DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on April 14 2026 is acknowledged. Claims 1, 11 and 42-62 are pending in the application and are being examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a 371 of PCT/IB2021/000351 (05/24/2021) which claims benefit of 63/029,060 (05/22/2020) as set forth in the filing receipt issued on March 21 2023.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on September 18 2023, November 3 2023, October 10 2024 and April 14 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 11 is objected to because of the following informalities :the acronyms “LNA” and “BNA” are not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claims. For the purposes of examination, the term “LNA” is interpreted to mean locked nucleic acid and the term “BNA” is interpreted to mean bridged nucleic acid.. Appropriate correction is required.
Claim 52 is objected to because of the following informalities :the acronym “MOE” is not defined in the claims. When an acronym is used in a claim set, it should be defined the first time it appears in the claim. For the purpose of examination the term “MOE” is interpreted to mean methoxyethyl. Appropriate correction is required.
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 60-61 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 60-61 as currently written are vague and indefinite. Claim 60 is directed to a composition comprising a plurality of nucleotides each of which is independently an oligonucleotide of claim 1, wherein: oligonucleotides of the plurality share a common constitution and 50-100% of all oligonucleotides in the composition that share the common constitution are oligonucleotides of the plurality. Claim 61 further limits the as stating 80-100% of all oligonucleotides in the composition that share the common constitution are oligonucleotides of the plurality. These claims are confusing. Firstly, the specification provides no limiting definition of “common constitution”. Therefore, the examiner is interpreting common constitution to mean the same structure (i.e. nucleotide sequence) but would allow for differences in stereochemistry or salt form. But even using that as the definition of common constitution claims 60-61 are confusion because on one hand the claim recites oligonucleotides of the plurality share a common constitution which means that the oligonucleotides of the plurality all have 100% common constitution but then the claim also recites that 50-100% of all oligonucleotides in the composition that share the common constitution are oligonucleotides of the plurality. This is of a different scope. How can the oligonucleotides of the plurality share a common constitution but then also 50% of the oligonucleotides that share the common constitution be the oligonucleotides of the plurality. The metes and bounds of the claim are unclear.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 11, 42-48 and 52-62 are rejected under 35 U.S.C. 103 as being unpatentable over Vargeese et al. (WO2018223056, cited on PTO Form 1449).
Applicant Claims
The instant application claims a double-stranded oligonucleotide, wherein the double stranded oligonucleotide comprising a guide strand and a passenger strand, wherein: a) the guide strand can hybridize to a target transcript and comprises an internucleotidic linkage having the structure of
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between the third (+3) and fourth (+4) nucleotides from the 5’-end of the guide strand, wherein the linkage phosphorus is in the Sp configuration; b) the passenger strand comprises one or more backbone chiral centers in the Rp or Sp configuration and c) the guide strand and the passenger strand each independently has a length of 15 to 49 nucleotides.
