DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
Receipt of Applicants’ Arguments, Remarks and amended claims filed on 03/23/2026 is acknowledged.
Claims 1-4, 6-16 and 18-20 are pending.
Claims 5, 17 and 21 remain cancelled.
Claims 1 and 13-16 are amended.
Claims 1-4, 6-16 and 18-20 are pending and under examination in this application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/23/2026 is in compliance with the provisions of 37 CFR 1.98. Accordingly, the information disclosure statements has been considered by the examiner. A signed copy of each has been attached to this office action.
Remarks Objections – Withdrawn
The objection to the Remarks is withdrawn. The corrected Remarks confirm that claims 1-4, 6-16, and 18-20 are pending in this application.
Claim Rejections - 35 USC § 112 - Withdrawn
Claims 1, 2, 7-10, 13-15 – § 112(b) Indefiniteness (Formulation Agent / “Configured to Degrade”) – Withdrawn
Applicant has amended the formulation agent limitation in claims 1, 2, 7-10, and 13-15 from “configured to bring the silicon hydride into contact with the aqueous medium found in a human or non-human animal body” to “configured to degrade in at least one physiological condition in a human or a non-human animal body, thereby bringing the silicon hydride into contact with the aqueous medium.” This amendment ties the functional language to a specific degradation mechanism in physiological conditions, providing sufficient structural/mechanistic clarity. The § 112(b) rejection of claims 1, 2, 7-10, and 13-15 based on the formulation agent limitation is hereby withdrawn.
Claims 1, 2, 7-10, 13-15 – § 112(b) Indefiniteness (“Releasing Dihydrogen as a Solute”) – Withdrawn
Applicant has amended “as a solute” to “in dissolved form” in claims 1, 13, 14, and 15. This amendment clarifies the limitation to mean molecular hydrogen dissolved in the aqueous medium, consistent with the specification’s usage, without importing the concentration/stability connotations the Examiner attributed to “solute.” The § 112(b) rejection based on this phrase is hereby withdrawn.
Claim 16 – § 112(b) and § 112(d) – Withdrawn
Applicant has amended claim 16 to recite that “the formulation agent is selected to degrade at a pH or physiological condition associated with” the listed administration routes, and has removed “oral” from the enumerated routes. As amended, claim 16 is directed to a property of the formulation agent (its degradation pH/condition), adding a structural/functional limitation to the device of claim 15, and the routes recited are consistent with the plaster/contact lens/implant forms of claim 15. The § 112(b) and § 112(d) rejections of claim 16 are hereby withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1-4, 6-16 and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Surface chemistry of porous silicon and implications for drug encapsulation and delivery applications (hereinafter the reference is referred as Jarvis) in view of Lucas (US 2015/0258136 A1) and further in view of a Tailoring Porous Silicon for Biomedical Applications: From Drug Delivery to Cancer Immunotherapy (hereinafter the reference is referred as Li).
Scope and Content of the Prior Art
The prior art of record is summarized as set forth in the previous Office action dated 12/23/2025, which is incorporated herein by reference. Key teachings are highlighted below as relevant to the amended claims.
Jarvis teaches non-passivated (native) porous silicon (pSi) characterized by a SiySiHx-terminated surface. Jarvis explicitly teaches that when native pSi is exposed to aqueous medium, it undergoes oxidation and dissolution according to the reactions: (1) Si + 2H₂O → SiO₂ + 2H₂ and (2) SiO₂ + 2H₂O → Si(OH)₄, wherein molecular hydrogen is generated in the oxidation step (page 31, left column, ¶ 3). Jarvis further teaches that dissolution of pSi decreases the pH of the medium due to orthosilicic acid formation and liberation of hydrogen from pore walls, and that surface chemistry governs the dissolution rate (page 31, left column, ¶ 3). Jarvis teaches native, non-passivated pSi with nanoscopic-sized porosity as the reactive starting material from which surface-modified variants are derived (page 27, right column, last ¶; page 28, last column, ¶ 2).
Lucas teaches a kit for treating oxidative stress using therapeutically active hydrogen molecules produced by reacting ionic hydrides with aqueous media. Lucas explicitly teaches that CaH₂ and MgH₂ react with water according to: H⁺ + H⁻ → H₂(g) (¶ 0045), and teaches calcium hydride and magnesium hydride in solid and powdered form as preferred ionic hydrides (¶¶ 0069, 0074-0086). Lucas further teaches that under aqueous conditions, the ionic hydride produces molecular hydrogen, and the reaction can be delayed by slow-release formulations or gastro-resistant encapsulation (¶¶ 0022-0023, 0050). Lucas discloses that hydrogen is soluble in water up to approximately 0.8 mmol/L and is pharmacologically effective at those concentrations (¶ 0046).
