Ex Parte Cannon et al

Patent Trial and Appeal Board

Jun 29, 2018

14040850 (P.T.A.B. Jun. 29, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/040,850 09/30/2013
66981 7590
HUGH MCTA VISH
MCT A VISH PA TENT FIRM
7460 Pinehurst Road
Pine Springs, MN 55115
06/29/2018
FIRST NAMED INVENTOR
Martin J. Cannon
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.
ll0.029US2 7558
EXAMINER
TIJEDES, AMYE
ART UNIT PAPER NUMBER
1644
MAILDATE DELIVERY MODE
06/29/2018 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARTIN J. CANNON, KELLIE KOZAK VAIDYA, and
TIMOTHY J. O'BRIEN 1
Appeal2017-008551
Application 14/040,8502
Technology Center 1600
Before RICHARD M. LEBOVITZ, FRANCISCO C. PRATS, and
ULRIKE W. JENKS, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to dendritic cells cultured in the
presence of GM-CSP, IL-4, IL-15, and a p38 MAP kinase inhibitor. The
Examiner rejected the claims as anticipated under 35 U.S.C. § 102 and as
obvious under 35 U.S.C. § 103. Appellants appeal the rejections pursuant to
35 U.S.C. § 134. We have jurisdiction under 35 U.S.C. § 6(b). The
rejections are reversed.
1 The Appeal Brief(" Appeal Br.") 3 lists the Board of Trustees of the
University of Arkansas as the real-party-in-interest.
2 The application's written description is referred to as the "Specification."
Appeal2017-008551
Application 14/040,850
STATEMENT OF THE CASE
Claims 1, 4, 5, 7, 8, 13, 24, and 25 stand rejected by the Examiner as
follows:
1. Claims 1, 8, 13, 24, and 25 as anticipated under pre-AIA 35 U.S.C.
§ 102(b) by Banerjee et al., Expansion of FOXPJhigh regulatory T cells by
human dendritic cells (DCs) in vitro and after injection of cytokine-matured
DCs in myelomapatients, 108 Blood 2655-2661 (2006) ("Banerjee") as
evidenced by Ackerman et al., Regulation of MHC Class I Transport in
Human Dendritic Cells and the Dendritic-Like Cell Line KG-i, 170 J
Immunol. 4178--4188 (2003) ("Ackerman"), Iwamoto et al., TNF-a Drives
Human CDi 4+ Monocytes to Differentiate into CD70+ Dendritic Cells
Evoking Thi and Thi 7 Responses, 179 J Immunol. 1449-1457 (2007)
("Iwamoto"), and Langenkamp et al., Kinetics and Expression patterns of
chemokine receptors in human CD4+ T lymphocytes primed by myeloid or
plasmacytoid dendritic cells, 33 Eur. J Immunol. 474--482 (2003)
("Langenkamp"). Examiner's Answer ("Ans.") 2.
2. Claims 1, 5, 7, 8, 13, 24, and 25 as obvious under pre-AIA
35 U.S.C. § 103(a) in view of Banerjee and Bondurant et al., Definition of an
Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum
Chymotryptic Enzyme, 11 Clin. Cancer Res. 3446-3454 (2005)
("Bondurant") as evidenced by Iwamoto and Langenkamp. Ans. 3.
3. Claims 1, 4, 7, 8, 24, and 25 as obvious under pre-AIA 35 U.S.C.
§ 103(a) in view of Banerjee, Bowdish et al., U.S. Publ. Pat. Appl.
2007 /0054378 Al (published Mar. 8, 2007) ("Bowdish '378"), and Lim et
al., Cutting Edge: Direct Suppression of B Cells by CD4 +cD25+ Regulatory
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Appeal2017-008551
Application 14/040,850
T Cells, 175 J Imnmnol. 4178--4188 (2005) ("Lim") as evidenced by
Iwamoto and Langenkamp. Ans. 4.
Claim 1, the only independent claim, on appeal, is reproduced below:
1. A therapeutic composition comprising:
(1) antigen-specific T cells prepared by culturing
adherent peripheral blood mononuclear cell (PBMC) dendritic
cell precursors ex vivo in the presence of GM-CSP, IL-4, IL-15
and a p38 MAP kinase inhibitor in amounts and for a time
effective to differentiate said precursors into dendritic cells that
function to reduce Treg activity and PoxP3 expression and
increase TNP-alpha expression and CCR4 expression in T cells,
and further by stimulating T cells ex vivo with said dendritic
cells that have been loaded with an antigen; or
(2) dendritic cells prepared by culturing adherent PBMC
dendritic cell precursors ex vivo in the presence of GM-CSP,
IL-4, IL-15 and a p3 8 MAP kinase inhibitor in amounts and for
a time effective to differentiate said precursors into dendritic
cells that function to reduce Treg activity and Poxp3 expression
and increase TNP-alpha expression and CCR4 expression in T
cells contacted with the dendritic cells, and loading the
dendritic cells with an antigen ex vivo.
