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 claims
Claims 1-20 are original, pending, and under examination.
Priority
This application claims priority to its parent application CN202410674385.3A, filed on 05/28/2024. Certified copies of papers required by 37 CFR 1.55 have been received, and acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/31/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 3, 5, 11, and 18-20 are objected to because of the following informalities:
Claims 1, 3, 5, and 18-20 recite “SAMe”. However, “SAMe” is an abbreviation for “S-adenosyl methionine”, which must be stated in claim 1 before its abbreviation is used
Claims 1, 5 and 18 are objected to for not including the conjunction “and” to connect the steps for the method claims (between steps 2 and 3 in claim 1, between steps A and B in claim 1, between steps II and III in claim 5, between steps 5 and 6 in claim 18, between steps v and vi in claim 18).
Claim 18 recites “40° C. 45° C.” in section vi). Proper syntax is 40° C. to 45° C.
Claim 11 and 18 recite “w” as an abbreviation for “watts” in multiple sections. Proper syntax for “watts” is a capitalized “W”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
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 1-20 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “mixing well” or “mixed well” or “mixing them well” in claims 1, 5, 6 and 18 is a relative term which renders the claim indefinite. The term “well” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For the purpose of compact prosecution, it will be assumed that any amount of mixing is “well” enough.
Claims 2-20 are also indefinite for being dependent on claim 1.
The term “thorough stirring” in claims 4, 6 is a relative term which renders the claim indefinite. The term “thorough” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For compact prosecution, it will be assumed that any amount of stirring is “thorough” enough.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance:
claim 4 recites the broad recitation “cyclodextrin”, and the claim also recites “preferably, the cyclodextrin is one or more selected from the group consisting of α-cyclodextrin, β-cyclodextrin and γ-cyclodextrin; preferably, the cyclodextrin accounts for 1 to 20 parts by weight”, which is the narrower statement of the range/limitation.
claim 11 recites the broad recitation “by stirring or ultrasonic treatment”, and the claim also recites preferably, the ultrasonic treatment is an ultrasonic treatment performed under negative pressure; preferably, the ultrasonic conditions are as follows: pressure is -0.07MPa to -0.1MPa, ultrasonic power is 240 to 480 w (preferably 300 to 400 w), and time is 6 to 8 minutes.”, which is the narrower statement of the range/limitation. Note having the item in parentheticals also creates an issue of uncertainty of whether it is part of the claim or exemplary.
claim 14 recites the broad recitation “the mixed dispersion is granulated and dried by spray drying to obtain microcapsules;”, and the claim also recites “preferably, the mixed dispersion is granulated and dried by spray fluidized-bed drying to obtain microcapsules”, which is the narrower statement of the range/limitation.
claim 18 recites the broad recitation “240 to 480 w”, and the claim also recites “preferably 300 to 400 w”, which is the narrower statement of the range/limitation.
claim 18 recites the broad recitation “The preparation method according to claim 1, comprising the following steps”, and the claim also recites “preferably, the preparation method comprises the following steps:” and (preferably 300 to 400 w), which is the narrower statement of the range/limitation.
Claim 18 recites the broad recitation of “negative pressure” and the narrower statement in parentheticals of (the pressure is -0.07MPa to 0.1MPa). It is unclear if what is in parentheticals is merely exemplary of pressures to be used or if these are meant to be part of the claim limitation.
Claim 20 recites the broad recitation of composition (can be any composition) and the narrower statement of “preferably the composition is a tablet, a soft capsule, a hard capsule, a powder, or a pill”.
The above claims are thus considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 5 and 6 recite the limitation "the sieved material". There is insufficient antecedent basis for this limitation in the claim. A suggested amendment is to alter the preceding language of claim 5 to “I. grinding SAMe and optional cyclodextrin, passing through an 80 to 120 mesh sieve and thereby producing sieved material.
