DETAILED ACTION
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention filed on 05/26/2026 in the matter of Application N° 18/146,499. Said documents are entered on the record. The Examiner further acknowledges the following:
The present application, filed on or after May 26, 2026, is being examined under the first inventor to file provisions of the AIA .
Thus, claims 1-3, 5-17, and 19-30 represent all claims currently under consideration.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 26, 2026 has been entered.
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.
Claims 1-3, 5-17, and 19-30 are rejected under 35 U.S.C. 103 as being unpatentable over Dusci (US10966990B2), in view of Chundury et al. (US20030232212A1).
Regarding claims 1, 5, 6, 7, 16, 20, and 21, Dusci teaches a flexible plastic bag that contains a terminally sterilized, preservative-free aqueous midazolam solution that contains 0.25 to 1.5 mg/ml of midazolam and has a pH between 2.5 and 3.5 (See Abstract, claim 1, and claim 7). Dusci teaches flexible plastic containers (bags) that are sold commercially, like Excel, are made of three layers of ethylene-polypropylene with an outer layer of polyester elastomer (See pg. 5, column 4, lines 13-16). Dusci teaches polypropylene, polyethylene, and ethylene/propylene copolymers are the main polymeric materials that can be utilized (See pg. 5, column 3, lines 48-51).
Regarding claims 2 and 3, Dusci teaches the preferred tonicity agent is sodium chloride. The formulation should contain about 9 mg/ml of the midazolam if sodium chloride is the tonicity adjusting agent and the midazolam concentration is around 1.0 mg/ml (See pg. 4, column 2, lines 51-56, table 1, and claim 3).
Regarding claim 4, Dusci teaches when the pH approaches around 3.2, midazolam at a dosage of 2 mg/mL dissolves in a solution of 0.9% NaCl (See pg. 5, column 3, lines 3-6).
It would have been obvious to one of ordinary skill in the art prior to the instant effective filing date to use the teachings of Dusci wherein the terminally sterilized, preservative-free aqueous midazolam solution, which has a pH of 2.5 to 3.5 and contains 0.25 to 1.5 mg/ml of midazolam, is contained in a flexible plastic bag.
Regarding claim 8, Dusci teaches the ready to-use aqueous midazolam solution, which contains about 0.5 mg/ml of midazolam and is terminally sterilized and preservative-free (See claim 5).
Regarding claim 9, Dusci teaches aqueous midazolam solution that is terminally sterilized and free of preservatives, containing 0.25 to 1.5 mg/ml of midazolam (See Abstract).
Regarding claim 10, Dusci teaches there are roughly 450 mg of sodium chloride in a 50 ml solution with a midazolam concentration of 1 mg/ml and 100 ml solution with a midazolam concentration of 1 mg/ml (See pg. 4, column 2, lines 55-59).
Regarding claims 11, 15, 17, 23, 24, and 25, Dusci teaches the current invention’s formulations will range in concentration from roughly 0.5 mg/ml to 1.25 mg/ml. The ideal concentration range for the formulation is between 0.5 and 1.0 mg/ml. The amount of sodium chloride to be included in the formulation is about 9 mg/ml of the midazolam solution, where in the pH is 2.5 to 3.5. The primary polymeric materials which may be used include, polypropylene, polyethylene, ethylene/propylene copolymers etc. Dusci teaches as part of anesthesia or when a patient is receiving treatment in a critical care unit, midazolam is used intramuscularly or intravenously for preoperative sedation anxiolysis, and amnesia (See pg. 4, column 2, lines 34-40, lines 55-56, claim 7, and pg. 5, column 4, lines 43-46 and See pg. 4, column 1, lines 22-23 and lines 37-40 and claims 4 and 5).
Regarding claim 12, Dusci teaches, the ready to use midazolam solution, which is terminally sterilized and free of preservatives, contains about 9 mg/ml of sodium chloride solution (See claim 12).
Regarding claim 13, Dusci teaches, the ideal concentration range for the formulation is between 0.5 and 1.0 mg/ml and midazolam at a dosage of 2 mg/mL dissolves in a solution of 0.9% NaCl (See pg. 4, column 2, lines 34-40 and pg. 5, column 3, lines 3-6 and claim 5).
Regarding claim 14, Dusci teaches, the ideal concentration range for the formulation is between 0.5 and 1.0 mg/ml and midazolam at a dosage of 2 mg/mL dissolves in a solution of 0.9% NaCl. If sodium chloride is the tonicity adjusting agent and the midazolam concentration is about 1.0 mg/ml, the amount of sodium chloride to be included in the formulation is about 9 mg/ml of the midazolam solution (See pg. 4, column 2, lines 34-40, and lines 53-56, and pg. 5, column 3, lines 3-6 and claims 1 and 6).
Regarding claim 18, Dusci teaches, stability studies were conducted to confirm that the formulation was stable. A graphical illustration of the premix formulation midazolam injections chemical stability after six months of storage under accelerated settings can be found in FIG. 1-4. The pH and color of the liquids inside Nexce bags did not change after six months of stability at 40 degrees Celsius. There was no apparent reduction in the Midazolam assay after six months at 40 degrees Celsius in comparison to T=0 sterilized. The formulations total impurities in the Nexcel bag are still equivalent to the outcomes at T=0 (See pg. 6, column 6, lines 26-36).
Regarding claim 19, Dusci teaches the amount of premixed formula determines the bag’s volume. Based on current midazolam dosage, the volume of the premixed formula can range from 10 ml to 1000 ml, with 50 ml and 100 ml being preferred (See pg. 5, column 3, lines 32-35).
Regarding claim 22, Dusci teaches for preoperative sedation, anxiolysis, and amnesia, midazolam is administered intramuscularly or intravenously. It can also be continuously infused into the veins to sedate patients who are intubated and on mechanical ventilation as part of anesthesia or while they are receiving treatment in a critical care unit (See pg. 4, column 1, lines 22-23 and lines 37-40).
Regarding claim 1, Chundury et al. teaches a PVC-free co-extruded multilayer thermoplastic film structure specifically adapted for forming medical fluid containers, such as intravenous solution bags (See paragraph 0008). Chundury et al. discloses that the multilayer film may be manufactured as a co-extruded blown film or as a co-extruded flat sheet and that the individual layers are simultaneously co-extruded without the use of adhesives (See paragraph 0009 and 0012). The inner and outer layers of the film comprise polypropylene-containing materials, including propylene-ethylene copolymers (See paragraph 0008 and 0009). Chundury et al. further teaches that medical containers formed from the co-extruded multilayer film exhibit desirable clarity, flexibility, toughness, tear resistance, barrier properties, and suitability for steam sterilization (See paragraph 0010).
It would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date at the time of the invention to fabricate the flexible plastic container of Dusci et al. from the co-extruded multilayer polypropylene-containing film taught by Chundury et al. one of ordinary skill in the art would have been motivated to make this modification because the secondary reference expressly identifies co-extruded multilayer polypropylene films as suitable for forming flexible medical-fluid and intravenous bags and teaches that such films provide predictable benefits, including flexibility, mechanical strength, barrier performance, optical clarity, and resistance to steam sterilization. The proposed modification would merely employ a known medical-container manufacturing technique and known polymeric materials for their established functions.
Response to Arguments
Applicant's arguments filed May 26, 2026 have been fully considered but they are not persuasive. Applicant argues that Dusci et al. neither discloses, suggests, nor exemplifies a midazolam formulation housed in a flexible plastic container fabricated from a co-extruded multilayer sheeting comprising one or more materials selected from polypropylene, polyamide, and polyethylene, as presently claimed. Specifically, Applicant contends that although Dusci et al. lists polypropylene and polyethylene among numerous polymeric materials that may be used for bags, ports, and closures, the refence does not disclose a co-extruded multilayer film forming the body of the flexible container. Applicant further asserts that Dusci et al. only discussion of co-extrusion pertains to port tubing or port sleeves rather than the bag body itself. Additionally, Applicant argues that the working examples of Dusci et al. are limited to midazolam formulations stored in Nexcel® bags having an innermost layer comprising a copolymerized ethylene-vinyl acetate material, rather than the presently claimed multilayer container.
The Applicant’s arguments are not persuasive. Dusci et al. expressly discloses terminally sterilized, preservative-free aqueous midazolam formulations having concentrations of about 0.25 to 1.5 mg/mL and a pH of about 2.5 to 3.5, stored in flexible plastic containers for pharmaceutical storage and administration. Dusci et al. further identifies polypropylene, polyethylene, and ethylene/propylene copolymers as suitable polymeric materials for constructing such flexible containers. Accordingly, Dusci et al. teaches both (1) substantially the same type of aqueous midazolam formulation, with concentrations that overlap those presently claimed, and (2) the use of polymeric container materials that encompass the polypropylene and polyethylene recited in the instant claims.
Applicant emphasis on the absence of an express disclosure of a co-extruded multilayer bag body is likewise unpersuasive. Obviousness under 35 U.S.C. 103 does not require that a single prior art reference expressly disclose every claimed structural detail in the precise form recited. Rather, the relevant inquiry is whether the prior art, as a whole, would have suggested the claimed subject matter to one of ordinary skill in the art with a reasonable expectation of success. Dusci et al. identifies the same pharmaceutical formulation and recognizes the claimed polymeric materials as suitable for flexible container construction. Selection of a known multilayer configuration employing these recognized polymeric materials would have constituted no more than the predictable use of prior art elements according to their established functions and would have been an obvious matter of routine engineering design choice.
Applicant’s arguments regarding the stability testing disclosed in Dusci et al. are also unpersuasive. The prior art is not required to disclose the identical storage duration or temperature conditions recited in the claims in order to support a conclusion of obviousness. Rather, it need only provide sufficient teachings to render the claimed formulation and packaging combination obvious to try with a reasonable expectation of success. Dusci et al. provides such teachings by disclosing the same class of preservative-free aqueous midazolam formulations together with suitable polymeric materials for flexible pharmaceutical containers. Optimization of the container configuration and selection among known polymeric materials for pharmaceutical packaging constitute routine experimentation well within the ordinary skill of the art. See MPEP 2143 and 2144.
Accordingly, Applicant has not demonstrated error in the Examiner’s factual findings or the conclusion of obviousness. Nor has Applicant identified any disclosure in Dusci et al. that teaches away from, criticizes, or otherwise discourages the use of multilayer flexible containers comprising polypropylene, polyamide, polyethylene, or combinations thereof. In the absence of such evidence, the Examiner maintains that employing these known polymeric materials in a co-extruded multilayer flexible container for the disclosed midazolam formulation would have been an obvious design choice for one of ordinary skill in the art at the time of the invention, yielding no more than predictable results. Therefore, the rejection under 35 U.S.C. 103 is maintained.
No claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Barber whose telephone number is (703) 756-5302. The examiner can normally be reached on Monday through Friday from 6:30 AM to 3:30 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax, can be reached at telephone number (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KIMBERLY BARBER/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights