Ex Parte Choo et al

Patent Trial and Appeal Board

Aug 23, 2013

11514850 (P.T.A.B. Aug. 23, 2013)

UNITED STATES PATENT AND TRADEMARK OFFICE
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BEFORE THE PATENT TRIAL AND APPEAL BOARD
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Ex parte YEN CHOO, AARON KLUG,
and MARK ISALAN
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Appeal 2011-006471
Application 11/514,850
Technology Center 1600
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Before TONI R. SCHEINER, DONALD E. ADAMS, and
MELANIE L. McCOLLUM, Administrative Patent Judges.

SCHEINER, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1 under 35 U.S.C. § 134 from the final rejection of
claims 1-8, directed to a method of making a zinc finger protein. The claims
have been rejected on the grounds of obviousness and non-statutory
obviousness-type double patenting. We have jurisdiction under 35 U.S.C.
§ 6(b).

1 Appellants identify the Real Party-In-Interest as Gendaq Ltd., a wholly
owned subsidiary of Sangamo Biosciences, Inc. (App. Br. 3).
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STATEMENT OF THE CASE
The present invention is directed to a method of making a three finger
zinc finger protein through randomization, selection, and recombination.
The Specification explains that a three-finger zinc finger protein (i.e., with
fingers F1, F2, and F3) may be generated by recombining zinc finger
proteins from first and second zinc finger libraries.
[A] three [finger] zinc finger polypeptide comprising fingers
F1, F2 and F3 may be presented in a set of two libraries, each
library comprising a two zinc finger polypeptide. A first library
is composed of polypeptides consisting essentially of F1 and
F2, whilst a second library is composed of polypeptides
consisting essentially of F2 and F3. The randomisation in each
library includes the overlap between F1 and F2, and F2 and F3
respectively.
Preferably, each library will comprise randomisation at at
least position 6 of a first finger and position 2 of a second
finger. Since these residues contact the same base pair on a
double stranded nucleic acid target, it is advantageous that they
be varied together.
In the case of a three [finger] zinc finger polypeptide, the
first library will be randomised in fingers F1 and F2, whilst the
second is randomised in F2 and F3. Polypeptides may be
recombined, post-selection, in the F2 sequence to create a
single polypeptide containing F1, F2 and F3. This polypeptide
will have been selected taking into account the overlap between
F1 and F2, and F2 and F3.
(Spec. 8: 30 - 9: 15.)
In order that the libraries may be recombined after
selection, the polypeptides are preferably designed to include a
suitable restriction site in the nucleic acid encoding the zinc
finger shared by two libraries. The position of the cleavage site
will dictate the precise site of the variations made in the shared
zinc finger in each library. Thus, in a set of two libraries
encoding a three zinc finger protein, if the cleavage site is
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between positions 3 and 5 of the α-helix, positions 3 and 5 may
be randomised in a first library and positions 5 and 6 in a
second.
(Id. at 9: 24-30.)
In a preferred embodiment, a two-library system for
selection of a three-finger protein is varied at F1 positions -1, 2,
3, 5, and 6 and F2 positions -1, 1, 2 and 3 in the first library.
The second library is varied at F2 positions 3 and 6 and F3
positions -1, 1, 2, 3, 5 and 6. In this case, the cleavage and
recombination point will be between residues 3 and 5,
preferably between residues 4 and 5, of the α-helix of F2.
(Id. at 10: 6-10.)
Claims 1-8 are pending and on appeal. Claim 1, the sole independent
claim, is representative of the subject matter on appeal:
1. A method of providing a zinc finger protein comprising first, second
and third zinc fingers, each having positions -1 to 9 with position 1
representing the first amino acid of an alpha-helix, the method comprising:
selecting a first zinc finger protein comprising first and second zinc
fingers from a first library of zinc finger proteins at least partially
randomized in at least positions 6 and 2 of the first and second fingers
respectively;
selecting a second zinc finger protein comprising second and third
zinc fingers from a second library of zinc finger proteins at least partially
randomized in at least positions 6 and 2 of the second and third fingers
respectively;
forming a third zinc finger protein comprising first, second and third
zinc fingers by recombination in the second zinc fingers of the first and
second zinc finger proteins.
The Examiner relies on the following evidence:
Choo et al. US 7,700,523 B2 Apr. 20, 2010
Harvey A. Greisman & Carl O. Pabo, A General Strategy for Selecting
High-Affinity Zinc Finger Proteins for Diverse DNA Target Sites, 275
SCIENCE 657-661 (1997).
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Claims 1-8 stand rejected under 35 U.S.C. § 103(a) as unpatentable
over Greisman (Ans. 5-11).
In addition, claims 1-8 stand rejected on the ground of non-statutory
obviousness-type double patenting as unpatentable over claims 1-8 of U.S.
Application 11/514,671, now U.S. Patent 7,700,523 (Ans. 4).
OBVIOUSNESS
Greisman discloses a method of selecting high-affinity zinc finger
proteins for diverse DNA target sites by “gradual assembly of a new zinc
finger protein at the desired binding site - adding and optimizing one finger
at a time” (Greisman 657).
[The] protocol includes three selection steps . . . one for each
finger of the new protein: (i) A finger that recognizes the 3' end
of the target site is selected by phage display . . . . At this stage,
two wildtype Zif fingers are used as temporary anchors to
position the library of randomized fingers over the target site
. . . . (ii) The selected finger is retained as part of a “growing”
protein and, after the distal Zif finger is discarded, phage
display is used to select a new finger that recognizes the central
region of the target site . . . . (iii) Finally, the remaining Zif
finger is discarded, and phage display is used to select a third
finger that recognizes the 5' region of the target site . . . .
