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 .
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The earliest effective filing date to which the instant application is entitled is 08/13/2019.
Information Disclosure Statement
Receipt of an information disclosure statement on 09/19/2025 is acknowledged. The signed and initialed PTO-1449 has been mailed with this action.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1, 5, 6, 12, 15, 19, 22, 24, 30, 33, 43, 44, 51, 53, 60, 70, 74, and 75) in the reply filed on 09/19/2025 is acknowledged. Claims 5, 6, 12, and 93 were cancelled in the amended claim set filed 09/19/2025. Claims 97-100 were added in the amended claim set filed 09/19/2025.
Additionally, regarding the species election set forth in the restriction requirement dated 03/21/2025, applicant has elected the nucleotide sequence of SEQ ID NO: 217 and of SEQ ID NO: 627 as the one specific sense strand and its complementary antisense strand, 2’-O-methyl nucleotide modification as the one specific modified nucleotide (from claim 15), position 6 of the sense strand as the one specific position or one specific combination of positions of lipophilic moiety (from claim 44), and C9orf72 ALS/FTD as the one specific disease/disorder (from claim 88). All elections were made without traverse.
Claims 77, 84, 87, 88, 93, and 94 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/19/2025.
Accordingly, claims 1, 15, 19, 22, 24, 30, 33, 43, 44, 51, 53, 60, 70, 74, 75, and 97-100 are pending and under consideration.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at least at page 19, line 30; page 19, line 32; page 20, line 10; and page 20, line 12. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification at least at Tables 13 and 14 are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 1, 15, and 100 are objected to because of the following informalities:
Instant claim 1 recites in part “a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of RPS25, or a salt thereof, wherein the dsRNA agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region, wherein and the antisense strand comprises at least 18 contiguous nucleotides…” (bolded emphasis added). The bolded “and” improperly separates “wherein” and “the antisense strand.” To comport with standard grammatical and/or linguistic conventions, it would be remedial to amend the instant claim language to remove the erroneous “and,” as set forth above.
Instant claim 15 recites in part “at least one of the nucleotide modifications is selected from the group a deoxy-nucleotide modification” (bolded emphasis added). This recitation erroneously omits the phrase of “consisting of” following “the group.” To comport with standard grammatical and/or linguistic conventions, it would be remedial to amend the instant claim language to add the phrase “consisting of” following “the group.”
Instant claim 100 recites “the saturated or unsaturated C16 hydrocarbon chain is conjugated to position 6, counting from the 5’-end of the sense strand.” While not technically improper, for purposes of clarity, it would be remedial to amend the instant claim language to more closely mirror the language of instant claims 43 and 44 such that the claim clearly and unambiguously recites conjugation of the saturated or unsaturated C16 hydrocarbon chain to position 6 on the sense strand, counting from the 5’-end of the sense strand.
Appropriate correction is required.
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 1, 15, 19, 22, 24, 30, 51, 60, 74, 75, and 97 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 2018/0305689 A1 (hereinafter Sætrom).
With regard to claim 1, which recites “a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of RPS25, or a salt thereof, wherein the dsRNA agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region, wherein…the antisense strand comprises at least 18 contiguous nucleotides from the nucleotide sequence [of SEQ ID NOs: 627 or 628], wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand comprise a nucleotide modification, and wherein the sense strand, the antisense strand, or both the sense strand and the antisense strand is conjugated to one or more lipophilic moieties,” Sætrom discloses a dsRNA agent targeting RPS25 that comprises at least 18 contiguous nucleotides from the nucleotide sequence of SEQ ID NO: 627 (paragraphs [0019], [0095], [0100], and [0118]). As shown in the alignment below, SEQ ID NO: 1081448 of Sætrom is 94.7% identical to instant SEQ ID NO: 627, comprising 18 contiguous nucleotides from instant SEQ ID NO: 627, as instantly claimed.
