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 .
1. Claims 1-11, 14, 18, 21, 22, 24, 26-36, 39, 40, 42, 45-51, 53-77, and 83-87 have been cancelled. Claims 12, 16, 19, 25, 37, 38, and 78-82 have been amended.
Claims 12, 13, 15-17, 19, 20, 23, 25, 37, 38, 41, 43, 44, 52, and 78-82 are pending and under examination.
2. All objections/rejections pertaining to claims 18 and 42 are moot because the claims were cancelled with the reply filed on 10/09/2025.
The objection to claims 25 and 38 are withdrawn in response to the amendments filed on 10/09/2025.
The rejection of claim 16 under 35 U.S.C. 112(d) is withdrawn in response to the amendment to delete the recitation of 0 mol% non-cationic lipid from the claim.
The rejection of claim 19 under 35 U.S.C. 103 as being unpatentable over Peer et al. (WO 18/087753), in view of both Weber et al. (Polymers, 2016, 8: 1-14) and Shunsaku et al. (JP 5142313, 2013), as evidenced by Leung et al. (J. Phys. Chem., 2012, 116: 18440-18450) is withdrawn in response to the amendment to delete the recitation BNT9 from the claim. New grounds of rejection for claim 19 are set forth below.
Claim Objections
3. Claim 19 should recite “wherein the cationic or cationically ionizable lipid or lipid-like material further comprises” in lines 1-2.
4. Claim 36 should recite:
“The composition of claim 12, wherein the polysarcosine-lipid conjugate or the conjugate of polysarcosine and the lipid-like material comprises:”
5. Claim 41 should recite “wherein the polysarcosine-lipid conjugate or the conjugate of polysarcosine and the lipid-like material is” 1n lines 1-2.
6. Claims 78-82 are objected to because of the recitation “a composition of”. As indicated in the non-final Office action, correction to “the composition of” is required.
7. Applicant is advised that should claim 79 be found allowable, claim 82 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k).
The arguments have been considered but not found persuasive. MPEP § 608.01(m) indicated by the applicant states that a mere difference in scope between claims has been held to be enough to restate the invention in a reasonable number of ways.
In this case, there is no difference in scope between claims 79 and 82. They both recite the same method using the same composition and the same step of using the composition to deliver an mRNA. There is only a slight difference in wording. Since an mRNA necessarily encodes a protein or peptide and since claim 79 is drawn to treatment, the encoded protein or peptide must be therapeutic.
Maintained Rejections
Double Patenting
8. 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 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.
9. Claims 12, 13, 15-17, 19, 20, 23, 25, 37, 38, 41, 43, 44, 52, and 78-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S, Patent No. 12,419,965 (filed as application 17/281,697), in view of both Peer et al. (WO 18/087753) and Semple et al. (Nature Biotechnol, 2010, 28: 172-176). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to: (1) the same LNPs comprising RNA, a polysarcosine-lipid, and a cationic ionizable lipid; and (2) the same methods of using the LNPs for RNA delivery and for treating or preventing a disease. The instant specification discloses that the nanoparticle have a size of 50-300 nm and a PDI within the range 0.131-0.2 (see p. 68, Table 1; p. 69, Table 2). The patent specification defines that the nanoparticles comprise 0-80 mol% non-cationic lipid and 0.25-50 mol% polysarcosine-lipid, cholesterol, and a phospholipid (such as DSPC or DPPC), and that polysarcosine comprises 20 sarcosine units (see p. 5, line 5 through p. 6, line 2; p. 10; p. 60 of the ‘697 application).
The patent claims do not recite BNT9 as required by the instant claims 12 and 25. Peer et al. teach cationic ionizable lipids suitable to formulate LNPs for the delivery of siRNAs or mRNAs (see Abstract; column 2, lines 22-25; p. 13, lines 5-8; p. 21, line 23 through p. 22, line 2; Table 1; p. 51, lines 3-7 and 17-20). Compound 14 disclosed in Table 1 has the formula:
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(see Table 1 on p. 24). This compound is identical to the compound disclosed by the specification as being BNT9 (see the specification, p. 35, lines 18-20). Furthermore, Semple et al. teach the need for screening cationic lipid libraries for novel materials capable of mediating efficient RNA delivery (see p. 172, column 2, last paragraph). Based on these teachings, modifying the patent claims by further adding the cationic lipids taught by Peer et al. and screening the resultant LNPs would have been obvious to one of skill in the art with the reasonable expectation that doing so would identify novel cationic lipids for efficient RNA delivery. MPEP 2144.06 [R-6] I states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
By doing so, one of skill in the art would have used compound 14 (i.e., BNT9). Thus, the instant claims and the patent claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No arguments were presented by the applicant.
