Ex Parte Chang et al

Patent Trial and Appeal Board

Jun 18, 2018

15378972 (P.T.A.B. Jun. 18, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
15/378,972 12/14/2016 Chien-Hsing Chang
63322 7590 06/20/2018
IMMUNOMEDICS, INC.
300 AMERICAN ROAD
MORRIS PLAINS, NJ 07950
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.
IMM328US3 2894
EXAMINER
TIJEDES, AMYE
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
06/20/2018 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):
tbrener@immunomedics.com
rnakashima@immunomedics.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHIEN-HSING CHANG and DAVID M. GOLDENBERG
Appeal2018-006236 1
Application 15/378,972
Technology Center 1600
Before FRANCISCO C. PRATS, MICHAEL J. FITZPATRICK, and
DAVID COTTA, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a method of
depleting human antigen-presenting cells (APCs) and dendritic cells (DCs ).
The Examiner rejected the claims for anticipation and obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We affirm.
STATEMENT OF THE CASE
The following rejections are before us for review:
(1) Claims 1, 2, 4, and 13-15, under 35 U.S.C. § 102(b) as anticipated
by or, in the alternative, under 35 U.S.C. § 103(a) as obvious over
1 The Real Party in Interest is Immunomedics, Inc. Br. 1.
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Application 15/378,972
Goldenberg,2 as evidenced by, or in view of Marland3 (Final Act. 2-3; Ans.
3--4); and
(2) Claims 1, 2, 4, 5, 8, 9, and 13-15, under 35 U.S.C. § I03(a) as
obvious over Goldenberg, Marland, and Sun4 (Final Act. 6; Ans. 4--5).
Claim 1, the only independent claim on appeal, is representative and
reads as follows:
1. A method of depleting human antigen-presenting cells
(APCs) and dendritic cells (DCs) comprising:
a) exposing the human antigen-presenting cells and
dendritic cells to an anti-HLA-DR IgG4 antibody
or antigen-binding fragment thereof in the
presence of human peripheral blood mononuclear
cells (PBMCs), wherein the anti-HLA-DR
antibody or fragment thereof competes for binding
to HLA-DR with, or binds to the same epitope of
HLA-DR as, a murine L243 antibody comprising
the heavy chain CDR sequences CDRI (NYGMN,
SEQ ID NO: 7), CDR2
(WINTYTREPTY ADDFKG, SEQ ID NO: 8), and
CDR3 (DITA VVPTGFDY, SEQ ID NO: 9) and
the light chain CDR sequences CDRI
(RASENIYSNLA, SEQ ID NO: 10), CDR2
(AASNLAD, SEQ ID NO: 11 ), and CDR3
(QHFWTTPWA, SEQ ID NO: 12); and
b) depleting all subsets of APCs, including mDC 1
(myeloid dendritic cell type 1 ), mDC2 (myeloid
2 US 2006/0210475 Al (published Sept. 21, 2006).
3 Gill Marland et al., Dendritic Cells in Immune Response Induction, 14
Stem Cells 501-507 (1996).
4 Kai Sun et al., Inhibition of acute graft-versus-host disease with retention
of graft-versus-tumor effects by the proteasome inhibitor bortezomib, 101
PNAS 8120-8125 (2004).
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Application 15/378,972
Br. 11.
dendritic cell type 2), pDCs (plasmacytoid
dendritic cells), B cells and monocytes, without
killing T cells.
DISCUSSION
The Examiner's Prima Facie Case
In rejecting claim 1 as anticipated by Goldenberg, the Examiner found
that Goldenberg describes a process in which an antibody identical to that
recited in claim 1 is administered to humans "for treating autoimmune
diseases, lymphomas, and immune dysregulatory diseases involving HLA-
DR expression (see page 29, in particular)." Final Act. 3. The Examiner
noted that Goldenberg also "teaches that the method can be performed for
treating organ transplant rejection or GVHD (see page 21 and 38, in
particular)." Id.
Based on these teachings, the Examiner reasoned that Goldenberg's
"method would inherently function to deplete HLA-DR expressing APCs,
including mDC 1, mDC2, pDCs, B cells, and monocytes by at [sic], without
killing T cells, since it is identical to the method of the instant claims, and
employs a structurally identical antibody as to the present claims." Id.
