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 .
Claims 64, 66-68, 73, 77-79 and 83-86 are pending are examined herein.
Status of the claims
Examiner notes that in the Office action mailed 17 April 2025, the Examiner objected to “claim 1” for several minor informalities. However, claim 1 was canceled by Applicant prior to the mailing of any Office actions and the objections should have been applied to “claim 64”. Examiner apologizes for any confusion.
All rejections of claims 72 and 74 are moot in light of Applicant’s cancellation of the claims.
All objections to claim 64 for minor informalities are withdrawn in light of Applicant’s amendment of the claims.
The rejection of claims 66-68 on the basis that they each contain an improper Markush grouping of alternatives is withdrawn in light of Applicant’s amendment of the claims.
The rejection of claims 67-68, 73, and 77-79 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of Applicant’s amendment of the claims.
The rejection of claims 64, 66-68, and 73 under 35 U.S.C. 102(a)(1) as being anticipated by Samalova et al (2005, The Plant Journal 41: 919-935) taken with the evidence of Craft et al (2005, The Plant Journal 41: 899-918) is withdrawn in light of Applicant’s amendment of the claims.
Claim Objections
Claim 66 is objected to because of the following informalities: the claim recites “wherein said gene is encoding a protein”. This is grammatically incorrect. Please amend the claim to recite “wherein said gene encodes a protein” or an equivalent limitation.
Appropriate correction is required.
Claim interpretation
For purpose of examination, the recitation of “inducible promoter” in claim 67 is interpreted to encompass the pOp promoter in light of the context of the specification and independent claim 64 (see Figure 2; Example 2; and Moore et al, 2006, The Plant Journal, 45: 651-683, throughout, cited by applicant on page 1 of the instant specification; Samalova et al, 2005, The Plant Journal 41: 919-935, page 920, column 1). The pOp promoter comprises a series of lac operators upstream of a minimal CaMV promoter and which is activated in the presence of a chimeric transcription factor, such as LhGR which comprises a lac repressor that binds the lac operator and is induced by application of dexamethasone. While the pOp promoter is not induced directly by dexamethasone, it is activated by an inducible transcription factor, e.g. LhGR. Furthermore, claim 67 depends from claim 64. Claim 64 requires that expression of the recombinant nucleic acid recited therein induces expression of a gene. Claim 67 is drawn to the recombinant nucleic acid of clam 64, wherein the nucleic acid “further comprises an inducible promoter operably linked to said gene”.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 64, 66-68, 73, 77-79 and 83-86 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Applicant has amended independent claims 64 and 73 to recited the new limitation “fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein” so that the claims now require a nucleic acid construct encoding a glucocorticoid receptor (GR), a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein, a LacI binding domain (BD), and a Gal4 activation domain (AD).
This limitation is New Matter because the instant specification fails to provide sufficient written support for it.
Applicant describes several embodiments of their claimed nucleic acid construct comprising GR, LACIBD and either GAL4AD or VP64 fused to an NLS (see, for example, page 9, lines 26-29; page 11-12, description of Figures 2-4; pages 21-22, Example 2, lines 27-30 and lines 18-20; and Figures 2 and 7a).
Applicant describes a nucleic acid construct comprising GAL4AD and VP64 fused to an NLS, but which does not comprise a glucocorticoid receptor (GR).
There is no description in the specification of a nucleic acid construct encoding a glucocorticoid receptor (GR), a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein, a LacI binding domain (BD), and a Gal4 activation domain (AD).
The added limitation, therefore constitutes New Matter.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 68 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 68 recites the limitation "said response inducing material" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claims 68 depends from claim 67, however claim 67 does not recite any limitations drawn to a response inducing material. Thus, it is not clear to which response inducing material claim 68 refers.
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.
Claims 64, 66, 67, 68, 73, and 77-79 are rejected under 35 U.S.C. 103 as being unpatentable over Samalova et al (2005, The Plant Journal 41: 919-935) taken with the evidence of Craft et al (2005, The Plant Journal 41: 899-918) in view of Samalova et al (2019, Current Protocols in Plant Biology 4(2): e20089; first available online 12 March 2019), Beerli et al (1998, PNAS 1995: 14628-14633) and Chavez et al (2015, Nature Methods 12:326-329). Due to Applicant' s amendment of the claims, the rejection is modified from the rejection set forth in the Office action mailed 17 April 2025. Applicant' s arguments filed 17 July 2025 have been fully considered but they are not persuasive.
The claims are broadly drawn to a genetically modified plant comprising recombinant nucleic acid molecule comprising a glucocorticoid receptor (GR), a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein, a LacI binding domain (LacIBD), and a Gal4 activation domain (Gal4AD), wherein expression of said recombinant nucleic acid induces expression of gene encoding a protein in said plant (instant claims 64 and 66); the plant of claim 64 said recombinant nucleic acid further comprises an inducible promoter operably linked to said gene (claim 67); the plant of claim 67 wherein the response inducing material is dexamethasone. The claims are further drawn to a method for generating a genetically modified plant comprising transforming a plant cell with a recombinant nucleic acid molecule comprising a glucocorticoid receptor (GR), a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein, a LacI binding domain (LacIBD), and a Gal4 activation domain (Gal4AD), wherein upon induction of expression of said recombinant nucleic acid expression of a gene encoding a protein in said plant is induced; regenerating a transformed plant from said plant cell; performing induction of said gene in the plant is at least 1 month after step (b) (claims 73); wherein said transforming step is performed by transfecting an agrobacterium with one inducible plasmid comprising (a) a promoter linked to a sequence encoding a synthetic transcription protein comprising a DNA binding domain and a transcription activating domain and (b) multiple operator sequences linked to at least one promoter and said promoter linked to at least one gene (claim 77); said method wherein the plasmid further comprises a sequence encoding NeoR/KanR (claim 78); and said method wherein the promoter is selected from a group which includes a minimal CaMV 35S promoter.
Samalova et al 2005 teaches genetically modified plants comprising the reporter/activator systems pOp/LhGR (lines S/N, S/I1-3, and S/C) and pOp6/LhGR (line 17S/N) , which are dexamethasone inducible plant expression systems, and their use to direct expression of genes encoding proteins in said plants, i.e. GUS and a cytokinin-biosynthetic gene ipt, upon induction with dexamethasone (Abstract; page 921, columns 1-2, bridging paragraph; page 925, column 2 paragraph 1; Figure 1; Figure 2; Figure 4). Samalova et al 2005 teaches that transformation was performed with pBIN-LhGR constructs (as described by Craft et al), wherein LhGR is recombinant nucleic acid constructs comprising a glucocorticoid receptor (GR), a nucleus localization signal (NLS), a LacI binding domain (LacIBD), and a Gal4 activation domain (Gal4AD) (page 932, column 1, “Construct preparation”; Figure 1). As described in Craft et al, Gal4AD comprises an NLS (page 900, column 2, final paragraph).
Samalova et al 2005 further discloses said genetically modified plants wherein the inducer dexamethasone is applied locally to an axillary bud and to the whole plant by painting or watering (page 923, column 2, “Different methods of dexamethasone application can result in different phenotypes”; page 927, column 2, “Expression characteristics of pOp6-GUS/LhGR plants in soil”). Samalova et al 2005 teaches inducing plants that are 4 weeks and 8 weeks old (see figure 3(d)(3) for example).
Samalova et al 2005 teaches methods of making said genetically modified plants comprising plant cells with the constructs encoding the LhGR (i.e. a recombinant nucleic acid encoding GR, NLS, LacIBD and Gal4AD) activators and the reporters pOp-GUS, pOp-ipt, pOp6-GUS and pOp60-ipt, regenerating transformed plants and inducing expression of the reporter gene (i.e. gene encoding a protein) when the plant is fully grown by watering soil grown plants with a dexamethasone treatment after 3 weeks of tissue culture and 3 weeks in soil (page 932 “Plant transformation and maintenance”, “Methods of dexamethasone application”; Figure 6(d) and corresponding figure legend), which would be at least“1 month after step (b) as recited in instant claim 73.
Samalova et al 2005 teaches a method of transforming a plant with an Agrobacterium comprising an inducible plasmid comprising a promoter (CaMV 35S) linked to a sequence encoding a synthetic transcription protein comprising a DNA binding domain (LacIBD) and a transcription activating domain (Gal4AD) (pBIN-LhGR-(N, I, and C); page 932 “Plant transformation and maintenance”, Figure 1) and a method of transforming a plant with an Agrobacterium comprising the reporter constructs pOp6-GUS and pOp6-ipt which comprise multiple lac operator sequences fused to a minimal promoter (pOp6) further fused to a gene encoding GUS or the cytokinin-biosynthetic gene ipt, respectively (page 932, “Construct preparation” and “Plant transformation and maintenance”; Figure 1).
The pBIN-LhGR-(N, I, and C) constructs of Samalova et al 2005 also further comprise kanamycin resistance markers (see Craft et al, page 901, Figure 1 legend).
Samalova et al does not teach a recombinant nucleic acid molecule comprising a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein.
Samalova et al 2005 does not teach a method wherein a plant is transformed with a single plasmid comprising both a promoter linked to a sequence encoding a synthetic transcription protein comprising a DNA binding domain and a transcription activating domain and multiple operator sequences linked to at least one promoter and said promoter linked to at least one gene.
Samalova et al 2019 teaches that the constructs taught in Samalova et al 2005 (i.e. the LhGR activator construct and the reporter comprising pOp6 and a gene of interest) can be introduced into plants as a single T-DNA (pages, 2-3, bridging paragraph).
Beerli et al teaches constructs for gene specific transcriptional regulation comprising a binding domain and a transcription activator comprising NLS fused to VP64, which is a tetrameric repeat of the transactivating site of VP16 (page 14632, paragraph bridging column 1-2, Figure 4). Beerli et teaches that VP64 produced 27 fold activation while VP16 produced 5 fold activation.
Chavez et al teaches that multimeric recruitment of transcription activation domains such as VP64 and p65 can lead to abundant increases in transcriptional activation (page 328, column 1). Chavez et al teaches that a transcription activator, VPR, combining three the domains of three transcription activators (VP64, p65 and Rta) was more effective than VP64 alone across several different DNA binding scaffolds (page 326, column 2).
At the time of filing, it would have been prima facie obvious to modify the method of Samalova et al 2005 to include an NLS fused to VP64. One would have been motivated to do so with a reasonable expectation of success given that NLS fused to VP64 (as taught by Beerli et al) has long been known in the art as an effective transcriptional activator and given that Chavez et al teaches that the presence of multiple transcriptional activators increases transcriptional activation of a gene. It would have been further obvious after this modification to combine the two constructs taught by Samalova et al 2005 into a single plasmid for plant transformation. One would have been motivated to do so with a reasonable expectation of success given the express suggestion of Samalova et al 2019 to do so and given the routine nature of constructing plasmids in the art.
Response to Applicant’s arguments:
In the Remarks filed on 17 July 2025, Applicant argues that none of the cited prior art references teaches a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein (page 8, Remarks). Applicant further argues that the prior art references do not provide a motivation to combine the claimed elements in a single construct nor does it make obvious the particular configuration and functional relationships (page 10, Remarks).
This is not found persuasive.
In light of Applicant’s claim amendments, Examiner has cited new prior art teaches drawn to a nucleus localization signal (NLS) fused to a VP64 protein comprising 4 repetitions of a transcription activating site of a VP16 protein, as set forth above in the rejection of claims 64, 66, 67, 68, 73, and 77-79 under 35 U.S.C. 103.
Regarding the motivation to combine the claimed elements into a single construct, Samalova et al 2019 provides explicit motivation to do so, as explained above. Furthermore, the claims as presented do not require any specific arrangement of the claimed elements, beyond their presence on a single plasmid.
For these reasons, 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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/ALEKSANDAR RADOSAVLJEVIC/ Examiner, Art Unit 1662
/BRENT T PAGE/ Primary Examiner, Art Unit 1663