Ex Parte Raibekas et al

Patent Trials and Appeals Board

Apr 15, 2019

11097993 - (D) (P.T.A.B. Apr. 15, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
11/097,993 04/01/2005 Andrei Raibekas
22852 7590 04/17/2019
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK A VENUE, NW
WASHINGTON, DC 20001-4413
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.
12641.0093-00000 5419
EXAMINER
XIE, XIAOZHEN
ART UNIT PAPER NUMBER
1646
NOTIFICATION DATE DELIVERY MODE
04/17/2019 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):
regional-desk@finnegan.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte ANDREI RAIBEKAS and BRUCE KERWIN
Appeal2017-010133
Application 11/097 ,993
Technology Center 1600
Before JEFFREY N. FREDMAN, ELIZABETH A. LA VIER, and
DAVID COTTA, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2 under 35 U.S.C. § 134(a) involving claims to a
method of reducing aggregation of an aggregating interleukin- I receptor
antagonist. The Examiner rejected the claims as anticipated, as obvious, and
on the ground of obviousness-type double patenting. An oral hearing took
place on April 9, 2019. We have jurisdiction under 35 U.S.C. § 6(b). We
affirm.
1 Appellants identify the Real Party in Interest as Swedish Orphan Biovitrum
AB (see App. Br. 3).
2 We have considered and herein refer to the Specification of Apr. 1, 2005
("Spec."); Final Office Action of Jan. 22, 2016 ("Final Act."); Appeal Brief
of Jan. 23, 2017 ("App. Br."); Examiner's Answer of May 26, 2017
("Ans."); and Reply Brief of July 26, 2017 ("Reply Br.").
Appeal2017-010133
Application 11/097 ,993
Statement of the Case
Background
"Interleukin-I receptor antagonist (IL-Ira) is a human protein that acts
as an inhibitor of interleukin- I activity and is a member of the IL- I family,
which also includes IL-I a and IL-I W' (Spec. ,r 64). "Anakinra, an E. coli-
produced version of IL- Ira, is marketed for treatment of rheumatoid
arthritis" (Spec. ,r 3). The Specification teaches "methods of improving drug
formulations comprising reducing aggregation of IL-Ira" (Spec. ,r 2).
The Claims
Claims 1-6, 8, and 9 are on appeal. Independent claim 1 is
representative and reads as follows:
1. A method of reducing aggregation of an aggregating
interleukin- I receptor antagonist (IL-Ira) in an aqueous
composition comprising reducing aggregation of the IL- Ira in
the aqueous composition by incubating the aqueous
composition comprising the IL-Ira with at least one accessory
molecule for at least two hours at 25 to 45 QC at a concentration
sufficient to reduce aggregation of the IL-Ira, wherein reduced
aggregation is determined when the optical density of the
aqueous composition of the IL-ra and the at least one accessory
molecule is less than 60% of the optical density of an aqueous
composition of the IL-Ira without an accessory molecule when
the optical density is measured at 405 nm after two hours of
incubation at 39°C, and wherein at least one of the at least one
accessory molecule is selected from a sugar at a concentration
of from 1 to 2 percent and a multiple-charge anion.
2
Appeal2017-010133
Application 11/097 ,993
The Issues
A. The Examiner rejected claims 1, 2, and 4 under 35 U.S.C. § I02(b) as
anticipated by Chang3 (Final Act. 2-7).
B. The Examiner rejected claims 1, 2, 4, and 5 under 35 U.S.C. § I03(a)
as obvious over Sabados4 and Burke5 (Final Act. 7-11).
C. The Examiner rejected claim 3 under 35 U.S.C. § I03(a) over
Sabados, Burke, and Prestrelski6 (Final Act. 11-15).
D. The Examiner rejected claims 8 and 9 under 35 U.S.C. § I03(a) over
Sabados, Burke, Light,7 and Dixon8 (Final Act. 16-18).
E. The Examiner rejected claims 1---6, 8, and on the ground of
nonstatutory obviousness-type double patenting as being unpatentable
over the claims of U.S. Patent No. 7,619,066 (Final Act. 18).
A. 35 US.C. § 102(b) over Chang