Analysis
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.
In the present case, having carefully considered all of the arguments
and evidence advanced by Appellants and the Examiner, we are persuaded
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that the preponderance of the evidence supports the Examiner's
determination that Goldenberg anticipates the process recited in Appellants'
claim 1.
Claim 1 recites a process of depleting human antigen-presenting cells
(APCs) and dendritic cells (DCs). Br. 11. Claim 1 requires exposing the
human antigen-presenting cells and dendritic cells to an anti- HLA-DR IgG4
antibody, or antigen-binding fragment thereof, in the presence of human
peripheral blood mononuclear cells (PBMCs). Id. Claim 1 requires the
antibody to bind to, or compete for binding with, the same epitope of HLA-
DR that binds to a murine L243 antibody having specific heavy and light
chain CDR sequences recited in the claim. Id.
Claim 1 also requires depleting all subsets of APCs, including mDC 1
(myeloid dendritic cell type 1 ), mDC2 (myeloid dendritic cell type 2), pDCs
(plasmacytoid dendritic cells), B cells, and monocytes, without killing T
cells. Id.
As the Examiner contends (Ans. 5---6 (citing Spec. ,r,r 23-25)),
Appellants' Specification discloses that human AP Cs and DCs can be
exposed to the therapeutic antibody in the presence of PBMCs as recited in
Appellants' claim 1, and all subsets of APCs can be depleted without killing
T cells, as also recited in claim 1, by administering the antibody to a patient
in vivo to treat an autoimmune disease, organ-graft rejection, or graft-versus-
host disease. See Spec. ,r 23 (disclosing "a method for treating and/or
diagnosing a disease or disorder that includes administering to a patient a
therapeutic and/or diagnostic composition that includes any of the
aforementioned antibodies or fragments thereof'); see id. ("In preferred
embodiments, the disease or disorder is an immune dysregulation disease, an
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autoimmune disease, organ-graft rejection or graft-versus-host disease."); id.
,r 24 (listing exemplary treatable autoimmune diseases); id. ,r 25 ("In
particularly preferred embodiments, administration of the ... anti-HLADR
antibodies or fragments thereof can deplete all subsets of APCs, but not T
cells, from human peripheral blood mononuclear cells (PBMCs ), including
myeloid DCs (mDCs), plasmacytoid DCs (pDCs), B cells, and
monocytes. ").
Appellants do not dispute that the process of claim 1 encompasses in
vivo administration of the claimed antibody to a patient suffering from an
autoimmune disease, organ-graft rejection, or graft-versus-host disease. To
the contrary, when explaining where the Specification supports claim 1 's
step of exposing APCs to the antibody in the presence of PMBCs,
Appellants cite ,r 24 of the Specification, which, as noted above, expounds
on the autoimmune disorders that are treatable by administering (i.e., in
vivo) the therapeutic antibody. See Br. 3. Moreover, when explaining where
the Specification supports claim 1 's step of depleting all subsets of APCs
without killing T cells, Appellants again cite ,r 24 of the Specification. See
id. at 4.
Given the disclosures in ,r,r 23-25 of the Specification, as well as
Appellants' reliance on ,r 24 as support for the exposing step recited in claim
1, we discern no error in the Examiner's determination that claim 1 's
exposing step encompasses in vivo administration of the claimed antibody to
a human patient suffering from an autoimmune disease, organ-graft
rejection, or graft-versus-host disease. Given the disclosures in ,r,r 23-25 of
the Specification, as well as Appellants' reliance on ,r 24 as support for the
APC depletion recited in claim 1, we also discern no error in the Examiner's
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determination that in vivo administration of the claimed antibody to a human
patient suffering from an autoimmune disease, organ-graft rejection, or
graft-versus-host disease, inherently results in the depletion of all subsets of
APCs without killing T cells, as required by claim 1.
We also discern no error in the Examiner's determination that
Goldenberg describes in vivo administration of the claimed antibody to a
human patient suffering from an autoimmune disease, organ-graft rejection,
or graft-versus-host disease.
