DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/07/2026, has been entered.
Status of Application
Receipt of the amendments to the claims and applicant arguments/remarks, filed 01/07/2026, is acknowledged.
Claims 17-36 are pending in this action. Claims 1-16 have been cancelled previously. Claims 17, 19-20, 22, 26-28, 31-32, 35-36 have been amended. Claims 17-36 are currently under consideration.
Any rejection or objection not reiterated in this action is withdrawn. Applicant's amendments necessitated new ground(s) of rejection presented in this office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Priority
This application is a 371 of PCT/JP2021/003258, filed January 29, 2021, which claims benefit of foreign priority to JP2020-021195, filed February 12, 2020. No English translations of the certified copies of both priority application(s) have been received. As stated previously, a certified translation of every foreign benefit application or Patent Cooperation Treaty (PCT) application not filed in English is required. 35 U.S.C. 119(b)(3), 372(b)(3) and 37 CFR 1.55(a)(4). Failure to provide a certified translation(s) may result in no benefit being accorded for the non-English application. 37 CFR 41.154(b) and 41.202(e).
Claim Objections
Claim 17-19, 26-27 are objected to because of the following informalities: As stated previously, the term “micro bubbles” recited in claim 17 should be corrected to “microbubbles” (see Specification, Abstract; Para. 0006, 0022, 0024-0031, 0033, 0038, 0075, 0077, 0104, 0142, 0144 published as US 2023/0095770). Similar is applied to claim 18-19, 26-27. Appropriate correction is required.
Claim Rejections - 35 USC § 112(1)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 17-36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
In the present case, newly introduced negative limitation “the micro bubbles do not comprise phospholipid” does not have any support in original claims and/or specification. To this point, it is noted that the instant specification teaches that microbubbles can be dispersed or localized to a part of the medium, e.g., in oily solvent (Para. 0026), and the medium may include vegetable oil (Para. 0043). Further, it is noted that it is well known in the field that vegetable oils inherently contain phospholipids. Therefore, the open language of specification does not specify the compounds that should be excluded from disclosed compositions to be used in the claimed method. Therefore, it is the examiner’s positions that said newly introduced negative limitation constitutes a new matter. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. Applicant is required to cancel the new matter in the reply to this Office Action.
Claim Rejections - 35 USC § 112(b)
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 17, 19, 20, 27 28 are 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 pre-AIA the applicant regards as the invention.
Newly amended claim 17 recites the limitation “wherein the micro bubbles comprise nitric oxide and at least another gas as a gas component” that is not reasonably clear. In the present case, it is unclear what is understood as “a gas component“ - “at least another gas”, OR “nitric oxide and at least another gas”. Similar is applied to claims 19, 27 regarding the limitation “proportion of nitric oxide in the gas component”; and/or to claims 20, 28 regarding the limitation “the gas component other than nitric oxide does not react with nitric oxide”. Clarification is required.
Claims 18, 21-26, 29-36 are rejected as being dependent on rejected independent claim 17 and failing to cure the defect.
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.
Claims 17-36 are rejected under 35 U.S.C. 103 as being unpatentable over Holland et al., US 2020/0000945A1 (cited in IDS; hereinafter referred to as Holland), in view of Kheir et al., US 2014/0010848 (hereinafter referred to as Kheir), and further in view of Eimer. US 2021/0361304 A1.
Holland teaches methods for promoting vasodilation, including treatment of myocardial infarction, infective endocarditis, cerebrovascular disease, stroke, cardiovascular disease, etc. in a patient in need thereof by delivering stabilized microbubbles encapsulating bioactive gas, e.g., nitric oxide, to a target diseased section of the patient's vasculature; and releasing the bioactive gas at the target diseased section (Claims 1, 3, 10-11; Abstract; Para. 0003, 0016, 0020 as applied to claim 17, 25, 30, 31).
