Capsugel Belgium NVDownload PDFPatent Trials and Appeals BoardJul 28, 20212020006281 (P.T.A.B. Jul. 28, 2021) 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. 15/500,493 01/30/2017 Keith Hutchison 9156-98107-02 3332 120501 7590 07/28/2021 Klarquist Sparkman, LLP (Capsugel) 121 SW Salmon Street, Suite 1600 Portland, OR 97204 EXAMINER ROSENTHAL, ANDREW S ART UNIT PAPER NUMBER 1613 NOTIFICATION DATE DELIVERY MODE 07/28/2021 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): docketing@klarquist.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte KEITH HUTCHISON and TAKAHISA TAKUBO Appeal 2020-006281 Application 15/500,493 Technology Center 1600 ____________ Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and TAWEN CHANG, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL The Examiner rejected the claims under 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 Capsugel Belgium NV. Appeal Br. 4. Appeal 2020-006281 Application 15/500,493 2 STATEMENT OF THE CASE The Examiner rejected claims 15, 17–19, 21–26, and 28–30 in the Non- Final Office Action (Dec. 5, 2019) (“Non-Final Act.”) as follows: Claims 15, 17–19, 21–26, and 28–30 under 35 U.S.C. § 103 as obvious in view of Uyama (JP2010202550 A, Sept. 16, 2010; in Japanese language; machine translation provided and relied upon herein) (“Uyama”), Kalepu et al., Acta Pharmaceutica Sinica B, 3(6): 361–372 (2013) (“Kalepu”), and Tochio et al. (WO 2006/070578 A1, July 6, 2006; in Japanese language; translation provided and relied upon herein) (“Tochio”). Non-Final Act. 10. Claims 15, 17–19, 21–26, and 28–30 under 35 U.S.C. § 103 as obvious in view of Capsugel Launch2 (March 7, 2011) (“Capsugel Launch”) and Kalepu, “as evidenced” by Capsugel Slides3 (May 24, 2016) (“Capsugel Slides”). Non-Final Act. 18. Independent claim is representative and copied below: 15. A dosage form, comprising: an acid resistant hard capsule comprising a water soluble film forming polymer and gellan gum, wherein the water soluble film forming polymer and the gellan gum are present at a weight ratio of 4 to 15 parts by weight of gellan gum relative to 100 parts by weight of the water soluble film forming polymer; and a fill composition encapsulated by the acid resistant capsule, the fill composition comprising an active ingredient selected from a pharmaceutical, a dietary supplement, a peptide, an amino acid, 2 https://www.capsugel.com/news/capsugel-launches-drcaps-capsules-for- acid-sensitive-products-taste-masking. 3 http://www.jigsawhealth.com/content/dr-capsules-from-capsugel- presentation.pdf). Appeal 2020-006281 Application 15/500,493 3 a protein, a glycoprotein, an enzyme fermented food, an enzyme, a coenzyme, a vitamin, a living microbe, a plant extract, propolis, or any combination thereof; and an oil acceptable for pharmaceuticals or foods, wherein the oil has a specific gravity of 0.95 or lower. OBVIOUSNESS REJECTIONS One rejection is based on Uyama, Kalepu, and Tochio, and the second rejection is based on Capsugel Launch and Kalepu. Because Appellant’s arguments are similar for both rejections, we have addressed them together. Claim 15 is directed to a “dosage form” that comprises an acid resistant hard capsule and a fill composition. The fill composition comprises an active ingredient and an oil which has a specific gravity of 0.95 or lower. The Examiner found that each of Uyama and Capsugel Launch describe a dosage form comprising an acid resistant hard capsule with the claimed characteristics and a fill composition as claimed. Non-Final Act. 10, 18. However, the Examiner found that Uyama and Capsugel Launch do not disclose that an oil is present in the fill composition as required by the claim. Id. at 12, 18. For this feature of the claim, the Examiner cited Kalepu. Id. The Examiner found that Kalepu teaches that “encapsulating a drug in a lipid excipient can lead to increased solubilization and absorption, resulting in enhanced bioavailability (abstract).” Id. The Examiner further found that Kalepu describes olive oil as one such lipid excipient, which has a specific gravity of 0.91, meeting the corresponding limitation of the claim. Id. at 12–13. The Examiner concluded it would have been obvious to one of ordinary skill in the art to use an oil in the acid resistant hard capsule of each of Uyama and Capsugel Launch to enhance the bioavailability of the encapsulated active ingredient. Id. at 13, 20. The Examiner relied on Tochio Appeal 2020-006281 Application 15/500,493 4 for describing certain minerals that can be included in a pharmaceutical dosage form. Id. at 12. Appellant