DETAILED ACTION
Claims 1-12 are currently pending. Claims 1-4, 6-7, 9-11 are currently under examination.
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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 06/25/2026 is acknowledged.
Claim 12 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 06/25/2026.
Applicant’s election without traverse of SS-OP:
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, DOPG and DEPC in the reply filed on 06/25/2026 is acknowledged.
Priority
The instant application is a national stage entry of PCT/JP2023/011850, filed 03/24/2023, which claims priority to JP2022-051918, filed 03/282022.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 12/27/2024 and 02/10/2026 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Claim Rejections - 35 USC § 112 (a) Written Description
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 1-4, 7 and 9-11 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The skilled artisan would not have adequate reason to believe that Applicant had possession of the claimed genus shown in claim 1 based on the information provided in the specification. Note that the extensive list of embodiments which may be used as groups for R and X are not viewed as equivalents in the art. The only working examples described in the specification (examples 1-9) falling within the scope of claim 1 are listed on Table 1 of disclosure (reproduced below):
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wherein R2a,b may be selected from an aliphatic hydrocarbon group and tocopherol, R1a,b = alkylene group, and Xa,b = an ester bond with the orientation –OC(=O).
The definition for variables Za and Zb as independently a divalent group derived from an aromatic compound having 3 - 16 carbon atoms and at least one aromatic ring”. the scope of “derived from” is only limited by the compound from which one begins. Any chemical reaction that changes a functional group produces a derivative of the original compounds. In other words, the state of the art is such that the term derivative is infinite in scope.
Within the specification, specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p). Note also the following:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 140.
Therefore, based on the lack of working examples and nature of the described genus, one would have assumed that Applicants were not in possession of the claimed genus.
Claim Rejections - 35 USC § 112 (b)
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 1-4, 6-7 and 9-11 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 1 contains the limitation “(in the formula (1)...”, “(in the formula (4)…”, “(in the formula (2)….” and “(in the formula (3)…1,000 to 3,000)”. It is unclear the purpose of the parenthesis, for example are the formulas meant to be broader than what is in the parenthesis, is what in the parentheses merely exemplary language or does the language in the parenthesis intended to limit the functional groups to what is in the parenthesis. Appropriate correction is required. In the interest of compact prosecution, the language in the parenthesis will be interested as what the structures are limited to and not merely exemplary language. It is suggested applicant delete the parenthesis. Claims 2-4, 6-7 and 9-11 are included in the rejection a they depend from and/or include all limitations of claim 1 and do not remedy what structures are required by the parenthesis.
Claim 1 recites in the definition of variables Ya, Yb of Markush formula I :” Ya and Yb are each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond”. However, it is not clear if Ya and Yb are group or a bond, which lead to two different reasonable interpretations: a) Ya, Yb are each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond;
or b) Ya, Yb are each independently an ester group, an amide group, a carbamate group, an ether or a urea group.
Additionally, the connectivity of Ya, Yb within the formula 1 is not clearly defined. For example when Ya is an ester group can have the orientation –OC(=O)- giving Za-O(C(=O)-Xa; or can have connectivity with the orientation –(O=C)O- , giving Za-–(O=C)O- Xa.
Claim 1 recites in the definition of variables Za and Zb of Markush formula I:’
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The specification does not provide any guidance regarding the structural limitations of ” Za and Zb are each independently a divalent group derived from an aromatic compound having 3 - 16 carbon atoms and at least one aromatic ring”. The limitation “divalent group” can be interpreted as an atom with two covalent bonds. Given that it is not clear if Za/Zb contains an aromatic group or is a fragment of product of a reacted aromatic group, rendering claim1 and its dependents indefinite.
The claim language defining variables Za, Zb as divalent group derived from aromatic compound is indefinite because is not clear how the divalent group derived groups are connected to the core structure, what is the chemical structure of the divalent groups and what is the point of covalent attachment to the core structure.
The limitation “derived from” any chemical reaction that changes a functional group produces a derivative of the original compounds. Therefore, metes and bounds of the instant claims are not clearly defined.
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.
Claim(s) 1-4, 6-7 and 9-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/046265 (Applicant provided).
