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 .
Requirement for Information
Applicant and the assignee of this application are required under 37 CFR 1.105 to provide the following information that the examiner has determined is reasonably necessary to the examination of this application.
The applicant here is the assignee and applicant in Prathap (US 2018/0228798; cited below). Prathap teaches the granules comprising posaconazole and enteric polymer are milled prior to mixing with further components for forming a tablet (paras.0029, 0032, 0035, 0038, 0041, 0044, 0047, 0050, 0053, 0056, 0059, 0066); however the particle size distribution is not discussed. Applicant is requested to provide information relevant to the particle or granule size resulting from the milling step which Prathap discloses.
The applicant is reminded that the reply to this requirement must be made with candor and good faith under 37 CFR 1.56. Where the applicant does not have or cannot readily obtain an item of required information, a statement that the item is unknown or cannot be readily obtained may be accepted as a complete reply to the requirement for that item.
This requirement is an attachment of the enclosed Office action. A complete reply to the enclosed Office action must include a complete reply to this requirement. The time period for reply to this requirement coincides with the time period for reply to the enclosed Office action.
Claim Objections
Claims 5-7, 17, and 18 are objected to because of the following informalities: “more preferred” is grammatically incorrect.
Claims 12-14 are objected to because of the following informalities: each claim should recite that the mixture “further” contains the respective component recited.
Claim 15 is objected to because of the following informalities: each of “the monomeric plasticizer, the sugar alcohol” and “the antioxidant” lacks antecedent basis.
Appropriate corrections are 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 5-14, 17, and 18 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.
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 5 recites the broad recitation “at least 60 µm”, and the claim also recites “preferably at least 75 μm, and more preferred at least 100 μm” which is the narrower statement of the range/limitation. Claim 5 also recites the broad recitation “not more than 250 μm”, and the claim also recites “preferably not more than 180 μm, and more preferred not more than 130 μm” which is the narrower statement of the range/limitation. In each instance of the broader and narrower statements of the range or limitation in the claims listed below, 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.
Claim 6 recites the broad recitation “at least 160 µm”, and the claim also recites “preferably at least 200 μm, and more preferred at least 250 μm” which is the narrower statement of the range/limitation. Claim 6 also recites the broad recitation “not more than 500 μm”, and the claim also recites “preferably not more than 400 μm, and more preferred not more than 320 μm” which is the narrower statement of the range/limitation.
Claim 7 recites the broad recitation “at least 300 µm”, and the claim also recites “preferably at least 400 μm, and more preferred at least 480 μm” which is the narrower statement of the range/limitation. Claim 7 also recites the broad recitation “not more than 1000 μm”, and the claim also recites “preferably not more than 800 μm, and more preferred not more than 600 μm” which is the narrower statement of the range/limitation.
Claim 8 recites the broad recitation “hypromellose derivatives, cellulose derivatives, polyvinylacetate derivatives and polymethacrylic acid derivatives”, and the claim also recites “preferably is a polymethacrylic acid derivative” which is the narrower statement of the range/limitation.
Claim 9 recites the broad recitation “hypromellose acetate succinate (HPMCAS) and/or a polymethacrylic acid derivative selected from poly(methacrylic acid/methyl methacrylate) and poly(methacrylic acid/ethyl acrylate)”, and the claim also recites “p preferably is poly(methacrylic acid/ethyl acrylate)” which is the narrower statement of the range/limitation.
Claim 10 recites the broad recitation “polyvinylpyrrolidone, poly(vinylpyrrolidone/vinylacetate), polyvinylcaprolactam/polyvinylacetate/polyethylene glycol graft copolymer, polyethylene glycol/polyvinyl alcohol graft copolymer, poly(ethylene oxide/propylene oxide), macrogolglycerol hydroxystearate, polyethylene glycol and a water soluble neutral or anionic polysaccharide”, and the claim also recites “preferably is a water soluble neutral or anionic polysaccharide” which is the narrower statement of the range/limitation.
