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 .
Application Status
The preliminary amendments filed 09 April 2025 acknowledged and have been entered. Claims 3-6, 8-9, 11, 24, 54, and 68 are amended. Claims 7, 10, 15-23, 25-33, 36-40, 42-53, 57-67, and 69-78 are cancelled. Claims 1-6, 8-9, 11-14, 24, 34-35, 41, 54-56, and 68 are pending and being examined on the merits.
Priority
The application is a 371 PCT of US2022/076723 filed 09/20/2022 which claims priority to applications 63/352,530 filed 06/15/2022 and 63/246,689 filed 09/21/2021.
Information Disclosure Statement
The information disclosure closure statements filed 8/01/2024 has been acknowledged.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located Figs. 5AC-5AJ.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specification
The disclosure is objected to because of the following informalities: There is no description of drawing from Figs. 5AC-5AJ.
Appropriate correction is required.
Claim Objections
Claim 54 is objected to because of the following informalities: it is missing “of” after “protein”. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 13 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 13 is drawn to a “cell.” The specification teaches that the method can be carried out in vivo [pg. 7, para 4; pg. 35; example 2; claim 55]. Thus, the term “cell” could reasonably be interpreted as encompassing cells within a human organism, which is non-statutory subject matter. The rejection may be obviated by requiring that the cell be an isolated cell, an in vitro human cell, or a non-human cell.
Claim Rejections - 35 USC § 112
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 2 is 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 2 recites “wherein the RNA effector protein is a Cas effector protein selected from the group consisting of Cas9, Cas12, Cas13, and Cas14”. Of these, Cas13 is the only Cas effector that targets and cleaves RNA. It is unclear how Cas9, Cas12, and Cas14 is to behave as an RNA effector protein as required by the claim.
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 1-6, 8-9, 11-14, 24, 34-35, 41, 54-56, and 68 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.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Independent claims 1, 14 and 34 and the claims depending therefrom recite fusion proteins comprising and RNA effector protein fused to a regulon moiety that stimulates and/or stabilizes the mRNA.
The claimed moiety is defined almost by the function it performs rather than by the objective structural characteristics. Although the specification identifies certain exemplary regulon moieties [pg.40-41], the claims encompass any protein, protein domain, or other molecule capable of stimulating and/or stabilizing a target mRNA when fused to an effector protein. The specification does not disclose representative species spanning the breath of the claimed genus; structural features common to members of the claimed genus; conserved sequence motifs; conserved structural domains; structure-function correlations that would permit one of ordinary kill in the art to recognize which additional molecules belong to the claimed genus.
The claims further encompass methods directed to endogenous mRNAs associated with haploinsufficiency disorders and, as described in the specification, extend to numerous unrelated genes [pg. 8-9, bridging paragraph]. While these genes are identified in the specification, merely listing target genes does not demonstrate possession of methods capable of successfully regulating expression of reach member of the claimed genus. The specification only provides a limited experimental examples and does not disclose representative embodiments demonstrating successful regulation across the broad diversity of claimed endogenous transcripts, which differ substantially with respect to transcript length, RNA secondary structure, untranslated regions, RNA-binding protein interactions, and cellular expression patterns.
The claims additionally encompass methods of treating and/or preventing numerous distinct haploinsufficiency disorders. These disorders involve diverse genes, tissues, pathogenic mechanisms, and therapeutic considerations. The specification provides only limited examples and does not reasonably convey possession of therapeutic methods applicable across the full breath of the claimed disorders. Accordingly, the disclosure does not demonstrate possession of the entire therapeutic genus encompassed by the claims.
Therefore, for the genus of regulon moiety, target gene, and therapeutic genes the specification does not provide a representative number of species covering the full scope of the claimed functional genus or structural features common to the members of the genus such that one of ordinary skill in the art could reasonably conclude that the Applicant possessed the entire claimed genus at the time of filing.
