13426973 (P.T.A.B. Sep. 1, 2016)

Ex Parte Bell et al

Patent Trial and Appeal BoardSep 1, 2016

13426973 (P.T.A.B. Sep. 1, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 13/426,973 03/22/2012 133485 7590 09/06/2016 Nelson Mullins Riley & Scarborough LLP/Alexion One Post Office Square 30th Floor Boston, MA 02109-2127 Leonard Bell 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. AXJ-114BUSCN 8851 EXAMINER ROGERS, JAMES L ART UNIT PAPER NUMBER 1644 NOTIFICATION DATE DELIVERY MODE 09/06/2016 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): ipboston.docketing@nelsonmullins.com chris.schlauch@nelsonmullins.com ipqualityassuranceboston@nelsonmullins.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte LEONARD BELL and RUSSELL P. ROTHER Appeal2015-000613 Application 13/426,973 1 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and RYAN H. FLAX, Administrative Patent Judges. FLAX, Administrative Patent Judge. DECISION ON APPEAL This is a decision on appeal under 35 U.S.C. Â§ 134(a) involving claims directed to a method of treating a patient afflicted with paroxysmal nocturnal hemoglobinuria (PNH) using eculizumab. Claims 91, 98, 100--- 106, 110---113, and 115 are on appeal as rejected under 35 U.S.C. Â§ 103(a). We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. 1 The Real Party in Interest is Alexion Pharmaceuticals, Inc. Br. 2. Appeal201S-000613 Application 13/426,973 STATEMENT OF THE CASE The appealed claims can be found in the Claims Appendix of the Appeal Brief. Claims 91, 112, 113, and 11 S are independent claims. Claim 113 is representative and reads as follows: 113. A method for treating a patient afflicted with paroxysmal nocturnal hemoglobinuria (PNH), the method comprising administering to the patient an effective amount of a pharmaceutical composition comprising a single unit dosage form of an anti-CS antibody that inhibits cleavage of complement component CS into fragments CSa and CSb, wherein the single unit dosage form comprises 300 mg of the anti-CS antibody, wherein the single unit dosage form comprises a 10 mg/mL solution of the anti-CS antibody, wherein the single unit dosage form has a volume of 30 mL, and wherein the anti-CS antibody is eculizumab. Br. 11-12 (Claims App'x). The following rejections are on appeal: 2 Claims 91, 98, 100-106, 112, and 113 rejected under 3S U.S.C. Â§ 103(a) over Hillmen,3 Hill,4 Evans,5 and Wang. 6 Final Action 2. 2 Each of the rejections set forth in the Final Action rely on the Examiner's determinations set forth in the Office Actions dated Aug. 20, 2012 and May 31, 2013. Final Action 2--4. 3 Peter Hillmen et al., Effect of Eculizumab on Hemolysis and Transfusion Requirements in Patients with Paroxysmal Nocturnal Hemoglobinuria, 3SO NEW ENGLAND J. MED. SS2-S9 (2004) (hereinafter "Hillmen"). 4 Anita Hill et al., Improvement in the Symptoms of Smooth Muscle Dystonia During Eculizumab Therapy in Paroxysmal Nocturnal Hemoglobinuria, 90 HAEMATOLOGICA!THE HEMATOLOGY J. 111-13 (200S) (hereinafter "Hill"). 5 U.S. Patent No. US 6,3SS,24S Bl (issued to Mark J. Evans et al. Mar. 12, 2002) (hereinafter "Evans") 6 U.S. Patent Application Pub. No. US 200S/0271660 Al (published Dec. 8, 200S) (hereinafter "Wang"). 2 Appeal2015-000613 Application 13/426,973 Claims 91, 98, 100-106, 110, 112, and 113 rejected under 35 U.S.C. Â§ 103(a) over Hillmen, Hill, Evans, Wang, and Garcia.7 Final Action 4. Claims 91, 98, 100-106, 111-113, and 115 rejected under 35 U.S.C. Â§ 103(a) over Hillmen, Hill, Evans, Wang, and Rosse. 