DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I and IpT1 in the reply filed on December 29 2025 is acknowledged. In light of discovered prior art, Group IV, drawn to an nucleotide comprising one or more compounds of formula VI, which includes IpT1 (as this corresponds to Formula VI wherein T1 and T2 are protecting groups) is rejoined. Claims 1-3. 6, 11, 18-19, 26-27, 37-43 and 45-48 are pending in the application. Claims 2, 11,18-19, 26-27, 40 and 46-48 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 28 2025. The examiner notes that the response indicates that claim 11 reads on the elected species but this not correct. Claim 11 depends from claim 2 which is directed to a non-elected species (i.e. the claim are directed to a non-elected R3 group). Therefore, in light of the species election claims 2, 11 and 40 are withdrawn.
Accordingly, claims 1, 3, 6, 37-39, 41-43 and 45 are being examined on the merits herein.
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 .
Priority
This application is a 371 of PCT/EP21/78980 (10/19/2021) which claims priority to EUROPEAN PATENT OFFICE (EPO) 20306243.5 (10/20/2020) as reflected in the filing receipt issued on November 3 2023.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 27 2023 and December 29 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1, 3, 6, 37-39, 41-43 and 45 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 1 as currently written is vague and indefinite. In the definition of A1, A2 and A3 there are numerous instances of (C1-C20) alkyl, (C3-C8) cycloalkyl, etc. specifically a recitation of a genus for example alkyl but then a narrowing limitation (C1-C20) for example in parentheses. Because alkyl (generic term) and C1-C20 (narrower species) are not identical in scope, the use of parentheses raises the question as to which term is required by the claim. The indefinite language also occurs in the definition of Z5 and Z6. Claim 6 additionally contains the same indefinite language in (i), (ii), (iv) and (v). Claim 37 additionally contains the same indefinite language in the definition of R3 (it is noted that C1-C25 hydrocarbon chain in L is NOT indefinite as it does not include the parentheses and therefore this claim is interpreted as requiring L to be a C1-C25 hydrocarbon).
Claim 3 as currently written is vague and indefinite. The claim in (ii) recites -(CO)- as a terminating group for L. However, this claim depends from claim 1 and in the definition of L in claim 1 it indicates that L can be terminated by C(O). The recitation (CO) is not the same as C(O) as (CO) is C-O whereas C(O) is C=O. Therefore, the metes and bounds of the claim are unclear.
Regarding claim 41, the phrase "such as" in line 2 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 37-30, 42-43 and 45 are included in the rejection as they depend on a rejected base claim and they do not clarify the issues.
Claim Interpretation
The claims repeatedly use the term(s) optional or optionally are used throughout. The broadest reasonable interpretation of this term is that everything following the limitation are not required to be present. Therefore, all of the claims are interpreted that the limitations following optionally are not required to be present.
Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1, 3, 6, 37-39, 41-43 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Hofmeister et al. (WO2019170731, published 9/12/19, cited on PTO Form 1449) in view of Clark et al. (PNAS, 2012), Hasegawa et al. (Carbohydrate Research 1980) and Manoharan et al. (USPGPUB No. 20180326070).
Applicant Claims
The instant application claims a compound of formula I.
The instant application claims an oligonucleotide comprising one or more compounds of formula (VI).
