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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55, specifically a copy of Korean application 10-2021-0073528. Applicant also supplied a certified translation of this document on 7/15/26. “The foreign application must be examined for the question of sufficiency of the disclosure under 35 U.S.C. 112 as well as to determine if there is a basis for the claims sought.” MPEP 216. The translation demonstrates that the KR ’528 document teaches an siTACE of SEQ ID NO: 1 (see Preparation Example 1) but not one of SEQ ID NO: 2. The KR ’528 document therefore does not support any of the claims under 35 U.S.C. 112(a) and cannot be relied upon to provide an earlier effective filing date since all claims either require SEQ ID NO: 2 or include it as an option. See MPEP 2152.01 (calculation of claimed invention’s effective filing date carried out on claim-by-claim basis).
The effective filing date of all claims is 6/3/22.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5, 7, and 11-18 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lee et al. (2021, Journal of Controlled Release 336: 344-353; 12/6/23 IDS NPL reference 3). Foreign priority has not been perfected for this application for the reasons discussed above, and Lee was published online on 6/18/21, so it is intervening prior art under 35 U.S.C. 102(a)(1). Lee names authors other than the four joint inventors on this application, so the exception under 35 U.S.C. 102(b)(1)(A) does not clearly apply. See MPEP 717.01(III)(A).
Lee teaches a gene-delivery system comprising siRNA against tumor necrosis factor-[Symbol font/0x61] converting enzyme (siTACE) and TKPR-9R (tuftsin peptide followed by nine arginine residues). (Abstract; page 345, column 1; sections 2.1 and 3.1.) Lee’s siTACE has a sequence 100% identical to SEQ ID NO: 1. (Section 2.1.) Lee’s construct has the full-length sequence CTKPRGGGGRRRRRRRRRC. (Section 2.1.) Lee teaches a weight ratio of 1-5. (Sections 2.2 and 3.1.) Regarding claim 5, Lee’s TKPR-9R delivers siTACE to macrophages. (Abstract; sections 2.5 and 3.1; Figure 3.) Regarding claim 7, Lee teaches combining siTACE with TKPR-9R and incubating at room temperature for 30 minutes. (Section 3.1.) Regarding claims 13-18, Lee teaches compositions of the siTACE/TKPR-9R complexes for intravenous injection into a mouse model of sepsis. (Sections 2.9 and 3.3.)
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.
Claims 1, 5, 7, and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kim (2014, “Development of Non-Viral RNA Interference System Against TACE (Tumor Necrosis Factor-[Symbol font/0x61] Converting Enzyme) for the Treatment of Inflammatory Diseases”; 12/6/23 IDS NPL reference 10; “Kim 2014”) taken in view of Shoenfeld et al. (US 20160256516), Kim et al. (US 20180193474; “Kim 2018”), and Kim et al. (US 20190300886; “Kim 2019”). This rejection addresses the embodiment in which the TACE siRNA comprises a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 1.
Kim 2014 teaches shRNA (short hairpin RNA) that suppresses the expression of TACE in a gene/carrier complex with reduced poly(oligo-D-arginine) (POA). (Pages 3-4.) Specifically, Kim 2014’s POA has the sequence Cys-(D-R9)-Cys. (Page 4.) Regarding claim 7 and its dependents, Kim teaches incubating reduced POA and shRNA at a weight ratio of 0.1, 0.5, 1.0, or 2.0 at room temperature for 20 minutes. (Section 2.5 at page 5.) Kim 2014 teaches that the complexes are useful for treating inflammatory diseases such as rheumatoid arthritis, acute lung injury, atherosclerosis, and inflammatory bowel disease. (Page 1.) Kim 2014 teaches that reduced POA targets macrophages and is an effective shRNA carrier. (Pages v, 14; Figures 4 and 5.)
Kim 2014 does not teach that the TACE-expression inhibitor is an siRNA. Kim 2014 does not teach including tuftsin peptide in the carrier peptide. Kim does not teach that the TACE siRNA comprises a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 1.
Shoenfeld teaches that tuftsin (the tetrapeptide TKPR) is known for its phagocytosis-stimulating activity and augmentation of antigen presenting capacity of macrophages in vitro and in vivo. (Paragraph 96.) Shoenfeld teaches that tuftsin has an immunomodulatory effect on the progression and development of colitis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) in vivo. (Paragraph 14.) Shoenfeld teaches that tuftsin peptide can be attached to a plurality of amino acids, for example arginine. (Paragraph 15.)