Optimization of this finger yields the new zinc finger protein.
(Id.)
Appellants contend that the claimed invention is directed to forming a
“third zinc finger protein comprising first, second and third zinc fingers by
recombination in the second zinc fingers of . . . first and second zinc finger
proteins, wherein the first and second zinc finger proteins have been selected
from first and second libraries in a previous step” (App. Br. 6). According
to Appellants, the “recombination step . . . allows a three finger zinc finger
protein to be constructed from approximately 1.5 fingers each of two
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component zinc finger proteins, each of which has undergone randomization
at positions 2 and 6 within the approximately 1.5 fingers of the protein that
are being recombined” (id.).
Appellants contend that Greisman “does not perform a recombination
between two previously selected zinc finger proteins at all, much less in the
second fingers of such proteins, as required by the present claims” (id.).
Rather, “[i]n Greisman’s method, recombination is performed between one
previously selected zinc finger protein and a zinc finger that has been
randomized but not yet selected . . . [and] the recombination occurs between
fingers not in the second fingers of two zinc proteins being recombined”
(id.).
Moreover, Appellants contend that Greisman neither discloses nor
suggests the claimed method because Greisman’s “method is self-sufficient
resulting in zinc finger proteins in which each of the fingers is successively
randomized and selected in a relevant structural context” (Reply Br. 5), thus,
“there would have been no purpose in performing the further step of
recombining first and second zinc finger proteins in their respective second
fingers to form a third zinc finger protein as required by the present claims”
(id.). Appellants contend that “such a step [of] forming new combinations
of selected zinc finger proteins would reassort fingers away from the context
in which they were originally selected” (id.).
The Examiner does not dispute that Greisman lacks the required
recombination step, but takes the position that “it would be within the
ordinary skill in the art at the time the invention was made to select the
claimed second finger proteins for recombination of the zinc finger protein”
(Ans. 18).
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Nevertheless, even if we accept the Examiner’s assertion that one of
ordinary skill in the art could have selected the second zinc fingers from two
sets of zinc finger proteins for recombination, we agree with Appellants that
the Examiner has not explained how or why Greisman “suggests the
desirability of the recombination step” of the claimed method (Reply Br. 5).
It is well settled that “[t]he mere fact that the prior art may be modified in
the manner suggested by the Examiner does not make the modification
obvious unless the prior art suggested the desirability of the modification.”
In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992).
Accordingly, the rejection of claim 1-8 as unpatentable over Greisman
is reversed.
DOUBLE PATENTING
Claims 1-8 stand rejected on the ground of non-statutory obviousness-
type double patenting as unpatentable over claims 1-8 of U.S. Application
11/514,671 (now U.S. Patent 7,700,523 B2).
Appellants contend that “[t]he present claims recite a step of
recombination of two zinc finger proteins in the finger 2 sequence of both
proteins to form a recombined zinc finger protein comprising three fingers
(i.e., one and a fraction finger comes from each of the component proteins)”
(App. Br. 4), but the patented claims “do not recite any step of forming a
zinc finger protein by recombination of fingers much less in the second
fingers of both zinc finger proteins as claimed” (id. at 5).
The Examiner acknowledges that “the argued recombination at the
second zinc finger of the obtained zinc finger protein . . . is not explicit in
the claims of the ‘671 application” (Ans. 13), but indicates that the
Specification of the ‘671 application, which the same as the present
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Specification, “is relied upon as to the specifics of the claimed method
steps” (id.), “in view of the broad claimed process steps of the ‘671
application” (id.).
Nevertheless,
As a general rule, obviousness-type double patenting
determinations turn on a comparison between a patentee’s
earlier and later claims, with the earlier patent’s written
description considered only to the extent necessary to construe
its claims. E.g., In re Avery, 518 F.2d 1228, 1232 (CCPA
1975). This is so because the non[-]claim portion of the earlier
patent ordinarily does not qualify as prior art against the
patentee and because obviousness-type double patenting is
concerned with the improper extension of exclusive rights -
rights conferred and defined by the claims. The focus of the
obviousness-type double patenting doctrine thus rests on
preventing a patentee from claiming an obvious variant of what
it has previously claimed, not what it has previously disclosed.
See generally [General Foods Corp. v. Studiengesellschaft
Kohle, 972 F.2d 1272, 1280-82 (Fed. Cir. 1992)].
Eli Lilly and Co. v. Teva Parenteral Medicines, Inc., 689 F.3d 1368, 1378-
79 (Fed. Cir. 2012).
We agree with Appellants that “[t]he specification is not being used
by the Examiner to interpret [or construe] a claim but rather to show [the]
presence of disclosure not found in the claim” (App. Br. 5), and we agree
that the Examiner’s reliance on the Specification is inappropriate in this
instance. Moreover, as with the obviousness rejection discussed above, the
Examiner has not explained why one of ordinary skill in the art would have
had reason to recombine the second zinc fingers from two sets of
randomized zinc finger proteins.
Accordingly, the rejection of claims 1-8 on the ground of non-
statutory obviousness-type double patenting is reversed.
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SUMMARY
The rejection of claims 1-8 as unpatentable over Greisman is reversed,
as is the rejection of claims 1-8 on the ground of non-statutory obviousness-
type double patenting.

REVERSED

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