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 with traverse of Group III in the reply filed on 10/09/2025 is acknowledged. The traversal is on the grounds that both groups are directed to a single inventive concept-namely, the development of an integrated system and process for generating hairpin loop-ended, self-complementary, covalently closed linear DNA vectors, and the resulting DNA molecules produced thereby. Applicant asserts that Group III is directed to process/system claims, while Group IV is directed to product claims stemming therefrom. Applicant has not presented any arguments traversing the restriction of Groups I or II.
In response, the traversal of the restriction between Groups III and IV is found persuasive. Groups III and IV are hereby rejoined and will be examined together as a single invention.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement between Groups I and II, and Groups III and IV (hereby rejoined), the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/09/2025.
Accordingly, upon rejoining of Groups III and IV, claims 31-35 are pending and under consideration.
In view of the above noted partial withdrawal of the restriction requirement, Applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest effective filing date to which the instant application is entitled is 08/06/2021.
Drawings
The drawings are objected to because:
Figure 3 is a schematic diagram showing a recombinant E. coli cell harboring the helper plasmid per paragraph [0032] of the instant specification. The text included in the figure is of insufficient quality to be clearly legible. It would be remedial to increase the image quality such that the text of the figure is clearly legible.
Figure 7 is a schematic diagram of the production process for manufacturing hairpin loop-ended, self-complementary, double-stranded, linear, covalently closed DNA molecules according to one embodiment of the instant invention per paragraph [0036] of the instant specification. The text included in the figure is of insufficient quality to be clearly legible. It would be remedial to increase the image quality such that the text of the figure is clearly legible.
Figure 13 is a schematic representation of the "rolling circle" replication per paragraph [0042] of the instant specification, including a key indicating “Rolling Circle Replication Protein” and “Host DNA Polymerase III.” However, the grayscale colors of said “Rolling Circle Replication Protein” and “Host DNA Polymerase III” are indistinguishable in the drawings as-filed. It would be remedial to update the key of Figure 13 such that the components shown therein are readily distinguishable.
Figure 16 is a schematic diagram of an alternative production process for the manufacturing of hairpin loop-ended, self-complementary, double-stranded, linear, covalently closed DNA molecules described in the instant application per paragraph [0045] of the instant specification. The text included in the figure is of insufficient quality to be clearly legible. It would be remedial to increase the image quality such that the text of the figure is clearly legible.
Figure 20 depicts agarose gel electrophoresis results per paragraph [0049] of the instant specification. Figure 20 also includes a schematic map that is not addressed in the instant specification. It appears that the schematic map may be depicting a queried region of DNA in the agarose gel electrophoresis results depicted herein, with arrow markers indicating primer binding sites. The text included in the map is of insufficient quality to be clearly legible. It would be remedial to increase the image quality such that the text of the map is clearly legible, as well as to amend the instant specification such that it is clear what the schematic map of figure 20 is depicting.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
The term “splitted” (disclosed at paragraphs [0040] and [0041] of the instant specification) is an archaic word that is no generally longer considered proper in standard usage. The proper term is “split.” It would generally be remedial to use “split” in place of “splitted.”
Appropriate correction is required.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 31-35 are objected to because of the following informalities:
Claims 31-35 all recite the preamble of “a [or the] hairpin loop ended self-complementary double-stranded linear covalently closed DNA vector…”, which is grammatically improper, as standard grammatical and/or linguistic conventions require commas separating multiple, sequential adjectives that modify a noun similarly or equally. In order to facilitate interpretation of the instant claim language and in order to comport with standard grammatical and/or linguistic conventions, it would be remedial to amend the instant claim language to recite, for example, “a [or the] hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vector,” or some similar structure. This is merely an example set forth by the Examiner that is not intended to be limiting.
With specific regard to claims 31 and 32, which recite in part “at least two engineered parental circular covalently closed synthetic plasmids DNA” (bolded emphasis added), these recitations are grammatically improper. While the recited and bolded “plasmids” are pluralized by the recitation of “at least two,” the bolded “DNA” is not pluralized and does not appear to be required in the instant claim language, as the instant specification repeatedly discloses that the claimed plasmids are built from DNA, as is also commonly known to those of ordinary skill in the art. In order to comport with standard grammatical and/or linguistic conventions, it would be remedial to amend the instant claim language to recite, for example, “at least two engineered parental circular covalently closed synthetic plasmids of claim 1,” or some similar structure. This is merely an example set forth by the Examiner that is not intended to be limiting.
