Ferring B.V.

Patent Trials and Appeals Board

Feb 23, 2022

2022000570 (P.T.A.B. Feb. 23, 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. 16/010,412 06/16/2018 Shweta Gupta 122060-0103 4961 22428 7590 02/23/2022 FOLEY & LARDNER LLP 3000 K STREET N.W. SUITE 600 WASHINGTON, DC 20007-5109 EXAMINER LEE, JIA-HAI ART UNIT PAPER NUMBER 1658 NOTIFICATION DATE DELIVERY MODE 02/23/2022 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 SHWETA GUPTA, VARINDER AHUJA, TEJAS GUNJIKAR, and KRISTIN WANNERBERGER Appeal 2022-000570 Application 16/010,412 Technology Center 1600 Before RICHARD M. LEBOVITZ, RYAN H. FLAX, and RACHEL H. TOWNSEND, Administrative Patent Judges. TOWNSEND, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims to an orodispersible pharmaceutical composition that dissolves within 10 seconds upon contact with an aqueous solution or with saliva as being obvious. An oral hearing was held on February 10, 2022. 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 Ferring B.V. (Appeal Br. 3.) Appeal 2022-000570 Application 16/010,412 2 STATEMENT OF THE CASE Appellant’s Specification states: “Fast dissolving pharmaceutical dosage forms which are designed to release an active ingredient in the oral cavity are well known.” (Spec. 1.) It is noted that In a fast dissolving dosage form, a drug may physically be trapped in a matrix composed of e.g. mannitol and fish gelatin (EP 1501534; EP 1165053), modified starch (US6509040), pullulan in combination with an amino acid (EP1803446), or maltodextrin in combination with sorbitol (US2004/0228919). (Id.) The Specification goes on to explain regarding these specific prior art formulations: The solution, suspension or dispersion of the drug and the carrier material may be filled into blister cavities, frozen and thereafter lyophilized. However, dosage forms produced in this manner are mostly fragile and brittle, have limited physical strength, and cannot withstand any pressure. In addition, dosage units so produced are difficult to pack and unpack. (Id.) Appellant’s claimed invention is directed to a similar fast dissolving dosage form, but one that has high tensile strength, which permits the dosage form to be easily removed from its container without disintegrating. Id. Claims 32-35, 38, 40-43, 46-51, and 54 are on appeal. Claim 32, reproduced below, is illustrative of the claimed subject matter: 32. A pharmaceutical composition comprising: (a) an open matrix network comprising at least one matrix- forming agent that is levan forming the open matrix network; and (b) at least one pharmaceutically active ingredient carried in the open matrix network, wherein the composition does not include fish gelatin and does not include modified starch, and wherein the composition is an orodispersible pharmaceutical dosage form wherein at least 80% of the Appeal 2022-000570 Application 16/010,412 3 composition dissolves within 10 seconds upon contact with an aqueous solution or with saliva. (Appeal Br. 22.) The prior art relied upon by the Examiner is: Name Reference Date Nilsson et al. EP 1501534 B1 July 26, 2006 J. Combie Chapter 13 Properties of Levan and Potential Medical Uses, In Marchessault, R. et al. Polysaccharides for Drug Delivery and Pharmaceutical Applications, ACS Symposium Series, Am. Chem. Soc’y, 263-69 2006 Masaaki Sugimoto et al. Effect of Formulated Ingredients on Rapidly Disintegrating Oral Tablets Prepared by the Crystalline Transition Method, 54(2) Chem. Pharm. Bull. 175-80 2006 The following grounds of rejection by the Examiner are before us on review: Claims 32-35, 38, 41-43, 46-51, and 54 under 35 U.S.C. § 103(a) as unpatentable over Nilsson and Combie. Claim 40 under 35 U.S.C. § 103(a) as unpatentable over Nilsson, Combie, and Sugimoto. Appeal 2022-000570 Application 16/010,412 4 DISCUSSION Claim 32 The Examiner found Nilsson teaches a composition of desmopressin acetate that disintegrates in the mouth within 10 seconds where the composition includes an open matrix network carrier material that “can be plant polysaccharides comprising xanthan, guar, agar and other carbohydrates.” (Final Action 4 (citing Nilsson ¶¶ 13, 61, 62, 65).) The Examiner further found that the composition includes “one or more bioadhesive polymer to improve the disintegration profile and the organoleptic properties of the dosage form.” (Id. at 5 (citing Nilsson ¶ 47).) The Examiner further found that “Combie teaches levan has stronger adhesive strength than natural polymers, e.g., polysaccharides of guar gum and xanthan gum, (p264, para 2)” and “is suitable as a drug carrier for making tablets (p264, para 3).” (Id.) The Examiner concluded from the foregoing teachings that “one of ordinary skill in the art would have [been] taught to use a water soluble levan with strong adhesive strength as a polysaccharide carrier (as an alternative to fish gelatin or modified starch) to make an orodispersible tablet as suggested by Nilsson et al. [0065].” (Id.) We agree with the Examiner that the teachings of Combie and Nilsson make prima facie obvious the claimed pharmaceutical