Ex Parte Cox et al

Board of Patent Appeals and Interferences

Oct 4, 2010

10986583 (B.P.A.I. Oct. 4, 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.
10/986,583 11/12/2004 George Norbert Cox III 8325-0002.05 7953
20855 7590 10/04/2010
ROBINS & PASTERNAK
1731 EMBARCADERO ROAD
SUITE 230
PALO ALTO, CA 94303
EXAMINER
KELLY, ROBERT M
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
10/04/2010 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 GEORGE NORBERT COX III,
CASEY CHRISTOPHER CASE, STEPHEN P. EISENBERG,
ERIC EDWARD JARVIS, and SHARON KAYE SPRATT
__________

Appeal 2010-004357
Application 10/986,583
Technology Center 1600
__________

Before ERIC GRIMES, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to a cell
comprising an engineered zinc finger protein which comprises an integrase.

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.
Appeal 2010-004357
Application 10/986,583

2
The Examiner rejected the claims as obvious and for nonstatutory
obviousness-type double patenting. We have jurisdiction under 35 U.S.C.
§ 6(b). We affirm.
Statement of the Case
The Claims
Claims 1-7 are on appeal. Claims 1 and 2 are representative
of the argued claims. The remaining claims have not been argued
separately and therefore stand or fall together. 37 C.F.R. §
41.37(c)(1)(vii). Claims 1 and 2 read as follows:
1. A cell comprising an engineered zinc finger
protein that binds to an endogenous cellular gene
in the cell, wherein the zinc finger protein further
comprises an integrase or a functional fragment
thereof.

2. The cell of claim 1, wherein the cell is a
plant cell.

The issues2
A. The Examiner rejected claims 1-7 on the ground of nonstatutory
obviousness-type double patenting (Ans. 6-8).
B. The Examiner rejected claims 1 and 3-7 under 35 U.S.C. § 103(a) as
obvious over Chow3 and Choo4 (Ans. 9-10).

2 We note, but do not address, the arguments over the petitionable
issue of identifying related appeals and interferences in an Appeal
Brief.
3 Chow et al., WO 97/20038 A1, published Jun. 5, 1997.
4 Choo et al., WO 96/06166 A1, published Feb. 29, 1996.
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C. The Examiner rejected claims 1 and 2 under 35 U.S.C. § 103(a) as
obvious over Chow, Choo, and Takatsuji5 (Ans. 10-11).
A. Nonstatutory obviousness-type double patenting
The Examiner finds that:
Each of the claims encompasses the composition of a zinc-
finger protein, which is also taught in the specifications to be
a fusion protein for inter alia an integrase or a functional
fragment thereof. Further, each of cellular genes, plant cells,
and human hematopoietic stem cells are taught. Hence,
common embodiments are claimed in each of the patents
with the presently claimed subject matter. Still further, in
none of the patents was the subject matter restricted such
that double-patenting rejections would not be allowed.

(Ans. 8.)
Appellants contend that
on October 15, 2008 Appellants submitted [] a Terminal
Disclaimer over the cited patents and applications. As noted
in § 802.04 of the MPEP submission of the terminal
disclaimer was not an admission that the rejections were
proper . . . the obviousness-type double patenting rejections
are improper and, in addition, have been obviated by the
filing of a Terminal Disclaimer.

(App. Br. 7.)
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s obviousness-type double patenting rejections?

5 H. Takatsuji, Zinc-finger transcription factors in plants, 54 CELL.
MOL. LIFE SCI. 582-596 (1998).
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Findings of Fact
1. The double patenting rejections are over U.S. Patents
7,067,317; 7,045,304; 7,026,462; 6,989,269; and 6,689,558; and
applications 11/486,994 and 11/115,922 (see Ans. 7-8).
2. A terminal disclaimer was filed on October 15, 2008 over U.S.
Patents 7,067,317; 7,045,304; 7,026,462; and 6,989,269 and any patent
issuing from U.S. Application Nos. 11/486,994 and 11/115,922.
3. While the terminal disclaimer acknowledges ownership of U.S.
Patent 6,689,558, there is no disclaimer regarding this patent.
4. Claim 1 of U.S. Patent 6,689,558 is reproduced below:
1. A method of screening a compound for
interaction with a molecular target comprising:
(a) contacting a first cell with the compound;
(b) determining a first value of a property of the first
cell, the property being responsive to, levels of the
molecular target;
(c) contacting a second cell with the compound,
wherein the second cell comprises a polynucleotide
encoding an exogenous zinc finger protein that directly or
indirectly modulates expression of the molecular target;
(d) determining a second value of the property in the
second cell, wherein a difference between the first and
second values provides an indication of interaction between
the compound and the molecular target.

