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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01 May 2026 has been entered.
Status of Claims
Receipt is acknowledged of the claim amendments filed on 01 May 2026.
Claims 1 and 51 have been amended.
Claims 2, 5-6, 20 and 27-46 are cancelled.
Claim 56-64 have been added.
Claims 1, 3-4, 7-19, 21-26 and 47-64 are examined herein to the extent that the composition is composition that is one combination and the compound stimulating enteroendocrine cells to release at least one enterokine is a carbohydrate, e.g., applicant's elected species.
Terminal Disclaimer
The terminal disclaimer filed on 05/01/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of any patent granted on Application Number 17/433867 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Rejections Withdrawn
The rejection of claims 1, 7-14, 21-26 and 47-50 under 35 U.S.C. 103(a) as being unpatentable over BLEIEL (WO 2019/170840 A1, cited in IDS filed 12/12/2022) in view of NOEL (US 2020/0230067 A1, effective filing date of 31 March 2020) as evidenced by the instant specification, FOX (US 5,360,614) and CETIN (“Formulation and In vitro Characterization of Eudragit® L100 and Eudragit®L100-PLGA Nanoparticles Containing Diclofenac Sodium”, AAPS PharmSciTech, Volume 11, Number 3, September 2010), is withdrawn in view of the claim amendments.
The rejection of claims 3-4 under 35 U.S.C. 103(a) as being unpatentable over Bleiel in view of Noel as evidenced by the instant specification, Fox and Cetin as applied to claims 1, 7-14, 21-26 and 47-50 above, and further in view of LEGRAND (US 2004/0234601 A1), is withdrawn in view of the claim amendments.
The rejection of claims 15-17 under 35 U.S.C. 103(a) as being unpatentable over Bleiel in view of Noel as evidenced by the instant specification, Fox and Cetin as applied to claims 1, 7-14, 21-26 and 47-50 above, and further in view of FAYAD (WO 2013/063527), is withdrawn in view of the claim amendments.
The rejection of claims 18-19 under 35 U.S.C. 103(a) as being unpatentable over Bleiel in view of Noel as evidenced by the instant specification, Fox and Cetin as applied to claims 1, 7-14, 21-26 and 47-50 above, and further in view of SPRENGER (WO 2017/129639 A1), is withdrawn in view of the claim amendments.
The provisional rejection of claims 1, 3-4, 7-19, 21-26 and 47-55 on the ground of nonstatutory double patenting as being unpatentable over including claims 1, 8-11, 23 and 26 of copending Application No. 17/433,867 (reference application, hereafter ‘867) in view of NOEL (US 2020/0230067 A1, filed 31 March 2020), is withdrawn in view of the terminal disclaimer filed 05/01/2026.
Rejections Modified as Necessitated by Claim Amendments and Maintained
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.
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 51-55 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over FAYAD (US 9,757,346 B2; patent date of 12 September 2017) in view of NOEL (US 2020/0230067 A1, effective filing date of 31 March 2020) and LEGRAND (US 2004/0234601 A1) as evidenced by the instant specification.
Fayad is primarily directed towards a dosage form comprising a controlled release composition, which comprises an enterically-coated, ileum hormone-stimulating amount of a nutritional substance in vivo upon reaching the subject’s ileum (abstract).
Regarding claims 51-52, Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses including at least about 50% of the total amount of the nutritional substance present in the composition (column 9, lines 48-60). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, therefore, necessarily provide release of the core in a terminal jejunum of a subject, the instant specification does not disclose a definition for the term “substantially”) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). The glucose (e.g., compound stimulating enteroendocrine cells to release at least one enterokine) coated with including Eudragit® S100 dissolved at pH 7 disclosed by Fayad is indentical or nearly identical as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species) until and unless applicant can provide evidence to the contrary, therefore, the glucose disclosed by Fayad necessarily has the same characteristics as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species), e.g., stimulates I cells, K cells or L cells. “Products of identical chemical composition cannot have mutually exclusive properties.” A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Fayad does not specifically teach that multiparticulate has a size of less than 3mm, 20000 to 30000 microparticulate, and that the composition further comprises one or more gelling agents. The deficiencies are made up for by the teachings of Noel and Legrand.
Noel is primarily directed towards a system and method of creating personalized doses of active pharmaceutical ingredients dispersed in a palatable oral formulation, wherein the active are encapsulated into microparticles that are dispersed with a thixotropic suspension vehicle to create a customized oral formulation (abstract).
Regarding claims 51 and 53-55, Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core that help break apart (e.g., burst) and release the active (paragraphs [0004] and [0065]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]).
Legrand is primarily directed towards a microparticulate system for releases of active principles (abstract).
Regarding claim 51, Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]). Therefore, the size and number microparticles is an art-recognized result-effective variable, e.g., provides prolonged residence time of the microparticles and reduced variability of the gastric emptying, which a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of ingredient amount would have been obvious at the time of Applicant's invention.
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose and a disintegrant (e.g., helps break apart (e.g., burst) for release of active), and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to about 7.3); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); wherein the core comprises including at least 50% glucose by weight percent; wherein the suspension media further includes a pH regulating agent; and wherein the amount of microparticles is greater than 10,000. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a composition that can provide different flavors and provides delayed dissolution of the active during storage by making microparticles uniformly dispersed in a suspension media comprising a hydrocolloid including alginates, xanthan gum, polyethylene glycols (e.g., gelling agents) and combination thereof (e.g., gelling composition) that is taught by Noel; and 2) obtain a composition with desired prolong residence time and reduction is variability of the gastric emptying by optimizing the size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying as taught by Legrand. The person of ordinary skill in the art would have reasonably expected success because Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses including at least about 50% of the total amount of the nutritional substance present in the composition (column 9, lines 48-60). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that components including pH regulating agents are added to the suspension (paragraph [0085]). Noel teaches that dissolution of API during storage can be delayed by tailoring the pH and viscosity of the suspending media (paragraph [0091]). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]). Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]).
Regarding the recitations “whereby the glucose is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, whereupon the oral dosage forms provide a burst release of the glucose in the subject's terminal jejunum, causing a blood GLP-1 increase in the subject starting at about 1.5 hours after administration of the pharmaceutical composition and lasting about 4 hours” (e.g., claim 51), although the combination of Fayad, Noel and Legrand, do not specifically teach glucose is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, oral dosage forms provide a burst release of the glucose in the subject's terminal jejunum and causing a blood GLP-1 increase in the subject starting at about 1.5 hours after administration of the pharmaceutical composition and lasting about 4 hours, the claimed composition of a pharmaceutical composition comprising 20000 to 30000 oral dosage forms having a core and an enteric coating and a largest dimension which is less than 3 mm; one or more gelling agents; the core comprising 40 to 70% w/w glucose and a disintegrant; the total glucose in the pharmaceutical composition being 7 g to 15 g; the enteric coating comprising a pH sensitive polymer which only substantially dissolves and/or is substantially degraded at a Ph value of about 7.2 to about 7.3 (column 9, lines 48-60, column 9, lines 60-62, column 10, lines 36-37 and column 19, lines 43-36 of Fayad; paragraphs [0004], [0021], [0028], [0065] and [0080] of Noel; and paragraphs [0128-0129] of Legrand) appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
New Grounds of Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-4, 7-19, 21-26 and 47-64 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. The courts have stated:
"To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966." Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
The factors considered in the Written Description requirement are (1) level of skill and knowledge in the art, (2) partial structure, (3) physical and/or chemical properties, (4) functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the (5) method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient." MPEP § 2163.
In the instant case, the claims are drawn to a pharmaceutical composition comprising multiple oral dosage forms and one or more gelling agents, each dosage form comprising a core and an enteric coating, wherein the core comprises at least one compound stimulating enteroendocrine cells to release at least one enterokine, wherein the size of the dosage forms, with respect to the largest dimension of the dosage forms is less than 3 mm, and wherein the core further comprises at least one disintegrant and the enteric coating comprises a pH sensitive polymer which only substantially dissolves and/or is substantially degraded at a pH value of about 7.2 to about 7.3 (e.g., claims 1 and 51) or about 7.2 (e.g., claim 57).
