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 1-17 are pending. Claim 17 stands withdrawn.
Claims 1-16 are under current examination.
All rejections not reiterated have been withdrawn.
Information Disclosure Statement
The examiner thanks Applicant for pointing to the location of the IDS size fee statement, the information disclosure statement is being considered by the examiner.
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 1-14 and16 are rejected under 35 U.S.C. 103 as being unpatentable over Castile et al. (WO2005/021041; publication date: 03/10/2005) and Mack et al. (US 2019/0275054; publication date: 09/12/2019; available as prior art under 35 USC 102(a)(1) and 102(a)(2); claiming priority to provisional application nos. 62/749,407, filed 10/23/20218 and 62/640,232, filed 03/08/2018).
Castile discloses an aqueous composition comprising 26-120 mg/mL meloxicam, a base, and solubility enhancing agents that may include cyclodextrins (abstract). For example, the composition may contain 30 to 90 mg/mL meloxicam (page 5, lines 1-2). All examples are made up in water (i.e. a pharmaceutically acceptable solvent). The composition is intended to be used as is (i.e. it is ready-to-use), the objective is to make a high concentration meloxicam solution (see e.g. page 2, lines 20-22) and the compositions remain stable for up to 6 months (see e.g. formulation L, which corresponds to example 17, see page 23, line 19 where formulations A to L are aligned to examples 6-17 and table 3, page 24 for stability data). Thus, the stability and clarity are considered inherent properties of Castile’s composition, absent evidence to the contrary. Additionally, the examiner points out that Castile’s objective is to formulate a stable solution and therefore optimizing the factors disclosed by Castile to influence this property would have been prima facie obvious to one of ordinary skill. Example 17 contains 55 mg/mL meloxicam, 200 mg/mL hydroxypropyl-b-cyclodextrin, and meglumine (page 23, lines 1-15). Although Castile discusses nasal administration, the composition is considered to fall within the scope of the limitation “injectable” nothing precludes delivery of the composition by injection.
Castile does not disclose formulating the composition such that it is suitable for intravenous administration.
Mack discloses the following: oral meloxicam, however, has a slow onset of action with tmax observed approximately 5 – 7 hours after administration and is therefore not used for treatment of acute pain (0004). There is a need for a method of administering meloxicam which can provide a faster onset of action, a longer therapeutic window, without the need for multiple injections a day (0006). Mack discloses a method of treating pain in a patient in need thereof with meloxicam, comprising administering to the patient a bolus dose of meloxicam intravenously, wherein the meloxicam is at a concentration of about 30 mg/mL (0007) in which the bolus dose of meloxicam is administered to the patient over the course of about 1 to about 60 seconds (0008). Mack discloses that the bolus dose of 30 mg/mL meloxicam can be used without dilution (0058) and will provide rapid onset of pain relief due to increased concentration of meloxicam (0057).
Thus, in view of Castile, the artisan of ordinary skill would have understood that meglumine and cyclodextrin derivatives can be used to improve meloxicam solubility in aqueous solution to values greater than 30 mg/mL (e.g. example 17 achieves a concentration of 55 mg/mL using a cyclodextrin derivative and meglumine). In view of Mack, one would have understood that improving the solubility of meloxicam allows for high doses, particularly 30 mg/mL, to provide rapid pain relief.
It would have been prima facie obvious to adapt Castile’s 30 mg/mL meloxicam solution for intravenous injection, including requisite sterility, viscosity, and osmolality. The skilled artisan would have been motivated to do so to provide rapid relief in a setting of acute onset pain and would have had reasonable expectation of success because Castile establishes such high concentrations can be achieved. Regarding the sterility, viscosity, and osmolality for intravenous injection, the examiner considers achieving these to have been a matter of routine for one of ordinary skill in the art.
Examples that contain meloxicam, meglumine, and a cyclodextrin derivative (see examples 2 and 17) contain meloxicam in an amount greater than “about 30 mg/mL”; however, it would have been prima facie obvious to formulate a composition containing meloxicam at “about 30 mg/mL” because this value is within the range disclosed for meloxicam by Castile. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). See also MPEP 2144.05.
With regard to claims 2-7, 10, 11, 13, and 14, Castile discloses that the amount of base (e.g. meglumine) is 0.7 to 1.8 moles per mole of meloxicam. The composition may also comprise from 10 – 1500 mg/mL cyclodextrin (page 9, lines 11-13). These ranges would provide one of ordinary skill with a starting point to optimize the amounts of the agents disclosed to solubilize meloxicam. See MPEP 2144.05: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955).