The recitation selected from…and is interpreted as allowing for a single, isolated choice (i.e. excluding combinations). This recitation is interpreted as forming a closed list as the recitation is not preceded by the recitation one or more. This language occurs in claims 11
The recitation “common constitution” is interpreted as referring to the same nucleotide sequence but the stereochemistry and/or salt form can be different.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Vargeese et al. is directed to oligonucleotide compositions and methods of use thereof. Taught are RNAi agent which are either single-stranded or double-stranded oligonucleotides. The RNAi agent may specifically bind to an RNA target (e.g. a transcript of a target gene). Structures include siRNA, dsRNA, etc. (paragraph 0254). It is taught that siRNA are double-stranded RNA molecules wherein each strand is about 21 nucleotides long. The two strands are reportedly an antisense (or “guide) strand, which recognizes and binds to a complementary sequence in the target transcript and a sense (or “passenger strand), which is complementary to the antisense strand (paragraph 00335). Taught is an oligonucleotide composition comprising a plurality of oligonucleotides which share a common base sequence; a common pattern of backbone linkages; common stereochemistry independently at least 1-30, 34, 40, 45 or 50 chiral internucleotidic linkages (“chirally controlled internucleotidic linkages”); which composition is chirally controlled in that level of plurality of oligonucleotides in the composition is predetermined (paragraph 0055). The chiral internucleotidic linkages are independently Rp or Sp (paragraph 0056). In some embodiments 1-100% of chiral internucleotidic linkages are chirally controlled (paragraph 0059).Up 99% of all oligonucleotides are of or comprise a common base sequence (paragraph 0062). It is taught oligonucleotide properties can be modulated through chemical modification. Specifically properties such as activities, toxicities, etc. can be modulated through chemical modifications of sugars, nucleobases and/or internucleotidic linkages (paragraph 0037). A specifically taught internucleotidic linkage is a non-negatively charged internucleotidic linkage which is a cyclic guanidine moiety of structure:
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. In some embodiments this linkage (i.e. comprising a cyclic guanidine moiety) is chirally controlled. Embodiments include at least one neutral internucleotidic linkage and at least one phosphorothioate internucleotidic linkage (paragraph 0038; claim 55; 00545; 00572; 00582). The cyclic guanidine moiety is sterochemically controlled (paragraph 00546). Taught is at least one non-negatively charged internucleotidic linkage wherein its linkage phosphorus is in the Sp configuration (paragraph 00582; 001459). Shown are various patterns of backbone linkages. These include an internucleotidic linkage which is not a phosphodiester at the linkage between the 3rd and 4th nucleotide as well as the 10th to 11th (paragraph 00598). Wherein the claims recite that the internucleotidic linkage immediately 3’ of the third nucleoside from the 5’ end is a non-natural internucleotidic linkage (claims 292-294). The neutral internucleotidic linkage improves the activity, delivery and/or stability of an oligonucleotide and/or the ability of an oligonucleotide to perform endosomal escape (paragraph 001459). Lengths of the oligonucleotide include 14-30 nt (paragraph 001464-001465). Properties of antisense oligonucleotides such as binding affinity, sequence specific binding to complementary RNA, stability to nucleases, are affected by, inter alia, chirality of the backbone phosphorus atoms (paragraph 00329).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Vargeese et al. teaches double stranded RNA which include a neutral internucleotidic linkage which is the same as instantly claimed, Vargeese et al. does not expressly teach a dsRNA with the instantly claimed internucleotidic linkage between the 3rd and 4th nucleotides from the 5’-end of the guide strand wherein the linkage phosphorus is in the Sp configuration.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 1, It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to form a double stranded RNA with a neutral internucleotidic linkage
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in the guide (aka antisense) strand. One skilled in the art would have been motivated to utilize this linkage as Vargeese et al. expressly teaches these linkages in the RNAi. Since Vargeese et al. teaches the RNAi can be a dsRNA, there is a reasonable expectation of success. Regarding the claimed configuration, Vargeese et al. teaches that the cyclic guanidine (i.e. the structure above) can be chirally controlled and be in the Sp configuration. Since there are only two choices (Rp and Sp), one skilled in the art would envision utilizing the Sp configuration. Since there are only two configurations and Vargeese et al. expressly teaches including phosphorothioate linkages which are either Rp or Sp, one skilled in the art would recognize that either can be utilized. Regarding the claimed length of the oligonucleotide, Vargeese et al. teaches a range falling within the scope. Therefore, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2143 KSR International Co. v. Teleflex Inc., 550 US 398, 82 USPQ 2d 1385 (2007).
Regarding claims 11 and 42, taught is a 5’-terminal phosphate and the first nucleoside is 2’-OMe (paragraph 001996). While this is expressly taught with a single-stranded RNAi agent, as taught these single-stranded RNA can be complementary to a second oligonucleotide to form a duplex (see pages page 991-1083; example embodiments paragraph 003176). The first nucleotide having a phosphate and 2’-OMe reads on this structure of claim 11:
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wherein R is OMe.
Regarding claims 43-45 and 58-59 , Vargeese et al. teaches that in embodiment 1018 that the oligonucleotides exists as salts such as sodium salt. See also paragraph 00244; 00354.
