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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 05/07/2025 has been entered.
Election/Restrictions
Claims 1, 6-7, 9-15, 20-23 and species ALI as a cause (cl. 10), pulmonary inflammation as a condition/disease (cl. 1), and topical delivery to the lung by inhalation are considered here.
Claims 1, 6, 7, 9, 10, 12-15, 20, 23 are examined, while claims 11, 21, and 22 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Claim 21 is “pre-compression pump” which is for nasal spray.
Priority
The benefit of U.S. Provisional Application 62/738352, filed on 09/28/2018, via the PCT/US2019/053418, filed on 09/27/2019, is recognized.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/06/2025 was filed before the mailing date of the first Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 objected to because of the following informalities: the claim requires addition of “chronic” before obstructive pulmonary disease (COPD). Appropriate correction is required.
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 1, 6, 7, 10, 12, 13, 14, 23 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.
Regarding claim 1, the phrase "e.g." renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 1 recites “e.g., IPAH, interstitial lung disease, and lung cancer. Also, the claim has an unmatched left parenthesis, so it is unclear which items are part of the parenthetical.
Dependent claims 6, 7, 10 do not overcome the indefiniteness and are also rejected for depending on cl. 1.
Regarding claim 12, 13, the claims recite “administered as an aerosol formulation, as a metered dose inhaler, as a dry powder composition for topical delivery to the lung by inhalation or as an intranasal spray.” The noted language is confusing because it lacks a disjunctive term “or” between the three alternatives of aerosol formulation, metered dose inhaler and dry powder composition.
Further, the claim also has a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 12 recites the broad recitation “aerosol formulation”, and the claim also recites “metered dose inhalers” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Dependent cl. 14 and 23 do not overcome the indefiniteness and thus are rejected.
In the interest of compact prosecution, the claim will be interpreted as following: “wherein the CNP linked to miRNA-146a is administered as an aerosol formulation or as a dry powder composition for topical delivery to the lung by inhalation or as an intranasal spray.”
Claim Rejections - 35 USC § 102
Rejection of claims 1, 6, 12-14, and 23 under 102(a)(1) is withdrawn due to claim amendments.
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.
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, 6, 9, 10 are rejected under 35 U.S.C. 103 as being unpatentable over Liechty (WO2017091700, pub. 06/01/2017, the reference is applicant’s own, but is outside the 102(b)(1) 1 yr. grace period, in IDS, referred as Liechty) and Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted, of record).
Liechty discloses a a pharmaceutical composition comprising miRNA146a-conjugated cerium oxide nanoparticles (CNPs, also called nanoceria), wherein the miRNA146a-conjugated cerium oxide nanoparticles (CNPs) are configured to synergistically reduce oxidative stress and inflammation, including of a diabetic subject or following a myocardial infarction (pars. 21, 63, 164, 175-176, rel. to cl. 1, 6). Fig. 45 shows reduced pro-inflammatory cytokines (TNFa, IL-6) and increased regenerative gene (MMP-8) following CNP-miR146a in-vitro treatment of macrophage cells, while figure 46 provides an illustration of a schematic model noting the process of decreased inflammation and reactive oxygen species (ROS) production following treatment with CNP-miR146a treatment (par. 67-68). Liechty also discloses that nanovehicles, including CNP, improve the therapeutic effect of miRNA by protecting it from degradation and mediating its entry into the cell (par. 119).
Liechty does not disclose treating pulmonary inflammation caused by ALI.
Zeng et al. discloses that upregulation of miR-146a contributed to the suppression of inflammatory responses in LPS-induced acute lung injury (ALI) in rats (title, rel. cl. 1, 10, 12, 13). Zeng et al. also treated culture cells with miR-146a mimics, which suppressed LPS-mediated inflammatory mediators, and concluded that miR-146a maybe used therapeutically to suppress inflammatory response following ALI (abstract, relevant to instant cl. 1, 9, 10).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the method of treating CNP-conjugated miRNA-146a to treat inflammation of Liechty to treat ALI-induced lung inflammation, since miR146a also suppresses lung inflammation, as taught by Zeng and arrive at the claimed invention with a reasonable expectation of success. Based on Liechty teaching of reducing inflammation with CNP-miR146a conjugate and with CNP having protective features and aids in delivery of miRNA, and on Zeng’s success of administering miR-146a mimics to suppress inflammatory mediators in acute lung injury in-vitro model, a skilled artisan would reasonably expect success in administering CNP-146a conjugate to treat pulmonary inflammation that is caused by ALI by protecting the miR146a. Thus, claims 1, 6, 9-10 are obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Liechty (WO2017091700, pub. 06/01/2017, the reference is applicant’s own, but is outside the 102(b)(1) 1 yr. grace period, in IDS, referred as Liechty) and Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted) as applied to claims 1, 6, 9-10 above, as evidenced by Wang et al. (2018, Langmuir, 34, pg. 7899-7905, of record).