contends that the claimed dosage form is not obvious because the inventors recognized a problem that was previously unknown and solved it by providing an oil with a specific gravity of 0.95 or less. Appeal Br. 7. Appellant also argues that there would have been no motivation to have combined the capsule of each of Uyama and Capsugel Launch with Kalepu’s oil and that any such combination is impermissible hindsight. Appeal Br. 9. We begin by determining whether the Examiner provided sufficient evidence to establish prima facie obviousness of claim 15. “An examiner bears the initial burden of presenting a prima facie case of obviousness.” In re Huai-Hung Kao, 639 F.3d 1057, 1066 (Fed. Cir. 2011). “The test for obviousness is what the combined teachings of the references would have suggested to one of ordinary skill in the art,” In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991); i.e., “whether the teachings of the prior art, taken as a whole, would have made obvious the claimed invention.” In re Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991). The Examiner’s reason to add an oil to the capsule described in each of Uyama and Capsugel Launch is based on Kalepu. Kalepu discloses: The formulation of drugs is carried out with the principle [sic] objective of enhancing their bioavailability. Poorly water soluble drugs are challenging for the formulation scientists with regard to solubility and bioavailability. Lipid-based drug delivery systems (LBDDS) are one of the emerging technologies designed to address such challenges. Encapsulating or solubilizing the drug in lipid excipients can lead to increased solubilization and absorption, resulting in enhanced bioavailability. Recent advances in these formulation Appeal 2020-006281 Application 15/500,493 5 technologies have led to the successful commercialization of lipid-based formulations. Kalepu 361 (Abstract). Kalepu further explains: A water-insoluble drug can be formulated as a lipid-based formulation when the drug itself is an oil-like substance (e.g., ethyl icosapentate, tocopherol nicotinate, teprenone, indomethacin farnesyl and dronabinol), or when conventional formulation approaches like granulation or soluble liquids in capsules do not enhance the oral bioavailability. A variety of lipid-based systems composed of simple oil solutions to complex mixtures of oils, cosolvents, surfactants and co- surfactants can be obtained based on the type of excipients and formulation variables. Indeed, these systems can be converted to solid intermediates (powders, granules and pellets) by various techniques and can be filled in hard gelatin capsules or can be compressed into tablets after blending with suitable tableting excipients. Kalepu 362. Kalepu further discloses that oral delivery is “preferred” and “popular” and states that the formulations comprising the oil can be “filled into capsules.” Kalepu 367. Kalepu also discloses that olive oil can be used as the oil in a lipid- based formulation for a poorly water soluble drug, which the Examiner found, based on the disclosure in the Specification, has a specific gravity of 0.91, within the claimed range of 0.95 of less. Kalepu 364 (Table 1); Spec. ¶ 12 (Table 1) Because Kalepu describes the advantages of an oil for increasing a drug’s bioavailability, as well as its use in a capsule, the Examiner’s conclusion that one of ordinary skill in the art would have had reason to use olive oil in the capsule described by Uyama and Capsugel Launch to Appeal 2020-006281 Application 15/500,493 6 increase the bioavailability of a “[p]oorly water soluble drug” when used as an active ingredient is supported by the evidence in this record. Appellant argues that “Uyama is solely concerned with solving the problem of high manufacturing costs (and low productivity) associated with adding enteric coatings to capsules by providing an acid resistant capsule that is inherently acid resistant.” Appeal Br. 9. Appellant also argues that “Capsugel Launch is concerned with solving the problem of high production costs and time associated with adding a separate chemical coating to the capsule to protect against early activation caused by stomach acid.” Id. at 17. Thus, Appellant argues that the addition of an oil to the capsule would not have been obvious because it would add to the cost of the product. Id. at 8– 10, 13. This argument is not persuasive. Appellant has not provided objective evidence that these factors would have deterred one of ordinary skill in the art from using oil in the capsule for its known and expected advantages. As held in