Ex Parte DeLuca et alDownload PDFPatent Trial and Appeal BoardJun 26, 201712955567 (P.T.A.B. Jun. 26, 2017) Copy Citation United States Patent and Trademark Office 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 APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 12/955,567 11/29/2010 Hector F. DeLuca 032026-1212 7723 81079 7590 06/28/2017 Wisconsin Alumni Research Foundation (WARF) C/O Foley & Lardner LLP 3000 K STREET N.W. SUITE 600 WASHINGTON, DC 20007-5109 EXAMINER BADIO, BARBARA P ART UNIT PAPER NUMBER 1628 NOTIFICATION DATE DELIVERY MODE 06/28/2017 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): ipdocketing @ foley. com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte HECTOR F. DELUCA, PAWEL GRZYWACZ, LORI A. PLUM, and MARGARET CLAGETT-DAME Appeal 2016-005782 Application 12/955,567 Technology Center 1600 Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and RACHEL H. TOWNSEND, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35U.S.C. § 134. The Examiner has rejected the claims for obviousness and obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We Affirm. Appeal 2016-005782 Application 12/955,567 STATEMENT OF CASE The following claim is representative. 1. A compound of formula I t I wherein X1 and X2 are independently selected from H and hydroxy protecting groups. Cited References DeLuca et al. DeLuca et al. Clagett-Dame et al. DeLuca et al. US 5,843,928 US 7,244,719 B2 US 8,188,064 B2 WO 2006/057886 A2 Dec. 1, 1998 (“DeLuca ’928”) July 17, 2007 (“DeLuca ’719”) May 29, 2012 (“Clagett-Dame”) June 1,2006 (“DeLuca ’886”) 2 Appeal 2016-005782 Application 12/955,567 Grounds of Rejection 1. Claims 1—19 are rejected under 35 U.S.C. § 103(a) as being unpatentable over DeLuca ’886 in view of Clagett-Dame. 2. Claims 1—19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims of U.S. Patent No. 7,244,719 in view of DeLuca ’928. FINDINGS OF FACT The Examiner’s findings of fact are set forth in the Answer at pages 2—13. The following facts are highlighted. 1. The claimed generic compound includes compound 26N, 2- methylene-19,26,27-trinor-(20S)-la-hydroxyvitamin D3, which has the following structure: i wherein XI and X2 are independently selected from H and hydroxy protecting groups. 2. The compound 2-methylene-19,26,27-trinor-(20S)-la- hydroxyvitamin D3 of DeLuca ’886 has the following structure: 3 Appeal 2016-005782 Application 12/955,567 where X1 and X2, which may be the same or different, are each selected from hydrogen or a hydroxy-protecting group. 3. The first Declaration of Hector F. DeLuca dated October 2, 2013, includes the following Exhibit A. Titbits. Iiutfcstfotsti CalciSMW Transport Activity «f Cnnspottuds I; Compound i Dtss>«: 0/M | Isierea&e in O/M. ahuve | 1 i in (Satosal OtSdsoa | mrsiHed oosstto? sues | S i pntoi ] .'Mswwssi CalcRsnil i § A**«y I None (utssfSKed cox*wt4) & s; 4,5 - ; 9,26,27- hvdro'KyvifsrtssR Rj fOM") 702» -s A 5,0 1 o.,25-^fevdfoxvYss.a!Tii« I'h eU5(OH)sRs") 7020 as119.5 =S A 6,0 Assay 2 Mcme Runu-tatied control) 0 «S-2 - S-fEietliyfsaie' 1- 2 US' l ti-hy siraxy vitamin R>s 7020 12,4 -A 7.2 Exhibit A shows the ratio of the serosal calcium concentration to the mucosal calcium concentration (“S/M”) measured in untreated control rats and in rats dosed at 7020 pmol with the compounds OM (DeLuca 4 Appeal 2016-005782 Application 12/955,567 ’886 compound), l,25(OH)2D3, and 26N (compound of claimed invention).” Declaration of DeLuca dated Oct. 2, 2013,15. 4. Specification, Figs. 5A and B are reproduced below. OTO. SA tn&Mrttrutt Calcium FIG, SB ai Csteia® Tsars* $>£>?? Figures 5 A and 5B of the Specification are bar graphs comparing the intestinal calcium transport activity of compound 26N with that of l,25(OH)2D3 at differing dosages. Spec. 6115. 5. Clagett-Dame discloses that 2-MbisP, 2-MP (U.S. Pat. No. 6,579,861) 2-Mpregna (U.S. Pat. No. 6,566,352), have little, if any, activity in mobilizing calcium from bone or in promoting intestinal calcium transport, whereas the native hormone calcitriol (la,25-(OH)2D3) is quite potent in both of these effects using a vitamin D deficient rat model. The above-cited patents are all hereby incorporated by reference in their entireties and for all purposes as if fully set forth herein. See also Plum L. A. et al., Proc. Natl. Acad. Sci. USA 101(18), 6900-9004 (2004). Likewise, 2a-methylP, (20R)2-MbisP, 2a-methylbisP, 5 Appeal 2016-005782 Application 12/955,567 2-MtrisP, (20S)-OM, and VIT-I, have very little bone calcium mobilization activity as compared to equimolar doses of the native hormone, la,25-(OH)2D3. Furthermore, these compounds have less activity as compared to that of l,25-(OH)2D3 in stimulating intestinal calcium transport. In normal vitamin D sufficient rats, very high oral doses of 2-MP and 2-MbisP may be administered without producing an increase in serum calcium whereas similar doses of the native hormone produce frank hypercalcemia and even death. Therefore, 2-MP, 2a-methylP, (20S) 2-MbisP, (20R)2-MbisP, 2a-methylbisP, 2MtrisP, OM and certain other vitamin D analogs may be used at much higher does than can the native hormone making them feasible for use in the treatment of obesity in humans and other animal subjects. ... VD-03 exhibits a relatively low ability to mobilize calcium from bone, yet retains approximately the same activity as the native hormone, la,25-(OH)2D3 in promoting intestinal calcium transport. Col. 133,1.35-Col. 134,1. 