PAION UK LIMITEDDownload PDFPatent Trials and Appeals BoardJun 17, 20212020006629 (P.T.A.B. Jun. 17, 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. 14/402,590 11/20/2014 John Aitken Graham ACAC-010N01US 322121-2045 2041 58249 7590 06/17/2021 COOLEY LLP ATTN: IP Docketing Department 1299 Pennsylvania Avenue, NW Suite 700 Washington, DC 20004 EXAMINER MCDOWELL, BRIAN E ART UNIT PAPER NUMBER 1624 NOTIFICATION DATE DELIVERY MODE 06/17/2021 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): zIPPatentDocketingMailboxUS@cooley.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte JOHN AITKEN GRAHAM, ALAN JAMES BAILLIE, KEVIN RICHARD WARD, and THOMAS PEACOCK ____________ Appeal 2020-006629 Application 14/402,5901 Technology Center 1600 ____________ Before JOHN G. NEW, RYAN H. FLAX, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a storage- stable composition of methyl 3-[(4S)-8-bromo-1-methyl-6-(pyridine-2-yl)- 4H-imidazo [1,2-a] [1,4]benzodiazepin-4-yl]propanoate besylate. The Examiner rejected the claims on appeal on under 35 U.S.C. § 103 as obvious. We heard oral argument on June 1, 2021. 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. According to Appellant, the real party in interest is Paion UK Ltd. Appeal Br. 2. Appeal 2020-006629 Application 14/402,590 2 STATEMENT OF THE CASE The Specification discloses that benzodiazepine compounds have therapeutic uses including for “sedation or hypnosis, induction of anxiolysis, induction of muscle relaxation, treatment of convulsions or induction and/or maintenance of anesthesia.” Spec. 1. According to the Specification “[p]roducts which are used as sedatives or anesthetic agents are normally stored at room temperature.” Id. at 2. The Specification discloses that “aqueous solutions” of benzodiazepine compounds lack “sufficient stability at room temperature and show strong degradation within a short period of time.” Id. In addition, the Specification discloses that lyophilization, a “known technique for stabilizing water-labile compounds[,] . . . did not result in satisfactory stability of . . . benzodiazepine.” Id. The Specification thus asserts that there is “a need to provide formulations of short-acting benzodiazepines, which exhibit sufficient stability at room temperature.” Id. The Specification discloses that it was “an object of the present invention to find pharmaceutically acceptable compositions with sufficient stability at room temperature for short-acting benzodiazepines.” Id. The Specification further discloses that “[t]he inventors have now found that stable lyophilized formulations can be obtained, when mixtures of the benzodiazepine with hygroscopic excipients are formulated and/or when the lyophilized formulation is at least in part amorphous.” Id. at 2–3. Claims 94–111 are on appeal. Claim 94 is representative and reads as follows: 94. A storage-stable pharmaceutical composition of methyl 3-[(4S)-8-bromo-1-methyl-6-(pyridine-2-yl)-4H-imidazo [1,2- a] [1,4]benzodiazepin-4-yl]propanoate besylate, consisting essentially of (a) methyl 3-[(4S)-8-bromo-1-methyl-6- Appeal 2020-006629 Application 14/402,590 3 (pyridine-2-yl )-4H-imidazo[1,2-a] [1,4]benzodiazepin-4- yl]propanoate besylate, (b) dextran having a molecular weight of less than 80 kD and (c) lactose, wherein the pharmaceutical composition is lyophilized and less than 1% of the carboxylic ester moiety of the methyl 3-[(4S)-8-bromo-1-methyl-6- (pyridine-2-yl)-4H-imidazo[l,2-a][l,4]benzodiazepin-4- yl]propanoate is hydrolyzed after storage of the pharmaceutical composition for at least 13 weeks at 25°C. Appeal Br. 30. The Examiner rejected claims 94–111 under 35 U.S.C. § 103(a) as obvious over the combination of Feldman,2 Baheti,3 and Tilbrook.4 ANALYSIS Appellant argues claims 94–111 together.5 Appeal Br. 6–28. We designate claim 94 as representative. 2 Feldman et al., US Patent No. 7,160,880 B1, issued Jan. 9, 2007 (“Feldman”). 3 Ankit Baheti et al., Excipients Used in Lyophilization of Small Molecules, 1(1) J. Excipients and Food Chem. 41–54 (2010) (“Baheti”). 4 Tilbrook et al., WO 2008/007071 A1, published Jan. 17, 2008 (“Tilbrook”). 5 At oral argument, counsel for Appellant appeared to suggest that claims requiring that dextran and/or lactose have a specific molecular weight or a specific weight ratios were independently patentable. Tr. 3. However, this argument is waived because it was not made in the appeal brief. 