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 .
DETAILED ACTION
Applicant’s response, affidavit, and claim amendments filed on 6/4/2026 are received and entered.
In response to the most recent action, claims 1 and 5-8 are amended and currently pending. Claims 9-14 were previously withdrawn.
Claims 1-8 are currently under examination of the merits.
Any rejections/objections NOT repeated/presented here are withdrawn.
Priority Claim
Regarding applicant’s foreign priority claim and certified copy of the original application, applicant discloses that a physical certified copy of the original application was mailed on 10/23/2023 and OPAP acknowledged receipt of the certified copy on 11/1/2023, as reflected in a return post card. In addition, applicant discloses that a corrected Application Data Sheet was submitted on 8/28/2023, that included the DAS code for the original application. The access code F164 has been verified as correctly corresponding to the original Chinese application 202210839969.2 from which foreign priority is claimed for the present application. Applicant states applicant has taken all possible steps to submit a certified copy of the original application to perfect the foreign priority claim pursuant to 37 C.F.R. §1.55.
Based on the review of the information, foreign priority cannot be granted until a certified copy of the original application has been received. It is noted that applicant filed a petition to remedy improper priority claim on 10/26/2023. On 10/31/2023, the petition under 37 CFR 1.55(c) for improper priority claim was granted. However, on 1/4/2024, there is a notice provided by the office wherein an attempt by the Office to electronically retrieve, under the priority document exchange program, the foreign application 202210839969.2 to which priority is claimed has failed (see document PD.RETR.FAIL). While the corrected ADS may have the included DAS code for the original application, the electronic filing system receipt (N417) filed on 10/26/2023 does not include any documents regarding foreign priority. Applicant has not provided a copy of the original application or a copy of the post card in the response to arguments document.
Response to Affidavit
Applicant’s affidavit declaration under 37 C.F.R. § 1.132 of Co-Inventor Binlei Liu has been received and acknowledge.
In the affidavit traversing rejections, Co-Inventor respectfully states that at the time of the invention, it was widely accepted in the field that an mRNA molecule required with (i) a 5’ cap structure or (ii) specialized stabilizing elements such as Xrn1-resistant sequence (xrRNA) to achieve sufficient stability and translational efficiency in vivo. Lemoine (US 2021/0214729 A1) exemplified this approach by teaching the combination of xrRNA and IRES sequences to replace the cap as a skilled person in the art would be led to believe that simply having an IRES without additional protective elements would result in rapid degradation and poor translation.
Examiner agrees with the assessment that the state of the prior art, at the time of the claimed effective filing date, is silent on an uncapped mRNA of linear structure consisting of a 5’ UTR containing an IRES sequence, a coding region, and a polyA tail, resulting in a minimalistic structure for the uncapped mRNA. However, as the claim is written, the claim recites a linear, uncapped mRNA with the structure A + B + C, wherein region A of the uncapped mRNA utilizes open language (comprises of), therefore region A can include an IRES and other elements, which Lemoine teaches (see paragraph 0015 of Lemoine). Lemoine also teaches where the 3’-UTR region is meant to be any region of nucleic acid located downstream of the translation termination codon and this region may include a polyadenylated tail, Lemoine is open and broad as to what constitutes the 3’ UTR region, encompassing a 3’ UTR region with only a poly A tail, regardless of working examples. As region C, recited in the instant claim, uses transitional language (the word “is”) that doesn’t “close” the interpretation of the claim (see MPEP § 2111.03), Lemoine teaching the 3’ UTR region comprises the poly A tail satisfies the limitations set forth in the claim. Therefore, Lemoine teaches a linear, uncapped mRNA with the structure A + B + C.
Applicant discloses that regarding their approach and unexpected findings, the minimalistic, uncapped, unmodified mRNA exhibited (i) high translational efficiency comparable to or better than capped/modified mRNAs, (ii) sufficient in vivo stability without xrRNA protection, and (iii) effective protein expression in both cell lines and animal models without the need for 3’ UTR or nucleoside modifications. Examiner responds by stating where the evidence of unexpected results must show “a greater than expect result is an evidentiary factor pertinent to the legal conclusion of obviousness” (see MPEP § 716.02(a). While comparable results can be acknowledged as unexpected when the disclosed structure is predicted to yield diminished results (such as a prediction where an uncapped, linear mRNA without a 5’ cap or xrRNA would yield unstable mRNA), these results are in comparison to traditional capped/modified mRNAs, which Lemoine already establishes their uncapped mRNA already yields surprising results which is translational efficiency comparable to traditional capped mRNAs (see paragraph 0154 of Lemoine). The results of the instant application fail to provide unexpected results where translational efficiency is greater, not merely comparable, to the disclosed structure of Lemoine.
With regards to the comparison of the instant invention to Lemoine and other documents, examiner agrees that the structure of Lemoine does teach a structure that embodies more elements than the claimed minimalistic structure of the instant application. However, the claim language of claim 1, as written, still recites an open ended interpretation in which the art of Lemoine satisfies. Examiner suggests that to render Lemoine non-obvious, amendments could be made to where region A and C of claim 1 consists of only a 5’ UTR IRES and a poly A tail.
Maintained Rejections
Claim Rejections – Improper Markush
Claims 1 and 2 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of region B is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: Applicant claims a gene of region B from a glycoprotein ectodomain from herpes simplex virus 2 (HSV2) set forth in SEQ ID NO: 1 and SEQ ID NO: 2, as well as a mutated gene encoding Delta strain SARS-CoV2 spike protein set forth in SEQ ID NO: 3. HSV2 glycoprotein ectodomain and CoV2 spike protein do not share structural similarities as being related to completely different viruses. Though applicant elected SEQ ID NO: 1, claims are examined on the full merit of the claim, regardless of elected species.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Response to Arguments
Applicant’s arguments filed on 6/4/2026 have been fully considered but they are not persuasive. Applicant argues that though the three sequences (SEQ ID NO: 1-3) are different, they each correspond to the coding region (region B) of the claimed mRNA. Applicant notes the inventive concept of the present application resides in the mRNA backbone structure (region A + B + C, uncapped, unmodified uridine, not in the selection of any particular open reading frame (ORF). Therefore, applicant asserts a proper overarching concept of the three sequences is “coding region/ORF of a GOI”, rather than the three GOIs/proteins themselves and the three ORFs actually share a common use- namely, translation into a protein.
In response to the arguments, though examiner acknowledges the applicant is correct in that the inventive concept of the present application resides in the mRNA backbone structure and not the selection of any particular ORF, the claim or invention, as written by the applicant, requires the coding region B to comprise any one of the following genes selected from SEQ ID NO: 1-3. As the sequences of the corresponding ORFs of the three genes are different, the final structure of the composition, which is an uncapped mRNA with A + B + C, will ultimately be different as the final ORF structure will comprise of specific sequences for a given coding region B. The evaluation of structural similarity does not merely reside in inventive concept and must consider all limitations that define the structural elements recited in the claimed invention, including what sequences make up the coding region. Therefore, it is clear that an uncapped mRNA with a coding region encoding a truncated D-type glycoprotein gene in HSV2 has no overlapping structure with an uncapped mRNA with a coding region encoding a mutated Delta strain SARS-CoV-2 spike protein gene.
Regarding the argument that the three ORFs actually share a common use, the recited common use of translation into a protein is immensely broad and is not specific. Given the breadth of the common use, a narrower scope of use would indicate that the species claimed do not constitute a proper Markush grouping.
This rejection is maintained.
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.
Claims 1 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Lemoine (US 2021/0214729, 7/15/2021) in view of Yang et al. (US9566325B2, 2/14/2017), in further view of Mauro et al. (A critical analysis of codon optimization in human therapeutics, Cell Press, Volume 20, Issue 11, Pgs. 604-613, 2014).
