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 with partial traverse of claims 8, 10, 12-20, 23-29, 32-33, 44, and 46 with species election of 118292-118317 of SEQ ID NO:2 and six subspecies including SEQ ID NO:744 in the reply filed on January 6, 2026 is acknowledged. The traversal is on the ground(s) that it is not undue burden to search and examine all six individual SEQ ID NOs. In response, it is noted that if all six sequences pointed out by applicant are truly within the elected range of SEQ ID NO:2, they would be fully examined.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 8, 10, 12-20, 23-29, 32-33, 44, 46, and 49-53 are currently pending in the instant application. Claims 49-53 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 8, 10, 12-20, 23-29, 32-33, 44, and 46 are under examination on the merits in the instant application.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on November 16, 2023 and January 6, 2026 have been considered by the examiner. Note that foreign patent document citation number 21 in the IDS of November 16, 2023 is in non-English language and no English language translation is attached. Hence, the aforementioned document is not considered.
Claim Objections
Claim 10 is objected to because of the following informalities: Claim 10 recites multiple duplicate SEQ ID NOs. See for instance SEQ ID NO:69 recited twice. Appropriate correction is required.
Claim Rejections - Improper Markush Grouping
Claims 8, 10, 12-20, 23-29, 32-33, 44, and 46 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination of process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP §706.03(y).
The Markush grouping of target sequences in claim 8 and dependent claims thereof is improper because the alternatives defined by the Markush grouping do not share a common nucleotide sequence as evidenced by the fact the target sequence of “nucleobases 4438-4475 of SEQ ID NO:2” and applicant’s elected target sequence of “nucleobases 118292-118317 of SEQ ID NO:2” shares no significant level of sequence similarity.
The Markush grouping of oligonucleotide sequence species of distinct SEQ ID NOs in claim 10 is improper because the alternatives defined by the Markush grouping do not share a common nucleotide sequence as evidenced by the fact SEQ ID NO:19 and applicant’s elected sequence of SEQ ID NO:744 shares no nucleotide sequence match when the two 20-mer sequences are aligned.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternatives within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
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 12 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 12 depends from claim 8 and requires that the oligonucleotide of claim 8 should be at least 80% complementary to an equal length sequence in one of SEQ ID NOs:1-3.
It is noted that claim 8 is limited to SEQ ID NO:2 as the target sequence such that the oligonucleotide of claim 8 should be complementary to a certain portion of SEQ ID NO:2. It is also noted that SEQ ID NO:1 and SEQ ID NO:3 at best comprises about a 1,000-mer nucleotide sequence beginning at the nucleotide position 223749 of SEQ ID NO:2, wherein such nucleotide sequence position is not claimed in claim 8. Hence, claim 12 reciting nucleotide sequences not claimed in claim 8 broadens the scope of the claim 8, thereby failing to further limit the subject matter of claim 8.
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.
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 8, 12-20, 23-29, 32-33, 44, and 46 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.
Claim 8 and dependent claims thereof recite the broad range of “nucleobases 116894-116951” and also simultaneously recite “nucleobases 116894-116937”, which is the narrower range of the aforementioned broad range. The claims are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language “nucleobases 116894-116937” is (a) merely exemplary of the broad range of “nucleobases 116894-116951”, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
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.
Claims 8, 10, 12-20, 23-29, 32-33, and 46 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bermingham et al. (US 2022/0072028 A1).
Bermingham discloses an MSH3-targeting 20-mer antisense oligonucleotide of SEQ ID NO:1300 (5’-ACACCTTGAATTTCATCCTT), which is 100% complementary to a 20-mer at nucleotide positions 116896-116915 of SEQ ID NO:2 claimed in the instant case, wherein the underlined 18-mer is present in SEQ ID NO:412 claimed in the instant case.
Bermingham teaches that the oligonucleotide can have a “gapmer” motif (e.g., “5-10-5 gapmer”) having a DNA gap flanked by modified wings comprising modifications such as 5’-methyl cytosine, bicyclic nucleosides (e.g., LNAs and cEt), sugars surrogates such as morpholino, 2’-O-methyl, 2’-MOE, and a ligand conjugate via a linker, wherein the oligonucleotide is formulated in a pharmaceutically acceptable carrier. See paragraphs 0016-0021, 0050-0053, 0061-0062, and 0125-0128.
Accordingly, claims 8, 10, 12-20, 23-29, 32-33, and 46 are described by Bermingham et al.
Claims 8, 10, 12-19, 23-29, 32-33, 44, and 46 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Khvorova et al. (US 2021/0355491 A1).
