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
Applicant’s amendments filed June 8, 2026, amending claims 4, 7-9, 11, 18, and 20 is acknowledged. Claims 1-2, 4, 7-11 and 15-26 are pending.
Applicant’s election without traverse in the reply filed on June 8, 2026 of group 1, encompassing claims 1-2, 4, 7-11 and 15-16, and election of the Myo7A promoter as a species of promoter are also acknowledged. Claims 17-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected groups, there being no allowable generic or linking claim.
Claims 1-2, 4, 7-11 and 15-16 are under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on pages 35 and 37. 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.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 11 depends from claim 10, which recites “a lentivirus expression vector comprising the nucleic acid sequence of SEQ ID NO: 1…”, which is interpreted as the vector requiring all of SEQ ID NO: 1 without any substitutions, deletions or internal additions. Claim 11 recites “wherein the nucleic acid which is at least 95% identical to SEQ ID NO: 1”. Thus, claim 11 appears to allow up to 5% substitutions or deletions from SEQ ID NO 1 in the nucleic acid. As such, claim 11 does not include all the limitations of claim 10, from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claims 10-11 and 15-16 are 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).
Claims 10-11 and 15-16 are drawn to a “cell”, “a stem cell” and “an induced pluripotent stem cell”. The specification does not provide a limiting definition of a cell, and does not expressly exclude cells within a human organism, especially because ex vivo cells, including induced pluripotent cells can be delivered back to humans. Thus, the term “cell”, “a stem cell” and “an induced pluripotent stem 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 ex vivo human cell, for example, as described in the Specification on page 63.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Simons (US 20210330814 A1, effectively filed as early as July 12, 2019).
Regarding claim 1, Simons teaches pITR201, a viral vector comprising a nucleic acid sequence encoding part of the STRC coding sequence operably linked to the CMV promoter (Fig 1). Simons also teaches that the STRC-expression nucleic acids can be comprised within a lentiviral vector ([0006]).
Simons does not teach in a single embodiment the STRC expression nucleic acids operably linked to the CMV promoter in a lentiviral vector.
However, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have cloned the CMV-STRC expression construct into a lentiviral vector. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the CMV-STRC construct could be incorporated into a lentiviral vector, and been motivated to have done so, because Simons suggests it.
Claims 2 and 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Simons (US 20210330814 A1, effectively filed as early as July 12, 2019), as applied to claim 1 above, and further in view of Pan (Pan et al., Neural Regeneration Research (2013), 8: 1551-1559) and Davis (Choosing Between Lentivirus and Adeno-associated Virus For DNA Delivery (2017), https://www.genecopoeia.com/resource/aav-vs-lentivirus-choosing-for-dna-delivery, [retrieved June 16, 2026]).
The teachings of Simons are recited above and applied as for claim 1. Simons also teaches the cDNA sequence of STRC (SEQ ID NO 2, pages 91-93), which comprises a sequence that is 98% identical to SEQ ID NO 1, only missing the first 79 nucleotides of the 5’ UTR of the STRC cDNA (see OA Appendix, pages 1-5). Simons teaches the length of the STRC cDNA is 5433 nucleotides. Simons teaches the STRC cDNA split between two AAV vectors that are used to reconstitute an active stereocilin gene ([0244]). Simons teaches delivering the AAV-STRC vectors to cochlea where STRC was efficiently expressed in outer and inner ear cells ([0273]-[0274]).
Simons does not teach the entirety of the STRC cDNA in a single lentiviral vector. Simons does not teach third-generation self-inactivating lentiviral vectors.
Pan teaches lentiviral vectors can be used to deliver transgenes to the organ of Corti cells for gene expression in hair-like structures (Abstract). Pan teaches the lentiviral vectors are third generation self-inactivating (SIN) lentiviral vectors (page 1556, ¶5).
Davis teaches differences between AAV vectors and lentiviral vectors. Davis teaches benefits of lentiviral vectors is they can deliver larger DNA sequences – up to about 6 kb in length – and drive stable gene expression in organs and tissues in vivo (page 4), whereas AAV vectors have a transgene capacity of up to 4 kb (page 6).
Regarding claims 2 and 7, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have included the entirety of the STRC cDNA taught in Simons under the control of the CMV promoter into a 3rd generation SIN lentiviral vector. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the entire promoter-STRC cDNA expression construct could be incorporated into a SIN lentiviral vector because the length of the construct is within the size capacity of lentiviral vectors. The skilled artisan would have been motivated to have done so because Pan teaches that lentiviral vectors are effective for gene delivery to the cochlea for transgene expression, which is the purpose of Simons’s AAV-STRC expression constructs.
Regarding claim 8, Simons teaches the entire coding sequence of STRC encodes a protein with amino acid sequence of SEQ ID NO 1 (pages 86-91). Simons’s SEQ ID NO 1 comprises an amino acid sequence having 98% identity with SEQ ID NO 2 of the examined application (see OA Appendix, pages 6-7).
Claims 4, 9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Simons (US 20210330814 A1, effectively filed as early as July 12, 2019), Davis (Choosing Between Lentivirus and Adeno-associated Virus For DNA Delivery (2017), https://www.genecopoeia.com/resource/aav-vs-lentivirus-choosing-for-dna-delivery, [retrieved June 16, 2026]) and Pan (Pan et al., Neural Regeneration Research (2013), 8: 1551-1559), as applied to claims 1-2 and 7-8 above, and further in view of Genbank1 (NG_009086.2, Homo sapiens myosin VIIA (MYO7A), RefSeqGene on chromosome 11, version available May 13, 2020).
For the purpose of examination, claim 11 is interpreted as only requiring a STRC-coding sequence that is at least 95% identity to SEQ ID NO 1.
The teachings of Simons, Davis and Pan are recited above and applied as for claims 1-2 and 7-8. Simons also teaches cochlea-specific promoters can be used to drive expression of the STRC transgene, including the MYO7A promoter ([0131]). Simons teaches Myo7A is expressed in both outer and inner hair cells ([0274]). Simons teaches the compositions comprising STRC-encoded viral vectors in pharmaceutical compositions ([0183]-[0189]).
Simons, Davis and Pan do not teach the sequence of the MYO7A promoter.
Genbank1 teaches the gene sequence of the human MYO7A gene. Genbank1 teaches the upstream sequence of the MYO7A transcript (i.e., the promoter sequence), which comprises a sequence with 100% identity to SEQ ID NO 4.
Regarding claims 4, 9 and 11, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have used the MYO7A promoter sequence provided in Genbank1 in place of the CMV promoter in the lentiviral vector rendered obvious above for claims 7-8. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the MYO7A sequence could have been used and been motivated to have used it because Simons suggests using the MYO7A promoter with a different STRC viral vector. The skilled artisan would have been motivated to specifically use SEQ ID NO 4 as the MYO7A promoter because Genbank1 teaches that is the upstream sequence for the MYO7A gene which is the region for eukaryotic gene promoters.
Claims 10 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Simons (US 20210330814 A1, effectively filed as early as July 12, 2019), Davis (Choosing Between Lentivirus and Adeno-associated Virus For DNA Delivery (2017), https://www.genecopoeia.com/resource/aav-vs-lentivirus-choosing-for-dna-delivery, [retrieved June 16, 2026]) and Pan (Pan et al., Neural Regeneration Research (2013), 8: 1551-1559), as applied to claims 1-2 and 7-8 above, and further in view of Genbank2 (NM_153700.2, Homo sapiens stereocilin (STRC), mRNA, version published July 1, 2020).
The teachings of Simons, Davis and Pan are recited above and applied as for claims 1-2 and 7-8. Simons also teaches including a 5’ UTR sequence and 3’ UTR sequence upstream and downstream, respectively, of the STRC cDNA sequence in the viral vectors (Figs 1 and 4). Simons also teaches delivering the STRC-encoding viral vectors to cochlear cells ([0273]-[0274]). Pan teaches delivering lentiviral vectors to cochlear cells (Abstract).
Simons, Davis and Pan do not teach a viral vector comprising SEQ ID NO 1, which is interpreted as requiring all the sequence of SEQ ID NO 1 without any substitutions, deletions or internal additions.
Genbank2 teaches the sequence of the stereocilin mRNA, which is 100% identical to the SEQ ID NO 1. Genbank2 teaches the 5’ UTR is the first 78 nucleotides of the mRNA. Genbank2 teaches nucleotides 5410 to the end is the 3’ UTR of the stereocilin mRNA (page 3, see cds coordinates).
Regarding claim 10, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have included the entirety of the STRC mRNA as taught in Genbank2 under the control of the CMV promoter in the lentiviral vector rendered obvious above for claim 7 for delivery to cells. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the Genbank2’s mRNA sequence could be included in a lentiviral vector because 1) Simons teaches including 5’ and 3’ UTRs in viral vectors for delivery and 2) the length of the mRNA including the 5’ and 3’ UTRs is within the size capacity of lentiviral vectors. The skilled artisan would have been motivated to have used Genbank2’s sequence because it is the art-accepted reference sequence for stereocilin.
Regarding claim 15, Pan teaches that lentiviral vectors can infect dividing cells like stem cells.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Simons (US 20210330814 A1, effectively filed as early as July 12, 2019), Davis (Choosing Between Lentivirus and Adeno-associated Virus For DNA Delivery (2017), https://www.genecopoeia.com/resource/aav-vs-lentivirus-choosing-for-dna-delivery, [retrieved June 16, 2026]), Pan (Pan et al., Neural Regeneration Research (2013), 8: 1551-1559) and Genbank2 (NM_153700.2, Homo sapiens stereocilin (STRC), mRNA, version published July 1, 2020), as applied to claims 1-2, 7-8, 10 and 15 above, and further in view of Zine (Zine et al., Stem Cells (2021), 39: 697-706).
The teachings of Simons, Davis, Pan and Genbank2 are recited above and applied as for claims 1, 7-8, 10 and 15.
Simons, Davis, Pan and Genbank2 do not teach delivering lentiviral vectors to induced pluripotent stem cells (iPSCs).
Zine teaches sensorineural hearing loss is caused by damage or loss to the mechanosensory hair cells and/or ganglion neurons (page 697, ¶1). Zine teaches the generation of inner ear sensory cells from in vitro differentiation of iPSCs is an obvious cell-based cell therapy to treating hearing loss caused by loss/damage to hair cells (page 698, ¶1). Zine teaches iPSCs allow derivation of patient-specific stem cells (Significance Statement).
Regarding claim 16, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to delivered the lentivirus comprising the STRC mRNA coding sequence rendered obvious above for claim 10 to iPSCs. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the Genbank2’s mRNA sequence in a lentiviral vector could be delivered to iPSCs since they are dividing cell type and Pan teaches lentiviral vectors can be used in dividing cell types. The skilled artisan would have been motivated to have delivered the LV-STRC vector to iPSCs for the purpose of providing a functional copy of STRC to patient-derived iPSCs and then used for cell-based therapy for treating hearing loss as described in Zine.
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 1-2 ,4, 7-11 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8-9 and 11-14 of copending Application No. 18254669. Claims 4, 7-11 and 15 are rejected in view of Simons (US 20210330814 A1, effectively filed as early as July 12, 2019), Genbank2 (NM_153700.2, Homo sapiens stereocilin (STRC), mRNA, version published July 1, 2020) and Genbank1 (NG_009086.2, Homo sapiens myosin VIIA (MYO7A), RefSeqGene on chromosome 11, version available May 13, 2020).
Copending claim1 recites “delivering a cargo nucleic acid to a cell of the inner ear… a composition comprising a 3rd generation lentiviral vector…, wherein the lentiviral vector comprises a cargo nucleic acid selected from the group consisting of a protein-coding gene…, and wherein the lentiviral vector comprises a) a 5' LTR with a deleted (SIN) U3 region…, c) an internal enhancer/promoter region operably linked to a cargo sequence…, and a 3' LTR with a deleted U3 (SIN) region” (i.e., a 3rd generation SIN lentiviral vector). Copending claim 8 recites “wherein the cargo sequence is a gene selection from the group consisting of STRC”. Therefore, copending claim 8 anticipates examined claims 1-2.
The copending claims do not recite a nucleotide sequence for STRC or specific promoter sequences.
Simons teaches viral vectors comprising nucleic acid sequences encoding STRC operably linked to a promoter (Fig 1). Simons teaches that the STRC-expression nucleic acids can be comprised within a lentiviral vector ([0006]). Simons teaches cochlea-specific promoters can be used to drive expression of the STRC transgene, including the MYO7A promoter ([0131]). Simons teaches Myo7A is expressed in both outer and inner hair cells ([0274]).
Genbank2 teaches the sequence of the stereocilin mRNA, which is 100% identical to the SEQ ID NO 1. Genbank2 teaches the 5’ UTR is the first 78 nucleotides of the mRNA. Genbank2 teaches nucleotides 5410 to the end is the 3’ UTR of the stereocilin mRNA (page 3, see cds coordinates).
Genbank1 teaches the gene sequence of the human MYO7A gene. Genbank1 teaches the upstream sequence of the MYO7A transcript (i.e., the promoter sequence), which comprises a sequence with 100% identity to SEQ ID NO 4.
Regarding claims 4, 7-11 and 15, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have 1) used the MYO7A promoter sequence provided in Genbank1 for the generic promoter, and 2) included the entirety of the STRC mRNA as taught in Genbank2 for the unspecific STRC cargo sequence in the 3rd generation SIN lentiviral vector recited in the copending claims. It would have amounted to the simple combination of elements by known means to yield predictable results. The skilled artisan would have predicted that the MYO7A promoter sequence provided by Genbank1 and STRC mRNA sequence provided by Genbank2 could be used in the copending lentiviral vector, and been motivated to include them because 1) Simons suggests using the MYO7A promoter with a different STRC viral vector, 2) Simons teaches including 5’ and 3’ UTRs in viral vectors for delivery and 3) the Genbank sequences are the accepted reference sequence for stereocilin and the MYO7A promoter.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE KONOPKA whose telephone number is (571)272-0330. The examiner can normally be reached Mon - Fri 7- 4.
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/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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