The Examiner finds Chang teaches "preparing an IL- Ira protein
formulation by adding a buffer containing 10 mM sodium citrate buffer (pH
6.5) (a multiple-charge anion) and 140 mM NaCl, with or without sucrose"
(Final Act. 4 ). The Examiner finds Chang then "stored the protein
3 Byeong S. Chang et al., Formation of an Active Dimer during Storage of
Interleukin-I Receptor Antagonist in Aqueous Solution, 71 Biophysical J.
3399-406 (1996).
4 Sabados et al., WO 94/06457 Al, published Mar. 31, 1994.
5 Burke et al., WO 2004/071439 A2, published Aug. 26, 2004.
6 Prestrelski et al., US 5,580,856, published Dec. 3, 1996.
7 Albert Light, Protein Solubility, Protein Modifications and Protein
Folding, 3 BioTechniques 298-306 (1985).
8 H.B. F. Dixon et al., Reversible Blocking of Amino Groups with
Citraconic Anhydride, 100 Biochemical J. 312-14 (1968).
3
Appeal2017-010133
Application 11/097 ,993
formulation for 2 months at 30°C, and determined the stability of the protein
by measuring the components" (id.).
The issue with respect to this rejection is: Does a preponderance of the
evidence of record support the Examiner's conclusion that Chang anticipates
claim 1?
Findings of Fact
1. The Specification teaches, "[ e ]xemplary multiple-charge anions
that may be accessory molecules include, but are not limited to,
pyrophosphate and citrate" (Spec. ,r 85).
2. The Specification teaches "[i]n certain embodiments, at least
one accessory molecule is 1 to 20 mM citrate" (Spec. ,r 9) and that "[i]n
certain embodiments, an accessory molecule may be present at a
concentration of 1 to 50 mM" (Spec. ,r 101 ).
3. Figure 3 of the Specification is reproduced below:
10
6
4
2
0
0
Figure 3
5/16/03
[IL~ 1 ra] ·= 140mg/mt
......- mM Sodium Phosphate vs Slope P
-+- mM Sodium Pyrophosphate vs Slop& PP Rep1
-- mM Sodium Citrate vii Slope C
..,.._ mM Sodium Pyiophosphata vs Slope PP Rep 2
40
.,,._ mM Sodfum Pyrophosphele II Stopa P
60
mM
4
BO 100 120 140
Appeal2017-010133
Application 11/097 ,993
"Figure 3 shows that in this experiment, the rate of aggregation of IL- Ira
decreased with increasing concentrations of citrate, phosphate, or
pyrophosphate. Notably, the rate of aggregation of IL-Ira in citrate or
pyrophosphate buffer decreased more rapidly than the rate of aggregation in
phosphate buffer" (Spec. ,r 140). The Specification teaches that the IL-Ira
solution "was dialyzed against 2 x 4L of 140 mM NaCl" prior to addition of
citrate (Spec. ,r 139). Thus, the final composition comprised IL-Ira in a
solution with 140 mM NaCl and varying amounts of citrate between 1 and
125 mM.
4. Chang teaches, "[ d]evelopment of a protein therapeutic agent
requires not only production of a sufficient quantity of homogeneous, highly
active protein, but also a stable formulation suitable for storage and
delivery" (Chang 3399, col. 1). Chang teaches a "goal of the current study
was to determine whether approaches used to ameliorate aggregation of
aFGF, bFGF, KGF, and IL- I would also attenuate formation of the dimeric
species ofrhIL-lra" (Chang 3400, col. 1).
5. Chang teaches:
Pharmaceutical-quality rhIL-lra was produced and purified at
Amgen Boulder (formerly Synergen). The protein was greater
than 99.5% homogeneous based on size-exclusion
chromatography and approximately 98% pure based on cation-
exchange chromatography. Protein solutions (100 mg/ml)
containing various concentrations of sugar were prepared in 10
mM sodium citrate buffer (pH 6.5 at 23°C) and 140 mM
sodium chloride, and stored at 30°C until analysis.
(Chang 3400, col. 1 ).
6. Chang teaches "long-term storage (at 30°C) of aqueous
solutions of rhIL-1 ra resulted [in] only a relatively small production of
5
Appeal2017-010133
Application 11/097 ,993
visible precipitates ( approximately < 1 % of total protein)" ( Chang 3401,
col. 1 ).
7. Figure 1 of Chang is reproduced below:
P2
} Oagradea
P~fifi