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 .
Status of Claims
Canceled claims: 1-7, 9, 14, 16-17, 19-20, 22-25, 29-31, 33, 41, 43, 46-64, 66, 68, and 70-87.
Pending claims: 8, 10-13, 15, 18, 21, 26-28, 32, 34-40, 42, 44-45, 65, 67, 69, and 88-92
Priority
Applicant’s claim for the benefit of a prior-filed applications under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims the benefit of U.S. Provisional Application No. 63/251,571, filed October 1, 2021; U.S. Provisional Application No. 63/252,554, filed October 5, 2021; U.S. Provisional Application No. 63/270,504, filed October 21, 2021; U.S. Provisional Application No. 63/283,175, filed November 24, 2021; and U.S. Provisional Application No. 63/287,969, filed December 9, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/31/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 36-40 and 42 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 36-37 recite “selected from any one of Formulae I-VIII,” and claims 38-40 and 42 recite “Ref ID NO(s). …,” which require reference to tables in the specification to determine the claimed subject matter.
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parteFressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
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 8, 10, 12, 15, 18, 21, 26-28, 32, 34-37, 44-45, 65, 67, 69, and 88-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. US12042509B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 1 and 21 of ‘509 are each directed to a compound comprising a first modified oligonucleotide and a second modified oligonucleotide having a region of complementarity thereto, wherein the compound corresponds in sequence and chemistry to the compound of instant claim 8. Specifically, DEQ ID NO: 312 of the ‘509 patent is identical to instant SEQ ID NO: 312, and the ‘509 patent’s SEQ ID NO: 619 (the complement of SEQ ID NO: 312, bearing a 5’-GalNAc-conjugated nucleoside) shares 100% identity with a portion of instant SEQ ID NO: 1, see alignments below:
SEQ ID NO: 312 to 312 alignment:
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213
623
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Greyscale
Instant SEQ ID NO: 312 alignment to ‘509 SEQ ID NO: 619:
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204
629
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Greyscale
Instant SEQ ID NO: 1 alignment to ‘506 SEQ ID NO: 619:
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199
618
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The compound of ‘509 claim 1 and claim 21 comprising a Gal-NAc-conjugated oligonucleotide based on SEQ ID NO: 619 of the formula in claim 21 in and a complementary oligonucleotide consisting the modified SEQ ID NO: 312 of the formula in claim 1 comprises the specific chemistry recited in the instant claims (i.e., terminal phosphorothioate linkages, 2’-F/2’-Moe sugar modifications, and numerical limits of 2’R content, formula X, H9 formula which is instant formulae III, and Gal-NAc attachment points); therefore, the ‘509 compound satisfies all the limitations of instant claims 8, 10, 12, 15, 18, 21, 26-28, 32, 34-37, and 89-92. Furthermore, claim 12 of ‘509 recites the pharmaceutically acceptable salt limitation of instant claims 44-45, and claims 14-15 of ‘509 recite the pharmaceutically acceptable carrier limitation of instant claim 65. Although the instant method claims recite “administering…thereby treating, preventing, or ameliorating,” while ‘509 patent recites “administering…wherein administering…inhibits or reduces or improves,” both claim sets recite the identical method step of administering the same compound for treatment of the same recited disease list, and differ only by verb choice, which is not a patentable distinction.
Claims 11 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of U.S. Patent No. US12042509B2 as applied to claim 8 above in view of Zamore P., et al., (US20050181382A1).
The teachings of ‘509 are incorporated herein by reference to the NSDP rejection above.
While the specification of ‘509 teaches introducing at least 1, 2, or 3 mismatches and that the mismatch is a wobble base pair, ‘509 does not claim introducing at least 1, 2, or 3 mismatches nor that the mismatch is a wobble base pair.
Zamore teaches that introducing 1, 2, or 3 mismatched base pairs (selected from G:A, C:U, and A:U, see [0015]) or a wobble base pair (e.g., G:U, see [0013]) “between the 5' end of the first or antisense strand and the 3' end of the second or sense strand” [0045] reduces base-pair strength at the terminus relative to the opposite terminus, thereby enhancing asymmetry and promoting selective loading of the guide strand into RISC, improving silencing and strand specificity.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date to modify the compound of ‘509 to incorporate 1-3 mismatches, including wobble G:U base pair. A PHOSITA would have been motivated because asymmetry enhances selective loading of the guide strand into RISC, improving silencing and strand specificity. A PHOSITA would have had a reasonable expectation of success because asymmetry-enhancing mismatch/wobble modification is a generically applicable design feature independent of the particular target sequence and were established routine practices in the art.
