DETAILED ACTION
The amendment filed on 01/12/2026 has been entered. New matter was added to claim 1 (see 35 U.S.C. 112 (a) rejection below)
Claims 1-9 and 11-19 are pending.
Claim 10 was canceled.
Claims 1-9 and 11-19 are pending and currently under examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/12/2026 has been entered.
Priority
This application is a U.S. National Phase Application of PCT Application No. PCT/EP2020/065980, filed June 9, 2020, which is a CON of U.S. Application No. 16/440,511, filed June 13, 2019.
Claim Objections
Claim 13 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112 (new matter)
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 1-9 and 11-19 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.
The claims are broadly drawn to “A method comprising: formulating a concatemer mixture comprising at least a first nucleic acid concatemer and a second nucleic acid concatemer having a predefined ratio to one another, wherein the first nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the second nucleic acid concatemer comprises tandem repeats of a second nucleic acid sequence; and co-expressing the concatemer mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence, wherein the first expression product is a nucleic acid product and the second expression product is a protein product and wherein the first expression product facilitates expression of the second expression product without being translated to protein.”.
Relevant to the lack of particular structural limitations in the rejected claims drawn to “the first expression product facilitates expression of the second expression product without being translated to protein.”, MPEP 2163 states:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art.
Additionally, at 2163IIA3(a), the MPEP states:
“…describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene “because it is only an indication of what the gene does, rather than what it is.”); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “[w]ithout such disclosure, the claimed methods cannot be said to have been described.”).
In the case of the instant claims, the functionality of a nucleic acid product facilitating protein expression without being translated to protein is a critical feature of the claimed methods.
The specification teaches:
[00109] In some embodiments, the expression sequence contains a non-coding sequence, wherein the non-coding sequence generates a desired RNA expression product. Such expression sequence does not contain any coding sequence. The non-coding sequence comprises a promoter and a transcription termination sequence. The non-coding sequence is generally devoid of an open reading frame. The expression sequence that contains a non-coding sequence is also referred to as an RNA expression sequence. In some embodiments, the expression sequence consists essentially of a noncoding sequence. In some other embodiments, the expression sequence includes both the coding and non- coding sequences, wherein the RNA can be generated from a non-coding sequence of an expression sequence. In such embodiments, a desired protein may also be subsequently generated from the coding sequence of the same expression sequence. In some embodiments, the generated RNA may be extracted from the eukaryotic cells for different downstream applications. In one embodiment, the extracted RNA may subsequently be packaged into a lentivirus system to deliver in another cell. The non-coding sequence may include, but is not limited to, a sequence for antisense RNA, a short interfering RNA (siRNA), a short hairpin RNA (shRNA), a microRNA (miRNA), a microRNA mimic, a transfer RNA (tRNA), a ribosomal RNA (rRNA), or combinations thereof. The non- coding sequence may also include CRISPR RNAs (tracrRNA, crRNA, sgRNA, or gRNA), small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Piwi interacting RNA (piRNA), telomerase RNA, spliceosome RNA, enhancer RNA, retrotransposons, X inactive specific transcript (Xist), RNAs encoded by RNA polymerase I and RNA polymerase III, or combinations thereof.
However, the specification does not explicitly teach the structure of any nucleic acid product capable of facilitating protein expression without being translated to protein.
While the skilled artisan may be capable of making a nucleic product with the claimed functionality of facilitating protein expression without being translated to protein, possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims encompass a genus of structurally undefined nucleic acid products.
For claims drawn to a genus, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. Further, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 held that:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“ [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Thus considering the breadth of the compounds required by the claimed methods, their specific required functionalities, and the teachings of the instant specification, it is the conclusion that the specification does not provide an adequate written description of the broadly claimed subject matter.
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 1, 9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.).
Goldsmith discloses a method related to concatemers of cassettes of nucleotide sequences and methods for preparing said concatemers. In a further aspect, the invention relates to a transgenic host cell comprising at least one concatemer according to the invention, and to a method for the preparation of said transgenic host cell. Finally, the present invention relates to a vector comprising a nucleotide cassette, a method for preparing said vector, a nucleotide library comprising at least two vectors each comprising a nucleotide cassette, a method for preparing said library (Abstract).
Regarding claim 1, Goldsmith teaches a method wherein “ A concatemer according to the present invention may comprise a selection of expressible nucleotide sequences” (e.g., Para 13) and “concatemers can be assembled in a mixture” (e.g., Para 21). “a selection of expressible nucleotide sequences” reads on selection of one or more expressible nucleotide sequences. “concatemers can be assembled in a mixture” reads on more than one concatemer is present in a mixture. Thus, Goldsmith teaches a method wherein formulating a concatemer mixture comprising at least a first nucleic acid concatemer and a second nucleic acid concatemer.