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Sætrom further discloses that the nucleotides of the dsRNA agents taught therein may comprise useful modifications to the sugar, the nucleobase, or the internucleoside linkage and further that the dsRNAs taught therein may be uniformly modified along the entire length of the molecule such that all nucleotides are modified (paragraphs [0116]-[0120]), as instantly claimed. Finally, Sætrom discloses that the modifications taught therein (and addressed above) may comprise conjugation to a lipophilic compound, such as cholesterol (paragraphs [0127] and [0135]), as instantly claimed.
Given that Sætrom discloses the recited sequence of and modifications to the dsRNA agent of claim 1, as set forth above, the dsRNA agents of both instant claim 1 and of Sætrom must be structurally identical and therefore must necessarily have identical functions. See MPEP § 2114 and § 2173.05(g). Thus, Sætrom anticipates each and every limitation of instant claim 1.
With regard to claim 15, which recites “at least one of the nucleotide modifications [of the dsRNA agent of claim 1] is…a 2’-O-methyl nucleotide modification,” as set forth above, Sætrom discloses that the dsRNA agents taught therein may comprise useful modifications to the sugar, the nucleobase, or the internucleoside linkage. The useful dsRNA modifications disclosed in Sætrom include the instantly claimed 2’-O-methyl (2’-OMe) (paragraphs [0116]-[0120]). Thus, Sætrom anticipates each and every limitation of instant claim 15.
With regard to claim 19, which recites “the dsRNA agent…of claim 15, further compris[es] at least one phosphorothioate internucleotide linkage,” as set forth above, Sætrom discloses that the dsRNA agents taught therein may comprise useful modifications to the sugar, the nucleobase, or the internucleoside linkage. The useful dsRNA modifications disclosed in Sætrom include the instantly claimed phosphorohioate linkage incorporated into the phosphate backbone (paragraph [0127]). Thus, Sætrom anticipates each and every limitation of instant claim 19.
With regard to claim 22, which recites “at least one strand [of the dsRNA agent of claim 1] comprises a 3’ overhang of at least 1 nucleotide,” Sætrom further discloses that the dsRNA agents taught therein may include one or more single-stranded nucleotide overhangs of at least one nucleotide (paragraphs [0082], [0096], and [0111]), as instantly claimed. Thus, Sætrom anticipates each and every limitation of instant claim 22.
With regard to claim 24, which recites “the double stranded region [of the dsRNA agent of claim 1] is 18-30 nucleotide pairs in length,” Sætrom further discloses that the duplex of the dsRNA agents taught therein may be hybridized over a length of at least 19 nucleotides (paragraph [0089]), which reads on the instantly claimed range of 18-30 nucleotide pairs. Thus, Sætrom anticipates each and every limitation of instant claim 24.
With regard to claim 30, which recites “each strand [of the dsRNA agent of claim 1] is independently 19-30 nucleotides in length,” Sætrom further discloses that each strand of the duplex of the dsRNA agents taught therein may be 19, 20, 21, or 22 nucleotides in length, and that the strands forming the dsRNA agent may be of equal of unequal lengths (i.e. their lengths are independent) (paragraph [0089]), as instantly claimed. Thus, Sætrom anticipates each and every limitation of instant claim 30.
With regard to claim 51, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 1] is an aliphatic, alicyclic, or polyalicyclic compound,” as set forth above, Sætrom discloses that the dsRNA agents taught therein may comprise conjugation to a lipophilic compound, such as cholesterol or an aliphatic chain (paragraphs [0127] and [0135]), as instantly claimed. Thus, Sætrom anticipates each and every limitation of instant claim 51.
With regard to claim 60, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 1] is conjugated to a nucleobase, sugar moiety, or internucleosidic linkage,” as set forth above, Sætrom discloses that the dsRNA agents taught therein may comprise useful modifications to the sugar, the nucleobase, or the internucleoside linkage (paragraphs [0116]-[0120]). The useful dsRNA modifications disclosed in Sætrom include the instantly claimed lipophilic moiety (paragraphs [0127] and [0135]). Thus, Sætrom anticipates each and every limitation of instant claim 60.
With regard to claim 74, which recites “an isolated cell containing the dsRNA agent, or a salt thereof, of claim 1,” as set forth above, Sætrom anticipates each and every limitation of the dsRNA agent of instant claim 1. Additionally, Sætrom discloses methods of delivering the dsRNA agents taught therein to cells (paragraphs [0270]-[0273]). Sætrom explicitly discloses transfection of the dsRNA agents taught therein into a monolayer of cells, followed by harvesting the same cells comprising said dsRNA agents for analysis (paragraph [0445]). Thus, Sætrom anticipates each and every limitation of instant claim 74.
With regard to claim 75, which recites “a pharmaceutical composition for inhibiting expression of a gene encoding RPS25, comprising the dsRNA agent, or a salt thereof, of claim 1,” as set forth above, Sætrom anticipates each and every limitation of the dsRNA agent of instant claim 1. Additionally, Sætrom discloses that the dsRNA agents taught therein may be provided in a pharmaceutical composition (paragraphs [0013] and [0019]), as instantly claimed. Thus, Sætrom anticipates each and every limitation of instant claim 75.
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With regard to claim 97, which recites “the sense strand [of the dsRNA agent of claim 1] comprises at least 18 contiguous nucleotides from the nucleotide sequence [of SEQ ID NOs: 217 or 218],” as shown in the alignment below, SEQ ID NO: 1081448 of Sætrom is 94.7% identical to instant SEQ ID NO: 217, comprising 18 contiguous nucleotides from instant SEQ ID NO: 217, as instantly claimed.
As set forth above, given that Sætrom discloses the recited sequence of the dsRNA agent of claim 97, as set forth above, the dsRNA agents of both instant claim 97 and of Sætrom must be structurally identical and therefore must necessarily have identical functions. See MPEP § 2114 and § 2173.05(g). Thus, Sætrom anticipates each and every limitation of instant claim 97.
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.
Claims 33, 43, 44, 53, and 98-100 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0305689 A1 (hereinafter Sætrom) as applied to claims 1 and 51 above (see section Claim Rejections - 35 USC § 102), and further in view of US 2015/0197746 A1 (hereinafter Rajeev) and US 2016/0376591 A1 (hereinafter Manoharan).
The disclosure of Sætrom is described above and applied as before. However, this disclosure does not teach the lipophilic moiety identities and conjugation sites of instant claims 33, 43, 44, 53, and 98-100.
With regard to claim 33, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 1] are conjugated to one or more of the internal positions on at least one strand,” as set forth above, Sætrom discloses the dsRNA agent of instant claim 1, including its conjugation to lipophilic moieties. However, Sætrom does not disclose that these lipophilic moieties are specifically conjugated to one or more internal positions on at least one strand. However, this deficiency is cured by Rajeev and Manoharan, which both disclose modified double-stranded interfering RNA (iRNA) agents (Rajeev: abstract, paragraphs [0001] and [0003]; Manoharan: abstract, paragraph [0004]). Rajeev specifically discloses the coupling of ligands such as lipophilic molecules to internal positions on either the sense strand, the antisense strand, or both strands of the double stranded iRNA agents taught therein (paragraphs [0117], [0126], and [0146]). Similarly, Manoharan discloses conjugation of ligands (such as lipophilic moieties including cholesterol) to internal positions of the double stranded iRNA agents taught therein (paragraphs [0244], [0474], and [0484]). Rajeev discloses that the lipophilic ligands taught therein can enhance uptake of the double stranded iRNA agents taught therein (paragraph 0123]), while Manoharan discloses that the lipophilic ligands taught therein facilitate targeting of said double stranded iRNA agents to the liver (paragraph [0436]). Thus, both Rajeev and Manoharan disclose the additional limitations of instant claim 33.
With regard to claim 43, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 1] are conjugated to one or more of the internal positions selected from the group consisting of positions 4-8 and 13-18 on the sense strand, and positions 6-10 and 15-18 on the antisense strand, counting from the 5’-end of each strand,” as set forth above, both Rajeev and Manoharan disclose conjugating lipophilic moieties (i.e. cholesterol) to internal positions of the double stranded iRNA agents taught therein. While neither Rajeev nor Manoharan specifically disclose the instantly claimed modified sense and antisense strand positions, there are a finite number of internal residues on both the sense and antisense strands. Given that Rajeev and Manoharan both teach conjugation of lipophilic moieties to internal residues of double stranded iRNA agents and that there are a finite number of internal residues on both the sense and antisense strands of said double stranded iRNA agents, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to test the effects of conjugating said lipophilic moieties to different internal residues, thereby optimizing the uptake and targeting of said double stranded iRNA agents, as disclosed in Rajeev and Manoharan. See MPEP § 2143(I)(E).
With regard to claim 44, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 43] are conjugated to one or more of the internal positions selected from the group consisting of positions 5, 6, 7, 15, and 17 on the sense strand, and positions 15 and 17 on the antisense strand, counting from the 5’-end of each strand,” as set forth above, both Rajeev and Manoharan disclose conjugating lipophilic moieties (i.e. cholesterol) to internal positions of the double stranded iRNA agents taught therein. While neither Rajeev nor Manoharan specifically disclose the instantly claimed modified sense and antisense strand positions, there are a finite number of internal residues on both the sense and antisense strands. Given that Rajeev and Manoharan both teach conjugation of lipophilic moieties to internal residues of double stranded iRNA agents and that there are a finite number of internal residues on both the sense and antisense strands of said double stranded iRNA agents, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to test the effects of conjugating said lipophilic moieties to different internal residues, thereby optimizing the uptake and targeting of said double stranded iRNA agents, as disclosed in Rajeev and Manoharan. See MPEP § 2143(I)(E).
With regard to claim 53, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 51] contains a saturated or unsaturated C4-C30 hydrocarbon chain,” Manoharan discloses that the conjugated ligands taught therein (i.e. lipophilic moieties (paragraphs [0244], [0425], and [0474])) may comprise saturated or unsaturated carbon moieties that can be C1-C100 (paragraphs [0383]-[0386]). Thus, Manoharan discloses the additional limitations of instant claim 53.
With regard to claim 98, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 53] contains a saturated or unsaturated C6-C18 hydrocarbon chain,” as set forth above, Manoharan discloses that the conjugated ligands taught therein (i.e. lipophilic moieties (paragraphs [0244], [0425], and [0474])) may comprise saturated or unsaturated carbon moieties that can be C1-C100 (paragraphs [0383]-[0386]). Thus, Manoharan discloses the additional limitations of instant claim 98.
With regard to claim 99, which recites “the one or more lipophilic moieties [of the dsRNA agent of claim 98] contains a saturated or unsaturated C16 hydrocarbon chain,” as set forth above, Manoharan discloses that the conjugated ligands taught therein (i.e. lipophilic moieties (paragraphs [0244], [0425], and [0474])) may comprise saturated or unsaturated carbon moieties that can be C1-C100 (paragraphs [0383]-[0385]). Manoharan specifically discloses that the conjugated saturated or unsaturated carbon moiety may be C16 (paragraphs [0385] and [0386]). Thus, Manoharan discloses the additional limitations of instant claim 99.
With regard to claim 100, which recites “the saturated or unsaturated C16 hydrocarbon chain [of the dsRNA agent of claim 99] is conjugated to position 6 [on the sense strand], counting from the 5’-end of the sense strand,” as set forth above, Manoharan discloses that the conjugated ligands taught therein (i.e. lipophilic moieties (paragraphs [0244], [0425] and [0474])) may comprise saturated or unsaturated carbon moieties that can be C1-C100 (paragraphs [0383]-[0385]). Manoharan specifically discloses that the conjugated saturated or unsaturated carbon moiety may be C16 (paragraphs [0385], [0386], and [0425]). Additionally, Manoharan discloses that the conjugated lipophilic ligands taught therein may be attached to internal residues, preferably on the sense strand (paragraph [0484]). While neither Manoharan nor Rajeev specifically disclose the instantly claimed conjugation to position 6 on the sense strand, there are a finite number of internal residues on the sense strand. Given that Rajeev and Manoharan both teach conjugation of lipophilic moieties to internal residues of double stranded iRNA agents (preferably on the sense strand (Manoharan paragraph [0484])) and that there are a finite number of internal residues on the sense strand of said double stranded iRNA agents, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to test the effects of conjugating said lipophilic moieties to different internal residues on the sense strand, thereby optimizing the uptake and targeting of said double stranded iRNA agents, as disclosed in Rajeev and Manoharan. See MPEP § 2143(I)(E).
Given that Sætrom discloses the dsRNA agent conjugated to at least one lipophilic moiety of instant claims 1 and 51 (as set forth above), and that Rajeev and Manoharan both disclose conjugation of lipophilic moieties (which may comprise the hydrocarbons disclosed in Manoharan) to internal residues of double stranded iRNA agents to improve uptake and targeting of said double stranded iRNA agents, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to conjugate the lipophilic moiety/moieties disclosed in Sætrom, Rajeev, and Manoharan to internal residues on either the sense or antisense strand of the double stranded iRNA agent (as disclosed in Rajeev and Manoharan) to predictably improve uptake and targeting of said double stranded iRNA agent. One would have been motivated to make such a modification in order to receive the expected benefit of improving uptake and targeting of said double stranded iRNA agent.
Claim 70 is rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0305689 A1 (hereinafter Sætrom) as applied to claim 1 above (see section Claim Rejections - 35 USC § 102), and further in view of Parmar et al., 2016 (hereinafter Parmar).
The disclosure of Sætrom is described above and applied as before. However, this disclosure does not teach the phosphate or phosphate mimic at the 5’-end of the antisense strand of instant claim 70.
With regard to claim 70, which recites “the dsRNA agent, or a salt thereof, of claim 1, further compris[es] a phosphate or phosphate mimic at the 5’-end of the antisense strand,” Parmar discloses that as double-stranded small interfering RNAs are loaded onto RISC, the sense strand is removed, while the antisense strand remains bound to RISC in a stable complex to direct the cleavage of target RNAs exhibiting sequence complementarity (page 985, column 1, paragraph 1). A phosphate moiety at the 5’-end of the antisense strand is believed to be a critical determinant for RISC loading in the initial step of the RNA interference pathway (page 985, column 1, paragraph 1). Parmar further discloses that the addition of a metabolically stable phosphate mimic (5’-(E)-vinylphosphonate) at the 5’-end of the antisense strand improved the in vivo activity of the interfering RNA, as it appears that the phosphate mimic improves RISC loading and metabolic stability (abstract; page 989, column 1, paragraph 3). Thus, Parmar discloses the additional limitations of instant claim 70.
Given that Sætrom discloses the dsRNA agent of instant claim 1 (as set forth above), and that Parmar discloses that the addition of a metabolically stable phosphate mimic at the 5’-end of the antisense strand improves in vivo activity of double-stranded small interfering RNA, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify the dsRNA agent disclosed in Sætrom to comprise metabolically stable phosphate mimic at the 5’-end of the antisense strand (as disclosed in Parmar) to predictably improve in vivo activity of the dsRNA agent disclosed in Sætrom. One would have been motivated to make such a modification in order to receive the expected benefit of improving in vivo activity of the dsRNA agent disclosed in Sætrom.
Conclusion
No claims are allowed.
Claims 1, 15, and 100 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Sarah E Allen whose telephone number is (571)272-0408. The examiner can normally be reached M-Th 8-5, F 8-12.
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/SARAH E ALLEN/Examiner, Art Unit 1637
/J. E. ANGELL, Ph.D./Primary Examiner, Art Unit 1637