Ex Parte Zang

Patent Trial and Appeal Board

Oct 13, 2016

12630228 (P.T.A.B. Oct. 13, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/630,228 12/03/2009
28381 7590 10/17/2016
Arnold & Porter LLP
601 Massachusetts Ave., NW
Washington, DC 20001-3743
FIRST NAMED INVENTOR
Ying C. Q. Zang
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
5203/US/3 9361
EXAMINER
EWOLDT, GERALD R
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
10/17/2016 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):
IP _Docketing@aporter.com
IP. Docketing@aporter.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte YING C.Q. ZANG1
Appeal2014-000982
Application 12/630,228
Technology Center 1600
Before DONALD E. ADAMS, CHRISTOPHER G. P AULRAJ, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
autologous T cell vaccine comprising an enriched CD8+ T cell population
reactive to at least two different fragments of MS associated antigens, which
have been rejected as obvious and as failing to comply with the written
description requirement. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
"Multiple sclerosis (MS) is a demyelinating and chronic inflammatory
disease of the central nervous system (CNS)." (Spec. i-f 3.) "[H]allmarks of
1 Appellant identifies the Real Party in Interest as Opexa Therapeutics Inc.
(Appeal Br. 1.)
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the disease include focal infiltration of both Cn4 + and ens+ T cells together
with other inflammatory cells in the white matter and demyelination with
evidence of some axonal damage." (Id.)
Experimental autoimmune encephalomyelitis (EAE) is "a classic
animal model for MS." (Spec. i-f 3.) Appellant's Specification indicates that
the prior art has shown that in EAE, cn4+ T cells recognizing myelin basic
protein ("MBP") "have been found to induce ... extensive inflammation and
mild demyelination." (Id.) The Specification further indicates that the prior
art has shown that "severe EAE" can be induced by ens+ T cells
recognizing short peptides of MBP, which cells cause "extensive
demyelination, closely resembling MS pathology in humans." (Id.)
Claims S, 10, 11, 13, 15, and 17-202 are on appeal. Claims S, 10, 11,
and 17-19 are representative and read as follows:
S. An autologous T cell vaccine made by a method comprising:
(a) enriching a population of peripheral blood
mononuclear cells comprising T cells from a patient to be
treated with the vaccine for ens+ T cells; and
(b) adding a plurality of at least two different fragments
of multiple sclerosis (MS) associated antigens selected from the
group consisting of a fragment from myelin basic protein, a
fragment from proteolipid protein, and a fragment from myelin
oligodendrocyte glycoprotein, and optionally antigen presenting
cells.
10. An autologous T cell vaccine comprising an enriched
population of ens+ T cells reactive to a plurality of at least two
different fragments of MS associated antigens selected from the
group consisting of a fragment from myelin basic protein, a
2 Claims 1-7 and 9 are also pending, but stand withdrawn from further
consideration. (Appeal Br. 3.)
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fragment proteolipid protein, and a fragment from myelin
oliogdendrocyte glycoprotein.
11. The vaccine of claim 10, wherein the population comprises
about 64% to about 80% CD8+ T cells.
17. The autologous T cell vaccine of claim 15, wherein said at
least one fragment from MBP comprises a sequence selected
from the group consisting of SEQ ID NO:l, SEQ ID N0:2, SEQ
ID N0:3, SEQ ID N0:4, amino acids 83-99 of MBP, and
amino acids 151-170 of _MBP.
18. The autologous T cell vaccine of claim 8, wherein step (b)
further comprises adding IL-2.
19. The autologous T cell vaccine of claim 8, wherein step (b)
further comprises adding a mitogen.
(Appeal Br. 17-18.)
The following grounds of rejection by the Examiner are before us on
review:
Claims 8. 10. 11. 13. 15. and 17-20 under 35 U.S.C. S 103(a) as beirn.?:
/ / / / / v '/ '-'
unpatentable over Zang3 and Jurewicz. 4
Claims 8, 10, 11, 13, 15, and 17-20 under 35 U.S.C. § 112, first
paragraph, as failing to comply with the written description requirement.
3 Zang, US Patent 7,658,926 B2, filed Sept. 14, 2001, issued Feb. 9, 2010.
4 Jurewicz et al., MHC Class I-Restricted Lysis of Human Oligodendrocytes
by Myelin Basic Protein Peptide-Specific CD8 T Lymphocytes, 160 J.
Immunol. 3056-59 (1998).
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Obviousness
DISCUSSION
Claim S is representative of the claims rejected for obviousness. The
Examiner finds that Zang teaches "an autologous T cell vaccine for the
treatment of MS [ that] comprises T cells specific for one or more MBP,
PLP, or MOG antigen fragments, including MBP S3-99 and MBP 151-170."
