Ex Parte Boulis

Board of Patent Appeals and Interferences

Oct 7, 2009

10854726 (B.P.A.I. Oct. 7, 2009)

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.
10/854,726 05/27/2004 Nicholas M. Boulis 12637/39 8744
23838 7590 10/08/2009
KENYON & KENYON LLP
1500 K STREET N.W.
SUITE 700
WASHINGTON, DC 20005
EXAMINER
SWARTZ, RODNEY P
ART UNIT PAPER NUMBER
1645
MAIL DATE DELIVERY MODE
10/08/2009 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

Ex parte NICHOLAS M. BOULIS
____________

Appeal 2009-003388
Application 10/854,726
Technology Center 1600
____________

Decided: October 8, 2009
____________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, and JEFFREY
N. FREDMAN, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims 1, 5-14 and 28-30.
Pending “[c]laims 15-27 and 31-33 have been withdrawn from
consideration” (App. Br. 2). We have jurisdiction under 35 U.S.C. § 6(b).

STATEMENT OF THE CASE
The claims are directed to a method of producing in a cell in vivo in a
mammalian body a clostridial neurotoxin light chain peptide (claims 1 and
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5-14) and a method of producing a clostridial neurotoxin light chain peptide
in cells transplanted into a target site of a body (claims 28-30). Claims 1 and
28 are illustrative:
1. A method of producing in a cell in vivo in a mammalian body a
clostridial neurotoxin light chain peptide, the method comprising:
delivering into a cell in vivo in a mammalian body, a nucleic acid
construct comprising (a) a nucleic acid encoding a clostridial neurotoxin
light chain peptide and (b) a regulatory sequence operably linked to the
nucleic acid to allow expression of the nucleic acid, wherein the expression
of the nucleic acid produces the clostridial neurotoxin light chain peptide in
the cell in vivo.

28. A method of producing a clostridial neurotoxin light chain peptide in
cells transplanted into a target site of a body, the method comprising:
transfecting cells in vitro with a nucleic acid construct comprising (a)
a nucleic acid encoding a clostridial neurotoxin light chain peptide and (b) a
regulatory sequence operably linked to the nucleic acid to allow expression
of the nucleic acid in the transfected cells,
selecting the transfected cells that express the nucleic acid and thereby
produce the clostridial neurotoxin light chain peptide; and
transplanting into a target site of a body the selected transfected cells
that produce a clostridial neurotoxin light chain peptide.

The Examiner relies on the following evidence:
Zdanovsky US 6,214,602 B1 Apr. 10, 2001
Nicholas M. Boulis, M.D., et al., Neuronal survival following remote
adenovirus gene delivery, 96 J. Neurosurg (Spine 2) 212-219 (2002).

Appellant relies on the following evidence:

Introducing Cloned Genes into Cultured Mammalian Cells in Molecular
Cloning: A Laboratory Manual Ch. 16, pp. 16.1-16.2 (Cold Spring Harbor
Laboratory Press (2001).

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The rejections presented by the Examiner are as follows:
1. Claims 1 and 5-14 stand rejected under 35 U.S.C. § 103(a) as
unpatentable over Zdanovsky.
2. Claims 28-30 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over the combination of Zdanovsky and Boulis.
We affirm the rejection over Zdanovsky and reverse the rejection over
the combination of Zdanovsky and Boulis.

PRINCIPLES OF LAW
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). On
appeal to this Board, Appellants must show that the Examiner has not
sustained the required burden. See Ex parte Yamaguchi, 88 USPQ2d 1606,
1608 and 1614 (BPAI 2008) (precedential); Ex parte Fu, 89 USPQ2d 1115,
1118 and 1123 (BPAI 2008) (precedential).
“The combination of familiar elements according to known methods is
likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). It is proper to “take
account of the inferences and creative steps that a person of ordinary skill in
the art would employ.” Id. at 418. See also id. at 421 (“A person of
ordinary skill is also a person of ordinary creativity, not an automaton.”).
35 U.S.C § 103(a) “forbids issuance of a patent when ‘the differences
between the subject matter sought to be patented and the prior art are such
that the subject matter as a whole would have been obvious at the time the
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invention was made to a person having ordinary skill in the art to which said
subject matter pertains.’” KSR, 550 U.S. at 405 (quoting 35 U.S.C.
§ 103(a)).
Argument by counsel cannot take the place of evidence. In re Cole,
326 F.2d 769, 773 (CCPA 1964); In re Geisler, 116 F.3d 1465, 1471 (Fed.
Cir. 1997).

Zdanovsky:
ISSUE

Has Appellant established error in the Examiner’s prima facie case of
obviousness?