With specific regard to claim 32, claim 32 is objected to for reciting stages “a.”, “b.”, “c.”, “d.”, and “e.” by including a period at the end of each indicated stage. According to MPEP 608.01(m), “Each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. See Fressola v. Manbeck, 36 USPQ2d 1211 (D.D.C. 1995)”. It would be remedial to replace “a.”, “b.”, “c.”, “d.”, and “e.” with “(a)”, “(b)”, “(c)”, “(d)”, and “(e)”.
Furthermore, claim 32 includes improper punctuation spacing at the final line of stage “a.” and line 5 of stage “d.”. At the final line of stage “a.”, there should not be a space preceding the semicolon separating the claimed stages. At line 5 of stage “d.”, there should not be a space preceding the comma separating “the helper plasmid” and “or subjecting the…”. It would be remedial to amend the instant claim language such that it comports with standard grammatical and/or linguistic conventions.
Claim 32 also recites “Linear DNA molecules” at line 3 of stage “d.”, which improperly capitalizes linear. It would be remedial to amend the instant claim language such that it comports with standard grammatical and/or linguistic conventions.
The Examiner notes that claim 32 is written and structured such that it is cumbersome to interpret the active steps recited therein. In order to facilitate interpretation and usage of the instantly claimed production process, it would be remedial to amend the instant claim language such that it is more readily interpreted. Furthermore, claim 32 recites several plasmids, including “pDNAv_Ac,” “pDNAv_Bc,” “pDNAv_ABc,” “pDNAv_ABc1,” and “pDNAv_ABc2,” none of which are commonly known in the art and none of which are accompanied by any more generic description (i.e. “parental plasmid” or “splitted [sic] plasmid”). While the instant specification and the instant drawings facilitate interpretation of these limitations, for purposes of facilitating interpretation and usage of the claimed production process, it would be remedial to indicate in the claim language itself which plasmids are parental plasmids (i.e. pDNAv_Ac and pDNAv_Bc (paragraphs [0037] and [0038])), cointegrate plasmids (i.e. pDNAv_ABc(paragraph [0039])), and split plasmids (i.e. pDNAv_ABc1 and pDNAv_ABc2 (paragraphs [0040] and [0042])). As set forth above, the Examiner further notes that the term “splitted” (disclosed at paragraphs [0040] and [0041] of the instant specification) is an archaic word that is no generally longer considered proper in standard usage. The proper term is “split.” It would generally be remedial to use “split” in place of “splitted.”
With regard to claim 34, which recites the order in which the genetic elements of the claimed DNA vector are operably linked, this recitation lacks a conjunction such as “and” linking the final genetic elements, namely the “at least one SV40E sequence” and the “single-stranded DNA loop.” It would be remedial to amend the instant claim language such that there is a conjunction linking the final genetic elements of the claimed DNA vector.
With regard to claim 35, which recites “the vector is applicable to prevent or treat infectious disorders, genetic and non-genetic conditions” (bolded emphasis added), this recitation is grammatically improper. When reciting prevention or treatment of infectious diseases and conditions that may be genetic or non-genetic, it is grammatically proper to separate the recited groups (i.e. infectious diseases and conditions that may be genetic or non-genetic) by structuring the claim language such that it recites prevention of treatment of “infectious disorders, as well as genetic and non-genetic conditions” (bolded emphasis added). This is merely an example set forth by the Examiner that is not intended to be limiting. It would be remedial to amend the instant claim language to comport with standard grammatical and/or linguistic conventions.
Appropriate correction is required.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 31 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 31 is drawn to a hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vector production system, said system comprising a recombinant cell, itself comprising a helper plasmid and at least two engineered parental circular, covalently closed synthetic plasmids. The instant specification defines “recombinant” as referring to a manipulated nucleic acid or a protein encoded by the same (paragraph [0275]). It is noted that this definition does not limit the claimed cell to a cell outside of a living organism, such as a human organism.
The instant specification discloses that the recombinant cells taught therein may be mammalian cells, such as (but not limited to) HEK-293 cells (paragraph [0199]). Furthermore, the instant specification envisions human hosts (paragraph [0279]). Neither the instant specification nor the instant claim set explicitly states that the claimed recombinant cell is not a human cell that under broadest reasonable interpretation encompasses a human cell in a human organism. Therefore, the broadest reasonable interpretation of the term “recombinant cell” embraces a human having the cell.
Accordingly, claim 31 is rejected under 35 U.S.C. § 101 as encompassing a human organism under broadest reasonable interpretation.
It is suggested to amend the claim to recite “isolated recombinant cell” to avoid the claim embracing a human organism.
Claim Rejections - 35 USC § 112(a)
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 31-35 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.
Claim 31 is drawn to a hairpin loop ended, self-complementary, double-stranded, linear covalently closed DNA vector production system, said production system comprising a recombinant cell comprising a helper plasmid (of claim 22) and at least two engineered parental circular, covalently closed, synthetic plasmids (of claim 1). The rejected claims thus encompass a recombinant cell comprising a helper plasmid and up to an unlimited number of engineered parental circular, covalently closed, synthetic plasmids of claim 1.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes recombinant cells comprising a helper plasmid and two engineered parental circular, covalently closed, synthetic plasmids of claim 1 (see section “ASSAYS AND EXPERIMENTS” at paragraphs [0239]-[0256] of the instant specification). No description is provided of recombinant cells comprising a helper plasmid and up to an unlimited number of engineered parental circular, covalently closed, synthetic plasmids of claim 1, as is encompassed by the instant claim language.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of a hairpin loop ended, self-complementary, double-stranded, linear covalently closed DNA vector production system comprising a recombinant cell comprising a helper plasmid and two engineered parental circular, covalently closed, synthetic plasmids of claim 1. The results are not necessarily predictive of the same production system comprising a recombinant cell comprising a helper plasmid and up to an unlimited number of engineered parental circular, covalently closed, synthetic plasmids of claim 1, as is encompassed by the instant claim language. Thus, it is impossible for one to extrapolate from the examples described herein those hairpin loop ended, self-complementary, double-stranded, linear covalently closed DNA vector production systems (comprising a recombinant cell comprising a helper plasmid and up to an unlimited number of engineered parental circular, covalently closed, synthetic plasmids of claim 1) that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of hairpin loop ended, self-complementary, double-stranded, linear covalently closed DNA vector production systems, said systems comprising a recombinant cell comprising a helper plasmid and up to an unlimited number of engineered parental circular, covalently closed, synthetic plasmids of claim 1.
With regard to claims 32-35, all of these claims directly recite or indirectly inherit the system of claim 31, which does not comply with the written description requirement, as set forth above. Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 32-35.
With specific regard to claim 34, claim 34 is drawn to a hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vector, wherein the genetic elements of the DNA vector are operably linked in the following order: a single-stranded DNA loop, optionally at least one SV40E sequence, optionally at least one S/MAR sequence, optionally at least one eukaryotic origin of replication, at least one promoter, optionally at least one 5’ untranslated region sequence, at least one coding sequence or sequence of interest, optionally one or more IRES, MIRES and/or 2A-peptide sequences, optionally at least one 3’ untranslated region sequence, at least one transcriptional terminator sequence, optionally at least one S/MAR sequence, optionally at least one eukaryotic origin of replication, optionally at least one SV40E sequence, and a single-stranded DNA loop, with suitable DNA spacer sequences optionally placed between at least two of the aforementioned elements. The rejected claim thus encompasses DNA vectors with up to unlimited numbers of SV40E sequences, S/MAR sequences, eukaryotic origins of replication, promoters, 5’ untranslated region sequences, coding sequences or sequences of interest, IRES, MIRES, and/or 2A-peptide sequences, 3’ untranslated region sequences, and transcriptional terminator sequences.
As set forth above, to provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. The specification describes molecules such as those depicted in Figures 17 and 18 (paragraphs [0046] and [0047]), both of which comprise one 5’ SV40E sequence, one 5’ S/MAR sequence, one 5’ eukaryotic origin of replication (SV40 ori), one 5’ spacer, one promoter, one 5’ UTR, one transcriptional unit, one 3’ UTR, one terminator, one 3’ spacer, one 3’ S/MAR sequence, and one 3’ SV40E sequence. No description is provided of any DNA vectors with up to unlimited numbers of SV40E sequences, S/MAR sequences, eukaryotic origins of replication, promoters, 5’ untranslated region sequences, coding sequences or sequences of interest, IRES, MIRES, and/or 2A-peptide sequences, 3’ untranslated region sequences, and transcriptional terminator sequences, as is encompassed by the instant claim language.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of DNA vectors with one 5’ SV40E sequence, one 5’ S/MAR sequence, one 5’ eukaryotic origin of replication (SV40 ori), one 5’ spacer, one promoter, one 5’ UTR, one transcriptional unit, one 3’ UTR, one terminator, one 3’ spacer, one 3’ S/MAR sequence, and one 3’ SV40E sequence. The results are not necessarily predictive of DNA vectors with up to unlimited numbers of SV40E sequences, S/MAR sequences, eukaryotic origins of replication, promoters, 5’ untranslated region sequences, coding sequences or sequences of interest, IRES, MIRES, and/or 2A-peptide sequences, 3’ untranslated region sequences, and transcriptional terminator sequences, as is encompassed by the instant claim language. Thus, it is impossible for one to extrapolate from the examples described herein those DNA vectors with up to unlimited numbers of SV40E sequences, S/MAR sequences, eukaryotic origins of replication, promoters, 5’ untranslated region sequences, coding sequences or sequences of interest, IRES, MIRES, and/or 2A-peptide sequences, 3’ untranslated region sequences, and transcriptional terminator sequences that would necessarily meet the structural/functional characteristics of the rejected claim.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of DNA vectors with up to unlimited numbers of SV40E sequences, S/MAR sequences, eukaryotic origins of replication, promoters, 5’ untranslated region sequences, coding sequences or sequences of interest, IRES, MIRES, and/or 2A-peptide sequences, 3’ untranslated region sequences, and transcriptional terminator sequences.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claim 34.
