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 .
Election/Restrictions
Applicant’s election without traverse of Group I and the species of an aluminum oxide precursor and a zinc oxide precursor” in the reply filed on 7/6/26 is acknowledged.
Claims 37, 39-45, 49 and 50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/8/26.
Claim Status
Claims 2-5, 9-13, 15-17, 19-21, 24-26, 28-31, 33-36, 38, 46-48 and 53-55 are cancelled.
Claims 1, 6-8, 14, 18, 22, 23, 27, 32, 37, 39-45 and 49-52 are pending.
Claims 37, 39-45, 49 and 50 are withdrawn.
Claims 1, 6-8, 14, 18, 22, 23, 27, 32, 51 and 52 are presented for examination on the merits as they read upon the elected subject matter.
Priority
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Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 9/27/24, 3/20/25, 8/27/25 and 3/6/26 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 7 is objected to because of the following informalities: claim 7 introduces the acronyms “DEZ” and “TMA” without first providing the full name. 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 51 and 52 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 51 recites the limitation "between steps d) and e); or after step g)" in the last line. Claim 51 depends from claim 1. There is no step e) or step g) in claim 1. There is insufficient antecedent basis for this limitation in the claim. Consequently, the scope of claim 51 is indefinite and cannot be further examined because to do so would require speculation as to the scope of the claims. See In re Steele, 305 F.2d 859, 862–63 (CCPA 1962). Dependent claim 52 is rejected as indefinite because it is dependent upon an indefinite claim. Claims 51 and 52 will not be treated further on the merits.
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, 6-8, 14, 18, 22, 23, 27 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Hoppu et al. (US20150250731; of record) and Lehtonen et al. (US20130337056; of record) and Kaariainen et al. (International Journal of Pharmaceutics 525 (2017) 160–174; of record) and Neikirk et al. (US11311491; of record).
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 a method of preparing coated particles comprising drug-containing core enclosed by an inorganic oxide coating as described in claim 1.
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). A scientist using atomic layer deposition (ALD) to coat drug particles requires interdisciplinary knowledge spanning materials science, surface chemistry, pharmaceutical engineering and they will have conventional knowledge of gas-phase precursor components for deposition, pharmaceutical active agents and excipients and how atomic-scale inorganic or hybrid layers control drug dissolution and release kinetics.
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 and 27, Hoppu et al. teach methods of coating of pharmaceutical substances, pharmaceutical ingredients or a blend which can be processed into a pharmaceutical dosage form where the method utilizes atomic layer deposition technology (Abstract; claims 1-9). Hoppu et al. teach in example 1:
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Thus, Hoppu et al. teach the sequential steps of loading drug particles into a reactor (a), performing a cycle of applying a vaporous inorganic oxide precursor TMA to the particles (b) by pulse, purging with inert nitrogen gas, applying a vaporous oxidant water by implicitly pushing from a vaporization source, a second inert gas nitrogen purge (b1-b4) followed by a similar sequence of the titanium oxide precursor TDMAT (c), hence a second number of second cycles (C1-C4), and repeating the cycle for 500 times (d) for both oxides. Please note that as the number of cycles increases, third and fourth different precursors (TMA and TDMAT) are repeatedly added, thus reading on the steps of claim 27.
Regarding claim 1, Hoppu et al. teach that: “The thickness of the coating layer may be controlled by varying the number of molecule layers in the coating.” [0011] Hoppu et al. teach: “Only one atomic layer is produced on the surface of the substrate during one ALD cycle. This self-controlled growth mode contributes several advantages. The thickness of the films can be controlled in a straightforward manner by controlling the number of reaction cycles, therefore enabling the controlled growth of sub-nanometer thin layers.” [0021].
Regarding claim 1, Hoppu et al. teach: “paracetamol is coated with one or more molecule layers of aluminum oxide Al2O3 . Trimethyl aluminum (CH3)3 Al is used as a precursor and water H2O as an oxygen source. In the present invention also other compounds, such as hydrogen peroxide H2O2 or ozone O3 may be used as the oxygen source instead of water.” [0023].
