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 .
Note: The previous non-final office action mailed on 11 June 2026 is replaced by the instant non-final office action to include omitted 35 USC 112 rejections as set forth below.
Formal Matters
Applicant’s response in the reply filed on 18 August 2025 and 16 January 2026 are acknowledged and have been fully considered. Claims 1-2 and 19-27 are pending. Claims 1 and 19-27 are under consideration in the instant office action. Claim 2 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 3-18 are canceled.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 16 January 2026, 18 August 2025, 26 February 2025, and 21 April 2023 are noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. Signed copies are attached herein.
Election/Restrictions
Applicant's election of Group I (claims 1 and 19-27) in the reply filed on 18 August 2025 is acknowledged. Additionally Applicant’s election of the species as follows in the reply filed on 18 August 2025 and 16 January 2026 is also acknowledged.
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Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
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 and 19-27 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.
Claim 1 recites in relevant parts “at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient;…”.. However, claim 1 also on line 16 recites “the gamma hydroxybutyrate drug”, which with the broadest claim interpretation the “at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient;…” recitation encompasses multiple gamma hydroxybutyrate actives. Because of the multiplicity (i.e., at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient), it is unclear whether the singular reference, i.e., “the gamma hydroxybutyrate drug” are intended to refer to just one, more than one, or all of the gamma hydroxybutyrate drug.
Claims 25 and 27 recite in relevant parts “at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient;…”. “the drug”. However, claims 25 and 27 recite “the drug”, which with the broadest claim interpretation the “at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient;…” recitation encompasses multiple gamma hydroxybutyrate actives. Because of the multiplicity (i.e., at least one gamma hydroxybutyrate or a salt, hydrate, tautomer, or solvate, or complex thereof as the active pharmaceutical ingredient), it is unclear whether the singular reference, i.e., “the drug” are intended to refer to just one, more than one, or all of the gamma hydroxybutyrate drug.
The recitations “the gamma hydroxybutyrate drug” in claim 1 and “the drug” in claims 25 and 27 lack antecedent basis on various grounds since it is unclear whether “the gamma hydroxybutyrate drug” and “the drug” are referencing the gamma hydroxybutyrate drug composition in the preamble of claim 1, or if it is referring to the “at least one gamma hydroxybutyrate active pharmaceutical ingredient and if the latter, whether one, more than one or all of the gamma hydroxybutyrate actives are being referenced by “the drug”.
The recitation “the non-toxic gas” in claim 1 also lacks antecedent basis because part (c) recites “a non-toxic gas generating agent”. The gas generating agent is not a gas (e.g., see claim 21), and it is unclear what gas is being referenced.
Note: The dependent claims are included in the rejection because they do not resolve the indefiniteness issues.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Note: The claims are examined with respect to the elected species as described above.
Claims 1 and 19-27 are rejected under 35 U.S.C. 103 as being unpatentable over Allphin et al. (US Patent No. 11,147,782 with effective filing date of February 18, 2025) in view of Prajapati et al. (International Journal of Pharmaceutical Investigation, 2(4), 176-182, 2012), Nirmal et al. (/Int. J. PharmTech Res., 2(2), 1398-1408, 2010), Lohani et al. (Journal of Drug Delivery Science and Technology 31 (2016) 53-64) and Rajinikanth et al. (Journal of Controlled Release 125 (2008) 33–41).
Applicants’ claims
Applicants claim an orally administrable gamma hydroxybutyrate drug composition comprising the ingredients as recited. Dependent claims thereof recite additional features.