Claim 88 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-36 of U.S. Patent No. US12042509B2 as applied to claims 8, 67, and 69 above in view of Viney N., et al., (US20200362340A1).
The teachings of ‘509 are incorporated herein by reference to the NSDP rejection above.
While the specification of ‘509 teaches dosing at once every three months, six months, and once every year, ‘509 does not claim this dosing interval in the method claims.
Viney teaches that Gal-NAc conjugation of an antisense oligonucleotide of the same class enables efficacious dosing at intervals of once a week, once a month, once every two months, or once every three months [0018], and that such extended dosing intervals are a direct consequence of the potency and pharmacokinetic enhancement conferred by the Gal-NAc conjugate, rather that of any target-specific property of the oligonucleotide.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date to administer the compound of ‘509 at a dosing interval of about once every three months with a reasonable expectation of success since the instant compound employs the same class of chemistry, delivery mechanism, and hepatic target-organ pharmacokinetics taught by Viney to achieve that dosing interval. Further extending the dosing interval to about once every six months or about once every year represents routine optimization within a technique already established by Viney. Given that Gal-NAc-conjugated oligonucleotides display increased potency and duration of action, a PHOSITA would have been motivated to optimize longer dosing intervals.
Claims 8, 10-12, 15, 18, 21, 26-28, 32, 34-35, 65, 67, 69, and 89-92 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91, 93-97, 101, 103-106, and 108-110 of copending Application No. 18/673,525 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the compound of reference application claim 91, read with dependent claims 96, 101, and 103-105, discloses the identical duplex compound recited in instant claim 8, comprising a Gal-NAc-conjugated oligonucleotide corresponding to SEQ ID NO: 619 and a complementary oligonucleotide corresponding to SEQ ID NO: 312, with the labels of “first” and “second” reversed between the two claim sets. As actually embodied in the reference application’s disclosed compound, SEQ ID NO: 619 comprises exactly five 2’-F sugar modifications and SEQ ID NO: 312 comprises exactly ten 2’-F sugar modifications, each interspersed with 2’-O-methy modifications and bearing phosphorothioate internucleoside linkages at booth the 5’ and 3’ termini (the first two and last two internucleoside linkages, respectively, of each oligonucleotide). The specific structural and chemical embodiments of the reference application’s compound is not patentably distinct from the instant compound of claim 8 further limited by instant claims 18 (terminal phosphorothioate linkages at termini of each oligonucleotide), 21 (each oligonucleotide comprising a 2’-F or 2’-Ome modification), 26 (sugar modification selected from a list including 2’F and 2’-OMe), 27 (no more that ten 2’F modifications in the first oligonucleotide), and 28 (no more than five 2’F modifications in the second oligonucleotide). The complementarity region, full complementarity, and mismatch limitations of instant claims 12, 15, and 11 are recited verbatim in reference application claims 94-95, and 93. The GalNAc conjugate limitations of instant claims 32 and 34 are recited verbatim in reference application claims 103-105. The Formula X recitation of instant claim 35 is identical to that of reference application claim 106. Instant claims 65, 67, and 69 are not patentably distinct from reference application claims 108-110, whose disease list is identical in substance notwithstanding the difference in verb choice. Instant claims 89-92 claim further limit instant claim 8 but do not recite any limitations that make them patentably distinct from the reference application compound for the same reasons above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 88 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 91, 93-97, 101, 103-106, and 108-110 of copending Application No. 18/673,525 (reference application) as applied to claims 8, 67, and 69 above in view of Viney N., et al., (US20200362340A1).
The teachings of reference application are incorporated herein by reference to the provisional NSDP rejection above.
While the specification of reference application teaches dosing at once every three months, six months, and once every year, reference application does not claim this dosing interval in the method claims.
Viney teaches that Gal-NAc conjugation of an antisense oligonucleotide of the same class enables efficacious dosing at intervals of once a week, once a month, once every two months, or once every three months [0018], and that such extended dosing intervals are a direct consequence of the potency and pharmacokinetic enhancement conferred by the Gal-NAc conjugate, rather that of any target-specific property of the oligonucleotide.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date to administer the compound of ‘509 at a dosing interval of about once every three months with a reasonable expectation of success since the instant compound employs the same class of chemistry, delivery mechanism, and hepatic target-organ pharmacokinetics taught by Viney to achieve that dosing interval. Further extending the dosing interval to about once every six months or about once every year represents routine optimization within a technique already established by Viney. Given that Gal-NAc-conjugated oligonucleotides display increased potency and duration of action, a PHOSITA would have been motivated to optimize longer dosing intervals.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to COREY LANE BRETZ whose telephone number is (571)272-7299. The examiner can normally be reached M-F 7:30am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (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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/COREY LANE BRETZ/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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