8 We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art. For emphasis we highlight the following: FINDINGS OF FACT FF 1. Hillmen disclosed, "patients with PNH received infusions of eculizumab ( 600 mg) every week for four weeks, followed one week later by a 900-mg dose and then by 900 mg every other week through week 12." Hillmen 552 and 554; see also Final Action 2-3, May 31, 2013 Office Action 3-7, and Ans. 3-7 (discussing Hillmen). FF2. Hillmen disclosed, "Eculizumab is a recombinant humanized monoclonal antibody that was designed to block the activation of terminal complement components. It binds specifically to the terminal complement protein C5, inhibiting its cleavage into C5a and C5b, thereby preventing the release of the inflammatory mediator C5a and the formation of the cytolyticpore C5b-C9." Hillmen 553; see also Final Action 2-3, May 31, 2013 Office Action 3-7, and Ans. 3-7 (discussing Hillmen). 7 Mildred Garcia et al., Effect of Preservatives on IgG Aggregation, Complement-activating Effect and Hypotensive Activity of Horse Polyvalent Antivenom Used in Snakebite Envenomation, 30 BIOLOGICALS 143-51 (2002) (hereinafter "Garcia"). 8 Wendell F. Rosse et al., Immune-Mediated Hemolytic Anemia, HEMATOLOGY, AM. Soc. HEMATOL. 48---62 (2004) (hereinafter "Rosse"). 3 Appeal2015-000613 Application 13/426,973 FF3. Hillmen disclosed "[a]ll patients were vaccinated against N. meningitidis (Mengivac (A+C), Aventis Pasteur) before treatment." Hillmen 554; see also Final Action 2-3, May 31, 2013 Office Action 3-7, and Ans. 3-7 (discussing Hillmen). FF4. Hillmen disclosed "[t]here was a rapid improvement in the quality of life during eculizumab therapy." Hillmen 558, see also 557; see also Final Action 2-3, May 31, 2013 Office Action 3-7, and Ans. 3-7 (discussing Hillmen). FF5. Hill corroborated the findings of Hillmen (see supra) and that eculizumab administered at a maintenance dose of 900 mg intravenously every 14 (or 12) days to treat PNH patients was safe, well tolerated, and effective. See generally Hill; see also Final Action 2-3, May 31, 2013 Office Action 4--7, and Ans. 3-7 (discussing Hill). FF6. Wang disclosed "eculizumab in Formulation 1 (FIG. 10) at 30 mg/ml can be effectively and efficiently nebulized" for pulmonary drug delivery. Wang i-f 171; see also May 31, 2013 Office Action 5, and Ans. 5 (discussing Wang). FF7. Evans disclosed treating patients with "154, 210, or 3 50 mg of [eculizumab] antibody for a 70kg adult human." See Evans col. 16, 11. 10- 30; see also Final Action 3, May 31, 2013 Office Action 5, and Ans. 4--6 (discussing Evans). FF8. Rosse disclosed: Eculizumab is a humanized chimeric antibody against C5 with a completely nonfunctional Fe domain. Eculizumab has a high affinity for C5 and thus when bound remains so until the complex is removed from the circulation. Recently a pilot study of eculizumab in 11 patients with transfusion-dependent PNH was 4 Appeal2015-000613 Application 13/426,973 reported. The antibody was given at a dose of 600 mg every week for 4 weeks and then at a dose of 900 mg every other week. The drug is given by intravenous infusion over 30 minutes and was extremely well tolerated. . . . There was a significant improvement in the quality of life when comparing before the start of eculizumab and at week 12. Rosse 53; see also Final Action 2-3, May 31, 2013 Office Action 7-8, and Aug. 20, 2012 Office Action 3-10 (discussing Rosse). DISCUSSION We address the three obviousness rejections together because the same determinative facts and arguments apply to each. Appellants contend the Examiner's rejection fails to "show some reason why a person of ordinary skill in the art would have thought to combine particular available elements of knowledge, as evidenced by the prior art, to reach the claimed invention." Br. 6 (emphasis original). Further, Appellants contend "[ n ]one of the cited references teach or suggest a method, which includes a pharmaceutical composition having the particularly claimed limitations," i.e., a single unit dosage of 300 mg eculizumab in 30 mL of a 10 mg/mL solution. Br. 6-7. Appellants argue: Br. 7. optimizing the dosage form ... is neither routine, obvious, nor a mere matter of convenience. At a very minimum, to arrive at the claimed solutions, the inventors had to know the solubility properties of the claimed antibody, eculizumab. Moreover, for a pharmaceutical solution to be commercially viable, the inventors had to know the shelf-life stability of eculizumab in solution. If its stability was too low, a pharmaceutical solution would not have been an option. None of that knowledge is disclosed or suggested by the cited references. 