Orthopedic Equip. Co., Inc. v. United States, 702 F.2d 1005, 1013 (Fed. Cir. 1983) (brackets in original): the fact that the two disclosed apparatus [sic] would not be combined by businessmen for economic reasons is not the same as saying that it could not be done because skilled persons in the art felt that there was some technological incompatibility that prevented their combination. Only the latter fact is telling on the issue of nonobviousness. See also Grit Energy Solutions, LLC v. Oren Technologies, LLC, 957 F.3d 1309, 1323–1324 (Fed. Cir. 2020) (“Thus, even if we accept the Board’s factual determination that swapping Eng Soon’s components would result in a more expensive system, that determination, standing alone, is insufficient Appeal 2020-006281 Application 15/500,493 7 to reject each of Grit Energy’s arguments as to why a skilled artisan would have been motivated to make the proposed swap.”) Appellant further argues that there is “no indication in Uyama that decreased bioavailability was of any concern with its dosage forms” and a person of ordinary skill in the art “would not have had any reason to believe that adding Kalepu’s oil to a fill for Uyama’s capsules would even be necessary to enhance bioavailability and/or that this would provide any additional advantage.” Appeal Br. 10. Appellant contends that the modification proposed by the Examiner “would amount to extra work and greater cost for no apparent reason other than solving the unrecognized problem that the present inventors discovered (as discussed above).” Id. With respect to Kalepu, Appellant states that the publication “is entirely directed to lipid-based drug delivery systems used to enhance bioavailability of poorly water soluble drugs and is completely unrelated to acid resistant capsules and issues associated with such capsules. Kalepu, Abstract.” Id. at 9. Appellant states that “Kalepu has no disclosure regarding any delivery systems other than gelatin capsules (or tablets).” Id. Appellant’s argument addresses each of the publications separately without considering what the combination would have suggested to one of ordinary skill in the art. An explicit suggestion to modify the prior art is unnecessary to establish obviousness. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 415 (2007). KSR held that an obviousness “analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 418. Here, while Uyama may have been silent on the existence of a problem with a drug in its Appeal 2020-006281 Application 15/500,493 8 capsule, such fact does not detract from the obviousness of utilizing Kalepu’s oil in each of Uyama’s and Capsugel Launch’s capsules. Specifically, Kalepu identifies a problem with the bioavailability of a poorly soluble drug and describes the solution to this problem as utilizing a lipid excipient for “increased solubilization and absorption, resulting in enhanced bioavailability.” Kalepu, Abstract. As indicated by Appellant, the focus of Uyama and Capsugel Launch is on creating an acid resistant capsule (e.g., Appeal Br. 9, 17), but as discussed by Kalepu, there are other problems to be addressed when using oral drug delivery systems, such as drug solubility. Appellant, by focusing on the publications individually, has failed to appreciate in their arguments that Uyama, Capsugel Launch, and Kalepu provide evidence that, when formulating a capsule for oral delivery that doesn’t dissolve in the stomach and that comprises a poorly soluble drug, the ordinarily skilled worker would be concerned with the drug bioavailability4 when released from the capsule and the ability of the capsule, itself, to resist 4 “With the advent of drug design, various molecules have been created that have a potential for therapeutic action. But most of the newly discovered chemical entities are of high molecular weight and belong to biopharmaceutical classification system (BCS) - II, with poor aqueous solubility and high membrane permeability. Hence these two characteristics limit the bioavailability of orally administered drugs. These drugs have low solubility which leads to low dissolution and limits absorption. This poor solubility not only gives low oral bioavailability but also leads to high inter- and intra-subject variability and lack of dose proportionality. Also, some of these drugs have enhanced bioavailability when coadministered along with food . . . In order to formulate such drugs in a safe and efficacious form, a balance must be maintained between bioavailability, toxicity and disposition within the body.” Kalepu 362 (footnotes omitted). Appeal 2020-006281 