4. 6. Structures of compounds 2-MP, 2MbisP, and 2MtrisP (disclosed in Clagett-Dame), and compound OM as reproduced from Appellants’ Brief, page 8, are shown below: 2-MP, 2Mh!»P, ami 2MteisP shtwn alongside OM below" In making our determination, we apply the preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 PRINCIPLES OF LAW 6 Appeal 2016-005782 Application 12/955,567 (Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings before the Office). “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). The predecessor court of the Court of Appeals for the Federal Circuit has also held that members of a homologous series must possess unexpected properties not possessed by the homologous compound disclosed by the prior art to be considered unobvious. In re Hass, 141 F.2d 127, 129 (CCPA 1944). The burden of demonstrating unexpected results rests on the party asserting them, and “it is not enough to show that results are obtained which differ from those obtained in the prior art: that difference must be shown to be an unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972). “Mere improvement in properties does not always suffice to show unexpected results.” In re Soni, 54 F.3d 746, 751 (Fed. Cir. 1995). Moreover, it has been long held that even though applicant’s modification results in great improvement and utility over the prior art, it may still not be patentable if the modification was within the capabilities of one skilled in the art, unless the claimed ranges “produce a new and unexpected result which is different in kind and not merely in degree from the results of the prior art.” In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996) (quoting In re Aller, 220 F.2d 454, 456 (CCPA 1955), and citing In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990)). 7 Appeal 2016-005782 Application 12/955,567 “An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470 (Fed. Cir. 1997). Obviousness Rejection 1- DeLuca ’886 and Clagett-Dame Appellants do not argue claims separately in the Appeal Brief. Therefore we select claim 1 as the representative claim. Appellants appear not to take issue with the Examiner’s prima facie case with respect to this rejection and rely solely on their evidence of unexpected results. App. Br. 6—7. The Examiner finds that • the claimed compounds are higher homologs of the prior art compounds [DeLuca ’866], i.e., the claimed compounds differ from the prior art compounds by a single CH2 group; • like the prior art compounds, the claimed compounds are useful in treating diseases such as multiple sclerosis, psoriasis, leukemia, Crohn’s disease, wrinkles, etc. and • the prior art teaches vitamin D compounds differing only in a single CH2 group have similar properties as evidenced by Clagett-Dame. Ans. 9. The Examiner further finds that the data of Declaration Exhibit A (FF3) is not commensurate in scope with the claim, which encompasses a range of dosages of the claimed compound, and that a single data point is not evidence that said result occurs irrespective of the dose, i.e., said higher intestinal calcium transport activity occurs at every dose of the claimed compound in comparison to the prior art compound at the same dose, over the entire range. Thus, applicant’s showing is not considered surprising or unexpected. 8 Appeal 2016-005782 Application 12/955,567 Ans. 13. Appellants contend that the prior art and two declarations claimed compounds exhibit surprising and unexpectedly higher intestinal calcium transport activity .... This conclusion is supported by unrebutted evidence from the art of record as well as two declarations from the inventor. The Examiner ignores the foregoing evidence and, contrary to law, requires additional evidence of surprising and unexpected results. App. Br. 6. Appellants further argue that it is undisputed that Appellant’s claimed compound at 7020 pmol provides ICTA[‘] that significantly surpasses the art- appreciated threshold for OM homologues. Based on Clagett Dame a POSA[1 2] would expect Appellant’s claimed compounds to exhibit similar ITCA as OM and its homologues - namely, never exhibit an ITCA higher than the native hormone. See FOA[3]at 4 (“the art teaches vitamin D compounds differing only in a single CH2 would have similar properties as evidenced by Clagett-Dame”). However, the evidence of record clearly shows the presently claimed compounds surprisingly exhibit an ITCA at 7020 pmol that is significantly higher than the native hormone and OM. 1st DeLuca Decl.[4], 17; 2nd DeLuca Decl.[5],H5-7. App. Br. 12. Appellants argue that 1ICTA means intestinal calcium transport activity. 2 POSA means person of ordinary skill in the art. 3 FOA stand for Final Office Action. 4 Declaration of Hector F. DeFuca dated October 2, 2013. 5 Declaration of Hector F. DeFuca dated December 10, 2014. 