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 the Claims
Claims 1, 2, 8, 10, 13, 15, 30, and 36 have been amended. Claims 19-24, and 39-45 have been withdrawn. Claims 2, 15, and 27 are withdrawn as they are directed at a non-elected species. Claims included in the prosecution are claims 1, 3-14, 16-18, 25-26, and 28-38.
Election/Restrictions
Applicant elected without traverse Group I, claims 1-18 and 25-38, directed to a single dose therapeutic beverage without traverse in the reply filed on Feb. 13, 2026, which is acknowledged. Applicant elected without traverse the following species: the percentage of APIs present in the liquid medium is from about 10% to about 50% w/v and the percentage of APIs present in the plurality of the spherical- and/or spheroidal-shaped particles is from about 50% to about 90% w/w (e.g., claims 2, 15, and 29); gelling agents: gellan gum, sodium alginate, and chitosan (e.g., claims 4 and 32); calcium chloride (e.g., claims 4 and 32); lecithin (e.g., claims 5 and 33); and corn oil (e.g., claims 6 and 34). These elections in the reply filed on Feb. 13, 2026, are acknowledged
Accordingly, claims 2, 15, 19-24, 27 and 39-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention/species, there being no allowable generic or linking claim.
Priority
This application has PRO of 63348688 filed June 3, 2022.
Information Disclosure Statement
The Information Disclosure Statement(s) (IDS) submitted on Sep. 25, 2023, Jan. 19, 2024, and Dec. 19, 2024, comply with provisions of 37 CFR 1.97. Accordingly, the IDS(s) have been considered by the Examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Spec., [00159]). Applicants are 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.
Claim Objections
Claims 15 and 29 are objected to because of the following informalities: “is from about” appears to be in duplicate in line 5 of claim 15 and line 17 of claim 29. Appropriate correction is required.
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 1, 6, 7, 13, 18, 25, 34-35 and dependent claims thereof 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 “partially” in claims 1, 13, and 25 is a relative term which renders the claim indefinite. The term “partially” 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.
Regarding claim 6 and 34, the phrase "and the like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "and the like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
Claims 13 and 25 recite the limitation "beverage like" in lines 13 and 16 of each claim. There is insufficient antecedent basis for this limitation in the claim.
Claims 7, 18, and 35 recite the plural of excipient. The claim is indefinite because it is not clear whether the selection of at least more than one (i.e., “excipients”) is from the species recited or not.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-14, 16-18, 25-26, and 28-38. are rejected under 35 U.S.C. § 103 as being unpatentable over Bortz et al. (US 20080181932 A1) and Patel et al. (US 20200009076 A1) with evidence from Belitz et al. (Food Chemistry Chapter 10 Milk and Dairy Products, Springer-Verlag Berlin Heidelberg 2004) and by Martinez et al. (ACS Omega Rheological and microstructural properties of acidified milk drink. 2022, 7, 19235-19242).
Bortz et al. disclose compositions for oral delivery of pharmaceutical active agents (title, abstract). The compositions comprise an outer layer formed over an inner core, the inner core comprising an inert material, the outer layer comprising a plurality of pharmaceutically active agents embedded in a matrix, the matrix being substantially erodible when contacted with an aqueous medium ([0002], [0006], claim 1).
Bortz et al. disclose that the matrix may be constructed from a variety of suitable excipients or combinations of excipients ([0017]). Suitable excipients typically will yield a matrix that is substantially erodible when contacted with an aqueous medium, which includes any medium having water, such as saliva or a liquid containing water ([0017]). In this context, "substantially erodible" means that the matrix typically will dissolve, disintegrate, or disperse when contacted with an aqueous medium and concomitantly, will then generally release the embedded pharmaceutically active agent or encapsulated pharmaceutically active agent ([0017]) The matrix will typically substantially erode from about one second to about five minutes after being contacted with an aqueous medium ([0017]).
In addition, Bortz et al. teach a pellet, bead, powder, and sachet as the oral delivery composition introduced into the subject's oral cavity ([0061]). In an exemplary embodiment, Bortz’ composition will be combined with an aqueous-based liquid prior to its introduction into the subject's oral cavity ([0062]). Non-limiting examples of a liquid beverage suitable for use include nutritional drinks ([0062]). The matrix erodes and releases the pharmaceutically active agent, which is administered to the subject as the beverage is consumed ([0062]). In some embodiments the inner core and portions of the matrix may substantially dissolve and be consumed by the subject together with the liquid beverage ([0062]). The composition is combined with an aqueous-based liquid prior to its introduction into the subject's oral cavity ([0062]). Non-limiting examples of a liquid beverage suitable for use include milk, flavored milk drinks, goat milk, liquid yogurt, soy milk, rice milk ([0062]). Here are the teachings of Bortz et al. read on a single dose therapeutic beverage and therapeutic beverage of the instant claims and teach the immediate dose of the API and wherein the API permeates into the liquid medium to read on instant claims 1, 13, and 25.
Bortz et al. disclose the outer layer includes one or more suitable excipients in addition to the matrix which may include a coloring agent, a flavor-modifying agent, an oral dispersing agent, a stabilizer, a preservative, a diluent, a lubricant, and a binder ([0022]). The excipient may comprise alginates ([0025]). The teachings of Bortz et al. meet the requirement of at least one species of the instant claims 7, 18, and 35.
Bortz et al. disclose the outer layer as being formulated to include any pharmaceutically active agent desired which may be encapsulated by a coating ([0035]). Irrespective of whether the pharmaceutically active is encapsulated, the pharmaceutically active agent may may comprise combinations of two, three, or four or more systemically distributable pharmaceutical ingredients or non-systemically distributable drugs ([0035]). This teaches and suggests the presence of more than one API; and at least one being different from the other(s). Non-opioid analgesic; non-steroidal anti-inflammatory; antitussive; antibiotic; antispasmodic; vitamin; mineral, and nutritional products are taught as suitable pharmaceutically active agents ([0036]) to read on at least one of the species of the instant claims 3, 17, 28, and 31.
Regarding claims 4 and 32, alginate, chitosan, and gellan gum are all taught by Bortz et al. as coating material for encapsulation ([0041]). Microencapsulation may include alginate beads ([0047]).
Regarding claims 8, 13, 25, and 29-30, Bortz et al. disclose spherical microcapsules having an average diameter of about 200 microns ([0046]).
Regarding the immediate release and delayed release requirement of the instant claims, to provide a means for its controlled release, Bortz et al. provide a microcapsule comprising a pharmaceutically active agent and a coating that encapsulates the pharmaceutically active agent ([0040]). In this respect, the outer layer comprises a plurality of microcapsules embedded in the matrix wherein the microcapsule will generally comprise any of the pharmaceutically active agents, or combinations of any of the pharmaceutically active agents encapsulated by a coating ([0040]). Bortz et al. describe how the matrix and actives relate as a percentage range of the outer layer. For instance, of the outer layer, the matrix is in an amount from about 1% to about 99% by weight and the pharmaceutically active agents are in an amount from about 0.001% to about 95% by weight and more typically, the matrix is from about 60-90% and the active is from about 0.1-30% (0050]).
Bortz et al. differ from the claimed invention insofar there is no explicit teaching the partitioning between the plurality of particles and the liquid medium containing the particles; “wherein the percentage of API is present in the liquid medium is from about 10% to about 50% w/v and the percentage of API is present in the plurality of the spherical- and/or spheroidal shaped particles is from about 50% to about 90% w/w” to meet the requirement of instant claims 1, 13, 25, and 29.
While Bortz et al. teach a first and a second API, Bortz et al. differ from the claimed invention insofar a first set and second set of the plurality of particles are not explicitly taught to meet the requirement of instant claims 12, 16, 26, 38.
However, Patel et al. disclose oral dosage units ([0015]). The oral dosage units comprise an immediate release formulation comprising phloroglucinol (i.e., antispasmodic to additionally read on instant claims 3, 17, 28, and 31), trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof, wherein at least about 90% by weight, based on the weight of the immediate release formulation, of phloroglucinol, trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof is released from the dosage unit from about 5 minutes to about 2 hours measured in 750 mL of an aqueous acidic solution ([0015], claim 1). The oral dosage units also comprise a modified release formulation comprising phloroglucinol, trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof, wherein at least about 90% by weight, based on the weight of the modified release formulation, of phloroglucinol, trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof, is released from the dosage unit after at least about 2 hours, as measured in about 1000 mL of an aqueous solution at a pH of about 6.8 ([0015], claim 1).
