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
Applicant’s election without traverse of Group III of invention (claim 4) in the reply filed on Feb 20, 2026 is acknowledged. The remaining nonelected Groups I, II, IV, and V of invention (claims 1-3, and 5-6) are cancelled. Accordingly, claims 4 and 7-29 are examined herein.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 14/741,071, filed on June 16, 2015.
Drawings
The drawings are objected to because 37 CFR 1.84 (u)(1) states “View numbers must be preceded by the abbreviation "FIG."" In the current case, the view numbers for Figures 1 to 8 are preceded by the word "Figure" instead of the abbreviation "FIG.".
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because it contains an embedded hyperlink ([00287], [00307]) and/or other form of browser-executable code. 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 Objections
Claim 4 is objected to because of the following informalities:
Claim 4 recites “wherein the polynucleic acid polymer hybridizes to a target region of the retained intron, wherein the target region of the retained intron to which the polynucleic acid polymer hybridizes” which repeats the same limitation and is redundant. For example, this claim can be made more concise by amending to “wherein the polynucleic acid polymer hybridizes to a target region of the retained intron, and wherein the target region (a) is an internal region of the retained intron, (b) does not comprise a 5’ splice site of the retained intron, and (c) does not comprise a 3’ splice site of the retained intron”.
Appropriate correction is required.
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.
Claims 20 and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “sub-normal” in claim 20 is a relative term which renders the claim indefinite. The term “sub-normal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what is considered as a “normal” production of the functional form of the protein to then consider what a “sub-normal” production is. It is unclear whether a normal production refers to mRNA or polypeptide expression of the functional form of the protein in a subject with or without autosomal recessive disorder. It is unclear which specific level of expression is considered as a normal production and below normal. For example, it is unclear whether a sub-normal production refers to be an expression level that is 10% or more, or less than a normal production because there is no standard for ascertaining the requisite degree.
Claim 25 recites the limitation “the incidence of intron retention” in line 2. There is insufficient antecedent basis for this limitation in the claim.
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 14 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 14 recites structural limitations of the functional form of the protein. The method of claim 4, the claim from which claim 14 depends also recites same subject matter in lines 7-10. A dependent claim must further limit the subject matter of the claim from which it depends and includes all of the limitations of that claim. Accordingly, claim 14 is of improper dependent form because it failed to further limit the subject matter of the claim 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.
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.
Claims 4 and 8-29 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 4 is directed to treating an autosomal recessive disorder that is characterized by impaired production of a functional form of a protein in a subject. Further, claim 4 is directed treatment by administering a polynucleic acid polymer that hybridizes to an internal region of a retained intron in a partially processed mRNA transcript and induces an increase in splicing out of the retained intron. The breadth of the claims is drawn to possession of a genus of autosomal recessive disorder that has a retained intro in partially processed mRNA transcripts.
The specification discloses “exemplary autosomal recessive disorder can include albinism, Medium-chain acyl-CoA dehydrogenase deficiency, cystic fibrosis, sickle-cell disease, Tay-Sachs disease, Niemann-Pick disease, spinal muscular atrophy, or Roberts syndrome” ([00148]) without providing further guidance regarding structural (e.g., sequences of retained intron) and or functional features (e.g., small nuclear ribonucleoprotein binding motifs) common to this claimed genus. Further, the specification is limited to one working example (type 1 diabetes) where splice-switching-oligonucleotides successfully induced decrease of intron 1 retention in proinsulin gene (INS) transcripts (Fig. 4 and [00290]). Accordingly, the specification fails to provide representative species across the breath of the claimed genus.
The state of the art teaches that autosomal recessive disorders arise from diverse and distinct mechanisms, many of which are not associated with a retained intron and would not reasonably be expected to be treatable by inducing splicing out of the retained intron. Havens et al (Targeting RNA splicing for disease therapy; WIREs RNA, 2013, 4:247-266) teaches that “many human genetic diseases are caused by mutations that cause splicing defects” and “splicing can be manipulated with tools including antisense oligonucleotides, modified small nuclear RNAs, trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms” (abstract and figures 1 to 3). Havens further teaches splicing-based therapeutic approaches for genetic diseases caused by splice site mutations, cryptic splice sites, regulatory sequence mutations, deregulated alternative splicing, knockdown of detrimental gene expression, and RNA reframing (Table 1). However, there is no reported genetic disease related to a retained intron in partially processed mRNA transcripts. The representative genetic diseases discussed by Havens demonstrates that autosomal recessive disorders are not uniformly characterized by impaired production of a functional form of a protein, specifically many do not involve retained introns and/or would be amenable to treatment by induced-splicing of retained intron.
Further, dependent claims 8-29 are also rejected for depending from a rejected claim and failing to remedy the lack of written description therein.