9 Appeal 2016-005782 Application 12/955,567 The ITCA of Appellant’s [sic] compounds is surprising and unexpected, especially in view of Clagett-Dame. A person of ordinary skill in the art (“POSA”) would have expected Appellant's claimed compounds to exhibit similar ITCA as OM and its homologues and, therefore, never exhibit an ITCA higher than the native hormone. See Examiner's Answer at 9 (“the art teaches vitamin D compounds differing only in a single CH2 would have similar properties as evidenced by Clagett-Dame”). The evidence of record clearly shows the presently claimed compounds exhibit an ITCA at 7020 pmol that is 1.2 SIM higher than the native hormone. 1st DeLuca Deck, 17 (explaining 26N “exhibits an increase in intestinal calcium transport activity significantly greater than both the native hormone l,25(OH)2D3 and the compound OM”; emphasis added). Further, this ITCA is at least 2.2 S/M higher than OM at the same dosage, an increase that is not only significantly larger {id.), but is also therapeutically significant (2nd DeLuca Deck, H5-7). Reply Br. 3. ANALYSIS We agree with the Examiner’s fact finding, statement of the rejection and responses to Appellants’ arguments as set forth in the Answer. We find that the Examiner has provided evidence to support a prima facie case of obviousness. We provide the following additional comment to the Examiner’s argument set forth in the Final Rejection and Answer. Claim 1 is directed to a compound. Pending claims 6 and 7, which are dependent upon claim 1, are directed to a pharmaceutical composition and include a large “effective amount” range, e.g., 0.01 pg to about 1 mg (claim 6) and 0.01 pg to about 500 pg (claim 7). Claim 1 is broader than claims 6 and 7 not only in the fact that it is directed to a compound, but because it encompasses any amount, including beyond the ranges recited in claims 6 10 Appeal 2016-005782 Application 12/955,567 and 7. See Comark Commc ’ns, Inc. v. Harris Corp., 156 F.3d 1182, 1187 (Fed. Cir. 1998) (. There is presumed to be a difference in meaning and scope when different words or phrases are used in separate claims. To the extent that the absence of such difference in meaning and scope would make a claim superfluous, the doctrine of claim differentiation states the presumption that the difference between claims is significant.) We agree with the Examiner that the data of record is not commensurate in scope with the pending claims. In particular, Appellants’ Declaration evidence shows one dosage amount, 7020 pmol of claimed compound 26N, provides a “therapeutically significant difference” in the ratio of the serosal calcium concentration to the mucosal calcium concentration (“S/M”). Declaration of Hector F. DeLuca dated December 10, 2014 | 6. By comparison the 260pmol dose of claimed compound 26N did not provide improved intestinal calcium transport over naturally occurring vitamin D. FF4 (Spec. Figs. 5A and B). Moreover, nowhere in either Declaration does the Declarant state that the results were unexpected or surprising. While the Declarant states that compound 26N, provides a “therapeutically significant difference” in the ratio of the serosal calcium concentration to the mucosal calcium concentration, this is insufficient to establish “unexpected results” as “it is not enough to show that results are obtained which differ from those obtained in the prior art: that difference must be shown to be an unexpected difference.” Klosak, 455 F.2d at 1080. “Mere improvement in properties does not always suffice to show unexpected results.” Soni, 54 F.3d at 751. 11 Appeal 2016-005782 Application 12/955,567 Nor are Appellants’ arguments of counsel (App. Br. 6—7 and Reply Br. 4—6), that the claimed invention provides unexpected results, persuasive. “Attorney’s argument in a brief cannot take the place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974); see also Gemtron Corp. v. Saint-Gobain Corp., 572 F.3d 1371, 1380 (Fed. Cir. 2009) (“[UJnswom attorney argument... is not evidence and cannot rebut [record evidence].”) The obviousness rejection is affirmed for the reasons of record. Obviousness-Type Double Patenting Claims 1—19 are rejected on the ground of nonstatutory obviousness- type double patenting as being unpatentable over claims of U.S. Patent No. 7,244,719 in view of 5,843,928. Claim 1 of the ‘719 patent is reproduced below. 1. A compound having the formula: where Xi and X2, which may be the same or different, are each selected from hydrogen or a hydroxy-protecting group. 12 Appeal 2016-005782 Application 12/955,567 Appellants do not contest the Examiner’s prima facie case of obviousness-type double patenting. Appellants rely on the same evidence of unexpected results for the obviousness-type double patenting rejection (App. Br. 7-10) as for the obviousness rejection (App. Br. 12) above. Having found Appellants’ evidence of unexpected results insufficient, we also affirm the obviousness-type double patenting rejection. CONCLUSION OF LAW The cited references support the Examiner’s obviousness rejection, and obviousness-type double patenting rejection, which are affirmed for the reasons of record. Appellants have not provided a preponderance of the evidence to rebut the Examiner’s prima facie cases. All pending, rejected claims fall with claim 1. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 41.50(f). AFFIRMED 13 Copy with citationCopy as parenthetical citation