Regarding spherical- and/or spheroidal-shaped particles Patel et al. teach oral dosage units comprising a plurality of beads ([0017], [0027], Fig. 7); granules ([0029], Fig. 9); and a sachet of the disclosure containing a mixture of immediate release and modified release granules or beads ([0034], Fig. 14, [0052]). Figure 20 shows a liquid vehicle of the disclosure containing coated, modified release drug particles, beads or granules ([0040], [0052]). Regardless of the form of the dosage unit, it may alternatively or in addition contain beads, granules, or a combination thereof ([0056]). The “beads” are solid particles that are prepared by extrusion and spheronization of the immediate release formulation, modified release formulation, or a combination thereof ([0056]). A plurality of beads and/or granules is incorporated into the dosage unit wherein “plurality” refers to numerous beads or granules that provide the amount of phloroglucinol, trimethyl phloroglucinol, or pharmaceutically acceptable salt required by the dosage unit ([0057]). Here the teachings read on plurality of spherical particles.
Regarding the partitioning between the plurality of particles and liquid medium, Patel et al. disclose beads or granules can have a core and one or more optional coating layers so that the core may contain one or both the immediate release or modified release formulation ([0059]). The core also contains an inactive pharmaceutical agent such as an excipient ([0059]). The dosage unit may have multiple cores of active with varying dissolution properties ([0060]). Specifically, the dosage unit may contain separate and discrete portions of the immediate release formulation and one or more modified release formulations, i.e., they are physically separated ([0079]). Thus, the dosage unit may contain an immediate release formulation and a modified release formulation ([0079]). In other embodiments, the dosage unit may contain an immediate release formulation, a first modified release formulation, and a second modified release formulation ([0079]).
Regarding percentages of APIs, Patel et al. disclose that the oral dosage unit contains at least one immediate release formulation and at least two modified release formulations, i.e., a first modified release formulation and a second modified release formulation ([0067]). The oral dosage unit comprises about 10 to about 50% by weight, based on the weight of the oral dosage unit, of the immediate release formulation ([0069]). The oral dosage unit comprises about 10 to about 50% by weight, based on the weight of the oral dosage unit, of the modified release formulation ([0070]) and Patel et al. teach that a sachet and/or liquid can be one or both the immediate release formulation or modified release formulation ([0071]).
Patel et al. teach that “immediate release” refers a dosage unit that, upon oral ingestion by a human, releases substantially all the phloroglucinol, trimethyl phloroglucinol or pharmaceutically acceptable salts thereof, into a portion of the gastrointestinal tract (e.g., the stomach or the intestine, preferably the stomach) in a short time ([0072]). Patel et al. shows at least about 90 % weight of the phloroglucinol, trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof, based on the weight of the immediate release formulation, is released into solution (i.e., acidic aqueous solution) ([0072]). The term “modified release” refers to the slow release of the phloroglucinol, trimethyl phloroglucinol, or a pharmaceutically acceptable salt thereof over several hours into the gastrointestinal tract (e.g., the stomach or the intestine) and colon for biological uptake over a long time ([0073]).
Regarding claims 1, 12-13, 16, 25-26, 29 and 38, It would have been prima facie obvious to expect the immediate release particles would be released in the beverage or once ingested because Patel et al. teach an immediate release (few minutes or less) in acidic (i.e., low pH) aqueous solution and a modified release (delayed, e.g., more than one hour) in a solution with a pH of about 6.8 ([0016], [0072 -0073], [0105], [0133]). Upon administration, the dosage form undergoes very rapid disintegration/dispersion of its solid matrix ([0186]). Patel et al. teach that the active and excipients in the matrix undergo rapid dispersion even when placed in a small volume of aqueous fluid, such as water, saliva, juice, milk, beverage, body fluid, soda, etc. ([0186]). As evidenced by Belitz et al., the pH of milk is 6.5-6.75 (i.e., 6.8) (Section 10.1.1, pg. 508, column 1, paragraph 1). Further evidence from Martinez et al. indicates that the final pH of acidified milk drink generally ranges from 3.6 to 4.6 (Introduction).
Further, it would have been obvious to one of ordinary skills in this art to combine the teachings of Patel et al. with those of Bortz et al. with expected results. Bortz et al. provide oral delivery compositions that can readily be combined with a beverage, to administer drugs, to subjects that have difficulty swallowing capsules or tablets, such as pediatric or elderly subjects ([0014]). Bortz et al. teach milk, flavored milk drinks, goat milk, liquid yogurt, soy milk, rice milk and infant formula as non-limiting examples of a liquid beverage suitable for use ([0062]). The teachings of Bortz et al. overlap with those of Patel et al. wherein, as mentioned above, antispasmodic agents (e.g., dicyclomine) are disclosed (see Bortz [0036], see Patel, dicyclomine hydrochloride [0097]). Additionally, Bortz et al. disclose a diameter of about 200 microns and Patel et al. disclose a diameter of about 50 to about 1500 μm ([0059]).
Considering these teachings, the claimed percentages of API released immediately and/or a modified release in the liquid medium are rendered obvious. The adjustment of conventional working conditions (e.g., adjustment of pH, coating of beads and granules) and routine optimization would have been well within the purview of the skilled artisan. Accordingly, this type of modification would have been well within the purview of the skilled artisan and no more than an effort to optimize results.
To reiterate, Bortz et al. teach emulsifier materials ([0032]), dispersing agents (claims 16, 33) and vegetable oils and mineral oils ([0031]); and spherical particles but do not teach lecithin (elected) as an emulsifying agent, corn oil (elected) as an oily dispersing agent, and calcium chloride (elected) as an agent for spherification (i.e., instant claims 5, 33; 6, 34; and 4, 32, respectively).
However, Patel et al. disclose lecithin such as phospholipids as surfactants ([0094]).
Patel et al. disclose corn oil, vegetable oil, and mineral oil ([0086]).
Patel et al. disclose spherical particles (beads) ([0208]) and extrusion and spheronization to produce spherical particles (beads) ([0240]). Polysaccharides and alginic acid ([0173]), sodium alginate, chitosan ([0083], [0141]) are taught. Ammonium calcium alginate is taught as a binder (i.e., gelling agent) ([0083]) to indicate the presence of calcium ions. One of ordinary skill in the art would recognize the presence of calcium ions in the alginate based gelling agent. A skilled artisan would know that a recognized salt of a gelling agent may be substituted with a specific salt, i.e., calcium chloride, for the same purpose of forming a gelling agent and/or spherification.
Regarding claims 7, 18, and 35 as mentioned above Bortz et al. teach stabilizers ([0022]). Patel et al. teach stabilizers as an exemplary excipient ([0082]).
Regarding claims 9, 25, and 29, Patel et al. disclose solutions of 750 mL and 1000 mL (claim 1).
Regarding claims 10 and 36, looking at the instant specification, Applicants describe "instant beverage" to mean that the composition is of a premix, which may be a dry powder (e.g., capsule or stick pack) of beverage flavor that can blend with the APIs and water and other solvents (see Spec., [0109]). Instant beverages premixes are available in powder, granules, and paste forms (see Spec., [0109]). Patel et al. and Bortz et al. teach forms that read on an instant beverage (see Bortz, pellet, powder, sachet and a drinking straw, claim 42; see Patel sachet containing a mixture of immediate release and modified release granules or beads, Fig. 14 [0034]).
Regarding claims 11 and 37 and the recitation of “for daily consumption once or more times a day,” is a recitation of intended use and must result in a structural difference between the claimed invention and the prior art to patentably distinguish the claimed invention from what is in the prior art. Where Applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that in the instant claims but is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. Thus, the therapeutic beverage with evidence from Belitz and Martinez is capable of being consumed once a day.
Regarding claim 12, 16, 26, and 38, Patel et al. a first modified release formulation and a second modified release formulation ([0067]) and at least two APIs which are phloroglucinol and trimethyl phloroglucinol where either phloroglucinol or trimethyl phloroglucinol in the immediate or the modified release set ([0068]).
Regarding claims 14, 25, and 29, Patel et al. teach the oral dosage unit as a liquid ([0071]) and discloses units thereof in milliliters (mL) (claim 1). This is art-known as a unit of measurement obtained by using graduated tools such as a measuring cup graduated cylinder, or syringe which feature a metric volume scale. Here the prior art reads on container of the claims.
Prior Art of Record
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Bortz et al. (US 20080226733 A1). Bortz et al. disclose an invention that relates to spatially arranging a plurality of particles in a device for the oral delivery of a pharmaceutical. In particular, the plurality of particles is utilized for the oral delivery of a pharmaceutical to a subject via the drinking device (abstract).
Conclusion
Claims 1, 3-14, 16-18, 25-26, and 28-38 are rejected. Claims 2, 15, 19-24, 27 and 39-45 are withdrawn. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 0830-1630.
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/Karen A Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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