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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Election filed January 15, 2026.
Claims 1-12, 14-17. 76, 79, 80 and 98 have been canceled. New claims 99-129 are acknowledged.
Claims 99-129 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on January 15, 2026 is acknowledged. Applicant’s further species election of SEQ ID NOs: 2947 and 3302 as the dsRNA agent in the reply filed on January 15, 2026 is also acknowledged.
Claims 124-129 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 January 15, 2026.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 99-123 have been examined on the merits as detailed below:
Drawings
The Drawings filed March 30, 2023 are acknowledged and have been accepted by the Examiner.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed January 15, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed July 13, 2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed March 30, 2203 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
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 99-123 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 pre-AIA the applicant regards as the invention.
The claims are indefinite because the term, “SNCA” is not clearly defined. Since abbreviations often have more than one meaning, it is suggested that inserting the full name of the Synuclein alpha gene would be appropriate.
Additionally, claim 103 recites the phrase, “wherein at least one of the nucleotide modifications”. There is insufficient antecedent basis for this limitation in the claim because claim 99, from which claim 103 depends, never makes reference to “at least one of the nucleotide modification”. Correction is required.
Also, claim 115 recites the limitation, “conjugated to position 6, counting from the 5’-end of the strand”. Claim 115 is dependent on claim 99, which recites, “a sense strand and an antisense strand”. MPEP § 2173.02 (II) states that one of the purposes of examination under 35 USC § 112, second paragraph is to determine whether the claim apprises one of ordinary skill in the art of its scope and, therefore, serves the notice function required by 35 U.S.C. 112, second paragraph, by providing clear warning to others as to what constitutes infringement of the patent. See, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). See also In re Larsen, No. 01-1092 (Fed. Cir. May 9, 2001) (unpublished). If the language of the claim is such that a person of ordinary skill in the art could not interpret the metes and bounds of the claim so as to understand how to avoid infringement, a rejection of the claim under 35 U.S.C. 112, second paragraph, would be appropriate. See Morton Int’l, Inc. v. Cardinal Chem. Co., 5 F.3d 1464, 1470, 28 USPQ2d 1190, 1195 (Fed. Cir. 1993). In this case, there is no “bright line” by which to evaluate “conjugated to position 6, counting from the 5’-end of the strand”, since it is unclear if the claim is referring the sense strand or the antisense strand. As presented, the term is not clear and precise and is ambiguous, and therefore the claim is indefinite.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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)(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 99, 102-108, 111-114, 118, 122 and 123 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2012/027713 (hereinafter, “Alnylam”) (submitted and made of record on the IDS filed March 30, 2023).
The claims are drawn to a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of SNCA, 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 sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides from the nucleotide sequence 5'- CAUGACAUUUCUCAAAGUUUA-3' of SEQ ID NO: 2947, and the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides from the nucleotide sequence 5'-UAAACUTUGAGAAAUGUCAUGAC-3' of SEQ ID NO: 3302, 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 or the antisense strand is conjugated to one or more lipophilic moieties.
Alnylam is relevant and relied upon in its entirety. Alnylam teach double-stranded ribonucleic acid (dsRNA) for inhibiting expression of alpha-synuclein (SNCA), comprising a sense strand and an antisense strand comprising a region of complementarity to an mRNA encoding SNCA. See Abstract.
Alnylam teach SNCA sense and antisense strand sequences with 2 base overhangs. See Table 2. Alnylam teach a particular SNCA sense strand sequence which comprises at least 17 contiguous nucleotides of SEQ NO: 2947 of the present invention. See Alnylam, Claim 1, Table 2, SEQ ID NO: 133, 5’-GUCAUGACAUUUCUCAAAG-3’, wherein bold and underline comprises at least 17 contiguous nucleotides of SEQ NO: 2947 of the present invention.
Alnylam disclose the dsRNA comprising SEQ ID NO: 133 of their invention comprises all 2'-O-methyl modified pyrimidines and the antisense strand comprises 2'-O-methyl modified pyrimidines. See claims 22-24, for example.
Alnylam also disclose another modification of the dsRNAs featured in the invention involves chemically linking to the dsRNA one or more moieties or conjugates which enhance the activity, cellular distribution or cellular uptake of the dsRNA. Such moieties include but are not limited to lipid moieties such as a cholesterol moiety, cholic acid, a thioether, e.g., beryl-S-tritylthiol, a thiocholesterol, an aliphatic chain, e.g., dodecandiol or undecyl residues.
Alnylam disclose conjugation protocols involve the synthesis of dsRNAs bearing an aminolinker at one or more positions of the sequence.
Alnylam disclose:
In yet another embodiment, the dsRNA for inhibiting expression of SNCA comprises at least one modified nucleotide. In a related embodiment, the modified nucleotide is selected from the group of: a 2'-0-methyl modified nucleotide, a nucleotide comprising a 5'-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. In another related embodiment, said modified nucleotide is chosen from the group of: a 2'-deoxy-2'-fluoro modified nucleotide, a 2'-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2'-amino-modified nucleotide, 2'-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.
Alnylam disclose conjugation protocols involve the synthesis of dsRNAs bearing an aminolinker at one or more positions of the sequence.
Alnylam disclose dsRNAs targeted to the alpha-synuclein (SNCA) gene for inhibiting expression of SNCA in a cell.
Alnylam disclose the invention provides a composition for inhibiting expression of a SNCA gene comprising one of the dsRNAs for inhibiting expression of SNCA and a pharmaceutical formulation.
Claim Rejections - 35 USC § 103
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.
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 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 pre-AIA 35 U.S.C. 103(a) 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.
Claims 99-114 and 116-123 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Publication 20100105134 A1 (hereinafter, “Quay et al.”).
The claims are as described above.
Quay et al. is relevant and relied upon in its entirety. Regarding claims 99-101 and 104-106, Quay et al. teach nucleic acid compounds for inhibiting target gene expression. See Abstract. Quay et al. teach the nucleic acid compounds are meroduplex (mdRNA) molecules (e.g. dsRNA agents) for inhibiting expression of target genes and comprise a sense strand and an antisense strand forming a double stranded region. See claim 1, for example. Quay et al. teach the nucleic acid compounds for inhibiting gene expression of their invention target and inhibit Synuclein alpha (SNCA). See claim 2.
Quay et al. teach a particular dsRNA which comprises SEQ ID NO: 2947 and SEQ ID NO: 3302 of Applicant’s invention. See below, respectively:
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Quay et al. teach, “the dsRNA may further comprise up to 100% phosphorothioate internucleoside linkages”; and “dsRNA will have from one to all ribothymidines and have up to 100% 2′-fluoro”.
Quay et al. also teach the dsRNA of their invention are conjugated to a lipophilic moiety, such as cholesterol. Additionally, the conjugate member is a glyceride lipid conjugate (e.g., a dialkyl glyceride derivatives), vitamin E conjugates, or thio-cholesterols. Also, the conjugate member is a lipophile, a terpene, a protein binding agent, a vitamin, a carbohydrate, or a peptide or peptide conjugate.
Regarding claims 102, 117 and 118, Quay et al. teach, “a conjugate molecule is covalently attached to a dsRNA or analog thereof that decreases expression of a target gene by RNAi via a biodegradable linker”. Quay et al. further teach the linker is a non-nucleotide linker comprised of an abasic nucleotide, polyether, polyamine, polyamide, peptide, carbohydrate, lipid, polyhydrocarbon, or other polymeric compounds.
Regarding claim 103, Quay et al. disclose:
This disclosure features substituted or modified dsRNA molecules, such as phosphate backbone modifications comprising one or more phosphorothioate, phosphorodithioate, methylphosphonate, phosphotriester, morpholino, amidate carbamate, carboxymethyl, acetamidate, polyamide, sulfonate, sulfonamide, sulfamate, formacetal, thioformacetal, or alkylsilyl substitutions.
Regarding claim 107, Quay et al. teach the dsRNA of their invention comprise an overhang of one to four nucleotides.
Regarding claims 108 and 109, Quay et al. teach, “In any of these exemplary methods for using multiply modified dsRNA, the dsRNA may further comprise up to 100% phosphorothioate internucleoside linkages”.
Regarding claims 110-112, Quay et al. teach the dsRNA of their invention are conjugated to a lipophilic moiety, such as cholesterol (e.g. aliphatic compound). Quay et al. further teach the conjugate molecule can be attached at the 3′-end of either the sense strand or the antisense strand. The recited internal positions of conjugation are a matter of design choice made during the course of routine optimization and experimentation.
Regarding claim 113-116, Quay et al. teach the dsRNA of their invention are conjugated to a lipophilic moiety, such as cholesterol. Additionally, the conjugate member is a glyceride lipid conjugate (e.g., a dialkyl glyceride derivatives), vitamin E conjugates, or thio-cholesterols. Also, the conjugate member is a lipophile, a terpene, a protein binding agent, a vitamin, a carbohydrate, or a peptide or peptide conjugate.
Quay et al. teach the lipophilic moieties comprise “alkenyl” refers to an unsaturated branched, straight-chain or cyclic alkyl group having 2 to 15 carbon atoms and having at least one carbon-carbon double bond; and/or alkynyl” as used herein refers to an unsaturated branched, straight-chain, or cyclic alkyl group having 2 to 10 carbon atoms and having at least one carbon-carbon triple bond.
Regarding claims 119-121, Quay et al. teach the dsRNA comprises exemplary monocyclic heterocyclo groups including pyrrolidinyl, pyrrolyl, indolyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, furyl, tetrahydrofuryl, thienyl, piperidinyl, piperazinyl, azepinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, dioxanyl, triazinyl and triazolyl; and methyl phosphonate, alkyl phosphonate, 3′-alkylene phosphonate, 5′-alkylene phosphonate, chiral phosphonate, phosphonoacetate, thiophosphonoacetate, phosphinate, phosphoramidate, 3′-amino phosphoramidate, aminoalkylphosphoramidate, thionophosphoramidate, thionoalkylphosphonate.
Regarding claim 122, Quay et al. teach the dsRNA of their invention are used in decreasing expression of a target gene in a cell. See Abstract.
Regarding claim 123, Quay et al. teach, “The dsRNA compositions of the instant disclosure can be effectively employed as pharmaceutically-acceptable formulations”.
Before the effective filing date of the claimed invention, a dsRNA agent for inhibiting expression of SNCA, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises SEQ ID NO: 2947 of the present invention, and the antisense strand comprises SEQ ID NO: 3302 of the present invention, 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 or the antisense strand is conjugated to one or more lipophilic moieties was taught and suggested by the prior art of Quay et al.
A person of ordinary skill in the art would have been motivated to chemically modify the dsRNA agent Quay et al. for the purpose of improving stability, bioavailability, minimize off-target effects or interferon response of the dsRNA nucleic acid compound for inhibiting gene expression.
A person of ordinary skill in the art would have expected reasonable success to devise the dsRNA agent as instantly claimed using the disclosures of Quay et al. as an exact blueprint for making nucleic acid compounds for inhibiting target gene in a cell or in a subject.
Therefore, the subject matter of claims 99-114 and 116-123 are obvious over Quay et al.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 122 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claimed invention is directed to non-statutory subject matter because Section 33(a) of the America Invents Act (AIA ) reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 122 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101). In the instant case, the claim is drawn to a cell containing a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of SNCA, 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 sense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides from the nucleotide sequence 5'-CAUGACAUUUCUCAAAGUUUA-3' of SEQ ID NO: 2947, and the antisense strand comprises a nucleotide sequence comprising at least 17 contiguous nucleotides from the nucleotide sequence 5'-UAAACUTUGAGAAAUGUCAUGAC-3' of SEQ ID NO: 3302, 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 or the antisense strand is conjugated to one or more lipophilic moieties. Since the claim is not limited to “an isolated cell”, the claim is broadly interpreted to encompass stem cells which ultimately, include a human subject. Applicant is reminded that a claim directed to or including within its scope a human being will not be considered to be patentable subject matter. Section 33(a) of the AIA clearly indicates that no patent may issue on a claim encompassing a human organism, therefore, the claim is rejected under 35 U.S.C. 101.
It is noted that amending the claim such that it is limited to “an isolated cell” would obviate this rejection.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635