Finally, with specific regard to claim 35, claim 35 is drawn to therapeutic hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vectors that are applicable to the prevention or treatment of infectious disorders as well as genetic and non-genetic conditions. Thus, the rejected claim comprises a set of therapeutic hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vectors that must prevent or treat infectious disorders as well as genetic and non-genetic conditions.
As set forth above, to provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof. While the instant specification envisions the prevention of treatment of oncology related diseases, infectious diseases, genetic disorders, diseases that may be treated by cell therapy approaches, as well as neurodegenerative disorders (paragraph [0231]), the examples therein only disclose in vitro experimentation (paragraphs [0239]-[0247] and [0250]-[0256]) and in vivo expression of EGFP in the biceps femoris muscles of mice (paragraphs [0248]-[0249]). No description is provided of any vectors with therapeutic potential or of any sequences with therapeutic potential, as is broadly envisioned at paragraph [0231].
Especially given that the instant specification envisions broad therapeutic potential in the prevention or treatment of numerous diseases with vastly different mechanisms of action (i.e. oncology related diseases involve unchecked cellular proliferation, while neurodegenerative disorders involve the progressive death of neurons), the working examples provided and set forth above are neither representative nor predictive of preventing or treating the envisioned diseases, as they are only drawn to in vitro proof-of-principle assays and in vivo expression of a fluorescent marker in mice. Furthermore, given that the envisioned diseases each have vastly different mechanisms of action, it is impossible for one to extrapolate from the instant disclosure those therapeutic vectors that would necessarily prevent and/or treat all of the envisioned diseases.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of therapeutic vectors that are capable of preventing and/or treating all of the envisioned diseases.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claim 35.
Claim 35 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. Although a working example is not required to enable an invention, the skilled artisan must be able to practice the claimed invention without undue experimentation. See also, MPEP §2164.02, which states in part: The specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970). Lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: Claim 35 is drawn to therapeutic hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vectors that are applicable to the prevention or treatment of infectious disorders as well as genetic and non-genetic conditions.
Breadth of the claims: The instant specification envisions the prevention of treatment of oncology related diseases, infectious diseases, genetic disorders, diseases that may be treated by cell therapy approaches, as well as neurodegenerative disorders (paragraph [0231]). Each of these diseases involve vastly different pathological mechanisms. For example, oncology related diseases involve unchecked cellular proliferation, while neurodegenerative disorders involve the progressive death of neurons. Each of the diseases envisioned therein has a different pathological mechanism and different hurdles to successful treatment of the same. Therefore, the complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The instant specification only discloses working examples illustrating in vitro experimentation (paragraphs [0239]-[0247] and [0250]-[0256]) and in vivo expression of EGFP in the biceps femoris muscles of mice (paragraphs [0248]-[0249]). No description is provided of any vectors with therapeutic potential, as is broadly envisioned at paragraph [0231], nor is there any guidance provided for designing or utilizing the therapeutic vectors envisioned therein.
Predictability and state of the art: In this case, the claims explicitly encompass preventing infectious disorders as well as genetic and non-genetic conditions in a subject. Looking to the prior art for guidance, a search of the prior art did not identify any methods which utilized therapeutic hairpin loop ended, self-complementary, double-stranded, linear, covalently closed DNA vectors that could effectively prevent infectious disorders as well as genetic and non-genetic conditions in a subject. In fact, no prior art was identified which taught effective prevention of infectious disorders as well as genetic and non-genetic conditions using any agent similar to the agents utilized in the instant claims. The specification also does not provide any working example demonstrating prevention of infectious disorders as well as genetic and non-genetic conditions in a subject. Therefore, given the lack of knowledge present in the prior art and the lack of guidance provided in the specification with respect to preventing infectious disorders as well as genetic and non-genetic conditions, further experimentation would be required. Considering that the additional experimentation would require de novo experimentation without a guarantee of success, and further considering that any positive results (i.e., successful prevention of infectious disorders as well as genetic and non-genetic conditions in a subject) would amount to a significant advancement in the state of the art, the additional experimentation required is considered undue.