Goldenberg describes the production of antibodies that bind to the
epitope recited in Appellants' claim 1. See Goldenberg, abstract
("Humanized antibodies are provided that specifically bind HLA-DR. The
antibodies recognize the epitope recognized by the murine monoclonal
antibody L243.").
Goldenberg describes a study in which one of its antibodies, "hL243-
IgG4," which undisputedly has the structure and properties required by
claim 1, was injected into mice that had received a previous injection of
lymphoma cells ("Raji cells"). Id. ,r 251.
Based on the results of that study, Goldenberg discloses administering
its antibody to humans with autoimmune diseases, among other disorders:
This study showed the concurrent retention of antitumor
efficacy and removal of complement binding activity of the
IgG4 construct of L243. Although, this study was performed in
mice, significant therapeutic benefits using the aforementioned
constructs may be achieved in all mammals suffering from
autoimmune diseases, lymphomas, or leukemias. In particular,
the aforementioned constructs can effectively be used in ...
humans, for the treatment of autoimmune diseases,
lymphomas, and leukemias, as well as immune dysregulatory,
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metabolic, and neurodegenerative diseases involving HLA-DR
express10n.
Id. ,r 252 ( emphasis added); see also id. ,r 195 ( describing "the use of the
antibodies ... for treatment of any of the following diseases or disorders,
where the disease or disorder is selected from the group consisting of an
immune dysregulation disease, an autoimmune disease, organ graft rejection,
graft versus host disease ... ").
Thus, on the current record, as the Examiner found, Goldenberg
describes administering an antibody undisputedly identical to that recited as
being within claim 1, to a human patient suffering from an autoimmune
disease, organ-graft rejection, or graft-versus-host disease. As noted above,
Appellants' Specification discloses that administering the claimed antibody
to that patient not only achieves the exposing step of claim 1, but also results
in depleting all subsets of APCs without killing T cells, as claim 1 requires.
Accordingly, Appellants do not persuade us (Br. 5-9) that the Examiner
lacked a sufficient evidentiary basis for determining that Goldenberg
describes a process having all of the steps and features of Appellants' claim
1, including the APC depletion.
It might be true, as Appellants contend (Br. 6-8), that certain passages
in Goldenberg identified by the Examiner in relation to cell killing do not
expressly disclose that administering Goldenberg's antibodies to human
patients results in depletion of all subsets of APCs without killing T cells. It
might also be true, as Appellants further contend (id. at 8), that Goldenberg's
examples all relate to the effects of the disclosed antibodies on lymphoma
cells.
Appellants' arguments, however, ignore the disclosures in
Goldenberg, identified by the Examiner, of administering its antibody,
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which is undisputedly identical to that recited in Appellants' claim 1, to a
patient suffering from an autoimmune disease, organ-graft rejection, or
graft-versus-host disease. Goldenberg ,r,r 195, 252. As discussed above,
that process is acknowledged by Appellants' own Specification as resulting
not only in exposure of the antibody to the patient's PMBCs, but also
depletion of all subsets of APCs without killing T cells, as claim 1 requires.
See Spec. ,r,r 23-25. Indeed, in contending that Goldenberg does not
describe the process recited in their claim 1, Appellants fail to address the
Examiner's rationale (Final Act. 3 ( citing Goldenberg at pp. 21 and 29);
Ans. 4--7) based on those disclosures in Goldenberg.
It might be true, as Appellants contend, that Goldenberg does not
expressly disclose that administering its antibody to a patient suffering from
an autoimmune disease, organ-graft rejection, or graft-versus-host disease,
results in the APC depletion required by Appellants' claim 1. That fact,
however, does not demonstrate error in the Examiner's finding of
anticipation. See Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246
F.3d 1368, 1376 (Fed. Cir. 2001) ("Newly discovered results of known
processes directed to the same purpose are not patentable because such
results are inherent.").
We acknowledge Goldenberg' s disclosure, identified by Appellants
(Br. 9), that when the effect of Goldenberg's humanized IgG4 anti-HLA-DR
antibody ( encompassed by Appellants' claim 1) was compared to its murine
counterpart in experiments in cultured cells, the humanized IgG4 antibody
did not "induce[] significant lysis of effector cells." Goldenberg ,r 247.
To the extent Appellants contend that ,r 247 of Goldenberg teaches
away from the process recited in claim 1, however, it is axiomatic that "the
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question whether a reference 'teaches away' from the invention is
inapplicable to an anticipation analysis." Celeritas Techs. Ltd. v. Rockwell
Int'! Corp., 150 F.3d 1354, 1361 (Fed. Cir. 1998) (citation omitted).
Appellants fail to explain, moreover, how the results of the
experiment described at ,r 24 7 of Goldenberg, involving cultured cells,
demonstrates that administering Goldenberg's antibody to a human patient
suffering from an autoimmune disease, organ-graft rejection, or graft-versus-
host disease, would not result in depletion of all subsets of APCs without
killing T cells, as disclosed in Appellants' Specification. In addition, as the
Examiner found, Goldenberg expressly discloses that its IgG4 antibody
encompassed by claim 1 induces apoptosis, i.e., cell killing. See Goldenberg
,r,r 272-276.
In sum, as discussed above, Appellants' Specification makes it clear
that claim 1 's exposing step and APC depletion may be performed by
administering the antibody recited in the claim to a human patient suffering
from an autoimmune disease, organ-graft rejection, or graft-versus-host
disease. See Spec. ,r,r 23-25; see also id. ,r 3 (similar disclosure). As also
discussed above, Goldenberg describes administering an antibody
undisputedly identical to that recited in claim 1, to a human patient suffering
from an autoimmune disease, organ-graft rejection, or graft-versus-host
disease. Goldenberg ,r,r 195, 252.
Because the preponderance of the evidence, therefore, supports the
Examiner's finding that Goldenberg describes a process having all of the
steps and features required by claim 1, we affirm the Examiner's rejection of
claim 1 as anticipated by Goldenberg. Because they were not separately
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argued, claims 2, 4, and 13-15 fall with claim 1. 37 C.F.R.
§ 4I.37(c)(l)(iv).
Because we affirm the Examiner's anticipation rejection of claims 1,
2, 4, and 13-15 over Goldenberg, we do not reach the Examiner's alternative
obviousness rejection of those claims over Goldenberg as evidenced by, or
in view of Marland.
The Examiner also entered a rejection of claims 1, 2, 4, 5, 8, 9, and
13-15, under 35 U.S.C. § 103(a) for obvious over Goldenberg, Marland, and
Sun. Final Act. 6; Ans. 4--5. The Examiner's rejection, essentially, was that
it would have been obvious in view of Sun to include bortezomib, as recited
in Appellants' dependent claims 8 and 9, in Goldenberg's treatment of graft-
versus-host disease. See Final Act. 6.
Appellants argue only that Marland and Sun fail to remedy the
deficiencies of Goldenberg discussed above in relation to claim 1. Br. 9-10.
As discussed above, however, Appellants do not persuade us that
Goldenberg fails to anticipate claim 1. Accordingly, we also affirm the
Examiner's obviousness rejection of claim 1 based Goldenberg. See In re
McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002) ("It is well settled that
'anticipation is the epitome of obviousness."') ( quoting Connell v. Sears,
Roebuck & Co., 722 F.2d 1542, 1548 (Fed. Cir. 1983)).
Because they were not argued separately, claims 2, 4, 5, 8, 9, and 13-
15 fall with claim 1. 37 C.F.R. § 4I.37(c)(l)(iv).
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SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 1, 2, 4, and 13-15, under 35 U.S.C. § 102(b) as anticipated by
Goldenberg.
For the reasons discussed, we do not reach the Examiner's alternative
rejection of claims 1, 2, 4, and 13-15, under 35 U.S.C. § 103(a) for
obviousness over Goldenberg, as evidenced by, or in view of Marland.
For the reasons discussed, we affirm the Examiner's rejection of
claims 1, 2, 4, 5, 8, 9, and 13-15, under 35 U.S.C. § 103(a) for obviousness
over Goldenberg, Marland, and Sun.
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)(l )(iv).
AFFIRMED
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