GALENICA AB

Patent Trials and Appeals Board

Mar 10, 2022

2021004852 (P.T.A.B. Mar. 10, 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. 14/187,997 02/24/2014 Henri Hansson 101616-0104 7708 22428 7590 03/10/2022 FOLEY & LARDNER LLP 3000 K STREET N.W. SUITE 600 WASHINGTON, DC 20007-5109 EXAMINER WESTERBERG, NISSA M ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 03/10/2022 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 HENRI HANSSON and ANNA KARIN MORÉN Appeal 2021-004852 Application 14/187,997 Technology Center 1600 ____________ Before RICHARD M. LEBOVITZ, RYAN H. FLAX, and RACHEL H. TOWNSEND, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL The Examiner rejected claims 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, and 61 under 35 U.S.C. § 103(a) as obvious. Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject the claims.2 We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE and, pursuant to 37 C.F.R. § 41.50, set forth a new ground of rejection under 35 U.S.C. § 112, second paragraph. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42 (2012). Appellant identifies the real party in interest as Galenica AB. Appeal Br. 3. 2 An oral hearing was held February 10, 2022. A transcript of the hearing will be entered into the record in due course. Appeal 2021-004852 Application 14/187,997 2 REJECTIONS The Examiner rejected claims 30-32, 35, 36, 38, 42-45, 47-53, 55, 56, 60, and 61 in the Final Office Action as follows: Claims 30-32, 35, 36, 38, 42, 48-53, 55, 56, 60, and 61 under pre- AIA 35 U.S.C. § 103(a) as obvious in view of Arkin et al. (WO 2008/126076 A2, published Oct. 23, 2008) (“Arkin”), Chen et al. (US 2002/0107265 A1, published Aug. 8, 2002) (“Chen”), Sznitowska et al. (Eur. J. Pharm. Sci. 12: 175-179 (2001)) (“Sznitowska”), Calis et al. (US 2007/0099883 A1, published May 3, 2007) (“Calis”), and Guentensberger et al. (US 5,952,003, issued Sept. 14, 1999) (“Guentensberger”). Final Act. 4- 5; Ans. 3.3 Claims 42-45, 47, and 48 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Arkin, Chen, Calis, Sznitowska, Guentensberger, “The HLB System” (1980), Saunier et al. (US 2005/0220823 A1, published Oct. 6, 2005) (“Saunier”), and Rovee et al. (US 4,282,216, issued Aug. 4, 1981) (“Rovee”). Final Act. 14; Ans. 10. Claim 30, the only independent claim on appeal, is reproduced below (annotated with bracketed numbers to reference the limitations in the claims): 3 Claim 34 is pending and was listed on the cover page of the Final Office as being rejected. However, there is no rejection of it in the Final Office Action or in the Answer. In an earlier Final Office Action dated December 4, 2019, claim 34 was rejected over the combination of Arkin, Chen, Calis, Sznitowska, Guentensberger, but the rejection of this claim was not repeated in subsequent Office Actions. Appeal 2021-004852 Application 14/187,997 3 30. An oil-in-water emulsion topical mometasone pharmaceutical composition formulated for application to skin, comprising [1] from 0.075% to 0.2% mometasone furoate; [2] from about 20 to about 45% w/w of propylene glycol; [3] from 5-15% w/w of coconut oil; [4] from 1-15% w/w of one or more emulsifying agents selected from glycerol alkyl esters, macrogol alkyl esters, polyoxyethyleneglycol alkyl esters, fatty acids, polyoxyethylene sorbitan esters, polyoxyethylene alkyl ethers, and galactolipids; and [5] water, wherein the w/w amounts are based on the total weight of the emulsion; wherein the emulsion comprises undissolved mometasone furoate in micronized form, wherein the micronized mometasone furoate has a particle size distribution such that 100% of the particles have a particle size ≤ 20 μm, 99% have a particle size ≤ 15 μm, and 80% have a particle size ≤ μM; and, wherein the emulsion is bioequivalent to ELOCON® cream 0.1 %, which is a water-in-oil emulsion which contains mometasone furoate USP in an amount of 1 mg/g of cream in a cream base comprising hexylene glycol NF in an amount of 120 mg/g of cream, propylene glycol stearate having a monoester content of 55% in an amount of 80 mg/g of cream, ceteareth-20 compounded with stearyl alcohol in an amount of 70 mg/g of cream, titanium dioxide USP in an amount