Ex Parte Charneau et al

Board of Patent Appeals and Interferences

Dec 12, 2011

11250616 (B.P.A.I. Dec. 12, 2011)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte PIERRE CHARNEAU and PHILIPPE DESPRES
__________

Appeal 2011-000378
Application 11/250,616
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and
FRANCISCO C. PRATS, Administrative Patent Judges.

PRATS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims to a lentiviral
vector that encodes a West Nile Virus antigen. The Examiner entered a
rejection for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b). We reverse.

Appeal 2011-000378
Application 11/250,616

2
STATEMENT OF THE CASE
Claims 64-73 and 86 stand rejected and appealed (see App. Br. 4).
1

Claim 64 illustrates the subject matter on appeal and reads as follows:
64. A lentiviral vector comprising a heterologous nucleic acid
encoding an antigen that induces an immunogenic response in vivo,
wherein the lentiviral vector is pTRIP ΔU3, and the vector
comprises a promoter selected from cytomegalovirus immediate early
promoter, CAG promoter, EF1alpha promoter, PGK promoter, SVero
promoter, and MND promoter; and
wherein the heterologous nucleic acid encodes envelope E-
glycoprotein of a West Nile Virus or a carboxyl terminal-truncated E
glycoprotein of West Nile Virus lacking the transmembrane anchoring
region.

The sole rejection before us for review is the Examiner‟s rejection of
claims 64-73 and 86 under 35 U.S.C. § 103(a) as obvious over Desprès,
2

Sirven,
3
and Rohrlich
4
(Ans. 4-6).

1
Appeal Brief filed August 6, 2009.
2
Philippe Desprès et al., Live Measles Vaccine Expressing the Secreted
Form of the West Nile Virus Envelope Glycoprotein Protects against West
Nile Virus Encephalitis, 191 JOURNAL OF INFECTIOUS DISEASES 207-214
(2005).
3
Aude Sirven et al., Enhanced Transgene Expression in Cord Blood CD34
+
-
Derived Hematopoietic Cells, Including Developing T Cells and NOD/SCID
Mouse Repopulating Cells, Following Transduction with Modified TRIP
Lentiviral Vectors, 3 MOLECULAR THERAPY 438-448 (2001).
4
Pierre S. Rohrlich et al., Use of a Lentiviral Vector Encoding a HCMV-
Chimeric IE1-pp65 Protein for Epitope Identification in HLA-Transgenic
Mice and For ex vivo Stimulation and Expansion of CD8
+
Cytotoxic T Cells
From Human Peripheral Blood Cells, 54 HUMAN IMMUNOLOGY 514-522
(2004).
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DISCUSSION
The Examiner cited Desprès as describing a recombinant measles
virus (MV) vector expressing a heterologous nucleic acid encoding West
Nile Virus (WNV) E glycoprotein (Ans. 4). The Examiner conceded that
Desprès differed from the rejected claims in that Desprès expressed the
WNV antigen using the measles virus vector rather than the claimed
lentiviral vector pTRIP ΔU3 (id.).
To address that deficiency, the Examiner cited Sirven as “expressing
heterologous proteins such as EGFP . . . with the [claimed] lentiviral
vectors” (id. at 5). The Examiner also cited Rohrlich as teaching “lentiviral
vector TRIP expressing human cytomegalovirus proteins” (id.).
Based on the references‟ combined teachings, the Examiner
concluded that an ordinary artisan would have considered it obvious to
“make the lentiviral vectors pTRIP ΔU3 and pTRIP ΔU3 CMV of the
present invention comprising a heterologous nucleic acid encoding West
Nile Virus E-glycoprotein” (id.). The Examiner reasoned:
One would have been motivated to substitute Sirven‟s
and Rohrlich‟s lentiviral vectors pTRIP ΔU3 and pTRIP ΔU3
CMV for Despres‟ recombinant measles virus vector, because
Sirven teaches that his lentiviral vectors allow long term
transgene expression and are important in gene transfer
technology (see Discussion and Abstract), and because
Rohrlich teaches that his lentiviral vectors make powerful
constructs that can be used to characterize new epitopes in
combination with immunization of human leukocyte antigen-
transgenic mice and to expand the effector T cells for adoptive
immunotherapy in humans (see page 514 and page 521).

(Id.)
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Appellants contend, for a variety of reasons, that the Examiner failed
to make a prima facie case of obviousness. In particular, Appellants argue
that the “premise of the Examiner‟s rejection is that the measles virus vector
and the lentiviral vector were interchangeable because they were known to
be equivalent to each other” (App. Br. 11). However, Appellants urge,
“[m]easles virus vectors and lentiviral vectors cannot be considered
interchangeable” (id.).
Appellants point out Desprès‟ teaching that, among other reasons, its
measles virus vector is advantageous for inducing a protective antibody
response to WNV “because „MV replicates exclusively in the cytoplasm,
ruling out the possibility of integration in host DNA‟” (id. at 24 (quoting
Desprès 207)). In contrast Appellants argue, as supported by publications of
record, “lentiviruses do not replicate exclusively in the cytoplasm, but do
integrate in host DNA” (id.; see also id. at Evidence Appendix (Exhibits 14
and 15)).
Appellants therefore urge that an ordinary artisan “would have been
motivated not to use lentiviral vectors to generate a humoral response upon
reading the Despres reference because of the differences in replication loci,
and Despres‟s preference for cytoplasmic replication. To do otherwise
would modify the principle of operation of the Despres reference” (App. Br.
24-25).
The Examiner responds that, in an obviousness analysis, “rationale
different from Applicant‟s is permissible (MPEP 2144)” (Ans. 7 (also citing
In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006))). Thus, the Examiner urges:
In the present case Sirven and Roh[r]lich provide the
motivation to use their pTRIP ΔU3 and pTRIP ΔU3 CMV
vectors to express Despres‟ West Nile Virus E glycoprotein and
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to substitute Sirven‟s and Rohrlich‟s lentiviral vectors pTRIP
ΔU3 and pTRIP ΔU3 CMV for Despres' recombinant measles
virus vector, because Sirven teaches that his lentiviral vectors
allow long term transgene expression and are important in gene
transfer technology (see Discussion and Abstract), and because
Rohrlich teaches that his lentiviral vectors make powerful
constructs that can be used to characterize new epitopes in
combination with immunization of human leukocyte antigen-
transgenic mice and to expand the effector T cells for adoptive
immunotherapy in humans (see page 514 and page 521).

(Id. at 7-8.)

We conclude that Appellants have the better position.
“In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima facie case of obviousness
based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir.
1992).
In KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007), while the
Supreme Court emphasized “an expansive and flexible approach” to the
obviousness question, it also reaffirmed the importance of determining
“whether there was an apparent reason to combine the known elements in
the fashion claimed by the patent at issue.” Id. at 418 (emphasis added).
Thus, “[o]bviousness requires more than a mere showing that the prior
art includes separate references covering each separate limitation in a claim
under examination.” Unigene Laboratories, Inc. v. Apotex, Inc., 655 F.3d
1352, 1360 (Fed. Cir. 2011).
Instead, “[i]n determining whether obviousness is established by
combining the teachings of the prior art, the test is what the combined
teachings of the references would have suggested to those of ordinary skill
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in the art.” In re GPAC Inc., 57 F.3d 1573, 1581 (Fed. Cir. 1995) (internal
quotations omitted).
We agree with Appellants that the teachings in the prior art
propounded by the Examiner in support of the obviousness conclusion
would not have prompted an ordinary artisan to practice the claimed subject
matter. All of the rejected claims recite, in some form or another, a specific
lentiviral vector, pTRIP ΔU3, which also encodes a WNV envelope
glycoprotein antigen.
It may be true that the prior art recognized that the claimed vector
provided “high long-term transgene expression in CD34
+
-derived T, B, NK,
and myeloid hematopoietic cells” (Sirven 438). It may also be true that such
a lentiviral vector was a “powerful construct both to characterize new
epitopes in combination with human leukocyte antigen-transgenic mice
immunization and to provide an alternative to the use of known infectious
and noninfectious approaches to expand effector T cells for adoptive
immunotherapy” (Rohrlich 514).
In our view, however, the Examiner has not adequately explained why
an ordinary artisan would have been prompted by those teachings to use the
lentiviral vector, rather than a measles virus-derived vector, in Desprès‟
method of inducing an antibody response to WNV glycoprotein. As
Appellants point out, Desprès teaches that its measles-derived vector has a
number of properties making it particularly desirable as a WNV antigen
carrier, including the fact that, unlike lentiviral vectors, it does not integrate
into host DNA, but instead replicates only in the cytosol (Desprès 207).
Thus, the Examiner has not presented a clear fact-based explanation
as to why the lentiviral vector‟s capacity to stably provide long-term
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expression of transgenes in hematopoietic cells, or its capacity to
characterize major histocompatibility epitopes and expand effector T cells
for adoptive immunotherapy, would have rendered it desirable in Desprès‟
process, particularly when the lentiviral vector undisputedly does not have
one of the key properties (lack of host genome integration) described as
making the measles-derived vector advantageous in Desprès‟ process.
Absent such a fact-based explanation, we are not persuaded that the
Examiner has carried the burden of making a prima facie case of
obviousness based on the cited references.
We acknowledge that subject matter suggested by the prior art is
prima facie obvious, even if the prior art‟s reason for practicing it is different
than the patent applicant‟s. Other than Desprès, however, the Examiner
does not cite or point to any specific teachings explaining the utility of WNV
envelope antigen, or prior art processes that might use a nucleic acid
encoding it. Thus, while the Examiner seems to urge that an ordinary artisan
would have reasonably inferred that nucleic acid encoding WNV envelope
would be useful in the processes of Sirven and Rohrlich, rather than in
Desprès‟ process, the Examiner has not provided an adequate explanation,
nor pointed to any specific teachings in Sirven or Rohrlich or Desprès, that
would support that inference.
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In sum, we are not persuaded that the Examiner has made a prima
facie case that an ordinary artisan would have considered the claimed
lentiviral vectors, or the host cells containing them, obvious in view of
Desprès, Sirven, and Rohrlich. We therefore REVERSE the Examiner‟s
obviousness rejection of claims 64-73 and 86 over Desprès, Sirven, and
Rohrlich.

REVERSED

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