Claim 11 recites the broad recitation “a gum, pectin, dextran, dextrin, a cellulose ether, pregelatinized starch and a starch ether”, and the claim also recites “preferably is a cellulose ether such as hydroxypropylcellulose” which is the narrower statement of the range/limitation. Also the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 12 recites the broad recitation “antioxidant”, and the claim also recites “preferably is selected from butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), sodium or potassium metabisulfite, sodium bisulfite, sodium sulfite, sodium thiosulfate, cysteine, acetyl cysteine, methionine, glutathione, sodium formaldehyde sulfoxylate, ascorbic acid and its derivatives like sodium ascorbate, ascorbyl palmitate, tocopherol and its derivatives, tocopheryl succinate, tocopheryl polyethylene glycol succinate (TPGS) and propyl gallate, and particularly preferred is propyl gallate” and “particularly preferred is propyl gallate” which are the narrower statements of the range/limitation.
Further regarding claim 12, the phrase "its derivatives like…" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 13 recites the broad recitation “monomeric plasticizer”, and the claim also recites “preferably is selected from triethyl citrate, triacetin, dibutyl sebacate, diethyl phthalate, glycerylmonostearate, glycerine and propylene glycol, and particularly preferred is triethyl citrate” which is the narrower statement of the range/limitation.
Claim 14 recites the broad recitation “sugar alcohol”, and the claim also recites “preferably is selected from xylitol, sorbitol, mannitol and maltitol, and particularly preferred is xylitol” which is the narrower statement of the range/limitation.
Claim 17 recites the broad recitation “a temperature of 100-170° C.”, and the claim also recites “preferably 100-160° C., more preferably 120-150° C.” which is the narrower statement of the range/limitation. Claim 17 also recites the broad recitation “at least 10 wt.-%”, and the claim also recites “preferably at least 20 wt.-%, more preferred at least 30 wt.-%, and even more preferred at least 40 wt.-%” which is the narrower statement of the range/limitation. Claim 17 also recites the broad recitation “but not more than 80 wt.-%”, and the claim also recites “preferably not more than 70 wt.-%, more preferred not more than 60 wt.-%, and even more preferred not more than 55 wt.-%” which is the narrower statement of the range/limitation. Lastly claim 17 recites the broad recitation “not higher than 50° C.,”, and the claim also recites “preferably not higher than 40° C.” which is the narrower statement of the range/limitation.
Claim 18 recites the broad recitation “150 rpm to 300 rpm”, and the claim also recites “preferably 200 rpm to 265 rpm, more preferred 225 rpm to 250 rpm” which is the narrower statement of the range/limitation.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 5-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 5 recites “d (0.1) of the granules is at least 60 μm…and/or is not more than 250 μm…”. “At least 60 µm” does not have an upper limit, and “not more than 250 µm” does not have a lower limit. Due to the underlined “or”, claim 5 in effect does not further limit claim 1 from which it depends. Similarly claim 6 recites “d (0.5) of the granules is at least 160 μm, …, and/or is not more than 500 μm,..”, and claim 7 recites “d (0.9) of the granules is at least 300 μm,…, and/or is not more than 1000 μm,…”. Due to the underlined “or”, claims 6 and 7 also do not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 5-9, 16, 19, 20, and 22 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Türkyilmaz (WO 2019/240698A2).
Türkyilmaz teaches “posaconazole in the form of the free base or in the form of pharmaceutically acceptable salts, crystalline polymorph, solvates, hydrates or esters thereof and a dispersion carrier” wherein the ratio of posaconazole to an enteric polymer carrier such as hydroxypropylcellulose-acetate succinate (HPMC-AS) “is in the range of between 4:1 to 1 :4 by weight, preferably between 3:1 to 1 :3 by weight” (p.4 lines 18-21, p.4 line 34-p.5 line 2). The “d (0.9) particle size of obtained extrudate using hot melt extrusion is less 250 μm”, meaning the “the size at which 90% by volume of the particles are finer” than 250 µm is 90% (p.3 lines 1-6). This leaves 10% by volume of the particles are 250 µm or greater, which meets the granule size limitation of instant claim 1. Although Türkyilmaz discusses the d(0.0) as volume- rather than weight-based as in claim 1, there is no basis to infer that the particles of Türkyilmaz, i.e., the granules comprising posaconazole and the carrier, are not homogeneous (affecting density) such that volume fraction and weight fraction would differ to a significant extent. Also it does not appear that the difference between sieve analysis of claim 1 and the “laser diffraction method (i.e., Malvern analysis)” of Türkyilmaz (p.3 lines 1-6) would result in a significant difference.
Regarding claims 5-7 Türkyilmaz teaches the d(0.1) of less than 50 µm, d(0.5) of less than 60 µm, and d(0.9) of less than 70 µm (p.3 lines 19-29).
Regarding claims 19, 20, and 22, Türkyilmaz teaches tablets and excipients (p.5 line 25-p.7 line 4) including those in claim 20.
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 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(s) 1 and 5-22 are rejected under 35 U.S.C. 103 as being unpatentable over Türkyilmaz (WO 2019/240698A2) in view of Prathap (US 2018/0228798).
Türkyilmaz teaches the non-enteric polymer and other excipients in instant claims 10-15 and 21 for forming a tablet (p.5 line 23-p.7 line 4). It does not specifically teach using them for forming the granule as in claims 10-15 or a specific embodiment of claim 21.
Regarding claims 17 and 18 Türkyilmaz teaches hot melt extrusion (p.8 line 4-p.10, p.13 lines 5-11). “The temperature of the hot melt extrusion is set in the range of about 40 ° C to about 160 ° C and the rotation speed of the screw is set in the range of about 150 to about 280 rpm.” (p.10 lines 4-5). Türkyilmaz does not teach a milling step as recited in claim 17 limitation (iii).
Prathap teaches “gastro-resistant pharmaceutical composition of the present invention comprises posaconazole molecularly dispersed in a mixture containing an enteric polymer and a non-enteric polymer, wherein the mixture is prepared by hot-melt extrusion” (abstract; see title; paras.0013-0066; claims 1-20). Prathap teaches using the excipients in claims 10-15 to form granules, e.g., Kollidon® VA 64 or N-vinylpyrrolidone (NVP) and vinyl acetate (VAc) (Examples; see, e.g., paras.0016-17, 0021, 0029, 0032). The granules Examples 7a and 7b after stage C comprise the components in claim 21 (paras.0045-47). The granules are milled prior to mixing with further components for forming a tablet (paras.0029, 0032, 0035, 0038, 0041, 0044, 0047, 0053, 0056, 0059, 0066).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to combine the teachings of Türkyilmaz and Prathap and formulate posaconazole granules as recited in the instant claim(s). The skilled person would have been motivated to do so because both references are drawn to granules comprising a solid solution of posaconazole and an enteric polymer, prepared by hot melt extrusion, for preparing tablets, and Prathap teaches the excipients that Türkyilmaz teaches for forming tablets can be used in forming the granules also. “The expectation of some advantage is the strongest rationale for combining references”. MPEP § 2144(II). “Because the desire to enhance commercial opportunities by improving a product or process is universal—and even common-sensical—we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves.” MPEP § 2144(II) (citations omitted). Here the skilled person would have found it advantageous to have the choice to formulate posaconazole tablets with the excipient incorporated at either the granule stage or at tablet compression.
Citation of Relevant Art
US 2011/0123627. Teaches posaconazole dissolved or molecularly dispersed in hydroxypropylmethylcellulose acetate succinate with particle size range of from about 75 micron to about 300 micron with a median particle size of 250 microns. The particle size distribution is not discussed in further details relevant to the range in claim 1.
Conclusion
This Office action has an attached requirement for information under 37 CFR 1.105. A complete reply to this Office action must include a complete reply to the attached requirement for information. The time period for reply to the attached requirement coincides with the time period for reply to this Office action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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, Ali Soroush can be reached at (571)272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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