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 .
Status of the Claims
Claims 1-45 are pending. Claims 16-21 and 23-45 have been withdrawn.
Claims 1-15 and 22 are currently under examination.
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.
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 1-15 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Loughlin et al. (US20180193332A1, Published 07/12/2018; cited in the IDS filed 01/05/2025) as evidenced by Walpole et al. (BMC Public Health 12, 439 (2012)).
Applicant’s Invention
Applicants claims are drawn to a formulation comprising: between 0.3% (w/v) and about 3.0 (w/v) naloxone or a pharmaceutically acceptable salt thereof, between about 0.3% (w/v) and about 3% (w/v) NaCl, between about 0.005% (w/v) and about 0.05% (w/v) BZK, between about 0.02% (w/v) and about 0.25% (w/v) EDTA, and between about 0.10% (w/v) and about 1.0% (w/v) citric acid.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1-8 and 12, Loughlin teaches pharmaceutical solutions are described herein. These solutions are useful for treating, inter alia, opioid overdose. In certain embodiments, the solutions comprise about 2 to about 20% (w/v) of naloxone, and between about 0.2% (w/v) and 1.8% (w/v) of an isotonicity agent such as NaCl (paragraph [0011]). Loughlin also teaches in certain embodiments, the naloxone solution described herein may also comprise a stabilizing agent between about 0.05% and about 0.5% (w/v) of the stabilizing agent such as EDTA (paragraph [0046]). Loughlin further teaches the naloxone solution described herein may also comprise a preservative selected from the group consisting BZK and citric acid and combinations thereof, between 0.005% and about 0.119 (w/v) (paragraph [0047]). Loughlin further teaches regardless of how naloxone is provided, the ultimate naloxone solution comprises between about 1% (w/v) and about 15% (w/v) of naloxone (paragraph [0042]).
Regarding claim 9, Loughlin teaches the solution contains a quantity of isotonicity agent sufficient to achieve an osmolality between about 300 mOsm and about 2500 mOsm (paragraph [0045]).
Regarding claims 10-11, Loughlin teaches that the solutions described herein will have a pH between about 3 and about 7 (paragraph [0049]).
Regarding claims 13-15, Loughlin teaches in tables 1-2 exemplary aqueous naloxone formulations comprising naloxone, propylene glycol, EDTA, NaCl and BZK, therefore the formulation does not comprise methylparaben, propylparaben, or alkylparabens (paragraphs [0057-0058]).
Regarding claim 22, Loughlin teaches pharmaceutical solutions are described herein. These solutions are useful for treating, inter alia, opioid overdose. In certain embodiments, the solutions comprise about 2 to about 20% (w/v) of naloxone, and between about 0.2% (w/v) and 1.8% (w/v) of an isotonicity agent such as NaCl (paragraph [0011]). Loughlin also teaches in certain embodiments, the naloxone solution described herein may also comprise a stabilizing agent between about 0.05% and about 0.5% (w/v) of the stabilizing agent such as EDTA (paragraph [0046]). Loughlin further teaches the naloxone solution described herein may also comprise a preservative selected from the group consisting BZK and citric acid and combinations thereof, between 0.005% and about 0.119 (w/v) (paragraph [0047]). Loughlin continues to teach devices containing solution to deliver 4 mg dose of naloxone. As evidenced by Walpole, Average body mass globally was 62 kg (results section, first paragraph). Therefore, Loughlin teaches administering to a subject 0.06 mg/kg of naloxone. Loughlin further teaches An advantage of the methods disclosed herein is that they achieve an acceptably high serum concentration of the opioid antagonist very quickly. For example, in certain embodiments the plasma concentration versus time curve of opioid antagonist (e.g., naloxone) in the patient has a tmax of less than 30 minutes. In certain embodiments, the patient experiences a geometric mean naloxone Cmax not less than about 3 ng/mL (paragraph [0070]).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Loughlin does not disclose a single embodiment or example where every limitation recited in the instant claims is taught.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
The claims are considered prima facie obvious to one of ordinary skill in the art at the time of filing because Loughlin teaches all of the claimed elements. It would have been prima facie obvious to one of ordinary skill in the art before the time of filing to make a formulation comprising: between 0.3% (w/v) and about 3.0 (w/v) naloxone or a pharmaceutically acceptable salt thereof, between about 0.3% (w/v) and about 3% (w/v) NaCl, between about 0.005% (w/v) and about 0.05% (w/v) BZK, between about 0.02% (w/v) and about 0.25% (w/v) EDTA, and between about 0.10% (w/v) and about 1.0% (w/v) citric acid because Loughlin teaches and contemplates all the elements required to make the composition.
With regards to claim 2, wherein the formulation comprises between about 0.20% (w/v) and about 0.50% (w/v) citric acid, it would have been obvious to one of ordinary skill in the art to vary the amounts of citric acid depending on the desired results. One would have understood in view of Loughlin that the solutions comprise citric acid between 0.005% and about 0.119 (w/v) (paragraph [0047]). Therefore, it would have been obvious to one of ordinary skill in the art to optimize the amount of citric acid using routine experimentation to obtain the desired amount because Loughlin teaches amounts of citric acid as a preservative. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). See MPEP 2144.05 (II). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07). The examiner further points out that about 0.119% (w/v) taught in Loughlin is merely close to the instantly claimed 0.20% (w/v) of citric acid. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See MPEP 2144.05 (I).
With regards to claim 22, wherein 0.15 mg/Kg to about 0.45 mg/Kg is administered to a subject in need, it would have been obvious to one of ordinary skill in the art to vary the dosage of naloxone solution administered depending on the desired results. One would have understood in view of Loughlin that devices containing solution to deliver 4 mg dose of naloxone. As evidenced by Walpole, Average body mass globally was 62 kg (results section, first paragraph). Therefore, Loughlin teaches administering to a subject 0.06 mg/kg of naloxone as 4mg divided by 62 kg equals 0.06 mg/kg. Therefore, it would have been obvious to one of ordinary skill in the art to optimize the dosage of naloxone solution based on the body mass of the subject in need using routine experimentation to obtain the desired amount because Loughlin teaches dosage of naloxone solution. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). See MPEP 2144.05 (II). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Response to Arguments
Applicant's arguments filed 02/24/2026 have been fully considered but they are not persuasive.
On pages 1-2 of Applicants remarks, Applicants argue that under §102(b)(2)(c), Loughlin is disqualified from use as prior art to support the instant obviousness rejection because Loughlin and the claimed invention in the instant application, are owned by Emergent BioSolutions, Inc.
This argument is not persuasive. The Examiner points out that Loughlin was applied as a §102(a)(1) reference because the Loughlin was published prior to the earliest effective filing date of the instant application. Applicants cite to the exceptions under §102(a)(2) which is for patents and applications that were published after the effective filing date, wherein their exceptions are under §102(b)(2). The Examiner further points out that since Loughlin is a §102(a)(1) reference, the only the §102(b)(1) exceptions apply, which one of the abilities to accept the exception is if the disclosures are made 1 year or less before the effective filing date of the claimed invention. In this case, Loughlin was published 07/12/2018 which is more than a year prior to the earliest effective filing date of the instant application, therefore, there are no exceptions that apply to Loughlin, and therefore, Loughlin is available as prior art against the instant claims. Due to foregoing reasons, the rejections are maintained.
Conclusion
No claims are allowed.
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 AFUA BAMFOAA BOATENG whose telephone number is (703)756-1358. The examiner can normally be reached Monday - Friday 9:00am - 5:00pm.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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