independent claim 1
as representative of those claims. 37 C.F.R. § 41.37(c)(1)(vii).
Claim 1 is drawn to a method that includes the steps of 1) presenting
one or more computable epitopes of at least one agent; 2) predicting, in a
computing device, one or more pattern changes in the one or more
computable epitopes of the at least one agent, wherein the pattern changes
are determined by analysis of past evolutionary progressions in the one or
more computable epitopes of the at least one agent;3) designating at least
one immune response component operable for modulating (a) at least one of
the one or more computable epitopes of the at least one agent or (b) at least
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one pattern-changed computable epitope; and 4) communicating, to at least
one user, the designated at least one immune response component.
Thus, the claim is very broad, and written at a very general, high
level, and covers a multitude of methods. Moreover, the Specification is
written very broadly, and there is nothing in the Specification that would
preclude interpreting claim 1 from reading on the computer implemented
method as taught by Chirino.
Specifically, Chirino teaches computer methods for identifying, that
is, presenting, MHC binding motifs, T cell receptors, and B cell receptor
binding sequences on a protein (see, e.g., FF8). The MHC binding motifs, T
cell receptors, and B cell receptor binding sequences read on the computable
epitope (see FFs 5 and 6) and the protein reads on an agent (see FF4). Thus,
Chirino teaches step 1 of the method of claim 1.
Chirino also teaches that sequence alignment may be used to identify
sequence variations in the protein (FFs 10-12). Next, Chirino teaches that
by using the sequence alignment, one can identify variable and conserved
residues, as well as the allowed sequence variations to define the amino
acids considered at each position during the computational screening (FF12).
Thus, by identifying variable residues and looking at allowed sequence
variations, Chirino teaches “predicting, in a computing device, one or more
pattern changes in the one or more computable epitopes of the at least one
agent, wherein the pattern changes are determined by analysis of past
evolutionary progressions in the one or more computable epitopes of the at
least one agent”. Chirino therefore teaches step 2 of the method of claim 1.
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Chirino then teaches an immunogenicity filter is used to identify those
variants that have enhanced immunogenicity with respect to MHC, TCR, or
BCR binding (which read on the immune response components). Thus,
Chirino teaches step 3 of the method of claim 1, that is “designating at least
one immune response component operable for modulating (a) at least one of
the one or more computable epitopes of the at least one agent or (b) at least
one pattern-changed computable epitope.”
Finally, Chirino teaches that the variant may be administered to a
patient. Thus, the computational system must necessarily have a step of
communicating, to at least one user, the results of the method. That is, as
Chirino teaches target protein variants having increased affinity to MHC,
TCR, or BCR, which are then tested and can be used therapeutically, Chirino
must necessarily communicate the results, that is the variants and the
immune response component to which it has increased affinity, and thus
enhanced immunogenicity, to a user. Thus, Chirino teaches step 4 of the
method of claim 1.
We thus agree with the Examiner that Chirino anticipates the method
of claim 1.
Appellants assert that the Examiner misconstrued Appellants’ claims
and misconstrued Chirino (App. Br. 35). Appellants further assert that the
rejection “does not compare the actual claim recitations to the actual text of
Chirino” (id.). Specifically, Appellants assert that the Examiner
misconstrued the claims, such as by ignoring antecedents recited in the claim
(id. at 36-39). Appellants also argue that the Examiner’s findings as to what
Chirino teaches are rebutted by the Declaration of Dr. Wayne Kindsvogel,
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(id. at 39-40), and that the Examiner’s interpretation of Chirino is not
supported by the actual text of Chirino (id. at 40-44).
Appellants’ attention is directed to an analysis of the claim and the
analysis of Chirino, and how it is applied to claim 1 above. In this regard,
we agree with the Examiner (Ans. 25-26) that Appellants are in large part
arguing that since there is not ipsis verbis support for the subject matter of
the claims in Chirino, Chirino cannot serve as an anticipatory reference. But
as discussed above, Appellants’ claims is very broad, and encompasses the
system taught by Chirino.
Specifically, as to the Declaration, Appellants assert
Dr. Kindsvogel declared that after reading Chirino, Dr.
Kindsvogel does not, inter alia, consider Chirino to describe a
method for “predicting one or more changes in the attributes.”
Moreover, Dr. Kindsvogel does not consider Chirino to
describe methods that project or predict changes relating to
amino acids within peptides. Dr. Kindsvogel stated that
Chirino’s methods generate libraries of variant protein
sequences by computation of variable amino acid residues on a
target protein backbone and selection of immunogenic
sequences from those variant protein libraries. Dr. Kindsvogel
also declared that he considers Chirino to not ensure the
production of polypeptides that act as linear epitopes. Dr.
Kindsvogel also understands Chirino’ s methods to not predict
response to a candidate variant protein or a therapeutic dose.
The Examiner has provided no objective evidence to refute any
part of the Rule 132 Declaration of Dr. Kindsvogel.

(App. Br. 39-40)
Specifically, Dr. Kindsvogel opines that “Chirino does not teach a
method for predicting changes in attributes, but instead, Chirino teaches a
method for identifying amino acid residues based on binding motifs for
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MHC molecules that are, in turn, based on MHC structure and peptide
sequences,” and also teaches the use of laboratory techniques to test for
altered immunogenicity (Kindsvogel Declaration, p. 3). Dr. Kindsvogel also
opines that “Chirino discusses ‘identifying and then altering potential amino
acid sequences that elicit an immune response in a host organism,” ’ which
is asserted not to be “equivalent with predicting or projection” (id. at 5).
We do not find the Declaration convincing. As discussed above,
Chirino teaches that variant libraries can be computationally generated by
using the variable residues in the target protein, which reads on predicting
one or more changes in the epitope, as the variations are in those residues
that are known to change, and Dr. Kindsvogel points to nothing in the
Specification which is written in very broad terms, that would preclude that
interpretation. Moreover, there is nothing in claim 1 that would exclude an
additional step of testing a variant for altered immunogenicity.
Dr. Kindsvogel also states that the Examiner omitted a component of
the method of Chirino—that is, the computational immunogenicity filter,
which Dr. Kindsvogel states “is essential” to the methods taught by Chirino
(Kindsvogel Declaration, p. 4). Dr. Kindsvogel also states that Chirino does
“not ensure the production of polypeptides that act as linear epitopes” (id.).
Dr. Kindsvogel also states that Chirino “does not predict response to a
candidate variant protein or therapeutic response” (id. at 5).
We have also considered the above statements by Dr. Kindsvogel in
the Declaration, but do not see their relevance to claim 1. Claim 1 is a
method claim that uses the transitional term of “comprising,” and thus does
not exclude the step of using a computational immunogenicity filter as
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taught by Chirino. Moreover, there is no requirement that the epitope be a
linear epitope, nor is there a step of predicting a therapeutic response in
independent claim 1.
As to dependent claim 5, Appellants assert that the
Examiner has not, inter alia, provided any reasoning or
evidence why “inputting a target protein backbone structure
with variable residue positions into a computer,
computationally generating a set of primary variant amino acid
sequences ... , and computationally analyzing said set of
primary variant amino acid sequences” (emphasis added) are
equivalent to the alleged “presenting amino acid sequences.”

(App. Br. 44-45).
Claim 5 is drawn to the method of claim 1, “wherein the presenting
one or more computable epitopes of at least one agent comprises: presenting
at least a part of at least one of an amino acid, a protein, a lipid, a capsid
protein, or a coat protein.” Chirino specifically teaches computer methods
for identifying, that is, presenting, MHC binding motifs, T cell receptors,
and B cell receptor binding sequences on a protein (see, e.g., FF8), and thus
teaches the method of claim 5 wherein the agent is a protein. Although
Appellants argue that “inputting” as taught by Chirino is not the same as
“presenting” as required by the computer implemented method of claim 1,
they point to no definition of presenting in the Specification that would
exclude inputting the protein sequence as taught by Chirino.
As to claims 6, 33, and 70, of which we choose claim 6 as
representative, Appellants argue that the Examiner’s finding that Chirino
“‘provides a library of sequences and proteins where the frequency of each
amino acid residue at each variable position is identified’” is based on a
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misconstruction of Chirino (App. Br. 45). Appellants assert that the
methods of Chirino are directed to “‘protein sequence libraries,’” based on a
“‘probability distribution table’” (App. Br. 46-47).
Claim 6 is drawn to the method of claim 1, “wherein the presenting
one or more computable epitopes of at least one agent comprises: presenting
one or more computable epitopes with a probable mutation-susceptible
region.” As Chirino recognized that variable regions of a target protein may
be identified using sequence alignment (FF12), and that the frequency of
amino acid residues at the variable positions can be determined (Chirino, ¶
198), Chirino teaches the use of target proteins with mutation-susceptible
regions, that is, regions of the target protein that have variable positions.
As to claims 12, 22, 23, and 31, of which we choose claim 12 as
representative, Appellants argue that the finding of the Examiner that
“Chirino ‘shows the production of polypeptides the act as linear epitopes and
ensuring this by structurally and chemically compensating for either the
removal or addition of amino acid residues encoding linear epitopes’” is not
supported by the text of Chirino (App. Br. 47-48). Appellants argue further
that the Examiner’s finding that “Chirino ‘shows residues which form the
active site of an enzyme such that may be important structurally or
biologically functional, may be fixed in conformation’” is based on a
misconstruction of Chirino (id. at 48-49), as is the finding that “Chirino
‘shows ... or variable positions may be classified as either a core, surface or
boundary residue position and kept structurally similar’” (id. at 50-51).
Claim 12 is drawn to the method of Claim 1, “wherein the presenting
one or more computable epitopes of at least one agent comprises: presenting
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one or more substantially linear computable epitopes.” Chirino notes that
the epitopes displayed by MHC class I and Class II molecules that are
recognized by T-cell Receptors (TCR) are peptide fragments, and are thus
linear epitopes (see Chirino, p. 5, ¶¶ 44-47 and p. 14, ¶ 131). Thus, by
looking for sequences that bind to MHC class I and class II molecules (the
computable epitope), one is looking at a linear epitope.
Appellants argue as to claims 27 and 28, of which we choose claim 27
as representative, that the Examiner’s finding that Chirino “‘shows
projecting (predicting) changes relating to the ammo acids within the
peptides’” is not supported by the text of Chirino (App. Br. 51-52), as is the
Examiner’s finding that “Chirino ‘shows ... response to a therapeutically
effective dose of a candidate variant protein’” (id. at 52-53).
Claim 27 is drawn to the method of claim 1, “wherein the predicting,
in a computing device, one or more pattern changes in the one or more
computable epitopes of the at least one agent comprises: associating the
predicted one or more pattern changes in the one or more computable
epitopes of the at least one agent with a predicted course of an immune
response.” As has already been discussed, Chirino teaches computational
methods for modulating the immunogenicity of proteins by identifying and
then altering potential amino acid sequences that elicit an immune response
in a host organism (FF8). Thus, Chirino teaches associating the pattern
changes with a predicted course of an immune response, that is, increased
immunogenicity.
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As to claim 29, Appellants argue that the Examiner’s finding that
“Chirino ‘shows the prediction of nucleotide changes in candidate variant
proteins’” is not supported by the text of Chirino (App. Br. 53-54).
Claim 29 is drawn to the method of claim 1, “ wherein the predicting,
in a computing device, one or more pattern changes in the one or more
computable epitopes of the at least one agent comprises: predicting one or
more nucleotide changes in the at least one agent.” As Chirino teaches that
the variant proteins determined by the computer implemented method
predicted to have enhanced immunogenicity may be made using
recombinant techniques (Chirino, ¶ 185), Chirino necessarily predicts
nucleotide changes that may occur in the nucleotide sequence that encodes
the target protein variant.
As to claim 35, Appellants argue that the Examiner’s finding that
Chirino “‘shows candidate variant library proteins wherein the variant
protein genes are expressed and thus are a set of differential expression
signatures sharing a significant intersection of genes (meta-signature) and
thus inferring a biological relatedness such as their similar
immunogenicity’” is not supported by the text of Chirino (id. at 54-55).
Claim 35 is drawn to the method of claim 1, “wherein the predicting,
in a computing device, one or more pattern changes in the one or more
computable epitopes of the at least one agent comprises: predicting one or
more pattern changes operable for providing at least one meta-signature.”
The Specification appears to define “meta-signature” as, for example,
“at least one sequence shared by one or more agents for modulating an
immune response, and/or at least one consensus sequence derived from one
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or more agents for modulating an immune response” (Spec. 47). Thus, as
Chirino teaches screening for MHC binding motifs, T cell receptor and B
cell receptor binding sequences, and then designing variants with enhanced
immunogenicity, Chirino teaches predicting one or more pattern changes
operable for providing at least one meta-signature.
As to claim 54, Appellants argue that the Examiner’s finding that
Chirino “‘shows that amino acid sequence variants are characterized by the
predetermined nature of the variation that sets them apart from interspecies
variation of the candidate variant sequence, likewise, the modulating of the
immune response to a target protein is altered so that if the protein solicits an
immune response in a give[n] species, the amino acid sequence of the target
protein is changed by reducing or enhancing protein in response’” is not
supported by the text of Chirino (App. Br. 55-56).
Claim 54 is drawn to the method of claim 1, “wherein the designating
at least one immune response component comprises: designating at least a
portion of a species-dependent antibody.” Chirino teaches that TCR-
peptide-MHC regulates immune responses, such as antibody producing T-
cells (Chirino, p. 1, ¶ 7; see also id. at 4-5, ¶¶41-44). Thus, when the
immune response component is a MHC or T-cell binding site, and one is
either increasing or decreasing immunogenicity, one is selecting for those
epitopes that with either increase or decrease antibody response. In addition,
since Chirino teaches using the variants therapeutically, Chirino would be
directed towards a species dependent antibody response, that is, the response
in the species of the patient, such as antibody response in humans.