37 C.F.R. § 41.37(c)(1)(iv) (“Except as provided for in §§ 41.41, 41.47 and 41.52, any arguments or authorities not included in the appeal brief will be refused consideration by the Board for purposes of the present appeal.”). The Appeal brief does include a brief discussion of the cited prior art in which Appellant asserts that individual references do not disclose certain features recited in the claims. See, e.g., Appeal Br. 8 (“There is no teaching in Feldman regarding the weight % ratio of the lactose to the dextran in order to prepare a storage-stable pharmaceutical composition comprising remimazolam besylate.”). This is insufficient to raise the issue on appeal. In re Lovin, 652 F.3d 1349, 1357 (Fed. Cir. 2011) (holding that “[T]he Board [has] reasonably interpreted Rule 41.37 to require more substantive Appeal 2020-006629 Application 14/402,590 4 In rejecting claim 94, the Examiner found that Feldman disclosed the free base form of the claimed compound, methyl 3-[(4S)-8-bromo-1-methyl- 6-(pyridine-2-yl)-4H-imidazo [1,2-a] [1,4]benzodiazepin-4-yl]propanoate” (“remimazolam”). Ans. 3. The Examiner further found that Feldman “taught generically that pharmaceutically acceptable salts (including the claimed besylate . . .) and lyophilized compositions thereof may readily be prepared for these classes of compounds.” Id. at 3–4. The Examiner found that Tilbrook included a similar disclosure that “reinforces what is taught in Feldman.” Id. at 4. More particularly, the Examiner found that Tilbrook disclosed that the free base form of remimazolam was unstable at high temperature but that the besylate salt of remimazolam “was readily isolated and showed good stability and low hygroscopicity.” Id. The Examiner also found that Tilbrook suggested lyophilized preparations and taught useful excipients to be used in the lyophilized formulation. Neither Feldman nor Tilbrook discloses the use of lactose and dextran as claimed. To address this deficiency, the Examiner relies on Baheti. Id. at 4–5. The Examiner found that Baheti disclosed lactose and dextran among a group of excipients commonly used in lyophilized formulations (id. at 5) and taught that the listed excipients could be used alone or in combination (id. at 6). The Examiner concluded that using old excipients, like lactose and dextran, was a “known improvement technique[] for getting a more useful version of [a] pharmaceutical” and thus that “it would have been obvious to arguments in an appeal brief than a mere recitation of the claim elements and a naked assertion that the corresponding elements were not found in the prior art.”). Appeal 2020-006629 Application 14/402,590 5 one of ordinary skill in the pharmaceutical art to have applied these known improvement techniques . . . to [remimazolam].” Id. at 7–8. We adopt the Examiner’s findings of fact and reasoning regarding the scope and content of the prior art and agree that the claims would have been obvious over the combination of Feldman, Tilbrook, and Baheti. We address Appellant’s arguments below. Appellant argues that “Tilbrook taught that the besylate salt of remimazolam had good stability in solid form as well as in multiple aqueous solutions.” Appeal Br. 19. According to Appellant, “the cited art teaches that stability issues of the free base can be solved by forming the besylate salt” and thus there was “no reason or motivation for one of skill in the art to ‘solve’ the storage stability problem by combining Tilbrook with Baheti.” Id. Appellant contends that the present claims are patentable because they “solve a formulation problem not recognized in the art prior to its discovery by the inventors.” Id. We do not find this argument persuasive because the motivation to include dextran and lactose in the composition suggested by Tilbrook and Baheti need not be the same as inventors’ motivation in arriving at the claimed composition. See Outdry Techs. Corp. v. Geox S.p.A., 859 F.3d 1364, 1370–71 (Fed. Cir. 2017) (“Any motivation to combine references, whether articulated in the references themselves or supported by evidence of the knowledge of a skilled artisan, is sufficient . . . . The motivation . . . need not be the same motivation articulated in the patent for making the claimed combination.”); PAR Pharm., Inc. v. TWI Pharm., Inc., 773 F.3d 1186, 1197 (Fed. Cir. 2014) (“[W]e are not limited to the same motivation that may have motivated the inventors.”); Alcon Research, Ltd. v. Apotex Inc., 687 F.3d Appeal 2020-006629 Application 14/402,590 6 1362, 1368 (Fed. Cir. 2012) (“We have repeatedly held that the motivation to modify a prior