It is noted that the “nucleobases” of the claimed nucleobase sequence claimed in claim 10 encompasses RNA bases as evidenced by the disclosure of page 54 of the instant specification.
Khvorova teaches making an MSH3-targeting oligomeric compound comprising a chemically modified oligonucleotide a 20-mer antisense sequence of SEQ ID NO:7 (5’-UGGCAAUAAAUAUUGAGCUC) targeted to a 20-mer within SEQ ID NO:1 (corresponding to positions 20242-20285 of SEQ ID NO:2 claimed in the instant case), wherein the underlined 13-mer is an RNA nucleobase sequence counterpart in SEQ ID NO:208 claimed in the instant case, wherein Khvorova’s entire 20-mer is 100% complementary to a 20-mer in SEQ ID NO:2 claimed in the instant case. See Table 5.
Khvorova teaches that the oligonucleotide comprises 2’-O-methyl, phosphorothioate linkages, 2’-O, 4’-C-ethylene-bridged nucleic acids (LNAs), 5-methyl-cytidine, and a morpholino nucleotide, wherein the oligonucleotide is conjugated to a moiety via a linker and forms a duplex with a complementary sequence and is formulated in a pharmaceutically acceptable carrier. See paragraphs 0077, 0115, 0443-0444, 0447, 0508, 0512, 0514, 0633; claims 1-3.
Accordingly, claims 8, 10, 12-19, 23-29, 32-33, 44, and 46 are described by Khvorova et al.
Claims 8, 10, 12-19, 23-29, 32-33, 44, and 46 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Khvorova et al. (WO 2021/216556 A2, of record, applicant’s citation).
It is noted that the “nucleobases” of the claimed nucleobase sequence claimed in claim 10 encompasses RNA bases as evidenced by the disclosure of page 54 of the instant specification.
Khvorova teaches making an MSH3-targeting oligomeric compound comprising a chemically modified oligonucleotide a 20-mer antisense sequence for “MSH_4315” (5’-CCUUAUUCCUUCUGUGCUCU) 100% complementary to a 20-mer at positions 224683-224702 of SEQ ID NO:2 claimed in the instant case, wherein the underlined 18-mer is an RNA nucleobase sequence counterpart in SEQ ID NO:399 claimed in the instant case. See Table 8 at page 141.
Khvorova teaches that the oligonucleotide comprises 2’-O-methyl, a locked nucleotide, a morpholino nucleotide, and phosphorothioate linkages, 2’-O, 4’-C-ethylene-bridged nucleic acids (LNAs), 5-methyl-cytidine, PNAs, and a morpholino nucleotide, wherein the oligonucleotide is conjugated to a moiety via a linker and forms a duplex with a complementary sequence and is formulated in a pharmaceutically acceptable carrier. See 030-032, 055-063, 0335-0337.
Accordingly, claims 8, 10, 12-19, 23-29, 32-33, 44, and 46 are described by Khvorova et al.
Claims 8, 10, 12-17, 23-29, 32-33, and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Giangrande et al. (US 2018/0134746 A1).
It is noted that the bridged sugar moiety comprising the 4’ to 2’ -O-CH2 bridge claimed in claim 15 is defined as “LNA” in the instant specification. See page 22.
Giangrande discloses a 20-mer DNA oligonucleotide of SEQ ID NO:3446, which is at least 80% complementary to a 20-mer sequence within nucleotide positions 118292-118317 of SEQ ID NO:2, wherein Giangrade’s SEQ ID NO:3446 (5’-CTTTCACTTACTTTCTACCG) comprises a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118295-118306 (5’-AGAAAGTAAGTG) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer (5’-CACTTACTTTCT) in SEQ ID NO:943 claimed in the instant case.
Giangrande teaches that the oligonucleotide comprises modifications such as 2’-O-methyl, locked nucleic acid (LNA), 5-methylcytosine, and phosphorothioate, wherein the oligonucleotide is linked to a molecule and is formulated as a pharmaceutical composition in a pharmaceutically acceptable carrier. See paragraphs 0006-0007, 0011-0013, 0092-0095, and 0103.
Accordingly, claims 8, 10, 12-17, 23-29, 32-33, and 46 are described by Giangrande et al.
Claims 8, 10, 13-20, 23-29, 32-33, 44, and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pandey et al. (WO 2006/127913 A2).
