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 .
DETAILED ACTION
Claims 1-13 are pending in the present application file.
Election/Restrictions
Applicant’s election of Group I (claims 1-7 and 11-13; drawn to particulate co-processed pre-formulated excipient composition for poorly soluble active pharmaceutical ingredients as well as a tablet formulation comprising the excipient composition and an active ingredient) without traverse in the reply filed January 26, 2026 is acknowledged by the Examiner.
As per MPEP 803.02, the examiner will determine whether the entire scope of the claims is patentable. Applicants' elected species is not allowable over the prior art as indicated in the rejection under 35 U.S.C 103.
As the Applicant’s elected species has been found not allowable, the Markush-type claims have been rejected and claims to the nonelected invention held withdrawn from further consideration. Claims 1-7 and 11-13 have been examined to the extent that they embrace and are readable on the elected embodiment and the above identified nonelected species. Claims 1-7 and 11-13 have been found to be not allowable over the prior art.
Claims 8-10 are withdrawn from consideration by the Examiner under 37 CFR 1.142(b) as being drawn to a non-elected invention.
Priority
The following continuity data is acknowledged in the present application file:
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Specification
The abstract of the disclosure is objected to for the following reasons:
The use of legal phraseology ("The present disclosure pertains ") in lines 1 and 2 of the abstract.
The use of legal phraseology ("wherein said excipient composition comprises") in line 6 of the abstract.
In lines 3-4 of the abstract, “enhancing dissolution rate of poorly soluble active pharmaceutical ingredient” should be changed to “enhancing the dissolution rate of a poorly soluble active pharmaceutical ingredient”
In lines 7-9 of the abstract, “good physical properties of excipient delivered good quality of tablet in terms tablet hardness, disintegration time and dissolution rate.”, should be changed to “good physical properties of excipient delivered, as well as good quality of tablet in terms tablet hardness, disintegration time and dissolution rate.”
Correction is required. See MPEP § 608.01(b).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The disclosure is objected to because of the following informalities:
In paragraph [0058], “Mostr preferably MCC”, should be changed to, “Most preferably MCC”.
Appropriate correction is required.
Claim Interpretation
Regarding the limitations “for poorly soluble active ingredients” or where composition “enhances dissolution rate of poorly soluble pharmaceutical active ingredient”, these limitations are interpreted as an intended use for the excipient composition of instant claim 1 and thus not given patentable weight. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art.
Regarding an intended use limitation, MPEP 2111.02(II) notes: “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020)”. In this situation, the limitation does not affect the structure of the compound of formula (I).
If the prior art structure is capable of performing the intended use, then it meets the claim. The present claims are interpreted for the purposes of applying prior art as an excipient composition based on total weight of the composition: filler-binder in an amount of 88.0% w/w to 97.8% w/w; glidant in an amount of 0.50% w/w to 3.0% w/w; disintegrant in an amount of 1.5% w/w to 6.0% w/w; solubility enhancer in an amount of 0.1% w/w to 1.0% w/w; and lubricant in an amount of 0.1% w/w to 2.0% w/w of instant claim 1, where the excipient composition must be co-processed, pre-formulated and ready-to-use.
Claim Rejections - 35 USC § 112
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.
Claim 12 is 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. Instant claim 12 further limits an optional limitation in instant parent claim 11. For embodiments of instant claim 11 where the optional limitation is not included, instant claim 12 does not further limit the scope of instant claim 11.
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 § 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.
Claims 1-7 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Van Gessel (US 2013/0177649 A1; Date Published: 07/11/2013), in view of Carpanzano (WO 2016/201119 A1; Date Published: 12/15/2016) and Mehta (WO 2020/012406 A1; Date Published: 01/16/2020).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Van Gessel discloses a co-processed excipient composition suitable for tableting, said composition comprising at least one filler-binder, at least one disintegrant, and at least one lubricant which have been subjected to granulation together. See abstract.
Regarding the filler-binder of the excipient composition, Van Gessel discloses the following in paragraph [0020] (emphasis added):
Filler-binders hold the ingredients in a tablet together. Filler-binders ensure that tablets and granules can be formed with required mechanical strength, and give volume to low active dose tablets. The amount of filler-binder(s)--based on the total dry weight of the co-processed excipient--typically ranges between 78-98.8 wt%, preferably between 90-97.0 wt%. Filler-binders are usually starches, sugars, cellulose or modified cellulose such as microcrystalline cellulose (MCC), hydroxypropyl cellulose, lactose, or sugar alcohols like xylitol, lactitol, mannitol, sorbitol or maltitol.
