{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 .
Summary
Claims 1, 15-18, 20-21, and 26-27 are pending in this office action. Claims 2-14, 19, 22-25, and 28-32 are cancelled. All pending claims are under examination in this application.
Priority
The current application was filed on May 30, 2023 is a 371 of PCT/US2021/061336 filed on December 1, 2021, which in turn claims domestic priority to provisional patent 63/120,449 filed on December 2, 2020.
Information Disclosure Statement
Receipt of the Information Disclosure Statements on December 8, 2025 is acknowledged. A signed copy of the document is attached to this office action.
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.
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 non-obviousness.
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, 15-18, 20-21, and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Colletti et al. (WO2013/116126A1) in view of Brown et al. (WO2013/059496A1) and Guild et al. (WO2012/170930A1).
[The Examiner is going to introduce each reference and then combine them where appropriate to reject the instant claims.]
1. Colletti et al.
Colletti et al. is regarded as being the prior art closest to the subject-matter of the present application as it discloses a novel low molecular weight, biodegradable cationic lipids for oligonucleotide delivery (see title). Furthermore, Colletti et al. disclose that the instant invention provides for novel cationic lipids that can be used in combination with other lipid components such as cholesterol and PEG-lipids to form lipid nanoparticles with oligonucleotides. It is an object of the instant invention to provide a cationic lipid scaffold that demonstrates enhanced efficacy along with lower liver toxicity as a result of lower lipid levels in the liver. The present invention employs low molecular weight cationic lipids with one short lipid chain coupled with inclusion of hydrolysable functionality in the lipid chains to enhance the efficiency and tolerability of in vivo delivery of siRNA (see abstract).
2. Brown et al.
Brown et al. teach amine cationic lipids and uses thereof (see title). In addition, Brown et al. disclose that the present invention relates to lipid compounds and uses thereof. In particular, the compounds include a class of cationic lipids having an amine moiety, such as an amino-amine or an amino-amide moiety. The lipid compounds are useful for in vivo or in vitro delivery of one or more agents (e.g., a polyanionic payload or an antisense payload, such as an RNAi agent) (see abstract).
3. Guild et al.
Guild et al. teach lipid nanoparticle compositions and methods for mRNA delivery (see title). Furthermore, Guild et al. disclose compositions and methods for modulating the production of a protein in a target cell. The compositions and methods disclosed herein are capable of ameliorating diseases associated with protein or enzyme deficiencies (see abstract).
Combination of Colletti et al. and Brown et al.
Regarding instant claim 1, Colletti et al. and Brown et al. teach a composition comprising a polynucleotide; and a lipid nanoparticle (LNP). The necessary citations within Colletti et al. and Brown et al. that correspond to instant claims 1, 17-18, and 21 are compiled within Table I.
Table I
Instant Claims 1, 17-18, and 21
Colletti et al. and Brown et al. Citations
A composition comprising: a polynucleotide; and a lipid nanoparticle (LNP) comprising
Colletti et al. disclose a composition comprising a polynucleotide and a lipid nanoparticle (LNP) comprising (see title and abstract within Colletti et al.).
(a) a monoester cationic lipid selected from the group consisting of: (Z)-non-2-en-1-yl 10-(2-(dimethylamino)ethyl)nonadecanoate; and (Z)-oct-2-en- l-yl 11 -(2-(dimethylamino)ethyl)icosanoate;
Colletti et al. disclose (Z)-non-2-en-1-yl 10-(2-(dimethylamino)ethyl)nonadecanoate [see page 47, Compound 157, (see structure next page); within Colletti et al.].
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(b) a phospholipid; (c) cholesterol; and (d) a PEG-lipid a-[8'-(1,2-dimyristoyl]-3-propanoxy)-carboxyamide-3',6'- dioxaoctanl]carbamoyl-o-methyl-poly(ethylene glycol) (PEG2000-DMG);wherein the polynucleotide is at least partially encapsulated in the LNP.
Colletti et al. also discloses a specific LNP with the molar ratio of cationic lipid/DSPC/ cholesterol/PEG-DMG corresponding to 58/10/30/2 (see page 59, line 27; also see claim 5; both within Colletti et al.). [DSPC = phospholipid; 1,2-Distearoyl-sn-glycero-3-phosphocholine; PEG-DMG = pegylated 1,2-dimyristoyl-sn-glycerol polyethylene glycol]; siRNA is encapsulated (see abstract; and page 58, lines 21-28 within Colletti et al.).
Colletti et al. does not disclose the use of PEG2000-DMG. However, Brown et al. does disclose this pegylated lipid.
Brown et al. disclose that the use of the PEG-lipid conjugate that can include one or more various modifications, such as substitutions with any lipid molecule described herein or with PEG moieties of different molecular weights (e.g., from 300 to 5,000 daltons). Exemplary substitutions include use of one or more of C14:0 (as in Table 4), C16 (PEG-DPPE, PEG-DPG, etc.), C18:0 (PEG-DSPE, PEG-DSG, etc.), or C18:1 (PEG-DOPE, PEG-DOG, etc.) in combination with a polyethylene glycol moiety (e.g., PEG2000, PEG3400, PEG5000, etc) to form a PEG-lipid conjugate (e.g., mPEG2000-DMG or PEG2000DMG). Examples of PEG moieties with various molecular weights include PEG350, PEG550, PEG750, PEG 1000, PEG2000, PEG3000, PEG3400, PEG4000, and PEG5000 (see page 49, lines 1-8 within Brown et al.).
[According to Colletti et al., the composition comprising the polynucleotide (siRNA) and the lipid nanoparticle is prepared in phosphate buffered saline (see Example 7, and page 57, line 33 within Colletti et al.).]
Therefore, the combination of the Colletti et al. and Brown et al. references make instant claim 1 obvious to a skilled artisan (POSITA; person of ordinary skill in the art).
[The remainder of the instant claims are either directly or indirectly dependent on instant claim 1, which is taught in full by the combination of Colletti et al. and Brown et al.]
Regarding instant claims 15 and 16, Colletti et al. and Brown et al. teach wherein the LNP has the desired mol% values. Colletti et al. disclose the following ranges for mol% values for cationic lipid [40-67.3 mol%], phospholipid [10 mol%], cholesterol [30-48 mol%], and PEG2000-DMG [2-5.4 mol%] (see pages 56-57 bridging, page 56 lines 19-22, page 57 lines 1-6 within Colletti et al.).
Regarding instant claim 20, Colletti et al. and Brown et al. teach wherein the PEG-lipid is PEG2000-DMG with the correct mol percent value. Brown et al. disclose that from about 1 mol % to about 20 mol % of the PEG-lipid conjugates, such as PEG2000-DMG, are used within the LNP formulation (see page 8, lines 17-18; also see page 49, lines 1-8 within Brown et al.).
Motivation to combine the lipids of Colletti et al. with those disclosed by Brown et al. is due to the use of novel of low molecular weight cationic lipids within Colletti et al. These lipids include a hydrolysable functionality in the lipid chains to enhance the efficiency and tolerability of in vivo delivery of siRNA (see page 2, lines 6-8 within Colletti et al.). One of ordinary skill in the art (POSITA; person of ordinary skill in the art) would be motivated to incorporate the cationic lipids from Collete et al. for the stated benefits that include enhancing the efficiency and tolerability of in vivo delivery of siRNA.
Combination of Colletti et al. and Guild et al.
Regarding instant claims 26 and 27, Colletti et al. and Guild et al. teach the intramuscular administration of the LNP providing the appropriate half-life of elimination. Colletti et al. disclose the buffered siRNA LNP composition that is considered suitable for administration as a vaccine (see PTO-892 NPL U). Guild et al. disclose suitable routes of administration include, for example, oral, rectal, vaginal, transmucosal, pulmonary including intratracheal or inhaled, or intestinal administration; parenteral delivery, including intramuscular, subcutaneous, intramedullary injections, as well as intrathecal, direct intraventricular, intravenous, intraperitoneal, intranasal, or intraocular injections. Additionally, Guild et al. disclose a terminal half-life of elimination of less than 100 hours after administration (see pages 45, paragraph 3; page 6, paragraph 5; page 12, paragraph 2; page 13, paragraph 2).
Motivation to combine the lipids of Colletti et al. with those disclosed by Brown et al. is due to the use of novel of low molecular weight cationic lipids within Colletti et al. These lipids include a hydrolysable functionality in the lipid chains to enhance the efficiency and tolerability of in vivo delivery of siRNA (see page 2, lines 6-8 within Colletti et al.). This makes the incorporation of the cationic lipids from Collett et al. attractive to a skilled artisan (POSITA).
Analogous Art
The Colletti et al., Brown et al., and Guild references are directed to the same field of endeavor as the instant claims, that is, a composition comprising a polynucleotide and an LNP.
Obviousness
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 modify the siRNA LNP comprising a monoester cationic lipid disclosed by Colletti et al., using the teachings of both Brown et al. and Guild et al. to incorporate the necessary claim limitations. Starting with Colletti et al., the skilled person only had to try the necessary claim limitations disclosed by both Brown et al. and Guild et al. The combination of Colletti et al., Brown et al., and Guild et al. would allow one to arrive at the present application without employing inventive skill. This combination of the siRNA LNP comprising a monoester cationic lipid taught by Colletti et al. along with the use the necessary claim limitations taught by both Brown et al. and Guild et al., would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the siRNA LNP comprising a monoester cationic lipid disclosed by Colletti et al. with the use of the necessary claim limitations taught by both Brown et al. and Guild et al. This combined modification would have led to an enhanced the siRNA LNP comprising a monoester cationic lipid that would be beneficial for patients.
Response to Arguments
Applicant's arguments filed January 14, 2026 have been fully considered but they are not persuasive.
The instant claim amendments were sufficient to address the 35 U.S.C. 112(b) rejections and the 35 U.S.C. §102. Therefore, they are both withdrawn from the Non-Final office action dated July 14, 2025.
The amendments did not necessitate a new ground of rejection.
Applicant Argument: The Applicant argues that the reduced inflammation and unexpected results within the instant specification warrants patentability.
Examiner’s Rebuttal: The Examiner respectfully disagrees. Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (Claims directed to a method of effecting analgesia without producing physical dependence by administering the levo isomer of a compound having a certain chemical structure were rejected as obvious over the prior art. Evidence that the compound was unexpectedly nonaddictive was sufficient to overcome the obviousness rejection. Although the compound also had the expected result of potent analgesia, there was evidence of record showing that the goal of research in this area was to produce an analgesic compound which was nonaddictive, enhancing the evidentiary value of the showing of nonaddictiveness as an indicium of nonobviousness.). [see M.P.E.P. 716.02(c)]. In this instance, the prior art of record is stronger than the unexpected results. The prima facie case for obviousness presented within the 35 U.S.C. §103 section of this office action affords a “direct pathway” of research and development for a skilled artisan (POSITA) to develop and obtain similar results as observed by the inventors.
Applicant Argument: The Applicant argues that that the half-life disclosed by Guild et al. is not applicable to the lipid portion of the LNP.
Examiner’s Rebuttal: The Examiner believes that the way instant claim 27 is currently constructed it does not focus on the half-life of the lipid portion of the LNP. The language within the claim does not support the increased degradation of lipids. The Applicant is encouraged to amend this claim accordingly. Guild et al. does disclose 1) circulation half-lives of secreted proteins (goal to have increased protein half-life (See Guild page 6, paragraph 5)); 2) chemical modification to RNA to increase RNA stability and half-life (See Guild page 12, paragraph 2); 3) RNA stability (See Guild page 13, paragraph 2); and 4) protein stability (See Guild page 45, paragraph 3). Guild does not discuss the stability and/or half-life of the lipid component of an LNP.
Thus, the 35 U.S.C. §103 rejection for instant claims 1, 15-18, 20-21, and 26-27 is maintained.
Conclusion
No claims are allowed.
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.
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/JOHN W LIPPERT III/[Examiner, Art Unit 1615 /Robert A Wax/Supervisory Patent Examiner, Art Unit 1615