Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Application
The Preliminary Amendment filed on 11/30/23 is acknowledged.
Claims 1-26 were cancelled.
New claims 27-52 were added on 11/30/23 and are included in the prosecution.
Priority
This Application is a 371 of PCT/GB2022/051381 filed on 05/31/22. This Application also claims foreign priority to PT117268 filed on 06/01/21. The certified copy of the foreign priority document was retrieved from WIPO and is attached with this office action.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 04/22/24 and 05/16/25 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the examiner is considering the information disclosure statements. Please see the attached copies of PTO-1449.
Specification
The disclosure is objected to because of the following informalities:
Although the section “References in the Figures include” is provided in the Specification ([069] on Page 16), there is no description of the figures and no section heading "BRIEF DESCRIPTION OF THE DRAWINGS." Based on MPEP § 608.01 (a) and (f), as well as 37 C.F.R. § 1.77(b), the Specification should be amended to recite the section heading "Brief Description of Drawings" and include a description of Figures 1-16.
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 30, 31, 34, 35, 41, 48, and 49 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 pre-AIA the applicant regards as the invention.
Regarding claim 35 (line 2) and claim 48 (line 3), the phrase "such as" is considered exemplary language and renders the claims indefinite because the claims include elements not actually disclosed (those encompassed by "such as"). See MPEP § 2173.05(d).
Claims 30, 31, 34, 35, 41, 48, and 49 each recite both a broad limitation together with narrow limitations.
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, instant claims 30, 31, 34, 35, 41, 48, and 49 recite the term “optionally” which means that the component or concentration recited after the term “optionally” may or may not be present. In the case when the component or concentration is present, each of the aforementioned claims recite a broad limitation and a narrow limitation. For instance, instant claim 30 recites the broad limitation “an aliphatic alcohol,” and the claim also recites “a C2-C8 aliphatic alcohol,” which is the narrower statement of the limitation.
Claim 41 recites the broad recitation “3.0% or less,” and the claim also recites “or 2.7% or less,” which is the narrower statement of the range/limitation. The claim(s) are 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.
Notice for all US Patent Applications filed on or after March 16, 2013
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 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 27-31, 39-41, and 50-51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”).
Instant claim 27 is drawn to a process for preparing ivermectin particles having reduced particle size, wherein the process comprises incorporating ivermectin particles in a liquid medium comprising a mixture of an organic solvent with water, and subjecting the medium comprising the particles to mixing in a high shear mixer.
Wang teaches the process of preparation of drug-loaded microparticles of ivermectin and hydrogenated castor oil (HCO) and the suspension of the drug-loaded microparticles in an aqueous solution of poloxamer 407 (P407) to prepare an in-situ gelled injection containing ivermectin (Abstract, [0002], Examples 1-2, claims 1-5). The preparation method includes heating HCO and ivermectin in a low-boiling-point organic solvent, which includes ethanol, until completely dissolved, cooling to 40-55°C, distilling under reduced pressure to remove ethanol, obtaining solid matter, crushing it, passing it through a 40-mesh sieve to obtain the ivermectin microparticles ([0019], [0022]), and further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension ([0019] (2) and [0022] (2)).
Regarding instant claims 27, 50, and 51, the limitations of a process for preparing ivermectin particles having reduced particle size are anticipated by the process of preparation of drug-loaded microparticles of ivermectin and HCO and the suspension of the drug-loaded microparticles in an aqueous solution of P407 to prepare an in-situ gelled injection containing ivermectin, wherein the particle size is less than 20 µm (Abstract, [0002], Examples 1-2, claims 1-5), as taught by Wang. The limitations of incorporating ivermectin particles in a liquid medium comprising a mixture of an organic solvent with water, and subjecting the medium comprising the particles to mixing in a high shear mixer are anticipated by the steps of heating HCO and ivermectin in a low-boiling-point organic solvent, which includes ethanol, until completely dissolved ([0019], [0022]), and further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension ([0019] (2) and [0022] (2)), as taught by Wang.
Regarding instant claim 28, the limitations of the particles of ivermectin suspended in the liquid medium is anticipated by the thick suspension containing the particles of ivermectin ([0019] (2) and [0022] (2)), as taught by Wang.
Regarding instant claims 29-31, the limitations of the organic solvent are anticipated by ethanol ([0019], [0022]), as taught by Wang.
Regarding instant claim 39, the limitation the Dv (90) of the ivermectin particles after mixing of less than 60 microns is anticipated by the particle size of less than 20 µm ([0019] (2) and [0022] (2)), as taught by Wang.
Regarding instant claims 40-41, the limitations of the reduction in total impurities as measured by HPLC (% area) of the resulting ivermectin particles compared to the initial ivermectin particles of 10% or more (instant claim 40) and the total impurities of 3.0% or less, optionally 2.8% or less, or 2.7% or less (instant claim 41) are anticipated by the resultant ivermectin particle size of less than 20 µm ([0019] (2) and [0022] (2)), as taught by Wang. The recited limitations are properties of the ivermectin particles and are inherently present in the ivermectin particles taught by Wang. Please see MPEP 2112.01. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990.) The burden is shifted to Applicant to show that the prior art product does not possess or render obvious the same properties as the instantly claimed product.
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 of this title, 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.
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 32-33, 35, and 47-49 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Wang et al. (CN 104 666 244 (A) – English Espacenet Translation – “Wang ‘244”).
Instant claim 32 is drawn to a process according to claim 27 wherein the medium comprising the particles further comprises an antioxidant.
The teaching of Wang is discussed above.
Wang does not expressly teach the incorporation of an antioxidant.
Wang ‘244 teaches the process of preparing veterinary antiparasitic preparations (Abstract), wherein the antiparasitic drugs include ivermectin ([0010], Example 5 – [0051]-[0056], Example 9 – [0071]-[0073], and claim 1). Example 5 discloses the preparation of an ivermectin injections solution ([0051] including the steps of mixing ivermectin with a purity of 97%, carnauba wax, and ethyl oleate, dissolving the carnauba wax, cooling to room temperature, using a high-speed shear homogenizer at 12000-16000 r/min for 1 hour ([0051]-[0056]). Antioxidants including tert-butyl-4-hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) are disclosed ([0014]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the process of preparing veterinary antiparasitic preparations, wherein the antiparasitic drugs include ivermectin, the process includes the steps of mixing ivermectin with organic compounds, using a high-speed shear homogenizer at 12000-16000 r/min for 1 hour, and wherein antioxidants such as BHA and BHT are included, as taught by Wang ‘244, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because the antioxidants preserve the stability of easily oxidizable components ([0014]) as taught by Wang ‘244.
From the 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 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claims 32-33, 35, and 47-49, the limitations of the antioxidant would have been obvious over the BHA and BHT ([0014]), as taught by Wang ‘244. One of ordinary skill in the art would have found it obvious to add the antioxidants taught by Wang ‘244 to the particles of ivermectin of Wang in order to have antioxidant activity to preserve or stabilize the ivermectin particles. The temperature range of from 0°C to 25°C recited in instant claim 49 includes room temperature. One of ordinary skill in the art would have found it obvious to add the antioxidant at room temperature since this does not require additional equipment or controls.
Claims 32-34 and 47-49 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Wang et al. (CN 104 666 244 (A) – English Espacenet Translation – “Wang ‘244”) and Paulsen et al. (US 2009/0280159 A1 – “Paulsen”).
Instant claim 34 is drawn to a process according to claim 33 wherein the antioxidant is an alkyl paraben, optionally methyl paraben.
The teachings of Wang and Wang ‘244 are discussed above.
Wang and Wang ‘244 do not expressly teach the incorporation of an alkyl paraben or optionally methyl paraben.
Paulsen teaches the process for manufacturing chewable dosage forms for drug delivery to an animal (Abstract). The drug is ivermectin (Examples 1 and 2 – [0048]-[0049], claims 1, 25, and 26). The formulation contains a preservative which includes BHA, BHT (claims 1, 12, and 22) and methylparaben (claims 29 and 31).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the process of preparing veterinary antiparasitic preparations, wherein the antiparasitic drugs include ivermectin, the process includes the steps of mixing ivermectin with organic compounds, using a high-speed shear homogenizer at 12000-16000 r/min for 1 hour, wherein antioxidants such as BHA and BHT are included, as taught by Wang ‘244, further in view of the use of methylparaben as a preservative in a formulation containing ivermectin, as taught by Paulsen, and produce the instant invention.
One of ordinary skill in the art would have been motivated to include various antioxidants or preservatives known to be used with ivermectin including the BHA and BHT taught by Wang ‘244 ([0014]) as well as the BHA, BHT (claim 22) and methylparaben (claim 31) taught by Paulsen because the antioxidants preserve and enhance the stability of the formulations.
