Ex Parte Choo et al

Board of Patent Appeals and Interferences

Aug 28, 2009

10397930 (B.P.A.I. Aug. 28, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte YEH CHOO, AARON KLUG,
and ISIDRO SANCHEZ-GARCIA
__________

Appeal 2009-010838
Application 10/397,930
Technology Center 2009-010838
__________

Decided: August 28, 2009

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Before TONI R.SCHEINER, ERIC GRIMES, and RICHARD M.
LEBOVITZ, Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to fusion
proteins that include a non-natural zinc finger domain. The Examiner has
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
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STATEMENT OF THE CASE
Claims 42-44 and 52 are on appeal.1 Claim 42, the only independent
claim, reads as follows:
42. An isolated polypeptide comprising a non-naturally occurring
zinc finger protein and a heterologous functional domain,
(a) wherein the non-naturally occurring zinc finger protein:
(i) has been designed to bind to a particular chromosomal
target DNA sequence, and
(ii) comprises a non-naturally occurring zinc finger
comprising an antiparallel beta sheet packed against an alpha
helix; and
(b) wherein the heterologous functional domain is selected from
the group consisting of an activation domain, a repression domain, a
catalytic domain from a restriction enzyme and a nuclear localization
signal.

The claims stand rejected under 35 U.S.C. § 103(a) as follows:
• Claims 42, 43, and 52 in view of Desjarlais,2 Courey,3 Anderson,4
and Narayan5 (Answer 4); and

1 Claims 45-47 and 50 are also pending but have been withdrawn from
consideration by the Examiner (Office action mailed Oct. 15, 2008, p. 1).
2 Desjarlais et al., “Use of a zinc-finger consensus sequence framework and
specificity rules to design specific DNA binding proteins,” 90 Proc. Natl.
Acad. Sci. USA 2256-2260 (1993).
3 Courey et al., “Synergistic Activation by the Glutamine-Rich Domains of
Human Transcription Factor Sp1,” 59 Cell 827-836 (1989).
4 Anderson et al., “Synergistic Activation of a Human Promoter in vivo by
Transcription Factor Sp1,” 11 Molecular and Cellular Biology 1935-1943
(1991).
5 Narayan et al., “Structures of Zinc Finger Domains from Transcription
Factor Sp1, 272 Journal of Biological Chemistry 7801-7809 (1997).
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• Claim 44 in view of Desjarlais, Courey, Anderson, Narayan, and
Sadowski6 (Answer 7-8).
OBVIOUSNESS
Issue
The Examiner has rejected claims 42, 43, and 52 in view of
Desjarlais, Courey, Anderson, and Narayan. The Examiner finds that
Desjarlais discloses a non-naturally occurring zinc finger protein that was
designed to bind to a particular target DNA (Answer 4-5) and that Narayan
shows that Desjarlais’ protein comprises the beta sheet/alpha helix structure
recited in the claims (id. at 5).
The Examiner also finds that Courey discloses a zinc-finger protein
comprising a heterologous activation domain (id. at 5-6) and that Anderson
discloses that a zinc-finger protein binds to binding sites that have been
inserted into chromosomal DNA (id. at 6). The Examiner concludes that it
would have been obvious to modify Desjarlais’ protein to include a
heterologous activation domain, as taught by Courey, and to insert the
binding site of the fusion protein into a chromosome, as taught by Anderson,
“in order to receive the expected benefit of making a protein that is capable
of activating transcription” and “put the target site into a cellular context
which closely resembles that of a single-copy gene” (id. at 7).
Appellants contend that “[t]here is nothing in the references or art as a
whole that would suggest that it was predictable that proteins as disclosed in
Desjarlais (the only reference . . . cited for teaching a non-naturally