of 10 mg/g of cream, gamma-irradiated aluminium starch octenylsuccinate in an amount of 100 mg/g of cream, white wax NF in an amount of 50 mg/g of cream, white petrolatum USP in an amount of 539 mg/g of cream, purified water USP in an amount of 30 mg/g of cream, and phosphoric acid NF in an amount used to adjust the pH of the purified water to pH 2.5 ± 0.2 charged as a 10% w/v solution. Appeal 2021-004852 Application 14/187,997 4 STATEMENT OF THE CASE Claim 30 is directed to an “oil-in-water emulsion” comprising mometasone furoate which is formulated for topical application to the skin. Mometasone furoate is a corticosteroid compound that has been described in the prior art as “useful as a topical anti-inflammatory compound.” Arkin ¶ 1. The emulsion “comprises undissolved mometasone furoate in micronized form.” The micronized mometasone has a particle size distribution. The Specification does not provide a definition of “micronized,” so we consulted a dictionary for its meaning. The dictionary defines “micronized” as a substance “reduced to a fine power” where the particles are measured in microns.4 This definition is consistent with the Specification which discloses that the mometasone is “in the form of fine particles, notably in micronized form.” Spec. 3:15-17. The claimed emulsion comprises five components: [1] mometasone furoate, [2] propylene glycol, [3] coconut oil, [4] one or more emulsifying agents, and [5] water. Each of components [1]-[4] are present in specifically recited amounts. The emulsion is claimed as bioequivalent to “ELOCON® cream 0.1 %, which is a water-in-oil emulsion which contains mometasone furoate.” The prior art explains that “[m]ometasone furoate cream is currently manufactured and sold as a topical cream under the trademark Elocon® Cream 0.1%.” Arkin ¶ 2. The Examiner finds that Arkin describes a topical cream comprising mometasone furoate ([1]) and the same four other components [2]-[5] 4 https://www.collinsdictionary.com/us/dictionary/english/micronized (last accessed Feb. 24, 2022). Appeal 2021-004852 Application 14/187,997 5 recited in claim 30. Ans. 3-5. The Examiner finds that the amounts of [2] propylene glycol and the [4] one or more emulsifying agents described by Arkin overlap with the amounts recited in the claim. Id. The Examiner finds that Arkin discloses that coconut oil can be present in its oil-in-water composition, but that Arkin doesn’t describe its presence in an amount of “from 5-15% w/w” as required by claim 30. Id. at 6. To meet this deficiency, the Examiner cites the Chen reference for its disclosure of an oil- in-water emulsion comprising coconut oil and other oils in amounts that overlap with the claimed amount. Id. Claim 30 further recites that the emulsion “comprises undissolved mometasone furoate in micronized form.” The Examiner acknowledges that Arkin does not describe this limitation. Ans. 7. The Examiner turns to Calis for its description of micronized anhydrous mometasone furoate. Id. To meet the limitation that the emulsion comprises “undissolved” mometasone furoate, the Examiner cites Sznitowska for its disclosure “that submicron emulsions can increase the solubility and bioavailability of drugs” and that the presence “of even significant amounts of drug in the solid phase did not influence the short term stability of the emulsion for drugs that were insoluble and stable emulsions were obtained when the substances were not easily wet by the emulsion.” Id. Based on this teaching, the Examiner concludes that it would have been obvious to one of ordinary skill in the art at the time of the invention to use the undissolved micronized mometasone furoate of Calis in Arkin’s emulsion because Sznitowska teaches that solids can be present in emulsions without affecting their stability and because the presence of the solid “can also increase the amount of drug that can be delivered using the formulation.” Ans. 8. Appeal 2021-004852 Application 14/187,997 6 With respect to the bioequivalence of the claimed emulsion to “ELOCON® cream 0.1%,” the Examiner finds that Guentensberger discloses that bioequivalence to an FDA approved drug is advantageous because it allows a formulation to be “marketed as generic equivalents of the approved product without performing new safety and efficacy studies, which add considerably to the cost of obtaining FDA approval to market a drug product (col 1, ln 40-50).” Ans. 9. The Examiner finds that one of ordinary skill in the art would have been motivated to formulate mometasone furoate as recited in claim 1 as bioequivalent to “ELOCON® cream 0.1%” for the reasons disclosed in Guentensberger. Id. ANALYSIS We review appealed rejections for reversible error based on the arguments and evidence an Appellant provides for each issue the Appellant identifies. 