Li teaches that porous silicon nanoparticles (PSi) can be formulated with biodegradable polymer coatings for controlled drug release, including pH-responsive polymers that degrade in the gastrointestinal environment (page 15, ¶ 3.1.2). Li further teaches that freshly etched (non-passivated) PSi undergoes fast dissolution, and surface stabilization detains dissolution (page 19, right column, last ¶), corresponding to the non-passivated porous silicon limitation. Li additionally teaches layer-by-layer coating strategies for achieving hierarchical targeted delivery (page 19, left column, ¶ 2).
Differences Between the Prior Art and the Claims at Issue
As acknowledged in the previous Office action (12/23/2025), Jarvis in view of Lucas and Li did not specifically address (a) the specific use of CaH₂ or MgH₂ in combination with porous silicon hydride in a single mixture, and (b) a plurality of formulation agents in successive concentric layers (claim 11). Applicant’s 03/23/2026 amendment to claims 1, 13, 14, 15 and 16 has added a further “wherein” clause reciting: “wherein the mixture of hydrides provides pH-dependent release of dihydrogen such that the ionic hydride releases dihydrogen and produces hydroxide ions at acidic pH, and the hydroxide ions react with the silicon hydride to induce release of dihydrogen from the silicon hydride”
The Examiner has fully considered this new limitation and finds that it does not confer patentability over the applied combination for the reasons set forth below.
Prima Facie Case of Obviousness – Amended Claims 1, 13, 14, 15.
The newly added “pH-dependent synergistic release” limitation describes a functional result that is the inherent chemical consequence of combining non-passivated porous silicon with ionic hydrides (CaH₂ or MgH₂) in an aqueous medium, as taught by the applied combination of Jarvis and Lucas. A claim limitation that merely describes an inherent property of an otherwise obvious combination does not render the claim patentable. See MPEP § 2112; Par Pharm., Inc. v. TWi Pharms., Inc., 773 F.3d 1186, 1194-96 (Fed. Cir. 2014).
Specifically:
(i) Lucas explicitly teaches the hydrolysis reaction of ionic hydrides (CaH₂, MgH₂) at acidic pH: H⁺ + H⁻ → H₂(g) (¶ 0045). This acid-driven reaction consumes protons and produces molecular hydrogen. The by-product of CaH₂ or MgH₂ hydrolysis in aqueous medium is Ca(OH)₂ or Mg(OH)₂ respectively, which dissociates to yield Ca²⁺/Mg²⁺ and hydroxide ions (OH⁻). This is established inorganic chemistry. Lucas’s disclosure that the hydrogen production is driven by acid (¶ 0045) inherently discloses that the ionic hydride consumes protons from the acidic medium, thereby generating the alkaline by-product (OH⁻) as a necessary consequence of the reaction stoichiometry.
(ii) Jarvis explicitly teaches that the rate of pSi dissolution and hydrogen generation from the SiySiHx surface is governed by the chemical environment of the aqueous medium, including pH effects (page 31, left column, ¶ 3). It is well-established in the porous silicon art, as evidenced by Jarvis, that the oxidation and dissolution of SiH-terminated pSi is accelerated under alkaline or nucleophilic conditions, as hydroxide ions are known to attack Si-H bonds. See Jarvis, page 31 (dissolution attributed to water-soluble SiySiHx groups; removal reduces dissolution). A PHOSITA would therefore immediately recognize that the OH⁻ generated by ionic hydride hydrolysis (as per Lucas) would accelerate the dissolution and concomitant H₂ release from the non-passivated pSi (as per Jarvis). The claimed “synergistic” cascade is the predictable chemical outcome of combining these two known reactive systems.
(iii) The claim does not require the applicant to have invented, characterized, optimized, or quantified the synergistic cascade. The claim merely recites that the mixture “provides” pH-dependent release according to this mechanism. Because a PHOSITA combining pSi with CaH₂/MgH₂ in aqueous medium would inherently produce a mixture that operates by exactly this mechanism — regardless of whether the PHOSITA was aware of or intended the cascade — the newly added limitation is inherent to the obvious combination and therefore does not distinguish over it.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate a composition comprising a mixture of non-passivated porous silicon hydride with CaH₂ or MgH₂ in solid form, with a formulation agent configured to degrade under physiological conditions, as taught by Jarvis in view of Lucas and further in view of Li. One would have been motivated to do so for at least the following reasons:
First, Jarvis teaches that non-passivated pSi reacts with aqueous medium to generate molecular hydrogen (equations (1) and (2), page 31), and that porosity, surface area, and pore morphology can be tuned to control dissolution and hydrogen yield (page 27-28). The highly reactive SiySiHx surface is explicitly identified as the hydrogen-generating species (page 31, ¶ 3). A PHOSITA would have recognized this as a platform for in vivo hydrogen generation.
