Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 27 May 2026 has been entered.
Claims 121-135 and 137-142 remain pending in the application.
Claims 121-123 and 138 are amended.
Claims 141 and 142 are new.
Claims 1-120, and 136 are cancelled.
Claims 140 and 142 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention. Claim 142 requires that the saturated lipid is the same as the cationic lipid, however, the elected saturated lipid is DSPC and is not cationic and would require a different species for claim 142.
Claims 121-135, 137-139, and 141 are under consideration to the extent of the elected species, i.e., that the saturated lipid is DSPC, the unsaturated cationic lipid is MC2, the unsaturated non-cationic lipid is DOPC, the multivalent cationic lipid is MVL5, the permanently charged cationic lipid is DOTAP, the hydrophilic polymer is PEG and the bile salt is deoxycholic acid.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 27 May 2026 is in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Objections Withdrawn
Objections to the Claims
The claim objections set forth in the Non-Final Office Action mailed 28 Nov 2025 are hereby withdrawn in light of applicant’s amendments of the claims.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of claims pursuant to 35 U.S.C. 112(b) set forth in the Non-Final Office Action mailed 28 Nov 2025 are hereby withdrawn in light of applicants amendment of the claims.
Rejections Maintained
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 121-135, and 137-139 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amendment filed 06 Nov 2025 has introduced new matter into the claims. Amended claim 121 recites that the “deoxycholate is “not conjugated to a component of the delivery vehicle.” The response filed 06 Nov 2025 indicates that support for amended claim 1 can be found at paragraphs [0087-0088], [0092], and [0106]. This has been fully considered but is not found persuasive. The originally filed disclosure does not provide support for the negative limitation that the bile salt (deoxycholate) is not conjugated to a component of the delivery vehicle. Instant claim 121 now recites limitations, which were not clearly disclosed in the specification as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in newly amended claim 121, which did not appear in the specification, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C 112. Applicant is required to provide sufficient written support for the limitations recited in present claim 121 in the specification or claims, as-filed, or remove these limitations from the claims in response to this Office Action.
Response to Arguments
Applicant's arguments filed 06 Nov 2025 have been fully considered but they are not persuasive. Applicant argues (pages 9 and 10 of remarks and ¶ 5-9 of the 1.132 declaration) that the specification describes LNPs formed with bile salts incorporated and not conjugated and that the specification does not describe functional groups and chemical reaction steps for conjugation. The examiner does not find this persuasive as sufficient support for establishing possession of the negative limitation that the deoxycholate is not conjugated to a component of the delivery vehicle. The examiner notes that the mere absence of a positive recitation is not basis for an exclusion. While the applicant may not conjugate the bile salts in their specification or teach means by which they may be conjugated, this is not the same as indicating that such a feature must not be present. Thus, the embodiments of the invention and the lack of teaching regarding conjugation do not sufficiently support the negative limitation that deoxycholate is not conjugated to a component of the delivery vehicle.
Claim Rejections - 35 USC § 103
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 121-128, 130-139 and 141 are rejected under 35 U.S.C. 103 as being unpatentable over Schariter et al. (WO 2019/046809, published 07 Mar 2019, filed 22 Nov 2017) in view of Arafat et al. (J PharmPharmSci 20, 305 - 318, 2017) as evidenced by Kaneshina et al. (Biochimica et Biophysica Acta 1374 (1998) 1-8).
Schariter teaches nucleic acid lipid nanoparticle compositions (abstract). Schariter teaches the process for forming the composition includes steps of mixing a lipid solution comprising an ionizable lipid with a solution comprising a nucleic acid ([0099]). These steps render obvious mixing dissolved lipid nanoparticle components with nucleic acid as in claim 141. Schariter teaches that the nucleic acid solution may be heated to an elevated temperature such as 65°C ([00111]), rendering obvious heating the nucleic acid as in step (2) of claim 141. Schariter teaches that the mixing may be by microfluidic mixing ([00111]). Schariter teaches the inclusion of cationic lipids ([00202]), PEG modified lipids ([00204]), one or more phospholipids such as DSPC, DOPE and DOPC ([00264]), and structural lipids such as two or more sterols, including cholesterol ([00254]). The DSPC renders obvious the inclusion of the saturated lipid of claims 121, 123, 132, 133 and 141 and the saturated lipid different from the cationic lipid of claim 138 and the 1,2-dialkyl-sn-glycero-3-phosphocholine of claim 124. Note that the phase transition temperature of DSPC is 55.6 °C, as evidenced by Kaneshina, which is above the 37°C of the instant claims. The DOPC renders obvious the unsaturated non-cationic lipid of claims 125, 126, and 128. The DOPE renders obvious claim 131. The cholesterol renders obvious claim 135. The PEG modified lipid renders obvious the conjugated lipid of claim 134. The cationic lipid described above renders obvious the inclusion of a cationic lipid as in claims 121 and 141. Schariter teaches that the phospholipid is present from about 0-30 mol% ([00436]), rendering obvious the greater than 10 mol% of saturated lipid as in claims 121 and 141. Schariter teaches the structural lipid at about 30-40 mol% ([00436]). Schariter teaches the inclusion of a ligand which permits tuning of cell targeting specificity and is selected based on the desired localization or function of the cell ([00483]), rendering obvious the ligand of claim 137. Schariter teaches the lipid nanoparticles with a diameter of 500 nm or less ([00520]), rendering obvious claim 127. Schariter teaches the dosage forms for oral administration ([00457], [00462], [00489]) and that its route of administration depends on factors such as its stability in various bodily environments such as the gastrointestinal tract ([00489]).
Schariter does not teach the bile salt of deoxycholate. This deficiency is made up for in the teachings of Arafat.
Arafat teaches the inclusion of bile salts into nanosized liposomes (title) which act as a stabilizer against physiological bile salts (Abstract). Arafat teaches the encapsulation of cefotaxime and that the vesicle had reduced leakage of the encapsulated cefotaxime in the gut due to the improved vesicle stability and that this enhances the oral bioavailability up to 5-fold (abstract-conclusion). Arafat teaches that bile salts are naturally occurring amphipathic sterol surfactants that enhance absorption and provide protection from degradation (page 306 left column middle). Arafat teaches that integration of bile salts in the bilayer membrane stabilize vesicles, preventing premature release of the drug in the harsh environment of the gastrointestinal tract. Arafat teaches sodium deoxycholate as a bile acid for improving stability (abstract, page 306 right top).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have incorporated the bile acid sodium deoxycholate into the lipid nanoparticles of Shariter. Lipid nanoparticles that comprise structural lipid sterols, and where the nanoparticles may be used in dosage forms for oral administration are known from Shariter. The inclusion of sodium deoxycholate into liposomes for improved stability during oral administration is known from Arafat, rendering it obvious to include sodium deoxycholate into the lipid nanoparticles of Schariter the benefits of improved stability during oral administration. One would have a reasonable expectation of success as the nanoparticles of Schariter include sterol components and may be used for oral administration and the sterol sodium deoxycholate incorporated into liposomes is known from Arafat to provide enhanced stability in the harsh environment of the gastrointestinal tract. It would be obvious to have the sodium deoxycholate from 30-40% as Schariter teaches the structural lipids in this range, rendering obvious claim 122. The incorporation of the deoxycholate into the nanoparticle renders obvious the incorporation into the delivery vehicle and not conjugated to a component as in claims 121. The incorporation of deoxycholate is known to improve stability in bile salt environments of the gastrointestinal tract, rendering obvious the vehicle having increased stability as in claim 130.
Regarding claim 141, Schariter teaches mixing solutions of nucleic acid and the lipid nanoparticle components and heating the nucleic acid solution to an elevated temperature such as 65°C. Schariter does not explicitly teach heating the lipid nanoparticle solution above the phase transition temperature as in step (1), however, it is noted that the steps in the claim are a product-by-process limitation. “Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted). In the instant case, the lipid nanoparticle with deoxycholate and formed by mixing solutions of lipid and nucleic acid components, as is obvious from Schariter and Arafat, appears to be the same product claimed.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Response to Arguments
Applicant's arguments filed 06 Nov 2025 have been fully considered but they are not persuasive. Applicant argues that Schariter does not teach or suggest incorporating bile salts into LNPS, that the proposed modification would alter Schariter’s manner of achieving stability, that Arafat does not provide a basis for modifying Schariter, and that there would have been no reasonable expectation of success (page 12 of remarks). The examiner does not find this persuasive. The examiner agrees that Schariter does not teach including bile salts into the nanoparticles, but it would have been obvious to include bile salts such as deoxycholate based on the teachings of Arafat. Deoxycholate is known to improve stability of liposome carriers in the gastrointestinal tract during oral administration, thus providing a reason for its inclusion. The applicant notes in the declaration (filed 05/27/2026 under 37 CFR 1.132) that bile salts do not have predictable stabilization as their stability effect depends on bile salt concentration and that such incorporation would have been expected to destabilize lipid assemblies (¶12). The examiner is not persuaded by this as it is well within the skill level of one of ordinary skill in the art to determine an appropriate concentration to include each component. Applicant further notes in the declaration (¶10-11) that the LNP systems have distinct structural forms from the liposomes of Arafat and asserts that Arafat thus does not provide meaningful guidance as Arafat is directed to liposomes. While the lipid nanoparticles of Schariter and the liposomes of Arafat may have distinct forms, there is a lot of similarity in that they are nanoparticle carriers made from lipid components. It is not persuasive that one of ordinary skill would merely disregard teaching of enhanced stability based on the nanoparticles with lipid components having distinct forms. Absent evidence to the contrary, the similarity between the dosage forms having nanoparticle size, lipid components and serving as drug carriers is understood to provide sufficient reasoning to one of ordinary skill in the art to incorporate the deoxycholate for improved stability with a reasonable expectation of success. Additionally, while Schariter may provide a means of achieving a level of stability with the nanoparticles, this would not discourage the incorporation of additional means of increasing stability and it is not clear why this would change the operation of Schariter, as asserted by the applicant. Further, as Schariter teaches lipid nanoparticles with a variety of different types of lipids, such as sterol lipids (e.g. [00253]) it is reasonable to expect that one of ordinary skill in the art would be able to incorporate the deoxycholate sterol lipid into the nanoparticles of Schariter.
Applicant further asserts unexpected results of improved stability by pointing to figure 4 of the instant specification and to data presented in the 1.132 declaration filed 11/06/2025 (page 13 of remarks). The teachings of Arafat indicate enhanced stability when deoxycholate is incorporated into liposomes. Thus, the unexpected result asserted by the applicant is the same as the benefit taught in the art and is not understood as unexpected but rather expected. Again, noting that there is a structural difference between liposomes and lipid nanoparticles is not in itself persuasive that the enhanced stability should be understood as unexpected. Further, in arguing that the results are commensurate in scope with the claims, the declaration argues that additional components such as the cationic MCL5 and KC2 are not expected to contribute to the observed stability (¶14). There is not a clear reasoning or data provided, however, indicating why these components may be neglected when assessing the commensurate nature of the claims to the results presented. Thus, the examiner is not persuade by the arguments and maintains that the claims are obvious over the applied prior art.
Claim 129 are rejected under 35 U.S.C. 103 as being unpatentable over Schariter et al. (WO 2019/046809, published 07 Mar 2019, filed 22 Nov 2017) in view of Arafat et al. (J PharmPharmSci 20, 305 - 318, 2017) as evidenced by Kaneshina et al. (Biochimica et Biophysica Acta 1374 (1998) 1-8) as applied to claims 121-128, 130-139 and 141 above and further in view of Prieve et al. (WO 2016/118697, published 28 July 2016).
The teachings of Schariter and Arafat are described supra.
Schariter and Arafat do not teach MVL5. This deficiency is made up for in the teachings of Prieve.
Prieve teaches lipid nanoparticles as effective drug delivery systems for biological compounds such as therapeutic nucleic acids ([2]) that can be administered various ways such as orally ([218]) . Prieve teaches lipid nanoparticle drug delivery systems as multi-component formulations comprising cationic lipids, helper lipids, and lipids containing polyethylene glycol ([5]). Prieve teaches the nanoparticles as typically less than 200 nm in size ([7]). Prieve teaches that cationic lipids for the nanoparticles include MVL5 ([8]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have included MVL5 in the particle compositions of Schariter and Arafat. The particles rendered obvious by Schariter and Arafat include various lipid components such as cationic lipids and are used for orally delivering therapeutic agents such as nucleic acids. The cationic lipid MVL5 is also known as a useful component for forming nanoparticles that can be used for oral delivery of components such as nucleic acid, as taught by Prieve. Thus, it would have been obvious to one of ordinary skill to have included MVL5 in the lipid nanoparticles as this is a known cationic lipid for forming therapeutic delivery particles and its inclusion merely represents using a known prior art element for the same purpose. One would have a reasonable expectation of success as the inclusion of cationic lipids are known to be suitable for the nanoparticles, as taught by Schariter
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/E.C.M./Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600
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