DETAILED ACTION
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 .
Claim Status
Applicant’s amendment filed 2/10/2026 has been entered. Claims 12-13, 22, and 33 are cancelled. Claims 1-11, 14-21, and 23-32 are pending. Claims 27-32 are withdrawn. Claims 1-10, 14-18, and 23-26 are amended. Claims 1-11, 14-21, and 23-26 are examined herein.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-11, 14-21 and 23-26 in the reply filed on 2/10/2026 is acknowledged.
Claims 27-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/10/2026.
Applicant further elected the species of (A – claims 8 and 10) a second cationic lipid having the structure of Compound 102 different from a first cationic lipid having the structure of Compound 101, (B – claim 11) a formulation compound having the structure of Compound 101, and (C - claim 18) a nucleic acid that is mRNA.
Claim 20 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/10/2026.
However, upon further consideration, the Office is rejoining claim 20.
Accordingly, claims 1-11, 14-21, and 23-26 are examined herein.
Drawings
The drawings are objected to for the following reasons: 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."”
In the current case, the view numbers for Figures 1-7 are preceded by the word "Figure" instead of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlinks and/or other form of browser-executable codes at pages 14, 42, and 43. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claims 14 and 16 are 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 14 recites the limitation "the PEG2000-C-DMA" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation “the cationic lipid Compound 101” in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 14 recites the limitation “the cationic lipid Compound 102” in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation "the PEG2000-C-DMA" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation “the cationic lipid Compound 101” in line 4. There is insufficient antecedent basis for this limitation in the claim.
Claim 16 recites the limitation “the cationic lipid Compound 102” in line 5. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-10, 18-21 and 23-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maclachlan et al. (WO2009127060A1, published 4/15/2009; cited in the 892).
Regarding claim 1, Maclachlan teaches nucleic acid-lipid particle formulations comprising a nucleic acid, a conjugated lipid that inhibits aggregation of particles comprising from about 0.5 mol % to about 2 mol % of the total lipid present in the particle (which teaches percentages between the claimed range of about 0.1 to about 0.9 mol %); a cationic lipid comprising from about 50 mol % to about 85 mol % of the total lipid present in the particle (which teaches percentages between the claimed range of about 40 to about 80 mol %); and a non-cationic lipid comprising from about 13 mol % to about 49.5 mol % of the total lipid present in the particle; and (entire document; claims 1-20; paras 0115-0121). Maclachlan teaches that these stable nucleic acid-lipid particle (SNALP) formulations that advantageously impart increased activity of the encapsulated nucleic acid and improved tolerability of the formulations in vivo, resulting in a significant increase in the therapeutic index as compared to nucleic acid-lipid particle compositions previously described (para 0045; entire document). Maclachlan further teaches that the compositions can be made into aerosol formulations (paras 0310-0313). Maclachlan further teaches the lipid conjugate (e.g., PEG-lipid) typically comprises from about 0.1 mol % to about 2 mol %, of the total lipid present in the particle (para 0281).
Regarding claims 2-7 and 9, Maclachlan teaches the nucleic acid-lipid particle comprising about 0.1 mol % to about 2 mol % , from about 0.5 mol % to about 2 mol %, from about 1 mol % to about 2 mol %, from about 0.6 mol % to about 1.9 mol %, from about 0.7 mol % to about 1.8 mol %, from about 0.8 mol % to about 1.7 mol %, from about 0.9 mol % to about 1.6 mol %, from about 0.9 mol % to about 1.8 mol %, from about 1 mol % to about 1.8 mol %, from about 1 mol % to about 1.7 mol %, from about 1.2 mol % to about 1.8 mol %, from about 1.2 mol % to about 1.7 mol %, from about 1.3 mol % to about 1.6 mol %, or from about 1.4 mol % to about 1.5 mol % of PEG-lipid conjugate (para 0281) and about 50 mol % to about 85 mol % and about 55 mol % to about 90 mol % of cationic lipid (claims 1 and 8-9; paras 0113-0114).
Regarding claims 8 and 10, Maclachlan teaches that lipid particles may comprise one or more different cationic lipids (paras 0111 and 0113-0115).
Regarding claims 18-19, Maclachlan teaches that the nucleic acid is Applicant’s elected species of mRNA (paras 0066). Maclachlan further teaches the nucleic acid can be Dicer-substrate dsRNA, small hairpin RNA (shRNA), asymmetrical interfering RNA (aiRNA), microRNA (miRNA), tRNA, rRNA, viral RNA (vRNA), self-amplifying RNA, and combinations thereof (paras 0014, 00566, 0069, 0094, 0163, and 0182).
Regarding claim 20, Maclachlan teaches that the nucleic acid can be small interfering RNA (siRNA) (paras 0066, 0069and 0094).
Regarding claim 21, Maclachlan teaches that the non-cationic lipid is cholesterol or a derivative thereof (claim 10; paras 01119-1311).
Regarding claim 23, Maclachlan teaches the PEG-lipid conjugate comprising PEG-C-DMA (paras 0044, 0143-0144, and 0269; Examples 1, 9, 11; Tables 2 and 4).
Regarding claim 24, Maclachlan teaches the PEG-lipid conjugate having an average molecular weight of about 2,000 daltons (paras 0258 and 0285; Example 1, Tables 2 and 4).