Kim 2018 teaches that TACE can be targeted with either shRNA or siRNA to inhibit its expression. (Paragraph 2.) Kim 2018 teaches that TACE is elevated in various inflammatory diseases, such as rheumatoid arthritis, acute lung injury, and inflammatory bowel disease, and that inhibiting TACE expression can treat and prevent these conditions. (Paragraph 2.)
Kim 2019 teaches SEQ ID NO: 1 is useful within a plasmid vector that is an RNA interference system. (Paragraph 70.) Kim 2019 teaches that this sequence selectively inhibits expression of only TACE. (Paragraph 70.)
It would have been obvious to incorporate Shoenfeld’s tuftsin peptide into Kim 2014’s Cys-(D-R9)-Cys peptide because Shoenfeld teaches that tuftsin peptide can be conjugated to arginine. The skilled artisan would have been motivated to add tuftsin peptide to Kim 2014’s peptide because Shoenfeld teaches that tuftsin targets macrophages in inflammation, which is the same utility disclosed for Kim 2014’s gene/carrier complexes. Making the combination would provide a predictable outcome with each component performing the same function as it does separately. See MPEP 2143(I)(A). Furthermore, it is prima facie obvious to combine two compositions, each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. MPEP 2144.06(I) (quoting In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (C.C.P.A. 1980)).
It would have been further obvious to substitute Kim 2018’s siRNA for Kim 2014’s shRNA because Kim 2018 teaches that both of these types of RNA are useful for inhibiting the expression of TACE. Making the substitution would provide a predictable outcome, namely inhibition of TACE expression, and the skilled artisan could have substituted one for the other by following the instructions of Kim 2018. See MPEP 2143(I)(B). Substituting equivalents known in the art for the same purpose is prima facie obvious. See MPEP 2144.06(II).
Finally, it would have been obvious to base the siRNA of Kim 2018 on the sequence disclosed by Kim 2019 because Kim 2019 teaches that SEQ ID NO: 1 is useful in RNA interference and specifically inhibits TACE expression.
Claims 19-26 are rejected under 35 U.S.C. 103 as being unpatentable over Kim 2014 taken in view of Shoenfeld, Kim 2018, and Kim 2019, further in view of Yanni et al. (2010, US Patent 7732421; reference A). This rejection addresses the embodiment in which the TACE siRNA comprises a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 2.
The teachings of Kim 2014, Shoenfeld, Kim 2018, and Kim 2019 are relied upon as above.
Kim 2014, Shoenfeld, Kim 2018, and Kim 2019 do not teach an siRNA comprising a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 2.
Yanni teaches an siRNA of SEQ ID NO: 11, which fully contains SEQ ID NO: 2:
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(Column 11, line 64; underlined portion is examined SEQ ID NO: 2.) Yanni teaches that SEQ ID NO: 11 is an siRNA that targets TACE. (Column 11, lines 57-58.)
Regarding claim 26, Yanni teaches that siRNA signaling TACE silences TNF[Symbol font/0x61] and is useful for treating inflammatory conditions such as ocular inflammation, allergic conjunctivitis, dermatitis, rhinitis, and asthma. (Column 2, lines 9-33.) Yanni teaches that interfering RNA may be delivered via aerosol, buccal, dermal, intradermal, inhaling, intramuscular, intranasal, intraocular, intrapulmonary, intravenous, intraperitoneal, nasal, ocular, oral, otic, parenteral, patch, subcutaneous, sublingual, topical, or transdermal administration. (Column 22, lines 55-60.)
It would have been obvious to substitute Yanni’s TACE-signaling siRNA (Yanni’s SEQ ID NO: 11, which fully contains examined SEQ ID NO: 2) for Kim 2019’s because Yanni teaches that SEQ ID NO: 11 is useful as an siRNA that targets TACE. The skilled artisan would have found it further obvious to administer Yanni’s TACE-signaling siRNA via any of the means identified by Yanni to treat an acute inflammatory disease because Yanni teaches that TACE-signaling siRNA downregulates TNF[Symbol font/0x61] and treats inflammatory diseases caused by that protein’s overactivity.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Kim 2014 taken in view of Shoenfeld, Kim 2018, Kim 2019, and Yanni as applied to claims 19-26 above and further in view of Weiner et al. (US 20050042202; reference B).
The teachings of Kim 2014, Shoenfeld, Kim 2018, Kim 2019, and Yanni are relied upon as above.
Kim 2014, Shoenfeld, Kim 2018, Kim 2019, and Yanni do not teach treating, for example, sepsis.
Weiner teaches that in sepsis, an infection becomes systemic and the TNF[Symbol font/0x61] induced blood vessel occlusion becomes catastrophic. The systemic release of TNF[Symbol font/0x61] causes vasodilation and loss of plasma volume due to increased vascular permeability, leading to shock. In septic shock, TNF[Symbol font/0x61] further triggers disseminated intravascular coagulation (blood clotting) leading to the generation of clots in the small vessels and the massive consumption of clotting proteins. (Paragraph 4.)
It would have been obvious to administer Yanni’s TACE-signaling siRNA via any of the means identified by Yanni to treat sepsis because Yanni teaches that TACE-signaling siRNA downregulates TNF[Symbol font/0x61] and treats inflammatory diseases caused by that protein’s overactivity, while Weiner teaches that sepsis is caused by overactivity of TNF[Symbol font/0x61].
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, 5, 7, and 9-18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,709,793 in view of Kim (2014, “Development of Non-Viral RNA Interference System Against TACE (Tumor Necrosis Factor-[Symbol font/0x61] Converting Enzyme) for the Treatment of Inflammatory Diseases”; 12/6/23 IDS NPL reference 10; “Kim 2014”), Shoenfeld et al. (US 20160256516; reference A), Kim et al. (US 20180193474; reference B; “Kim 2018”), and Kim et al. (US 20190300886; “Kim 2019”). This rejection addresses the embodiment in which the TACE siRNA comprises a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 1.
The ’793 patent claims a gene/carrier complex comprising one or more shRNAs that inhibit expression of TACE and a nonviral gene carrier comprising a TFA salt of poly(oligo-aspartic acid)(oligo-arginine). Regarding examined claims 3 and 9, the ’793 patent’s carrier has cysteines at both ends. (Claims 2 and 9.) Regarding examined claims 6 and 11, the ’793 patent claims a weight ratio of 1:1.5 to 8. (Claim 4.) Regarding examined claim 7, the ’793 patent claims a method of mixing shRNA with the nonviral carrier. Regarding examined claim 12, the ’793 patent claims incubating the shRNA with the nonviral carrier for 20-40 minutes at 20-40oC. (Claim 8.) Regarding examined claims 14-18, the ’793 patent claims a method of treating rheumatoid arthritis, an acute inflammatory disease, by administering the gene/carrier complex according to any of several modalities. (Claims 13 and 14.)
The ’793 patent does not claim that the TACE-expression inhibitor is siRNA comprising a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 1. The ’793 patent does not claim including tuftsin peptide in the nonviral gene carrier. Regarding claim 14, the ’793 patent does not claim that the treated disease is one from the enumerated list.
Kim 2014 teaches shRNA (short hairpin RNA) that suppresses the expression of TACE in a gene/carrier complex with reduced poly(oligo-D-arginine) (POA). (Pages 3-4.) Specifically, Kim 2014’s POA has the sequence Cys-(D-R9)-Cys. (Page 4.) Regarding claim 7 and its dependents, Kim teaches incubating reduced ROA and shRNA at a weight ratio of 0.1, 0.5, 1.0, or 2.0 at room temperature for 20 minutes. (Section 2.5 at page 5.) Kim 2014 teaches that the complexes are useful for treating inflammatory diseases such as rheumatoid arthritis, acute lung injury, atherosclerosis, and inflammatory bowel disease. (Page 1.) Kim 2014 teaches that reduced POA targets macrophages and is an effective shRNA carrier. (Pages v, 14; Figures 4 and 5.)
Shoenfeld teaches that tuftsin (the tetrapeptide TKPR) is known for its phagocytosis-stimulating activity and augmentation of antigen presenting capacity of macrophages in vitro and in vivo. (Paragraph 96.) Shoenfeld teaches that tuftsin has an immunomodulatory effect on the progression and development of colitis, rheumatoid arthritis, and systemic lupus erythematosus (SLE) in vivo. (Paragraph 14.) Shoenfeld teaches that tuftsin peptide can be attached to a plurality of amino acids, for example arginine. (Paragraph 15.)
Kim 2018 teaches that TACE can be targeted with either shRNA or siRNA to inhibit its expression. (Paragraph 2.) Kim 2018 teaches that TACE is elevated in various inflammatory diseases, such as rheumatoid arthritis, acute lung injury, and inflammatory bowel disease, and that inhibiting TACE expression can treat and prevent these conditions. (Paragraph 2.)
