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 .
Claims Summary
Claims 1-12, 21 and 22
Claim 1 is directed to a composition comprising a self-amplifying RNA (saRNA) (which is also known as self-replicating RNA (srRNA) comprising:
A 5’ cap; represented by Formula II (claim 4); the nucleotide immediately downstream (5’ to 3’) of the cap comprises guanine (claim 6)
A 5’ UTR; having at least 70% sequence identity to SEQ ID NO: 12 (claim 2), representing a VEEV 5’ UTR
A coding region for a nonstructural protein derived from an alphavirus comprising a polynucleotide sequence having at least 70% sequence identity to SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15 and SEQ ID NO: 16 (claim 2), representing NSP1-4 of VEEV strain TC83
A first subgenomic promoter derived from an alphavirus; comprising a polynucleotide sequence having at least 70% sequence identity to SEQ ID NO: 17 (claim 2), representing a VEEV subgenomic promoter
A first ORF encoding a first gene of interest derived from influenza virus HA; comprising a polynucleotide having at least 70% sequence identity to SEQ ID NO: 18 (claim 2), representing HA of A/Wisconsin/588/2019 H1N1
A second subgenomic promoter derived from an alphavirus; comprising a polynucleotide having at least 70% sequence identity to SEQ ID NO: 19 (claim 2), representing a VEEV subgenomic promoter
A second ORF encoding a second gene of interest derived from influenza virus; encodes any one polypeptide selected from HA, NA, NP, M1, M2, NS1 and NS2 (claim 3)
A 3’ UTR; comprising a polynucleotide having at least 70% sequence identity to SEQ ID NO: 21 (claim 2), representing a VEEV 3’ UTR, and
A 3’ polyA sequence; comprising at least 20 consecutive adenines (claim 2), or comprises 30-200 adenines (claim 12)
At least 10% of the total nucleotides in the saRNA are replaced with modified or unnatural nucleotides, such as pseudouridine, among others (claim 5). At least 50% of the total saRNA molecules is full length (claim 7), or at least 80% (claim 8). According to the specification at paragraph [0010] of the published application (US 20240009296) “full length” includes a 5’ cap and a polyA tail. The saRNA is complexed or associated with an LNP comprising an ionizable lipid, a neutral lipid, a steroid, and a polymer-conjugated lipid (claim 9). The saRNA is complexed or associated with an LNP comprising at least one cationic lipid comprising ALC-0315, at least one neutral lipid comprising DSPC, at least one steroid comprising cholesterol, and at least one PEG-lipid comprising ALC-0159 wherein n has a mean value ranging from 30-60 (claim 10), having a molar ratio of about 20-60% cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-lipid (claim 11). The composition comprises a plurality of the saRNA, such as four (claim 22), encapsulated in an LNP (claim 21).
Claims 13-18
Claim 13 is directed to a composition comprising an saRNA, comprising:
A 5’ cap; represented by Formula II (claim 14); the nucleotide immediately downstream (5’ to 3’) of the cap comprises guanine (claim 15)
A 5’ UTR
A coding region for a nonstructural protein derived from an alphavirus
A subgenomic promoter derived from an alphavirus
An ORF encoding a gene of interest derived from influenza virus
A 3’ UTR, and
A 3’ polyA sequence
At least 25% of a total population of a particular nucleotide in the saRNA has been replaced with one or more modified or unnatural nucleotides selected from the group consisting of 5-methyluridine, N1-methylpseudouridine, 5-methoxyuridine, and 5-methylcytosine. The saRNA molecule is encapsulated in, bound to, or adsorbed on a liposome, an LNP, among others (claim 16). At least 50% of the total saRNA molecules is full length (claim 17), or at least 80% (claim 18).
Claims 19 and 20
Claim 19 is directed to a method for inducing an immune response in a subject comprising a composition comprising an saRNA, comprising:
A 5’ cap
A 5’ UTR
A coding region for a nonstructural protein derived from an alphavirus
A first subgenomic promoter derived from an alphavirus
A first ORF encoding a gene of interest derived from influenza virus HA
A second subgenomic promoter derived from an alphavirus
A second ORF encoding a second gene of interest derived from influenza virus
A 3’ UTR, and
A 3’ polyA sequence
The composition elicits an immune response comprising a T cell response (claim 20).
