911
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 Application
Claims 37 and 39-54 are pending.
Receipt and consideration of Applicants' amended claim set and remarks/arguments filed on 10/28/2025 are acknowledged. Claims 39-40, 47-48, and 53-54 remain withdrawn, as being drawn to an unelected invention or specie. Claims 37, 41, and 49-52 are amended. Claims under consideration in the instant office action are claims 37, 41-46, and 49-52.
Applicants' arguments, filed 10/28/2025, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
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 20 and 41 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “bitterness” in claims 20 and 41 is a relative term which renders the claim indefinite. The term “bitterness” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims 20 and 41 recite the limitation “provided (a), (b) and (c) are in amounts such that bitterness of (a) is reduced to a greater extent than a sum of bitterness reduction provided by the amount of (b) and bitterness reduction provided by the amount of (c).” which does not provide a determination of the requisite degree of bitterness and bitterness reduction given that bitterness is subjective. Additionally, what may be bitter to one person may not be bitter to another. There is no clear definition of what defines “bitter” so it is difficult to ascertain levels of bitterness as provided for in the claims.
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.
Claims 37, 41-46, and 49-52 are rejected under 35 U.S.C. 103 as being unpatentable over Phillips (WO 03/009846, as disclosed by IDS) in view of Ley et al. (Evaluation of Bitter Masking Flavanones from Herba Santa (Eriodictyon californicum (H. & A.) Torr., Hydrophyllaceae), J. Agric. Food Chem., 2005, 53, pp. 6061-6066, already of record).
Phillips teaches compositions comprising substituted benzimidazole proton pump inhibitors such as omeprazole (see abstract, pg. 17, lines 13-20), but that omeprazole has a bitter taste (pg. 45, lines 14-15). Phillips teaches omeprazole can be formulated as low as 2 mg/day (pg. 18, lines 7-11), which if formulated in a tablet formulation would result in a concentration of 2,156 ppm (2 mg / 927.5 mg = 0.2156% x 10,000 ppm/% = 2,156 ppm) (see B2 Formulation, Example 1).
Phillips does not teach a composition further comprising eriodyctiol and homoeriodyctiol.
Ley et al. is drawn towards the use of flavanones such eriodictyol and homoeriodictyol to reduce the bitter taste of pharmaceutical actives (see abstract). Regarding the limitation “wherein (b) and (c) are in amounts such that bitterness of (a) is reduced to a greater extent than a sum of bitterness reduction provided by the amount of (b) and bitterness reduction provided by the amount of (c)”, Ley teaches formulations wherein flavonoids are present in an amount of 100 ppm (see Fig. 2), which reads on the recited amounts in claims 20 and 49, and would thereby exhibit such bitterness reduction. Ley teaches that “For the strongly bitter compound amarogentin, we performed a dose-activity study analogously to caffeine (cf. Figure 6). A slight increase of inhibitory activity was found, and the plateau was reached at 200-500 ppm 1-Na. The maximum activities against caffeine and amarogentin bitterness were similar (30-40% reduction).” (pg. 6064, right column, second paragraph). Regarding the limitation wherein “(a) and (b) in a weight ratio of about 4: 1 to 200: 1 ((a):(b))” and “(a) and (c) in a weight ratio of about 4: 1 to 200: 1 ((a):(c))” as recited in claims 42-44 and 50-52, Phillips teaches omeprazole can be formulated as low as 2 mg/day (pg. 18, lines 7-11), which if formulated in a tablet formulation would result in a concentration of 2,133 ppm (2 mg / 937.5 mg = 0.2133% x 10,000 ppm/% = 2,133 ppm) (see B2 Formulation, Example 1), which is a ratio of 21.33:1 given that eriodictyol (b) and homoeriodictyol (c) can be formulated in an amount of 100 ppm individually. Ley teaches homoeriodictyol in its sodium salt form (see abstract). The molecular weight of omeprazole, eriodictyol and homoeriodyctiol are 345.4 g/mol, 288.25 g/mol, and 302.27 g/mol respectively.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to formulate a composition further comprising eriodyctiol and/or homoeriodyctiol, as suggested by Ley et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to do so since eriodictyol and homoeriodictyol can be formulated with omeprazole to reduce the bitter taste of omeprazole as a pharmaceutical active as taught by Ley, with a reasonable expectation of success absent evidence of criticality of the particular formulation.
Even though the range for concentrations as taught by Ley et al. is not the same as the claimed concentrations, Ley et al. does teach an overlapping range of concentrations, and it has been held that 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). See MPEP § 2144.05(I). Furthermore, the determination of concentrations is well within the purview of those skilled in the art through routine experimentation, and it has been held that “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 MPEP § 2144.05(II). It would have been obvious to one of ordinary skill in the art to optimize the concentrations of eriodyctiol and homoeriodyctiol in order to increase the efficacy of the composition.
The amounts of active agents to be used, the pharmaceutical forms, e.g., tablets, etc; mode of administration, flavors, surfactant are all deemed obvious since they are all within the knowledge of the skilled pharmacologist and represent conventional formulations and modes of administration.
Furthermore, no unobviousness is seen in the ratio claimed because once the usefulness of a compound is known to treat a condition, it is within the skill of the artisan to determine the optimum ratio.
Response to Arguments
Applicant argues in the Affidavit, filed 10/28/2025, that “so long as each flavanone is present at receptor-active levels (as recited in the claims) and omeprazole is above its taste threshold yet within normal formulation levels, the greater-than-additive (synergistic) effect is expected to hold. Edge cases in which omeprazole is below sensory detection or at levels that overwhelm the modulators are outside typical use and, in any event, are excluded by the claimed ratios and by the claims' functional proviso.” The Examiner respectfully disagrees since Applicant has only established synergism for a combination of eriodyctiol and homoeriodyctiol at a concentration of 100 ppm each. Applicant has not demonstrated that the flavanones are at receptor-active levels at the lower bound of the concentration range of 50 ppm each. Applicant has only asserted that “Because bitter-taste receptor responses are concentration-dependent and these receptor interactions do not require a fixed stoichiometry, the synergy is expected across a range of at least 50 to 200 ppm.” (paragraph 5) without providing evidentiary support for such activity regarding eriodyctiol and homoeriodyctiol.
Applicant also argues that “Referring to a bitterness being reduced to a greater extent relative to an alternative is like referring to a "greater length" relative to an alternative. For example, consider a claim ref erring to two elements, A and B, wherein A is longer than B. The term "element A is longer" is not indefinite (and does not exist in isolation) because the claim language provides an alternative against which the length of A is ascertained. Similarly, providing that the claimed method reduces bitterness is not indefinite (and does not exist in isolation) because the claim language provides an alternative against which the bitterness is assessed.” The Examiner respectfully disagrees since although the claim language provides a relationship between elements, it is still unclear as what level of bitterness the elements are. The claim language does not provide a determination of the requisite degree of bitterness and bitterness reduction given that bitterness is subjective. Additionally, what may be bitter to one person may not be bitter to another.
Conclusion
Claims 37, 41-46, and 49-52 are rejected.
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 ANDREW P LEE whose telephone number is (571)270-1016. The examiner can normally be reached Monday-Friday 9am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Renee Claytor can be reached at (571)272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANDREW P LEE/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691