composition. Moreover, we determine that Appellant has not provided rebuttal evidence that is sufficient, when considered together with the evidence adduced by the Examiner, to establish non-obviousness. Appellant argues the Examiner erred because, for open matrix network formulations, “Nilsson emphasizes those based on fish gelatin . . . See, e.g., Nilsson, paragraph [0063], and Examples 1-7,” which the claims Appeal 2022-000570 Application 16/010,412 5 exclude (Appeal Br. 12.) Appellant argues that one of ordinary skill in the art would not have read paragraphs 64 and 65 of Nilsson as describing “a genus of ‘polysaccharide’ carriers (of which levan would be a species).” (Id. at 13.) Appellant notes also that Nilsson does not use the phrase “plant polysaccharides” in identifying alternative carrier materials that may be used in place of partially hydrolyzed gelatin or fish gelatin as the open matrix network-forming agent (Appeal Br. 16), but rather states in paragraph 64 that the alternative may be: for example polysaccharides such as hydrolysed dextran, dextrin and alginates (e.g. sodium alginate) or mixtures of above mentioned carriers with each other or with other carrier materials such as polyvinyl alcohol, polyvinylpyrrolidine or acacia. Modified starch may also be used in place of gelatin, (Appeal Br. 13 (quoting paragraph 64).) And Appellant notes that Nilsson, in paragraph 65, states: Other carrier materials which may be present in addition to, or in some cases in place of, the above carriers include: gums such as tragacanth, xanthan, carageenan, and guar; mucilages including linseed mucilage and agar; polysaccharides and other carbohydrates such as pectin and starch and its derivatives, particularly soluble starch and dextrates; water soluble cellulose derivatives, such as hydroxyethylmethyl cellulose, hydroxypropylmethyl cellulose and hydroxypropyl cellulose; and carbomer. (Id. (quoting paragraph 65).) According to Appellant, although Nilsson discloses alternative carrier materials in paragraphs 64 and 65, one of ordinary skill in the art “would have been led to use one of the polysaccharides disclosed to be suitable for that purpose in Nilsson, e.g., hydrolyzed dextran, dextrin, alginates or modified starch” and “would not have had a reason to go further afield and try using levan.” (Id.) Appeal 2022-000570 Application 16/010,412 6 We do not find the foregoing arguments by Appellant persuasive. First, that Nilsson describes fish gelatin as a preferred carrier material (Nilsson ¶ 63), does not detract from the fact that Nilsson also teaches that alternative materials may be used instead, including a polysaccharide (Nilsson ¶¶ 64, 65). “‘[T]he fact that a specific [embodiment] is taught to be preferred is not controlling [for obviousness], since all disclosures of the prior art, including unpreferred embodiments, must be considered.’” Merck & Co. Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (quoting In re Lamberti, 545 F.2d 747, 750 (CCPA 1976).) Moreover, we do not find persuasive Appellant’s argument, unsupported by evidence, that one of ordinary skill in the art would read Nilsson paragraphs 64 and 65 as being limited to only those compounds specifically enumerated as alternatives (Appeal Br. 13), rather than understanding the term “polysaccharide” used therein to embrace a genus of compounds and identifying but a few exemplary members within that genus. A plain reading of those paragraphs is that they describe that other materials besides hydrolyzed gelatin or fish gelatin may be used as the open matrix carrier material for an orodispersible formulation. Paragraph 64 provides “for example polysaccharides such as . . .” “may be used in place of” the gelatins and that “[m]odified starch may also be used in place of gelatin.” (Nilsson ¶ 64.) Paragraph 65 provides an enumeration of still “[o]ther carrier materials which may be present in addition to, or in some cases in place of, the above carriers include: gums such as tragacanth, xanthan, carrageenan, and guar . . . polysaccharides and other carbohydrates such as pectin and starch and its derivatives, particularly soluble starch and dextrates . . . .” (Id. ¶ 65.) The language “for example. . . such as” and “include” reasonably can Appeal 2022-000570 Application 16/010,412 7 be read as being exemplary of types of polysaccharides that can be used. “Attorney’s argument in a brief cannot take the place of evidence.” In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Furthermore, while it is true that Nilsson does not use the phrase “plant” polysaccharides in characterizing xanthan, carageenan, guar and other polysaccharides that can be used as an alternative to fish gelatin or partially hydrolyzed gelatin, it is nevertheless true that Nilsson does list a number of plant polysaccharides. Thus, we do not find error in the Examiner’s statement that Nilsson teaches that plant polysaccharides may be used as an alternative to fish gelatin or partially hydrolyzed gelatin. Appellant further argues that the Examiner’s reliance for motivation to combine the