Heron Therapeutics, Inc.

Patent Trials and Appeals Board

Feb 3, 2022

2022000100 (P.T.A.B. Feb. 3, 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. 16/261,459 01/29/2019 Thomas B. Ottoboni 092459-0243/8035.US00 2699 108547 7590 02/03/2022 McDermott Will & Emery LLP 500 North Capitol Street NW Washington, DC 20001 EXAMINER NEAGU, IRINA ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 02/03/2022 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): mweipdocket@mwe.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte THOMAS B. OTTOBONI and BARRY D. QUART Appeal 2022-000100 Application 16/261,459 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and TAWEN CHANG, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1-12, 14, and 17-30. 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 Heron Therapeutics, Inc. Appeal Br. 1. Appeal 2022-000100 Application 16/261,459 2 STATEMENT OF THE CASE According to the Specification, “[t]he disclosure relates generally to a method of administering emulsion formulations of an NK-1 receptor antagonist for treatment of emesis and/or for prevention of acute and delayed nausea and vomiting. The emulsion formulations are stable for prolonged periods of time.” Spec. ¶ 2. CLAIMED SUBJECT MATTER The claims are directed to a method for treating a subject in need thereof, comprising intravenously administering to the subject a single dose of a stable emulsion comprising an NK-1 receptor antagonist. Claim 1 is illustrative: 1. A method for treating a subject in need thereof, comprising: intravenously administering to the subject a single dose of a stable emulsion at an average rate of about 6.5 to 70 mg/minute of an NK-1 receptor antagonist, wherein the stable emulsion comprises the NK-1 receptor antagonist; 11 wt/wt % to 15 wt/wt% of an emulsifier; an oil; a co-surfactant which comprises an alcohol; a tonicity agent; a pH modifier; and water; wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %), wherein the pH of the emulsion ranges from about 7.5 to 9.0. Appeal Br. 13 (Claims App.). Appeal 2022-000100 Application 16/261,459 3 REJECTION(S) A. Claims 1-12, 14, and 17-30 are rejected under 35 U.S.C. § 103 as being unpatentable over CINVANTI™.2 Ans. 3. B. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable at least over claims 1-14, 16 of U.S. Patent 10,624,850. Ans. 4. C. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18- 35 of U.S. Application 16/669,262, now claims 1-18 of U.S. Patent 10,953,018. Final Act. 9; Ans. 5. D. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent 9,808,465. Ans. 6. E. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent 9,974,793. Ans. 7. F. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent 9,561,229. Ans. 8. 2 CINVANTI™ Prescribing Information, http://www.accessdata.fda.gov/ drugsatfda_docs/label/2017/209296s000lbl.pdf (Nov. 2017). CINVANTI™ was listed in the Notice of References Cited (form PTO-892) filed April 17, 2020 in the instant application. Our citations are to the copy of CINVANTI™ that is filed with the Notice of References Cited. Appeal 2022-000100 Application 16/261,459 4 G. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent 10,500,208. Ans. 9. H. Claims 1-12, 14, and 17-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent 9,974,794. Ans. 9. OPINION A. Obviousness rejection over CINVANTI™ (claims 1-12, 14, 17-30) 1. Issue The Examiner finds that CINVANTI™ teaches “a method of treating nausea and vomiting associated with courses of highly emetogenic cancer therapy (HEC)” that meets almost all of the limitations of claim 1, except that CINVANTI™ does not teach administering the NK-1 receptor antagonist (aprepitant in CINVANTI™) at the recited rate of 6.5 to 70 mg/min. Ans. 3. However, the Examiner concludes that it would have been obvious to a skilled artisan to “use the teachings of CINVANTI™ to arrive at the instant invention,” because “[d]etermining the optimum rate of drug administration in mg/min, in a known method of treatment, using a known drug formulation, is routine, well within the skill of the artisan.” Id. at 4. Appellant contends that CINVANTI™ “fails to describe or suggest a method of treatment in which an NK-1 receptor antagonist is administered at an average rate of about 6.5 mg/minute to 70 mg/minute.” Appeal Br. 6. Appellant contends that a skilled artisan would not have had a reason to modify the rate of administration set forth in CINVANTI™, or to expect the