THE UNIVERSITY OF MELBOURNE

Patent Trials and Appeals Board

Jan 12, 2022

2021004901 (P.T.A.B. Jan. 12, 2022)

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. 15/609,564 05/31/2017 Eric Charles Reynolds 040268-0220 8095 22428 7590 01/12/2022 FOLEY & LARDNER LLP 3000 K STREET N.W. SUITE 600 WASHINGTON, DC 20007-5109 EXAMINER WEBB, WALTER E ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 01/12/2022 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 ERIC CHARLES REYNOLDS __________ Appeal 2021-004901 Application 15/609,564 Technology Center 1600 __________ Before RICHARD M. LEBOVITZ, JEFFREY N. FREDMAN, and ULRIKE W. JENKS, Administrative Patent Judges. FREDMAN, Administrative Patent Judge. DECISION ON APPEAL This is an appeal1 under 35 U.S.C. § 134 involving claims to a method of mineralizing a dental surface or subsurface. The Examiner rejected the claims as anticipated and as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We reverse. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the Real Party in Interest as The University of Melbourne (see Appeal Br. 2). We have considered the Specification filed May 31, 2017 (“Spec.”); Final Office Action of July 15, 2020 (“Final Act.”); Appeal Brief filed Mar. 31, 2021 (“Appeal Br.”); Examiner’s Answer filed June 14, 2021 (“Ans.”); and Reply Brief filed Aug. 12, 2021 (“Reply Br.”). An oral hearing was held on Dec. 15, 2021. Appeal 2021-004901 Application 15/609,564 2 Statement of the Case Background “Fluoride-containing dentifrices and mouthrinses have been demonstrated to significantly reduce caries experience . . . Fluoride ions in plaque immediately promote the formation of fluorhydroxyapatite” (id. at 1:19-27). “However, fluoride ions can also promote the remineralization of previously demineralized enamel if enough salivary or plaque calcium and phosphate ions are available when the fluoride is applied” (id. at 2:2-4). The Specification teaches “as fluoride treatments can lead to fluorosis, particularly in children, it would be advantageous to produce dental treatment compositions having the highest efficacy for the amount of fluoride present, to reduce the overall quantity of fluoride necessary to achieve the mineralization effect” (Spec. 2:9-12). The Claims Claims 13-35 are on appeal. Claim 13 is an independent claim, is representative, and reads as follows (paragraphs added for clarity): 13. A method of mineralizing a dental surface or subsurface comprising providing a composition to contact the dental surface or subsurface, wherein the composition, prior to contacting the dental surface or subsurface, comprises (i) about 0.01 % to 50% by weight casein phosphopeptide-stabilized amorphous calcium phosphate or casein phosphopeptide-stabilized amorphous calcium fluoride phosphate, and, separately, (ii) free fluoride ions in an amount of from at least 400 ppm to about 3,000ppm, and wherein the composition does not include a calcium chelator and does not include an additional phosphate buffer. Appeal 2021-004901 Application 15/609,564 3 The Rejections A. The Examiner rejected claims 13-19, 21, 22, 24, 26, 28, 30, 32, and 34 under 35 U.S.C. § 102(b) as anticipated by Reynolds2 (Final Act. 2-4). B. The Examiner rejected claims 13-35 under 35 U.S.C. § 103(a) as obvious over Reynolds (Final Act. 4-6). A. 35 U.S.C. § 102(b) over Reynolds The Examiner finds “Reynolds teaches stabilized amorphous calcium phosphate (ACP) and amorphous calcium fluoride phosphate (ACFP) (see Abstract). Reynolds teaches, at Example 8, ‘[a]n synergistic anticariogenic effect of the 1.0% CPP-ACP together with 500 ppm F-‘ (free fluoride ions; p. 26, lines 14-15)” (Final Act. 2; emphasis omitted). The Examiner finds the “amorphous form of calcium phosphate is stabilized by casein phosphopeptide (CPP-ACP), and is the most soluble, basic form of non- crystalline calcium phosphate” (id. at 3). The Examiner finds “Reynolds teaches a specific embodiment of a mouthwash formulation comprising 2.0% CPP-ACFP, water (~75%), and 0.3% (3000ppm) sodium monofluorophosphates (source of free fluoride ion) (Example 10, formulation 1 at p. 30)” (id. at 3; emphasis omitted). The issue with respect to this rejection is: Does a preponderance of the evidence of record support the Examiner’s conclusion that Reynolds anticipates the claimed methods? 