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 .
Priority
Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. § 119 (a)-(d). Acknowledgement is also made of Applicant's submission of the English translation of the certified copy and a statement that the translation is accurate in the reply dated 06/18/2026. The effective filing date is 03-16-2022.
Status of the Claims
Amendments dated 06/18/2026 are entered.
Claims 26 and 34-36 are cancelled.
Claims 25, 27-33 and 37-44 are pending and are examined herein.
Status of Objections and Rejections
All previous objections and rejections not set forth below have been withdrawn in view of Applicant’s amendments and/or upon consideration of Applicant’s arguments.
The text of those sections of Title 35 U.S. Code, not included in this action, can be found in a prior Office action.
Informalities
Claims 25, 31, 39, and 40 contain the following informalities:
Lack of an Oxford comma, the final comma in a list of three or more items (e.g., on line 6 of claim 25, there should be a comma after “comprising the nucleotide sequence of SEQ ID NO: 2”).
Claim Interpretation
Regarding claims 25, 27-33, and 37-44, page 10 of Remarks dated 06/18/2026 states that "consisting of the nucleotide sequence of SEO ID NO: 1" recited in claim 25 means “[c]losing the Figwort fragment to SEQ ID NO: 1 fixes it to the upstream region (-270 to -63, excluding the core)”, with the goal of distinguishing it from the TATA-core Figwort fragment (FS-l/FS-2, -151 to +31) used in Kumar.
Claim Rejections - 35 USC § 112
Indefiniteness
Response to Applicant’s arguments:
Amendments made to the claims filed in Applicant’s response submitted on 18 June 2026 overcame the rejection of record.
Claim Rejections – 35 U.S.C. 103
Applicant’s claim amendments and accompanying Remarks (see Claim Interpretation above) require the Examiner to conduct a new search and consideration. Accordingly, the new claim amendments necessitated new grounds of rejections under 35 USC § 103.
. Claims 25, 27, 37, 39, 41 and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Maiti-1 (cited in IDS; U.S. Patent No. 6420547 B1, by Indu B. Maiti, Nrisingha Dey, and Robert J. Shepherd, published 16 July 2002), Maiti-2 (U.S. Patent No. 6930182 B1, by Indu B. Maiti, and Nrisingha Dey, published 2005), Kumar (cited in IDS; Kumar D, Patro S, Ranjan R, Sahoo DK, Maiti IB, et al. (2011) Development of Useful Recombinant Promoter and Its Expression Analysis in Different Plant Cells Using Confocal Laser Scanning Microscopy. PLOS ONE 6(9): e24627, https://doi.org/10.1371/ journal.pone.0024627, published 9/9/2011), Ranjan (Ranjan R, Maiti IB, et al. Development and functional analysis of novel genetic promoters using DNA shuffling, hybridization and a combination thereof. PLoS One. 2012;7(3):e31931. doi: 10.1371/journal.pone.0031931. Epub 2012 Mar 14. PMID: 22431969; PMCID: PMC3303778., published 2012), and Mizutani (cited in IDS; MIZUTANI, A. et al. Regions of GAL4 critical for binding to a promoter in vivo revealed by a visual DNA-binding analysis. The EMBO Journal. 2003, vol. 22, no. 9, pp. 2178-2187, published 2003).
Claim 25 is listed below for reference within this document.
25. (currently amended): A gene construct for expression of a gene of a protein
of interest, comprising an FMM-UD promoter in which the following (i) and (ii) are sequentially
linked:
(i) an FMM promoter in which a Figwort subgenomic transcript promoter gene fragment
consisting of the nucleotide sequence of SEO ID NO: 1, a Mirabilis mosaic virus subgenomic
transcript promoter gene fragment comprising the nucleotide sequence of SEO ID NO: 2 and a
Mirabilis mosaic virus full-length transcript promoter gene fragment comprising the nucleotide
sequence of SEO ID NO: 3 are sequentially linked; and
(ii) an upstream DNA (UD) sequence with 4 repetitions of an upstream activation
sequence (UAS), which is a GAL4-binding site of yeast, linked to the 5' end of the FMM
promoter.