Kim 2019 teaches SEQ ID NO: 1 is useful within a plasmid vector that is an RNA interference system. (Paragraph 70.) Kim 2019 teaches that this sequence selectively inhibits expression of only TACE. (Paragraph 70.)
It would have been obvious to incorporate Shoenfeld’s tuftsin peptide into the ’793 patent’s peptide because Shoenfeld teaches that tuftsin peptide can be conjugated to arginine. The skilled artisan would have been motivated to add tuftsin peptide to the ’793 patent’s peptide because Shoenfeld teaches that tuftsin targets macrophages in inflammation, which is the same utility disclosed for the ’793 patent’s gene/carrier complexes. Making the combination would provide a predictable outcome with each component performing the same function as it does separately. See MPEP 2143(I)(A). Furthermore, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art. MPEP 2144.06(I) (quoting In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (C.C.P.A. 1980)).
It would have been further obvious to substitute siRNA targeting TACE for the ’793 patent’s shRNA targeting TACE because Kim 2018 teaches that both of these types of RNA are useful for inhibiting the expression of TACE. Making the substitution would provide a predictable outcome, namely inhibition of TACE expression. See MPEP 2143(I)(B). Substituting equivalents known in the art for the same purpose is prima facie obvious. See MPEP 2144.06(II).
Finally, it would have been obvious to base the siRNA on the sequence disclosed by Kim 2019 because Kim 2019 teaches that SEQ ID NO: 1 is useful in RNA interference and specifically inhibits TACE expression.
Claims 19-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,709,793 in view of Kim 2014 taken in view of Shoenfeld, Kim 2018, and Kim 2019, further in view of Yanni et al. 2010, US Patent 7732421). This rejection addresses the embodiment in which the TACE siRNA comprises a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 2.
The claims of the ’793 patent and the teachings of Kim 2014, Shoenfeld, Kim 2018, and Kim 2019 are relied upon as above.
The ’793 patent does not claim, and Kim 2014, Shoenfeld, Kim 2018, and Kim 2019 do not teach, an siRNA comprising a sense sequence that is an RNA sequence corresponding to the entire length of SEQ ID NO: 2.
Yanni teaches an siRNA of SEQ ID NO: 11, which fully contains SEQ ID NO: 2:
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(Column 11, line 64; underlined portion is examined SEQ ID NO: 2.) Yanni teaches that SEQ ID NO: 11 is an siRNA that targets TACE. (Column 11, lines 57-58.)
Regarding claim 26, Yanni teaches that siRNA signaling TACE silences TNF[Symbol font/0x61] and is useful for treating inflammatory conditions such as ocular inflammation, allergic conjunctivitis, dermatitis, rhinitis, and asthma. (Column 2, lines 9-33.) Yanni teaches that interfering RNA may be delivered via aerosol, buccal, dermal, intradermal, inhaling, intramuscular, intranasal, intraocular, intrapulmonary, intravenous, intraperitoneal, nasal, ocular, oral, otic, parenteral, patch, subcutaneous, sublingual, topical, or transdermal administration. (Column 22, lines 55-60.)
It would have been obvious to substitute Yanni’s TACE-signaling siRNA (Yanni’s SEQ ID NO: 11, which fully contains examined SEQ ID NO: 2) for the ’793 patent’s because Yanni teaches that SEQ ID NO: 11 is useful as an siRNA that targets TACE. The skilled artisan would have found it further obvious to administer Yanni’s TACE-signaling siRNA via any of the means identified by Yanni to treat an acute inflammatory disease because Yanni teaches that TACE-signaling siRNA downregulates TNF[Symbol font/0x61] and treats inflammatory diseases caused by that protein’s overactivity.
Claim 27 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10,709,793 in view of Kim 2014 taken in view of Shoenfeld, Kim 2018, Kim 2019, and Yanni, and further in view of Weiner et al. (US 20050042202).
The claims of the ’793 patent and the teachings of Kim 2014, Shoenfeld, Kim 2018, Kim 2019, and Yanni are relied upon as above.
The ’793 patent does not claim, and Kim 2014, Shoenfeld, Kim 2018, Kim 2019, and Yanni do not teach treating, for example, sepsis.
Weiner teaches that in sepsis, an infection becomes systemic and the TNF[Symbol font/0x61] induced blood vessel occlusion becomes catastrophic. The systemic release of TNF[Symbol font/0x61] causes vasodilation and loss of plasma volume due to increased vascular permeability, leading to shock. In septic shock, TNF[Symbol font/0x61] further triggers disseminated intravascular coagulation (blood clotting) leading to the generation of clots in the small vessels and the massive consumption of clotting proteins. (Paragraph 4.)
