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 response of June 25, 2026, to the non-final action mailed April 8, 2026, has been entered. Claim 1 has been amended, claim 6 has been cancelled, and no claims have been newly added. Claims 1-5 are pending and under current examination.
Withdrawn Claim Rejections - 35 USC § 112
Claims 1 and 4-5 were rejected in the previous Office action mailed April 8, 2026, 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. Applicant’s amendment to claim 1 renders the rejection moot. Applicants have amended claim 1 to delete the parentheses. Accordingly, the rejections are hereby withdrawn.
Withdrawn Claim Rejections -Non-Statutory Double Patenting
Claims 1-5 were provisionally rejected in the previous Office action mailed April 8, 2026 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/697,213 (reference application). Applicant’s argument concerning the structural differences of the claimed LPN and the LPN of ‘’213 have been found persuasive. Accordingly, the rejections are hereby withdrawn.
Response and Maintained 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 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 1-5 remain rejected under 35 U.S.C. 103 as obvious over Su et al. (Pub. No.: WO 2021/046265; Pub. Date: March 11, 2021) for reasons of record.
Regarding claims 1-3, Su discloses a pharmaceutical composition comprising a lipid nanoparticle with a SS-cleavable lipid of Formula I
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(claims 1 and 3) which reads on the ionic lipid of general formula (1) of claim 1 and the specific embodiment of instant claim 3. Wherein the lipid nanoparticle further comprise the sterol cholesterol (claims 4 and 5), the lipid nanoparticle further comprise PEG specifically PEG2000-DMG (Claim 7 and page 52 lines 14-15) which reads on instant formula (2) of claim 1, and wherein the lipid nanoparticle further comprises non-cationic lipid DEPC (claim 9).
With respect to the limitation wherein the nanoparticle is for use in delivering a nucleic acid to a peripheral blood mononuclear cell this is an intended use. Applicant should note that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. As Su discloses each of the claimed components of the lipid nanoparticle, it would be expected to able to deliver a nucleic acid to a peripheral blood mononuclear cell, until and unless Applicant can provide evidence to the contrary.
With respect to the language that “R3a and R3b are each a residue derived from a reaction product of a liposoluble vitamin having a hydroxyl group….” this is product by process language directed toRegarding claims 16 and 17, each is a product by process claim directed towards a portion of structural formula (1). Su discloses the structure of formula (1) including the specific structure of instant claim 3 as fully set forth above. In accordance with MPEP §2113 “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433” Furthermore, according to MPEP §2113, “[E]ven 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) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.).
Regarding claim 4, Su additionally discloses wherein the SS-cleavable lipid is from 60-80 molar %, wherein the cholesterol is from 20-40 molar percent, wherein the non-cationic lipid is from 2.5 to 12.5 molar %, and wherein the PEG lipid is from 1.5-3 molar % of the components of the lipid nanoparticle (Claims 11-18 and page 52 lines 30-36). Pursuant to MPEP 2144.05 In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
Regarding claim 5, Su discloses administering the lipid nanoparticle encapsulating nucleic acid to a target site (abstract and claim 99) including administering the nucleic acid containing lipid nanoparticle to monocytes and dendritic cells (page 72 bottom paragraph through page 73 top paragraph) and can be administered to any site including brain (page 85 lines 34-36), intravenous to contact the T and B cells (page 85 line 28), and liver/lung to contact the macrophages (page 39 line 32 through page 40 line 4).
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 combine a SS-cleavable lipid of Formula I (claims 1 and 3), the sterol cholesterol (claims 4 and 5), the PEG polymer specifically PEG2000-DMG (Claim 7 and page 52 lines 14-15), and the non-cationic lipid DEPC (claim 9) into a lipid nanoparticle to encapsulate a nucleic acid for use as a pharmaceutical composition as disclosed by Su, as instantly claimed, with a reasonable expectation of success as a matter of design choice. Said design choice amounting to combining prior art elements according to known methods to yield predictable results. On of ordinary skill in the art would be motivated to do so and have a reasonable expectation of success because Su had already disclosed a lipid nanoparticle with each of the claimed components for use in delivering nucleic acids that has improved ceDNA delivery and better tolerability as compared to other lipids (Su page 4 lines11-25). It would have only required routine experimentation to modify the composition of Komatsu for a lipid nanoparticle administered to a peripheral blood mononuclear cell comprising thie instantly claimed ionic lipid, the instantly claimed phospholipid, cholesterol, and the instantly claimed PEG.
Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Response to arguments:
To the extent that Applicants’ arguments are pertinent to the standing rejection, they are addressed as follows:
Applicant traverses the 103 type rejection arguing that Su may broadly claims a pharmaceutical composition comprising a LPN comprising a Ss-cleavable lipid but does not exemplify it. The examples are for compositions targeting hepatocytes and does not teach or suggest LPM can achieve gene transfer into PMBCs. .
