Ex Parte Raibekas et alDownload PDFPatent Trials and Appeals BoardApr 15, 201911097993 - (D) (P.T.A.B. Apr. 15, 2019) Copy Citation 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~fifiCopy with citationCopy as parenthetical citation