Claim Objections
Claim 2 is objected to because of the following informality:
Claim 2, line 2, has a typographical error in “70%, sequence identity”. Appropriate correction is required.
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 7, 8, 11, 17 and 18 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.
Claims 7, 8, 17 and 18 recite the limitation “wherein at least 50% the total saRNA molecules is full length”, and “wherein at least 80% the total saRNA molecules is full length”, respectively. There is insufficient antecedent basis for “saRNA molecules” [emphasis added] in claims 1 and 13, respectively. Claims 1 and 13 are directed to a composition comprising an saRNA molecule, not molecules.
Claim 11 recites the limitation "wherein (i) to (iv) are in a molar ratio", etc., in claim 1. There is insufficient antecedent basis for this limitation in the claim. Claim 11 will be treated as if dependent on claim 10, for purposes of compact prosecution.
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.
Claim 2 is 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 2 is directed embodiments wherein the various elements of the saRNA are defined by sequences. The claim encompasses a large genus of saRNA having the following elements:
The 5’ UTR having at least 70% sequence identity to SEQ ID NO: 12 (44 nt), allowing for up to about 13 nt changes
The coding regions for NSP1-4 have at least 70% sequence identity to:
SEQ ID NO: 13 (1605 nt), allowing for up to about 481 nt changes
SEQ ID NO: 14 (2382 nt), allowing for up to about 714 nt changes
SEQ ID NO: 15 (1671 nt), allowing for up to about 501 nt changes
SEQ ID NO: 16 (1825 nt), allowing for up to about 547 nt changes
A first subgenomic promoter having at least 70% sequence identity to SEQ ID NO: 17 (61 nt), allowing for up to about 18 nt changes
A first ORF encoding a first gene of interest comprising a polynucleotide having at least 70% sequence identity to SEQ ID NO: 18 (1706), allowing for up to about 511 nt changes
A second subgenomic promoter comprising a polynucleotide having at least 70% sequence identity to SEQ ID NO: 19 (59 nt), allowing for up to about 17 nt changes
A 3’ UTR having at least 70% sequence identity to SEQ ID NO: 21 (117 nt), allowing for up to about 35 nt changes
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
In this case, the claims provide a partial structure in the form of a recitation of percent identity. As outlined above, there are many permutations encompassed by the degree of sequence identity. The functions provided for the various elements are, respectively, UTRs, coding regions for replicase, ORFs, and subgenomic promoters. However, there is no identification of which portions of the claimed sequences must be retained in order for the respective functions to remain intact. Table outlines the claimed construct, but no variants of that construct appear to have been made within the confines of the percent identity limitations. The specification does not appear to provide a nexus between the partial structures and the necessary functions. The specification does not appear to provide any examples of variants having the required functions. While variants within the recited percent identities can be made, one would not know where to make the changes and still reasonably expect to have a functional UTR, replicase, ORFs, and subgenomic promoters, all functioning as an saRNA. The one species provided for each of the elements (SEQ ID NO: 12-19 and 21, respectively) does not represent the genus claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 4, 6, 12, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Kamrud et al. (US 2018/0104359) in view of Magini et al. (PLoS ONE, 11(8):e0161193, published August 15, 2016, of record in the IDS filed 06/21/2024). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Kamrud discloses viral-based expression systems for the production of molecules of interest (see abstract) and their administration to animals and humans (see paragraphs [0100]- [0103]) (claim 19). Figure 3 is a schematic of a replicon comprising a 5’ cap, 5’UTR with T2G mutation, NSP1-4, a 26S subgenomic promoter, influenza HA, a 3’UTR and a polyA tail, having, for example, 40 A residues (see paragraph [0116]) (claims 1, 6 and 12). Kamrud contemplates more than one expression cassette, each comprises a 26S subgenomic promoter (see paragraphs [0010]) (claim 1). Kamrud does not teach which antigen to use in the additional expression cassettes, but suggests any gene of interest encoding any polypeptide of interest (see paragraph [0011]). It would have been obvious to have selected any other influenza antigen, such as NP or M1, as disclosed by Magini. Magini teaches self-amplifying mRNA vectors expressing influenza NP and M1 (see abstract). Magini suggests the use of NP and M1 because they are internal, highly conserved proteins across various strains, in contrast to HA which is strain-specific (see abstract). By including both HA and NP, for example, one would generate an immune response that targets a specific strain (using HA) as well as a broader range of strains (using NP or M1) (claims 1 and 3). One would have had a reasonable expectation of success given the similar replicon constructs and Kamrud’s suggestion to use any polypeptide of interest (see paragraph [0011]).
Kamrud’s Figure 3 indicates the presence of a CleanCap®, but the trademark does not indicate the type of cap. Magini’s Figure 1a shows a schematic of a self-amplifying mRNA vector comprising a m7G cap (claim 4), a 5’-UTR (stem/loop structure), NSP1-4, a 26S subgenomic promoter, influenza M1, a second 26S subgenomic promoter, influenza NP. It would have been obvious to have used an m7G cap in Kamrud’s replicon given the similarity of the replicon constructs with a reasonable expectation of success.
Regarding the induction of a T-cell response, Kamrud does not appear to comment on this, aside from disclosing the induction of an immune response (see paragraph [0038]). However, since the same antigens are being used in Kamrud’s construct as in Applicant’s claimed construct, i.e., influenza HA and a second influenza protein, then the effect of eliciting a T cell response is a natural outcome of doing what the prior art suggests (claim 20). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 5 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Kamrud et al. (US 2018/0104359) in view of Magini et al. (PLoS ONE, 11(8):e0161193, published August 15, 2016) as applied to claim 1 above, and further in view of Geall et al. (US 2011/0300205 A1, “Geall”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
The combined teachings of Kamrud and Magini are outlined above (claims 13-15). Kamrud and Magini do not disclose the replacement of at least 10% or at least 25% of certain nucleotides with modified or unnatural nucleotides. However, it would have been obvious to have done so with a reasonable expectation of success in view of Geall. Geall discloses self-replicating RNA molecules that contain 1-25% modified nucleotides, such as pseudouridine or 5’methyluridine (see abstract and paragraphs [0066]-[0068]). One would have been motivated to modify Kamrud’s construct with modified or unnatural nucleotides in order to increase stability and resistance to degradation and clearance in vivo, among other advantages (see paragraph [0044]) (claims 5 and 13).
Kamrud and Magini do not suggest formulation of their RNA constructs with, for example, liposomes. However, it would have been obvious to have done so with a reasonable expectation of success. One would have been motivated by Gaell’s disclosure that RNA constructs encapsulated in, bound to or adsorbed onto a liposome, among other options, are protected from RNase digestion (see paragraphs [0024] and [0095]) (claim 16). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 9-11, 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Kamrud et al. (US 2018/0104359) in view of Magini et al. (PLoS ONE, 11(8):e0161193, published August 15, 2016), as applied to claim 1 above, and further in view of Rauch et al. (US 2021/0379181 A1, published December 9, 2021, filed April 15, 2021, “Rauch”). The claims are summarized above and correlated with the teachings of the prior art in bold font below.
Claim 9-11, respectively, are directed to embodiments wherein the saRNA is complexed or associated with an LNP comprising at least one cationic lipid, ALC-0315, at least one neutral lipid, DSPC, at least one steroid, cholesterol, and at least one PEG-lipid, ALC-0159, wherein n has a mean value ranging from 30-60 (claim 10), having a molar ratio of about 20-60% cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-lipid. The composition comprises a plurality of the saRNA, such as four (claim 22), encapsulated in an LNP (claim 21).
