DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of claims 115-116 with species election of SEQ ID NO:85 in the reply filed on September 9, 2025 is acknowledged.
Status of Claims
Claims 115-130 are currently pending and under examination on the merits in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on July 10, 2023, June 24, 2024, October 3, 2024, and September 9, 2025 have been considered by the examiner, except the NPL (“C6”) filed on June 24, 2024 because the NPL reference is not legible as required by 37 CFR 1.98(a)(2), which requires a legible copy of each cited non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. The “Chinese language with English abstract” listed in the citation information is in non-recognizable characters thus illegible. See the following portion reproduced from the first page submitted by applicant.
PNG
media_image1.png
392
760
media_image1.png
Greyscale
Specification
The disclosure is objected to because of the following informalities:
1. The specification is not arranged as provided in 37 CFR 1.77(b). For instance, “Brief description of the drawings” at page 72 must precede “Detailed Description of the invention” at page 8. Appropriate correction is required.
2. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. See page 79. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 115-130 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. This includes a new matter rejection.
Claims 115-120 and 122-130 are drawn to a method of treating a subject comprising administering (i) and (ii), wherein (ii) is an antagonist of “5 to 25 nucleotides in length comprising a 2’-O-methylated RNA nucleotide.”
It is noted that the instant specification at best describes co-transfection of mRNA and a 9-mer oligonucleotide complexed with DOTAP, wherein the 9-mer oligonucleotide comprises a 2’-O-methylated RNA at position 3 or position 5. See Table 6. The 9-mer oligonucleotide is not representative of “5 to 25 nucleotides in length” for (ii), especially in view of the fact that the antagonist activity was known to be length-dependent as evidenced by Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation), who demonstrate that the 9-mer length was deemed the most optimal length for providing TLR7/8 inhibition function in PBMCs transfected with bacterial RNA. See Figure 4A. In addition, the “2-O-methylated RNA nucleotide” at position 3 or position 5 within the 9-mer is not representative of the entire genus encompassing the presence of 2’-O-methylated RNA nucleotide” at any position within the oligonucleotide of “5 to 25 nucleotides in length” because it was known in the art that the antagonistic function of the oligonucleotide depends on the specific position of the 2’-O-methylated nucleotide as evidenced by Figure 4B of Schmitt, who determined that position 3 and position 5 of a 9-mer oligonucleotide are optimal for the antagonistic function.
In view of the highly unpredictable nature of 2’-O-methyl RNA-containing oligonucleotides whose function is highly dependent on the length as well as the specific position of the 2’-O-methyl RNA as evidenced by Schmitt, the instant specification’s in vitro transfection use of the instantly exemplified 9-mer oligonucleotide is not representative of the instantly claimed in vivo method encompassing a substantial structural variation of (ii) claimed in the instant case.
Accordingly, the instant specification fails to adequately describe the entire genus and thus fails to reasonably convey that the instant co-inventors had possession of the entire genus as of the filing date sought in the instant application.
Claims 115-124 and 126-130 as written read on the RNA whose ORF comprises “at least one modified nucleotide”. The instant specification does not expressly disclose that it is the ORF that comprises one of the recited modified nucleotide in the RNA molecule that is administered to a subject for treatment. There is no disclosure in the specification that specifies the location/position of the modified nucleotide.
Regarding claim 125 that recites the negative limitation that “the mRNA molecule does not comprise a modified nucleotide in the ORF”, the instant specification is completely silent regarding such exclusory limitation as there is no adequate description that the “ORF” comprises a modified nucleotide as explained above.
Accordingly, claims 115-130 introduce new matter that is not described in the specification as originally filed.
Claim Rejections - 35 USC § 103
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.
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 115-121, 123, 125, and 128-130 are rejected under 35 U.S.C. 103 as being unpatentable over Shen et al. (WO 2018/140826 A1, of record) in view of Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Shen teaches a method of treating a subject comprising administering a pharmaceutical composition comprising lipoplex (LPP)-encapsulated RNA encoding a vaccine or “human tumor-specific polypeptide” and “an immunomodulatory compound” or “an immunomodulatory agent”, “thereby further enhancing/extending the activity of the vaccine in selected cells and patients.” See claims 1, 4, 12, 15, 24-26, 32-37, and 39; paragraph 0212.
