Ex Parte Raschke et al

Board of Patent Appeals and Interferences

Jan 4, 2012

09844662 (B.P.A.I. Jan. 4, 2012)

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.
09/844,662 04/27/2001 Eva Raschke 8325-0012 9004
20855 7590 01/05/2012
ROBINS & PASTERNAK
1731 EMBARCADERO ROAD
SUITE 230
PALO ALTO, CA 94303
EXAMINER
KELLY, ROBERT M
ART UNIT PAPER NUMBER
1633
MAIL DATE DELIVERY MODE
01/05/2012 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 EVA RASCHKE, ALAN P. WOLFFE, and
CASEY C. CASE
__________

Appeal 2011-007277
Application 09/844,662
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and STEPHEN WALSH,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This appeal under 35 U.S.C. § 134 involves claims related to a non-
naturally occurring zinc finger protein. The Examiner has rejected the
claims for lack of adequate written description, anticipation, and
obviousness. We have jurisdiction under 35 U.S.C. § 6(b). We reverse the
written description rejections but affirm the rejections based on prior art.
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STATEMENT OF THE CASE
Claims 57 and 68-71 are on appeal. Claim 57 is representative and
reads as follows:
57. A cell comprising a complex between
a non-naturally occurring zinc finger protein comprising 3 or more
zinc finger domains, wherein the zinc finger domains comprise a non-
naturally occurring recognition helix and
chromosomal cellular chromatin;
wherein the zinc finger protein is bound to a target site in a region of
the cellular chromatin that is sensitive to digestion with DNAseI.

The claims stand rejected as follows:
• Claims 57 and 68-71 under 35 U.S.C. § 112, first paragraph, “for
being drawn to new matter” (Answer 6);
• Claims 57 and 68-71 under 35 U.S.C. § 112, first paragraph, “as
failing to comply with the written description requirement and the new
matter portion of written description” (Answer 7);
• Claims 57, 68, 70, and 71 under 35 U.S.C. § 102(e) as anticipated
by Choo1 (Answer 8); and
• Claims 57 and 68-71 under 35 U.S.C. § 103(a) as obvious based on
Choo and Dangl2 (Answer 9).
I.
The Examiner has rejected all of the claims on appeal for failing to
comply with the written description provision of 35 U.S.C. § 112, first
paragraph (Answer 6-7). The Examiner sets out two separate rejections
supported by different lines of reasoning.

1 Choo et al., US 6,013,453, Jan. 11, 2000
2 Dangl et al. WO 98/37755, Sept. 3, 1998
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In his first line of reasoning, the Examiner characterizes the claims as
being directed to “complexes in cells, in which a generic zinc finger
comprising at least 3 fingers, one of which recognizes a generic non-
naturally occur[r]ing finger is bound to cellular chromatin in a region
sensitive to digestion with DNAse I” (id. at 6). The Examiner finds that
“[t]here is simply no implicit or explicit description in the original claims
and/or specification to demonstrate that Appellant had considered such
genera to be the invention” (id.).
Appellants argue that “the skilled artisan would have no doubt . . . that
Appellants were in possession of [the claimed] non-naturally occurring zinc
finger proteins at the time of filing” (Appeal Br. 6). Appellants quote
numerous passages from the Specification that, in their view, demonstrate
possession of the claimed subject matter to a person of ordinary skill in the
art (id. at 6-9).
We agree with Appellants that the cited passages would have been
recognized by those of ordinary skill in the art as showing possession of the
claimed subject matter within the standard required by 35 U.S.C. § 112, first
paragraph. The rejection based on new matter is reversed.
The Examiner’s second line of reasoning is that the claims encompass
non-naturally occurring zinc finger proteins but the Specification “does not
teach the structure of all zinc finger proteins, nor does it teach what
mutations are non-naturally occurring” and therefore does not show
possession of the genus of non-naturally occurring zinc finger proteins
(Answer 7-8).
Appellants argue that adequacy of written description must be
considered in the context of what is known in the art at the time of filing
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(Appeal Br. 9) and that “there are a myriad of references cited in the
specification regarding zinc finger proteins containing non-naturally
occurring recognition helices and how to make and use these proteins” (id.).
Appellants cite several passages from the Specification to support their
position (id. at 9-10).
Again, we agree with Appellants. The test of adequate written
description is “whether the disclosure of the application relied upon
reasonably conveys to those skilled in the art that the inventor had
possession of the claimed subject matter as of the filing date.” Ariad
Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010). “The
descriptive text needed to meet these requirements varies with the nature and
scope of the invention at issue, and with the scientific and technologic
knowledge already in existence.” Capon v. Eshhar, 418 F.3d 1349, 1357
(Fed. Cir. 2005).
Appellants have pointed to evidence that a variety of non-naturally
occurring zinc finger proteins were known in the art. Appellants also point
out that Choo (discussed infra) discloses that zinc finger motifs had been
well studied and were known to bind specific sites according to known rules
(see Appeal Br. 10-11). In view of the state of the art, the Examiner has not
adequately explained why a description of “the structure of all zinc finger
proteins . . . [or] what mutations are non-naturally occurring” (Answer 7)
would be required in order for a skilled worker to recognize possession of
the claimed invention in Appellants’ Specification. The second rejection for
lack of adequate written description is reversed.
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II.
Issue
The Examiner has rejected claims 57, 68, 70, and 71 as anticipated by
Choo (Answer 8). The Examiner cites Choo’s working example that shows
“the making of a mutant Zinc finger protein, which has 3 fingers, and binds
to the coding sequence for a specific ras mutation which commonly occurs
and causes oncogenesis” (Answer 8-93). The Examiner finds that “Choo
teaches that the mutant Zinc finger protein can be used to bind the mutant
ras gene in human cells in research” (id. at 9).
Appellants contend that the claims require a zinc finger protein bound
to “chromosomal cellular chromatin,” which the Specification defines as
endogenous chromatin (Appeal Br. 12), and “Choo’s Bcr-Abl site is
synthesized and then inserted into the genome. Thus, Choo’s protein is not
binding to endogenous chromosomal cellular chromatin.” (Id. at 13.)
Appellants argue that “Choo also fails to explicitly or inherently teach the
claim element of binding to an endogenous chromosomal site that is
sensitive to digestion with DNAseI” (Reply Br. 14).
The issue with respect to this rejection is: Does the evidence support
the Examiner’s finding that Choo discloses a cell meeting the limitations of
claim 57?
Findings of Fact
1. Choo discloses that the “human ras gene is susceptible to a number
of different mutations, which can convert it into an oncogene. . . . One

