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 .
Priority
This application filed 05/31/2023, claims the benefit of 371 of PCT/MX2020/050051 filed 12/04/2020.
DETAILED ACTION
Applicant amendment and arguments filed on 03/02/2026 have been received and have been fully considered.
Claims 1 and 4-20 were amended, and claims 2-3 were cancelled. Claims 1-20 are pending.
Withdrawn Claim Objections
Objection to claim 9 for the typographical error, is withdrawn in view of Applicant’s amendment filed on 03/02/2026 that amended claim 9 by deleting “(degrees 25, 30,60,090)” and the extra “or”.
Withdrawn Claim Rejections - 35 U.S.C. 112(b)
Rejection to claims 9 and 10 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for the recitation of the parentheses, is withdrawn in view of Applicant’s amendment filed on 03/02/2026 that amended claim 9 by deleting “(degrees 200 to 6000)” and “(degrees 25, 30,60,090)”.
Rejection Maintained
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 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.
Claims 1 and 4-20 remain rejected under 35 U.S.C. 103 as being unpatentable over A. Dagar et al. (US PG-Pub 2007/0286875 A1, 12/13/2007, “Dagar” cited in the PTO-892 dated 12/01/2025) in view of S. Asotra et al. (US PG-Pub 2005/0175642 A1, 08/11/2005, “Asotra” cited in the PTO-892 dated 12/01/2025) and S. Gao et al. (US PG-Pub 2004/0258716 A1, 12/23/2004, “Gao” cited in the PTO-892 dated 12/01/2025).
Dagar teaches an oral liquid formulation including an effective amount of loratadine, or a pharmaceutically acceptable salt or metabolite thereof; and a pharmaceutically acceptable carrier. [Abstract].
Dagar teaches that the oral liquid loratadine compositions is administered in combination with an analgesically effective amount of ibuprofen in a pharmaceutically acceptable carrier, wherein the ibuprofen be included in the loratadine liquid compositions, wherein the composition is used for the symptomatic relief of cold, cold-like and flu-related symptoms including coryza, nasal congestion, upper respiratory infections, allergic rhinitis, otitis, and sinusitis, by the administration of appropriate dosages of the pharmaceutical compositions. [0078].
Dagar teaches an exemplary oral liquid composition comprising 5 mg/5 mL (1 mg/mL) loratadine and pharmaceutically acceptable excipients e.g., water, glycerin, propylene glycol, flavoring agent, sweetener agent, and preservative. [0088].
In the same field of endeavor of preparing oral liquid loratadine composition, Asotra teaches a pharmaceutical liquid suspension for oral administration having a pharmaceutically effective amount of an antihistamine, loratadine. [Abstract]. Asotra teaches that the composition contains additional active pharmaceutical ingredients, such as, analgesics, for example, ibuprofen, [0048], wherein the liquid suspension is for treating a human in need of an antihistamine. [Claim 12]. Asotra teaches the composition in Example 1 [0052]:
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Asotra’s above suspension comprises loratadine, suspending agents (Carbomer), solubilizers (sorbitol), co-solvents (glycerin), sweeteners (sucralose), flavorings (peach flavor), preservatives or antimicrobial agents (butylparaben), solvent (water), and colorants.
While Dagar and Asotra explicitly teach that ibuprofen can be included within the liquid composition of loratadine, the oral liquid compositions of Dagar and Asotra differ from the instantly claimed composition to the extent that one of ordinary skill in the art needs to specifically pick ibuprofen from Dagar’s or Asotra’s list of active ingredients. However, Gao provides motivation to one of ordinary skill in the art to pick ibuprofen and include it in Dagar’s and Asotra’s compositions.