As elected the compound of formula I is IpT1:
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Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Hofmeister et al. is directed to nucleotide precursors, nucleotide analogs and oligomeric compounds containing the same. Claimed is a compound of formula I:
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which is substantially similar to the instant claims (claim 1). A specific compound taught is IgT1 (compound 36) (Table A):
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. Claimed is an oligonucleotide comprising one or more compounds of formula (II):
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wherein L1 and L2 have the same definition as instantly claimed T1 and T2 (claim 35). As claimed R3 is N-acetyl-galactosamine (claim 48). A double stranded oligonucleotide comprising one or more of the compounds of formula II is claimed (claim 50). A small interfering RNA (siRNA) comprising one or more compounds of formula (II) (claim 51). Stability increase has been shown for siRNAs wherein the compounds of formula II are present at an overhang of the sense strand and antisense strand including siRNAs where the compounds of formula II are present at the 3’-end or 5’-end or both of the sense strand (page 48, lines 7-18). As claimed Y can be N-C(O)-R1 wherein R1 is a C1-C20 alkyl optionally substituted by one or more including -C(=J)- wherein J is O (claim 1). Y can be NR1 with R1 being C(O)m-R2-(O-CH2-CH2)p-R3 wherein p is 0, m is 1 and R2 is a C1-C20 alkylene group and R3 is a cell targeting moiety (claim 10; 21).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Hofmeister et al. teaches compounds similar to the instant claims, the difference between the compounds of Hofmeister et al. and the instant claims is Hofmeister et al. teaches a N-acetyl-galactosamine whereas the instant claim include a piperidine iminosugar (see box in compound 36 above). This deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
Clark et al. is directed to pharmacological chaperones for human α-N-acetylgalactosaminidase. DGJNAc, is the iminosugar analog of GalNAc:
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(page 17404, left column, last paragraph; Fig. 1).
Hasegawa et al. is directed to the synthesis of a 2-acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl derivative. It is taught that there has been a great deal of activity in the synthesis of heterosugars in which the ring-oxygen atom of aldoses have been replaced by nitrogen, phosphorus or sulfur. These sugars are interesting, not only from the point of view of the chemistry involved, but also for their various, biological activities (page 277, introduction). A specific derivative taught is the di-N-acetyl-di-O-acetyl derivative (compound 12):
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(page 279; page 283). These are 2-amino sugar derivatives having nitrogen in the ring (page 277, introduction). Ligands include carbohydrates including galactose, N-acetyl-galactosamine, N-acetyl-glucosamine, mannose, fucose, etc. (page 79, lines 6-13).
Manoharan et al. is directed to carbohydrate conjugates as delivery agents for oligonucleotides. Taught are iRNA agents that are conjugated with at least one carbohydrate ligand such as monosaccharides (paragraph 0016). Monosaccharides include N-acetyl-galactosamine as well as imino sugar (ring oxygen replaced by nitrogen) (paragraph 0166). As shown in Figure 1, the monosaccharide can be conjugated via a CO, NH, O, S OC(O), NHC(O) or CH2.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Hofmeister et al., Clark et al., Hasegawa et al. and Manoharan et al. and utilize a compound of:
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as the targeting ligand in place of GalNAc as taught by Hofmeister et al. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring. Since Hofmeister et al. teaches the ligands can be carbohydrates and specifically point to sugars, one skilled in the art would have a reasonable expectation of success.
Regarding the elected species and claim 1, 3 and 6, as set forth above, 1pT1 is the same as instantly elected except for:
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. Hofmeister et al. teaches the linker between the ligand includes alkyl groups which can include a C(O). For ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of 1pT1 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, Hofmeister et al. teaches the compound can be a double stranded oligonucleotide comprising one or more of the compounds of formula II or a small interfering RNA (siRNA) comprising one or more compounds of formula (II). The compound of formula (VI) is the same as elected except for one of P1 or P2 (i.e. the ODMT or
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being the point of attachment to the oligonucleotide. This is also taught by Hofmeister et al. as Hofmeister et al. teaches in formula II L1 and L2 have the same definition as instantly claimed T1 and T2
Regarding claim 41, Hofmeister et al. teaches attachment of the compound to double stranded oligonucleotides.
Regarding claim 42, Hofmeister et al. teaches a RNAi which is double-stranded comprising a sense and antisense strand.
Regarding claims 43 and 45, Hofmeister et al. teaches that stability increase has been shown for siRNAs wherein the compounds of formula II are present at an overhang of the sense strand and antisense strand including siRNAs where the compounds of formula II are present at the 3’-end or 5’-end or both of the sense strand.
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, 3 and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11897911 in view of Clark et al. (PNAS, 2012), Hasegawa et al. (Carbohydrate Research 1980) and Manoharan et al. (USPGPUB No. 20180326070). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a compound of formula I.
