Ex Parte Kinsella

Patent Trial and Appeal Board

Oct 27, 2016

12965714 (P.T.A.B. Oct. 27, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/965,714 12/10/2010 Todd M. Kinsella
83092 7590 10/31/2016
Rigel Pharmaceuticals, Inc.
Bozicevic, Field & Francis LLP
1900 University Ave, Suite 200
Suite 200
East Palo Alto, CA 94303
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
RIGL-021DIV 7359
EXAMINER
GROSS, CHRISTOPHER M
ART UNIT PAPER NUMBER
1639
NOTIFICATION DATE DELIVERY MODE
10/31/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
docket@bozpat.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Exparte TODD M. KINSELLA1
Appeal2014-001115
Application 12/965,714
Technology Center 1600
Before ULRIKE W. JENKS, TINA E. HULSE, and TA WEN CHANG,
Administrative Patent Judges.
JENKS, Administrative Patent Judge.
uECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims directed
to a method of making a cyclic polymer. The Examiner rejects the claims as
obvious and on the ground of nonstatutory obviousness-type double
patenting. We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.
1 According to Appellant, the real party in interest is Rigel Pharmaceuticals,
Inc. (App. Br. 3.)
Appeal2014-001115
Application 12/965,714
STATEMENT OF THE CASE
According to the Specification, the "methods find particular use in
production of cyclic polymers. In particular, the subject methods find
particular use in producing cyclic polymers (e.g., cyclic peptides) that are
not genetically encodable, using a cell-free system." (Spec. i-f 117). The
Specification describes a
"semi-synthetic" composition in which a first part of the
composition (i.e., the C and N-terminal intein domains) are
made in a cell, and a second part of the composition (i.e., the
polymer) is made synthetically. As discussed above, the
polymer region of an intein composition may contain one or
many non-naturally occurring amino acids and in certain
embodiments, may contain only non-naturally occurring amino
acids.
(Spec. ,-r 104.)
Claims 19-22 and 24--26 are on appeal, and can be found in the
Claims Appendix of the Appeal Brief. Claim 19 is representative of the
claims on appeal, and reads as follows (emphasis added):
19. A method for making a cyclic polymer, comprising:
incubating a compound of the structure:
D1-Xcn)-D2
wherein D1 is a first catalytic domain of an intein;
wherein Xcn) is a polymer comprising n residues of a
monomer X, n is at least 2, the polymer is not genetically
encodable and is not made by a cell, and the polymer has a first
reactive site for said intein at its N-terminus; and
wherein D2 is a second catalytic domain of an intein,
having at its N-terminus
a second reactive site for said intein;
under intein reaction conditions to produce said cyclic
polymer.
(App. Br. 12, Claims Appendix)
2
Appeal2014-001115
Application 12/965,714
Appellant seeks review of the following rejections:
I. claims 19-22 and 24--26 under 35 U.S.C. § 103(a) as
unpatentable over Benkovic2 in view of Wyrick;3 and
II. claims 19-22 and 24--26 on the grounds of nonstatutory
obviousness-type double patenting over claims 1, 2, and 6 of
the '571 patent4 in view of Benkovic and further in view of
Wyrick.
Obviousness over Benkovic and Wyrick
The Examiner finds that Benkovic teaches compounds having the
following structure Di-Xcn)-D2 but acknowledges that the reference "does not
teach X-monomers that are not made by a cell" as required by the claim
limitation "wherein the polymer that is made up of monomer X is not
genetically encodable" (Ans. 4). The Examiner looks to Wyrick for teaching
methods of modifying proteins by crosslinking them with DNA (see Ans. 4).
The combination of references, according to the Examiner, results in the
modification of the genetically encodable cyclic proteins as disclosed in
Benkovic with the art-recognized crosslinking modification as disclosed in
Wyrick to arrive at a polymer containing monomers that are not genetically
encodable (see Ans. 5). According to the Examiner, Figs. 16-19 of
Benkovic "explicitly suggest cyclic DNA binding proteins, which constitutes
the precise type of protein of interest to Wyrick" (Advisory Action. 5 4). The
2 Benkovic et al., US 2007/0207502 Al, published Sept. 6, 2007
("Benkovic").
