DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 18554748, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-8, 12-13, 15-18, and 25-30 are pending.
Priority
The filing receipt, mailed 3/7/2023, states that this application was filed 10/10/2023, and states that this application, 18554748, is a 371 of PCT/US22/24415, filed 04/12/2022 and claims benefit of 63/173,885, filed 04/12/2021 and claims benefit of 63/187,883, filed 05/12/2021 and claims benefit of 63/293,505, filed 12/23/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/25/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
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.
Claims 3, 4, 5, 6, 27, 28, 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.
Claim 3 requires SEQ ID NO: 2 having up to 10 substitutions at any location. Claim 4 requires SEQ ID NO: 3 having up to 10 substitutions at any location. Claim 5 requires SEQ ID NO: 4 or SEQ ID NO: 5, having up to 30 substitutions at any location. Claim 6 requires SEQ ID NO:11 or SEQ ID NO: 12 having up to 60 substitutions at any location. Claim 27 requires SEQ ID NO: 2 having up to 10 substitutions at any location. Claim 28 requires SEQ ID NO: 3 having up to 10 substitutions at any location. However, the specification does not adequately describe the structure required for the function. The specification demonstrates delivery of SEQ ID NOs: 2-5, 11-12, which are species that are not representative of the entire claimed genus.
As evidenced by Kehl et al. (Oncotarget, 2017, Vol. 8, (No. 63), pp: 107167- 107175), miRNAs repress gene expression by binding to the 3' UTR, a process that is dominated by the eight-base seed region of the miRNA (abstract). The instant claims allow for this complete region to be substituted and would therefore not likely have the structure for the required function.
Krutzfeldt et al. (Nucleic Acids Research, 2007, 35, 9, 2885-2892) teach that miRNA antagomirs having four, two, or even a single mismatch at a specific position was sufficient to prevent downregulation of the target miRNA (page 2888). Additionally, Krutzfeldt et al. teach that specificity of drug-like oligonucleotides is important to minimize off-target effects and to discriminate between related miRNAs that sometimes differ by only a single nucleotide (page 2890).
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University V. Hoffman-La Roche Inc., Nos. 07- 1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification's disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California V. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ") Regents of the University of California V. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being sequences that differ from, e.g., SEQ ID NO: 2 at up to any 10 positions that have the required function.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, "Written Description" Requirement", published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for sequences within the instant genus that have the required function. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
1. Claim(s) 1, 7, 8, 12, 13, 15, 16, 17, 18, 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, Wilson, US20200056205A1, (‘205 PGP), and Cortes,2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4.
Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, teaches throughout the publication and abstract, use of an expression cassette in an AAV vector to diminish the toxic gain of function in the mutant androgen receptor (AR), which plays a role in the pathogenesis of spinal and bulbar muscular atrophy (SBMA). Pourshafie reports miRNA treatment strategy to target human AR, using miR-298 by intravenous delivery with AAV serotype 9 which resulted in amelioration of disease phenotype in SBMA mice.
Pourshafie describes the recombinant AAV9 comprising an expression cassette comprising a sequence encoding the hairpin forming miRNA miR-298 which inhibits expression of the human androgen receptor (AR) The AAV is used for the treatment of spinal and bulbar muscular atrophy (SBMA) (Abstract; Pages 937-940).
Pourshafie does not teach AAV hu68 capsid for vectors.
Wilson, US20200056205A1, ‘205 Publication, (published 2/20/2020, Serial No. 16487690), at para 227, 451, teaches throughout the publication and abstract, treatment of spinal muscular atrophy (SMA) comprising a rAAV vector with an AAVhu68 capsid and at least one expression cassette that comprises a nucleic acid encoding a functional survival of motor neuron 1 (SMN 1) protein and e.g., Wilson‘205 Publication, at para 57, 74, 76, 77, 215, 219, 221, 228, 386, 397, 438 teaches AAV hu68 capsid for vectors used to treat spinal muscular atrophy.
Example 10, para 273 intrathecal administration in rhesus macaques; at e.g., para 7, 228, teach CB7 promoters in an AAV vector, as in instant claims 8, 30; at para 107, teaches WRPE, as in instant claims 7 and 29; at para [144]-[145], teaches suboccipital / intracisternal administration to the cisterna magna, as in instant claims 17, 18; teaches at para 121, 274, 285, 290 reference claim 22, teaches injection into the cisterna magna or lumbar puncture of 3.3x1011 GC/g brain as in instant claims 15-16
Cortes 2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, teaches throughout the publication and abstract, and e.g., at p. 1, teaches that neurodegenerative disorders as including Spinal and Bulbar Muscular Atrophy (SBMA), and spinal muscular atrophy (SMA). Cortes, at p. 1-2, bridging paragraph, teaches that SBMA is a neuromuscular disorder, and has muscle weakness due to lower motor neuron degeneration in the spinal cord and brain stem. Cortes, at p. 2, para 3-6 to teaches that Androgen Receptor-poly glutamine in skeletal muscle plays a role in SBMA pathogenesis.
Cortes, at p. 2, para 7, states: “[o]ur results predict that muscle-directed therapies hold great promise as definitive treatments for SBMA motor neuron disease.” To support this, Cortex targeted skeletal muscle polyQ (glutamine) Androgen Receptor using antisense oligonucleotide technology to target the expanded AR mRNA for destruction. Cortes highlights skeletal muscle as an appealing target for SBMA therapy development.
Cortes, at p. 3, para 4-5, compares SBMA to other motor neuron diseases (MND), including spinal muscular atrophy (SMA). Cortes at para 5, states that muscle homeostasis directly contributes to neuronal survival and may play a key role in “related motor neuron disorders, such as ALS [amyotrophic lateral sclerosis] and SMA.” Cortex, at p. 3, para 5, teaches that SMA is a recessive neurodegenerative motor neuron disorder caused by mutations leading to reduced expression of survival motor neuron (SMN) protein. Cortes teaches that peripheral delivery of antisense oligonucleotides that promoter splicing of SMN2 is a highly effective therapy in mice.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson that binds a miRNA target site on human androgen receptor mRNA, as taught by Pourshafie.
One of ordinary skill in the art would have motivated to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson, ‘205 Publication, that binds a miRNA target site on human androgen receptor mRNA, as taught by Pourshafie, because Cortes teaches that SMA, as disclosed by Wilson, ‘205 Publication, and SBMA, as instantly claimed, are both neuromuscular diseases that are treatable by delivery of antisense oligonucleotides to lower motor neurons. Thus, it would have been desirable to one of ordinary skill in the art, to have delivered miRNA targeting androgen receptor, to the same cell type targeted by the rAAVhu68 of Wilson, ‘205 Publication. Even though Wilson teaches delivery of a different nucleic acid sequence, the practitioner would have been motivated to deliver miRNA targeting androgen receptor expression to the same type of target cell, in view of the teachings of Cortes.
2. Claim(s) 2-4 and 26-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, Wilson, US20200056205A1, (‘205 PGP), and Cortes, 2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, as applied to claims 1, 7, 8, 12, 13, 15, 16, 17, 18, 25 above, and further in view of Brown, US 8,927,515.
Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, Wilson, US20200056205A1, (‘205 PGP), and Cortes,2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, are relied upon as set above.
Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, Wilson, US20200056205A1, (‘205 PGP), and Cortes,2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, are relied upon as set above, do not teach or suggest SEQ ID NOs: 1-3 and 27 in an AAVhu68 vector for targeting human androgen receptor.
Brown, US 8,927,515, teaches Dicer at col. 11, line 41-col. 12, line 26 and compositions possessing Androgen Receptor inhibitory activity comprising dsRNA and more particularly at col. 11, line 62, col. 12, line 5, teaches SEQ ID NOs: 3121-3765, which teaches instant SEQ 1 at reference seq 3414; teaches instant SEQ ID 27 at reference SEQ ID NO: 3417, instant SEQ ID NO; 2, at reference SEQ ID NO: 3414; instant SEQ ID NO: 3 at reference SEQ ID NO: 3417. Brown, at col. 27, line 60-col. 28, line 23, teaches “Dicer” as referring to an endoribonuclease that cleaves e.g., pre-microRNA (miRNA) into double-stranded nucleic acid fragments 19-25 nucleotides long. Dicer catalyzes the first step in the RNA interference pathway, which consequently results in the degradation of a target RNA.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined SEQ ID NOs: 1-3 and 27, as taught by Brown, in an AAVhu68 vector for targeting human androgen receptor, as taught and suggested by Pourshafie, Wilson, (‘205 PGP), and Cortes.
One of ordinary skill in the art would have motivated to have combined SEQ ID NOs: 1-3 and 27 in an AAVhu68 vector for targeting human androgen receptor because Brown suggests the use of SEQ ID NOs: 1-3 and 27 in nucleic acids for reducing expression of androgen receptor.
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.
1. Claims 1, 7, 8, 12, 13, 15, 16, 17, 18, 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of Wilson, U.S. Patent No. 11,578,341, (‘341 Patent, formerly Serial No. 16487690), in view of Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, and Cortes,2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4.
Wilson, ‘341 Patent, at claims 1-15, claim a recombinant adeno-associated viral (rAAV) vector comprising an AAVhu68 capsid and at least one expression cassette, wherein the at least one expression cassette comprises a nucleic acid sequences encoding a functional survival of motor neuron (SMN) 1 protein and expression control sequences that direct expression of the SMN1 protein in a host cell, wherein the rAAV has an AAVhu68 capsid comprising: AAVhu68 VP1 proteins, AAVhu68 VP2 proteins and AAVhu68 VP3 proteins expressed from a nucleic acid sequence encoding SEQ ID NO: 8.
Wilson, ‘341 Patent does not claim miRNA that target mutant androgen receptor (AR).
Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, teaches throughout the publication and abstract, use of an expression cassette in an AAV vector to diminish the toxic gain of function in the mutant androgen receptor (AR), which plays a role in the pathogenesis of spinal and bulbar muscular atrophy (SBMA). Pourshafie reports miRNA treatment strategy to target human AR, using miR-298 by intravenous delivery with AAV serotype 9 which resulted in amelioration of disease phenotype in SBMA mice.
Pourshafie describes the recombinant AAV9 comprising an expression cassette comprising a sequence encoding the hairpin forming miRNA miR-298 which inhibits expression of the human androgen receptor (AR) The AAV is used for the treatment of spinal and bulbar muscular atrophy (SBMA) (Abstract; Pages 937-940).
Wilson, US20200056205A1, ‘341 Patent, (published 2/20/2020, Serial No. 16487690), at para 227, 451, teaches throughout the publication and abstract, treatment of spinal muscular atrophy (SMA) comprising a rAAV vector with an AAVhu68 capsid and at least one expression cassette that comprises a nucleic acid encoding a functional survival of motor neuron 1 (SMN 1) protein and e.g., Wilson at para 57, 74, 76, 77, 215, 219, 221, 228, 386, 397, 438 teaches AAV hu68 capsid for vectors used to treat spinal muscular atrophy.
Cortes 2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, teaches throughout the publication and abstract, and e.g., at p. 1, teaches that neurodegenerative disorders as including Spinal and Bulbar Muscular Atrophy (SBMA), and spinal muscular atrophy (SMA). Cortes, at p. 1-2, bridging paragraph, teaches that SBMA is a neuromuscular disorder, and has muscle weakness due to lower motor neuron degeneration in the spinal cord and brain stem. Cortes, at p. 2, para 3-6 to teaches that Androgen Receptor-poly glutamine in skeletal muscle plays a role in SBMA pathogenesis.
Cortes, at p. 2, para 7, states: “[o]ur results predict that muscle-directed therapies hold great promise as definitive treatments for SBMA motor neuron disease.” To support this, Cortex targeted skeletal muscle polyQ (glutamine) Androgen Receptor using antisense oligonucleotide technology to target the expanded AR mRNA for destruction. Cortes highlights skeletal muscle as an appealing target for SBMA therapy development.
Cortes, at p. 3, para 4-5, compares SBMA to other motor neuron diseases (MND), including spinal muscular atrophy (SMA). Cortes at para 5, states that muscle homeostasis directly contributes to neuronal survival and may play a key role in “related motor neuron disorders, such as ALS [amyotrophic lateral sclerosis] and SMA.” Cortex, at p. 3, para 5, teaches that SMA is a recessive neurodegenerative motor neuron disorder caused by mutations leading to reduced expression of survival motor neuron (SMN) protein. Cortes teaches that peripheral delivery of antisense oligonucleotides that promoter splicing of SMN2 is a highly effective therapy in mice.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson that binds a miRNA target site on human androgen receptor mRNA, as taught by Pourshafie.
One of ordinary skill in the art would have motivated to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson, ‘341 Patent, that binds a miRNA target site on human androgen receptor mRNA, as taught by Pourshafie, because Cortes teaches that SMN caused disease, as claimed by Wilson, ‘341 Patent, and SBMA, as instantly claimed, are both neuromuscular diseases that are treatable by delivery of antisense oligonucleotides to lower motor neurons. Thus, it would have been desirable for one of ordinary skill in the art, to have delivered miRNA targeting androgen receptor, to the same cell type targeted by the rAAVhu68 of Wilson, ‘341 Patent. Even though Wilson teaches delivery of a different nucleic acid sequence, the practitioner would have been motivated to deliver miRNA to the same target cell, in view of the teachings of Cortes.
2. Claims 1, 7, 8, 12, 13, 15, 16, 17, 18, 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5-15 of copending Wilson, Application Serial No. 18/485,352, (‘352 Application), in view of Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, Wilson, US20200056205A1, (‘205 PGP), and Cortes,2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4. This is a provisional nonstatutory double patenting rejection.
Wilson, ‘352 Application, claims 1-16 are drawn to an adeno-associated virus (AAV) comprising an AAVhu68 capsid having packaged therein a vector genome, the vector genome comprising an expression cassette comprising a nucleic acid sequence encoding at least one hairpin forming miRNA that comprises a targeting sequence that binds a miRNA target site on the mRNA of human androgen receptor, operably linked to regulatory sequences which direct expression of the nucleic acid sequence in the subject, wherein the miRNA inhibits expression of human androgen receptor, and wherein the vector genome comprises a) an AAV 5' ITR; b) a CMV enhancer; c) a CBA promoter; d) a chimeric intron; e) SEQ ID NO: 4 or a sequence having up to 10 substitutions; f) a woodchuck post-regulatory element (WPRE); g) a poly A; and h) an AAV 3' ITR. Reference Claim 1 claims reference SEQ ID NO: 4, which is the same as instant SEQ ID NO: 4.
Wilson, ‘352 Application does not claim AAV hu68 capsid for vectors.
Pourshafie, 2016, Molecular Therapy, vol. 24, number 5, pages 941 to 945, teaches throughout the publication and abstract, use of an expression cassette in an AAV vector to diminish the toxic gain of function in the mutant androgen receptor (AR), which plays a role in the pathogenesis of spinal and bulbar muscular atrophy (SBMA). Pourshafie reports miRNA treatment strategy to target human AR, using miR-298 by intravenous delivery with AAV serotype 9 which resulted in amelioration of disease phenotype in SBMA mice.
Pourshafie describes the recombinant AAV9 comprising an expression cassette comprising a sequence encoding the hairpin forming miRNA miR-298 which inhibits expression of the human androgen receptor (AR) The AAV is used for the treatment of spinal and bulbar muscular atrophy (SBMA) (Abstract; Pages 937-940).
Wilson, US20200056205A1, ‘341 Patent, (published 2/20/2020, Serial No. 16487690), at para 227, 451, teaches throughout the publication and abstract, treatment of spinal muscular atrophy (SMA) comprising a rAAV vector with an AAVhu68 capsid and at least one expression cassette that comprises a nucleic acid encoding a functional survival of motor neuron 1 (SMN 1) protein and e.g., Wilson at para 57, 74, 76, 77, 215, 219, 221, 228, 386, 397, 438 teaches AAV hu68 capsid for vectors used to treat spinal muscular atrophy.
Example 10, para 273 intrathecal administration in rhesus macaques; at e.g., para 7, 228, teach CB7 promoters in an AAV vector, as in instant claims 8, 30; at para 107, teaches WRPE, as in instant claims 7 and 29; at para [144]-[145], teaches suboccipital / intracisternal administration to the cisterna magna, as in instant claims 17, 18; teaches at para 121, 274, 285, 290 reference claim 22, teaches injection into the cisterna magna or lumbar puncture of 3.3x1011 GC/g brain as in instant claims 15-16
Cortes 2014 Rare Diseases vol 2, number 1, e962402, pages 1 to 4, teaches throughout the publication and abstract, and e.g., at p. 1, teaches that neurodegenerative disorders as including Spinal and Bulbar Muscular Atrophy (SBMA), and spinal muscular atrophy (SMA). Cortes, at p. 1-2, bridging paragraph, teaches that SBMA is a neuromuscular disorder, and has muscle weakness due to lower motor neuron degeneration in the spinal cord and brain stem. Cortes, at p. 2, para 3-6 to teaches that Androgen Receptor-poly glutamine in skeletal muscle plays a role in SBMA pathogenesis.
Cortes, at p. 2, para 7, states: “[o]ur results predict that muscle-directed therapies hold great promise as definitive treatments for SBMA motor neuron disease.” To support this, Cortex targeted skeletal muscle polyQ (glutamine) Androgen Receptor using antisense oligonucleotide technology to target the expanded AR mRNA for destruction. Cortes highlights skeletal muscle as an appealing target for SBMA therapy development.
Cortes, at p. 3, para 4-5, compares SBMA to other motor neuron diseases (MND), including spinal muscular atrophy (SMA). Cortes at para 5, states that muscle homeostasis directly contributes to neuronal survival and may play a key role in “related motor neuron disorders, such as ALS [amyotrophic lateral sclerosis] and SMA.” Cortex, at p. 3, para 5, teaches that SMA is a recessive neurodegenerative motor neuron disorder caused by mutations leading to reduced expression of survival motor neuron (SMN) protein. Cortes teaches that peripheral delivery of antisense oligonucleotides that promoter splicing of SMN2 is a highly effective therapy in mice.
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson that binds a miRNA target site on human androgen receptor mRNA, as taught by Wilson, ‘352 Application and Pourshafie.
One of ordinary skill in the art would have motivated to have combined nucleic acid comprised within an AAVhu68 vector, as taught by Wilson, ‘205 Patent, that binds a miRNA target site on human androgen receptor mRNA, as taught by Wilson, ‘352 Application and Pourshafie, because Cortes teaches that SMA, as disclosed by Wilson, ‘205 Patent, and SBMA, as instantly claimed, are both neuromuscular diseases that are treatable by delivery of antisense oligonucleotides to lower motor neurons. Thus, it would have been desirable to one of ordinary skill in the art, to have delivered miRNA targeting androgen receptor, to the same cell type targeted by the rAAVhu68 of Wilson, ‘205. Even though Wilson teaches delivery of a different nucleic acid sequence, the practitioner would have been motivated to deliver miRNA to the same target cell, in view of the teachings of Cortes.
Conclusion
1. Claims 1-8, 12-13, 15-18, and 25-30 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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, James (Doug) 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.
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.
MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631