JINA PHARMACEUTICALS, INC.Download PDFPatent Trials and Appeals BoardMay 11, 202015204826 - (D) (P.T.A.B. May. 11, 2020) 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. 15/204,826 07/07/2016 Shoukath M. Ali JINA-13269.302 2938 72960 7590 05/11/2020 Casimir Jones, S.C. 2275 Deming Way Ste 310 Middleton, WI 53562 EXAMINER PEEBLES, KATHERINE ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 05/11/2020 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@casimirjones.com pto.correspondence@casimirjones.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte SHOUKATH M. ALI, MOGHIS U. AHMAD, ATEEQ AHMAD, SAIFUDDIN SHEIKH, and IMRAN AHMAD 1 Appeal 2019–006342 Application 15/204,826 Technology Center 1600 Before ERIC B. GRIMES, ULRIKE W. JENKS, and JOHN G. NEW, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a process for preparing a lipid formulation of an active compound, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellant identifies the real party in interest as Jina Pharmaceuticals, Inc. Appeal Br. 3. We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appeal 2019-006342 Application 15/204,826 2 STATEMENT OF THE CASE “The present invention relates to new methods of preparing active compounds complexed with lipids, and methods of using the complexes in treating a subject.” Spec. ¶ 13. More specifically, the “invention relates to the preparation of [a] suspension . . . in an aqueous system.” Spec. ¶ 73. In embodiments, the methods of the invention can involve “dissolving active compound . . . in water and mixing the dissolved antibiotic and the lipid(s) together,” “mixing lipid(s) and sodium deoxycholate together in water and then adding active compound,” or “mixing active compound . . . and one or more lipids in any suitable sequence such that the resulting composition of the present invention comprises active compound . . . and one or more lipids.” Spec. ¶¶ 109, 110, 113. Claims 39–49 are on appeal. Claim 39, reproduced below, is illustrative: 39. A process for preparing a lipid formulation of an active compound without use of an organic solvent, said process comprising: i) to a first aqueous medium consisting of water, or of sodium chloride dissolved in water, or of a buffering agent dissolved in water, adding at least one lipid in solid form and at least one active compound in solid form, wherein said active compound is a partially water soluble or water insoluble drug; ii) treating the mixture consisting of said aqueous medium, said lipid in solid form and said active compound in solid form of step i) together to form a lipid-compound suspension of defined particle size; iii) lyophilizing the lipid-compound suspension of defined particle size of step ii) to form lyophilized material; and Appeal 2019-006342 Application 15/204,826 3 iv) reconstituting said lyophilized material of step iii) with a second aqueous medium to obtain a suspension of lipid formulation of defined particle size, said defined particle size having a mean particle size of less than 5 microns, wherein said at least one lipid comprises at least one phospholipid, and cholesterol or a cholesterol derivative selected from the group consisting of cholesterol sulfate and salts thereof, cholesterol hemisuccinate and salts thereof, and cholesterol phosphate and salts thereof. The claims stand rejected as follows: Claims 39, 41–45, 47, and 49 under 35 U.S.C. § 103 as being unpatentable over Muller2 in view of Haynes3 (Ans. 4–7); Claim 40 under 35 U.S.C. § 103 as being unpatentable over Muller in view of Haynes in view of Strott4 (Ans. 7–8); and Claims 46 and 48 under 35 U.S.C. § 103 as being unpatentable over Muller in view of Haynes further in view of Kurka5 further in view of Kullenberg6 (Ans. 8–10). OPINION Obviousness based on Muller and Haynes Claims 39, 41–45, 47, and 49 stand rejected under 35 U.S.C. § 103 as being obvious over Muller and Haynes. Ans. 4. The Examiner finds that “Muller teaches a method of making a drug carrier comprising subjecting at 2 US 5,858,410; issued Jan. 12, 1999. 3 US 5,091,187; issued Feb. 25, 1992 4 Charles A. Strott & Yuko Higashi, Cholesterol sulfate in human physiology: what’s it all about?, J. Lipid Research 44:1268–1278 (2003). 5 CA 2,091,113; published Nov. 9, 1993. 6 US 5,084,269; issued Jan. 28, 1992. Appeal 2019-006342 Application 15/204,826 4 least one sparingly water soluble solid therapeutically active compound dispersed in a solvent to high pressure homogenization to form particles having an average particle diameter of between 40 - 100 nm.” Ans. 5. The Examiner finds that “[t]he carrier comprises one or more dispersion- stabilizing substances . . . which include soy lecithin and/or cholesterol.” Id. The Examiner finds that Muller’s Example 9C “discloses a composition made by exposing RMKP 22 (the sparingly soluble active compound), 0.6% phospholipon (i.e. a phospholipid), and water to [homogenization] . . . result[ing] in a composition with particle diameter of 0.286 microns.” Id. The Examiner reasons that claim 39 “does not specify an order of addition for the lipid and the drug, therefore lipid may be added first, drug may be added first, or they both may be added simultaneously.” Ans. 12. The Examiner finds that claim 39 does not “preclude a step wherein ‘a solution of surfactant’ (i.e., the Phospholipon in Muller’s Example 9C) as disclosed by Muller and the aqueous medium is formed prior to addition of the drug in solid form.” Ans. 13. The Examiner finds, “the MSDS sheet[7] indicates that Phospholipon is a powder (i.e. in solid form . . . ).” Ans. 13. The Examiner thus finds, “Phospholipon 90 is in solid form when added to the water. . . . There is nothing else added and no description of method steps to form a solution.” Ans. 14. The Examiner reasons that applying Muller’s statement that “[a]lternatively, the drug powder can also be introduced into a surfactant solution by stirring” to Example 9C renders obvious the step of forming a 7 Phospholipon 90 H Material Data Safety Sheet (MSDS), Phospholipid (2007) (of record). Appeal 2019-006342 Application 15/204,826 5 mixture of water and Phospholipon 90 to which the drug powder is added while stirring. Id. The Examiner thus concludes that Muller makes obvious a process meeting all of the limitations of claim 39 except the reconstitution step. The Examiner finds that Haynes “discloses that lyophilized preparations of drug- containing lecithin particles may be reconstituted in aqueous solution for delivery.” Ans. 6. The Examiner concludes that it would have been obvious “to resuspend the particles disclosed by Muller in aqueous solution because this system would be compatible for multiple routes of drug administration including oral and parenteral routes.” Id. Appellant states that “Muller is not ambiguous about the steps employed to form the nanosuspensions.” Appeal Br. 6. Specifically, Muller “instruct[s] that the active compound is first mixed with a surfactant solution.” Id. at 10. Appellant argues that “[n]either Muller nor the Office provide any basis or argument that supports the Office’s contention that the surfactant in the ‘surfactant solution’ of Muller can be ‘in solid form’ as set forth in Appellant’s claim 39.” Id. Appellant argues that according to Muller, “a surfactant solution must be formed prior to the addition of the drug. Nowhere does Muller suggest that solid Phospholipon 90 in water, in accordance with the Office’s interpretation could be considered a ‘surfactant solution.’” Appeal Br. 11. Appellant also argues that, while “claim 39 does not require simultaneous addition of the lipid in solid form and the active compound in solid form, the claim does recite that both are added [] in solid form to an aqueous medium.” Id. Appeal 2019-006342 Application 15/204,826 6 Appellant argues that “claim 39 excludes adding the solid active compound to a surfactant solution (however prepared), and excludes forming a solution of the recited lipids prior to combination with the solid active compound or, vice versa.” Id. Appellant concludes that the appealed claims “exclude the process of Muller’s example 9C, and Muller does not teach or suggest Appellant’s claimed method.” Appeal Br. 12. We agree with the Examiner, however, that the claimed process would have been obvious to a person of ordinary skill in the art based upon the teachings of Muller and Haynes. Muller discloses a drug carrier comprising particles of an active compound, having an average diameter of 10 nm to 1000 nm. Muller, Abstract. Muller states that “[s]uspensions were prepared with a drug, which was ground in an air jet, in an aqueous surfactant solution. . . . RMKP 22 was employed as the model drug.” Id. at 5:27–30. In Example 9C of Muller, RMKP 22, Phospholipon,8 and water are combined to prepare a nanosuspension “as described in example 1.” Muller at 15:8–10. In Example 1, Muller explains that “[t]he powdered drug . . . was rubbed in a grinding dish with a concentrated surfactant solution for wetting, and the remaining aqua dest. was then added, while stirring.” Id. at 11:27–30. Muller states that, “[a]lternatively, the drug powder can also be introduced into a surfactant solution by stirring.” Muller at 11:30–31. The Examiner has cited the Phospholipon 90 MSDS as evidence that Muller’s Phospholipon is a solid powder. Thus, it would have been obvious 8 Muller states that the composition included “0.6% Phospholipon 90%.” Muller 15:8. However, “90%” appears to be a typo and “0.6% Phospholipon 90” appears to be intended. Cf. id. at 12:58 (“Phospholipon 90 0.6”). Appeal 2019-006342 Application 15/204,826 7 to form the “surfactant solution” suggested by Muller by adding solid Phospholipon to water. Muller describes RMKP 22 as a powder (a solid). Thus, preparing Example 9C of Muller according to the expressly suggested alternative method of Example 1 adds solid lipid (Phospholipon) to water (forming a solution), then adds solid active compound (RMKP 22) to the solution to form a nanosuspension. Claim 39 requires “adding at least one lipid in solid form and at least one active compound in solid form” to a first aqueous medium. The claim does not require the lipid to remain in solid form in the aqueous medium until the solid active compound is added. Thus, claim 39 reads on a process of adding a lipid in solid form to an aqueous medium, dissolving the lipid to form a surfactant solution, and then adding an active compound in solid form to that solution. “[A] claim must be read in view of the specification of which it is a part.” Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1248 (Fed. Cir. 1998). As noted above, the instant Specification states that “[i]n some embodiments, the method of the present invention involves mixing lipid(s) and sodium deoxycholate[9] together in water and then adding active compound.” Spec. ¶ 110. This embodiment describes mixing of lipid in water prior to addition of active compound, as Muller teaches. Thus, claim 39, read in light of the instant Specification, does not preclude the formation of a lipid solution prior to adding active compound to water. In Example 9C 9 “The commercial preparation of amphotericin B, FUNGIZONE is a mixture of amphotericin B, a detergent deoxycholate, and a buffer.” Spec. ¶ 77. We thus understand sodium deoxycholate to be a detergent in the embodiment discussed above. Appeal 2019-006342 Application 15/204,826 8 of Muller, both lipid and active compound are added to an aqueous medium in solid form, meeting the limitations of claim 39. Appellant argues that “Muller teaches that the surfactant must be in a solution first, i.e., that the insoluble drug cannot be added directly to water.” Appeal Br. 12. Claim 39 does not require that drug be added directly to water alone. As Appellant notes, while “claim 39 does not require simultaneous addition of the lipid in solid form and the active compound in solid form, the claim does recite that both are added to in solid form to an aqueous medium . . .” Appeal Br. 11. As discussed above, Muller suggests forming a surfactant solution—e.g., by adding powdered Phospholipon to water—then adding an active compound in solid form. Additionally, the claim does not specify an order of addition. “Unless the steps of a method actually recite an order, the steps are not ordinarily construed to require one.” Interactive Gift Express, Inc. v. CompuServe Inc., 231 F.3d 859, 875 (Fed. Cir. 2000). As noted above, the instant Specification states that “[i]n some embodiments, the present invention comprises mixing active compound . . . and one or more lipids in any suitable sequence such that the