claimed method using the recited rate of administration to be successful. Id. Appeal 2022-000100 Application 16/261,459 5 at 7. Appellant makes similar arguments with respect to independent claim 2, which recites intravenously administering the claimed emulsion “over about 30 seconds to 15 minutes.” Id. at 10. Appellant does not separately argue the claims. Accordingly, we focus our analysis on claims 1 and 2 as representative. The issues with respect to this rejection are whether CINVANTI™ would have suggested to a skilled artisan a method in which the emulsion comprising the NK-1 receptor antagonist is intravenously administered at the rates recited in claims 1 and 2, and whether the skilled artisan would have had reason to administer the emulsion at such rates with a reasonable expectation of success. 2. Analysis Except as otherwise noted, we adopt the Examiner’s findings of fact and reasoning regarding the Examiner’s rejection of claims 1 and 2 under 35 U.S.C. § 103 as obvious over CINVANTI™ (Final Act. 2-4, 5-7; Ans. 3-4, 11-16). Only those arguments timely made by Appellant in the briefs have been considered; arguments not so presented in the briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2020); see also Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived.”). We highlight the following points for emphasis. Appellant has not disputed that CINVANTI™ discloses the emulsion recited in claim 1. However, Appellant contends that CINVANTI™ “fails to describe or suggest a method of treatment in which an NK-1 receptor antagonist is administered “at an average rate of about 6.5 mg/minute to 70 mg/minute,” as recited in claim 1, because an average administration rate of Appeal 2022-000100 Application 16/261,459 6 6.5 mg/minute would require administration of the 130 mg aprepitant in CINVANTI™ over 20 minutes, whereas the recommended dosage of CINVANTI™ is 130 mg over 30 minutes. Appeal Br. 5-6. We are not persuaded. Even if CINVANTI™ does not explicitly teach the recited rate of administration,3 “[a] claim can be obvious even where all of the claimed features are not found in specific prior art references, where ‘there is a showing of a suggestion or motivation to modify the teachings of [the prior art] to the claimed invention.’” Ormco Corp. v. Align Technology Inc., 463 F.3d 1299, 1307 (Fed. Cir. 2006) (citation omitted). In this case, as the Examiner explains, a skilled artisan would have been motivated to modify CINVANTI™ to arrive at the recited rate of administration because determining suitable rate of drug administration requires only routine optimization. Ans. 4; In re Aller, 220 F.2d 454, 456 (CCPA 1955) (“[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”). 3 We note that CINVANTI™ discusses a clinical study in which 150 mg of fosaprepitant, a prodrug of aprepitant, was administered intravenously over 20 to 30 minutes. CINVANTI™ 6, 18. This would result in an average administration rate of 5-7.5 mg/minute, which overlaps the rate range recited in claim 1 (i.e., 6.5 to 70 mg/minute). Appellant admits that fosaprepitant is an NK-1 receptor antagonist. Appeal Br. 8 (describing EMEND™ as the tradename of an FDA approved drug product comprising an “infusion of the NK1 antagonist fosaprepitant”). We further note that CINVANTI™ teaches that 150 mg fosaprepitant corresponds to 130 mg CINVANTI™. CINVANTI™ 15. Thus, CINVANTI™ appears to suggest administering 130 mg CINVANTI™ over 20 to 30 minutes, i.e., at a rate of 4.3 to 6.5 mg/min, which also overlaps the recited rate range at its end point. Appeal 2022-000100 Application 16/261,459 7 Appellant contends that the Examiner relies only on alleged “routine practice or common sense” to satisfy the limitation regarding the rate of administration, that “[t]he Examiner has not provided any evidence of record which would support such an assertion of a hypothetical skilled artisan’s ‘basic knowledge,’” and that it is “never appropriate to rely solely on “common knowledge” in the art without evidentiary support in the record[] as the principal evidence upon which a rejection is based.” Appeal Br. 6-7 (citing In re Zurko, 258 F.3d 1379, 1385 (Fed. Cir. 2001)); see also Reply Br. 4 (arguing that “the rate is an important limitation that is not evidently and indisputably within the common knowledge of those in the art” and that the Examiner also has not “establish[ed] why the specifically claimed rate is common sense”). We are not persuaded