DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed 07/07/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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) 1-4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Harashima et al (US 2020/0129431 A1), in view of WO 2015/178343 A1 (with an English translation provided by Sato et al (US 10,182,987 B2)).
Harashima taught a lipid nanoparticle (LNP), comprising a pH-sensitive cationic lipid (CL4H6), disclosed as CL4H6-LNP, and modified with methoxy polyethyleneglycol 2000 distearoylglycerol (PEG-DSG 2000). The molar ratio of the cationic lipid to the PEG lipid was 50:0.75 to 1.5 [0256, 0270]. The structure of CL4H6 was shown on the bottom of page 17 [last compound], and is reproduced below:
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The LNP of Harashima was as a lipid membrane structure for delivering a target substance, such as mRNA (e.g., as instantly elected; also reads on nucleic acid as a gene that is expressed in a splenic dendritic cell) [0116].
Harashima was not specific the particle diameter as equal to or greater than 150 nm, as recited in claim 1.
However, at ¶ [0143], Harashima incorporated by reference patent literature 6, disclosed at ¶ [0018] as WO 2015/178343 (e.g., with an English translation provided by Sato et al.)
Sato taught lipid membrane structures with particle sizes of about 120 to 300 nm, preferably about 150 to 250 nm, more preferably about 180 nm [col 9, lines 18-21].
The instant claim 1 recites 40 to 70 mol % of the pH-sensitive cationic lipid; 0.5 to 1.75 mol % of the PEG-modified lipid; particle diameter equal to or greater than 150 nm.
The instant claim 2 recites a particle diameter of equal to or smaller than 600 nm.
Harashima taught 50 mol % of the pH-sensitive cationic lipid; 0.75 to 1.5 mol % of the PEG-modified lipid. Harashima incorporated Sato by reference to teach particle sizes of about 120 to 300 nm. 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.
Harashima, in view of Sato, reads on claims 1-3 and 7.
Claim 4 is rendered prima facie obvious because Harashima taught cholesterol [0112].
Response to Arguments
Applicant's arguments, filed 07/07/2026, have been fully considered but they are not persuasive.
Applicant argued that the Examiner did not address the previous claim 8 limitation (now incorporated into claim 1) “wherein the nucleic acid comprises a gene that is to be expressed in a splenic dendritic cell.”
The Examiner disagrees. At the 2nd paragraph of the rejection, the Examiner stated that Harashima taught that mRNA reads on the recited limitation.
Furthermore, for the purposes of argument only, the instant Specification at ¶s [0121-0122] states that mRNA may be included within the lipid nanoparticle to control the expression of genes in splenic dendritic cells. It appears that the lipid nanoparticles of the instant claims (lipid nanoparticle comprising pH-sensitive cationic lipid, nucleic acid and PEG-modified lipid) and those of the prior art (CL4H6-LNP, mRNA, mPEGDSG2000) would reasonably be expected to have substantially the same physical and chemical properties (gene expression in a splenic dendritic cell).
Inherent features need not be recognized at the time of the invention. There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. MPEP 2112 II. It should be noted that a chemical composition and its properties are inseparable. If the prior art teaches the identical chemical compounds, then the properties that the Applicant discloses and/or claims are necessarily present.
Applicant argued unexpected results in gene expression in splenic dendritic cells. Applicant cited to Examples 1-2, and Figures 4, 6, 7, 9A and 9B.
The Examiner disagrees that the Applicant has shown evidence of unexpected results. The instant Specification, at ¶ [0195-0196] and at Table 6, disclosed that the instant lipid composition described in Example 1, namely A-11 (which was responsible for high spleen expression, and which falls within the claimed range) is CL4H6/DOPE/Chol/mPEG2k-DSG = 60:10:30:1.5. Additionally, paragraph [0187] of the instant Specification disclosed that CL4H6 was used as the pH-sensitive cationic lipid, in view of its main effect to influence the increase in the gene expression in the spleen.
The Examiner maintains that the combined Harashima and Sato taught the claimed lipid nanoparticle (e.g., Harashima taught CL4H6-LNP) at amounts (of the cationic and PEG lipids, and diameter) that fall within the claimed range. It does not appear that the combined teachings of the art are patentably different from the claimed subject matter.
