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 .
DETAILED ACTION
Status of claims
The amendment filed on Jan. 19, 2026 is entered. Claims 2-4, 6 and 10 have been canceled and claims 7-9 has been withdrawn. Claims 1 and 5 are under examination in the instant office action.
Applicants' arguments, filed on Jan. 19, 2026, have been fully considered but they are not deemed to be persuasive or moot in view of new grounds of rejection, which are necessitated by the amendments (newly added limitations). Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied in view of amendments. They constitute the complete set presently being applied to the instant application.
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 1 and 5 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.
The claim 1 as amended recites “the amount of celecoxib or pharmaceutically acceptable salts thereof is 100 mg/day and the amount of methocarbamol or pharmaceutically acceptable salts thereof is 50 mg/day”.
First, there is insufficient antecedent basis for the limitation, “the amount” before celecoxib and methocarbamol. Also, the amount appears to be intended for an amount which is present in the composition. However, “the unit”, mg/day is generally used for a dose to be administered. Thus, it is unclear whether it is an amount to be preset in a composition or a dose to be administered. If it is intended to be the amount present in the composition, it does not make sense. Is it intended to mean that the combination comprise celecoxib in a daily dosage amount of 100 mg and methocarbamol in a daily dosage amount of 50 mg? Also, if the amount is a dose to be administered to a subject, it would be intended use limitation, which does not further limit the claimed composition.
The way the claims recites leads to confusion over the intended scope of the claim. As such, one of ordinary skill in the art cannot determine the metes and bounds of these claims. Appropriate correction is required.
For the examination, it is interpreted to be a daily dose to be administered in light of the specification.
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 of this title, 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 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over US 2004/0204413 (hereafter, Faour) in view of US 20020015735 (hereafter, Hedden) and US 2010/0016265 (hereafter, Yusurf)
Faour discloses a pharmaceutical composition and dosage form for oral administration containing in combination a COX-II inhibitor such as rofecoxib, celecoxib, and meloxicam and a muscle relaxant and at least one pharmaceutical excipient and their use in treating pain related disorders, in particular muscular or skeletal pain disorders, such as muscle pain, arthritis, osteoarthritis, inflammation, muscle pain, acute and chronic pain, chemoprevention, dental pain, dysmenorrhea, gout, headache, tendonitis, bursitis, and rheumatoid arthritis when administered to a mammal including human (abstract, [0001], [0027], [0040], [0124], and claim 1). Methocarbamol is specifically disclosed as one of the muscle relaxants and celecoxib as one of COX-II inhibitors ([0010] and claim 1).
Faour teaches that the COX-II inhibitor and muscle relaxant together provide an improved, additive or synergistic therapeutic effect when administered to a subject ([0028], [0097] and claim 1).
Faour further discloses that when the pharmaceutical composition is included in a dosage form, each unit dose will contain therapeutically effective amounts of the COX-II inhibitor and the muscle relaxant and the unit dose is provided as a single therapeutic administration ([0001], [0028] and [0097]).
In addition, Faour discloses the pharmaceutical composition is contained within a dosage form such as a gel, cream, ointment, pill, tablet, capsule, liquid, suspension, osmotic device, bead, granule, spheroid, particulate, paste, pill, reconstitutable solid, or powder; and the pharmaceutical composition can be adapted for oral or buccal delivery ([0010]).
While Faour does not specifically disclose an example comprising celecoxib and methocarbamol, the prior art explicitly teaches the combination of a muscle relaxant and a COX-II inhibitor wherein methocarbamol and celecoxib are specifically listed and claimed as one of the muscle relaxants and one of COX-II inhibitors, respectively (see [0010] and claim 1). Thus, one of ordinary skill in the art would at once envisage the combination of methocarbamol as a muscle relaxant and celecoxib as a COX-II inhibitor, which are selected from the limited number of clearly named species of muscle relaxants and COX-II inhibitors. See MPEP 2131.02 III.