See instant claims 1 and 2.
Regarding the disintegrant of the excipient composition, Van Gessel discloses the following in paragraph [0022] (emphasis added):
Disintegrants ensure that when the tablet is in contact with water, it rapidly breaks down into smaller fragments, thereby facilitating dissolution. The amount of disintegrant(s)--based on the total dry weight of the co-processed excipient--typically ranges between 1.0-10.0 wt%, preferably between 2.0-6.0 wt%. Examples of disintegrants include crosslinked polyvinyl pyrrolidone, sodium starch glycolate, crosslinked sodium carboxymethyl cellulose (crosscarmellose).
Van Gessel discloses where croscarmellose sodium is another suitable disintegrant. See instant claim 2.
Regarding the lubricant of the excipient composition, Van Gessel discloses the inclusion of lubricant in ranges of 0.2-2.2 wt.% based on the weight of the total composition. See paragraph [0019] of Van Gessel. Van Gessel discloses where magnesium stearate is a suitable lubricant in the excipient composition. See instant claims 1 and 2. Van Gessel also provides where sodium lauryl sulphate is a suitable lubricant.
Van Gessel provides where all but the API(s) are co-processed into a tableting excipient formulation, which is ready-to-use and marketed for tableting together with the API(s). See paragraph [0011] and instant claim 7.
Van Gessel provides where the typical particle size of the excipient composition is less than 500 microns (based on the largest particle cross-section). See paragraph [0017]. Van Gessel discloses where the moisture content of the composition is less than 7%. See paragraph [0018] and instant claim 5. Van Gessel teaches where the excipient composition exhibits a poured bulk density of about 0.40-0.60 g/ml, and/or a tapped bulk density of about 0.40-0.70 g/ml. See instant claim 6.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Van Gessel does not disclose where the excipient composition comprises 0.5-3.0% w/w% of glidant, or further where the glidant of the excipient composition is colloidal silicon dioxide. Van Gessel does not disclose where the excipient composition comprises solubility enhancer in an amount of 0.1% w/w to 1.0% w/w; or further where sodium lauryl sulphate used as solubility enhancer. See instant claims 1 and 2.
Van Gessel does not teach wherein the particulates have an average particle size of 50 µm to 250 µm. See instant claim 3.
Van Gessel does not disclose wherein the pH of the excipient composition is 5.0-7.5. See instant claim 4.
Van Gessel does not disclose a tablet formulation comprising
the particulate co-processed pre-formulated excipient composition as claimed in instant claim 1 in an amount ranging between 35% w/w and 65% w/w; a poorly soluble active pharmaceutical ingredient in an amount ranging between 35% w/w and 65% w/w; and optionally one or more excipients in an amount ranging between 1% w/w and 10% w/w. See instant claims 11-13.
Finding of prima facie obviousness --- rationale and motivation (See
MPEP § 2142-2143)
Carpanzano discloses a novel excipient for use in the manufacture of pharmaceuticals and/or nutraceuticals, and in particular, solid dosage forms such as tablets which include one or more active ingredients. See paragraph [0002]. Carpanzano discloses where the novel excipient is a particulate excipient composition comprising microcrystalline cellulose, a silicate-based adsorbant carrier and colloidal silicon dioxide (as compressability augmenting agent).
Carpanzano discloses the following regarding MCC in paragraph [0082]:
When utilized in pharmaceutical applications, microcrystalline cellulose is typically used as a tablet binder/diluent in wet granulation and direct compression formulations in amounts of 5-30% of the formulation, or more. However, it is known to use more or less microcrystalline cellulose in pharmaceutical products, depending upon the requirements of the formulation.
Carpanzano discloses the following regarding colloidal silicon dioxide in excipient compositions (emphasis added):
Prior to the present invention, silicon dioxide, and in particular colloidal silicon dioxide, was used mainly as a glidant and anti-adherent in tableting processes and encapsulation, promoting the flowability of the granulation. The amount of silicon dioxide included in such tablets for those applications is very limited, 0.1- 0.5% by weight.
See instant claims 1 and 2.