Shen demonstrates that the combination of mRNA vaccine and ODN2095 substantially reduces the cytokine levels, wherein ODN2095 is a “TLR7/8 inhibitor”. See Figure 14; paragraph 0065.
It is noted that Shen’s LPP can comprise EDOPC, DOPE, DSPE-PEG-2000, cholesteryl hemisuccinate (CHEMS), and DOTAP, wherein the LPP-encapsulated “mRNA vaccine particles are within 40-200 nm range” and the LPP-containing pharmaceutical composition is comprised within “nanoparticles”. See paragraphs 0180 and 0208; claim 18.
Shen does not teach that the immunomodulatory compound/agent included in the LPP in nanoparticles is SEQ ID NO:85 (5’-GAGCGmGCCA).
Schmitt teaches that a 9-mer oligonucleotide having a 2’-O-methylated guanosine (“Gm”) at position 5 reduces TNF levels and “potently attenuates TLR7/8-induced immune responses” thus is useful to “antagonize TLR7 and TLR8 stimulation by RNA” in therapeutic applications, wherein the oligonucleotide is 5’-gagcGmGCca, which is found 100% identical to SEQ ID NO:85 claimed in the instant case. See pages 1347-1348; Figure 4B.
It would have been obvious to one of ordinary skill in the art before the effective filing date to administer an LPP/LNP composition comprising a combination of mRNA vaccine and a TLR7/8 inhibitor to a subject for treatment, wherein the TLR7/8 inhibitor is Schmitt’s oligonucleotide of 5’-gagcGmGCca. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to enhance the activity of the mRNA vaccine in the subject because administration of a combination of an mRNA vaccine and an immunomodulatory agent was suggested to be useful for “further enhancing/extending the activity of the vaccine in selected cells and patients” as taught by Shen, and a “TLR7/8 inhibitor” was an art-recognized immunomodulatory agent as taught by Shen, wherein one of ordinary skill in the art would have readily recognized that Schmitt’s 9-mer 2’-O-methylated guanosine-containing oligonucleotide qualifies as the “TLR7/8 inhibitor” as evidenced by the teachings of Schmitt.
In view of the foregoing, claims 115-121, 123, 125, and 128-130 taken as a whole would have been prima facie obvious before the effective filing date.
Claims 115-130 are rejected under 35 U.S.C. 103 as being unpatentable over Kariko et al. (US 2013/0197068 A1) in view of Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Kariko teaches a method of treating a mammal comprising administering a modified RNA (e.g., messenger RNA (mRNA)) encoding a protein of interest, wherein the modified RNA comprises 5-methylcytidine and 1-methyl-pseudouridine, wherein the RNA further comprises a 5’ cap, polyA tail, and 5’ and 3’ UTRs, wherein the modified RNA is encapsulated in a lipid nanoparticle, and wherein “the modified RNA induces a detectably lower innate immune response” such as lower levels of “cytokines” such as “TLR7, and TLR8 signaling molecules” than the unmodified RNA, wherein the modified RNA results in “detectable expression of the encoded protein”, whereas the unmodified RNA “does detectably reduce expression of the encoded protein” because an immune response is “sufficient to detectably reduce” or “sufficient to eliminate detectable expression” of the encoded protein of interest. See claims 1-21; paragraphs 0006 and 0285-0289.
Kariko teaches that “gene therapy vectors” can comprise modified nucleosides such as 5-methylcytidine and 1-methyl-pseudouridine by “engineering the vector to contain a pseudouridine or a modified nucleoside base, thereby decreasing TNF-a production in response to a gene therapy vector in a subject”, “thereby reducing an immunogenicity of a gene therapy vector.” See paragraphs 0010, 0148-0150.