(Final Action 3; Ans.3.) The Examiner further finds that Zang teaches "[t]he
vaccine is produced employing said fragments and stimulation with IL-2,
and additionally, phytohemagglutinin, Con A, or pokeweed mitogen." (Id.)
The Examiner notes that Zang does not teach the vaccine recited in
claim S is "enriched for CDS+ T cells." (Id.) The Examiner finds that it
would have been obvious to modify Zang, though, to "further enrich[] the
vaccine for CDS+ T cells given the teachings of Jurewicz." (Final Action 3;
Ans. 4.) In particular, the Examiner finds that Jurewicz "teaches that some
CDS+ T cells are effector cells in MS contributing to tissue injury" and that
others are "protective of disease given that the reference teaches that the
elimination of all CD s+ T cells exacerbates disease." (Final Action 3; Ans.
3--4.) The Examiner finds that Jurewicz teaches "the claimed CDS+ T cell
vaccine wherein the MS associated antigen fragment is SEQ ID N0:2[, and
that] IL-2, which can be considered to be a mitogen, is employed in the
method of preparing the vaccine." (Id.) The Examiner finds that one of
ordinary skill in the art would have been motivated to modify the vaccine of
Zang with an enriched CDS+ T cell population "because it would have been
more specific for the effector cells causing MS than would have been a
vaccine that targeted all T cells." (Id.) The Examiner also finds that "the
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ordinarily skilled artisan would have been motivated to target only the
pathogenic ens+ T cells given the additional teachings of Jurewicz et al.
that some ens+ T cells are protective of disease." (Id.)
We agree with the Examiner's factual findings and conclusion that the
claimed vaccine compositions would have been obvious.
Appellant argues that in light of "unpredictability in the art" and the
fact that the prior art, including the cited references, taught "away from
ens+ T cells as primary effector cells during multiple sclerosis
pathogenesis," one of ordinary skill in the art "would simply not have made
the composition as presently claimed" (Appeal Br. 7-10; Reply Br. 1--4).
Regarding the "teaching away" argument, Appellant notes that Zang
"mentions ens+ T cells only as playing an important role in the anti-
idiotypic response elicited by an autologous T cell vaccine, not as playing an
important role in the pathogenesis of multiple sclerosis." (Appeal Br. S.)
Appellant further notes that Jurewicz "specifically cites studies" indicating
that "ens+ depletion in vivo results in increased frequency of
encephalomyelitis relapse" or suggesting that "ens+ T cells play a role in
resistance against a second induction of encephalomyelitis" and thus teaches
"away from a T cell vaccine enriched for ens+ T cells and/or that may result
in ens+ T cell depletion in vivo when administered." (Appeal Br. S.)
Appellant also cites Friese5 as "evidence[] that skilled artisans were still
debating whether ens+ T cells played any pathogenic role at all in the
5 Friese and Fugger, Autoreactive CD8+ T cells in multiple sclerosis: a new
target for therapy, 12S Brain 1747- 63 (2005).
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progression of multiple sclerosis even two years after the instant priority
date." (Appeal Br. 9; Reply Br. 1-2.) Appellant argues
[s]ince the prevailing view focused on pathogenic CD4+ T cells,
and since autoreactive CDS+ T cells were thought to be
regulatory in nature with few effector functions, the art clearly
taught away from using a vaccine enriched for CDS+ T cells, as
the depletion of these cells could result in the removal of their
assumed protective effect and possibly exacerbate disease.
(Appeal Br. 9-10.) Moreover, Appellant argues that "in light of the art, an
ordinarily skilled artisan would not have considered a vaccine enriched for
CDS+ T cells at the expense of CD4+ T cells." (Appeal Br. 10; Reply Br. 4.)
We do not find these arguments persuasive.
As to Appellant's unpredictability point, we note that Appellant does
not point to any evidence, nor do we discern any from the record on appeal,
that making a vaccine having the claimed components is unpredictable.
Moreover, we note that Appellant does not dispute that Jurewicz teaches
making a CDS+ T-cell enriched composition reactive to the MS associated
antigen fragment SEQ ID N0:2, or that IL-2 is employed in the method of
preparing that CDS+ T-cell enriched composition. (Jurewicz 3056.) In light
of the foregoing, Appellant's "unpredictability" argument is not well-
founded.