Second, Lucas teaches that ionic hydrides (CaH₂, MgH₂) are safe, biocompatible sources of molecular hydrogen that react with aqueous media in a controlled manner, and that slow-release formulations can be used to target hydrogen delivery to specific tissues or organs (¶¶ 0005-0010, 0022-0023). Lucas teaches that hydrogen has therapeutic value in treating oxidative stress and cardiovascular/neurodegenerative conditions (¶¶ 0029-0035). A PHOSITA seeking to maximize hydrogen yield from a solid-state formulation would have been motivated to combine multiple hydrogen-generating hydride sources within a single platform.
Third, Li teaches that pSi nanoparticles can be formulated with biodegradable polymer encapsulants and pH-responsive coatings to achieve controlled, site-specific release in biological environments (page 15, ¶ 3.1.2; page 19, left column, ¶ 2). A PHOSITA would have been motivated to apply Li’s polymer coating strategies to the pSi-hydride platform taught by Jarvis and Lucas to achieve the desired physiological degradation and controlled contact with aqueous medium.
The motivation to combine is further supported by the fact that all three references operate in the same technical field — solid-state hydrogen delivery for therapeutic applications — and share a common goal of achieving controlled hydrogen release in biological environments. Combining known elements from the same field to yield a predictable result is the hallmark of obviousness. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
A PHOSITA would have had a reasonable expectation of success in combining these teachings because: (a) the chemistry of pSi hydrolysis in aqueous medium is well-characterized and predictable; (b) the chemistry of ionic hydride hydrolysis is well-characterized and predictable; (c) polymer encapsulation strategies for controlling degradation of reactive solid particles in biological environments were routine in the art, as taught by Li; and (d) the claimed hydride ratios (silicon hydride ≥24 wt% and <96 wt%, with at least some proportion of ionic hydride) represent nothing more than the full compositional space of a binary hydride mixture excluding the pure-component extremes, optimization of which was routine in the art once the combination itself was known.
Regarding the specific weight percentage range (silicon hydride ≥24 wt% to <96 wt%): as set forth in the previous Office action, a PHOSITA would have been motivated to optimize the ratio of silicon hydride to ionic hydride in order to yield a desired amount of molecular hydrogen in the reaction. Such routine optimization of component ratios, where the combination itself was known and predictable, does not support patentability. In re Aller, 220 F.2d 454, 456 (CCPA 1955).
Regarding claims 1, 3 and 6, Jarvis teaches native porous silicon, surface modification can also be used to add functionalities to the pSi surface to enable use in specific applications, and porosity has been shown to influence surface chemistry of pSi (¶ 3.1). Porosity has been shown to influence surface chemistry of pSi, and as the porosity of the pSi increases, the concentration of SiySiHx species increases. Such behavior can be explained by the fact that pSi with higher porosities has a greater surface area and therefore a greater number of SiySiHx groups (¶ 3.1, ¶ 2 last 5 lines). The native porous silicon corresponds to instant limitation of non-passivated porous silicon and the morphology of the pSi produced is dependent on the anodization parameters such as hydrofluoric acid (HF) concentration, current density, anodization time and temperature (page 27, left column, ¶ 1 last 3 lines) and the pore morphologies that may exist in pSi are closed pores which do not have an opening to the surface or through pores which extend all the way through a porous membrane and a wide range of surface areas (<1 m2/g for macroporous to 800 m2/g for microporous) can be produced in pSi and are dependent on fabrication parameters (page 27, right column, last ¶) and the effect of various HF concentrations on pSi formation was investigated by producing pSi electrochemically using 80% or 20% HF solutions and a current density of 30 mA/cm2. The pSi produced in the concentrated solution was mesoporous and had pore diameters of 3–8 nm, and had a porosity of 60%. Dilute HF produced macroporous
pSi with pore diameters of 0.5–3 μm and a porosity of 86% (page 28, last column ¶ 2) corresponding to instant nanoscopic sized porosity. Jarvis explicitly teaches non-passivated porous silicon and porosity modification parameters as noted above. Moreover, Jarvis discloses when pSi is exposed to physiological conditions, the native SiHx terminated surface undergoes oxidation and subsequently dissolves into non-toxic orthosilicic acid (Si(OH)4), and orthosilicic acid is the soluble form of silicon and the major form of silicon in the human body which is required in both bone and collagen growth. Orthosilicic acid has also been shown to stimulate calcification and produce a negligible inflammatory tissue response. High levels of orthosilicic acid can be toxic, however the urine excretion of orthosilicic acid from the human body is efficient at expelling all ingested silicon the dissolution of porous silicon in aqueous solution can be simplified to the following equations;
(1) Si + 2H2O→SiO2 + 2H2
(2) SiO2 + 2H2O→Si(OH)4
hydrogen is generated in the oxidation step while the final product is orthosilicic acid and dissolution of pSi decreases the pH of the medium due to orthosilicic acid formation and the liberation of hydrogen from the pore walls. The modification of pSi surface chemistry by thermal oxidation has a significant effect on the dissolution rate. The dissolution of pSi is attributed to the water soluble SiySiHx groups on the surface therefore removal of these species reduces dissolution (page 31, left column, ¶ 3). Therefore, Jarvis explicitly teaches the limitations of non-passivated porous silicon, nanoscopic sized porosity, hydrides in contact with aqueous medium for hydrogen generation.