Applicant’s argument has been fully considered, but not found persuasive. The instant rejection is 103 rejection and not a 102 and therefore there is not requirement that the prior art exemplify the lipid nanoparticle for use in delivering a nucleic acid to a peripheral blook mononuclear cell, rather is the instantly claimed ionic lipid of formula (I0 to be used as a delivery system for nucleic acid into PMBC obvious. In this case Su discloses di exemplify making a lipid nanoparticle comprising
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encapsulating a nucleic acid (Page 99 Table 1 ss-OP), which is the specific ionic lipid in instant claim 3, furthermore the example of nanoparticle of Su includes the instantly cholesterol, and (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol PEG2000, (Page 99 Table 1 ss-OP). Additionally, Su discloses wherein the SS-cleavable lipid is from 60-80 molar %, wherein the cholesterol is from 20-40 molar percent, wherein the non-cationic lipid is from 2.5 to 12.5 molar %, and wherein the PEG lipid is from 1.5-3 molar % of the components of the lipid nanoparticle (Claims 11-18 and page 52 lines 30-36), which overlaps the instantly claimed range. Su discloses administering the lipid nanoparticle encapsulating nucleic acid to a target site (abstract and claim 99) including administering the nucleic acid containing lipid nanoparticle to monocytes and dendritic cells (page 72 bottom paragraph through page 73 top paragraph) and can be administered to any site including brain (page 85 lines 34-36). Therefore, the instantly claimed. 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 combine a SS-cleavable lipid of Formula I (claims 1 and 3), the sterol cholesterol (claims 4 and 5), the PEG polymer specifically PEG2000-DMG (Claim 7 and page 52 lines 14-15), and the non-cationic lipid DEPC (claim 9) into a lipid nanoparticle to encapsulate a nucleic acid for use to deliver nucleic acid to PBMC as disclosed by Su, as instantly claimed, with a reasonable expectation of success as Su discloses that the NPLs that have increased/enhanced delivery of nucleic acids to targets as compared with conventional lipid nanoparticles known in the art (page 44 paragraph 1)
With respect to Applicants argument concerning LPNs are not easily taken up into PMBS and Comparative examples 1 and 2 have compositions similar to the formulation of Su and are ineffective for gene transfer into T cells as compared to example 1 of the present application, this has been fully considered, but not found persuasive. MPEP 716.02 provides the guidelines for evaluating unexpected/superior results. Pursuant to MPEP 716.02 (e) the claimed subject matter must be compared to the closest prior art to effectively rebut a prima facie case of obviousness. In this case Su is the closest prior art, Applicant has not compared the instant claimed composition to that found in Su. Instead, Applicant points to “compositions that are “similar”, which does not meet the guideline set for the by the MPEP. With respect to the comparative examples POPE is present in the LPN, Su does not disclose the presence of the POPE and applicant has provided no argument or evidence as to why the LPN of Su would be expected to behave the same as the comparative examples.
MPEP 716.02(d) requires the unexpected results be commensurate in scope with the claimed invention. In this case the Examples of the instant spec is very narrow to include a single lipid nanoparticle composition with varying amounts of each component. The claims are much broader in lipid nanoparticle composition with only claim 4 requiring a range of each component. The scope of the claims are not commensurate with applicants alleged unexpected results.
Thus, the rejection is maintained for claims 1-5 for reason of record and foregoing discussion.
Response & Maintained Non-Statutory 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, 3, and 5 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-4 of copending Application No. 18/697,239 (reference application) for reasons of record. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and reference application claims are directed to a lipid nanoparticle for delivering nucleic acid comprising ionic lipid of formula (I) with identical species of claim 3, cholesterol, dimyristoylglycerol PEG of formula (2) wherein the lipid nanoparticle containing nucleic acid is administered to a subject. The non-statutory double patenting rejection is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3, and 5 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1and 12-15 of copending Application No. 18/697,265 (reference application) for reasons of record. Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and reference application claims are directed to a lipid nanoparticle for delivering nucleic acid comprising ionic lipid of formula (I) and dimyristoylglycerol PEG (PEG and ligand) wherein the lipid nanoparticle containing nucleic acid is administered to a subject/cells, wherein the type of cells are overlapping. The non-statutory double patenting rejection is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments:
Applicant traverses the obviousness type double patenting rejection over claims 1, 3, and 4 of ‘239 arguing that ‘239 is directed to LPNs that enhance delivery efficiency in the lymphatic endothelial cells by comprising at least 3 mol percent of Peg, while the instant claims are directed to a LPN that enhanced delivery to the PMBs, which results in a different environment.
Applicant’s argument has been fully considered, but not found persuasive. Instant claims are directed to an open-ended composition for a LPN with no amounts of any component. Application ‘239 is directed to the same structure of LPN for delivery of a a nucleic acid. Even though the intended use of target sites may be different the claimed composition of the LPN are the same with the same purpose of delivering nucleic acids to a target. Applicant has provided no evidence that the claimed composition of ‘239 would not be able to act the same as the instant claims. Accordingly, the rejection is maintained.
Applicant request that the obviousness-type double patenting rejection based on ‘265 be held in abeyance.
The policy of the Office is to make all rejections as the earlies part of the patent prosecution process. Accordingly, the rejection 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANNA R FALKOWITZ whose telephone number is (571)270-3386. The examiner can normally be reached Monday - Friday 9am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Zachariah Lucas can be reached at (571) 272-0905. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600
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