Ex Parte Bangera et al

Patent Trial and Appeal Board

Feb 24, 2017

11807336 (P.T.A.B. Feb. 24, 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.
11/807,336 05/25/2007 Mahalaxmi Gita Bangera 1003-002-002L-000000 4541
44765 7590 02/28/2017
INTELLECTUAL VENTURES - ISF
ATTN: DOCKETING, ISF
3150- 139th Ave SE
Bldg. 4
Bellevue, WA 98005
EXAMINER
BRUSCA, JOHN S
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
02/28/2017 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):
ISFDocketInbox@intven.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MAHALAZMI GITA BANGERA, MURIEL Y. ISHIKAWA,
EDWARD K.Y. JUNG, NATHAN P. MYHRVOLD,
ELIZABETH A. SWEENEY, RICHA WILSON and
LOWELL L. WOOD, JR.
Appeal 2014-0041541
Application 11/807,3362
Technology Center 1600
Before LORA M. GREEN, RICHARD M. LEBOVITZ, and
ULRIKH W. JENKS, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to systems, circuitry, and
computer-implemented methods for aiding identification of one or more
immune response components associated with the pattern of predicted
changes in one or more computable epitopes of the at least one agent. The
1 The Appeal Brief (“Appeal Br.”) lists Searete, LLC, in Bellevue, WA.
Searete, LLC, an affiliate of The Invention Science Fund I, L.L.C., as the
real-party-in-interest.
2 “The ’336 Application.”
Appeal 2014-004154
Application 11/807,336
Examiner rejected the claims as lacking a written description under 35
U.S.C. § 112, first paragraph, and as obvious under 35 U.S.C. § 103(a). We
have jurisdiction under 35 U.S.C. § 134. The written description rejection is
reversed. The obviousness rejections are affirmed. A new ground of
rejection under 35 U.S.C. § 103 is set forth pursuant to 37 C.F.R. 41.50(b).
STATEMENT OF CASE
Appellants appeal from the rejection by the Examiner of pending
claims 1—6, 8—24, 26-42, and 44—54. Final Rej. Summary. The claims
stand rejected by the Examiner as follows:
1. Claims 13, 31, and 49 under 35 U.S.C. § 112, first paragraph, as
failing to comply with the written description requirement. Final Rej. 4.
2. Claims 1-6, 10-12, 14—24, 28-30, 32-42, 46-48, and 50-54 under
35 U.S.C. § 103(a) as obvious in view of Chirino3 and Smirnov.4 Final Rej.
5-6.
3. Claims 1, 8, 9, 19, 26, 27, 37, 44, and 45 under 35 U.S.C. § 103(a)
as obvious in view of Chirino, Smirnov, and Tewari.5 Final Rej. 10.
3 US 2003/002285 Al, published Jan. 30, 2003. Also referred to as “the
Chirino Application.” During the prosecution of the Chirino Application, a
Final Rejection was issued by the USPTO. This Final Rejection is cited in
this Decision.
4 Y.A. Smirnov et al., Prevention and treatment of bronchopneumonia in mice
caused by mouse-adapted variant of avian H5N2 influenza A virus using
monoclonal antibody against conserved epitope in the HA stem region, Arch
Virol (2000) 145: 1733-1741.
5 Mona K. Tewari et al., A cytosol pathway for MHC class Il-restricted
antigen processing that is proteasome and TAP dependent, Nature
Immunology (2005) 6: 287—294.
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Application 11/807,336
Rejection 1 is reversed. Rejections 2 and 3 are affirmed. A new
ground of rejection is set forth of claims 13, 31, and 49 under 35 U.S.C.
§ 103(a) as obvious in view of Chirino and Smirnov.
Claim 1, reproduced below, is representative (for reference, bracketed
numbers have been added to the claim to number the clauses; this numbering
system was utilized by Appellants in their discussion of the claim):
1. A system comprising:
at least one computer program on a recordable-type
medium for use with at least one computer system and wherein
the computer program includes a plurality of instructions
including but not limited to:
[1] one or more instructions for designating one or more
computable epitopes of at least one agent,
wherein the one or more computable epitopes arise from
a substantially non linear form;
[2] one or more instructions for identifying a pattern of
past epidemiological variations of the one or more computable
epitopes of the at least one agent;
[3] one or more instructions for extrapolating a pattern of
one or more predicted future changes in the one or more
computable epitopes from the identified pattern of past
epidemiological variations;
[4] one or more instructions for aiding identification of
one or more immune response components associated with the
pattern of predicted changes in the one or more computable
epitopes of the at least one agent; and
[5] one or more instructions for displaying the identified
one or more immune response components.
THE PERSON OF ORDINARY SKILL IN THE ART
When making a patentability determination under 35 U.S.C., we
consider the claims and the scope and content of the prior art to be directed
to one of ordinary skill in the art. Thus, a determination as to whether the
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claims conform to the patentability requirements of 35 U.S.C., including the
requirements of 35 U.S.C. §§ 103 and 112, is made from the perspective of
one of ordinary skill in the art. In this case, the claimed subject matter
involves a computer system, instructions, and circuitry for performing
bioinformatics on the components (proteins, antibodies, epitopes) of an
immune response. The cited prior art includes a published patent application
and peer-reviewed scientific journal publications. The latter is the forum for
scientists who typically have Ph.D. or are working towards a Ph.D. or have
master’s degree in the pertinent field. Here, the pertinent fields are
molecular biology, immunology, and bioinformatics as evidenced by the
subject matter of the cited prior art publications. Accordingly, the person of
ordinary skill in the art is a scientist, who publishes work in peer-reviewed
scientific publications, has at least a post-graduate level understanding of
molecular biology, immunology, and bioinformatics, and is able to perform
bioinformatics analysis on proteins.
1. WRITTEN DESCRIPTION REJECTION
The Examiner rejected claims 13, 31, and 49 as lacking written
description under 35 U.S.C. § 112, first paragraph. The Examiner found that
the ’336 Application “describes a database of epidemiological factors on
page 16, line 4. The specification describes aiding identification of an
epitope with a probable sequence match to a host at page 14, lines 26-28 and
page 37.” Final Rej. 4. However, the Examiner found that the ’336
Application does not describe “a process of extrapolating a pattern of one or
more predicted future changes in a computable epitope from an identified
pattern of past epidemiological variations, combined with a step of aiding
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identification of an epitope with a probable sequence match to a host
sequence” as required by claims 13,31, and 49. Id.
We agree with Appellants that the claims are supported by the original
disclosure. The complete passage, on page 14 of the ’336 Application,
referenced by the Examiner (Final Rej. 4) is reproduced below:
The at least one computer program 102 may include one or
more instructions for predicting one or more changes in the
one or more computable epitopes of the at least one agent
104. The at least one computer program 102 may include one or
more instructions for aiding identification of one or 25 more
immune response components associated with the one or more
computable epitopes of the at least one agent 105. The at least
one computer program 102 may include one or more
instructions for aiding identification of one or more epitopes
with a probable sequence match to a host sequence 600. The
at least one computer program 102 may include one or more
instructions for designating at least one of the 30 one or more
computable epitopes having a substantially similar structural
match with an entity 602.
’336 Application, 14:21—31 (emphasis added).
As indicated in this passage (bolded), the Application describes
predicting changes and host sequence matches in a single system. This
paragraph does not discloses the changes as being predicted from past
epidemiological variations as claimed. However, the Application discloses
epidemiological variation as one basis for predicting changes. Id., 33: 1—7;
45: 2—15. Consequently, the evidence supports Appellants’ position that the
original specification describes claims 13,31, and 49. The written
description rejection is reversed.
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2. OBVIOUSNESS REJECTION OVER CHIRINO & SMIRNOV
The Examiner found that Chirino describes the steps carried out by
the instructions of the claimed computer system, but specifically found, inter
alia, that Chirino does not “show extrapolating changes in an epitope from
past epidemiological variations” as recited in clauses 2 and 3 of claim 1; nor
does Chirino “explicitly show that conformational epitopes can be nonlinear
epitopes” as in clause 1. Final Rej. 8. For these features, the Examiner cited
Smirnov’s teaching of identifying “a conformational epitope in the middle of
the stem region of the H2 subtype that is neutralized by Cl 79 monoclonal
antibody” which is formed from two regions of hemagglutinin. Id. The
Examiner also found that Smirnov teaches that this epitope changes during
different epidemic outbreaks. Id., 9. Based on this disclosure, the Examiner
concluded that it would have been obvious to one of ordinary skill in the art:
to designate an antibody directed against a nonlinear epitope
that was extrapolated from a pattern of past epidemiological
variations because Smirnov et al. shows that a non-linear
conformational epitope of the influenza virus hemagglutin [sic,
hemagglutinin] glycoprotein is recognized by a neutralizing
monoclonal antibody. . . . Smirnov et al. shows that the epitope
evolved through a series of different epidemic isolates of the
HI, H2, and H5 subtypes, and it would have been obvious to
use the process of Chirino et al. to generate an epitope based on
the past epidemiologically isolated sequences for the purpose of
making an effective vaccine, as noted in Chirino at paragraph
255.
Id., 9-10.
“computable epitope”
Appellants contend that the Examiner misconstrued the claim term
“computable epitope” as including “any epitope,” including a physical
epitope, and therefore read the express limitation of “computable” out from
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the claim. Appeal Br. 31. Appellants construe “computable epitope” to
mean an “epitope that be utilized within a computing-device system or
method.” Id. We adopt this interpretation.