(1) Level of skill and knowledge in the art:
The level of skill and knowledge in the art is high due to the large amount of different pH sensitive polymers and large amount of combination of pH sensitive polymers, in addition the specific amounts of each specific pH sensitive polymers needed in an enteric coating, to provide a coating that dissolves and/or degrades at a pH value of about 7.2 to about 7.3 or about 7.2.
(2) Partial structure:
Different pH sensitive polymers have different structures.
(3) Physical and/or chemical properties:
Different pH sensitive polymers dissolve at different pH and combination of different pH sensitive polymers can be used at optimal amounts each in order to obtain coatings that dissolve and/or degrades at a specific pH.
(4) Functional characteristics:
Different pH sensitive polymers dissolve at different pH. The pH that each pH sensitive polymer dissolve at is typically the threshold pH and the polymers dissolve as a function of rising pH, e.g., pH sensitive polymer that dissolves at pH 6 will dissolve at pH equal to 6 and greater than 6.
(5) Method of making the claimed invention:
The multiple dosage forms of the instant claims are prepared by a method that comprises, preparing a mixture comprising at least one compound stimulating enteroendocrine cells to release at least one enterokine, preferably in combination with at least one disintegrant as defined above,
(b) compressing the mixture obtained in step (a); and (c) applying to the compressed mixture at least one enteric coating, preferably comprising at least one pH sensitive polymer (page 25, lines 1-10).
While having written description pH sensitive polymers including Eudragit® L30D and Eudragit® FS30D that begin to degrade and/or dissolve at a pH value of about 5.5 and 7, respectively, the specification is devoid of pH sensitive polymer that only substantially degrade and/or dissolve at a pH value about 7.2 to about 7.3 (e.g., does not dissolve and/or degrade at higher pH of above about 7.3) or about 7.2 (e.g., does not dissolve and/or degrade at higher pH of above about 7.2).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
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, 3-4, 7-19, 21-26 and 47-64 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.
Claims 1, 51 and 57, and dependent claims 3-4, 7-19, 21-26,47-50, 52-56 and 58-64, respectively, are indefinite due to the recitation of “substantially dissolves…substantially degraded” (emphasis added) because it is unclear what percent of the pH sensitive polymer is dissolved or degraded at a pH value of about 7.2 to about 7.3 or about 7.2. The instant specification does not disclose a definition for the term “substantially”.
Claim 3 and claim 4 which is dependent on claim 3, are rejected because the claims are incomplete for being directly or indirectly dependent on cancelled claim 2.
Claims 1, 7-17, 21-26, 47-50 and 56 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over FAYAD (US 9,757,346 B2; patent date of 12 September 2017) in view of NOEL (US 2020/0230067 A1, effective filing date of 31 March 2020) as evidenced by the instant specification.
Fayad is primarily directed towards a dosage form comprising a controlled release composition, which comprises an enterically-coated, ileum hormone-stimulating amount of a nutritional substance in vivo upon reaching the subject’s ileum (abstract).
Regarding claims 1, 7-14 and 48-50, Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses including at least about 50% of the total amount of the nutritional substance present in the composition (column 9, lines 48-60). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). The glucose (e.g., compound stimulating enteroendocrine cells to release at least one enterokine) coated with including Eudragit® S100 dissolved at pH 7 disclosed by Fayad is substantially the same as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species), therefore, the glucose disclosed by Fayad necessarily has the same characteristics as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species), e.g., stimulates I cells, K cells or L cells.
Regarding claims 15-17, Fayad discloses that other traditional bioactive agents can be combined together in the core and includes stimulants including caffeine (e.g., substance enhances release of GLP-1 and/or PYY by L cells) (column 7, lines 49-60).
Fayad does not specifically teach that the composition further comprises one or more gelling agents. Fayad does not specifically teach that multiparticulate (e.g., multiple oral dosage forms) has a size of less than 3mm and 10000 to 40000 or 20000 to 30000 microparticulate (e.g., multiple oral dosage forms; claims 3-4). The deficiencies are made up for by the teachings of Noel.
Noel is primarily directed towards a system and method of creating personalized doses of active pharmaceutical ingredients dispersed in a palatable oral formulation, wherein the active are encapsulated into microparticles that are dispersed with a thixotropic suspension vehicle to create a customized oral formulation (abstract).
