DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 6-22-23.
Claims 1-16 are pending in the instant application.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-5, 7, 9, 12 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Christou et al (Nucleic Acid Therapeutics, Vol. 30, No. 2, pages 80-93 (2020)).
Christou et al (Nucleic Acid Therapeutics, Vol. 30, No. 2, pages 80-93 (2020)) teach antisense comprising CAG trinucleotides repeated between 5-13 times, which antisense further comprises a 2-MOE and/or one or more modified nucleotide analogs bridged between the 2’-position and the 4’ position of the ribose optionally comprising an ENA, LNA and/or cEt, and optionally further comprising at least one phosphorothioate internucleotide linkage (see esp. the abstract on page 80, text on page 81, bridging para pages 81-82, Table 1 on page 82, Fig. 1 on page 85).
Claim(s) 1-5, 7, 9, 12 and 13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gonzalez-Barriga (Molecular Therapy-Nucleic Acids, Vol. 2, e81, pages 1-12 (2013)).
Gonzalez-Barriga (Molecular Therapy-Nucleic Acids, Vol. 2, e81, pages 1-12 (2013)) teach pharmaceutical compositions comprising antisense comprising a minimal length of 5 tracts of CAG repeats, 2’-O-methyl modified sugars, phosphorothioate internucleotide linkages, and 2’-O,4’-C-ethylene bridged nucleic acid (ENA) modified oligonucleotides, which compositions provided significant reduction of expanded DM protein kinase (DMPK) mRNAs (see esp. the abstract on page 1, Figure 1 on page 3).
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.
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.
Claims 1-16 is/are rejected under 35 U.S.C. 103 as being obvious over Christou et al (Nucleic Acid Therapeutics, Vol. 30, No. 2, pages 80-93 (2020)) and Gonzalez-Barriga (Molecular Therapy-Nucleic Acids, Vol. 2, e81, pages 1-12 (2013)), the combination in view of Morita et al (Bioorganic and Medicinal Chem. Letters, Vol. 12, pages 73-76 (2002)), Gagnon et al (Biochem., Vol. 49, pages 10166-10178 (2010)), Lee et al (Genes, Vol. 8, 67, pages 1-11 (2010)) and Mulders et al (PNAS, Vol. 106, No. 33, pages 13915-13920 (2009)), the combination further in view of Littman et al (AU 2014/310360).
The claims are drawn to pharmaceutical compositions comprising oligonucleotides having a base sequence of a repeated sequence in which cytosine-adenine-guanine tri-nucleotides are repeated 5 to 13 times from the 5' end to the 3' end, or optionally comprising an oligonucleotide consisting of a base sequence of any of SEQ ID NOs: 1 to 9, or optionally comprising an oligonucleotide consisting of a base sequence consisting of adenine-guanine, a base sequence of any of SEQ ID NOs: 1 to 9, and cytosine, from the 5' end to the 3' end, or an oligonucleotide consisting of a base sequence consisting of guanine, a base sequence of any of SEQ ID NOs: 1 to 9, and cytosine-adenine, from the 5' end to the 3' end, and at least two types of RNase H inactive nucleotide analogs optionally comprising a 2'-OMe-nucleotide analog and/or a MOE-nucleotide analog, or comprising a nucleotide analog bridged between the 2'-position and the 4'-position of ribose optionally comprising β-D-oxy-L-LNA, β-D-ENA and/or R type cEt, which nucleotide analogs modified at the 2'-position of ribose all have the same modified sugar or at least two different modified sugars, or wherein the modified nucleotide analogs bridged between the 2' -position and the 4'-position of ribose all have the same modified sugar, or at least two different modified sugars, and optionally further comprising a modified internucleotide linkage selected from the group consisting of phosphorothioate, phosphorodithioate, and boranophosphate, which compositions optionally further comprising a cellular membrane permeation carrier and/or a carrier for intranuclear delivery, or parenteral, transdermal, intraocular, intra-lens, gastrointestinal tract, intramucosal, gastrointestinal tract submucosal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, intracranial, intrathecal administration, and used for treating any of the symptoms of myotonic dystrophy type 1 disease.