Kariko teaches that “using retroviral-mediated gene transfer” is known. See paragraph 0282.
Kariko does not teach further administering a TLR7/8 antagonist that is SEQ ID NO:85 (5’-GAGCGmGCCA).
Schmitt teaches that a 9-mer oligonucleotide having a 2’-O-methylated guanosine (“Gm”) at position 5 reduces TNF levels and “potently attenuates TLR7/8-induced immune responses” thus is useful to “antagonize TLR7 and TLR8 stimulation by RNA” in therapeutic applications, wherein the oligonucleotide is 5’-gagcGmGCca, which is found 100% identical to SEQ ID NO:85 claimed in the instant case. See pages 1347-1348; Figure 4B.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify Kariko’s method by further including Schmitt’s oligonucleotide of 5’-gagcGmGCca in the lipid nanoparticle encapsulating the modified RNA of Kariko. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success in order to further lower TLR7/8 signaling molecules, thereby further enhancing the expression level of the protein encoded by Kariko’s modified RNA comprising 1-methyl-pseudouridine in a subject for treatment, because reduction of cytokines including TLR7/8 signaling molecules was taught to correlate with “detectable expression of the encoded protein” as the immune responses involving cytokines were known to be “sufficient to detectably reduce” or “sufficient to eliminate detectable expression” of the encoded protein of interest as taught by Kariko, and because Schmitt’s 9-mer 2’-O-methylated oligonucleotide of 5’-gagcGmGCca was known to “antagonize TLR7 and TLR8 stimulation by RNA” thus functions as a TLR7/TLR8 antagonist that “potently attenuates TLR7/8-induced immune responses” as taught by Schmitt.
It would also have been obvious to utilize a replicating RNA virus vector that is engineered to comprise 1-methyl-pseudouridine as a carrier of the protein-encoding RNA. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because it was known in the art to make and use a less immunogenic gene transfer vector by “engineering the vector to contain a pseudouridine or a modified nucleoside base, thereby decreasing TNF-a production in response to a gene therapy vector in a subject”, “thereby reducing an immunogenicity of a gene therapy vector” as taught by Kariko.
In view of the foregoing, claims 115-130 taken as a whole would have been prima facie obvious before the effective filing date.
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 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 22 of U.S. Patent No. 9,683,233 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘233 patent claim drawn to a method of expressing a polypeptide in a subject comprising administering an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further administer SEQ ID NO:85 claimed in the instant case when practicing the method of the ‘233 patent claim in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘233 patent claim. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘233 patent claim in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the RNA of the ‘233 patent claim in an LNP for administration to the subject because such LNP encapsulation was an art-recognized administration methodology as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘233 patent claim so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 19-20 of U.S. Patent No. 10,738,306 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘306 patent claims drawn to a method of treating a subject comprising administering a pharmaceutical composition comprising an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case into the pharmaceutical composition of the ‘306 patent claims in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘306 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘306 patent claims in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the pharmaceutical composition of the ‘306 patent claims in an LNP for administration to the subject because an LNP formulation was an art-recognized pharmaceutical formulation for RNA administration as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘306 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 10,080,809 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘809 patent claim drawn to a method of expressing a polypeptide in a subject comprising administering an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further administer SEQ ID NO:85 claimed in the instant case when practicing the method of the ‘809 patent claim in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘809 patent claim. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘809 patent claim in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the RNA of the ‘809 patent claim in an LNP for administration to the subject because such LNP encapsulation was an art-recognized administration methodology as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘809 patent claim so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 10,988,754 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘754 patent claims drawn to a method of treating a subject comprising administering an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further administer SEQ ID NO:85 claimed in the instant case when practicing the method of the ‘754 patent claims in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘754 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘754 patent claims in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the RNA of the ‘754 patent claims in an LNP for administration to the subject because such LNP encapsulation was an art-recognized administration methodology as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘754 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,078,247 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘247 