5 Appeal2015-000613 Application 13/426,973 The Examiner has set forth a prima facie case for obviousness, as the cited prior art disclose all but the specific single unit dosage of the claims. See, e.g., FF1-FF8. A 300 mg single unit dosage would be obvious over effective working examples requiring therapeutic dosages that are simple multiples thereof, i.e., the effective 600 mg and 900 mg dosages of Hillmen, Hill, and Rosse (a 300 mg dose would be a convenience). Id. Moreover, the Examiner has determined that the point of distinction identified by Appellants, that is, the single unit dosage of 300 mg of eculizumab in a 30 mL formulation, i.e., at a concentration of 10 mg/mL, was obvious as mere optimization of the formulations disclosed by the combined prior art and achievable by routine experimentation. Ans. 4. A preponderance of the evidence of record supports the Examiner's determinations. "[I]t is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955); see also In re Peterson, 315 F.3d 1325 (Fed. Cir. 2003). "Only if the 'results of optimizing a variable' are 'unexpectedly good' can a patent be obtained for the claimed critical range." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997) (quoting In re Antonie, 559 F.2d 618, 620 (CCPA 1977)). "[D]iscovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 27 6 (CCP A 1980). Appellants' claims and arguments fail under these tests. Contrary to Appellants' arguments, the claims do not recite that their pharmaceutical composition is commercially viable or has a specific shelf- life or has a specific stability. Nor does the Specification discuss these qualities or suggest that they were even considered by Appellants in relation 6 Appeal2015-000613 Application 13/426,973 to the single unit dosage of the claims. Similarly, the Appellants-argued points on mitigation of waste, and storage, waiting, and drug vial multiplication do not address claim limitations and are not discussed in the Specification. See Br. 7-8. In fact, the Specification does not indicate a single advantage of the single unit dosage of the claims. Moreover, Appellants present no compelling evidence of secondary indicia of non- obviousness to rebut the Examiner's prima facie case of obviousness. Thus, there is no evidence that the optimization of the single unit dosage was anything but routine and it is well settled that arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984). Where, as here, the experimentation needed to arrive at the subject matter claimed was "nothing more than routine" application of a well-known problem-solving strategy, we must conclude it is not invention. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1368 (Fed. Cir. 2007). For the above reasons, we find that the evidence of record supports the Examiner's determination that the claims would have been obvious over the cited prior art combination. The claims were not separately argued by Appellants and fall as a group. 37 C.F.R. Â§ 41.37(c)(l)(iv). 7 Appeal2015-000613 Application 13/426,973 SUMMARY The rejection claims 91, 98, 100-106, 112, and 113 under 35 U.S.C. Â§ 103(a) over Hillmen, Hill, Evans, and Wang is affirmed. The rejection of claims 91, 98, 100-106, 110, 112, and 113 under 35 U.S.C. Â§ 103(a) over Hillmen, Hill, Evans, Wang, and Garcia is affirmed. The rejection of claims 91, 98, 100-106, 111-113, and 115 under 35 U.S.C. Â§ 103(a) over Hillmen, Hill, Evans, Wang, and Rosse is affirmed. 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. Â§ 1.136(a). AFFIRMED 8