Christou et al (Nucleic Acid Therapeutics, Vol. 30, No. 2, pages 80-93 (2020)) (see IDS filed 9-18-23) teach antisense comprising CAG trinucleotides repeated between 5-13 times, which antisense further comprises a 2-MOE and/or one or more modified nucleotide analogs bridged between the 2’-position and the 4’ position of the ribose optionally comprising an ENA, LNA and/or cEt, and optionally further comprising at least one phosphorothioate internucleotide linkage (see esp. the abstract on page 80, text on page 81, bridging para pages 81-82, Table 1 on page 82, Fig. 1 on page 85).
Gonzalez-Barriga (Molecular Therapy-Nucleic Acids, Vol. 2, e81, pages 1-12 (2013)) (see IDS filed 9-18-23) teach pharmaceutical compositions comprising antisense comprising a minimal length of 5 tracts of CAG repeats, 2’-O-methyl modified sugars, phosphorothioate internucleotide linkages, and 2’-O,4’-C-ethylene bridged nucleic acid (ENA) modified oligonucleotides, which compositions provided significant reduction of expanded DM protein kinase (DMPK) mRNAs (see esp. the abstract on page 1, Figure 1 on page 3).
Morita et al (Bioorganic and Medicinal Chem. Letters, Vol. 12, pages 73-76 (2002)) (see IDS filed 9-18-23) teach 2’-O, 4’-C-ethylene nucleic acids (ENA), producing highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drugs. Morita synthesized 2’-O, 4’-C-bridged 2’deoxynucleotisides and compared them to BNA/LNA bridged nucleosides. Morita compared ENA with 2’-O,4’-C-methylene for their affinity for target sequences and for their stability against nucleases (see esp. the abstract and introduction on page 73, Table 1 on page 74).
Gagnon et al (Biochem, Vol. 49, pages 10166-10178 (2010)) (see IDS filed 9-18-23) teach antisense oligonucleotides targeting the expanded CAG repeat region of mutant mRNA for achieving allele selective inhibition. The oligonucleotides targeting the CAG repeat region were modified with bridged nucleic acids (BNA) including LNAs comprising a bridge composed of a methylene between the 2’-O and the 4’C positions. LNA was found to enhance base stacking and to increase hybridization and thermal stability. Three BNA modifications were tested, 2’-O,4’-C-ethylene bridged nucleic acids (ENA), 2’-4’-constrained ethyl nucleic acid (S-cEt ) and 2’-4’-carbocyclic LNA. (see esp. bridging para page text on pages 10169, 10170-10171, Fig. 2 on page 10170).
Lee et al (Genes, Vol. 8, 67, pages 1-11 (2010)) (see IDS filed 9-18-23) teach exon skipping using 2’-O-methyl RNA/2’-O,4’-C-ethylene nucleic acid (ENA) chimera antisense oligonucleotides in vitro and in vivo (see esp. the abstract on page 1, text on page 2,Fig. 1 and text on page 3, Fig. 4 on page 6).
Mulders et al (PNAS, Vol. 106, No. 33, pages 13915-13920 (2009)) (see IDS filed 9-18-23) teach antisense oligonucleotide, (CAG)7, targeting CUG and causing 90% reduction in CUG500 mRNA, which antisense comprised a 2’-MOE and phosphorothioate internucleotide linkage (see esp. abstract on page 13915, text on pages 13916-13917).
The primary references do not teach compositions for intranuclear delivery or for the various routes of parenteral administration.
Littman et al (AU 2014/310360) teach pharmaceutical compositions for parenteral and intranuclear delivery (see esp. para 00118 and 00257).
It would have been obvious to design and optimize the instantly claimed compositions because the prior art routinely taught pharmaceutical compositions for treating myotonic dystrophy type 1 disease and comprising CAG repeat antisense and further comprising 2’-O-methyl, 2’-O-MOE and 2’-O,4’-C-ethylene bridged nucleic acids (ENA). One would have been motivated to optimize the positions of modifications as instantly claimed because the chemistry for modifying the sugar residues and the means of testing the affinities and stability of variously modified CAG repeat antisense involved routine experimentation, as illustrated in the teachings of Christou, Gonzalez-Barriga, Morita, Gagnon, Lee and Mulders.
For these and the aforementioned reasons, the instant invention would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
5-12-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
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