While we agree with Appellants’ interpretation of “computable
epitope,” the evidence of record does not support the contention that the
Examiner construed the disputed term to mean a physical epitope as
Appellants assert the Examiner did. Id., 31—32. This argument ignores the
Examiner’s explicit findings in the Final Rejection that Chirino describes
“computational methods” and “[cjomputer mediated analysis” of sequence
information and applies it to produce modified sequences in the computing
device. Final Rej. 6—7. The Examiner cited various pages from Chirino in
which disclosure appeared describing computerized computation of
epitopes. The following disclosures support the Examiner’s findings that the
Chirino describes computational modification of epitopes (emphasis added):
[0022] The computational design algorithm may be applied
prior to or after the application of the computational
immunogenicity filter. Alternatively, the computational protein
design algorithm comprises the computational filter as a scoring
function.
[0023] The computationally generating step, may include
applying a computational immunogenicity filter comprising a
scoring function for MHC class I motifs, MHC class II motifs,
B cell epitopes or T cell epitopes. Other computational steps
include a Dead-End Elimination (DEE) computation, a Monte
Carlo search, or use of a genetic algorithm. Additional scoring
functions include Van der Waals potential scoring function, a
hydrogen bond potential scoring function, an atomic solvation
scoring function, a secondary structure propensity scoring
function and electrostatic scoring function.
[0037] There are also situations where it is desirable to increase
the immunogenicity of a target protein. For example, activating
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populations of T cells toward a specific epitope has
implications for controlling or eliminating viral pathogens or
neoplasia. In this case, computational methods can be used
to introduce T cell epitopes anywhere within the target
protein. In addition, using the computational methods
described herein, T cell epitopes also can be introduced into
less rigid, less structurally restricted regions of a target protein,
such as a loop region. Computational methods can then be used
to modify the residues adjacent to the epitope insertion,
ensuring energetic compatibility between the native protein and
the grafted epitope.
Thus, it is evident from this disclosure that Chirino was properly cited
by the Examiner for describing “computational epitopes,” i.e., an epitope
that has been determined computationally. It would be evident to one of
ordinary skill in the art from this disclosure of Chirino (e.g., ]Hf 22, 23, 37)
that Chirino is describing identifying and modifying sequences epitopes in a
computing device for later use as a vaccine or other means for controlling
viral pathogens or neoplasia.
The Examiner’s broad construction of epitope had nothing to do with
it being a “physical epitope” manipulated outside the computer device as
misunderstood by Appellants. Rather, it was reference to the broad
definition of epitope in the ’336 Application that includes a single amino
acid or nucleotide:
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 peptide, a glycoprotein, a carbohydrate, a polysaccharide, an
oligosaccharide, a saccharide, a lipopolysaccharide, a
glycolipid, a glycoprotein, a lipid, a fatty acid, a phospholipid, a
glycolipid, a sphingolipid, a glycerolipid, a lipoprotein, and/or
at least a part of a cell, an organism, or a virus.
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Application 32: 7-13. See Appeal Br. 32 citing this definition.
Claim 1
Clauses 1 to 5 of claim 1 and others
In setting forth the obviousness rejection of claim 1, Appellants
contend that the Examiner “committed reversible error by not supporting his
allegations with factual underpinnings based on the references of record.”
Appeal Br. 35. We address each clause of claim 1 below.
[1] one or more instructions for designating one or more computable
epitopes of at least one agent, wherein the one or more computable
epitopes arise from a substantially non linear form
Appellants contend that the Examiner did not establish that clause 1 of
claim 1 is “taught by any one of the cited references.” Appeal Br. 34.
The rejection is not based on one publication. Consequently,
Appellants contention that clause 1 is not described “by any one of the cited
references” is irrelevant because the rejection is based on two publications,
namely Chirino and Smirnov, not one alone. It is clear from the Final
Rejection that the Examiner’s rejection required both publications because in
the statement and reasoning of the rejection the Examiner invoked factual
teachings in each publication to reach the claimed subject matter. Final Rej.
6-10.
The Examiner’s findings about Chirino and Smirnov are clearly
applicable to clause 1 because they mentioned Chirino’s teaching about
conformational and three-dimensional epitopes and Smirnov’s teaching of a
non-linear epitope (emphasis added):
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At page 14, paragraphs 131-132, Chirino et al. states that the
method can remove or add amino acid residues that encode
linear epitopes or conformational epitopes. On pages 27-28,
paragraph 257 states that a sequence may be inserted that
encodes a conformational epitope. At page 17, paragraph 154 . .
. At page 28, paragraph 257, the variant protein may comprise a
conformational three dimensional epitope.
Final Rej. 7.
At page 17, paragraph 158 [of Chirino], B cell epitopes are
introduced in the process, which produces epitopes that will
bind to antibody molecules.
Final Rej. 7.
Smirnov et al. shows a monoclonal antibody that recognizes a
conformational epitope of the hemagglutinin protein of
influenza virus. Smirnov et al. shows in line 2 of page 1734 that
hemagglutinin is a glycoprotein. Smirnov et al. show on page
1734 that a region of the hemagglutinin contains a
conformational epitope in the middle of the stem region of the
H2 subtype that is neutralized by Cl 79 monoclonal antibody.