Holland teaches the preparation of nitric oxide microbubbles (Para. 0063) encapsulating 100% of nitric oxide (Fig. 5; Para. 0067 as applied to claims 19, 20, 27, 28), and further teaches that said microbubbles can be incorporated into lipid dispersions (Para. 0057, 0063 as applied to claims 21, 29); and/or can be formulated into intravenous compositions and injected or otherwise administered to the subject (Para. 0046 as applied to claim 32).
Holland does not teach the use of a kit comprising vasodilator compositions and other component in isolated compartments (claims 22-24, 33-36).
Kheir teaches gas-filled microbubbles and systems for gas delivery, wherein said gas-filled microbubbles each comprise a gas core, e.g., nitric oxide, surrounded by a lipid membrane (Claims 1, 5; Title; Abstract; Para. 0007). Kheir further teaches that delivery systems for gas delivery may include: (i) a 1st chamber comprising the gas microbubbles; (ii) a 2nd chamber comprising additional components, e.g., aqueous composition; and (iii) additional 3rd clamber isolating the 1st and the 2nd chambers, i.e., having a first port connected to the 1st chamber/container, a 2nd port connected to the 2nd chamber/container, a 3rd port for releasing trapped gas, and a 4th port for connecting to a drug delivery device (e.g., a syringe). (Fig. 1; Para. 0060-0063). Kheir also teaches that the delivery systems can be a syringe-based gas infusion apparatus comprising: (i) a chamber for housing gas-filled microbubbles, (ii) a chamber for housing an aqueous diluent; and wherein (iii) said chambers are separated by a filter plate (Fig. 4A, Para. 0067-0072). Kheir teaches that said delivery systems can be used to deliver a gas into a subject for treating various diseases and conditions, e.g., vascular diseases, myocardial infarction, cerebral damage, heart disease, infection, etc. by an intravenous injection (Claim 19; Para. 0016, 0017, 0038, 0067, 0082-0098).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a kit/system for delivery of gas-filled microbubbles as taught by Kheir to deliver stabilized microbubbles encapsulating nitric oxide to a target diseased section for promoting vasodilation as taught by Holland. One would do so with expectation of beneficial results, because Kheir teaches that said delivery systems can be used to rapidly mix and infuse any suspension, to mix and deliver gas-filled microbubbles, are easy to use in an emergency, allow for rapid administration of high volumes of fluid, and can filter out entrapped gas (Para. 0072).
Further, the cited prior art does not teach the use microbubbles that do not comprise phospholipid (Claim 17).
Eimer teaches a method of producing microbubbles of nitric oxide having a targeted size in a solution that may include saline or dextrose, and intravenously directing the solution into a patient's venous circulatory system and to the right side of the patient's heart (Abstract; Para. 0004-0009). Eimer teaches that such microbubbles from nitric oxide can be used for target delivery of nitric oxide to specific portions of the pulmonary arteries, as a vasodilator, without the deleterious effects (Para. 0034).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use/try microbubbles of nitric oxide as taught by Eimer in methods for promoting vasodilation and taught by Holland. One would do so with expectation of beneficial results, because Eimer teaches microbubbles from nitric oxide that can be used as a vasodilator without deleterious effects. Claims 18, 24, 26 are rejected as being dependent on rejected independent claims 17 and 25.
Response to Arguments
Applicant's arguments, filed 01/07/2026, have been fully considered, but they were not found to be persuasive for the reasons set forth above. New rejections have been added to the record to address newly introduced amendments and/or to clarify the position of the examiner. Applicant is advised to clarify the claim language, the structure of the compositions to be used in the claimed method, and clearly point out the patentable novelty, which the applicant thinks the claims present in view of the state of the art disclosed by the references cited, to place the application in condition for allowance.
Conclusion
No claim is allowed at this time.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA V. TCHERKASSKAYA whose telephone number is (571)270-3672. The examiner can normally be reached 9 am - 6 pm, Monday - Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax can be reached on (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/OLGA V. TCHERKASSKAYA/
Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615