Ex Parte Zang

Patent Trial and Appeal Board

Oct 27, 2014

11060848 (P.T.A.B. Oct. 27, 2014)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte JINGWU Z. ZANG
____________

Appeal 2012-010856
Application 11/060,848
Technology Center 1600
____________

Before DONALD E. ADAMS, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.

JENKS, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 involving claims directed to
a method of improving the clinical course of multiple sclerosis (MS) by
administering an autologous T-cell vaccine to patients. The Examiner
rejects the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
“For a T-cell to recognize and bind to an antigen, the antigen has to be
processed by another type of cell, called an antigen presenting cell (APC).

1 Appellant identifies Opexa Therapeutics, Inc. as the Real Party in Interest.
(App. Br. 1.)
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APCs have an important molecule on their surface called the major
histocompatibility complex (MHC) molecule, which binds the antigen.”
(Markovic-Plese,2 Introduction; see also 1st Cohen Decl.3 ¶ 5.) The binding
of the T-cell receptor to an antigen presented by the MHC molecule on the
APC is called the trimolecular complex. “Once the TCR [(T-cell receptor)]
binds the antigen-MHC complex, the TCR will signal the T-cell to
respond. . . . The T-cell replicates itself into a clone of cells that recognize
the same antigen, and every cell in the clone can secrete powerful immune
chemicals that may mobilize other cells to attack.” (Markovic-Plese,
Introduction.) It is the activation of the T-cell response that leads to
inflammation. At the time of filing, MS treatment strategies under active
investigation included: (1) the T-cell vaccine approach; (2) the altered
peptide ligand approach, (3) the T-cell receptor peptide approach; and (4)
the DNA-encoding peptide therapy approach (Ans. 8; see also Hohlfeld4).
Each of these approaches targets the trimolecular complex by different
mechanisms.
The Specification explains that “[t]here is growing evidence
suggesting that autoimmune T cell responses to myelin antigens, including
myelin basic protein (MBP), are engaged in the pathogenesis of multiple
sclerosis (MS)” (Spec. 1). “Although there is indirect evidence suggesting
potential association of myelin-reactive T[-]cells with the disease processes

2 Markovic-Plese et al., Modulation of Inflammatory Response in Multiple
Sclerosis by Altered Peptide Ligand (APL), United Spinal MS Scene (2005).
3 Declaration by Irun R. Cohen, signed April 19, 2009.
4 Reinhard Hohlfeld & Hartmut Wekerle, Autoimmune concepts of multiple
sclerosis as a basis for selective immunotherapy: From pipe dreams to
(therapeutic) pipelines, 101 PNAS 14599–14606 (2004).
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in MS (Zhang et al., 1994 Chou et al., 1992, Allegretta et al., 1990), it has
been difficult to establish or reject the role of myelin-reactive T cells in the
pathogenesis of MS.” (Spec. 5.)
Claims 8–17 are on appeal, and can be found in the Claims Appendix
of the Appeal Brief (App. Br. 38–39). Claim 8 is representative of the
claims on appeal, and reads as follows (first emphasis added):
8. A method for treating multiple sclerosis comprising
administering to a patient in need thereof an autologous T cell
vaccine, wherein the vaccine is made by a process comprising:
(a) priming in vitro a sample of peripheral blood
mononuclear cells (PBMCs) and/or cerebrospinal fluid
mononuclear cells (CSFMCs) comprising T cells with a
combination of fragments of at least one multiple sclerosis
associated antigen, wherein the sample is obtained from the
patient to be treated with the vaccine;
(b) stimulating the cells of (a) with antigen presenting
cells and the fragment;
(c) propagating the stimulated cells of (b) for
vaccination; and
(d) attenuating the propagated cells of ( c);
wherein said administration improves the clinical course
of the disease.
The following grounds of rejection are before us for review:
I. claims 8, 9, and 11–15 under 35 U.S.C. § 103(a) as being
unpatentable over Zhang5 in view of Kozovska;6 and

5 Zhang et al., MHC-Restricted Depletion of Human Myelin Basic Protein-
Reactive T Cells by T Cell Vaccination, 261 Science 1451–1454 (1993).
6 Kozovska et al., T cell recognition motifs of an immunodominant peptide of
myelin basic protein in patients with multiple sclerosis: structural
requirements and clinical implications, 28 Eur. J. Immunol. 1894–1901
(1998).
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II. claims 10, 16, and 17 under 35 U.S.C. § 103(a) as being
unpatentable over Zhang in view of Kozovska, in further view
of Greer.7
As Appellant does not argue the claims separately, we focus our
analysis on claim 8, and claims 9 and 11–15 stand or fall with that claim.
37 C.F.R. § 41.37 (c)(1).

I. The Issue: Obviousness over Zhang in view of Kozovska
Does the preponderance of evidence of record support the Examiner’s
conclusion that given the state of the art at the time the invention was filed
there was a reasonable expectation of success in arriving at a T-cell vaccine
using an antigen fragment based on the combination of Zhang and
Kozovska?
Findings of Fact
FF1. The Examiner provides sound fact-based reasoning for
combining Zhang and Kozovska. We adopt the fact finding and analysis of
the Examiner as our own (Ans. 4–18).
We highlight the following facts for reference convenience:
FF2. Zhang discloses the production of a T-cell vaccine using
full-length myelin basic protein (MBP) as the antigen (Zhang, Abstract).
FF3. Kozovska discloses that:
To generate specific T cell lines . . . , PBMC [peripheral blood
mononuclear cells ] were plated out at 200000 cells/well in
round-bottom plates in the presence of the MBP83-99 peptide
[myelin basic protein] (10 μg/ml). Seven days later, all cultures

7 Greer et al., Immunogenic and Encephalitogenic Epitope Clusters of
Myelin Proteolipid Protein, 156 J. Immunol. 371–379 (1996).
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were restimulated with irradiated PBMC pulsed with the
peptide as a source of APC [antigen presenting cells]. After
another week, each culture was examined for specific
proliferation to the MBP83-99 peptide in proliferation assays.
(Kozovska 1900, see 4.2.)
FF4. Kozovska discloses the production of 36 independent T-cells
clones from 11 MS patients using the MBP83-99 peptide. Of the 36 clones, 27
responded to the MPB83-99 peptide presented by antigen presenting cells
(Kozovska 1895, see 2.1.) Summarizing these findings, Kozovska states
that “[t]he T cell response to the 83-99 region of MBP represents a dominant
autoreactive response to MBP in MS patients of DR2 haplotype” (Kozovska,
Abstract).
Principle of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). In determining
whether obviousness is established by combining the teachings of the prior
art, “the test is what the combined teachings of the references would have
suggested to those of ordinary skill in the art.” In re Keller, 642 F.2d 413,
425 (CCPA 1981).
Picking one of a finite number of known solutions to a known
problem is obvious. KSR, 550 U.S. at 421:
When there is a design need or market pressure to solve a
problem and there are a finite number of identified, predictable
solutions, a person of ordinary skill has good reason to pursue
the known options within his or her technical grasp. If this
leads to the anticipated success, it is likely the product not of
innovation but of ordinary skill and common sense. In that