Principles of Law
Obviousness-type double patenting … requires
rejection of an application claim when the claimed subject
matter is not patentably distinct from the subject matter
claimed in a commonly owned patent. Its purpose is to
prevent an unjustified extension of the term of the right to
exclude granted by a patent by allowing a second patent
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claiming an obvious variant of the same invention to issue to
the same owner later.

In re Berg, 140 F.3d 1428, 1431-1432 (Fed. Cir. 1998) (citations omitted).
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).
The Supreme Court has emphasized that “the [obviousness] analysis
need not seek out precise teachings directed to the specific subject matter of
the challenged claim, for a court can take account of the inferences and
creative steps that a person of ordinary skill in the art would employ.” KSR
Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
We can summarily reverse the double patenting rejections over U.S.
Patents 7,067,317; 7,045,304; 7,026,462; and 6,989,269 and the provisional
double patenting rejections over U.S. Application Nos. 11/486,994 and
11/115,922 since Appellants have filed a terminal disclaimer which was
accepted by the Office, mooting these rejections (FF 2).
The terminal disclaimer does not address U.S. Patent 6,689,558 (FF
3).
However, claim 1 (and the dependent claims) of U.S. Patent
6,689,558 do not teach or suggest the use of an integrase in a zinc finger
protein (see, e.g., FF 4). Without any teaching of an integrase required by
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the instant claim 1, we conclude the Examiner has not shown that instant
claim 1 would be obvious over the claims of U.S. Patent 6,689,558.
The Examiner argues that the “presently claimed zinc finger protein is
a protein which is taught in each specification as optionally-linked to an
integrase” (Ans. 15).
We are not persuaded. The teaching of an “integrase” is only found in
the specification and not in the claims of U.S. Patent 6,689,558. Therefore,
the Examiner improperly relies upon the specification of U.S. Patent
6,689,558 as prior art in the double patenting inquiry. See In re Kaplan, 789
F.2d 1574, 1580 (Fed. Cir. 1986) (“There is no way the board could have
found appellants' claimed invention to be an obvious variation of what
Kaplan claims except by treating the Kaplan patent disclosure as though it
were prior art. This has repeatedly been held in our precedents to be
impermissible.”)
Conclusion of Law
The evidence of record does not support the Examiner’s obviousness-
type double patenting rejection over the ‘558 patent claims.
B. 35 U.S.C. § 103(a) over Chow and Choo
The Examiner finds that the “broadest reasonable interpretation of the
limitation claimed of ‘an engineered zinc finger protein’ is any zinc finger
protein modified by the hand of man, and further considering that the
modification may be to remove the zinc finger domain and attach it to the
claimed linked-integrase” (Ans. 17). The Examiner finds it obvious to “to
modify the cells of Chow et al. to comprise engineered zinc finger domains
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as shown in Choo et al. because Choo et al. shows that zinc finger domains
can be engineered to bind to a desired DNA sequence” (id. at 10).
Appellants contend that “as clearly defined throughout the as-filed
specification, an ‘engineered’ zinc finger protein is one in which at least one
recognition helix of a component zinc finger is altered, as compared to a
naturally occurring zinc finger, to bind to a pre-selected target site” (App.
Br. 8-9).
Appellants contend that “the evidence of record establishes, Choo and
the art as a whole, clearly demonstrate that engineered zinc finger proteins
were not expected to bind to endogenous cellular genes” (id. at 10).
Appellants contend that “as late as 2000, the skilled artisan is on the record
as stating that endogenous gene regulation with engineered zinc finger
proteins was unexpected” (id. at 12).
The issue with respect to this rejection is: Does the evidence of record
support the Examiner’s conclusion that Choo and Chow render obvious a
cell comprising an “engineered” zinc finger protein that binds to an
endogenous cellular gene and further comprises an integrase?
Findings of Fact
5. The Specification teaches that the “present invention thus
provides zinc finger DNA binding proteins that have been engineered to
specifically recognize, with high efficacy, endogenous cellular genes” (Spec.
10, ll. 19-21).
6. The Specification teaches that the “ZFPs [zinc finger proteins]
of the invention are engineered to recognize a selected target site in the
endogenous gene of choice . . . A number of methods can then be used to
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design and select a ZFP with a high affinity for its target” (Spec. 21, ll. 10-
15).
7. The Specification teaches that “[a]ny suitable method known in
the art can be used to design and construct nucleic acids encoding ZFPs, e.g.,
phage display, random mutagenesis, combinatorial libraries,
computer/rational design, affinity selection, PCR, cloning from cDNA or
genomic libraries, synthetic construction and the like” (Spec. 21, ll. 21-24).
8. The Specification teaches that:
After a target segment has been selected, a ZFP that
binds to the segment can be provided by a variety of
approaches. The simplest of approaches is to provide a
precharacterized ZFP from an existing collection that is
already known to bind to the target site. However, in many
instances, such ZFPs do not exist. An alternative approach
can also be used to design new ZFPs, which uses the
information in a database of existing ZFPs and their
respective binding affinities. A further approach is to design
a ZFP based on substitution rules as discussed above. A still
further alternative is to select a ZFP with specificity for a
given target by an empirical process such as phage display.

