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 .
Detailed Action
Election/Restrictions
Applicant’s election without traverse of Group 1 (claims 1-18) in the reply filed on 08/28/2025 is acknowledged.
Claims 1-20 are pending.
Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected Group, there being no allowable generic or linking claim.
Priority
Applicant’s claim for the benefit of a prior-filed parent provisional application 63249992, filed on 09/29/2021 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest priority date for the instant application is 09/29/2021.
Claims Status
Claims 19-20 have been withdrawn from consideration as being drawn to non-elected subject matter, and claims 1-18 have been considered on the merits. All arguments have been considered.
Withdrawn Objections & Rejections
Applicant's response filed 01/21/2026 has been considered. Rejections and/or objections not reiterated from the previous Office action mailed 10/21/2025 are hereby withdrawn.
The objections and rejections presented herein represent the full set of objections and rejections currently pending in the application.
Claim Rejections - 35 USC § 102 (Maintained)
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-4, 11-14 and 17-18 stand rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Farhadi et al (WO 2020/146379 A1) as evidenced by Takara (Tet systems overview [online] Takara [retrieved on 10/11/2025]. Retrieved from the internet: < https://www.takarabio.com/learning-centers/gene-function/inducible-systems/tet-inducible-systems/tet-systems-overview#:~:text=Each).
Regarding claim 1: The claim recites “gas vesicle structural proteins”. The instant specification is silent on an explicit definition of this term.
Farhadi define gas vesicle structural proteins as “proteins forming part of a gas-filled protein structure intracellularly expressed by certain bacteria or archaea and can be used as a mechanism to regulate cellular buoyancy in aqueous environments” (p23 0010). Farhadi teach gvpA and gvpB and gvpC are gas vesicle structural proteins (p23 0010).
The claim recites “gas vesicle assembly proteins”. The instant specification is silent on an explicit definition of this term.
Farhadi define gas vesicle assembly proteins as “proteins with various putative functions such as nucleators and/or chaperons as well as proteins with an unknown specific function related to the assembly of the GV” (p28 0022). Farhadi further teach gvpN and gvpF are gas vesicle assembly proteins (p28 0023).
The instant claims are interpreted using the definitions as taught by Farhadi.
Farhadi teach expression of gas vesicle (GV) constructs in a mammalian cell using expression vectors such as viral vectors (p51/52 00116). Farhadi teach the gene expression cassette comprises one or more GvpA or GvpB genes (claim 1). This reads on gas vesicle structural (GVS) gene.
Farhadi also teach one or more additional GV gene cluster (other than GvpA and GvpB) wherein the expression cassette is operably linked by regulatory sequences allowing co-expression of the GV proteins and formation of the GV in the mammalian cell (claim 1).
Farhadi further teach the gvp gene cluster comprises the gvpN (claim 8). This reads on a vesicle assembly (GVA) gene.
Farhadi further teach the coding regions of the GV genes comprise regulatory sequences comprising promoters (p38 0063).
Regarding claims 2-4: The claim recites “context-dependent promoter”. The instant specification is silent on an explicit definition for this term. The broadest reasonable interpretation of “context-dependent promoter” is any promoter for which activity is regulated by a specific cellular condition.
Farhadi teach a chemically inducible gene circuit in which the gene cassettes are under the control of the doxycycline-inducible TRE3G promotor (TRE), with expression triggered by incubation with doxycycline (p13 0047). This reads on a context-dependent promoter wherein the transactivator transcript is capable of being translated to generate a transactivator.
As evidenced by Takara, the TRE3G promoter binds the TetR transactivator in the presence of doxycycline (Takara p3). Thus the TRE3G system disclosed by Farhadi comprises a context-dependent promoter (doxycycline dependent) operably linked to a transactivatory polynucleotide comprising a transactivator gene (TetR). The activity of the context-dependent promoter is dependent on a unique cell state, a cell state comprising doxycycline.
Takara also disclose the TREG3G promoter comprises tetO repeats (p2). This reads on more than one copy of a tet operator.
As evidenced by Takara, the TRE3G system comprises a transactivator which only strongly binds the transactivator in the presence of doxycycline (Takara p3). This reads on a reverse tetracycline-controlled transactivator.
Regarding claim 11: Farhadi teach the gas vesicle gene cluster comprises gvp genes from B. megaterium (claim 9).
Regarding claim 12: Farhadi teach GVA (gvpA) gene from Anabaena flos-aquae and gvpN from B. megaterium (claim 12).
Regarding claim 13: The teachings of Farhadi are discussed supra. Farhadi also teach the gas vesicle gene cluster comprises GvpA, GvpN, GvpJ, GvpK, GvpF, GvpG, GvpW, GvpV (claim 11).
Farhadi also teach the GVPA gene expression cassette is under the control of a mammalian promoter and additional mammalian regulatory regions and the one or more additional gvp gene expression cassettes comprising the gvp genes of the GV gene cluster other than gvpA under control of a mammalian promoter and additional regulatory regions in a configuration allowing expression of the GV proteins in the mammalian cell wherein each of the additional gvp gene expression cassette further comprises a separation element between the two or more gvp genes configured to provide a separate expression of the corresponding GV protein and the GVP cassettes are operably linked by regulatory sequence allowing co-expression of the GV proteins (claim 1).
Thus each of the GV polynucleotides is operably connected to a tandem gene expression element; a regulatory sequence allowing co-expression of the GV proteins.
Regarding claim 14: The teachings of Farhadi are discussed supra. Farhadi also teach gas vesicle genetic circuit can be introduced into mammalian cells using transformation techniques such as lenti-virus (p72 00187).
Regarding claim 17: The teachings of Farhadi are discussed supra.
Farhadi also teach the gas vesicle expression system can comprise a separation element placed between two adjacent coding genes allowing for separate transcription or translation of the two adjacent coding genes (p42 0081). Farhadi further teach the separation element can be an internal ribosome entry site (IRES) (p42 ¶0082).
Farhadi also teach the gene expression cassette can comprise a UTR with a combination of a woodchuck hepatitis post-translational regulatory element (WPRE) and a polyA tail, which is expected to result in highest expression.
One of ordinary skill in the art would understand the polyA tail and WPRE would be present in the 5’ UTR of the transgene polynucleotide.
Regarding claim 18: The teachings of Farhadi are discussed supra. Farhadi also teach the vector can be a viral particle (p53 00119).
One of ordinary skill in the art would understand a vector that is viral particle comprises a viral vector encapsidated in a viral particle.
Thus the teachings of Farhadi anticipate the invention as claimed.
Claim Rejections - 35 USC § 103 (Maintained)
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.
Claims 5-10 stand rejected under 35 U.S.C. 103 as being unpatentable over Farhadi et al (WO 2020/146379 A1) as evidenced by Takara (Tet systems overview [online] Takara [retrieved on 10/11/2025]. Retrieved from the internet: < https://www.takarabio.com/learning-centers/gene-function/inducible-systems/tet-inducible-systems/tet-systems-overview#:~:text=Each) and as applied to claim 1-4, 11-14 and 17-18 above, and further in view of Gallo et al (Frontiers in Behavioral Neuroscience (2018)12:79;1-16).
Claims 1-4, 11-14 and 17-18 are anticipated by Farhadi, and thus are also rendered obvious (see above).
Regarding claims 5-10: The teachings of Farhadi are discussed supra. Farhadi do not teach the degree of expression of the transactivator is positively correlated with presence and/or amount of a unique cell type and/or a unique cell state. The limitations required by the instant claim (degree of expression correlated with unique cell type/cell state) would be determined by use of a specific promoter (for example a cell-type specific promoter) to drive transgene expression.
Gallo teach the Immediate Early Gene (IEG) c-fos is selectively and promptly upregulated in neuronal subpopulations (abstract). Gallo teach c-fos is an example of a gene who’s increased expression is used as an indicator for neuronal activation (p3 col1 para3). Gallo also teach c-fos is one of the most commonly used marker to map neuronal activity (p2 col1 para1) and that the c-fos promoter has been used with optical sensitive proteins to mark and manipulate subsets of cells (p3 col2 para5). This reads on a unique gene expression pattern associated with the expression of one or more endogenous proteins whose expression is regulated by the endogenous context-dependent promoter. Gallo teach c-Fos is part of the AP-1 signaling complex whose downstream targets have yet to be fully characterized (p3 col2 para4). Thus this reads on the unique cell type is characterized by signal transduction. Expression of c-Fos is used to map neuronal activity and thus reads on a tissue-specific promotor (specific to neuronal tissue) and reads on a neuronal activity-dependent promoter.
It would have been obvious to one of ordinary skill in the art to adapt the viral vector taught of Farhadi by using the c-fos promoter as taught by Gallo to express the gas vesicle gene cassette in a subset of cell.
Accordingly, one of ordinary skill in the art would have been motivated to modify the viral vector as taught by Farhadi to for the purposes of expressing the gas vesicle gene cassette in a neuronal cell population.
One would have had a reasonable expectation of success because Gallo discloses successful use of the c-fos promoter to mark and manipulate a subset of cells and one of ordinary skill in the art would understand that the same promoter used to direct expression of different transgenes would have a reasonable expectation of functioning as described in the art.
Claim 15 stands rejected under 35 U.S.C. 103 as being unpatentable over Farhadi et al (WO 2020/146379 A1) as evidenced by Takara (Tet systems overview [online] Takara [retrieved on 10/11/2025]. Retrieved from the internet: < https://www.takarabio.com/learning-centers/gene-function/inducible-systems/tet-inducible-systems/tet-systems-overview#:~:text=Each) and as applied to claim 1-4, 11-14 and 17-18 above, and further in view of Esmaeili et al (Biomedicine & Pharmacotherapy (2020)128;1-11).
Claims 1-4, 11-14 and 17-18 are anticipated by Farhadi, and thus are also rendered obvious (see above).
Regarding claim 15: The teachings of Farhadi are discussed supra. Farhadi teach gas vesicle genetic circuit can be introduced into mammalian cells using transformation techniques such as lenti-virus (p72 00187).
Farhadi do not teach the single viral vector is a lentiviral vector comprising a lentivirus vector comprising HIV-1.
Esmaeili teach lentiviral systems for gene delivery can achieve a high transduction rate and methods for large-scale production of the vectors have been developed (p7 col1 para3). Esmaeili also teach HIV-1 based lentiviral vectors have been the vectors of choice due to the HIV’s capability to integrate specific genes into dividing and non-dividing cells irreversibly in order to express the gene of interest permanently (p1 col1 para2).
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit comprising a lentiviral vector as taught by Farhadi by using an HIV-1 based lentiviral vector as taught by Esmaeili because Esmaeili teaches HIV-1 based lentiviral vectors can integrate specific genes into dividing and non-dividing cells irreversibly.
Accordingly, one of ordinary skill in the art would have been motivated to modify the gas vesicle genetic circuit as taught by Farhadi by using an HIV-1 based lentiviral vector to for the purposes of stable integration of the gene expression cassette into mammalian cells.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a widely used vector is well characterized and thus the results would be predictable.
Claim 16 stands rejected under 35 U.S.C. 103 as being unpatentable over Farhadi et al (WO 2020/146379 A1) as evidenced by Takara (Tet systems overview [online] Takara [retrieved on 10/11/2025]. Retrieved from the internet: < https://www.takarabio.com/learning-centers/gene-function/inducible-systems/tet-inducible-systems/tet-systems-overview#:~:text=Each) and as applied to claim 1-4, 11-14 and 17-18 above, and further in view Bulcha et al (Signal Transduction and Targeted Therapy (2021) 6:53;1-24) and Esmaeili et al (Biomedicine & Pharmacotherapy (2020)128;1-11).
Claims 1-4, 11-14 and 17-18 are anticipated by Farhadi, and thus are also rendered obvious (see above).
Regarding claim 16: The teachings of Farhadi are discussed supra. Farhadi do not teach the viral vector comprises a left (5’) retroviral long terminal repeat wherein the promoter of the 5’ LTR is replaced with a heterologous promoter.
Bulcha teach lentivirus vectors are a robust vector for genetically modified cell therapies (p15 para 3; title). Bulcha further teach the HIV-1 a lentiviral vector in which the genome comprises a 5’ LTR (p15 para 3).
Figure 5 teaches the third generation HIV-1-based lentiviral vector comprises a the 5’ LTR in which the 5’ U3 sequence is replaced by the CMV promoter. One of ordinary skill in the art would understand the CMV promoter is derived from a non-HIV-1 virus and thus reads on heterologous promoter, and that the 5’ U3 sequence of HIV comprises the HIV promoter.
Figure 5 also teaches the 3’ LTR comprises a deletion of part of the U3 sequence and thus reads on the 3’ LTR comprises one or more modifications and/or deletions.
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit as taught by Farhadi by using a 5’ LTR comprising a heterologous promoter as taught by Bulcha because Bulcha teach a third-generation HIV-1-based lentiviral vector comprises a 5’ LTR in which the U3 sequence is replaced by a strong viral promoter such as CMV.
Accordingly, one of ordinary skill in the art would have been motivated to modify the 5’ LTR as taught by Bulcha to for the purposes of having strong expression of the gene cassette.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a gene vector with a strong promoter would result in a more efficient gene vector.
Thus the invention is rendered obvious by the combined teachings of Farhadi, Gallo, Esmaeili and Bulcha.
Double Patenting (Maintained)
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
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 stands provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18/066,814 in view of Farhadi et al (WO 2020/146379 A1).
Regarding claim 1: Copending claims 1 and 2 each recite one or more promoters operably connected to one or more gas vesicle polynucleotides comprising one or more gas vesicle assembly (GVA) gene(s) encoding one or more GVA protein(s), and one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s), wherein the one or more GVA protein(s) and the one or more GVS protein(s) are capable of forming gas vesicles (GVs) upon expression in a cell.
Copending claims 1 and 2 do not teach one or more promoters are comprised within a viral vector.
Farhadi teach the expression of gas vesicle constructs in a mammalian cell wherein the expression vectors can comprise viral vectors (p52 00116).
It would have been obvious for one of ordinary skill in the to combine copending claims 1 or 2 with the disclosure of Farhadi because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Combining the gas vesicle expression system taught by the copending claims with the disclosure of Farhadi, use of a viral expression vector, would have led to predictable results with a reasonable expectation of success because both inventions are drawn to expression of gas vesicles in a cell.
Claims 1, 11, 15, 16, and 18 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/317,915 in view of Farhadi et al (WO 2020/146379 A1), Esmaeili et al (Biomedicine & Pharmacotherapy (2020)128;1-11) and Bulcha et al (Signal Transduction and Targeted Therapy (2021) 6:53;1-24).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 1: Copending claim 1 teaches a Gas Vesicle Expression System (GVES) configured of one or more gene clusters of gas vesicle protein (gvp) genes encoding gas vesicle (GV) proteins capable of forming a gas vesicle. Copending claim 1 further recites gene expression under the control of a promoter allowing expression in a cell. Copending claim 1 teaches expression of gvpA and gvpN. This reads on one or more gas vesicle assembly gene and one or more gas vesicle structural genes.
Copending claim 1 does not teach the GVES comprises a viral vector.
Farhadi teach the expression of gas vesicle constructs in a mammalian cell wherein the expression vectors can comprise viral vectors (p52 00116).
It would have been obvious for one of ordinary skill in the to combine copending claim 1 with the disclosure of Farhadi because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Combining the gas vesicle expression system taught by the copending claim with the disclosure of Farhadi, use of a viral expression vector, would have led to predictable results with a reasonable expectation of success because both inventions are drawn to expression of gas vesicles in a cell.
Regarding claim 11: Copending claim 1 also teaches the gas vesicle protein genes comprise a GVGC having gvpB, gvpN, gvpF, gvpG, gvpL, gvpS, gvpK, gvpJ, and gvpU from B. megateriu.
Regarding claim 15: The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi teach gas vesicle genetic circuit can be introduced into mammalian cells using transformation techniques such as lenti-virus (p72 00187).
Farhadi do not teach the single viral vector is a lentiviral vector comprising a lentivirus vector comprising HIV-1.
Esmaeili teach lentiviral systems for gene delivery can achieve a high transduction rate and methods for large-scale production of the vectors have been developed (p7 col1 para3). Esmaeili also teach HIV-1 based lentiviral vectors have been the vectors of choice due to the HIV’s capability to integrate specific genes into dividing and non-dividing cells irreversibly in order to express the gene of interest permanently (p1 col1 para2).
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit comprising a lentiviral vector as taught by Farhadi by using an HIV-1 based lentiviral vector as taught by Esmaeili because Esmaeili teaches HIV-1 based lentiviral vectors can integrate specific genes into dividing and non-dividing cells irreversibly.
Accordingly, one of ordinary skill in the art would have been motivated to modify the gas vesicle genetic circuit as taught by Farhadi by using an HIV-1 based lentiviral vector to for the purposes of stable integration of the gene expression cassette into mammalian cells.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a widely used vector is well characterized and thus the results would be predictable.
Regarding claim 16: The claim recites “one or more of” followed by a list of alternatives “a left (5') retroviral LTR, a Psi (Psi) packaging signal, a central polypurine tract/DNA flap (cPPT/FLAP), a retroviral export element”. As discussed supra, this is interpreted as open claim language that requires one of the elements recited in the alternative and does not exclude additional elements not recited in the claim.
The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi do not teach the viral vector comprises a left (5’) retroviral long terminal repeat wherein the promoter of the 5’ LTR is replaced with a heterologous promoter.
Bulcha teach lentivirus vectors are a robust vector for genetically modified cell therapies (p15 para 3; title). Bulcha further teach the HIV-1 a lentiviral vector in which the genome comprises a 5’ LTR (p15 para 3).
Figure 5 teaches the third generation HIV-1-based lentiviral vector comprises a the 5’ LTR in which the 5’ U3 sequence is replaced by the CMV promoter. One of ordinary skill in the art would understand the CMV promoter is derived from a non-HIV-1 virus and thus reads on heterologous promoter, and that the 5’ U3 sequence of HIV comprises the HIV promoter.
Figure 5 also teaches the 3’ LTR comprises a deletion of part of the U3 sequence and thus reads on the 3’ LTR comprises one or more modifications and/or deletions.
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit as taught by Farhadi by using a 5’ LTR comprising a heterologous promoter as taught by Bulcha because Bulcha teach a third-generation HIV-1-based lentiviral vector comprises a 5’ LTR in which the U3 sequence is replaced by a strong viral promoter such as CMV.
Accordingly, one of ordinary skill in the art would have been motivated to modify the 5’ LTR as taught by Bulcha to for the purposes of having strong expression of the gene cassette.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a gene vector with a strong promoter would result in a more efficient gene vector.
Regarding claim 18: The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi also teach the vector can be a viral particle (p53 00119).
One of ordinary skill in the art would understand a vector that is viral particle comprises a viral vector encapsidated in a viral particle.
Claims 1, 11, 15, 16, and 18 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/060,598 in view of Farhadi et al (WO 2020/146379 A1), Esmaeili et al (Biomedicine & Pharmacotherapy (2020)128;1-11) and Bulcha et al (Signal Transduction and Targeted Therapy (2021) 6:53;1-24.
This is a provisional nonstatutory double patenting rejection.
Regarding claims 1 and 11: Copending claim 1 teaches a gas vesicle expression system configured for expression a mammalian cell encoding gas vesicle proteins capable of forming a gas vesicle. Copending claim 1 further teaches the gene expression cassette comprises gas vesicle genes under control of a mammalian promoter. This reads on comprising one or more first promoters operably connected to one or more gas vesicle poly nucleotides of the instant claim.
Copending claim 1 further teaches the expression cassette comprises gbpA an one or more gvp cassette. Copending claim 10 teaches the gas vesicle gene cluster comprises gvpB, gvpN gvpF, gvpG, gvpL gvpS, gvpK, gvpJ, and gvpU from B. megaterium. This reads on one or more gas vesicle assembly gene and one or more gas vesicle structural gene.
Copending claim 1 does not teach the gas vesicle expression system comprises a viral vector.
Farhadi teach the expression of gas vesicle constructs in a mammalian cell wherein the expression vectors can comprise viral vectors (p52 00116).
It would have been obvious for one of ordinary skill in the to combine copending claim 1 with the disclosure of Farhadi because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Combining the gas vesicle expression system taught by the copending claim with the disclosure of Farhadi, use of a viral expression vector, would have led to predictable results with a reasonable expectation of success because both inventions are drawn to expression of gas vesicles in a cell.
Regarding claim 15: The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi also teach gas vesicle genetic circuit can be introduced into mammalian cells using transformation techniques such as lenti-virus (p72 00187).
Farhadi do not teach the single viral vector is a lentiviral vector comprising a lentivirus vector comprising HIV-1.
Esmaeili teach lentiviral systems for gene delivery can achieve a high transduction rate and methods for large-scale production of the vectors have been developed (p7 col1 para3). Esmaeili also teach HIV-1 based lentiviral vectors have been the vectors of choice due to the HIV’s capability to integrate specific genes into dividing and non-dividing cells irreversibly in order to express the gene of interest permanently (p1 col1 para2).
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit comprising a lentiviral vector as taught by Farhadi by using an HIV-1 based lentiviral vector as taught by Esmaeili because Esmaeili teaches HIV-1 based lentiviral vectors can integrate specific genes into dividing and non-dividing cells irreversibly.
Accordingly, one of ordinary skill in the art would have been motivated to modify the gas vesicle genetic circuit as taught by Farhadi by using an HIV-1 based lentiviral vector to for the purposes of stable integration of the gene expression cassette into mammalian cells.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a widely used vector is well characterized and thus the results would be predictable.
Regarding claim 16: The claim recites “one or more of” followed by a list of alternatives “a left (5') retroviral LTR, a Psi (Psi) packaging signal, a central polypurine tract/DNA flap (cPPT/FLAP), a retroviral export element”. As discussed supra, this is interpreted as open claim language that requires one of the elements recited in the alternative and does not exclude additional elements not recited in the claim.
The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi do not teach the viral vector comprises a left (5’) retroviral long terminal repeat wherein the promoter of the 5’ LTR is replaced with a heterologous promoter.
Bulcha teach lentivirus vectors are a robust vector for genetically modified cell therapies (p15 para 3; title). Bulcha further teach the HIV-1 a lentiviral vector in which the genome comprises a 5’ LTR (p15 para 3).
Figure 5 teaches the third generation HIV-1-based lentiviral vector comprises a the 5’ LTR in which the 5’ U3 sequence is replaced by the CMV promoter. One of ordinary skill in the art would understand the CMV promoter is derived from a non-HIV-1 virus and thus reads on heterologous promoter, and that the 5’ U3 sequence of HIV comprises the HIV promoter.
Figure 5 also teaches the 3’ LTR comprises a deletion of part of the U3 sequence and thus reads on the 3’ LTR comprises one or more modifications and/or deletions.
It would have been obvious to one of ordinary skill in the art to adapt the gas vesicle genetic circuit as taught by Farhadi by using a 5’ LTR comprising a heterologous promoter as taught by Bulcha because Bulcha teach a third-generation HIV-1-based lentiviral vector comprises a 5’ LTR in which the U3 sequence is replaced by a strong viral promoter such as CMV.