for the reasons discussed above, namely that CINVANTI™ discloses the “general conditions” of the claim, and the case law is clear that where this is the case “it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d at 456. Appellant’s citation to In re Zurko, 258 F.3d 1379, 1385 (Fed. Cir. 2001), is inapposite. In Zurko, the court held that the Board’s assertions that “it is basic knowledge that communication in trusted environments is performed over trusted paths” and that “verifying the trusted command in UNIX over a trusted path is ‘nothing more than good common sense,’” cannot remedy the deficiencies in the cited references with respect to “core factual findings in a determination of patentability,” where the claim recites “[a] machine-executed method for executing a trusted command issued by a user on a computer system” that includes a “trusted” and “untrusted” Appeal 2022-000100 Application 16/261,459 8 computing environment, comprising a step of “communication between a trusted environment and the user along a trusted path.” Id. at 1385-1386. In short, in Zurko common sense, rather than prior art, is cited for disclosing the “general conditions” of the claim. In contrast, the rejection in this case is not based on the Examiner’s (or the Board’s) understanding of what is “common sense” in the art; rather, it is based on the “normal desire of scientists or artisans to improve upon what is already generally known,” e.g., by determining an optimal rate of administering the known emulsion comprising an NK-1 receptor antagonist. Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1318, 1368-69 (Fed. Cir. 2007) (quoting In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003)). In the Reply Brief, Appellant also contends that “there is no evidence offered by the Examiner that rate of drug administration is a result-effective variable, and there is no evidence offered by the Examiner that increasing or decreasing the rate of administration of a drug formulation will achieve a certain result.” Reply Br. 10. Appellant contends that “Appellant has submitted evidence to establish that rate of drug administration is not a result-effective variable since a difference result - e.g., Cmax - can and does result from different rates of administration.” Id. Appellant did not raise these arguments in the Appeal Brief, and the arguments are thus waived. 37 C.F.R. § 41.41(b)(2)); Ex parte Nakashima, 93 USPQ2d 1834, 1837 (BPAI 2010) (informative) (arguments not timely presented in the principal Brief will not be considered in a Reply, absent a showing of good cause why the argument could not have been presented in the principal Brief). In any event, we are not persuaded. CINVANTI™, for example, teaches establishing the safety and efficacy of its drug formulation Appeal 2022-000100 Application 16/261,459 9 by relying on clinical studies in which the same or similar drugs are administered via different routes and/or rates of administration (e.g., orally for 3 days or intravenous over 20 to 30 minutes). CINVANTI™ 17-19. We further note Appellant’s argument that administration rate is not a result effective variable contradicts its arguments that a skilled artisan would not have modify the administration rate of CINVANTI™ because he or she would have expected the safety of the method of treatment to be impacted by such a change. Finally, as to Appellant’s argument that “a difference result - e.g., Cmax - can and does result from different rates of administration,” Reply Br. 10, we note that a variable may be result effective without affecting all results relevant to a method of treatment. Appellant contends that the Examiner has not established that “determining the optimum rate of drug administration in mg/min, in a known method of treatment, using a known drug formulation is routine, well within the skill of the artisan.” Reply Br. 5. We are not persuaded. CINVANTI™, for example, discloses clinical studies in which NK-1 receptor antagonists such as aprepitant and fosaprepitant were administered via different routes and/or rates of administration (e.g., orally for 3 days or intravenous over 20 to 30 minutes) for purposes of determining safety and efficacy. CINVANTI™ 17-19. Appellant contends that a skilled artisan would not have had a reason to modify CINVANTI™ to arrive at the recited rate of administration, with a reasonable expectation of success. In particular, Appellant contends that “[t]he Examiner . . . has not articulated a reason why a skilled person . . . would have ‘routinely’ diverted from the explicit instructions provided on Appeal 2022-000100 Application 16/261,459 10 the label of a prescription drug.” Appeal Br. 7. Appellant disputes the Examiner’s alleged assumptions that (1) [] if a drug is approved by the FDA, then any means of delivering said drug is safe, (2) [] adjusting the rate of delivery of a known formulation is routine and is predictably and expectedly safe, and (3) [] adjusting the rate of delivery of an active pharmaceutical ingredient will necessarily achieve the expected, known method and effect of unmodified treatment (e.g., the desired therapeutic effect). Id. Appellant contends that “[a] person of ordinary skill in the art would have assumed the very opposite of the Examiner’s assumptions.” Id. We are not persuaded. The rejection does not suggest that “any means of delivering” a FDA-approved drug is safe; rather, it is based on the Examiner’s finding that injection rate of an injectable drug is a known result effective variable that is routinely optimized by those of skill in the art. Ans. 4. As to Appellant’s argument that adjusting the rate of delivery of a known formulation is not “routine” or “predictably and expectedly safe,” we note that, for purposes of obviousness, “the expectation of success need only be reasonable, not absolute.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007). “[C]ase law is clear that obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” Id. In this case, CINVANTI™ teaches administering 130 mg aprepitant as an intravenous infusion over 30 minutes (i.e., at an average rate of 4.3 mg/min). CINVANTI™ also teaches that its safety and efficacy have been established based on, among other things, a study of a single-dose of intravenous fosaprepitant, a prodrug of aprepitant, in which 150 mg fosaprepitant Appeal 2022-000100 Application 16/261,459 11 (corresponding to 130 mg aprepitant) was administered intravenously over 20 to 30 minutes (i.e., at an average rate of 5 to 7.5 mg/min fosaprepitant). CINVANTI™ 15, 17-19. Given the above, we agree with the Examiner that a skilled artisan would have had a reasonable expectation of success of modifying the administration rate of CINVANTI™ to arrive at the claimed invention. Finally, we note that claims 1 and 2 do not recite any required effect for performing the claimed method. Thus, to find the claim obvious over the prior art it is not required that a skilled artisan reasonably expect the claimed method to achieve results identical to the prior art method. For the reasons discussed above, we are similarly unpersuaded by Appellant’s contention that “[t]he Examiner has not . . . articulated why a faster administration would be advantageous or even effective or safe.” Appeal Br. 9. As the Federal Circuit did in Pfizer, “[w]e find this case analogous to the optimization of a range or other variable within the claims that flows from the ‘normal desire of scientists or artisans to improve upon what is already generally known.’” 480 F.3d at 1368-69 (quoting In re Peterson, 315 F.3d at 1330). That is, CINVANTI™ teaches a process of intravenously administering the recited emulsion to a subject, and the normal desire of scientists or artisans to improve upon the process would have led the skilled artisan to determine the optimum or workable ranges of the rate of administration, including a faster rate of administration. Cf. Dystar Textilfarben Gmbh & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1368 (Fed. Cir. 2006) (“[A]n implicit motivation to combine exists . . . when . . . the combination of references results in a product or process that is Appeal 2022-000100 Application 16/261,459 12 more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient.”). Appellant contends that “[a] reasonable healthcare professional (e.g., a pharmacist or nurse) would not have simply (a) disregarded the explicit instructions provided by the label of an FDA-approved product and (b) replaced the provided administration instructions with his or her own personal interpretation or preferences.” Appeal Br. 9. Appellant contends that at the time of filing a skilled artisan “would have understood that unpredictable risks are associated with modifying . . . an intravenous infusion to be administered more quickly,” particularly when “modifying an infusion (or ‘IV drip’) to be an all-at-once intravenous injection (or ‘IV push’ or ‘IV bolus.’)” Id. at 8. Thus, Appellant contends that an ordinarily skilled artisan “would have regarded the modification of an intravenous infusion to . . . pose an unjustifiable risk to a patient receiving such an ad hoc treatment.” Id. at 9. We are not persuaded. The issue is not whether a skilled artisan would have disregarded the administration rate set forth on the product when administering the emulsion to a patient, but whether the claimed rate would have been obvious to the skilled artisan. Appeal 2022-000100 Application 16/261,459 13 Appellant cites to Hojsak,4 Ottoboni,5 and Lundberg6 to support its arguments regarding lack of motivation to combine and expectation of success. Appeal Br. 7-9. We are not persuaded for the reasons discussed below. Appellant contends that Hojsak teaches that “rapid intravenous infusion of lipid emulsions can cause spontaneous hemorrhage, respiratory distress, hepatosplenomegaly, jaundice, fever, and headaches” and that, given that at the time of filing CINVANTI™ “was known to be safely and effectively administered at a single rate[ of] 4.33 mg/minute,” a skilled artisan “would not have expected that the claimed method would be successful.” Id. at 7. We acknowledge that Hojsak teaches that “[f]at overload syndrome is a well-known complication of intravenous lipid emulsion therapy.”7 Hojsak 4 Iva Hojsak & Sanja Kolaček, Fat Overload Syndrome After the Rapid Infusion of SMOFlipid Emulsion, 120 J. PARENTERAL & ENTERAL NUTRITION 119 (2014). 5 Thomas Ottoboni et al., HTX-019 via 2-min Injection of 30-min Infusion in Healthy Subjects, 15 FUTURE ONCOLOGY 865 (2019). 6 Jordan D. Lundberg et al., Incidence of Infusion-site Reactions Associated with Peripheral Intravenous Administration of Fosaprepitant, 22 SUPPORT CARE CANCER 1461 (2014). 7 To the extent the Examiner finds that Hojsak teaches fat overload syndrome after rapid infusion of lipid emulsion containing “20% soy oil,” “reports the first case of fat overload syndrome,” or suggests that fat overload syndrome occurs only in infants and children, Ans. 14, we do not adopt these findings and do not rely on them in our decision. As noted above, Hojsak teaches that “[f]at overload syndrome is a well-known complication of intravenous lipid emulsion therapy.” Hojsak Abstract. Similarly, Hojsak states that the emulsion at issue is SMOFlipid, “a 20% soy oil, medium-chain triglyceride, olive and fish oil-based lipid emulsion.” Id. Thus, we understand the emulsion at issue in Hojsak to contain 20% lipids Appeal 2022-000100 Application 16/261,459 14 Abstract. Appellant has not cited to persuasive evidence, however, that a skilled artisan would be concerned with fat overload syndrome for the particular emulsion at issue (i.e., CINVANTI™) at the rate of administration recited in claim 1. Hojsak, for example, appears to discuss a scenario in which 20 grams of lipids was administered accidentally to the subject (a two year old girl) over 30 minutes. Id. at 119, right column. In contrast, a single-dose vial of CINVANTI™ containing 130 mg aprepitant contains only 1.7 grams of soybean oil. CINVANTI™ 12. “Attorneys’ argument is no substitute for evidence.” Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989). Appellant cites to Ottoboni as showing that “maximum blood concentration (Cmax) is tied to rate of intravenous delivery.” Appeal Br. 8. Appellant contends that “[a] person of ordinary skill in the art would have readily understood that adverse events are tied to Cmax” and that, “[t]hus, any assumption that adjusting the rate of delivery to be faster or slower than a known rate will be effective and/or safe is baseless and incorrect.” Id.; see also Reply Br. 7. Once again, however, Appellant’s argument relies on attorney arguments rather than evidence, Johnston, 885 F.2d at 1581, and also fails to including soy oil, medium-chain triglyceride, olive and fish oil, not 20% soy oil. Nevertheless, while we do not consider or rely on the additional references relating to fat overload syndrome cited for the first time in Appellant’s Reply Brief, we note that at least some of these references also teach that fat overload syndrome is a “rare” complication of intravenous fat emulsion therapy. L.M. Haber, Fat Overload Syndrome. An Autopsy Study with Evaluation of the Coagulopathy, 90 AM. J. CLINICAL PATHOLOGY 223 (1988). Appeal 2022-000100 Application 16/261,459 15 tie any alleged concern over increased Cmax to the