Regarding claims 1-4, 6, the limitation of a lipid nanoparticle for use in delivery a nucleic acid to a spleen tissue is met by the ‘265 publication teaching lipid formulations comprising a lipid and capsid free, non-viral vector. The lipid formulations can be use to delivery a capsid free, non-viral DNA vector to a target site of interest (e.g. cel, tissue, organ and the like). As the ‘265 publication discloses each of the claimed components of the lipid nanoparticle as discussed below, it would be expected to be able to deliver a nucleic acid to a spleen tissue, until and unless Applicant can provide evidence to the contrary.
The limitation of (A) an ionic lipid represented by formula I is met by the ‘265 publication teaching the elected
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(page 4, lines 10-15, page 44, lines 15-25).
The limitation of an anionic phospholipid or a compound represented by the formula (2) is met by the ‘265 publication teaching the lipid particle (e.g. lipid nanoparticles) can further comprise a non-cationic lipid. The non-cationic lipid can serve to increase fusogenicity and also increase stability of the LNP during formation. Non-cationic lipids include amphipathic lipids, neutral lipid and anionic lipids. Exemplary non-cationic lipids include but are not limited to the elected DOPG (page 49, lines 1-20).
The limitation of cholesterol is met by the ‘265 publication teaching cholesterol as an exemplary sterol that can be used in the lipid particles to provide membrane integrity and stability of the lipid particle (page 51, lines 1-15).
The limitation of a dimyristoylglycerol PEG represented by the formula (3) is met by ‘265 publication teaching the lipid nanoparticle can further comprise a PEG or a conjugated lipid molecule. Conjugated lipid molecule is a PEG-lipid conjugate, for example PEG2000-DMG (dimyristoylglycerol) (page 51, lines 24-37).
The ‘265 publication teaches specific examples of SS-OP:DOPC:Chol:DMB-PEG2000 (Table 1).
Regarding claims 7 and 9-10, the limitation of wherein a neutral phospholipid is optionally comprise as a component of the lipid nanoparticle and selected from a group including DEPC is met by the ‘265 publication teaching the lipid particle (e.g. lipid nanoparticles) can further comprise a non-cationic lipid. The non-cationic lipid can serve to increase fusogenicity and also increase stability of the LNP during formation. Non-cationic lipids include amphipathic lipids, neutral lipid and anionic lipids. Exemplary non-cationic lipids include but are not limited a group including DOPG and DEPC or mixtures thereof (page 49, lines 5-30). It is noted that neutral phospholipid is taught as optional and therefore not required. Additionally, the ratio of DOPG to DEPC can be optimized, if present, to obtain the optimized stability of the LNP, including wherein DEPC is at 0%. As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
Regarding claim 11, the limitation of wherein the ionic lipid is 30-70 mol%, the anionic phospholipid is 2.5-15 mol%, the neutral phospholipid is 0-15 mol%, the cholesterol is 20-60mol% and the dimyristroylglycerol PEG is 0.5-1.5 mol% is met by the ‘265 publication teaching SS-OP:DOPC:Chol:DMB-PEG2000 50:10:38.5:1.5 (Table 1), wherein mixture of non-cationic lipids are taught to be used. Ragnes of SS-cleable lipids, cholesterol and non-cationic lipid ranges are taught (claims 11-18, page 52, lines 30-36). As MPEP 2144.05 recites “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine optimization”.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been obvious to have selected various combinations of disclosed ingredients (for example SS-OP, DOPG, DEPC, Chol and DMB-PEG2000 ) from within the prior art disclosure of the ‘265 publication, to arrive at the instantly claimed lipid nanoparticle “yielding no more than one would have expected from such an arrangement”.
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 1-4, 6-7 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of copending Application No. 18/851,857 in view of WO2021046265. The ‘857 application teaches a lipid nanoparticle of use in delivery a nucleic acid comprising an ionic lipid represented by the formula (I), wherein R1a, R1b, Xa, Xb, R2a, R2b, Ya, Yb, Za, Zb, R3a, R3b overlap, phospholipid of DEPC, cholesterol and dimyristoylglycerol PEG. The ‘857 application does not specifically teach anionic phospholipid, such as DOPG.