In the alternative, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select celecoxib from the limited number of specifically listed COX-2 inhibitors and methocarbamol from the limited number of specifically listed muscle relaxants for preparing a combination with a reasonable expectation of success because Faour already teaches, motivates and suggests such combination for improved or synergistic therapeutic effects in the treatment of muscular pain and inflammation. The skilled artisan would have been motivated to prepare the claimed combination for obtaining an alternative combination in the treatment of muscular pain and inflammation on a reasonable expectation that the resulting combination would provide improved or synergistic therapeutic effects similar to the exemplary combination specifically disclosed in Faour.
Faour does not specifically disclose the specific amount of celecoxib and methocarbamol as amended. However, it was known in the art that celecoxib compositions comprise celecoxib in a daily dosage amount of about 10 mg to about 1000 mg, and still more preferably about 100 mg to about 200 mg as evidenced by Hedden ([0265]). Hedden further discloses that the amount of celecoxib in each dose unit is about 100 mg to about 200 mg and once a day administration is preferred for pain management (claims 14 and 15). The range overlap the claimed range of celecoxib.
Also, Yusuf teaches a pharmaceutical formulation for treating pain comprising methocarbamol in combination with other drugs, wherein the pharmaceutical formulation contains 40 mg to 100 mg of methocarbamol (abstract and claim 17). The range overlap the claimed range of methocarbamol.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Faour and the amount ranges of celecoxib and methocarbamol taught by Hidden and Yusuf because of the following reasons: Faour explicitly teaches and suggest a pharmaceutical combination comprising COX-II inhibitor such as celecoxib and a muscle relaxant such as methocarbamol in therapeutically effective amounts for treating pain. Also, Hedden and Yusuf teach therapeutically effective amounts of celecoxib and methocarbamol for treating pain, which overlap claimed amount of celecoxib and methocarbamol. Thus, the skilled artisan would have been motivated to optimize the therapeutically effective amounts of celecoxib and methocarbamol taught by Hedden and Yusuf for combinational use in a single dosing unit to obtain desired therapeutic effects.
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); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Also, a rejection under 35 USC §103 is proper for that portion of the range that overlaps as it would have been prima facie obvious to have selected the overlapping portion of the range. See MPEP 2144.05 Obviousness of Ranges:
In addition, it is well-established that merely selecting proportions and ranges is not patentable absent a showing of criticality. In re Becket, 33 USPQ 33; In re Russell, 169 USPQ 426. “[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); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”)
Response to Applicant’s arguments
Responses are limited to Applicants' arguments relevant to either reiterated or newly applied rejections.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is important to note that in an obvious rejection, it is not necessary that one reference addresses any limitation in a particular claim but that the references, when combined, do so. In this case, while Faour does not specifically disclose an example comprising celecoxib and methocarbamol, the prior art explicitly teaches the combination of a muscle relaxant and a COX-II inhibitor wherein methocarbamol and celecoxib are specifically listed and claimed as one of the muscle relaxants and one of COX-II inhibitors, respectively (see [0010] and claim 1). Thus, one of ordinary skill in the art would at once envisage the combination of methocarbamol as a muscle relaxant and celecoxib as a COX-II inhibitor, which are selected from the limited number of clearly named species of muscle relaxants and COX-II inhibitors. See MPEP 2131.02 III. In addition, Faour explicitly teaches, motivates and suggests a combination of a muscle relaxants and a COX-II inhibitor for improved or synergistic therapeutic effects in the treatment of muscular pain and inflammation. The skilled artisan would have been motivated to prepare the claimed combination for obtaining an alternative combination in the treatment of muscular pain and inflammation on a reasonable expectation that the resulting combination would provide improved or synergistic therapeutic effects similar to the exemplary combination specifically disclosed in Faour. Also, Hedden and Yusuf are cited for known therapeutically effective amounts of celecoxib and methocarbamol for treating pain, which overlap claimed amount of celecoxib and methocarbamol. Thus, the skilled artisan would have been motivated to optimize the therapeutically effective amounts of celecoxib and methocarbamol taught by Hedden and Yusuf for combinational use in a single dosing unit to obtain desired therapeutic effects. Also, 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. See MPEP 2144.05 IIA. Applicant has not demonstrated the criticality of claimed parameter.
Applicant again argued that the combination of cited art dose not teach or suggest the unexpected and synergistic results of the claimed combination that is a triple effect: analgesic, anti-inflammatory, and muscle relaxant, being better tolerated and with less adverse effects in patient with pain, inflammation and muscular contractions, referring to Fig. 3.