specific modification at issue in the rejection (i.e., at most adjusting the average rate of administration from, e.g., about 4.3 mg/minute (the recommended dosage in CINVANTI™ of 130 mg aprepitant administered intravenously over 30 minutes) to about 6.5 mg/minute). Neither is the rejection premised on an assumption, as Appellant alleges, that adjusting the rate of delivery to be faster or slower than a known rate will necessarily be effective and/or safe: The “case law is clear that . . . the expectation of success need only be reasonable, not absolute.” Pfizer, 480 F.3d at 1364, and the rejection is based on the premise that a skilled artisan would have been motivated to optimize the rate of administration of the active NK-1 receptor antagonist in CINVANTI™. Appellant contends that Ottoboni surprisingly showed that “the rate of reporting at least one treatment-emergent adverse event (TEAe) by subjects receiving the 2-minute injection . . . and receiving the 30-minute infusion . . . were substantially similar, despite the significant increase in Cmax measured after the injection.” Reply Br. 7. Appellant contends that the Examiner “fails to address the unexpected findings set forth in Ottoboni.” Id. at 8; see also id. at 10. We are not persuaded. Appellants have not explained why they could not have raised arguments regarding unexpected results in the Appeal Brief, and the arguments are thus waived. 37 C.F.R. § 41.41(b)(2)). In any event, we are not persuaded because, as discussed above, attorney arguments in the briefs cannot substitute for evidence, and Appellant cites no persuasive evidence that the results discussed in Ottoboni was unexpected. Johnston, 885 F.2d at 1581. Appeal 2022-000100 Application 16/261,459 16 Finally, Appellant contends that a skilled artisan “would . . . have known that infusion of the NK-1 antagonist fosaprepitant, an FDA approved drug product under the tradename EMEND™, is known to cause infusion site reactions . . . when given according to its approved delivery method of an infusion over 20 minutes” and that, as described in Lundberg, “[a] retrospective study of the infusion-site reactions due to 20 minute infusion of EMEND™ resulted in a recommendation to further dilute the approved product and administer it more slowly - over 30 minutes instead of 20 minutes - to reduce the infusion-site reactions.” Appeal Br. 8. Appellant contends that, accordingly, “a skilled artisan “using common sense and the general knowledge in the art . . . would have opted to slow the delivery time/infusion [of CINVANTI™] because this is what skilled persons recommended for another NK-1 receptor antagonist composition.” Id. We are not persuaded. To the extent Appellant contends that the administration rate of EMEND™ is relevant to that of CINVANTI™, we note that, despite the alleged infusion-site reactions, Appellant states that the FDA approved EMEND™ for infusion over 20 minutes. Thus, Lundberg does not support Appellant’s position that a skilled artisan would not have found a method obvious merely because it may also result in adverse reactions. See, e.g., CINVANTI™ 1 (describing adverse reactions with 3- day oral aprepitant regimen in conjunction with moderately emetogenic cancer chemotherapy, single-dose fosaprepitant regimen in conjunction with highly emetogenic cancer chemotherapy, and single-dose CINVANTI).8 8 To the extent the Examiner suggests that Lundberg teaches that “there is less safety concern with [intravenously administered] aprepitant” as compared to intravenously administered fosaprepitant, or that “no such side Appeal 2022-000100 Application 16/261,459 17 We are similarly unpersuaded by Appellant’s argument that the rejection is based on impermissible hindsight. Appeal Br. 8. As the predecessor to our reviewing court has explained, Any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper. In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). Appellant makes similar arguments with respect to claim 2, which differs from the method of claim 1 in that it recites administering the recited emulsion “over about 30 seconds to 15 minutes.” Appeal Br. 10, 13 (Claims App.). We are not persuaded for the reasons already discussed. Accordingly, we affirm the Examiner’s rejection of claims 1 and 2 as obvious over CINVANTI™. Claims 3-12, 14, and 17-30, which are not separately argued, fall with claims 1 and 2. B. Nonstatutory double patenting rejections (claims 1-12, 14, 