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 .
Election/Restrictions
Applicant's election with traverse of claims 1-5, 7, 9-11, and 13 with species election of C13-20 alkyl for R21 and R22 and C1-6 alkyl for R23-R26 in the reply filed on January 22, 2026 is acknowledged. As an initial matter, it is noted that the range (13-20 and 1-6 for alkyl chain numbers) elected by applicant is not compliant because such range is not a single species election. It is additionally noted that applicant did elect a single structure shown below.
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The traversal is on the ground(s) that there is no “serious search or examination burden” to search and examine all pending claims as they are all related. This is not found persuasive because the mere fact that claims are “related” do not mean that they are all same such that a single search/examination would apply to all pending claims. For instance, search/examination of formula (II) in group II would not be applicable to lipids in group III.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claim 1-19 are currently pending in the instant application. Claims 6, 8, 12, and 14-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 1-5, 7, 9-11, and 13 are under examination on the merits in the instant application.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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 1-5, 7, 9-11, and 13 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.
The instant claims recite “a Long-Acting SusTained delivering lipid”. This term is not an art-recognized term. As such, one skilled in the art cannot clearly ascertain the metes and bounds of the claimed limitation, thereby rendering the claims under examination indefinite.
Solely in the interest of compact prosecution, the aforementioned term will be interpreted as referring to any art-recognized “permanently cationic lipid” in light of claim 5 reciting “wherein the Long-Acting SusTained delivering lipid is a permanently cationic lipid” or “a permanently cationic lipid containing a quaternary ammonium structure.”
Claim 1 recites the limitation "the injection site" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 2 recites “muscle or tumor tissue, alternatively muscle”. It is unclear what is meant by “alternatively muscle”. That is, it is unclear whether the limitation “alternatively muscle” is a required limitation or merely exemplary of “muscle or tumor tissue”.
Claim 3 recites the limitation "the tissue or organ" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 recites the broad recitation “the compound of formula (II)”, and the claim also recites multiple “compounds” having specific structures, which are the narrower statement of the “formula (II)” limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). For examination purpose, the 12 specific “compounds” will be interpreted as being a required limitation in view of applicant’s species election.
Claim 9 recites the broad range “>0 mol% -30 mol%” and also simultaneously recites multiple narrower ranges within the broad range. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim.
Claim 9 recites “>0 mol%”. It is noted that greater than 0 mol% reads on any mol% (e.g., 1, 2.5, 5, 10, 20, and 30) that is recited in the claim. Hence, it is unclear which numerical value is encompassed by “>0 mol%” within the range of “>0 mol% -30 mol%”.
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.
Claims 1-5, 7, 9-11, and 13 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 instant claims are drawn to a lipid nanoparticle that does not comprise a neutral phospholipid as evidenced by the claim language that expressly excludes a neutral phospholipid, while requiring at least a permanently cationic lipid and an ionizable lipid. The claims also recite that “the lipid nanoparticle acts at the injection site” and “is capable of reducing off-target effects in tissues or organs at a non-injection site”.
As evidenced by the review article by Godbout et al. (Pharmaceutics, 2022, 14:2129, applicant’s citation), there does not appear to be any prior art lipid nanoparticle (LNP) comprising a permanently cationic lipid, an ionizable lipid, a structural lipid (e.g., cholesterol), and a PEG-modified lipid without a neutral phospholipid. That is, LNP compositions were conventionally synthesized by including a neutral phospholipid before the effective filing date. Furthermore, the LNP formulations disclosed in the review article do have widely variable molar ratios depending on the actual lipids includes in the LNP formulations. See Tables 1-6. That is, there was no art-recognized, uniform mol% ratio for distinct lipid species included in an LNP formulation.
Now, consistent with the prior art’s LNP formulations comprising distinct lipids at various mol% ratios, it is noted that the instant specification discloses neutral phospholipid-free LNP compositions comprising applicant’s elected species at starkly different mol% depending on the type of ionizable lipid. For instance, the mol% ratio for “Compound 133”; ionizable cationic lipid (“Compound 20”); cholesterol; and PEG2K-DMG included in “Formulation 5-2” is 2.5:49.5:46.5:1.5. See Table 9. Now, the mol% is dramatically changed when a different ionizable cationic lipid (“DLin-MC3-DMA”) is used in “Formulation 6-2” such that the mol% ratio of the four elements is 10:50:38.5:1.5. See Table 11. See also “Formulation 8-2” comprising the mol% of 10:47.5:40.5:2 when the ionizable cationic lipid is “Compound 46”. See Table 15. In addition, the aforementioned LNP compositions are at best described to be predominantly localized in the muscle compared to the liver after intramuscular injection. This disclosure is not descriptive of the claimed embodiment wherein the injection site is any topical location including the tumor tissue. In view of the widely variable mol% for the four elements included in LNP formulations having applicant’s elected species, and further in view of the fact that LNP formulations comprise distinct lipid species at variable mol% ratios for intended target tissues as reviewed by Godbout, one of ordinary skill in the art would not reasonably deem the LNP formulation species having distinct mol% ratios as representing the entire genus of the instantly claimed lipid nanoparticle, which does not recite any particular species for the “ionizable lipid”, “structured lipid”, and “polymer-conjugated lipid”.
Accordingly, it is concluded that the instant specification fails to describe the entire genus of the claimed subject matter in such a manner to reasonably convey that the instant co-inventors had possession of the entire genus as of the filing date sought in the instant application.
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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 1-5, 7, 9-10, and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cheng et al. (US 2022/0071916 A1).
Cheng discloses a lipid nanoparticle composition comprising “an ionizable cationic lipid” and “a cationic selective organ targeting (SORT) lipid”, “wherein said cationic SORT lipid is a permanently cationic SORT lipid” or “comprises a quaternary ammonium ion.” See claims 73 and 76-77. Note that Cheng’s claims do not require a neutral phospholipid.
Cheng discloses a lipid nanoparticle composition comprising “1) a permanently cationic lipid, 2) an ionizable cationic lipid, and 3) a phospholipid and further comprising “cholesterol and lipid PEG”, wherein the composition is formulated for “topical injections” including “intra-muscle”. See paragraphs 0132, 0239, and 0480.
Cheng discloses “permanently cationic lipid” having formula (IA) in paragraphs 0027 as shown below:
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Cheng discloses that “R1 and R2 are each independently alkyl (C8-C24)”, thereby reading on C17 for each of R1 and R2.
Cheng exemplifies a “permanently cationic lipid” having the structure of formula (IA) in paragraph 0034 as reproduced below:
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Cheng teaches that the permanently cationic lipid is present “from about 28% to about 34%” and the cholesterol is present at the molar percentage of “about 40 to about 46.” See paragraphs 0289 and 0326.
Since all structural limitations set forth in the claimed product are fully satisfied by Cheng’s lipid nanoparticle composition, it necessarily follows that Cheng’s lipid nanoparticle would inherently possess all functional and intended use limitations recited in the instant claims, absent objective evidence to the contrary.
“[T]he patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure.” Catalina Mkt. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). That is, “[f]rom the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing.” In re Papesch, 315 F.2d 381, 391 (CCPA 1963).
Accordingly, claims 1-5, 7, 9-10, and 13 are described by Cheng et al.
Claims 1-5, 9-11, and 13 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Whitehead et al. (WO 2022/236093 A1, applicant’s citation).
Whitehead discloses a lipid nanoparticle composition comprising a permanently cationic lipid (e.g., “18:1 EPC”) at 10-50 mol%, a cholesterol at 10-46.5 mol%, a PEGylated lipid at 1.25-2.5 mol%, and an ionizable lipid at 20-45 mol%, which thus does not comprise a neutral phospholipid. See paragraphs 0009-0018.
Since all structural limitations set forth in the claimed product are fully satisfied by Whitehead’s lipid nanoparticle composition, it necessarily follows that Whitehead’s lipid nanoparticle would inherently possess all functional and intended use limitations recited in the instant claims, absent objective evidence to the contrary.
“[T]he patentability of apparatus or composition claims depends on the claimed structure, not on the use or purpose of that structure.” Catalina Mkt. Int’l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). That is, “[f]rom the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing.” In re Papesch, 315 F.2d 381, 391 (CCPA 1963).
Accordingly, claims 1-5, 9-11, and 13 are described by Whitehead et al.
Claims 1-5, 7, 9, and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheng et al. (US 2021/0259980 A1, applicant’s citation).
Cheng discloses a lipid nanoparticle composition comprising an ionizable cationic lipid and a “permanently cationic lipid” having formula (IA) shown below:
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See paragraphs 0007, 0014, and 0025.
Cheng discloses that “R1 and R2 are each independently alkyl (C8-C24)”, thereby reading on C17 for each of R1 and R2. See paragraph 0026.
Cheng exemplifies a “permanently cationic lipid” having the structure of formula (IA) in paragraph 0032 as reproduced below:
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Cheng teaches that the permanently cationic lipid is present “from about 28% to about 34%.” See paragraph 0211.
Cheng teaches that the lipid nanoparticle further comprises a PEG modified lipid, a phospholipid, and a cholesterol, wherein the cholesterol is at the molar percentage of “about 40 to about 46.” See paragraph 0246.
Cheng teaches that the lipid nanoparticle composition provides “preferential delivery of the composition to an organ other than the liver.” See paragraphs 0081-0085.
Cheng teaches that the lipid nanoparticle composition can be formulated for “topical injection” including “intra-muscle”. See paragraphs 0066 and 0398.
Since all structural limitations set forth in the claimed product are fully satisfied by Cheng’s lipid nanoparticle composition, it necessarily follows that Cheng’s lipid nanoparticle would inherently possess all functional and intended use limitations recited in the instant claims, absent objective evidence to the contrary.
Accordingly, claims 1-5, 7, 9, and 13 are described by Cheng et al.
Claims 1-5, 7, 9-11, and 13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Toyonaga et al. (US 2025/0049713 A1).
Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Toyonaga discloses a lipid nanoparticle composition comprising “an ionizable lipid and a fully saturated cationic lipid, wherein said lipid nanoparticle does not contain a zwitterionic phospholipid.” See paragraph 0066 and claim 1.
Toyonaga discloses the structure of the cationic lipid having formula IV in paragraph 0159 as reproduced below:
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Toyonaga teaches that the lipid nanoparticle can further comprises “a PEG-lipid” such as “DMG-mPEG2000” and a cholesterol such that the mol% ratio for ionizable lipid; cationic lipid; cholesterol; MDG-mPEG2000 is 50:20:28.5:1.5. See Table 1.
Toyonaga teaches that the lipid nanoparticle can be formulated for intramuscular administration. See paragraph 0607.
Since all structural limitations set forth in the claimed product are fully satisfied by Toyonaga’s lipid nanoparticle composition, it necessarily follows that Toyonaga’s lipid nanoparticle would inherently possess all functional and intended use limitations recited in the instant claims, absent objective evidence to the contrary.
Accordingly, claims 1-5, 7, 9-11, and 13 are described by Toyonaga et al.
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 1-5, 7, 9-11, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-7, 9, 16, 18-23, 27, and 30-32 of copending Application No. 18/688,308.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated by and/or overlap in scope with the ‘308 claims drawn to a lipid nanoparticle comprising an ionizable lipid and a permanently cationic lipid having the structural limitations claimed and encompassed by the instant claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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