Mallen Huang

Patent Trials and Appeals Board

Feb 3, 2020

10551804 - (D) (P.T.A.B. Feb. 3, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
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
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
10/551,804 08/03/2006 Mallen Huang 4017174-214504 6727
23570 7590 02/03/2020
PORTER WRIGHT MORRIS & ARTHUR, LLP
INTELLECTUAL PROPERTY GROUP
41 SOUTH HIGH STREET
29TH FLOOR
COLUMBUS, OH 43215
EXAMINER
GAMBEL, PHILLIP
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
02/03/2020 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):
ipdocket@porterwright.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MALLEN HUANG
__________

Appeal 2019-000281
Application 10/551,804
Technology Center 1600
__________

Before FRANCISCO C. PRATS, JEFFREY N. FREDMAN, and
TAWEN CHANG, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to a
therapeutic composition. The Examiner rejected the claims as obvious. We
have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as the inventor,
Dr. Mallen Huang (see Appeal Br. 1).
2 We have considered and refer to the Specification of Sept. 30, 2005
(“Spec.”); Final Action of Non-Final Office Action of Sept. 26, 2017 (“Non-
Final Act.”); Appeal Brief of Apr. 23, 2018 (“Appeal Br.”); Examiner’s
Answer of Aug. 7, 2018 (“Ans.”); and Reply Brief of Oct. 9, 2018 (“Reply
Br.”).
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Statement of the Case
Background
“Vaccination approaches utilizing nucleotide sequences, including
DNA or RNA sequences, have been developed during the last decade. DNA
vaccines are easy to construct, stable and cost effective to produce” (Spec.
1:9–11). “[O]nce injected into a subject, the nucleotide sequence or
nucleotide-sequence-comprising vector will be taken up by the subject’s
cells and expressed” (Spec. 16: 21–23). Then, “professional APCs [antigen
presenting cells] either directly acquire antigen or take up antigens released
from other transfected cells” (Spec. 16:25–27). “These APCs display
peptide fragments of protein antigens, in association with MHC molecules,
on its surface, and activates antigen-specific T cells” (Spec. 10:15–17).
The Claims
Claims 75, 76, 79–89, and 91–97 are on appeal. Claim 75 is
representative and reads as follows:
75. A therapeutic composition, comprising a combined
mixture of:
a nucleic acid having a nucleotide sequence encoding a
tumor associated antigen, wherein said nucleic acid is provided
in a vector and under transcriptional control of a promoter, said
vector comprises an unmethylated cytidine phosphate
guanosine (CpG) sequence, and said vector is selected from at
least one of virus vector, non-viral vector, plasmid, microbe-
derived vector, liposome and small molecule carrier; and
professional antigen-presenting cells in the form of
plasmacytoid dendritic cells expressing Toll-like receptor 9 and
modified for stable expression of at least one of CD40 ligand
and GM-CSF encoded by a nucleotide sequence engineered
into said antigen-presenting cells.

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The issues
The Examiner rejected claims 75, 76, 79–89, and 91–97 under 35
U.S.C. § 103(a) as obvious over Crystal,3 Hwu,4 Krieg ’067,5 Schetter,6
Schultze,7 Krug,8 Hornung,9 Krieg ’680,10 Fonteneau,11 Pullarkat,12 and
Brenner13 (Ans. 3–6).
The Examiner rejected claims 75, 76, 79–89, and 91–97 under 35
U.S.C. § 103(a) as obvious over Crystal, Hwu, Krieg ’067, Schetter,
Schultze, Krug, Hornung, Krieg ’680, Fonteneau, Pullarkat, Brenner, Ni,14