Regarding claims 1, 21-26 and 47-48, Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that components including pH regulating agents (e.g., pH modifiers) are added to the suspension (paragraph [0085]). Noel teaches that dissolution of API during storage can be delayed by tailoring the pH and viscosity of the suspending media (paragraph [0091]). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose and a disintegrant, and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); and wherein the suspension media further includes a pH regulating agent (e.g., pH modifier). The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition that can provide different flavors and provides delayed dissolution of the active during storage by making microparticles uniformly dispersed in a suspension media comprising a hydrocolloid including alginates, xanthan gum, polyethylene glycols (e.g., gelling agents) and combination thereof (e.g., gelling composition) that is taught by Noel. The person of ordinary skill in the art would have reasonably expected success because Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that components including pH regulating agents are added to the suspension (paragraph [0085]). Noel teaches that dissolution of API during storage can be delayed by tailoring the pH and viscosity of the suspending media (paragraph [0091]). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]).
Regarding the recitations “such that the at least one compound stimulating enteroendocrine cells is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, whereupon the oral dosage forms provide a burst release of the glucose in the subject's terminal jejunum, thereby stimulating GLP-1 release from enteroendocrine cells located in the subject’s terminal jejunum and distal small intestine, and thereby causing a blood GLP-1 increase in the subject starting at about 1.5 hours after administration of the pharmaceutical composition and lasting about 4 hours” (e.g., claim 1) and claim 56, although the combination of Fayad and Noel do not specifically teach glucose (e.g., at least one compound stimulating enteroendocrine cells) is not released from the core until the oral dosage forms reach the terminal jejunum of a subject , thereby stimulating GLP-1 release from enteroendocrine cells located in the subject’s terminal jejunum and distal small intestine, oral dosage forms provide a burst release of the glucose in the subject's terminal jejunum and causing a blood GLP-1 increase in the subject starting at about 1.5 hours after administration of the pharmaceutical composition and lasting about 4 hours and the blood GLP-1 of the subject peaks at between about 2.5 to about 3.5 hours after administration of the pharmaceutical composition, the claimed composition of a pharmaceutical composition comprising multiple oral dosage forms and one or more gelling agents, each dosage form comprising a core and an enteric coating, wherein the core comprises at least one compound stimulating enteroendocrine cells to release at least one enterokine, wherein the size of the dosage forms, with respect to the largest dimension of the dosage forms is less than 3 mm, and wherein the core further comprises at least one disintegrant and the enteric coating comprises a pH sensitive polymer selected such that the coating which only substantially dissolves and/or is substantially degraded at a pH value of about 7.2 to about 7.3 (column 9, lines 48-60, column 9, lines 60-62, column 10, lines 36-37 and column 19, lines 43-36 of Fayad; and paragraphs [0004], [0021], [0028], [0065] and [0080] of Noel) appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Fayad in view of Noel as evidenced by the instant specification as applied to claims 1, 7-14, 21-26, 47-50 and 56 above, and further in view of LEGRAND (US 2004/0234601 A1).
Regarding claims 3-4, the composition of claim 1 is described above in section 14.
Fayad and Noel as evidenced by the instant specification does not specifically teach that the composition comprises 10000 to 40000 or 20000 to 30000 microparticles (e.g., multiple oral dosage forms). The deficiencies are made up for by the teachings of Legrand.
Legrand is primarily directed towards a microparticulate system for releases of active principles (abstract).
Regarding claims 3-4, Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]). Therefore, the size and number microparticles is an art-recognized result-effective variable, e.g., provides prolonged residence time of the microparticles and reduced variability of the gastric emptying, which a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of ingredient amount would have been obvious at the time of Applicant's invention.
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose and a disintegrant, and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, the instant specification does not disclose a definition for the term “substantially”); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); wherein the suspension media further includes a pH regulating agent (e.g., pH modifier); and wherein the amount of microparticles is greater than 10,000. The person of ordinary skill in the art would have been motivated to make those modifications to obtain a composition with desired prolong residence time and reduction is variability of the gastric emptying by optimizing the size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying as taught by Legrand. The person of ordinary skill in the art would have reasonably expected success because Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]).