Application 15/500,493 9 dissolution in the acidic stomach environment.5 “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). Appellant also argues a lack of motivation to combine the publications because Kalepu describes a gelatin capsule, which is different from the capsule described in Uyama and Capsugel Launch. Appeal Br. 8, 9, 17. This argument is not persuasive because Kalepu has more general disclosure about using capsules for oral delivery (Kalepu 367) and also because Kalepu was concerned by the bioavailability of the drug inside a capsule, and not the capsule, itself. Appellant has not provided objective evidence that using a different capsule would affect the ability of its contents to become more bioavailable when formulated with an oil and released in the intestine, once its dissolves. Appellant has not established a relationship between the properties of the capsule to resist degradation in the stomach and the availability of the drug when the capsule dissolves in the intestine, releasing its content. Appellant further argues that the inventors were the first to recognize that the recited specific gravity of 0.95 or lower is a result-effective variable and thus it would not have been routine optimization to have selected it. Id. at 9–10, 18. 5 “It was found that an enteric film capable of forming a capsule by a dipping method can be prepared and the thus prepared capsule has acid resistance and is sparingly soluble in an acidic solution equivalent to gastric juice [.] On the other hand, it was confirmed that it is easily soluble in a neutral to weak alkaline solution equivalent to the intestinal environment.” Uyama ¶ 7. Appeal 2020-006281 Application 15/500,493 10 This argument is not persuasive because the Examiner found that Kalepu discloses olive oil as a lipid excipient, which falls within the scope of the claim. Non-Final Act. 13. Consequently, there is no optimization necessary to have arrived at an oil within the scope of the claim. For the foregoing reason, we are not persuaded that the Examiner’s reasoning invoked “post-hoc motivation.” Appeal Br. 9. In arguing the nonobviousness of the claimed invention, Appellant explains that the inventors “discovered that even though acid resistant hard capsules do not dissolve in gastric fluid, gastric fluid can nonetheless permeate into the capsule and degrade the active material. The inventors believed that this was due, at least in part, to the presence of hydrophilic component(s) present in the shell.” Appeal Br. 7. Appellant states that “[t]his previously unrecognized problem is discussed in Appellant’s specification.” Id. The Specification discloses: However, while studying enteric capsule formulations that include an acid resistant hard capsule, surprisingly the present inventors found that even though the capsule does not disintegrate in the stomach, over time gastric acid gradually enters through the capsule membrane because the capsule membrane contains a hydrophilic material. Therefore, even if a capsule is used wherein the capsule membrane itself is acid resistant, in cases wherein the efficacy of an encapsulated active ingredient is reduced by a small amount of gastric acid (gastric juice), there is a possibility that the active ingredient will deteriorate (changes/be dispersed/be annihilated) when the active ingredient comes in contact with acid (gastric acid), and the expected effect will not be obtained sufficiently. Spec. ¶ 5. The Specification discloses that the “the present inventors found that the above problems could be resolved by developing a capsule formulation Appeal 2020-006281 Application 15/500,493 11 having the following configuration.” Spec. ¶ 6. The configuration described in the Specification includes: (1) A capsule formulation comprising an active ingredient and oil, wherein said capsule of said formulation is an enteric capsule including a water soluble film forming polymer and gellan gum, said oil is an oil acceptable for pharmaceuticals or food, and said active ingredient is encapsulated in said capsule together with said oil. Spec. ¶ 9. (3) The capsule formulation according to (1) or (2), wherein the weight ratio of said water soluble film forming polymer and said gellan gum in said capsule is 4 to 15 parts by weight of gellan gum relative to 100 parts by weight of said water soluble film forming polymer. Spec. ¶ 11. While the description in the Specification of the capsule formulation that resolves the stated problem discloses the presence of an oil in the capsule, it does not solely attribute the solution to the oil nor