3 Crystal et al., US 2003/0202963 A1, published Oct. 30, 2003.
4 Hwu et al., US 2004/0146492 A1, published July 29, 2004.
5 Krieg et al., US 2004/0186067 A1, published Sept. 23, 2004.
6 Schetter et al., US 2003/0181406 A1, published Sept. 25, 2003.
7 Schultze et al., US 7,385,023 B1, issued June 10, 2008.
8 Krug et al., Toll-like receptor expression reveals CpG DNA as a unique
microbial stimulus for plasmacytoid dendritic cells which synergizes with
CD40 ligand to induce high amounts of IL-12, 31 Eur. J. Immunology 3026–
37 (2001).
9 Hornung et al., Quantitative Expression of Toll-Like Receptor 1-10 mRNA
in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and
Sensitivity to CpG Oligodeoxynucleotides, 168 J. Immunology 4531–7
(2002).
10 Krieg, US 2004/0198680 A1, published Oct. 7, 2004.
11 Fonteneau et al., Activation of influenza virus specific CD4+ and CDS+ T
cells: a new role for plasmacytoid dendritic cells in adaptive immunity,
Blood 1–48 (2003).
12 Pullarkat et al., Lymphoid Dendritic Cells Mobilized with Pregeniporitin
Inducer Th1 and Peptide-Specific Cytotoxic T Cell Response, Blood 297a,
Abstract 1254 (2001), text unreadable.
13 Brenner et al, Transfusion Medicine: New Clinical Applications of
Cellular Immunotherapy, Hematology 356–75 (2000).
14 Ni et al., Detection of bcr/abl fusion transcripts by semiquantitative
multiplex RT-PCR combined with a colormetric assay in Ph positive
leukemia, 124 Cancer Letters 173–80 (1998).
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and Tanaka15 (Ans. 6–7).
Because both of these rejections rely upon the same combination of
references and Ni and Tanaka are solely added to address SEQ ID NOs: 3–5
(see Ans. 6), we will consider these rejections together.
The Examiner finds Crystal teaches “the applicability of antigen
presenting cells, including dendritic cells . . . to treat cancer” by
“transducing dendritic cells with dendritic cell-mediators, including CD40L
and GM–CSF” to allow “CD40L to self-activate tumor antigen to CD8+
CTL” (Ans. 3). The Examiner finds Crystal teaches “in vitro/ ex vivo
manipulation of the dendritic cells” (id.).
The Examiner acknowledges that Crystal does not teach “a nucleotide
compositions comprising a nucleotide sequence encoding a TAA and CpG
in a vector and professional antigen-presenting cells / dendritic cells
modified to express CD40L and/or GM-CSF” (Ans. 3).
The Examiner finds Hwu teaches “making recombinant antigen
presenting dendritic cells . . . including transducing said cells with CD40
ligand GM-CSF . . . to produce highly potent antigen presenting cells that
are capable of activating quiescent T cells and stimulate effective anti-tumor
immune responses, including CD8+ CTL” (Ans. 3).
The Examiner finds Krieg ’067 teaches “immunomodulatory
unmethylated CpG in vaccines” (Ans. 3). The Examiner finds Schetter
teaches “the use of CpG nucleic acids in cancer vaccines, including
professional antigen presenting cells/ dendritic cells” (id. 4).

15 Tanaka et al., Generation of HLA-DRB1*1501-restricted p190 minor bcr-
abl (ela2)-specific CD4 + T lymphocytes, 109 Br. J. Haematology 435–7
(2000).
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The Examiner finds Kung teaches “that TLR9 is critically involved in
recognition by CpG motifs, that plasmacytoid dendritic cells express TLR9,
that the CD40 pathway in addition to CpG played an important role in
signaling pathways and immune responses” (Ans. 4). The Examiner
similarly finds Hornung teaches “TLR9 is critical for recognition of CpG
motifs” (id.). The Examiner also finds Krieg ’680 teaches “the applicability
of CpG to induce high levels of immune stimulation . . . including dendritic
cells and the role of GM-CSF . . . to enhance immune responses, including
cancer therapies and vaccines . . . which immune activation / stimulation
relies upon TLR9” (id.).
The Examiner finds Fonteneau teaches the role of plasmacytoid
dendritic cells in adaptive immunity and Pullarkat teaches “that human
lymphoid dendritic cells activated with CD40L and influenza virus induced
strong p-100 melanoma peptide-specific autologous CTL responses” (Ans.
4). The Examiner finds Brenner teaches “plasmacytoid dendritic cells and
their use immune adjuvants in dendritic cell vaccines to elicit antitumor and
antiviral immunity” (id. 5).
The Examiner finds the ordinary artisan would have been motivated
to provide nucleotide compositions comprising a nucleotide
sequence encoding a TAA and CpG in a vector and professional
antigen-presenting cells / dendritic cells, including TLR9
expressing plasmacytoid dendritic cells, modified to express
CD40L and/or GM-CSF in composition form, consistent with
the teachings of the prior art of combining such elements to
achieve potent immunization against cancer/ tumor antigens,
given the teachings . . . to enhance immune response to
antigens, including cancer/ tumor antigens of interest.
(Ans. 5).
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The issue with respect to this rejection is: Does the evidence of
record support the Examiner’s finding that the prior art render the claims
obvious?
Findings of Fact
1. Crystal teaches “a method of treating cancer in a mammal. This
method comprises administering a dendritic cell-mediator to the mammal in
combination with dendritic cells” (Crystal ¶ 71).
2. Crystal teaches that “[p]referably, the DC [dendritic cell] is
modified in the context of the present inventive methods by contacting the
DC with a nucleic acid molecule comprising a nucleic acid sequence
encoding a dendritic cell-mediator” (Crystal ¶ 83).
3. Crystal teaches “[e]xamples of DC-mediators include . . .
granulocyte-macrophage colony stimulating factor (GM-CSF) (Crystal
¶ 79).
4. Crystal teaches a “preferred dendritic cell-mediator that
increases DC maturation is CD40 ligand (CD40L)” (Crystal ¶ 79).
5. Crystal teaches “[a]dministration to a mammal of a . . .
modified dendritic cell that expresses a DC-mediator, alone or in further
combination with an antigen” (Crystal ¶ 126).
6. Crystal teaches that “where the mammal has a cancer, the
antigen is a cancer antigen” (Crystal ¶ 107).
7. Hwu teaches “new methods of making recombinant antigen
presenting dendritic cells (DCs)”; that “recombinant cells expressing
antigenic peptides were found to be competent to activate T-cells against
target cells expressing selected antigens in vivo”; and that “[t]his provides
powerful new treatments for cancers” (Hwu ¶ 7).
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8. Hwu teaches “cytokine genes, such as GM-CSF can be
introduced into dendritic cells, to potentially enhance their survival,
immunogenicity or therapeutic effect. . . . Stimulatory ligands, such as
CD40L, can be introduced in dendritic cells, to enhance their survival,
immunogenicity or therapeutic effects” (Hwu ¶ 50).
Hwu also teaches tumor associated antigens, where “[e]xamples of
MHC class I bound antigens include prostate specific antigen (PSA . . .
Melanoma antigens (e.g. MAGE-1, MART-1 and gp 100), Colon cancer
antigens (e.g., CEA), breast cancer antigens (e.g. HER-2)” (Hwu ¶ 54).
9. Hwu teaches “[d]endritic cells have been effective against
established tumors. Dendritic cells have several advantages over other
forms of anti-tumor immunization . . . dendritic cell immunizations can be
used in combination with other methods of immunization” (Hwu ¶ 48).
10. Krieg ’067 teaches that “DNA vaccine vectors can be improved
. . . by the addition of CpG-S motifs” (Krieg ’067 ¶ 28).
11. Krieg ’067 teaches “an effective amount of a nucleic acid
construct containing at least one unmethylated CpG for treating a disorder
could be that amount necessary to induce an immune response of sufficient
magnitude to eliminate a tumor, cancer, or bacterial, parasitic, viral or fungal
infection” (Krieg ’067 ¶ 62).
12. Schetter teaches “a dendritic cell vaccine which includes whole
dendritic cells which have been exposed to a cancer antigen or a cancer-
associated antigen in vitro” and explains that the “use of CpG-like nucleic
acids in conjunction with cancer vaccines provides an improved antigen-
specific humoral and cell-mediated immune response” (Schetter ¶¶ 276–
277).
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13. Hornung teaches “plasmacytoid dendritic cell (PDC) has been
identified as a primary target cell for CpG ODN” (Hornung 4531, col. 1).
14. Hornung teaches that “TLR9 is essential for recognition of
CpG ODN in mice and confers responsiveness to CpG ODN in human cell
lines” (Hornung 4536, col. 1).
15. Krug teaches “TLR9, which is critically involved in the
recognition of CpG motifs in mice, was present in PDC [plasmacytoid
dendritic cells] but not in MDC [myeloid dendritic cells]. . . CpG ODN acts
as an enhancer of T cell help, while T cell-controlled restriction to foreign
antigens is maintained” (Krug, abstract).
16. Brenner teaches “there is great promise in the application of
DCs [dendritic cells] as immune adjuvants for treating cancer” (Brenner 365,
col. 2). Brenner further explains that “the BCR/ABL CML-specific gene
products would serve as the ideal target antigen for adoptive
immunotherapy” (Brenner 366, col. 2).
Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including: (1) the scope and content of the prior art;
(2) the level of ordinary skill in the art; (3) the differences between the
claimed invention and the prior art; and (4) secondary considerations of
nonobviousness, if any. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
Graham Factors
Level of Ordinary Skill in the Art
We note that the asserted prior art of record reflects a level of ordinary
skill in the art that represents Ph.D. and/or M.D. scientists with several years
of experience (see, e.g., Hornung 4531, ft. 1 “This work is part of the
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dissertation of V.H.” and ft. 3 “Dr. Gunther Hartmann”; Brenner 356
“Malcolm Brenner M.D., Ph.D”). See Okajima v. Bourdeau, 261 F.3d 1350,
1355 (Fed. Cir. 2001); In re GPAC Inc., 57 F.3d 1573, 1579 (Fed. Cir.
1995); In re Oelrich, 579 F.2d 86, 91 (CCPA 1978).
Scope and Content of the Prior Art16
Crystal teaches therapeutic cancer vaccine compositions that include
two components: antigens (FF 5) and modified dendritic cells that express a
dendritic cell mediator (FF 4–5) where the mediator may include GM-CSF
(FF 2) and/or CD40 ligand (FF 3). Hwu teaches that reasons to incorporate
tumor associated antigens as well as GM-CSF and CD40 ligand into
dendritic cells for cancer vaccines include enhanced “survival,
immunogenicity or therapeutic effects” (FF 8).
Crystal and Hwu do not teach CpG as the antigen in the cancer
vaccine. Also, neither Crystal nor Hwu suggest which of the two types of
dendritic cells should be used in the vaccine, plasmacytoid or myeloid.
Schetter teaches the “use of CpG-like nucleic acids in conjunction
with cancer vaccines provides an improved antigen-specific humoral and
cell-mediated immune response” (FF 12). Krieg ’067 teaches an amount of
“unmethylated CpG for treating a disorder could be that amount necessary to
induce an immune response of sufficient magnitude to eliminate a tumor”
(FF 11).
Hornung teaches “plasmacytoid dendritic cell (PDC) has been
identified as a primary target cell for CpG” and that “TLR9 is essential for

16 We note the Board may rely on less than all of the references applied by
the Examiner in an obviousness rationale without designating it as a new
ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
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recognition of CpG ODN in mice and confers responsiveness to CpG ODN
in human cell lines” (FF 13–14). Krug confirms that “TLR9, which is
critically involved in the recognition of CpG motifs in mice, was present in
PDC [plasmacytoid dendritic cells] but not in MDC [myeloid dendritic
cells]” (FF 15).
Differences from Claimed Invention and the Prior Art
We recognize that Crystal does not anticipate the instant claims and
that the cancer vaccine of Crystal differs from the cancer vaccine of the
claimed invention by failing to specifically identify CpG as the antigen and
plasmacytoid cells as the dendritic cells.
However, we agree with the Examiner that the ordinary artisan would
have had reason to make a cancer vaccine that combined a CpG antigen of
Schetter and Krieg ’067 with the GM-CSF and/or CD40 ligand modified
dendritic cells of Crystal and Hwu because: a) Crystal teaches that dendritic
cell cancer vaccines may include antigens (FF 5); b) Schetter teaches that
CpG used with cancer vaccines results in improved immune response (FF
12); and c) Krieg ’067 teaches that CpG in appropriate doses helps mount an
immune response sufficient to eliminate tumors and cancer (FF 11) (see
Ans. 5).
We also agree with the Examiner that the ordinary artisan would have
had reason to select plasmacytoid cells rather than myeloid cells for a cancer
vaccine that combined CpG antigen and dendritic cells because Hornung
teaches that plasmacytoid cells are the target of CpG and Krug teaches that
the TLR9 component of plasmacytoid cells is critical for recognition of CpG
and this TLR9 component is not found in myeloid dendritic cells (FF 13–
15). Thus, the ordinary artisan, interested in a cancer vaccine that combined
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dendritic cells and CpG, necessarily needed to select a type of dendritic cell
that would interact with CpG. Krug evidences that only the plasmacytoid
dendritic cells expressing TLR interact with CpG (FF 15), thus suggesting
their use in vaccines that include CpG.
Secondary Considerations
Figure 15 of the Specification is reproduced below:

Figure 15 shows that tumor-bearing mice treated repeatedly with pVAXela2
and DC/CD40L develop efficient anti-tumor immunity sufficient to protect
mice against rechallenge of tumor cells and approximately 80 % mice were
protected and remained tumor free” (Spec. 36:32 to 37:3).
Appellant contends “neither the vector-contained nucleic acid
component alone nor the antigen-presenting cells component alone provided
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the efficient anti-tumor immunity of the claimed composition . . . Thus, the
claimed combination provides a significant therapeutic improvement in
cancer treatment over the individual components” (Appeal Br. 11).
Appellant’s position is supported by Dr. Morein,17 who states “this vaccine
formulation is surprisingly generating protective and therapeutic anti-tumor
effects” (Morein Decl. ¶ 7). Dr. Morein further notes the “potent immune
response evoked by the use of the combined vaccine composition is not
proposed by the cited references and the vaccine of this invention cannot
simply done by one skilled in the art without information from the present
invention or being the inventor” (id.).
Analysis
Claim 75
We agree with the Examiner that the evidence of record, when
considered as a whole, renders claim 75 obvious. We address Appellant’s
arguments below.
Appellant points to the data in the Specification and contends “these
comparisons further demonstrate the surprising improvements of the claimed
compositions and methods of the present invention” (Appeal Br. 12).
Appellant contends “the improvement obtained by the present composition,
comprising both the vector-contained nucleic acid component and the
plasmacytoid dendritic cells modified for expression of CD40 ligand, is
indeed surprising and anything but predictable from the results obtained by
use of each component alone” (id. 13).

17 Declaration of Dr. Bror Morein, dated Mar. 24, 2017.
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As to claim 75, we find this argument unpersuasive, because the data
in figures 15 and 17 of the Specification is solely drawn to cells with CD40
ligand and solely to the use of the e1a2 tumor associated antigen, and does
not demonstrate any result for cells with GM-CSF or with any other tumor
antigens.18 Thus, the results are not commensurate with the scope of claim
75 which requires only “at least one of CD40 Ligand and GM-CSF” and “a
tumor associated antigen” and does not necessarily require CD40 Ligand or
the specific e1a2 tumor antigen tested. Unexpected results must be
“commensurate in scope with the degree of protection sought by the claimed
subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005).
Appellant contends
the rejection fails to provide any apparent reasoning that would
motivate one of ordinary skill in the art to select and combine
all the teachings of the various cited references along the lines
of the composition of claim 75 and the method of claim 86, as
opposed, for example, along the lines of the comparative
compositions (d)-(g) noted above with respect to Fig. 17.
(Appeal Br. 12; cf. Appeal Br. 13).
We find this argument unpersuasive because, as discussed above, we
agree with the Examiner that the ordinary artisan would have had reason to
incorporate GM-CSF and CD-40 ligand into the cancer vaccine of Crystal

18 We note the Specification lists a variety of antigens, teaching: “Non-
limiting examples of tumor-specific or tumor-associated antigens, the coding
sequence of which may be used in the vaccine composition of the invention,
include KS 1/4 pan-carcinoma antigen, ovarian carcinoma antigen (CA125),
prostatic acid phosphate, prostate specific antigen, melanoma-associated
antigen p97, melanoma antigen gp75, high molecular weight melanoma
antigen, the MAGE family of antigens, T cell receptor γ chain alternate
reading frame protein (TARP) antigen, prostate specific membrane antigen
and ela2 fusion protein antigen and bcr/abl fusion protein” (Spec. 20:12–20).
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because Hwu teaches these result in enhanced “survival, immunogenicity or
therapeutic effects” (FF 8). Further, Crystal teaches the use of an antigen
(FF 5) and Schetter and Krieg teach CpG is an antigen that improves cancer
vaccines (FF 10–11).
Appellant specifically contends that “none of these references would
have given one of ordinary skill in the art any apparent reason to employ
dendritic cells expressing TLR9 in Crystal, or any reasonable expectation of
success in doing so” (Appeal Br. 14). Appellant further contends:
neither Krug nor Hornung provides any teaching of
plasmacytoid dendritic cells modified for stable expression of
CD40 ligand or GM-CSF as required by claims 75 and 86.
Neither of these references provide one of ordinary skill in the
art with any reason to employ plasmacytoid dendritic cells
expressing TLR9 in the method of Crystal, and therefore one of
ordinary skill in the art could not have had any reasonable
expectation from these references of success by using
plasmacytoid dendritic cells expressing TLR9, modified to
express CD40 ligand or GM-CSF, in the method of Crystal.
(Appeal Br. 15).
We are not persuaded because we agree with the Examiner that the
ordinary artisan, taught by Crystal to use dendritic cells (FF 1), would have
selected plasmacytoid dendritic cells rather than myeloid dendritic cells,
from the two known types of dendritic cells, because Hornung teaches that
plasmacytoid cells are the target of CpG and Krug teaches that the TLR9
component of plasmacytoid cells is critical for recognition of CpG and this
TLR9 component is not found in myeloid dendritic cells (FF 13–15).
Hornung and Krug provide evidence that one would expect greater success
with plasmacytoid cells that express TLR9 rather than myeloid dendritic
cells because CpG would be expected to function as an “enhancer of T cell
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help” in the plasmacytoid dendritic cells (FF 15). “Obviousness does not
require absolute predictability of success . . . all that is required is a
reasonable expectation of success.” In re Kubin, 561 F.3d 1351, 1360 (Fed.
Cir. 2009).
Appellant then separately argues that Hwu and Schultze do not teach
the claimed invention (see Appeal Br. 16); that Schetter does not teach the
use of plasmacytoid dendritic cells (id.); and that Fonteneau, Pullarkat, and
Brenner also don’t provide reasons to select plasmacytoid dendritic cells (id.
17–18).
While we do not rely on Fonteneau, Pullarkat, and Brenner, we find
these arguments unpersuasive generally because “the test for obviousness is
not whether the features of a secondary reference may be bodily
incorporated into the structure of the primary reference . . . Rather, 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). For the reasons already given above, we agree with the Examiner
that the ordinary artisan would have had reason to use plasmacytoid cells
that inherently express TLR9 in the cancer vaccine of Crystal with CpG as
the antigen (FF 1–15).
Appellant relies on the Morein Declaration, asserting that “Dr. Morein
notes that he does not find any information from Crystal, Hwu, Kreig, or
Hornung for using plasmacytoid dendritic cells to efficiently treat a tumor
and to induce tumor-specific immune response” (Appeal Br. 19–20).
Specifically, Dr. Morein states:
As one skilled in the art, I do not find any information in the
studies from the following publications; Crystal et al, US
2003/0202963 Al, Hwu et al, US 2004/0146492 Al, Kreig et al,
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US 2004/0186067 Al, Hornung et al, J lmmunol., 168:4531-
4537 (2002) (Hornung), that can be related to and relevantly
oppose to the present vaccine formulation of using the
plasmacytoid dendritic cells to efficiently be used for treating
tumor and to inducing tumor-specific immune responses.
(Morein Decl. ¶ 4).
We find Dr. Morein’s conclusory statement unpersuasive because Dr.
Morein does not persuasively explain why the combination of teachings of
Hornung and Krug do not suggest using plasmacytoid dendritic cells when
following Krieg and Schetter’s guidance to use the CpG antigen in cancer
vaccines (FF 10–12). When CpG is the antigen of interest, Krug teaches
“TLR9, which is critically involved in the recognition of CpG motifs in
mice, was present in PDC [plasmacytoid dendritic cells] but not in MDC
[myeloid dendritic cells]” (FF 15). This is a direct teaching that CpG will
only function with plasmacytoid cells and not myeloid cells, reasonably
suggesting to the ordinary artisan, interested in the enhanced immune
response provided by CpG, to select plasmacytoid dendritic cells rather than
myeloid dendritic cells. Hornung reinforces that point in teaching
“plasmacytoid dendritic cell (PDC) has been identified as a primary target
cell for CpG ODN” (FF 13).
We find the absence of reasoning significantly weakens the persuasive
power of Dr. Morein’s position. “[T]he PTAB is permitted to weigh expert
testimony and other record evidence and, in so doing, rely on certain
portions of an expert’s declaration while disregarding others.” Icon Health
and Fitness, Inc. v. Strava, Inc., 849 F.3d 1034, 1041 (Fed. Cir. 2017). See
In re American Academy of Science Tech Center, 367 F.3d 1359, 1370 (Fed.
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Cir. 2004) (“[T]he Board is entitled to give such weight to declarations as it
deems appropriate.”)
Claim 92
Appellant separately contends that “one of ordinary skill in the art
would not have had any reasonable expectation of the significant therapeutic
improvement in cancer tumor treatment provided by the composition of
claim 92” (Appeal Br. 24).
We find this argument unpersuasive for the same reasons as given
above. While the Specification does provide data of superior results for a
composition comprising the specific CD40 ligand and e1a2 antigen (see
Spec. Fig. 15) and claim 92 is limited to CD40 ligand, claim 92 is not
limited to the e1a2 peptide that was tested. The evidence of record does not
demonstrate that the result for the particular e1a2 tumor associated antigen
would necessarily occur using other tumor associated antigens, such as those
disclosed by Hwu for use in a dendritic cell cancer vaccine (FF 8) and
therefore the results in Figure 15 of the Specification are not commensurate
in scope with claim 92. Harris, 409 F.3d at 1344.
Claim 95
Appellant contends
the Official Action does not indicate where in any of the
references plasmacytoid dendritic cells expressing TLR9,
CD8α+ and B220+ are modified for stable expression of CD40
ligand encoded by a nucleotide sequence engineered into the
cells, particularly with any suggestion to combine and incubate
such modified cells with a nucleic acid provided in a plasma
vector as required by claim 95.
(Appeal Br. 25).
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We find this argument persuasive based on the recitation of TLR9,
CD8α+ and B220+ in claim 95. While Krug reasonably evidences that
plasmacytoid cells inherently comprise TLR9 (FF 13), the Examiner has not
provided a persuasive reason to include the CD8α+ and B220+ in the
plasmacytoid dendritic cells nor has the Examiner established that these
antigens are inherently naturally expressed by plasmacytoid dendritic cells.
To the extent that Fonteneau teaches that the immune response to influenza
involves CD8α+ and B220+ antigens, we are not persuaded that this is
relevant. We therefore agree with Appellants that Examiner has provided no
persuasive reason to generate the modified dendritic cell required by the
cancer vaccine of claim 95.
Claims 76 and 87
Appellant contends
the Official Action does not indicate where in any of the
references one of ordinary skill in the art would find a reason to
incubate plasmacytoid dendritic cells modified for stable
expression of CD40 ligand encoded by a nucleotide sequence
engineered into the cells with a nucleic acid provided in a
plasma vector as required by claims 76 and 87.
(Appeal Br. 26).
We find this argument unpersuasive because we agree with the
Examiner that “pre-incubated combined mixture of said nucleic acids and
said modified antigen-presenting cells would have been a necessary or
obvious step in combining the nucleic acids and antigen presenting cells”
(Ans. 23). We also note that Crystal teaching of administration of “a
modified dendritic cell that expresses a DC-mediator . . . in further
combination with an antigen” (FF 5) reasonably suggests that the
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components are mixed together prior to administration.
Claim 82
Appellant contends that “the experimental showings in the
specification are specifically representative of the composition of claim 82
wherein the plasmacytoid dendritic cells are modified for stable expression
of CD40 ligand” (Appeal Br. 26).
We find this argument unpersuasive for the reasons already given. In
particular, while claim 82 recites CD40 ligand, claim 82 is inclusive of any
antigen, not just the e1a2 antigen tested in figures 15 and 17. Therefore,
claim 82 is not commensurate in scope of the argued results. Harris, 409
F.3d at 1344.
Claims 83–85, 91, 93
Appellant contends
neither Ni nor Tanaka teach or suggest a therapeutic
composition including a nucleic acid as required by any of
claims 83-85, 91 and 93 in combination with plasmacytoid
dendritic cells modified to express CD40 ligand or GM-CSF or
the significant therapeutic effect obtained by such a
combination. That the e1a peptide or bcr-abl fusion protein
antigen are known does not resolve the deficiencies of the
remaining references in failing to lead one of ordinary skill in
the art to the claimed combinations with a reasonable
expectation of the significant therapeutic improvement provide
by the claimed compositions as demonstrated in the present
specification.
(Appeal Br. 33).
We begin by noting that SEQ ID NO: 5 is “referred to as ela2
peptide” (Spec. 26:28) and that claim 83 is limited to SEQ ID NO: 5, but
depends from claim 75 and therefore is not limited to the CD40 ligand.
Claims 84 and 85, drawn to other e1a2 fusion proteins (see Spec 31:32),
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similarly depend from claim 75 and are not limited to the CD40 ligand.
Claim 91 is more broadly drawn to any bcr-abl fusion protein, depends from
claim 75, and therefore is not limited to either the CD40 ligand or the e1a2
tumor associated antigen tested. While claim 93 depends from claim 92, and
therefore is limited to the CD40 ligand, claim 93 broadly encompasses either
a bcr-abl fusion protein or the specific tested e1a2 fusion peptide. Claim 93
is therefore not limited to the specific tumor associated antigen demonstrated
in the results. Therefore, claims 83–85, 91, and 93 are not commensurate in
scope of the argued results. Harris, 409 F.3d at 1344.
Claims 94 and 97
Having found claim 95 unobvious for the reasons given above, we
also find dependent claim 97 unobvious for the same reasons.
As to claim 94, Appellant contends “the evidence of record simply
fails to teach that the art recognizes that any combination of known elements
in a mixture achieves such potent immunization against cancer/tumor
antigen as demonstrated in the present application” (Appeal Br. 35).
We find this argument unpersuasive for the reasons already given. In
particular, while claim 94 recites an improved tumor killing result by the
combination of the CpG and modified plasmacytoid dendritic cell, claim 94
is inclusive of any antigen, not just the e1a2 antigen tested in figures 15 and
17. Therefore, claim 82 is not commensurate in scope of the argued results.
Harris, 409 F.3d at 1344. In addition, Krieg provides evidence that
vaccines, and cancer vaccines in particular, are improved by including CpG
(FF 10). Indeed, Schetter specifically states that the “use of CpG-like
nucleic acids in conjunction with cancer vaccines provides an improved
antigen-specific humoral and cell-mediated immune response” (FF 12).
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This supports the conclusion that the result of claim 94 is an expected, not
unexpected result.
Claim 96
Having found claim 95 unobvious for the reasons given above, we
also find dependent claim 96 unobvious for the same reasons.
Conclusion of Law
Except as otherwise noted above regarding claims 95–97, the
evidence of record supports the Examiner’s finding that the prior art renders
the claims obvious.

DECISION
In summary:

Claims
Rejected
35 U.S.C. § Basis Affirmed Reversed
75, 76, 79–
89, 91–97
103(a) Crystal, Hwu, Krieg
’067, Schetter,
Schultze, Krug,
Hornung, Krieg ’680,
Fonteneau, Pullarkat,
Brenner
75, 76, 79–
89, 91–94
95–97
75, 76, 79–
89, 91–97
103(a) Crystal, Hwu, Krieg
’067, Schetter,
Schultze, Krug,
Hornung, Krieg ’680,
Fonteneau, Pullarkat,
Brenner, Ni, Tanaka
75, 76, 79–
89, 91–94
95–97
Overall
Outcome
75, 76, 79–
89, 91–94
95–97

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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-IN-PART