It is again noted that it is applicant's burden to demonstrate unexpected results over the prior art. See MPEP 716.02, also 716.02 (a) - (g). Furthermore, the unexpected results should be demonstrated with evidence that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). Moreover, evidence as to any unexpected benefits must be "clear and convincing" In re Lohr, 137 USPQ 548 (CCPA 1963), and be of a scope reasonably commensurate with the scope of the subject matter claimed, In re Linder, 173 USPQ 356 (CCPA 1972).
First, the alleged unexpected result is not commensurate with the scope of the claimed invention. Claim 1 as amended recites that the amount of celecoxib is 100 mg/day and the amount of methocarbamol is 50 mg/day. However, the test results disclosed in the specification are based on the administration of 100 mg/kg celecoxib and 50 mg/kg methocarbamol to rats. For example, when the dosage for rats is converted to human dosage based on the human equivalent dose calculation (dividing rat dose by 6.2), the dosages for rats (100 mg/kg celecoxib and 50 mg/kg methocarbamol) can be converted to 16.1mg/kg and 8.06 mg/kg for the human dosage. See Table 1 for the human equivalent dose calculation in Nair et al. (J. Basic Clin Pharma 2016; 7:27-31, art of record cited in the office action mailed 3/20/2025), which is only cited as evidentiary purpose. When the combination is intended for an adult human having an average weight of 60 kg, the dose may be about 966 mg celecoxib and 484 mg of methocarbamol to be corresponding to the disclosed dosing amounts and to provide similar effects disclosed in the specification. Thus, the alleged unexpected result is not commensurate with the claimed range. Also, it was noted that Fig. 1 only showed the effect of celecoxib alone and Fig. 3 showed the effect of the administration of 100 mg/kg celecoxib and 50 mg/kg methocarbamol to rats. The results of Fig. 1 and Fig. 3 were obtained from two separate tests, which might have different test conditions and variables. In addition, 100 mg/kg celecoxib alone showed about 55% antinociception at 4-hour mark (Fig. 1) and 100 mg/kg celecoxib with 50 mg/kg methocarbamol showed about 60% antinociception at 4-hour mark (Fig. 3). It is unclear that the difference (less than 5 %) between 100 mg/kg celecoxib alone and the combination is statistically significant and unobvious when considering the standard deviations, (see Fig. 1 and 3). One of ordinary skill in the art would not make a conclusion that there was unexpected synergy based on the direct comparison of results obtained from two separate tests without considering potential differences in test conditions of two tests and analyzing statistical significance. Furthermore, the specification or Fig. 3 does not show that the claimed combination has analgesic, anti-inflammatory, and muscle relaxant effects with better tolerance and less adverse effects in patient with pain, inflammation and muscular contractions as the attorney alleged. Arguments of counsel cannot take the place of evidence in the record. See: In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965).
Even if the claimed combination assumed to have synergistic effect, the alleged synergistic effect would have been expected in view of Faour. Improved or synergistic effects of the combination of a COX-II inhibitor and a muscle relaxant appear to commonly occur as evidenced by Faour (see [0097]). If something were routinely reported, it could not be unexpected, even if it is not predictable. For example, the result of a coin flip is not predictable. Heads and tails are “just as routinely reported”. Both heads and tails are (equally) expected; neither result is unexpected. Obviousness does not require absolute predictability; however, at least some degree of predictability is required. See MPEP 2143.02(II). In this case, there is a reasonable expectation of success for having improved or synergistic effects of the combination comprising celecoxib and methocarbamol having triple effects because celecoxib as a COX-II inhibitor has analgesic and anti-inflammatory effects and methocarbamol as muscle relaxant has analgesic and muscle relaxing effects as evidenced by the prior art. Evidence showing synergistic effects greater than resulting from the claimed combination was not sufficient to outweigh the evidence of obviousness because the teachings of the prior art lead to a general expectation of improved or synergistic effects when a COX-II inhibitor used in combination with a muscle relaxant. See MPEP 716.02 (a).
For the foregoing reasons, Applicant’s arguments have not been found to be persuasive.
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 extension fee 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 date of this final action.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611