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 .
Claims 1-20 are pending and under examination.
Priority
This application is a continuation of 15/779,123 filed on 5/25/2018, which is a national stage entry of PCT/US16/63540 filed on 11/23/2016, which claims priority from US provisional applications 62/378,997 filed on 8/24/2016 and 62/259,909 filed on 11/25/2015.
In regards to the claims that provide for myocardial infarction, claims 8, and 11-15, this is provided with the support of 62/378,997 filed on 8/24/2016 as this is the first document where myocardial infarction treatment appears.
Examiner Comments
Applicant’s arguments from 3/24/2026 are convincing toward claims 10-20 where “miRNA 146a covalently attached at a 3’ end to the cerium oxide via an amide linkage” in regards to the rejections under USC 103 and under double patenting for US copending applications 17/428,447 and 17/281,049. However, the examiner responds to arguments over the rejections over the remaining claims.
Maintained Rejections
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.
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) 1-4, 9 are rejected under 35 U.S.C. 103 as being unpatentable over Kalashnikova, Soumen, et al (Nanoceria-miRNA as modulator of inflammation in diabetic wounds, April 2015 based on applicant’s IDS, document found in parent application, in applicant’s IDS) and Yu et al (AAPS J, 2009, volume 11, pages 195-203) as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167).
Kalashnikova teaches that miRNA146a was attached to hydroxyl groups (covalent) of CNP using 1,1-carbonyldiimidazole (methods). Kalashnikova teaches treating non-diabetic and diabetic mice that were wounded were provided with a single intradermal injection of the CNP-miRNA146a or CNP or vehicle (methods). Kalashnikova teaches decreased gene expression of TRAF6, IRAK1, NF-kappa b, IL-6 and IL-8/MIP-2) and increased macrophage cells to the wounded site (Results), and thus, modulating inflammation. Figure 2 shows the results of the wound treatment. Thus, the administration of compositions of the miRNA146a-CNPs was known for wound treatment in diabetic subjects and were effective. Kalashnikova mentions attachment to the hydroxyl groups of the miRNA (methods), but does not specify which one.
In regards to claim 9, these are effects provided by the treating of the subject. As Kalashnikova does the treatment with the conjugate, these effects will occur in the subject receiving treatment as these are expression of genes affected by the treatment.
Mittal evidences under inflammatory conditions there is oxidative stress (abstract) and there is an intricate relationship between oxidative stress and inflammation (Conclusion and Future Remarking).
Kalashnikova does not teach the miRNA attached at the 3’ end or the amide bond being at the 3’ end.
Yu teaches targeted delivery systems for oligonucleotide therapeutics (abstract). Yu teaches modifications of the 5’ or 3’ ends of oligonucleotides (HDL/LDL mediated delivery section). Yu teaches connecting ligands to the termini of oligonucleotides (Conjugation Chemistry for Attaching Ligand to Ons). Here, Yu also mentions that thioether, disulfide and amide covalent linkages are frequently used for targeting ligands to termini of oligonucleotides or the surface of nanoparticles. Thus, amide covalent linkages are known to connect oligonucleotides to other molecules and both termini (3’ or 5’ end) may be used for these attachments.
One of ordinary skill in the art before the time of filing would have used such routine techniques of the prior art to attach oligonucleotides like an miRNA or siRNA (oligoRNA) to other items as either the 3’ and 5’ end of the RNA are available for linkages and amide covalent linkages were commonly used as by teachings of Yu. Therefore, there was a reasonable expectation of success of using the 3’ end of an oligo RNA like the miRNA and to add an amide covalent linkage to attach it where Kalashnikova provides for the conjugation of the miRNA and the cerium oxide nanoparticle via covalent means. Since oxidative stress is associated with the inflammation by evidence of Mittal, the oxidative stress will be present in the wound and treated as well.
Claims 5-7 in addition to Claim(s) 1-4, 9, 10, and 16-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kalashnikova, Soumen, et al (Nanoceria-miRNA as modulator of inflammation in diabetic wounds, April 2015 based on applicant’s IDS, in applicant’s IDS), Yu et al (AAPS J, 2009, volume 11, pages 195-203) and Sudipta US 20130195927 as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167).
Kalashnikova and Yu teach the claims as discussed above.
Kalashnikova and Yu do not teach topical treatment of the wound (teaches intradermal injection), does not teach plurality of times or daily.
Sudipta teaches treatment and promotion of wound healing with ceria nanoparticles (abstract). Sudipta teaches topical administration (claim 2 of Sudipta). Sudipta teaches daily administration for multiple days and at least once daily (paragraphs 7 and 41). Sudipta teaches diabetic ulcer (claim 9 of Sudipta). Paragraph 33 teaches various topical compositions.