CLAIM INTERPRET A TI ON
The elected invention is drawn to dendritic cells. Response to
Restriction (Sept. 25, 2015). Dendritic precursor cells are cultured in the
presence of 1) GM-CSP, 2) IL-4, 3) IL-15, and 4) a p38 MAP kinase
inhibitor "in amounts and for a time effective to differentiate said precursors
into dendritic cells that function to reduce Treg activity ... in T cells
contacted with the dendritic cells." The Examiner interpreted the reduction
in Treg activity to be a property of the total population of T cells. Ans. 6.
Appellant, on the other hand, argues that the Treg activity is reduced in an
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Application 14/040,850
individual T cell, and not only in the total cell population when measured as
a whole. Appeal Br. 6.
During patent examination proceedings, claim terms are given "the
broadest reasonable meaning ... 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). In this case, the Specification
teaches that an embodiment of the "invention is based on the discovery that
interleukin-15 (IL-15) antagonizes or down-regulates the activity of
regulatory T cells (Treg cells)." Spec 3:3--4. Thus, consistent with the claim
language that the Treg activity is reduced "in T cells," the Specification
refers to down-regulating the activity of a Treg cell, indicating it is the
property of a cell which is being regulated, rather than a population of cells
as asserted by the Examiner.
Despite the express language in the claims, the Examiner's reason for
interpreting the claim as relating to a population of cells is based on Figure 3
of the Specification, that the Examiner states shows "assessing the ability of
the total T cell population resulting after culture with IL-15 treated DC, or
with IL-15, to inhibit T cell proliferation." Ans. 6. Figure 3 of the
Specification is described as follows:
Preferably, where it is stated that dendritic cells or T cells
are [cultured] in IL-15 or a combination of IL-15 and a MAP
kinase inhibitor at concentrations and for a time effective to
reduce Treg activity of antigen-specific T cells, the antigen-
specific T cells inhibit alloreactive CD4+ T cell proliferation, as
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Application 14/040,850
assayed in the experiments whose data are shown in FIG.3
herein, by less than 70%, more preferably by less than 60%.
Spec. 10: 22-26.
Thus, although the Examiner states Figure 3 shows Treg activity in a
total cell population, the Specification characterizes the Treg activity "of the
antigen-specific T cells" and directly states later in the Specification that the
data "reflects Treg activity of the antigen-specific T cells." Id. at 11: 1.
Moreover, the Specification distinguishes between Treg activity in a
cell and in cell population: "The use of IL-15 is shown here to reduce Treg
activity. Treg cells can also be selectively depleted." Spec. 13: 1-2. In other
words, the Treg activity in an individual cell can be reduced, or Treg activity
can be reduced in a cell population by depleting cells with Treg activity.
The claims expressly refer to reducing Treg activity "in T cells," a reference
to the former activity rather than the latter in altering the activity of a cell
population.
The Specification defines the reduction of Treg activity as compared
to T cells cultured conventionally:
Inhibition of Treg activity is inhibition as compared to T cells
cultured conventionally (i.e., without IL-15) with stimulation of
dendritic cells cultured conventionally (i.e., without IL-15 and
without a MAP kinase inhibitor).
Spec. 8:23-25.
In sum, we interpret the recitation in claim 1 that the dendritic cells
"reduce Treg activity ... in T cells contacted with the dendritic cells" to
require a reduction in the Treg activity of a T cell.
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Application 14/040,850
REJECTION
The claims are directed to a therapeutic composition comprising (1)
antigen-specific T cells or (2) dendritic cells. Dendritic cells are elected.
The dendritic cells are claimed as product of a process of culturing
precursor dendritic cells "in the presence of [1)] GM-CSP, [2)] IL-4, [3)] IL-
15, and [4)] a p38 MAP kinase inhibitor in amounts and for a time effective
to differentiate said precursors into dendritic cells that function to reduce
Treg activity ... in T cells contacted with the dendritic cells." Thus, the (2)
precursor dendritic cells when cultured with the recited factors differentiate
into dendritic cells that, inter alia, reduce Treg activity in T cells.
The Examiner rejected the claims as anticipated by Banerjee. Ans. 2.
The Examiner acknowledged that Banerjee "produced said dendritic cells by
a process different than that of the instant claims (i.e. contacting with LPS,
GM-CSP, and IL-4, instead of GM-CSP, IL-4, IL-15 and a p38 Map kinase
inhibitor [as claimed])," but found that "the instant claims are directed to a
product, and the patentability of a product does not depend on its method of
production in the absence of a difference in the claimed product." Id. The
Examiner explained how the requirements in claim 1 of reduced PoxP3
expression increased TNP-alpha and CCR4 expression in T cells contacted
with Banerjee's dendritic cells were met by Banerjee, citing Iwamoto and
Langenkamp as evidence that the limitations are met. Id. at 3.
With respect to the Treg activity, the Examiner found that Banerjee
"teach that when T cells are contacted with LPS matured dendritic cells,
there is less induction and expansion of Tregs compared to cytokine matured
dendritic cells." Ans. 5, 6.
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DISCUSSION
Claim 1 is a product-by-process claim because the product - dendritic
cells - is claimed as a product of a process of culturing precursor dendritic
cells with four specifically recited factors. A product-by-process limitation
defines a product in terms of how it is made. SmithKline Beecham Corp. v.
Apotex Corp., 439 F.3d 1312, 1315 (Fed. Cir. 2006). "[E]ven though
product-by-process claims are limited by and defined by the process,
determination of patentability is based on the product itself." In re Thorpe,
777 F.2d 695, 697 (Fed. Cir. 1985). Consequently, when comparing the
claimed dendritic cells to the prior art, we must determine whether the
recited process steps impart a characteristic to the cells that distinguish them
from cells made by other processes.
The PTO has the initial burden of providing a rationale to show that
the dendritic cells produced by Banerjee' s process would produce the same
dendritic cells that are claimed. While that burden was initially met by the
Examiner's findings with regard to the properties of the dendritic cells in
Banerjee (Ans. 2-3), Appellants provided evidence that Banerjee's dendritic
cells, upon culturing in LPS, GM-CSP, and IL-4, do not have the same
ability to reduce Treg activity in T cells as the claimed cells cultured in the
presence of GM-CSP, IL-4, IL-15 and a p38 MAP kinase inhibitor.
Specifically, Appellants identified the following statement in Banerjee that
its dendritic cells, after culture, do not decrease Treg activity in T cells as
compared to dendritic cells cultured conventionally (Appeal Br. 6):
Although Cyt-DCs [dendritic cells induced by inflammatory
cytokines] induced larger numbers of Treg' s than DCs matured
in other ways (eg, blockade of the inhibitory Fe receptor with
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Application 14/040,850
2B6 mAb ), the suppressive properties of the elicited Treg' s
were comparable (Figure 6C).
Banerjee 2658-59.
Thus, dendritic cells cultured under the conditions described in
Banerjee did not reduce Treg activity in T cells, but had "comparable"
activity to cells cultured under other conditions. Id. The Examiner did not
deny or disagree with Appellants' contention that Treg activity was not
reduced in individual T cells, but rather interpreted the claim to include "a
reduction in Treg activity in the T cell population that is cultured with the
dendritic cells," i.e., "a decrease in the number of Treg cells" in the T cell
population. Ans. 6. However, as discussed above, the Examiner's
interpretation is not the broadest reasonable interpretation of the claim based
on the plain meaning of the words "reduce Treg activity ... in T cells" and
how they would be understood in the context of the Specification. Because
the claims require that the Treg activity is reduced in individual T cells, and
Banerjee's T cells do not have this property (Banerjee 2658-59), the
anticipation rejection of claim 1 and dependent claims 8, 13, 24, and 25 is
reversed.
The obviousness rejection of claims 1, 5, 7, 8, 13, 24, and 25 based on
Banerjee, Bondurant, Iwamoto, and Langenkamp is also reversed because
Bondurant was not found by the Examiner to provide further suggestion of
reducing Treg activity in T cells, and thus does not meet the deficiency
found in Banerjee. Ans. 4.
The obviousness rejection of claims 1, 4, 7, 8, 13, 24, and 25 based on
Banerjee, Bowdish '378, Lim, Iwamoto, and Langenkamp is also reversed
because, while the Examiner further cited Bowdish '378 as teaching
administration of IL-15 as an adjuvant, the Examiner did not provide a
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Application 14/040,850
reason for culturing precursor dendritic cells in the presence of IL-15 as
required by the rejected claims. Ans. 4--5.
In reversing the rejections, we note that the Examiner originally made
a restriction requirement in which Appellants elected a therapeutic
composition comprising dendritic cells (Group III). Response to Restriction
(Sept. 25, 2015). The rejections address dendritic cells, but not T cells
which are also recited claim 1, but which were restricted from the claim by
the Examiner and not elected by Appellants. Restriction Requirement
(Groups I and II) (June 2, 2015).
REVERSED
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