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
Allphin et al. teach a formulation of gamma-hydroxybutyrate comprising: a plurality of immediate release particles comprising gamma-hydroxybutyrate; a plurality of modified release particles comprising gamma-hydroxybutyrate; a viscosity enhancing agent; and an acid; wherein the viscosity enhancing agent and the acid are separate from the immediate release particles and the modified release particles (see claim 1). The formulations and dosage forms of the present invention can also include an immediate release component. The immediate release component can form part of a solid controlled release unit dosage form or liquid dosage form (e.g., combined with a controlled release GHB resinate component) or may be a separate immediate release composition. Therefore, an immediate release component may be provided, for example, as a dry powder formulation, an immediate release tablet, an encapsulated formulation, or a liquid solution or suspension. However, the immediate release component may also be formulated as part of a single dosage form that integrates both the above components. The immediate release component can furthermore be an oxybate salt such as sodium, potassium, calcium, or magnesium, the immediate release component can also comprise the GHB resinate particles without modification to retard release, or a combination of these GHB forms (column 5, lines 46-62). In one embodiment, suitable ion-exchange resins include anion exchange resins, such as have been described in the art and are commercially available. These resins are particularly well suited for use with acidic drugs including GHB, as well as prodrugs such as GBL, salts, isomers, polymorphs, and solvates thereof, as well as other acidic drugs identified herein and/or known in the art such as salicylates, nicotinic acid, mefanimic acid, methotrexate, furosemide, phenolic drugs such as paracetamol, morphine, and levothyroxine, warfarin, phenylbutazone, indomethacin, barbiturates, phenytoin, sulphonamides, etc. (column 8, lines 23-33). Allphin et al. clearly teach oxybate-resin complexes as stable, controlled release particulates for reconstitution. Allphin et al. teach viscosity enhancers (e.g., xanthan gum, celluloses) and separate acids/excipients.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Allphin et al. do not specifically teach floating interpenetrating network (IPN) forming system as claimed; the IPN forming blends as claimed carrageenan combined with gellan gum, a crosslinker like calcium chloride, potassium carbonate for ionic crosslinking and/or carbon dioxide generation for buoyancy; self-assembly into floating IPN in situ following oral ingestion; and the combination with the oxybate-resin complex in the recited system. These deficiencies are cured by the teachings of Prajapati et al., Nirmal et al., Lohan et al., and Rajinikanth et al.
Prajapati et al. teach formulating raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent (see abstract). Prajapati et al. teach polysaccharide blends such as gellan gum and carrageenan can form networks via Ca2+ (from calcium chloride) and K+ (from potassium bicarbonate); carbonates generate carbon dioxide. A raft-forming formulation requires sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide, which becomes entrapped within the gel precipitate, converting it into foam, which floats on the surface of the gastric contents. The antacid components contained in formulations provide a relatively pH-neutral barrier. Calcium carbonate can be used as an antacid as well as a raft-strengthening agent. It releases calcium ions, which react with alginate and form an insoluble gel. Various polymers, especially different polysaccharides, have been used in various research works. Alginic acid, alginates and pectin are the most widely used raft-forming agents. Other polysaccharides are also being used, which include guar gum, locust bean gum, carrageenan, pectin and isapgol (pages 176-177). For different batches see Table 1.
Nirmal et al. in situ formation based on chemical reactions Chemical reactions that results in situ gelation may involve precipitation of inorganic solids from supersaturated ionic solutions, enzymatic processes, and photo-initiated processes Polymers may undergo phase transition in presence of various ions. Some of the polysaccharides fall into the class of ion-sensitive ones. While k-carrageenan forms rigid, brittle gels in reply of small amount of K+, i-carrageenan forms elastic gels mainly in the presence of Ca2+. Gellan gum commercially available as Gelrite® is an anionic polysaccharide that undergoes in situ gelling in the presence of mono- and divalent cations, including Ca2+, Mg2+, K+ and Na+. Gelation of the low-methoxy pectins can be caused by divalent cations, especially Ca2+. Likewise, alginic acid undergoes gelation in presence of divalent/polyvalent cations e. g. Ca2+ due to the interaction with guluronic acid block in alginate chains (see page 1400).
Lohani et al. teach Interpenetrating polymer network (IPN) beads of k-Carrageenan and sodium carboxymethyl cellulose (SCMC) containing Ibuprofen were prepared by water-in-water emulsion gelation process using AlCl3 as a cross-linking agent. The impact of different formulation variables like polymer ratio, gelation time, concentration of crosslinker on physico-chemical parameters and in-vitro drug release were studied. The IPN beads were investigated through Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. The prepared beads were slightly rough, folded spherical in shape and reflected improved drug encapsulation efficiency. Swelling ability and drug release of beads in alkaline medium was substantial as that of acidic medium. Formulations showed non-Fickian transport mechanism. The results of the study indicate that drug-loaded pH sensitive IPN beads could be used to diminish drug release in an acidic medium and to regulate the drug release in alkaline medium, which would help to minimize the gastric side effects of the model NSAID ibuprofen (see abstract). Previously many pharmaceutical scientists have extensively investigated on the synthesis of IPN based on natural polymers for controlled or targeted drug delivery. Among the most abundant natural polymers, polysaccharides (alginic acid, chitosan, gellan gum, locust bean gum, xanthan gum, carrageenan, etc.) have been studied in absolute feature in preparing gastro-protective IPN beads to protect the gastric mucosa from the irritant action of drug (see introduction).
Rajinikanth et al. teach Floating in situ gelling system of clarithromycin (FIGC) was prepared using gellan as gelling polymer and calcium carbonate as floating agent for potentially treating gastric ulcers, associated with Helicobacter pylori. Gellan based FIGC was prepared by dissolving varying concentrations of gellan in deionized water to which varying concentrations of drug and sucralfate were dispersed well. The formulation parameters like concentrations of gellan gum and sucralfate influenced the rate and extent of in vitro drug release significantly from FIGC. The addition of sucralfate to the formulation significantly suppressed the degradation of clarithromycin at low pH. The in vivo H. pylori clearance efficacy of prepared FIGC and clarithromycin suspension following oral administration, to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. FIGC showed a significant anti-H. pylori effect than that of clarithromycin suspension. The in situ gel formulation with sucralfate cleared H. pylori more effectively than that of formulation without sucralfate. In addition, the required amount of clarithromycin for eradication of H. pylori was found to be less from FIGC than from the corresponding clarithromycin suspension. It was concluded that prolonged gastrointestinal residence time and enhanced clarithromycin stability resulting from the floating in situ gel of clarithromycin might contribute better for complete clearance of H. pylori (see abstract).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill before the effective filing date of the instant invention to modify the teachings of Allphin et al. by controlled release drug containing ion-exchange resins with the gastroprotective systems as recited because Prajapati et al. teach formulating raft-forming chewable tablets of H2 antagonist (Famotidine) using a raft-forming agent along with an antacid- and gas-generating agent (see abstract). Prajapati et al. teach polysaccharide blends such as gellan gum and carrageenan can form networks via Ca2+ (from calcium chloride) and K+ (from potassium bicarbonate); carbonates generate carbon dioxide. A raft-forming formulation requires sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide, which becomes entrapped within the gel precipitate, converting it into foam, which floats on the surface of the gastric contents. The antacid components contained in formulations provide a relatively pH-neutral barrier. Calcium carbonate can be used as an antacid as well as a raft-strengthening agent. It releases calcium ions, which react with alginate and form an insoluble gel. Various polymers, especially different polysaccharides, have been used in various research works. Alginic acid, alginates and pectin are the most widely used raft-forming agents. Other polysaccharides are also being used, which include guar gum, locust bean gum, carrageenan, pectin and isapgol (pages 176-177). For different batches see Table 1. Furthermore, Nirmal et al. in situ formation based on chemical reactions Chemical reactions that results in situ gelation may involve precipitation of inorganic solids from supersaturated ionic solutions, enzymatic processes, and photo-initiated processes Polymers may undergo phase transition in presence of various ions. Some of the polysaccharides fall into the class of ion-sensitive ones. While k-carrageenan forms rigid, brittle gels in reply of small amount of K+, i-carrageenan forms elastic gels mainly in the presence of Ca2+. Gellan gum commercially