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 .
Response to Arguments
Applicant’s arguments, see p. 6, filed 05/26/2026, with respect to the objection to claim 12 have been fully considered and are persuasive. Amendments overcome the objection. The objection of 02/26/2026 has been withdrawn.
Applicant's arguments filed 05/26/2026 with respect to the rejection of claims 1-12 under 35 U.S.C. 103 and the provisional nonstatutory double patenting rejection of claims 1-12 over claims 1-12 of copending U.S. Patent Application No. 19/135,429 have been fully considered but they are not persuasive.
Applicant argues on pp. 8-10 that Kasai et al. does not describe dimers in which SN-38 are linked via a disulfide bond, nor does it provide specific disclosure regarding compounds in which the tertiary hydroxy groups of SN-38 are linked to one another. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). See MPEP 2145(IV). The same applies to the assertion on p. 10-11 that Jiang et al. does not describe carrier-free nanoparticles.
Applicant argues on p. 10 that the present invention is aimed at achieving dispersion stability as a carrier-free nanoparticle using a dimer of SN-38 derivatives and selective drug release. The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006). That the references suggest different intents or motivations for various teachings, i.e. the cleavage of disulfide bonds by DTT, does not support a conclusion of nonobviousness. This further applies to applicant’s arguments on p. 7-8, referencing paragraphs [0007] to [0011] of the specification, detailing the problems discovered and allegedly overcome as a result of the inventor’s experimentation.
Applicant appears to suggest unexpected results at pp. 7-12. See p. 7 “the presently claimed invention provides nanoparticles that are carrier-free, possess stability under dispersion, and are capable of selective drug release in tumor tissue”. Applicant also details the discovery of challenges the inventors have overcome. Applicant points to Test Examples 1 to 3 on p. 10. While the Examples show in vitro and in vivo efficacy of the claimed compound(s), it is unclear how they show unexpected results nor is there sufficient showing of the challenges allegedly overcome by the inventors. Similarly, Fig. 1-4 show efficacy of claimed compounds but nothing that appears to suggest unexpected results. Applicant is reminded that the burden is on applicant to establish results are unexpected and significant and that applicants have burden of explaining proffered data. See MPEP 716.02(b). Applicant is also reminded that the showing of unexpectedresults must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). See MPEP 716.02(d). The results presently disclosed are insufficient to support a conclusion of nonobviouness based upon unexpected results commensurate in scope with the claimed invention.
It remains that Jiang et al. is directed toward camptothecin dimers. Camptothecin is an analog of SN-38, and as such a PHOSITA would consider art regarding the drug design of camptothecin dimers as analogous to the disclosure of Kasai et al. directed toward SN-38 dimers. Accordingly, modifying the SN-38 dimers of Kasai et al. to have the same linker and attachment point of the camptothecin dimers taught by Jiang et al. would have been obvious. Arguments apply in equal or greater force to the nonstatutory double patenting rejection. Accordingly, the rejections are maintained.
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.
The factual inquiries 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 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kasai et al. “Creation of Pure Nanodrugs and Their Anticancer Properties” Angew. Chem. Int. Ed. 2012, 51, 10315 –10318 in view of CN107669626 (Jiang et al., 08/28/2023 IDS Foreign Patent Number 3).
Kasai et al. teaches anticancer SN-38 dimers with various linkers (carbamate, ester and ether) at the phenolic hydroxy group of the parent molecule. See Scheme 1. SN-38 is a prodrug of Irinotecan which is a derivative of camptothecin. Roughly spherical 30-50 nm nanoparticles of the carbamate dimer are taught (p. 10317).
The claimed compounds such as SN0DC differ from the prior art compounds in that they utilize carbonate-alkylene-disulfide linkers which are attached to the lactone hydroxy group of SN-38.
Jiang et al. teaches camptothecin dimers with carbonate-alkylene-disfulfide linkers which are attached to the lactone hydroxy group of camptothecin. See claim 1. Para. [0003] states “the drug delivery system has a drug loading of 1% to 12.6% %, and the drug delivery system has reduction sensitivity, good biocompatibility and the ability to inhibit tumor cell proliferation, and can be used to prepare slow-controlled release and targeted anticancer drugs.” A PHOSITA would have been motivated to form an SN-38 dimer with carbonate-alkylene-disulfide linker attached to the lactone hydroxy group of SN-38 based upon the teachings of Kasai et al. in view of Jiang et al. in order to prepare slow-controlled release and targeted anticancer drugs. This would result in the claimed compound SNC0DC wherein R1 is hydroxy and R2 is ethylene with respect to claims 1-12. There would have been a reasonable expectation of success in producing effective anticancer drugs because the parent molecules of each compound, SN-38 and camptothecin, are recognized in the art as analogous. With respect to claims 2 and 4, ClogP is an inherent property that would have necessarily flowed from the combined teachings of the prior art. With respect to claim 4, Kasai et al. teaches roughly spherical 30-50 nm nanoparticles of the carbamate dimer are taught (Figure 1b, p. 10316). With respect to claims 5-6 and 8-9, anticancer activity is taught by both prior art and claim 6 is drawn to an intended use which does not structurally limit the product and therefore is not given patentable weight. With respect to claim 7, Kasai et al. teaches that said synthetic methods are routine in the art (p. 10315, last paragraph) and are applied to the prior art nanoparticles (p. 10316, first paragraph). Accordingly, claims 1-12 are 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 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 19135429 in view of CN107669626 (Jiang et al.).
Claims 1-12 of copending Application No. 19135429 are drawn to compounds of General Formula (1) and nanoparticles, medicines and methods of use thereof.
The compounds differ from those instantly claimed in that they have an ester-alkylene-disulfide linker attached to the phenolic hydroxy group of each SN-38 moiety.
Jiang et al. teaches camptothecin dimers with carbonate-alkylene-disfulfide linkers which are attached to the lactone hydroxy group of camptothecin. See claim 1. Para. [0003] states “the drug delivery system has a drug loading of 1% to 12.6% %, and the drug delivery system has reduction sensitivity, good biocompatibility and the ability to inhibit tumor cell proliferation, and can be used to prepare slow-controlled release and targeted anticancer drugs.” A PHOSITA would have been motivated to form an SN-38 dimer with carbonate-alkylene-disulfide linker attached to the lactone hydroxy group of SN-38 based upon the copending claims in view of Jiang et al. in order to prepare slow-controlled release and targeted anticancer drugs. This would result in the claimed compound SNC0DC wherein R1 is hydroxy and R2 is ethylene with respect to claims 1-12. There would have been a reasonable expectation of success in producing effective anticancer drugs because the parent molecules of each compound, SN-38 and camptothecin, are recognized in the art as analogous.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-12 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JED A KUCHARCZK whose telephone number is (571)270-5206. The examiner can normally be reached Mon-Fri 7:30 to 5.
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/JED A KUCHARCZK/ Examiner, Art Unit 1623
/VALERIE RODRIGUEZ-GARCIA/ Primary Examiner, Art Unit 1621
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