The ‘265 publication teaching lipid formulations comprising a lipid and capsid free, non-viral vector. The lipid formulations can be use to delivery a capsid free, non-viral DNA vector to a target site of interest (e.g. cel, tissue, organ and the like). The ‘265 publication teaching the elected
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(page 4, lines 10-15, page 44, lines 15-25). The ‘265 publication teaching the lipid particle (e.g. lipid nanoparticles) can further comprise a non-cationic lipid. The non-cationic lipid can serve to increase fusogenicity and also increase stability of the LNP during formation. Non-cationic lipids include amphipathic lipids, neutral lipid and anionic lipids. Exemplary non-cationic lipids include but are not limited to the elected DOPG, DEPC and mixtures thereof (page 49, lines 1-20).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of DOPG and DPEC as the ‘265 publication teaches mixtures of DOPG and DPEC being used in lipid nanoparticles comprising a cationic phospholipid and the ‘857 publication is directed to lipid nanoparticles comprising cationic phospholipids and DEPC, thus it would have been obvious to one of ordinary skill in the art a combination of DEPC and DOPG could be used in lipid nanoparticles.
This is a provisional nonstatutory double patenting rejection.
Claims 1-4. 6-7 and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,622,979 in view of WO2021046265. The ‘979 patent teaches a lipid nanoparticle of use in delivery a nucleic acid comprising an ionic lipid represented by the formula (I), wherein R1a, R1b, Xa, Xb, R2a, R2b, Ya, Yb, Za, Zb, R3a, R3b overlap, phospholipid, cholesterol and dimyristoylglycerol PEG. The ‘979 patent does not specifically teach anionic phospholipid, such as DOPG and neutral phospholipid, such as DEPC.
The ‘265 publication teaching lipid formulations comprising a lipid and capsid free, non-viral vector. The lipid formulations can be use to delivery a capsid free, non-viral DNA vector to a target site of interest (e.g. cel, tissue, organ and the like). The ‘265 publication teaching the elected
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(page 4, lines 10-15, page 44, lines 15-25). The ‘265 publication teaching the lipid particle (e.g. lipid nanoparticles) can further comprise a non-cationic lipid. The non-cationic lipid can serve to increase fusogenicity and also increase stability of the LNP during formation. Non-cationic lipids include amphipathic lipids, neutral lipid and anionic lipids. Exemplary non-cationic lipids include but are not limited to the elected DOPG, DEPC and mixtures thereof (page 49, lines 1-20).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of DOPG and DPEC as the ‘265 publication teaches mixtures of DOPG and DPEC being used in lipid nanoparticles comprising a cationic phospholipid and the ‘979 patent is directed to lipid nanoparticles comprising cationic phospholipids and secondary phospholipids, thus it would have been obvious to one of ordinary skill in the art a combination of DEPC and DOPG could be used in lipid nanoparticles.
Claims 1-4, 6-7 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/994,768 in view of WO2021046265. The ‘768 application teaches a lipid nanoparticle of use in delivery a nucleic acid comprising an ionic lipid represented by the formula (I), wherein R1a, R1b, Xa, Xb, R2a, R2b, Ya, Yb, Za, Zb, R3a, R3b overlap, phospholipid, cholesterol and dimyristoylglycerol PEG. The ‘857 application does not specifically teach anionic phospholipid, such as DOPG.
The ‘265 publication teaching lipid formulations comprising a lipid and capsid free, non-viral vector. The lipid formulations can be use to delivery a capsid free, non-viral DNA vector to a target site of interest (e.g. cel, tissue, organ and the like). The ‘265 publication teaching the elected
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(page 4, lines 10-15, page 44, lines 15-25). The ‘265 publication teaching the lipid particle (e.g. lipid nanoparticles) can further comprise a non-cationic lipid. The non-cationic lipid can serve to increase fusogenicity and also increase stability of the LNP during formation. Non-cationic lipids include amphipathic lipids, neutral lipid and anionic lipids. Exemplary non-cationic lipids include but are not limited to the elected DOPG, DEPC and mixtures thereof (page 49, lines 1-20).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of DOPG and DPEC as the ‘265 publication teaches mixtures of DOPG and DPEC being used in lipid nanoparticles comprising a cationic phospholipid and the ‘768 application is directed to lipid nanoparticles comprising cationic phospholipids and DEPC, thus it would have been obvious to one of ordinary skill in the art a combination of DEPC and DOPG could be used in lipid nanoparticles.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LYNDSEY M BECKHARDT/ Examiner, Art Unit 1613
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