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
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06 Nov 2025 has been entered.
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 06 Nov 2025 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Claims 140 and 142 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.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 06 Nov 2025 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.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 103
The rejection of claims 121-128 and 130-139 under 35 U.S.C. 103 as being unpatentable over Hope et al. (WO 2011/075656, published 23 June 2011, listed in IDS filed 14 Dec 2021) in view of Bae et al. (WO 2016070082, published 06 May 2016, listed in IDS filed 14 Dec 2021) as evidenced by Kaneshina et al. (Biochimica et Biophysica Acta 1374 (1998) 1-8) is withdrawn in light of applicant’s amendment of the claims, and in favor of the new grounds of rejection set forth below.
The rejection of claim 129 under 35 U.S.C. 103 as being unpatentable over Hope et al. (WO 2011/075656, published 23 June 2011, listed in IDS filed 14 Dec 2021) in view of Bae et al. (WO 2016070082, published 06 May 2016, listed in IDS filed 14 Dec 2021) as evidenced by Kaneshina et al. (Biochimica et Biophysica Acta 1374 (1998) 1-8) as applied to claims 121-128 and 130-139 and further in view of Prieve et al. (WO 2016/118697, published 28 July 2016) is withdrawn in light of applicant’s amendment of the claims, and in favor of the new grounds of rejection set forth below.
New Grounds of Objections/Rejections
Claim Objections
Claims 131 and 141 are objected to because of the following informalities: Claim 131 recites “N-(2,3dioleoyloxy)propyl)-N,N,N-trimethylamntonium chloride (DODAP).” The trimethylamntonium is misspelled.
Claim 141 recites in step (3) “the lipid particle.” This should be “the lipid nanoparticle” for consistency within the claim.
Appropriate correction is required.
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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 131 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 131 recites “N-(2,3dioleoyloxy)propyl)-N,N,N-trimethylamntonium chloride (DODAP)” and “1,2-dioleoyl-3-dimethylammonium-propane (DODAP).” The same abbreviation “DODAP” is given for each of these compounds and it is unclear if these are intended to refer to the same compound or different compounds.
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. The light of the applicant’s amendments of the claims, the examiner has withdrawn the previous rejections in favor of the rejection with Schariter and Arafat as detailed above. The arguments regarding the bile acid-ligand surface decorated liposomes of Bae and Hope are thus moot. The rejection with Schariter in view of Arafat results in the incorporation of deoxycholate into the lipid layer and thus renders obvious the same product as claimed. The applicant further included a declaration under CFR 1.132 and asserts unexpected superior stability (page 2 of the declaration). The declaration asserts that Fig 4 of the specification indicates improved stability in the formulation with a saturated lipid and deoxycholate in comparison to formulations lacking these components (page 2 of declaration). The examiner does not find the data in Fig 4 to be persuasive as the data does not show significant differences in results. The error bars overlap between the formulations 14-16 and the data in insufficient to draw the conclusions asserted by the applicant. The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). The declaration further looks to Figure A to establish the improved stability of the liposomes with deoxycholate over cholesterol (page 2 of declaration) and Figure B to assert the significance of more than 10 mol% of the saturated lipid (page 3 of declaration). The examiner does not find this persuasive as there is a general understanding that the incorporation of bile salts such as deoxycholate improves stability in bile acids. Arafat et al. (applied in the rejection above) teaches improved bile acid stability when bile acids such as sodium deoxycholate are used. Thus, the art teaches the same result asserted by the applicant, namely improved stability in bile acids, and the results presented are not found to be unexpected but rather expected. Regarding Fig B and the purported improvement with more than 10 mol% saturated lipid the examiner does not find this persuasive as unexpected results. Schariter teaches lipid amounts above 10%, as noted in the rejection above, and determining the optimal percentage for a given formulation is a routine process in development. An improvement in stability when the lipid is above 10% in a particular formulation does not establish why this result is to be understood as unexpected. The declaration further argues that the results presented are commensurate in scope with the claims (page 3 of declaration) but the examiner disagrees with this assessment. The results are very broad in the limitations on the lipid nanoparticles as they only require a saturated and a cationic lipid. The data presented was shown with nanoparticles that had a greater number and more specific lipid components, such as MVL5 and KC2. Overall, the data presented by the applicant is insufficient to overcome the prima facie case of obvious presented in the rejection above.
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 claim is allowed.
Correspondence
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
/BENNETT M CELSA/Quality Assurance Specialist , Art Unit 1600