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 Group I, claims 1, 4, 6, 7, 10-14, 16-18, 31 in the reply filed on 07/21/2025 is acknowledged.
Claims 23-24, 32-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/21/2005.
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 1, 4, 6, 7, 10-14, 16-18, 31 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.
Claims are broadly drawn to engineered nucleic acids whose nucleotide sequence includes a sequence element that is or is a complement of an oncoselective translation sequence element, wherein the oncoselective translation sequence element is or comprises an oncoselective read-through motif comprising a sequence selected from the group comprising: VNNNNNNMNNMWK, NNNVWNNKGHHNH, DVHVNNNCWNNNB, MWBNNNNNNNNNN, WGNNSNHNHDNNN, VNNNNNNMNNMWK or VMNNWNKNNNNNN, wherein V stands for A, C or G, M stands for A or C, W stands for A or T/U, K stands for G or T/U, H stands for A, C or T/U, D stands for A,G or T/U, B stands for C, G or T/U, S stands for G or C, N stands for any nucleotide; and wherein the oncoselective read-through motif is within or upstream of an open reading frame and directs read-through of mRNA stop codons specifically in cancer cells relative to appropriately comparable non-cancer cells.
Claims encompass a wide and varied genus of nucleic acids comprising an oncoselective motif, which can be as short as only 3 specific nucleotides such as in MWBNNNNNNNNNN, such motif located upstream or within of an open reading frame and directs read-through of mRNA stop codons specifically in cancer cells relative to appropriately comparable non-cancer cells.
Instant specification presents evidence of specific sequences (see Table 1) carrying out the claimed oncoselective function, which are much longer than consensus sequences from instant claim 1, further pointing out that oncoselective motif forms a complex secondary structure (see paragraph [0168]), such structure is important for the motif functionality. Example 3 shows that a specific sequence comprising motifs claimed provides oncoselectivity in lung cancer cells. Table 2 presents oncoselective motifs as claimed with corresponding specific sequences, each motif represented by only one specific sequence. It is not clear if the same motif included in a different sequence would possess the required oncoselective function. No evidence is shown that the same sequences will be oncoselective in any different type of cancer cells than lung cells. There is no evidence that sequence complementary to oncoselective motif as claimed will be oncoselective as well.
Specification does not describe structure for representative species of Applicant’s broadly claimed genus. Thus their function of oncoselectivity is either unknown or unpredictable.
The genus encompasses a large number of unknown structures and one of skilled in the art cannot reliably predict which member of the genus would successfully be oncoselective, and which will not.
There is no description of the necessary and sufficient elements of the species encompassed by the breadth of the claims.
The only species described in specification are sequences in Table 2. Applicant fails to describe representative members of Applicant's broadly claimed genus.
One of the skill in the art would not recognize that Applicant was in possession of the necessary common attributes or features of the genus in view of the disclosed species. Since the disclosure fails to describe the common attributes that identify members of the genus, and because the genus is highly variant, sequences in Table 2 are not sufficient to describe the claimed genus. Therefore, given the lack of written description in the specification with regard to the structural and functional characteristics of the claimed compositions, it is not clear that Applicant was in possession of the claimed genus at the time this application was filed.
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.
Claim 6 recites the limitation "the downstream flanking sequence" in the third line. There is insufficient antecedent basis for this limitation in the claim.
For the purpose of examination it will be considered that claim 6 depends on claim 4, but appropriate correction is required.