Claim 10 recites the limitation "the stirring". There is insufficient antecedent basis for this limitation in the claim, as no stirring is mentioned in claim 1 for step B.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim 1, 2, 7-11, 13-14, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031).
In regard to claim 19, this is a product-by-process claim (MPEP 2113). It is considered for the components and structure to the composition as materially similar products may be made by different processes.
Regarding Claim 1:
Head concerns microencapsulated pharmaceutical/nutritional agents and expressly introduces a process of microencapsulating the material [¶¶1-3, 34]. Head selects the biologically active core, including therapeutics and pharmaceuticals [¶35], and disperses the protein and carbohydrate encapsulating materials in an aqueous phase [¶36]. Head expressly teaches mixing the core with the encapsulant (i.e., protein-carbohydrate mixture) to obtain an emulsion, with the core surrounded by the encapsulant [¶37]. Head expressly teaches spray-drying the emulsion to obtain a powdered formulation in which the core is surrounded by the encapsulated matrix [¶38]. Head teaches the use of resistant starches such as high-methoxy pectin, alginate, carrageenan, and guar gum in the formulations [¶42]. Head teaches protecting the encapsulated material through the stomach/upper GI tract [¶30-32] and specifically identifies resistant starch-containing delivery systems [¶31]. Head teaches proteins including sodium caseinate, whey protein isolate, hydrolyzed casein, and hydrolyzed whey protein can be used as encapsulants [¶¶36, 42, 46, 49]. Head expressly states that protein was dissolved in 60°C of water, using a high-shear mixer [¶49]. Head expressly teaches encapsulant polysaccharides functioning as prebiotics [¶31], with such prebiotics being oligofructose [¶47]. Head expressly teaches heating the protein-carbohydrate mixture at 98°C for 30 minutes [¶49].
However, Head fails to teach the remaining limitations of claim 1, including SAMe as the active core material, an acid-resistant filler as part of the microcapsule core, and an alkaline formulation pH that is above 10.
Rao provides a novel soft gelatin capsule comprising a fill material consisting essentially of S-adenosylmethionine (SAMe) salt disposed within an enteric coated soft gelatin film [¶abstract]. Rao specifically teaches a capsule containing S-adenosylmethionine (SAMe) [¶21]. Rao expressly teaches that the fill material comprises a core of SAMe salt [¶22]. Rao teaches a method of coating SAMe, converting it to granules, then suspending it [¶¶32-37]. Rao additionally describes the method as coating SAMe salt to obtain granules, forming a lipid suspension, encapsulating it, and enteric coating the capsule [¶¶39-43]. Rao teaches that the SAMe-containing drug material is dispersed using a mixer, dried, milled, and sieved [¶82-83].
Kang teaches a microcapsule having a pellet core separate from an outer wall, wherein the core itself comprises an embedded active substance and microcapsule core material [¶¶99-101]. Kang teaches that such active substances include peptides/amino acids and other biologically active materials [¶¶103-105]. Kang teaches that the microcapsule core material may comprise acid-resistant fillers such as sodium alginate, xanthan gum, and chitosan [¶112-116]. Kang teaches that in such microencapsulation technology, the coating material, the embedding method, the granulation method and the drying method in the preparation process are very important for the function of the microcapsule [¶5]. Kang teaches Gi protection, explaining that the microcapsule coating protects the embedded substance from gastric acid so that it reaches the human intestine [¶122].
