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
Claims 1-13, 16, and 19 are pending. Claims 6-9, 11-13 and 16 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species (Claims 6-9,11-13) and nonelected invention (Claims 16 and 19 - syringe). Therefore, Claims 1-5 and 10 are presented for examination.
Election/Restrictions
Applicant's election with traverse of Composition G
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148
534
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(see Table 21 at 0206 on p. 37) in the reply filed on 12/30/2025 is acknowledged. The traversal is on the ground that the species requirement does not require election of specific amounts. However, the original requirement requested identification of a single specific composition. A composition defined by a concentration range encompasses multiple embodiments and does not constitute a single species. Applicant also argues that no specific reason was provided to show serious search burden. This is not found persuasive because the restriction requirement properly identified distinct inventions requiring separate examination and was made in accordance with 35 U.S.C. 121 and MPEP 803.
The requirement is still deemed proper and is therefore made FINAL.
Claims 6-9, 11-13 and 16 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species (Claims 6-13) and nonelected invention (Claims 16 and 19 - syringe), there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/30/2025.
Priority
This application is a CON of PCT/EP2024/051756, filed 01/25/2024, which claims priority benefit to:
PRO 63/481,814, filed 01/27/2023, and
PRO 63/511,863, filed 07/04/2023.
Information Disclosure Statement
The Information Disclosure Statement filed 7/22/2025 has been considered by the Examiner. The submission is in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Specifically, see “https://www.americanpharmaceuticalreview.com/Featured-Articles/163483-Taste-Masking-Techniques-in-the-Pharmaceutical-Industry/)” at 0003.
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 1-5 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al. (“Quantitative prediction of the bitterness of atomoxetine hydrochloride and taste-masked using hydroxypropyl-β-cyclodextrin: A biosensor evaluation and interaction study.” Asian Journal of Pharmaceutical Sciences (July 2020); Volume 15, Issue 4:492-505) in view of Stenberg, K. (US 2014/0011893).
Claimed invention
Claim 1: An oral solution, comprising:
a bitter active pharmaceutical ingredient (e.g., atomoxetine HCl);
5-50 mg/mL Vitamin E TPGS; and
water,
wherein sodium benzoate is absent from the solution.
Prior art
Li teaches aqueous solutions of atomoxetine (ATX) hydrochloride. Li describes solution preparations of ATX hydrochloride (0.003–1.0 mg/ml) dissolved in water at varying concentrations for evaluation of bitterness intensity (see abstract; see also sections 2.2 to 2.3 at pp. 493-494). Li demonstrates that ATX HCl forms stable aqueous solutions and that bitterness increases in a concentration-dependent manner.
While Li teaches an aqueous solution with ATX HCl dissolved in water and recognizes formulation concerns with its bitterness, Li does not expressly teach incorporation of Vitamin E TPGS.
However, it was known that Vitamin E TPGS is a pharmaceutically acceptable, water-compatible surfactant used in oral drug formulations to modify drug dispersion characteristics in aqueous media. For example, Stenberg teaches pharmaceutical compositions comprising d-alpha-tocopheryl polyethylene glycol 1000 succinate (Vitamin E TPGS or “TPGS”) and a biologically active substance. Stenberg discloses that TPGS is water soluble (up to approximately 20% by weight) that is a taste-masking and penetration-enhancing agent that forms micelles in aqueous systems (see 0109-0110). Stenberg further discloses TPGS may be incorporated with an active pharmaceutical ingredient to improve dispersion and homogeneity of the active substance in aqueous formulations and may function as a taste-masking agent for bitterness of the active. See 0110. Stenberg discloses inclusion levels of TPGS in pharmaceutical compositions and establishes its compatibility with aqueous media and oral dosage forms.
A person of ordinary skill in the art (POSA) would have found it obvious to modify the aqueous ATX HCl solution taught by Li to further include TPGS as taught by Stenberg because Li establishes that ATX HCl forms aqueous solutions and recognizes taste/bitterness considerations associated with such formulations while Stenberg teaches that TPGS is a pharmaceutically acceptable, water soluble taste-masking and penetration-enhancing agent that forms micelles in aqueous media and is incorporated with active pharmaceutical ingredients to improve dispersion and homogeneity in aqueous formulations. Given that TPGS was known to be compatible with water and suitable for oral drug formulations, a POSA would have had a reasonably select TPGS for incorporation into Li’s aqueous ATX HCl solution as a routine formulation optimization with added bitterness-masking effect. The modification merely applies a known dispersing agent to a known aqueous bitter drug solution to achieve its established function of modifying dispersion characteristics and masking-bitterness.
The claimed concentration of 2.5g TPGS per 100 mL (approximately (2.5% w/v) falls within the known aqueous solubility limits disclosed by Stenberg (up to ~20%) and is reasonably close to the inclusion levels disclosed therein. Selection of an amount of TPGS as a dispersing and/or taste-masking agent to achieve desired dispersion or masking properties would have been a matter of routine optimization within the skill of the POSA, particularly given the established micelle-forming behavior of TPGS in aqueous systems.
Thus, the combination of Li and Stenberg suggest a composition containing ATX HCl, TPGS and water and wherein sodium benzoate is absent as claimed. Because Li teaches ATX hydrochloride at 0.003–1.0 mg/ml and TPGS water solubility of up to approximately 20% by weight, the claimed amounts are also met by the prior art.
Claim 2 limits claim 1, wherein the bitter active pharmaceutical ingredient is atomoxetine hydrochloride. Claim 3 limits claim 2, wherein the palatable oral solution comprises 4-8 mg/ml atomoxetine hydrochloride.
Li teaches ATX hydrochloride at 0.003–1.0 mg/ml.
Claims 4, 5 and 10 limit Claim 1, wherein no other active pharmaceutical ingredient, no ion exchange resin, and no sorbitol are present (Claim 10).
The prior art does not require the presence of any of these.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H. Alstrum-Acevedo can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622