Ex Parte Case et al

Board of Patent Appeals and Interferences

Sep 22, 2010

11148794 (B.P.A.I. Sep. 22, 2010)

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.
11/148,794 06/08/2005 Casey C. Case 8325-0002.11 9554
20855 7590 09/22/2010
ROBINS & PASTERNAK
1731 EMBARCADERO ROAD
SUITE 230
PALO ALTO, CA 94303
EXAMINER
KELLY, ROBERT M
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
09/22/2010 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 CASEY C. CASE, GEORGE N. COX III,
STEPHEN P. EISENBERG, QIANG LIU, and EDWARD J. REBAR
____________

Appeal 2010-004265
Application 11/148,794
Technology Center 1600
____________

Before TONI R. SCHEINER, DONALD E. ADAMS, and
DEMETRA J. MILLS, Administrative Patent Judges.

ADAMS, Administrative Patent Judge.

DECISION ON APPEAL1
This appeal under 35 U.S.C. § 134 involves claims 1-12, the only
claims pending in this application. We have jurisdiction under 35 U.S.C. §
6(b).

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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STATEMENT OF THE CASE
The claims are directed to a method for modulating expression of an
endogenous gene in a cell. Claim 1 is representative and is reproduced in
the “Claims Appendix” of Appellants’ Brief (App. Br. 19).
As a preliminary matter Appellants request “clarification as to
whether the intended purpose of . . . 37 C.F.R. § 41.37(c)(ii) is for
Appellants to disclose every prior and pending Appeal in the same
technology area . . . by the Real Party of Interest or whether it is sufficient to
disclose Appeals in the same series” (App. Br. 3). The clarification
Appellants request is found in the rule itself:
Related appeals and interferences. A statement
identifying by application, patent, appeal or interference
number all other prior and pending appeals, interferences or
judicial proceedings known to appellant, the appellant’s legal
representative, or assignee which may be related to, directly
affect or be directly affected by or have a bearing on the
Board’s decision in the pending appeal.

37 C.F.R. § 41.37(c)(ii). As explained in the Manual of Patent Examining
Procedure (MPEP):
The requirement to identify related proceedings requires
appellant to identify every related proceeding (e.g., commonly
owned applications having common subject matter, claim to a
common priority application) which may be related to, directly
affect or be directly affected by or have a bearing on the
Board’s decision in the pending appeal.

MPEP § 1205.02, 8th ed., July 2010. We have considered the merits
of the rejections presented for our review with the presumption that
the briefings Appellants made of record in this Appeal are in
compliance with this Rule.
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The rejections presented by the Examiner follow:
1. Claims 1-12 stand rejected under the written description provision of 35
U.S.C. § 112, first paragraph.
2. Claims 1, 5, 6, 9, 10, and 12 stand rejected under 35 U.S.C. § 102(e) as
being anticipated by Barbas.2
3. Claims 1, 5-10, and 12 stand rejected under 35 U.S.C § 103(a) as
unpatentable over Barbas.
4. Claims 1 and 4-12 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Barbas and Choo ‘229.3
5. Claims 1 and 3-12 stand rejected under 35 U.S.C § 103(a) as
unpatentable over the combination of Barbas, Choo ‘229, and Pal.4
6. Claims 1-12 stand rejected under 35 U.S.C § 103(a) as unpatentable over
the combination of Barbas, Choo ‘229, Pal, and Liu.5
We reverse the written description rejection and affirm the rejections
under 35 U.S.C. § 102(e) and 35 U.S.C § 103(a).