2 Reynolds, E., WO 98/40406 A1, published Sept. 17, 1998. Appeal 2021-004901 Application 15/609,564 4 Findings of Fact 1. Reynolds teaches “stable calcium phosphate complex, comprising amorphous calcium phosphate or a derivative thereof stabilised by a phosphopeptide” “which complex acts as a delivery vehicle that co- localises ions including, but not limited to calcium, fluoride and phosphate ions at a target site” (Reynolds 4:2-4; 5:1-4). 2. Reynolds teaches the “calcium complex may comprise 0.05- 50% by weight of the composition, preferably 1.0-50%. For oral compositions, it is preferred that the amount of the CPP-ACP and/or CPP- ACFP administered is 0.05 - 50% by weight, preferably 1.0% - 50% by weight of the composition” (Reynolds 5:9-12). 3. Reynolds teaches a “10% w/v casein or caseinate solution was prepared . . . CaCl2, sodium phosphate and NaF were added to the final concentrations of 100 mM, 60 mM and 12 mM respectively” (Reynolds 13:2-11). 4. Reynolds teaches: a 10% w/v CPP-ACFP solution containing 640 mM Ca, 400 mM phosphate and 80 mM F (1,520 ppm F-) at pH 9.0 has been prepared as well as a 20% CPP gel containing 1.28 M Ca, 800 mM phosphate and 160 mM F (3,040 ppm F-) at pH 9.0. This solution and gel exhibit a significantly greater anticariogenicity relative to the fluoride alone and therefore are superior additives to toothpaste and mouthwash and for professional application to improve the efficacy of the current fluoride- containing dentifrices and professionally-applied products. (Reynolds 13:19-26). 5. Reynolds teaches, in Example 5, A clinical trial of a mouthwash used thrice daily containing 3.0% CPP-ACP pH 9.0 showed that the calcium content of Appeal 2021-004901 Application 15/609,564 5 supragingival plaque (lower anterior teeth excluded) increased from 169 ± 103 μmol/g dry weight to 610 ± 234 μmol/g after use of the mouthwash for a three day period, and inorganic phosphate increased from 242 ± 60 μmol/g dry weight to 551 ± 164 μmol/g. These post-mouthwash levels of calcium and inorganic phosphate are the highest ever reported for non- mineralised supragingival plaque. (Reynolds 21:22-28). 6. Reynolds teaches, in Example 7, The 3.0% CPP-ACFP solution used as a mouthwash for four days contained 192 mM bound calcium ions, 120 mM bound phosphate ions and 24mM (456 ppm) bound F ions stabilised by CPP. The use of the mouthwash resulted in a 1.9 fold increase in plaque calcium, a 1.5 fold increase in plaque phosphate and a dramatic 18 fold increase in plaque fluoride ion. (Reynolds 24:23-28). 7. Reynolds teaches, in Example 8, Analysis of the solution containing 1.0% CPP, 60 mM CaC12, 36 mM sodium phosphate and 500 ppm F (26.3 mM NaF) pH 7.0 after ultrafiltration revealed that nearly half of the fluoride ion had incorporated into the ACP phase stabilised by the CPP to produce an amorphous calcium fluoride phosphate phase of composition Ca8(PO4)5F.xH2O, with 24 Ca, 15 PO4 and 3F molecules per CPP molecule. (Reynolds 26:15-20). 8. Reynolds teaches, in Example 11, a lozenge formulation as shown below: Appeal 2021-004901 Application 15/609,564 6 The lozenge of Example 11 included 3 % CPP-ACFP and a range of 0.01 to 0.05 % NaF that corresponds to 100 to 500 ppm (Reynolds 31:1-9). Principles of Law Anticipation under 35 U.S.C. § 102 requires that “‘each and every element as set forth in the claim is found, either expressly or inherently described, in a single prior art reference.”’ In re Robertson, 169 F.3d 743, 745 (Fed. Cir. 1999). Analysis Appellant contends that: As Dr. Walsh explained, “reconstitution” of powdered CPP- ACFP as described in Reynolds does “not result in the release of free ions from the CPP-ACFP complexes.” Second Walsh Declaration3, ¶ 6. Rather, “reconstitution” refers to reconstituting the dry powder into the solution or gel. The calcium, phosphate, and fluoride remain bound in the complexes, encapsulated by the casein phosphopeptide, “otherwise there would be no point to having formed the CPP- ACFP complexes in the first place.” Id. Thus, a person of ordinary skill in the art would “understand the amounts 3 Declaration of Laurence Walsh, dated June 30, 2016 (“Second Walsh Declaration”). Appeal 2021-004901 Application 15/609,564 7 referenced at page 13, lines 19- 23, to be the amounts of each of calcium, fluoride and phosphate as complexed in the CPP- ACFP.” Id. In this regard, Dr. Wash advised, “it is important to understand that in the field it is common to refer to fluoride as a molar concentration or as parts per million (ppm), such that the reference to ‘1,520 ppm F-‘ is not a reference to free fluoride ions, but rather is a common way of reporting the amount of fluoride that is present in the CPP-ACFP complex.” Id. (Appeal Br. 14). Appellant relies on similar reasoning for the other examples (generally Appeal Br.). As to Example 11 of Reynolds, the Reynolds Declaration4 states: As the lozenge formulation is almost exclusively made up of substances that bind water molecules, I do not expect there to be any 'free' water molecules available to hydrolyze the sodium fluoride into free sodium and free fluoride ions. Consequently, I do not believe that it is possible that the lozenge formulation would contain free fluoride ions. (Reynolds Decl. ¶ 11). The Examiner responds: This is a matter of claim interpretation. Instant claim 13 states, “prior to contacting the dental surface or subsurface” the composition comprises “about 0.01 % to 50% by weight of casein phosphopeptide-stabilized amorphous calcium phosphate . . . and separately, (ii) free fluoride ions in an amount of from at least 400 ppm to about 3,000ppm.” Claim 13 is anticipated insofar as Example 8 clearly showed, prior to the rat caries study, a solution comprising 1.0% CPP-ACP and 500 ppm F. (Ans. 4). 4 Declaration of Dr. Eric Reynolds, May 6, 2014. Appeal 2021-004901 Application 15/609,564 8 We review appealed rejections for reversible error based on the arguments and evidence the Patent Owners provide for each issue the Patent Owners identify. 37 C.F.R. § 41.37(c)(1)(iv); Ex parte Frye, 94 USPQ2d 1072, 1075 (BPAI 2010) (precedential) (cited with approval in In re Jung, 637 F.3d 1356, 1365 (Fed. Cir. 2011) (explaining that even if the Examiner had failed to make a prima facie case, “it has long been the Board’s practice to require an applicant to identify the alleged error in the examiner’s rejections”)). In the discussion of the CPP-ACP and 500 ppm F solution, Example 8 states that “nearly half of the fluoride ion had incorporated into the ACP phase stabilised by the CPP to produce an amorphous calcium fluoride phosphate phase” (FF 7). The reasonable interpretation of this paragraph is that the final solution used to treat teeth comprises at least half of the 500 ppm fluoride ions, leaving significantly less remaining in free fluoride form than the 400 ppm required by claims 13, 18, 19, and 21. We are not persuaded that the claims are reasonably understood as meaning that at any time during the process of making the treatment composition, so long as there is a 400 ppm or more free fluoride in the solution, the claims are anticipated. We find that the reasonable interpretation of this phrase is that immediately before administration, when the composition is complete and ready for use, there remains at least 400 ppm or more free fluoride as required by the claims. Under this interpretation, the composition recited in Example 8 does not retain 400 or more ppm fluoride when complete and ready for use and therefore does not anticipate. Conclusion