DETAILED ACTION
This Action is in response to the communication filed on 12/23/2025.
Claims 31-50 are pending.
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 the indicated species in the reply filed on 12/23/2025 is acknowledged.
Claims 37-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/23/2025.
Claims 31-36, 40-50 are under consideration.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
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 31-36, 40-50 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20170035796 (hereinafter “Wooddell”; of record – IDS citation) in view of U.S. 20200038506 (hereinafter “Sepp-Lorenzino”).
Regarding claim 31, 34-36,Wooddell teaches double stranded short interfering nucleic acid (siNA) molecules for inhibiting Hepatitis B virus gene expression including an siNA having a sense strand oligonucleotide represented by 5’- AAAABABBBAAAAAAAAAA wherein each A is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (i.e., 2’-F at positions 5 and 7-9, all other positions 2’-O-methyl)), identified as AM04659-SS in Table 1B (see page 18). The AM04659 modified oligonucleotide meets the structural limitations of the elected species for the sense strand wherein each n is defined as in claim 35. Wooddell does not teach the antisense strand having the elected species of modification pattern required by Formula (VIII) as set forth in claims 31 and 36. It is noted, however, that Wooddell teaches an antisense strand having a modification pattern very similar to the antisense strand modification pattern required by the claims. The elected sense strand oligonucleotide modification pattern is ABAAABAAAAAAABABAAACC wherein each A and C is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (i.e., 2’-F positions at 2, 6, 14, 16, all other positions 2’-O-methyl). Wooddell teaches an antisense oligonucleotide with a modification pattern ABAAABABBAAAABABAAAAA (i.e., 2’-F positions at 2, 6, 8-9, 14, 16, all other positions 2’-O-methyl) identified as AM04661-AS in Table 1A on page 11), which is similar to the required modification pattern. It is noted that Wooddell teaches a duplex of AM04659-SS and AM04661-AS, identified as AD03669 in Table 2 on page 21, which is a duplex as a sense strand having the required modification pattern and an antisense strand having a modification pattern very similar to the required modification pattern.
Although Wooddell does not teach that the antisense strand has the modification pattern ABAAABAAAAAAABABAAACC, the prior art does teach double stranded siNA molecules for inhibiting Hepatitis B virus gene expression including an siNA having an antisense strand with the required modification pattern. For instance, Sepp-Lorenzino teaches an siNA for inhibiting Hepatitis B virus gene expression with antisense strand A-127930 (see Table 3 on page 61), having the modification pattern ABAAABAAAAAAABABAAACC wherein each A and C is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (where 2’-F is at positions 2, 6, 14, 16, all other positions 2’-O-methyl)
Regarding claims 32-33. Wooddell teaches the sense strand sequence can be a sequence that is at least 80% identical to SEQ ID NO: 40 (e.g., see SEQ ID NOs: 201, 202, 204, 208 of Table 1B on page 19), and Sepp-Lorenzino explicitly identifies a HBV target sequence that is identical to SEQ ID NO: 40 (see Table 12, SEQ ID NO: 1294 gugguggacuucucucaau, on page 77).
Regarding claim 40, Wooddell teaches that the nucleotides at positions 1-2 and 2-3 from the 5’end of the sense strand are connected by phosphorothioate internucleoside linkages (see AM04659 on page 18 where “s” indicates a phosphorothioate internucleoside linkage), and Sepp-Lorenzino teaches the nucleotides at the positions 1-2, 2-3, 19-20, and 20-21 from the 5' end of the antisense strand are connected by phosphorothioate internucleoside linkages (see A-127930 in Table 3 on page 61).
Regarding claims 41-44, Wooddell teaches a conjugated moiety attached to the sense strand, wherein the conjugate moiety is a galactosamine, specifically N-Acetylgalactosamine (GalNAc or NAG) (e.g., see AM04659-SS on page 18 where “(NAG13)” is an N-acetylgalactosamine). It is noted that Sepp-Lorenzino also teaches an N-acetylglucosamine conjugated to the sense strand of siNA (e.g., see A-127905 on page 61). Although Wooddell teaches that the siNA can comprise a galactosamine and further explicitly indicates that the galactosamine can be N-acetylgalactosamine including multiple (multimeric) galactosamines (see [0107]), and specifically teaches a siNA with a trimer n-acetylgalactosamine identified as [NAG25], Wooddell does not teach the use of the GalNAc of Formula (VII).
It is noted that Wooddell teaches,
“The affinities of numerous galactose derivatives for the asialoglycoprotein receptor have been studied… or are readily determined using methods well known and commonly used in the art. Other terms common in the art for galactose trimer having three terminal galactose derivatives include tri-antennary galactose, tri-valent galactose. Other terms common in the art for galactose trimer include galactose cluster. It is known that tri-antennary galactose derivative clusters are bound to the ASGPr with greater affinity than bi-antennary or mono-antennary galactose derivative structures…” (References to citations removed).
Regarding claims 45-46, Wooddell teaches that the 5’-end of the antisense strand can have a 5’-end stabilizing cap, specifically a vinyl phosphonate (e.g., see [0045], [0053], [0112], antisense oligonucleotides AM04747-AS, AM04750-AS, AM04753-AS in Table 2).
Regarding claims 47-50, Wooddell teaches that the siNA can comprise modifications attached to the nucleotide at the 5’-end and 3’-end of the sense strand and antisense strand, such as cholesterol, galactose trimer, polymer, terminal cap, inverted deoxy abasic group, etc. which would act as a phosphorylation blocker (e.g., see [0011] , [0051], [0112]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to combine the teachings of Wooddell and Sepp-Lorenzino and arrive at the double stranded siNA molecule required by the claims, with a reasonable expectation of success. That is, since siNA were known as effective inhibitors of HBV gene expression, including siNAs were in the sense strand has the required modification pattern (as taught by Wooddell) and the antisense strand has the required modification pattern (as taught by Sepp-Lorenzino), it would have been a matter of being obvious to try combining what was already known in the prior art to arrive at the claimed invention. There would have been a reasonable expectation of success based on the positive results indicated in the prior art.
It also would have been further prima facie obvious to one of ordinary skill in the art prior to the day the claimed invention was filed to further modify the modified siNA duplex taught by Wooddell as indicated above and use a different known tri-valent GalNAc, including a GalNAc of Formula (VII) with a reasonable expectation of success. KSR’s rationales (A), (B), and/or (E), as indicated below apply here. Official notice is taken that the GalNAc of Formula (VII) was previously known in the art.
It is noted that KSR forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness. See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http://www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
The combination of prior art cited above in all rejections under 35 U.S.C. 103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007): “Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
Therefore, the claimed invention, as a whole, is prima facie obvious.
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 31-36, 40-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-30 of U.S. Patent No. 12,129,469. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The following rejection is in view of the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
The instant claims are drawn to a double stranded siNA molecule represented by Formula (VIII) as indicated in claim 31.
The indicated claims of the ‘469 patent are drawn to a method of treating HBV comprising administering a double stranded siNA that is encompassed by the instant claims. Accordingly, the instant claims and the indicated claims of the ‘469 patent are related as a product and a method of using that product disclosed in the specification of the application. It is noted that although claim 1 of the ‘469 patent includes limitations not present in claim 31 of the instant application, instant claim 31 is broader in scope and fully encompasses the double stranded siNA molecule recited in claim 1 of the issued patent. Accordingly, a non-statutory double patenting rejection is appropriate.
Instant claims 32-34 correspond to limitations in at least claim 1 of the ‘469 patent.
Instant claims 35-36 correspond to at least claim 5 of the ‘469 patent.
Instant claim 40 corresponds to at least claim 6 of the ‘469 patent.
Instant claims 41-44 correspond to at least limitations in claims 4, 7-8, 11-12, 24, 27, 30 of the ‘469 patent.
Although the limitations of instant claims 45-46 are not recited in the claims of the ‘469 patent, using the specification of the issued patent to define the scope and obvious variants of the claimed invention, it is clear that the specification of the ‘469 patent defines the scope of the claimed invention as encompassing a 5’ stabilizing end cap at the 5’ end of the antisense strand, wherein the cap is a vinyl phosphonate. For instance, see column 78.
Although the limitations of instant claims 47-50 are not recited in the claims of the ‘469 patent, using the specification of the issued patent to define the scope and obvious variants of the claimed invention, it is clear that the specification of the ‘469 patent defines the scope of the claimed invention as encompassing a phosphorylation blocker at the 5’ end and 3’ end of the sense strand and the antisense strand. For instance, see column 78.
MPEP 804 II B 1 states:
The specification can be used as a dictionary to learn the meaning of a term in the patent claim. Toro Co. v. White Consol. Indus., Inc., 199 F.3d 1295, 1299, 53 USPQ2d 1065, 1067 (Fed. Cir. 1999)… Further, those portions of the specification which provide support for the patent claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the patent. In re Vogel, 422 F.2d 438, 441-42, 164 USPQ 619, 622 (CCPA 1970).
Claims 31-36, 40-50 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-30 of U.S. Patent No. 11,549,110. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Although claim 1 of the ‘110 patent includes limitations not present in claim 31 of the instant application, instant claim 31 is broader in scope and fully encompasses the double stranded siNA molecule recited in claim 1 of the issued patent. Accordingly, a non-statutory double patenting rejection is appropriate.
Instant claims 32-34 correspond to limitations in at least claim 1 of the ‘110 patent.
Instant claims 35-36 correspond to at least claim 5 of the ‘110 patent.
Instant claim 40 corresponds to at least claim 6 of the ‘110 patent.
Instant claims 41-44 correspond to at least limitations in claims 4, 7-8, 11-12, 24, 27, 30 of the ‘110 patent.
Although the limitations of instant claims 45-46 are not recited in the claims of the ‘110 patent, using the specification of the issued patent to define the scope and obvious variants of the claimed invention, it is clear that the specification of the ‘110 patent defines the scope of the claimed invention as encompassing a 5’ stabilizing end cap at the 5’ end of the antisense strand, wherein the cap is a vinyl phosphonate. For instance, see columns 78-79.
Although the limitations of instant claims 47-50 are not recited in the claims of the ‘110 patent, using the specification of the issued patent to define the scope and obvious variants of the claimed invention, it is clear that the specification of the ‘110 patent defines the scope of the claimed invention as encompassing a phosphorylation blocker at the 5’ end and 3’ end of the sense strand and the antisense strand. For instance, see columns 78-79.
See MPEP 804 II B 1 as indicated above.
Claims 31-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 20, 74 of copending Application No. 17/194079 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant claim 31 corresponds to claim 20 of the ‘079 application. It is noted that claim 20 of the ‘079 application is broader in scope than claim 20 of the ‘079 application, as claim 20 includes limitations to SEQ ID NOs: 1-56, which are not included in instant claim 1. Since instant claims 31 is broader in scope than claim 20 of the ‘079 application, claim 31 is anticipated by claim 20 of the ‘079 application.
Regarding claims 32-33, it is noted that the limitations of claim 32-33 correspond to limitations recited in claim 20 of the ‘079 application. The limitations of claim 32-33 correspond to limitations recited in claim 74 of the ‘079 application. That is, claims 32 and 33 further limit instant claim 31 by requiring the first (sense) nucleotide sequence to be a sequence of SEQ ID NO: 40 and the second (antisense) nucleotide sequence to be a sequence complementary to a sequence of SEQ ID NO: 40. Claim 20 of the ‘079 application indicates that the sense strand can comprise a sequence that explicitly includes SEQ ID NO: 40, and the antisense strand can comprise a sequence that explicitly includes a sequence complementary to SEQ ID NO: 40 (e.g., SEQ ID NO: 98). Similarly, claim 70 of the ‘079 application also indicates that the sense strand can comprise a sequence that includes instant SEQ ID NO: 40 (e.g., see SEQ ID NO: 435 of the ‘079 application which does not include modifications in the sequence listing), and the antisense strand can comprise a sequence that includes a sequence complementary to SEQ ID NO: 40 (e.g., SEQ ID NO: 501 of the ‘079 application which does not include modifications in the sequence listing).
Therefore, a non-statutory double patenting rejection over the indicated claims of the ‘079 application is appropriate.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637
Prosecution Insights