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Conclusion of Law
We conclude that the Examiner has established by a preponderance of
the evidence that Chirino anticipates the claimed methods. We thus affirm
the rejection of claims 1, 5, 6, 12, 22, 23, 27-31, 33, 35, 41, 43, 46, 47, 51,
54, 55, 57, 58, 70, and 80 under 35 U.S.C. § 102(b) as being anticipated by
Chirino.

ISSUE (Rejections II-XVIII)
Has the Examiner established by a preponderance of the evidence that
the claims rejected in each of the provisional obviousness-type double
patenting rejections is rendered obvious by the claims cited in each of the
copending applications?

Findings of Fact
FF15. The Examiner’s statement of the rejections may be found at pages8-25
of the Answer.
FF16. As to Rejection II over USSN 10/925,905, the Examiner concludes:
Although the conflicting claims are not identical, they are not
patentably distinct from each other because the difference
between the instant claims and claim 9 of '905 is that claim 9
recites analysis of the pattern of past variations of a computable
epitope whereas the instant claims recite pattern changes of past
evolutionary progressions in a computable epitope. A pattern
of past variations is necessarily related to a pattern of past
evolutionary progressions. Therefore claim 9’s recitation of
analysis of the pattern of past variations of a computable
epitope makes obvious the instantly recited pattern changes
determined by analysis of past evolutionary progressions in
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computable epitopes. It is obvious to automate a method (see
In re Venner, 262 F.2d 91, 95, 120 USPQ 193, 194 (CCPA
1958), therefore the system of the copending application makes
the apparatus for performing the method obvious, and thus
instant claim 1 is obvious.

(Ans. 9-10.)
FF17. Claim 9 of USSN 10/925,905 reads as follows:
A system, comprising:
circuitry configured by a computer program for
identifying an association of at least a portion of one or more
agents with at least a part of an immune response;
circuitry configured by a computer program for
identifying a pattern of past variations of the at least one
computable epitope;
circuitry configured by a computer program for
extrapolating a pattern of one or more predicted changes
determined by analysis of the pattern of past variations of the at
least one computable epitope;
circuitry configured by a computer program for selecting
one or more immune response components responsive to said
circuitry for extrapolating; and
circuitry configured by a computer program for
communicating at least one of the one or more immune
response components to at least one user.

Analysis
Appellants argue that “the Examiner made general assertions
ungrounded in specific facts and unsupported by evidence of record”,
asserting that “the Examiner did not provide a reasoned, fact-based
explanation for the double patenting allegations, only mere allegations and
assertions” (App. Br. 65).
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We disagree, as each rejection explains the Examiner’s reasoning as
to why the appealed claims are rendered obvious by the claims relied upon
by the Examiner in making the rejection.
Appellants argue that Rejections III and XVI over USSNs 11/900,442
and 11/904,636 are improper as the instant application is the earlier-filed
application (App. Br. 67). The rejections, however, are only provisional.

Appellants specifically argue three of the rejections as examples: the
rejection over USSN 10/925,904, the rejection over USSN 10/925,905; and
the rejection over USSN 11/001,259 (App. Br. 69-72). As USSNs
10/925,904 and USSN 11/001,259 have been abandoned, we only address
the arguments as to USSN 10/925,905 (Rejection II).
Appellants assert that the Examiner notes that a “‘pattern
of past variations is necessarily related to a pattern of past evolutionary
progressions,’” but argue that “[a]llegations of what ‘necessarily is related’
is not sufficient to demonstrate a ‘reasoned, fact-based explanation
supported by the evidence of record’” (App. Br. 70).
Appellants’ arguments are not convincing. As has been previously
discussed, Appellants Specification and claims are written at a very high,
very broad, level, and thus we agree with the Examiner that “past variations”
as used in claim 9 of the ’905 application encompasses “past evolutionary
progressions in the . . . epitopes” as is recited in appealed claim 1.
Moreover, Appellants have pointed to nothing in the Specification as
defining “past evolutionary progressions in the . . . epitopes” as excluding
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“past variations” that may have occurred in the epitope. We thus affirm
Rejection II.
As Appellants did not present separate arguments as to the remaining
rejections, we also affirm Rejections III-XVI.

Conclusion of Law
We conclude that the Examiner established by a preponderance of the
evidence that the claims rejected in each of the provisional obviousness-type
double patenting rejections is rendered obvious by the claims cited in each
of the copending applications. We thus affirm Rejections II-XVI.

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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