In contrast, dependent claim 7 reciting specific species of the claimed genus is adequately described because the state of the art provides guidance on complete structure and correlation between structure and function of these species.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and the state of prior art including the knowledge of autosomal recessive disorders with retained introns, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of autosomal recessive disorder that can be treated by administering a polynucleic acid polymer that hybridizes to an internal region of a retained intron in partially processed mRNA transcripts.
Claims 4 and 7-29 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the specification coupled with information known in the art without undue experimentation (United States v. Telectronics., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based upon a single factor but rather is a conclusion reached by weighing many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988), and the most relevant factors are indicated below:
Nature of the Invention and Breadth of the Claims
Claim 4 is directed to a method of treating any autosomal recessive disorder comprising correction of intron retention in partially processed mRNA transcripts by administering a polynucleic acid polymer that hybridizes to a retained intron and induces splicing out of the retained intron. Thus, the breadth of claim 4 is drawn to a genus of autosomal recessive disorder that has a retained intro in partially processed mRNA transcripts. In contrast, claim 7, which depends on claim 4, is drawn to selected species including cystic fibrosis, spinal muscular atrophy and six additional disorders.
Guidance of the Specification
The specification discloses “exemplary autosomal recessive disorder can include albinism, Medium-chain acyl-CoA dehydrogenase deficiency, cystic fibrosis, sickle-cell disease, Tay-Sachs disease, Niemann-Pick disease, spinal muscular atrophy, or Roberts syndrome” ([00148]) without providing further guidance regarding structural (e.g., sequences of retained intron) and or functional features (e.g., small nuclear ribonucleoprotein binding motifs) common to this claimed genus. Further, the specification is limited to one working example (type 1 diabetes) where splice-switching-oligonucleotides successfully induced decrease of intron 1 retention in proinsulin gene (INS) transcripts in cells (Fig. 4 and [00290]). However, the specification discloses diabetes as an exemplary hereditary disease ([00143]), not an exemplary autosomal recessive disorder. Accordingly, the specification fails to provide any working examples of the claimed method, as well as any guidance to make and/or use the claimed method.
State of the Art
At the time of filling, the state of the art teaches that autosomal recessive disorders arise from diverse and distinct mechanisms, many of which are not associated with a retained intron and would not reasonably be expected to be treatable by inducing splicing out of the retained intron. Havens et al (Targeting RNA splicing for disease therapy; WIREs RNA, 2013, 4:247-266) teaches that “many human genetic diseases are caused by mutations that cause splicing defects” and “splicing can be manipulated with tools including antisense oligonucleotides, modified small nuclear RNAs, trans-splicing, and small molecule compounds, all of which have been used to increase specific alternatively spliced isoforms” (abstract and figures 1 to 3). Havens further teaches splicing-based therapeutic approaches for genetic diseases caused by splice site mutations, cryptic splice sites, regulatory sequence mutations, deregulated alternative splicing, knockdown of detrimental gene expression, and RNA reframing (Table 1). However, there is no reported genetic disease related to a retained intron in partially processed mRNA transcripts. The representative genetic diseases discussed by Havens demonstrates that autosomal recessive disorders are not uniformly characterized by impaired production of a functional form of a protein, specifically many do not involve retained introns and/or would be amenable to treatment by induced-splicing of retained intron.
In addition, the state of the art demonstrates the treatment for spinial muscular atrophy, one of the species recited in claim 7, does not involve targeting a retained intron. Hua et al (Antisense Masking of an hnRNO A1/A2 Intronic Splicing Silencer Corrects SMN2 Splicing in Transgenic Mic; The American Journal of Human Genetics; 2008, 82:834-848) discloses modified antisense oligonucleotides targeting intronic splicing silencers hnRNPA1 or hnRNPA2 motifs in intron 7 of SMN2 gene in the treatment of spinal muscular atrophy, which involves promoting inclusion of exon 7 skipping rather than removal of a retained intron (pg. 835, right-column, second paragraph).
In addition, Applicant’s own work, Kralovicova et al (Optimal antisense target reducing INS intron 1 retention is adjacent to a parallel G quadruplex; NAR, 2014, 42 (12): 8161-8173; Published date: June 17, 2014) discloses “the first use of antisense technology to reduce retention of the entire intron in mature transcripts and to modify the haplotype-dependent proinsulin gene (INS) expression using SSOs” (splice-switching oligonucleotides) (pg. 8170, left-column, second paragraph). The teachings of Kralovicova et al indicate that claimed method can be used to splice out a retained intron in partially processed mRNA transcripts of INS that is a known modifier for type-1 diabetes, which is not an exemplary autosomal recessive disorder defined in the specification ([00148]). The teachings of Kralovicova also demonstrates that treatment of any disease or condition using the claimed method is not well-known in the art prior to the filling date.
The combination of prior art’s teachings demonstrates there is a high level of unpredictability in practicing the claimed method to treat a vast genus of diseases or conditions encompassed by claim 4 or specific species recited in claim 7 because it is not known whether these diseases comprise a retained intron in partially processed mRNA transcripts and/or can be amenable to treatment by inducing splicing out the retained intron.
Experimentation Required
In order to practice the claimed invention, an immense amount of experimentation would be required. For example, it would be necessary for one of ordinary skill in the art to characterize which autosomal recessive disorder comprises a retained intron in mature mRNA transcripts and which disorder can be treated via the claimed method.
Conclusion
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an unreasonable amount experimentation would be required to make and use the invention as claimed. Therefore, claims 4 and 7 are not considered to be enabled by the instant disclosure.
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 4, 8-9, and 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 5, 8-9, 11, 14, and 16 of U.S. Patent No. 10,196,639 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method of treating a disease or condition is achieved via the same method of ‘639.
Regarding instant claim 4, claims 2 and 14 of ‘639 teaches a method of modulating protein expression and treating a disease or condition, respectively, (i.e., treating a condition characterized by impaired production of functional protein form of a protein), comprising a “non-sense mediated RNA decay switch exon (NSE) repressor agent” (i.e., polynucleic acid polymer) that interacts with a target motif within an intronic region in a pre-processed mRNA transcript to modulate exclusion of an NSE (i.e., hybridizes to (a)-(c) in instant claim 4 and induces a portion of the pool of the partially processed mRNA transcripts to undergo splicing to remove the retained intron). Claims 1 and 12 from which claims 2 and 14 depend on, respectively, further teach mRNA transcripts comprising intronic region between two canonical exons (i.e., mRNA transcripts comprising a retained intron, an exon flanking a 5’ splice site of the retained intron, and an exon flanking 3’ splice site of the retained intron).
Regarding instant claims 8 and 9, ‘639 recites wherein a protein translated from the processed mRNA is a wild-type protein (claim 11) or a full-length protein (claim 16).
Regarding instant claims 26-28, claims 5, 8, and 9 of ‘639 recite the same type of modifications and length for polynucleic acid polymer.
Claims 4, and 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-5, 10, 12, and 15-16 of U.S. Patent No. 10,538,764 B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding instant claim 4, claims 4 and 5 of ‘764 teach “a method of treating a disease or condition characterized by an impaired production of a functional protein” in a subject to correct intron retention in gene transcripts, comprising administering to the subject a therapeutic agent which is a polynucleic acid polymer that hybridizes to a retained intron of a partially processed mRNA transcript and induces splicing out of the entire retained intron from the partially processed mRNA transcript. Claim 5 of ‘764 further teach that the partially processed mRNA transcript encodes a protein and comprises an entire retained intron. The additional recitations in the instant claim regarding exons with flanking splice sites of the retained intron are not patentably distinct over ‘764 because it is inherent that a retained intron lies between exons and is bound by a 5’ and a 3’ splice junctions. Claim 10 of ‘764 teach wherein the hybridization occurs on an intronic sequence (i.e., polynucleic acid polymer hybridizes to (a)-(c) in instant claim 4).
Regarding instant claims 26-28, claims 12, 15, and 16 of ‘764 also recites the same length and modifications for polynucleic acid polymer.
Claims 4, and 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 5-6, 10, and 14 of U.S. Patent No. 9,714,422 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method of treating a disease or condition is achieved via the same method steps of ‘422.
Regarding instant claim 4, ‘422 teaches a method of inducing processing of a partially processed mRNA transcript that is capable of encoding the functional form of a protein and comprises at least one entire retained intron (claim 1), which induces a disease of condition (claim 3). ‘422 further teaches the method comprises a polynucleic acid polymer that facilitates removal of an entire retained intron to produce a fully processed mRNA transcript that encodes a functional form of a protein” (claim 1) (i.e., wherein the polynucleic acid polymer induces splicing to remove the retained intron), by hybridizing to “a target sequence within a retained intron of a partially processed mRNA transcript” (claim 10) (i.e., polynucleic acid polymer hybridizes to (a)-(c) in instant claim 4). The additional recitations in the instant claim regarding exons with flanking splice sites of the retained intron are not patentably distinct over ‘764 because it is inherent that a retained intron lies between exons and is bound by a 5’ and a 3’ splice junctions.
Regarding instant claims 26-28, claims 5-6 and 14 of ‘422 also recites the same length and modifications for polynucleic acid polymer.
Claims 4, and 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, and 11-12 of U.S. Patent No. 11, 891,605 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method of treating a disease or condition is achieved via the polynucleic acid made by the method of ‘605.
Regarding instant claim 4, claim 1 of ‘605 teaches a polynucleic acid that induces splicing out a retained intron from a partially processed mRNA transcript, which is capable of encoding the functional form of a protein and comprises at least one retained intron. Claim 5 of ‘605 teaches each partially processed mRNA transcript comprises a retained intron that consists of a canonical intronic sequence between two canonical exons (i.e., mRNA transcripts comprising a retained intron, an exon flanking a 5’ splice site of the retained intron, and an exon flanking 3’ splice site of the retained intron). Claim 1 of ‘605 further teaches the polynucleic acid “facilitates removal of a retained intron to produce a fully processed mRNA transcript that encodes a functional form of a protein”, and claim 2 of ‘605 teaches wherein the polynucleic acid “hybridizes to the wild-type target sequence of the partially processed mRNA transcript”. Further, the specification of ‘605 discloses “wild-type target sequence” in Table 1 as an intronic sequence (i.e., limitations (a) to (c) in instant claim 1).
Regarding instant claims 26-28, claims 1, 11, and 12 of ‘605 also recites the same length and modifications for polynucleic acid polymer.
Claims 4, and 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 6, and 11-13 of U.S. Patent No. 9,745,577 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method of treating a disease or condition is achieved via the polynucleic acid of ‘577.
Regarding instant claim 4, claim 1 of ‘577 teaches a polynucleic acid polymer “induces splicing out of an entire retained intron from a partially processed mRNA transcript, wherein the partially processed mRNA transcripts encodes a protein and comprises an entire retained intron. The additional recitations in the instant claim regarding exons with flanking splice sites of the retained intron are not patentably distinct over ‘764 because it is inherent that a retained intron lies between exons and is bound by a 5’ and a 3’ splice junctions. Claims 4 and 6 of ‘577 also teach wherein the polynucleic acid polymer hybridizes to an intronic sequence (i.e., hybridizes to (a)-(c) in instant claim 4).
Regarding instant claims 26-28, claims 1, 12, and 13 of ‘577 also recites the same length and modifications for polynucleic acid polymer.
Claims 4, 16, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 7, 14, and 18 of U.S. Patent No. 11, 390, 869 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method of treating a disease or condition is achieved via the polynucleic acid of ‘869.
Regarding instant claim 4, claim 18 of ‘869 teaches “a method of treating or preventing a disease or condition characterized by an impaired production of a functional protein…comprising correction of intron retention in gene transcripts, the method comprising administering to the subject” the pharmaceutical composition of claim 1. Claim 2, dependent of claim 1, comprises a polynucleic acid polymer that induces splicing out an entire retained intron from a partially processed mRNA transcript that encodes a protein via hybridization to a wild-type target sequence within the entire retained intron (i.e., hybridizes to (a)-(c) in instant claim 4). Further, claim 14 of ‘869 teaches wherein the partially processed mRNA transcript induces a disease (i.e., disease or condition characterized by impaired production of a functional form of a protein). The additional recitations in the instant claim regarding exons with flanking splice sites of the retained intron are not patentably distinct over ‘764 because it is inherent that a retained intron lies between exons and is bound by a 5’ and a 3’ splice junctions.
Regarding instant claims 16 and 26, claims 1 and 7 of ‘869 recite the same length and binding site of the polynucleic acid polymer in instant claims 26 and 16, respectively.
Claims 4, 7-9, 15-17, 20, and 24-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-4, 6, 8-14, 16-22, and 25-27 of copending Application No. 19/456,908 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant method to treat a disease or condition is achieved by the same method steps of ‘908 and claims of ‘908 recite the same instant limitations in the same combination. For compact prosecution, the following table outlines the instant claims that corresponds to claims of ‘908.
Instant claims
Claims of ‘908
4
1, 9, 13, 19, 26, 27
7
4, 18, 20, 27
8
6, 16
9
8
15
2, 11-12, 19, 27
16
3, 11-12, 19, 27
17
1, 13, 19, 27
20
14
24
22
25
21
26
10, 17, 25
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. For
Based on the preponderance of the evidence, including the relevant teachings of the specification, working examples of SSOs targeting INS intron 1, and the state of prior art including the knowledge of antisense oligonucleotides targeting retained introns, one skilled in the art would conclude that instantly claimed method to treat a condition, specifically INS intron 1 isoforms, characterized by impaired production of a functional form of a protein encoded by a gene in a subject, comprising administering a polynucleic acid polymer that hybridizes to an internal region of a retained intron in partially processed mRNA transcripts transcribed from the gene to induce splicing to remove the retained intron is allowable subject matter.
Conclusion
No claims are allowable.
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QIWEN SU-TOBON
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636