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 1-4, of record 4/7/2023 are acknowledged. Prosecution on the merits commences for claims 1-4.
PRIORITY
The instant application, filed 04/07/2023, is a CONTINUATION of US Patent No. 11,642,423, filed 06/16/2020, which is a CONTINUATION of US Patent No. 10,729,790, filed 11/22/2017, which is a 371 of PCT/US2016/033914, filed 05/24/2016, which claims priority to US Provisional Application No. 62/268,357 filed 12/16/2015, US Provisional Application No. 62/168,755, filed 05/30/2015 and US Provisional Application No. 62/166,677, filed 05/26/2015. Thus, the earliest possible priority for the instant application is 5/26/2015.
SPECIFICATION
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The instant specification recites browser-executable code at paragraph [0221] of the published specification.
CLAIMS
Independent claim 1 is drawn to:
A recombinant nucleic acid comprising
a motor neuron-specific promoter nucleic acid sequence comprising SEQ ID NO: 1,
operably linked to a fluorescent protein.
SEQ ID NO: 1, recited in claim 1, is a 908 base pair fragment of the 7.6 kb promoter for the mir218-2 gene (Specification, paragraph [0182], FIG. 17B). Mir218-2 and its promoter sequences are encoded within intronic sequences of the SLIT3 gene (paragraphs [0039], [0057], [0193], [0228]; FIGs 13A; 26F; 31A-C). The 7.6 kb promoter for mir218-2 is encoded within Slit3 intron 5, and mir218-2 is encoded within slit3 intron 14. SEQ ID NO:1 is a 3’ fragment isolated from the larger 7.6 kb mir218-2 promoter sequence (FIGs 14A-F, 17B; 26D-E).
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A non-limiting visualization of the generation of a nucleic acid comprising SEQ ID NO:1 according to the specification is provided:
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SEQ ID NO:1 comprises motor neuron-specific transcription factor binding sites for Isl1 , Lhx3 and Phox2a (paragraphs [0228], FIGs 16, 26E-F, 31A-C).
The specification shows both the 7.6 kb mir218-2 promoter (218p:eGFP long) and the 908 base pair fragment (218p:eGFP short; SEQ ID NO:1) drive motor neuron-specific expression of operably linked GFP (paragraphs [0028]-[0034], [0040], [0057]; FIGs 2A-B, 3A-B, 4A-C, 5-8, 14A-F, 31A-C).
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Claim Objections
Claims 1 and 3-4 are objected to because of the following informalities:
Claim 1, as written encompasses a recombinant nucleic acid comprising a nucleic acid sequence comprising SEQ ID NO: 1, operably linked to a fluorescent protein. The claim should be amended to recite wherein SEQ ID NO:1 is operably linked to a nucleic acid sequence encoding a fluorescent protein. Appropriate correction is required.
Claim 3 recites alternative species of viral vectors, wherein “the viral vector is an adenovirus…. parvovirus or lentivirus.” The claim should be amended to utilize proper Markush language such as “the viral vector is selected from the group consisting of an adenovirus…. parvovirus [[or]] and a lentivirus.”
Claim 4 has the same issues as those of claim 3. Claim 4 recites alternative species of fluorescent proteins, and should be amended to utilize proper Markush language such as “wherein the fluorescent protein is selected from the group consisting of green fluorescent protein (GFP) …. Cyan fluorescent protein (CYP), [[or]] and yellow fluorescent protein (YFP).”
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.
Claims 1 and4 are rejected under 35 U.S.C. 103 as being unpatentable over Punnamoottil et al., Motor Neuron-Expressed MicroRNAs 218 and Their Enhancers are Nested Within Introns of Slit2/3 Genes. Genesis, 2015. 53:321-328; published online April 10, 2015, of record, cited on Applicant’s IDS dated 04/07/2023, taken in view of Little et al. Conserved Modularity and potential for Alternate Splicing in Mouse and Human Slit Genes. International Journal of Developmental Biology, 2002. 46: 385-391, of record, cited on Applicant’s IDS dated 04/07/2023, Small et al., MicroRNA-218 Regulates Vascular Patterning by Modulation of Slit-Robo Signaling. Circulation Research, 2010. 107:1336-1344, and Genbank Accession No. NC_000077, earliest publication date 2009, of record, cited on Applicant’s IDS dated 04/07/2023. As stated above, claim 1 encompasses a composition comprising a nucleic acid encoding SEQ ID NO: 1 operably linked to a nucleic acid encoding GFP.
With regard to claim 1, Punnamoottil discloses the gene encoding mir218-2 is embedded within intron 14 of the slit3 gene in human chromosome 5 (FIG 2a). Punnamoottil identifies of 2 motor neuron-specific enhancer sequences (hs1 and hs2) that lie in intronic portions of the human slit3 gene upstream of the human mir-218-2 gene, that drive mir218-2 expression in vivo (table 1; FIG 2). Punnamoottil discloses hs1 is 1252 bp in length and is 130 kb upstream of mir218-2 in the slit3 gene, and hs2 is 1590 bp in length and is 76 kb upstream of mir218-2 in the slit3 gene (Table 1). Punnamoottil isolates hs1 and hs2, operatively links each of them to GFP gene in an expression vector, and shows both hs1 and hs2 drive motor neuron-specific GFP expression (page 324; Table 1, Fig 2a).
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Transgenic mice comprising the human hs2-gfp constructs showed GFP expression in cranial motor neurons and spinal cord motor neurons similar to endogenous mir218 expression patterns in cranial motor neurons and spinal cord motor neurons (FIG 2a, page 324, FIG. 4).
Punnamoottil provides the human chromosome 5 coordinates for the hs1 and hs2 enhancer region and the mir218-2 gene (Table 1), and further provides the primers used to clone the hs1 and hs2 genomic sequences (page 325).
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Punnamoottil discloses human and mouse slit-3 genomic non-coding sequences are highly conserved, wherein the highest density of the conserved non-coding sequences are about 100 kb of the mir218-2 gene (FIG 1a).
However, Punnamoottil does not disclose the sequence (specifically) for the human hs1 or hs2 enhancers, or that the human hs1 or hs2 enhancers are SEQ ID NO:1, as required by instant claim 1.
Little discloses the genomic human and murine Slit genes (slit 1, slit-2 and slit-3) are highly conserved (page 386) and the mouse genes have the same number of exons as the human gene counterpart (page 338).
Small discloses the mouse slit-3 gene is located on mouse chromosome 11, and mir218-2 is encoded within intron 14 of the gene (FIG 1a).
Accession No. NC_000077 (displaying region 35121456 to 35708507) discloses murine chromosome 11, which encodes the murine slit-3 gene (nucleotides 1-587052 therein). NC_000077 also discloses the gene for mir218-2 (495361-495470 therein). Instant SEQ ID NO:1 is 100% identical to sequences 422,221-423670 therein.
It would have been obvious to combine the disclosure of Punnamoottil of a recombinant nucleic acid comprising a motor neuron-specific promoter isolated from the human slit-3 gene, operably linked to a nucleic acid encoding a fluorescent protein further with the known sequences of murine chromosome 11 encoding the slit-3 gene and mir218-2 gene to arrive at the claimed invention. Little shows the murine and human slit-3 sequences are highly conserved. Small discloses the mouse slit-3 gene is located on mouse chromosome 11. Punnamoottil discloses the human sequences were based on the conservative nature of murine sequences, and provides the coordinates of the corresponding human sequences and the sequences of the primers used to clone the enhancer. The arrival of the instant invention of a nucleic acid comprising SEQ ID NO: 1 would have been merely a matter of routine experimentation utilizing known searching tools based on known sequences.
With regard to claim 4, Punnamoottil discloses the fluorescent protein is GFP (page 324; Table 1, Fig 2a).
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Punnamoottil et al., Little et al., Small et al., and Genbank Accession No. NC_000077 as applied to claims 1 and 4 above, and further in view of Ishibashi et al. Using Zebrafish Transgenesis to Test Human Genomic Sequences for Specific Enhancer Activity. Methods, 2013. 62:216-225 and US Patent Application Publication No. 2011/0027235 to Gregory.
Punnamoottil, Little, Small, and Genbank Accession No. NC_000077 are applied as in the 103 rejection above, the content of which is incorporated herein in its entirety. Punnamoottil, Little, Small, and Genbank Accession No. NC_000077 combine to render obvious a recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein.
Punnamoottil isolates the putative hs1 and hs2 enhancer sequences, operatively links each of them to GFP gene in an expression vector, and shows both hs1 and hs2 drive motor neuron-specific GFP expression (page 324; Table 1, Fig 2a). Punnamoottil discloses the hsp1 and hsp2 sequences are inserted into a Tol2 GFP destination vector, and injected into fertilized eggs and screened for positive founder fish, as disclosed by Ishibashi, 2013 (page 327).
Punnamoottil does not disclose wherein the recombinant nucleic acid comprising the motor neuron specific promoter operably linked to GFP is comprised within a viral vector, as required by claims 2 and 3.
Ishibashi discloses methods of identification and evaluation of putative enhancer sequences (abstract). Ishibashi discloses identification of putative enhancer sequences is based, in part, on highly conserved non-coding sequences (page 217, 219). The putative enhancer sequences are then clones and inserted into a Tol2-GFP reporter vector. The vector comprises inserting the putative enhancer sequence upstream of a basal gata2 promoter which is operably linked to the GFP gene. The vector further comprises flanking tol2 transposon sequences (FIGs 1-2). The recombinant Tol2-GFP vector is co-injected with mRNA encoding the transposase into fertilized eggs and screened for positive founder fish (Fig 1, page 220). Expression of the transposase mediates the integration of the vector into the genome (page 221). Ishibashi discloses use of the Tol2-GFP transgenesis has high yield and rapid generation of transgenic fish (page 218, 221).
Ishibashi discloses the Tol2 transposon system results in random integration events only within transcriptionally active chromatin (page 224). As such, enhancer activity exhibited by the system may be influenced by surrounding cis-acting regulatory sequences which may increase, decrease or altogether inhibit enhancer activity (page 222-224). For enhancers that are influenced by cis-acting regulatory Ishibashi teaches the site of integration is “critical” in order to identify and define the enhancer. Ishibashi suggests integration of the enhancer-GFP constructs into defined permissive sites/neutral landing genomic sites will be important to further evaluate enhancer function (page 225).
Gregory discloses viral vectors comprising transgene cassettes for targeted delivery to a safe harbor locus (Abstract). The transgene cassette encodes lineage-specific or cell fate reporter constructs. Such constructs comprise lineage-specific or cell fate regulatory elements, including promoters and/or enhancers operably linked to a GFP reporter gene (paragraphs [0018], [0028], [0092]-[0094], [0105]). The transgene cassette further comprises left and right homology arms targeting the desired safe harbor locus for integration (Examples). The transgene cassette comprising the lineage-specific promoter and/or enhancer and reporter gene are packaged within viral vectors for delivery. Suitable viral vectors include non-integrating lentiviral vectors, adenoviral vectors, adeno-associated viral vectors, retroviral vectors, herpes viruses (paragraphs [0026], [0146], [0154]-[0159]).
Following transduction of a host cell, targeted integration of the transgene cassette occurs following co-expression of zinc-finger nucleases targeted to the desired safe harbor locus via homology directed repair (paragraphs [0121], [0182], [0007]). The reporter constructs can include lineage-specific or cell specific regulatory sequences for motor neurons (Table 1). Safe harbor genes accept integration of a transgene without resulting in negative effects on the host cell, and where the transgene is not subjected to endogenous cis-acting regulatory sequences. Examples of safe harbor genes include CCR5 and AAVS1 (paragraphs [0090], [0170]). Gregory discloses the integrated reporter constructs can be used to further define the lineage-specific expression sequences (promoters/enhancer sequences) within regulatory regions of genes (paragraphs [0102], [0109], [0170]).
In one embodiment Gregory discloses a cell specific cassette comprising an aP2 enhancer sequence operably linked to the basal aP2 promoter which is operably linked to a gene encoding GFP. The cell specific cassette is packaged into a non-integrating viral vector (Example 1).
Gregory discloses the use of viral vectors comprising cassettes encoding lineage-specific promoters and/or enhancers and a reporter gene for targeted delivery of the cassette to a safe harbor gene overcomes many problems associated with stable integration of transgenes in the art. Results from random insertions of transgenes are varied, not just from the cis-acting sequences surrounding any one transgene, but because the insertion of transgenes across founders occurs in different genomic locations, and are thus subject to different cis-acting sequences, and/or result in insertional mutagenesis (paragraphs [0006], [0172]).
With Gregory’s system, the targeted insertion of the lineage-specific promoter and/or enhancer and reporter construct are not subjected to positional effects because all integrated reporter cassettes will have the same chromatin environment, therefore are uniformly expressed in different cells. In addition, targeted integration also allows for expression of the transgene ( e.g., lineage-specific or cell fate reporter construct) in only selected lineages maturing from the stem cell. (paragraphs [0009], [0172]). Use of non-integrating viral vectors prevents any toxicities from the viral genome (paragraphs [0006], [0007]).
It would have been obvious to combine the recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein of Punnamoottil, Little, Small, and Genbank Accession No. NC_000077 further with Ishibashi and Gregory to arrive at the claimed invention. Ishibashi acknowledges that due to the random integration of the enhancer-GFP constructs the enhancer activity exhibited by the system may be influenced by surrounding cis-acting regulatory sequences which may increase, decrease or altogether inhibit enhancer activity, and suggests integration of the enhancer-GFP constructs into defined permissive sites/neutral landing genomic sites will be important to further evaluate enhancer function. Gregory’s system specifically addresses Ishibashi’s concerns. Gregory’s system comprising a non-integrating viral vector encoding the lineage specific promoter and/or enhancer-GFP construct allows for the stable integration of the construct in a specific genomic locus, where the safe harbor locus prevents endogenous cis-acting regulation of the insertion while preventing toxicity due to integrated viral vector genes. A skilled artisan would have had a reasonable expectation of success in practicing the claimed invention as nucleic acid constructs comprising enhancer sequences operably linked to reporter genes comprised within viral vectors was known in the art at the time of the invention.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,729,790 in view of Punnamoottil et al., Motor Neuron-Expressed MicroRNAs 218 and Their Enhancers are Nested Within Introns of Slit2/3 Genes. Genesis, 2015. 53:321-328; published online April 10, 2015, of record, cited on Applicant’s IDS dated 04/07/2023, in view of Little et al. Conserved Modularity and potential for Alternate Splicing in Mouse and Human Slit Genes. International Journal of Developmental Biology, 2002. 46: 385-391, of record, cited on Applicant’s IDS dated 04/07/2023, Small et al., MicroRNA-218 Regulates Vascular Patterning by Modulation of Slit-Robo Signaling. Circulation Research, 2010. 107:1336-1344, Genbank Accession No. NC_000077, earliest publication date 2009, of record, cited on Applicant’s IDS dated 04/07/2023, Ishibashi et al. Using Zebrafish Transgenesis to Test Human Genomic Sequences for Specific Enhancer Activity. Methods, 2013. 62:216-225 and US Patent Application Publication No. 2011/0027235 to Gregory.
The disclosures of Punnamoottil, Little, Small, Genbank Accession No. NC_000077, Ishibashi and Gregory are applied as in the 103 rejections above, the content of which is incorporated herein in their entirety.
The instant Application is a CONTINUATION of US Patent No. 11,642,423, which is a CONTINUATION of US Patent No. 10,729,790. Thus, the instant application and the ‘790 patent share the same specification and effective filing date. The provisions of 35 USC 121 prohibit the use of a patent issuing on an application in which a requirement for restriction has been made, or on an application filed as a result of such a requirement, as a reference against any divisional application in a nonstatutory double patenting rejection, if the divisional application is filed before the issuance of the patent. The provisions of US 121 do not prevent double patenting rejections when a subsequence application is filed as a CONTINUATION, such as in the instant application.
This rejection is necessitated by the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent containing such patentably indistinct claims.
The instant specification teaches the promoter of SEQ ID NO:1 can be operably linked to therapeutic genes and used in methods of treating motor neuron disease (Section 5.2 “Therapeutic Nucleic Acids Operably Linked to Motor Neuron-Specific Promoter Section, from paragraphs [0124]-[0144]). In this section, the therapeutic nucleic acids are genes encoding ISL1, ISL2, LhX, ISL-Lhx3 fusion proteins and Phox2a (paragraph [0140]). In this section, the therapeutic nucleic acids are genes encoding detectable proteins including fluorescent proteins (paragraph [0143]).
The instant specification teaches the promoter of SEQ ID NO:1 can be operably linked to genes encoding ISL1, ISL2, LhX, ISL-Lhx3 fusion proteins and Phox2a to increase miRNA-218 in methods of treating motor neuron disease: see paragraphs [0011]-[0023], [0140], [0169]-[0177], Example 1, Example 2).
The instant specification also teaches the promoter of SEQ ID NO:1 can be operably linked to a gene encoding a fluorescent protein and used to asses motor neuron viability (paragraphs [0143]-[0144]).
Claim 1 of US Patent No. 10,729,790 is drawn to a method of treating a human subject comprising an effective amount of a composition comprising a nucleic acid that encodes a compound that increases miR-218 expression, wherein the compound that increases miR-218 expression encodes a transcription factor selected from the group consisting of ISL1, ISL2, LUX, ISL-Lhx3 fusion proteins and Phox2a.
Instant claim 1 is directed to a recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein.
Punnamoottil, Little, Small, and Genbank Accession No. NC_000077 combine to render obvious a recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein, for the reasons stated above in the 103 rejection.
With regard to instant claim 1, it would have been obvious to the skilled artisan to modify the claims of the ‘790 patent to recite the recombinant nucleic acids comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein as presently claimed. It would have been obvious to claim the motor neuron specific promoter of the ‘790 claims as a claim comprising a motor neuron promoter according to SEQ ID NO:1, in light of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), or further in light of Punnamoottil, Little, Small, and Genbank Accession No. NC_000077. It would have been obvious to encode a fluorescence protein in light of in light of the Court of Appeals for the Federal Circuit in Pfizer Inc. v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), or further in light of Punnamoottil, Little, Small, and Genbank Accession No. NC_000077.
Instant claims 2-4 are obvious over the disclosures of Punnamoottil, Little, Small, Genbank Accession No. NC_000077, Ishibashi and Gregory for the reasons stated in the 103 rejections above.
Claims 1-4 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of US Patent No. 11,642,423 taken in view of Punnamoottil et al., Motor Neuron-Expressed MicroRNAs 218 and Their Enhancers are Nested Within Introns of Slit2/3 Genes. Genesis, 2015. 53:321-328; published online April 10, 2015, of record, cited on Applicant’s IDS dated 04/07/2023, in view of Little et al. Conserved Modularity and potential for Alternate Splicing in Mouse and Human Slit Genes. International Journal of Developmental Biology, 2002. 46: 385-391, of record, cited on Applicant’s IDS dated 04/07/2023, Small et al., MicroRNA-218 Regulates Vascular Patterning by Modulation of Slit-Robo Signaling. Circulation Research, 2010. 107:1336-1344, Genbank Accession No. NC_000077, earliest publication date 2009, of record, cited on Applicant’s IDS dated 04/07/2023, Ishibashi et al. Using Zebrafish Transgenesis to Test Human Genomic Sequences for Specific Enhancer Activity. Methods, 2013. 62:216-225 and US Patent Application Publication No. 2011/0027235 to Gregory.
The disclosures of Punnamoottil, Little, Small, Genbank Accession No. NC_000077, Ishibashi and Gregory are applied as in the 103 rejections above, the content of which is incorporated herein in their entirety.
The instant Application is a CONTINUATION of US Patent No. 11,642,423.
Claims 1 and 8 of US Patent No.11,642,423 is directed to a recombinant nucleic acid comprising a motor neuron-specific promoter nucleic acid sequence comprising SEQ ID NO:1, operatively linked to a first nucleic acid sequence encoding a compound that increases miR-218 expression, wherein the first nucleic acid sequence is a transcription factor selected from the group consisting of ISL1, ISL2, LUX, ISL-Lhx3 fusion proteins and Phox2a, or a pharmaceutical composition comprising the recombinant nucleic acid.
Instant claim 1 is directed to a recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein.
Punnamoottil, Little, Small, and Genbank Accession No. NC_000077 combine to render obvious a recombinant nucleic acid comprising a motor neuron specific promoter comprising SEQ ID NO:1 operably linked to a nucleic acid encoding a fluorescent protein, for the reasons stated above in the 103 rejection.
Thus, it would have been obvious to modify the claims of the ‘423 patent to substitute the claimed transcription factor with a fluorescent protein.
Instant claims 2-3 are obvious over patented claims 5-7 or the prior art for the reasons stated above.
Instant claim 4 is obvious over the prior art for the reasons stated above.
Conclusion
No claims are allowed.
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/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633