Ex Parte Singh et al

Patent Trial and Appeal Board

Jul 26, 2013

12055151 (P.T.A.B. Jul. 26, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte HARPREET SINGH,
NIELS EMMERICH, NORBERT HILF,
STEFFEN WALTER, and TONI WEINSCHENK
__________

Appeal 2012-000942
Application 12/055,151
Technology Center 1600
__________

Before TONI R. SCHEINER, FRANCISCO C. PRATS, and
GEORGIANNA W. BRADEN, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal
1
under 35 U.S.C. § 134 involves claims to a method of
treating a neoplastic disorder. The Examiner entered rejections for new
matter and obviousness.
We have jurisdiction under 35 U.S.C. § 6(b).
We reverse the new matter rejection.
We affirm the Examiner‟s obviousness rejections, however.

1
Appellants indicate that the Real Party-In-Interest is Immatics
Biotechnologies GmbH (App. Br. 3).
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Application 12/055,151

2
STATEMENT OF THE CASE
Appellants‟ invention is directed to the treatment of a neoplastic
disorder, such as cancer, by administering the combination of a tumor-
associated peptide vaccine and a multi-kinase inhibitor.
Claims 1, 2, 4, and 6-16 stand rejected and appealed (App. Br. 3).
Claims 1 and 4 illustrate the appealed subject matter and read as follows:
1. A method of treating a neoplastic disorder in a mammal
comprising administering to the mammal a composition comprising a
vaccine and a multi-kinase inhibitor, wherein the vaccine comprises
an isolated tumor associated peptide having the ability to bind to a
molecule of the human major histocompatibility complex (MHC)
class-I or class-II and wherein the neoplastic disorder expresses at
least one peptide comprising a sequence selected from the group
consisting of SEQ ID NO: 1 (SVASTITGV); SEQ ID NO: 2
(VMAGDIYSV); SEQ ID NO: 3 (ALADGVQKV); SEQ ID NO: 4
(LLGATCMFV); SEQ ID NO: 5 (SVFAGVVGV); SEQ ID NO: 6
(ALFDGDPHL); SEQ ID NO: 7 (YVDPVITSI); SEQ ID NO: 8
(SQDDIKGIQKLYGKRS); SEQ ID NO: 9 (STAPPVHNV); and
SEQ ID NO: 10 (LAALPHSCL).

4. The method of claim 1 wherein the vaccine comprises at least
one peptide selected from the group consisting of SEQ ID NO: 1
(SVASTITGV); SEQ ID NO: 2 (VMAGDIYSV); SEQ ID NO: 3
(ALADGVQKV); SEQ ID NO: 4 (LLGATCMFV); SEQ ID NO: 5
(SVFAGVVGV); SEQ ID NO: 6 (ALFDGDPHL); SEQ ID NO: 7
(YVDPVITSI); SEQ ID NO: 8 (SQDDIKGIQKLYGKRS); SEQ ID
NO: 9 (STAPPVHNV); and SEQ ID NO: 10 (LAALPHSCL).

The following rejections are before us for review:
(1) Claims 1, 2, 4, and 6-14, under 35 U.S.C. § 112, first paragraph, as
lacking adequate descriptive support in the Specification and therefore
containing new matter (Ans. 5-6);
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(2) Claims 1, 2, 4, 6, 7, 10, 15, and 16, under 35 U.S.C. § 103(a) as
obvious over Brossart „712,
2
Brossart I,
3
Brossart II,
4
and Cabebe
5
(Ans. 7-
10);
(3) Claims 8, 9, and 11-14, under 35 U.S.C. § 103(a) as obvious over
Brossart „712, Brossart I, Brossart II, Cabebe, and Capizzi
6
(Ans. 10-14).
In response to a species election requirement, Appellants elected
sunitinib maleate as the multi-kinase inhibitor and SEQ ID NO: 9 from
among the recited peptides, for prosecution on the merits (see App. Br. 4).
Accordingly, in addressing the rejections based on prior art, we limit our
analysis to the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461
(BPAI 1987).
NEW MATTER
The Examiner found that the limitation in claim 1, “„wherein the
neoplastic disorder expresses at least one peptide comprising a sequence
selected from the group consisting of SEQ ID NO:1-10‟ has no clear support
in the specification and the claims as originally filed” (Ans. 5). Specifically,