The conformational epitope is described on page 1734 and
Table 2 as comprising two regions from amino acids 318-322
of the HA1-A region and amino acids 47-58 of the HA2-B
region of hemagglutinin. The conformational epitope is
nonlinear with respect to the hemagglutinin sequence.
Final Rej. 8.
Appellants did not identify an error in these findings made by the
Examiner.
“computable epitopes arise from a substantially non linear form ”
Appellants contend that the Examiner did not establish that either
Chirino or Smirnov teach the claimed “computable epitopes [which] arise
from a substantially non linear form” as required by the claim. Appeal Br.
35-36.
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This argument failed to address the Examiner’s findings and
conclusions as set forth in the Final Rejection.
We begin with the interpretation of the term “non linear epitope.”
During patent prosecution, we give the terms in a claim their “broadest
reasonable meaning of the words in their ordinary usage as they would be
understood by one of ordinary skill in the art, taking into account whatever
enlightenment by way of definitions or otherwise that may be afforded by
the written description contained in the applicant’s specification.” In re
Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997). Based on the disclosure in
the ’336 Application, we interpret a “non linear” epitope” to be an antigenic
determinant6 which for example comprise “a conformational antigen such as
a protein with amino acids that are non-adjacent in the protein sequence but
become adjacent upon protein folding.” ’336 Application 19: 10—12.
The Examiner found that Chirino teaches “that the method can
remove or add amino acid residues that encode linear epitopes or
conformational epitopes.” Final Rej. 7. The Examiner cited paragraph 131—
132 to support this finding. Id. Consistently, in paragraph 132, Chirino
teaches that “the PDA™ technology is used to structurally and chemically
compensate for either the removal or addition of amino acid residues
encoding conformational epitopes.” Smirnov, on the other hand, specifically
teaches a conformational epitope formed from non-adjacent regions, meeting
the definition of a non-linear epitope as set forth in the ’336 Application.
Smirnov teaches:
6 “As used herein, the term ‘epitope’ may, if appropriate to context, be used
interchangeably with antigen, paratope binding site, antigenic determinant,
and/or determinant.” ’336 Application 32: 13—15.
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Furthermore, Okuno et al. . . . find and described a
conformational antigenic epitope in the middle of the stem
region of HA of H2 subtype consisting of two regions (aa 318-
322 of the HA1 — A region, and aa 47-58 of the HA2 — B
region), which was conserved among HAs of all studied viruses
belonging of HI and H2 subtypes.
Smirnov 1734.
The amino acid sequences of A and B regions forming
conformational epitope in HA of HI and H2 viruses studied
previously in mice model with MAb Cl79 . . . and H5 strains
are presented in Table 2.
Smirnov 1738.
The Examiner also provided an explicit reason to have utilized
Smirnov’s non-linear, conformational epitope in Chirino’s computation
system. The Examiner stated that Smirnov’s shows the evolution of the
epitope in different influenza virus subtypes, providing a reason to apply that
information in making an effective vaccine according to the computational
model described in Chirino. Final Rej. 9—10.
The Examiner further cited paragraph 255 of Chirino which describes
methods for making vaccines and immuno-therapeutics more immunogenic.
Subsequent paragraph 257 of Chirino specifically refers to conformational
three dimensional epitopes. It also evident from reading Chirino that the
Chirino begins computationally when making its improved vaccines, e.g.,
paragraphs 197—200 describe probability distribution tables and sequence
alignment programs to generate sequences that are used in the later methods
to generate vaccines.
Accordingly, while we have considered Appellants statements about
the lack of a teachings to use a conformational and computable epitopes
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(Appeal Br. 35—36), we find that the Examiner’s findings are factually-
supported by a preponderance of the evidence in this record.
[2] one or more instructions for identifying a pattern ofpast
epidemiological variations of the one or more computable epitopes of
the at least one agent
Appellants stated in bolded lettering that the “Examiner identified no
teaching” from Chirino and “the Examiner identified no teaching from
Smirnov” that teach clause 2. Appeal Br. 37. Appellants’ argument is not
supported by the evidence in this record. The Examiner described
Smirnov’s teaching in Table 2 of variations in an epitope of influenza A
recognized by monoclonal antibody Cl79 during different “epidemic
outbreaks,” providing evidence of the claimed “past epidemiological
variations of the one or more computable epitopes of the at least one agent.”
Final Rej.12. The Examiner also explained why Smirnov’s teaching would
be used in Chirino. Id. Appellants did not identify an error in the
Examiner’s findings nor reasoning. In sum, it is not correct that the
Examiner identified “no teachings” the cited publications of clause 2 of
claim 1.
