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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/20/2026 has been entered.
Claim Status
Amended claims 1, 4, 8, 13, 14, 19, 22, 23, 108, 110-112, 115-117 are pending.
Claims 1, 4, 8, 13, 14, 19, 22, 23, 108, 110-112, 115-117 and the elected species of coding RNA, DMSO, lipid, and ionizable lipid are examined here.
Priority
Applicant’s claim of domestic benefit of U.S. Provisional Application 63/116602, filed on 11/20/2020 is acknowledged.
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Application No. 63/116,602 (referred as ‘602), fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Claims have been amended and recite “an aqueous solution” and “one polar aprotic fluid” (cl. 1), which were not limitations in prior examined version of the claims. ‘602 does not disclose the sub-genus of “polar aprotic fluid.” ‘602 discloses the genus of aprotic fluid, which comprises non-polar aprotic fluids and polar-aprotic fluids, and the species of DMSO. Thus, all the claims enjoy the benefit of instant non-provisional application (11/19/2021).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/20/2026 was filed before the mailing date of this Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
Claim 1 in element a) recites “at least one polar aprotic fluid” and then element b) recites “all polar aprotic fluids,” (underline added for emphasis); claim 1 is interpreted that there can be more than one type of polar aprotic fluid in the composition.
Claim Rejections - 35 USC § 112
35 U.S.C. 112(b)
Rejection of cl. 112 under 112(b) is withdrawn.
35 U.S.C. 112(a)
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 4, 13, 14, 109 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.
Claim 4 recites composition “comprising a cellular uptake agent”. Claim 13 recites “at least one cellular uptake agents comprising at least one lipid.” Claim 14 limits lipid comprising an ionizable lipid. Claim 109, dependent of cl. 1, is also directed to composition further comprising at least one cellular uptake agent including at least one lipid, with the polar aprotic fluid and cellular uptake agent is at least 55% by weight.
The specification defines/describes cellular uptake agent as “one or more RNA substance also comprises one or more substance either at least partially complexed with the RNA, and/or one or more substance that at least partially encapsulates the RNA, to promote the RNA's ability to enter cells (herein referred to as cellular uptake agents)” (pg. 49, lines 10-14). It provides numerous substances as cellular uptake agents, including lipid, micelles, lipid membranes, lipid bilayers and membrane vesicles (pg. 49, lines 14-20).
When claims 4, 13, 14 and 109 are analyzed in light of the specification, instant invention encompasses lipid, lipid membranes and membrane vesicles that encapsulate or are complexed with the RNA and aid in RNA’s ability to enter cells.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, although numerous species are disclosed, the specification is not in possession of cellular uptake agent that is able to perform the claimed cellular uptake function.
The issue is raised in the Remarks of 03/23/2026 regarding the composition of claimed polar aprotic fluids between 50% and 90% and lipid structures described as cellular uptake agents. The Remarks summarizes the issue properly: “a POSITA would not reasonably expect to maintain stable lipid structures when stored in a composition comprising at least 50% DMSO. It is well known in the art that lipid membranes can lose structural integrity in the presence of DMSO above certain concentrations.” (pg. 13). Citing various studies the Remarks indicate the following:
“[I]n the presence of DMSO above 10 mol%, liposomes rapidly form pores” thus resulting in disintegration of the bilayer structure. (pg. 14).
At 20% DMSO, there are “dramatic changes in membrane structural integrity with multiple large pores,” which take up considerable amount of water resulting in failing of membrane integrity and “deviates significantly from that of a conventional lipid bilayer” (pg. 14).
“[E]ffects of DMSO on cell membranes, experimentally confirmed that at DMSO concentrations above 30 vol% the structural integrity of the lipid membrane is physically disrupted resulting in membrane blebbing and membrane dysmorphia” with “the permeabilization is fast and starts after the contact with the DMSO” (pg. 16).
The Remarks conclude that “DMSO above a critical concentration results in loss of membrane integrity and destabilization of the lipid membrane” (pg. 17).
The specification does not provide exemplary embodiments of composition that comprises of cellular uptake agent, claimed DMSO concentrations and RNA.
In conclusion, Applicant’s lack of disclosure of claimed composition of claims 4, 13, 14 and 109 of the claimed broad genus of cellular uptake agent, lipid, ionizable lipid is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
Thus claims 4, 13, 14, and 109 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
Claim Rejections - 35 USC § 102
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.
Claim 112 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by a DailyMed Prescribing Information of RIMSO-50® dimethyl sulfoxide irrigant (dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=58b25d79-78f2-4953-b0c6-61658dc4ef0d, prescribing information revised 3/2021, accessed 09/03/2026, 8 pg.), as evidenced by Henry Schein Rimso-50 product # 6745717750 (henryschein.com/us-en/Shopping/ProductDetails.aspx?productid=6343374&cdivId=international_d&CatalogName=B_DENTAL&name=Rimso-50%20Solution%2050mL%200.5%20Sterile%20Vial%20Ea&did=international_d&ShowProductCompare=true&FullPageMode=true, accessed 09/03/2026).
Claim 112 is directed to a kit comprising a) a sealed chamber with an access port; and b) a solution contained within the sealed chamber comprising water and DMSO, with DMSO is at least 50%; and c) the solution is configured to stabilize the extracellular coding RNA substance upon combining with the solution.