Li studied the use of sodium caseinate (NaCas)-lactose complex; conjugated via the Maillard reaction, as encapsulating materials, and investigated the effect of pH on the stability of protein-polysaccharide oil-in-water (O/W) emulsions. Subsequently, the properties of spray dried oil microcapsules were analyzed [¶abstract]. Li teaches preparing a protein wall-material dispersion by reconstituting sodium caseinate in water at 60 °C and mixing until completely dissolved. In Its methods [p. 122, col. 1-2, “preparation of emulsions”]: Li teaches adding lactose to the sodium-caseinate (solution and mixing until complete hydration. Li teaches adjusting the pH of the sodium-caseinate/lactose mixture to 7.5-11, thereby expressly teaching an alkaline protein dispersion having a pH above 10 (i.e., pH of 11). Li taught that better NaCas-lactose interactions were achieved at pH of 11, with enhanced adsorption of the conjugates at the oil droplet particles and subsequently better emulsifying properties and stability. Additionally, better oil entrapment by the cross-linked protein and lactose was achieved when the pH of NaCas-lactose mixture was adjusted to 11 as compared to a pH of 7.5 [¶abstract]. Li et al. Teaches using the resulting protein-carbohydrate conjugates as encapsulating materials for spray-dried microcapsules [¶¶abstract, conclusion].
Regarding Claim 2:
Kang expressly discloses core materials including sodium alginate, xanthan gum, and chitosan [claim 46 of Kang]; and wall materials including soy protein, corn protein/zein, whey protein, and casein [¶¶68-74]].
Head expressly uses oligofructose/raftilose P95, which explicitly fits the FOS species [¶47].
Regarding Claim 7:
Li Teaches pH of 11 for their encapsulating system [¶abstract].
Regarding Claim 8:
Head teaches protein/oligofructose systems heated to 98°C [¶49]. Per 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. In this case, "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties” (see MPEP 2144.05, Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)).
Regarding Claim 9:
Head Heats protein/oligofructose systems for 30 minutes [¶49].
Regarding Claim 10:
Head heats the relevant wall system, while Kang expressly heats whey protein solution while agitating at 95 rpm for 45 mins [¶383].
Regarding Claim 11:
Kang teaches the process of stirring and homogenizing the composition [¶¶338-339].
Regarding Claim 13:
Kang retains microparticles after 50-80 mesh screening [¶158].
Regarding Claim 14:
Head directly teaches combining the core and protein/carbohydrate encapsulant and spray-drying the resulting emulsion (as discussed in A.i.).
Meanwhile, Kang expressly teaches fluidized-bed spray granulation/coating of microcapsules [¶20].
Regarding Claim 19 and 20:
See section A.i-iv above.
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the microencapsulation process of Head by selecting SAMe as the biologically active core, as taught by Rao. This is because Rao demonstrates SAMe as known pharmaceutical materials suitable for coating, granulation, dispersion, and encapsulation. It would have further been obvious to incorporate the acid-resistant core materials taught by Kang to improve protection of encapsulated active form gastric acid, consistent with Kang’s stated purpose of permitting the embedded substances to reach the intestine. Additionally, a POSITA would have been motivated to adjust the protein/carbohydrate wall-forming system to an alkaline pH of 11 as taught by Li because Li reports improved protein-carbohydrate interactions, emulsifying stability, and entrapment at that pH level. Adjusting the dissolved protein to the desired alkaline pH before adding carbohydrate would have been an obvious process-order variation because the components, target pH, and wall-forming reaction remain the same and no criticality in the order of addition is apparent. A POSITA would have had a reasonable expectation of success because Head, Kang, and Li employ conventional aqueous/protein/carbohydrate microencapsulation techniques using known mixing, heating, granulation, and drying operations, while Rao establishes SAMe as a compatible pharmaceutical core material; thus, the proposed modifications merely employ known materials and process conditions according to their established functions to predictably obtain a protected SAMe microcapsule.
Claims 3 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Malakhov (US20090098207A1).
Head, Rao, Kang, and Li collectively teach all the required limitations of claim 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claims 3 and 12.
Malakhov discloses the methods of making a microparticle, the microparticles themselves, combinations, and articles of manufacture [¶7]. D2 teaches that the compositions can be orally administered [¶138].
Regarding Claim 3:
Malakhov teaches that active ingredients can be included [¶29], excipients can be included [¶158], with such compounds in the microparticle being present in amounts ranging from 0.1% to 99% w/w [¶42].