3 The Examiner cites Choo’s Example 4 but the work described by the
Examiner is part of Choo’s Example 5 (Choo, cols. 31-32).
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particular mutation is known as the G12V mutation.” (Choo, col. 31, ll. 2-
5.)
2. Choo discloses that a “three finger protein has been designed
which can recognise the G12V mutant of ras. The protein was produced
using rational design based on the known specificity rules.” (Id. at col. 31,
ll. 10-12.)
3. Choo describes construction of the G12V-binding zinc finger
protein (see id. at col. 31, l. 11 to col. 32, l. 16).
4. Choo discloses that “[a]ssay of the protein in eukaryotes (e.g. to
drive CAT reporter production) requires the use of a weak [p]romoter. . . .
For this reason, a regulatable promoter (e.g. for tetracycline) will be used to
deliver the protein in therapeutic applications.” (Id. at col. 32, ll. 28-34.)
5. Choo discloses that “[s]ince the G12V mutation is a naturally
occurring genomic mutation (not only a cDNA mutation as was the p190
bcr-abl) human cell lines and other animal models can be used in research”
(id. at col. 32, ll. 37-40).
6. In a different example, Choo describes “creat[ing] a three finger
polypeptide able to bind site-specifically to a unique 9 bp region of a BCR-
ABL fusion oncogene” (id. at col. 25, ll. 45-47).
7. Choo states that “the primary aim here is to prove the principle of
protein design, and to assess the feasibility of in vivo binding to
chromosomal DNA in available model systems” (id. at col. 26, ll. 42-45).
8. Choo discloses that the designed polypeptide (“referred to as the
anti-BCR-ABL peptide,” id. at col. 27, ll. 29-30) bound site-specifically to
plasmid DNA in vivo (id. at col. 28, ll. 39-42).
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9. Choo stated that “the true target site for this and most other DNA-
binding proteins is in genomic DNA. This might well present significant
problems, not least since this DNA is physically separated from the cytosol
by the nuclear membrane, but also since it may be packaged within
chromatin.” (Id. at col. 28, ll. 42-47.)
10. Choo carried out an experiment to test binding of the anti-BCR-
ABL peptide to a target site in genomic DNA (see id. at col. 28, l. 49 to col.
30, l. 4).
11. Choo concluded that “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”
(id. at col. 30, ll. 5-9).
Analysis
Choo discloses a man-made (and therefore non-naturally occurring)
zinc finger protein comprising three zinc finger domains having recognition
helices designed to bind to the sequence of a mutant ras oncogene (FFs 1-3).
Choo discloses expression of this protein in eukaryotic cells under control of
a regulatable promoter (FF 4) for use in “human cell lines and other animal
models . . . in research” (FF 5).
We agree with the Examiner that Choo’s Example 5 anticipates claim
57. Although Choo does not describe carrying out the disclosed expression
of its G12V-binding protein in human cells, “anticipation does not require
actual performance of suggestions in a disclosure. Rather, anticipation only
requires that those suggestions be enabling to one of skill in the art.”
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Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1379
(Fed. Cir. 2001).
The facts of this case are similar to those of Bristol-Myers Squibb. In
that case, the ‘537 patent claimed a method of treating a tumor with a
specific regimen of taxol after premedicating the patient. 246 F.3d at 1371.
The Kris reference disclosed the same taxol treatment regimen and stated
that “[f]urther studies are needed to see if pretreatment regimens, alternative
schedules . . . or a reformulated preparation will permit the safe
administration of this compound.” Id. at 1372 (alterations by the Bristol-
Myers Squibb court). “Kris did not employ the suggested pretreatment
regimens in that study.” Id.
The court held that the relevant claims of the ‘537 patent were
anticipated by Kris, id. at 1378, because “although he did not actually
premedicate the patients himself, anticipation does not require actual
performance of suggestions in a disclosure. Rather, anticipation only
requires that those suggestions be enabling to one of skill in the art.” Id. at
1379.
Here, as in Bristol-Myers Squibb, although Choo did not actually
transform human or animal cells with the G12V-binding polypeptide, it