Claim Rejections - 35 USC § 103
10. 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.
11. Claims 12, 13, 15-17, 20, 23, 25, 37, 38, 41, 43, 44, 52, and 78-82 are rejected under 35 U.S.C. 103 as being unpatentable over Peer et al. (WO 18/087753), in view of both Weber et al. (Polymers, 2016, 8: 1-14) and Shunsaku et al. (JP 5142313, 2013; English translation attached), as evidenced by Leung et al. (J. Phys. Chem., 2012, 116: 18440-18450).
Peer et al. teach lipid nanoparticles (LNPs) having a size of 44 nm and comprising an RNA (such as siRNA), DSPC, cholesterol, a PEG-lipid, and Compound 14, an ionizable cationic lipid having the formula:
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Compound 14, DSPC, cholesterol, and the PEG-lipid are present at a molar ratio of 50:10:38:2, respectively (claims 12, 13, 15-17, 20, 23, 25, and 52); (see Abstract; p. 2, lines 22-25; p. 13, lines 5-8; p. 21, line 23 through p. 22, line 2; Table 1; p. 50, line 25 through p. 51, line 21; p. 65, lines 7-13; p. 66, lines 8-15; Example 3 on p. 92).
Peer et al. also teach that the RNA could be mRNA (see p. 13, lines 5-8; p. 50, line 25 through p. 51, line 21) (claim 12). Thus, one of skill in the art would have found obvious to replace the siRNA with an mRNA, with the reasonable expectation that doing so would lead to a composition suitable for mRNA delivery, when mRNA delivery was desired.
Peer et al. teach obtaining the LNPs by using a microfluidic device and rapid mixing at 2 ml/min (see p. 66, lines 8-15). As evidenced by Leung et al., rapid mixing in a microfluidic device at 2ml/min results in LNPs having a nanostructured core (claim 43) (see Abstract; p. 18441, column 1, last paragraph; p. 18449 column 1, last paragraph).
With respect to claims 78-80 and 82, Peer et al. teach administering the LNPs to deliver therapeutic mRNAs to treat subjects in need of therapy (see p. 9, lines 21-26; p. 13, lines 5-8; p. 50, line 25 through p. 51, line 21).
With respect to claim 81, Peer et al. teach that LNPs could be administered intramuscularly (see p. 96, lines 10-17). While this embodiment is disclosed in conjunction with LNPs which do not comprise BNT9, one of skill in the art would have reasonably concluded that any LNP comprising BNT9 could also be administered via the intramuscular route and would have found obvious to do so when intramuscular administration was needed.
Peer et al. teach a PEG-lipid, not a polysarcosine-lipid (claims 12 and 25). Weber et al. teach that PEG is not biodegradable and induces immune responses towards the PEGylated nanoparticles leading to their accelerated clearance from blood; Weber et al. teach polysarcosine-lipids as particularly suited to replace PEG-lipids because polysarcosine is based on a naturally-occurring amino acid (i.e., N-methylated glycine or sarcosine) and it also provides stealth properties to liposomes (see p. 2, first paragraph; p. 11, last paragraph). The polysarcosine lipids taught by Weber et al. have the formula:
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(see p. 7, Scheme 1). Thus, Weber et al. teach polysarcosine-lipids set forth by any of the formulae I-III (claims 37 and 38). Shunsaku et al. teach incorporating polysarcosine-lipids into liposomes. The polysarcosine lipid taught by Shunsaku et al. has the formula:
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, where n=23 (i.e., set forth by the formulae I-II and comprising 23 sarcosine units; claims 12, 37, and 38) (see p. 1, formula 2; p. 18, [0078]; see the attached English translation, p. 5).
Based on these teachings, one of skill in the art would have found obvious to modify Peer et al. by replacing the PEG-lipid with a polysarcosine-lipid as taught by Weber et al. or Shunsaku et al., where the polysarcosine comprises 23 monomers, to achieve the predictable result of obtaining LNPs suitable for the delivery of RNA in vitro or in vivo.