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 this case, we are persuaded by the evidence of record that the Examiner erred in determining that it would have been obvious to one of ordinary skill in the art at the time of the invention to formulate the emulsion described by Arkin with “undissolved mometasone furoate in micronized form,” as claimed. Appeal 2021-004852 Application 14/187,997 7 Arkin describes a topical composition comprising mometasone furoate to be applied on the skin. Arkin ¶¶ 16, 17. As the Examiner finds, Arkin’s composition contains the same components [1]-[5] recited in claim 30 and can be formulated as an oil-in-water emulsion as required by rejected claim 30. Id. ¶¶ 17, 19, 20, 23-26, 33. In Example 1 in which Arkin prepares a cream comprising mometasone furoate, “mometasone furoate USP is dissolved in heated propylene glycol” to form an “active solution.” Id. ¶ 49. The Examiner did not find that there is undissolved mometasone furoate in the “active solution.” To make the emulsion, Arkin prepares a water phase and oily phase. Id. ¶¶ 48, 50. Arkin teaches that the active solution and oily phase are added to the water phase and that the “resulting emulsion is cooled.” Id. ¶¶ 51, 52. The Examiner did not find that there is undissolved mometasone furoate in the “resulting emulsion.” Because Arkin describes dissolving the mometasone furoate in the propylene glycol, the Examiner turned to Sznitowska to find a reason to use “undissolved micronized mometasone furoate” in Arkin’s emulsion. First, Calis is cited by the Examiner for disclosing the micronized mometasone furoate. Calis ¶ 9. The composition described by Calis is “a stable aqueous anhydrous mometasone furoate suspension” (id. ¶ 5); it is not described as being an oil-in-water emulsion. The Examiner cited Sznitowska as providing the reason to use Calis’s micronized mometasone in Arkin’s emulsion. The Sznitowska reference describes submicron emulsions as drug carriers. Sznitowska 175 (“Abstract”). A submicron emulsion is not defined in Sznitowska, but Sznitowska describes making an emulsion and then filtering it through a Appeal 2021-004852 Application 14/187,997 8 0.45-μm filter, which we understand would result in a filtered emulsion comprising submicron droplets by virtue of passing the emulsion through the submicron filter. Sznitowska 176 (“2.2.1 Emulsion preparation”). Sznitowska discloses that “submicron emulsions have gained increasing attention as drug carriers” for parenteral, ocular, and topical applications. Sznitowska 175 (“I. Introduction”). Sznitowska describes the “main advantage” of these systems as “the potential to increase the solubility as well as the bioavailability of drugs.” Id. However, Sznitowska discloses that “submicron emulsions are thermodynamically unstable which may lead to aggregation, flocculation, coalescence and eventual phase separation.” Id. Sznitowska discloses “short-term stability studies” of 35 drugs “with regard to their compatibility with 20 or 5% parenteral fat emulsions.” Id. (“Abstract”). To make the emulsion, Sznitowska describes first mixing soya- bean oil with an aqueous phase of lecithin and glycerol, next preparing a primary emulsion of the oil and aqueous phases, and then filtering the emulsion through a 0.45-μm filter to make the submicron emulsion. Id. 176 (“2.2.1 Emulsion preparation”). Drugs were added by Sznitowska to the emulsion. Id. (“2.2.2. Introduction of drugs to the emulsion”). Sznitowska discloses that “stable emulsions were obtained when the undissolved substance was not easily wet by the emulsion, which was the case