(Spec. 24, ll. 23-30.)
9. Chow teaches that a “further aspect of the present invention is a
fusion protein comprising a catalytic domain of retroviral integrase and an
N-terminal zinc finger domain having binding specificity for a DNA
molecule. In this case, the zinc finger domain is other than a zinc finger
domain naturally occurring with the catalytic domain in a retroviral
integrase” (Chow 14, ll. 23-27).
10. Chow teaches that:
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The present example provides another potential
approach for engineering integration proteins having site-
specificity for binding to DNA. The present inventors
envision the replacement of the N-terminal zinc-finger motif
of integrase (from about amino acids 1-50) with other zinc-
finger protein domains having binding specificity for DNA
sequences (Berg, 1990; Klug and Rhodes, 1987). In this
approach, the zinc-finger motif of integrase will be deleted
and replaced with other zinc-finger motif that recognizes
specific DNA sequences. By exchanging the zinc-finger
motif, the resulting hybrid protein may retain the integration
activity and may gain an added ability to recognize specific
DNA sequences.

(Chow 61, ll. 19-27.)
11. Choo teaches that “the zinc finger polypeptide may
advantageously comprise functional domains from other proteins (e.g.
catalytic domains from . . . integrases and the like)” (Choo 12).
12. Choo teaches
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 . . . .

(Choo 12).
13. Choo teaches that
it should be well within the capability of one of normal skill
in the art to design a zinc finger polypeptide capable of
binding to any desired target DNA sequence simply by
considering the sequence of triplets present in the target
DNA and combining in the appropriate order zinc fingers
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comprising zinc finger binding motifs having the necessary
binding characteristics to bind thereto.

(Choo 9.)
14. Choo teaches that
the inventors have created a three finger polypeptide able to
bind site-specifically to a unique 9bp region of a 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.

(Choo 40.)
15. Choo teaches that in “summary, the inventors have
demonstrated that a DNA-binding protein designed to recognise a specific
DNA sequence in vitro, is active in vivo where, directed to the nucleus by an
appended localisation signal, it can bind its target sequence in chromosomal
DNA” (Choo 47).
16. Beerli6 teaches “[w]hile our early experiments have focused on
the regulation of genes transiently introduced into cells, we realized that the
willful and specific regulation of endogenous genes with designed
transcription factors has remained an unmet challenge in biology” (Beerli
1495, col. 1).