Carpanzano discloses where the excipient composition may further include surfactants (as compressibility augmenting agent) such as sodium lauryl sulphate. See paragraphs [0042], [0085], [0091]-[0092] and [0165]. Carpanzano discloses where the surfactant or sodium lauryl sulphate is included in amounts up to 0.1% by weight and “when an anionic surfactant such as sodium lauryl sulfate is coprocessed with microcrystalline cellulose in the amounts described herein, improved microcrystalline cellulose products of the invention result.”
Further regarding the usefulness of sodium lauryl sulphate in microcrystalline cellulose formulations Carpanzano discloses the following in paragraph [0097]:
[I]t has been discovered that the compressibility of microcrystalline cellulose which is wet granulated is significantly improved by coprocessing the microcrystalline cellulose with an anionic surfactant such as sodium lauryl sulfate.
Carpanzano discloses the following regarding the average particle size of the excipient composition in paragraph [0126]:
The average particle size of the excipient of the present invention ranges from about 10 microns to about 1000 microns. Particle sizes of about 10-500 microns are preferred, particle sizes of about 30-250 microns are more preferred and particle sizes of about 40-200 microns are most preferred.
See instant claim 3.
Regarding the pH of the excipient composition, Carpanzano discloses where the pH of the particles is most preferably about neutral, although granulates having a pH of from about 3.0 to about 8.5 are possible. See paragraph [0127] and instant claim 4.
Carpanzano discloses where the moisture content of the excipient particles will preferably broadly range from about 0.5% to about 15%, preferably from about 2.5% to about 6%, and most preferably from about 3.0% to about 5% by weight. Carpanzano also provides where The excipient of the present invention preferably has a bulk (loose) density ranging from about 0.2 g/ml to about 0.6 g/ml, and most preferably from about 0.35 g/ml to about 0.55 g/ml.
Carpanzano discloses a pharmaceutical solid dosage form comprising an excipient composition and an oily active ingredient with poor solubility. Carpanzano discloses where the solid dosage form is a tablet and where the active ingredient is present in an amount up to 35% wt in the tablet. Carpanzano discloses where the tablet can be prepared by either wet granulation or dry granulation; however, Carpanzano discloses where wet granulation is the preferred method, both in the state of the art and in the Carpanzano disclosure. See paragraphs [0052]-[0053], [0058], [0135]-[0164]. Carpanzano also discloses a compressed solid dosage form comprising an active ingredients) and the novel excipient described herein, wherein the active ingredients) and excipient have been directly compressed into the solid dosage form. See paragraphs [0059] and [0129]. See instant claims 11-13.
Mehta discloses a high drug load solid oral pharmaceutical composition comprising spinosad and at least one pharmaceutically acceptable excipient, selected from the group consisting of diluent, glidant, binder, disintegrant, lubricant, surfactant, flavor, colorant and other pharmaceutical excipients.
Mehta provides a formulation comprising:
i) about 30% to about 80% by weight of spinosad,
ii) about 10% to about 50% by weight of diluent,
iii) about 0% to about 10% by weight of glidant,
iv) about 1% to about 30% by weight of disintegrant, and
v) about 0.5% to about 3% by weight of lubricant.
See claim 1 of Mehta.
Metha discloses the following regarding surfactants as solubility enhancers:
Surfactants or surface-active agents improve wettability of the dosage form and/or enhance its dissolution. Surfactants contemplated in the present invention include but are not limited to anionic surfactants, amphoteric surfactants, non-ionic surfactants and macromolecular surfactants. Suitable examples of anionic surfactants include but are not limited to sodium lauryl sulphate, sodium cetyl stearyl sulphate or sodium dioctyl sulphosuccinate etc. Suitable example of an amphoteric surfactant include but is not limited to lecithin. Suitable examples of non-ionic surfactants include but is not limited to cetyl alcohol, stearyl alcohol, cetyl stearyl alcohol, cholesterol, sorbitan fatty acid esters such as sorbitan mono-oleate, polyoxyethylene sorbitan fatty acid esters such as polysorbate 80, polysorbate 20, polyoxyethylene fatty acid glycerides such as macrogol 1000 glycerol monostearate, polyoxyethylene fatty acid esters such as polyoxyl 40 stearate, polyoxyethylene fatty alcohol ethers such as polyoxyl 10 oleyl ether, glycerol fatty acid esters such as glycerol monostearate, commercially available Sepitrap® 80 or Sepitrap® 4000, etc. Surfactants are present in the range from about 0% to about 0.5% w/w of the uncoated composition
See instant claims 1 and 2.
