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 II, encompassing claims 15, 16, 18, 20, 21, 23, 25, 28, 34, and 35, the antisense strand of P1 b18 as and the sense strand of P1 b12 s in the reply filed on 28 January 2026 is acknowledged.
Therefore, claims 1-4, 7, 36, 37, 40, 42, and 43 are canceled. Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, and 35 are amended; and claims 45-54 are newly added. Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are pending and being examined on the merits.
Priority
The application claims priority to application 63/342,393 filed 05/16/2022.
Information Disclosure Statement
The information disclosure statement filed 06/06/2024 and 01/21/2026 have been considered.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
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 34-35 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.
Claims 34 and 35 contains antisense and sense strand chemical modification patterns. The specification describes every symbol except “N”. Therefore, the scope of the symbol “N” cannot be explicitly determined. For examination purposes, “N” will be interpreted as meaning any nucleotide.
Claim Rejections - 35 USC § 102
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 15, 16, 18, 20, 21, 23, 25, 28, and 45-52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Milstein (WO 2020/132227 A2).
Regarding claim 15, Milstein teaches a double-stranded RNA (dsRNA) molecule comprising an antisense strand and a sense strand forming an RNA interference duplex [see, e.g., definitions and RNAi agent disclosures throughout the specification, including pages 22-25 and 40; abstract; claim 1]. Milstein further teaches chemically modified nucleotides including 2’-O-alkyl nucleotides, 2’-C-alkyl modified nucleotides, alkoxyalkyl modifications, alkylamino modifications, and alkyl substituents containing C1-C10 alkyl groups [pages 22-25; 59]. Thus, Milstein teaches a dsRNA molecule wherein the antisense strand comprises at least one alkyl modification. Milstein further teaches alkyl-containing nucleotide modifications including 2’-O-hexadecyl, alkyl-substituted sugar modifications, cyclobutyl sugar mimetics, and alkyl groups including methyl, ethyl, propyl, isopropyl, butyl, pentyl, and hexyl attached to RNA nucleotides and sugars [pg. 92, lines 1-7].
Regarding claim 16, 18 and 45, Milstein teaches antisense strands having lengths overlapping and encompassing 15-2-5 nucleotides, including disclosed strand lengths of approximately 15-30 nucleotides and related overlapping ranges [claim 1; pg. 30, lines 18-25].
Regarding claim 20, Milstein teach that each of the sense strand and the antisense strand of the RNAi agent includes a 5'-terminus and a 3'-terminus, and the RNAi agent includes between one and four 2'-C-alkyl-modified nucleotides; Optionally, the 2'-C-alkylmodified nucleotide is a 2'-C16-modified nucleotide [pg. 22, lines 21-27]. Milstein teaches modified nucleotides positioned throughout the antisense strand and specifically teaches modified nucleotides at antisense positions 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 from the 5’ end of the antisense strand [pg. 23; lines 6-15].
Regarding claims 21 and 47, Milstein teach numerous non-alkyl modified nucleotides, including 2’-fluoro nucleotides, GNA nucleotides, 2'-O-methyl, constrained nucleotides, and other modified nucleotides distinct from the disclosed alkyl-modified nucleotides [pg. 22, line 1 – pg. 23, line 15].
Regarding claims 23, 25, and 48, Milstein teaches that the RNAi agent comprising 4-6 phosphorothioate linkages [pg. 76; pg. 119, lines 1-16].
Regarding claims 28 and 51, Milstein teaches that at least one strand includes a 3' overhang of at least 1 or 2 nucleotides [pg. 7, lines 19-20; pg. 32, lines 6-11]
Regarding claim 46, Milstein teaches sense strand comprises at least 15 contiguous nucleotides [claim 1].
Regarding claim 49, Milstein teaches that the term "modified nucleotide" refers to a nucleotide having a modified sugar moiety [pg. 37, lines 2-4].
Regarding claim 50, Milstein teaches blunt end dsRNA molecules [pg. 40, lines 6-13].
Regarding claim 52, Milstein teach where the that the overhangs can be up to 5 nucleotides in length [pg. 39, lines, 26-28].
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, 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 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, 45-54 are rejected under 35 U.S.C. 103 as being unpatentable over Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2).
Regarding claim 15, Milstein teaches a double-stranded RNA (dsRNA) molecule comprising an antisense strand and a sense strand forming an RNA interference duplex [see, e.g., definitions and RNAi agent disclosures throughout the specification, including pages 22-25 and 40; abstract; claim 1]. Milstein further teaches chemically modified nucleotides including 2’-O-alkyl nucleotides, 2’-C-alkyl modified nucleotides, alkoxyalkyl modifications, alkylamino modifications, and alkyl substituents containing C1-C10 alkyl groups [pages 22-25; 59]. Thus, Milstein teaches a dsRNA molecule wherein the antisense strand comprises at least one alkyl modification. Milstein further teaches alkyl-containing nucleotide modifications including 2’-O-hexadecyl, alkyl-substituted sugar modifications, cyclobutyl sugar mimetics, and alkyl groups including methyl, ethyl, propyl, isopropyl, butyl, pentyl, and hexyl attached to RNA nucleotides and sugars [pg. 92, lines 1-7]. Milstein teaches the modification of dsRNA to enhance stability or other beneficial characteristics [pg. 56, lines 20-25]. Milstein teaches a dsRNA molecule can be optimized for RNA interference by incorporating thermally destabilizing modifications in the seed region of the antisense strand [pg. 99, lines 7-9].
Regarding claim 16, 18 and 45, Milstein teaches antisense strands having lengths overlapping and encompassing 15-2-5 nucleotides, including disclosed strand lengths of approximately 15-30 nucleotides and related overlapping ranges [claim 1; pg. 30, lines 18-25].
Regarding claim 20, Milstein teach that each of the sense strand and the antisense strand of the RNAi agent includes a 5'-terminus and a 3'-terminus, and the RNAi agent includes between one and four 2'-C-alkyl-modified nucleotides; Optionally, the 2'-C-alkylmodified nucleotide is a 2'-C16-modified nucleotide [pg. 22, lines 21-27]. Milstein teaches modified nucleotides positioned throughout the antisense strand and specifically teaches modified nucleotides at antisense positions 1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, and 23 from the 5’ end of the antisense strand [pg. 23; lines 6-15].
Regarding claims 21 and 47, Milstein teach numerous non-alkyl modified nucleotides, including 2’-fluoro nucleotides, GNA nucleotides, 2'-O-methyl, constrained nucleotides, and other modified nucleotides distinct from the disclosed alkyl-modified nucleotides [pg. 22, line 1 – pg. 23, line 15].
Regarding claims 23, 25, and 48, Milstein teaches that the RNAi agent comprising 4-6 phosphorothioate linkages [pg. 76; pg. 119, lines 1-16].
Regarding claims 28 and 51, Milstein teaches that at least one strand includes a 3' overhang of at least 1 or 2 nucleotides [pg. 7, lines 19-20; pg. 32, lines 6-11]
Regarding claim 46, Milstein teaches sense strand comprises at least 15 contiguous nucleotides [claim 1].
Regarding claim 49, Milstein teaches that the term "modified nucleotide" refers to a nucleotide having a modified sugar moiety [pg. 37, lines 2-4].
Regarding claim 50, Milstein teaches blunt end dsRNA molecules [pg. 40, lines 6-13].
Regarding claim 52, Milstein teach where the that the overhangs can be up to 5 nucleotides in length [pg. 39, lines, 26-28].
Ladine teaches that the siRNA in the gene silencing composition can be modified into increase specificity and/or stability [00106]. Ladine teaches increasing the efficiency of
producing biotherapeutic agents is through biochemical optimization [0004-0006]. Ladine teaches siRNA molecules containing 2’-O-aliphatic modifications and expressly teaches that the aliphatic group may be an alkyl group, including 2’-O-methyl, 2’-O-ethyl, 2’-O-propyl, 2’-O-isopropyl, 2’-O-butyl, and 2’-O-isobutyl modifications [00110]. Ladine teaches where the siRNA pair is a 19 base pair duplex and where the sense and antisense strand ranges in size from 18 to 30 nucleotides [claim 6, 00147]. Ladine teaches where the siRNA can include a 2'-O-aliphatic modification on the first sense and second sense nucleotides, a 2 '-O-aliphatic modification on none or at least one through all of the sense pyrimidine nucleotides, a 2'-halogen modification on at least one through all of the antisense pyrimidine nucleotides [00110]. Ladine expressly teaches: 2’-O-butyl modifications; 2’-O-methyl modifications; 2’-fluoro (halogen) modifications; and mixed modification architectures in which different modification types are present within the same duplex [00109-00112]. Ladine further teaches that there is no requirement that each modified nucleotide contain the same modification and teaches use of methyl modifications throughout one strand and fluoro modifications throughout another strand [00111]. Ladine teaches that alkyl-modified overhang nucleotides and teaches that modifications may be present on multiple nucleotides throughout the duplex and overhang regions [00103, 00147, 00110-00111].
Regarding claim 15, it would have been obvious to employ Ladine’s expressly taught alkyl-modified nucleotides within Milstein’s chemically modified RNAi duplexes because both references seek to improve stability, potency, and pharmacological performance of siRNA molecules through nucleotide modification.
Regarding claim 20, because Ladine expressly teaches alkyl modifications at specific antisense positions and throughout antisense pyrimidines, a person of ordinary skill in the art would have found it obvious to place Milstein’s alkyl-modified nucleotides at antisense positions within the claimed 1-25 position range.
Regarding claim 34, it would have been obvious to combine the known butyl, methyl, and fluoro modifications taught by Ladine with the modification-placement teachings of Milstein to arrive at the claimed modification architecture because both references teach optimization of siRNA medicinal chemistry through positional placement of chemically modified nucleotides. The claimed modification arrangement represents an obvious selection from the finite set of modification chemistries and modification locations taught by the combined references.
Regarding claims 53-54, it would have been obvious to a skilled artisan that the overhangs in the siRNA of Milstein could comprise 2, 3, 4, or 5 alkyl modifications and that selecting two, three, four, or five modified overhang nucleotides would have represented routine optimization of a known result-effective variable. This modification also would have been obvious to a person of ordinary skill in the art seeking to optimize stability and pharmacological properties of the siRNA duplex given the teaching. A skilled artisan would be motivated to make the modification with an expectation of success since both Milstein and Ladine each teach modified siRNA molecules with overhangs.
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 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 26, 27, 32, 45, 68, 71, 72, 78, 83-88, 156, 175, 178, and 179 of copending Application No. 18430581 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 32, 45, 54, 57, 61, 67, 71, 75, 147, and 164 of copending Application No. 18393044 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 45, 78, 83, 85, 134, 157-158, and 192-199 of copending Application No. 18142852 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 45, 78-79, 83, 85, 134, 157-158, and 192-199 of copending Application No. 18134167 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 45, 79, 85, 157-158, and 177-184 of copending Application No. 18120030 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 45, 68, 187-193, and 195-203 of copending Application No. 18094695 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 45, 68, 71-72, 85, 89, 134, 157-158, 176, 179-181, and 190 of copending Application No. 18082654 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 45, 68, 192, 194-199, 201-204, and 206-211 of copending Application No. 18082657 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 32, 45, 50, 52, 68, 121, 132, 138-139, 141, 166, 182, and 189-193 of copending Application No. 17982993 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 58, 70-73, 77-78, and 82-103 of copending Application No. 17846526 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of US Patent US12077758B2 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The patent does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 87, 158, 190-182, and 194-204 of copending Application No. 17704915 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 32, 37-38, 45, 52, 66, 69, and 151-168 of copending Application No. 17532636 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 5, 22, 34, 38, 40, 47-48, 69, 80, 86, and 188-204 of copending Application No. 17391475 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-7, 15, 20, 26, 29, 38, 40, 44-45, 48, 50, 52, 54, 56, 57, 62-70, 72-77, 79-82, and 84-94 of copending Application No. 17377632 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 87, 97, 157-158, 162, 166-167, 176, 198-199, 202-206, 208, and 201-228 of copending Application No. 17235153 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of US Patent US 12258566 B2 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The patent does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46, 92, 122, 129-133, and 135-146 of copending Application No. 16833107 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 46, 55, 56, 68-70, 72, 89, 122, 125-128, and 131-134 of copending Application No. 16818563 in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The copending application does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the copending claims. To the extent that there are limitations that are not provided for by the copending claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the copending claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
This is a provisional nonstatutory double patenting rejection.
Claims 15, 16, 18, 20, 21, 23, 25, 28, 34, 35, and 45-54 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-41 of US Patent 9809817 B2in view of Milstein (WO 2020/132227 A2) in view of Ladine (WO 2009/012173 A2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claim claims a compound I comprising a double stranded nucleic acid comprising 15 to 35 bases in length, a sense strand, and an antisense strand where the sense strand and antisense strand each comprises chemical modifications and the compound comprises an alkyl chain and has a spacer comprising an alkyl chain. The patent does not specifically teach that the antisense stand comprises at least one alkyl modification.
The teachings of Milstein and Ladine are discussed above.
It would have been obvious to employ Ladine’s and Milstein’s expressly taught alkyl-modified nucleotides on the antisense strand of the compound for the advantage of improving stability of the compound. One of ordinary skill would have been motivated to make the modification with a reasonable expectation of success because both references seek to improve stability, potency, and pharmacological performance of siRNA (i.e., dsRNA molecules) molecules through nucleotide modification.
For additional limitations of the instant claims, see the additional teachings of the patented claims. To the extent that there are limitations that are not provided for by the patented claims, the teachings of Milstein and Ladine are discussed above. It would have been obvious to have modified the subject matter of the patented claims to arrive at the subject matter of the instant claims for substantially the same reasons as discussed above in view of the teachings of these references.
Conclusion
No claims allowed.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
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