As elected the compound of formula I is IpT1:
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Patent ‘911 claims a compound of formula I:
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wherein Y can be N-C(O)-R1 wherein R1 can be R2-R3 wherein R2 is a C1-C20 alkylene group and R3 is a cell targeting moiety (claim 1). Specific R3 claimed is:
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The difference between the instant claims and Patent ‘911 is that Patent ‘911 does not claim a nitrogen in the ring and this is the point of attachment via an amide. However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
Clark et al. is directed to pharmacological chaperones for human α-N-acetylgalactosaminidase. DGJNAc, is the iminosugar analog of GalNAc:
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(page 17404, left column, last paragraph; Fig. 1).
Hasegawa et al. is directed to the synthesis of a 2-acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl derivative. It is taught that there has been a great deal of activity in the synthesis of heterosugars in which the ring-oxygen atom of aldoses have been replaced by nitrogen, phosphorus or sulfur. These sugars are interesting, not only from the point of view of the chemistry involved, but also for their various, biological activities (page 277, introduction). A specific derivative taught is the di-N-acetyl-di-O-acetyl derivative (compound 12):
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(page 279; page 283). These are 2-amino sugar derivatives having nitrogen in the ring (page 277, introduction). Ligands include carbohydrates including galactose, N-acetyl-galactosamine, N-acetyl-glucosamine, mannose, fucose, etc. (page 79, lines 6-13).
Manoharan et al. is directed to carbohydrate conjugates as delivery agents for oligonucleotides. Taught are iRNA agents that are conjugated with at least one carbohydrate ligand such as monosaccharides (paragraph 0016). Monosaccharides include N-acetyl-galactosamine as well as imino sugar (ring oxygen replaced by nitrogen) (paragraph 0166). As shown in Figure 1, the monosaccharide can be conjugated via a CO, NH, O, S OC(O), NHC(O) or CH2.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘911, Clark et al., Hasegawa et al. and Manoharan et al. and utilize a compound of:
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as the R3 in place of GalNAc as claimed by Patent ‘911. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds claimed in patent ‘911with C(O)-iminosugar would result in the elected compound.
Claims 37-39, 41-43 and 45 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11897911 in view of Clark et al., Hasegawa et al. and Manoharan et al. as applied to claims 1, 3 and 6 above and in further view of Hofmeister et al. (WO2019170731, published 9/12/19, cited on PTO Form 1449). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims an oligonucleotide comprising one or more compounds of formula (VI).
As elected the compound of formula I is IpT1:
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The claims of Patent ‘911 are set forth above.
While Patent ‘911 claims B is a heterocyclic nucleobase, Patent ‘911 does not claim an oligonucleotide with the claimed compound. However, this deficiency is cured by Hofmeister et al.
Hofmeister et al. is directed to nucleotide precursors, nucleotide analogs and oligomeric compounds containing the same. Claimed is a compound of formula I:
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which is substantially similar to the instant claims (claim 1). A specific compound taught is IgT1 (compound 36) (Table A):
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. Claimed is an oligonucleotide comprising one or more compounds of formula (II):
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wherein L1 and L2 have the same definition as instantly claimed T1 and T2 (claim 35). As claimed R3 is N-acetyl-galactosamine (claim 48). A double stranded oligonucleotide comprising one or more of the compounds of formula II is claimed (claim 50). A small interfering RNA (siRNA) comprising one or more compounds of formula (II) (claim 51). Stability increase has been shown for siRNAs wherein the compounds of formula II are present at an overhang of the sense strand and antisense strand including siRNAs where the compounds of formula II are present at the 3’-end or 5’-end or both of the sense strand (page 48, lines 7-18). As claimed Y can be N-C(O)-R1 wherein R1 is a C1-C20 alkyl optionally substituted by one or more including -C(=J)- wherein J is O (claim 1). Y can be NR1 with R1 being C(O)m-R2-(O-CH2-CH2)p-R3 wherein p is 0, m is 1 and R2 is a C1-C20 alkylene group and R3 is a cell targeting moiety (claim 10; 21).