[3] one or more instructions for extrapolating a pattern of one or
more predicted future changes in the one or more computable
epitopes from the identified pattern ofpast epidemiological variations
With respect to clause 3, Appellants contend that “Nothing in the
record demonstrates that the Examiner established that either of the cited
references, taken alone or in combination, teach clause 3 of claim 1.”
Appeal Br. 38.
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This contention has no factual basis. The Examiner cited express
support for making modifications of protein based on computer methods:
Computer mediated analysis of sequence modification is shown
[in Chirino] at page 8, paragraph 71, at page 9, paragraph 85, at
pages 14-15, paragraph 133, at page 17, paragraph 158, and at
page 21, paragraph 199.
Final Rej. 6.
Modification of a protein with a known structure is shown at
page 6, paragraph 61 [of Chirino]. At pages 8-9, paragraphs 81-
82, comparison of structure of proteins can be used to align and
compare proteins. Computer mediated structural comparison is
shown at pages 8-9, paragraph 81.
Final Rej. 7.
The Examiner also stated that it would have been further “obvious to
designate an antibody directed against a nonlinear epitope that was
extrapolated from a pattern of past epidemiological variations because
Smirnov et al. shows that a non-linear conformational epitope of the
influenza virus hemagglutin [sic, hemagglutinin] glycoprotein is recognized
by a neutralizing monoclonal antibody.” Final Rej. 9. The Examiner also
found that the “neutralizing antibody can prevent disease if used as passive
immunotherapy” and that “it would have been obvious to use the process of
Chirino et al. to generate an epitope based on the past epidemiologically
isolated sequences for the purpose of making an effective vaccine.” Id., 9—
10. Appellants did not identify a factual error in the Examiner’s findings nor
conclusion, but just generally deny that the Examiner addressed clause 3
(Appeal Br. 39), which as demonstrated above, is clearly incorrect and
inconsistent with the record.
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[4] one or more instructions for aiding identification of one or more
immune response components associated with the pattern of predicted
changes in the one or more computable epitopes of the at least one
agent
Appellants states that the Examiner cited teachings in Chirino about
vaccines, but contend that vaccines are not instructions “for aiding
identification of one or more immune response components associated with
the pattern of predicted changes in the one or more computable epitopes of
the at least one agent” as required by the claim. Appeal Br. 74.
The term “immune response component” is defined in the ’336
Application to include antibodies. ’336 Application 26: 1—26. We therefore
interpret “instructions for aiding identification of one or more immune
response components” to include the identification of antibodies that react
with the epidemiologically predicted epitopes. Appellants did not direct us
to a definition or description of “instructions for aiding” identification.
Consequently, we interpret it broadly to include any instruction which assists
or supports identifying an antibody.
The Examiner found, as already discussed, that Smirnov describes
epitopes that occur during epidemics and therefore constitute changes which
are predicted to occur in the influenza virus, meeting the limitation of “the
pattern of predicted changes in the one or more computable epitopes of the
at least one agent.” The Examiner found that it would have been obvious to
a person of ordinary skill in the art at the time the invention was made to
modify the process of Chirino “by extending the computer mediated process
of designing variant proteins with enhanced immunogenicity to include
designation of antibodies that bind the variant protein and informing the user
of the designated antibody because Chirino et al. shows that one use of the
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variant protein produced by the computer mediated method of Chirino et al.
is to make a vaccine.” Final Rej. 9.
The claim does not require how the identification of the antibody
(“immune response”) is accomplished. Appellants also have not explained
what is meant by “aiding identification” of an immune response component.
Consequently, the Examiner’s position that designing variant proteins
(epitopes) with enhanced immunogenicity by the computer device of Chirino
would “aid” in identifying antibodies because such protein variants are used
to generate the antibodies (“immune response component”) is the broadest
reasonable interpretation of the claim. Even if the antibody generation is
accomplished outside the computer, such computable epitopes assist and
support (“aid in identification”) the identification of the antibodies because
they are used to generate the antibodies.
For the forgoing reasons, we do not agree with Appellants that the
Examiner failed to establish the obviousness of clause 4. Appellants did not
identify an error in the Examiner’s findings nor reasoning as explained
above.
[5] one or more instructions for displaying the identified one or more
immune response components.
The Examiner found that it would have been obvious to inform the
user of the designated antibody because the purpose of Chirino is to make
vaccines. Final Rej. 9. The Examiner found it was within the skill of one of
ordinary skill in the art to write a bioinformatics computer program to
indicate the result to a user. Id. Appellants contend that the Examiner cited
no evidence to support his conclusions. Appeal Br. 41^42.
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Chirino expressly teaches the computer modification of epitopes to
develop more effective vaccines comprising antibodies. Chirino, Abstract.
It is commonsense that it would be necessary to communicate such
information produced by the computer to the user. “A person of ordinary
skill is also a person of ordinary creativity, not an automaton.” KSR Int’l Co.
v. Teleflex Inc., 550 U.S. 398, 421 (2007). Consequently, Appellants
contentions do not persuasively demonstrate that the Examiner erred in
finding that Chirino and Smirnov reasonably suggest clause 5 of claim 1.