Regarding claims 6-7 and 23, Hoppu et al. teach that the inorganic materials include silicon oxide or zinc oxide [0026].
Regarding claims 1 and 8, Hoppu et al. teach: “The layer thickness can be defined by ALD cycles. For example, one ALD cycle of TMA and water results 0,1 nm thick Al2O3 coating. In one embodiment of the present invention, wherein trimethyl aluminum (CH3)3 Al is used as a precursor, the thickness of the coating is within the range of 1 nm to 500 nm, more preferably in the range of 1 of 100 nm, most preferably from 5 to 15 nm. However, the coating layer may have any thickness between 1 nm and 500 µm. The thickness of the coating layer depends on the pharmaceutical substance, pharmaceutical ingredients and the desired final dosage form.” [0028].
Regarding claim 14, Hoppu et al. teach allowing a holding time to pass in [0050]: “One deposition cycle for Al2O3 consisted of a 2 seconds metal precursor (TMA) pulse, 2.5 seconds N2 purge, 0.5 second water pulse and 1 second N2 purge. Similarly the timing sequence used for TiO2 deposition was 1-5-1.5-2 seconds.” The steps are repeated at least once.
Regarding claim 18, Hoppu et al. teach growing films at 41°C [0050]. Hoppu et al. teach: “The temperature used in the coating process depends on the substrate properties and on the chosen precursor chemistry…In the present invention a coating layer is deposited over a pharmaceutical substrate and therefore heat degradation of the pharmaceutical substrate is to be avoided or reduced. For example, the melting point of ibuprofen is around 74-77° C., whereas the melting point of paracetamol is around 169-172° C. The coating temperature may be from room temperature (RT) up to 350° C.” [0029]. That overlaps the claimed range of between 25-60°C.
Regarding claims 1, 6, 7 and 23, Lehtonen et al. teach methods of coating pharmaceutical preparations by using atomic layer deposition (Abstract; claim 12) where the precursors can be trimethylaluminum (TMA) and diethyl zinc (DEZ) (Claim 13; [0035, 0059-0060]) that are applied in pulse/purges (Table 1 [0060]) at a temperature of about 40° C to about 150° C [0019].
Regarding claims 1, 6, 7, 14, 23 and 27, Kaariainen et al. teach surface modification of acetaminophen particles by atomic layer deposition of Al2O3, TiO2 and ZnO (Title; Abstract) using precursors TMA and DEZ (Page 162, left column). Kaariainen et al. teach the sequential steps of: The reactant exposure sequence for each ALD cycle was the following: 1) exposure of metal precursor at a vapor pressure of 0.5–2 Torr, 2) hold for metal precursor reaction time, 3) pump out excess metal precursor and reaction products, 4) dose N2 at 10–20 Torr for purging the reactor, 5) pump out N2, 6) expose H2O at 1–2 Torr, 7) hold for H2O reaction time, 8) pump out excess H2O and reaction products, 9) dose N2 at 10– 20 Torr for purging the reactor, and 10) pump out N2. The reaction times were between 60 and 240 s. The pump out times used for the precursors were between 60 and 360 s. The N2 exposure time was 60 s and pump out time for the N2 was 60 s. After each reactant exposure and pump out 5 N2 exposure – pump out purging steps were applied. (Page 162, left column last paragraph).