Regarding claim 46-48, Vargeese et al. teaches various different modification patterns. These include all of the nucleotides having the internucleotidic linkage as well as embodiments that include the nucleotide between 3rd and 4th as well as between the 10th and 11th having a neutral internucleotidic linkage. Since these linkages are taught by Vargeese et al. as providing advantages such as improving the activity, delivery and/or stability of an oligonucleotide and/or the ability of an oligonucleotide to perform endosomal escape, one skilled in the art would manipulate the number and location of the linkages in order to achieve the optimal effect. This includes including the internucleotidic linkage in both the guide (antisense) strand as well as the passenger (sense) strand. The examiner notes the open claim language of comprising does not exclude the linkages at additional positions other than those expressly claimed.
Regarding claims 52-54, Vargeese et al. teaches that non-liming examples of sugars with 2’-modifications include 2’-F, LNA, 2’-OMe and 2’-MOE modifications (paragraph 0049). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize any of the specifically taught modifications as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007). Since modifications in general are taught as being useful to modulate the properties of the oligonucleotide, one skilled in the art would have been motivated to manipulate the modifications utilized in order to achieve the desired effect.
Regarding claims 56-57, Vargeese et al. teaches the oligonucleotide can be conjugated with an additional chemical moiety such as a moiety that binds to asialoglycoprotein receptor or ASGPR, e.g. a GalNAc moiety which can have a significant impact on oligonucleotide properties or activities. These moieties provide for targeted delivery of the oligonucleotide to the liver (paragraph 0003; 002470, 002474; 002484).
Regarding claims 60-61, Vargeese et al. teaches compositions comprising a plurality of oligonucleotides which share a common base sequence (aka common constitution) (paragraph 0060) and all oligonucleotides provided in a composition that are of or comprise a common base sequence are at least 99% of all oligonucleotides in the composition (paragraph 0062).
Regarding claim 62, Vargeese et al. teaches a pharmaceutically acceptable carrier which is involved in carrying or transporting the subject compound from one organ to another (paragraph 00243). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a pharmaceutically carrier with the dsRNA in order to transport or carrying the compound as taught by Vargeese et al.
Claims 49-51 are rejected under 35 U.S.C. 103 as being unpatentable over Vargeese et al. as applied to claims 1, 11, 42-48 and 52-62 above and in view of Manoharan et al. (WO2019126651, cited on PTO Form 1449).
Applicant Claims
The instant application claims the passenger strand (sense strand) comprises one or more phosphorothioate linkages in the Sp configuration.
The instant application claims the guide strand (antisense strand) comprises one or more phosphorothioate internucleotidic linkages in the Sp configuration.
The instant application claims the guide strand (antisense strand) comprises a phosphorothioate internucleotidic linkage in the Sp configuration between the 5' terminal (+1) nucleotide and the immediately downstream (+2) nucleotide and a phosphorothioate internucleotidic linkage in the Rp configuration between the +2 nucleotide and the immediately downstream (+3) nucleotide.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Vargeese et al. are set forth above. Vargeese et al. teaches double stranded oligonucleotides with phosphorothioate linkages and chiral control.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Vargeese et al. suggests double stranded oligonucleotides with phosphorothioate linkages and chiral control, Vargeese et al. does not expressly teach a double stranded oligonucleotide with Sp configurations. However, these deficiencies are cured by Manoharan et al.
Manoharan et al. is directed to chirally-enriched double-stranded RNA agents. Claimed are chirally modified double stranded RNA (dsRNA) comprising a sense strand and antisense strand having 14 to 240 nucleotides wherein the sense strand comprises one or more terminal, chirally-modified internucleotide linkages at the 5’ end; and the antisense strand comprises one or more terminal, chirally-modified intemucleotide linkages at the 5’ end and one or more terminal, chirally-modified intemucleotide linkages at the 3’ end (claim 1). The terminal, chiral modification occurs at the first intemucleotide linkage at the 3’ end of the antisense strand, and the linkage phosphorus atom is in Sp configuration (claim 4). A terminal, chiral modification occurs at the first intemucleotide linkage at the 5’ end of the sense strand, and the linkage phosphorous atom is in either Rp configuration or Sp configuration (claim 6). One or more chirally-modified internucleotide linkages (e.g. at terminal) at 5’ end. In one embodiment, a chiral modification occurs at the first internucleotide linkage from the 6’ end of the anti-sense strand and the linkage phosphorus atom is in the Sp configuration. In one embodiment a chiral modification occurs at the second internucleotide linkage from the 5’ end of the antisense stand and the linkage is in the Rp configuration (page 6). In one embodiment, chemical modifications occurs at the first and second internucleotide linkages from the 5’ end of the antisense strand and the configuration is in combination of Rp and Sp such as SpRp (page 7). The dsRNA agents can be conjugated to a ligand (page 2). These stereochemical solutions for dsRNA agents optionally conjugated to at least one ligand are advantageous for inhibition of target gene expression as well as RNAi compositions suitable for therapeutic use (page 43). The embodiments demonstrate that the dsRNA agents can show different stability and/or activity from each other. For instance, stability improvements achieved through inclusion of chirally-modified internucleoside linkages at site specific locations can be comparable to, or even better than those achieved through use of modified backbone linkages, bases and/or sugars (page 44).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Vargeese et al. and Manoharan et al. and utilize one or more Sp linkages in the passenger and/or guide strand. Both Vargeese et al. and Manoharan et al. are directed to dsRNA of similar length which contain chiral modifications. Both references suggest that either Sp or Rp configurations can be utilized. Manoharan et al. teaches stability improvements achieved through inclusion of chirally-modified internucleotidic linkages at site specific locations can be comparable to, or even better than those achieved through use of modified backbone linkages, bases and/or sugars. Therefore, one skilled in the art would manipulate and modify the type and locations of the linkages as well as modifications in order to achieve the desired stability and interference.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 11, 42, 46-54 and 60-61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18667824 (USPGPUB No. 20240384273). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant application claims a double-stranded oligonucleotide, wherein the double stranded oligonucleotide comprising a guide strand and a passenger strand, wherein: a) the guide strand can hybridize to a target transcript and comprises an internucleotidic linkage having the structure of
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between the third (+3) and fourth (+4) nucleotides from the 5’-end of the guide strand, wherein the linkage phosphorus is in the Sp configuration; b) the passenger strand comprises one or more backbone chiral centers in the Rp or Sp configuration and c) the guide strand and the passenger strand each independently has a length of 15 to 49 nucleotides.
Copending ‘824 claims a double-stranded RNAi (dsRNAi) agent comprising a guide strand and a passenger strand wherein :
a) the guide strand is complementary or substantially complementary to an HSD17B13 target RNA sequence, and comprises:
backbone phosphorothioate chiral centers in Sp configuration between the 3' terminal nucleotide and the penultimate (N-1) nucleotide and as between the penultimate (N-1) nucleotide and the immediately upstream (N-2) nucleotide,
ii. backbone phosphorothioate chiral centers in Rp, Sp, or alternating configurations between the 5' terminal (+1) nucleotide and the immediately downstream (+2) nucleotide and between the +2 nucleotide and the immediately downstream (+3) nucleotide;
iii. one or more backbone phosphorothioate chiral centers in Rp or Sp configuration upstream of backbone phosphorothioate chiral centers in Sp configuration between the 3' terminal nucleotide and the penultimate (N-1) nucleotide and as between the penultimate (N-1) nucleotide and the immediately upstream (N-2) nucleotide; and/or
iv. one or more backbone phosphorothioate chiral centers in Rp or Sp configuration between the 5' terminal (+1) nucleotide and the immediately downstream (+2) nucleotide and between the (+2) nucleotide and the immediately downstream (+3) nucleotide, as well as between one or both of: (a) the (+3) nucleotide and the (+4) nucleotide; and (b) the (+5) nucleotide and the (+6) nucleotide;
b) the guide strand comprises one or more Rp, Sp, or stereorandom non-negatively charged internucleotidic linkage occurs between any two adjacent nucleotides between the second (+2) nucleotide relative to the 5' terminal nucleotide of the guide strand and the penultimate 3' (N-1) nucleotide of the guide strand, where N is the 3' terminal nucleotide;
c) the guide strand comprises a 2' modification, of the 3' nucleotide of a nucleotide pair linked by an Rp, Sp, or stereorandom non-negatively charged internucleotidic linkage;
d) the passenger strand comprises one or both of: i. 0-n Rp, Sp, or stereorandom non-negatively charged internucleotidic linkages, where n is about 1 to 49, and ii. one or more backbone chiral centers in Rp or Sp configuration,
e) each strand of the dsRNAi agent independently has a length of about 15 to about 49 nucleotides; f) the dsRNAi is capable of directing HSD17B13-specific RNA interference (claim 1). Claimed is a chirally controlled oligonucleotide composition comprising ds oligonucleotides characterized by a common base sequence and length (claim 2). Claimed is a neutral backbone internucleotidic linkage:
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which is the same as instantly claimed.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to form a dsRNA with a neutral backbone internucleotidic linkage. One skilled in the art would have been motivated to form a dsRNA with this linkage as copending ‘824 claims this linkage.
Regarding the claimed configurations and modifications, copending ‘824 claims either an Rp, Sp or both. Copending’ 824 also claims the same modifications to the sugar bases (i.e. 2’-F, 2’-OMe). One skilled in the art would manipulate the location and type of modifications and choose any of those specifically claimed in copending ‘824. It is noted that copending ’824 claims and/or suggesting one or all of the various configurations can be utilized. Since copending ‘824 claims the non-negatively charged internucleotidic linkage occurs between any two adjacent nucleotides between the second nt relative to the 5’ and the penultimate 3’ nt, this suggests the linkage as claimed in claim 5 as between the 10th and 11th nt.
Regarding claim 11 and 42, copending ‘824 claims the same bases in claim 3.
Claims 43-45, 55-59 and 62 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18667824 (USPGPUB No. 20240384273) as applied to claims 1, 11, 42, 46-54 and 60-61 above and in view of Vargeese et al. (WO2018223056, cited on PTO Form 1449). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims the double stranded oligonucleotide is a pharmaceutically acceptable salt.
The instant application claims a carbohydrate or lipid moiety is connected to the double stranded oligonucleotide.
The instant application claims a composition with a pharmaceutically acceptable carrier.
The claims of copending ‘824 are set forth above. While Copending ‘824 claims a dsRNA, copending ‘824 does not claim a salt. While copending ‘824 claims a composition, copending ‘824 does not expressly claim a carrier. However, these deficiencies are cured by Vargeese et al.
Regarding claims 43-45 and 58-59 , Vargeese et al. teaches that in embodiment 1018 that the oligonucleotides exists as salts such as sodium salt. See also paragraph 00244; 00354. Vargeese et al. teaches that phosphate linkages exist as a salt form at physiological pH (paragraph 0037). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘824 and Vargeese et al. and utilize a salt form of the oligonucleotide as these are forms of phosphate linkages which are known to exist at physiological pH as taught by Vargeese et al.
Regarding claim 62, Vargeese et al. teaches a pharmaceutically acceptable carrier which is involved in carrying or transporting the subject compound from one organ to another (paragraph 00243). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘824 and Vargeese et al. and utilize a pharmaceutically carrier with the dsRNA in order to transport or carrying the compound as taught by Vargeese et al.
Claims 1, 11, 42-54 and 58-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54-71 of copending Application No. 19314882 (USPGPUB No. 20250382617). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Copending ‘882 claims a double-stranded oligonucleotide, wherein the double-stranded oligonucleotide comprises a guide strand and a passenger strand, wherein:
the guide strand is
p[Rm5d5m] (U) [Rsp] [fl2r] (C) [Rsp]m(U) [n001S][fl2r] (A)pm(C)p[fl2r] (U)pm(U) [n001S][fl2r](G) pm(U)p[fl2r] (G)pm(U)pm(U)pm(A) [Ssp] [fl2r] (C) [Ssp]m(A) [Ssp] [fl2r] (G) [Ssp]m(C) [Ssp] [fl2r] (A)[n001S]m(C)[Ssp][fl2r](A)[Ssp]m(G)[Ssp]m(U)[Ssp]m(U) (SEQ ID NO: 778) or a salt thereof, and
the passenger strand is
m(C) [Ssp]m(U)p[fl2r] (G)pm(U)p[fl2r](G)pm(C)p[fl2r](U) [n001 R]m(G)p[fl2r](U)p [fl2r] (A)p[fl2 r](A)pm(C)p[fl2r] (A)pm(C)p[fl2r] (A) [n001 R]m(A)p[fl2r](G)pm(U)p[fl2r](A)pm(G) [Ssp]m(A) (SEQ ID NO: 762) or a salt thereof;
wherein:
m represents a 2'-OMe modification;
[fl2r] represents a 2'-F modification;
p represents a phosphate linkage;
[Rsp] represents a Rp phosphorothioate linkage;
[Ssp] represents a Sp phosphorothioate linkage;
P[Rm5d5m](U) represents
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Regarding claim 1, copending ‘882 claims a dsRNA as shown in the sequence for the guide strand between the third and fourth nucleotides is n001S which corresponds to the instantly claimed internucleotidic linkage having the same structure and in the Sp configuration. As shown in the sequence above, the passenger strand includes one or more backbone chiral centers in the Rp or Sp configuration. The length is 23 nt which reads on the instant claims.
Regarding claims 11 and 42, the 5’ end of the guide strand of copending ‘882 is P[Rm5d5m](U) which falls within the scope of claim 11 (corresponding to the second structure in the second line of structures) wherein R is OMe.
Regarding claims 43-45, 58-59, pharmaceutically acceptable salts including sodium salt is claimed (see claims 55-57).
Regarding claim 47-48, the passenger strand includes n001R both 5’ and 3’ of the central nucleotide.
Regarding claims 49-50, both the guide and the passenger strand include Ssp.
Regarding claims 46 and 51, claim 66 of copending ‘882 claims an Ssp linkage between the first and second nucleotides and a RSP between the second and third and n001R between the 10th and 11th nucleotides.
Regarding claims 52-54, the same modifications are shown.
Regarding claims 55-57, claim 66 of pending ‘882 shows a GalNAc connected.
Claims 60-62 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54-71 of copending Application No. 19314882 (USPGPUB No. 20250382617) as applied to claims 1, 11, 42-54 and 58-59 above and in view of Vargeese et al. (WO2018223056, cited on PTO Form 1449). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a pharmaceutical composition comprising a plurality of oligonucleotides. The instant application claims a composition comprising the double stranded oligonucleotide and a carrier.
While copending ‘881 claims the same dsRNA, copending ‘881 does not expressly claim a composition. However, this deficiency is cured by Vargeese et al.
The teachings of Vargeese et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘882 and Vargeese et al. and utilize a compositions comprising the ds oligonucleotides.
Regarding claims 60-61, Vargeese et al. teaches compositions comprising a plurality of oligonucleotides which share a common base sequence (aka common constitution) (paragraph 0060) and all oligonucleotides provided in a composition that are of or comprise a common base sequence are at least 99% of all oligonucleotides in the composition (paragraph 0062). Therefore, use of a plurality of oligonucleotides in a composition is obvious as the oligonucleotides of Vargeese et al. are of a similar nature to copending ‘882.
Regarding claim 62, Vargeese et al. teaches a pharmaceutically acceptable carrier which is involved in carrying or transporting the subject compound from one organ to another (paragraph 00243). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘882 and Vargeese et al. and utilize a pharmaceutically carrier with the dsRNA in order to transport or carrying the compound as taught by Vargeese et al.
Conclusion
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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