Claim 19
Claim 19 is directed to a system with “circuitry.” The Examiner
included claim 19 in the same rejection as claim 1 because the “circuitry” is
recited to accomplish the same steps (clauses 1—4) as the “instructions” in
claim 1. Claim 19, however, lacks clause 5.
Appellants did not point to a definition of “circuitry” in the
Application or provide guidance as to its meaning. The Application
describes “electrical circuitry” as “forming a general purpose computing
device configured by a computer program” (’336 Application 64: 30 —
65:13), but does not clarity the meaning of the term “circuitry” that is not
“electrical circuitry.”
Appellants argue that the Examiner did not demonstrate prima facie
obviousness of clauses 1 to 4 of claim 19. Appeal Br. 44. However, we
have compared the arguments made for claim 1 to those made for claim 19
and they appear to be substantially the same, if not duplicative in certain
instances for both claims. Compare, e.g., Appeal Br. 40-41 (clause 4 of
claim 1) to Appeal Br. 48-49 (clause 4 of claim 19). Consequently, because
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Appellants have not distinguished claim 1 from claim 19, we affirm the
rejection of claim 19 for the same reasons as for claim 1.
Claims 2-6, 10-12, and 14-18
The Examiner rejected dependent claims 2—6, 10-12, and 14—18
under 35 U.S.C. § 103(a) as obvious over the combination of Chirino and
Smirnov. Appellants contend that the Examiner made “no specific
allegations regarding the specific recitations” of these claims. Appeal Br.
43.
While the Examiner did not identify the claims by number, the
Examiner addressed the limitations in the claims in the discussion of Chirino
and Smirnov. For example:
For claim 3 reciting a meta-signature which can comprise protein
sequence and epitope information (’336 Application 38:10-31; 40:20-23),
the Examiner cited Chirino’s disclosure of modifying proteins with known
structures and epitopes (Final Rej. 7).
For claim 5 of an immunogenic epitope, the Examiner cited Chirino’s
disclosure of making proteins more immunogenic {id., 8:1, 9:6).
For claim 6 of a glycoprotein, the Examiner cited Chirino’s disclosure
of a glycoprotein {id., 7:10).
For claim 10 of an antigen not entirely composed of protein, the
Examiner cited Chirino’s disclosure of a polypeptide having a sugar {id.,
7:11).
For claims 11 and 17 of disease states, the Examiner cited Smirnov’s
disclosure of influenza epidemics {id., 8—9).
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For claim 12 of a predicted course of an immune response, the
Examiner cited Smirnov’s disclosure of how “the epitope evolved through a
series of different epidemic isolates of the HI, H2, and H5 subtypes” {id., 9:
19-20).
For claim 14 of having a substantially similar structural match with an
entity, the Examiner cited Chirino’s disclosure of sequence similarities and
sequence comparisons {id., 7: 12—18).
For claim 15 of ranking of epitopes, the Examiner cited Chirino’s
disclosure of “ranking of results” {id., 8: 5—6).
For claim 16 of progression of an immune response in a host, the
Examiner cited Smirnov’s disclosure of mice adapted to H5 subtype and
then treated with an antibody {id., 8—9)
For claim 18 of at least one user chosen parameter for a computable
epitope, the Examiner cited disclosure throughout Chirino of modifying and
choosing epitopes in accordance with a user’s goals {id., 6—8).
Claim 2 is directed to the system of claim 1 further comprising
instructions for an epitope elicited by an immune response (“evocation” of
an immune response); the latter is described throughout Chirino as discussed
by the Examiner {id., 6—8).
Claim 4 involves display of the computable epitope, which as found
by the Examiner and discussed above, would have been obvious to display
results to a user {id., 9).
Claim 37 and dependent claims 38-42, 46-48, and 50-54
Claim 37 is directed to a computer implemented method comprising
the same steps as in claim 1. As with claim 19, Appellants contend that the
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claim is not obvious over the combination of Chirino and Smirnov, but rely
the same unpersuasive arguments as they did for claim 1. Appeal Br. 51—59.
Appellants also contend that the Examiner did not make specific
allegations regarding claims 38—42, 46-48, and 50—54. Id., 60. However,
these claims involve the same limitations already discussed for claims 2—6,
10—12, and 14—18. Consequently, for the reasons discussed, we find that the
Examiner provided adequate unrebutted evidence of their obviousness.
Motivation to combine
Appellants contend that there would have been “no motivation to
combine” Chirino and Smirnov.
There would be no motivation to combine the “computational
methods for modulating the immunogenicity of proteins” of Chirino
with the in vivo mouse study of Smirnov, the principle of operation
would be changed for the computational methods of Chirino.
Appeal. Br. 61.