art reference to arrive at the claimed invention need not be the same motivation that the patentee had.”). Here, Feldman discloses the besylate salt of remimazolam as “pharmaceutically acceptable” (Feldman, 51:31–42) and Tilbrook teaches that “besylate salts . . . are easily isolated from a range of pharmaceutically acceptable solvents and show good thermal stability, low hygroscopicity and high aqueous solubility” (Tilbrook 2). In view of these disclosures, we agree with the Examiner that the ordinary artisan would have found it obvious to start with the besylate salt of remimazolam as a target for optimization and development. Ans. 11. Feldman also teaches that remimazolam “may be presented as lyophilized solids for reconstitution with water (for injection) or dextrose or saline solutions.” Feldman, 52:8–11. And Tilbrook teaches that a “preferred formulation of a salt of [Tilbrook’s] invention is a lyophilized formulation.” Tilbrook, 8. Together with Feldman’s and Tilbrook’s teachings regarding the besylate salt, this supports that the ordinary artisan would have found it obvious to use a lyophilized formulation of the besylate salt of remimazolam. We recognize that Feldman does not disclose excipients and Tilbrook discloses different excipients than those recited in the present claims in their lyophilized formulations. Feldman, 52:8–11 (disclosing that remimazolam may be lyophilized without identifying excipients for use in lyophilized compound); Tilbrook, 8 (disclosing a lyophilized formulation comprising “at least one of the following agents: ascorbic acid, citric acid, malic acid, phosphoric acid, glycine, glycine hydrochloride, succinic acid or tartaric Appeal 2020-006629 Application 14/402,590 7 acid”). However, Tilbrook also discloses that its formulation is not limited to the excipients it lists, explaining that “[i]n some cases it may be beneficial to include sodium chloride, mannitol, polyvinylpyrrolidone, or other ingredients in the formulation.” Id. (emphasis added). In addition, Baheti discloses that “[i]n the majority of lyophilized formulations, excipients are included to improve the functional properties and stability of the lyophilized product.” Baheti 42–43. According to Baheti, “[e]xcipients also provide an aesthetic appeal to the product” and “help[] in developing a robust and economical lyophilization process.” Id. at 43. Baheti classifies excipients by type and provides reason why each category of excipient should be used in a lyophilized preparation. Id. at 43– 52. Figure 5 of Baheti, reproduced below, discloses a number excipients commonly used in lyophilization. Baheti 46. Appeal 2020-006629 Application 14/402,590 8 Figure 5 is a “[c]lassification of commonly used excipients used in lyophilization of small molecules.” Id. Figure 5 identifies dextran and lactose among a group of 12 bulking agents. Other categories of excipients identified in Figure 5 include buffering agents, solubilizing agents, tonicifying agents, antimicrobial agents, and collapse temperature modifiers. Id. In addition to the disclosure of Figure 5, Baheti discloses that “[m]annitol and glycine, are the most commonly used bulking agents, Appeal 2020-006629 Application 14/402,590 9 followed by glucose, sucrose, lactose, trehalose and dextran.” Id. These disclosures support that, absent a teaching to the contrary not present here, it would have been obvious to include dextran and lactose in a lyophilized formulation, like the lyophilized formulation of the besylate salt of remimazolam suggested by Feldman and Tilbrook. Appellant argues that Baheti offers too many choices to render the selection of dextran and lactose non-obvious. Appellant explains: Baheti offers 12 exemplary bulking agents among the classes. Baheti also discloses buffering and pH adjusting agents, 15 in total. Baheti also suggests the potential need for a solubilizing agent such as complexing agents, 3 in total, possibly a surfactant (1 listed), and possibly a co-solvent, offering 6 of these. Among other possibly required agents to establish a stabilized lyophilized product are tonicifying agents (4 in total), antimicrobial agents (5), and collapse temperature modifiers (indicating 4 such agents). See, Baheti at Figure 5. Nothing in Baheti teaches or suggests the isolation of only one category of agents to make a lyophilized formulation. The prior art teaching must be taken as a whole, yet the Office has overlooked the extremely broad scope of teaching, and lack of specific guidance, in Baheti. Moreover, the present claims include two bulking agents. Nothing in Baheti suggests selecting more than one agent out of any one category. Armed with nothing from the Baheti teachings, the combinations become staggeringly large. Appeal Br. 24. We do not find this argument persuasive. The fact that Baheti discloses dextran and maltose as one among twelve bulking agents and one among fifty excipients does not make their use in the claimed lyophilized composition nonobvious. Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 335 (1945) (“Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put into the last opening in a jig- Appeal 2020-006629 Application 14/402,590 10 saw puzzle.”); see also Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989) (“That the ’813 patent discloses a multitude of effective combinations does not render any particular formulation less obvious.”). Absent evidence of unexpected results or criticality, we agree with the Examiner that it would have been obvious to use lactose and dextran in a lyophilized composition of remimazolam. Appellant argues that the inventors “surprisingly discovered that lyophilized formulations comprising the besylate salt of remimazolam and dextran or lactose have significantly improved stability (as compared to [the] besylate salt of remimazolam alone or with the excipients disclosed in Tilbrook, i.e., mannitol, glycine and povidone).” Appeal Br. 21. Appellant argues that as compared to Tilbrook’s formulations, “[t]he inventors discovered that remimazolam besylate salt degradation was significantly improved, with degradation rates less than 1% (Figure 4), when the compositions comprise dextran or lactose.” Id. at 23. As support, Appellant cites the Declaration of Luigi Moro. Id. (citing Moro Decl. ¶¶ 9–15).6 Mr. Moro testifies that the inventors tested 12 different formulations of remimazolam, including formulations using three of the excipients disclosed as being useful in lyophilized formulations in Tilbrook. Moro Decl. ¶¶ 9–10. Mr. Moro presents the results of this testing in the below table, which he reproduced from Figure 4 of the pending application. 6 Declaration of Luigi Moro Under 37 C.F.R. § 1.132, filed June 5, 2017 (“Moro Declaration” or “Moro Decl.”). Appeal 2020-006629 Application 14/402,590 11 Id. ¶ 11. According to Mr. Moro, the Figure 4 “indicates the percentage of hydrolysis degradant of remimazolam (formed by hydrolysis of the ester bond) that is present in the tested formulations of remimazolam after 13 weeks of storage at either 25°C and 60% relative humidity or at 40°C with 75% relative humidity.” Id. ¶ 12. Mr. Moro testifies that Figure 4 shows that formulations of remimazolam alone, and of remimazolam with mannitol, povidone, or glycine resulted in undesirable high levels of degradation. Id. ¶ 13. Mr. Moro asserts that these results were “not expected based on the specific teachings of Tillbrook [sic] that useful lyophilized formulations of the besylate salt of remimazolam could be made using mannitol, povidone and glycine.” Id. Mr. Moro states that these results contrast with the results for formulations of “remimazolam with either lactose, trehalose, sucrose, maltose, or dextran at a 1:9 ratio [which were] able to keep hydrolysis degradant levels at a desirable level of below 1% at both tested temperatures and humidity levels.” Id. ¶ 14. According to Mr. Moro, these results are “unexpected based on the disclosures of . . . Baheti . . . which . . . discloses Appeal 2020-006629 Application 14/402,590 12 mannitol, lactose, sucrose, trehalose, glycine and dextran as interchangeable ‘bulking agents.’” Id. ¶ 15. We are not persuaded. As an initial matter, with the exception of formulation # 10 (which is directed to a formulation of remimazolam, lactose, and mannitol), the data in Figure 4 above is directed to remimazolam alone or with specific amounts of individual excipients. Id. ¶ 11. Consistent with the data, the arguments in Appellant’s Appeal Brief are worded to encompass the alleged superiority of individual excipients rather than the claimed combination of excipients. See, e.g., Appeal Br. 21 (“[T]he inventors surprisingly discovered that lyophilized formulations comprising the besylate salt of remimazolam and dextran or lactose have significantly improved stability (as compared to besylate salt of remimazolam alone or with the excipients disclosed in Tilbrook, i.e., mannitol, glycine and povidone).”) (emphasis added), 23 (“The inventors discovered that