Regarding claims 1, 8, 14, 18 and 27, Neikirk et al. teach a method of preparing a pharmaceutical composition having a drug-containing core enclosed by one or more metal oxide materials is provided. The method includes the sequential steps of (a) loading the particles comprising the drug into a reactor, (b) applying a vaporous or gaseous metal precursor to the particles in the reactor, (c) performing one or more pump-purge cycles of the reactor using inert gas, (d) applying a vaporous or gaseous oxidant to the particles in the reactor, and (e) performing one or more pump-purge cycles of the reactor using inert gas. The temperature of the particles does not exceed 35° C. (Abstract; see also claims 1-7; column 11, line 64 through column 12, line 21). Neikirk et al. teach wherein the drug is a small molecule, virus particle, polypeptide, polynucleotide, a composition comprising polypeptide and lipid, or a composition comprising polynucleotide and lipid (Claim 8). Neikirk et al. teach that “the sequential steps (b)-(m) are optionally repeated one or more times to increase the total thickness of the one or more metal oxide materials that enclose the solid core of the coated particles.” (Column 12, lines 23-25). Neikirk et al. teaches: “The cycle of the first reactant half-cycle, first purge cycle, second reactant half cycle and second purge cycle can be repeated a number of times set by the recipe, e.g., one to ten times.” (Column 11, lines 22-25; see also Figure 1 and column 10, line 22 through column 11 line 21).
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 Hoppu et al. is that Hoppu et al. do not expressly teach a method with the zinc precursor DEZ or wherein in each repeat of step (b)/step (e) the first/third number is independently selected from 1-10 or 1-20; and in each repeat of step (c)/step (f) the second/fourth number is independently selected from 1-10 or 1-20 or wherein each repeat of step (b) the first number is the same and selected from 1-10; and in each repeat of step (c) the second number is the same and selected from 1-10 or wherein the coating constitutes 1-20% wt/wt of the coated particles. This deficiency in Hoppu et al. is cured by the teachings of Lehtonen et al., Kaariainen et al. and Neikirk et al.
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 Hoppu et al. with the zinc precursor DEZ, as suggested by Lehtonen et al. and Kaariainen et al., and the same claimed number of repeat cycles, as suggested by Neikirk et al., to arrive at a coating that constitutes 1-20% wt/wt of the coated particles and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because for the following sound articulated reasoning with rational underpinning based upon the evidence. Hoppu et al. teach zinc oxide as an inorganic material for the method [0026]. Lehtonen et al. and Kaariainen et al. direct the artisan to DEZ as the precursor for the ALD coating process. The artisan would employ DEZ in the method of Hoppu et al. in place of the titanium dioxide precursor of Example 1 to have the first inorganic precursor TMA and the second inorganic precursor DEZ with a reasonable expectation of success. Regarding the number of repeat cycles, that is merely optimization of the coating thickness by the ordinary artisan where Neikirk et al. suggest 1-10 cycles and Hoppu et al. teach: “Layer thickness can be defined by ALD cycles…The thickness of the coating layer depends on the pharmaceutical substance, pharmaceutical ingredients and the desired final dosage form.” [0028]; and “The thickness of the films can be controlled in a straightforward manner by controlling the number of reaction cycles, therefore enabling the controlled growth of sub-nanometer thin layers.” [0021]. Thus, thickness is a result effective variable and the coating weight is proportional to the number of layers. For example, Hoppu et al. teach that the thickness of the coating layer may be controlled by varying the number of molecule layers in the coating and the coating thickness can be between 1 nm and 500 microns [0011]. Hoppu et al. teach that 1 ALD cycle of TMA and water produces a 0.1 nm thick Al2O3 coating [0028]. Consequently it is merely routine optimization of the number of repeat cycles, whether it is 1-10 or 1-20 or 1-10 for each repeat step where the second number is the same as the first, to arrive at a coating that constitutes 1-20% wt/wt of the coated particles with a reasonable expectation of success.
The difference between the instant application and Hoppu et al. is that Hoppu et al. do not expressly teach a method wherein each pump-purge cycle comprises flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr and repeating the steps of flowing the inert gas into the reactor chamber to a desired pressure and after a delay time pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr. However, flowing the inert gas into the reactor chamber to a desired pressure and pumping the inert gas out of the reactor until the pressure of the inert gas is below 1 torr appears obvious to do because the purging and/or evacuating of the chamber removes non-reacted precursors as taught by Lehtonen et al. in (Claim 12; [0036]) and Kaariainen et al. Thus, the artisan would pump out the inert gas an and any unreacted precursors until the pressure of the inert gas is below 1 torr with a reasonable expectation of success.
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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