for estradiol, denotivir and disulfiram.” Id. 178. However, not all the emulsions showed such stability. Of nineteen drugs prepared in a 5% oily phase, eight exhibited destabilization problems: four were described as “Unstable” and four showed “Phase separation.” Id. 179 (Table 3). Based on these experiments, Sznitowska concludes that “it is difficult to predict Appeal 2021-004852 Application 14/187,997 9 changes in the physical stability of the system.” Sznitowska (Abstract). Sznitowska explains: The study has shown that interaction of drugs with submicron emulsions is complex in nature. Taking into consideration the physicochemical properties of a drug e.g. lipophilicity or ionization, it is difficult to predict changes in the physical stability of the system. If destabilization occurs it is maximal at saturated concentrations and the presence of even significant amounts of the solid phase formed by undissolved drug does not influence the short-term stability of the system. Due to the increased ratio of emulgator to oil, emulsions containing 5% of oily phase are less susceptible to destabilization than 20% emulsions. Id. While some of these emulsions described by Sznitowska may comprise undissolved drug and still maintain their stability (id. 1775), the Examiner did not direct us to a statement in Sznitowska where an advantage to undissolved drug in the emulsion is described as asserted in the Answer (“solids can be present in drug delivery emulsions . . . and can also increase the amount of drug that can be delivered using the formulation”). Ans. 8. Indeed, Sznitowska explains that, for damazol and haloperidol, “increasing the amount of the solid phase of” each “did not influence their interaction with the system.” Sznitowska 178. The Examiner’s reason to combine Arkin and Sznitowska is therefore deficient. Sznitowska does not describe how to overcome the stability problem with drugs or how to predict which ones would be stable. As explained above, Sznitowska - after studying 35 different drugs- concluded that “it 5 “[T]he presence of even significant amounts of the solid phase formed by undissolved drug did not influence the short-term stability of the emulsions.” Appeal 2021-004852 Application 14/187,997 10 is difficult to predict changes in the physical stability of the system.” Sznitowska (“Abstract”). Also, as explained above, in one experiment described by Sznitowska, 8 of 19 drugs were either unstable or exhibited phase separation. Id. 179 (Table 3). The Examiner did not provide an adequate reason as to why one of ordinary skill in the art would have followed Sznitowska’s process for making a submicron drug emulsion by adding drug directly to the submicron emulsion (id. (“2.2.2. Introduction of drugs to the emulsion”)), rather than dissolving it first in heated propylene glycol as described by Arkin (Arkin ¶ 49), when Sznitowska teaches it is unpredictable to formulate stable drug submicron emulsions. To further support their position that the Examiner erred in combining Arkin, Calis, and Sznitowska, Appellant cites a patent by Munayyer6 which describes “an elegant, stable, self-preserving cream” containing mometasone furoate. Munayyer (Abstract). Munayyer discloses that when mometasone furoate “was partially dissolved and partially suspended in propylene glycol based cream formulations, the resulting formulations did not possess the necessary efficacy.” Id. 1:21-24. To avoid this problem Munayyer prepares its formulations by dissolving mometasone furoate in hexylene glycol/water at 60-65°C and heating to 70°C. Id. 3:29-31. The approach suggested by the Examiner, of providing undissolved mometasone in the cream formulation of Arkin, is therefore disparaged by Munayyer and raises doubt that a bioequivalence to ELOCON® cream 0.1 % could be obtained. A prima facie case for obviousness requires “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. 