Regarding claims 2, 7-15, Jarvis teaches the subject matter and features of the formulation agent that will degrade in response to a sufficient level of an external or an internal stimulus with features of gastro-resistant materials, in aqueous medium. Particularly, Jarvis teaches surface modification can be used to easily tune the dissolution of a pSi sample in solution. Faster pSi dissolution can be used to produce sustained drug release by releasing the drug from the pores during dissolution while slower pSi dissolution can be used to enhance drug release via diffusion from the
pores while the pSi remains intact (page 32, left column, ¶ 1). Moreover, Jarvis teaches coating applied to native PSi (page 34, right column, ¶ 2; and coated surface of PSi (page 30, left column, last ¶).
Regarding claim 12, Jarvis teaches titanium agent (page 31, left column ¶ 4.1). A person skill in the art would have known that titanium can be considered as a detection agent upon ingestion.
Regarding claims 13, 14, and 15, in addition to the limitations above, Jarvis teaches a medicant composition, a therapeutic composition, and devices (¶ intro.) comprising non-passivated porous silicon, hydrides that will dissolve on contact with an aqueous medium, thereby releasing hydrogen (page 32, ¶ 5.1).
Regarding claims 16, 18 and 19, Jarvis teaches administration route of oral (pages 34 & 35, right column, last ¶), intraocular injection (page 31, right column, ¶ 3) and the manufacture of implantable such as micro-needles with PSi tips which can be loaded with drugs and then delivered trans dermally (page 33, left column, ¶ 1). Regarding amended claim 16, the amended limitation recites that the formulation agent of the device of claim 15 “is selected to degrade at a pH or physiological condition associated with” the enumerated administration routes. Lucas explicitly teaches that formulation agents (encapsulants) are selected based on the pH conditions at the target administration site, specifically, that a hydride encapsulant is selected to release hydrogen in reaction with acidic gastric juice in the stomach (¶ 0022), and that slow-release formulations are designed based on the pH environment of the intended release site (¶¶ 0022-0023, 0050). Li explicitly teaches pH-responsive polymer coatings for pSi that are selected to degrade at the pH associated with specific gastrointestinal sites, including encapsulation in pH-responsive polymers that protect cargo through the stomach and degrade at small intestine pH for site-specific release (page 15, ¶ 3.1.2). A PHOSITA would therefore have known to select a formulation agent whose degradation pH or physiological trigger corresponds to the intended administration site, as a matter of routine formulation design. The amended limitation of claim 16 is therefore obvious by Lucas and Li for at least these reasons.
Regarding claim 20, the claim recites a method for releasing hydrogen molecules in a human or non-human animal body using the composition of claim 1. As noted above, Jarvis teaches Hydrogen is generated in the oxidation step (page 31, ¶ 4.1). Thus the releasing hydrogen molecules is taught. The method of claim 20 adds no patentably distinct limitation beyond the administration of the composition of claim 1, as the act of releasing hydrogen molecules is the inherent functional consequence of administering the composition to a biological environment containing aqueous medium. Because the composition of claim 1 is unpatentable over Jarvis in view of Lucas and further in view of Li, the method of using that composition is likewise unpatentable. See Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1375-76 (Fed. Cir. 2001) (method of using an obvious composition is itself obvious).
Jarvis fails to specifically teach use of calcium and magnesium hydrides in porous silicon and the specific use of hydrogen molecules solely for intention in hydrogen therapy. However, Jarvis teaches the scope and subject matter that encompass instant claims limitations of non-passivated porous silicon, metal hydrides and generation of hydrogen molecules, the impact of porosity and surface chemistry modification parameters affecting drug stability, dissolution and delivering in vivo.
Lucas teaches a kit for preventing or treating oxidative stress in humans or animals by means of therapeutically active hydrogen molecules, where the hydrogen molecules are formed by reacting a base metal with aqueous acids or bases and by reacting a saline hydride with water or aqueous acids (abstract).