Kamrud and Magini do not suggest formulation of their RNA constructs with, for example, lipid nanoparticles. However, it would have been obvious to have done so with a reasonable expectation of success. One would have been motivated by Rauch’s disclosure that RNA constructs complexed with or encapsulated in LNPs are protected from degradation (see paragraphs [0818]) (claim 21). Rauch’s LNP formulation comprises, for example, ALC-0315, DSPC, cholesterol (steroid), and a PEG-lipid ALC-0159, where n is 45, in a ratio of 50:10:38.5:1.5 (see paragraph [0879] (claims 9-11). As for the composition comprising a plurality of saRNA molecules, such as four molecules, this would have been obvious to one of ordinary skill in the art with a reasonable expectation of success. Including more than a single molecule of saRNA, or more than four in the composition would improve the immunogenicity of the composition because more immunogen would be produced (claims 21 and 22). Therefore, the claimed embodiments would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
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, 3 and 19-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of copending Application No. 19/150,960 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other. Copending claim 7 is directed to a composition comprising a self-amplifying RNA encoding an influenza HA and NS1 protein, and a second RNA molecule encoding an influenza NS1 protein. The difference between copending claim 7 and instant claim 1 is that the second influenza gene of interest is generically recited in instant claim 1, although it is recited in instant claim 3 as an option among other influenza polypeptides. In that sense, copending claim 7 is a species of claim 1. Another difference between copending claim 7 and instant claim 1 is that copending claim 7 requires the presence of a second RNA molecule. Instant claim 1 does not require the presence of a second RNA molecule, however, the composition of instant claim 1 is open to other elements (“a composition…comprising”). Thus, copending claim 7 renders obvious instant claim 1. Other limitations of copending claims 1-6 and 8-17 are either species of the instantly claimed genus, or inherent characteristics of the constructs. Copending claims 18 and 19 are directed to methods of administering the compositions, which render obvious the compositions themselves as well as the methods of inducing an immune response by administering the compositions. Although the copending claims do not specifically state that a plurality of saRNA molecules, such as more than four molecules, are present in the composition, this would have been obvious to one of ordinary skill in the art with a reasonable expectation of success. Including more than a single molecule of saRNA, or more than four in the composition would improve the immunogenicity of the composition because more immunogen would be produced in the subject receiving the composition. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 4 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of copending Application No. 19/150,960 (reference application) as applied to claim 1 above, and further in view of Magini et al. (PLoS ONE, 11(8):e0161193, published August 15, 2016). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 4 is directed to an embodiment wherein the 5’ cap is represented by Formula II. The copending claim does not specify the formula of the 5’ cap. However, it would have been obvious to have used any known 5’ cap suitable for saRNA constructs with a reasonable expectation of success. Magini’s Figure 1a shows a schematic of a self-amplifying mRNA vector comprising a m7G cap (claim 4), a 5’-UTR (stem/loop structure), NSP1-4, a 26S subgenomic promoter, influenza M1, a second 26S subgenomic promoter, influenza NP. It would have been obvious to have used an m7G cap in the copending embodiment given the similarity of the replicon constructs. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claim has not in fact been patented.
Claims 5 and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 and 7 of copending Application No. 19/150,960 (reference application) as applied to claim 1 above, and further in view of Geall et al. (US 2011/0300205 A1, “Geall”). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 5 is directed to an embodiment wherein at least 10% of the total nucleotides in the saRNA are replaced with modified nucleotides, such as pseudouridine. Instant claim 13 is directed to an embodiment wherein at least 25% of a total population of a particular nucleotide in the saRNA is replaced with one or more modified nucleotides, including 5’methyluridine.
Copending claim 6 is directed to an embodiment wherein less than about 50% of the nucleic acids in the saRNA are modified nucleotides. However, no particular modified nucleotides are mentioned. It would have been obvious to have claimed pseudouridine or 5’methyluridine. Geall discloses self-replicating RNA molecules that contain 1-25% modified nucleotides, such as pseudouridine or 5’methyluridine (see abstract and paragraphs [0066]-[0068]). One would have been motivated to use these modified nucleotides in order to increase stability and resistance to degradation and clearance in vivo, among other advantages (see paragraph [0044]).
Instant claim 16 is directed to an embodiment wherein the saRNA molecule is encapsuled in, for example, a liposome. The copending claims do not recite this embodiment. However, it would have been obvious to have claimed encapsulation in a liposome with a reasonable expectation of success. Gaell teaches that RNA constructs encapsulated in a liposome are protected from RNase digestion (see paragraphs [0024] and [0095]). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 6 and 12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 7 of copending Application No. 19/150,960 (reference application) as applied to claim 1 above, and further in view of Kamrud et al. (US 2018/0104359). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 6 is directed to an embodiment wherein the nucleotide immediately downstream of the 5’ Cap comprises guanine. Instant claim 12 is directed to an embodiment wherein the polyA tail comprises 30 to 200 adenosine nucleotides. The copending claims do not recite these limitations. However, it would have been obvious to claimed these embodiments with a reasonable expectation of success. Kamrud discloses viral-based expression systems for the production of molecules of interest (see abstract) and their administration to animals and humans (see paragraphs [0100]- [0103]). Kamrud’s Figure 3 is a schematic of a replicon comprising a 5’ cap, 5’UTR with T2G mutation, NSP1-4, a 26S subgenomic promoter, influenza HA, a 3’UTR and a polyA tail, having, for example, 40 A residues (see paragraph [0116]). Kamrud teaches that the T2G mutation is made to improve expression (see paragraph [0113]), thus one would have been motivated to claim this embodiment. The use of 40 A residues for the polyA tail would have been obvious to claim since the copending claims are generic with regard to the number of A residues, and one would have had a reasonable expectation of success given the similarity of the constructs. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 9-11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7 and 16 of copending Application No. 19/150,960 (reference application) as applied to claim 1 above, and further in view Rauch et al. (US 2021/0379181 A1, published December 9, 2021, filed April 15, 2021, “Rauch”).
Instant claims 9-11, respectively, are directed to embodiments wherein the saRNA is complexed or associated with an LNP comprising at least one cationic lipid, ALC-0315, at least one neutral lipid, DSPC, at least one steroid, cholesterol, and at least one PEG-lipid, ALC-0159, wherein n has a mean value ranging from 30-60, having a molar ratio of about 20-60% cationic lipid, 5-25% neutral lipid, 25-55% sterol, and 0.5-15% PEG-lipid.
Copending claim 16 does not specify the formulation of the LNPs, as outlined in instant claims 9-11 above. However, it would have been obvious to have claimed such with a reasonable expectation of success. One would have been motivated by Rauch’s disclosure that RNA constructs complexed with or encapsulated in LNPs are protected from degradation (see paragraphs [0818]). Rauch’s LNP formulation comprises, for example, ALC-0315, DSPC, cholesterol (steroid), and a PEG-lipid ALC-0159, where n is 45, in a ratio of 50:10:38.5:1.5 (see paragraph [0879]. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 14 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 and 7 of copending Application No. 19/150,960 (reference application) in view of Geall et al. (US 2011/0300205 A1, “Geall”) as applied to claim 13, and further in view of Magini et al. (PLoS ONE, 11(8):e0161193, published August 15, 2016). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 14 is directed to an embodiment wherein the 5’ cap is represented by Formula II. The copending claims do not specify the formula of the 5’ cap. However, it would have been obvious to have used any known 5’ cap suitable for saRNA constructs with a reasonable expectation of success. Magini’s Figure 1a shows a schematic of a self-amplifying mRNA vector comprising a m7G cap, a 5’-UTR (stem/loop structure), NSP1-4, a 26S subgenomic promoter, influenza M1, a second 26S subgenomic promoter, influenza NP. It would have been obvious to have used an m7G cap in the copending embodiment given the similarity of the replicon constructs. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claim has not in fact been patented.
Claim 15 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 6 and 7 of copending Application No. 19/150,960 (reference application) in view of Geall et al. (US 2011/0300205 A1, “Geall”) as applied to claim 13 above, and further in view of Kamrud et al. (US 2018/0104359). Although the claims at issue are not identical, they are not patentably distinct from each other.
Instant claim 15 is directed to an embodiment wherein the nucleotide immediately downstream of the 5’ Cap comprises guanine. The copending claims do not recite this limitation. However, it would have been obvious to claim this embodiment with a reasonable expectation of success. Kamrud discloses viral-based expression systems for the production of molecules of interest (see abstract) and their administration to animals and humans (see paragraphs [0100]- [0103]). Kamrud’s Figure 3 is a schematic of a replicon comprising a 5’ cap, 5’UTR with T2G mutation, NSP1-4, a 26S subgenomic promoter, influenza HA, a 3’UTR and a polyA tail, having, for example, 40 A residues (see paragraph [0116]). Kamrud teaches that the T2G mutation is made to improve expression (see paragraph [0113]), thus one would have been motivated to claim this embodiment. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claim has not in fact been patented.
Conclusion
No claim is allowed.
The combination of sequences SEQ ID NO: 12-18 and 21 in a single saRNA molecule is free of the prior art of record.
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/STACY B CHEN/Primary Examiner, Art Unit 1672