With regard to claim 8, the composition may have a pH in the range of from 6 to 10.5 (page 11, lines 7-8). This range overlaps with the range recited in the instant claims. See MPEP 2144.05.
With regard to claim 9, the composition should have an osmolality of 0.25 to 1.10 osmol/kg, i.e. 250 to 1100 mOsm, as 1 mOsm is 0.001 osmol/L and 1kg is approximately 1 L of aqueous solution. This range overlaps with the range recited in the instant claims. See MPEP 2144.05.
With regard to claims 12 and 13, as noted above, Castile discloses hydroxypropyl-b-cyclodextrin as a preferred and exemplary cyclodextrin derivative to solubilize meloxicam.
With regard to claim 16, as noted above all examples are made up in water (i.e. a pharmaceutically acceptable solvent) and the abstract indicates that the solution is aqueous.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Castile et al. (WO2005/021041; publication date: 03/10/2005) and Mack et al. (US 2019/0275054; publication date: 09/12/2019; available as prior art under 35 USC 102(a)(1) and 102(a)(2); claiming priority to provisional application nos. 62/749,407, filed 10/23/20218 and 62/640,232, filed 03/08/2018) as applied to claims 1-14 and 16 above, and further in view of Yang et al. (US20160022822A1; publication date: 01/28/2016).
The relevant disclosure of Castile is set forth above.
Castile is silent with respect to including povidone in the composition.
Yang discloses that in addition to substances such as meglumine, povidone was known to function as a stabilizer for meloxicam (see e.g. abstract).
It would have been prima facie obvious to add povidone to Castile’s meloxicam formulation. The artisan of ordinary skill would have been motivated to do so in order to lend further stability to the solution and would have had reasonable expectation of success because povidone had been disclosed in the prior art to provide this property to meloxicam solutions.
Response to Arguments
Applicant's arguments filed 09/09/2025 have been fully considered but they are not persuasive.
On pages 7-8, Applicant argues that Castile is limited to intranasal administration of meloxicam and therefore does not disclose intravenous formulations. Applicant argues further that formulations may not be suitable for intravenous administration that may not be isotonic as needed for intravenous injection and may have excessive viscosity.
As an initial matter, the examiner notes that Castile discloses formulations having osmolality overlapping with the ranges for this parameter cited in the instant claims, and is considered, therefore, to disclose osmolality suitable for intravenous injection. With regard to expressly formulating the composition for intravenous injection, this new limitation has been addressed by the new grounds of rejection set forth above over Castile and Mack.
On pages 7-8, Applicant argues that Castile does not teach the specific combination of meglumine and a cyclodextrin derivative as the solubilizer when the meloxicam concentration is as low as recited in the instant claims. Applicant cites Castile’s statement indicating that an additional solubility enhancer (e.g. cyclodextrin) can be added when the concentration of meloxicam is 50 mg/mL or higher.
This argument is not persuasive because (1) one having ordinary skill would have recognized that if cyclodextrin can be used to solubilize meloxicam in aqueous solution at 50 mg/mL it would certainly also be effective at 30 mg/mL and (2) Mack discloses 30 mg/mL is a preferred dose of meloxicam. Achieving solubility at 30 mg/mL with a combination of recognized solubilizing agents (meglumine and cyclodextrin) would have merely been optimization for one of ordinary skill. See MPEP 2144.05.
On page 8, Applicant argues that Castile describes drawbacks of intravenous administration.
This argument is not persuasive because one having ordinary skill in the art would have known that intravenous administration of meloxicam would have benefits in terms of rapid onset of action in the acute pain setting, as established by Mack.
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 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12263176.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims anticipate the instant claims. The invention of the ‘176 patent falls entirely within the scope of the instant claims.
Response to Arguments
Applicant's arguments filed 09/09/2025 have been fully considered but they are not persuasive.
On page 9, Applicant argues that the instant claims are patentable for the same reasons discussed for the obviousness rejection.
This argument is not persuasive because the reasoning underlying the obviousness rejection as well as the references cited are totally different from the reasons for the double patenting rejection.
Regarding Applicant's argument that the double patenting rejections should be held in abeyance, the double patenting rejections apply to the claims as they are currently written, therefore these double patenting rejections are maintained. Further, Applicants’ request to hold the rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Thus, the rejection is maintained in the absence of a terminal disclaimer.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617