2
U.S. Patent No. 7,087,712 B1 (issued Aug. 8, 2006).
3
Peter Brossart et al., Identification of HLA-A2-Restricted T-Cell Epitopes
Derived From the MUC1 Tumor Antigen for Broadly Applicable Vaccine
Therapies, 93 BLOOD 4309-4317 (1999).
4
Peter Brossart et al., Induction of cytotoxic T-Iymphocyte responses in vivo
after vaccinations with peptide-pulsed dendritic cells, 96 BLOOD 3102-3108
(2000).
5
Elwyn Cabebe and Heather Wakelee, SUNITINIB: A NEWLY APPROVED
SMALL-MOLECULE INHIBITOR OF ANGIOGENESIS, 42 DRUGS OF
TODAY 387-398 (2006).
6
Robert L. Capizzi, Curative chemotherapy for acute myeloid leukemia: the
development of high-dose ara-C from the laboratory to bedside, 14
INVESTIGATIONAL NEW DRUGS 249-256 (1996).
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the Examiner found that the Specification “only contemplates administering
said peptides, but does not disclose any support for any tumors, malignant
neoplastic cells, benign neoplastic cells, abnormal cell growth, or cancer (as
encompassed by „neoplastic disorder‟) expressing such peptides” (id. at 6).
The Examiner noted the Specification‟s disclosure that renal cell
carcinoma (RCC) expresses MUC-1, an antigen which undisputedly includes
peptides having sequences encompassed by the claims, but found that
“MUC-1 is a whole antigen” (id.). Thus, the Examiner reasoned, “the
claimed peptides are not actually expressed by the „neoplastic disorders‟
being treated in the claims, but rather these peptides arise from antigen
presenting cells digesting MUC-1 and presenting antigenic epitopes to T-
cells” (id.).
As stated in TurboCare Div. of Demag Delaval Turbomachinery
Corp. v. General Elec. Co., 264 F.3d 1111, 1118 (Fed. Cir. 2001):
The written description requirement and its corollary, the new
matter prohibition of 35 U.S.C. § 132, both serve to ensure that
the patent applicant was in full possession of the claimed
subject matter on the application filing date. When the applicant
adds a claim or otherwise amends his specification after the
original filing date . . ., the new claims or other added material
must find support in the original specification.

We agree with Appellants that the Examiner has not shown that
Appellants‟ Specification fails to describe treating patients suffering from a
a disorder that expresses at least one peptide comprising a sequence set forth
in SEQ ID numbers 1 through 10, as recited in claim 1.
As the Specification explains, the claimed method targets neoplastic
disorders in which the diseased cells, such as cancer or tumor cells, express
“an antigen that is selectively or abundantly expressed” (Spec. 17). As the
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Specification further explains, the MUC-1 antigen expressed by the kidney
cancer cell line A498 (see id. at 30), includes a peptide having the amino
acid sequence STAPPVHNV, which is the sequence set forth in SEQ ID
NO: 9 (see id. at 18).
Thus, because the Specification describes treating neoplastic disorders
characterized by expression of an antigen that contains within it a peptide
having a sequence recited in claim 1, we agree with Appellants that the
Specification has sufficient support for the current claim language.
The Examiner further finds that “the plain meaning of „peptide‟ . . .
[is] a short sequence or fragment of a polypeptide” (Ans. 16).
The Examiner does not, however, point to any clear or specific
evidence of record to support interpreting the claims as being limited to
treating diseases that express relatively short molecules that include the
amino acid sequences recited in the claims.
Moreover, as our reviewing court has pointed out, during
examination, the PTO must interpret terms in a claim using “the 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) (emphasis added).
We are not persuaded that an ordinary artisan, viewing claim 1 in light
of the Specification‟s description of the invention, discussed above, would
consider it reasonable to interpret the claimed methods as being limited to
treating disorders that express relatively short molecules that include the
amino acid sequences recited in the claims. Thus, as we are not persuaded
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that Appellants‟ Specification fails to provide adequate descriptive support
for the language at issue in claim 1, we reverse the Examiner‟s rejection of
that claim, and its dependents, under 35 U.S.C. § 112, first paragraph.
OBVIOUSNESS
In rejecting claim 1 as obvious, the Examiner cited Brossart „712 as
teaching the administration, to a mammal, of a vaccine including a peptide
having the sequence of SEQ ID NO: 9, and noted in particular that cytotoxic
T cells (CTLs) activated by the vaccine “were able to lyse tumor cells
expressing MUC-1 including breast cancer, renal carcinoma cancer (RCC)
cells, and pancreatic cancer cells” (Ans. 7).
The Examiner cited Brossart I as teaching similar results using the
same peptide having SEQ ID NO: 9 against breast cancer, RCC, and
pancreatic cancer cells, and further noted Brossart I‟s teaching that “the
MUC-1 antigen is expressed in many tumors and suggests MUC-1 peptides
are a broadly applicable vaccine therapy” (id. at 8).
The Examiner cited Brossart II as teaching that a similar peptide,
differing from the peptide of SEQ ID NO: 9 by only a single amino acid,
“was able to induce peptide-specific CTL responses in vivo in breast cancer
patients” (id.). The Examiner further found that Brossart II “suggest[ed]
treating patients with pancreatic cancer and RCC, cancers known to express
MUC-1” (id.).
The Examiner conceded that the Brossart references differed from
claim 1 in that they did not teach “combining the peptide vaccine with the
multi-kinase inhibitor sunitinib malate for cancer treatment” (id. at 7).
To address that deficiency the Examiner cited Cabebe as teaching
“treating breast cancer and RCC by administering to patients the multi-
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kinase inhibitor sunitinib malate” (id. at 8). The Examiner also noted that
Cabebe “suggest[ed] using sunitinib malate in combination therapies” (id.
(citing Cabebe 395)).
Based on the references‟ combined teachings, the Examiner
concluded that an ordinary artisan would have considered it obvious to
combine a peptide having a sequence of SEQ ID NO: 9 and sunitinib “in
order to treat cancer, particularly breast cancer and RCC” (id. at 9). The
Examiner reasoned that an ordinary artisan would have been prompted to
combine the two agents “in view of the importance of eliminating breast
cancer or RCC tumor cells” (id.).
The Examiner further reasoned that the rationale set out in In re
Kerkhoven, 205 USPQ 1069 (CCPA 1980), would have been applicable
because the idea of combining sunitinib and a vaccine containing a peptide
of SEQ ID NO: 9 “would have logically followed from their having been
individually taught in the prior art to be useful as agents for the same
purpose of treating cancer, particularly breast cancer and RCC” (Ans. 9).
Still further, the Examiner reasoned, an ordinary artisan “would have
reasonably expected to obtain effective treatment of cancer, particularly
breast cancer and RCC, with either or both of these agents since both had
been taught in the prior art to treat or kill cancer cells, particularly breast
cancer and RCC” (id.).
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden . . . of presenting a
prima facie case of unpatentability. . . .
After evidence or argument is submitted by the applicant
in response, patentability is determined on the totality of the
record, by a preponderance of evidence with due consideration
to persuasiveness of argument.
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Appellants‟ arguments do not persuade us that the preponderance of
the evidence fails to support the Examiner‟s prima facie case of obviousness
as to claim 1. We are also not persuaded that the evidence of unexpected
results advanced by Appellants is sufficient to outweigh the evidence of
prima facie obviousness.
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme
Court reaffirmed that “when a patent „simply arranges old elements with
each performing the same function it had been known to perform‟ and yields
no more than one would expect from such an arrangement, the combination
is obvious.” Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273
(1976)).
The Court explained:
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
instance the fact that a combination was obvious to try might
show that it was obvious under § 103.

Id. at 421.
In the instant case, claim 1 recites a method of treating a neoplastic
disorder by administering a composition containing a multi-kinase inhibitor,
which may be sunitinib, and a vaccine having a peptide including an amino
acid sequence as set forth in SEQ ID NO: 9. The Examiner found, and
Appellants do not dispute, that the cited references establish that both of the
claimed agents were known in the art to be useful for treating the same types
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of cancer (kidney cancer (RCC) and breast cancer). Moreover, as the
Examiner pointed out, Cabebe expressly disclosed that “[c]ombinations of
sunitinib with other therapies such as chemotherapy and targeted small
molecules may further augment efficacy” (Cabebe 395).
It may be true, as Appellants argue (see App. Br. 11), that the two
agents do not operate by a common mechanism. Indeed, we note that both
Cabebe and Appellants‟ Specification characterize sunitinib as an agent that
targets tumor angiogenesis (see Cabebe 388 (sunitinib “has demonstrated
direct antitumor activity and antiangiogenic action”); see also Spec. 13
(describing sunitinib as “a potent and selective anti-angiogenesis agent”)),
whereas the Brossart references disclose that administering a peptide having
the sequence in SEQ ID NO: 9 triggers an immune response against tumor
cells exhibiting the MUC-1 antigen (see, e.g., Brossart „712, col. 8, ll. 1-27
(“[T]he peptides according to the invention are suitable for triggering an
immune reaction against certain tumor cells also within the scope of a
therapy.”)).
However, given the cited references‟ undisputed teachings that both
agents were known to be useful for treating kidney and breast cancers, and
further given Cabebe‟s express disclosure of the suitability of combining
sunitinib with other therapies, we are not persuaded that the references
would have failed to provide a reasonable expectation that administering a
combination of the two ingredients would treat kidney or breast cancer. As
our reviewing court has noted, “[o]bviousness does not require absolute
predictability of success . . . . For obviousness under § 103, all that is
required is a reasonable expectation of success.”In re O’Farrell, 853 F.2d
894, 903-04 (Fed. Cir. 1988).
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Moreover, given the cited references‟ teachings regarding the
suitability of the claimed agents for treating cancer, Appellants‟ arguments
(see App. Br. 11-12) do not persuade us that the Examiner misapportioned
the burden of establishing a prima facie case of obviousness by pointing out,
in response to arguments urging a lack of a reasonable expectation of
success, that Appellants had not supported their arguments with clear or
specific prior art evidence, in either of the references or elsewhere in the
record.
In that regard, we note Appellants‟ argument that, although Cabebe
teaches that sunitinib may be used in combination therapies, “the
combination therapies disclosed by the reference generally fall within the
class of chemotherapeutics, which, as pointed out in the specification, would
be expected to have a detrimental effect on the immune system” (Reply Br.
8 (citing Specification 4:9-13)); see also App. Br. 12 (activities of sunitinib
and MUC-1 peptide vaccine urged as being “potentially antagonistic”)).
We acknowledge the portion of Specification cited by Appellants:
Virtually all chemotherapeutics, including kinase inhibitors
cause depression of the immune system when used in
therapeutical doses, often by paralysing the bone marrow and
leading to a decrease of white blood cells, red blood cells and
platelets. Depending on their target, some monoclonal
antibodies used in cancer therapy also have a detrimental effect
on the immune system.

(Spec. 4.) We further acknowledge that the actual sunitinib combination
therapy trials described in Cabebe primarily involved sunitinib combined
with other chemotherapeutics (see Cabebe 394).
However, as noted above, Cabebe also provided a more general
teaching of combining sunitinib with other therapies, chemotherapeutics
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being merely one example of a potential complementary therapy (see id. 395
(“Combinations of sunitinib with other therapies such as chemotherapy and
targeted small molecules may further augment efficacy.”) (Emphasis
added.)). Moreover, the Specification also discloses that a number of
chemotherapeutic agents, including paclitaxel and cyclophosphamide, had
been used alongside cancer vaccines (Spec. 3-4 (section entitled
“Conventional chemotherapeutics in combination with active
immunotherapy”)).
Thus, while chemotherapeutic agents, as a general class of drug,
might have been viewed as having the potential for interfering with vaccine-
based cancer treatments, we are not persuaded that the state of the art at the
time of Appellants‟ invention was such that an ordinary artisan lacked a
reasonable expectation of success whenever combining any
chemotherapeutic agent with a vaccine-based therapy. Moreover,
Appellants have not advanced any clear or specific evidence suggesting that
the selective antiangiogenic properties of sunitinib, in particular, would have
led an ordinary artisan to expect sunitinib to antagonize the cancer vaccine
treatments suggested in the Brossart references.
Therefore, we are not persuaded that Appellants have advanced an
adequate evidentiary basis for refuting the Examiner‟s finding that, in light
of the references‟ teachings, an ordinary artisan would have had a reasonable
expectation that combining sunitinib with a cancer vaccine, such as
Brossart‟s peptide, would result in a cancer-treating composition suitable for
administration to a patient suffering from a kidney or breast cancer that
expressed the MUC-1 antigen, as encompassed by claim 1. Appellants‟
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arguments, therefore, do not persuade us that the Examiner failed to make
out a prima facie case of obviousness as to claim 1.
We are also not persuaded that the evidence advanced by Appellants
is sufficient to outweigh the evidence of prima facie obviousness.
As Appellants argue (App. Br. 12), the Specification discloses that
sunitinib reduces the number of CD4+/CD25+ regulatory T-cells (Tregs) in
the total store of CD4+ T-cells in a mouse model (see Spec. 44:18-30 and
Fig. 8)). As Appellants also argue, the Specification discloses that clinical
patients exhibiting a greater number of immune responses to the claimed
peptide cancer vaccines, including the elected species of peptide (see id. at
45), also exhibited lower numbers of regulatory T-cells (see id. at 46
(“[T]here was a clear tendency that Treg frequencies correlate inversely with
the number of responses against different peptides among patients. Patients
with 2-3 peptide immune responses have significantly lower Treg levels than
patients with 0-1 peptide responses . . . .”)).
Although Appellants argue that the evidence provided in the
Specification shows that sunitinib “could enhance the immunological
outcome of the vaccine” (App. Br. 12 (emphasis added); see also Reply Br.
10), Appellants have not directed us to any evidence of record describing the
result of co-administering sunitinib and a peptide having the amino acid
sequence of SEQ ID NO: 9.
Thus, Appellants have not presented any data actually demonstrating
that sunitinib substantially potentiates, that is, substantially improves, the
effect of a vaccine containing the elected species of peptide recited in claim
1, as Appellants posit. Compare In re Soni, 54 F.3d 746, 751 (Fed. Cir.
1995) (“Mere improvement in properties does not always suffice to show
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unexpected results . . . . [W]hen an applicant demonstrates substantially
improved results . . . and states that the results were unexpected, this should
suffice to establish unexpected results in the absence of evidence to the
contrary.”).
Moreover, because Appellants have not compared the results of co-
administering sunitinib and a peptide having SEQ ID NO: 9 to the results
obtained by administering those agents by themselves, we are not persuaded
that the evidence advanced by Appellants is adequate to show that the
claimed process would have produced the unexpected result Appellants
urge. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991)
(“[W]hen unexpected results are used as evidence of nonobviousness, the
results must be shown to be unexpected compared with the closest prior
art.”).
Appellants argue that, as shown in the Specification, “sunitinib
unexpectedly reduces the number of Treg cells, which correlates with an
increase in the number of peptide specific responses” (Reply Br. 10). While
we again note the Specification‟s disclosure that sunitinib, when
administered by itself, reduces the relative number of Tregs in a mouse
model (see Spec. 44), sunitinib had already been administered to cancer
patients in the prior art, as evidenced by Cabebe.
Thus, it may not have been recognized in the art that administering
sunitinib would reduce the relative number of Tregs in cancer patients. We
are not persuaded, however, that that latent effect, by itself, is an unexpected
result sufficient to overcome the Examiner‟s prima facie case of
obviousness, in the absence of the actual comparative data discussed above.
See Baxter Travenol Labs., 952 F.2d at 392 (“Mere recognition of latent
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properties in the prior art does not render nonobvious an otherwise known
invention.”).
In sum, as discussed above, Appellants‟ arguments do not persuade us
that the Examiner failed to make out a prima facie case of obviousness as to
claim 1. As we are not persuaded that the evidence of unexpected results
advanced by Appellants is sufficient to outweigh the evidence of prima facie
obviousness, we affirm the Examiner‟s obviousness rejection of claim 1 over
the Brossart references and Cabebe.
As they were not argued separately, claims 2, 4, 6, 7, 10, 15, and 16
fall with claim 1. See 37 C.F.R. § 41.37(c)(1)(vii).
The Examiner also rejected claims 8, 9, and 11-14, all of which
depend from claim 1, as obvious over Brossart „712, Brossart I, Brossart II,
Cabebe, and Capizzi (Ans. 10-14).
Specifically, the Examiner found that the combined Brossart
references and Cabebe failed to teach or suggest the administration modes
and sequences recited in the dependent claims, and cited Capizzi as evidence
that an ordinary artisan would have considered it obvious to administer the
claimed agents in the manner recited in those claims (see id. at 11-14). As
Appellants do not present any clear or specific arguments alleging error in
the Examiner‟s prima facie case or factual basis underlying the ultimate
conclusion of obviousness as to these claims, we affirm this rejection as
well.
SUMMARY
We reverse the Examiner‟s rejection of claims 1, 2, 4, and 6-14, under
35 U.S.C. § 112, first paragraph, as containing new matter.
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We affirm the Examiner‟s obviousness rejection of claims 1, 2, 4, 6,
7, 10, 15, and 16 over Brossart „712, Brossart I, Brossart II, and Cabebe.
We also affirm the Examiner‟s obviousness rejection of claims 8, 9,
and 11-14 over Brossart „712, Brossart I, Brossart II, Cabebe, and Capizzi.

TIME PERIOD
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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