Regarding claim 37-39, Hofmeister et al. teaches the compound can be a double stranded oligonucleotide comprising one or more of the compounds of formula II (which is the same as Patent ‘911) or a small interfering RNA (siRNA) comprising one or more compounds of formula (II). The compound of formula (VI) is the same as elected except for one of P1 or P2 (i.e. the ODMT or
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being the point of attachment to the oligonucleotide. This is also taught by Hofmeister et al. as Hofmeister et al. teaches in formula II L1 and L2 have the same definition as instantly claimed T1 and T2
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘911, Clark et al., Hasegawa et al., Manoharan et al. and Hofmeister et al. and utilize the compound of formula I with an oligonucleotide. One skilled in the art would have been motivated to utilize the compound with an oligonucleotide in order to increase stability as taught by Hofmeister et al.
Regarding claim 41, Hofmeister et al. teaches attachment of the compound to double stranded oligonucleotides.
Regarding claim 42, Hofmeister et al. teaches a RNAi which is double-stranded comprising a sense and antisense strand.
Regarding claims 43 and 45, Hofmeister et al. teaches that stability increase has been shown for siRNAs wherein the compounds of formula II are present at an overhang of the sense strand and antisense strand including siRNAs where the compounds of formula II are present at the 3’-end or 5’-end or both of the sense strand.
Claims 1, 3, 6, 37-39, 41-43 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 11-12, 22, 28, 32, 35-36, 44,48 and 50-58 of copending Application No. 18532319 (USPGPUB No. 20240376137) in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘319 claims a compound of Formula I:
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wherein R3 is:
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(claims 1 and 28). Claimed is an oligonucleotide comprising one or more compounds of formula II (claim 35). A double stranded oligonucleotide is claimed (claim 50). A siRNA comprising the compound is claimed (claim 51).
The difference between the instant claims and copending ‘319 is that copending ‘319 does not claim a nitrogen in the ring and this is the point of attachment via an amide. However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘319, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
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as R3 in place of GalNAc as taught by copending ‘319. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘319 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘319 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula II or a small interfering RNA (siRNA) comprising one or more compounds of formula (II).
Regarding claim 41-43 and 45, copending ‘319 teaches attachment of the compound to double stranded oligonucleotides. Copending ‘319 teaches a RNAi which is double-stranded comprising a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘319, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Claims 1, 3, 6, 37-39, 41-43 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6, 9, 11, 14-15, 19, 22-23, 25-26, 29, 32-33, 35-37 and 39 of copending Application No. 18248974 (USPGPUB No. 20240035029) in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘974 claims a double stranded RNA. The dsRNA includes a 5’ overhang, a 3’ overhang or both. One or both of the strands of the dsRNA comprise one or more compounds of Formula I:
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wherein R3 is:
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(claims 1; 22). A double stranded oligonucleotide is claimed (claim 22).
The difference between the instant claims and copending ‘974 is that copending ‘974 does not claim a nitrogen in the ring and this is the point of attachment via an amide. However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘974, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
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as R3 in place of GalNAc as taught by copending ‘974. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘974 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘974 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula I.
Regarding claim 41-43 and 45, copending ‘974 claims attachment of the compound to double stranded oligonucleotides wherein the dsRNA comprises a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘974, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Claims 1, 3, 6, 37-39, 41-43 and 45 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 9, 11, 15, 17-22, 30-31, 34-36 and 40-42 of copending Application No. 18248982 (USPGPUB No. 20230383294) in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘982 claims a double stranded RNA (claim 1). The dsRNA includes a 5’ overhang, a 3’ overhang or both (claim 11). One or both of the strands of the dsRNA comprise one or more compounds of Formula I:
PNG
media_image11.png
146
225
media_image11.png
Greyscale
wherein R3 is:
PNG
media_image13.png
348
407
media_image13.png
Greyscale
(claim 20; 22).
The difference between the instant claims and copending ‘982 is that copending ‘982 does not claim a nitrogen in the ring and this is the point of attachment via an amide. However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘982, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
PNG
media_image7.png
157
176
media_image7.png
Greyscale
as R3 in place of GalNAc as taught by copending ‘982. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘982 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘982 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula I.
Regarding claim 41-43 and 45, copending ‘982 claims attachment of the compound to double stranded oligonucleotides wherein the dsRNA comprises a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘982, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Claims 1, 3, 6, 37-39 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-9, 15 and 17-28 of copending Application No. 17641014 (USPGPUB No. 20220372063) in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘014 claims a double stranded RNA comprising a sense and antisense strand that comprises one or more nucleotide analogs of formula I-A:
PNG
media_image14.png
158
263
media_image14.png
Greyscale
wherein R3 can be a heterocycle or a cell targeting agent (claim 1;7).
The difference between the instant claims and copending ‘014 is that copending ‘014 does not claim the instantly claimed R3 However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘014, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
PNG
media_image7.png
157
176
media_image7.png
Greyscale
as R3 in copending ‘014. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘014 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘014 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula I.
Regarding claim 41-43, copending ‘014 claims attachment of the compound to double stranded oligonucleotides wherein the dsRNA comprises a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘014, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Claims 1, 3, 6, 37-39 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-7, 9-21 and 23-39 of copending Application No. 17638339 (USPGPUB No. 20220290156) in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘339 claims a double stranded RNA comprising a sense and antisense strand (claim 1) that comprises one or more compounds of formula I:
PNG
media_image15.png
410
609
media_image15.png
Greyscale
wherein R3 can be formula II
PNG
media_image16.png
347
376
media_image16.png
Greyscale
(claims 11; 14) The dsRNA includes a 5’ overhang, a 3’ overhang or both (claim 11). A 5’ and/or 3’ overhang is claimed (claim 10).
The difference between the instant claims and copending ‘339 is that copending ‘339 does not claim the instantly claimed R3 However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘339, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
PNG
media_image7.png
157
176
media_image7.png
Greyscale
as R3 in copending ‘339. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘339 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘339 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula I.
Regarding claim 41-43, copending ‘339 claims attachment of the compound to double stranded oligonucleotides wherein the dsRNA comprises a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘339, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Claims 1, 3, 6, 37-39 and 41-43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-58 of copending Application No. 19407739 in view of Clark et al., Hasegawa et al. and Manoharan et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘739 claims a compound of formula I (claim 1):
PNG
media_image15.png
410
609
media_image15.png
Greyscale
wherein R3 can be formula III:
PNG
media_image17.png
113
173
media_image17.png
Greyscale
(claim 27). An oligonucleotide comprising one or more compounds of formula II is claimed (claim 35). A double stranded oligonucleotide is claimed (claim 50).
The difference between the instant claims and copending ‘739 is that copending ‘739 does not claim the instantly claimed R3 However, this deficiency is cured by Clark et al., Hasegawa et al. and Manoharan et al.
The teachings of Clark et al., Hasegawa et al. and Manoharan et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘739, Clark et al., Hasegawa et al .and Manoharan et al. and utilize a compound of:
PNG
media_image7.png
157
176
media_image7.png
Greyscale
as R3 in copending ‘739. One skilled in the art would have been motivated to utilize this compound as Clark et al. teaches that a similar compound DGJNAc is an iminosugar analog of GalNAc and Manoharan et al. teaches that both GalNAc and imino sugars are known to be used as monosaccharides for conjugation to oligonucleotides. Hasegawa et al. teaches that replacement of the oxygen with a nitrogen in aldose sugars has been of great interest not only from the point of view of the chemistry involved, but also for their various, biological activities and specifically teaches that compound 12 is a specific derivative of 2-amino sugars with nitrogen in the ring.
Regarding the elected species and claim 1, 3 and 6, for ease of synthesis, the use of a carbonyl to couple the nitrogen with a C(O). There is a reasonable expectation of success as Manoharan et al. suggests that NHC(O) can be utilized to conjugate sugar moieties. Therefore replacement of the sugar moiety and one of the carbons of the compounds of copending ‘739 with C(O)-iminosugar would result in the elected compound.
Regarding claim 37-39, copending ‘739 claims the compounds can be a double stranded oligonucleotide comprising one or more of the compounds of formula I.
Regarding claim 41-43, copending ‘739 claims attachment of the compound to double stranded oligonucleotides wherein the dsRNA comprises a sense and antisense strand. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘739, Clark et al., Hasegawa et al .and Manoharan et al. and attach the compound at any position on the oligonucleotide.
Conclusion
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/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636