DETAILED ACTION
Previous Rejections
Applicant’s arguments, filed June 08, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 (Maintained)
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 13, 15, 63-65, and 70 are rejected under 35 U.S.C. 103 as being as being obvious over Leavitt et al. (WO 2020/077007 A1).
Claim 1 is rendered prima facie obvious because Leavitt discloses mixing lipid components (ionizable cationic lipids, phospholipids, cholesterol, and PEG-lipid) and 25 mM sodium acetate pH 4 buffer to form transfection competent vesicles to be delivered to patients [00053]-[00055] [00017]-[00018] [00049]. The vesicles are formed before being mixed with cargoes, and are therefore empty. Leavitt further teaches at claim 1 that a water-based solution is provided comprising the lipid-based TCV (which is empty; claim 13) and the water-based solution is a 25 mM to 100 mM acetate buffer (claim 11).
Leavitt is not believed to be anticipatory because Leavitt teaches at [00054] that 25 mM sodium acetate buffer is used and the instant claim recites that the aqueous buffer has a buffer concentration of 30 mM or greater.
However, in the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05 A.
Furthermore, it is prima facie obvious to combine prior art elements according to known methods, to yield predictable results. In the instant case, all the claimed elements (e.g., empty lipid nanoparticle with claimed lipids; 25 mM to 100 mM acetate buffer) were known in the prior art (e.g., Leavitt) 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 yielding nothing more than predictable results (e.g., an empty nanoparticle composition) to one of ordinary skill in the art. MPEP 2143.A.
Regarding claim 13, the process of Leavitt produces empty lipid nanoparticles [00053]-[00055] [00017]-[00018]. While the diameter of the empty lipid nanoparticles increasing less than about 150% over 25 hours is not explicitly disclosed, a chemical composition and its properties are inseparable. MPEP 2112.01 II. Therefore, because the prior art teaches an empty lipid nanoparticle with the same components (ionizable cationic lipid, phospholipid, cholesterol, and PEG-lipid), the properties the applicant discloses and/or claims are reasonably expected to be necessarily present.
Claim 15 is rendered prima facie obvious because Leavitt discloses the process of preparation further includes exchanging buffer of the composition [00053]-[00056].
Claim 63 is rendered prima facie obvious because Leavitt discloses DSPC as the phospholipid [00014] [00053].
Claim 64 is rendered prima facie obvious because Leavitt discloses cholesterol [00053]-[00054] [00014].
Claim 65 is rendered prima facie obvious because Leavitt discloses PEG-DMG [00053].
Claim 70 is rendered prima facie obvious because Leavitt discloses the empty-lipid based vesicles contain lipid components in a ratio of DODMA (ionizable lipid)/DSPC/Cholesterol/PEG-lipid at 50/10/39/1 mol %. [00014]. A prima facie case of obviousness exists because of overlap, as previously discussed. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2144.05 A.
Response to Arguments
Applicant's arguments filed 06/08/2026 have been fully considered but they are not persuasive.
Applicant argues at pg. 10 that Leavitt relates to a method of encapsulating a selected cargo into a pre-formed lipid-based transfection competent vesicle and therefore, the disclosure does not pertain to a process of preparing an empty lipid nanoparticle composition as claimed.
The Examiner disagrees because the disclosure of Leavitt does teach forming empty lipid nanoparticle compositions because the lipid nanoparticles are formed before being combined with any cargo. In the example taught at [00054] the lipid components are mixed with 25 mM sodium acetate pH 4 buffer to form transfection competent vesicles. The vesicles are formed before being mixed with cargoes, and are therefore empty. Leavitt further discloses providing a water-based solution comprising the lipid-based TCV (which are empty; claim 13) where the water-based solution is a 25 mM to 100 mM acetate buffer (claim 11), thereby forming an empty lipid nanoparticle composition.
Claims 4, 8 and 10 are rejected under 35 U.S.C. 103 as being as being obvious over Leavitt et al. (WO 2020/077007 A1) in view of Cullis et al. (US 2012/0276209 A1).
The 35 U.S.C. 103 rejection over Leavitt was previously discussed.
Regarding claim 4, Leavitt does not disclose that the aqueous buffer has an ionic strength of about 15 mM or less.
Cullis discloses lipid particles and methods of making lipid particles [abstract] and teaches that ionic strength has an influence on lipid particle size and encapsulation efficiency [0004].
Leavitt is not silent as to the ionic strength of the buffer. Leavitt discloses 25 mM acetate buffer at pH 4 [00053]-[00055]. However, ionic strength is recognized to have different effects (lipid particle size and encapsulation efficiency, Cullis [0004]) with changing amounts. As such, result effective variables can be optimized by routine experimentation and it would have been prima facie obvious to optimize the ionic strength of the buffer to achieve the optimal particle size and encapsulation efficiency, as taught by Cullis. See MPEP 2144.05.
Regarding claim 8, Leavitt discloses a total lipid concentration of 20-35 mM [00054].
Leavitt does not disclose that the lipid solution has a lipid concentration of about 5 to about 100 mg/mL, as recited in claim 8.
Cullis discloses lipid particles and methods of making lipid particles [abstract] and teaches that the lipid concentration has an influence on the lipid nanoparticle particle size [0066] [0004].
Leavitt is not silent as to the total lipid concentration. Leavitt discloses that the total lipid concentration is 20-35 mM [00054]. However, lipid concentration is recognized to have different effects (changing lipid particle size, Cullis [0066] [0004]) with changing concentrations used. As such, result effective variables can be optimized by routine experimentation, and it would have been prima facie obvious to optimize the total lipid concentration to achieve the optimal particle size, as taught by Cullis. See MPEP 2144.05.
Regarding claim 10, Leavitt does not disclose that the particles have an average diameter of about 30 nm or less.
Cullis teaches lipid particles with a diameter from 15 to 100 nm. Cullis teaches that these particles generally exhibit increased circulatory lifetime in vivo compared to larger particles [0141].
Since Leavitt generally teaches lipid particles to be delivered to patients, it would have been prima facie obvious to one of ordinary skill in the art to have particles with a diameter from 15 to 100 nm, within the teachings of Leavitt, because Cullis teaches lipid particles of this size to be delivered to patients. An ordinarily skilled artisan would be motivated to use particles of this size because Cullis teaches that these particles generally exhibit increased circulatory lifetime in vivo compared to larger particles [0141]. A prima facie case of obviousness exists because of overlap, as previously discussed.
Claim 6 is rejected under 35 U.S.C. 103 as being as being obvious over Leavitt et al. (WO 2020/077007 A1) in view of Shastri et al. (US 2006/0083781 A1).
The 35 U.S.C. 103 rejection over Leavitt was previously discussed.
Leavitt does not teach a zeta potential of about 35 mV or more, as recited in claim 6.
Shastri teaches lipid nanoparticles with a zeta potential of greater than 35 mV [0206]. Shastri teaches that the greater the zeta potential, the more likely a suspension is to be stable because the charged particles repel one another and thus overcome the natural tendency to aggregate [0203].
Since Leavitt generally teaches lipid particles, it would have been prima facie obvious to have a zeta potential of greater than 35 mV, within the teachings of Leavitt, because Shastri teaches lipid nanoparticles with this zeta potential. An ordinarily skilled artisan would be motivated to have a zeta potential greater than 35 mV because Shastri teaches that the greater the zeta potential, the more likely a suspension is to be stable because the charged particles repel one another and thus overcome the natural tendency to aggregate [0203].
Claim 62 is rejected under 35 U.S.C. 103 as being as being obvious over Leavitt et al. (WO 2020/077007 A1) in view of Benenato et al. (US 2017/0210697 A1).
The 35 U.S.C. 103 rejection over Leavitt was previously discussed.
Regarding claim 62, Leavitt does not disclose the elected ionizable lipid.
Benenato teaches Compound 25 (pg. 17) as a cationic ionizable lipid to be used in a nanoparticle composition along with phospholipids, structural lipids, and PEG lipids [0252] [0305] [abstract]. Benenato teaches that the lipids described (such as Compound 25) have little or no immunogenicity (i.e., the lipid does not provoke an immune response) [0134].
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Since Leavitt generally teaches a lipid particle with cationic ionizable lipids, phospholipids, structural lipids, and PEG lipids, it would have been prima facie obvious to one of ordinary skill in the art to include Compound 25, within the teachings of Leavitt, because Benenato teaches Compound 25 as a cationic ionizable lipid to be used in a nanoparticle composition along with phospholipids, structural lipids, and PEG lipids. An ordinarily skilled artisan would be motivated to use a cationic ionizable lipid taught by Benenato (such as Compound 25) because Benenato teaches that the lipids have little or no immunogenicity [0134].
Additionally, generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. In the instant case, since Leavitt generally taught cationic ionizable lipids, it is prima facie obvious to select Compound 25 for incorporation into a lipid particle based on its recognized suitability for the intended use as a cationic ionizable lipid, as taught by Benenato.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. 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, 6, 8, 10, 13, 15, 62-65, and 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,667,543 in view of Leavitt et al. (WO 2020/077007 A1).
Claims 1, 4, 6, 8, 10, 13, 15, 62-65, and 70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent Application No. 18/291,710 (notice of allowance mailed 06/22/2026) in view of Leavitt et al. (WO 2020/077007 A1).
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims recite all of the features instantly recited for the composition except for a buffer concentration of about 30 mM or greater.
Leavitt discloses mixing lipid components (ionizable cationic lipids, phospholipids, cholesterol, and PEG-lipid) to form transfection competent vesicles [00053]-[00055]. Leavitt teaches at claim 1 that a water-based solution is provided comprising the lipid-based TCV and the water-based solution is a 25 mM to 100 mM acetate buffer (claim 11).
It would have been prima facie obvious to one of ordinary skill in the art to include a buffer concentration of 30 mM or greater, within the claims. The ordinarily skilled artisan would have been motivated to prepare the lipid particle composition as taught by Leavitt (claim 11).
Response to Arguments
Applicant's arguments filed 06/08/2026 have been fully considered but they are not persuasive.
Applicant argues that Leavitt does not render obvious the claimed subject matter, accordingly the OTDP rejections should be withdrawn.
The Examiner disagrees because Leavitt does render obvious the claimed subject matter, as discussed above.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ashlee E Wertz whose telephone number is (571)270-7663. The examiner can normally be reached Monday - Friday, 8 AM - 5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at 571-272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ASHLEE E WERTZ/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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