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 .
Claim Objections
Claim 3 is objected to because of the following informalities: the claim recites the term “claim1” in line 1 of the claim. The phrase is grammatically incorrect. Examiner suggests amending the claim to recite “claim 1”. Appropriate correction is required.
Claim Interpretation
Regarding claims 2-3 and 15-16, it is noted that the instant specification describes “a variant” of a sequence as being directed towards a sequence that has at least 50% identity to a particular nucleic acid sequence of interest (Instant specification; pg. 18). Accordingly, the claims are interpreted as claiming sequences that have at least 50% identity to the claimed SEQ ID NOs.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 3-13, and 17-18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784).
Regarding claim 1, Rondon is directed towards a study concerned with biological programming structure that leverages a system of engineered transcription factors and complementary genetic architectures (Abstract). Rondon teaches the use of regulatory protein templates that comprise a dimeric transcription factor alongside its corresponding ligand and cognate DNA operator (pg. 2; see Fig. 1). Rondon teaches that the transcription factor comprises a regulatory core domain and an alternate DNA recognition unit (i.e., a DNA binding domain) (pg. 2; see Fig. 1). Rondon teaches that the DNA recognition unit is linked to the regulatory core domain (pg. 2; see Fig. 1). Rondon teaches that the DNA recognition unit recognizes the DNA operator element such that, in the presence or absence of a specific inducer molecule, gene expression can be modulated as desired (pg. 2; see Fig. 1). Rondon teaches that two or more regulatory protein templates (i.e., two or more regulatory core domains) can be utilized together to create Boolean logical AND and OR gates (pg. 5-7; see Fig. 5). Rondon further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a bacterial cell (pg. 11).
Regarding claim 3, Rondon teaches the use of a vector encoding a LacI YQR that comprises 100% identity to the claimed SEQ ID NO: 1 (pg. 11; see attached sequence alignment). Rondon teaches the use of a promoter that comprises 99.9% identity to the claimed SEQ ID NO: 2 (pg. 11; see attached sequence alignment). Rondon teaches that the DNA operators are located downstream of a promoter element such that they can be expressed in a target cell of interest (pg. 3).
Regarding claims 4-5, Rondon teaches that the AND gate can be constructed via the use of two engineered regulatory protein templates that comprise repressor regulatory core domains (i.e., both regulatory core domains may comprise a repressor) (pg. 6-7; see Fig. 5b).
Regarding claims 6 and 8, Rondon teaches that the two regulatory core domains in the Boolean logic gates are each specifically recognized by a first and second agent (pg. 6-7; see Fig. 5).
Regarding claims 7 and 9, Rondon teaches the use of an asymmetric parallel system, denoted AND[PARA]HAND, that required the use of two regulatory core domains that could recognize a first IPTG input and a second D-ribose input (pg. 9; see Fig. 7b).
Regarding claims 10-11, Rondon teaches the use of regulatory core domains that can be linked to the same, or different, DNA binding domains and function within the Boolean logic gates (pg. 4, 8; see Figs. 2 and 6).
Regarding claim 12, Rondon teaches the use of an asymmetric parallel system, denoted AND[PARA]HAND, that required the use of two sets of two regulatory core domains (i.e., I+YQR, E+TAN, R+HQN, and R+HQN) that could be linked to one of three DNA binding domains (i.e., YQR, TAN, and HQN) that could be recognized by three different DNA operator elements (pg. 9; see Fig. 7b).
Regarding claim 13, Rondon teaches that the Boolean logic gate can be operably connected to a GFP reporter protein (pg. 6; see Fig. 5).
Regarding claims 17-18, Rondon teaches that the Boolean logic gates may be utilized in an E. coli K12 strain that had the LacI and lac operon deleted (pg. 11).
Claim(s) 1-20 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Huang ("Transcriptional programming in a Bacteroides consortium." Nature communications 13.1 (6 July 2022): 3901).
Regarding claim 1, Huang is directed towards a study concerned with the development of two-input genetic circuits dependent on the inputs isopropyl-β-D-1-thiogalactopyranoside and D-ribose (Abstract). Huang teaches the use of regulatory protein templates that comprise a dimeric transcription factor alongside its corresponding ligand and cognate DNA operator (pg. 3; see Fig. 1). Huang teaches that the transcription factor comprises a regulatory core domain and an alternate DNA recognition unit (i.e., a DNA binding domain) (pg. 3; see Fig. 1). Huang teaches that the DNA recognition unit is linked to the regulatory core domain (pg. 3; see Fig. 1). Huang teaches that the DNA recognition unit recognizes the DNA operator element such that, in the presence or absence of a specific inducer molecule, gene expression can be modulated as desired (pg. 3; see Fig. 1). Huang teaches that two or more regulatory protein templates (i.e., two or more regulatory core domains) can be utilized together to create Boolean logical AND and OR gates (pg. 4; see Fig. 2). Huang further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a B. thetaiotaomicron cell (pg. 11-12).
Regarding claim 2, Huang teaches the use of a vector comprising a “BUFFER Gate” comprising LacI(ADR) that has 100% identity to the claimed SEQ ID NO: 31 (pg. 8; see Fig. 4 and atatcehd sueqence alignment).
Regarding claim 3, Huang teaches the use of a vector encoding a LacI YQR that comprises 100% identity to the claimed SEQ ID NO: 1 (pg. 7-8; see attached sequence alignment). Huang teaches the use of a RbsR (YQR) that comprises 100% identity to the claimed SEQ ID NO: 2 (pg. 7-8; see attached sequence alignment). Huang teaches that the LacI YQR could be located downstream of the Pcfxa promoter (pg.8; see Figure 8).
Regarding claims 4-5, Huang teaches that the AND gate can be constructed via the use of two engineered regulatory protein templates that comprise repressor regulatory core domains (i.e., both regulatory core domains may comprise a repressor) (pg. 4; see Fig. 2).
Regarding claims 6-9, Huang teaches that the two regulatory core domains in the Boolean logic gates are each specifically recognized by a first and second agent selected from IPTG and D-Ribose (pg. 4; see Fig. 2).
Regarding claims 10-11, Huang teaches the use of regulatory core domains that can be linked to the same, or different, DNA binding domains and function within the Boolean logic gates (pg. 4; see Fig. 2).
Regarding claim 12, Huang teaches the of two different sets of regulatory core domains (i.e., I+ADR, R+ADR, IAADR, and RAADR) that could be linked to one of five different DNA binding domains that could be recognized by three different DNA operator elements in a B. thetaiotaomicron cell (see Supplemental Figures 1-3).
Regarding claim 13, Huang teaches that the Boolean logic gate can be operably connected to a pNBU2 plasmid containing a NanoLuc reporter gene fused to 1 of the 5 promoter/operator pairs (pg. 12).
Regarding claim 14, Huang teaches that the genetic logic gates can be operably linked to a dCas9 and a sgRNA (pg. 8; see Fig. 4).
Regarding claim 15, Huang teaches the use of a dCas9 that comprises 100% identity to the claimed SEQ ID NO: 6 (pg. 8; see Fig. 4 and attached sequence alignment). Huang teaches the use of an sgRNA that comprises 100% identity to the claimed SEQ ID NO: 16 (pg. 8; see Fig. 4 and attached sequence alignment). Huang teaches that the dCas9 and the sgRNA may be present on the same nucleic acid construct (pg. 8; see Fig. 4).
Regarding claim 16, Huang teaches the use of a pNBU2 vector comprising 100% identity to the claimed SEQ ID NO: 70 (pg. 10; see attached sequence alignment).
Regarding claims 17-19, Huang teaches that the Boolean logic gates may be utilized in a B. thetaiotaomicron cell (pg. 11-12).