does it require that the oil to have a specific gravity of 0.95 or lower as required by the claim. Spec. ¶¶ 7–14. The Specification further explains: One aspect of the capsule formulation according to the present invention is being able to protect an active ingredient that may deteriorate (change/be dispersed/be annihilated) when it comes into contact with acid (gastric acid) seeping into a capsule. That is, even if oil is mixed with acid (gastric acid), due to having separating immiscible properties, acid (gastric acid) seeping into the capsule sinks to the bottom of the capsule because of the difference in the specific gravity of oil without being diffused into an encapsulated oil acceptable for pharmaceuticals or food. Therefore, contact between an acid and an active ingredient can be effectively reduced by separating both the Appeal 2020-006281 Application 15/500,493 12 aqueous phase (including acid) and the oil phase (including an active ingredient) within a capsule. Spec. ¶ 22. Thus, the Specification teaches how the oil protects the active ingredient from deteriorating in the capsule, but does not require its specific gravity to be 0.95 or lower as required by the claims. Rather, the value of 0.95 or lower is described as one of the preferred ranges: [I]t is preferable that the specific gravity (density ratio with water as a standard) of oil in the present invention be 0.96 or lower, wherein 0.955 or lower is more preferable, 0.95 or lower is even more preferable, 0.945 or lower is still more preferable, and 0.94 or lower is still even more preferable. Surprisingly, the present inventors found that the more the specific gravity of oil is separated from that of water, the easier it became to physically separate within the capsule the oil (oil phase) and acid (aqueous phase) seeping into the capsule, and the acid and oil (including an active ingredient or the like) mixed less easily, protecting the active ingredient or the like from the acid. Spec. ¶ 34. To address Appellant’s argument that the claimed subject matter is not obvious because the inventors solved an unrecognized problem, we must consider two legal principles. First, as explained In re Baxter Travenol Labs, 952 F.2d 388, 392 (Fed. Cir. 1991), [m]ere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Prindle, 297 F.2d 251, 254, 132 USPQ 282, 283–84 (CCPA 1962). Since the prior art bags plasticized with DEHP were inherently suppressing hemolysis, albeit unknown at the time of the Becker document, this hemolysis-suppressing function is not a basis for rebutting a prima facie finding of obviousness. Appeal 2020-006281 Application 15/500,493 13 The second principle has to do with “criticality.” As explained in In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990): 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 showing that the claimed range achieves unexpected results relative to the prior art range. As explained above, Kalepu provides a reason to use oil in a capsule. When Kalepu’s guidance is followed, the bioavailability of the poorly soluble drug would be enhanced and the drug would be protected from the deleterious effects of gastric acid when encapsulated in the capsule described by each of Uyama and Capsugel Launch. Therefore, using the oil as described in Kalepu, would inherently impart protection against gastric acid, albeit not recognized at the time of the publication. The observed property for the oil described in the Specification (see ¶¶ 22, 34) is “latent” or “inherent” to using the oil for the purpose described in Kalepu. This determination is consistent with Baxter. In Baxter, blood bags plasticized with DEHP had been used in the prior art. Baxter, 952 F.2d at 392. The inventors discovered that such blood bag also suppressed hemolysis of the blood. Id. But the court found this newly discovered property to insufficient to rebut the prima facie finding of obviousness because it was a latent, inherent property of using the blood bag. Id. Similarly, while the inventors discovered that oil has an additional beneficial property when used in a capsule, Kalepu disclosed adding an oil to an active ingredient in a capsule, and therefore the capsule would have exhibited this property, despite the property not being recognized at the time of Kalepu’s publication. Appeal 2020-006281 Application 15/500,493 14 We therefore must next ask whether there is anything critical about the selection of the oil having a specific gravity of 0.95 or less. In other words, to establish non-obviousness, Appellant must show the “criticality” of the range of specific