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
This action is in response to the papers filed February 18, 2026.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/18/2026 has been entered.
Claim Amendments
Applicant’s amendment to the claims filed on 02/18/2026 is acknowledged.
Claims 2-19, 22-87, 90-91, 93, 103-104 have been cancelled.
Claims 1, 20-21, and 106 are amended.
Claims 1, 20-21, 88-89, 92, 94-102, 105-108 are pending.
Claim 88-89, 92, 94-102, and 105 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1, 20-21, 106-108 are under examination.
Election/Restrictions
Applicant’s elections:
The examiner’s restriction/election requirements were set forth in the Office action mailed on 03/14/2025.
In applicant’s response filed on 05/14/2025, applicant elected without traverse:
Group 1, drawn to a recombinant transgene or viral vector comprising a polynucleotide encoding a delta-catenin protein;
the delta-catenin protein according to SEQ ID NO: 21 (amino acid sequence) and encoded by the sequence of SEQ ID NO: 20 (nucleic acid sequence);
the promoter of synapsin 1; and
the additional therapy of GSK3β inhibitor.
Please note that SEQ ID NO: 31 is identical to elected SEQ ID NO: 21, and, therefore, SEQ ID NO: 31 reads on the elected invention.
Rejoinders:
In the amendment to the claims filed on 02/18/2026, applicant amended the claims to exclude the elected invention of the delta-catenin protein according to SEQ ID NO: 21 (amino acid sequence) and encoded by the sequence of SEQ ID NO: 20 (nucleic acid sequence). In particular, the claims have been amended to recite only the non-elected invention of a delta-catenin protein encoded the nucleic acid sequence according to SEQ ID NO: 26, which has the amino acid sequence according to SEQ ID NO: 27 (see, pg. 77-79 of the specification). Therefore, the examiner will shift prosecution to the non-elected invention of the delta-catenin protein according to SEQ ID NO: 27 (amino acid sequence) and encoded by the sequence of SEQ ID NO: 26 (nucleic acid sequence).
Applicant’s amendment further necessitates rejoinder of claims 106-108, which were previously withdrawn from consideration, because claims 106-108 are directed to the nucleic acid sequence set forth in SEQ ID NO: 26, which is presently under examination.
In view of the above rejoinders, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Withdrawn claims:
Claims 88-89, 92, 94-102, and 105 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. In particular, claims 88-89, 92, 94-102, and 105 are drawn to non-elected Group 2 (methods). Election was made without traverse in the reply filed on 05/14/2025.
Priority
The instant application 17/637,760 was filed on 02/23/2022. This application is a national stage of international application PCT/US2020/047655 filed 08/24/2020, claiming priority based on U.S. Provisional Application 62/890,710 filed 08/23/2019.
Effective filing dates:
In remarks filed on 02/18/2026, applicant argues that SEQ ID NO: 26, as claimed in claims 1, 20-21, 106-108, possesses sufficient written support in provisional application 62/890,710, and, therefore, the claims 1, 20-21, 106-108, have an effective filing date of 08/23/2019 based on the provisional application. In particular, applicant argues that page 51, paragraph 2, of the provisional application discloses: "[p]lasmid containing human δ-catenin (CTNND2, NM_ 001288717) open reading frame...," and this same statement is included in paragraph 198 of the present national phase entry application, U.S. Application No. 17/637,760. Thus, since a sequence alignment shows that the CTNND2 sequence provided by NM_ 001288717 is identical across all 5323 bp to the sequence set forth in SEQ ID NO:26, the provisional application provides written description for SEQ ID NO:26. See page 6, first paragraph, and page 7, second full paragraph, of applicant’s remarks.
Applicant’s remarks have been carefully considered, but are not found persuasive for the following reasons.
37 CFR 1.57(c), (d), and (e) state:
c) Except as provided in paragraphs (a) or (b) of this section, an incorporation by reference must be set forth in the specification and must:
(1) Express a clear intent to incorporate by reference by using the root words "incorporat(e)" and "reference" ( e.g. , "incorporate by reference"); and
(2) Clearly identify the referenced patent, application, or publication.
(d) "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. "Essential material" is material that is necessary to:
(1) Provide a written description of the claimed 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 set forth the best mode contemplated by the inventor of carrying out the invention as required by 35 U.S.C. 112(a);
(2) Describe the claimed invention in terms that particularly point out and distinctly claim the invention as required by 35 U.S.C. 112(b); or
(3) Describe the structure, material, or acts that correspond to a claimed means or step for performing a specified function as required by 35 U.S.C. 112(f).
(e) Other material ("Nonessential material") may be incorporated by reference to U.S. patents, U.S. patent application publications, foreign patents, foreign published applications, prior and concurrently filed commonly owned U.S. applications, or non-patent publications. An incorporation by reference by hyperlink or other form of browser executable code is not permitted.
See also MPEP 608.01(p).
In this case, the provisional application refers to a nucleotide sequence by a database accession number “NM_ 001288717” (page 51, paragraph 2, of the provisional application), which applicant asserts provides the sequence set forth in SEQ ID NO: 26 of the present national phase entry application, U.S. Application No. 17/637,760. The examiner found that SEQ ID NO: 26 is identical to the sequence provided by GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI). See, Alignments below.
Nonetheless, the provisional application is not found to provide sufficient written support for SEQ ID NO: 26 for at least the following reasons:
An incorporation by reference must express a clear intent to incorporate by reference by using the root words "incorporat(e)" and "reference" (e.g., "incorporate by reference"), as set forth by 37 CFR 1.57(c)(1). In this case, there is no clear intent to incorporate by reference, by using the root words "incorporat(e)" and "reference," the sequence disclosed by database accession number “NM_ 001288717” found in the specification of the provisional application.
An incorporation by reference in the specification must clearly identify the referenced patent, application or publication, as set forth by 37 CFR 1.57(c)(2). In this case, the specification of the provisional application only refers the database accession number “NM_ 001288717;” but the reference neither clearly identifies the particular database from which the accession number was obtained, nor the record version and/or publication date of the database entry. Moreover, even if applicant intended to refer to the GenBank sequence database (produced and maintained by the NCBI), the accession number “NM_ 001288717” had two different record versions (each corresponding to a different sequence) prior to the filing date of the provisional application, i.e., prior to 08/23/2019. In particular, the Revision History for GenBank accession number NM_ 001288717 shows that the sequence was updated from “version 1” (i.e., NM_ 001288717.1) to “version 2” (i.e., NM_ 001288717.2) on 05/19/2019. (A copy of the Revision History is submitted with this Office action and cited as: Revision History of GenBank, NCBI Reference Sequence: NM_001288717.2, National Library of Medicine (US), National Center for Biotechnology Information (NCBI), online webpage, accessed on 10-Mar-2026, 2 pages). Therefore, when the specification of the provisional application refers the database accession number “NM_ 001288717,” it is unclear whether the specification intends to reference the sequence according to “version 1” (i.e., NM_ 001288717.1) or “version 2” (i.e., NM_ 001288717.2) in the GenBank sequence database. For these reasons, the specification of the provisional application is not found to clearly identify the referenced publication, as required by 37 CFR 1.57(c)(2). (The examiner further notes that page 77 of the specification of the present national phase entry application, U.S. Application No. 17/637,760, describes SEQ ID NO: 26 by the database accession number “NM_001288717.1,” but SEQ ID NO: 26 is only identical to version 2 of NM_001288717, i.e., NM_001288717.2).
“Essential material” may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference, as set forth by 37 CFR 1.57(d). In this case, SEQ ID NO: 26, as claimed in claims 1, 20-21, 106-108, is “essential material” as defined under 37 CFR 1.57(d)(1)-(3). However, the database accession number “NM_ 001288717” (i.e., the reference which applicant relies upon for describing “essential material” of SEQ ID NO: 26) is not a reference to a U.S. patent or U.S. patent application publication, as required by 37 CFR 1.57(d).
For at least these reasons, written support for SEQ ID NO: 26, as claimed in claims 1, 20-21, 106-108, is not identified in the provisional application.
In addition, the limitations of (1) a non-viral delivery vehicle, as claimed in claim 107, and (2) wherein the non-viral vehicle comprises a liposomes, a nanocapsule, a microparticle, a microspheres, a lipid particles, or a vesicle, as claimed in claim 108, are also not found to possess sufficient written support in the provisional application.
Accordingly, claims 1, 20-21, 106-108 are found to have an effective filing date of 08/24/2020 based on the international application, PCT/US2020/047655. Please see MPEP 608.01(p) for further guidance.
Withdrawal of Prior Rejections/Objections
Rejections and/or objections not reiterated from the previous Office action mailed 11/03/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Claim Objections
Claim 108 is objected to because of the following informalities:
The phrase “a liposomes” should be “a liposome” or “liposomes”; the phrase “a microspheres” should be “a microsphere” or “microspheres”; the phrase “a lipid particles” should be “a lipid particle” or “lipid particles”.
Appropriate action 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.
Claims 106-108 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
This rejection is newly applied.
The claims are directed to product, which is a statutory category of invention.
The claims are directed to a polynucleotide encoding human delta-catenin protein, which natural product and judicial exception.
The claims do not recite additional elements that integrate the judicial exception into a practical application because the additional elements, considered individually or in combination, do not confer markedly different characteristics to the judicial exception as compared to its naturally occurring counterpart.
First, claim 106 recites the polynucleotide is a “recombinant” polynucleotide. The recitation does not confer markedly different characteristics because it does not clearly impart a structural or functional characteristics markedly different from its naturally-occurring counterpart. In this case, the recitation may suggest that the claimed polynucleotide was (1) isolated from its natural environment and/ or (2) synthetically created. In the former case, the incidental changes resulting from isolation of a gene sequence are not enough to make the isolated gene markedly different. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. See, MPEP 2106.04(c). In the latter case, a process limitation is not viewed as positively limiting the claimed product absent a showing that the process imparts a novel or unexpected property to the claimed product, as it is assumed that equivalent products are obtainable by multiple routes. The patentability of a product does not depend on its method of production. See, MPEP 2113.
Second, claim 106 recites the sequence encoding human delta-catenin protein is set forth in SEQ ID NO: 26. However, SEQ ID NO: 26 is identical to the naturally-occurring mRNA sequence for Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, as evidenced by GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI). See, Alignments below.
Third, claim 106 recites that the coding sequence is operably linked to a promoter sequence. However, the coding sequence of human delta-catenin protein is operably linked to a promoter sequence in nature, i.e., in the genome of a human cell.
For these reasons, claim 106 does not recite additional elements that confer markedly different characteristics to the judicial exception as compared to its naturally occurring counterpart.
Regarding dependent claim 107, the limitation “non-viral delivery vehicle” broadly reads on a host cellular organism. Human cells naturally comprise, in the genome, the coding sequence of human delta-catenin protein operably linked to a promoter sequence.
Regarding dependent claim 108, a human cell (reading on, “non-viral delivery vehicle”) naturally “comprises” liposomes, lipid particles and vesicles.
For these reasons, dependent claims 107-108 do not recite additional elements that confer markedly different characteristics to the judicial exception as compared to its naturally occurring counterpart.
Accordingly, the claims are not considered to recite additional elements that amount to significantly more than the judicial exception itself because the additional elements, considered individually or in combination, do confer not markedly different from their naturally occurring counterpart. Therefore, claims 1-2 are not patent eligible subject matter.
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.
Claims 106-108 are rejected under 35 U.S.C. 102(a)(1) as being in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention as evidenced by GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI).
This rejection is newly applied, necessitated by amendment.
In this case, as set forth under 35 U.S.C. 101 above, claims 106-108 broadly read on a naturally-occurring human cell (reading on, “non-viral delivery vehicle”) comprising a genome comprising a sequence encoding a human delta-catenin protein operably linked to a promoter sequence. The sequence set forth in SEQ ID NO: 26 is identical to the wild-type mRNA sequence of human CTNND2, transcript variant 4, as evidenced by GenBank accession NM_001288717.2. See, Alignments below. Human cells (reading on, “non-viral delivery vehicle”) also naturally “comprise” liposomes, lipid particles and vesicles, as recited by dependent claim 108.
For these reasons, the products of nature recited in claims 106-108 were inherent (necessarily present) in human tissue prior to the effective filing date of the claimed invention, as evidenced by GenBank accession NM_001288717.2, and, therefore, said products of nature recited in claims 106-108 were in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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.
Claims 1, 20 and 106 are rejected under 35 U.S.C. 103 as being unpatentable over Yeo et al. (12-Sep-2019) “Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission,” Pre-print on bioRxiv, version 1; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI).
This rejection is newly applied, necessitated by amendment. Regarding applicant’s remarks that the “Yeo” disclosure does not qualify as prior art, because the disclosure is preceded by applicant’s provisional application, please see the examiner’s remarks under the Priority section, above. Claims 1, 20-21, 106-108 are found to have an effective filing date of 08/24/2020 based on applicant’s international application, PCT/US2020/047655.
Regarding claims 1 and 106, Yeo discloses a human delta-catenin transgene cloned onto an AAV9 viral vector and operably linked to a human synapsin I (hSyn) promoter. See Results: δ-cat spinal transgenesis is analgesic in nerve constriction injury, and Methods: δ-catenin DNA constructs, transgenesis vectors.
Yeo does not disclose that the polynucleotide comprises the sequence according to SEQ ID NO: 26.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 20. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the viral vector of Yeo by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because Yeo teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing Yeo’s viral vector, as disclosed by GenBank.
For these reasons, claims 1 and 106 would have been prima facie obvious over the prior art.
Regarding dependent claim 20, Yeo discloses a human delta-catenin transgene cloned onto an AAV9 vector. See Results: δ-cat spinal transgenesis is analgesic in nerve constriction injury, and Methods: δ-catenin DNA constructs, transgenesis vectors.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Yeo et al. (12-Sep-2019) “Repurposing cell growth-regulating compounds identifies kenpaullone which ameliorates pathologic pain via normalization of inhibitory neurotransmission,” Pre-print on bioRxiv, version 1; and GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI), as applied to claims 1, 20 and 106 above; in further view of Gray et al. (2012) “Design and Construction of Functional AAV Vectors” In: Snyder, R., Moullier, P. (eds), Adeno-Associated Virus: Methods in Molecular Biology, vol. 807, Chapter 2, pg. 25-46, Springer Protocols, Humana Press.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 21, Yeo does not expressly disclose that the AAV9 vector further comprises one or more of (a) an inverted terminal repeat sequence (ITR); (b) an intron; (c) transcription terminator; (d) a flanking inverted terminal repeat sequence (ITR); and (e) a polyA tail, as instantly claimed.
Gray is relevant prior art for teaching the basic design of an AAV vector is relatively simple, in that it consists of an appropriately sized expression cassette flanked by inverted terminal repeats (ITRs), which mediate the replication and packaging of the vector genome by the AAV replication protein Rep and associated factors in vector producer cells. Pg. 25-26, bridging paragraph.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the AAV9 vector of Yeo to further comprise an ITR sequence, as taught by Gray, with a reasonable expectation of success because ITRs are part of the basic design of AAV vectors, required to mediate the replication and packaging of the vector genome in vector producer cells.
Claims 106-108 are rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI).
This rejection is newly applied, necessitated by amendment.
St. George-Hyslop discloses a gene therapy vector encoding human Neural Plakophilin Related Armadillo Protein (hNPRAP). See, e.g., Abstract. The hNPRAP gene is synonymous with the human CTNND2 gene, which encodes human delta-catenin. The gene therapy vector stimulates nerve growth and regeneration by contacting nerve cells with hNPRAP. See, e.g., Abstract.
St. George-Hyslop further discloses promoter sequences operably linked to the hNPRAP transgene. See, e.g., pg. 3, ll. 17-20; pg. 13, ll. 14-31.
For these reasons, St. George-Hyslop is found to teach or fairly suggest a recombinant gene therapy vector comprising a transgene encoding human delta-catenin operably linked to a promoter sequence.
St. George-Hyslop does not disclose that the coding sequence according to SEQ ID NO: 26, as instantly claimed.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 26. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because St. George-Hyslop teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing St. George-Hyslop’s gene therapy vector.
For these reasons, claim 106 would have been prima facie obvious over the prior art.
Regarding dependent claims 107-108, St. George-Hyslop discloses liposomes comprising a plasmid vector encoding human delta-catenin operably linked to a promoter sequence. See, pg. 14, ll. 2-18.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; in view of GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI); and Liu et al. (2008) "Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivo" BMC biotechnology 8:1-8.
This rejection is newly applied, necessitated by amendment.
St. George-Hyslop discloses a gene therapy vector encoding human Neural Plakophilin Related Armadillo Protein (hNPRAP). See, e.g., Abstract. The hNPRAP gene is synonymous with the human CTNND2 gene, which encodes human delta-catenin. The gene therapy vector stimulates nerve growth and regeneration by contacting nerve cells with hNPRAP. See, e.g., Abstract.
St. George-Hyslop further discloses that the gene therapy vector is a viral vector. See, e.g., pg. 6, ll. 5-8; pg. 12, ll. 18, to pg. 13, ll. 13.
St. George-Hyslop further discloses promoter sequences operably linked to the hNPRAP transgene. See, e.g., pg. 3, ll. 17-20; pg. 13, ll. 14-31.
For these reasons, St. George-Hyslop is found to teach or fairly suggest a recombinant viral vector comprising a transgene encoding human delta-catenin operably linked to a promoter sequence.
St. George-Hyslop does not disclose that the coding sequence according to SEQ ID NO: 26, as instantly claimed.
GenBank, NCBI Reference Sequence: NM_001288717.2, is relevant prior art for providing the nucleic acid sequence of human catenin delta 2 (CTNND2), transcript variant 4. The reference sequence is identical to the sequence according to SEQ ID NO: 26. See Alignments below.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by including the nucleic acid sequence according to SEQ ID NO: 26, as found in the GenBank accession NM_001288717.2, with a reasonable expectation of success because St. George-Hyslop teaches that the viral vector contains a nucleic acid sequence encoding human delta-catenin protein, and one of ordinary skill in the art would have sought a known, wild-type coding sequence of human delta-catenin for use in constructing St. George-Hyslop’s gene therapy vector.
St. George-Hyslop does not disclose the promoter is a synapsin I promoter, as instantly claimed.
Liu is relevant prior art for teaching cell-specific promoters are advantageous for gene therapy by restricting gene expression to particular cells. Failure to do so results in gene expression in non-target cells that confounds data interpretation and may lead to undesirable side effects. In addition, cell-type-specific promoters are advantageous since they are less likely to activate host cell defense machinery and are less sensitive to cytokine-induced promoter inactivation than viral promoters. As such, improved stability and longevity of gene expression can be expected. See, e.g., Abstract; pg. 1-2, joining paragraph.
Liu further teaches that the human synapsin-I (SYN) promoter provides cell-specific gene expression in neurons and glia in the central nervous system (CNS). See, e.g., Abstract; pg. 2, left column; Figures 1-2.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by using a synapsin-I promoter, as taught by Liu, with a reasonable expectation of success because the target cell type of St. George-Hyslop’s vector is neuronal cells, and the synapsin-I promoter is selectively active in the target neuronal cells. Failure to restrict gene expression results in expression in non-target cells that confounds data interpretation and may lead to undesirable side effects. In addition, cell-type-specific promoters are advantageous since they are less likely to activate host cell defense machinery and are less sensitive to cytokine-induced promoter inactivation than viral promoters. As such, improved stability and longevity of gene expression can be expected.
For these reasons, claim 1 would have been prima facie obvious over the prior art.
Claims 20-21 are rejected under 35 U.S.C. 103 as being unpatentable over by WO 00/47615 A2 to St. George-Hyslop et al.; GenBank, NCBI Reference Sequence: NM_001288717.2, “Homo sapiens catenin delta 2 (CTNND2), transcript variant 4, mRNA”, version 2, entry dated: 31-May-2019, National Library of Medicine (US), National Center for Biotechnology Information (NCBI); and Liu et al. (2008) "Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivo" BMC biotechnology 8:1-8, as applied to claim 1 above; in further view of Foust et al. (2009) “Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes” Nature biotechnology, 27(1), 59-65.
This rejection is newly applied, necessitated by amendment.
Regarding dependent claim 20, St. George-Hyslop does not disclose that the viral vector is an adeno-associated viral (AAV) vector, as instantly claimed.
Foust is relevant prior art for teaching AAV9 vector is capable of bypassing the blood-brain barrier (BBB) and efficiently targets cells of the central nervous system (CNS), showing extensive transduction of dorsal root ganglia and motor neurons throughout the spinal cord and widespread transduction of neurons throughout the brain, including the neocortex, hippocampus and cerebellum. See, e.g., Abstract.
Therefore, prior to the effective filing date of the instantly claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the gene therapy vector of St. George-Hyslop by using an AAV vector, as taught by Foust, with a reasonable expectation of success because the target cell type of St. George-Hyslop’s vector is neuronal cells, and the AAV9 vector has been shown to efficiently target neuronal cells.
Regarding dependent claim 21, Foust discloses the AAV vector comprises an inverted terminal repeat (ITR) sequence. See, e.g., pg. 63, Methods: Virus.
Alignments
SEQ ID NO: 26 (Qy) and NCBI Reference Sequence: NM_001288717.2 (Db)
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1009
582
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948
593
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1010
597
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1006
599
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1013
607
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657
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Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES J GRABER whose telephone number is (571)270-3988. The examiner can normally be reached Monday-Thursday: 9:00 am - 4:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James D Schultz can be reached at (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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/JAMES JOSEPH GRABER/Examiner, Art Unit 1631