Regarding claim 20, Huang teaches that the genetic circuits can be utilized in Bacteroides species that are present and stable within a human’s gastrointestinal tract (i.e., within a gastrointestinal tract microbiome) such that the bacteria are engineered as therapeutic bacteria that could modulate their host’s immune system by executing bespoke genetic programs, in addition to facilitating the programmed delivery of therapeutic payloads (pg. 2).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 14, and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784) as applied to claims 1, 3-13, and 17-18 above, and further in view of Lu (PG Pub No. US 2018/0163216 A1).
Regarding claims 2, 14, and 19-20, Rondon anticipates claims 1, 3-13, and 17-18 as described above. Rondon further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a bacterial cell (pg. 11).
Rondon does not teach or suggest that the construct further comprises a variant of SEQ ID NO: 34 (Claim 2). Rondon does not teach or suggest that the construct further comprises a nucleic acid sequence encoding a dCas9 and a sgRNA (Claim 14). Rondon does not teach or suggest that the bacterial cell is B. thetaiotaomicron (Claim 19). Rondon does not teach or suggest that the construct could be utilized in a method of modifying a gastrointestinal tract microbiome in a subject (Claim 20).
However, one of ordinary skill in the art would have considered the teachings of Lu as both references are common fields of endeavor pertaining to the use of transcription factors and their expression within cells of interest.
Lu is directed towards a study concerned with methods, compositions and nucleic acids for building genetic circuits in Bacteroides and Parabacteroides bacteria (Abstract). Lu teaches the use of vectors that can be used to manipulate gene expression in a variety of Bacteroides and Parabacteroides species ([0004]). Lu teaches that B. thetaiotaomicron cells are candidates for modulating the gut ecosystem and that utilizing genetic circuits to control gene expression in B. thetaiotaomicron cells would allow for the therapeutic delivery of the cells to the human microbiome ([0004]). Lu teaches the use of a nucleic acid encoding a dCas9 and sgRNA that could repress endogenous genes of interest in B. thetaiotaomicron cells ([0026]-[0027]). Lu teaches that genetic inducible systems, CRISPRi, and genetic memory switches were validated in B. thetaiotaomicron cells colonizing the mouse gut ([0004]). Lu teaches the use of a pNBU1 vector that comprises a sequence that has 70.9% identity to the claimed SEQ ID NO: 34 ([0098]; see SEQ ID NO: 209 in attached sequence alignment). Lu teaches that the pNBU1 vector was created to introduce recombinant DNA intro a wide range of Bacteroides species ([0097]). Lu teaches that the pNBU1 vector showed a greater host range and efficiency relative to a pNBU2 plasmid and that the pNBU1 vector was capable of facilitating recombinant gene expression in multiple Bacteroides species, including B. thetaiotaomicron, B. fragilis, B. ovatus, B. vulgatus, B. caccae, B. eggerthii and Parabacteroides distasonis ([0097]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the bacterial cell and vector of Rondon for a B. thetaiotaomicron cell and a pNBU1 vector comprising a sequence that has 70.9% identity to the claimed SEQ ID NO: 34, as described by Lu. A person of ordinary skill in the art would have been motivated to utilize the pNBU1 vector in order to have the ability to insert the bacterial genetic logic gate described by Rondon into a B. thetaiotaomicron cell in order to therapeutically deliver the cells to the human microbiome. A person of ordinary skill in the art would have had a reasonable expectation of success because Rondon teaches the use of a genetic circuit that can control the expression of genes within a bacterial cell while Lu teaches the use of a vector that can insert recombinant DNA into a B. thetaiotaomicron cell.
It would have also been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further utilize a nucleic acid encoding a dCas9 and an sgRNA, and modify the gastrointestinal tract microbiome of a subject, as described by Lu. A person of ordinary skill in the art would have been motivated to do so in order to repress endogenous genes within the B. thetaiotaomicron cell in order to therapeutically deliver the modified cells to a gastrointestinal tract microbiome of a subject. A person of ordinary skill in the art would have had a reasonable expectation of success because Rondon teaches the use of a genetic circuit that can control the expression of genes within a bacterial cell while Lu teaches that dCas9 and sgRNAs can be utilized alongside genetic circuits to provide further control over the endogenous expression of target genes of interest within B. thetaiotaomicron cells.
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784) as applied to claims 1, 3-13, and 17-18 above, and further in view of Mimee ("Programming a human commensal bacterium, Bacteroides thetaiotaomicron, to sense and respond to stimuli in the murine gut microbiota." Cell systems 1.1 (2015): 62-71), Lu (PG Pub No. WO 2016/201174 A2), and Boitano (PG Pub No. US 2019/0010495 A1).
Regarding claim 15, Rondon anticipates claims 1, 3-13, and 17-18 as described above. Rondon further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a cell of interest to express a nucleic acid of interest (pg. 11).
Rondon does not teach or suggest that the construct comprises a combination of variants of SEQ ID NOs: 6 and 16 (Claim 15).
However, one of ordinary skill in the art would have considered the teachings of Mimee, Boitano and Marco as both references are common fields of endeavor pertaining to the use of nucleic acids that can be expressed in cells of interest.
Mimee is drawn towards a study concerned with synthetic genetic circuits that are operably linked to a dCas9 and an sgRNA to alter the metabolic capacity of B. thetaiotaomicron and its resistance to antimicrobial peptides (Abstract). Mimee teaches the use of a vector encoding a dCas9 and an sgRNA that are operably linked to a synthetic genetic circuit that can alter the expression of a NanoLuc luciferase reporter (pg. 63-64). Mimee teaches the use of a 20 nucleotide RNA guide sequence that comprises 100% identity to the first 20 nucleotides of the claimed SEQ ID NO: 16 and can target a NanoLuc reporter sequence (see “NL4” in Supplementary Table S5). Mimee teaches that the NanoLuc reporter was able to be knocked down by the IPTG induction of the dCas9 in order to determine if the genetic gate was functional in a B. thetaiotaomicron cell (pg. 67).
Boitano is directed towards an invention concerned with genome editing systems, reagents and methods for the treatment of hemoglobinopathies (Abstract). Boitano teaches the use of a nucleic acid molecule encoding multiple guide RNAs and a CRISPR/Cas9 molecule ([0030]). Boitano teaches that promoters for the Cas9 and guide RNAs can be inducible (i.e., the expression of the Cas9 and guide RNA may be inducible) ([0489]). Boitano teaches the use of a guide RNA that comprises 87.1% identity to the claimed SEQ ID NO: 16 and comprises an RNA scaffold sequence that has 100% identity to nucleotides 21-100 of the claimed SEQ ID NO: 16 ([0098]; see SEQ ID NO: 1772 in attached sequence alignment).
Lu is directed towards an invention concerned with building genetic circuits in Bacteroides bacteria (Abstract). Lu teaches the use of a dCas9 that has 99.9% sequence identity to the claimed SEQ ID NO: 6 (pg. 4; see SEQ ID NO: 157 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Rondon such that it controlled the transcription of a dCas9 molecule having 99.9% sequence identity to the claimed SEQ ID NO: 6, as described by Lu, and a guide RNA that comprises a guide sequence that has 100% identity to the first 20 nucleotides of the claimed SEQ ID NO: 16 and a scaffold sequence that has 100% identity to nucleotides 21-100 of the claimed SEQ ID NO: 16 in order to arrive at a Cas9 guide RNA that comprises 100% identity to the claimed SEQ ID NO: 16, as described by Mimee and Boitano. A person of ordinary skill in the art would have been motivated to do so in order to target knockdown of a reporter protein in order to validate if the genetic logic gate is functional in Bacteroides bacteria. A person of ordinary skill in the art would have had a reasonable expectation of success because Rondon teaches that the construct can be utilized to modulate the transcription of a downstream nucleic acids while Mimee teaches that utilizing genetic logic gates to modulate the expression of a dCas9 and an sgRNA can control the expression of a reporter protein. Further, both Mimee and Boitano teach that the claimed SEQ ID NO: 16 is a combination of a known Cas9 guide RNA sequence and a known Cas9 guide RNA scaffold sequence.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784) as applied to claims 1, 3-13, and 17-18 above, and further in view of Needham (PG Pub No. US 2019/0374588 A1).
Regarding claim 15, Rondon anticipates claims 1, 3-13, and 17-18 as described above. Rondon further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a cell of interest to express a nucleic acid of interest (pg. 11).
Rondon does not teach or suggest that the construct comprises a variant of the claimed SEQ ID NO: 70 (Claim 16).
However, one of ordinary skill in the art would have considered the teachings of Needham as both references are common fields of endeavor pertaining to the use of nucleic acids that can be expressed in cells of interest.
Needham is drawn towards an invention concerned with genetically engineered bacterial strains for modulation of 4EP and 4EPS (Abstract). Needham teaches the use of a pNBU2 plasmid that can comprise a recombinant gene encoding a native B. ovatus BACOCA_01194 gene and a recombinant gene encoding a Bacillus subtilis PAD enzyme that can be chromosomally inserted into a mutant B. ovatus bacteria in order to confer erythromycin resistance to the mutant strain (i.e., the pNBU2 plasmid may be utilized to insert recombinant DNA into the chromosome of a mutant B. ovatus strain) ([0063]-[0064]). Needham teaches that the pNBU2 vector comprises a sequence that has 52.5% identity to the claimed SEQ ID NO: 70 ([0063]; see SEQ ID NO: 3 in attached sequence alignment).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the vector of Rondon for a vector comprising a variant of the claimed SEQ ID NO: 70, as described by Needham. A person of ordinary skill in the art would have had a reasonable expectation of success because both Rondon and Needham teach the use of vectors that can be delivered to bacterial cells of interest in order to express recombinant DNA from the cell’s chromosomes.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784) as applied to claims 1, 3-13, and 17-18 above, and further in view of Mimee ("Programming a human commensal bacterium, Bacteroides thetaiotaomicron, to sense and respond to stimuli in the murine gut microbiota." Cell systems 1.1 (2015): 62-71), and Lu (PG Pub No. WO 2016/201174 A2), Boitano (PG Pub No. US 2019/0010495 A1).
Regarding claim 16, it is noted that the claimed SEQ ID NO: 70 is directed towards a pNBU2 vector utilized for LacI-controlled sgRNA for NanoLuc knockdown and comprises LacI(YQR) as defined by SEQ ID NO: 1 (pg. 60-61), CFXA promoters as defined by SEQ ID NO: 7 (pg. 65), and nano4sgRNA as defined by SEQ ID NO: 16 (pg. 65) (see pg. 59).
Rondon anticipates claims 1, 3-13, and 17-18 as described above. Rondon further teaches that the transcription factors may be encoded on a vector in order to express the Boolean logic gates in a cell of interest to express a nucleic acid of interest (pg. 11).
Rondon does not teach or suggest that the construct comprises a variant of the claimed SEQ ID NO: 70 (Claim 16).
However, as discussed above, Rondon teaches the use of a vector encoding a LacI(YQR) that comprises 100% identity to the claimed SEQ ID NO: 1 (pg. 11; see attached sequence alignment).
Further, as discussed above, Mimee and Boitano render obvious the use of an sgRNA that comprises 100% sequence identity to the claimed SEQ ID NO: 16.