Furthermore, regarding the state of the art, Tang (Tang et al. Frontiers in Cell and Developmental Biology 9 (2021): 677587) reviews the state of Cas13-mediated RNA editing and explains that different RNA modification enzymes have distinct mechanisms and that practical implementation depends on optimization for editing efficiency, off-target effects, delivery, and transcript-specific behavior; therefore at the time of filing, programmable dCAs13-mediated RNA modifications was an emerging and developing technology in which different RNA modification enzymes exhibited distinct biological activities and required target-specific optimization. Thus disclosure of only a limited number of exemplified RNA regulatory domains would not reasonably convey possession of the full functional genus recited in the claims.
Wiener (Wiener & Schwartz Nat. Rev. Genet. 2021) explains that more than 170 RNA modifications exists and that different modifications regulate RNA fate though different mechanisms affecting stability, translation, localization, and RNA-protein interaction. Wiener also discusses the complexity and context dependence of RNA modifications [abstract; entire article]. Therefore, one cannot infer that all RNA regulatory proteins will function interchangeably simply because a few examples are disclosed.
Accordingly, in view of the limited amount of guidance provided by the specification and the art, one of ordinary skill in the art would conclude that Applicant was not in possession of the claimed invention.
Claims 1-6, 8-9, 11-14, 24, 34-35, 41, 54-56, and 68 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a protein/complex/system and method of the claimed invention where the effector protein fused to PABPC1 or NAT10 targets the SCN1A, MECP2, SYNGAP115, SHANK316, CHD217, and PTEN18 genes in a method for treating (not preventing) Dravet syndrome does not reasonably provide enablement for the a protein/complex/system and method of the claimed invention where the effector protein is fused to any regulon moiety, targets any gene and is used in a method for treating and preventing any haploinsufficiency disorder. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Nature of the Invention
The claims broadly encompass fusion proteins comprising an RNA effector protein fused to a “regulon moiety that stimulated and/or stimulates the mRNA,” together with methods employing such fusion proteins to increase expression of endogenous mRNA associated with haploinsufficiency disorders.
State of the Art
Regarding the state of the art, Tang (Tang et al. Frontiers in Cell and Developmental Biology 9 (2021): 677587) reviews the state of Cas13-mediated RNA editing and explains that different RNA modification enzymes have distinct mechanisms and that practical implementation depends on optimization for editing efficiency, off-target effects, delivery, and transcript-specific behavior; therefore at the time of filing, programmable dCAs13-mediated RNA modifications was an emerging and developing technology in which different RNA modification enzymes exhibited distinct biological activities and required target-specific optimization. Thus disclosure of only a limited number of exemplified RNA regulatory domains would not reasonably convey possession of the full functional genus recited in the claims. Wiener (Wiener & Schwartz Nat. Rev. Genet. 2021) explains that more than 170 RNA modifications exists and that different modifications regulate RNA fate though different mechanisms affecting stability, translation, localization, and RNA-protein interaction. Wiener also discusses the complexity and context dependence of RNA modifications [abstract; entire article]. Therefore, one cannot infer that all RNA regulatory proteins will function interchangeably simply because a few examples are disclosed.
Breadth of the claims
The claim encompasses numerous RNA effector proteins, a broad functional genus of regulon moieties, guide RNAs targeting numerous endogenous transcripts, numerous unrelated haploinsufficient genes, and methods of treating and preventing numerous genetically distinct haploinsufficiency disorders.
Guidance of the Specification
Although the specification provides examples involving selected programmable RNA-targeting constructs and a limited number of RNA regulatory domains, it does not teach how to successfully practice the invention across the full breath of the claimed genus. For example, while the specification identifies numerous haploinsufficient disorders and genes [Table 1 and 2; pg. 8-9, bridging paragraph]. It does not provide working examples demonstrating successful regulation of these diverse endogenous transcripts and disorders.
Likewise, although the claims encompass any regulon moiety capable of stimulating and/or stabilizing an mRNA, the specification provides only limited examples and does not teach how to identify or predict additional regulon moieties that will function across the claimed scope.
Furthermore, while the claims encompass methods of preventing haploinsufficient disorders, the specification primarily describes increasing expression of endogenous genes using dCas13b and does not provide sufficient guidance demonstrating that prophylactic administration prevents the onset of numerous genetically distinct disorders encompassed by the claims.
Experimentation Required
Accordingly, a person of ordinary skill in the art seeking to practice the full scope of the claimed invention would be required to determine, for each target transcript, regulon moiety and haploinsufficient disorders, suitable guide RNA sites; transcript accessibility in light of RNA secondary structure; compatibility between the selected RNA effector protein and regulon moiety; whether a particular regulon increases translation, stabilizes mRNA, or both; whether therapeutic protein expression can be achieved without unacceptable off-target effects, etc.
Therefore, taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an undue experimentation would be required to make and use the invention as claimed.
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, 6, 8-9, 11-14, 34, 41, and 54-55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li (Li et al. Nucleic Acids Research, 2020, Vol. 48, No. 10; 5684–5694).
Regarding claims 1-4, 14, 34, 41, and 54, Li teaches the construction and characterization of a CRISPR–Cas13b-based tool for targeted demethylation of specific mRNA [abstract]. Li teaches a fusion protein, named dm6ACRISPR, was created by linking a catalytically inactive Type VI-B Cas13 enzyme from Prevotella sp. P5–125 (dPspCas13b) to m6A demethylase AlkB homolog 5 (ALKBH5). Li taches that dm6ACRISPR specifically demethylates m6A of targeted mRNA such as cytochrome b5 form A (CYB5A) to increase its mRNA stability, and can also demethylate b-catenin-encoding CTNNB1 mRNA (i.e., a haploinsufficient gene as disclosed by the current specification) that contains multiple m6A sites to trigger its translation [abstract]. Li teaches the gRNA directed dCas13b-ALKBH5 endogenous mRNA targeting (i.e., a system or complex) [Fig. 1; pg. 5685, col. 1, para 2; pg. 5686, col. 2, para 3 – pg. 5678, col 1, para 2; Fig. 2-3]. Thereby, Li teaches the use of a fusion protein comprising the RNA effector protein of dPspCas13b that targets mRNA of an active allele of a gene and the regulon moiety of ALKBH5 in a method that causes demethylation of the haploinsufficient gene CTNNB1 mRNA to stimulate transcription.
Regarding claims 6, 8 and 9, Li teaches fusing ALKBH5 to the N- or C-terminus of inactive Cas13b (dCas13b)with a six amino-acid (GSGGGG) linker [pg. 5686, col. 2, para 1; Figure 1A and B].
Regarding claim 11, Li teaches a PspCas13b-Alkbh5 or Alkbh5-PspCas13b plasmid [pg. 5685, col. 1, para 3].
Regarding claim 12-13, Li teaches HEK293T cells transfected with vector control (pcDNA3.1), pcDNA/ALKBH5, or dCas13b-ALKBH5.
Regarding claim 55, Li teaches in vivo manipulation.
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, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-4, 6, 8-9, 11-14, 24, 34, 41, 54-56 and 68 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al. Nucleic Acids Research, 2020, Vol. 48, No. 10; 5684–5694) in view of Anderson (WO 2021/158982; published 8/12/2021) and Aznarez (US 2020/0024603 A1, published 1/23/2020).
Regarding claims 1-4, 14, 34, 41, and 54, Li teaches the construction and characterization of a CRISPR–Cas13b-based tool for targeted demethylation of specific mRNA [abstract]. Li teaches a fusion protein, named dm6ACRISPR, was created by linking a catalytically inactive Type VI-B Cas13 enzyme from Prevotella sp. P5–125 (dPspCas13b) to m6A demethylase AlkB homolog 5 (ALKBH5). Li taches that dm6ACRISPR specifically demethylates m6A of targeted mRNA such as cytochrome b5 form A (CYB5A) to increase its mRNA stability, and can also demethylate b-catenin-encoding CTNNB1 mRNA (i.e., a haploinsufficient gene) that contains multiple m6A sites to trigger its translation [abstract]. Li teaches the gRNA directed dCas13b-ALKBH5 endogenous mRNA targeting (i.e., a system or complex) [Fig. 1; pg. 5685, col. 1, para 2; pg. 5686, col. 2, para 3 – pg. 5678, col 1, para 2; Fig. 2-3]. Thereby, Li teaches the use of a fusion protein comprising the RNA effector protein of dPspCas13b that targets mRNA of an active allele of a gene and the regulon moiety of ALKBH5 in a method that causes demethylation of the haploinsufficient gene CTNNB1 mRNA to stimulate transcription.
Regarding claims 6, 8 and 9, Li teaches fusing ALKBH5 to the N- or C-terminus of inactive Cas13b (dCas13b)with a six amino-acid (GSGGGG) linker [pg. 5686, col. 2, para 1; Figure 1A and B].
Regarding claim 11, Li teaches a dPspCas13b-Alkbh5 or Alkbh5-dPspCas13b plasmid [pg. 5685, col. 1, para 3].
Regarding claim 12-13, Li teaches HEK293T cells transfected with vector control (pcDNA3.1), pcDNA/ALKBH5, or dCas13b-ALKBH5.
Regarding claim 55, Li teaches in vivo manipulation.
Regarding claims 24, 56, and 68, Li do not teach where the gRNA targets an mRNA encoding SCN1A. Li do not teach that the fusion protein gRNA system in a method for treating a haploinsufficiency disorder such as Dravet syndrome.
Anderson teaches that programmable dCas13 fusion proteins may be employed therapeutically to increase protein production from endogenous mRNAs associated with diseases caused by insufficient protein expression [pg. 51, para 2 and 4]. Specifically, Anderson teaches fusion of catalytically inactive Cas13 proteins with translation-promoting proteins such as eIF4G and teaches administering the fusion protein together with a guide RNA complementary to an endogenous target mRNA to increase translation of the encoded protein. Anderson further teaches treatment of disorders caused by reduced protein expression, including haploinsufficiency disorders, and expressly identifies Dravet syndrome as one example [example 1; pg. 51, para 2 and 4].
Aznarez teaches that SCN1A haploinsufficiency causes Dravet syndrome and teaches therapeutic strategies directed toward increasing productive SCN1A transcript and protein expression in affected subjects [abstract; 0002-0004; 0058].’
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to modify the dPspCas13b system of Li by fusing the dCas13 protein to the eIF4G protein as taught by Anderson and targeting the SCN1A as the endogenous target transcript for therapeutically treating Dravet syndrome because Aznarez teaches that increasing productive SCN1A expression is therapeutically beneficial in Dravet syndrome caused by SCN1A haploinsufficiency. One of ordinary skill would have a reasonable expectation of success because both Li and Anderson employ guide-directed Cas13 fusion protein to modulate endogenous mRNA in mammalian cells.
Claims 5 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Li (Li et al. Nucleic Acids Research, 2020, Vol. 48, No. 10; 5684–5694) in view Shinichi (JP2015221026).
The teachings of Li are discussed above as applied to claims 1 and 34 and similarly apply to claims 5 and 35.
Li does not teach where the regulon moiety is PABPC1.
Shinichi teaches that poly(A)-binding protein cytoplasmic (PABPC1) is a translation-producing regulatory protein that enhances translation when recruited to target mRNA. Shinichi specifically demonstrated tethering PABPC1 to mRNA through an RNA-binding system, resulting in increased translation and protein production from the target transcript [0006-0007]. Therefore, Shinichi teaches that PABPC1 functions as an RNA regulatory effector capable of stimulating expression of a target mRNA.
It would have been obvious to one ordinary skilled in the art before the effective filing date of the claimed invention to substitute the PABPC1 translation-promoting effector taught by Shinichi for the ALKBH5 RNA regulatory domain of Li. This modification would amount to a simple substitution of one known regulon for another, both to achieve the same outcome of increased gene expression since both Li and Shinichi employ recruitment of an RNA-associated effector to selected target mRNA to increase gene expression through post-transcriptional regulation.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at 571-272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
Prosecution Insights