It would have been obvious to administer Yanni’s TACE-signaling siRNA via any of the means identified by Yanni to treat sepsis because Yanni teaches that TACE-signaling siRNA downregulates TNF[Symbol font/0x61] and treats inflammatory diseases caused by that protein’s overactivity, while Weiner teaches that sepsis is caused by overactivity of TNF[Symbol font/0x61].
Response to Arguments
Regarding the rejection under 35 U.S.C. 102(a)(1), applicant alleges that Lee is not prior art. (Reply at 7.) Because the KR ’528 application does not provide support as set forth in 35 U.S.C. 112(a) for the full scope of claims 1, 5, 7, and 11-18, however, the effective filing date of those claims is the filing date of PCT KR2022/007935—6/3/22.
Regarding the base rejection under 35 U.S.C. 103, applicant alleges that Kim 2014, Shoenfeld, and Kim 2018 do not address the limitations of canceled claims 2 and 8 (i.e., an siRNA based on SEQ ID NO: 1 or 2). (Reply at 8.) This concern is fully addressed by the new rejection that also relies on Kim 2019, which teaches that SEQ ID NO: 1 is useful in siRNA targeting TACE.
Regarding the rejection of record over canceled claims 2 and 8, applicant alleges that the specification shows evidence of unexpected results. (Reply at 9-10.) Specifically, applicant alleges that the peptide of SEQ ID NO: 5 (Cys-TKPR-9R-Cys) enhances macrophage-specific delivery and anti-inflammatory efficiency relative to the TACE siRNA alone. (Reply at 9, citing Figures 2A and 5B.) Applicant concludes that this effect “would not have been expected from a mere combination of tuftsin [TKPR] with the carrier disclosed in Kim (2014).” (Reply at 9.) The examiner disagrees that the results would have been unexpected. Figure 2A compares the ability of PEI (polyethyleneimine) and TKPR-9R to enhance knockdown of TACE expression. It does not provide any comparison of either PEI or TKPR-9R to TKPR alone. Figure 2A appears to show that including a gene carrier—whether it be PEI or TKPR-9R—significantly reduces TACE expression:
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This finding is fully compatible with the teachings of Kim 2014, which demonstrates that Cys-9R-Cys enhances the effect of siRNA on TACE expression reduction. The basis for concluding that the effect of Cys-9R-Cys (a known gene carrier) combined with Shoenfeld’s tuftsin would not have been expected is unclear.
Similarly, Figure 5B compares macrophage targeting by siRNA-FAM (presumably fluorescein amidite) compared to siRNA-FAM complexed with Cys-TKPR-9R-Cys but does not compare either of these to siRNA-FAM complexed with TKPR or with Cys-9R-Cys. Figure 5B appears to demonstrate that naked siRNA-FAM is delivered less efficiently to macrophages than siRNA-FAM complexed with a gene carrier:
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Again, in the absence of comparative data, the basis for concluding that the effect of Cys-9R-Cys (a known gene carrier) combined with Shoenfeld’s tuftsin would not have been expected is unclear.
Applicant makes similar statements about the data in Figures 2B and 2D with respect to the claimed weight ratios within the complex. (Reply at 9-10.) Again, however, the data in Figures 2B and 2D only compares the effect of naked TACE siRNA to that of TACE siRNA complexed with a gene carrier. There is no data comparing Cys-TKPR-9R-Cys to either Cys-9R-Cys or TKPR alone—or to any other gene carrier. There is also no data comparing the 1:2-1:5 weight ratios to any other weight ratios, so Figures 2B and 2D do not establish criticality of these ratios.
Regarding the new claims, applicant alleges that an siRNA sequence corresponding to the entire length of SEQ ID NO: 2 is not taught or suggested by the art—a requirement introduced into the claims in the 7/15/26 reply. (Reply at 11.) This concern is fully addressed by Yanni’s teachings.
Regarding the double-patenting rejection of record, applicant indicates that a terminal disclaimer will be filed when all other rejections are withdrawn. (Reply at 11.) Until the rejection is overcome, it will be maintained.
Conclusion
No claims are allowed. No claims are free of the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Lora E Barnhart Driscoll, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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/Lora E Barnhart Driscoll/Primary Examiner, Art Unit 3991
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