2 Barbas, III et al., US 6,242,568 B1, issued June 5, 2001.
3 Choo et al., US RE39,229 E, reissued August 8, 2006.
4 Pal et al., Activation of Sp1-mediated Vascular Permeability
Factor/Vascular Endothelial Growth Factor Transcription Requires Specific
Interaction with Protein Kinase C ζ, 273(41) J. BIOL. CHEM. 26277-26280
(1998).
5 Qiang Liu et al., Design of polydactyl zinc-finger proteins for unique
addressing within complex genomes, 94 PROC. NATL. ACAD. SCI. USA 5525-
5530 (1997).
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Written Description:
ISSUE

Does the preponderance of evidence on this record support the
Examiner’s conclusion that Appellants’ Specification fails to provide written
descriptive support for the claimed invention?
ANALYSIS
Upon consideration of the evidence and argument of record, including
Choo ’94,6 we find that the Examiner has not established a factual basis to
support a conclusion that Appellants’ Specification lacks written descriptive
support for the claimed invention. Accordingly, we will not sustain the
Examiner’s rejection for essentially those reasons expressed in the Principal
and Reply Briefs on Appeal. Specifically, we agree with Appellants’
contention that the “written description requirement of Section 112 does not
necessitate that Appellants demonstrate the structure of all partially
randomized zinc finger proteins that bind to endogenous genes. Rather, the
relevant inquiry is whether the as-filed specification, in light of the state of
the art, adequately describes the claimed subject matter” (Reply Br. 6-7).
CONCLUSION OF LAW
The preponderance of evidence on this record fails to support the
Examiner’s conclusion that Appellants’ Specification fails to provide written
descriptive support for the claimed invention.
The rejection of claims 1-12 under the written description provision of
35 U.S.C. § 112, first paragraph is reversed.

6 Yen Choo and Aaron Klug, Toward a code for the interactions of zinc
fingers with DNA:Selection of randomized fingers displayed on phage, 91
PROC. NATL. ACAD. SCI. USA 11163-11167 (1994).
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Anticipation:
ISSUE
Does the preponderance of evidence on this record support the
Examiner’s finding that Barbas teaches the claimed invention?
FINDINGS OF FACT
FF 1. Appellants’ Specification discloses that “the stably expressed gene
described by Choo et al.7 is randomly integrated into the genome and is not
found in a native chromatin environment as compared to an endogenous
gene” (Spec. 5: 27-29).
FF 2. The Examiner finds that
Barbas claims methods of isolating partially-randomized zinc-
finger proteins, thereby making libraries which are selected for
binding to a target DNA . . ., and also modulating transcription
of a cellular nucleotide sequence associated with a zinc-finger
binding motif, comprising contacting the nucleotide in a cell
with a zinc finger protein (e.g., Claim 22), which may be
introduced by way of an expression vector. . . . Moreover, the
specification teaches that the cellular nucleotide sequence may
be a naturally occurring sequence in the cell (e.g.,
S[pecification], cols. 2-3, paragraph bridging).

(Ans. 10.)
FF 3. Barbas’ claim 22 is drawn to a
[M]ethod of modulating transcription of a cellular nucleotide
sequence associated with a zinc finger-nucleotide binding
motif, comprising contacting the zinc finger-nucleotide in cells
in vitro with an effective amount of a zinc finger-nucleotide
binding polypeptide variant comprised of at least two zinc
finger modules that binds to the zinc finger-nucleotide binding
motif, wherein the amino acid sequence of each module that

7 Appellants identify “Choo et al.” as “Choo et al., Nature 372:642-645
(1994)” (Spec. 5: 15).
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binds the motif comprises two cysteines and two histidines
whereby both cysteines are amino proximal to both histidines
and wherein each of two modules of said variant has at least
one amino acid sequence modification, thereby modulating
transcriptional activity of the cellular nucleotide sequence.

(Barbas, col 82, ll. 1-13.)