Regarding claim 1, Lemoine teaches a stable, uncapped linear mRNA molecule which can be translated with high efficiency (see paragraph 0012 and 0013). Lemoine further teaches that the first aspect of the invention referring to a mRNA molecule lacking a cap molecule comprises of a 5’-UTR region comprising of a consensus sequence, and at least one copy of an internal ribosome entry site (IRES) RNA sequence (see paragraph 0019). In addition, Lemoine discloses that in another embodiment of the invention, a 3’-UTR region comprises of a poly(A) sequence is included, where the preferred embodiment includes a polyadenylated tail (see paragraph 0114-0116). Lemoine further teaches the term “mRNA molecule” means any linear chain of ribonucleotides (see paragraph 0013).
Regarding claim 2, Lemoine teaches where according to another aspect, the invention relates to a host cell comprising said vector. The term “host cell” is intended to refer to a cell in which recombinant expression vector has been introduced in order to express the mRNA of the invention (see paragraph 0142). In this case, it is widely known that a vector is a broad term that refers to any DNA molecule used to deliver foreign genetic material into a host cell, including a plasmid. Furthermore, Lemoine discloses that preferably, the vector of the invention is a plasmid (see paragraph 0140).
Lemoine teaches there the protein of interest coded by the mRNA may also be an antigen, capable of generating an immune response in humans or animals, for the realization of vaccines. They may in particular be antigenic proteins specific for the Epstein Barr virus, the HIV virus, and the hepatitis B virus (see paragraph 0099).
Lemoine teaches that the use of stable uncapped, linear mRNA molecules are particularly advantageous as its production cost is much lower than that of a conventional mRNA comprising a cap molecule or an analog thereof (see paragraph 0012).
Lemoine does not teach where a coding region for translation as to generate a protein, wherein the coding region comprises of a truncated D-type envelope glycoprotein ectodomain coding gene from herpes simplex virus 2 (HSV2), as set forth in SEQ ID NO: 1.
Yang teaches therapeutic vaccines for treating herpes simplex virus-type 2 infections where the antigen is an HSV-2 antigen, which can include gD glycoproteins or derivatives thereof. Furthermore, Yang teaches that truncated variants of gD glycoproteins can be used where the truncated extracellular domain of gD (amino acids 1-314) are presented as SEQ ID NO: 2. SEQ ID NO: 2 of Yang and the protein translated nucleotide sequence of SEQ ID NO: 1 of the instant application share a 94% similarity with 100% similarity between amino acids 1-305. The instant application SEQ ID NO: 1 encodes for 306 nucleotides with the last amino acid being a stop codon. Yang does not teach a 100% identity to the nucleotide sequence SEQ ID NO: 1 of the instant application.
Mauro teaches that codon optimization can be used for increased protein expression, wherein the attempt to produce more protein by altering codon assignments has led to the broad use of codon-optimized mRNAs for the bioproduction of protein pharmaceuticals and nucleic acid therapies (see pg. 605).
Mauro further teaches this prospect of codon optimization has led to the development of numerous codon-optimization programs and commercial services (see pg. 605) including genetic vaccines (see Pg. 611).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to have utilized the uncapped, linear mRNA presented in Lemoine, to manufacture a stable mRNA with reduced manufacturing costs, as Lemoine states “this (uncapped, linear) mRNA is particularly advantageous as its production cost is much lower than that of a conventional mRNA comprising a cap molecule” (see paragraph 0012), and combine it with the truncated glycoprotein ectodomain coding gene (gD) from HSV2 of the instant application encoded by SEQ ID NO:1. Though SEQ ID NO: 1 does not have a clear nucleotide sequence match to prior art as it is codon optimized for the instant application, the translated amino acid sequence has 94% identity to a truncated HSV2 glycoprotein D presented in Yang, with the first 305 amino acids sharing 100% similarity. The nucleotide sequence encoding the truncated extracellular domain gD of HSV2 was known in the art, and making a vaccine against HSV2 was an art-recognized goal as taught by Yang before the effective filing date.
