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 2-1-24.
Claims 16-32 are pending in the instant application.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claim 32 is rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the expression of recombinant RPGR ORF15 protein in a high level in vitro, and for the rescue of RPGR knockout mice when injected with various recombinant AAV (rAAV) particles expressing the recombinant RPGR recombinant proteins following bilateral subretinal injection, does not reasonably enable methods for treating any neuromuscular or any musculoskeletal disease comprising the administration, via any route, of any oligomeric compound comprising one or more tricyclo-deoxyribonucleic acid (tc-DNA) nucleosides and a lipid moiety, and which oligomer binds a selected target to induce exon skipping in the human dystrophin gene and comprises a tc-DNA nucleoside of Formula (1).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
The following factors have been considered in determining that the specification does not enable the skilled artisan to make and/or use the invention over the broad scope claimed.
The breadth of the claims:
The claims are drawn to methods of treating a neuromuscular or musculoskeletal disease selected from Duchenne muscular dystrophy, familial dysautonomia, spinal muscular atrophy, ataxia telangiectasia, congenital disorder of glycosylation, fronto-temporal dementia, Parkinsonism linked to chromosome 17, Niemann-Pick disease type C, neurofibromatosis type 1, neurofibromatosis type 2, megalencephalic leukoencephalopathy with subcortical cysts type 1, Pelizaeus-Merzbacher disease, Pompe disease, myotonic dystrophy type 2 (DM2 or proximal myotonic myopathy), and myotonic dystrophy type 1 (DM1 or Steinert disease), comprising administering to a subject an oligomeric compound comprising one or more tricyclo-deoxyribonucleic acid (tc-DNA) nucleosides, and a lipid moiety selected from a fatty acid moiety, a fatty diacid moiety, a glycerolipid moiety, a glycerophospholipid moiety, a sphingolipid moiety, a phospholipid, an alkylphosphate moiety, and an alkylphosphonate moiety, which compound binds a selected target to induce exon skipping in the human dystrophin gene, and comprising a tc-DNA nucleoside of Formula (1).
Teachings in the specification:
The specification teaches the following:
[0019] FIGs. lA-B show that the codon-optimized RPGR polynucleotide sequence can express recombinant RPGR ORF15 protein in a high level in vitro.
FIG. lA shows a representative image of a western blot of the recombinant RPGR ORF15 proteins expressed from various codon-optimized RPGR ORF15 cDNA constructs in the HEK293T cells. The cells were transfected with the plasmids carrying a set of expression constructs listed in TABLE 2. The lysates of the transfected cells were analyzed by western blot. The RPGR ORF15 (ORF15) protein was identified using an anti-RPGR antibody. The glutamylated RPGR ORF15 protein (ORF15) glutamylation was identified using an anti-GT335 antibody. All constructs expressed a higher level of RPGR ORF15 proteins relative to that of the no plasmid control group. The recombinant RPGR ORF15 protein expressed were also glutamylated, suggesting that they had normal post-translational modification of a wild-type protein.
FIG. 1B shows a representative image of a western blot of the recombinant RPGR ORF15 proteins expressed from various codon-optimized RPGR ORF15 cDNA constructs in the HEK293T cells. The cells were transfected with recombinant AAV (rAAV) particles carrying another set of constructs listed in TABLE 2.
[0020] FIGs. 2A-C show that the recombinant RPGR ORF15 protein expressed from the codon- optimized constructs are functional in vivo in the eye.
FIG. 2A shows the scotopic A-wave defects of the RPGR knockout mice could be statistically significantly rescued when injected with various recombinant AAV (rAAV) particles expressing the recombinant RPGR recombinant proteins.
FIG. 2B shows the scotopic B-wave defect of the RPGR knockout mice could be statistically significantly rescued when injected with various recombinant AAV (rAAV) particles expressing the recombinant RPGR recombinant proteins.
FIG. 2C shows the photopic B-wave defect of the RPGR knockout mice could be rescued when injected with several recombinant AAV (rAAV) particles expressing the recombinant RPGR recombinant proteins.
In FIGs 2A-C, the mice were injected with the same number of viral particles containing the codon-optimized RPGR constructs. Wild type mice (C57) and RPGR knockout mice injected with a formulation buffer (Vehicle) were used as a positive and negative control, respectively. The injection was carried out using bilateral subretinal injection. The number of eyes injected are summarized in TABLE 3. The scotopic A-wave, scotopic B-wave, and photopic B-wave were measured by electroretinography (ERG) one-month post-injection.
[Emphases added][Citations omitted].
The examples provided in the instant specification, of the expression of recombinant RPGR ORF15 protein in a high level in vitro, and for the rescue of RPGR knockout mice when injected with various recombinant AAV (rAAV) particles expressing the recombinant RPGR recombinant proteins following bilateral subretinal injection, are not representative or correlative of the ability to treat any neuromuscular or any musculoskeletal disease in a subject as instantly claimed.
In light of the teachings in the art and the specification, one skilled in the art would not accept on its face the examples provided in the instant disclosure as being correlative or representative of the ability to provide treatment effects in a subject. Since the specification fails to provide the requisite guidance for the treatment of any neuromuscular or musculoskeletal disease in any subject, and since determination of the factors required for accomplishing this in any subject is highly unpredictable, it would require undue experimentation to practice the invention over the broad scope claimed.
For these reasons, the instant rejection for lacking enablement over the full scope claimed is proper.
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 16-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,872,239. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to oligomeric compounds comprising one or more tricyclo-deoxyribonucleic acid (tc-DNA) nucleosides, and a lipid moiety selected from a fatty acid moiety, a fatty diacid moiety, a glycerolipid moiety, a glycerophospholipid moiety, a sphingolipid moiety, a phospholipid, an alkylphosphate moiety, and an alkylphosphonate moiety, which compound binds a selected target to induce exon skipping in the human dystrophin gene, and comprises a tc-DNA nucleoside of Formula (1).
Claims 1-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 11,118,179 in view of Wilton et al (US 2018/0104273).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to oligomeric compounds comprising one or more tricyclo deoxyribonucleic acid nucleosides and 2’ modified RNA nucleosides.
Wilton et al (US 2018/0104273) teach oligomeric compounds comprising tricyclo deoxyribonucleic acid nucleosides for exon skipping and further comprising lipids and tricyclic moieties (see esp. paragraphs 0061, 0085 and 0125). It would have been obvious to design and optimize the oligonucleotides with the addition of lipid moieties for enhancing cellular uptake of the oligonucleotides.
Claims 1-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,059,947 in view of Wilton et al (US 2018/0104273.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to methods of treatment comprising the administration of oligomeric compounds comprising one or more tricyclo deoxyribonucleic acid nucleosides and phosphorothioate internucleotide linkages.
Wilton et al (US 2018/0104273) teach oligomeric compounds comprising tricyclo deoxyribonucleic acid nucleosides for exon skipping and further comprising lipids and tricyclic moieties (see esp. paragraphs 0061, 0085 and 0125). It would have been obvious to design and optimize the oligonucleotides with the addition of lipid moieties for enhancing cellular uptake of the oligonucleotides.
Claims 1-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,104,903 in view of Wilton et al (US 2018/0104273.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to oligomeric compounds comprising one or more tricyclo deoxyribonucleic acid nucleosides and phosphorothioate internucleotide linkages.
Wilton et al (US 2018/0104273) teach oligomeric compounds comprising tricyclo deoxyribonucleic acid nucleosides for exon skipping and further comprising lipids and tricyclic moieties (see esp. paragraphs 0061, 0085 and 0125). It would have been obvious to design and optimize the oligonucleotides with the addition of lipid moieties for enhancing cellular uptake of the oligonucleotides.
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
7-8-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
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