The term “preferably” in claim 6 is a relative term which renders the claim indefinite. The term “preferably” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear if the term “preferably” is required in the claim 6, making metes and bounds of the claim indefinite.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 4, 10, 16-18, 31 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural product without significantly more. The claim(s) recite(s) engineered nucleic acids whose nucleotide sequence includes a sequence element that is or is a complement of an oncoselective translation sequence element, wherein the oncoselective translation sequence element is or comprises an oncoselective read-through motif comprising a sequence selected from the group comprising: VNNNNNNMNNMWK, NNNVWNNKGHHNH, DVHVNNNCWNNNB, MWBNNNNNNNNNN, WGNNSNHNHDNNN, VNNNNNNMNNMWK or VMNNWNKNNNNNN, wherein V stands for A, C or G, M stands for A or C, W stands for A or T/U, K stands for G or T/U, H stands for A, C or T/U, D stands for A,G or T/U, B stands for C, G or T/U, S stands for G or C, N stands for any nucleotide. Instant specification does not provide specific definition of “engineered” nucleic acid, therefore in light of broadest reasonable interpretation any synthetic nucleic acid can be considered “engineered”. For example, natural mRNA encoding p53 protein (see GenBank AB082923.1, 2003, pages 1-2), which is a suicide protein according to instant specification paragraph [0115], comprises CAC sequence (shown below in bold) with upstream and downstream flanking regions:
1 cgtgctttcc acgacggtga cacgcttccc tggattggcc agactgcctt ccgggtcact
61 gccatggagg agccgcagtc agatcctagc gtcgagcccc ctctgagtca ggaaacattt
Such CAC sequence satisfies requirements of instant oncoselective motif MWBNNNNNNNNNN, therefore such mRNA satisfies structural requirements of instant claims 1, 4, 10, 16-18. Claim 31 simply claims oncoselective motif such as above, therefore such CAC sequence satisfies structural requirements of the claim. Such mRNA or CAC sequence are compositions of matter, therefore satisfying Step 1 of 101 eligibility analysis. Further, such mRNA or CAC sequence are products of nature, satisfying Step 2A Prong One of eligibility analysis. Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S.576, 589-90 (2013) (naturally occurring things are “products of nature” which cannot be patented). Accordingly, the claims recite a judicial exception, and the analysis must therefore proceed to Step 2A Prong Two. For analysis in this Step this judicial exception is not integrated into a practical application because claims are drawn to simple products. Because the recited judicial exception is not integrated into practical application, the claims are still directed to judicial exception. Proceeding to Step 2B of eligibility analysis the claim(s) do not include additional elements that are sufficient to amount to significantly more than the judicial exception because other limitations in the claims simply define a location of oncoselective motif or include nucleic acid in pharmaceutical compositions, which are not sufficient to amount to significantly more.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 16, 31 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by GenBank AB082923.1, 2003, pages 1-2.
Concerning claims 1, 16, 31 GenBank AB082923.1 presents mRNA sequence of p53 protein (see pages 1-2), such protein is a suicide protein according to instant specification paragraph [0115], comprises CAC sequence (shown below in bold) with upstream and downstream flanking regions:
1 cgtgctttcc acgacggtga cacgcttccc tggattggcc agactgcctt ccgggtcact
61 gccatggagg agccgcagtc agatcctagc gtcgagcccc ctctgagtca ggaaacattt
Such CAC sequence satisfies requirements of instant oncoselective motif MWBNNNNNNNNNN, therefore such mRNA satisfies structural requirements of instant claims 1, 16, 31. The functional limitation of claim 1 of read-through of mRNA stop codon is expected to happen in the absence of evidence to the contrary.
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.
Claim(s) 16-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al (WO 2018/089688, May 2018) and in further view of GenBank AB082923.1, 2003, pages 1-2, above.
Shi et al teach delivery of p53 mRNA using nanoparticles (see lines 19-23 on page 20).
Shi et al do not teach the presence of MWBNNNNNNNNNN motif in the mRNA delivered.
Teachings of GenBank AB082923.1 are discussed above.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to deliver mRNA taught by GenBank AB082923.1 using nanoparticles taught by Shi et al. One of the ordinary skill in the art would be motivated to do so because Shi et al teach delivery of p53 mRNA using nanoparticles and GenBank AB082923.1 teach one of such mRNA sequences.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 4, 6, 7, 10-14, 16-18, 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/269,258 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘258 recite methods of transcription of mRNA comprising oncoselective motifs. Using specification as a dictionary to define what such motifs can be, paragraph [0050] of ‘258 specification recites motifs identical to instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 4, 6, 7, 10-14, 16-18, 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 8, 10-12, 14-15, 18, 21-23, 26, 32, 45-46, 50, 53, 57 of copending Application No. 18/656,385 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims from ‘385 recite engineered nucleic acids of SEQ ID NOs: 41-110, which comprise oncoselective motifs identical to instantly claimed.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637