Disclosure of cl. 1, 6, 9-10 is noted above.
Liechty and Zeng do not disclose miRNA-146a is non-covalently associated with the CNP.
Wang et al. (2018, Langmuir, 34, pg. 7899-7905) discloses that a nucleotide (includes both DNA/RNA) molecule with phosphate backbone is adsorbed by nanoceria surface (pg. 7899). Thus, based on the teachings of Wang, the miRNA with its phosphate backbone would be strongly adsorbed by the surface of the nanoceria and is thus non-covalently associated or linked with the CNP (relevant to instant cl. 7). Thus, cl. 7 is obvious.
Claims 12, 13, 14, 23, 15, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Liechty (WO2017091700, pub. 06/01/2017, the reference is applicant’s own, but is outside the 102(b)(1) 1 yr. grace period, in IDS, referred as Liechty) and Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted) as applied to claims 1, 6, 9-10 above, and further in view of Chan (2003, Expert Opinion. Ther. Patents, 13, 1333-1343).
Claim 13 recites “promoting lung repair,” and the specification defines “promoting” or “promote” as reducing time for lung repair/injuries/damages by reducing or suppressing inflammation in the lungs (pg. 6, line 15-18).
Disclosure pertaining to rejection of claims 1, 6, 9-10 is noted above. Further, Liechty discloses that a CNP-146a pharmaceutical composition can be for topical administration in the form of a powder, suspensions, or solutions (par. 79, rel. cl. 12, 13). Liechty also teaches treating or preventing inflammation in a subject, including human, in need (par. 21, 83, rel. cl. 14, 23).
Liechty and Zeng do not disclose administration of CNP-miR146a as an aerosol formulation for topical delivery to the lung by inhalation.
Chan discloses propellant metered-dose inhalers (MDI) as the most popular form of drug delivery, since they are small, convenient, and self-powered by the propellant to form the aerosol (pg. 1334, rel. cl. 12, 13, 15, 20). Chan discloses that inhalation aerosols are widely used for direct administration of drugs to the respiratory tract for local treatment of asthma and COPD (pg. 1333, rel. cl. 12, 13). Further, Chan discloses MDI formulation as a suspension, or a mixture of suspension and solution types (pg. 1334).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified Liechty’s CNP-miR146a solution/suspensions formulation in view of Chan and arrive at the claimed invention with a reasonable expectation of success. Due to the popularity of MDI as a form of drug delivery and teachings of modifying solution/suspension for MDI formulation, one of ordinary skill in the art would have been motivated to modify the Liechty’s CNP-miR146a solution/suspension formulation for use as a MDI since they are small, convenient and self-powered to deliver an aerosol form of a drug as taught by Chan. Thus, claims 12, 13, 14, 15, 20, 23 are obvious.
Response to Arguments
Applicant's arguments filed on 05/07/2025 (“the Remarks”) have been fully considered but they are moot, since the argument is addressed primarily to the teachings of Sandford, which is no longer used in this action.
Double Patenting
The rejection of examined claims under double patenting is maintained.
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, 6, 9, 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10 of U.S. Patent No. 11833172 in view of Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted)
Regarding instant cl. 1, 9, 10, ‘172, claim 1 teaches a method for treating or preventing inflammation in a human subject in need thereof, the method comprising: administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising microRNA-conjugated cerium oxide nanoparticles (CNPs), wherein the microRNA is miRNA 146a covalently attached at a 3′ end to the cerium oxide nanoparticle via an amide linkage, and wherein the inflammation is associated with a wound. The specification of ‘172 defines “wound” as an injury to any tissue (Col. 9, line 7).
Claim 1 of ‘172 does not teach wound inflammation association with a pulmonary inflammation caused by ALI.
Zeng et al. discloses that upregulation of miR-146a contributed to the suppression of inflammatory responses in LPS-induced acute lung injury (ALI) in rats (title, rel. cl. 1, 10, 12, 13). Zeng et al. also treated culture cells with miR-146a mimics, which suppressed LPS-mediated inflammatory mediators and concluded that miR-146a maybe used therapeutically to suppress inflammatory response following ALI (abstract, relevant to instant cl. 1, 9, 10).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified the method of treating or preventing inflammation associated with a wound in a human subject by administering CNP-miRNA146a conjugate of ‘172 in view of Zeng and arrive at the claimed invention with a reasonable expectation of success. Since Zeng’s demonstrates using miRNA146a mimic to reduce inflammatory response in lung caused by ALI and since ‘172 teaches a method of treating wound inflammation in a human subject by administering CNP-miR146a conjugate, a skilled artisan would reasonably expect success of treating lung inflammation caused by ALI to a human subject by administering CNP-miRNA146a conjugate. Thus, claims 1, 9, 10 are obvious.
Regarding cl. 6, cl. 1 and 10 of ‘172 teach a covalent linkage of the miRNA146a to CNP.
Claim 7 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11833172 in view of and Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted) as applied to claims 1, 6, 9-10 above, and further in view of Wang et al. (2018, Langmuir, 34, pg. 7899-7905).
Disclosure of cl. 1, 6, 9-10 is noted above.
‘172 claims and Zeng do not disclose miRNA-146a is non-covalently associated with the CNP.
Wang et al. (2018, Langmuir, 34, pg. 7899-7905) discloses that a nucleotide (includes both DNA/RNA) molecule with phosphate backbone can be adsorbed by nanoceria surface (pg. 7899). Thus, based on the teachings of Wang, it would be obvious that the miRNA with its phosphate backbone would be strongly adsorbed by the surface of the nanoceria and is thus non-covalently associated or linked with the CNP (relevant to instant cl. 7). Thus, cl. 7 is obvious.
Claims 12, 13, 14, 15, 20, 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10, of U.S. Patent No. 11833172 in view of and Zeng et al. (2013, Exp. Lung Research, 39, pg. 275–282; only abstract submitted) as applied to claims 1, 6, 9-10 above in view of Chan (2003, Expert Opinion. Ther. Patents, 13, 1333-1343).
Claim 13 recites “promoting lung repair,” and the specification defines “promoting” or “promote” as reducing time for lung repair/injuries/damages by reducing or suppressing inflammation in the lungs (pg. 6, line 15-18).
Disclosure pertaining to rejection of claims 1, 6, 9-10 is noted above. Further, cl. 1 discloses a pharmaceutical composition comprising CNP-miRNA146a conjugate.
‘172 and Zeng do not disclose administration of CNP-miR146a as an aerosol formulation for topical delivery to the lung by inhalation.
Chan discloses propellant metered-dose inhalers (MDI) as the most popular form of drug delivery, since they are small, convenient, and self-powered by the propellant to form the aerosol (pg. 1334, rel. cl. 12, 13, 15, 20). Chan discloses that inhalation aerosols are widely used for direct administration of drugs to the respiratory tract for local treatment of asthma and COPD (pg. 1333, rel. cl. 12, 13). Further, Chan discloses MDI formulation as a suspension, or a mixture of suspension and solution types (pg. 1334).
One of the KSR rationale that may be used to support a conclusion of obviousness is that there is some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, it would have been prima facie obvious for one of ordinary skill in the art before the filing date of the claimed invention to have modified ‘172’s pharmaceutical composition comprising CNP-miR146a conjugate in view of Chan and arrive at the claimed invention with a reasonable expectation of success. Due to the popularity of MDI as a form of drug delivery and teachings of modifying solution/suspension for MDI formulation, one of ordinary skill in the art would have been motivated to modify the 172’s CNP-miR146a pharmaceutical composition for use as a MDI since they are small, convenient and self-powered to deliver an aerosol form of a drug as taught by Chan. Thus, claims 12, 13, 14, 15, 20, 23 are obvious.
Response to Arguments
Applicant's arguments filed 05/07/2025 have been fully considered but they are not persuasive. The argument argues that due to the amendment the claims overcome the double patenting rejection (pg. 7).
The argument is not persuasive, the rejection is noted above and based on additional references the instant claims are obvious.
Conclusion
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/KEYUR A VYAS/Examiner, Art Unit 1637
/Soren Harward/Primary Examiner, TC 1600