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instance the fact that a combination was obvious to try might
show that it was obvious under § 103.
(Id.)
“Obviousness does not require absolute predictability of success . . .
all that is required is a reasonable expectation of success.” In re Droge, 695
F.3d 1334, 1338 (Fed. Cir. 2012) (quoting In re Kubin, 561 F.3d 1351, 1360
(Fed. Cir. 2009) (citing In re O’Farrell, 853 F.2d 894, 903–04 (Fed. Cir.
1988)).
Analysis
The Examiner finds, and Appellant does not contest, that Zhang
discloses the production of T-cell vaccines using full-length myelin basic
protein (MBP) as the antigen (FF2, see Ans. 4–6; see also App. Br. 5; Reply
Br. 2). The Examiner looks to Kozovska for teaching immunodominant
epitopes associated with multiple sclerosis (MS). Kozovska states that
“[t]he T cell response to the 83-99 region of MBP represents a dominant
autoreactive response to MBP in MS patients of DR2 haplotype” (Kozovska
Abstract) and further discloses the use of peripheral blood mononucleocites
(PBMC) for the priming and stimulation steps in the production of T-cell
clones using the MBP83-99 fragment (FF3). Specifically noting Kozovska’s
teaching that MBP 83-99 comprises “a potential treatment for MS because
‘suppression of these T cells would eradicate major T cell responses to MBP
in a large portion of MS patients’” (Ans. 5), the Examiner concludes that it
would have been prima facie obvious to employ the treatment methods of
Zhang with the MBP fragment-derived T-cell clones of Kozovska
“comprising the immunodominant determinants (epitopes) . . . rather than
whole MBP [(disclosed in Zhang)]” because “[i]t is more efficient and
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elegant to target specific T cells known to be aberrant than to try to target T
cells to all possible T cell epitopes that likely do not even exist” (Ans. 5, 12).
We conclude that the Examiner has met the burden of presenting a
prima facie case based on the combination of Zhang and Kozovska.
Because the Examiner presents a prima facie case of obviousness, we
consider whether Appellant submits sufficient evidence or argument in
rebuttal. In re Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993). “When prima
facie obviousness is established and evidence is submitted in rebuttal, the
decision-maker must start over.” In re Rinehart, 531 F.2d 1048, 1052
(CCPA 1976); In re Hedges, 783 F.2d 1038, 1039 (Fed. Cir. 1986) (“If a
prima facie case is made in the first instance, and if the applicant comes
forward with reasonable rebuttal, whether buttressed by experiment, prior art
references, or argument, the entire merits of the matter are to be
reweighed”).
In response, Appellant contends that at the time of filing the present
application the art taught away from treating MS with fragment-primed T-
cells (App. Br. 8–25 and 35–36); that the Examiner disregarded portions of
the art that would lead away from the claimed invention (App. Br. 25–28);
and that the Examiner has provided no rational underpinning to support a
finding of obviousness (App. Br. 28–35). In support of these allegations
Appellant contends that: (1) the disease relevant fragment of MBP was
unknown (see App. Br. 10–13, 19; 21, 26, 29; see also Reply Br. 4); (2) the
function of autoreactive T-cells was unknown (see App. Br. 10, 11, 18, 23);
and (3) the autoreactive T-cell response is heterogeneous among MS patients
(see App. Br. 10, 11, 19; 21, 23). Appellant concludes that only the use of
full-length MBP for the purpose of priming cells would have been
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considered reasonable at the time of the invention (App. Br. 10, 11; Reply
Br. 4; see also 1st Cohen Decl. ¶ 11, 14, 24; 2nd Cohen Decl. ¶ 13).
We have carefully reviewed the Examiner’s response in light of
Appellant’s contentions; we find that the Examiner has sufficiently
addressed each of the allegations in the Answer (FF1). Accordingly, we
sustain the Examiner’s rejection of claim 8 for the reasons set forth in detail
in the Answer, which we incorporate herein by reference (id.). During oral
argument, held on October 7, 2014, Appellant reiterates that the Examiner
has not given the proffered declarations and other evidence sufficient weight
to arrive at the conclusion that there was no reasonable expectation of
success when using peptides for a T-cell vaccine production.
In response to Appellant’s concerns, we note that the 1st Cohen
declaration specifically acknowledges that the disease-relevant peptides for
MS are unknown (1st Cohen Decl. ¶ 7). The declaration also indicates that it
is unknown whether activated T-cells are involved in the clinical
exacerbation of MS (1st Cohen Decl. ¶ 10). Cohen opines that a “researcher
in the field of multiple sclerosis would not have chosen to use myelin
peptides, such as MBP83-99 and MBP151-170, as antigens in the production of a
T cell vaccine for multiple sclerosis at the time the Zang Application was
filed, but instead would have chosen full-length myelin proteins.” (1st
Cohen Decl. ¶¶ 11, 14, 24; see also 2nd Cohen Decl. ¶¶ 11–13; see also App.
Br. 12, 13, 19, 21, 29.) To buttress this opinion, Dr. Cohen points to the
Weiner grant application as evidence of a consensus view in that art that
using full-length myelin proteins will target the broadest repertoire of
autoantigens and have the best chance of stopping disease progression in MS
patients (2nd Cohen Decl. ¶¶ 5–7).
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We are not persuaded that the totality of the evidence presented in the
Cohen declarations would have directed the ordinary artisan away from
using peptides to prime and stimulate T-cell clones from MS patients for the
production of a T-cell vaccine. We understand that priming and stimulating
the T-cells with only a peptide representing a portion of MBP will not
produce the broadest repertoire of T-cells reactive along the entire length of
MBP. However, the claims are not directed at producing the broadest
repertoire of T-cells that are reactive along the entire length of MBP.
Furthermore, as pointed out by the Examiner, Zhang shows a clonotypic
response even though the protocol uses full-length MBP for the priming and
stimulating steps (Ans. 10). We agree with the Examiner that Zhang’s
T-cell clones used as a vaccine in the patients were reactive to peptides
spanning MBP, specifically to amino acids 84–102, 90–170, and 143–168
(Zhang 1453). T-cell clone 1B7-E4 from subject BC had a reactivity to full-
length MBP of 42.5 ± 3.1 while the same clone had a reactivity to the
peptide MBP84-102 of 43.8 ± 2.2 (id.). Thus, as recognized by the Examiner,
even when priming with full-length MBP the population of T-cell clones that
are expanded are not equally reactive to peptides along the entire length of
MBP. Even if the epitopes vary slightly within the immunodominant region,
as asserted by Appellant (App. Br. 11; see also 1st Cohen Declaration ¶¶ 20–
21), the process of expanding the T-cell clones as claimed will expand a
heterogeneous T-cell population from a patient recognizing that antigen.
Here, Kozovska has established the feasibility of priming and stimulating T-
cells derived from MS patients using the peptide antigen MBP83-99 (FF3–4).
We recognize that not all MS patients react to MBP83-99 (1st Cohen
Decl. ¶¶ 19–21). This, however, would not dissuade the ordinary artisan
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from following the path of developing a peptide primed T-cell vaccine. The
heterogeneity of the immune response in the MS population merely indicates
that “a one size fits all” treatment strategy may not be applicable in every
MS patient. We understand that there is heterogeneity among patients in the
peptide processing and presentation by the APC as well as in the TCR
recognizing the presented peptide. We note that the claims are not directed
at a treatment protocol that has to be effective in all MS patients equally.
Indeed, the claims are directed at an “autologous T-cell vaccine,” meaning
that the T-cells are removed and put back into the same patient. Even if a
subset of patients in the MS population does not contain T-cells directed to
the MBP83-99 epitope (as suggest in 1st Cohen Decl. ¶¶ 19–21), that simply
means that these patients would not be candidates for the treatment with the
T-cell vaccine directed to MBP83-99 epitope. The PBMCs from this patient
population will not respond to priming and stimulation with the peptide to
produce the requisite population of expanded T-cells needed for the vaccine
production. Thus, the argument that there is heterogeneity in the T-cell
response is not persuasive because those patients that do not have T-cells
reactive to the MBP83-99 are easily identified. However, in those patients that
do have reactive T-cells directed to the immunodominant MBP83-99 epitope
as shown by Kozovska (FF3), reintroducing these attenuated propagated
cells would reasonably lead to a depletion of those T-cells in a patient that
are reactive to the peptide as shown in Zhang’s protocol.
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With reference to the 2nd Zhang declaration,8
Appellant[] respectfully assert[s] that the difference
between the prior art method and the instant claims is not
merely the use of full-length antigen versus the use of
fragments in producing a T cell vaccine for the treatment of
MS, but rather the use of full-length antigen versus the use of
fragments as the priming antigen
(App. Br. 27). The 2nd Zhang Declaration asserts that “priming with full-
length MBP was considered the only way to expand all possible autoreactive
clones over the entire MBP-specific T cell repertoire for an individual
patient.” (Zhang Decl. ¶ 15.)
We are not persuaded. Here, the claims are not directed to expanding
all possible autoreactive clones against MBP for use as a vaccine. In
addition, Kozovska established that MBP peptide fragments can be used
both for priming T-cells and for stimulating those T-cells for further
propagation (FF3–4). Thus, the argument that only full-length MBP can
prime a T-cell response is not persuasive.
“One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of ‘unexpected results[.]’” In re Soni, 54
F.3d 746, 750 (Fed. Cir. 1995). We recognize, but are not persuaded by,
Appellant’s contention that “T cell vaccination of the instant application are
comparable to, and sometimes better than, the results of the pilot study”
(Zhang Decl. ¶ 16). Appellant has not presented persuasive evidence, in the
form of data, that can be reviewed and evaluated. An assertion that
something is “comparable to” does not necessarily indicate that it is better,
or unexpected. To be simply “comparable to” can mean that the results