Gao teaches an oral liquid suspension comprising Ibuprofen and pharmaceutically acceptable excipients. [0008]. Gao teaches the ibuprofen suspension in Example 1, which is substantially identical to Asotra’s composition with only ibuprofen in place of loratadine, [0102]:
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In view of the foregoing discussion, it would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to include ibuprofen in Dagar’s and Asotra’s oral liquid compositions. One of ordinary skill in the art would have been motivated to do so with reasonable expectation of success because: Dagar explicitly teaches that the loratadine liquid compositions is administered in combination with ibuprofen in a pharmaceutically acceptable carrier and that the ibuprofen included in the loratadine liquid compositions for the symptomatic relief of cold, cold-like and flu-related symptoms including coryza and the symptoms that effect nose and ear; Asotra teaches a liquid suspension of loratadine and teaches that the suspension contains additional active analgesics i.e., ibuprofen for treating a human in need of an antihistamine; and Gao teaches a stable ibuprofen liquid suspension with improve patient conveniency [0007], wherein Gao’s ibuprofen suspension is substantially identical to Asotra’s liquid suspension, see Example a of Asotra and Example 1 of Gao, which indicates the compatibility of ibuprofen with the excipients of Asotra. The compatibility of ibuprofen with Asotra’s excipients would motivate skilled artisan to include ibuprofen in Asotra’s liquid composition, especially because Dagar teaches that ibuprofen is included within the liquid composition. Furthermore, Dager and Asotra’s composition is for treating cold and cold-like symptoms and its well-known in the art that analgesics i.e., ibuprofen are used and needed for relieving cold and cold-like symptoms which would motivate skilled artisan looking for relieving the cold and cold-like symptoms to add ibuprofen to Dagar and Asotra’s liquid composition.
Claim 1 b) is met because Dagar teaches that the concentration of loratadine is 5 mg/5 mL (1 mg/mL). The claimed amount of 0.1 g/100 mL is equivalent to 1 mg/mL. [0088].
Claim 1 c) is met because the Dagar teaches that the loratadine liquid composition includes pharmaceutically acceptable excipients e.g., water, glycerin, propylene glycol, flavoring agent, sweetener agent, and preservative. [0088].
Claim 1 a) is met for the following reasons: Gao teaches that the concentration of ibuprofen ranges from 0.01% up to about 50%. [0010]. Because Gao teaches that 1.79% equivalent to 100mg/5mL, the ibuprofen range calculates to: (0.01%/1,79%*100mg/5mL = 0.11mg/mL; and 50%/1.79%*100mg/5mL = 558.66 mg/mL). Thus, Gao’s ibuprofen amount is between about 0.11 mg/mL to about 559 mg/mL, which encompasses the claimed amount of 80 mg/mL. Gao also teaches ibuprofen suspension comprises from about 0.5% to about 5%. [0016]. The ibuprofen range calculates to: (0.5%/1,79%*100mg/5mL = 5.6 mg/mL; and 5%/1.79%*100mg/5mL = 55.9 mg/mL). Thus, Gao’s ibuprofen suspension is between about 5.6 mg/mL to about 55.9 mg/mL. Dagar teaches that the composition is administered once or twice a day [0024]. When the composition of Dagar, Asotra, and Gao is administered twice a day, the concentration of ibuprofen is between 11.2 mg/mL and 111.8 mg/mL, which also encompasses the claimed amount of 80 mg/mL. As provided in MPEP 2144.05, in the case where the claimed amount "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) "[A] prior art reference that discloses a range encompassing a somewhat narrower claimed range or amount is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). Moreover, The optimization of known amounts for known active agents is considered well within the competence level of an artisan of ordinary skill in the pharmaceutical sciences; it has been held that the selection of optimal parameters, such as amounts of active agents, to achieve a beneficial effect, is within the skill in the art of an ordinary artisan. See In re Boesch, 205 USPT 215 (CCPA 1980) and MPEP 2144.05. "[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). As such, an artisan having ordinary skill in the art would have been motivated to modify the amounts to achieve ibuprofen concentration of 80 mg/mL.
The term “immediate release” is met because Dagar, Asotra, and Gao teach a composition for treating respiratory diseases comprising analgesic, antihistamine, and pharmaceutically acceptable excipients. Dagar, Asotra, and Gao are silent on the immediate release of the composition but otherwise teaches a substantially identical composition as claimed. As such, it is reasonable to presume that the resulting composition is inherently immediate-release composition. The burden is on Applicant(s) to show that this property is different from those taught by the prior art and to establish patentable differences. See MPEP 2112.
Therefore, the combination of Dagar, Asotra, and Gao meet each and every limitation of claim 1.
Claim 4 is met because the concentration of ibuprofen of 80mg/mL (400mg/5mL) is established above.
Claim 5 is met because Dagar teaches that the concentration of loratadine in 1 mg/mL (5mg/5mL. [0088].
Claims 6, 7, 9, 11, and 16 are met because the Asotra’s (or Gao) above suspension of Example 1 comprises loratadine, suspending agents (Carbomer), solubilizers (sorbitol), co-solvents (glycerin), sweeteners (sucralose), flavorings (peach/berry flavor), preservatives or antimicrobial agents (butylparaben), solvent (water), and colorants.
Regarding claim 8, Gao’s above suspension of Example 1 comprises carbomer at 0.48%, whereas the claimed amount is 0.42%. As provided in MPEP 2144.05, 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).
Regarding claim 10, Asotra teaches that sorbitol concentration is up to about 20%, and Asotra’s above suspension of Example 1 comprises sorbitol at 5.0%, whereas the claimed amount is 6.94%. As provided in MPEP 2144.05, 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). Moreover, "[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 12, Asotra teaches that suspension comprises propylene glycol of about 20% and glycerin of about 50% (claimed amount is 20% propylene glycol and 60% glycerin). [0037]. As explained MPEP 2144.05.II.A: “generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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).”
Claim 13 is met because Gao’s liquid suspension comprises 0.4% sucralose, whereas the claimed amount is 0.42%. As provided in MPEP 2144.05, 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).
Claim 14 is met because Gao teaches that the colorant is color red number 40. [0011].
Claim 15 is met because Asotra teaches that the suspension has propylparaben (up to about 0.04%) and butylparaben as preservative [0038], and Asotra’s suspension of Example 1 above include butylparaben preservative if less than 1% (0.018%).
Claims 17 and 18 are met because the above compositions are suspensions.
Claim 19 and 20 are met because Dagar teaches that the composition is used for the symptomatic relief of cold, cold-like and flu-related symptoms including coryza (other name for acute upper respiratory tract infections), nasal congestion, upper respiratory infections, allergic rhinitis, otitis, and sinusitis, by the administration of appropriate dosages of the pharmaceutical compositions. [0078].
Response to Arguments
Applicant argues:
The pharmaceutical composition of claim 1 exhibits improved bioavailability and enhanced storage stability. Bioavailability, however, cannot be evaluated in isolation from the intended therapeutic objective. In the context of the ibuprofen and loratadine combination, optimization of the immediate release profile of both active agents results in a synergistic effect that would not have been predictable from general formulation principles. In particular, the adequate bioavailability of ibuprofen at the selected concentrations ensures rapid and sufficient systemic absorption to provide prompt anti- inflammatory and antipyretic activity. Concurrently, the optimized bioavailability of loratadine permits attainment of therapeutically effective plasma levels sufficient to antagonize histamine receptors without inducing sedation. This specific balance, achieved through the deliberate selection of concentrations and corresponding formulation parameters, produces a pharmacodynamic synergy. The resulting composition does not merely provide an additive effect of the individual active ingredients but rather yields an enhanced clinical response in the treatment of acute respiratory conditions. The bioavailability of a drug determines the amount of active ingredients that reach the systemic circulation and, therefore, the effective concentration in the target tissues. In the case of a combination such as ibuprofen and loratadine, the optimal bioavailability of each compound is critical for both to simultaneously reach therapeutic plasma levels, allowing their complementary mechanisms of action to exert themselves in a coordinated manner. Ibuprofen exerts its therapeutic effect through inhibition of cyclooxygenase enzymes (COX-1 and COX-2), thereby reducing prostaglandin synthesis and consequently inflammation and fever. Loratadine, in turn, selectively antagonizes peripheral histamine H1 receptors in the respiratory mucosa, decreasing edema and nasal secretions. A true pharmacodynamic synergistic effect arises only when both active agents are present at therapeutically effective concentrations at the appropriate time and site of action. Under such coordinated conditions, the combined attenuation of inflammatory and histamine- mediated pathways exceeds the additive effects of the individual agents due to their complementary modulation of inflammatory mediators and immunological responses. From a pharmacokinetic standpoint, this synergy is directly dependent upon the immediate release and efficient absorption of both drugs. Suboptimal bioavailability of either component would impair the functional interplay between COX inhibition and H1 receptor blockade, thereby diminishing or eliminating the synergistic interaction. Physiologically, temporal coordination between the anti-inflammatory activity of ibuprofen and the antihistaminic action of loratadine enables accelerated control of the inflammatory cascade associated with acute respiratory infections. This coordinated activity modulates the production of pro-inflammatory cytokines, including IL-6 and TNF- a, as well as histamine release from mast cells and basophils. Bioavailability, therefore, is not merely an isolated pharmacokinetic parameter, but a critical determinant of the synergistic therapeutic efficacy of the claimed combination, resulting in a superior and unexpected clinical outcome relative to administration of each drug alone. The unexpected results demonstrated in the Examples of the Specification (see Table 2) establish a direct nexus between the optimized bioavailability profile and the observed pharmacodynamic synergy. Neither Dagar, Asotra and Gao, alone or in combination, nor the general knowledge of a person of ordinary skill in the art, would have provided a reasonable expectation that combining these active agents at the presently claimed concentrations would yield such an enhanced therapeutic effect. Nor would one of ordinary skill in the art have been motivated to anticipate that optimization of the bioavailability of both agents would result in the demonstrated synergistic outcome.
Examiner response:
Applicant’s arguments have been fully considered but they are not persuasive. As provided in MPEP 2145, If a prima facie case of obviousness is established, the burden shifts to the applicant to come forward with arguments and/or evidence to rebut the prima facie case. See, e.g., In re Dillon, 919 F.2d 688, 692, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). Rebuttal evidence and arguments can be presented in the specification, In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995), by counsel, In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir. 1995), or by way of an affidavit or declaration under 37 CFR 1.132, e.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745 F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984). However, arguments of counsel cannot take the place of factually supported objective evidence. See, e.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). While Applicant is attempting to explain the asserted improved bioavailability by describing the mechanism of action of each agent, ibuprofen and loratadine, discussing the pharmacokinetics of drugs in general, the possibility of a synergistic effect of the combination of ibuprofen and loratadine, and criticality of the combining amount, Applicant does not provide factually supported objective evidence. Applicant appears to rely of Table 2 to claim unexpected clinical outcomes. However, As provided in MPEP 716 (b), the evidence relied upon should establish "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). "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Table 2, page 16 of the instant specification, described the comparison between the pharmacokinetic parameters of the combination compared to each agent alone. The asserted unexpected results are not of statistical and practical significance. For example, in Table 2, the Cmax of ibuprofen and loratadine alone is 54,644.30 ± 9,602.67 and 7.77 ± 7.51, respectively, and Cmax of the combination of ibuprofen/loratadine is 72,715.70 ± 19,773.65 (ibuprofen)/7.68 ± 7.72 (loratadine). These results are not of statistical and practical significance because the Cmax of loratadine is about the same between the combination and the drug alone, and the Cmax of ibuprofen and loratadine alone and the Cmax of the combination of ibuprogen and loratadine is also very close between the combination and the drug alone (72,715.70 - 19,773.65 = 53, which close to the Cmax of the ibuprofen alone, 54). Therefore, these results are insignificant and insufficient. As a result, the Examiner finds that the instant claims remain obvious over the combined teachings of Dagar, Asotra and Gao.
With respect to Applicant’s asserted synergistic outcome, as discussed above, the presented results in the specification do not support this assertion, and arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). For example, there is no analysis of the synergistic effect, combination index, etc. Moreover, Dagar teaches that loratadine is administered in combination with one or more therapeutic agents to provide synergistic effect in preventing, treating, or managing a condition or disease as noted herein, or any other disease or condition for which the same patient may require prevention, treatment, or management thereof, wherein the agent may be incorporated in the loratadine liquid solution or may be administered in a separate dosage form, [0076]. Dagar teaches that the liquid loratadine compositions is administered in connection with an analgesically effective amount of ibuprofen. Therefore, Applicant argument is not persuasive.
Conclusion
Claims 1 and 4-20 are rejected. No claim is 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.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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