available as Gelrite® is an anionic polysaccharide that undergoes in situ gelling in the presence of mono- and divalent cations, including Ca2+, Mg2+, K+ and Na+. Gelation of the low-methoxy pectins can be caused by divalent cations, especially Ca2+. Likewise, alginic acid undergoes gelation in presence of divalent/polyvalent cations e. g. Ca2+ due to the interaction with guluronic acid block in alginate chains (see page 1400). Regrading the formation if the IPN network system using gellan gum and carrageenan Lohani et al. teach Interpenetrating polymer network (IPN) beads of k-Carrageenan and sodium carboxymethyl cellulose (SCMC) containing Ibuprofen were prepared by water-in-water emulsion gelation process using AlCl3 as a cross-linking agent. The impact of different formulation variables like polymer ratio, gelation time, concentration of crosslinker on physico-chemical parameters and in-vitro drug release were studied. The IPN beads were investigated through Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analysis. The prepared beads were slightly rough, folded spherical in shape and reflected improved drug encapsulation efficiency. Swelling ability and drug release of beads in alkaline medium was substantial as that of acidic medium. Formulations showed non-Fickian transport mechanism. The results of the study indicate that drug-loaded pH sensitive IPN beads could be used to diminish drug release in an acidic medium and to regulate the drug release in alkaline medium, which would help to minimize the gastric side effects of the model NSAID ibuprofen (see abstract). Previously many pharmaceutical scientists have extensively investigated on the synthesis of IPN based on natural polymers for controlled or targeted drug delivery. Among the most abundant natural polymers, polysaccharides (alginic acid, chitosan, gellan gum, locust bean gum, xanthan gum, carrageenan, etc.) have been studied in absolute feature in preparing gastro-protective IPN beads to protect the gastric mucosa from the irritant action of drug (see introduction). With regard to the formation of an oral suspension Rajinikanth et al. teach Floating in situ gelling system of clarithromycin (FIGC) was prepared using gellan as gelling polymer and calcium carbonate as floating agent for potentially treating gastric ulcers, associated with Helicobacter pylori. Gellan based FIGC was prepared by dissolving varying concentrations of gellan in deionized water to which varying concentrations of drug and sucralfate were dispersed well. The formulation parameters like concentrations of gellan gum and sucralfate influenced the rate and extent of in vitro drug release significantly from FIGC. The addition of sucralfate to the formulation significantly suppressed the degradation of clarithromycin at low pH. The in vivo H. pylori clearance efficacy of prepared FIGC and clarithromycin suspension following oral administration, to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. FIGC showed a significant anti-H. pylori effect than that of clarithromycin suspension. The in situ gel formulation with sucralfate cleared H. pylori more effectively than that of formulation without sucralfate. In addition, the required amount of clarithromycin for eradication of H. pylori was found to be less from FIGC than from the corresponding clarithromycin suspension. It was concluded that prolonged gastrointestinal residence time and enhanced clarithromycin stability resulting from the floating in situ gel of clarithromycin might contribute better for complete clearance of H. pylori (see abstract). One of ordinary skill in the art would have been motivated to combine ion-exchange resins complexes (for controlled release of drugs like GHB) with a gastroretentive floating in situ gelling/raft systems to extend gastric residence time, improve bioavailability, and enable once or twice nightly dosing for GHB (used in narcolepy, where nocturnal administration is key). GHB’s short half-life and need for sustained exposure made floating systems predictable solutions to gastric emptying issues. Using a powder for oral suspension format was conventional for reconstitutable resin particulates and raft powders. The specific IPN blend recited in the current claims would be an obvious substitution/variation for the known raft forming polysaccharide blends, yielding predictable ionic crosslinking , carbon dioxide entrapment, and floating IPN formation in situ.. Furthermore, the IPN blend is also taught by Lohani et al. as described above. One of ordinary skill in the art would have had a reasonable chance of success in combining the teachings Allphin et al., Prajapati et al., Nirmal et al., Lohani et al., and Rajinikanth et al. because the combination produces no more than predictable results (prolonged gastric retention and release of resin bound oxybate based on the teachings of the references as described above.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIGABU KASSA/Primary Examiner, Art Unit 1619
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