Regarding claims 1,11-15 Lucas teaches hydrogen dissolved in water and the disadvantages and challenges of delivering hydrogen molecules to targeted specific tissues or organs (stomach, bowel) (entire ¶ 0003). However, Lucas specifically teaches producing hydrogen molecules with reacting with base metals comprising calcium hydride, magnesium hydride or titanium, with the goal to supply hydrogen to specific organs and tissues in a targeted manner (¶ 0005-0010). Moreover, Lucas discloses at least two reactants are always required to produced hydrogen chemically, for example (1) Acid+metal→H2 (g)+salt and (2) H+ + H- → H2(g) (¶ 0045). Furthermore, Lucas teaches the production of hydrogen is not just limited to magnesium; hydrogen can generally be produced from the combination of an acid and a metal and metals that are beneficial on the milligram scale include sodium, potassium, calcium, manganese, zinc, and iron. Sodium and potassium are of limited suitability due to their violent reaction with water. The chemical reaction should be delayed by a slow-release formulation when these are used. This applies similarly to calcium (¶ 0070). Therefore, calcium and magnesium hydrides are explicitly taught (¶ 0074-0086), in solid (¶ 0069) and powdered form (¶ 0050 & ¶ 0087). Additionally, Lucas discloses under standard conditions (room temperature, standard air pressure) hydrogen dissolves in water at a maximum concentration of about 0.8 mmol. Since one mole of hydrogen (H2 ) has a mass of 2 g, this corresponds to about 1.6 mg of hydrogen per liter of water. Despite this relatively low mass, 0.8 millimole of hydrogen still amounts to about 4.8*1020 hydrogen molecules. It would be sufficient to achieve a therapeutic effect in the cases described if the hydrogen saturation of the water was under 50% and amounts of one liter were consumed. The lower limit of hydrogen that has to be supplied to the body to still achieve detectable positive effects has not yet been exactly quantitatively determined. But it can safely be assumed that a quantity of 0.4 mmol or 0.8 mg of hydrogen per day is pharmacologically effective (¶ 0046). Therefore, the limitation of hydrogen as a solute (dissolved in water) is taught.
Regarding the limitation of silicon hydride is greater than or equal to 24 % and less than 96% and the proportion of the at least one other ionic hydride is greater than zero. It would have been obvious to a person having skill in the art to optimize hydride ratios for maximum reactivity without overload in order to yield a desired amount of hydrogen molecules in the composition.
Regarding claims 7 and 8, Lucas teaches the production of hydrogen can be coupled with the taking of acetylsalicylic acid, wherein a synergistic effect of the known effects of acetylsalicylic acid and the elimination of Reactive Oxygen Species (ROS) in the body can be achieved, and in another embodiment, a metal is encapsulated such that it only causes the release of hydrogen after it has been swallowed, in a reaction with the acidic gastric juice in the stomach (¶ 0022). In another embodiment, a hydride is used that is encapsulated and released in a targeted manner in the stomach or bowel. In both cases, the hydride reacts with water or the gastric juice, thereby releasing molecular hydrogen (¶ 0023). Therefore, the limitation of gastro-resistant materials, soluble on contact with the aqueous medium in a pH range associated with a predetermined administration site on the human or non-human body, degrade in response to a sufficient level of an external or an internal stimulus, and material soluble on contact with aqueous medium is met. It is noted that degradation is understood as the release of dihydrogen in the physiological condition observable in the human or animal body, wherein the presence of water, temperature, pH, the concentration of mineral salts, etc., could be observed at the level of at least one location of the human or animal body as defined in specification (page 4, lines 12-24).
Regarding claims 9 and 10, Lucas teaches one or more of the base metal or saline hydride and water that when react with one another with release of hydrogen may be encapsulated to prevent a premature reaction of these components (¶ 0007), and in another embodiment, a metal is encapsulated such that it only causes the release of hydrogen after it has been swallowed, in a reaction with the acidic gastric juice in the stomach (¶ 0022). Moreover, Lucas discloses when the formulation as a powder, the hydrogen partially dissolves in water, which is visible directly in that the bubble size decrease, the reaction takes about 5 minutes to minutes, depending on the size of the magnesium particles, the water enriched with hydrogen is the manner is drunk to administer the hydrogen (¶ 0050). Therefore, this suggests that there is a degradation rate (release of hydrogen) after swallowed and hydrogen released in the stomach, and an induce dissolution thereof on the release of dihydrogen. Therefore, the limitation of degradation rate, aqueous medium found at a predetermined site on the human or animal body and the formulation as a powder is semi-permeable is taught.
Regarding claims 13 and 14, Lucas teaches medical, non-medical indications, and medically unexplained syndromes (¶ 0029-0035) and that hydrogen can also be used for prevention or simply for increasing well-being (wellness) in many cases in which pharmacological intervention is not required (¶ 0029). Furthermore, Lucas discloses hydrogen can help to reduce the further destruction of tissue in the event of stroke and myocardial infarction (¶ 0031), Therefore, the limitation of a medicament and a therapeutic composition for the treatment in cardiovascular disease is taught.
Regarding claim 18, Lucas teaches hydrogen formulations in oral form of administration (¶ 0015, claim 13), hydrogen by inhalation (respiratory) administration (¶ 0028), drinking of hydrogen-enriched water (oral administration) (¶ 0028), or injection of hydrogen-enriched solutions can reduce the amount of free radicals in the body (¶ 0028).