Regarding instant claims 32-34 and 47-49, the limitations of the antioxidants would have been obvious over the methyl paraben (claim 31), as taught by Paulsen. One of ordinary skill in the art would have found it obvious to add the antioxidant taught by Paulsen to the particles of ivermectin of Wang in order to have antioxidant activity to preserve or stabilize the ivermectin particles. The temperature range of 0°C to 25°C recited in instant claim 49 includes room temperature. One of ordinary skill in the art would have found it obvious to add the antioxidant at room temperature since this does not require additional equipment or controls.
Claims 36-38 and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Roberts et al. (US 4,413,118 – “Roberts”).
Instant claim 36 is drawn to a process according to claim 27 wherein the medium comprising the particles further comprises a stabilizer to minimize desolvation of the ivermectin.
The teachings of Wang are discussed above.
Wang does not expressly teach the incorporation of a stabilizer to minimize desolvation of the ivermectin.
Roberts teaches a process for preparing ivermectin comprising a step (d) of treating the ethanol solution with formamide and water to cause crystallization of the product (Col. 3, lines 1-4 and claim 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the process of preparing ivermectin comprising a step of treating the ethanol solution with formamide, as taught by Roberts, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the methods taught by Wang and Roberts because they are both drawn to processes of preparing formulations of ivermectin. It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A). Furthermore, Roberts teaches that treating the ethanol solution with formamide and water causes crystallization of the product (Col. 3, lines 1-4 and claim 2).
Regarding instant claims 36-38, the limitations of the stabilizer would have been obvious over the formamide (Col. 3, lines 1-4 and claim 2), as taught by Roberts.
Regarding instant claims 36-38 and 52, the limitation of the organic solvent which is ethanol would have been obvious over the ethanol ([0019], [0022]), as taught by Wang. The limitation of the stabilizer comprising formamide would have been obvious over the formamide (Col. 3, lines 1-4 and claim 2), as taught by Roberts.
Claim 42 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Paulsen et al. (US 2009/0280159 A1 – “Paulsen”), and Roberts et al. (US 4,413,118 – “Roberts”).
Instant claim 42 is drawn to a process according to claim 27 wherein the medium comprises water; ethanol or isopropanol as the organic solvent; methylparaben as antioxidant, and formamide as a stabilizer.
The teachings of Wang are discussed above.
Wang does not expressly teach methylparaben as antioxidant, and formamide as a stabilizer.
The teachings of Paulsen with respect to the antioxidant methyl paraben and the teaching of Roberts with respect to formamide are discussed above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the use of methylparaben as a preservative in a formulation containing ivermectin, as taught by Paulsen, and the process of preparing ivermectin comprising a step of treating the ethanol solution with formamide, as taught by Roberts, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the methods taught by Wang, Paulsen, and Roberts because they are all drawn to processes of preparing formulations of ivermectin. It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
Regarding instant claim 42, the limitation of the medium comprising the particles comprising water and ethanol would have been obvious over the steps of heating HCO and ivermectin in a low-boiling-point organic solvent, which includes ethanol, until completely dissolved ([0019], [0022]), and further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension ([0019] (2) and [0022] (2)), as taught by Wang.
Regarding instant claim 42, the limitation of the methylparaben as antioxidant would have been obvious over the methyl paraben (claim 31), as taught by Paulsen.
Regarding instant claim 42, the limitation of the formamide as a stabilizer would have been obvious over the formamide (Col. 3, lines 1-4 and claim 2), as taught by Roberts.
Claim 43 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Wang et al. (CN 103 720 652 (B) – English Espacenet Translation – “Wang ‘652”).
Instant claim 43 is drawn to a process according to claim 27 wherein in the mixing step a suspension of ivermectin is recirculated at a range of rotations per minute of the high shear mixer of from 500 RPM to 9000 RPM.
The teachings of Wang are discussed above.
Wang does not expressly teach a range of rotations per minute of the high shear mixer of from 500 RPM to 9000 RPM.
Wang ‘652 teaches drug-loaded microparticles homogenized multiple times in a high shear homogenizer at an overlapping range of 5,000-10,000 rpm ([0020]) and ivermectin loaded microparticles homogenized at about 5000 RPM to obtain ivermectin injection with a particle size of less than 20 µm ([0032] and [0035]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the drug-loaded microparticles homogenized multiple times in a high shear homogenizer at an overlapping range of 5,000-10,000 rpm, as taught by Wang ‘652, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the methods taught by Wang and Wang ‘652 because they are all drawn to the same processes of preparing microparticulate formulations of ivermectin. It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
Regarding instant claim 43, the limitation of a suspension of ivermectin recirculated at a range of rotations per minute of the high shear mixer of from 500 RPM to 9000 RPM would have been obvious over the drug-loaded microparticles homogenized multiple times in a high shear homogenizer at an overlapping range of 5,000-10,000 rpm ([0020]) and ivermectin loaded microparticles homogenized at about 5000 RPM to obtain ivermectin injection with a particle size of less than 20 µm ([0032] and [0035]), as taught by Wang ‘652.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Wang et al. (CN 103 720 652 (B) – English Espacenet Translation – “Wang ‘652”) and Stuart et al. (WO 2021/022056 A1 – “Stuart”).