patent claims drawn to a method of treating hereditary spastic paraplegia in a subject comprising administering an RNA (“mRNA” or “a replicon RNA”) encapsulated in an LNP, wherein the RNA comprises a 5’ cap, 5’-UTR, ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘247 patent claims in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA for improved treatment effect of treating hereditary spastic paraplegia because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘247 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘247 patent claims in order to further reduce immune responses, thereby further improving the protein expression encoded by the administered RNA in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 11,141,474 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘474 patent claim drawn to a method of treating a subject comprising administering an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further administer SEQ ID NO:85 claimed in the instant case when practicing the method of the ‘474 patent claim in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘474 patent claim. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘474 patent claim in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the RNA of the ‘474 patent claim in an LNP for administration to the subject because such LNP encapsulation was an art-recognized administration methodology as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘474 patent claim so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,141,476 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘476 patent claims drawn to a method of treating MERS coronavirus infection in a subject comprising administering a composition comprising an mRNA encoding an antigenic protein for “stimulating a humoral immune response to the antigenic protein”, wherein the mRNA is associated with an LNP and comprises a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘476 patent claims in order to prevent reduction of the expression of the antigen encoded by the administered RNA for improved treatment effect of treating MERS coronavirus infection because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘476 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘476 patent claims in order to further reduce immune responses, thereby further improving the antigen expression encoded by the administered RNA in view of the teachings of Kariko. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘476 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-18 of U.S. Patent No. 11,254,951 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘951 patent claims drawn to a method of treating a subject comprising administering an RNA comprising a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further administer SEQ ID NO:85 claimed in the instant case when practicing the method of the ‘951 patent claims in order to prevent reduction of the expression of the polypeptide encoded by the administered RNA because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘951 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘951 patent claims in order to reduce immune responses in view of the teachings of Kariko, and furthermore, it would also have been obvious to formulate the RNA of the ‘951 patent claims in an LNP for administration to the subject because such LNP encapsulation was an art-recognized administration methodology as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘951 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,464,836 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘836 patent claims drawn to a method of treating liver fibrosis in a subject comprising administering an RNA (e.g., “an mRNA” or “a replicant RNA”) encapsulated in an LNP, wherein the RNA comprises a 5’ cap, 5’-UTR, ORF, 3’-UTR, and a polyA and is modified with 1-methyl-pseudouridine.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘836 patent claims in order to further prevent reduction of the expression of the polypeptide encoded by the administered RNA modified with 1-methyl-pseudouridine for improved treatment effect of treating liver fibrosis because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the 1-methyl-pseudouridine-modified RNA administered in the ‘836 patent claims. It would also have been obvious to incorporate the modification, 1-methyl-pseudouridine, in any of the 5’-UTR, ORF, 3’-UTR, and a polyA as the ‘836 patent claims do not expressly require a specific position of the modification in the RNA.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-18 of U.S. Patent No. 11,464,847 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘847 patent claims drawn to a method of treating lassa infection in a subject comprising administering a composition comprising an mRNA encoding a GPC of a lassa virus complexed with an LNP, wherein the mRNA comprises a 5’ cap, 5’-UTR, ORF, 3’-UTR, and a polyA
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘847 patent claims in order to prevent reduction of the expression of the GPC of a lassa virus encoded by the administered RNA for improved treatment effect of treating lassa infection because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘847 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘847 patent claims in order to further reduce immune responses, thereby further improving the antigen expression encoded by the administered RNA in view of the teachings of Kariko. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘847 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,478,552 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘552 patent claims drawn to a method of treating a subject comprising administering a composition comprising an RNA (“mRNA”, “replicon RNA”) complexed with an LNP.