6 Sadowski et al., “GAL4-VP16 is an unusually potent transcriptional
activator,” 335 Nature 563-564 (1988).
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occurring zinc finger protein, although not one that is designed to bind a
chromosomal target site) would bind to chromosomal targets” (Appeal Br.
8). Appellants also contend that the claims “clearly require that the non-
naturally occurring zinc finger protein be designed to bind a chromosomal
target and . . . it is clear that the target is within a chromosome when it is
bound by the non-naturally occurring protein” (Reply Br. 7).
In response to Appellants’ argument that the references do not teach a
fusion protein designed to bind a chromosomal target DNA sequence, the
Examiner reasons that a
chromosomal target DNA sequence is a target DNA sequence
found in a chromosome. A sequence synthesized in vitro could
be the same sequence found in a chromosome. Furthermore,
Anderson et al teach it is within the skill of the art to insert a
DNA target sequence into a chromosome. . . . Thus, any DNA
sequence may be described as a chromosomal target sequence.
(Answer 11-12.)
The issue presented is: Did the Examiner err in concluding that the
cited references would have suggested a fusion protein “designed to bind to
a particular chromosomal target DNA sequence,” as required by the claims?
Findings of Fact
1. Desjarlais discloses three zinc-finger proteins designed to bind to
three different DNA sequences, each nine nucleotides in length (Desjarlais,
abstract).
2. Desjarlais assayed binding of the proteins to their predicted
binding sites using purified proteins (id. at 2256, right col.); i.e., in vitro.
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3. Courey discloses a fusion protein comprising the naturally
occurring zinc-finger domain of transcription factor Sp1 and a glutamine-
rich domain of the Drosophila Antennapedia protein (Courey 828, left col.).
4. Courey discloses that the fusion protein stimulated expression in
cells of “a reporter plasmid containing the CAT gene under control of the
Sp1-dependent SV40 early promoter” (id.).
5. Anderson discloses that three Sp1 binding sites in the human
arginosuccinate synthetase (AS) promoter “were mutated to abolish Sp1
binding, individually and in all possible combinations, to generate a series of
AS promoter-chloramphenicol acetyltransferase (CAT) expression
constructs” (Anderson, abstract).
6. Anderson discloses that plasmids comprising the mutant AS
promoter-CAT constructs were stably transfected into a human cell line (id.
at 1939, paragraph bridging the columns).
7. Stably transfected cell lines have the exogenous DNA integrated
into the chromosome of the cells. (See id.: “Any positional effect of the
chromosomal integration site on expression of the transfected plasmids
should be averaged out.”)
8. The Specification discloses “a method of altering the expression of
a gene of interest in a target cell, comprising: determining (if necessary) at
least part of the DNA sequence of the structural region and/or a regulatory
region of the gene of interest; designing a zinc finger polypeptide to bind to
the DNA of known sequence, and causing said zinc finger polypeptide to be
present in the target cell” (Spec., col. 7, l. 64 to col. 8, l. 4).
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9. The Specification provides a working example describing “a three
finger polypeptide able to bind site-specifically to a unique 9 bp region of
the BCR-ABL fusion oncogene and to discriminate it from the parent
genomic sequences. . . . Using transformed cells in culture as a model, it is
shown that binding to the target oncogene in chromosomal DNA is possible,
resulting in blockage of transcription” (id. at col. 25, ll. 53-60).
Principles of Law
“[T]he PTO applies to the verbiage of the proposed claims the
broadest reasonable meaning of the words in their ordinary usage as they
would be understood by one of ordinary skill in the art, taking into account
whatever enlightenment by way of definitions or otherwise that may be
afforded by the written description contained in the applicant’s
specification.” In re Morris, 127 F.3d 1048, 1054 (Fed. Cir. 1997).
“A claim can be obvious even where all of the claimed features are
not found in specific prior art references, where ‘there is a showing of a
suggestion or motivation to modify the teachings of [the prior art] to the
claimed invention.’” Ormco Corp. v. Align Technology Inc., 463 F.3d 1299,
1307 (Fed. Cir. 2006).
However, 35 U.S.C. § 103 requires “a searching comparison of the
claimed invention – including all its limitations – with the teaching of the
prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
“In rejecting claims under 35 U.S.C. § 103, the examiner bears the
initial burden of presenting a prima facie case of obviousness.” In re
Rijckaert, 9 F.3d 1531, 1532 (Fed. Cir. 1993).
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Analysis
The claims are directed to a fusion protein comprising a non-naturally
occurring zinc finger protein and a heterologous functional domain, where
the zinc finger protein “has been designed to bind to a particular
chromosomal target DNA sequence” (claim 42). The Examiner
acknowledges that none of the references relied on to show obviousness
disclose a zinc finger protein that binds to a chromosomal DNA target, but
reasons that “chromosomal DNA” includes any DNA that is, or could be,
part of a chromosome (Answer 11-12), and since Anderson teaches how to
insert exogenous DNA into a chromosome, “any DNA sequence may be
described as a chromosomal target sequence” (id. at 12).
We disagree with the Examiner’s interpretation of the claim language.
To those of ordinary skill in the art, “chromosomal DNA” denotes a
category of DNA that occurs naturally as part of a chromosome, as opposed
to synthetic DNA having a sequence determined by the synthesizer. The
Specification also makes clear that a chromosomal target sequence is one
that resides in a chromosome when it is bound by a zinc finger protein. See
FF 9 (“a three finger polypeptide able to bind site-specifically to a unique 9
bp region of the BCR-ABL fusion oncogene . . . show[s] that binding to the
target oncogene in chromosomal DNA is possible,” emphasis added). In
addition to this, the Specification refers to designing zinc finger proteins to
other natural occurring mutations that reside in the genomic, and therefore
chromosomal, DNA (col. 32, l. 10 to col. 32, 56). Therefore, when read in
light of the Specification, “a particular chromosomal target DNA sequence”
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means a particular sequence that is found in a chromosome as a naturally
occurring part of it.
The Examiner has not shown that a zinc finger fusion protein that
binds to a particular sequence that is found in a chromosome as a naturally
occurring part of it is either disclosed or suggested by the references relied
on to show obviousness. Because the Examiner has not shown that a
product meeting all of the limitations of the claims would have been obvious
based on the prior art and the knowledge of a person of ordinary skill, she
has not made out a prima facie case of obviousness under 35 U.S.C. § 103.
Conclusions of Law
The Examiner erred in concluding that the cited references would
have suggested a fusion protein “designed to bind to a particular
chromosomal target DNA sequence,” as required by the claims.
SUMMARY
We reverse the rejection of claims 42, 43, and 52 based on Desjarlais,
Courey, Anderson, and Narayan and the rejection of claim 44 based on
Desjarlais, Courey, Anderson, Narayan, and Sadowski.

REVERSED

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