Regarding Claim 12:
Malakhov teaches that such compositions can be stored at temperatures below 55°C [¶28].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the component amounts and storage conditions taught by Malakhov in the modified microencapsulation processes collectively taught by Head, Rao, Kang, and Li. This is because Malakhov teaches microparticle formulations containing active ingredients and excipients over a broad range of 0.1-90 wt.% and further teaches storage of such compositions at temperatures below 55ۣ°C, thereby encompassing the claimed relative amounts and claimed 35-45°C storage range. A POSITA would have been motivated to select the appropriate amounts of the known microparticle components and suitable storage temperatures to obtain a workable, stable formulation, and the selection of values within Malakhov’s disclosed ranges would have constituted no more than routine optimization of known formulation parameters. Because Malakhov teaches these amounts and storage conditions for analogous particle compositions to those collectively taught by Head, Rao, Kang, and Li, a POSITA would have had a reasonable expectation of success that applying them to the modified process would successfully produce and maintain the desired microcapsule composition.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Mac (US20110027342A1).
Head, Rao, Kang, and Li collectively teach all the required limitations of claim 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claim 4.
Mac discloses SAMe oral pharmaceutical formulations specifically designed to improve SAMe absorption through the gastrointestinal tract [¶2].
Regarding Claim 4:
Mac expressly discloses compositions comprising SAMe together with cyclodextrins including alpha-cyclodextrin, beta-cyclodextrin, or gamma-cyclodextrin [¶56, claim 6 and 11 of Mac], which serves as an absorption/permeability enhancer [¶¶56, 133].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to incorporate the cyclodextrin taught by Mac into the SAMe-containing core material of the modified microencapsulation processes collectively taught by Head, Rao, Kang, and Li. This is because Mac expressly teaches combining SAMe with alpha, beta, and gamma cyclodextrin to enhance absorption and permeability of orally administered SAMe. A POSITA would have therefore been motivated to include cyclodextrin with the SAMe core to retain this known absorption enhancing function in the resulting microcapsule, with a reasonable expectation of success because Mac demonstrates the compatibility and intended pharmaceutical use of cyclodextrins with SAMe formulations, such as those collectively taught by Head, Rao, Kang, and Li.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Lu (US20090326025A1).
Head, Rao, Kang, and Li collectively teach all the required limitations of claim 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claim 5.
Lu discloses a new pharmaceutical composition for treating cardiovascular disease [¶abstract]. Lu teaches that the present invention provides a pharmaceutical composition containing an active pharmaceutical ingredient, and can be in the form of powders, granules, dripping pills, micro-pills, tablets, capsules [¶7]. D1 teaches that the composition may contain fillers [¶20].
Regarding Claim 5:
In a non-limiting example [Example A8, ¶100], Lu teaches that fillers (eg., Hypromellose 603) is dissolved in water. Lu teaches that the active agent is then ground and passed through an 80-mesh sieve, and both the active agent and filler are dispersed into water.
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the grinding, sieving, aqueous dispersion, and filler incorporation techniques taught by Lu in preparing the SAMe-containing core material of the modified microencapsulation process collectively taught by Head, Rao, Kang, and Li. This is because Lu teaches pharmaceutical processing in which an active material ground, passed through an 80-mesh sieve, dispersed in water, and combined with a pharmaceutical filler. A POSITA would have been motivated to apply these known processing operations to the SAMe and acid-resistant filler already present in the modified formulation to provide controlled particle size and facilitate uniform dispersion and mixing of the core components. Selection of the order in which the active and filler are introduced into the aqueous phase would have been routine process variation, absent any demonstrated criticality associated with the order of addition, and a POSITA would have had a reasonable expectation of success because Lu demonstrates that these conventional operations are suitable for preparing pharmaceutical active/filler dispersions.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Lu (US20090326025A1) in further view of Lillard (US20070224280A1) in further view of Yang (US20070281031A1).