gravity values selected for the oil, alone, or in combination with the claimed capsule. To address this, we look at the data disclosed in the Specification. The Specification describe an experiment in which a capsule within the scope of the claim was prepared with an active ingredient formulated with an oil and compared to the same capsule in which a surfactant (glycerin fatty acid ester or sorbitan fatty acid ester) was placed in the capsule instead of the oil. Spec. ¶¶ 48, 51. The capsules were submerged in an acid solution “to simulate the gastric acid inside a living organism.” Spec. ¶ 49. A litmus reagent, which changes color from blue to red in an acid environment, was used as the active ingredient to determine whether the oil protected the active ingredient when placed in the acid solution. Id. Table 1 of the Specification shows the eight different oils (1- safflower, 2-olive, 3-soybean, 4-linseed, 5-DHA, 6-rice germ, 7-vitamin E, 8-vitamin A) which were tested. Spec. ¶ 51. Seven of the oils were rated as “excellent” with respect to protecting against acidification inside the capsule, while only one oil (DHA) was “passable.” DHA has a specific gravity of 0.95, while the other oils were from 0.91 to 0.94. The Specification states: Importantly, all oils that obtained a “++” result had a specific gravity of 0.94 or lower. This suggests that the more the specific gravity of oil is separated from that of water, the easier it becomes to physically separate oil from acid seeping into the capsule, and the less easily it is mixed with acid. Spec. ¶ 52. Appeal 2020-006281 Application 15/500,493 15 The data provided in the Specification does not show that the range of 0.95 or lower is critical to preventing acidification of the active ingredient. No values of an oil having a specific gravity above 0.95 were shown, and the Specification, itself, only describes 0.95 or lower as “more preferable.” Spec. ¶ 34. The data shows that a value of 0.94 or lower is better than 0.95, but this range is not claimed. Thus, it cannot be discerned from this data that the choice of an oil having a specific gravity of 0.95 or lower provided any benefit that is not possessed by the oils described in Kalepu having a higher specific gravity. The proper comparison to establish criticality and nonobviousness of the claimed range is with the oils described in Kalepu because the comparison must be with the closest prior art and Kalepu is the closest prior art. Baxter, 952 F.2d at 392. Appellant did not provide evidence that the oils described in Kalepu having a specific gravity higher than 0.95 would not inherently provide the advantages described in the Specification. While we agree with Appellant that their data shows that specific gravity is a result- effective variable with respect to reducing acidification in a gastric acid simulated environment (Appeal Br. 15), this property is still, absent evidence to the contrary, inherent to the teaching in Kalepu to use oil in a capsule because Appellant did not establish the criticality of the claimed range in preventing or reducing acidification of the active ingredient. We also must consider whether it has been established that the claimed capsule in combination with an oil of specific gravity of 0.95 or lower, is critical to reducing the deterioration of an active ingredient when in contact with gastric acid. Appeal 2020-006281 Application 15/500,493 16 While Kalepu refers to gelatin capsules, as explained above, there is broader disclosure on capsules generally. Appellant did not show that the choice of the capsule is critical, namely, that the capsule described in Uyama and Capsugel Launch behaves any differently with respect to active agent bioavailability as compared to other capsule types, such as the gelatin capsule describe by Kalepu. Only one type of capsule is used in the experiments described in the Specification. Therefore, Appellant has not demonstrated the criticality of the combination of capsule and oil having a specific gravity of 0.95 or lower. Appellant argues that Leo Pharmaceutical Products, Ltd. v. Rea, 726 F.3d 1346 (Fed. Cir. 2013) dictates a different result. Appeal Br. 8. We do not agree. Leo was an appeal from a decision by the Board affirming an obviousness rejection in a reexamination of a patent. In Leo, the claim was directed to a pharmaceutical composition for dermal use which comprised a vitamin D analogue, a corticosteroid, and a specific type of solvent. Leo, 726 F.3d. at 1349. The claims were rejected as obvious under 35 U.S.C. § 103. Two publications were cited in the