DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of claims 19-21, 23-24, 27, 30, 32, and 34 with species election of siRNA and the third structure in claim 30 in the reply filed on March 20, 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Status of Claims
Claims 1-2, 5-7, 9-10, 13, 17, 19-21, 23-24, 27, 30, 32, and 34-42 are currently pending in the instant application. Claims 1-2, 5-7, 9-10, 13, 17, and 35-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Accordingly, claims 19-21, 23-24, 27, 30, 32, and 34 are under examination on the merits in the instant application.
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. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos. 63/089,936, 63/113,801, 63/131,317, 63/141,300, 63/146,276, and 63/251,580 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. It appears that none of the prior-filed provisional applications discloses the instantly claimed structure of Formula (XV-a).
Accordingly, claims 19-21, 23-24, 27, 30, 32, and 34 are not entitled to an earlier filing date. Hence, the effective filing date for claims 19-21, 23-24, 27, 30, 32, and 34 will be the PCT application filing date, which is October 8, 2021.
Claim Rejections - Improper Markush Grouping
Claim 32 is rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). See MPEP §706.03(y).
Note that the instant rejection is judicially approved as set forth in “Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. 112 and for Treatment of Related Issues in Patent Applications” in Federal Register, Volume 76, Number 27, published on February 9, 2011, which expressly states the following:
“A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” or (2) the species do not share a common use…When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.” See page 7166, middle column.
Note that “the phrase "Markush claim” means any claim that recites a list of alternatively useable species regardless of format.” See MPEP §2173.05(h).
The Markush grouping of an siRNA, a miRNA, an ADAR recruiting molecule, an ADAR targeting molecule, a guide RNA, and an antisense nucleic acid is improper because the alternatives defined by the Markush grouping do not share a single structural similarity, nor do they share a common use. For instance, an siRNA comprises an antisense strand sequence that is complementary to a target mRNA sequence, whereas a miRNA comprises a short seed sequence that forms base pairs with a target mRNA in the 3’ UTR or in an intron region. In addition, an siRNA has a use in target sequence-specific silencing, whereas a miRNA has a use in repressing multiple targets having the sequence that is complementary to the seed sequence of the miRNA. Hence, the alternatives recited in claim 32 do not all share a single structural similarity, nor do they all share a common use.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternatives within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 19-21, 23-24, 27, 32, and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are broadly drawn to a compound of Formula (XV-a) comprising an “oligonucleotide” such as “an siRNA”, wherein each of Y1 and Y2 is “O, CH2, CH2, or optionally substituted NH”; each of Y3 and Y4 is “CO, SO2, P(O)O, CH2-O-C(O), CH2-NH-C(O), CH2-NH-SO2 or CH2”; “n2 is 0, 1, 2, 3, 4, 5, or 6”; and “each of n1, n3, n4, and n5 is independently 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.”
It is noted that the instant specification does not provide any actual species of oligonucleotide (R2)-conjugated compound of Formula (XV-a), wherein the oligonucleotide is an siRNA. In addition, it appears that the specification at best envisions “O” for each of Y1 and Y2, “C=O” for each of Y3 and Y4, wherein each of n1 and n2 is 1, and each of n3, n4, and n5 is 3-5. The limited structural variants encompassed by the broad genus do not constitute a representative number of species of diverse structural variants because the GalNAc-conjugated compound’s function was known to be highly unpredictable unless actually tested such that two GalNAc conjugate structures do provide different intracellular delivery of a conjugated siRNA molecule, thereby providing very different siRNA-mediated target inhibition. That is, it was art-recognized knowledge that the siRNA intracellular delivery function of a GalNAc conjugate is highly dependent on the conjugate’s structure, wherein highly similar structures are known to provide a widely different siRNA targeting/inhibition effect in a cell. See for instance “NAG30” and “NAG31” as the GalNAc conjugate at the 5’ end of a sense strand of an siRNA molecule having the same nucleotide sequences/modifications, wherein AD03540 comprising “NAG30” provided “16% knockdown” of target levels, whereas AD03629 comprising “NAG31” provided “55% knockdown” of target levels. See paragraphs 0553-0560 of Li et al. (US 2018/0064819 A1). Since the instant specification is completely silent regarding any structure-function correlation for even a single compound within the claimed genus, and since there is no relevant prior art submitted by applicant in IDS of record or searched by the examiner pertaining to the structure-function correlation for the claimed compound, it remains unknown whether structurally different species including those recited in claim 30 would have the intended utility and function, especially in view of the art-recognized unpredictable nature of the GalNAc conjugates.
Accordingly, it is concluded that the instant specification fails to adequately describe the instantly claimed in sufficient detail in such a manner to reasonably convey that the instant co-inventors had possession of the subject matter as now claimed as of the filing date sought or granted in the instant application.
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 19-21, 23-24, 27, 30, 32, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. 12,042,509 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘509 patent claims that require a compound comprising a chemically modified double-stranded RNA oligonucleotide that is an siRNA molecule, wherein the oligonucleotide comprises a GalNAc conjugate having the following structure:
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It is noted that the above structure fully satisfies a structure claimed in claim 30 of the instant application.
Claims 19-21, 23-24, 27, 30, 32, and 34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,595,477 B2.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘477 patent claims that require a compound comprising a chemically modified double-stranded RNA oligonucleotide that is an siRNA molecule, wherein the oligonucleotide comprises a GalNAc conjugate having the following structure:
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It is noted that the above structure fully satisfies a structure claimed in claim 30 of the instant application.
Claims 19-21, 23-24, 27, 30, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7-8, 13, 18-19, 26-27, 35, 38-40, 56-58, 62-63, 65, 67-69, and 86 of copending Application No. 18/194,203.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘203 claims that require an AGT-targeting siRNA compound, which is conjugated to a GalNAc conjugate having the structure that encompasses species claimed in claim 30.
Claims 19-21, 23-24, 27, 30, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 89-113 of copending Application No. 18/673,525.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘525 claims that require a compound comprising a chemically modified PKK-targeting double-stranded RNA oligonucleotide that is an siRNA molecule, wherein the oligonucleotide comprises a GalNAc conjugate having the structure that encompasses species claimed in claim 30.
Claims 19-21, 23-24, 27, 30, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 67-93 of copending Application No. 18/697,165.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘165 claims that require an AGT-targeting siRNA compound, which is conjugated to a GalNAc conjugate having the structure that encompasses species claimed in claim 30.
Claims 19-21, 23-24, 27, 30, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8, 10-13, 15, 18, 21, 26-28, 32, 34-40, 42, 44-45, 65, 67, 69, and 88-92 of copending Application No. 18/697,180.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘180 claims that require a compound comprising a chemically modified PKK-targeting double-stranded RNA oligonucleotide that is an siRNA molecule, wherein the oligonucleotide comprises a GalNAc conjugate having the structure that encompasses species claimed in claim 30.
Claims 19-21, 23-24, 27, 30, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 86-105 of copending Application No. 19/630,043.
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are anticipated and/or encompassed by the ‘043 claims that require an AGT-targeting siRNA compound, which is conjugated to a GalNAc conjugate having the structure that encompasses species claimed in claim 30.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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