of Law A preponderance of the evidence of record support the Examiner’s Appeal 2021-004901 Application 15/609,564 9 conclusion that Reynolds anticipates the claimed methods. A. 35 U.S.C. § 103(a) over Reynolds The Examiner finds it obvious “for the compositions to comprise free fluoride ions prior to use, especially given the synergistic recognition of NaF in combination with CPP-ACP (see Example 8 pp. 26-31) and the teaching of mouthwash formulations and liquid dentifrices” (Final Act. 6). The issues with respect to this rejection are: (i) Does a preponderance of the evidence of record support the Examiner’s conclusion that Reynolds renders the use of free fluoride with CPP-ACP or CPP-ACFP obvious? (ii) If so, has Appellant provided evidence of unexpected results that, when weighed with evidence supporting the prima facie case of obviousness, supports a finding of nonobviousness? Findings of Fact 9. The Reynolds Declaration shows a comparison with and without the use of added free fluoride that is reproduced below: Appeal 2021-004901 Application 15/609,564 10 The table shows “the surprising and unexpected increase in efficacy achieved using compositions as set forth in the claims across the full range of concentrations of CPP-ACP and free fluoride ions claimed” (Reynolds Decl. ¶¶ 10-11). Principles of Law A prima facie case for obviousness “requires a suggestion of all limitations in a claim,” CFMT, Inc. v. Yieldup Int’l Corp., 349 F.3d 1333, Appeal 2021-004901 Application 15/609,564 11 1342 (Fed. Cir. 2003) and “a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Prima facie obviousness can be rebutted by presenting evidence of secondary considerations and when such evidence is submitted, all of the evidence must be considered anew. In re Piasecki, 745 F.2d 1468, 1472- 1473 (Fed. Cir. 1984). Secondary considerations include: long-felt but unsolved needs, failure of others, unexpected results, commercial success, copying, licensing, and praise. In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998). Analysis While we find that the Examiner established an initial case of prima facie obviousness, and are not persuaded by Appellant’s arguments otherwise, we agree with Appellant that the evidence of unexpected results, when considered with the prima facie case, supports a finding that the claims would have been non-obvious to one of ordinary skill in the art. As the table reproduced in FF 9 shows, four different values of free fluoride substantially covering the claimed range and four different values of CPP-ACP within the claimed range showed unexpected results for remineralisation that were both statistically significant and nearly two fold improvements. The Reynolds Declaration states that these results are unexpected (FF 9). Thus, this data reasonably shows an unexpected difference in degree (see In re Huang, 100 F.3d 135, 139 (Fed. Cir. 1996)) that is “commensurate in scope with the degree of protection sought by the claimed subject matter.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005). Appeal 2021-004901 Application 15/609,564 12 When these unexpected results are considered with the prima facie case of obviousness, we agree with Appellant that “the evidence of record is sufficient to demonstrate that the claimed methods achieve surprising and unexpected results that further support patentability” (Reply Br. 8). Conclusions of Law (i) A preponderance of the evidence of record supports the Examiner’s conclusion that Reynolds renders the use of free fluoride with CPP-ACP or CPP-ACFP obvious. (ii) Appellant has provided evidence of unexpected results that, when weighed with evidence supporting the prima facie case of obviousness, supports a finding of nonobviousness. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Basis Affirmed Reversed 13-19, 21, 22, 24, 26, 28, 30, 32, 34 102 Reynolds 13-19, 21, 22, 24, 26, 28, 30, 32, 34 13-35 103 Reynolds 13-35 Overall Outcome 13-35 REVERSED