GALENICA AB

Patent Trials and Appeals Board

Mar 1, 2022

2021004847 (P.T.A.B. Mar. 1, 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. 15/890,610 02/07/2018 Henri Hansson 101616-0105 6077 22428 7590 03/01/2022 FOLEY & LARDNER LLP 3000 K STREET N.W. SUITE 600 WASHINGTON, DC 20007-5109 EXAMINER BROWE, DAVID ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 03/01/2022 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 2021-004847 Application 15/890,610 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 33, 34, 37-41, and 45 under pre-AIA 35 U.S.C. § 103 as obvious. Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject the claims. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 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 Galenica AB. Appeal Br. 3. Appeal 2021-004847 Application 15/890,610 2 STATEMENT OF THE CASE The Examiner rejects claims 33, 34, 37-41, and 45 in the Final Office Action as follows: 1. Claims 33, 34, and 37-41 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Narui et al. (US Patent No. 5,094,851, issued Mar. 10, 1992) (“Narui”) and Yuen et al. (US Patent No. 6,127,353, issued Oct. 3, 2000) (“Yuen”). Final Act. 4. 2. Claim 45 under pre-AIA 35 U.S.C. § 103(a) as obvious in view of Narui and Calis et al. (US Patent Application Pub. No. 2007/0099883 A1, published May 3, 2007) (“Calis”). Final Act. 7. An oral hearing was held February 10, 2022. A written transcript will be entered into the record in due course. Independent claim 33, the only independent claim on appeal, is reproduced below: 33. A non-foaming topical mometasone pharmaceutical cream composition in the form of an oil-in-water emulsion, comprising: 0.05%-0.2% w/w mometasone furoate or a molar equivalent amount of mometasone or a molar equivalent amount of another pharmaceutically acceptable ester thereof; 15-45 % w/w of butylene glycol; 3-30 % w/w vegetable oil; 1-15 % w/w of one or more emulsifying agents optionally, 0.1-1% w/w of a pH adjusting agent, optionally, 5-15% w/w viscosity increasing agent, and water. Dependent claim 33 is argued separately and is reproduced below: Appeal 2021-004847 Application 15/890,610 3 37. The composition of claim 33, wherein, after topical application, the composition achieves an AUC (area under the curve) of blanching index as a function of time that is at least 85% that of Elocon® cream 0.1%, which contains mometasone furoate USP in an amount of 1 mg/g of cream in a cream base comprising hexylene glycol NF, phosphoric acid NF, propylene glycol stearate having a monoester content of 55%, stearyl alcohol, ceteareth-20, titanium dioxide USP, gamma-irradiated aluminium starch octenylsuccinate, white wax NF, white petrolatum USP, and purified water USP. ANALYSIS The Examiner finds that Narui describes a topical cream composition comprising amounts of butylene glycol, vegetable oil, and emulsifying agents that overlap with the amounts recited in claim 33. Final Act. 4. The Examiner finds that the topical cream described by Narui comprises the corticosteroid deprodone, not the corticosteroid mometasone as required by claim 33. Id. at 5. The Examiner also finds that Narui does not disclose the claimed amount of the pH adjusting agent. Id. However, the Examiner finds that this deficiency is “cured” by Yuen, which describes an aqueous composition comprising the claimed mometasone and a pH adjusting agent in the claimed amounts. Id. at 6. The Examiner finds that one of ordinary skill in the art would have had reason to employ mometasone in Narui’s cream to improve its stability and treat skin inflammation as a topical cream. Id. The Examiner rejects dependent claim 45, which recites that “the mometasone furoate or mometasone or other pharmaceutically acceptable ester thereof is present in the anhydrous form,” based on the Narui and Calis references. Final Act. 7. The Examiner cites Narui for the same disclosure relied upon in the rejection of claim 33, upon which claim 45 depends. Id. at Appeal 2021-004847 Application 15/890,610 4 7-8. The Examiner relies on the disclosure in Calis of anhydrous mometasone, finding it obvious to use it in a topical cream as described by Narui for “improved stability under long term storage, . . . more convenient to dose, and . . . at least as effective at treating skin inflammation upon topical administration.” Id. at 9. Appellant argues, citing Desai,2 that “a composition for topical application depends on the physicochemical properties of the compound, including, e.g., molecular weight, functional groups, and solubility.” Appeal Br. 10. Appellant argues that deprodone propionate and mometasone furoate, while classified as corticosteroids, “exhibit such different physicochemical properties that a person of ordinary skill in the art would not have been motivated to formulate mometasone furoate in a formulation said to be useful for deprodone propionate, or had a reasonable expectation that mometasone furoate would be stable in such a formulation.” Id. Appellant identifies three differences between deprodone propionate and mometasone furoate. First, that deprodone propionate has a molecular weight of 400.5 g/mol, while mometasone furoate has a molecular weight of 521.4 g/mol. Appeal Br. 10-11. Second, that deprodone propionate has a LogP value of 2.6, while mometasone furoate has a LogP value of 5.06. Id. The LogP value, Appellant explains, is “the partition coefficient of the compound between two immiscible solvents at equilibrium, e.g., 1-octanol and water (logKow).” Id. at 11. Appellant states that the difference in the LogP values between the two compounds “reflects a large difference in 2 Archana Desai & Mary Lee, Topical and Transdermal Delivery Systems, in GIBALDI’S DRUG DELIVERY SYSTEMS IN PHARMACEUTICAL CARE, (Desai and Lee, eds.) (Am. Soc. Health-System Pharmacists) 43-50 (2007). Appeal 2021-004847 Application 15/890,610 5 lipophilicity that would be understood to impact formulation requirements, especially for oil-in-water (or water-in-oil) emulsion compositions.” Id. Third, that each of deprodone propionate and mometasone furoate have different chemical structures which would affect their ability to be formulated in Narui’s topical cream. Id. Molecular weight Appellant states, citing Andrews,3 “that it is known in the art that skin barrier properties prevent large molecular weight drugs (>500 Da) from penetrating intact skin.” Appeal Br. 12. Appellant argues that “the molecular weight of mometasone furoate is 121 Da higher than that of deprodone propionate, and actually exceeds the size generally understood to be capable of skin penetration.” Appellant also cites Magnusson4 as “determining that molecular weight is the main predictor of drug flux across skin for a series a [of] tested compounds.” Id. Appellant argues that difference between the molecular weights of deprodone propionate and mometasone furoate would have given the skilled worker “reason to question whether mometasone furoate could be readily formulated for topical/transdermal use in a formulation said to be useful for deprodone propionate, which has a molecular weight well-below the 500 kDa cut-off.” Id. This evidence does not persuade us that the Examiner erred. The Andrews publication describes transdermal delivery of a drug. Andrews’s 3 Samantha N. Andrews et al., Transdermal Delivery of Molecules is Limited by Full Epidermis, Not Just Stratum Corneum., 30(4) Pharm. Res. 1099- 1109 (2013). 4 Beatrice M. Magnusson et al. Molecular Size as the Main Determinant of Solute Maximum Flux Across the Skin., 122 J. Invest. Dermatol. 993-99 (2004). Appeal 2021-004847 Application 15/890,610 6 objective is to deliver the drug into the systemic circulation. Andrews 2.5 In contrast, it appears that Narui wants to limit systemic delivery: “It has therefore been desired to develop a corticosteroid-containing ointment which has high curative effects and which gives less side effects to the whole body or a part thereof and has higher safety.” Narui 1:44-47 (emphasis added). Appellant did not establish that Andrews and Narui have the same goal of promoting systemic delivery of a drug. The molecular weight barrier for transdermal delivery described by Andrews is for “hydrophilic and large molecular weight drugs (>500 Da)”. Andrews 2. Appellant did not establish that mometasone furoate is a hydrophilic drug and that such molecular weight barrier would apply to it. In sum, Andrews does not provide adequate support for Appellant’s argument that mometasone furoate could not be formulated as a “topical” cream. Reply Br. 3-4. Magnusson also is concerned with “systemic penetration after topical application” of a drug. Magnusson 993 (abstract). As indicated above, systemic penetration does not appear to be Narui’s main goal. Narui 1:44- 47. Nevertheless, to the extent that molecular weight is a factor in skin penetration, Magnusson mentions it as a determinant of systemic penetration, but not the only factor and does not reveal a specific molecular weight cut-off. Id. Thus, while mometasone might penetrate the skin more slowly or in less amounts than deprodone propionate, Magnusson does not teach not to use it or suggest that it would not be effective in a topical cream. 5 “There is a rich capillary bed in the superficial dermis just below the epidermis, which is the primary site of drug update into systemic circulation. Thus, successful transdermal drug delivery typically involves drug transport across the epidermis to the superficial dermal capillary bed.” Appeal 2021-004847 Application 15/890,610 7 Even if mometasone would have been believed to be inferior to deprodone in its ability to penetrate the skin because of its higher molecular weight, this fact is still insufficient to establish the non-obviousness of the claimed subject matter. A “teaching away” requires a reference to actually criticize, discredit, or otherwise discourage one of ordinary skill in the art from adopting an approach in the prior art. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004) (“The prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed”). Simply because mometasone might be inferior to deprodone in its ability to penetrate the skin, “does not mean that” the “inferior combination” of Narui and Yuen or Calis “is inapt for obviousness purposes.” In re Mouttet, 686 F.3d 1322, 1334 (Fed. Cir. 2012). “[A] reference may teach away from a use when that use would render the result inoperable.” In re ICON Health and Fitness, Inc., 496 F.3d 1374, 1381 (Fed. Cir. 2007). Appellant does not provide evidence that employing mometasone in Narui’s cream would result in an inoperable cream for the purpose of topical application of it. LogP values To support its position about the criticality of the difference between the LogP values of deprodone propionate and mometasone furoate, Appellant further cited Magnusson for disclosing “that for a series [of] tested compounds with similar molecular weights, maximum flux through skin was associated with a log Kow of 2.5-3.” Appeal Br. 12. Appellant concludes: “Narui’s deprodone propionate falls within the range, but mometasone furoate does not.” Id. Appeal 2021-004847 Application 15/890,610 8 Appellant does not direct us to where in Magnusson this statement is made. However, it appears to be from page 994 of Magnusson which discloses: “The maximum flux for certain series of solutes with a similar MW has been reported to be associated with a log Kow of 2.5-3.” This statement by Magnusson characterizes a “maximum flux” for solutes of a certain undisclosed molecular weight. It does not establish that mometasone furoate with a molecular weight of 521.4 and LogP of 5.06 would not have flux into or through the skin. Appellant has not provided evidence that achieving a “maximum flux” is necessary for one of ordinary skill in the art to have had a reasonable expectation of success of formulating mometasone furoate in Narui’s cream. In addition, as discussed above, even if mometasone is inferior to deprodone in its flux through the skin, Appellant did not establish that a person of ordinary skill in the art would not have been dissuaded from using it in Narui’s cream. Chemical structures As noted by the Examiner, both deprodone propionate and mometasone furoate have the same steroid core (Ans. 5): The structures are copied (Appeal Br. 11) below: deprodone propionate mometasone furoate Appeal 2021-004847 Application 15/890,610 9 The chemical structures of deprodone propionate (left) and mometasone furoate (right) are shown above.6 Appellant has not provided evidence that the structural differences between the two compounds, particularly in view of the similarity in their steroid core structure, would have led the skilled worker to doubt that mometasone furoate could be formulated in Narui’s cream in place of deprodone propionate. Yuen and Calis Appellant provided a declaration under 37 C.F.R. § 1.132 by Henri Hansson,7 Ph.D. (“Hansson Decl.”) in support of its arguments. Dr. Hansson is a co-inventor of the application in this appeal. Dr. Hansson did not specifically address the rejection based on Narui and Yuen or Calis, but instead addressed an earlier rejection citing “Tamarkin” in place of Narui, presumably the pending rejection at the time for the declaration was filed. Hansson Decl. ¶ 4. Dr. Hansson testifies that Yuen is “directed to a specific crystalline of mometasone furoate . . . which is said to more stable against precipitation when formulated in an aqueous suspension.” Hansson Decl. ¶ 14. Dr. Hansson testifies that Example 3 of Yuen is an “aqueous suspension for nasal administration.” Id. Dr. Hansson further states a “person of ordinary skill in the field preparing a foamable composition according to Tamarkin would not have had reason to modify Tamarkin’s foamable based on Yuen’s disclosure of an aqueous nasal suspension.” Id. 6 This is the best quality of the reproduced chemical structure made available to us by Appellant. 7 Declaration of Henri Hansson, Ph.D., dated Mar. 20, 2020. Appeal 2021-004847 Application 15/890,610 10 Dr. Hansson testifies that Calis is directed to “a stable, aqueous suspension of anhydrous mometasone furoate.” Hansson Decl. ¶ 16. Dr. Hansson further states that “given that Calis states in paragraph [0004] that its compositions address the instability of anhydrous mometasone furoate discussed in Yuen, a person of ordinary skill in the field would not have been motivated by Calis to use anhydrous mometasone furoate in a different composition, such as Tamarkin’s foamable compositions.” Id. Dr. Hansson is addressing the question of whether one of ordinary skill in the art would have had reason to use mometasone furoate in a foamable composition, when each of Yuen and Calis describe it in an aqueous suspension. Appellant generalizes from Dr. Hansson’s testimony that there is a lack of reason, and expectation of success, to formulate mometasone furoate in a composition which is not an aqueous suspension. Appeal Br. 14. We have considered Dr. Hansson’s testimony and Appellant’s argument, but they do not provide persuasive evidence of reversible Examiner error.8 Dr. Hansson did not address the obviousness of formulating mometasone furoate in the topical cream described by Narui. Indeed, the Specification, in which Dr. Hansson is named as a co-inventor, sheds light on this issue. The Specification describes three examples of 8 We review appealed rejections for reversible error based on the arguments and evidence Appellant provides for each issue identified by Appellant. 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”)). Appeal 2021-004847 Application 15/890,610 11 topical formulations of mometasone in its background section. The Specification discloses in its “Background of the invention”: US patent No. 4,808,610 (Schering Corp) and US patent No. 7,312,207 (Taro Pharmaceuticals) relate to mometasone containing compositions for topical use, wherein the composition is in the form of a water-in-oil (w/o) emulsion. WO 91/08733 (Schering Corp) relates to an oil-in-water (o/w) emulsion comprising a lipophilic active drug substance (e.g. mometasone). The examples show the necessity of using N- methyl-2-pyrrolidone in order to enhance the vasoconstrictor effect. In the examples propylene glycol is used in a concentration of 10% w/w. WO 2008/126076 (Perrigo Israel Pharmaceuticals Ltd.) relates to a low-dose mometasone formulation. Exemplary formulations are creams containing 0.075% mometasone, a polyol, a gelling agent, an oily phase and water. A low-dose mometasone formulation is desired in order to reduce the toxicity of a mometasone formulation. It is believed that a formulation of WO 2008/126076 has a relatively low systemic steroid absorption. No in vivo studies are reported. Spec. 1:21-36 (emphasis omitted). In view of the admitted prior art disclosing that mometsone was actually formulated in a topical water-in-oil composition, in an oil-in-water composition, and in a cream, it strikes us as inconsistent to argue that one ordinary skill in the art would not have had a reason to provide the mometasone furoate of Yuen and Calis in the cream of Narui comprising water and oil (Narui 2:10-17), and an expectation of success in doing so. See Appeal Br. 13, 14. For this additional reason, we are not persuaded that the differences between mometasone furoate and deprodone propionate would “have been expected to impact how they would be formulated to arrive at a topical pharmaceutical composition.” Id. at 15. Appellant has not identified Appeal 2021-004847 Application 15/890,610 12 any additional step that would be necessary to formulate mometasone in Narui’s composition. Claim 37 Claim 37, depends from claim 33, and further recites, that after application, “achieves an AUC (area under the curve) of blanching index as a function of time that is at least 85% that of Elocon® cream 0.1%, which contains mometasone furoate USP in an amount of 1 mg/g of cream in a cream base.” Appellant contends: neither Yuen nor Calis mention that topically applied mometasone furoate has a blanching effect. See, e.g., Hansson Declaration, ¶ 17. Thus, none of the cited references disclose, or provide any guidance on how to formulate, a mometasone furoate composition bioequivalent to Elocon® cream 0.1%. Rather, as Dr. Hansson attests with reference to FIG. 5 of the application, “it is only the present Application that describes the blanching effects of a composition as claimed.” Appeal Br. 17. Appellant also argues: Even if blanching is a known effect of certain topically applied corticosteroids-which the present record does not establish- there is no evidence that a person of ordinary skill in the art would have expected that formulating mometasone furoate in the manner Narui discloses for deprodone propionate would obtain a composition that is bioequivalent to Elocon® cream 0.1%, as assessed by blanching index. Appeal Br. 17 (underlining omitted). We have considered these arguments but they do not persuade us that the Examiner erred. Appeal 2021-004847 Application 15/890,610 13 Narui describes testing its cream for vasoconstriction and determining “the degrees or the presence or absence of skin paleness due to vasoconstriction.” Narui 8:3-35, 45-46. The skin blanching described in the Specification is disclosed as part of a “vasoconstrictor assay.” Spec. 19:30- 20:5. Skin blanching and skin paleness appear to be different names for the same activity. Consequently, the evidence indicates that determining skin paleness or blanching is a known effect of both deprodone propionate and mometasone furoate, as well as a known way to determine the efficacy of a topical composition formulated with these corticosteroids. As indicated by the Examiner, Narui describes a composition with overlapping amounts of butylene glycol, vegetable oil, and emulsifying agents. Final Act. 4-6. Appellant did not provide persuasive argument or evidence to challenge these findings by the Examiner. It is well established that, when there is a range disclosed in the prior art, and the claimed range overlaps or falls within that range, there is a presumption of obviousness. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). The skilled worker would have routinely optimized the amounts of each component to achieve the desired properties in vasoconstriction as described by Narui. See Narui 2:45-52). “[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). As held in Peterson, there is a “normal desire of scientists or artisans to improve upon what is already generally known.” Peterson, 315 F.3d at 1329-30. The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims . . . in such a situation, the applicant must show that the particular range is critical, generally by Appeal 2021-004847 Application 15/890,610 14 showing that the claimed range achieves unexpected results relative to the prior art range. In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990) (emphasis omitted). CONCLUSION The Examiner’s decision to reject claims 33 and 37 as obvious in view of Narui and Yuen is affirmed. Claims 34, 38-41, and 45 were not argued separately and fall with claim 33. 37 C.F.R. § 41.37(c)(1)(iv). DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 33, 34, 37- 41 103 Narui, Yuen 33, 34, 37- 41 45 103 Narui, Calis 45 Overall Outcome 33, 34, 37- 41, 45 TIME PERIOD No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(1)(iv). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED