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 .
Election/Restrictions
Claims 1, 2, 3, 6, 10, 11, 14, 16-18, 22, 26, 27, 54, 58-60, 62, 65, and 68 are pending. Applicant’s election without traverse of group II (claims 2, 3, 6, 10, 11, 14, 16-18, 22, 26, 27, 54, 58-60, 62, 65, and 68) in the remarks filed 10/22/25 is acknowledged. Applicant elects the species 1) The chemical compound of claim 54 as the small molecule that increases SMN function; and 2) For order of administration, Applicant elects the small molecule and ASO administered sequentially.
Claims 1, 10, 11, 14, 16-18, 22, 26, 62, and 65 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Examination on the merits commences on claims 2-3, 6, 27, 54, 58-60, and 68.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO’s electronic filing system (see Section I.1 of the Legal Framework for EFS-Web or Patent Center (https://www.uspto.gov/patents-application- process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via EFS-Web or Patent Center as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via EFS-Web or Patent Center as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Specifically, the incorporation by reference statement in the substitute specification filed 2/14/22 is missing and lacks file description of B115270095US01-SEQ-LJG.txt sequence file of 7216 bytes.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 2, 3, 27, and 68 recite, “a small molecule that increases SMN function.” Examiner is interpreting “SMN” as “SMN protein”, however it is recommended that “protein” is added after “SMN” for enhanced clarity.
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.
Claim(s) 2, 6, 58, 59, and 68 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.).
Examiner is interpreting “SMN” recited in claims 2, 3, 27, and 68 to mean the SMN protein.
Regarding claim 2, in a method of treating SMA (Spinal Muscular Atrophy), Bennett teaches an antisense oligonucleotide ASO compound which increases SMN1 protein [0027 and 0128] and which can be accompanied in co-therapy by additional small molecules drugs such as Valproic Acid [0013] where the composition co-therapy ameliorates at least one symptom of SMA in the subject [0024]. Regarding the ASO, Bennett teaches methods of increasing inclusion of exon 7 of SMN2 mRNA in a motoneuron in a subject comprising administering to the subject an antisense compound comprising an antisense oligonucleotide complementary to intron 7 of a nucleic acid encoding human SMN2 and thereby increasing inclusion of exon 7 of SMN2 mRNA in the motoneuron in the subject [0016]. Regarding a small molecule, Bennett teaches the methods comprise co-administration of the antisense compound and at least one other therapy wherein the other therapy includes the small molecules valproic acid and riluzole [0013]. Bennet further teaches the subject has SMA. [0018].
Bennett is silent as to the specific action of valproic acid. However, Sumner teaches Valproic acid increases SMN levels in SMA patient cells (abstract and title).
Regarding claim 6, Bennett teaches use of known animal mouse models in the ASO method of treating SMA including Smn−/− mouse models with the SMA phenotype (such as example 7) for administering the ASO SEQ ID NO: 1 in a Smn−/− SMN Transgenic homozygous (-) for the SMN, i.e. wherein the subject has a deletion or mutation in each survival motor neuron 1 (SMN1) allele [0271]. Bennett teaches SMA mice treated with SEQ ID NO: 1 ASO produced a significant increase in median survival as shown in FIG. 7 [0275].
Regarding claim 58, as described above, Bennett teaches methods of increasing inclusion of exon 7 of SMN2 mRNA in a motoneuron in a subject comprising administering to the subject an antisense compound comprising an antisense oligonucleotide complementary to intron 7 of a nucleic acid encoding human SMN2 and thereby increasing inclusion of exon 7 of SMN2 mRNA in the motoneuron in the subject [0016].
Regarding claim 59, Bennett teaches the ASO has a sequence of SEQ ID NO: 1 which has 100% identity to instant SEQ ID NO: 1 (0027).
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Regarding claim 68, Bennett teaches the methods comprise co-administration of the antisense compound and at least one other therapy and wherein the antisense compound is administered after administration (i.e. sequentially) of the at least one other therapy and wherein the other therapy includes the small molecule agent [0013].
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(s) 2, 3, is/are rejected under 35 U.S.C. 103 as being unpatentable over Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.) as applied to claim 2, in view of Wilson (Wilson, J., WO2018160585A2).