Lucas fails to specifically teach plurality of formulation agents configured together in successive concentric layers.
Li teaches porous silicon (PSi) with controllable geometry, tunable nanoporous structure, large pore volume/high specific surface area, and versatile surface chemistry, PSi shows significant advantages over conventional drug carriers, where the surface chemistry and modification of PSi are discussed in relation to the strengthening of its performance in drug delivery and bioimaging (abstract). Notably, Li discloses besides biocompatibility, physiological stability, and dispersity, the biodegradability of PSi is another key factor to evaluate its further clinical application. The inherent factors that
influencing PSi degradation are also its overall size, porosity, pore size, and surface functionalization. For example, the increase of porosity increases the diffusion rate of species in and out the pores, and thus, accelerates the dissolution rate of the silicon network, the decreased size of PSi will also accelerate the degradation rate due to the augmented surface/volume ratio. Freshly etched PSi (corresponding to non-passivated porous silicon) will undergo fast dissolution, and surface stabilization, such as oxidation and carbonization, will generate a protection layer which can detain the dissolution process of PSi (page 19, right column, last ¶).
Regarding claims 2, and 7-11, Li teaches many strategies have been developed in recent years in terms of controlled drug release for PSi using surface modification and/or physical encapsulation, and the surface modification of PSi nanoparticles with temperature responsive polymer enabled to controlled drug release in response to the heating induced by infrared or radiofrequency radiation and the physical encapsulation of PSi nanoparticles in pH-responsive polymers protected GLP-1 and insulin from the harsh conditions of the gastrointestinal tract, and provided site specific drug release in small intestines for enhanced absorption (page 2 left column, ¶ 3 bottom). Furthermore, Li discloses protection of PSi nanoparticles from administration sites to the target sites comprising liposomes, micelles, polymer nanoparticles, albumin-bound (page 6, ¶ 2.2.2), and surface modification of PSi for controlled drug or cargo release comprising β-cyclodextrin, and a pH-sensitive release behavior was observed by applying a stimuli-responsive polymer, polyethylene glycol-block-poly(l-histidine) (page 15, ¶ 3.1.2) corresponding to the formulation agent consisting of gastro-resistant materials (β-cyclodextrin). Moreover, Li discloses Surface modification of PSi with special ligand will endow the carrier with enhanced adhesion to specific cells, therefore increasing the particle and the drug accumulation at lesion sites and different kinds of targeting ligands are applied for multiple diseases. For example, chitosan modified PSi with mucoadhesive property was applied for the oral administration of insulin, Atrial natriuretic peptide (ANP), a heart homing peptide, was also conjugated to PSi for chronic heart failure reverse. In vivo biodistribution of PSi modified with ANP was monitored in Wistar rats. Animals received subcutaneous injection of isoprenaline (5 mg kg−1) 24 h before intravenous administration of radiolabeled peptide modified PSi nanoparticles for establishing the infarcted heart model. Results showed up to threefold PSi accumulation within the heart after the peptide modification (Figure 8a) and (page 17, ¶ 3.2), and other convenient way to achieve hierarchy targeting is layer-by-layer coating, and PSi conjugated with targeting ligand can be encapsulated within a protection matrix, when reaching the lesion sites the matrix will degrade and further expose the targeting moiety (page 19, left column, ¶ 2).
Regarding claim 4, Li teaches the average size of obtained PSi particles can be
tuned from a few micrometers to hundreds of nanometers (page 3, left column, last ¶) and PSi layers can also be milled into powders (page 3, right column, ¶ 2).
Response to Arguments
Applicant's arguments filed 03/23/2026 have been fully considered but they are not persuasive for the following reasons.
Argument 1: Jarvis “teaches away” from using reactive porous silicon.
Applicant argues that Jarvis describes the reactive native pSi surface as a problem to be solved through surface modification, not a feature to be exploited, and therefore teaches away from using non-passivated pSi in combination with reactive ionic hydrides.