FF 4. Barbas defines the term “cellular nucleotide sequence” as “a
nucleotide sequence which is present within the cell. It is not necessary that
the sequence be a naturally occurring sequence of the cell. For example, a
retroviral genome which is integrated within a host’s cellular DNA, would
be considered a ‘cellular nucleotide sequence’” (Barbas, col. 5, ll. 56-59).
FF 5. Barbas teaches that “[t]he cellular nucleotide sequence may be a
sequence which is a naturally occurring sequence in the cell, or it may be a
viral-derived nucleotide sequence in the cell” (Barbas, col. 3, ll. 5-8; Ans.
10).
FF 6. Appellants’ Specification defines the term “endogenous gene” as “a
microbial or viral gene that is part of a naturally occurring microbial or viral
genome in a microbially or virally infected cell. The microbial or viral
genome can be extrachromosomal or integrated into the host chromosome.
This term also encompasses endogenous cellular genes” (Spec. 14: 11-14).
FF 7. Appellants’ Specification defines the term “endogenous cellular
gene” as “a gene that is native to a cell, which is in its normal genomic and
chromatin context, and which is not heterologous to the cell” (Spec. 14: 7-8).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 1 is representative.
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Appellants contend that
Barbas does not claim “treating endogenous genes” because this
reference does not enable the skilled artisan to use partially
randomized zinc finger proteins to modulate expression of the
endogenous genes. Instead, Barbas teaches only zinc finger
proteins that were selected to bind to a non-endogenous
sequence . . . . See, e.g., page 5, lines 27-29 of . . .
[Appellants’] [S]pecification.

(App. Br. 10.) We are not persuaded by Appellants’ contention, because
page 5, lines 27-29 of Appellants’ Specification does not relate to Barbas
(FF 1).
Appellants contend that both Barman8 and Beerli9 teach that “at the
time of [Appellants’] filing, the art, including Barbas, taught that zinc finger
proteins were not known to bind to endogenous genes” (App. Br. 10; see
also Reply Br. 9-11). We are not persuaded.
Barbas’ claim 22 is drawn to a “method of modulating transcription of
a cellular nucleotide sequence associated with a zinc finger-nucleotide
binding motif, comprising contacting the zinc finger-nucleotide in cells in
vitro with an effective amount of a zinc finger-nucleotide binding
polypeptide variant” (FF 2-3). Appellants do not dispute that the zinc
finger-nucleotide binding polypeptide variant is within the scope of the
“engineered zinc finger protein” of Appellants’ claim 1.
Barbas defines the term “cellular nucleotide sequence” as those
sequences that (1) naturally occur in a cell or (2) are viral-derived nucleotide

8 Stu Borman, DNA-Binding Proteins Turn Genes On And Off, C&EN 34-35
(February 21, 2000).
9 Roger R. Beerli et al., Positive and negative regulation of endogenous
genes by designed transcription factors, 97(4) PROC. NATL. ACAD. SCI.
1495-1500 (February 15, 2000).
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sequence in a cell (FF 4-5). According to Barbas, an example of a viral-
derived nucleotide sequence in a cell would be “a retroviral genome which is
integrated within a host’s cellular DNA” sequences (FF 4). We find no
difference in the scope of Barbas’ term “a cellular nucleotide sequence” and
Appellants’ term “endogenous gene” (Cf. FF 4-5 with FF 6-7).
For the foregoing reasons, we are not persuaded by Appellants’
contention that their use of the term “endogenous gene” is different than
Barbas’ use of the term “cellular DNA sequences” (Reply Br. 10-11). In
addition, we are not persuaded by Appellants’ contention that “Barbas is
silent as to endogenous genes and the ‘cellular nucleotide sequences’ of this
reference are clearly reporter constructs, which are not encompassed by the
pending claims” (Reply Br. 11-12) “A patent shall be presumed valid.” 35
U.S.C. § 282. Accordingly the weight of the evidence falls in favor of the
Examiner’s prima facie case of anticipation.
CONCLUSION OF LAW
The preponderance of evidence on this record supports the
Examiner’s finding that Barbas teaches the claimed invention.
The rejection of claim 1 under 35 U.S.C. § 102(e) as being anticipated
by Barbas is affirmed. Claims 5, 6, 9, 10, and 12 fall together with claim 1.

Obviousness:
Barbas:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
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FINDINGS OF FACT
FF 8. Barbas is relied upon as discussed above (Ans. 11).
FF 9. The Examiner finds that “Barbas teaches that the derived zinc-finger
proteins may be used to inhibit HIV in a cell (e.g., col. 27, paragraph 2),”
which relates to subject matter found in dependent claims, e.g., Appellants’
claim 5 (Ans. 12).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 1 is representative.
Appellants contend that “[f]or the reasons of record and detailed
above, Barbas does not teach or suggest that zinc finger proteins which
modulate endogenous gene expression were predictable” (App. Br. 17; see
also Reply Br. 12).
We are not persuaded for the reasons set forth with regard to the
anticipation rejection. Accordingly, we find no error in the Examiner’s
conclusion that claim 1 is prima facie obvious over the cited art.
CONCLUSION OF LAW
The preponderance of evidence on this record supports a conclusion
of obviousness.
The rejection of claim 1 under 35 U.S.C § 103(a) as unpatentable over
Barbas is affirmed. Claims 5-10 and 12 fall together with claim 1.