remimazolam besylate salt degradation was significantly improved, with degradation rates less than 1% (Figure 4), when the compositions comprise dextran or lactose.”) (emphasis added). Because Appellant’s evidence and argument is not commensurate with the scope of claim 94, which requires a composition consisting essentially of unspecified quantities of remimazolam, dextran, and lactose, it is not persuasive of unexpected results. In re Huai-Hung Kao, 639 F.3d 1057, 1068 (Fed. Cir. 2011) (“Evidence of secondary considerations must be reasonably commensurate with the scope of the claims.”); In re Harris, 409 F.3d 1339, 1344 (Fed. Cir. 2005) (“Even assuming that the results were unexpected, Harris needed to show results covering the scope of the claimed range.”). At oral argument, Appellant’s counsel pointed us to data in the Specification regarding a formulation comprising remimazolam, dextran, Appeal 2020-006629 Application 14/402,590 13 and lactose. Tr. 5, 7. However, the Appeal Brief does not include argument based on this data. See generally Appeal Br. The Moro Declaration makes reference to this data, but argument based on this testimony is waived because the Appeal Brief does not cite this portion of the Moro Declaration. 37 C.F.R. § 41.37(c)(1)(iv). Even if we were to consider Mr. Moro’s testimony on this point, Mr. Moro does not testify that the claimed combination of excipients demonstrates unexpected stability as compared to any other composition, but only that the data shows that the claimed composition is “desirable and stable, and suitable for use via injection.” Moro Decl. ¶ 19. This is particularly significant given that several of the individual excipients identified in Figure 4 appear to demonstrate stability properties well within those recited by the claim – i.e., “less than 1% of the carboxylic ester moiety . . . is hydrolyzed after storage of the pharmaceutical composition for at least 13 weeks at 25ºC.” See id. ¶ 11 (showing formulations of remimazolam with just lactose, trehalose, sucrose, maltose, dextran, and povidone as having the stability recited in the wherein clause of claim 94); see also Tr. 7 (oral argument where counsel for Appellant was asked to speak to the issue that individual excipients performed similarly to the claimed combination of excipients and counsel acknowledged that “with certain molecular weights of dextran, you can get pretty decent results as well”). Accordingly, the current record does not support that the formulation recited in claim 94 demonstrates unexpectedly superior stability. In the Reply Brief, Appellant argues that the Examiner failed to consider evidence that a formulation of remimazolam, dextran, and lactose exhibited a reduced time for reconstitution as compared to a formulation of just remimazolam and dextran. Reply Br. 3 (citing Moro Decl. ¶¶ 17, 18). Appeal 2020-006629 Application 14/402,590 14 We do not consider this argument because it was not presented in the Appeal Brief, thus depriving us of the Examiner’s response. 37 C.F.R. § 41(c)(1)(iv). Even if we were to consider this argument, we would not find it persuasive of unexpected results because the evidence presented is directed to a single formulation comprising specific amounts of remimazolam, dextran, and lactose (Moro Decl. ¶ 17), and Appellant does not direct us to persuasive evidence that this specific formulation is representative of all of the quantities of remimazolam, dextran, and lactose encompassed by claim 94. Appellant argues that Baheti demonstrates that there is unpredictability among the performance of the excipients it discloses. Appeal Br. 26. For example, Appellant points to Baheti’s teachings that: 1) “for a particular compound, cyclophosphamide, mannitol performed better than lactose,” 2) the bulking agent may crystallize after lyophilization and that such crystallization “might adversely affect the stability of the product,” 3) “methylprednisolone sodium succinate provided a less stable product with mannitol than lactose,” and 4) “the bulking agent may crystallize into different polymorphic forms which ‘could also have serious implications on physical stability.’” Id. We are not persuaded. “[The] 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.” Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364 (Fed. Cir. 2007) (finding besylate salt of known compound obvious even though “it was generally unpredictable as to whether a particular salt would form and what its exact properties would be” explaining that if the law were to the contrary “any new salt . . . would be Appeal 2020-006629 Application 14/402,590 15 separately patentable, simply because the formation and properties of each salt must be verified through testing”). Here, Baheti teaches that dextran and lactose are among “the most commonly used bulking agents” in lyophilized formulations. Baheti, 46. Mr. Moro describes Baheti as “disclos[ing] mannitol, lactose, sucrose, trehalose, glycine and dextran as interchangeable ‘bulking agents.’” Moro Decl. ¶ 15. We find that Baheti’s teaching of differences in the performance of individual excipients, and of potential issues regarding crystallization of bulking agents, is insufficient to undermine the reasonable expectation of the ordinary artisan that including commonly used bulking agents, like lactose and dextran, in a lyophilized formulation of the besylate salt of remimazolam would be successful. Appellant argues that Baheti discloses that “control of pH is critical to avoid degradation,” and thus it is “surprising that the present claims do not encompass the use of a pH control agent as the formulation consists essentially of the besylate salt of remimazolam with lactose and dextran, but no pH control agent.” Appeal Br. 26. We are not persuaded. The phrase “consisting essentially of” is used to signal a partially open claim in a patent. PPG Indus. v. Guardian Indus. Gorp., 156 F.3d 1351, 1354 (Fed. Cir. 1998). A claim using the phrase “consisting essentially of” is generally understood to encompass the components that follow the transitional phrase as well as additional unlisted ingredients that do not “materially affect the basic and novel properties of the invention.” Id. Appellant argues, implicitly, that the addition of a pH control agent would materially affect the basic and novel properties of the claimed composition. Appeal Br. 26. Appeal 2020-006629 Application 14/402,590 16 We turn to the Specification for guidance. As an initial matter, the Specification does not identify any components as being excluded from the claimed supplement nor does it define what constitutes a “material change” in the properties of the composition. See PPG Indus., 156 F.3d at 1355 (noting that the patentee “could have defined the scope of the phrase ‘consisting essentially of’ for purposes of its patent by making clear in its specification what it regarded as constituting a material change in the basic and novel characteristics of the invention”). The Specification does provide some guidance as to what the inventors considered to be the novel properties of the claimed invention in its discussion of the problems solved. It teaches that “there is a need to provide formulations of short-acting benzodiazepines, which exhibit sufficient stability at room temperature.” Spec. 2. Appellant solved the problems in the art by using lyophilized formulations of “mixtures of the benzodiazepine with hygroscopic excipients.” Id. Accordingly, we find that the basic and novel properties of the claimed composition are that it exhibits sufficient stability at room temperature. Having identified the alleged basic and novel properties of Appellant’s composition, we next address Appellant’s argument that the claims exclude a pH control agent. Baheti teaches that “[c]ontrol of pH is critical to avoid degradation of drug during processing, storage, and reconstitution, thereby necessitating [the] addition of [a] buffering agent in the lyophilized formulation.” Baheti 49. This suggests that the addition of a buffer can materially impact the stability of a lyophilized composition. However, according to Appellant, the claimed composition is already stable at room temperature. Appellant does not provide persuasive evidence that the addition of a pH control agent would materially affect the room- Appeal 2020-006629 Application 14/402,590 17 temperature stability of an already storage-stable composition or, more specifically, the stability of the claimed composition. Accordingly, we are not persuaded by Appellant’s argument that the claims exclude the addition of a pH control agent. For the reasons discussed above, we affirm the Examiner’s rejection of claim 94 over the combination of Feldman, Baheti, and Tilbrook. Because they were not argued separately, claims 95–111 fall with claim 94. CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 94–111 103(a) Feldman, Baheti, Tilbrook 94–111 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 Copy with citationCopy as parenthetical citation