Furthermore, Mauro teaches that one would codon optimize in order to achieve higher levels of protein expression, including for making nucleic acid vaccines using “codon-optimized programs and commercial services” which at the time of the invention, would have also been well known in the art.
SEQ ID NO:1, although truncated, does encode for a wild type human HSV2 glycoprotein D that was well-known in the art at the filing date of the invention. Since the wild type HSV2 gD comprises of a finite number of amino acids, one would use the rationale of codon optimization present in Mauro, to optimize the wild type nucleic acid sequence of human HSV2 gD to eventually reach the codon optimized nucleic acid sequence presented in SEQ ID NO: 1 of the instant application, with a reasonable expectation of success.
In view of the foregoing, claims 1 and 2 would have been prima facie obvious before the effective filing date.
Response to Arguments
Applicant’s arguments filed on 6/4/2026 have been fully considered but they are not persuasive. Applicant argues that the assertion of obviousness is based on impermissible hindsight reconstruction that ignores the critical structural differences between Lemoine’s mandatory xrRNA-containing mRNA and the applicant’s minimalist, xrRNA-free mRNA.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Examiner acknowledges that Lemoine teaches a relatively complex uncapped mRNA structure, requiring xrRNA (at least one, preferably two) plus IRES at the 5’ end (see paragraph 0015), which compensates for the absence of a cap. However, as written, the language of claim 1 and 2 specifies that the region A is “a 5’-untranslated region (UTR) comprising an internal ribosome entry site for mediating internal entry of a ribosomal subunit as to guide translation of the mRNA”. Lemoine satisfies the limitations of region A as Lemoine teaches the 5’ UTR end comprises of an IRES (see paragraph 0015). The presence of other elements, such as xrRNA, elements may be encompassed in the open-ended language for the structural limitations of region A. If applicant intends to limit the structure of region A to only consist of the IRES, then the claim language of claims 1 and 2 with regards to region A should reflect that.
Furthermore, applicant argues that Lemoine does not teach the simplistic structure of 3’ end without a 3’ UTR, a stem-loop, an aptamer, or any additional stabilizing elements. Applicant argues in working examples, Lemoine uses mRNAs that contain a 3’ UTR and other structures. Examiner respectfully disagrees as Lemoine teaches “by “3’-UTR region” is meant any region of nucleic acid which is located downstream of the translation termination codon. This region may influence the expression and/or stability of the mRNA…This region may include, e.g. such elements as a polyadenylated tail (Poly(A)), a histone-stem loop structure…etc.)….In a preferred embodiment, the mRNA comprises a polyadenylated tail, comprising a nucleotide sequence of adenine or an analog or variant thereof…” (see paragraph 0116). The teachings of Lemoine indicate the 3’ UTR region is open ended, and can be interpreted to comprise of merely a poly A tail or region, absent evidence to the contrary. Though the working examples of Lemoine teaches a 3’ UTR with other elements, the prophetic teachings of Lemoine satisfies the structural limitations of the instant claim. Furthermore, claim 1 as written, reads “the region C is a poly A region for mediating a translation efficiency of the mRNA”. The word “is” is a transitional phrase, however, does not provide direct guidance on whether the limitation is open or closed ended (see MPEP § 2111.03), simply that the structure must include a poly A region, which is satisfied by teachings of Lemoine. If applicant intends to claim a linear uncapped mRNA structure wherein region C is merely a poly A region, the use of closed language should be considered.
Applicant further argues the non-obviousness of the claimed invention over Lemoine is also demonstrated by these unexpected results. Regarding unexpected results, please see MPEP § 716.02(a), where the evidence of unexpected results must show “a greater than expect result is an evidentiary factor pertinent to the legal conclusion of obviousness”, however, in page 3 and 4 of the instant specification and the affidavit submitted on 6/4/2024, applicant states the unexpected results includes high translational efficiency comparable to or better than capped/modified mRNAs and sufficient in vivo stability without xrRNA protection, however, 1) results “comparable to” does indicated surprising results that one would deem unexpected, 2) absent evidence to the contrary, these results are unexpected as they are comparable to or exceeds results obtained from circularized mRNA or modified mRNA, but not the uncapped linear mRNA presented in Lemoine, and 3) Lemoine does disclose where the linear uncapped mRNA of Lemoine showed unexpected results, which are at least comparable to capped mRNA molecules, but applicant does not disclose or show how the results of the instant application would exceed or be unexpected to the results of Lemoine.
Applicant argues that Yang is directed to protein/polypeptide vaccines for treating HSV2, not mRNA. Examiner argues, as written, the uncapped, linear mRNA of the instant application has a coding region that is translated to generate a protein. Claim 1 of Yang recites a method where a mammal is administered a composition, the composition comprising a vector encoding an HSV-2 antigen under the control of a promoter, wherein the vector encodes a full-length gD sequence comprising a sequence of SEQ ID NO: 1. One skilled in the art would understand that the vector of Yang could comprise mRNA that encodes an amino acid sequence or protein, such as a HSV2 gD protein, and that such nucleotides would be derived from a gene of the corresponding generated protein.
Applicant argues Mauro discusses codon optimization, which is unrelated to the core mRNA backbone structure. Applicant argues the core structure of the invention is an uncapped linear-mRNA with A + B + C. However, examiner argues that the applicant requires the coding region B to comprise any one of the following genes selected from SEQ ID NO: 1-3. Therefore, the nucleic acid sequence of these genes are a structural limitation that is being claimed in the composition and will dictate the final structure of said composition. Examiner argues that the introduction of Mauro is necessary to provide an obviousness rationale for the structural limitations of SEQ ID NOs 1-3, recited in the instant application.
To conclude, examiner argues that Lemoine satisfies the closed-ended structural limitations of an uncapped mRNA of linear structure consisting of regions A, B, and C, as Lemoine teaches region A (which as written is open ended and can comprise other elements besides an IRES), region B (a coding region for a gene), and region C (which the language of Lemoine is open-ended with regards to what comprises the 3’ UTR region, and the instant claim does not include proper transitional phrases that narrow the scope of the invention), without any other additional elements.
This rejection is maintained.
Claim Rejections - 35 USC § 103
Claim(s) 3, 4, 5, 6, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Lemoine (US 2021/0214729A1, 7/15/2021), Yang (US9566325B2, 2/14/2017), and Mauro (A critical analysis of codon optimization in human therapeutics, Cell Press, Volume 20, Issue 11, Pgs. 604-613, 2014) as applied to claims 1 and 2 above, and further in view and Cui et al. (CN114163345A with an effective filing date of 03/11/2022) and Drummond (WO 2022/115645 A1, priority date of 11/25/2020).
Regarding these claims, the use of uncapped mRNA of claims 1 and 2 in genetic vaccines, wherein the mRNA can be a viral antigen, are described above in Lemoine. Furthermore, Yang and Mauro teach how codon optimization would allow for the use of an uncapped mRNA encoding SEQ ID NO:1 can be used to express a truncated glycoprotein D from HSV2.
All these prior arts are silent on the formation of a lipid nanoparticle comprising an uncapped mRNA.
Regarding claim 3, Drummond discloses that lipid nanoparticles are used for the delivery of therapeutic nucleic acids to cells. Examples can include LNP pharmaceutical compositions employed in vaccines to deliver mRNA therapeutics and lipid nanoparticles typically include an ionizable cationic lipid (ICL) (See page 1, line 25).
Regarding claim 4, Cui teaches a cationic lipid (named compound 1) that has a 100% identity to formula 1 presented in claim 4 (see section with example 1).
Regarding claim 5, Cui discloses the formation of auxiliary lipid molecules in tangent with the lipid nanoparticle wherein the auxiliary lipid molecules include cholesterol and distearoylphosphatidylcholine (DSPC) (see contents of invention section, paragraph n0129 of English translation).