rejection, Dikstein and Serup, which “attempt the combination of a vitamin D analog with a corticosteroid” but “neither discloses or addresses the stability problems of combining vitamin D analogs and corticosteroids into one pharmaceutical formulation.” Id. at 1354. The Board had cited Turi for the solvent POP-15-SE that fell within the scope of the claimed solvent. Id. at 1350. Turi disclosed pharmaceutical compositions comprising a steroid and POP-15-SE, but not vitamin D. Id. at 1350. The Board found it obvious to use POP-15-SE as the solvent for the Appeal 2020-006281 Application 15/500,493 17 combination of steroid and vitamin D of Dikstein and Serup, but the court reversed the Board’s decision. The court held: because neither Dikstein nor Serup recognized or disclosed the stability problem, the record shows no reason for one of ordinary skill in the art to attempt to improve upon either Dikstein or Serup using Turi. The ordinary artisan would first have needed to recognize the problem, i.e., that the formulations disclosed in Dikstein and Serup were not storage stable. Id. at 1354. The facts are not the same in this appeal. In Leo, unlike here, the court found there was no reason that would have prompted one of ordinary skill in the art to have used POP-15-SE in the pharmaceutical compositions of Dikstein and Serup, both of which were aqueous compositions, while Turi’s was not. Leo established that its composition containing all three ingredients was storage-stable, as compared to the “significant degradation” observed in the Dikstein and Serup compositions which was determined to be a “a strong indication that the . . . patent’s combination of known elements yields more than just predictable results.” Id. at 1358. The court concluded that “[t]his record shows ‘extensive experimental evidence’ of unexpected results.” Id. Here, the Examiner established an adequate reason, supported by a preponderance of the evidence, to have used an oil in the specific type of capsule described by each of Uyama and Capsugel Launch. Such oil was in fact disclosed as useful in a capsule and thus adding it to the capsule of each of Uyama and Capsugel Launch was merely following the straightforward guidance in Kalepu and using the oil for its expected benefit in enhancing bioavailability. In contrast, the court in Leo decided there was no reason to use the POP-15-SE solvent in Dikstein and Serup, and Turi had not Appeal 2020-006281 Application 15/500,493 18 described the solvent as useful for both vitamin D and the steroid. Leo’s evidence was also considered to establish unexpected results, a finding lacking in this record. Appellant also cited In re Omeprazole Patent Litigation, 536 F.3d 1361 (Fed. Cir. 2008), in arguing the nonobviousness of the claim. Appeal Br. 8, 13. However, Omeprazole is distinguishable because in that case the Federal Circuit found a lack of a reason to have combined the cited publications. Id. at 1380–1381. But, here, a fact-based and logical reason, supported by the evidence in this record, establishes a reason to combine the oil of Kalepu with capsules of Uyama and Capsugel Launch. In sum, for the foregoing reasons, we affirm the Examiner’s conclusion that claim 15 is obvious over each of Uyama and Capsugel Launch, and Kalepu. Appellant acknowledges that dependent claims 17, 19, 21–25, 28, and 29, which depend from independent claim 15, fall with it. Appeal Br. 18. Claim 18 Claim 18 depends from claim 15 and further recites “wherein the oil is present in an amount not less than 40% by weight of a total amount of the fill composition.” Appellant contends that the Examiner’s rejection is based on the presence of surfactant, but a surfactant is not required by the claim. Appeal Br. 18. This argument is unavailing because the claim is open-ended and therefore a surfactant is not excluded from the claim. Appeal 2020-006281 Application 15/500,493 19 Claims 26, 30 Appellant makes substantially the same argument for claim 26 as for claim 15. Appeal Br. 19–21. The obviousness rejections of claim 26 are therefore affirmed for the same reasons. Appellant acknowledges that dependent claim 30, which depends from claim 26, falls with it. Appeal Br. 21. CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 15, 17– 19, 21– 26, 28– 30 103 Uyamu, Kalepu, Tochio 15, 17–19, 21–26, 28– 30 15, 17– 19, 21– 26, 28– 30 103 Capsugel Launch, Kalepu, Capsugel Slides 15, 17–19, 21–26, 28– 30 Overall Outcome 15, 17–19, 21–26, 28– 30 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). AFFIRMED Copy with citationCopy as parenthetical citation