FINDINGS OF FACT
FF 1. There is no dispute that “Zdanovsky teaches the nucleic acid
constructs of the claims” (Ans. 3).
FF 2. There is no dispute that Zdanovsky teaches microinjection (id.).
FF 3. The Examiner finds that Zdanovsky teaches that nucleic acid
constructs within the scope of Appellant’s claims “can be transferred via
vectors into host cells” including eukaryotic cells (id.).
FF 4. Zdanovsky teaches that “[t]he term ‘transfection’ as used herein
refers to the introduction of foreign DNA into cells (eukaryotic or
prokaryotic)” (Zdanovsky, col. 15, ll. 1-3).
FF 5. Appellant’s Specification discloses “[a]n assortment of delivery
devices can be employed to deliver the CNLC (clostridium neurotoxin light
chain) nucleic acid construct to the desired cells of the target site. For
example, the delivery device can include a hollow microneedle having an
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opening at its distal end through which the CNLC nucleic acid construct can
be injected” (Spec. 21: 12-15).

ANALYSIS
Appellant contends that microinjection “has nothing to do with
delivering nucleic acid constructs into a mammalian body in vivo” (App. Br.
4). In support of this assertion Appellant directs attention to “Molecular
Cloning: A Laboratory Manual” which allegedly teaches that “transfection is
a method that can be only used to ferry foreign nucleic acid constructs into
cells in a dish” (id.). We disagree. Chapter 16 of the Molecular Cloning
manual relied upon by Appellant is directed to the concept of “Introducing
Cloned Genes into Cultured Mammalian Cells” (see Molecular Cloning: A
Laboratory Manual, ch. 16, Title). This document does not restrict
transfection to cultured cells.
Further, contrary to Appellant’s contention, Zdanovsky teaches that
the term “transfection” has a broader meaning and refers to “the introduction
of foreign DNA into cells” (FF 4). Zdanovsky does not limit the term
“transfection” to in vitro or ex vivo environments. Accordingly, we are not
persuaded by Appellant’s contention that the term “transfection” is
exclusively limited to the introduction of foreign DNA into cells that are not
in an in vivo environment. Simply stated, Appellant has provided no
evidence on this record that expressly teaches that the term “transfection” is
limited to an in vitro or ex vivo environment.
As the Examiner points out, “[t]he instant claims do not restrict the
method of delivery . . . but permit any method which delivers into a cell in
vivo[ ] a nucleic acid construct” (Ans. 5). Appellant’s Specification
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discloses “[a]n assortment of delivery devices can be employed to deliver
the CNLC nucleic acid construct to the desired cells of the target site. For
example, the delivery device can include a hollow microneedle having an
opening at its distal end through which the CNLC nucleic acid construct can
be injected” (FF 5). Appellant fails to identify any evidence on this record
that microinjection can not be used to “transfect” nucleic acid into a cell in
vivo.
In addition, Appellant fails to direct our attention to any evidence on
this record to support the contention that there was no “reasonable
expectation of success that just because a clostridial neurotoxin which is
expressed and harvested in vitro” exhibits a biological activity that this same
construct would exhibit a biological effect when expressed in vivo (App. Br.
6-7). Unsupported argument by counsel cannot take the place of evidence.
In re Cole, 326 F.2d at 773; In re Geisler, 116 F.3d at 1471.
In sum, the weight of the evidence falls in favor of the Examiner.

CONCLUSION OF LAW
Appellant failed to establish error in the Examiner’s prima facie case
of obviousness. The rejection of claim 1 under 35 U.S.C. § 103(a) as
unpatentable over Zdanovsky is affirmed. Since they are not separately
argued claims 5-14 fall together with claim 1. 37 C.F.R. § 41.37(c)(1)(vii).

Zdanovsky and Boulis:
ISSUE

Has Appellant established error in the Examiner’s prima facie case of
obviousness?
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Application 10/854,726

7
FINDINGS OF FACT
FF 6. The Examiner relies on Zdanovsky as discussed above (Ans. 4).
FF 7. The Examiner relies on Boulis to “teach injecting a host vector into
[the] central nervous system in order to deliver a gene to the central nervous
[system] cells” (id.).
FF 8. Boulis’s host vector is an adenoviral vector (Boulis, 214, col. 1, ll. 1-
17).

ANALYSIS
Claim 28 requires, inter alia, the transplantation of cells that are
transfected in vitro into a target site of a body (claim 28). Claims 29 and 30
depend from claim 28.
Appellant contends that “Zdanovsky does not even hint to
transplanting transfected cells into a body” (App. Br. 3). The Examiner
identifies no teaching in Zdanovsky that teaches the transplantation of
transfected cells into a body. Boulis speaks of the injection of a viral vector,
not transfected cells, and therefore fails to make up for the deficiency in
Zdanovsky. Accordingly, we disagree with the Examiner’s conclusion that
“it would be obvious to utilize the transplantation method of Boulis et al in
order to deliver cells producing neurotoxin into a target site of a host body”
(Ans. 4).

CONCLUSION OF LAW
Appellant established error in the Examiner’s prima facie case of
obviousness. The rejection of claims 28-30 under 35 U.S.C. § 103(a) as
unpatentable over the combination of Zdanovsky and Boulis is reversed.
Appeal 2009-003388
Application 10/854,726

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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-IN-PART

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