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 .
Claim Status
Claims 1-24 are pending.
Priority
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 12/27/24 and 12/31/24 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 5 is objected to because of the following informalities: claim 5 recites: “0.01 wt% to 2.31”. For consistency, “wt%” should be added after “2.31”. See claim 9. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 6, 9, 11 and 20 contain the trademark/trade name Aerosil®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe the coating agents and, accordingly, the identification/description is indefinite.
Claims 6, 9, 11 and 20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 6, 9, 11 and 20 contain parentheses which raises the question as to which term is required by the claim because the subject matter in the parentheses is not identical in scope. Essentially, the claims use both narrow “(Aerosil® R972P)” “(Aerosil® A200)” and broad limitations (hydrophobic nano-fumed silica microcrystalline cellulose and hydrophilic nano-fumed silica microcrystalline cellulose). Claims 9, 11 and 20 have a similar analysis. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Dave et al. (US20180055775) and Dave et al. (US20140106059; hereinafter Dave2014).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims; for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical formulation research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical formulation and possess conventional knowledge in drug delivery, material science, and physical chemistry to convert active pharmaceutical ingredients (APIs) into stable, effective medicines. They understand how to select excipients (inactive ingredients), optimize stability, and ensure compliance with regulatory standards (FDA, GMP). Their knowledge covers formulation development, dosage form design, and manufacturing processes and such an educated artisan will draw conventional ideas from those areas without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 3-5, 7, 10, 13-14 and 17-19, Dave et al. teach a pharmaceutical blend with an active ingredient having a flow function coefficient ranging from about 1.0 to 3.5 (Claims 1 and 6; [0134]) and a dry coated pharmaceutical excipient comprising a core and a shell comprising hydrophilic silica or functionalized hydrophobic silica (Claims 1, 3 and 4). Dave et al. suggest dry coating combinations of both hydrophilic and hydrophobic silica such as one or more of hydrophilic fumed silica Aerosil A200 and hydrophobic Aerosil R972P ([0105] Tables 14 and 16, for example), which when combined would make both the hydrophobic dry coating agent and the hydrophilic dry coating agent are used in a blend for a pharmaceutical composition. Thus, use of binary coating agents in powder coating for cohesive particles is suggested by Dave et al. Dave et al. also teach dry coating micronized acetaminophen with Aerosil A200 (Example 20, Table 16; [0202-0203]), which the instant specification teaches is a BCS I classified drug [00255] and is a single API. Dave et al. teach methods of making dry coated excipients where: “In some embodiments, the amount of host material may range from about 95% to about 99.99%, based on the total weight of the mixture. In some embodiments, the amount of guest material may range from 0.01 % to about 5%, based on the total weight of the mixture.” [0111-0116] and the shell is present from about 0.05 wt% to about 1.0 wt% (Claim 8) or even from about 0.01 wt% to about 1 wt% (Claim 15). Thus, the amount of dry coating agents can be less than 1 wt% and overlaps the range of 0.01 wt% to 2.31 and can be at least 0.01 wt% in the blend. The hydrophobic dry coating agent and the hydrophilic dry coating agent must be in some weight percentage ratio or a ratio of the normalized SAC for the dry coated component. No values are claimed by Applicant. Regarding the functional limitation of: “providing by the binary dry coating flowability, bulk density, deagglomeration, and dissolution properties that are substantially different for the binary dry coated component and/or a blend containing the binary dry coated component as compared to using the hydrophobic or the hydrophilic dry coating agents alone or no dry coating agents used” is implicit in the method of Dave et al. In fact, Dave et al. report that: “The blends using dry coated excipients had improved flowability” [0169]; and: “These results show surprising advantageous properties, such as simultaneously improved flow, bulk density, and compaction properties” [0170]; and: “The results show that the surface engineered excipients not only improved the bulk density and flowability of the processed excipients, but also enhanced the compaction properties of the prepared tablets compared with as received materials.” [0201]. Similarly, the limitations of instant claim 3 are implicit in the method of Dave et al. The dry coating implicitly provides a
drug dissolution rate of a blend higher than that compared to an untreated blend.
Regarding claim 2, Dave et al. teach: “the guest particles are uniformly coated on to host particles, and that the amount is only sufficient to create a monolayer, the relationship between the guest wt % and percentage SAC (in range 0 to 100) is given by the Equation (1).” [0011]. And: “the SAC can range from 1% to 150%. In some embodiments, SAC can range from 10% to 90%.” [0106]. See also Table 3 and [0118].
Regarding claims 8 and 10, Dave et al. teach a particle size range of about 2 microns to about 500 microns and more narrowly of about 10 microns to about 120 microns [0104], which overlaps the claimed range of 10 microns to 15 microns and less than 50 microns of instant claim 10.
Regarding claim 9, Dave et al. report in [0105]:
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Regarding claim 16, Dave et al. teach adding one or more of magnesium stearate, steric[sic] acid and sodium dodecyl sulfate (Claim 3).
Regarding claim 22, Dave et al teach a tablet made from the dry coated components with a tensile strength of about 1 MPa to about 10 MPa (Claims 18-20) and report improved tensile strength [0203] as well as higher flowability in the coated excipients compared to the uncoated [0198]. Dave et al. report: “The results show that the surface engineered excipients not only improved the bulk density and flowability of the processed excipients, but also enhanced the compaction properties of the prepared tablets compared with as received materials.” [0201].
Regarding claim 24, Dave et al. teach a flow function coefficient of 3 to 30 (Claim 12; Figure 8; [0107]), which overlaps the claimed range of greater than 10 FFC.
Regarding claims 1, 10, 11, 13, 17, 18-21 and 23, Dave2014 teaches that: “more than one type of silica may be used in combination. For example, TS5 and Aerosil R972 may be used together to coat the API core particles.” Thus, Dave2014 renders obvious dry coating an API with both hydrophilic (TS5) and hydrophobic (Aerosil R972) silicas.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Dave et al. is that Dave et al. do not expressly teach simultaneously dry coating with both a hydrophobic dry coating agent and a hydrophilic dry coating agents on a surface of the API or the excipient or both the API and the excipient for forming a dry coated component wherein the normalized surface area coverage (SAC) ratio of 1 to 4 with the dry coating is obtained or wherein a ratio of the hydrophobic dry coating agent and the hydrophilic dry coating agent has a weight percent ratio of between 1 to 3 or from 5 to 1 and increase dissolution and blend flowability as well as tablet tensile strength and blend flowability and an API dissolved weight percentage of at least 70 wt% after a dissolution time of 100 minutes.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of Dave et al. by simultaneously dry coating with both a hydrophobic dry coating agent and a hydrophilic dry coating agents on a surface of the API or the excipient or both the API and the excipient for forming a dry coated component wherein the normalized surface area coverage (SAC) ratio of 1 to 4 with the dry coating is obtained and wherein a ratio of the hydrophobic dry coating agent and the hydrophilic dry coating agent has a weight percent ratio of between 1 to 3 or from 5 to 1 and increase dissolution and blend flowability as well as tablet tensile strength and blend flowability and an API dissolved weight percentage of at least 70 wt% after a dissolution time of 100 minutes, and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because Dave et al. teach and suggest combining both hydrophilic and hydrophobic silica as claimed and Dave2014, which is the same inventor, knows to apply both hydrophilic and hydrophobic silicas to an API. The obvious weight ratio to combine them is at least a 1:1 ratio. Dave et al. teach and suggest dry coating both excipients and an active mAPAP, which Applicant also exemplifies (Example 7). The same coated excipients and/or active agents with the same binary hydrophilic and hydrophobic silicas will naturally result in the claimed functional limitations of increased dissolution, blend flowability and an API dissolved weight percentage of at least 70 wt% after a dissolution time of 100 minutes. In other words, the artisan following the guidance of Dave et al. by combining the hydrophilic and hydrophobic silicas to dry coat an API or excipient or both would observe binary dry coating flowability, bulk density, deagglomeration, and dissolution properties that are substantially different for the binary dry coated component and/or a blend containing the binary dry coated component as compared to using the hydrophobic or the hydrophilic dry coating agents alone or no dry coating agents used. Regarding the limitation of wherein the normalized surface area coverage (SAC) ratio of 1 to 4 with the dry coating is obtained, that appears to be nothing more than routine optimization by the ordinary artisan. Especially when Dave et al. teach: “Examples 2.1 through 2.7 were made by added an amount of the guest material as shown in Table 1 to achieve a SAC ranging from 0% to 100%.” ([0149], Table 6). Dave et al. also explains: “there are three contact forms, namely host-host, host-guest, and guest-guest during a contact between original particles in the presence of nano-sized guest particles. When there are few guest particles, the majority of particle contacts are host-host, and the interparticle forces are the greatest and are calculated by Equation (5), which is a simplified version of Rumpf’s equation. When there is a sparse, but uniform, guest coating, host-guest contact becomes the dominant particle interaction, where the interparticle force is calculated by Equation (6). The transition from host-host to host-guest contact occurs at very low guest amounts, typically when SAC is approaching to about a value under 1 %. When there is a dense coating of nanoparticles, a guest-guest contact is the dominant interaction. The transitional SAC from host-guest to guest-guest particle interaction may be of the order of about 30% for fine spherical host particles with typical nano-silica coating.” [0146]. Thus, the amount of surface area coverage can be optimized by the ordinary artisan.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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