One of ordinary skill in the art before the time of filing would have considered topical treatments for daily treatments as this is recognized for nanoceria wound treatments of the prior art and Kalasknikova also provides a wound treatment with a nanoceria particle. The time of dosing would be routine to one of ordinary skill in the art who desires to achieve the optimal wound treatment and Sudipta recognizes the use of topical, daily treatments for wounds. Thus, there was a reasonable expectation of success in offering the treatment as a topical, daily, multi-use method by the teachings of the prior art.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Kalashnikova, Soumen, et al (Nanoceria-miRNA as modulator of inflammation in diabetic wounds, April 2015 based on applicant’s IDS, document found in parent application, in applicant’s IDS) and Yu et al (AAPS J, 2009, volume 11, pages 195-203) and Hori et al (Cardiovascular Research, 2009, volume 81, pages 457-464) as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167).
Kalashnikova and Yu teach the claims as above.
Kalashnikova and Yu do not teach myocardial infarction but do provide for control of inflammation with the composition having miRNA146a-nanoceria.
Hori teaches that ROS and inflammation occur in myocardial infarction (abstract). Hori teaches antioxidant and anti-inflammatory treatment for reverse remodeling of the heart (section 7 and conclusions) and left ventricular remodeling (abstract). In section 7, the importance of dose is provided as well as timing of administration.
One of ordinary skill in the art at the time of filing would have considered myocardial infarction as one of the inflammation/oxidative stress conditions to be treated by reducing inflammation and oxidative stress with the treatment of Kalashnikova based on the teachings of Hori that shows myocardial infarction is characterized by inflammation. One of ordinary skill in the art would administer the dosage of anti-inflammatory as soon as possible after the event has occurred and for as many times as would be necessary. One of ordinary skill in the art would also consider injecting at the site of injury as with the wound in Kalashnikova. In providing such an antioxidant and anti-inflammatory treatment, one would expect some restoration/maintenance of the heart function as compared to untreated control since Hori teaches such expectations are possible. There is a reasonable expectation of success in providing such a form of treatment to individuals who had myocardial infarction as the condition is characterized by oxidative stress and inflammation which are treatable with the Kalashnikova’s method and expecting less damage, some degree of healing.
Response to Arguments
Applicant argues that Yu’s teachings of is that Yu fails to describe the conjugation of the 3’ end of the miRNA (in this case miRNA 146a) to a CNP via an amide linkage. This is most applicable to claim 10 that carries this full limitation. Claim 1 only indicates there is a covalent attachment at the 3’ end to the cerium oxide nanoparticle without providing the covalent linkage type. In the case of attachment points on the oligo RNA, the main options would be the 3’ or the 5’ ends as provided in Yu. The teachings of attaching miRNA 146a to a cerium oxide nanoparticle for wound treatments comes from the disclosure of Kalashnikova. Therefore, as the prior art recognizes the attachments and the choices of the 5’ or 3’ end of an RNA and as Kalashnikova provides for linking miRNA 146a (an oligo RNA) to a cerium oxide nanoparticle, there is a reasonable expectation of success of providing any covalent linkage from a 3’ end to a cerium oxide nanoparticle to provide for the miRNA conjugated cerium oxide nanoparticles of the method of applicant’s claims with the combined teachings of the references. Therefore, these rejections under USC 103 are maintained for their teachings as covering claims 1-9. Rejections to claims 10-20 are being withdrawn per the applicant’s argument regarding the particular amide linkage at the 3’end.
Non-Statutory 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 1-7, 9-10, 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9-10 of U.S. Patent No. 11833172 as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for treating or preventing inflammation in a wound with a conjugate of cerium oxide and miRNA-146a as claimed. Mittal evidences under inflammatory conditions there is oxidative stress (abstract) and there is an intricate relationship between oxidative stress and inflammation (Conclusion and Future Remarking).
Claims 1-7, 9-10, 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 9-10 of U.S. Patent No. 11833172 as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for treating or preventing inflammation in a wound with a conjugate of cerium oxide and miRNA-146a as claimed. Mittal evidences under inflammatory conditions there is oxidative stress (abstract) and there is an intricate relationship between oxidative stress and inflammation (Conclusion and Future Remarking).
Claims 1 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 6, 9, 10-12 of copending Application No. 17/281,049 (reference application) and Yu et al (AAPS J, 2009, volume 11, pages 195-203) as evidenced by Mittal et al (Antioxidants and Redox Signaling, Mar 2014, volume 20, pages 1126-1167). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for treating or preventing inflammation in a condition (pulmonary disease or condition) with a conjugate of cerium oxide and miRNA-146a. Mittal evidences under inflammatory conditions there is oxidative stress (abstract) and there is an intricate relationship between oxidative stress and inflammation (Conclusion and Future Remarking).
‘049 does not teach in what way the miRNA is bound to the cerium oxide nanoparticle.
Yu teaches targeted delivery systems for oligonucleotide therapeutics (abstract). Yu teaches modifications of the 5’ or 3’ ends of oligonucleotides (HDL/LDL mediated delivery section). Yu teaches connecting ligands to the termini of oligonucleotides (Conjugation Chemistry for Attaching Ligand to Ons). Here, Yu also mentions that thioether, disulfide and amide covalent linkages are frequently used for targeting ligands to termini of oligonucleotides or the surface of nanoparticles. Thus, amide covalent linkages are known to connect oligonucleotides to other molecules and both termini (3’ or 5’ end) may be used for these attachments.
One of ordinary skill in the art before the time of filing would have used such routine techniques of the prior art to attach oligonucleotides like an miRNA (oligoRNA) to other items as both the 3’ and 5’ end of the RNA are available for linkages and amide covalent linkages were commonly used. Therefore, there was a reasonable expectation of success of using the 3’ end of the miRNA and to add an amide covalent linkage to attach it where ‘049 provides for the conjugation of the miRNA and the cerium oxide nanoparticle.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7, and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5, 8-10 of copending Application No. 17/428,447. (reference application) and Yu et al (AAPS J, 2009, volume 11, pages 195-203). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for treating or preventing inflammation in a condition with a conjugate of cerium oxide and miRNA-146a.
‘447 claims do not teach in what way the miRNA is bound to the cerium oxide nanoparticle.
Yu teaches targeted delivery systems for oligonucleotide therapeutics (abstract). Yu teaches modifications of the 5’ or 3’ ends of oligonucleotides (HDL/LDL mediated delivery section). Yu teaches connecting ligands to the termini of oligonucleotides (Conjugation Chemistry for Attaching Ligand to Ons). Here, Yu also mentions that thioether, disulfide and amide covalent linkages are frequently used for targeting ligands to termini of oligonucleotides or the surface of nanoparticles. Thus, amide covalent linkages are known to connect oligonucleotides to other molecules and both termini (3’ or 5’ end) may be used for these attachments.
One of ordinary skill in the art before the time of filing would have used such routine techniques of the prior art to attach oligonucleotides like an miRNA (oligoRNA) to other items as both the 3’ and 5’ end of the RNA are available for linkages and amide covalent linkages were commonly used. Therefore, there was a reasonable expectation of success of using the 3’ end of the miRNA and to add an amide covalent linkage to attach it where ‘049 provides for the conjugation of the miRNA and the cerium oxide nanoparticle.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-5, 8-10 of copending Application No. 17/428,447. (reference application), Yu et al (AAPS J, 2009, volume 11, pages 195-203) and Hori et al (Cardiovascular Research, 2009, volume 81, pages 457-464). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets provide for treating or preventing inflammation in a condition with a conjugate of cerium oxide and miRNA-146a.
Claims of ‘447 and Yu provide for the claims above.
Claims of ‘447 and Yu do not provide for myocardial infarction.
The claims of ‘447 provide for treatment or prevention of inflammation (genus of conditions that involve inflammation). Claim 10 of ‘447 provides for treating or preventing of oxidative stress. Hori teaches that ROS and inflammation occur in myocardial infarction (abstract). Hori teaches antioxidant and anti-inflammatory treatment for reverse remodeling of the heart (section 7 and conclusions). In section 7, the importance of dose is provided as well as timing of administration.
One of ordinary skill in the art at the time of filing would have considered myocardial infarction as one of the inflammation/oxidative stress conditions to be treated by reducing inflammation and oxidative stress with the treatment of 447 based on the teachings of Hori that shows myocardial infarction is characterized by inflammation. One of ordinary skill in the art would administer the dosage of anti-inflammatory as soon as possible after the event has occurred and for as many times as would be necessary. One of ordinary skill in the art would also consider injecting at the site of injury as with the wound in 447. In providing such an antioxidant and anti-inflammatory treatment, one would expect some restoration/maintenance of the heart function as compared to untreated control since Hori teaches such expectations are possible. There is a reasonable expectation of success in providing such a form of treatment to individuals who had myocardial infarction as the condition is characterized by oxidative stress and inflammation which are treatable with the 447’s method and expecting less damage, some degree of healing.
Claim Objections
Claims 11-15 are objected to for being dependent on a claim (claim 10) that is rejected under non-statutory double patenting (a rejected base claim). Applicant may file an appropriate terminal disclaimer to obviate the non-statutory double patenting rejection, or alternatively amend claim 10 to incorporate the limitations of claim 11 into claim 10 to make an allowable claim.
Examiner Notes
The examiner called applicant’s representative to discuss the addition of “via an amide linkage” to the end of claim 1 and the filing of terminal disclaimers as appropriate, which would namely be a terminal disclaimer to US Patent 11833172 after this amendment is made to claim 1. Applicant responded to leave a message on 5/15/2026 noting that applicant may be amenable to the amendment and that it was taking time to file the terminal disclaimer. The applicant may file an after final response to provide the amendment to claim 1 in addition to the terminal disclaimer.
Conclusion
No claim is allowed. Claims 11-15 are objected to.
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 MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613
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