Furthermore, while nucleic acid-based therapies such as the delivery of DNA comprising a therapeutic gene (i.e. gene therapy) have made enormous strides in treating diseases such as neurodegenerative diseases and cancer, there are still hurdles to such treatments that must be considered. For example, safe, efficient, and selective delivery of gene products into the central nervous system remains a challenge in treating neurodegenerative diseases (reviewed in Sun and Roy, 2021), while gene therapy for cancer treatment carries risks for toxicity, mutagenicity, and immunogenicity from viral vectors, as well as resistance to treatment following gene therapy (reviewed in Amer, 2014). While gene therapy treatments have successfully been developed for certain neurodegenerative diseases and cancers, these treatments were carefully and individually designed and tested to ensure efficacy and safety. While such design and experimentation thereof are both within the realm of experimentation by those of ordinary skill in the art, the breadth of diseases encompassed by the instant claim set would require substantial and repeated experimentation for numerous, disparate diseases such that the additional experimental required is considered undue.
Amount of experimentation necessary: As set forth above, the quantity of experimentation required to make and use the full scope of the claimed invention would be large. While the required experimentation is theoretically within the realm of experimentation by those of ordinary skill in the art, the breadth of diseases encompassed by the instant claim set would require substantial and repeated experimentation for numerous, disparate diseases such that the additional experimental required is considered undue.
Furthermore, other than contemplating the utility of the claimed DNA vector in preventing of treating infectious disorders as well as genetic and non-genetic conditions, the specification does not disclose how to design or use any of the therapeutic genes required to treat a subject in need thereof using the instantly claimed vector. As clearly stated in Genentech Inc. v. Novo Nordisk NS (CAFC) 42 USPQ2d 1001: "Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in the context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention." Applicant cannot rely on the knowledge of one skilled in the art to supply information on the novel aspects of the claimed invention, to which the instantly filed disclosure is largely silent as set forth above.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claim 35 is not considered to be enabled by the instant disclosure.
Claim Rejections - 35 USC § 112(b)
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 32 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 32 recites the limitation "the cointegrate plasmid pDNAv_ABc" in stages “b.”, “c.”, and “d.”. There is insufficient antecedent basis for this limitation in the claim. It would be remedial to amend the instant claim set such that there is sufficient antecedent basis for all claim limitations.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Williams (US PGPub 2023/0235337 A1; issued as patent 12,503,705 on 12/23/2025) discloses a circular RNA molecule and methods for producing thereof. In contrast to the publication’s circular RNA molecule, the instant application is drawn to a covalently closed linear DNA molecule.
Williams (application number 18/799,681; issued as patent 12,509,711 on 12/30/2025) discloses systems and processes for in vivo production of nanostructure-ended, double-stranded, covalently-closed linear DNA molecules. While the plasmids disclosed therein include several components that are shared with the instant application, the instant application does not disclose a variety of additional components disclosed in the ‘681 application, such as a nanostructure sequence within a retron module.
Nafissi and Slavcev, 2012 disclose methods of preparing closed DNA vectors in vivo, said methods including a parent eukaryotic expression vector comprising a specialized manufactured multi-target site (“Super Sequence”) and engineered E. coli cells that conditionally produce phage-derived recombinases to facilitate rapid, efficient, and one step in vivo generation of mini linear covalently closed or mini circular covalently closed DNA constructs separated from the backbone plasmid DNA (abstract; figures 2-4). However, Nafissi and Slavcev, 2012 do not disclose the myriad components of the instant application, nor does their system require at least two parental plasmids within a recombinant cell for successful production of mini linear covalently closed DNA constructs, as is recited at instant claim 31.
Additionally, while WO 2020/154645 A1 (hereinafter Kerr) discloses plasmids for the production of therapeutic close-ended DNA (ceDNA) molecules (abstract; figure 4B; paragraphs [00197]-[00200]), these plasmids and methods of using them do not include additional elements, including the repressors under the control of constitutive promoters of the helper plasmid recited at instant claim 22 (and required by the recombinant cell of instant claim 31).
Thus, while in vivo, plasmid-based methods of producing closed, linear DNA vectors are known in the art, there is not disclosure found in any document or set of documents of the instantly claimed plasmids and methods of using the same for the production of closed, linear DNA vectors.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-Th 8-5, F 8-12.
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/SARAH E ALLEN/ Examiner, Art Unit 1637
/J. E. ANGELL, Ph.D./ Primary Examiner, Art Unit 1637