Regarding claim 6 and 7, Cui teaches a composition where compounds 1, 2, and 3 are dissolved and mixed with DSPC, cholesterol, and 1,2-dimyristol-rac-glycero-3-methoxypolyethylene glycol-2000 (DMG-PEG2000) at a molar ratio of 50: 10: 38.5: 1.5 (see section titled embodiment 4, paragraph n0129 of English translation). Though the instant application claims a molar ratio of 50: 10: 38: 2, this molar ratio of LNP and auxiliary lipid molecules are well known in the art. It would have been obvious to adjust 38.5 to 38 and 1.5 to 2.
Regarding claim 8, previous art of Lemoine, Yang, Mauro, and Drummond teach the prior art of an uncapped mRNA being used as a vaccine for an antigen response with viruses. Furthermore, Lemoine teaches where preferably, said composition will be supplemented with an excipient and/or a pharmaceutically acceptable vehicle (see paragraph 0161).
It would have been obvious to combine the uncapped mRNA with the lipid nanoparticle of formula 1, presented in Cui, to create a vaccine in a pharmaceutically acceptable excipient, for the purpose of expressing the glycoprotein ectodomain of HSV2 in generating an immune response. Drummond discloses that mRNA-LNPs may promote efficient uptake of the mRNA by immune cells, including tissue macrophages and dendritic cells.
Drummond discloses the LNP has the function of providing efficient delivery of an mRNA coding for antigen specific for infectious viruses, and subsequent presentation of that antigen to elicit the desired immune response to protect against corresponding infections (see pg. 30, line 15).
One with ordinary skill in the art would have been motivated to combine an uncapped linear mRNA structure disclosed in Lemoine with a region encoding for a codon optimized gD protein from HSV2, described in Yang and Mauro, with the cationic lipid disclosed in formula 1 of Cui for the formation of a LNP, with a reasonable expectation of success. One with ordinary skill in the art would have been further motivated to include this mRNA-LNP composition will further comprise a pharmaceutically acceptable excipient and formulate the mRNA-LNP composition as a vaccine or medicament as described in Lemoine.
One would be motivated to do so in order to efficiently deliver the mRNA encoding the antigen for HSV2 to an immune cell with a LNP, to avoid mRNA degradation, in order to express the antigen for HSV2, to generate an immune response. This is because an LNP was known to have the function of providing efficient delivery of an mRNA coding for a gene eliciting an antigen specific response for infectious viruses as taught by Drummond (see pg. 30, line 15). This makes an mRNA-LNP composition an art-recognized goal and was deemed technically feasible as evidence by Drummond.
In view of the foregoing, claims 3, 4, 5, 6, 7, and 8 would have been prima facie obvious before the effective filing date.
Claim(s) 3, 4, 5, 6, 7, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Lemoine (US 2021/0214729A1, 7/15/2021), Yang (US9566325B2, 2/14/2017), and Mauro (A critical analysis of codon optimization in human therapeutics, Cell Press, Volume 20, Issue 11, Pgs. 604-613, 2014) as applied to claims 1 and 2 above, and further in view of Drummond et al. (WO 2022/115645 A1, priority date of 11/25/2020).
Lemoine teaches the use of uncapped mRNA and a viral antigen for generating an immune response as described above in claims 1 and 2.
Lemoine does not teach a mRNA-lipid nanoparticle comprising an uncapped mRNA and an LNP.
Regarding claim 3 and 4, Drummond teaches ionizable cationic lipids for lipid nanoparticles. Drummond discloses that lipid nanoparticles are used for the delivery of therapeutic nucleic acids to cells. Examples can include LNP pharmaceutical compositions employed in vaccines to deliver mRNA therapeutics and lipid nanoparticles typically include an ionizable cationic lipid (ICL) (See page 1, line 25). However, ICL compounds are undesirably sensitive to oxidation during storage.
Drummond discloses a cationic lipid that is engineered with improved stability to oxidative degradation while in storage, while retaining high transfection activity or potency in cells (see pg. 2, line 15). Drummond further teaches that in one aspect, the nucleic acid LNP composition comprises a nucleic acid, an ionizable cationic lipid selected from KC2OA, KC2, KC2-01, ALC-0315, and SM102 (see page 23, line 11). SM102 is synonymous with 8-[(2-hydroxyethyl)[6-oxo-6-(undecyloxy)hexyl]amino]-octanoic acid, as claimed in claim 4 of the instant application.