With respect to claim 41, Peer et al. teach that the PEG-lipid is PEG-DMG or PEG-DSPE. One of skill in the art would have considered modifying these lipids by replacing PEG with polysarcosine as an obvious variant to using the a polysarcosine-lipid taught by Weber et al. and Shunsaku et al., with the reasonable expectation that doing so would result in polysarcosine-lipids suitable for obtaining LNPs for the delivery of RNA in vitro or in vivo.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Response to Arguments
12. The arguments have been considered but not found persuasive.
As set forth in the rejection above, Shunsaku teaches polysarcosine consisting of 23 monomers.
The argument of lack of reasonable expectation of success is not found persuasive because it is just an argument not supported by any evidence.
Firstly, Peer does not have to specifically exemplify mRNA delivery by using BNT9 nanoparticles. Lack of specific exemplification with BNT9 does not equal lack of reasonable expectation of success. Just because Peer exemplifies mRNA delivery with lipids 38 and 54, does not mean that the other lipids are not suitable for mRNA delivery. Peer does teach lipid 38 for siRNA delivery, evidencing that the same lipids could mediate the delivery of both siRNA and mRNA (see p. 98, lines 16-28).
It is also noted that lipid 38 is structurally similar to lipid 14 (i.e., BNT9) except that BNT9 lacks the ethylene linker linking the -(CO)-O group to N (see Table 1). One of skill in the art would have reasonably expected that lipids so similar in structure will have similar properties. The applicant did not provide any evidence indicating that the presence of the ethylene linker (the only difference between lipid 38 and BNT9) is essential for mediating mRNA delivery.
Secondly, neither of Weber and Shunsaku has to provide the reasonable expectation that BNT9 would be suitable for mRNA delivery. As noted above, the reasonable expectation of success is provided by Peer.
The argument of unexpected results is not found persuasive. Example 8 compares BNT9 nanoparticles with DODMA or MC3 nanoparticles. Except for the ionizable cationic lipid, the nanoparticle composition is the same. Thus, the higher expression in the liver is due to the presence of BNT9 in the nanoparticles. However, the rejection is not based on replacing DODMA or MC3 with BNT9. Peer already teaches BNT9 nanoparticles. While Peer’s BNT9 nanoparticles contain PEG and not polysarcosine, the applicant did not provide any evidence indicating that replacing PEG with polysarcosine provides for more than was expected from the teachings in the prior art. Weber teaches that PEG is not bio-based and induces immune responses towards the PEGylated nanoparticles, leading to their accelerated clearance from blood. Weber teaches that the bio-based polysarcosine provides higher micelle stability as compared to PEG (see Abstract; p. 2, first paragraph; paragraph bridging p. 10 and 11; p. 11, last paragraph). Furthermore, it was known in the prior art that polysarcosine is non-immunogenic (see Birke, Progress in Polymer Science, 2018, 81: Abstract). Based on the teachings in the prior art as a whole, one of skill in the art would have reasonably concluded that polysarcosine would impart better retention in blood compared to PEG and would have thus reasonably expected superior expression compared to PEG.
New Rejections
Claim Rejections - 35 USC § 103
13. 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.
14. Claims 12, 13, 15-17, 19, 20, 23, 25, 37, 38, 41, 43, 44, 52, and 78-82 are rejected under 35 U.S.C. 103 as being unpatentable over Peer et al. taken with both Weber et al. and Shunsaku et al., as evidenced by Leung et al., in further view of Grabbe et al. (Nanomedicine, London, 2016, 11: 2723-2734).
The teachings of Peer et al., Weber et al., and Shunsaku et al. are applied as above for claims 12, 13, 15-17, 20, 23, 25, 37, 38, 41, 43, 44, 52, and 78-82. Peer et al., Weber et al., and Shunsaku et al. do not teach an additional cationic lipid such as DOTAP or DOTMA (claim 19). Grabbe et al. teach that mRNA can be delivered by LNPs comprising DOTAP or DOTMA (see p. 2727-2728; p. 2729. Fig. 7; p. 2733, paragraph bridging columns 1 and 2). One of skill in the art would have found obvious to modify the LNPs of Peer et al., Weber et al., and Shunsaku et al. by further adding DOTAP or DOTMA, to achieve the predictable result of obtaining LNPs suitable for mRNA delivery. MPEP 2144.06 [R-6] I states:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
Conclusion
15. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Birke (Progress in Polymer Science, 2018, 81: Abstract) was cited in response to the argument of unexpected results. The reference provides evidence that improved expression when using polysarcosine over PEG was expected from the teachings in the prior art.
16. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/ILEANA POPA/Primary Examiner, Art Unit 1633
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