6 U.S. Patent Number 4,808,610, issued Feb. 28, 1989. Appeal 2021-004852 Application 14/187,997 11 Teleflex Inc., 550 U.S. 398, 418 (2007). One of ordinary skill in the art must also have a reasonable expectation that the prior art, when combined, would succeed in making the claimed invention. Accorda Therapeutics, Inc. v. Roxane Laboratories, Inc., 903 F.3d 1310, 1333 (Fed. Cir. 2018). Here, the Examiner did not provide a sufficient reason to have combined the micronized mometasone furoate of Calis with Arkin’s emulsion to have arrived at the claimed oil-in-water emulsion comprising “undissolved mometasone furoate in micronized form” nor a reasonable expectation of success in doing so. For the foregoing reasons, the rejection of claim 30 is reversed. Dependent claims 31, 32, 35, 36, 38, 42-45, 47-53, 55, 56, 60, and 61 are reversed for the same reasons. NEW GROUND OF REJECTION Claims 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, and 61 are rejected under 35 U.S.C. § 112, second paragraph, as indefinite. This is a new ground of rejection pursuant to 37 C.F.R. § 41.50(b) (2011). Under 35 U.S.C. § 112, second paragraph, a “specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.” The statute requires the claims “to be cast in clear-as opposed to ambiguous, vague, indefinite-terms.” In re Packard, 751 F.3d 1307, 1313 (Fed. Cir. 2014). The rationale for requiring such “reasonable precision” in claim language is because “[i]t is the claims that notify the public of what is within the protections of the patent, and what is not.” Id. Appeal 2021-004852 Application 14/187,997 12 Claim 30 recites that the “oil-in-water emulsion topical mometasone pharmaceutical composition formulated for application to skin” is “bioequivalent to ELOCON® cream 0.1%.” The claim does not recite what activity of the claimed composition is “bioequivalent” to the activity of the ELOCON® cream or how the bioequivalence is measured. The Specification refers to “skin blanching” as a measure of the bioequivalence of the topical cream, but skin blanching is not recited in the claim. Spec. 18- 19. We decline to import limitations from the Specification into the claims. “[A] particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.” SuperGuide Corp. v. DirecTV Enters., Inc., 358 F.3d 870, 875 (Fed. Cir. 2004). The claim is indefinite under 35 U.S.C. 112, second paragraph, because the meaning of the term “bioequivalence” is not clear. It cannot be determined from the claim what bioequivalent activity of the claimed emulsion that the claim seeks to protect. CONCLUSION The Examiner’s decision to reject claims 30-32, 35, 36, 38, 42-45, 47-53, 55, 56, 60, and 61 is reversed. A new ground of rejection is set forth over claims 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, and 61. Appeal 2021-004852 Application 14/187,997 13 DECISION SUMMARY Claims Rejected 35 U.S.C. § Reference(s)/ Basis Affirmed Reversed New Ground 30-32, 35, 36, 38, 42, 48-53, 55, 56, 60, 61 103(a) Arkin, Chen, Calis, Sznitowska, Guentensberg er 30-32, 35, 36, 38, 42, 48-53, 55, 56, 60, 61 42-45, 47, 48 103(a) Arkin, Chen, Calis, Sznitowska, Guentensberg er, “The HLB System,” Saunier, Rovee 42-45, 47, 48 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, 61 112 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, 61 Overall Outcome 30-32, 35, 36, 38, 42-45, 47-53, 55, 56, 60, 61 30-32, 34-36, 38, 42-45, 47-53, 55, 56, 60, 61 TIME PERIOD FOR RESPONSE This decision contains a new ground of rejection pursuant to 37 C.F.R. § 41.50(b). 37 C.F.R. § 41.50(b) provides “[a] new ground of Appeal 2021-004852 Application 14/187,997 14 rejection pursuant to this paragraph shall not be considered final for judicial review.” 37 C.F.R. § 41.50(b) also provides that the Appellant, WITHIN TWO MONTHS FROM THE DATE OF THE DECISION, must exercise one of the following two options with respect to the new ground of rejection to avoid termination of the appeal as to the rejected claims: (1) Reopen prosecution. Submit an appropriate amendment of the claims so rejected or new Evidence relating to the claims so rejected, or both, and have the matter reconsidered by the examiner, in which event the proceeding will be remanded to the examiner. . . . (2) Request rehearing. Request that the proceeding be reheard under § 41.52 by the Board upon the same Record. . . . Further guidance on responding to a new ground of rejection can be found in the Manual of Patent Examining Procedure § 1214.01. REVERSED; 37 C.F.R. 41.50(b)