6 Beerli et al., Positive and negative regulation of endogenous
genes by designed transcription factors, 97 PROC. NAT’L ACAD.
SCI. USA 1495-1500 (2000).
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17. Borman7 quotes Barbas as saying “[t]his is the first time we've
been able to show that these designed transcription factors work on real
genes and real chromosomes, not genes or binding sites that have been
introduced into cells” (Borman 34).
18. Borman reports that “Choo, Klug, and coworkers have already
developed a new zinc finger display strategy that makes it possible to target
more or less any 18-base-pair DNA sequence – not just repeating GNN
triplets . . . some of the information has already appeared in patent
applications filed by Gendaq Ltd” (Borman 35).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR, 550 U.S. 398, 416 (2007). “If a person of ordinary skill can implement
a predictable variation, § 103 likely bars its patentability.” Id. at 417. As
noted by the Court in KSR, “[a] person of ordinary skill is also a person of
ordinary creativity, not an automaton.” 550 U.S. at 421.
Kubin stated that “[r]esponding to concerns about uncertainty in the
prior art influencing the purported success of the claimed combination, this
court [in O’Farrell] stated: ‘[o]bviousness 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) (citing In re
O’Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)).

7 Borman, S., DNA-Binding Proteins Turn Genes On and Off, CHEMICAL
ENGINEERING NEWS 34-35 (Feb. 1, 2000).

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Claim terms are interpreted using the broadest reasonable
interpretation in light of the Specification. See, e.g., In re Hyatt, 211 F.3d
1367, 1372 (Fed. Cir. 2000) (“[D]uring examination proceedings, claims are
given their broadest reasonable interpretation consistent with the
specification.”).
Analysis
Claim Interpretation
Claim interpretation is at the heart of patent examination because
before a claim is properly interpreted, its scope cannot be compared to the
prior art. Appellants challenge the Examiner’s interpretation of the term
“engineered” in Claim 1. Appellants contend that “as clearly defined
throughout the as-filed specification, an ‘engineered’ zinc finger protein is
one in which at least one recognition helix of a component zinc finger is
altered, as compared to a naturally occurring zinc finger, to bind to a pre-
selected target site” (App. Br. 8-9).
During prosecution, claim terms are given their broadest reasonable
interpretation as they would be understood by persons of ordinary skill in the
art in the light of the Specification. Therefore, we first turn to the
Specification to determine whether the meaning of the term “engineered”
can be discerned.
There is no specific definition of the term “engineered” in the
Specification. While the Specification teaches zinc finger DNA binding
proteins “that have been engineered to specifically recognize, with high
efficacy, endogenous cellular genes” (Spec. 10, ll. 19-21; FF 5), the
Specification expressly recognizes that “a ZFP that binds to the segment can
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be provided by a variety of approaches. The simplest of approaches is to
provide a precharacterized ZFP from an existing collection that is already
known to bind to the target site” (Spec. 24, ll. 23-26; FF 8).
Thus, the broadest reasonable interpretation of the Specification is that
zinc binding proteins may be “engineered” by identifying precharacterized
existing proteins, as well as by synthesizing or modifying known proteins
(see FF 6-7).
Chow and Choo
Chow teaches “a fusion protein comprising a catalytic domain of
retroviral integrase and an N-terminal zinc finger domain having binding
specificity for a DNA molecule. In this case, the zinc finger domain is other
than a zinc finger domain naturally occurring with the catalytic domain in a
retroviral integrase” (Chow 14, ll. 23-27; FF 9).
Choo teaches
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.

(Choo 12; FF 12.)
Choo teaches that “the zinc finger polypeptide may advantageously
comprise functional domains from other proteins (e.g. catalytic domains
from . . . integrases and the like)” (Choo 12; FF 11). Choo teaches “to
design a zinc finger polypeptide capable of binding to any desired target
DNA sequence simply by considering the sequence of triplets present in the
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target DNA and combining in the appropriate order zinc fingers comprising
zinc finger binding motifs having the necessary binding characteristics to
bind thereto” (Choo 9; FF 13).
Applying the KSR standard of obviousness to the findings of fact, we
conclude that the person of ordinary creativity would have predictably
formed a cell which comprises Chow’s fusion protein of a zinc finger fused
to an integrase (FF 9-10), where the fusion protein is designed as taught by
Choo to bind to a DNA regulatory region of a known gene of interest (FF
11-13). Such a combination is merely a “predictable use of prior art
elements according to their established functions.” KSR, 550 U.S. at 417.
Whether we accept Appellants narrow interpretation of “engineered”
or the Examiner’s broader interpretation, the only reasonable interpretation
of Choo’s teaching to design a zinc finger to bind to any desired target DNA
sequence is that such a designed protein would be “engineered” to bind to
the desired target (see FF 13). Therefore even applying Appellants’ narrow
interpretation of “engineered,” we conclude that Choo teaches an
“engineered” zinc finger protein (FF 11-14).
Appellants contend that as “the evidence of record establishes, Choo
and the art as a whole, clearly demonstrate that engineered zinc finger
proteins were not expected to bind to endogenous cellular genes” (App. Br.
10). Appellants contend that the “cited reference, Choo, clearly teaches it
was not predicted that engineered zinc finger proteins would bind to
endogenous cellular genes because of their context within chromatin” (id. at
11).
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We are not persuaded. The very next sentence in Choo after that
quoted by Appellants directly addresses the question, stating “[t]o study
whether genomic targeting is possible, a construct was made” (Choo 45).
Choo performed the experiment and concluded that in “summary, the
inventors have demonstrated that a DNA-binding protein designed to
recognise a specific DNA sequence in vitro, is active in vivo where, directed
to the nucleus by an appended localisation signal, it can bind its target
sequence in chromosomal DNA” (Choo 47; FF 15). Choo expressly
demonstrates success where by 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” (Choo 40; FF 14).
Thus, contrary to Appellants’ argument, Choo clearly teaches that the
engineered zinc finger proteins function in actual model systems to bind
cellular genes (FF 14-15).
Appellants contend that “as late as 2000, the skilled artisan is on the
record as stating that endogenous gene regulation with engineered zinc
finger proteins was unexpected” (App. Br. 12).
We are not persuaded. Appellants are relying upon the teachings in
Beerli and Borman (see App. Br. 11-12). However, Beerli does not teach
that Choo or Chow will not function, nor does Beerli demonstrate
knowledge of the Choo or Chow patent publications.
Further, while Borman reports the statement made by Beerli, Borman
also makes reference to Choo, noting that “Choo, Klug, and coworkers have
already developed a new zinc finger display strategy that makes it possible
to target more or less any 18-base-pair DNA sequence – not just repeating
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GNN triplets . . . some of the information has already appeared in patent
applications filed by Gendaq Ltd” (Borman 35; FF 18).
Given the express teaching by Chow to form a fusion protein of a zinc
finger and an integrase (FF 9-10), and the demonstrated success by Choo in
targeting model systems with designed zinc finger proteins (FF 11-15), we
conclude that the prior art provided a reasonable expectation of success. See
Kubin, 561 F.3d at 1360 (citing In re O’Farrell, 853 F.2d at 903-904). In
the instant case, we have much more than a “reasonable” expectation of
success given the demonstrated success shown by Choo (FF 14-15).
Conclusion of Law
The evidence of record supports the Examiner’s conclusion that Choo
and Chow render obvious a cell comprising an “engineered” zinc finger
protein that binds to an endogenous cellular gene and further comprises an
integrase.
C. 35 U.S.C. § 103(a) over Chow, Choo, and Takatsuji
The Examiner finds it obvious “to modify the cells of Chow et al. in
view of Choo et al. as applied to claims 1 and 3-7 above by use of plant cells
because Takatsuji et al. shows that plant cells are useful hosts to study zinc
finger regulation of gene expression” (Ans. 11).
The Examiner provides sound fact-based reasoning for combining
Chow, Choo, and Takatsuji. As Appellants do not identify any material
defect in the Examiner's reasoning, and only argue the underlying rejection
of Chow and Choo which we affirmed above, we affirm the this rejection for
the reasons stated by the Examiner.

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SUMMARY
In summary, we reverse the rejection of claims 1-7 under on the
ground of nonstatutory obviousness-type double patenting over U.S. Patent
6,689,558.
We affirm the rejection of claim 1 under 35 U.S.C. § 103(a) as
obvious over Chow and Choo. Pursuant to 37 C.F.R. §
41.37(c)(1)(vii)(2006), we also affirm the rejection of claims 3-7 as these
claims were not argued separately.
We affirm the rejection of claims 1 and 2 under 35 U.S.C. § 103(a) as
obvious over Chow, Choo, and Takatsuji.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv)(2006).

AFFIRMED

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