“Concatemer” reads on a DNA molecule containing covalently joined, head-to-tail repeats of a unique base sequence as evidenced by Skalka (e.g., Abstract). Goldsmith teaches “Concatemers are used to represent a number of tandemly linked nucleotide cassettes, where at least two tandemly linked nucleotide units have the basic structure” (Para. 121). Thus, Goldsmith teaches a method wherein the first nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the second nucleic acid concatemer comprises tandem repeats of a second nucleic acid sequence.
Regarding claim 1, Goldsmith teaches “a concatemer comprising a number of cassettes is introduced into a host cell capable of maintaining the concatemer and co-expressing an expressible nucleotide sequence” (e.g., Para 188). The number of cassettes reads on one or more. Thus, Goldsmith teaches a method wherein co-expressing the concatemer mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence.
However, Goldsmith does not teach “having a predefined ratio to one another” (claim 1) and “first expression product is a nucleic acid product and the second expression product is a protein product and wherein the first expression product facilitates expression of the second expression product without being translated to protein.” (claim 1).
Qu discloses methods of transducing/transfecting cells with a molecule, such as a nucleic acid (e.g., plasmid), at high efficiency. Such high efficiency transduced cells can, when transduced with a nucleic acid (plasmid) that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, can produce protein and/or transcript at high efficiency. Additionally, such cells when transduced with sequences, such as plasmids that encode viral packaging proteins and/or helper proteins and a transgene that encodes a protein or is transcribed into a transcript of interest, can produce recombinant vectors that include the transgene that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, which in turn produces recombinant viral vectors at high yield (Abstract).
Regarding claim 1, Qu teaches “plasmids (i) and (ii) are in a molar ratio range of about 1:0.01 to about 1:100, or are in a molar ratio range of about 100:1 to about 1:0.01” (Para. 22). Qu also teaches “A vector nucleic acid sequence generally contains at least an origin of replication for propagation in a cell and optionally additional elements, such as … ITR(s)... For purposes of the invention, a "vector" as set forth herein is within the scope of a "plasmid" as this term is used herein” (Para.153). Plasmid (i) and (ii) read on a first and second concatemer comprising a tandem repeat nucleic acid sequence. Thus, Goldsmith and Qu teach concatemer having a predefined ratio to one another, wherein the first nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the second nucleic acid concatemer comprises tandem repeats of a second nucleic acid sequence.
Regarding claim 1, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5). Plasmids encoding proteins reads on plasmids deemed to express the encoded protein. The transgene is able to be interpreted as containing nucleic acids. “transcribed into transcript of interest” reads on nucleic acid product. Furthermore, Qu teaches “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” (Para. 123) “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” reads on nucleic acid product capable of facilitating expression of a nucleic acid product. Thus, Goldsmith and Qu teach a method wherein the first expression product is a nucleic acid product and the second expression product is a protein product and wherein the first expression product facilitates expression of the second expression product without being translated to protein.
Goldsmith and Qu are both considered to be analogous to the claimed invention because they are in the same field of genetic engineering. Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of formulation and co-expression of a concatemer mixture as taught by Goldsmith to incorporate the method comprising concatemers at a predefined molar ratio range, wherein the first expression product is a nucleic acid product and the second expression product is a protein product as taught by Qu and provide a method according to the limitations of claim 1. Doing so would provide a mixture for co-expression of a nucleic acid transcript of interest and protein of interest with the reasonable expectation of ratiometric control of product expression levels.
The teachings of Goldsmith and Qu are documented above in the rejection of claim 1 under 35 U.S.C. 103. Claims 9 and 11-12 depends on claim 1.
Regarding claim 9, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5) and “thereby making transfected cells that produce recombinant rAAV vector” (Para. 5). Plasmids encoding proteins reads on plasmids deemed to express the encoded protein. Thus, Goldsmith and Qu teach wherein the first expression product is an envelope or packing protein of a virus and the second expression product comprises a transgene of the virus, wherein the first expression product and the second expression product form a viral vector for delivering the transgene.
Regarding claim 11, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5) and “thereby making transfected cells that produce recombinant rAAV vector” (Para. 5). Packaging proteins reads on expressed encapsulating proteins. Transgene reads on gene payload incorporated into rAAV or expressed RNA transcript (cargo) either of which are able to be encapsulated within (forms a complex with) expressed packaging proteins. Thus, Qu teaches a method wherein the first expression product forms a complex with the second expression product.
Regarding claim 12, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5) and “thereby making transfected cells that produce recombinant rAAV vector” (Para. 5). “One or more plasmids” reads on three concatemers in the context of claim 12, in which the transgene containing concatemer would express a nucleic acid product. “mixture of components” allows for the components to act on one another. Thus, Qu teaches a method wherein the first expression product acts on a third nucleic acid concatemer in the concatemer mixture.
Response to Arguments
Applicant's arguments filed 1/12/2026 (Pg. 6-8) with respect to claims 1, 9 and 11-12 have been fully considered but are moot because the arguments filed 1/12/2026 do not apply to the new grounds of rejections. To clarify some instances argued in the response filed 1/12/2026 that remains relevant to the new grounds of 103 rejection documented in this Non-Final Office Action, examiner's responses to each relevant argument made by Applicant are provided below:
Applicants’ argument: “Goldsmith and Qu do not disclose or suggest a concatemer co-expressed into a first expression product from a first nucleic acid sequence and a second expression product from a second nucleic acid sequence, where the first expression product is a nucleic acid product and the second expression product is a protein product, and that the first expression product facilitates expression of the second expression product without being translated to protein.”
Response: Applicant's arguments filed 1/12/2026 do not apply to the new grounds of rejections.
Applicants’ argument: “Qu does not disclose or suggest co-expression of a defined ratio of a concatemer comprising tandem repeats of a first nucleic acid encoding a first expression product that is a nucleic acid product and a concatemer comprising tandem repeats of a second nucleic acid encoding a second expression product that is a protein product.”
Response: In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant’s argument: “Qu's transgene, which is expressed as an RNA transcript of interest, is not a nucleic acid product that facilitates expression of the protein expression product without being translated as a protein, as currently claimed. Qu provides examples of nucleic acid transcripts that are RNA and inhibitory to impede expression of proteins. (Qu, paragraphs [0123]-[0124]). Qu therefore necessarily teaches away from a nucleic acid expression product as claimed, because the nucleic acid transcript of Qu inhibits, rather than facilitates, expression of protein as required by Applicant's amended claims.”
Response: Applicant’s arguments have been fully considered and found unpersuasive because as stated on Pg. 10 of this non-final office above and admitted in the argument filed on 01/12/206. Qu provides examples of nucleic acid transcripts that are RNA (Para. 123-124) As recited in Qu, “[0123] A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA, such as inhibitory RNA (RNAi, e.g., small or short hairpin (sh)RNA, microRNA (miRNA), small or short interfering (si)RNA, trans-splicing RNA, or antisense RNA). [0124] Non-limiting examples include inhibitory nucleic acids that inhibit expression”. “can be RNA” reads on any RNA molecule including RNA that facilitates protein expression. “Non-limiting examples” reads on the examples listed do not limit the scope of the aforementioned transcript that can be RNA. Therefore, Qu does not teach away from a nucleic acid expression product according to the claims, because the nucleic acid transcript of Qu is not limited to inhibition, thus a RNA is capable of facilitating expression of the second expression product without being translated to protein as required by Applicant's amended claims.
Claims 2-5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.), as applied to claim 1 above, and further in view of Nelson et al. (“Nelson”, Patent App. Pub. No. US 20170321239 A1, November 9, 2017, US Patent App. 15/145838).
The teachings of Goldsmith and Qu are documented above in the rejection of claims 1, 9 and 11-12 under 35 U.S.C. 103. Claims 2, 4-5 and 7 depend on claim 1. Claim 3 depends on claim 2, which depends on claim 1. However, Goldsmith and Qu do not explicitly teach “generating the first nucleic acid concatemer and the second nucleic acid concatemer using rolling circle amplification” (claim 2).
Nelson discloses methods for in vitro transcription and translation from an RCA product are provided. The methods comprise providing a double-stranded RCA product, wherein the double-stranded RCA product consists essentially of tandem repeats of a minimalistic expression sequence. The methods further comprise expressing a protein from the double-stranded RCA product in a cell-free expression system.
Regarding claim 2, Nelson teaches “rolling circle amplification generates RCA products that are tandem repeat units (concatemers) of the template nucleic acid sequence” (e.g., Para. 5) Thus, Nelson teaches a method comprising generating the first nucleic acid concatemer and the second nucleic acid concatemer using rolling circle amplification.
Goldsmith, Qu and Nelson are considered to be analogous to the claimed invention because they are in the same field of genetic engineering. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the known method of amplification of circular DNA comprising tandem repeats by a method of RCA as taught by Nelson to the formulation of a concatemer mixture at a predefined ratio and co-expression of the concatemers as taught by Goldsmith and Qu according to the limitations of claim 2 to have yielded the predictable result of amplification of each circular or plasmid DNA in preparation for co-expression of the RCA products/concatemer.
Regarding claim 3, Nelson teaches a method wherein “DNA mini-circle 14 is amplified by RCA. The amplification reaction generates a concatemer RCA product 16 having tandem repeat units of the expression construct 10” (e.g., Para. 59; Fig 1. element 16; Para. 25). Thus, Nelson teaches a method comprising using the rolling circle amplification to amplify circular or plasmid DNA to generate the first nucleic acid concatemer and/or the second nucleic acid concatemer.
Regarding claim 4, Nelson teaches a method wherein “DNA mini-circle 14 is amplified by RCA. The amplification reaction generates a concatemer RCA product 16 having tandem repeat units of the expression construct 10” (e.g., Para. 59; Fig 1. element 16; Para. 25). Thus, Nelson teaches a method wherein the first tandem repeats and/or the second tandem repeats are tandem repeats of at least a portion of the circular or plasmid DNA.
Regarding claim 5, Nelson teaches a method of “improved cell-free protein expression systems that involve in vitro transcription and translation of the rolling circle amplification product.” (e.g., Para. 2; Para. 26). Thus, Nelson teaches a method comprising transfecting cultured cells with the concatemer mixture to cause the co-expressing or wherein the co-expressing is in a cell-free expression system.
Regarding claim 7, Nelson teaches a method wherein the expressed proteins were collected from cell-free expression reactions (e.g., Para. 77). Thus, Nelson teaches a method comprising collecting the first expression product and the second expression product.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.), as applied to claim 1 above, and further in view of Nakai et al. (“Nakai” WO Patent App. Pub. No. WO 0166782 A1, September 13, 2001).
The teachings of Goldsmith and Qu are documented above in the rejection of claims 1, 9 and 11-12 under 35 U.S.C. 103. Claims 2, 4-5 and 7 depend on claim 1. Claim 3 depends on claim 2, which depends on claim 1. However, Goldsmith and Qu do not explicitly teach wherein the first nucleic acid concatemer, the second nucleic acid concatemer, or both are over 10kb in length.
Nakai discloses a method for introducing an expression cassette into a cell using a population, plurality or collection of at least two distinct adeno-associated 25 viral vectors.
Regarding claim 6, Nakai teaches a method wherein the expression cassettes may range in length from about 5 to 20 kb (e.g., Pg. 5 ln 4-5). Expression cassette reads on long nucleic acid sequences as suggested on Pg.1 ln 33. It is interpreted that if a nucleotide sequence can be over 10 kb, then the concatemer comprising the cassette is over 10 kb. Thus, Nakai teaches a method wherein the first nucleic acid concatemer, the second nucleic acid concatemer, or both are over 10kb in length.
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising the formulation of a concatemer mixture at a predefined ratio and co-expression of the concatemers as taught by Goldsmith and Qu to incorporate the teachings of the of length expression cassette ranging from about 5 to 20 kb as taught by Nakai, according to the limitations of claim 6. Doing so would improve methods of gene transfer allowing for the transfer of longer expression cassettes or gene of interest.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.), as applied to claim 1 above, and further in view of Nelson et al. (“Nelson” US Patent App. Pub. US 20100008939 A1, January 14, 2010).
The teachings of Goldsmith and Qu are documented above in the rejection of claim 1, 9 and 11-12 under 35 U.S.C. 103. Claims 2, 4-5 and 7 depend on claim 1. Claim 3 depends on claim 2, which depends on claim 1. However, Goldsmith and Qu do not explicitly teach one or both of the first nucleic acid concatemer or the second nucleic acid concatemer is unprocessed before the co-expressing.
Nelson discloses a method that relates generally to DNA replication and to the use of an unprocessed (non-cleaved, non-circularized, and non-supercoiled) rolling circle amplification (RCA) product. Such use comprises, for example, use in the production of a DNA vaccine, in the elicitation of an immune response in an organism, and in the transfection of a living cell (Abstract).
Regarding claim 8, Nelson teaches “embodiments of the invention provide methods related to, and compositions comprising, unprocessed (i.e., not deliberately or intentionally cleaved, circularized, and/or supercoiled) rolling circle amplification (RCA) product”(e.g., Para. 6; Para. 18). “(RCA) product” reads on concatemer. Thus, Nelson teaches a method wherein one or both of the first nucleic acid concatemer or the second nucleic acid concatemer is unprocessed before the co-expressing.
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising the formulation of a concatemer mixture at a predefined ratio and co-expression of the concatemers as taught by Goldsmith and Qu to incorporate the teachings of unprocessed RCA product (concatemer) as taught by Nelson, according to the limitations of claim 8. Doing so would decrease the time and expense to the produce an RCA product suitable for use in expression or therapeutic application.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.)
Goldsmith discloses a method related to concatemers of cassettes of nucleotide sequences and methods for preparing said concatemers. In a further aspect, the invention relates to a transgenic host cell comprising at least one concatemer according to the invention, and to a method for the preparation of said transgenic host cell. Finally, the present invention relates to a vector comprising a nucleotide cassette, a method for preparing said vector, a nucleotide library comprising at least two vectors each comprising a nucleotide cassette, a method for preparing said library (Abstract).
Regarding claim 13, Goldsmith teaches a method wherein “ A concatemer according to the present invention may comprise a selection of expressible nucleotide sequences” (e.g., Para 13) and “concatemers can be assembled in a mixture” (e.g., Para 21). “a selection of expressible nucleotide sequences” reads on selection of one or more expressible nucleotide sequences. “concatemers can be assembled in a mixture” reads on more than one concatemer is present in a mixture. Thus, Goldsmith teaches a method wherein “ formulating a concatemer mixture comprising at least two nucleic acid concatemers.
“Concatemer” reads on a DNA molecule containing covalently joined, head-to-tail repeats of a unique base sequence as evidenced by Skalka (e.g., Abstract). Goldsmith teaches “Concatemers are used to represent a number of tandemly linked nucleotide cassettes, where at least two tandemly linked nucleotide units have the basic structure” (Para. 121) . Thus, Goldsmith teaches a method wherein “wherein each of the nucleic acid concatemers comprises tandem repeats of two or more nucleic acid sequences.”
Goldsmith teaches “a concatemer comprising a number of cassettes is introduced into a host cell capable of maintaining the concatemer and co-expressing an expressible nucleotide sequence” (e.g., Para 188). The number of cassettes reads on one or more. Thus, Goldsmith teaches a method wherein “co-expressing the concatemer mixture to generate two or more expression products from each nucleic acid concatemer in the mixture.”
However, Goldsmith does not explicitly teach “concatemers in a predefined ratio” (claim 13).
Qu discloses methods of transducing/transfecting cells with a molecule, such as a nucleic acid (e.g., plasmid), at high efficiency. Such high efficiency transduced cells can, when transduced with a nucleic acid (plasmid) that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, can produce protein and/or transcript at high efficiency. Additionally, such cells when transduced with sequences, such as plasmids that encode viral packaging proteins and/or helper proteins and a transgene that encodes a protein or is transcribed into a transcript of interest, can produce recombinant vectors that include the transgene that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, which in turn produces recombinant viral vectors at high yield (Abstract).
Regarding claim 13, Qu teaches “plasmids (i) and (ii) are in a molar ratio range of about 1:0.01 to about 1:100, or are in a molar ratio range of about 100:1 to about 1:0.01” (Para. 22). Qu also teaches “A vector nucleic acid sequence generally contains at least an origin of replication for propagation in a cell and optionally additional elements, such as … ITR(s)... For purposes of the invention, a "vector" as set forth herein is within the scope of a "plasmid" as this term is used herein” (Para.153). Plasmid (i) and (ii) reads on a fist and second concatemer comprising a tandem repeat nucleic acid sequence. Thus, Goldsmith and Qu teach a method comprising at least two nucleic acid concatamers having a predefined ratio to one another, wherein each of the nucleic acid concatamers comprises tandem repeats of two or more nucleic acid sequences.
Regarding claim 13, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5). Plasmids encoding proteins reads on plasmids deemed to express the encoded protein. The transgene is able to be interpreted as containing nucleic acids. “transcribed into transcript of interest” reads on nucleic acid product. Furthermore, Qu teaches “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” (Para. 123) “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” reads on nucleic acid product capable of facilitating expression of a nucleic acid product. Thus, Goldsmith and Qu teach a method wherein the first expression product is a nucleic acid product and the second expression product is a protein product, and wherein the first expression product facilitates expression of the second expression product without being translated to protein.
Goldsmith and Qu are both considered to be analogous to the claimed invention because they are in the same field of genetic engineering. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising formulation and co-expression of a concatemer mixture as taught by Goldsmith to incorporate a first and second plasmid in a molar ratio range and a plurality of expression sequences as taught by Qu to provide a method according to the limitations of claim 13. Doing so would provide a mixture for co-expression of a nucleic acid transcript of interest and protein of interest with the reasonable expectation of ratiometric control of product expression levels.
The teachings of Goldsmith and Qu are documented above in the rejection of claim 13 under 35 U.S.C. 103. Claim 14 depends on claim 13.
Regarding claim 14, Qu teaches a method wherein “(i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins (e.g., Para. 5 and 69-70). Thus, Goldsmith and Qu teach a method wherein the nucleic acid sequence of an individual concatemer in the concatemer mixture comprises a plurality of expression sequences that, when expressed to generate the two or more expression products, generate a plurality of proteins.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018) and Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.), as applied to claim 13 above, and further in view of Wadsworth et al. (“Wadsworth” US Patent App. Pub. No. US 20020045250 A1, April 18, 2002).
The teachings of Goldsmith and Qu are documented above in the rejection of claims 13 and 14 under 35 U.S.C. 103. Claims 15 depends on claim 13. However, Goldsmith and Qu do not explicitly teach wherein the nucleic acid sequence of an individual concatemer in the concatemer mixture comprises a plurality of expression sequences that, when expressed to generate the two or more expression products, generate a mix comprising at least one protein expression product and at least one nucleic acid expression product.
Wadsworth discloses an invention directed to novel systems for the high level production of purified recombinant adeno-associated virus (rAAV) vector stocks comprising producer cell lines and helper adenoviruses. These systems provide high level production of rAAV vector stocks that are not contaminated by helper viruses or have very minimal contamination with helper virus. The invention is also directed to methods for the production of high yield, purified rAAV vector stocks using the systems of the invention.
Regarding claim 15, Wadsworth teaches a method wherein “a rAAV vector genome and AAV helper genes are provided together on one plasmid” (e.g., Para. 45). The transgene and helper proteins reads on to be expressed. rAAV vector genome reads on a vector comprising a transgene of interest. AAV helper genes reads on to be expressed as helper virus proteins. Thus, Goldsmith, Qu and Wadsworth teach a method wherein the nucleic acid sequence of an individual concatemer in the concatemer mixture comprises a plurality of expression sequences that, when expressed to generate the two or more expression products, generate a mix comprising at least one protein expression product and at least one nucleic acid expression product.
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified method comprising the formulation of a concatemer mixture at a predefined ratio and co-expression of the concatemers as taught by Goldsmith and Qu to incorporate the teachings including a transgene and AAV helper genes in one plasmid as taught by Wadsworth and provide an individual concatemer comprising at least one protein expression product and at least one nucleic acid expression product. Doing so would decrease the number of different concatemers needed in rAAV production.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
Claims 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A) in view of Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018), Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.) and Nelson et al. (“Nelson”, Patent App. Pub. No. US 20170321239 A1, November 9, 2017, US Patent App. 15/145838).
Goldsmith discloses a method related to concatemers of cassettes of nucleotide sequences and methods for preparing said concatemers. In a further aspect, the invention relates to a transgenic host cell comprising at least one concatemer according to the invention, and to a method for the preparation of said transgenic host cell. Finally, the present invention relates to a vector comprising a nucleotide cassette, a method for preparing said vector, a nucleotide library comprising at least two vectors each comprising a nucleotide cassette, a method for preparing said library (Abstract).
Regarding claim 16, Goldsmith teaches a method wherein “A concatemer according to the present invention may comprise a selection of expressible nucleotide sequences” (e.g., Para 13) and “concatemers can be assembled in a mixture” (e.g., Para 21). “a selection of expressible nucleotide sequences” reads on selection of one or more expressible nucleotide sequences. “concatemers can be assembled in a mixture” reads on more than one concatemer is present in a mixture and contacting each other. Thus, Goldsmith teaches a method wherein “contacting the first concatemer with a second concatemer comprising tandem repeats of a second nucleic acid sequence to form a concatemer mixture.
“Concatemer” reads on a DNA molecule containing covalently joined, head-to-tail repeats of a unique base sequence as evidenced by Skalka (e.g., Abstract). Goldsmith teaches “Concatemers are used to represent a number of tandemly linked nucleotide cassettes, where at least two tandemly linked nucleotide units have the basic structure” (Para. 121). Thus, Goldsmith teaches a method wherein “wherein each of the nucleic acid concatemers comprises tandem repeats of two or more nucleic acid sequences.”
Goldsmith teaches “a concatemer comprising a number of cassettes is introduced into a host cell capable of maintaining the concatemer and co-expressing an expressible nucleotide sequence” (e.g., Para 188). The number of cassettes reads on one or more. Thus, Goldsmith teaches a method wherein “co-expressing the concatemer mixture to generate two or more expression products from each nucleic acid concatemer in the mixture.”
However, Goldsmith does not explicitly teach “concatemer mixture having a predefined ratio” and “wherein a ratio of the first expression product to the second expression product is proportional to the predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer in the concatemer mixture, wherein the first expression product is a nucleic acid product and the second expression product is a protein product; and wherein the first expression product facilitates expression of the second expression product without being translated to protein.”.
Qu discloses methods of transducing/transfecting cells with a molecule, such as a nucleic acid (e.g., plasmid), at high efficiency. Such high efficiency transduced cells can, when transduced with a nucleic acid (plasmid) that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, can produce protein and/or transcript at high efficiency. Additionally, such cells when transduced with sequences, such as plasmids that encode viral packaging proteins and/or helper proteins and a transgene that encodes a protein or is transcribed into a transcript of interest, can produce recombinant vectors that include the transgene that encodes a protein or comprises a sequence that is transcribed into a transcript of interest, which in turn produces recombinant viral vectors at high yield (Abstract).