teachings of Combie with Nilsson based on the “adhesive” teaching in Nilsson paragraph 47 is inapt because “this portion of Nilsson relates to embodiments comprising an effervescent agent,” not the open matrix network embodiments. (Appeal Br. 15.) Appellant explains that “Nilsson does not teach or suggest that a bioadhesive polymer would be suitable as the open matrix network-forming agent of an open matrix network-type orodispersible dosage form” but rather teaches that in the open matrix network formulations, a “water-soluble or water dispersible carrier material that is inert towards desmopressin” is what is used. (Id. (citing Nilsson ¶ 55).) Appellant explains that one of ordinary skill in the art would not have considered improved area of contact between the dosage form and the oral mucosa achieved with a bioadhesive polymer in an effervescent formulation to be “germane to an orodispersible dosage form wherein at least 80% of the composition dissolves within 10 seconds.” (Id. at 15-16.) According to Appellant, that is because “[i]mproved residence time is not Appeal 2022-000570 Application 16/010,412 8 relevant to a composition intended to dissolve within 10 seconds.” (Id. at 16). Thus, Appellant concludes that “the Examiner has not provided any evidence or scientific reasoning why the adhesive properties of levan discussed in Combie would have been expected to make it suitable for a fast- dissolving composition as claimed.” (Id.) We agree with Appellant that the Examiner inappropriately relied on an alleged improved bioadhesive property of levan over xanthan or guar gum as a motivation to select levan for use as the open matrix carrier in an orodispersible formula based on Nilsson’s teaching at paragraph 47. The paragraph 47 teaching is concerned with formulations other than the open matrix network formulations. As Appellant notes, the open matrix network formulations are described as something different from “the above described formulations” such as described in paragraph 47. (Nilsson ¶ 55.) Nevertheless, we agree with the Examiner that Combie with Nilsson would have been combined by the one having ordinary skill in the art and that the teachings of these references establish a reason to formulate levan into an orodispersible open matrix carrier formulation. As the Examiner noted, Combie teaches that levan is water soluble and has potential use in tablets “when dissolution is desired shortly after ingestion.” (Combie 264.) Combie teaches that “[i]f a more gradual breakup of the tablet is desired, a more water resistant fructan would be useful.” (Id.) We conclude from the foregoing that Combie suggests the use of levan in a tablet that includes an active agent when rapid dissolution of that tablet by water is desired. Combie explains that the moieties responsible for the adhesive properties of levan are also responsible for the interaction with water (Combie 264-65) which provides some rationale for Combie’s Appeal 2022-000570 Application 16/010,412 9 teaching that levan can bond tablets but it also provides for dissolution of the tablet shortly after ingestion. (Id. at 264.) We disagree with Appellant that the Examiner “overstates the relevance of Combie” (Appeal Br. 14). That Combie does not provide any more extensive discussion of tablets (id. at 13) is not rebuttal “evidence” demonstrating non-obviousness. “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). While Combie does not describe the tablet form, Nilsson teaches some forms that can achieve a disintegration of 10 seconds or less, where the preferred form is an open-matrix network formulation. (Nilsson ¶¶ 55, 56.) Nilsson explains: The open matrix network which is similar in structure to a solid foam enables a liquid to enter the product through the interstices and permeate through the interior. Permeation by aqueous media exposes the carrier material of both the interior and exterior of the product to the action of the aqueous media whereby the network of carrier material is rapidly disintegrated. (Id. ¶ 61.) Nilsson teaches that “any” water soluble or water-dispersible material that is pharmaceutically acceptable and is capable of forming a rapidly disintegratable open matrix may be used as a carrier in an orodispersible formulation (Nilsson ¶¶ 61, 62), and that polysaccharides from plants are such a material that may be used as the carrier (id. ¶ 65). Appellant argues that Combie “does not teach or suggest that levan would be useful as a matrix forming agent to form an open matrix network for an orodispersible dosage form.” (Appeal Br. 14; see also Reply Br. 5.) Appeal 2022-000570 Application 16/010,412 10 However, Nilsson teaches that numerous water-soluble polysaccharides including those from plants may be used to make such a matrix. Thus, one of ordinary skill in the art would have had a reasonable expectation that the water-soluble polysaccharide, levan, just like the other polysaccharides suggested in Nilsson (including plant based polysaccharides), could be used in the methodology described for making the open matrix orodispersible dosage forms described in Nilsson. (See, e.g., Nilsson Example 1.) Thus, the Examiner had fact-based reasons to conclude that one of ordinary skill in the art would have been taught by Combie to use water soluble levan to make an orodispersible tablet described by Nilsson. Appellant argues that the experimental data of record teaches that not all water-soluble polysaccharides can be used as the matrix forming agent to result in dissolution times of less than 10 seconds and “undermine[s] the fundamental premise of the rejection-that any water-soluble polysaccharide could be used in place of Nilsson’s fish gelatin” with a reasonable expectation of succeeding in obtaining the claimed dissolution times. (Appeal Br. 17-18.) In other words, Appellant argues that the evidence of record establishes there is not a reasonable expectation that substitution of levan for water soluble polysaccharides generally disclosed in Nilsson as being an alternative to fish gelatin would result in the claim requirement of dissolution of 80% of the composition within 10 seconds. (Id. at 18.) We do not find this argument persuasive. As noted already, Combie itself suggests the use of levan in combination with an active agent. The rapid dissolution time is an inherent property of levan. That some of the polysaccharides suggested for use in Nilsson do not achieve the claimed dissolution time does not negate the fact that the swift dissolution time is a latent property of Appeal 2022-000570 Application 16/010,412 11 the levan taught to be used in a tablet for oral ingestion where dissolution is desired shortly thereafter. Persion Pharmaceuticals LLC. V. Alvogen Malta Operations Ltd., 945 F.3d 1184, 1190-91 (Fed. Cir. 2019) (“Our predecessor court similarly concluded that it ‘is not the law’ that ‘a structure suggested by the prior art, and, hence, potentially in the possession of the public, is patentable . . . because it also possesses an [i]nherent, but hitherto unknown, function which [the patentees] claim to have discovered.’” In re Wiseman, 596 F.2d 1019, 1023 (CCPA 1979) (alterations in original)); id. at 1195 (concluding that the district court did not err in discounting evidence of unexpected results where that evidence did not account for teachings of the prior art); see also In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention.”). For the foregoing reasons, we affirm the Examiner’s rejection of claim 32 under 35 U.S.C. § 103(a) as unpatentable over Nilsson and Combie. Claims 33-35, 38, 41-43, 46-51, and 54 have not been argued separately and therefore fall with claim 32. 37 C.F.R. § 41.37(c)(1)(iv). Claim 40 Appellant argues that claim 40 is separately patentable “because the cited combination of references does not suggest or provide a reasonable expectation of success for a pharmaceutical composition as claimed that exhibits the tensile strength recited in claim 40.” (Appeal Br. 20.) We recognize that the Examiner relied on Sugimoto in combination with Combie and Nilsson to establish the obviousness of making Nilsson’s orodisperisble tablet having the claimed tensile strength. (Final Action7.) We do not find it necessary to rely on any teachings of Sugimoto in Appeal 2022-000570 Application 16/010,412 12 affirming the Examiner’s rejection of claim 40 for obviousness. That is because, like the limitation that 80% of the composition dissolves within 10 seconds upon contact with an aqueous solution or saliva, the limitation that the composition has a particular tensile strength is a latent property of the composition that has levan and the active agent. As Appellant’s Specification demonstrates, the claimed tensile strength is achieved with or without an active agent being present. Examples 1-6 and 14 do not include any drug, just a formulation of Levan and water that was frozen and lyophilized (Spec. 21 (“Method for preparing Placebo formulation” (emphasis omitted)), id. at 22, id. at 24) and the tensile strength is within the claimed range (id. at 42 (Table 1)). Examples 23-25, 27, and 28 include desmopressin, levan, a pH adjuster, and water that was frozen and lyophilized (Spec. 26 (“Method for preparing dosage forms containing Desmopressin” (emphasis omitted)), id. at 27-8) and the tensile strength is also within the claimed range (id. at 43 (Table 1)). Thus, we affirm the Examiner’s rejection of claim 40 under 35 U.S.C. § 103(a) as unpatentable over Nilsson, Combie, and Sugimoto. In affirming a multiple reference rejection under 35 U.S.C. § 103, the Board may rely on fewer than all of the references relied on by the Examiner in an obviousness rationale without designating it as a new ground of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961). Appeal 2022-000570 Application 16/010,412 13 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 32-35, 38, 41-43, 46- 51, 54 103 Nilsson, Combie, 32-35, 38, 41-43, 46- 51, 54 40 103 Nilsson, Combie, Sugimoto 40 Overall Outcome 32-35, 38, 40-43, 46- 51, 54 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. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRM