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 I (claims 1,5,146-148,151-154,262 and 338) and as Species A, SEQ ID NO: 159 which is complementary to at least 15 contiguous nucleobases at positions 876-901 of SEQ ID NO: 5151 in the reply filed on 08/27/2026 is acknowledged.
Upon further consideration, the species have been expanded to include the oligonucleotide sequences taught in Ionis and Khvorova in the rejections below.
Claims 341,346,348-354 and 362 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/27/2026.
Claims 1,5,146-148,151-154,262 and 338 are under examination.
Priority
This application is a 371 of PCT/US2022/032128, filed 06/03/2022 which claims benefit of 63/196,896, filed 06/04/2021 as reflected by the most recent filing receipt.
Specification
The disclosure is objected to because it contains an embedded hyperlink 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. See at least page 33, paragraph 0056 and page 234, paragraph 0320.
The use of the term “Lipofectamine”, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1,5,262 and 338 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more.
Regarding Step 1 of the Eligibility Analysis for 35 USC 101, claims 1,5 and 262 recite a single-stranded oligonucleotide of 15-30 linked nucleotides in length, and claim 338 recites a pharmaceutical composition and is directed to a product, which is one of the statutory categories of invention.
Regarding Step 2A Prong One of the Eligibility Analysis, claims 1,5 and 262 recite at least one judicial exception that is a product of nature, which is a single stranded oligonucleotide of 15-30 linked nucleotides in length, wherein the oligonucleotide, or a portion thereof is at least 95% complementary to at least 15 or 17-23 contiguous nucleobases at specific recited positions of SEQ ID NO: 5151 and claim 262 recites a specific oligonucleotide sequence (SEQ ID NO: 159). Based on the broadest reasonable interpretation, the oligonucleotide reads on a product of nature as SEQ ID NO: 5151 is the mRNA sequence of MSH3 of NM_002439.4 (page 234 of instant specification) and therefore all or a portion of the recited oligonucleotide sequences would be found in the antisense strand of the MSH3 gene as found in nature. Claims 1,5 and 262 do not have markedly different characteristics from the oligonucleotide sequence found in nature as there are no modifications recited in the compound.
Next then, Step 2A Prong Two is analyzed to determine if the claim recites additional elements that integrate the judicial exception into a practical application. Regarding claims 1,5 and 262, no additional elements are recited. Therefore, the claims do not recite additional elements that integrate the judicial into a practical application.
Next, Step 2B of the Eligibility Analysis on whether a claim amounts to significantly more than the judicial exception is evaluated. Claims 1,5 and 262 do not include any additional elements in addition to the antisense oligonucleotide.
With respect to instant claim 338 directed to a pharmaceutical composition comprising one or more of the oligonucleotides, or pharmaceutically acceptable salts thereof, or claim 1 and a pharmaceutically acceptable carrier or excipient, although the limitations in these claims indicate that the oligonucleotide is in a composition comprising a carrier or excipient, the BRI of this encompasses the oligonucleotide in water. Because an oligonucleotide must be placed in a composition in order to store and use it, merely reciting a generic “composition” thus fails to meaningfully limit the claim because it is at best the equivalent of merely adding the words “apply it” to the judicial exception. The claims do not add significantly more because generally linking the use of the judicial exception to a particular technological environment or filed of use. See MPEP 2106.05(h).
Therefore, it is concluded that claims 1,5,262 and 338 fail all of the steps of the test for subject matter eligibility under 35 USC 101.
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.
Claim 262 is 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.
Claim 262 recites the oligonucleotide is selected from the group consisting of Antisense Oligo Nos. 1-5176 of Table 3. See MPEP 2173.05(s). “Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)”.
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)(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.
Claims 1,5,146-148,151-154 and 338 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Ionis (WO 2021252799, EFD 29 June 2020).
Regarding claims 1 and 5, Ionis teach oligomeric compounds that comprise an oligonucleotide comprising a region that is complementary to an MSH3 nucleic acid, and in some embodiments the MSH3 nucleic acid has the sequence set forth in SEQ ID NO: 1 (GenBank Accession No NM_002439.4) (page 39, lines 21-23). It is noted that the instant specification also discloses that the mRNA sequence of MSH3 is NM_002439.4 which is also instant SEQ ID NO: 5151 (page 234, paragraph 0320).
Ionis recites a single-stranded oligomeric compound (claim 41), and the oligomeric compound comprises a modified oligonucleotide which consists of 12-50 linked nucleosides and has a nucleobase sequence comprising at least 8-20 contiguous nucleobases of any of SEQ ID NOs: 10-2196 (claim 3).
SEQ ID NO: 1825 of Ionis (Db) is 20 nucleotides in length and nucleotides 1-20 are complementary to nucleotides 897-878 of instant SEQ ID NO: 5151 shown in the alignment below:
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Additionally, SEQ ID NO: 1966 of Ionis (Db) is 20 nucleotides long and nucleotides 1-20 are complementary to nucleotides 895-876 of instant SEQ ID NO: 5151 shown in the alignment below:
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167
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Therefore, Ionis teach the limitations of claims 1 and 5.
Regarding claim 146, Ionis recites the modified oligonucleotide has a sugar motif comprising a 5’ region consisting of 1-5 linked 5’-region nucleosides (5’ flanking sequence of instant claim 146), a central region consisting of 6-10 linked central region nucleosides (DNA core sequence of instant claim 146), and a 3’- region consisting of 1-5 linked 3’-region nucleosides (3’ flanking sequence of instant claim 146); wherein each of the 5’-region nucleosides and each of the 3’-region nucleosides comprises a modified sugar moiety, and each of the central region nucleosides comprises an unmodified 2’-deoxyribosyl sugar moiety (DNA core sequence of instant claim 146) (claim 20). In addition, Ionis specifically teaches the sequence of SEQ ID NOs: 1825 and 1966 as gapmers, which are 5-10-5 gapmers with mixed internucleoside linkages in Table 29, page 107 for SEQ ID NO: 1825, and Table 30, page 110 for SEQ ID NO: 1966.
Regarding claims 147 and 148, Ionis recites the modified oligonucleotide comprises at least one modified internucleoside linkage, which is a phosphorothioate internucleoside linkage (claim 25).
Regarding claims 151 and 152, Ionis recites the modified oligonucleotide comprises at least one modified nucleobase which is a 5’-methyl cytosine (claim 29).
Regarding claims 153 and 154, Ionis recites the modified oligonucleotide has a modified sugar moiety which is a bicyclic sugar moiety (claims 14-15) or a 2’-Ome sugar moiety (claim 17).
Regarding claim 338, Ionis recites a pharmaceutical composition comprising an oligomeric compound of any of claims 1-43 or antisense compound of claim 45 and a pharmaceutically acceptable carrier or diluent (claims 46-48).
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.
Claims 262 is rejected under 35 U.S.C. 103 as being unpatentable over Ionis as applied to claims 1,5,146-148,151-154 and 338 above.
The teachings of Ionis as applicable to claims 1,5,146-148,151-154 and 338 have been described above.
Ionis doesn’t explicitly teach the single-stranded oligomeric compound having all 23 nucleotides of the sequence of instant SEQ ID NO: 159 (Applicant’s elected sequence).
However, SEQ ID NO: 1825 of Ionis (Db) is 20 nucleotides in length and has 100% identity to nucleotides 2-21 of instant SEQ ID NO: 159 (Qy) shown in the alignment below:
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Additionally, SEQ ID NO: 1966 of Ionis (Db) is 20 nucleotides long and has 100% identity to nucleotides 4-23 of instant SEQ ID NO: 159 (Qy) shown in the alignment below:
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107
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It is also noted that nucleotides 1-23 of instant SEQ ID NO: 159 (Q) align with nucleotides 898-920 of SEQ ID NO: 1 of Ionis (S), which is identified as an MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4)(page 39, lines 21-23).
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Ionis recites and teaches the oligonucleotide can be 12-50 nucleotides in length and teach oligomeric compound sequences including both SEQ ID NOs: 1825 which align with nucleotides 2-21 of SEQ ID NO: 159 and teach SEQ ID NO: 1966 which align with nucleotides 4-23 of instant SEQ ID NO: 159, and all 23 nucleotides of instant SEQ ID NO: 159 align with the MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4 disclosed in the instant specification as well as identified as SEQ ID NO: 1 of Ionis, and therefore are targeting the same region of MSH3.
Therefore, it would have been obvious to one of ordinary skill in the art to have arrived at a single-stranded oligonucleotide of SEQ ID NO: 159 with a reasonable expectation of success based on the single-stranded oligonucleotide sequences of Ionis cited above, which includes multiple overlapping oligonucleotide sequences of SEQ ID NO: 1825 and 1966 and knowing the mRNA sequence of MSH3 with a reasonable expectation of success. There would be a reasonable expectation of success because Ionis recites and teaches the oligonucleotide can be 12-50 nucleotides in length and teach both SEQ ID NOs: 1825 which align with nucleotides 2-21 of SEQ ID NO: 159 and teach SEQ ID NO: 1966 which align with nucleotides 4-23 of instant SEQ ID NO: 159, and all 23 nucleotides of instant SEQ ID NO: 159 align with the MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4 disclosed in the instant specification as well as identified as SEQ ID NO: 1 of Ionis, and therefore are targeting the same region of MSH3. One of ordinary skill in the art would have been motivated to do so to arrive at a different length single-stranded oligonucleotide targeting MSH3 based on Ionis teaching that the oligonucleotide can have a length of 12-50 nucleotides, and teaching sequences of SEQ ID NO: 1825 and SEQ ID NO: 1966 which overlap and target the same region of MSH3 and an ordinary artisan would be able to design and arrive at a 23-mer based on these teachings and sequences with a reasonable expectation of success.
Accordingly, the limitations of claim 262 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claims 1,5,147,148,153,154 and 338 are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova et al. (US 20210355491, EFD 20 April 2020).
Regarding claims 1 and 5, Khvorova et al. teach an antisense sequence targeting MSH3 that is 20 nucleotides in length, of SEQ ID NO: 7 (Table 5, page 55, see below).
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The alignment below shows that nucleotides 20-4 of the antisense sequence of SEQ ID NO: 7 of Khvorova et al. (Db) are 100% complementary to 17 contiguous nucleobases of positions 876-901 of instant SEQ ID NO: 5151 (Qy) shown in the alignment below
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Khvorova et al. teach the antisense sequence of SEQ ID NO: 7 is the antisense strand of an siRNA, having an antisense and sense strand and therefore is not a single-stranded oligonucleotide as recited in claim 1.
However, Khvorova et al. also teach DNA and RNA can be single-stranded (i.e., ssRNA and ssDNA, respectively) or multi-stranded (e.g., double stranded, i.e., dsRNA and dsDNA, respectively) (paragraph 0244), and because RNAi is believed to progress via at least one single-stranded RNA intermediate, the skilled artisan will appreciate that ss-siRNAs (e.g., the antisense strand of a ds-siRNA) can also be designed (0315). In addition, Khvorova et al. teach the disclosure provides novel anti-MSH3 RNA silencing agents (e.g., siRNA, shRNA, and antisense oligonucleotides), and the RNA silencing agents comprise an antisense strand which has sufficient complementarity to a target MSH3 mRNA to mediate and RNA-mediated silencing mechanism (paragraph 0317).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date, to have provided the antisense sequence of SEQ ID NO: 7 that targets MSH3 of Khvorova et al. as a single-stranded antisense oligonucleotide rather than in a double-stranded siRNA with a reasonable expectation of success. There would be a reasonable expectation of success because Khvorova et al. suggests that the novel anti-MSH3 RNA silencing agents can be antisense oligonucleotides and teach single-stranded oligonucleotides. One of ordinary skill in the art would have been motivated to provide the antisense sequence as a single-stranded oligonucleotide because Khvorova et al. teach because RNAi is believed to progress via at least one single-stranded RNA intermediate, the skilled artisan will appreciate that ss-siRNAs (e.g., the antisense strand of a ds-siRNA) can also be designed and teach novel anti-MSH3 RNA silencing agents (e.g., siRNA, shRNA, and antisense oligonucleotides), and the RNA silencing agents comprise an antisense strand which has sufficient complementarity to a target MSH3 mRNA to mediate and RNA-mediated silencing mechanism (paragraph 0317).
Accordingly, the limitations of claims 1 and 5 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Regarding the modifications in claims 147,148,153 and 154, Khvorova et al. teach modified anti-MSH3 RNA silencing agents and that an RNA silencing agent (or any portion thereof) of the present application, as described supra, may be modified, such that the activity of the agent is further improved. For example, the RNA silencing agents described in Section II supra, may be modified with any of the modifications described infra. The modifications can, in part, serve to further enhance target discrimination, to enhance stability of the agent (e.g., to prevent degradation), to promote cellular uptake, to enhance the target efficiency, to improve efficacy in binding (e.g., to the targets), to improve patient tolerance to the agent, and/or to reduce toxicity. Khvorova et al. teach the antisense strand having a sequence complementary to a MSH3 nucleic acid sequence has nucleotides connected to each other via phosphorothioate internucleotide linkages (paragraph 0058). Khvorova et al. teach the antisense strand having a sequence complementary to a MSH3 nucleic acid sequence has at least 85% 2’-O-methyl modifications (paragraph 0058).
It would have been obvious to one of ordinary skill in the art before the effective filing date, to have provided the antisense sequence of SEQ ID NO: 7 that targets MSH3 of Khvorova et al. as a single-stranded antisense oligonucleotide and to provide chemical modifications including a phosphorothioate internucleoside linkage, or an alternative sugar moiety which is 2’-Ome with a reasonable expectation of success as this would have amounted to applying a known technical of chemical modification to a known product with a ready for improvement to yield predictable results. One of ordinary skill in the art would have been motivated to do so based on Khvorova et al. teaching modified anti-MSH3 RNA silencing agents in order for the activity of the agent is further improved such as to further enhance target discrimination, to enhance stability of the agent (e.g., to prevent degradation), to promote cellular uptake, to enhance the target efficiency, to improve efficacy in binding (e.g., to the targets), to improve patient tolerance to the agent, and/or to reduce toxicity, and teach various modifications that can do so including phosphorothioate internucleotide linkages and modified sugars including 2’-Ome.
Accordingly, the limitations of claims 147,148,153 and 154, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Regarding claim 338, Khvorova et al. teach a pharmaceutical composition for inhibiting the expression of MSH3 gene in an organism, comprising a compound recited above and a pharmaceutically acceptable carrier (paragraph 0207).
It would have been obvious to one of ordinary skill in the art before the effective filing date, to have provided the antisense sequence of SEQ ID NO: 7 that targets MSH3 of Khvorova et al. as a single-stranded antisense oligonucleotide and to provide a pharmaceutical composition thereof with a pharmaceutically acceptable carrier or excipient to administer to an organism or subject to inhibit MSH3 expression. One of ordinary skill in the art would have been motivated to do so because Khvorova et al. teach a pharmaceutical composition for inhibiting the expression of MSH3 gene in an organism, comprising a compound recited above and a pharmaceutically acceptable carrier.
Accordingly, the limitations of claim 338 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
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 1,5,146-148,151-154 and 338 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4,24,35-38,40,42-43 and 51 of copending Application No. 17/299,186 (‘186) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘186 are also drawn to a single-stranded oligonucleotide, 20 nucleosides in length which target the MSH3 gene and recite specific sequences of the oligonucleotide including SEQ ID NOs: 1581,1582,1606 or 1610 and recite a specific gapmer structure. Nucleotides 1-20 of SEQ ID NO: 1581 of ‘186 are complementary to nucleotides 2791-2772 of instant SEQ ID NO: 5151 of instant claim 1. Nucleotides 1-20 of SEQ ID NO: 1582 of ‘186 are complementary to nucleotides 2792-2773 of instant SEQ ID NO: 5151. Nucleotides 1-20 of SEQ ID NO: 1606 of ‘186 are complementary to nucleotides 2838-2819 of instant SEQ ID NO: 5151, and nucleotides 1-20 of SEQ ID NO: 1610 of ‘186 are complementary to nucleotides 2842-2823 of SEQ ID NO: 5151, and therefore the sequences of ‘186 are species of and are anticipated by the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 262 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4,24,35-38,40,42-43 and 51 of copending Application No. 17/299,186 (‘186) in view of Ionis cited above.
The claims of ‘186 are also drawn to a single-stranded oligonucleotide, 20 nucleosides in length which target the MSH3 gene and recite specific sequences of the oligonucleotide including SEQ ID NOs: 1581,1582,1606 or 1610 and recite a specific gapmer structure.
‘186 do not recite the oligonucleotide has the sequence of SEQ ID NO: 159.
However, SEQ ID NO: 1825 of Ionis (Db) is 20 nucleotides in length and has 100% identity to nucleotides 2-21 of instant SEQ ID NO: 159 (Qy) shown in the alignment below:
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Additionally, SEQ ID NO: 1966 of Ionis (Db) is 20 nucleotides long and has 100% identity to nucleotides 4-23 of instant SEQ ID NO: 159 (Qy) shown in the alignment below:
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Also nucleotides 1-23 of instant SEQ ID NO: 159 (Q) align with nucleotides 898-920 of SEQ ID NO: 1 of Ionis (S), which is identified as an MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4)(page 39, lines 21-23).
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Ionis recites and teaches the oligonucleotide can be 12-50 nucleotides in length and teach oligomeric compound sequences including both SEQ ID NOs: 1825 which align with nucleotides 2-21 of SEQ ID NO: 159 and teach SEQ ID NO: 1966 which align with nucleotides 4-23 of instant SEQ ID NO: 159, and all 23 nucleotides of instant SEQ ID NO: 159 align with the MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4 disclosed in the instant specification as well as identified as SEQ ID NO: 1 of Ionis, and therefore are targeting the same region of MSH3.
Therefore, it would have been obvious to one of ordinary skill in the art to have modified the claims of ‘186 by substituting the oligonucleotide sequences of ‘186 with the sequences of Ionis to arrive at a single-stranded oligonucleotide of SEQ ID NO: 159 with a reasonable expectation of success based on the single-stranded oligonucleotide sequences of Ionis cited above, which includes multiple overlapping oligonucleotide sequences of SEQ ID NO: 1825 and 1966 with a reasonable expectation of success. There would be a reasonable expectation of success because Ionis recites and teaches the oligonucleotide can be 12-50 nucleotides in length and teach both SEQ ID NOs: 1825 which align with nucleotides 2-21 of SEQ ID NO: 159 and teach SEQ ID NO: 1966 which align with nucleotides 4-23 of instant SEQ ID NO: 159, and all 23 nucleotides of instant SEQ ID NO: 159 align with the MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4 disclosed in the instant specification as well as identified as SEQ ID NO: 1 of Ionis, and therefore are targeting the same region of MSH3. One of ordinary skill in the art would have been motivated to do so to arrive at a different length single-stranded oligonucleotide targeting a different region of MSH3 based on Ionis teaching that the oligonucleotide can have a length of 12-50 nucleotides, and teaching sequences of SEQ ID NO: 1825 and SEQ ID NO: 1966 which overlap and target the same region of MSH3 and an ordinary artisan would be able to design and arrive at a 23-mer based on these teachings and sequences with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection.
Claims 1,5,146-148,151-154 and 338 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,408,000, Issued 9 Aug 2022. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent are also drawn to a single-stranded oligonucleotide, 15-30 nucleotides in length wherein the oligonucleotide or a portion thereof is at least 95% complementary to at least 15 contiguous nucleobases at positions 2685-2714 of SEQ ID NO: 614 and recites a gapmer structure. Instant claim 1 recites the single-stranded oligonucleotide of 15-30 linked nucleotides have at least 95% complementary to at least 15 contiguous nucleobases at positions 2685-2710. SEQ ID NO: 614 of the patent is 100% identical to instant SEQ ID NO: 5151. Claim 8 of the patent recites the oligonucleotide consists of the nucleobase sequence that is SEQ ID NO: 289. All 20 nucleotides SEQ ID NO: 289 are complementary to nucleotides 2708-2689 of instant SEQ ID NO: 5151. Therefore, the claims of the patent fall within the scope of the instant claims or recite species of and are anticipated by the instant claims.
Claim 262 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,408,000, Issued 9 Aug 2022 in view of Ionis cited above.
The claims of the patent do not recite the oligonucleotide has the sequence of SEQ ID NO: 159.
The teachings and sequences of Ionis have been described in the 103 and double patent rejections above.
Therefore, it would have been obvious to one of ordinary skill in the art to have modified the claims of the patent by substituting the oligonucleotide sequences of the patent with the sequences of Ionis to arrive at a single-stranded oligonucleotide of SEQ ID NO: 159 with a reasonable expectation of success based on the single-stranded oligonucleotide sequences of Ionis cited above, which includes multiple overlapping oligonucleotide sequences of SEQ ID NO: 1825 and 1966 with a reasonable expectation of success. There would be a reasonable expectation of success because Ionis recites and teaches the oligonucleotide can be 12-50 nucleotides in length and teach both SEQ ID NOs: 1825 which align with nucleotides 2-21 of SEQ ID NO: 159 and teach SEQ ID NO: 1966 which align with nucleotides 4-23 of instant SEQ ID NO: 159, and all 23 nucleotides of instant SEQ ID NO: 159 align with the MSH3 nucleic acid sequence of GenBank Accession No. NM_002439.4 disclosed in the instant specification as well as identified as SEQ ID NO: 1 of Ionis, and therefore are targeting the same region of MSH3. One of ordinary skill in the art would have been motivated to do so to arrive at a different length single-stranded oligonucleotide targeting a different region of MSH3 based on Ionis teaching that the oligonucleotide can have a length of 12-50 nucleotides, and teaching sequences of SEQ ID NO: 1825 and SEQ ID NO: 1966 which overlap and target the same region of MSH3 and an ordinary artisan would be able to design and arrive at a 23-mer based on these teachings and sequences with a reasonable expectation of success.
Conclusion
Claims 1,5,146-148,151-154,262 and 338 are rejected.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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