Head, Rao, Kang, Li, and Lu collectively teach all the required limitations of claims 1 and 5.
However, Head, Rao, Kang, Li, and Lu fail to collectively teach all the required limitations of claim 6.
Lillard discloses nanoparticles comprising a biologically active agent, at least one biopolymer and a coating containing at least one coating which is a polymer or ligand are produced using milling and coating technique [¶abstract].
Regarding claim 6:
Lillard teaches preparing nano and microparticles containing biologically active ingredients in a biopolymer excipient, including alginate, cellulose, starch, or collagen [¶¶9, 11] Lillard teaches planetary ball-milling of active-containing compositions to generate microparticles [¶¶14, 15]. Lillard teaches that for sizing microparticles, the ball-milling grinding speed may be maintained at 200 to 400 rpm for a duration of 10 minutes [¶25]. Lillard further shows embodiments wherein the milling speed and time is 100 to 200 rpm for 20 minutes, and 200 to 300 rpm for 20 minutes [¶34], which yielded different particle sizes.
Yang teaches microparticle preparation in an aqueous system, wherein the active agent is dissolved in the reaction medium and mixed with an aqueous microparticle suspension, thereby forming an active-containing mixture [¶75].
Regarding Claim 6:
Yang teaches maintaining the active-containing aqueous mixture under continuous agitation at 40°C or less [¶75]. Yang teaches adding additional formulation components to the active-containing mixture and mixing it under continuous agitation at the same temperature [¶75]. Yang defines agitation as stirring [¶67].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the ball-milling conditions taught by Lillard and the aqueous processing conditions taught by Yang in preparing the core material of the modified microencapsulation process collectively taught by Head, Rao, Kang, Li, and Lu. This is because Lillard teaches ball-milling biologically active compositions at speeds encompassing 100-300rpm for 20 minutes to obtain particles of desired size, while Yang teaches preparing active-containing aqueous mixtures at temperatures of 40°C or less under continuous stirring. A POSITA would have been motivated to employ these known milling, temperature, and stirring conditions to control particle size and promote uniform dispersion while mixing the components. A POSITA would have had a reasonable expectation of success because Lillard and Yang demonstrate that these conventional processing conditions are suitable for preparing biologically active particulate and aqueous pharmaceutical compositions.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Ming (US20180326078A1) in further view of George (US20110189353A1).
This rejection is made to account for “preferably” conditions.
Head, Rao, Kang, and Li collectively teach all the required limitations of claim 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claim 11.
Ming discloses an improved microparticle or lyophilized or otherwise reconstitute microparticle composition. Ming teaches that techniques such as spray-drying may be incorporated into such processes [¶1291].
Regarding Claim 11:
Ming teaches that the microparticles may be vacuumed at a strength less than 40 Torr absolute, corresponding to less than 96 kPA vacuum, or less than -0.096 MPa gauge––for a duration of 1 to 15 minutes [¶51], which would remove the adhered air form the particles [¶132]. Ming teaches that sonication can be used with a vacuum for at least 3 minutes [¶202], which further decreases the adhered gas [¶25].
George discloses a method for the encapsulation and delivery of bioactive components using a protein to extract and retain the flavor [¶3]. George teaches processes where the dispersion of the substance to be encapsulated in a carrier material, which is typically a modified starch, as a suspension in water to form a slurry [¶7]. Geroge teaches that spray-drying may be used in such processes to create spherical microparticles [¶¶14, 40].
Regarding Claim 11:
George teaches that that sonication may occur after mixing and before drying to help form the mono-dispersion [¶51], performed for a duration of 2-10 minutes [¶35]. George further teaches sonication at 300 watts [¶51].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the vacuum-assisted sonication taught by Ming and the sonication taught by George in the modified microencapsulation process collectively taught by Head, Rao, Kang, and Li. This is because Ming teaches applying sonication under vacuum to microparticle compositions to decrease adhered gas, while George teaches sonication of an encapsulation dispersion after mixing and before drying at 300 W for 2-10 minutes to promote formation of a uniform dispersion. A POSITA would have been motivated to employ these known sonication conditions to reduce residual gas and improve dispersion uniformity prior to drying, and would have had a reasonable expectation of success in doing so because both references demonstrate the suitability of sonication for processing microparticle and encapsulation dispersions.
Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Malakhov (US20090098207A1) in further view of Gruber (US20020068088A1).
Head, Rao, Kang, and Li collectively teach all the required limitations of claims 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claims 15 and 16.
Gruber discloses an easy to swallow pharmaceutical composition consists of one or several coated particles with a core which contains an active substance and a coat with one or several layers [¶abstract].
Regarding Claims 15 and 16:
Gruber teaches that the application of the coating layers to the active ingredient-containing particles can be done via spraying the solution (which is a homogenous mixture) of coating material [¶49]. Gruber teaches that the coating layer may comprise of viscosity-regulating substances such as silicone dioxide and tableting substances such as corn starch [¶38].
Malakhov discloses the methods of making a microparticle, the microparticles themselves, combinations, and articles of manufacture [¶7]. D2 teaches that the compositions can be orally administered [¶138].
Regarding Claim 16:
Malakhov teaches that active ingredients can be included [¶29], excipients can be included [¶158], with such compounds in the microparticle being present in amounts ranging from 0.1% to 99% w/w [¶42].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the silicon dioxide- and corn starch-containing coating taught by Gruber in the spray-fluidized bed microencapsulation process collectively taught by Head, Rao, Kang, and Li, and to select suitable amounts thereof within the broad excipient ranges taught by Malakhov. This is because Gruber expressly identifies silicon dioxide and corn starch as suitable pharmaceutical coating-layer components and teaches application of coating materials by spraying, while Malakhov teaches that such excipients may be incorporated into microparticles over a broad range of amounts overlapping with those claimed. A POSITA would have been motivated to employ these known coating materials and routinely optimize their relative amounts to obtain suitable coating and processing properties, with a reasonable expectation of success because both references demonstrate their use in pharmaceutical particulate compositions.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Gruber (US20020068088A1) in further view of Bittorf (US20100011610A1) in further view of Guy (US20080268036A1).
Head, Rao, Kang, Li, and Gruber collectively teach all the required limitations of claims 1 and 15.
However, Head, Rao, Kang, Li, and Gruber fail to collectively teach all the required limitations of claim 17.
Bittorf teaches methods of fluidized spray drying [¶abstract]. Bittorf generally explains that fluidized spray-drying combines spray-drying and fluid-bed drying technologies, with materials sprayed into the drying chamber toward the fluid bed and resulting particles subsequently entering the fluid bed [¶¶49-50]. Bittorf teaches that the method includes solutions of active agents and excipients and atomizing the feed solution upon delivery into the drying chamber of a spray dryer and further drying the chamber with heated air or gas [¶8]. Bittorf teaches microparticles resulting from such methods [¶31].
Regarding Claim 17:
Bittorf teaches that the operating conditions of the fluidized spray-dryer inlet temperature may be varied, expressly identifying spray-drying inlet temperature and the temperature of set points of the fluidized beds as adjustable process parameters [¶54]. Bittorf teaches an inlet temperature ranging from 50-200°C [¶73]. For the fluidized bed temperature, Bittorf teaches such temperatures set points ranging from room temperature (i.e., 21±4°C) to 100°C [¶75].
Guy teaches spray-drying pharmaceutical and nutraceutical materials, including active agents and excipients, by supplying a liquid dispersion to an atomizer for the formation of dried particles [¶2].
Regarding Claim 17:
In various non-limiting embodiments, Guy further expressly operates pharmaceutical spray-drying processes at an atomization frequency of 25 Hz [¶¶107, 114].
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to employ the spray-drying operating conditions taught by Bittorf and Guy in the spray fluidized-bed process collectively taught by Head, Rao, Kang, Li, and Gruber. This is because Bittorf identifies inlet temperature as adjustable process parameters and teaches ranges of 50-200°C and approximate room temperature to 100°C, respectively, which encompass the claimed 140-160°C inlet temperature and 40-45°C fluidized-bed temperature, while Guy expressly teaches pharmaceutical spray-drying at an atomization frequency of 25 Hz, within the claimed 24-26 Hz range. A POSITA would have been motivated to select these known operating conditions to achieve effective atomization, drying, and particle formation, and selection of values within the disclosed ranges would have amounted to routine optimization of known process parameters, with a reasonable expectation of success because Bittorf and Guy demonstrate their suitability in spray-drying particulate pharmaceutical compositions.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Head (US20070218125A1) in View of Rao (US20020164369A1) in further view of Kang (US20220395466A1) in further view of Li (Li K, Woo MW, Patel H, Selomulya C. Enhancing the stability of protein-polysaccharides emulsions via Maillard reaction for better oil encapsulation in spray-dried powders by pH adjustment. Food Hydrocolloids. 2017;69:121-131. doi:10.1016/j.foodhyd.2017.01.031) in further view of Mac (US20110027342A1) ) in further view of Lu (US20090326025A1) in further view of Lillard (US20070224280A1) in further view of Yang (US20070281031A1) in further view of Ming (US20180326078A1) in further view of George (US20110189353A1) in further view Gruber (US20020068088A1) in further view of Bittorf (US20100011610A1) in further view of Guy (US20080268036A1).
Head, Rao, Kang, and Li collectively teach all the required limitations of claim 1.
However, Head, Rao, Kang, and Li fail to collectively teach all the required limitations of claim 18.
Regarding claim 18:
See sections A., C. to I., M. to S., and U. to V. above.
It would have been obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to modify the SAMe microencapsulation process collectively taught by Head, Rao, Kang, and Li by incorporating the additional processing techniques taught by Mac, Lu, Lillard, Yang, Ming, George, Gruber, Bittorf, and Guy. Mac teaches combining SAMe with cyclodextrin; Lu, Lillard, and Yang teach conventional grinding, sieving, ball-milling, aqueous dispersion, temperature, and stirring conditions for pharmaceutical particulate compositions; Ming and George teach vacuum-assisted sonication under conditions suitable for producing uniform particulate dispersions; Gruber teaches silicone dioxide and corn starch as pharmaceutical coating materials; and Bittorf and Guy teach spray fluidized-bed drying conditions encompassing the claimed inlet temperature, bed temperature, and atomization frequency. A POSITA would have been motivated to employ these known techniques to control particle size, promote uniform dispersion and mixing, reduce entrained gas, provide an effective pharmaceutical coating, and achieve efficient spray drying of the SAMe microcapsules. Because each of these cited references demonstrates suitability of these conventional materials and processing conditions/steps for pharmaceutical or microparticle preparation, a POSITA would have had a reasonable expectation of success in applying them to the modified SAMe microencapsulation process to obtain the claimed microcapsules.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 19 and 20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the following claims of co-pending U.S. Patent Application No. 18/814,339 (referred to as co-pending ‘339): 14 and 19 (for present claims 19 and 20).
Each of the above claims (or claim groups) of co-pending ‘339 teach all limitations of their corresponding claim(s) listed in the present application. Accordingly, the present claims differ from the claims of co-pending ‘339 only by an obvious variation that does not impart a patentable distinction.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims of co-pending ‘339 have not in fact been patented.
Conclusion
No claim is found allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARYA AHMADI BAZARGANI whose telephone number is (571)272-0211. The examiner can normally be reached Monday - Friday 9:00AM - 5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571) 272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Arya A. Bazargani, Ph.D.
Patent Examiner
Art Unit 1613
/MARK V STEVENS/Primary Examiner, Art Unit 1613
Prosecution Insights