Claims 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Fayad in view of Noel as evidenced by the instant specification as applied to claims 1, 7-14, 21-26, 47-50 and 56 above, and further in view of SPRENGER (WO 2017/129639 A1).
Regarding claims 18-19, the composition of claim 1 is described above in section 14.
Fayad and Noel as evidenced by the instant specification does not specifically teach that the composition further comprises human milk oligosaccharide (e.g., an enteroendocrine cell maturation agent). The deficiency is made up for by the teachings of Sprenger.
Sprenger is primarily directed towards a composition comprising at least one human milk oligosaccharide for use in preventing or treating a health disorder in an infant or young child by increasing GLP-1 in said infant or young child (abstract).
Regarding claims 18-19, Sprenger teaches a composition comprising at least one human milk oligosaccharide for use in preventing and/or treating a health disorder including obesity or type 2 diabetes in and infant or young child by increasing GLP-1 secretion in said infant or young child (page 1, lines7-10).
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose, a human milk oligosaccharide (e.g., an enteroendocrine cell maturation agent) and a disintegrant, and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); and wherein the suspension media further includes a pH regulating agent (e.g., pH modifier). The person of ordinary skill in the art would have been motivated to make those modifications to include additional actives for treating obesity and/or type 2 diabetes by including human milk oligosaccharides (e.g., an enteroendocrine cell maturation agent) that can be used to treat including obesity or type 2 diabetes, as taught by Sprenger. The person of ordinary skill in the art would have reasonably expected success because Sprenger teaches a composition comprising at least one human milk oligosaccharide for use in preventing and/or treating a health disorder including obesity or type 2 diabetes in and infant or young child by increasing GLP-1 secretion in said infant or young child (page 1, lines7-10).
Claims 57-64 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over FAYAD (US 9,757,346 B2; patent date of 12 September 2017) in view of NOEL (US 2020/0230067 A1, effective filing date of 31 March 2020) and LEGRAND (US 2004/0234601 A1) as evidenced by the instant specification.
Fayad is primarily directed towards a dosage form comprising a controlled release composition, which comprises an enterically-coated, ileum hormone-stimulating amount of a nutritional substance in vivo upon reaching the subject’s ileum (abstract).
Regarding claims 57-58, Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). The glucose (e.g., compound stimulating enteroendocrine cells to release at least one enterokine) coated with including Eudragit® S100 dissolved at pH 7 disclosed by Fayad is substantially the same as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species), therefore, the glucose disclosed by Fayad necessarily has the same characteristics as the instantly claimed “compound stimulating enteroendocrine cells to release at least one enterokine” (e.g., carbohydrate is applicant elected species), e.g., stimulates I cells, K cells or L cells.
Fayad does not specifically teach that multiparticulate (e.g., oral dosage forms) has a size of less than 3mm, at least about 10000 microparticulate (e.g., oral dosage forms), and that the composition further comprises one or more gelling agents. The deficiencies are made up for by the teachings of Noel and Legrand.
Noel is primarily directed towards a system and method of creating personalized doses of active pharmaceutical ingredients dispersed in a palatable oral formulation, wherein the active are encapsulated into microparticles that are dispersed with a thixotropic suspension vehicle to create a customized oral formulation (abstract).
Regarding claims 57 and 59-61, Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that components including pH regulating agents are added to the suspension (paragraph [0085]). Noel teaches that dissolution of API during storage can be delayed by tailoring the pH and viscosity of the suspending media (paragraph [0091]). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]).
Legrand is primarily directed towards a microparticulate system for releases of active principles (abstract).
Regarding claim 57, Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]). Therefore, the size and number microparticles is an art-recognized result-effective variable, e.g., provides prolonged residence time of the microparticles and reduced variability of the gastric emptying, which a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying. Thus, absent some demonstration of unexpected results from the claimed parameters, this optimization of ingredient amount would have been obvious at the time of Applicant's invention.
It would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose and a disintegrant, and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); and wherein the amount of microparticles is greater than 10,000. The person of ordinary skill in the art would have been motivated to make those modifications to: 1) obtain a composition that can provide different flavors and provides delayed dissolution of the active during storage by making microparticles uniformly dispersed in a suspension media comprising a hydrocolloid including alginates, xanthan gum, polyethylene glycols (e.g., gelling agents) and combination thereof (e.g., gelling composition) that is taught by Noel; and 2) obtain a composition with desired prolong residence time and reduction is variability of the gastric emptying by optimizing the size and number of microparticles (e.g., using number of microparticles of less than or greater than 10,000) in order to obtain microparticles with desired prolong residence time and reduction is variability of the gastric emptying as taught by Legrand. The person of ordinary skill in the art would have reasonably expected success because Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that components including pH regulating agents are added to the suspension (paragraph [0085]). Noel teaches that dissolution of API during storage can be delayed by tailoring the pH and viscosity of the suspending media (paragraph [0091]). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]). Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]).
Regarding the recitations “whereby the glucose is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, the core provides a burst release of the glucose in the subject's terminal jejunum, thereby stimulating GLP-1 release from enteroendocrine cells located in the subject’s terminal jejunum and distal small intestine, and thereby causing a blood GLP-1 increase in the subject after administration of the pharmaceutical composition” (e.g., claim 57), and claims 62-64, although the combination of Fayad, Noel and Legrand, do not specifically teach glucose is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, the core provides a burst release of the glucose in the subject's terminal jejunum, thereby stimulating GLP-1 release from enteroendocrine cells located in the subject’s terminal jejunum and distal small intestine, thereby causing a blood GLP-1 increase in the subject after administration of the pharmaceutical composition, burst release of the glucose in the subject’s terminal jejunum, causes a blood GLP-1 increase int eh subject starting at about 1.5 hours after administration of the pharmaceutical composition, the blood GLP-1 of the subject peaks at between about 2.5 to about 3.5 hours after administration of the pharmaceutical composition, and the blood GLP-1 increase in the subject lasts about 4 hours after it has started, the claimed composition of a pharmaceutical composition comprising at least about 10000 oral dosage forms having a core and an enteric coating and a largest dimension which is less than 3 mm; one or more gelling agents; the core comprising glucose and a disintegrant; the total glucose in the pharmaceutical composition being 5 g to 20 g; the enteric coating comprising a pH sensitive polymer which only substantially dissolves and/or is substantially degraded at a Ph value of about 7.2 to about 7.3 (column 9, lines 48-60, column 9, lines 60-62, column 10, lines 36-37 and column 19, lines 43-36 of Fayad; paragraphs [0004], [0021], [0028], [0065] and [0080] of Noel; and paragraphs [0128-0129] of Legrand) appears to be the same as the prior art, absent a showing of unobvious differences. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Response to Arguments
Applicant’s arguments will be addressed as they pertain to the rejections maintained and the new grounds of rejection above.
Applicant argues on page 15-16 that Fayad and Noel do not teach or make it obvious to provide the instantly claimed composition comprising multiple small dosage forms in combination with a gelling composition, the small dosage forms comprising an enterokin-releasing compound and a disintegrant surrounded by an enteric coating which only substantially dissolves and/or is substantially degraded at a pH value of about 7.2 to 7.3 or no less than about 7.2 that provides a targeted burst release of the enterokin-releasing compound in the terminal jejunum of a subject. Applicant argues that the claims now specifies that the pH sensitive polymer only dissolves or degrades at a specific minimum pH (e.g., about 7.2 to about 7.3 or about 7.2). Applicant argues that the instantly claimed composition has superior results in that blood plasma GLP-1 levels are increased consistently within 1.5 hours and lasting around 4 hours by oral consumption of the composition, but the composition does not cause a detrimental increase in blood glucose levels which would lead to an immediate increased insulin level directly triggered though sensing of the absorbed glucose by the Langerhans islet cells in the pancreas. Applicant argues that the superior results provided by the instantly claimed composition are result of the combination of claimed elements, namely, that the coating only substantially dissolves and/or is substantially degraded at a pH value of about 7.2 to 7.3. Applicant argues that Applicant’s invention recognizes that the pH dissolution range of the coating on the cores is a critical variable which had not previously been recognized. Applicant argues that the instantly claimed composition provides and GLP-1 response without increasing blood glucose which would cause an undesirable direct increase of insulin by Langerhans cells in the pancreas which sense the glucose absorbed into the blood stream.