This argument is not persuasive. A reference does not teach away merely because it discloses an alternative approach or notes that one property of a material can be disadvantageous in some contexts. In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994) (“A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant”). Jarvis is a comprehensive review of pSi surface chemistry that explicitly teaches — and not merely as a problem statement — the hydrogen generation reaction of native pSi in aqueous medium (page 31, equations (1) and (2)), the dissolution kinetics of non-passivated pSi, and the ability to tune those kinetics through fabrication parameters such as porosity, pore size, and HF concentration (pages 27-28). Jarvis expressly discloses that the hydrogen generated during pSi dissolution has been identified and characterized. Jarvis’s discussion of surface modification strategies to stabilize pSi for drug loading applications does not negate or discourage the use of native pSi for its reactive hydrogen-generating properties. A PHOSITA would understand from Jarvis that native pSi can be used deliberately where controlled hydrogen generation is the desired outcome, which is precisely the application disclosed by the claimed invention. The Examiner finds no “clear discouragement” of the claimed combination in Jarvis. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
The Examiner further notes that Jarvis provides an affirmative, not merely permissive, disclosure of native non-passivated pSi’s hydrogen-generating behavior in aqueous medium. Specifically, Jarvis states that when pSi is exposed to physiological conditions, the native SiHx-terminated surface undergoes oxidation and subsequently dissolves into non-toxic orthosilicic acid (Si(OH)₄), and that hydrogen is generated in the oxidation step according to the reactions Si + 2H₂O → SiO₂ + 2H₂ and SiO₂ + 2H₂O → Si(OH)₄ (page 31, left column, ¶ 3). Jarvis characterizes this dissolution behavior in detail across multiple pages (pages 27-32), quantifies its dependence on porosity, pore size, and fabrication parameters, and identifies it as a well-understood property of native pSi that governs its behavior in biological environments. Applicant’s argument that Jarvis teaches away from exploiting native pSi’s reactivity conflates Jarvis’s teaching that surface modification is one option for drug loading applications with a categorical discouragement of using native pSi for its reactive properties. A reference teaches away only when it would lead a PHOSITA away from the claimed invention, not merely when it discloses an alternative. In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004). Jarvis does not discourage the use of native pSi; it characterizes native pSi’s reactivity in precise detail, making that reactivity available to a PHOSITA who wishes to exploit rather than suppress it. Specifically, Jarvis teaches that the same Si-H surface reactivity that is problematic for passive drug loading is precisely the property responsible for hydrogen generation in aqueous medium — and a PHOSITA reading Jarvis in the context of Lucas’s hydrogen therapy platform would immediately recognize native pSi’s aqueous reactivity as an asset, not a liability.
Argument 2: Lucas does not teach combining ionic hydrides with silicon hydride, nor does it teach the synergistic OH⁻-mediated mechanism.
Applicant argues that Lucas uses ionic hydrides independently and never suggests combining them with silicon hydride, and does not teach the claimed hydroxide-mediated synergistic cascade.
This argument is not persuasive. The legal standard for obviousness does not require that the prior art explicitly describe the claimed combination or explicitly recognize the synergistic mechanism that results from it. KSR, 550 U.S. at 418-19. The Examiner’s rejection is based on combining the teachings of Jarvis (pSi + aqueous → H₂) and Lucas (CaH₂/MgH₂ + aqueous → H₂) in a manner that would have been obvious to a PHOSITA seeking to maximize the hydrogen output of a therapeutic formulation. As noted above, the pH-dependent synergistic cascade newly recited in claim 1 is the inherent chemical consequence of placing these two reactive solid hydrides in contact with acidic aqueous medium — it is not a separately taught or invented feature that applicant discovered. The claim does not recite any structural feature or operational step that would distinguish the composition from the obvious combination; it merely describes what the chemistry does. Furthermore, applicant’s own specification confirms the mechanism (spec. p. 24, cited in the Remarks), which demonstrates that the mechanism flows directly from the known chemistry of the components, further supporting that the mechanism is inherent rather than unexpected.
The Examiner acknowledges that the inherency of the OH⁻-mediated cascade is the central contested limitation and that the rejection is strengthened by explicit prior art support for the alkaline acceleration of silicon hydride dissolution. The Examiner notes that the underlying chemistry is not novel: it is well established in the silicon chemistry literature that Si-H bonds are susceptible to nucleophilic attack by hydroxide ions, and that the rate of oxidative dissolution of SiH-terminated silicon surfaces increases under alkaline conditions. Jarvis itself teaches that the dissolution of pSi is attributed to the water-soluble SiySiHx groups on the surface (page 31, left column, ¶ 3), and that removal of those groups reduces dissolution — directly implying that any condition that accelerates attack on Si-H bonds will accelerate dissolution and concomitant H₂ release. Lucas teaches that hydrolysis of CaH₂ or MgH₂ at acidic pH proceeds according to H⁺ + H⁻ → H₂(g) (¶ 0045), a reaction whose stoichiometric byproduct under aqueous conditions is Ca(OH)₂ or Mg(OH)₂, which dissociates to yield OH⁻. The sequence — ionic hydride consumes protons at acidic pH → OH⁻ byproduct generated → OH⁻ accelerates Si-H bond cleavage and pSi dissolution → additional H₂ released from pSi — is the direct and necessary chemical consequence of placing these two known reactive systems in the same aqueous environment. A PHOSITA would have recognized this cascade as an inherent outcome of the combination, not as a separately invented feature. Applicant’s own specification confirms this mechanism at page 24, stating that dissolution of the ionic hydride could cause release of dihydrogen and production of hydroxide ions, which could then react with the silicon hydride to induce further release of dihydrogen. The fact that applicant’s specification describes the cascade in terms of known component chemistry, without presenting it as a surprising or unexpected discovery, is further evidence that the mechanism is the predictable result of combining known reactive hydrides, rather than an independently patentable contribution. Should applicant submit a § 1.132 declaration purporting to show that the synergistic cascade does not occur inherently, or that the H₂ yield of the combination is unexpectedly superior to the sum of the individual components, the Examiner will evaluate such evidence at that time. However, the legal burden to rebut an inherency finding rests with applicant, and attorney argument alone is insufficient to overcome the Examiner’s prima facie showing. In re Rijckaert, 9 F.3d 1531, 1534 (Fed. Cir. 1993).
