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 .
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, 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.
Claim(s) 1, 3, 5-6, 8-9, 11, 18-19, 23, 29, 34, 38, 43-44, 46, 71, 75-76, 87, 90-92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Javanbakht et al (WO 2017/211791, December 2017, of record) and in further view of Koser et al (WO 2019/079781, April 2019, cited from IDS) and Guo et al (WO 2015/132276, September 2015, cited from IDS).
Javanbakht teach combination therapy comprising administration of an HBsAg inhibitor and a TLR7 agonist for treatment of hepatitis B patient (see Abstract). The TLR7 agonist can be compound 9 (see Table 1), identical to compound (III) of instant invention with R1 of -OH and R2 of 1-hydroxymethyl:
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Further Javanbakht teach compound 7 (see Table 1), identical to instant compound (VI):
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Javanbakht teach pharmaceutical compositions and kits comprising combinations taught (see lines 15-20 on page 3 and lines 5-15 on page 36).
Javanbakht do not teach that combination comprises therapeutic RNAi oligonucleotide such as of SEQ ID NO: 33 comprising sense strand 19-50 nucleotides in length of SEQ ID NO: 41 and antisense strand 19-30 nucleotides in length of SEQ ID NO: 38, which can further comprise modifications as in instant claims 18-19, 23, 29, 43, 44, modified nucleotide or modified internucleotide linkage, or the oligonucleotide is HBV(s)-219, or combination further comprises CpAM.
Koser teach oligonucleotides for reducing HBsAg expression and treating HBV infection (see Abstract). Such oligonucleotides can comprise sense strand of 19-50 nucleotides in length and antisense strand complementary to it forming a duplex region such antisense strand can be complementary to SEQ ID NO: 1, identical to instant SEQ ID NO: 33 (see paragraphs [0006-0007]). Such sense strand can be of SEQ ID NO: 8, which is identical to instant SEQ ID NO: 41 (see paragraph [0009]). Antisense strand can be of SEQ ID NO: 5.1, which is identical to instant SEQ ID NO: 38 (see paragraph [0008]). Further Koser teach that such sense strand of SEQ ID NO: 8 comprises 2'-fluoro modified nucleotides at positions 3, 8-10, 12, 13 and 17; 2'-O-methyl modified nucleotides at positions 1, 2, 4-7, 11, 14-16, 18-26 and 31-36, and at least one phosphorothioate internucleotide linkage, wherein the sense strand is conjugated to one or more N-acetylgalactosamine (GalNAc) moiety; and the antisense of SEQ ID NO: 5.1 comprises 2'-fluoro modified nucleotides at positions 2, 3, 5, 7, 8, 10, 12, 14, 16 and 19; 2'-0- methyl modified nucleotides at positions 1, 4, 6, 9, 11, 13, 15, 17, 18 and 20-22; and at least three phosphorothioate internucleotide linkages, wherein the 4'-carbon of the sugar of the 5'- nucleotide of the antisense strand comprises a phosphate analog (see paragraph [00011]), therefore describing the same modifications the same as in instant claims 18-19. Koser teach that one or more of the nucleotides of the -GAAA- sequence on the sense strand is conjugated to a monovalent GalNAc moiety (see paragraph [00014]), same as in instant claim 23. Koser teach that the sense strand can comprise at its 3'- end a stem-loop set forth as: S1-L-S2, wherein S1 is complementary to S2, and wherein L forms a loop between S1 and S2 of up to 6 nucleotides in length (see paragraph [00018]), same as in instant claim 29. Further Koser teach that the sense strand of SEQ ID NO: 8 can comprise 2'-fluoro modified nucleotides at positions 3, 8-10, 12, 13 and 17; 2'-O-methyl modified nucleotides at positions 1, 2, 4-7, 11, 14-16, 18-26 and 31-36, and one phosphorothioate internucleotide linkage between the nucleotides at positions 1 and 2, wherein each of the nucleotides of the -GAAA- sequence on the sense strand is conjugated to a monovalent GalNAc moiety, wherein the -GAAA- sequence comprises the structure:
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and the antisense strand can comprise SEQ ID NO: 5.1, which comprises 2'-fluoro modified nucleotides at positions 2, 3, 5, 7, 8, 10, 12, 14, 16 and 19; 2'-O-methyl modified nucleotides at positions 1, 4, 6, 9, 11, 13, 15, 17, 18 and 20-22, and five phosphorothioate internucleotide linkages between nucleotides 1 and 2, 2 and 3, 3 and 4, 20 and 21, and 21 and 22, wherein the 4'-carbon of the sugar of the 5'-nucleotide of the antisense strand has the following structure:
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same as in instant claims 43-44 (see paragraph [00025]). Koser further teach HBV(s)-219 oligonucleotide shown in Figure 10, fully identical to instantly claimed HBV(s)-219 oligonucleotide as presented in Figure 20 of instant specification.
Guo teach compounds for HBV therapy (see Abstract), including compound in Example 76 (see page 159), identical to instant compound CpAM2:
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It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to combine TLR7 agonists taught by Javanbakht with HBsAg inhibitors taught by Koser and compounds taught by Guo arriving at instant invention. One of the ordinary skill in the art would be motivated to do so, because Javanbakht suggest combination therapy for HBV treatment comprising TLR7 agonists and inhibitors of HBsAg, and Koser teach several of such inhibitors. Further it would be obvious to add compound taught by Guo for combination treatment, because such compound is intended for treatment of HBV as well. According to MPEP 2143, Section I, example (E) it is obvious to try by choosing from a finite number of identified, predictable solutions with a reasonable expectation of success. The secondary references provide such a finite number of identified, predictable solutions, which can be introduced into combination treatment described by Javanbakht.
Claim(s) 1, 47-48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Javanbakht et al (WO 2017/211791, December 2017, of record) and in further view of Javanbakht-2 et al (US 2016/0010093, January 2016, of record).
Teachings of Javanbakht are discussed above.
Javanbakht do not teach that the therapeutic oligonucleotide is GalNAc conjugated antisense oligonucleotide 13-22 nucleotides long and fully complementary to nucleotides 1530- 1543 of instant SEQ ID NO: 1.
Javanbakht-2 teach conjugated antisense oligonucleotides targeting HBV (see Abstract). Such oligonucleotides can be conjugated to GalNAc (see paragraph [0118]). One of such oligonucleotides is of SEQ ID NO: 147 (see Table 1 on page 54), 16 nucleotides long and fully complementary to nucleotides 1530-1545 of instant SEQ ID NO: 1:
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It would have been obvious to one of the ordinary skill in the art before the effective filing date of the claimed invention to create a combination of TLR7 agonists taught by Javanbakht with the conjugate taught by Javanbakht-2, arriving at instant invention. One of the ordinary skill in the art would be motivated to do so to improve treatment for HBV, because both Javanbakht and Javanbakht-2 teach compounds for such treatments and Javanbakht suggests combination treatments combining TLR7 agonists and HBV inhibitors, while Javanbakht-2 provides examples of such HBV inhibitors. According to MPEP 2143, Section I, example (E) it is obvious to try by choosing from a finite number of identified, predictable solutions with a reasonable expectation of success. The secondary reference provides such a finite number of identified, predictable solutions, which can be introduced into combination treatment described by Javanbakht.
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, 3, 5-6, 8-9, 11, 18-19, 23, 29, 34, 38, 43-44, 46-48, 71, 75-76, 87, 90-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 54 of U.S. Patent No. 9,441,008 in view of Koser, above, and Javanbakht-2, above. Claims from '008 recite the same TLR agonists as in instant claims for treatment of HBV infections. Teachings of Koser and Javanbakht-2 are discussed above. It would have been obvious to one of the ordinary skill in the art to combine treatments for HBV from '008 with treatments taught by Koser and Javanbakht-2, arriving at instant invention.
Claims 1, 3, 5-6, 8-9, 11, 18-19, 23, 29, 34, 38, 43-44, 46-48, 71, 75-76, 87, 90-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 18 of U.S. Patent No. 10,040,815 in view of Koser, above, and Javanbakht-2, above. Claims from '815 recite the same TLR agonists as in instant claims for treatment of HBV infections. Teachings of Koser and Javanbakht-2 are discussed above. It would have been obvious to one of the ordinary skill in the art to combine treatments for HBV from '815 with treatments taught by Koser and Javanbakht-2, arriving at instant invention.
Claims 1, 3, 5-6, 8-9, 11, 18-19, 23, 29, 34, 38, 43-44, 46-48, 71, 75-76, 87, 90-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 22 of U.S. Patent No. 10,618,929 in view of Koser, above, and Javanbakht-2, above. Claims from '929 recite the same TLR agonists as in instant claims for treatment of HBV infections. Teachings of Koser and Javanbakht-2 are discussed above. It would have been obvious to one of the ordinary skill in the art to combine treatments for HBV from '929 with treatments taught by Koser and Javanbakht-2, arriving at instant invention.
Claims 1, 3, 5-6, 8-9, 11, 18-19, 23, 29, 34, 38, 43-44, 46-48, 71, 75-76, 87, 90-92 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1- 32 of U.S. Patent No. 11,771,699 in view of Koser, above, and Javanbakht-2, above. Claims from '699 recite the same TLR agonists as in instant claims for treatment of HBV infections. Teachings of Koser and Javanbakht-2 are discussed above. It would have been obvious to one of the ordinary skill in the art to combine treatments for HBV from '699 with treatments taught by Koser and Javanbakht-2, arriving at instant invention.
Response to Arguments
Applicant's arguments filed 02/10/2026 have been fully considered but they are not persuasive.
Previous objections to claims are withdrawn in view of new amendments.
Concerning 103 rejection Applicant argues that Example 5 from Javanbakht reference teaches away from using Compound 7, identical to instant compound (VI), because its activity is lower than Compound 8 as shown in Table 2 of the Example. In response activity of Compounds 7 and 8 is comparably similar as shown in Table 2, therefore it can be reasonable to use any of Compounds 7 or 8. There is no evidence in the Example that Compound 7 is inactive. Such evidence would be teaching away. Further Applicant argues that the reference does not show any results concerning Compound 9, therefore suggesting use of Compound 8, for which results are provided. In response the reference suggests a number of small molecules to use, therefore it would be obvious to try any compounds disclosed.
Further Applicant argues that Javanbakht reference does not teach RNAi oligonucleotides. In response the reference suggests using TLR7 agonists in combination with HBsAg inhibitors (see Abstract) as stated in the rejection above. Secondary reference by Koser teach such inhibitors, which are RNAi oligonucleotides.
Further Applicant argues that the references do not teach TLR7 agonists. In response Compounds 7 and 9 from Javanbakht reference are TLR7 agonists.
Further Applicant argues that references do not suggest combining TLR7 agonists and RNAi oligonucleotides. In response as already stated above Javanbakht reference clearly suggests such combination. The reference does not explicitly recite RNAi oligonucleotides, but suggests HBsAg inhibitors, such oligonucleotides are a type of HBsAg inhibitors. Rejection is maintained.
Concerning 103 rejection based on Javanbakht and Javanbakht-2 references Applicant argues that Javanbakht-2 reference teaches only antisense oligonucleotides. In response rejected claims 47 and 48 recite only antisense oligonucleotides. Rejection is maintained.
Concerning double patenting rejection Applicant provides the same arguments as in obviousness rejection above. In response the same response as above applies and the rejections are maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637
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