Configured is interpreted as capable of stabilizing the coding RNA and that the RNA is not in the kit.
RIMSO-50® dimethyl sulfoxide irrigant is a 50% w/w DMSO in water and is in a vial. Access port as described by the specification includes “resealable plug or cap or closure that may be penetrated” (pg. 80, line 14-15). Also specification defines all composition percentages herein are weight percent (pg. 22, lines 2).
Although the prescribing information does not include the image of vial with a cap, the same product is distributed by Henry Schein and provides an image with a cap.
Thus, RIMSO-50® is in a vial with a cap and is 50% DMSO in water, thus anticipates claim 112.
Claim Rejections - 35 USC § 103
Rejection of amended claims 1, 4, 8, 13, 14, 19, 22, 23, 108-111, 115-117 under 103 is withdrawn.
Response to Arguments
Applicant’s arguments, see pg. 3 (argument 2 and 5) and further explanation of arguments 2 (pg. 13-15) and 5 (pg. 19-20), filed 08/20/2026, with respect to cl. 1, 4, 8, 13, 14, 19, 22, 23, 108-111, 115-117 have been fully considered and are persuasive. The rejection of claims 1, 4, 8, 13, 19, 22, 23, 108-111, 115-117 has been withdrawn.
A quick summary of the persuasive argument is that “Baker does not demonstrate the criticality of particular polar aprotic fluid, DMSO or DESO concentrations, . . . ” (pg. 17, argument 2) and that ethanol in nanoemulsion formulation of Baker is not a polar aprotic solvent and Baker only uses ~5% of the polar protic ethanol (pg. 15, 19-20, arguments 2, 5).
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, 8, 13, 14, 19, 22, 23, 109-110, 115-117 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 293, 299, 304, 363, 367, 370, 371, 401, and 404 of copending Application No. 17/932,978 (‘978). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 293 of ‘978 teaches a composition comprising
at least one RNA substance, comprising a coding RNA and 3’UTR, 5’UTR or poly-A;
at least one RNA stabilizing substance, which is at least 0.1% zwitterionic betaine-containing substance,
and at least one cellular uptake agent
10% to 98% water by weight.
Claim 299 teaches at least one second RNA stabilizing substance comprising at least one polar aprotic substance. Claim 304 teaches polar aprotic substance as DMSO. Claim 363 teaches that total weight percentage of all polar aprotic substance in said composition is at least 0.1 percent.
Here, the claims 293, 299, 304 and 363 correspond to instant cl. 1, which is a composition comprising a solution comprising extracellular coding RNA substance and polar aprotic fluid between 50% and 90%, which intimately contacts at least part of said one extracellular coding RNA in a storage environment and the polar aprotic fluid is either DMSO or DESO. Fluid in mixture is intimately in contact with each of the components.
Here, the differences are in the range of the components: water of ‘978 is 10% to 98%, while for instant claims it is 10 to 50%; for aprotic fluids of ‘978, including DMSO, the range is at least 0.1% to 89.9%, and for instant claims it’s 50 to 90%. Since there is sufficient overlap in range of the components, the claims 293, 299, 304, 363 of ‘978 render claim 1, 4, 110, 115-117 obvious.
Regarding instant cl. 8, the DMSO of ‘978 remains at a physiologic pH in mixture.
Regarding instant cl. 13 and 109, claim 404 of ‘978 teaches cellular uptake agent is at least one lipid.
Regarding instant cl. 14, Claim 401 of ‘978 teaches an ionizable lipid.
Regarding instant cl. 19, Claim 367 of ‘978 teaches one coding RNA comprising mRNA and/or self-amplifying RNA.
Regarding instant cl. 22, Claim 370 of ‘978 teaches composition is “part of a pharmaceutical composition.”
Regarding instant cl. 23, Claim 371 of ‘978 teaches a medicament.
Claims 108, 111 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 293, 299, 304, 363, 367, 370, 371, 401, and 404 of copending Application No. 17/932,978 (‘978) in view of Chakraborty et al. (US Pat. 9,597,380, issued 3/21/2017, in IDS).
The claims of ‘978 are noted above.
‘978 does not teach vaccine (cl. 111) or that the vaccine can be administered by injection, orally or nasally.
Chakraborty discloses composition for manufacture of modified and/or optimized mRNA (Col. 1, line 43-45). Chakraborty contemplates that the mRNA is effective as a vaccine (Col. 297, lines 45). Chakraborty discloses the pharmaceutical composition can be formulated for intranasal or in injectable use (Col. 352, line 1-5). Chakraborty discloses that the mRNA of the invention can be formulated in any excipient (Col. 305, line 67 to Col. 306, line 21).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the composition comprising the stabilizing substances, including at least at 0.1% DMSO, and coding RNA of ‘978 in view of Chakraborty and arrive at the claimed invention with a reasonable expectation of success. One of ordinary skill in the art would have substituted the coding RNA, which can be mRNA, within the composition comprising RNA stabilizing substances of ‘978 with the mRNA that is vaccine and can be administered intranasally of Chakraborty, to stabilize the mRNA of Chakraborty.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEYUR A. VYAS whose telephone number is (571)272-0924. The examiner can normally be reached M-F 9am - 4 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached on 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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