Regarding claim 25, Maclachlan teaches the lipid to nucleic acid ratios from 12.4:1 to 24.7:1 (Table 2) and further teaches lipid:nucleic acid ratios from 8.7:1 to 23.6:1 (Table 4), (thus teaching a range greater than Applicant’s claimed 12:1 to 20:1).
Regarding claim 26, Maclachlan teaches the lipid to nucleic acid ratios of about 20:1 (Tables 2 and 4).
Maclachlan teaches each and every limitation of claims 1-10, 18-21, and 23-26, and therefore Maclachlan anticipates claims 1-10, 18-21, and 23-26.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 11 and 14-17 are rejected under 35 U.S.C. 103 as being unpatentable over Maclachlan et al. (WO2009127060A1, published 4/15/2009; cited in the 892) as applied to claims 1-10, 18-21, and 23-26 above, and further in view of Abrams (WO2020097520A1).
Maclachlan’s teachings are applied to claims 11 and 14-17 as they were applied to claims 1-10, 18-21, and 23-26 in the 102 discussion above.
Maclachlan’s disclosure is directed to novel, serum-stable lipid particles comprising one or more active agents or therapeutic agents, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for the treatment of a disease or disorder) (para 0011; entire document). Maclachlan teaches the strong need in the art for novel and more efficient methods and compositions for introducing nucleic acids such as siRNA into cells and for methods of downregulating the expression of genes of interest to treat or prevent diseases and disorders such as cancer and atherosclerosis (para 0010). Maclachlan teaches lipid particles comprising from about 50 mol % to about 85 mol % of a cationic lipid, from about 13 mol % to about 49.5 mol % of a non-cationic lipid, and from about 0.5 mol % to about 2 mol % of a lipid conjugate provide advantages when used for the in vitro or in vivo delivery of an active agent, such as a therapeutic nucleic acid (para 0045). Maclachlan teaches stable nucleic acid-lipid particles (SNALP) that advantageously impart increased activity of the encapsulated nucleic acid (e.g., an interfering RNA such as siRNA) and improved tolerability of the formulations in vivo, resulting in a significant increase in the therapeutic index as compared to nucleic acid-lipid particle compositions previously described (para 0045).
Regarding claims 14-17, Maclachlan teaches the lipid conjugate (PEG-lipid conjugate) typically comprises from about 0.1 mol % to about 2 mol %, of the total lipid present in the particle (para 0281). Maclachlan further teaches the non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, where the phospholipid can be DSPC (paras 0119-0131 and 0255). Maclachlan teaches that preferred embodiments of the non-cationic lipid comprise (i) a phospholipid of from about 10 mol % to about 20 mol % or about 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 mol % (or any fraction thereof or range therein) of the total lipid present in the particle, and (ii) cholesterol or a derivative thereof of from about 10 mol % to about 30 mol %, or about 10, 11 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 mol % (or any fraction thereof or range therein) of the total lipid present in the particle (paras 0129-0131).
However, Maclachlan does not specifically teach the cationic lipids of formula (I) (claim 11), Compounds 101 and 102 (claims 14-17), or the exact mol % of cholesterol and DSPC of claims 15 and 17.
Abrams’ disclosure is directed to cationic lipids containing silicon (entire document). Abram teaches cationic lipids that can be prepared using less expensive and more efficient processes and that are effective for delivering an active agent or therapeutic agent, such as a nucleic acid, when incorporated into lipid nanoparticles (p. 1). Abram further teaches cationic lipids are also biodegradable, such that associated lipid nanoparticles better degrade following delivery of an active agent or a therapeutic agent (p. 1). Abrams further teaches aerosol compositions suitable for inhalation (p. 82, lines 10-23).
Regarding claim 11, Abrams teaches cationic lipids having formula (I) (see below; and page 64).
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Regarding claims 14-17, Abrams teaches the cationic lipids of Compound 101 (Example 4, p. 91; see below) and 102 (Example 8, p. 92; see below). Abrams further teaches nucleic acid-lipid nanoparticles comprising 0.6% PEG2000-C-DMA, 33% cholesterol, 11% of DSPC and 55% Applicant’s Compound 4 (Example 24).
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(Abrams, p. 91)
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(Abrams, p. 92)
It would have been obvious to have modified Maclachlan’s nucleic acid-lipid particles with the silicon compounds of Abrams with a reasonable expectation of success. One would be motivated to make such a modification because Maclachlan teaches the strong need in the art for novel and more efficient methods (para 0010) and Abrams teaches novel and more efficient methods using cationic lipids that are less expensive and that are effective for delivering a nucleic acid, when incorporated into lipid nanoparticles and teaches cationic lipids are also biodegradable, such that associated lipid nanoparticles better degrade following delivery of a nucleic acid (p. 1). It would have been further obvious to arrive at the specific mol % of the components through routine optimization. See MPEP 2143(I)E-G. One would have had a reasonable expectation of success because both Maclachlan and Abrams are directed to improvements in nucleic acid-lipid nanoparticles compositions comprising PEG2000-C-DMA, cholesterol, and cationic lipid mixtures. Thus, the claimed invention as a whole is prima facie obvious.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/BRIAN WHITEMAN/Primary Examiner, Art Unit 1636
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