disclosed the transformed cells sufficiently to be enabling to one of skill in
the art. The enabling nature of Choo’s disclosure is evidenced by its
Example 3, which demonstrates that a designed zinc finger protein binds to
its target even when that target is located in chromosomal DNA (see FFs 6-
11).
Appellants argue that “chromosomal cellular chromatin” is limited to
endogenous chromatin when the claim language is read in light of the
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Specification (Appeal Br. 12) and Choo’s Example 3 does not anticipate the
claims, because the target site in that example was inserted, not endogenous
(id. at 13).
This argument is not persuasive because the Examiner’s rejection is
based on Choo’s disclosure of a zinc finger protein designed to bind the
naturally occurring G12V ras mutation (Example 5) not the BCR-ABL-
binding polypeptide disclosed in Example 3.
Appellants also argue that Choo does not expressly or implicitly
describe “binding to an endogenous chromosomal site that is sensitive to
digestion with DNAseI” (Reply Br. 14).
However, as the Examiner has pointed out (Answer 9), the
Specification does not provide any definition of the claim language that
limits the size of the “region of the cellular chromatin” or the degree of
“sensitiv[ity] to digestion with DNAseI” that is required by the claims.
Therefore, it is reasonable to conclude that the ras mutation bound by
Choo’s G12V-binding protein meets the broadest reasonable interpretation
of being located in some “region of the cellular chromatin” that is to some
degree “sensitive to digestion with DNAseI.”
Conclusion of Law
The evidence support the Examiner’s finding that Choo discloses a
cell meeting the limitations of claim 57. Claims 68, 70, and 71 were not
argued separately and therefore fall with claim 57. 37 C.F.R.
§ 41.37(c)(1)(vii).
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III.
Issue
The Examiner has rejected all of the claims on appeal as obvious
based on Choo and Dangl (Answer 9). The Examiner notes that Choo does
not disclose plant cells, as recited in claim 69, but finds that “Dangl
demonstrates that zinc fingers occur, and regulate pathways . . . in plant
cells” (id. at 10). The Examiner concludes that it would have been obvious
to practice Choo’s methods in plant cells in order to study point mutations in
plant cells (id.).
We agree with the Examiner’s reasoning. Dangl discloses that a
family of zinc finger proteins regulate a plant cell death pathway and
apparently control the plant cells’ response to pathogens (Dangl, abstract).
Choo discloses that custom-designed zinc finger proteins are useful in
research (FF 5). Therefore, it would have been obvious to a person of
ordinary skill in the art to combine Choo’s method of designing and
expressing zinc finger proteins with target sites in plant cells in order to
conduct research into plant cells’ response to pathogens.
Appellants argue that they have “provided ample evidence
establishing that binding of zinc finger proteins to a sequence randomly
inserted into the cell is entirely unlike binding of zinc finger proteins to
chromosomal cellular chromatin as claimed” (Appeal Br. 14). Appellants
cite the Beerli and Borman references as evidence supporting their position
(id. at 14-15).
However, the Examiner states that Beerli and Borman “have not been
officially considered . . . because Appellant provided them in the After-final
argument without explaining good and sufficient reasons why it could not
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have been presented earlier” (Answer 21). Since Beerli and Borman are not
part of the official record, we have not considered them. In any event, as
discussed above in the context of anticipation, the Examiner’s rejections are
based on Choo’s disclosure of zinc-finger proteins designed to bind to
endogenous sites such as the G12V ras mutation and therefore any
differences in binding to an endogenous site and a target site inserted into a
chromosome do not appear to be relevant to the reasoning underlying the
Examiner’s rejections.
SUMMARY
We reverse both of the rejections of claims 57 and 68-71 based on 35
U.S.C. § 112, first paragraph. We affirm the rejection of claims 57, 68, 70,
and 71 based on 35 U.S.C. § 102(e) and the rejection of claims 57 and 68-71
based on 35 U.S.C. § 103(a).
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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