Regarding Appellant's argument concerning the uncertainty of the
role of CDS+ T cells in the pathogenesis of MS, we note that a prima facie
case of obviousness does not require absolute certainty: a suggestion, along
with a reasonable expectation of success, suffices. In re Kubin, 561 F.3d
1351, 135S---60 (Fed. Cir. 2009). There can be no dispute that regardless of
whether there was or was not a "consensus view" of the role that CDS+ T-
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cells play in the pathogenesis of MS (Reply Br. 1--4; Appeal Br. 9-11), there
were investigations into the role of CDS+ T-cells in MS, and scientific
evidence that CDS+ T-cells were implicated as effectors. (Friese 1754--55
("Contributions of CDS+ T cells in animal models" (noting that early studies
in the EAE model, which "is not an ideal way of inducing CDS+ responses,"
"led to the neglect of CDS+ T cells" and noting that 2001 studies in other
models demonstrated CDS+ T cell involvement in disease that resembled MS
more so than in conventional EAE and resulting in severe demyelination));
Ans 9 (citing Jurewicz abstract, which notes "[t]hese results support the
postulate that autoreactive CDS cytotoxic T cells can contribute to the tissue
injury in MS") see also Ans. 10 (citing Lassman6 and its teaching that
"CDS+ T cells outnumber CD4 + T cells in MS lesions in all stages of their
development' (page 134) and that they can be pathogenic in the Theiler's
murine model of MS).") And as the Examiner noted, not only does Jurewicz
undisputedly teach making a CDS+ T-cell enriched composition reactive to
the MS associated antigen fragment SEQ ID N0:2, (Jurewicz 3056), other
prior art references cited in Friese relied upon by Appellant for an alleged
teaching away from a CDS+ T-cell enriched vaccine form MS, suggest a new
therapeutic approach in MS such as "protection against CTL-mediated
[CDS+ T cells] damage." (Ans. 10 (citing Neumann7 ("' ... protection against
6 Lassman et al., The CD4-Thl model for multiple sclerosis: a
critical [correction of crucial] re-appraisal, 25 Trends Immunol.
132-7 (2004).
7 Neumann et al., Cytotoxic T lymphocytes in autoimmune and degenerative
CNS diseases, 25 Trends Neurosci. 313-19 (2002).
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CTL-mediated [ens+ T cells] damage should be considered as a new
therapeutic approach in MS' (Abstract)").)
Thus, irrespective of whether scientists were still contesting "the role
of ens+ T cells during disease progression" (Reply Br. 1 ), we agree with the
Examiner that Jurewicz would have motivated one of ordinary skill in the art
to modify the Zang vaccine in light of the scientific evidence supporting the
postulate that ens+ cytotoxic T cells contribute to the tissue injury in MS.
"Scientific confirmation of what was already believed to be true may be a
valuable contribution, but it does not give rise to a patentable invention."
PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491F.3d1342, 1363---64
(Fed. Cir. 2007); cf Pfizer, Inc. v. Apotex, Inc., 4SO F.3d 134S, 1364, 1367-
69 (Fed. Cir. 2007) (simply because the formation and properties of a new
compound must be verified through testing does not mean that the
compound satisfies the test for patentability "since the expectation of
success need only be reasonable, not absolute"); In re Merck & Co., SOO
F.2d 1091, 1097 (Fed. Cir. 19S6) ("Obviousness does not require absolute
predictability.")
We disagree that the prior art cited by the Examiner or by Appellant
teach away from the foregoing. "A reference may be said to teach away
when a person of ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or would be led
in a direction divergent from the path that was taken by the applicant." In re
Kubin, 561 F.3d at 1357 (quoting In re Gurley, 27 F.3d 551, 553 (Fed. Cir.
1994)). In light of the evidence in Friese that ens+ T cells contribute to MS
disease, and the references cited therein noted by the Examiner which
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provide scientific evidence that CDS+ T cells contribute to MS disease, we
do not find the art teaches away from modifying the Zang vaccine with an
enriched population of CDS+ T cells reactive to at least the MS associated
antigen fragment SEQ ID N0:2 as taught by Jurewicz.
For the foregoing reasons, Appellant does not persuade us that the
Examiner erred in rejecting claim S for obviousness over Zang and Jurewicz.
Claims 10, 11, 13, 15, and 17-20 have not been argued separately and
therefore fall with claim S. 37 C.F.R. § 41.37(c)(l)(iv).
II
Written Description
According to the Examiner claims S, 10, 11, 13, 15, and 17-20
contain "subject matter which was not described in the specification in such
a way as to reasonably convey to one skilled in the relevant art that the
inventor( s ), at the time the application was filed, had possession of the
claimed invention." (Final Action 5-7.) Regarding claims Sand 10, the
Examiner finds that "[ n ]either the claims, nor the specification recite a
vaccine comprising at least two different fragments of MBP, PLP, or MOG."
(Final Action 7; Ans. 13; Appeal Br. 13-14 (responding to Examiner's
rejection of claims Sand 10.)) Along similar lines, with respect to claim 17,
the Examiner finds that "the specification does not support the limitation of
'at least one' of the peptides recited in the claim" because it includes more
than one MBP peptide fragment from the selected group. (Ans. 5, 11.)
With respect to claims 11 and 15, the Examiner finds that "the
specification does not support the limitation of a vaccine population
comprising about 64% to SO% CDS+ T cells," noting that Figure 1 to which
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Appellant's referred to as providing support, "does not disclose the generic
autologous T cell vaccine of the claims, i.e., the disclosure of a single
species does not provide broad support for claims drawn to a genus" and it
"does not disclose 'about'." (Ans. 5, 11.)
With respect to claims 18-20, the Examiner finds that the original
claims only "support[] a vaccine produced employing a single, whole MS-
associated antigen and not a vaccine produced employing a fragment of an
MS-associated antigen" and that the Specification only supports "a vaccine
produced employing MBP fragments" and not the addition of "IL-2" or "a
mitogen," much less the specific mitogens enumerated in claim 20. (Ans. 5-
6.) According to the Examiner, to the extent the limitations would have
been obvious, that is not adequate written description. (Ans. 12.)
We disagree with the Examiner as to each of the foregoing. As
Appellant urges (Appeal Br. 12-14; Reply Br. 4), the Specification
reasonably conveys to those skilled in the art that Appellant was in
possession of the invention as set forth in claims 8, 10, 11, 13, 15, and 17-20
at the time the application was filed. Ariad Pharms., Inc. v. Eli Lilly &
Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane) (citing Vas-Cath Inc. v.
Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991)). Regarding the recitation
in claims 8 and 10 "of at least two different fragments of multiple sclerosis
(MS) associated antigens" selected from the group consisting of a fragment
from MBP, from PLP and MOG, and claim 17 embracing more than one
fragment, original claim 2' s recitation of MS antigens being selected from
the group of MBP, PLP MOG and "combinations thereof' supports finding
the Appellant's Specification supports a vaccine with at least two different
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fragments of MS associated antigen from the group of antigen fragments
claimed. Paragraph 5 of the Specification notes that "[t]he present invention
is directed to the isolation of ens+ cytotoxic T cells that recognize multiple
sclerosis related antigens," and identifies MBP, PLP, and MOG as the MS
related antigens as the group of antigens that the isolated ens+ T cells
would be able to recognize. (Spec. i-f 5 (emphasis added).) Moreover, the
Specification describes incubating the ens+ T cells with "one or more
peptides" ofMBP-fragments. (Spec. i-f 7.) The "or more" includes "at least
two different."
We agree with Appellant that Figure 1 and the description thereof
(Spec. i-f 34) noting that "[t]he resulting en4-depleted fractions typically
contained 72 ±S% ens+ T cells as determined by flow cytometric analysis"
provides support for the limitation "about 64% to SO%." Flow cytometry is
an automated quantification, and while error rate can be very low, reported
percentages would be understood by one of ordinary skill in the art to
encompass some uncertainty due to error rate around the endpoints of a
range embraced by Figure 1 and the reported 72 ±S%. Further, we disagree
with the Examiner that the "representative experiment" depicted in Figure 1
(Spec. i-f 34) "does not disclose the generic autologous T cell vaccine of the
claims" (Ans. 11 ).
Regarding claims lS-20, as Appellant noted (Appeal Br. 13), original
claims 5-7 recite these very same limitations in a method of making a
vaccine. This, in combination with the Specification paragraphs 5-7
describing making a vaccine with "one or more peptide" fragments of MBP,
PLP, or MOG, including stimulating the ens+ T cells specifically
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responsive to MBP, PLP, or MOG with, for example a mitogen, reasonably
conveys to those skilled in the art that Appellant was in possession of the
invention as set forth in claims 18-20 at the time the application was filed.
Ariad, 598 F.3d at 1351.
For the foregoing reasons, we reversed the Examiner's rejection of
Claims 8, 10, 11, 13, 15, and 17-20 under 35 U.S.C. § 112, first paragraph,
as failing to comply with the written description requirement.
SUMMARY
We affirm the rejection of Claims 8, 10, 11, 13, 15, and 17-20 under
35 U.S.C. § 103(a) as being unpatentable over Zang in view of Jurewicz.
We reverse the rejection of Claims 8, 10, 11, 13, 15, and 17-20 under
35 U.S.C. § 112, first paragraph, as failing to comply with the written
description requirement.
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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