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
Claim status
Claims 1-35 are pending
Claims 12, 14, 19, 32, 34, 35 are withdrawn
Claims 1-11, 13, 15-18, 20-29, and 33 are under examination
Election/Restrictions
Applicant’s election of the following invention without traverse in the reply filed on 2/02/2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Group I, claims 1-18, and 20-33, drawn to methods of gene modulation.
Claims 19, 34, and 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable linking claim.
Applicant’s election of the following species is acknowledged.
Lentiviral vector;
VP16 as the transcription modulating protein or functional domain thereof;
NPR1 as the salicylic acid binding domain;
Target genes non-native to the cell.
Rejoinder
The species election requirement between transcription modulating proteins or functional domains thereof, as set forth in the Office action mailed on 10/02/2026, has been reconsidered in view of the prior art. dCas9 is rejoined as a transcription modulating protein or functional domain thereof.
Claims 12, 14, and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/26/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
However, Applicant is reminded that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Objection to Specification
The specification pg. 29, last line refers to “SEQ ID NO:874”. However, no “Sequence Listing” has been filed and no other SEQ ID NOs have been recited.
Claim Objections
Claim 6 is objected to because of the following informalities: instant claim uses the abbreviation “sgRNA”, which has not been spelled out upon first use. Although claims are allowed abbreviations, if an abbreviation is not spelled out upon first use Applicant should only use abbreviations that are well known and would be clear to someone who had not read the invention description.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-11, 13, and 15-18 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 pre-AIA the applicant regards as the invention.
Claim 1 recites the limitation "the transcription modulating protein or functional domain thereof" in regard to a transcriptional element modulated by “a transcription modulating protein”. There is insufficient antecedent basis for this limitation in the claim because there is no prior recitation of a transcriptional element modulated by a “functional domain” of a transcription modulating protein, thereby rendering Claim 1 indefinite as to the modulation of the transcriptional element. Claims 2-11, 13, 15-18, are included in the basis of this rejection because they do not clarify the transcriptional element is modulated by a functional domain of a transcription modulating protein.
Regarding claims 3 and 11, the phrase "such as" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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, 4-10, 13, 15, 18, 20-28, and 33 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Klavins et al., (US2017/0369892, filed 6/22/2017, published 12/28/2917).
In regard to claims 1 and 20, Klavins teaches and claims a system and method for gene regulation in an engineered cell comprising
A target gene under control of a transcriptional element (e.g., minimal, weak CMV promoter driving GFP) modulated by a transcriptional modulating protein (e.g., dCas9-VP64);
[AltContent: textbox ([img-media_image1.png])]A chimeric molecule comprising a transcriptional modulating protein or functional fragment thereof (e.g., dCas9-VP64 activation domain “AD”), a phytohormone degron (e.g., salicylic acid binding domain), and a NLS (see excerpt from Fig. 1A);
wherein the cell is contacted with salicylic acid (SA) to modulate gene expression (see Example 7, [0123-0125, ]claims 1-7 of Klavins). Note that in regard to claim 20, Klavins teaches the entirety of the NPR1 protein is used [0123], and the transitional phrase “comprising” allows other elements in the salicylic acid responsive transcription modulating protein such as the dCas9.
In regard to claim 4, Klavins indicates the chimeric molecule is expressed from an element integrated into the chromosome of the cells [0123].
In regard to claim 5, as stated supra, Klavins teaches the VP64 activation domain, which is 4 (four) copies of the herpesvirus herpes simplex VP16 domain.
In regard to claim 6, as stated supra, Klavins teaches Cas9, and Klavins teaches the sgRNA that specifically target the promoter are expressed with a constitutive U6 promoter [0039].
In regard to claim 7, Klavins teaches the NLS is from SV40 [0108], while the salicylic acid binding domain is from the plant protein NPR1 [0084, 0123].
In regard to claim 8, as stated supra, Klavins teaches the entirety of the NPR1 protein is used [0123].
In regard to claim 9, Klavins teaches the salicylic acid binding domain is from a NPR1 protein [0084, 0123].
In regard to claim 10, Klavins teaches the NLS is from SV40 [0108].
In regard to claim 13, as stated supra, Klavins teaches the target gene and transcriptional element (e.g., CMV and GFP) are not native to the cell.
In regard to claim 15, as stated supra, Klavins teaches a functional domain of the transcription modulating chimeric protein is an inducer of transcription (e.g., VP64).
In regard to claim 18, as stated supra, Klavins teaches a functional fragment of the transcriptional modulatory protein comprising a VP64 activation domain, and the acidic regions of each VP16 subdomain of VP64 are known to improve solubility.
In regard to claim 21, Klavins teaches the cell is a plant cell [0123].
In regard to claims 22 and 23, as stated supra, Klavins teaches that the transcription modulating chimeric protein further comprises a VP64 transactivation domain, which comprises 4 (four) copies of the herpesvirus herpes simplex VP16 domain.
In regard to claims 24-25, and 33, as stated supra, Klavins teaches the plant derived NRP1 protein, which is a well-known inducer of plant defense-related genes.
In regard to claims 26-28, as stated supra, Klavins teaches the target gene and transcriptional element (e.g., CMV and GFP) are not native to the cell, and the NLS-dCas9-NR1-VP64 transcription modulating protein is not native to the cell.
Accordingly, Klavins anticipates instant claims.
Claim Rejections - 35 USC § 103
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Klavins et al., (US2017/0369892, filed 6/22/2017, published 12/28/2917)
As stated supra, Klavins teaches a method and system for gene modulation comprising a cell comprising a heterologous target gene under control of a transcriptional element modulated by a SA responsive transcriptional modulated protein, and a NLS-dCas9-NR1-VP64 chimeric transcription modulating protein, and contacting the cell with SA.
In regard to claims 2-3, although Klavins provides a preferred embodiment in a plant cell line that has the system genomically integrated, they also teaches that plasmids comprising components of the system can be transformed into the cells as extrachromosomal elements ([0039, 0057, 0126], see Fig. 12A, 15A).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to use an extrachromosomal element such as a plasmid transferred into the cells to encode the chimeric protein and guide RNA with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because it is faster and more convenient to screen cells that transiently transformed to express the chimeric protein for optimization of domain types and orders compared to establishing cell lines for each and every variant [0091]. Furthermore, it would have been obvious to one having ordinary skill in the art at the time the invention was filed to practice said method with plasmid transformation because each of the individual elements of the instant claims are independently presented by Klavins as embodiments (see Figs. 12A & 15A for plasmid transformation) and are taught that they can be combined in various embodiments; therefore a combination of all the elements into a single embodiment would be apparent to an artisan skilled in plant cell engineering in light of the Supreme Court’s KSR decision (see MPEP 2143 Exemplary Rationale (A)).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 11, 16-17, 21, 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Klavins et al., (US2017/0369892, filed 6/22/2017, published 12/28/2917)
As stated supra, Klavins teaches a method and system for gene modulation comprising a cell comprising a heterologous target gene under control of a transcriptional element modulated by a SA responsive transcriptional modulated protein, and a NLS-dCas9-NR1-VP64 chimeric transcription modulating protein, and contacting the cell with SA.
In regard to claims 11, 21, and 31, although Klavins provides a preferred embodiment in a plant cell, they also teach that mammalian cells can be used [0063, 0078, 0081].
Furthermore, in regard to claims 16-17, and 29-30, Klavins teaches that the method and system can be used to design novel therapies in mammals for hormone dysregulation pathologies such as diabetes [0081], which makes obvious insulin as a target gene.
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time of filing to practice the method of Klavins in a mammalian cell for hormone regulation with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because of the clinical benefits of modulating gene expression in mammals.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631