The teachings of Bennett and Sumner applied above to claim 2 are incorporated here.
Regarding claim 3, Bennet does not teach in the co-therapy treatment method of SMA including a recombinant nucleic acid that encodes the SMN1 protein is in the form of a recombinant adeno associated virus (rAAV).
However, in an SMA treatment method, Wilson teaches a recombinant nucleic acid that encodes the survival of motor neuron 1 (SMN1) protein, wherein the recombinant nucleic acid that encodes the SMN1 protein is in the form of a recombinant adeno associated virus (rAAV)(pg 2 line 24). Wilson teaches the AAV/SMN1 protein treatment methods for SMA combined with other therapies for treatment of SMA or the symptoms thereof such as the ASO nusinersen, which is an SMN2 pre-messenger ribonucleic acid (mRNA)-targeting antisense oligonucleotide (ASO) (pg 36 line 23).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified the SMA co-therapy treatment method of Bennett which includes an ASO that increases SMN2 mRNA along with a small molecule that increases SMN function to also include the recombinant AAV/SMN1 protein therapy of Wilson in the treatment of SMA. It would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that the recombinant AAV/SMN1 protein therapy of Wilson could be effectively applied within Bennett’s co-therapy compositions because Wilson already teaches effective co-therapy for SMA using the recombinant AAV/SMN1 protein therapy plus an ASO. It would have been predictable that a co-therapy method including the three compositions (ASO, small molecule, and AAV/SMN1) would effectively treat SMA. Therefore, the skilled artisan would be motivated to modify Bennett’s co-therapy method of treating SMA to also include Wilson’s recombinant AAV/SMN1 protein therapy from Wilson’s co-therapy treatment method to enhance the combination composition’s effectiveness in treating a subject with SMA.
Claim(s) 2, 27, 54, is/are rejected under 35 U.S.C. 103 as being unpatentable over Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.) as applied to claim 2, in view of Poirier (Poirier, Agnès, et al. "Risdiplam distributes and increases SMN protein in both the central nervous system and peripheral organs." Pharmacology research & perspectives 6.6 (2018): e00447.), as evidenced by Risdiplam (Risdiplam formula, https://www.pharmaffiliates.com/en/1825352-65-5-risdiplam-api-pa181410000.html#:~:text=CAS%20No%20:%201825352%2D65%2D5%20%7C%20Product%20Name,%7C%20Chemical%20Name%20:%20Risdiplam%20%7C%20Pharmaffiliates, retrieved 11/5/2025, printed as page 1/1 to 1/1).
The teachings of Bennett and Sumner applied above to claim 2 are incorporated here.
Regarding claims 27 and 54, Bennet does not teach in the co-therapy treatment method of SMA wherein the small molecule that increases SMN function is a pyridazine of the formula:
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However, Risdiplam teaches the small molecule risdiplam has the molecular formula which is identical to the claimed formula of claim 27 and 54 (page 1):
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Poirier teaches the small molecule risdiplam increases SMN protein function (abstract). Poirier teaches both the ASO oligonucleotide nusinersen (Spinraza) and risdiplam (having different molecular targets) both act by promoting exon 7 inclusion in SMN2 mRNA, leading to increased production of functional SMN protein.
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified the SMA co-therapy treatment method of Bennett which includes an ASO that increases SMN2 mRNA along with a small molecule valproic acid which increases SMN function to include in place of valproic acid the small molecule risdiplam (with formula of claim 27 and 54). It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation that the small molecule risdiplam (with formula of claim 27 and 54, as evidenced by Risdiplam) would effectively treat SMA because Poirier teaches the small molecule risdiplam increases SMN protein function in a treatment method of SMA. It would have been predictable that a co-therapy method including the ASO and risdiplam would effectively treat SMA because Bennet already taught co-therapy of an ASO with a small molecule that increases SMN function as effective for treating subjects with SMA. Therefore, the skilled artisan would be motivated to modify Bennett’s co-therapy method of treating SMA to substitute risdiplam for valproic acid in the co-therapy treatment method to enhance the combination composition’s effectiveness in treating a subject with SMA.
Claim(s) 2 and 60 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.) as applied to claim 2, in further view Goodkey (Goodkey, Kara, et al. "Nusinersen in the treatment of spinal muscular atrophy." Exon skipping and inclusion therapies: Methods and protocols (2018): 69-76.).
The teachings of Bennett and Sumner applied above to claim 2 are incorporated here.
Although, Bennett teachings the reference SEQ ID NO: 1 which is a 100% sequence match for instant SEQ ID NO: 1, Bennett does not teach SEQ ID NO: 1 is modified such that the ASO is nusinersen. However, Goodkey teaches Nusinersen is engineered as an 18-base pair sequence of TCACTTTCATAATGCTGG (100% identity to instant SEQ ID NO: 1 and reference SEQ ID NO: 1) is designed as an intronic splicing silencer oligonucleotide that binds and disrupts the function of ISS-N1 in intron 7 of the SMN2 gene allowing for functional mRNA reading frame and protein production (pg 71 para 2). Goodkey further teaches Nusinersen is a 2′-O-methoxyethyl (2′MOE) modified AO whose structure differs from traditional nucleotides in two locations with the addition of a methoxy group at the 2′-hydroxyl position and a phosphorothioate backbone modification (as shown in Fig. 1) where the phosphorothioate backbone increases the stability of the structure, making it resistant to nuclease activity and therefore increasing the RNA hybridization affinity (pg 71 para 2).
It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have employed nusinersen as the ASO in Bennett’s co-therapy method of treating SMA. It would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. The skilled artisan would have had a reasonable expectation of that nusinersen could effectively target and increase SMN2 mRNA because Goodkey teaches the 2′-O-methoxyethyl (2′MOE) modified ASO nusinersen is effective at targeting and increasing SMN2 protein production due to the ASOs enhanced resistance to nuclease activity. The skilled artisan would therefore be motivated to include nusinersen as the ASO in Bennett’s method of targeting and increasing SMN2 mRNA for enhanced treatment of SMA.
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.
Claim 2-3, 6, 58-60, and 68 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-3 of issued patent number US9717750B2, in view of Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.), claim 60 as evidenced by Goodkey (Goodkey, Kara, et al. "Nusinersen in the treatment of spinal muscular atrophy." Exon skipping and inclusion therapies: Methods and protocols (2018): 69-76.), as applied to claims 2 and 3, and in view of Wilson (Wilson, J., WO2018160585A2), as applied to claims 2 and 3.
Examiner notes that the reference SEQ ID NO: 1 has 100% identity to instant SEQ ID NO: 1 and functions as an ASO that increases SMN2 mRNA, as described in the 103 rejection above.
The reference teachings applied above to claims 2-3, 6, 58-60, and 68 are incorporated here.
The reference claims do not teach the method of treating SMA wherein the method includes a small molecule that increases SMN function as well as includes a recombinant nucleic acid that encodes the survival of motor neuron 1 (SMN1) protein, wherein the recombinant nucleic acid that encodes the SMN1 protein is in the form of a recombinant adeno associated virus (rAAV). However, It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified the reference claims to arrive at the claimed invention, given the obviousness rationale applied above for claims 2-3, 6, 27, 54, 58-60, and 68.
Regarding instant claims 1-4, 6, 7, 10, 13 and 15-17, the reference claims teach:
1. A method comprising administering by a bolus injection into the intrathecal space of a human subject having type II spinal muscular atrophy (SMA) an antisense compound comprising an antisense oligonucleotide consisting of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence SEQ ID NO: 1, wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, wherein each nucleoside of the oligonucleotide is a 2′-MOE nucleoside, and wherein the administering of the antisense compound ameliorates at least one symptom of SMA in the human subject.
2. The method of claim 1, wherein the antisense compound is administered at a dose from 0.01 to 10 milligrams of antisense compound per kilogram of body weight of the subject.
3. The method of claim 1, wherein inclusion of exon 7 of SMN2 mRNA in a motoneuron in the subject is increased.
Claim 2-3, 6, 58-60, and 68 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-17 of co-pending Application No.18/283,925, in view of Bennett (Bennett, C., US20120190728A1), as evidenced by Sumner (Sumner, Charlotte J., et al. "Valproic acid increases SMN levels in spinal muscular atrophy patient cells." Annals of Neurology: Official Journal of the American Neurological Association and the Child Neurology Society 54.5 (2003): 647-654.), claim 60 as evidenced by Goodkey (Goodkey, Kara, et al. "Nusinersen in the treatment of spinal muscular atrophy." Exon skipping and inclusion therapies: Methods and protocols (2018): 69-76.), as applied to claims 2 and 3, and in view of Wilson (Wilson, J., WO2018160585A2), as applied to claims 2 and 3.
Examiner notes that the reference ASO SEQ ID NO: 1 is a 100% match to instant SEQ ID NO: 1 and functions as an ASO that increases SMN2 mRNA, as described in the 103 rejection above.
The reference teachings applied above to claims 2-3, 6, 58-60, and 68 are incorporated here.
The reference claims do not teach the method of treating SMA wherein the method includes an ASO co-therapy small molecule that increases SMN function or includes a recombinant nucleic acid that encodes the survival of motor neuron 1 (SMN1) protein, wherein the recombinant nucleic acid that encodes the SMN1 protein is in the form of a recombinant adeno associated virus (rAAV). However, It would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have modified the reference claims to arrive at the claimed invention, given the obviousness rationale applied above for claims 2-3, 6, 58-60, and 68.
Regarding instant claims 1-4, 6, 7, 10, 13 and 15-17, the reference claims teach:
1. A central nervous system (CNS) delivery composition comprising a polymeric nanocarrier and an antisense oligonucleotide, wherein the antisense oligonucleotide is encapsulated within the polymeric nanocarrier, and wherein the antisense oligonucleotide is directly pre-complexed with a cationic molecule.
9. The CNS delivery composition of any one of claims 1 to 8, further comprising a therapeutic agent.
10. The CNS delivery composition of claim 9, wherein the therapeutic agent is selected from the group consisting of a small molecule, a cDNA, an mRNA, an siRNA, an miRNA, an aptamer, and a ribozyme.
11. The CNS delivery composition of any one of claims 1 to 10, formulated for intrathecal delivery to a human subject.
12. The CNS delivery composition of any one of claims 1 to 11, wherein the antisense oligonucleotide is a gapmer or a splice switching antisense oligonucleotide.
13. The CNS delivery composition of any one of claims 1 to 11, wherein the antisense oligonucleotide consists of a nucleic sequence set forth in SEQ ID NO:1.
14. The CNS delivery composition of any one of claims 1 to 11, wherein the antisense oligonucleotide consists of 18 linked nucleosides, wherein the oligonucleotide has a nucleobase sequence consisting of the nucleobase sequence .sup.MeU.sup.MeCA.sup.MeC.sup.MeU.sup.MeU.sup.MeU.sup.MeCA.sup.MeUAA.sup.MeUG.sup.MeC.sup.MeUGG (SEQ ID NO:1), wherein each internucleoside linkage of the oligonucleotide is a phosphorothioate linkage, each nucleoside of the oligonucleotide is a 2′-methoxyethyl nucleoside, .sup.MeU is a 5-methyl-uracil, and .sup.MeC is a 5-methylcytosine.
15. A method of treating a CNS disorder in a human subject in need thereof, the method comprising administering to the human subject a therapeutically effective amount of the CNS delivery composition of any one of claims 1 to 14.
16. The method of claim 15, wherein the administering is by intrathecal injection.
17. A method of treating spinal muscular atrophy (SMA), increasing inclusion of exon 7 in SMN2 messenger ribonucleic acid (mRNA) transcripts in a human subject having loss of both functional copies of the SMN1 gene, or increasing exon 7 inclusion in SMN2 messenger ribonucleic acid (mRNA) transcripts in a human subject having mutations in the SMN1 gene that lead to functional SMN protein deficiency, in a human subject in need thereof, the method comprising administering by an injection into the intrathecal space of the human subject the CNS delivery composition of claim 14.
This is a provisional rejection because the copending claims have not yet been patented.
Conclusion
Claims 2-3, 6, 27, 54, 58-60, and 68 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN CHARLES MCKILLOP whose telephone number is (703)756-1089. The examiner can normally be reached Mon-Fri 8:30-5:30.
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/JOHN CHARLES MCKILLOP/Examiner, Art Unit 1637
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637