resulting composition of the present invention comprises active compound . . . and one or more lipids.” Spec. ¶ 113, emphasis added. Thus, the instant Specification indicates that the order of addition is not critical to the claimed method. Appellant argues that “the process of Muller exemplified by Example 9C is labor-intensive” while “Appellant has surprisingly shown that [] a much simpler process can be used to produce a stable nanosuspension having particles of defined size.” Appeal Br. 12. Appeal 2019-006342 Application 15/204,826 9 This argument is unpersuasive. The preamble of claim 39 recites the transition term “comprising.” “The transition ‘comprising’ in a method claim indicates that the claim is open-ended and allows for additional steps.” Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1368 (Fed. Cir. 2003). Thus, claim 39 allows for the additional steps cited by Appellant (Appeal Br. 12), such as air-jet grinding of the drug to form a powder. We conclude that the rejection of claims 39, 41–45, 47, and 49 under 35 U.S.C. § 103 based on Muller in view of Haynes is supported by a preponderance of the evidence, and we therefore affirm it. Obviousness based on Muller, Haynes, and Strott Claim 40 stands rejected under 35 U.S.C. § 103 as being obvious over Muller, Haynes, and Strott. Ans. 7. The Examiner finds that Muller and Haynes are silent with respect to cholesterol sulfate, but finds that “Strott discloses . . . that cholesterol sulfate interacts with phospholipids in a manner similar to that observed for cholesterol and has the ability to induce hydrocarbon ordering in lipid bilayers and to stabilize model membranes.” Ans. 8. The Examiner concludes that it would have been obvious to use cholesterol sulfate in Muller’s method because cholesterol sulfate is structurally similar to the cholesterol suggested by Muller, and cholesterol sulfate “was known to increase the stability of phospholipid structures.” Id. We agree with the Examiner’s fact-finding and conclusion. Appellant argues that “Strott fails to cure the deficiencies of Muller and Haynes with respect to the process recited in Appellant’s claim 39.” Appeal 2019-006342 Application 15/204,826 10 Appeal Br. 14. We find this argument unpersuasive for the reasons discussed above. Appellant additionally argues that Strott “is limited in its discussion of this compound with respect to membranes to the function of cholesterol sulfate in cell membranes” and “[n]othing in Strott teaches or suggests what effect cholesterol sulfate might have on solid/microcrystalline lipid nanoparticles disclosed by Muller and Haynes.” Id. We agree with Examiner, however, that the teachings of Strott are properly combined with those of Muller. As the Examiner found, “Muller discloses that combinations of cholesterol and phospholipid can be used in the method of making the drug carrier.” Ans. 8. Specifically, Muller suggests including “mixtures of . . . lecithins with one or more phospholipid components, cholesterol, cholesterol palmitate, or stigmasterol.” Muller 19:8–10. As the Examiner has pointed out “cholesterol and cholesterol sulfate were known to be structurally similar,” Ans. 8; thus, it would have been obvious to substitute cholesterol sulfate for Muller’s cholesterol. Obviousness based on Muller, Haynes, Kurka, and Kullenberg Claims 46 and 48 stand rejected under 35 U.S.C. § 103 as being obvious over Muller, Haynes, Kurka, and Kullenberg. Ans. 8. Appellant argues that Kurka and Kullenberg “do[] not cure the deficiencies of Muller and Haynes with respect to adding drug and lipid to a specific selection of aqueous media.” Appeal Br. 15. Because we do not find any deficiency in the combination of Muller and Haynes, and Appellant has waived arguments directed to Kurka or Appeal 2019-006342 Application 15/204,826 11 Kullenberg, we affirm the rejection of claims 46 and 48 for the reasons given by the Examiner and as discussed above. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 39, 41–45, 47, 49 103 Muller, Haynes 39, 41–45, 47, 49 40 103 Muller, Haynes, Strott 40 46, 48 103 Muller, Haynes, Kurka, Kullenberg 46, 48 Overall Outcome 39–49 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