DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 12/23/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103 - Obviousness
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-6, 8-11, 13-18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kikuchi et al (US 2012/0128757 A1).
Kikuchi taught pharmaceutical compositions [0164] comprising liposomes in a liposome dispersion liquid [see claim 1], comprising a lipid bilayer and an internal aqueous phase [see claims 1 and 6; see also ¶ 0072], said liposomes comprising one or more phospholipids [0097] at 10 to 80 mole % [0099], prostaglandins (e.g., weak acid) [0088] and ammonium acetate (e.g., carboxylic acid salt) [0147]. As per Kikuchi, the liposome of the disclosure “may also” include sterols such as cholesterol [0100]. There were no particular limitations on the mixing amount (mole fraction) of the sterols that were used when preparing the liposome, but when included, the sterols were included at 1 to 60% (e.g., reads on less than 15 mole %), relative to the entire liposome membrane composition [0101].
Claim 1 is rendered prima facie obvious over the teachings of Kikuchi, because it is prima facie obvious to combine prior art elements according to known methods, in order to yield predictable results. In the instant case, all the claimed elements (e.g., liposome comprising phospholipids, cholesterol and amounts thereof, weak acid, carboxylic acid salt) were known in the prior art (e.g., Kikuchi) and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results (e.g., a pharmaceutical composition) to one of ordinary skill in the art. MPEP 2143.A.
The instant claim 1 recites 75-99 mole % first phospholipid; 0.1-25 mole % second phospholipid; optionally less than 15 mole % sterol.
The instant claim 3 recites less than 13 mole % sterol.
The instant claim 4 recites less than 10 mole % sterol.
The instant claim 5 recites substantially free of sterol.
Kikuchi taught one or more phospholipids at 10 to 80 mole %; optional inclusion of cholesterol, and when included, 1 to 60 mole % cholesterol. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art", a prima facie case of obviousness exists. MPEP 2144.05 A.
Kikuchi reads on claims 1, 3-6, 13 and 17.
Claim 2 is rendered prima facie obvious because Kikuchi taught citric acid [0145].
Claims 8-11 are rendered prima facie obvious because Kikuchi taught phosphatidylcholine (PC), phosphatidyl glycerol (PG), phosphatidic acid (PA) [0097]; PEG-DSPE2000 [0104]; and, HSPC [0212].
Claim 14 is rendered prima facie obvious over the teachings of Kikuchi because bicarbonate salts are not required of claim 1, and claim 1 is rendered prima facie obvious over Kikuchi (see the above Obviousness rejection of claim 1 over Kikuchi et al).
Claim 15 is rendered prima facie obvious because Kikuchi taught the liposome further containing cyclodextrin in the liposome internal phase [abstract].
Regarding claim 16, Kikuchi was not specific the drug to cyclodextrin ratio, as instantly recited. Nonetheless, when led by the guidance of Kikuchi, it is prima facie obvious to one of ordinary skill in the art to empirically determine the ratio, with a reasonable expectation of success, and without undue experimentation. This is because Kikuchi taught that the cyclodextrin concentration could be adjusted based on the solubility of the active agent [0075, 0077, 0130, 0144].
Claim 18 is rendered prima facie obvious because Kikuchi taught dexamethasone [0088].
Claim 20 is rendered prima facie obvious because Kikuchi taught an encapsulation efficiency of 75.9 % encapsulation efficiency without cyclodextrin, and 98.4-99.4 % encapsulation efficiency with cyclodextrin [Table 1].
The instant claim 20 recites over 70 % encapsulation efficiency. Kikuchi taught 75.9-99.4 % encapsulation efficiency. A prima facie case of obviousness exists because of overlap, as previously discussed.
Response to Arguments
Applicant's arguments, filed 12/23/2025, have been fully considered but they are not persuasive.
Applicant alleged that the instant composition unexpectedly reduces drug release (less than 65 % release within 1 hour) as mole % of cholesterol reduces (< 15 % cholesterol). Applicant cited to Table 1 and 2 of the present application (renumbered to Table 2 and Table 3 in the Applicant’s Remarks).
The Examiner agrees that the instant application reduced drug release [see Tables 2 and 3 of Applicant’s remarks]. At Tables 2 and 3, when the amount of cholesterol was less than 15 mole %, and the amount of the first lipid (HSPC) increased, the % drug release decreased.
The % drug release decreases in the instant invention, whereas as the reverse is true by the showing of the closest prior art [Kikuchi et al]. Kikuchi’s drug release decreased as the amount of cholesterol increased [Table 1, Remarks, page 10]. The ordinarily skilled artisan would expect drug release to decrease with increased cholesterol (e.g., Kikuchi taught 37.5 mole percent cholesterol), as shown in Kikuchi. This effect, by the instantly reduced amounts of cholesterol, is not recognized by the prior art, and thus, the effect (reduced drug release) is unexpected.
However, once unexpectedness has been established, the probative value of the evidence as compared to the invention as claimed must be determined, i.e., claims must be “commensurate in scope” with the showing. See MPEP 716.02(d). In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. And this is not considered to be the case with the instant claims.
The instant claim 1 does not limit the phospholipids, and only requires “a first phospholipid” and “a second phospholipid”, generally. And for both limitations, the data is not considered to be commensurate in scope.
The three lipids tested were HSPC (1st lipid); and, DSPE-mPeg or DSPG (2nd lipid). HSPC is neutrally charged; DSPE-mPeg exhibits a neutral or slightly negative charge; and, DSPG is negatively charged. The claims are drawn to weak acid drugs and weak acid salts (carboxylic acid or bicarbonate salts), which would produce negative charges in aqueous media.
Other lipids (e.g., cationic lipids) that don’t make the type of ionic interactions, as between negatively or neutrally charged lipids with negatively charged drugs, would be expected to interact differently. And, it is unclear whether the effect would be present when there are other ionic interactions between the lipid and the active agent. It is noted that the instant claim 21 limits the 1st and 2nd phospholipids, and is considered commensurate in scope, in this respect.
Claim Objections
Claims 19 and 21 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The Applicant has shown evidence that appears to be unexpected over the closest prior art; claims 19 and 21 are considered commensurate in scope with the showing of the evidence [see the above discussion].
Nonstatutory Double Patenting
A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7, 8-11 and 13-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 12,064,406.
Claims 1-7, 8-11 and 13-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,964,050.
Claims 1-7, 8-11 and 13-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,229,616.
Claims 1-7, 8-11 and 13-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,833,125.
Claims 1-7, 8-11 and 13-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 25-53, of copending Application No. 18/493,581.
Claims 1-7, 8-11 and 13-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,220,483.
Claims 1-7, 8-11 and 13-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20, of copending Application No. 18/779,280.
Claims 1-7, 8-11 and 13-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20, of copending Application No. 19/011,752.
Although the claims at issue are not identical, they are not patentably distinct from each other because the species (pharmaceutical compositions of weak acid drugs and methods of administration) recited in the claims of the issued patents and copending claims fall within the genus (pharmaceutical compositions for controlled release of weak acid drugs and uses thereof) recited in the claims of the instant application, and thus read on the instant claims.
Response to Arguments
Applicant's arguments filed 12/23/2025 have been fully considered but they are not persuasive.
Applicant requested holding the rejections in abeyance until indication of allowable subject matter.
The Examiner responds that Terminal disclaimers are required to obviate the obviousness-type nonstatutory double patenting rejections.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612