Regarding claim 25, Maiti-1 is a 2002 patent in the field of promoters and teaches that the “full-length transcript promoter from Mirabilis mosaic caulimovirus (MMV)… functions as a strong and uniform promoter for chimeric genes inserted into plant cells” (i.e., Mirabilis mosaic virus full-length transcript fragment )(emphasis provided; abstract). Maiti-1 also teaches in the abstract that “the MMV FLT promoter shows greater activity (14 to 24 fold) than the CaMV 35S promoter” (emphasis provided).
Maiti-1’s SEQ ID NO: 4 discloses the MMV full length transcript promoter DNA sequence and is a 100 percent match of instant SEQ ID NO: 3. (i.e., the Mirabilis mosaic virus full-length transcript promoter gene comprises a nucleotide sequence of SEQ ID NO: 3).
Maiti-1 teaches that the Caulimovirus genome generally contains two transcriptional promoters, one for the full-length transcript and the other for the subgenomic transcript (Sgt) which are respectively comparable to the CaMV p35S and 19S transcripts (col 1, lines 33-54) and that “the genomes of… [other] caulimoviruses [including]…figwort mosaic caulimovirus (FMV)… have been fully sequenced [and] transcriptional promoters have been derived from the genomes”; col 2, lines 16-37). This means that FMV has a Sgt promoter.
As indicated above, Maiti-1 teaches the instant claim 25’s Figwort mosaic caulimovirus promoters MMV Sgt promoter Mirabilis mosaic virus full-length transcript promoter gene comprising a nucleotide sequence of SEQ ID NO: 3, Mirabilis mosaic virus full-length transcript promoter, but does not explicitly teach the remaining limitations of the instant amended claim 25.
Maiti-2, a 2005 patent in the field of promoters, shares inventors with Maiti-1 and teaches that “a 333 bp MMV Sgt [Mirabilis mosaic caulimovirus sub genomic transcript] promoter fragment (sequence −306 to +27 from the transcription start site, TSS) was found to be sufficient for strongest promoter activity[,] shows comparable promoter activity to the MMV FLt promoter both in transgenic plants and in protoplasts[, and] demonstrates much greater activity compared to Cauliflower mosaic virus (CaMV) 19S promoter and 35S promoter” (emphasis provided; abstract).
Maiti-2 also teaches that “several Caulimoviridae genomes [including “Figwort mosaic virus (FMV)”] have been fully sequenced and characterized” where “transcript promoters from caulimoviruses,.. MMV and FMV are active in all plant organs” (col 1, lines 35-64).
Maiti-2 teaches SEQ ID NO: 2, which discloses the MMV Sgt promoter DNA sequence and is a 100 percent match of instant SEQ ID NO: 2 (i.e., a Mirabilis mosaic virus subgenomic transcript promoter gene fragment comprising the nucleotide sequence of SEQ ID NO: 2), and insertion and deletion analysis of “several regulatory domains found in… caulimovirus promoters and their coordinates in the MMV Sgt promoter [e.g., “the MMV Sgt promoter TATAA sequence (coordinates −65 to −61 from the Transcription Start Site (TSS) in FIG. 1) and the CAAT sequence (coordinates −110 to −70 from TSS in FIG. 1) located 41 bp upstream of the TATA box”]”(col 7, lines 16-42; col 7 line 43 to col 9 line 21).
Maiti-2 additionally teaches that “The strength of the MMV Sgt promoter is compatible with the MMV FLt promoter,” and that “the MMV Sgt promoter has only one copy of an ‘as-1’-like or ‘as-2’-like motif [enhancer elements ; whereas, duplicated copies are present in full-length transcript promoters of… FMV and MMV” (col 7, lines 16-42).
Maiti-2 adds that “there is very limited sequence homology between the MMV Sgt promoter with other caulimovirus promoters, although they are functionally analogous,” (col 11, lines 38-42). “The use of different promoters having non-homologous sequences may be useful in order to avoid genetic instability due to recombination between identical promoter sequences[, and,] thus, the present MMV Sgt promoter constructs will lend themselves handily to such studies, when used to drive the expression of a plant metabolic gene or genes in conjunction with other chimeric constructs driven by other, nonhomologous promoters” (col 11, lines 48-54).
As indicated above, Maiti-2, taken with the teachings of Maiti-1, teaches the limitation of the MMV [mirabilis mosaic caulimovirus] Sgt promoter fragment, Mirabilis mosaic virus full-length transcript promoter, and Figwort mosaic caulimovirus promoters but does not explicitly teach the remaining limitations of the instant amended claim 25.
Kumar, a 2011 article in the field of recombinant promoters, is coauthored by inventors of the Maiti-2 patent and teaches a plant expression vector carrying a recombinant promoter (MSgt-FSgt) in which the Figwort (FMV) subgenomic promoter supplies the TATA core and the Mirabilis (MMV) subgenomic promoter serves as the upstream element (Abstract).
Kumar also teaches, in the introduction para 1, that “several recombinant/synthetic promoters have been created earlier by (a) ligating the upstream activation sequence (UAS) of one promoter with the TATA box containing domain of another promoter; like tacI/tacII hybrid promoters…, E4/E8 hybrid promoters… and chimeric plant promoter (Mac promoter) [9]; (b) placing desired cis-elements in conjunction with heterologous promoters…; (c) bringing together cis-elements from different promoters.”
In introduction para 2, Kumar teaches that the “Risk of successive transformation by single promoter is that it might lead to silencing of transgenes in successive generations by homologous recombination [such that] use of different heterologous promoters is necessary during pyramiding (stacking) of genes in a single plant cell for developing a particular trait in plants.”
Kumar then teaches, GUS activity varied significantly depending on which regions of MS8 and FS3 were used in the two-fragment recombinant promoters that were limited to "Mirabilis upstream + Figwort core" framework (see Figure 1 of Kumar). Also see Table 1 of Kumar for regions of the Upstream Activation Sequence (UAS) of MS8 and downstream TATA containing sequence of FS3 present in each recombinant promoter.
Reading Maiti-2 and Kumar, one of ordinary skill in the art, interested in ascertaining enhanced “high-level constitutive expression of transgenes in a wide variety of plant cells” (Kumar Abstract) by pyramiding or stacking multiple genes in a single plant or plant cell would be motivated to try the opposite combination of Kumar’s Mirabilis upstream + Figwort core leading to synthetic recombinant promoters comprising Figwort subgenomic promoter upstream regions that lack the TATA core and Mirabilis mosaic virus sub-genomic transcript promoter regions that include the TATA core. A person having ordinary skill in the art would have a finite number of Figwort upstream regions, some of which would include instant SEQ ID NO: 1 while avoiding the TATA core region. Absent evidence to the contrary and criticality of the coordinates (-270 to -63) of Figwort upstream region chosen by Applicant, Figwort upstream regions chosen by a person having ordinary skill in the art would have a similar function as Applicant’s SEQ ID NO: 1, so long as the TATA core is absent. Mirabilis mosaic virus sub-genomic transcript promoter regions that include the TATA core would also comprise some of the nucleotide sequence of SEQ ID NO: 2.
Ranjan, a 2012 article in the field of recombinant promoters, is also coauthored by inventors of the Maiti-2 patent, cites Kumar, and teaches “using the Figwort mosaic virus (FMV) full-length transcript promoter (F) and the sub-genomic transcript promoter (FS) sequences, we generated… two hybrid promoters (FuasFScp and FSuasFcp)” where “FuasFScp and FSuasFcp showed enhanced activities compared to F, FS and CaMV 35S in both transient and transgenic Nicotiana tabacum and Arabidopsis plants” (Abstract).
Ranjan Figure 1(a) and caption teach “the coordinates of the respective promoters Figwort mosaic virus (FMV) full-length transcript promoter (F, −249 to +64), FMV sub-genomic transcript promoter (FS, −270 to +31)” and hybrid promoter (FSuasFcp, −449 to +64). The figure also teaches that Ranjan’s FSuasFcp consists of FS upstream activation sequence (FSuas, -270 to -60) and F core-promoter (Fcp, -239 to +64).
Ranjan Figure 8b shows that the second highest level of accumulation of uidA transcripts as measured by RT-PCR was observed in transgenic plants carrying the FSuasFcp promoter.
Like Kumar, Ranjan also teaches “ligating the upstream activation sequence (UAS) from one promoter to the TATA box-containing domain of another promoter” (introduction para 2). In the same paragraph, Ranjan adds that “DNA shuffling has the real potential to generate promoter libraries consisting of functional promoters of varying strength” (both constitutive and tissue specific; emphasis provided).
Reading this, one of ordinary skill in the art, interested in ascertaining enhanced “high-level constitutive expression of transgenes in a wide variety of plant cells” (Kumar Abstract) by pyramiding or stacking multiple genes in a single plant or plant cell, would be motivated to try “hybridization… techniques using two well characterized (heterologous) promoters”(Ranjan) of another caulimovirus, namely, Mirabilis mosaic virus full-length and sub-genomic-transcript promoters which are described by Maiti-2 and given the finite number of predictable outcomes would arrive upon a hybrid MM promoter in which a Mirabilis mosaic virus sub genomic transcript promoter gene fragment comprising the nucleotide sequence of instant SEO ID NO: 2 and a Mirabilis mosaic virus full-length transcript promoter gene fragment comprising the nucleotide sequence of instant SEO ID NO: 3 are sequentially linked.
Mizutani, also in the field of recombinant promoters, teaches that transcription activators are allowed to effectively bind to promoters having four GAL4-binding sites (i.e., an upstream DNA having four repeated copies of an upstream activation sequence (UAS), which is a GAL4-binding site of yeast) (see title, abstract, and figure 1). Mizutani also teaches that the 4 GAL4 copies are located upstream of the coding sequence of a gene of interest, RFP, where the promoter is typically placed and thus would make sense for the 4X GAL4 to be downstream of a promoter sequence like FMM (i.e., linked to the 5' end of the FMM promoter) (Figure 7).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine and to modify:
Maiti-1’s teaching of SEQ ID NO: 4 (i.e., the Mirabilis mosaic virus full-length transcript promoter gene comprises a nucleotide sequence of SEQ ID NO: 3),
Maiti-2’s teachings of regulatory domains in the Mirabilis full length and sub-genomic-transcript promoters, the effect of deletion fragments (cols 7-9), the very limited sequence homology between the MMV Sgt promoter with other caulimovirus promoters, and Maiti-2’s SEQ ID NO: 2 (i.e., i.e., a Mirabilis mosaic virus subgenomic transcript promoter gene fragment comprising the nucleotide sequence of SEQ ID NO: 2),
Kumar’s teachings of ligating the upstream activation sequence (UAS) of one promoter with the TATA box containing domain of another promoter,
Ranjan’s teachings of hybridization of the full-length and sub-genomic-transcript promoters of a Caulimovirus, of the regulatory domains in Figwort full-length and sub-genomic-transcript promoters, and FS upstream activation sequence (FSuas, -260 to -60) (i.e., an FMM promoter in which a Figwort subgenomic transcript promoter gene fragment), and
Mizutani’s four copies of GAL4‐binding site,
thus arriving at the instant invention with reasonable expectation of success and without surprising results. Recognizing the potential of Ranjan’s 2012 teachings of hybridization of the full-length and sub-genomic-transcript promoters of a caulimovirus and ligating the upstream activation sequence (UAS) from one promoter to the TATA box-containing domain of another promoter against the background of Maiti-1 and Maiti-2’s combined 2002 and 2005 teachings of sequences and regulatory domains in the Mirabilis full length and sub-genomic-transcript promoters and the effect of deletion fragments it would have been obvious to a person having ordinary skill in the art to try making a MM promoter in which a Mirabilis mosaic caulimovirus sub genomic transcript promoter gene fragment (Maiti-2’s SEQ ID NO: 2) without the TATA box and a Mirabilis mosaic caulimovirus full-length transcript promoter gene fragment (Maiti-1 SEQ ID NO: 4) are sequentially linked. Further, knowledge of Kumar’s 2011 and Ranjan’s 2012 teachings of ligating the UAS from one promoter to the TATA box-containing domain of another promoter and Ranjan’s 2012 teaching of the Figwort mosaic caulimovirus sub genomic transcript promoter’s upstream activation sequence (FSuas, -260 to -60) which excludes the core (c.f., instant SEQ ID NO: 1, see Claim Interpretation) along with the motivation to “generate promoter libraries consisting of functional promoters of varying strength” (Ranjan, Introduction para 2; emphasis supplied), it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further combine the putative MM promoter with another characterized promoter, the Figwort mosaic caulimovirus sub genomic transcript promoter being one of the finite options, arriving at a FMM promoter in which a Figwort mosaic caulimovirus subgenomic transcript promoter gene fragment, (e.g., Ranjan’s FSuas) a Mirabilis mosaic caulimovirus sub genomic transcript promoter gene fragment and a Mirabilis mosaic caulimovirus full-length transcript promoter gene fragment are sequentially linked. In an effort to further enhance expression and vary promoter strength by “placing desired cis-elements in conjunction with heterologous promoters [or] bringing together cis-elements from different promoters” (Kumar, introduction para 1), a person having ordinary skill in the art reading about strong recombinant promoter elements in Mizutani would recognize the utility of 4 copies of the GAL4-binding site upstream of the coding sequence of a gene of interest(i.e., an upstream DNA having four repeated copies of an upstream activation sequence (UAS), which is a GAL4-binding site of yeast and it would have been obvious to said person having ordinary skill in the art to further combine this teaching with the combined teachings of Maiti-1, Maiti-2, Kumar, and Ranjan by placing 4 copies of the GAL4 binding site at the 3’ end of the putative FMM promoter, thus arriving at the claimed invention with a reasonable expectation of success and no surprising results.
It is noted that Ranjan’s FS upstream activation sequence (FSuas, -260 to -60) differs from the instant SEQ ID NO: 1 by 3 nucleotides. Absent evidence to the contrary and criticality of the coordinates (-270 to -63) of Figwort upstream region chosen by Applicant, Figwort upstream regions chosen by a person having ordinary skill in the art would have a similar function as Applicant’s SEQ ID NO: 1, so long as the TATA core is absent. Since the Patent Office does not have the facilities to examine and compare the Applicant’s SEQ ID NO: 3 with Ranjan’s FSuas, the burden of proof is upon the Applicant to show an unobvious distinction between the claimed plant and the plant of the prior art. See In re Best, 562F.2d 1252, 195 USPQ 430 (CCPA 1977).
Regarding claim 27, which depends from claim 25, one of ordinary skill in the art before the filing of the claimed invention would have been motivated and able use standard procedures in art recombine the sequences into a Binary vector plasmid, like pINDEX1, that comprises at least a 93 percent match to SEQ ID NO: 4 (i.e., the gene construct of claim 25, FMM-UD promoter gene comprises a nucleotide sequence of SEQ ID NO: 4) in order to ascertain enhanced “high-level constitutive expression of transgenes in a wide variety of plant cells” (Kumar Abstract).
Regarding claims 37 and 39, which depend from claim 25, Kumar teaches “promoter-GUS vectors” where the GUS gene encodes the reporter protein GUS and can be replaced by other genes encoding proteins of interest like GFP (i.e., the protein of interest is a reporter gene) (page 2, col 2, last 3 para). Maiti teaches “a chimeric gene construct containing… multiple enhancer domains… and a coding sequence for a protein of interest” (see column 1 lines 7-23).
Regarding claims 41 and 43, which depend from claim 37 and ultimately depend from claim 25, Ranjan teaches a plant expression vector and Agrobacterium transformed with the vector (i.e., a transformant for high expression of a gene of a protein of interest, transformed with the recombinant expression vector of claim 37) and that twelve independent plant lines were generated [by “Agrobacterium tumefaciens mediated plant transformation”] for each construct [i.e., vector]” and maintained under greenhouse conditions (i.e., a plant, into which the transformant is introduced) (Materials and methods, para 12).
Claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani as applied to claim 25 above, further in view of Limphong (cited in IDS; U.S. Patent Application Publication No. 2019/0002906A1, published 1/3/2019).
Maiti teaches “a 3′ untranslated region downstream of the promoter's TATA box” (claim 2) (i.e., the TATA box sequence is comprised at a 3' end of the promoter).
Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani do not explicitly teach a 5' UTR gene is linked to a 5' end of the FMM-UD promoter.
Limphong is in the field of target gene expression like Kumar and teaches expression of a target plant gene using an mRNA construct comprising a 5' UTR represented by SEQ ID NO: 10 which is identical to SEQ ID NO: 5 in the present application (i.e., the 5' UTR gene comprises a nucleotide sequence of SEQ ID NO: 5). Regarding the positioning of the 5' UTR gene being linked to the 5' end of the FMM-UD promoter, a person having ordinary skill in the art would recognize the need to put the 5’ UTR downstream of the promoter region and any gene insertion region when constructing an expression vector.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani as applied to claim 25 above, further in view of Mason (cited in IDS; U.S. Patent Application Publication No. 2020/0407741A1, published 8/31/2020).
The claim is drawn to a vector with a promoter, FMM-UD promoter, and a terminator, 3PR terminator.
Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani teach the limitations of claim 25, which includes the FMM-UD promoter but do not explicitly teach a further comprised 3PR terminator in which a cauliflower mosaic virus 35S terminator gene, a 3' region of a potato proteinase inhibitor II gene, and a gene of an RB7 scaffold attachment site are sequentially linked.
Mason is in the field of recombinant expression vectors for protein production in plants and teaches that “an expression cassette comprises three components: a promoter sequence (part of the 5′ untranslated region, 5′ UTR), an open reading frame, and a 3′ untranslated region (3′ UTR) [where] regulatory sequences are found in the 5′ UTR and the 3′ UTR.” (para 39). Regulatory sequences include promoters and terminators meaning Expression cassettes or vectors comprise a promoter and a terminator regions.
Mason also teaches a vector carrying a terminator region, “35S-Pin2”, in which a cauliflower mosaic virus 35S terminator is fused to the 3' UTR region of potato proteinase inhibitor II (Pin2) and adds that “in some aspects, the vector further comprises a chromatin scaffold/matrix attachment region (MAR)” (Abstract) and that the MAR is Rb7 (i.e., a terminator in which a cauliflower mosaic virus 35S terminator gene, a 3' region of a potato proteinase inhibitor II gene, and a gene of an RB7 scaffold attachment site are linked) (see claims 1-5 and 14 and paragraphs [0044] and [0108]).
Mason teaches that the terminators are linked sequentially in the following order 35S-Pin2” and RB7 (see paragraph 0010), but Applicants recite the terminators are sequentially linked where the list begins with Pin2, then 35S, and then RB7. Absent evidence to the contrary, the order of terminators does not appear to be to a matter of criticality nor would it produce an unexpected result.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the filing of the claimed invention to combine the enhanced promoter teachings of Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani with the optimized terminator teachings of Mason arriving at the claimed invention because the art clearly recognizes that gene expression is controlled by both 5’UTR/promoter strength (Kumar, Maiti, and Mizutani) and 3' UTR/terminator efficiency (Mason). The Supreme Court in KSR Int'l Co. v. Teleflex Inc. held that combining prior art elements (Promoter + Terminator) according to known methods to yield predictable results is generally considered prima facie obvious. A person of ordinary skill in the art motivated to maximize expression of a gene of interest would look to optimize both regulatory ends of the cassette5’UTR/promoter strength and 3' UTR/terminator regions.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over Maiti-1, Maiti-2, Kumar, Ranjan, Mizutani, and Mason as applied to claim 30 above, further in view of Islam (Islam et al (2020). In Vivo Removal of N-Terminal Fusion Domains From Recombinant Target Proteins Produced in Nicotiana benthamiana. Front. Plant Sci. 11:440. doi: 10.3389/fpls.2020.00440, published 4/8/2020) and Hwang (U.S. Patent Application Publication No. 20200354737A1, published 11/12/2020).
The specification states that the mannosylated peptide region (MP) recited in claim 31 is “a fragment consisting of 60 amino acid residues from alanine at position 231 to aspartic acid at position 290 of protein tyrosine phosphatase, receptor type, C (PTPRC), and these are for increasing the level of protein expression” (para 75). Glycosylation includes the addition of mannose sugars or mannosylation.
Islam teaches an expression cassettes comprising BiP, M domain, CBM3, SUMO, human leukemia inhibitory factor (hLIF), and HDEL between an enhanced promoter region and a terminator region (see snippet of Figure 2A below) where the M domain is “a highly glycosylated domain derived from human CD45 which is a known protein tyrosine phosphatase receptor type C (PTPRC)” (page 7 col2, last para) and hLIF is the gene encoding the protein of interest (i.e., an expression cassette comprising a chaperone binding protein (BiP) gene, a mannosylated peptide region (MP) gene, a cellulose-binding module 3 (CBM3) gene, a small ubiquitin-related modifier (SUMO) gene, a gene encoding a protein of interest and a gene encoding His-Asp-Glu-Leu (HDEL) between the FMM-UD promoter and the 3PR terminator).
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Therefore, it would have been obvious to one of ordinary skill in the art before the filing of the claimed invention to combine and modify the teachings of Maiti-1, Maiti-2, Kumar, Ranjan, Mizutani, and Mason with the expression cassettes taught by Islam and Hwang arriving at the claimed invention. One would have been motivated to this in order to enhance translation, increase the solubility of the recombinant protein, and increase targeting to the ER (Islam page 7, col 2, first partial para; Hwang para 0034).
Claims 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Maiti-1, Maiti-2, Kumar, Ranjan, Mizutani, Mason, Islam and Hwang as applied to claim 31 above, further in view of Lee (U.S. Patent Application Publication No. 2020/0087351A1, published 4/3/2019).
Islam teaches: “the BiP leader sequence (BAA13947; amino acid positions 1 to 34)” (page 3, col 1. para 2) which is 100% identical to SEQ ID NO: 11 of the instant application, and “SUMO domain (amino acids 21-97) of bdSUMO (XP_003564931.1)” (page 2 col 2 last para) which is 100% identical to SEQ ID NO: 19 of the instant application.
Islam does not explicitly teach an amino acid sequence of the MP comprises an amino acid sequence of SEQ ID NO: 13 and an amino acid sequence of the CBM3 comprises an amino acid sequence of SEQ ID NO: 17.
Hwang is in the field of recombinant vectors for expressing target protein in plant cells and teaches the amino acid sequence of the M domain comprises an amino acid sequence of SEQ ID NO: 2 which is 100% identical to SEQ ID NO: 13 of the instant application.
Lee is in the field of recombinant vectors for expressing target protein in plant cells and teaches the amino acid sequence for CBM3 comprises an amino acid sequence of SEQ ID NO: 14 which is 100% identical to SEQ ID NO: 17 of the instant application.
Therefore, it would have been obvious to one of ordinary skill in the art before the filing of the claimed invention to combine and modify the teachings of Maiti-1, Maiti-2, Kumar, Ranjan, Mizutani, Mason, Islam, and Hwang with the teachings of Lee arriving at the claimed invention. One would have been motivated to this in order to increase the solubility of the recombinant protein (Islam page 7, col 2, first partial para).
Regarding claim 33, which depends from Claim 31, Hwang teaches that a nucleotide sequence Recombinant vector BiP:Leptin:M comprises a nucleotide sequence of SEQ ID NO: 10 which is 100% identical to SEQ ID NO: 10 of the instant application and a nucleotide sequence M domain coding nucleic acid sequence comprises a nucleotide sequence of SEQ ID NO: 1 which is 100% identical to SEQ ID NO: 12 of the instant application (i.e., the BiP gene comprises a nucleotide sequence of SEQ ID NO: 10, and the MP gene comprises a nucleotide sequence of SEQ ID NO: 12).
Lee teaches a nucleotide sequence of DNA sequence for CBM3 comprises a nucleotide sequence of SEQ ID NO: 13 which is 100% identical to SEQ ID NO: 16 of the instant application (i.e., the CBM3 gene comprises a nucleotide sequence of SEQ ID NO: 16).
Regarding claim 33’s limitation that the SUMO gene comprises a nucleotide sequence of SEQ ID NO: 18, Islam teaches the NCBI amino acid accession XP_003564931.1 which is derived from Brachypodium distachyon, has a corresponding nucleotide sequence and then teaches codon optimization of the nucleotide sequence based on the codon usage of the plant into which the gene will be transformed (page 2 col 2 last para). It is noted that the Applicant also stated that “the SUMO gene may be derived from Brachypodium distachyon” (para 72). Even though Islam does not recite the exact sequence of instant SEQ ID NO: 18, SEQ ID NO: 18 is interpreted as being codon optimized for the would-be transformed plant (i.e., the SUMO gene comprises a nucleotide sequence of SEQ ID NO: 18).
Claims 38, 40, 42, and 44 are rejected under 35 U.S.C. § 103 as being unpatentable over Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani as applied to claim 37 above, further in view of Mason (U.S. Patent Application Publication No. 2020/0407741A1, published 8/31/2020).
Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani does not explicitly teach a 3PR terminator in which a cauliflower mosaic virus 35S terminator gene, a 3' region of a potato proteinase inhibitor II gene, and a gene of an RB7 scaffold attachment site are sequentially linked.
Mason is in the field of recombinant expression vectors for protein production in plants and teaches that “an expression cassette comprises three components: a promoter sequence (part of the 5′ untranslated region, 5′ UTR), an open reading frame, and a 3′ untranslated region (3′ UTR) [where] regulatory sequences are found in the 5′ UTR and the 3′ UTR.” (para 39). Regulatory sequences include promoters and terminators meaning expression cassettes or vectors comprise a promoter and a terminator regions.
Mason also teaches a vector carrying a terminator region, “35S-Pin2”, in which a cauliflower mosaic virus 35S terminator is fused to the 3' UTR region of potato proteinase inhibitor II (Pin2) and adds that “in some aspects, the vector further comprises a chromatin scaffold/matrix attachment region (MAR)” (Abstract) and that the MAR is Rb7 (i.e., A gene construct for high expression of a gene of a protein of interest, comprising a 3PR terminator in which a cauliflower mosaic virus 35S terminator gene, a 3' region of a potato proteinase inhibitor II gene, and a gene of an RB7 scaffold attachment site are linked) (see claims 1-5 and 14 and paragraphs [0044] and [0108]).
Mason teaches that the terminators are linked sequentially in the following order 35S-Pin2” and RB7 (see paragraph 0010), but Applicants recite the terminators are sequentially linked where the list begins with Pin2, then 35S, and then RB7. Absent evidence to the contrary, the order of terminators does not appear to be to a matter of criticality nor would it produce an unexpected result. \
Therefore, it would have been obvious to one of ordinary skill in the art before the filing of the claimed invention to recombine and modify the teachings of Maiti-1, Maiti-2, Kumar, Ranjan, and Mizutani as applied to claim 25 above with that of Mason, in order to optimize the terminator region of a gene expression vector (Mason, abstract).
Regarding claim 40, which depends from claim 38, Mason teaches and claims a “recombinant protein” (see Abstract, claim 45 of Mason) and a “gene of interest” (i.e., gene encoding a protein of interest) (FIGS. 1A and 1B description) wherein the gene of interest encodes a reporter protein like GFP or GUS (i.e., the protein of interest is a reporter gene).
Regarding claims 42 and 44, which depend from claim 38, Mason teaches that “vectors were separately introduced into Agrobacterium tumefaciens” (i.e., a transformant for high expression of a gene of a protein of interest, transformed with the recombinant expression vector of claim 38), and that the vector transforms the plant or plant part using agrobacterium, for example, Agrobacterium tumefaciens” (i.e., a plant, into which the transformant of claim 42 is introduced) (paragraphs [0152] and [0012]).
Response to Applicant’s arguments:
Applicant traverses the rejection of the claims under 35 U.S.C. § 103 presented in the previous Office Action. The traversal is on the grounds that “as amended, the claims are distinguishable from the cited references at least by virtue of their promoter architecture [and that] the claimed promoter architecture is associated with unexpected results, which further supports the patentability of the claims” (Remarks, page 10, para 3).
Initially, it is noted that the above rejection under 35 U.S.C. § 103 is newly made due to Applicant’s remarks and amendments to the claims. Thus, the claims are rejected for the reasons described above.
Regarding the allegations of unexpected results, as described above, the cited prior art and the state of the art in general point to the instantly claimed invention as being obvious. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. See MPEP § 716.02. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986) (differences in sedative and anticholinergic effects between prior art and claimed antidepressants were not unexpected). In In re Waymouth, 499 F.2d 1273, 1276, 182 USPQ 290, 293 (CCPA 1974), the court held that unexpected results for a claimed range as compared with the range disclosed in the prior art had been shown by a demonstration of "a marked improvement, over the results achieved under other ratios, as to be classified as a difference in kind, rather than one of degree." Compare In re Wagner, 371 F.2d 877, 884, 152 USPQ 552, 560 (CCPA 1967) (differences in properties cannot be disregarded on the ground they are differences in degree rather than in kind); Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) ("we generally consider a discussion of results in terms of ‘differences in degree’ as compared to ‘differences in kind’ …to have very little meaning in a relevant legal sense").
Thus, Applicant’s argument is not found to be persuasive. For the reasons of record and those reasons stated above, the rejection is maintained.
Summary
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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BRATISLAV STANKOVIC, JD, PhD
Supervisory Patent Examiner
Art Units 1661 & 1662
/BRATISLAV STANKOVIC/SPE, Art Units 1661 & 1662
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