Pandey discloses a 20-mer DNA oligonucleotide of SEQ ID NO:253 (5’-GCACACTTACTTTCTCTTTA) comprising a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118294-118307 (5’-GAGAAAGTAAGTGT) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer (5’-ACACTTACTTTCTC) in SEQ ID NO:943 claimed in the instant case. See page 61 of Pandey’s sequence listing or Table 7.
Pandey teaches that the oligonucleotide can have a 5-10-5 gapmer modification motif, wherein the wing regions are modified with 2’-O-methyl, 2’-MOE, bicyclic nucleic acid (BNA) such as LNA, 5-methyl cytosine, phosphorothioates, peptide nucleic acids (PNA), and morpholino, wherein the oligonucleotide is attached to conjugate groups via a linker and is formulated as a pharmaceutical composition comprising a pharmaceutically acceptable carrier. See pages 15-19; Table 7.
Pandey teaches that the oligonucleotide can be included in a duplex compound. See page 13.
Accordingly, claims 8, 10, 13-20, 23-29, 32-33, 44, and 46 are described by Pandey et al.
Claims 8, 10, 12-13, 16-17, 23-29, 32-33, 44, and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khvorova et al. (US 2007/0031844 A1, applicant’s citation).
It is noted that the “nucleobases” of the claimed nucleobase sequence claimed in claim 10 encompasses RNA bases as evidenced by the disclosure of page 54 of the instant specification.
Khvorova discloses a 19-mer RNA oligonucleotide of SEQ ID NO:1224076 (5’-GCACUUACACCCACGUUCU) comprising a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118304-118313 (5’-GTGTAAGTGC) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer RNA base counterpart of 5’-GCACTTACAC in SEQ ID NO:943 claimed in the instant case. It is noted that Khvorova’s 19-mer of SEQ ID NO:1224076 is at least 80% complementary to a 19-mer sequence within nucleotide positions 118292-118317 of SEQ ID NO:2.
Khvorova discloses a 19-mer RNA oligonucleotide of SEQ ID NO:1454014 (5’-CAACUUCCACUUACUUUCC) comprising a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118296-118306 (5’-GAAAGTAAGTG) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer RNA base counterpart of 5’-CACTTACTTTC in SEQ ID NO:943 claimed in the instant case.
Khvorova discloses a 19-mer RNA oligonucleotide of SEQ ID NO:317457 (5’-GCCCUUACACUUACUGUUG) comprising a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118299-118310 (5’-AGTAAGTGTAAG) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer RNA base counterpart of 5’-CTTACACTTACT in SEQ ID NO:943 claimed in the instant case.
Khvorova teaches that the disclosed 19-mer RNA oligonucleotide form a duplex with a complementary oligonucleotide and comprises at least one modification such as 2’-O-methyl, 5-methylcytidine, phosphorothioates, and “conjugations for other molecules” “to facilitate delivery”, wherein the duplex is formulated for in vivo use “in a physiological acceptable solution.” See paragraphs 0119-0121 and 0277.
Accordingly, claims 8, 10, 12-13, 16-17, 23-29, 32-33, 44, and 46 are described by Khvorova et al.
Claims 8, 10, 13, 16-19, 23-29, 32-33, and 46 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kabadi et al. (US 2019/0374655 A1).
Kabadi discloses a 20-mer oligonucleotide of SEQ ID NO:128285 comprising a sequence of at least 8 consecutive nucleotides complementary to at least an 8-mer sequence at nucleotide positions 118298-118309 (5’-AAGTAAGTGTAA) of SEQ ID NO:2 claimed in the instant application and comprises at least an 8-mer (5’-TTACACTTACTT) in SEQ ID NO:744 claimed and elected by applicant. See Kabadi’s SEQ ID NO:128285 by accessing the “Sequence Listing” in the electronic form as instructed at page 49, wherein Kabadi’s SEQ ID NO:128285 in the electronic form of the “Sequence Listing” is reproduced below.
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Kabadi teaches that the oligonucleotide comprises at least one modification including “2’-O-methyl modifications”, “peptide nucleic acid (PNA)”, “phosphorothioate backbones”, and “5-methylcytosine”, wherein the oligonucleotide can be “chemically linked to one or more moieties or conjugates” such as “cholesterols” and formulated as a pharmaceutical composition with a pharmaceutically acceptable carrier. See paragraph 0314-0315, 0322, 0325-0327, and 0417.
Accordingly, claims 8, 10, 13, 16-19, 23-29, 32-33, and 46 are described by Kabadi et al.
Conclusion
No claim is allowed.
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/DANA H SHIN/Primary Examiner, Art Unit 1635