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘552 patent claims in order to prevent reduction of the expression of the protein encoded by the administered RNA for improved treatment effect because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘552 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the mRNA of the ‘552 patent claims in order to further reduce immune responses, thereby further improving the protein expression encoded by the administered RNA in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-6 of U.S. Patent No. 11,865,084 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘084 patent claims drawn to a method of treating MERS coronavirus infection in a subject comprising administering a composition comprising an mRNA encoding a spike protein, wherein the mRNA is associated with an LNP and comprises a 5’ cap, 5’-UTR, an ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘084 patent claims in order to prevent reduction of the expression of the spike protein encoded by the administered RNA for improved treatment effect of treating MERS coronavirus infection because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘084 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the RNA of the ‘084 patent claims in order to further reduce immune responses, thereby further improving the antigen expression encoded by the administered RNA in view of the teachings of Kariko. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘084 patent claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,227,549 B2 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘549 patent claims drawn to a method of treating propionic acidemia in a subject comprising administering a composition comprising an RNA (“mRNA”, “replicon RNA”) encoding a protein formulated in an LNP, wherein the RNA comprises a 5’ cap, 5’-UTR, ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘549 patent claims in order to prevent reduction of the expression of the protein encoded by the administered RNA for improved treatment effect of treating propionic acidemia because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the administered RNA in the ‘549 patent claims. It would also have been obvious to incorporate art-recognized modified nucleotides such as 1-methyl-pseudouridine in any of the 5’-UTR, an ORF, 3’-UTR, and a polyA of the mRNA of the ‘549 patent claims in order to further reduce immune responses, thereby further improving the protein expression encoded by the administered RNA in view of the teachings of Kariko.
Claims 115-130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-41 of copending Application No. 17/136,724 (now allowed) in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Note that this rejection will change to a non-provisional rejection once an issue fee is paid in the ‘724 application.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘724 claims drawn to a method of expressing a biologically active polypeptide in a subject comprising administering a pharmaceutical composition comprising an RNA (“mRNA”) encoding a protein, wherein the RNA comprises a 5’ cap, a 5’-UTR, a coding sequence, a 3’-UTR, and a polyA, and the RNA is modified with 1-methyl-pseudouridine.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the pharmaceutical composition of the ‘724 claims in order to further prevent reduction of the expression of the polypeptide encoded by the administered RNA modified with 1-methyl-pseudouridine for improved polypeptide expression because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as an antagonist of TLR7/8, thereby reducing immune responses, which would in turn help improve the protein expression level encoded by the 1-methyl-pseudouridine-modified RNA administered in the ‘724 claims. It would also have been obvious to incorporate the modification, 1-methyl-pseudouridine, in any of the 5’-UTR, ORF, 3’-UTR, and a polyA as the ‘724 claims do not expressly require a specific position of the modification in the RNA. It would also have been obvious to formulate the pharmaceutical composition of the ‘724 claims in an LNP for administration to the subject because an LNP formulation was an art-recognized pharmaceutical formulation for RNA administration as evidenced by Kariko. It would also have been obvious to further include Schmitt’s 9-mer oligonucleotide into the RNA-encapsulated LNP for simultaneous administration of the two agents. It would also have been obvious to utilize a replicating viral vector comprising a modified nucleotide as the carrier of the RNA administered in the ‘724 claims so as to deliver the RNA to the subject without causing immunogenicity in view of the teachings of Kariko.
Claims 115-130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 82-83 of copending Application No. 19/218,992 in view of Kariko et al. (US 2013/0197068 A1) and Schmitt et al. (RNA, 2017, 23:1344-1351, applicant’s citation).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are an obvious variation of the ‘992 claims drawn to a method of treating a subject comprising administering a pharmaceutical composition comprising an mRNA encoding a protein encapsulated in an LNP, wherein the mRNA comprises a 5’ cap, 5’-UTR, ORF, 3’-UTR, and a polyA.
It would have been obvious to further include SEQ ID NO:85 claimed in the instant case in the LNP of the ‘992 claims in order to prevent reduction of the expression of the protein encoded by the administered RNA for improved treatment effect because it was known in the art that RNA administration induces innate immune responses that contribute to reduction in protein expression encoded by the RNA as taught by Kariko, and because one skilled in the art would have reasonably deemed Schmitt’s 9-mer oligonucleotide that is identical to SEQ ID NO:85 claimed in the instant case function as