Accordingly, one of ordinary skill in the art would have been motivated to modify the 5’ LTR as taught by Bulcha to for the purposes of having strong expression of the gene cassette.
One would have had a reasonable expectation of success because Esmaeili discloses HIV-1 based lentiviral vectors are the vectors of choice (widely used) and one of ordinary skill in the art would understand that a gene vector with a strong promoter would result in a more efficient gene vector.
Regarding claim 18: The teachings of copending claim 1 and Farhadi are discussed supra. Farhadi also teach the vector can be a viral particle (p53 00119).
One of ordinary skill in the art would understand a vector that is viral particle comprises a viral vector encapsidated in a viral particle.
Response to Arguments
The responses are directed to the Arguments filed 08/28/2025. The arguments have been fully considered.
Regarding Arguments directed to 35 USC § 112:
Regarding claims 2, 3, 4, 6, 9, 10 and 17:
The claims were rejected because they recite or refer to the term “unique”. The claim term “unique” is indefinite because it is a relative term.
Applicant argues one of ordinary skill in the art would understand the term “unique” in the context of cell type and cell state means being the only one of its kind.
This is persuasive and the rejection is withdrawn.
Regarding claim 16: The claim is amended to recite “elements selected from the group consisting of”. This overcomes the rejection as written. The rejection under 11(b) regarding claim 16 is withdrawn.
Regarding Arguments directed to 35 USC § 102:
Applicant argues that Farhadi teach two gene expression cassettes and thus do not read on the instant invention which requires a single viral vector.
The Office agrees that Farhadi teach two gene expression cassettes, however disagrees with the interpretation that two gene expression cassettes require separate viral vectors.
In fact, Farhadi teach “the GVPB cassette can be comprised on a same polynucleotide construct together with the cassette comprising gvpN, gvpF, gvpG, gvpL, gvpS, gvpK, gvpJ and gvpU” (Farhadi p50 [00111]). This clearly demonstrates the teachings of Farhadi encompass multiple cassettes on a single vector (a same polynucleotide construct).
The rejection is maintained.
Regarding Arguments directed to 35 USC § 103:
Applicant argues that Farhadi teach at least two gene expression cassettes and Applicant doesn’t provide additional arguments against the additional references. The arguments directed to Farhadi are discussed supra. As Applicant does not present additional specific arguments that could be rebutted, the arguments are considered not persuasive.
The rejection is maintained.
Regarding Arguments directed to Double Patenting:
Regarding the rejection over 18/066,814 (‘814): Applicant argues that claim 1 of ‘814 is drawn to a cell composition as opposed to the vector of the instant invention and that the combination of ‘814 and Farhadi would result in a cell comprising cell "comprising at least two gene expression cassettes, one for expressing GV A genes and another one for expressing GVS gene”.
This argument is not persuasive because the combination would comprise a vector as claimed, as discussed in the previous rejection restated in the instant action: “Farhadi teach the expression of gas vesicle constructs in a mammalian cell wherein the expression vectors can comprise viral vectors (p52 00116)”. Thus the combination would read on the viral vector of the instant invention
The rejection is maintained.
Regarding the rejection over 18/317,915 (‘915):
Applicant argues that the invention of ‘915 differs from the instant invention because ‘915 is drawn to a method rather than the vector of the instant disclosure.
This argument is not persuasive because the method of ‘915 teaches a method which uses (introduces) a gas vesicle expression system which renders obvious the claimed invention; a vector comprising the GVPA/B gene expression cassette.
Thus the combination of ‘915 and Farhadi, Esmaeili and Bulcha would render obvious the invention as claimed. The rejection is maintained.
Regarding the rejection over 19/060,598 (‘598):
Applicant does not present new arguments and thus the arguments are unpersuasive and the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ANDREA LYNNE MORRIS SPENCER/Examiner, Art Unit 1631
/TAEYOON KIM/Primary Examiner, Art Unit 1631
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