3 Wyrick et al., US 7,575,869 B2, issued Aug. 18, 2009 ("Wyrick").
4 Kinsella, US 7 ,208,571 B2, issued Apr. 24, 2007 ("the '571 patent").
5 Advisory Action mailed Feb. 6, 2013
3
Appeal2014-001115
Application 12/965,714
Examiner reasons that you would make this modification in order to produce
a cyclic compound that is crosslinked with DNA to study regulatory
networks of DNA binding (Final Action6 5). "One of ordinary skill in the art
would have had a reasonable expectation of success in applying
formaldehyde per Wyrick et al[.] toward modifying the cyclic proteins
prepared in the manner of Benkovic et al[.] because formaldehyde
crosslinking constitutes an art-recognized robust technique exploited in the
art for decades" (id.).
Appellant contends that the Examiner's rationale is flawed because
"DNA binding proteins are linear molecules. They are not cyclic, and there
is no reason to expect that a cyclic version of a linear DNA binding protein
(especially one that has been cross-linked using formaldehyde) would retain
the ability to bind to DNA" (App. Br. 5). Appellant contends that based on
the combination of references "one of skill would [not] have a reason to
study transcription factors that have been treated with formaldehyde and
then cyclized" (Reply Br. 2). Appellant contends that the Examiner has not
sufficiently articulated why one of ordinary skill would look to first cyclize a
DNA binding protein and then treat it with formaldehyde in order to create a
cyclic polymer Di-Xcn)-D2 that is not genetically encoded and made by a cell
as claimed (see App. Br. 9).
The issue is: Does the evidence of record support the Examiner's
conclusion that the combination of references renders obvious the claimed
method of making a cyclic polymer with monomers that are not genetically
encodable and not made by a cell?
6 Final Action mailed Nov. 16, 2012 ("Final Act.").
4
Appeal2014-001115
Application 12/965,714
Findings of Fact
FF 1. Fig. 16 of Benkovic is reproduced below:
F!G.16A
F!G.168
In this method, an active intein intermediate (specie 1) is
mutagenized ... to introduce a DNA-binding domain
downstream of IN (step B) to yield specie 2. The intein-
mediated cyclization reaction will proceed until the lariat
intermediate (specie 3) is formed (step C). IN and le form a
strong non-covalent complex. The resulting lariat intermediate
is then co-expressed with a target protein attached to a DNA-
binding domain (step D). Interaction of the lariat intermediate
with the target protein (specie 4) causes activation of a
promoter region (step E) leading to expression of the reporter
gene(*). This method can be modified such that a known
molecule (in place of an unknown target protein) is attached to
a DNA-binding domain, so that lariat intermediates displaying a
looped peptide that binds the known molecule can be identified.
(Benkovic i-f 134).
5
Appeal2014-001115
Application 12/965,714
FF2. Wyrick teaches that "DNA binding protein of a cell is linked (e.g.,
covalently crosslinked) to genomic DNA of a cell" (Wyrick,
Abstract). Specifically, the "cells are fixed with formaldehyde,
harvested by sonication, and DNA fragments that are crosslinked to a
protein of interest are enriched by immunopercipitaion with a specific
antibody" (Wyrick 10:67-11:1).
Principle of Law
"An examiner bears the initial burden of presenting a prima facie case
of obviousness." In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir.
2011 ). In satisfying this initial burden, "[i]t is impermissible to use the
claimed invention as an instruction manual or 'template' to piece together
the teachings of the prior art so that the claimed invention is rendered
obvious." In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992). Stated
differently, to establish obviousness, there must be "an apparent reason to
combine the known elements in the fashion" recited in the claims. KSR Int 'l
Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
Analysis
Appellant acknowledges that "Benkovic teaches that a cyclic peptide
can be appended to a transcription factor . . . . Benkovic does not teach a
cyclic transcription factor" (Reply Br. 7). Similarly, Appellant argues that
Wyrick also does not mention cyclic transcription factors but is rather "cited
to provide [a] method in which proteins are cross-linked using
formaldehyde" (App. Br. 4). According to Appellant, "[i]t is unclear how
either of the cited references alone or in combination could teach or suggest
6
Appeal2014-001115
Application 12/965,714
a cyclic transcription factor when nether [sic] of the references even so much
as mentions such a thing" (Reply Br. 7). In other words, Appellant contends
that the Examiner has not sufficiently articulated why one of ordinary skill
would look to cyclize a DNA binding protein and then cross link this protein
with formaldehyde (see App. Br. 9 ("none of the references provide any
motivation to cyclize a DNA binding protein")).
We find that Appellant has the better position. The Examiner
acknowledges that Benkovic teaches compounds having the structure
Di-Xcn)-D2 but does not teach that X should be a polymer that is "not
genetically encodable and is not made by a cell" (Ans. 4). The Examiner
reasons that if Benkovic's molecule Di-Xcn)-D2 is modified after production
then the polymer X is no longer genetically encodable or made by the cell.
The Examiner looks to the teachings of Wyrick to suggest using
formaldehyde modification to arrive at a polymer that is not genetically
encodable (see Ans. 4 ("crosslink with DNA via formaldehyde treatment in
the manner of Wyrick")). In particular, the Examiner notes that
"[f]ormaldehyde reacts with proteins for instance at lysine residues to form a
side chain bearing a reactive immonium cation functional group, constituting
an amino acid monomer not made by cells" (Final Act. 5). The Examiner
reasons that a skilled artisan would be motivated to perform these
modifications because Benkovic "explicitly indicate[ s] DNA binding
proteins are of particular interest and (ii) characterization of regulatory
networks of DNA binding proteins is useful toward mapping the cell cycle
as well as identifying gene function, each important according to Wyrick"
(Ans. 5). We are not persuaded by the Examiner's rationale. Just because
protein modifications are known in the art does not explain why one of
7
Appeal2014-001115
Application 12/965,714
ordinary skill in the art would want to make such modifications especially to
polymer X that is to be cyclized.
The Examiner's reason for combining the references is that both
Benkovic and Wyrick suggest studying DNA binding protein interactions
with genomic DNA (see Ans. 5). It is true that both references disclose
using DNA binding protein domains; however, an interest in studying DNA
binding does not explain why a person of ordinary skill in the art would
want to move the DNA binding domain from the position shown in
Benkovic's Fig. 16 (FFl, see also Benkovic Fig. 17-19) to the position
where it becomes cyclized. Wyrick discloses crosslinking DNA binding
protein with genomic DNA to precipitate and obtain DNA fragments in
order to determine what genomic sequences the DNA protein binds (FF2).
Benkovic' s molecules without any modification would be expected to work
in Wyrick's methods (FFl & FF2). In other words, the DNA binding
domains that are not cyclized as shown in Benkovic (see FFl) would
function similarly to the DNA binding proteins in Wyrick. Wyrick's
formaldehyde crosslinking methods "facilitate the dissection of the cells[']
regulatory network of gene expression across the entire genome and aid in
the identification of gene function .... [The work] forms the foundation for
a complete map of the transcriptional regulatory network that controls the
yeast cell cycle" (Wyrick 3:50-57; Ans. 5). This however does not explain
why the ordinary artisan would look to place the DNA binding domain
protein in between the split inteins as disclosed in structure Di-Xcn)-D2. We
agree with Appellant's position that the Examiner has not adequately
explained why the ordinary artisan would move the DNA binding domain
from the current position disclosed in Benkovic' s molecules (see FF 1) into
8
Appeal2014-001115
Application 12/965,714
the target protein position that is cyclized by the split inteins. See KSR Int'!
Co. v. Teleflex Inc., 550 U.S at 418 (obviousness rejections require "some
articulated reasoning with some rational underpinning").
As the Examiner has failed to adequately articulate any other rationale
explaining how the combination of references discloses a cyclic polymer
that is not genetically encodable and is not made by a cell, we are
constrained to reverse each rejection that relies on Benkovic and Wyrick.
Nonstatutory Obviousness-Type Double Patenting of the '571 Patent in View
of Benkovic and Wyrick
With respect to the nonstatutory obviousness-type double patenting
rejection of the '571 patent in view of Benkovic and Wyrick, the Examiner
applies the same rationale as disclosed for the obviousness rejections above,
which we found unpersuasive. We agree with Appellant's position that the
Examiner has not adequately explained why the ordinary artisan would
move the DNA binding domain from the current position disclosed in
Benkovic's molecules (see FFl) into the target protein position that is
cyclized by the split inteins.
9
Appeal2014-001115
Application 12/965,714
SUMMARY
We reverse the rejection of claims 19-22 and 24--26 under 35 U.S.C.
§ 103(a) as unpatentable over Benkovic in view of Wyrick.
We reverse the rejection of claims 19-22 and 24--26 on the grounds of
nonatatutory obviousness-type double patenting over claims 1, 2, and 6 of
the '571 patent in view ofBenkovic and further in view of Wyrick.
REVERSED
10