Regarding claim 16, Qu teaches “plasmids (i) and (ii) are in a molar ratio range of about 1:0.01 to about 1:100, or are in a molar ratio range of about 100:1 to about 1:0.01” (Para. 22). Qu also teaches “A vector nucleic acid sequence generally contains at least an origin of replication for propagation in a cell and optionally additional elements, such as … ITR(s)... For purposes of the invention, a "vector" as set forth herein is within the scope of a "plasmid" as this term is used herein” (Para.153). Plasmid (i) and (ii) reads on a first and second concatemer comprising a tandem repeat nucleic acid sequence. Thus, Goldsmith and Qu teach a method comprising at “contacting the first concatemer with a second concatemer comprising tandem repeats of a second nucleic acid sequence to form a concatemer mixture having a predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer”. Plasmid prepared in a molar ratio are interpreted to be expressed proportionally dependent on size of concatemer. Thus, Goldsmith and Qu teach a method, wherein a ratio of the first expression product to the second expression product is proportional to the predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer in the concatemer mixture.
Regarding claims 16, Qu teaches a method that “includes: (a) providing a PEI/plasmid mixture of components (i), (ii) and (iii), in which (i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins; (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5). Plasmids encoding proteins reads on plasmids deemed to express the encoded protein. The transgene is able to be interpreted as containing nucleic acids. “transcribed into transcript of interest” reads on nucleic acid product. Furthermore, Qu teaches “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” (Para. 123) “A nucleic acid or plasmid can also refer to a sequence which produces a transcript when transcribed. Such transcripts can be RNA” reads on nucleic acid product capable of facilitating expression of a nucleic acid product. Thus, Goldsmith and Qu teach a method wherein contacting the first concatemer with a second concatemer comprising tandem repeats of a second nucleic acid sequence to form a concatemer mixture having a predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer; and wherein the first expression product facilitates expression of the second expression product without being translated to protein.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method comprising the formulation and co-expression of a concatemer mixture as taught by Goldsmith to incorporate a first and second plasmid in a molar ratio range as taught by Qu to provide a method according to the limitations of claim 16, with the predictable result of enhancing expression efficiency of an expression product. Doing so would provide a mixture for co-expression of a nucleic acid transcript of interest and protein of interest with the reasonable expectation of ratiometric control of product expression levels.
However, Goldsmith and Qu do not teach “amplifying at least one template comprising a first nucleic acid sequence using strand-displacement rolling circle amplification to a generate a first concatemer comprising tandem repeats of the first nucleic acid sequence”.
Nelson discloses methods for in vitro transcription and translation from an RCA product are provided. The methods comprise providing a double-stranded RCA product, wherein the double-stranded RCA product consists essentially of tandem repeats of a minimalistic expression sequence. The methods further comprise expressing a protein from the double-stranded RCA product in a cell-free expression system.(Abstract)
Regarding claim 16, Nelson teaches a method wherein “rolling circle amplification generates RCA products that are tandem repeat units (concatemers) of the template nucleic acid sequence” (e.g., Para. 5). Nelson teaches RCA may be performed in vitro under isothermal conditions using a suitable nucleic acid polymerase such as Phi29 DNA polymerase. Nelson also teaches suitable polymerases possess strand displacement DNA synthesis ability (e.g., Para. 25). Thus, Goldsmith, Qu and Nelson teach a method comprising amplifying at least one template comprising a first nucleic acid sequence using strand- displacement rolling circle amplification to a generate a first concatemer comprising tandem repeats of the first nucleic acid sequence.
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to have modified method comprising the formulation of a concatemer mixture at a predefined ratio and co-expression of the concatemers as taught by Goldsmith and Qu to incorporate the teachings of rolling circle amplification performed by polymerases that possess strand displacement DNA synthesis ability as taught by Nelson. Doing so would allow for efficient amplification of concatemers.
The teachings of Goldsmith, Qu and Nelson are documented above in the rejection of claim 16 under 35 U.S.C. 103. Claims 17-19 depend on claim 15.
Regarding claim 17, Qu teaches a method wherein “(i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins (e.g., Para. 5 and 69-70). (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5) and “thereby making transfected cells that produce recombinant rAAV vector” (Para. 5). Transgene reads on gene payload incorporated into rAAV or RNA transcript (cargo) either of which are able to be encapsulated within (forms a complex with) expressed packaging proteins. Thus, Qu teaches a method comprising allowing the first expression product to form a complex with the second expression product.
Regarding claim 18, Qu teaches a method wherein one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins” (e.g., Para. 139). AAV reads on adeno-associated virus. Thus, Qu teaches a method wherein the first expression product and the second expression product comprise different viral products from a same virus, such as an adenovirus.
Regarding claim 19, Qu teaches a method wherein “(i) is one or more plasmids comprising nucleic acids encoding AAV packaging proteins and/or nucleic acids encoding helper proteins (e.g., Para. 5 and 69-70). (ii) is a plasmid comprising a transgene that encodes a protein or is transcribed into a transcript of interest” (e.g., Para. 5). “transcribed into a transcript” reads on into an RNA transcript. Thus, Qu teaches a method wherein the first expression product comprises a viral mRNA and the second expression product comprises a plurality of viral packaging proteins.
Response to Arguments
Applicant's arguments filed 1/12/2026 have been fully considered but they are not persuasive. Arguments against Goldsmith, Qu and Skalka on Pg. 6-8 are not persuasive as discussed above.
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, 6, 13 and 16 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 16 and 21 of copending Application. No. 16/440,511. (U.S. Patent App. ‘511) in view of Goldsmith et al. (“Goldsmith”, Foreign Patent App. Pub. No. JP 2004525623 A, August 26, 2004, JP App. No. JP 2002559583 A), Qu et al. (“Qu”, Patent App. No. WO 2018/226887, December 13, 2018), Skalka et al. (“Skalka” “Identification of repeating units in DNA concatemers.” Methods in enzymology vol. 29 (1974): 459-66.) and Nakai et al. (“Nakai” WO Patent App. Pub. No. WO 0166782 A1, September 13, 2001).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed invention is made obvious over the claims of copending Application. No. 16/440,511 in view of Goldsmith, Qu, Skalka and Nakai.
The claims of copending Application. No. 16/440,511 are drawn to:
“1. A method comprising: formulating a concatemer mixture comprising at least a first nucleic acid concatemer and a second nucleic acid concatemer having a predefined ratio to one another, wherein the first nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the second nucleic acid concatemer comprises tandem repeats of a second nucleic acid sequence; and co-expressing the concatemer mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence, wherein the first nucleic acid concatemer, the second nucleic acid concatemer, or both are over 10kb in length, wherein the ratio of first expression product to the second expression product is proportional to the predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer in the concatemer mixture, and wherein the molar ratio of the first concatemer to the second concatemer is between 1:1 and 1:10.”
“16. A method, comprising: amplifying at least one template comprising a first nucleic acid sequence using strand-displacement rolling circle amplification to a generate a first concatemer comprising tandem repeats of the first nucleic acid sequence; contacting the first concatemer with a second concatemer comprising tandem repeats of a second nucleic acid sequence to form a concatemer mixture having a predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer; and co-expressing the concatemer mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence, wherein a ratio of the first expression product to the second expression product is proportional to the predefined ratio of the first nucleic acid concatemer to the second nucleic acid concatemer in the concatemer mixture, wherein the molar ratio of the first concatemer to the second concatemer is between 1:1 and 1:10, and wherein the first concatemer, the second concatemer, or both are over 10kb in length.”
“21. A method comprising: formulating a mixture comprising at least one nucleic acid concatemer and at least one plasmid having a predefined ratio to one another, wherein the at least one nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the at least one plasmid comprises a second nucleic acid sequence; and co-expressing the mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence, wherein the molar ratio of the first concatemer to the plasmid is between 1:1 and 1:10, wherein the first nucleic acid concatemer is over 10kb in length, and wherein the co-expression of the first expression product and the second expression product is ratiometric based on the predefined ratio.”
The teachings of Goldsmith, Qu, Skalka and Nakai are documented above in the rejection of claims 1,6, 9, and 11-14 under 35 U.S.C. 103.
Therefore, the inventions as recited in claims 1, 6, 13 and 16 are prima facie obvious over claims 1, 16 and 21 of the copending Application No. 16/440,511 in view of Goldsmith, Qu, Skalka and Nakai. One of ordinary skill in the art would have had a reasonable expectation of success given the lack of novelty. It would have been obvious to provide a method comprising: formulating a concatemer mixture comprising at least a first nucleic acid concatemer and a second nucleic acid concatemer having a predefined ratio to one another, wherein the first nucleic acid concatemer comprises tandem repeats of a first nucleic acid sequence and wherein the second nucleic acid concatemer comprises tandem repeats of a second nucleic acid sequence; and co-expressing the concatemer mixture to generate a first expression product from the first nucleic acid sequence and a second expression product from the second nucleic acid sequence, according to the limitations recited in claims 1, 6, 13 and 16 of the instant application based on claims 1, 16 and 21 of copending Application No. 16/440,511 in view of Goldsmith, Qu, Skalka and Nakai.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant will consider filing a terminal disclaimer, if appropriate, upon receiving indication that the claims are otherwise allowable. Accordingly, claims 1, 6, 13 and 16 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 16 and 21 of copending U.S. Patent App. No. 16/440,511. because no terminal disclaimer has been filed. Note, that a notice of allowance has been mailed for U.S. Patent App. No. 16/440,511, however no fees have been paid. Once the fees have been paid for U.S. Patent App. No. 16/440,511 allowance, this rejection will be considered rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 16 and 21 of the US patented case.
Conclusion
No claims are in condition for allowance. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KENDRA R VANN-OJUEKAIYE whose telephone number is (571)270-7529. The examiner can normally be reached M-F 9:00 AM- 5:00 PM.
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/KENDRA R VANN-OJUEKAIYE/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682