Applicant's arguments filed on 01 May 2026 have been fully considered but they are not persuasive. In response, Fayad discloses a controlled release oral dosage form comprising an effective amount of a nutritional substance preferably D-glucose in an amount effective when released in the ileum to stimulate or inhibit the release of hormones in that portion of the small intestine of a subject (paragraph bridging columns 6 and 7). Fayad discloses that the that the nutritional component is coated using a polymeric, preferably aqueous pH-sensitive coating to effect a natural physiological response within the subject’s ileum with favorable results (column 8, lines 3-11). Fayad discloses including at least about 50% of the total amount of the nutritional substance present in the composition (column 9, lines 48-60). Fayad discloses D-glucose amount of including at least about 7.5 grams (column 9, lines 60-62). Fayad discloses that the nutritional substance including D-glucose is combined with including a delayed release component including copolymers of methacrylic acid and methylmethacrylate having a pH dissolution profile that delays release in vivo of the majority of the nutritional substance until the dosage form reaches the ileum, including Eudragit® S100 alone (column 10, lines 26-31). Fayad discloses that Eudragit® S100 dissolved at pH 7 and upwards (e.g., substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3, provide release of the core in a terminal jejunum of a subject) (column 10, 36-37). Fayad discloses that dosage forms including multiparticulate systems (column 18, lines 11-14). Fayad discloses delayed release oral dosage form comprising a core containing an ileum hormonal-stimulating amount of a nutritional substance that is coated by an enteric coating (column 19, lines 43-46). Fayad discloses that the dosage form pharmaceutically acceptable additives (column 19, 59-60). Fayad discloses that pharmaceutically acceptable additives include disintegrating agents (column 20, line 4). Noel teaches a suspension comprising a uniform dispersion of microparticles (e.g., a heterogeneous mixture), wherein each microparticle comprises a core and a coating, wherein the core comprises about 20-99 weight percent of at least one active pharmaceutical ingredient (paragraph [0028]). Noel teaches that the microparticles comprises a disintegrant in the core (paragraph [0004]). Noel teaches microparticles having an average particle size of between about 100-1000 microns (paragraph [0021]). Noel teaches a semisolid thixotropic hydrocolloid suspension media (paragraph [0028]). Noel teaches that hydrocolloid is aqueous-based (e.g., contains aqueous solution/gelling agent) (paragraph [0077]). Noel teaches that hydrocolloid are molecules that are dispersible in water or an aqueous solution and includes alginate, xanthan gum and polyethylene glycol (e.g., gelling agents) and combinations thereof (e.g., gelling composition) (paragraph [0080]). As evidenced by the instant specification, gelling agents includes polysaccharides including alginates, xanthan gum and polyethylene glycols (page 5, lines 5-9). Noel teaches that system create a customized formulation that has desired including food substances, flavors and/or textures (paragraph [0096]). Legrand teaches in cases where the dose of active is high including 500 mg or more, a monolithic form is too large to be swallowed easily. It is then of particular value to have a microparticulate form (paragraph [0019]). Legrand teaches dose of active to be administered spread over a large number of microcapsules including typically 10,000 for a dose of 500 mg which has advantages including residence time of the microcapsules can be prolonged and variability of the gastric emptying is reduced because of the emptying (paragraphs [0128-0129]). Thus, from the disclosure of Fayad and the teachings of Noel and Legrand, it would have been prima facie obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to produce a composition comprising microparticles uniformly dispersed in a suspension media (e.g., gelling agent) comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) that is in an aqueous solution; wherein the microparticles comprises a core comprising glucose and a disintegrant, and a coating comprising a polymer that provides ileal release; wherein the polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3); wherein the microparticles have a size of between about 100-1000 microns (e.g., .1 to 1 mm); and wherein the amount of microparticles is greater than 10,000. Thus, the composition comprising suspension media comprising a hydrocolloid including alginates, xanthan gum and polyethylene glycols (e.g., gelling agents) and combinations thereof (e.g., gelling composition) and microparticles (e.g., multiple oral dosage from) that is prima facie obvious in light of the disclosure of Fayad and the teachings of Noel and Legrand, wherein each microparticle comprise a core and enteric coating of a pH sensitive polymer, wherein the core comprises D-glucose and a disintegrant, and pH sensitive polymer includes Eudragit® S100 that dissolved at pH 7 and upwards (e.g., which only substantially dissolves or is substantially degraded at a pH value of about 7.2 to 7.3); the composition that is prima facie obvious in light of the disclosure of Fayad and the teachings of Noel and Legrand is the same as the instantly claimed composition and would necessarily have the same characteristics when administered to a subject, e.g., glucose is not released from the core until the oral dosage forms reach the terminal jejunum of a subject, the core provides a burst release of the glucose in the subject's terminal jejunum, thereby stimulating GLP-1 release from enteroendocrine cells located in the subject’s terminal jejunum and distal small intestine, thereby causing a blood GLP-1 increase in the subject after administration of the pharmaceutical composition, burst release of the glucose in the subject’s terminal jejunum, causes a blood GLP-1 increase int eh subject starting at about 1.5 hours after administration of the pharmaceutical composition, the blood GLP-1 of the subject peaks at between about 2.5 to about 3.5 hours after administration of the pharmaceutical composition, and the blood GLP-1 increase in the subject lasts about 4 hours after it has started. The office does not have the facilities and resources to provide the factual evidence needed in order to establish that the composition of the prior art does not possess the same material, structural and steps-like characteristics of the claimed composition. In the absence of evidence to the contrary, the burden is on Applicant to prove that the claimed composition is different from that taught by the prior art and to establish patentable differences. See In re Best 562F .2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2nd 1992 (PTO Bd. Pat. App. & Int. 1989).
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.). MPEP 2112.01 (I).
Additionally, the pH sensitive polymer disclosed by Fayad of including Eudragit® S100 that dissolves at pH 7 and upwards is considered to be “about 7.2 to 7.3” and “about 7.2” or close enough to render it obvious. See 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) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0, explaining "[t]hat which infringes if later anticipates if earlier"); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Waite, 168 F.2d 104, 108 (CCPA 1948); In re Scherl, 156 F.2d 72, 74-75 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Swenson, 132 F.2d 1020, 1022 (CCPA 1942); In re Bergen, 120 F.2d 329, 332 (CCPA 1941); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934 (CCPA 1934); In re Lilienfeld, 67 F.2d 920, 924 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); Gentiluomo v. Brunswick Bowling and Billiards Corp., 36 Fed. App'x 433 (Fed. Cir. 2002)(non-precedential)(disagreeing with argument that overlapping ranges were required to find a claim prima facie obvious). As evidenced by the instant specification, the preferred pH sensitive polymers include Eudragit® FS30D, which as evidenced by Bristol (WO 2019/183208 A1), dissolve at rising pH of pH >7.0 (paragraph [0116] of Bristol). Therefore, pH sensitive polymers that dissolve at rising pH of pH >7 including Eudragit® S100 and Eudragit® FS30D that dissolves at pH 7 and upwards reads on a pH sensitive polymer that substantially dissolves and/or is substantially degraded at a pH value of about 7.2 to about 7.3.
Further, Applicant has not provided clear evidence of unexpected results/superior results because Fayad discloses oral administration of including glucose to ileum, using polymer including Eudragit® S100 that dissolves at pH 7 and upwards (column 10, lines 26-34), shows result in normalized blood sugar and insulin levels (column 8, lines 16-26). Therefore, a composition that releases glucose at including a pH of 7 or higher using including Eudragit® S100 when administered to a subject is expected to not increase blood glucose in a subject after administration of the composition.
Further, the instant specification does not disclose a definition for the term “substantially”, therefore, there is no objective measurement of a range providing the alleged superior results that commensurate with the instantly claimed composition.
Thus, for the reasons of record and for the reasons presented above claims 1, 3-4, 7-19, 21-26 and 47-64 are rejected under 35 U.S.C. 103(a).
Conclusion and Correspondence
No claims are allowed.
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/JOHN P NGUYEN/
Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Quality Assurance Spec., Art Unit 1600
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