DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Note
The examiner has changed for this application, the new examiner is Robert A. Wax, SPE of Art Unit 1615.
Response to Amendment/Arguments
Applicant’s response of May 15, 2026, has been received and entered into the application file. Claims 1,4-5,7,9-12,14,16-19 and 21-24 are pending in this application. Claims 10-12,14 and 16-19 are withdrawn from consideration. New claim 24 has been added. Claims 1, 4, 5, 7, 9, 19 and 21-24 are under examination in this application.
Applicant’s arguments with respect to the rejections of claim(s) 1, 4-5, 7, 9, 19 and 21-23 under 35 USC 103 have been fully considered and are persuasive. Specifically, the arguments that Singh et al. differ from the claimed process because they create the (non-surface-reacted) calcium carbonate particles in situ are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground of rejection is made, see below.
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, 4-5, 7, 9, 19, and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al., (US 2018/0344650 A1, Dec. 06, 2018) in view of Preisig et al. as evidenced by Budde et al., Richardson et al. and Huwyler et al., (US 2019/0022012 A1, Jan. 24, 2019) and
Singh discloses a core-shell composite material comprising a core comprising an active ingredient compound; a shell structure comprising at least two alternating layers; the alternating layers being a protein layer and a polyphenol layer (Abstract). The core-shell composite material may be a micro-sized particle ([0028]) and the protein layer and polyphenol layer form a multi-layered shell structure encapsulating the active ingredient core (i.e., microcapsule) ([0046]). The compound or active ingredient to be transported may be a pharmaceutically active compound, such as lactoferrin ([0045]). The protein and polyphenol layers are formed using layer-by-layer deposition ([0047]). The active ingredient may be adsorbed or absorbed onto a solid support, e.g., CaCO3 ([0051]). The core-shell composite is used in therapy, e.g., as a pharmaceutically acceptable vehicle for drug delivery (i.e., pharmaceutical product). In the preparation method disclosed in Example 1-1 a calcium chloride (CaCl2) solution (720 mL, 1M) is added to aqueous lactoferrin (Lf) (i.e., active ingredient) solution (1.8 mL, 1-30 mg/mL). Then, sodium carbonate (Na2CO3) solution (480 mL, 1M) is injected in one shot under vigorous agitation, resulting in Lf being absorbed to CaCO3 microparticles (i.e., loaded) ([0081-0082]). Further, in Example 1-2, the CaCO3 microparticles with absorbed Lf from Example 1-1 are re-suspended in aqueous bovine serum albumin (BSA) (i.e., protein, i.e., first encapsulant) solution (2 mL, 2 mg/mL) (pH 5.8) and are shaken for at least 15 min. The resultant microparticles are collected by centrifugation and the residual BSA is removed by washing twice with deionized water (i.e., a first solvent). Subsequently, the microparticles are immersed into aqueous tannic acid (TA) (i.e., polyphenol, i.e., second encapsulant) solution (2 mL, 2 mg/mL) (pH 3) and are shaken for at least 15 min. The resultant microparticles are collected by centrifugation and the residual TA is removed by washing twice with deionized water (i.e., a second solvent). This procedure is repeated until a total of four BSA-TA bilayers are deposited on the microparticles ([0085]). Then in Example 1-3, the microparticles of Example 1-2 are collected by centrifugation and re-dispersed in deionized water (1 mL). Then, HCl solution (i.e., acidic compound) (1M) is added drop-wise to the dispersion until the about pH 3. FIG. 1-c shows the SEM image of the PLL-(BSA-TA)4 shells with the encapsulated Lf wherein the CaCO3 cores are completely dissolved (i.e., decomposed) ([0087]). FIG. 2-b shows the distribution of the amount of Lf encapsulated by the PLL-(BSA-TA)4 shells for a batch of Lf encapsulated shells ([0089]). The composition may be freeze dried ([0094]).
Singh et al. differs from the instantly claimed process by preparing the calcium carbonate particles from solution instead of using preformed partices in the coating process and not disclosing the claimed surface-reacted calcium carbonate having the claimed source and characteristics.
Preisig et al., on page 549, teach the use of functionalized calcium carbonate (FCC) particles as drug carriers and discuss the reasons why calcium carbonate particles with larger pore volume providing higher loading capacity are desired. They also mention that FCC FCC is able to absorb 10 times more fluid with faster absorption rate than conventional calcium carbonate.
Budde et al. establishes that FCC and surface-modified calcium carbonate are alternative names for the same thing.
Richardson et al. discuss layer-by-layer assembly of nanofilms onto substrates. On page aaa2491-1 near the top of the third column they describe immersive assembly, also known as dip assembly The process is, “ manually immersing a planar substrate into a solution of the desired material (references omitted), followed by three washing steps to remove unbound material (reference omitted). Particulate substrates can also be layered using immersion; however, the washing and deposition steps are generally broken up by centrifugation to pellet the particles.” This is precisely the layer-by-layer coating method used by Singh et al.
Huwyler et al. teach the use of a surface-reacted calcium carbonate for improving the friability of a pharmaceutical delivery system (Abstract). A method for producing a pharmaceutical delivery system comprising the steps of: a) providing a surface-reacted calcium carbonate, which is a reaction product of natural ground or precipitated calcium carbonate with carbon dioxide and one or more acids in an aqueous medium, wherein the carbon dioxide is formed in situ by the acid treatment (Claim 1). The acid is an H3O+ ion provider ([0045]). The surface-reacted calcium carbonate has a BET specific surface area of from 20.0 g/m2 to 200.0 g/m2 ([0113]). The surface-reacted calcium carbonate comprises particles having a volume median grain diameter d50 of from 2.0 to 50.0 μm ([0114]). The surface-reacted calcium carbonate comprises particles having a volume top cut particle size (d98) in the range of from 5.0 to 40 μm ([0115]). The surface-reacted calcium carbonate has an intra-particle intruded specific pore volume within the range of 0.15 to 1.35 cm3/g ([0116]). The pharmaceutical delivery system may be a capsule ([0031]).
It would have been obvious to one of ordinary skill in the art, prior to the instant effective filing date, to alter the process of Singh et al. to the extent of starting with already-formed dry particles of SRCC as taught by Richardson et al. instead of forming them in situ and continue with the layer-by-layer coating process with the expectation of achieving superior drug carrier particles. Preisig et al. teach the advantages of FCC over other forms of calcium carbonate, which provides motivation to use FCC as the calcium carbonate particles. Huwyler have incorporated the surface-reacted calcium carbonate of Huwyler et al. into the drug delivery system of Singh since it is a known and effective calcium carbonate particle for drug delivery and it also improves friability of a pharmaceutical delivery system as taught by Huwyler et al..
Regarding claim 7 reciting the steps of incubating, as discussed above, Singh
discloses wherein the CaCO3 microparticles were suspended in aqueous bovine serum albumin and shaken for at least 15 min then immersed into aqueous tannic acid solution and shaken for at least 15 min. The act of having the CaCO3 microparticles in contact with the solutions for 15 mins may be interpreted as incubating. The claim does not limit how the incubation is conducted or for how long it occurs.
Regarding claims 22-23 reciting the active ingredient or inactive precursor thereof in an amount of at least 10 wt.% and 25 wt.% based on the total weight of the capsule, as discussed above, Singh teaches that lactoferrin is an active pharmaceutical ingredient added in solution at 1.8 mL, 1-30 mg/ml. Further, FIG. 2-b shows the distribution of the amount of Lf encapsulated by the PLL-(BSA-TA)4 shells. Accordingly, one of ordinary skill in the art would have arrived at the claimed amount of active ingredient through routine experimentation depending on the level of lactoferrin necessary to be pharmaceutically active, as taught by Singh. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
Response to Applicant’s Arguments
Applicant’s arguments have been fully considered and were persuasive to the extent of necessitating a new ground of rejection. However, the arguments related to the loading efficiency are not found persuasive. Preisig et al. used FCC as a drug carrier and, at page 549, full paragraph on the right column, state, “Due to small pore size and enlarged surface area, FCC is able to absorb 10 times more fluid with faster absorption rate than conventional calcium carbonate.” This shows that the results demonstrated by applicant were not at all unexpected.
Conclusion
No claim is allowed.
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/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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