Instant claim 44 is drawn to a process according to claim 43 wherein a suspension of ivermectin is recirculated at a range of rotations per minute of the high shear mixer of from 1000 RPM to 2000 RPM.
The teachings of Wang and Wang ‘652 are discussed above.
Wang and Wang ‘652 do not expressly teach a range of rotations per minute of the high shear mixer of from 1000 RPM to 2000 RPM.
Stuart teaches methods of preparing compositions (Abstract). In one or more embodiments, the active agent is micronized so that the diameter of 90% of the particles (d(0.9)), is less than about 30 microns or less than about 20 microns, or less than about 10 microns ([00200]). The active agent ivermectin is disclosed ([00350]-[00351]). High shear mixing is used at a speed of 2000 rpm for a short period such as 10 minutes ([00754]), or a speed ranging from 1000 rpm or 2000 rpm (Page 346 - embodiment 4, lines 2-5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the drug-loaded microparticles homogenized multiple times in a high shear homogenizer at an overlapping range of 5,000-10,000 rpm, as taught by Wang ‘652, further in view of high shear mixing at a speed of 2000 rpm or at a speed ranging from 1000 rpm or 2000 rpm, as taught by Stuart, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the methods taught by Wang, Wang ‘652, and Stuart because they are all drawn to the same processes of preparing microparticulate formulations of ivermectin. It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
Regarding instant claim 44, the limitation of a suspension of ivermectin recirculated at a range of rotations per minute of the high shear mixer of from 1000 RPM to 2000 RPM would have been obvious over the high shear mixing at a speed of 2000 rpm ([00754]), or a speed ranging from 1000 rpm or 2000 rpm (Page 346 - embodiment 4, lines 2-5), as taught by Stuart.
Claims 45-46 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (CN 103 721 266 (A) – English Espacenet Translation – “Wang”), as applied to claims 27-31, 39-41, and 50-51 above, in view of Hassan et al. (US 2011/0268659 A1 – “Hassan”).
Instant claim 45 is drawn to a process according to claim 27 wherein in the mixing step the medium comprising the ivermectin particles is recirculated at a temperature of from 0°C to 25°C.
The teachings of Wang are discussed above.
Wang does not expressly teach a temperature of from 0°C to 25°C.
Hassan teaches a method of high shear application in drug delivery (Abstract). In FIG. 2B, a therapeutic fluid 5 containing a drug are transported and stored in a vessel 20 with a temperature control unit 30; a pump 10 is configured for continuous or semi-continuous operation, and the temperature of the shear device 40 is maintained by the temperature control unit 30 which has the capacity to maintain a temperature between 0-100°C within ± 2°C ([0054]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the method of preparing drug-loaded microparticles of ivermectin by heating the ivermectin in an organic solvent, which includes ethanol, obtaining the ivermectin microparticles, further mixing the drug-loaded microparticles with an aqueous solution comprising P407, shearing the mixture 3-5 times with a high shear homogenizer, grinding it with a colloid mill until the particle size is less than 80 µm, then grinding it with a sand mill until the particle size is less than 20 µm to obtain a thick suspension, as taught by Wang, in view of the high shear processing of a therapeutic fluid containing a drug where the temperature is in the range of 0-100°C, as taught by Hassan, and produce the instant invention.
One of ordinary skill in the art would have been motivated to combine the methods taught by Wang and Hassan because both references are drawn to high shear processes for preparing drug particles. Furthermore, Hassan teaches that the high shear processing allows for creation of dispersion having a narrow distribution of the desired bubble size and particle size ([0034]). It is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
Regarding instant claims 45-46, the limitations of a temperature of 0°C to 25°C (instant claim 45) and 0°C and 5°C (instant claim 46) would have been obvious over the temperature control unit 30 which has the capacity to maintain a temperature in the overlapping range of between 0-100°C within ± 2°C ([0054]), as taught by Hassan. According to MPEP 2144.05, “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.”
Conclusion
No claims are allowed.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615