Additionally, Lu further teaches the use of a PcfxA promoter that comprises 100% identity to the claimed SEQ ID NO: 7 (pg. 2; see SEQ ID NO: 151 in attached sequence alignment). Lu also teaches the use of a pNBU2 integration vector that was able to encode the promoters and genetic circuits of the invention and insert the elements into a B. thetaiotaomicron chromosome (pg. 21).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the vector of Rondon such that it comprised LacI(YQR) as defined by SEQ ID NO: 1, CFXA promoters as defined by SEQ ID NO: 7, and a nano4sgRNA as defined by SEQ ID NO: 16 within a pNBU2 insertion vector, as described by Mimee, Boitano, and Lu. A person of ordinary skill in the art would have been motivated to do so in order to insert and test the genetic logic gate within a B. thetaiotaomicron host cell and test the functionality of the genetic logic gate via the use of a known reporter that can be knocked down by dCas9 and an sgRNA targeting NanoLuc. A person of ordinary skill in the art would have had a reasonable expectation of success because the claimed SEQ ID NO: 70 comprises known a LacI(YQR) sequence, known CFXA promoter sequences, and a known nano4sgRNA sequence within a well-known insertion vector.
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.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/790,573 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the instant claims. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 1 claims a synthetic memory system, comprising: a recombinase; a modified transcription factor (i.e., a DNA binding domain); and a first nucleic acid comprising a first attachment site (i.e., a first group of one regulatory core domain), a second attachment site (i.e., a second group of one regulatory core domain), and a target gene between said first attachment site and said second attachment site; wherein at least one of the first attachment site and the second attachment site comprises a modified DNA operator to which the modified transcription factor can reversibly bind; and wherein, when the modified transcription factor is bound to the modified DNA operator, the recombinase is blocked from binding to the attachment site comprising said modified DNA operator (see copending claim 1).
Claims 3-13 and 17-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/790,573 in view of Rondon (“Transcriptional programming using engineered systems of transcription factors and genetic architectures” Nature Communications 10.1 (2019): 4784).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 3-13 and 17-1, copending claim 1 anticipates instant claim 1.
The copending claims do not teach or suggest that the plurality of nucleic acid sequence comprise a combination of variants of SEQ ID NOs: 1 and 2 (Claim 3). The copending claims do not teach or suggest that the first group or second group of regulatory core domains comprise a repressor (Claims 4-5). The copending claims do not teach or suggest that the first group of regulatory core domains is recognized by IPTG (Claims 6-7). The copending claims do not teach or suggest that the second group of regulatory core domains is recognized by D-ribose (Claims 8-9). The copending claims do not teach or suggest that the first and second group of regulatory core domains are linked to the same or different DNA binding domains (Claims 10-11). The copending claims do not teach or suggest the use of three DNA binding domains as claimed in claim 12 (Claim 12). The copending claims do not teach or suggest that the construct further comprises a nucleic acid encoding a reporter (Claim 13). The copending claims do not teach or suggest a cell comprising the construct (Claim 17), selected from a bacterial cell (Claim 18).
However, one of ordinary skill in the art would have considered the teachings of Rondon as both references are common fields of endeavor pertaining to the use of constructs comprising DNA regulatory core domains and DNA binding domains.
The applicable teachings of Rondon are discussed above as applied to claims 3-13 and 17-18.
Therefore, it would have been obvious to modify the copending claims in order to arrive at instant claims 3-13 and 17-18. A person of ordinary skill in the art would have been motivated to do so in order to utilize known DNA binding domains, DNA operators, and DNA regulatory domains that can be recognized by a first and second agents in a cell, as described by Rondon. A person of ordinary skill in the art would have had a reasonable expectation of success because both the copending claims and Rondon teach the use of constructs comprising regulatory core domains, DNA binding domains, and DNA operator elements that can be utilized to modulate the transcription of a target nucleic acid of interest.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KYLE T REGA whose telephone number is (571)272-2073. The examiner can normally be reached M-R 8:30-4:30, every other F 8:30-4:30 (EDT/EST).
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636