The combination of Barbas and Choo ‘229:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
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FINDINGS OF FACT
FF 10. Barbas is relied upon as discussed above (Ans. 12).
FF 11. The Examiner relies on Choo ‘299 to suggest the limitations of
claims 4 and 11 (Ans. 13).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 1 is representative.
Appellants contend that “the skilled artisan would have no reason to
use Barbas or Choo’s zinc finger proteins as, prior to the present disclosure,
it was entirely unpredictable that partially randomized engineered ZFPs
would actually bind endogenous genes” (App. Br. 13; see also Reply Br. 12-
17).
We are not persuaded for the reasons set forth with regard to the
anticipation rejection. Accordingly, we find no error in the Examiner’s
conclusion that claim 1 is prima facie obvious over the cited art.
CONCLUSION OF LAW
The preponderance of evidence on this record supports a conclusion
of obviousness.
The rejection of claim 1 under 35 U.S.C § 103(a) as unpatentable over
the combination of Barbas and Choo ‘229 is affirmed. Claims 4-12 fall
together with claim 1.

The combination of Barbas, Choo ‘229, and Pal:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
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FINDINGS OF FACT
FF 12. Barbas and Choo ‘229 are relied upon as discussed above (Ans. 14).
FF 13. The Examiner relies on Pal to suggest the limitations of claim 3
(Ans. 14).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 1 is representative.
Appellants contend that “Barbas and Choo do not teach methods of
modulating endogenous gene expression” and “Pal is entirely silent as to
using partially randomized zinc finger proteins to modulate VEGF
expression. Therefore, there is no combination of these references that
would result in the claimed methods” (App. Br. 16; see also Reply Br. 17).
We are not persuaded for the reasons set forth with regard to the
anticipation rejection. Accordingly, we find no error in the Examiner’s
conclusion that claim 1 is prima facie obvious over the cited art.
CONCLUSION OF LAW
The preponderance of evidence on this record supports a conclusion
of obviousness.
The rejection of claim 1 under 35 U.S.C § 103(a) as unpatentable over
the combination of Barbas, Choo ‘229, and Pal is affirmed. Claims 3-12 fall
together with claim 1.

The combination of Barbas, Choo ‘229, Pal, and Liu:
ISSUE
Does the preponderance of evidence on this record support a
conclusion of obviousness?
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FINDINGS OF FACT
FF 14. Barbas, Choo ‘229, and Pal are relied upon as discussed above (Ans.
15).
FF 15. The Examiner relies on Liu to suggest the limitations of claim 2
(Ans. 15).
ANALYSIS
The claims have not been argued separately and therefore stand or fall
together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 1 is representative.
Appellants contend that “[f]or the reasons of record and reiterated
herein, there is no combination of Barbas, Choo and Pal that teaches or
suggests the claimed subject matter. Liu does not in any way make up the
deficiencies of this combination” (App. Br. 16; see also Reply Br. 17).
We are not persuaded for the reasons set forth with regard to the
anticipation rejection. Accordingly, we find no error in the Examiner’s
conclusion that claim 1 is prima facie obvious over the cited art.
CONCLUSION OF LAW
The preponderance of evidence on this record supports a conclusion
of obviousness.
The rejection of claim 1 under 35 U.S.C § 103(a) as unpatentable over
the combination of Barbas, Choo ‘229, Pal, and Liu is affirmed. Claims 2-12
fall together with claim 1.
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
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Application 11/148,794

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cdc

ROBINS & PASTERNAK
1731 EMBARCADERO ROAD
SUITE 230
PALO ALTO, CA 94303