8 The Evidence Appendix does not list the first Zhang declaration, and we
note this declaration is not referenced in the Appeal Brief.
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obtained with T-cells primed with MBP peptide are equivalent, modestly
better, or modestly worse, some or all of the time than results using T-cells
primed with full-length MBP. Appellant has not provided sufficient
evidence that the claimed combination provides an unexpected result. Thus,
the evidence on this record fails to support a conclusion that the results
obtained through the use of Appellant’s claimed method achieves more than
the reasonable expectation required for finding the combination “obvious to
try.” KSR, 550 U.S. at 421.
Appellant also directs our attention to the Healey Declaration
asserting that one treatment method for MS under active investigation at the
time of filing turned out to be ineffective (App. Br. 16). Specifically, Healey
discusses that antigen presenting ligand (APL) therapies have failed to
improve clinical outcomes (Healey Decl. ¶ 13). Unpredictability with this
APL therapy “led researchers to conclude that MBP83-99 ‘is clearly only
one of the relevant autoantigens in MS and is not responsible for all MS
attacks’” (Healey Decl. ¶ 16).
We agree with the Examiner’s position regarding the relevance of the
Healey Declaration (Ans. 11–12). That a protocol involving a particular
epitope and mechanism of action has failed, is not persuasive evidence that a
different protocol involving the same epitope will also fail. Even though
Healey acknowledges that MBP83-99 is only one of the relevant autoantigens
this would not dissuade the ordinary artisan from using that epitope target in
a different treatment protocol. Again, it is important to note that the claims
are not directed at targeting all relevant autoantigens of MBP.
Finally, Appellant also contends that the Examiner has not given the
Hohlfeld reference sufficient weight (Reply Br. 6).
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We are not persuaded by Appellant’s contention that the Examiner has
not addressed the rebuttal evidence presented with respect to Hohlfeld. We
agree with the Examiner’s response as presented in the Answer (Ans. 8–9).
We find that Hohlfeld’s review summarizes that, of the three treatment
protocols under active consideration at the time the filing, the APL and TCR
vaccine protocols did not show sufficient therapeutic effect to warrant
further investigation. Specifically, the reference indicates that “[t]he search
for a target antigen of MS is hindered by the fact that human MS is very
heterogeneous” (Hohlfeld 14599).
[I]n humans, some MBP epitopes are recognized more
frequently than others, both at the population level and in
individual subjects. These relatively immunodominant epitopes
include region MBP 85-99, which is presented in the context of
the HLA allele DRB1*1501, and is associated with MS. It
should be noted, however, that the human T cell response to
MBP region 85-99 shows remarkable microheterogeneity, both
in terms of fine epitope specificity and TCR use (23).
(Hohlfeld 14600.) Hohlfeld indicates that Phase II trials using APL therapy
derived from the immunodominant MBP83–99 peptide were halted
prematurely due to observed exacerbations of symptoms and other side
effects (Hohlfeld 14604). “[P]ilot studies of TCR vaccination have not yet
demonstrated significant clinical benefits, but further results are needed. . . .
[It is] anticipated that TCR vaccination will work only if patients are treated
with individualized, ‘tailor-designed’ vaccines” (Hohlfeld 14605).
Vaccination with autologous T-cells is promising but needs further testing in
larger trials (Hohlfeld 14604).
As noted by the Examiner “the only MS-specific epitope taught by the
reference is variously referred to as MBP 83-99, 85-99, or 84-102” (Ans. 9).
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Even though the APL and TCR treatment approaches targeting the recited
MBP peptides were eventually found unsuccessful (Ans. 11), we agree with
the Examiner’s position that there is nothing in the reference that would
dissuade the ordinary artisan from using the same immunodominant target
using a different therapeutic mechanism, specifically, the T-cell vaccine.
We agree with the Examiner’s position “that T cell vaccination was a
method that had been known to be successful for nearly a decade . . . [and
that] the MBP 83-99 peptide had been known to be an immunodominant MS
epitope for at least that long” (Ans. 12). Using the MBP83-99 peptide for the
priming and stimulation of patients T-cells (FF3–4) “is not a misguided
‘obvious to try’ type rejection, but rather it is a rejection based on what
would have been an obvious combination to the ordinarily skilled artisan at
the time of the invention” (Ans. 12). Even though Zhang primed and
stimulated T-cells using full-length MBP, clones derived from this protocol
were reactive with peptides spanning amino acids 83–170 of MBP (see
Zhang table 1). Thus, Zhang alone provides guidance for selecting T-cells
that are reactive to only a portion of the MBP. Kozovska showed the
feasibility of priming and stimulation with peptides for the production of T-
cell clones from MS (FF3–4). We agree with the Examiner that this
combination is not some “lucky stab at success” (Ans. 12), but flows from
the combined teachings of Zhang and Kozovska. See KSR, 550 U.S. at 421.
“The normal desire of scientists or artisans to improve upon what is already
generally known provides the motivation to determine” the optimum
reactive MBP fragments for use in priming and stimulating Tcells from an
MS patient. See In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003).
After considering the evidence and rebuttal arguments, we conclude
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that the evidence on this record favors the Examiner’s conclusion of
obviousness. We affirm the rejection of claim 8 over Zhang and Kozovska.
Appellant does not separately argue dependent claims 9 and 11–15.
Therefore, these claims fall with claim 8. 37 C.F.R. § 41.37(c)(1).