The Examiner further notes that applicant’s own specification describes the claimed cascade using contingent language – “could cause” and “could then react” – rather than language indicating a surprising or unexpected discovery (Spec. page 24, quoted in Remarks). This framing confirms that the cascade is presented as a predictable chemical possibility flowing from the known properties of the components, not as an independently discovered phenomenon. Where the specification itself describes a claimed mechanism as a predictable consequence of combining known reactive components, that mechanism cannot serve as the basis for patentability over an otherwise obvious combination. Cf. Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir.2012) (predictable results from known combination do not support nonobviousness).
Argument 3: The Office’s combination relies on hindsight reconstruction.
Applicant argues that the motivation to combine the references relies on hindsight using applicant’s disclosure as a roadmap.
This argument is not persuasive. The motivation to combine does not depend on the claimed invention. The motivation flows from the shared technical goal of each reference — maximizing controlled delivery of therapeutic molecular hydrogen in biological environments — and from the routine practice of combining multiple hydrogen-generating materials and biodegradable delivery platforms in the same field. The Examiner points to specific teachings in each reference (Jarvis’s characterization of pSi dissolution and H₂ yield; Lucas’s therapeutic hydrogen platform using ionic hydrides with formulated slow-release properties; Li’s biodegradable polymer coating strategies for pSi) that would have led a PHOSITA to the claimed combination without access to applicant’s disclosure.
Applicant argues that Jarvis and Li address pSi for drug delivery while Lucas addresses hydrogen therapy, and that a PHOSITA would therefore not have been motivated to combine teachings across these separate purposes. This argument is not persuasive. The field of porous silicon therapeutics is not so compartmentalized that a PHOSITA would read only drug delivery literature or only hydrogen therapy literature. Jarvis explicitly identifies hydrogen generation as a direct consequence of pSi dissolution in physiological conditions (page 31), and specifically notes that orthosilicic acid — the dissolution product — is the major form of silicon in the human body and is required for bone and collagen growth, stimulates calcification, and produces a negligible inflammatory tissue response (pages 9-10 of the OA summary; Jarvis, page 31). Jarvis thus bridges the drug delivery and biological response literature by characterizing pSi dissolution as a physiologically relevant, therapeutically significant event. Lucas teaches that molecular hydrogen is a potent antioxidant for treating cardiovascular and neurodegenerative disease (¶¶ 0029-0035), and explicitly teaches the need for controlled, targeted delivery of hydrogen to specific organs and tissues — a delivery challenge that Jarvis’s pSi platform directly addresses. Li confirms that pSi particles are established therapeutic delivery vehicles with tunable, biodegradable properties (abstract). A PHOSITA working at the intersection of pSi-based therapeutics and hydrogen therapy — a person of ordinary skill who is presumed to be familiar with the pertinent literature across these overlapping fields — would have had clear motivation to combine Lucas’s ionic hydride hydrogen sources with Jarvis’s and Li’s pSi delivery platform. The shared goal of controlled, site-specific hydrogen release in biological environments is explicit in all three references and constitutes an independent, articulated motivation to combine that does not rely on hindsight.
Argument 4: The specific weight percentage range is not taught or suggested.
Applicant argues that the weight ratio range (SiH ≥24 wt%, <96 wt%) is not taught or suggested by any reference, and that the routine optimization rationale is improper where the prior art does not even teach the combination.
Applicant’s argument that routine optimization is improper where the prior art does not teach the combination is contingent on the premise that the combination itself is not obvious. Because the Examiner maintains, for the reasons set forth above, that the combination of pSi with CaH₂/MgH₂ as a mixed solid hydride formulation is itself prima facie obvious over Jarvis in view of Lucas, applicant’s predicate fails and the routine optimization rationale is properly applied. The weight percentage range of silicon hydride ≥24 wt% to <96 wt% with at least some ionic hydride defines nothing more than full interior of the binary composition space, excluding only the trivial pure-component endpoints. Applicant has not identified any criticality, unexpected result, or functional distinction associated with any particular value within this range versus values outside it.
Absent such a showing, optimization of component ratios within a known reactive mixture is squarely within routine experimentation. In re Aller, 220 F.2d 454, 456 (CCPA 1955); In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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