This argument does not persuade us that the Examiner erred. Chirino
describes computation methods to design immunogenic proteins which are
useful to elicit an immune response — an in vivo result as described in
Smirnov. Chirino 2, 17, 21. For example, Chirino teaches:
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., 121.
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Consequently, Appellants’ argument that Chirino is a computation
method ignores the purpose of Chirino and its explicit disclosure about using
the computation method in in vivo experiments.
Summary
Because the Examiner’s rejection is supported by a preponderance of
the evidence, we affirm it.
OBVIOUSNESS IN VIEW OF CHIRINO, SMIRNOV, & TEWARI
The Examiner rejected claims 1, 8, 9, 19, 26, 27, 37, 44, and 45 in
view of Chirino, Smirnov, and Tewari. Tewari was cited by the Examiner
for its teaching of epitopes associated with viral infection that arise from
proteasomal processing. Final Rej. 11. The Examiner found it obvious to
have utilized such epitopes in Chirino’s method to identify antibodies
specific for influenza hemagglutinin. Id. Appellants contend that the
Examiner did not establish the obviousness of the claims, but failed to
address or identify a defect in the Examiner’s findings or determination.
Appeal Br. 61—62.
The Examiner included independent claims 1,19, and 37 in the
rejection, although these claims were rejected over Chirino and Smirnov.
Appellants have misread the Final Rejection to admit that Chirino and
Smirnov are “deficient” by rejecting claims 1,19, and 37 over the
additionally cited Tewari publication. Id., 63. The statement of the rejection
included the independent claims because the dependent claims incorporate
their limitations; however, the rejection stated that claims 1, 8, 9,19, 26, 27,
37, 44, and 45 are unpatentable over Chirino and Smirnov “as applied to
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claims 1—6, 10-12, 14—24, 28—30, 32-42, 46-48, and 50—54 above, and
further in view of Tewari.” Final Rej. 10. We see no error in the
Examiner’s statement of rejection nor in his explanation that Tewari is only
cited for its teaching of proteasomal processing which the Examiner found
missing from Chirino and Smirnov. Id.
Because the Examiner’s rejection is supported by a preponderance of
the evidence, we affirm it.
DECLARATION
A declaration under 37 C.F.R § 1.132 by Wayne Kindsvogel, Ph.D.,
was submitted by Appellants during prosecution. Appellants contend that
the Examiner did not address the declaration. Appeal Br. 66. Appellants
also state did not provide “any countervailing evidence to refute the
substance of the evidence presented in the Declaration.” Id., 67.
We have reviewed the record and do not find this to be accurate. The
Examiner stated in the Final Rejection that the declaration had been
determined to be “insufficient to overcome the rejection.” Final Rej. 11.
The Examiner explained that the “declaration notes that conformational
epitopes may be linear, however the cited prior art shows nonlinear
conformational epitopes.” Id., 12.
The Examiner’s explanation is supported by the evidence. Smirnov
describes an epitope that comprises two non-adjacent amino acid regions,
which is therefore nonlinear. Smirnov 1734.
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CHIRINO ENABLEMENT
During the prosecution of the cited Chirino Application, the Examiner
rejected the application claims under 35U.S.C. § 112, second paragraph,
and under § 112, first paragraph, as lacking a written description of
“immunogenicity filter.” Chirino Application Final Rejection 4. The
Examiner also made an enablement rejection under § 112, first paragraph,
stating that the application did not enable one of ordinary skill in the art to
make and use the invention as claimed. Id., 7—9. The Examiner specifically
found the “immunogenicity filter” recited in the claims to lack enablement.
Id. Second, the Examiner found the effect of replacing amino acids in the
claimed target protein structure to be unpredictable. Id. Chirino abandoned
the application. Notice of Express Abandonment (May 31, 2005).
Appellants point to the statements made by the Examiner in the
Chirino Final Rejection about the lack of enablement to argue that Chirino is
defective as prior art against the rejected claims in this appeal. Appeal Br.
70.
Appellants’ argument does not persuade us that the Examiner erred in
rejecting the claims as obvious in view of Chirino and Smirnov.
“When the reference relied on expressly anticipates or makes obvious
all of the elements of the claimed invention, the reference is presumed to be
operable. Once such a reference is found, the burden is on applicant to
provide facts rebutting the presumption of operability. In re Sasse, 629 F.2d
675, 207 USPQ 107 (CCPA 1980).” MPEP § 2121.1. In this case,
Appellants have the burden of demonstrating that Chirino is not enabled.
Appellants’ evidence that Chirino is not enabled is based solely on a
determination by an Examiner in that application to reject the pending
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claims for lack of enablement (and written description) under § 112, first
paragraph.
First, we are not bound by the determination of an Examiner in a
different, unrelated case.
Second, and independently, the Examiner’s determination was that the
claims of the Chirino Application were not enabled. This determination
does not necessarily mean that the portions of the disclosure relied upon by
the Examiner in this present appeal are also non-enabled. (“[A] prior art
reference need not enable its full disclosure; it only needs to enable the
portions of its disclosure alleged to anticipate the claimed invention.” In re
Antor Media Corp., 689 F.3d 1282, 1290 (Fed. Cir. 2012)). Appellants did
not establish that the portions of Chirino specification relied upon and cited
by the Examiner did not enable one of ordinary skill in the art at the time of
the invention, when combined with Smirnov, to have made the claimed
subject matter.
Third, we considered the basis of the enablement rejection in Chirino
and how it relates to the claims in this appeal and find that it does not
undermine the operability of the rejection based on Chirino in this appeal.
The claims in Chirino had steps of a) inputting three dimensional
coordinates to a target structure and then applying: “i) at least one
computational protein design algorithm using at least two scoring functions;
ii) an immunogenicity filter that modifies at least one T cell epitope of said
target protein by creating a variant of said T cell epitope.” The Examiner’s
rejection in the Chirino Application was based on the lack of written
description and enablement of these steps. Chirino Final Rej. 4, 7, 8.
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The rejection in this appeal is based on Chirino and Smirnov,
Smirnov is cited by the Examiner for its teaching of a non-linear epitope and
making changes to the epitope based on the changes that are predicted to
occur it during an influenza epidemic. Final Rej. 8—9, Thus, the starting
point for the claim does not necessarily require inputting three dimensional
coordinates and then using a design algorithm and immunogenieity filter as
required by the claims of Chirino and determined by the Chirino Examiner
to lack enablement:. Consequently, the Examiner’s finding that the
“description and enablement of the claimed subject matter of the Chirino
application is not relevant” to whether Chirino makes the rejected claims
obvious in combination with Smirnov and Tewari {id., 14) is supported by
the evidence.
In sum, Appellants did not provide persuasive evidence that Chirino
lacks enablement for the specific teachings relied upon by the Examiner.
NEW GROUND OF REJECITON
Claims 13, 31, and 49 depend from independent claims 1, 19, and 37,
respectively, and further comprise instructions for aiding identification of
one or more computable epitopes with a probable sequence match to a host
sequence. Such instructions, circuitry, and implementation for aiding in
identifying protein sequence matches would be reasonably understood by
one of ordinary skill in the art to include standard sequence comparison
programs where a sequence database is searched for a match. Chirino
describes performing sequence comparisons utilizing known databases such
as GenBank. Chirino H 76, 77. Smirnov provides an express reason to
perform database searching: “search of such highly conserved antigenic and
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cross-neutralizing epitope[e]s among phylogenetical[l]y closed subtypes of
influenza A viruses might be useful approach for development of vaccines
and antiviral drugs of broad activity.” Smirnov 1739. Consequently, it
would have been obvious to one of ordinary skill in the art at the time of the
invention to have implemented a protein sequence comparison program in
Chirino, where a sequence database is searched for other potentially useful
epitopes. Such a search, when conducted in a known database such as
GenBank, would be capable of identifying sequences that match the host
sequence. This is a new ground of rejection pursuant to 37 C.F.R. 41.50(b).
SUMMARY
1. The written description rejection of claims 13,21, and 49 is
reversed.
2. The obviousness rejection of claims 1—6, 10-12, 14—24, 28—30,
32-42, 46-48, and 50-54 under 35 U.S.C. § 103(a) in view of Chirino and
Smirnov is affirmed.
3. The obviousness rejection of 1, 8, 9, 19, 26, 27, 37, 44, and 45
under 35 U.S.C. § 103(a) in view of Chirino, Smirnov, and Tewari is
affirmed.
4. A new ground of rejection of claims 13,21, and 49 is entered
pursuant to 37 C.F.R. § 41.50(b) as obvious under 35 U.S.C. § 103(a) in
view of Chirino and Smirnov.
NEW GROUNDS OF REJECTION
This decision contains new grounds of rejection pursuant to 37
C.F.R. § 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960
(August 12, 2004), 1286 Off. Gaz. Pat. Office 21 (September 7,
2004)). 37 C.F.R. § 41.50(b) provides that “[a] new ground of rejection
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pursuant to this paragraph shall not be considered final for judicial
review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new evidence relating to the claims so rejected,
or both, and have the matter reconsidered by the Examiner, in which
event the proceeding will be remanded to the Examiner. . . .
(2) Request rehearing. Request that the proceeding be reheard under §
41.52 by the Board upon the same record. . .
The amendment and/or new evidence under 37 C.F.R. § 41.50(b)(1),
or the request for rehearing under 37 C.F.R. § 41.50(b)(2), must be filed
within 2 months from the date of the Board’s decision. In accordance with
37 C.F.R. § 41.50(f), this 2-month time period may not be extended by the
filing of a petition and fee under 37 C.F.R. § 1.136(a), but only under the
provisions of 37 C.F.R. § 1.136(b).
AFFIRMED: $ 41,501b)
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