Regarding claim 5, Drummond teaches the LNP composition further comprises cholesterol and a second phospholipid select from a group consisting of: DSPC, DPPC, and DOPC. This reads on the helper molecules or auxiliary lipids included in the LNP formulation.
Regarding claims 6 and 7, Drummond teaches, in some embodiments, the lipidic nanoparticle comprises ICL (a cationic lipid such as SM102), DSPC, cholesterol, and polymer-conjugated lipid in a about 49.5: 10.3: 39.5: 2.5 molar ratio (see pg. 64, line 19). Furthermore, in some embodiments, the polymer-conjugated lipid is PEG(2000)-dimyristoylglycerol (see pg. 64, line 21). Though claim 7 specifically recites a molar ratio of 50: 10: 38: 2, this molar ratio is well known in the art and Drummond recites an approximation that is identical to what is claimed in the instant application.
Regarding claim 8, Drummond discloses where in some embodiments, the composition further comprises a pharmaceutical excipient (see pg. 93, line 11). Furthermore, claim 27 of Drummond recites a method of preventing a bacterial or viral infection, the method comprising administering to a subject in need thereof an effective amount of composition, and a pharmaceutical excipient, wherein administration elicits an immune response (see claim 27).
It would have been obvious to one with ordinary skill in the art, before the effective filing date, to combine the uncapped, linear mRNA of claims 1-2 rendered obvious above, with the lipid nanoparticle composition presented by Drummond, for generating a vaccine or medicament with a reasonable expectation of success. The process of creating a stable, uncapped linear mRNA will help with production costs (see Lemoine, paragraph 0012). The LNPs, presented by Drummond, was known to promote efficient uptake by target immune cells, including tissue macrophages and dendritic cells. The efficient delivery of nucleic acids coding for antigen specific for infectious viruses or bacteria, and subsequent presentation of that antigen to elicit the desired immune response to protect against corresponding infections is a result (see pg. 30, line 15).
One with ordinary skill in the art could combine an uncapped linear mRNA structure disclosed in Lemoine with a region encoding for a codon optimized gD protein from HSV2, described in Yang and Mauro, with the LNP presented in Drummond, with a reasonable expectation of success. This mRNA-LNP composition will further comprise a pharmaceutically acceptable excipient and be administered as a vaccine or medicament.
One would be motivated to do so in order to efficiently deliver the mRNA encoding the antigen for HSV2 to an immune cell with a LNP, to avoid mRNA degradation, in order to express the antigen for HSV2, to generate an immune response. This is because an LNP was known to have the function of providing efficient delivery of an mRNA coding for a gene eliciting an antigen specific response for infectious viruses as taught by Drummond (see pg. 30, line 15). This makes an mRNA-LNP composition an art-recognized goal and was deemed technically feasible as evidence by Drummond.
In view of the foregoing, claims 3, 4, 5, 6, 7, and 8 would have been prima facie obvious before the effective filing date.
Response to Arguments
Applicant's arguments filed 6/4/2026 have been fully considered but they are not persuasive. Applicant argues that for the reasons discussed above, the mRNA structure of claim 1 is non-obvious over the suggested addition of Cui and Drummond. Cui and Drummond does not teach or suggest any mRNA structural features that remedy the deficiencies in Lemoine’s teachings regarding the claimed minimalist mRNA structure. As claims 3-8 are dependent on claim 1, the rejection is improper as claims 3-8 are non-obvious over the cited art.
Examiner respectfully disagrees and argues that the claims, as written, do not properly narrow the scope or limitations of the invention to where the teachings of Lemoine would be considered non-obvious. Please see the rationale stated above.
This 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 DAVID YU whose telephone number is (571)272-1118. The examiner can normally be reached Monday-Friday 7:30 am -5 pm.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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