The Examiner maintains that Harashima taught mRNA, which the Specification states is a functional nucleic acid that controls gene expression in splenic dendritic cells. Given the broadest reasonable interpretation consistent with the Specification, and since the claims are not further limited beyond “nucleic acid”, it does not appear that the instant invention is patentably distinct from the combined teachings of the cited prior art.
The Obviousness rejection is maintained. No claims are allowed.
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 1-4 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,458,605, in view of Harashima et al (US 2020/0129431 A1), further in view of WO 2015/178343 A1 (with an English translation provided by Sato et al (US 10,182,987 B2)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims require that the pH-sensitive cationic lipid is further limited to CL4H6, which is not required of the issued claims. Additionally, the instant claims are further limited to amounts of the CL4H6 and PEG, and to a particle size of the LNP, each of which are not required by the issued claims.
Harashima taught a lipid nanoparticle (LNP), comprising a pH-sensitive cationic lipid (CL4H6), disclosed as CL4H6-LNP, and modified with methoxy polyethyleneglycol 2000 distearoylglycerol (PEG-DSG 2000). The molar ratio of the cationic lipid to the PEG was 50:0.75 to 1.5.
Harashima incorporated by reference patent literature 6, disclosed as WO 2015/178343 (with an English translation provided by Sato et al).
Sato taught lipid membrane structures with particle sizes of about 120 to 300 nm, preferably about 150 to 250 nm, more preferably about 180 nm.
It would have been prima facie obvious to one of ordinary skill in the art to include, within the issued claims, CL4H6, and at amounts disclosed by Harashima; amounts of the modified-PEG; and, particle sizes of the LNP, as taught by Harashima. The ordinarily skilled artisan would have been motivated to provide a lipid membrane structure for delivering a delivery target substance, as taught by Harashima.
Response to Arguments
Applicant's arguments, filed 07/07/2026, have been fully considered but they are not persuasive.
Applicant argued that the combined cited art fail to teach a nucleic acid expressed in splenic dendritic cells. Applicant argued unexpected results over the cited art.
The Examiner disagrees. Harashima taught mRNA (see the Examnier’s arguments above). The Examiner disagrees that evidence of unexpectedness were shown. See the above analysis of the Applicant’s results.
Claims 1-4 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/277,409, in view of Harashima et al (US 2020/0129431 A1), further in view of WO 2015/178343 A1 (with an English translation provided by Sato et al (US 10,182,987 B2)).
Claims 1-4 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 18/851,300, in view of Harashima et al (US 2020/0129431 A1), further in view of WO 2015/178343 A1 (with an English translation provided by Sato et al (US 10,182,987 B2)).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims require that the pH-sensitive cationic lipid is further limited to CL4H6, which is not required of the copending claims. Additionally, The instant claims are further limited to amounts of the CL4H6 and PEG, and to a particle size of the LNP, each of which are not required by the copending claims.
Harashima taught a lipid nanoparticle (LNP), comprising a pH-sensitive cationic lipid (CL4H6), disclosed as CL4H6-LNP, and modified with methoxy polyethyleneglycol 2000 distearoylglycerol (PEG-DSG 2000). The molar ratio of the cationic lipid to the PEG was 50:0.75 to 1.5.
Harashima incorporated by reference patent literature 6, disclosed as WO 2015/178343 (with an English translation provided by Sato et al).
Sato taught lipid membrane structures with particle sizes of about 120 to 300 nm, preferably about 150 to 250 nm, more preferably about 180 nm.
It would have been prima facie obvious to one of ordinary skill in the art to include, within the copending claims, CL4H6, and at amounts disclosed by Harashima; amounts of the modified-PEG; and, particle sizes of the LNP, as taught by Harashima. The ordinarily skilled artisan would have been motivated to provide a lipid membrane structure for delivering a delivery target substance, as taught by Harashima.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 07/07/2026 have been fully considered but they are not persuasive.
Applicant argued that the combined cited art fail to teach a nucleic acid expressed in splenic dendritic cells. Applicant argued unexpected results over the cited art.
The Examiner disagrees. Harashima taught mRNA (see the Examnier’s arguments above). The Examiner disagrees that evidence of unexpectedness were shown. See the above analysis of the Applicant’s results.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELESTE A RONEY whose telephone number is (571)272-5192. The examiner can normally be reached Monday-Friday; 8 AM-6 PM.
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/CELESTE A RONEY/Primary Examiner, Art Unit 1612
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