II. The Issue: Obviousness over Zhang, Kozovska, and Greer
The rejection of claims 10, 16, and 17 relies on the underlying
obviousness rejection over Zhang in view of Kozovska. Appellant contends
that “the identification of immunodominant peptides did not resolve the
uncertainties surrounding the pathogenesis of MS” (App. Br. 10). We are
not persuaded. Just because there are uncertainties with respect to the
pathogenesis of a disease does not mean that the ordinary artisan would not
have considered these immunodominant peptides as a therapeutic target (see
Martin,9 Zhang-2001,10 Zhang-1996,11 Bielekova,12 Kappos,13).

9 Martin et al., Diversity in fine specificity and T-cell receptor usage of the
human CD4+ cytotoxic T cell response specific for the immunodominant
myelin basic protein peptide 87–106, 148 J. Immunol. 1359–1366 (1992).
10 Zhang, T-Cell Vaccination in Multiple Sclerosis: Immunoregulatory
Mechanism and Prospects for Therapy, 21 Critical Reviews in Immunol.
41–55 (2001).
11 Zhang et al., T cell vaccination: clinical application in autoimmune
diseases, 74 J. Mol. Med. 653–662 (1996).
12 Bielekova et al., Encephalitogenic potential of the myelin basic protein
peptide (amino acids 83-99) in multiple sclerosis: Results of a phase II
clinical trial with an altered peptide ligand, 6 Nature Medicine 1167–1175
(2000).
13 Kappos et al., Induction of a non-encephalitogenic type 2 T helper-cell
autoimmune response in multiple sclerosis after administration of an altered
peptide ligand in a placebo controlled, randomized phase II trial, 6 Nature
Medicine 1176–1182 (2000).
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Appellant recognizes that Greer is directed at “determining fragments
of proteolipid protein that may be encephalitogenic (i.e., involved in the
pathogenesis of MS) and immunodominant (i.e., encephalitogenic in a
majority of MS patients).” (App. Br. 10; see also 18, 23, 24, 25.) Appellant,
however, contends that “the Office does not cite any portion of Greer as
providing teaching or suggestion that would motivate an ordinarily skilled
artisan to treat MS with a T cell vaccine produced by priming an autologous
sample in vitro with a fragment of a multiple sclerosis associated antigen”
(App. Br. 31).
We are not persuaded by Appellant’s contentions. The Examiner
particularly points to Greer’s abstract as providing evidence of PLP’s
encephalitogenic epitopes (Ans. 6). With respect to the priming and
stimulation of T-cell lines, Greer discloses:
CD4+ T cell lines generated from PBL of MS patients by
stimulation with PLP peptides within the regions 40–60 and
89–154 predominantly responded to peptides 40–60 and 89–
106. Several other groups have also derived T cell lines and
clones from blood of MS patients by stimulation with PLP
peptides in the 100-119 region . . . have found that T cell lines
from MS patients and controls stimulated with whole PLP and
then tested against overlapping peptides respond predominantly
to peptides in regions 30–49 and 180–199.
(Greer 378.) We agree with the Examiner’s conclusion that it would be
obvious to improve on the methods of treating MS as disclosed in the
combination of Zhang and Kozovska “by employing the additional
immunodominant PLP fragments identified by Greer et al., thus providing
an even more effective treatment” (Ans. 6). Having found no error in the
Examiner’s rationale based on the combination of Zhang in view of
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Kozovska (see above I.), we are equally unpersuaded that the combination in
in further view of Greer is in error.

SUMMARY
We affirm the rejection of claims 8, 9, and 11–15 under 35 U.S.C.
§ 103(a) as being unpatentable over Zhang in view of Kozovska.
We affirm the rejection of claims 10, 16, and 17 are rejected under
35 U.S.C. § 103(a) as being unpatentable over Zhang in view of Kozovska,
in further view of Greer.

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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