17-30) In responding to the double patenting rejections, Appellant relies on arguments similar to those made above with respect to the obviousness rejection. More particularly, Appellant contends that “there is simply no guidance or mention in the claims of the Reference Patents which would have led a skilled person to administer an NK-1 receptor antagonist intravenously at any rate, let alone the specific rates as claimed.” Appeal Br. 11. Appellant further contends that there is no basis to assert that a skilled reactions occur with aprepitant,” Ans. 15, we do not adopt such a finding or rely on it in our decision. Appeal 2022-000100 Application 16/261,459 18 artisan “would have modified the mode of administration recited in the Reference Patent claims in view of the literature of which a skilled artisan would have been knowledgeable,” and that, “[u]nderstanding that rapid infusion of a lipid emulsion causes adverse reactions and serious complications,” a skilled artisan “would have had no reason to expect an increased injection rate to be therapeutically effective or safe.” Appeal Br. 11; see also id. at 12 (making the same arguments with respect to Reference Application9). Appellant does not separately argue the rejections; we therefore consider all of the rejections together. The table below sets forth claim 1 of the ’850 patent, one of the reference patents, and claim 1 on appeal: Claim 1 of the ’850 Patent Claim 1 on Appeal 1. A method for treating a subject, comprising administering to the subject an injectable pharmaceutical emulsion, wherein the emulsion comprises: a neurokinase-1 (NK-1) receptor antagonist; 11 wt/wt % to 15 wt/wt % of an emulsifier; an oil; a co-surfactant which comprises an alcohol; a tonicity agent; a pH modifier; and water; wherein the pH of the emulsion ranges from about 7.5 to 9.0, and the ratio of the emulsifier 1. A method for treating a subject in need thereof, comprising: intravenously administering to the subject a single dose of a stable emulsion at an average rate of about 6.5 to 70 mg/minute of an NK-1 receptor antagonist, wherein the stable emulsion comprises the NK-1 receptor antagonist; 11 wt/wt % to 15 wt/wt % of an emulsifier; an oil; a co-surfactant which comprises an alcohol; a tonicity agent; a pH modifier; and water; wherein the ratio of the emulsifier to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt %), wherein the pH of the 9 Reference Application refers to U.S. Patent Application 16/669,262, Appeal Br. 4, which, as noted above, has issued as U.S. Patent 10,953,018 Appeal 2022-000100 Application 16/261,459 19 Claim 1 of the ’850 Patent Claim 1 on Appeal to the NK-1 receptor antagonist ranges from about 18:1 to 22:1 (wt/wt%), and wherein the subject is at risk of or is suffering from nausea and/or vomiting. emulsion ranges from about 7.5 to 9.0. As to Appellant’s argument that there is no guidance or mention reference patent claims that would have led a skilled artisan to administer the NK-1 receptor antagonist intravenously, we are not persuaded: Claim 1 of the ’850 patent, for example, teaches a method of administering an injectable pharmaceutical emulsion. Given that intravenous injection is one of the common ways to administer an injection, we find that the limitation of “intravenously administering” the emulsion in the appealed claim 1 is an obvious variation over claim 1 of the ’850 patent. Likewise, we are unpersuaded by Appellant’s arguments regarding lack of motivation and/or reasonable expectation of success, for the same reasons already discussed with respect to the obviousness rejection. Accordingly, for the reasons above, we affirm the Examiner’s double patenting rejections. CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-12, 14, 17-30 103 CINVANTI™ 1-12, 14, 17-30 Appeal 2022-000100 Application 16/261,459 20 Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1-12, 14, 17-30 Nonstatutory Double Patenting: US 10,624,850 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 10,953,018 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 9,808,465 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 9,974,793 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 9,561,229 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 10,500,208 1-12, 14, 17-30 1-12, 14, 17-30 Nonstatutory Double Patenting: US 9,974,794 1-12, 14, 17-30 Overall Outcome 1-12, 14, 17-30 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). AFFIRMED