Mehta discloses the following exemplary composition in Example 1:
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where the active ingredient is present in 60% w/w and the excipient composition is present in 40% w/w. See instant claims 11-12. Mehta discloses wherein the composition is prepared by dry blending, dry granulation, wet granulation or direct compression. See instant claim 13.
Van Gessel discloses an excipient composition comprising filler-binder in ranges between 78-98.8 wt%, preferably between 90-97.0 wt%; disinfectant in ranges between 1.0-10.0 wt%, preferably between 2.0-6.0 wt%; lubricant ranges between 0.2 and 2.2 wt%, preferably up to 1.0 wt; and where all but the API(s) are co-processed into a tableting excipient formulation, which is ready-to-use and marketed for tableting together with the API(s).
Carpanzano provides an excipient composition for use in the manufacture of solid dosage forms, such as tablets, comprising microcrystalline cellulose, a silicate adsorbant carrier, colloidal silicon dioxide as glidant promoting the flowability of the granulation, and surfactants such as sodium lauryl sulphate. Carpanzano discloses where the amount of microcrystalline cellulose is typically included in amounts of 5-30% wt., or more; however, it is known in the prior art to adjust the amount of microcrystalline cellulose as needed for the formulation. Carpanzano teaches where the amount of colloidal silicon dioxide included in such tablets for those applications is very limited, 0.1-0.5% by weight, and where the surfactant of sodium lauryl sulphate is included in amounts up to 0.1% by weight. Carpanzano teaches that when an anionic surfactant such as sodium lauryl sulfate is coprocessed with microcrystalline cellulose in the amounts described herein, improved microcrystalline cellulose products of the invention result.
Metha discloses a pharmaceutical composition comprising filler, glidant, disintergrant, lubricant and surfactant as well as processing with an API (spinosad). Mehta discloses where the Spinosad is present in amount from about 30-80% by weight, filler is present in amount from about 10-50% by weight, glidant is present in amount from about 0-10% by weight, disintegrant is present in an amount from about 1-30%, lubricant is present in an amount from about 0.5-3% by weight and surfactant in up to 0.5% by weight of the total composition. Mehta teaches the surfactants as solubility enhancer or agents which improve wettability of the dosage form and/or enhance its dissolution as well as teaches the utility and several alternative examples for excipients of the composition.
It would have been prima facie obvious for one of ordinary skill in the art to combine Van Gessel and Carpanzano, which disclose a co-processed pre-formulated excipient composition, comprising filler-binder, glidant, disintegrant, solubility enhancer and lubricant as well as methods of improving tableting, co-processing, solubility and flowability of the compositions, to provide the excipient composition of the present claims. Van Gessel and Carpanzano provide the excipient components in ranges which overlap with the presently claimed ranges. See MPEP 2144.05. There would be a reasonable expectation of success based on the exemplary ready-to-use formulations of Van Gessel and utility disclosed by Carpanzano and Mehta for each component of the presently claimed composition.
Therefore, instant claims 1-7 are prima facie obvious and properly rejected.
Regarding the tablet formulation of instant claims 11-13, the combination of Van Gessel, Carpanzano and Mehta disclose the excipient composition of instant claim 1. Carpanzano discloses a pharmaceutical solid dosage form comprising an excipient composition and an oily active ingredient with poor solubility. Carpanzano discloses where the solid dosage form is a tablet and where the active ingredient is present in an amount up to 35% wt in the tablet. Carpanzano discloses where the tablet can be prepared by either wet granulation or dry granulation. Mehta discloses a tablet solid dosage form comprising a poorly soluble active pharmaceutical ingredient (Spinosad) and an excipient composition. Mehta provides an exemplary formulation in Table 1 of Example 1 where the active ingredient is present in 60% w/w and the excipient composition is present in 40% w/w. and where the formulation can be prepared by wet granulation or direct compression.
Therefore, present claims 11-13 are prima facie obvious and similarly rejected.
Conclusion
Claims 1-7 and 11-13 are rejected.
Claims 8-10 are withdrawn.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QUINCY A MCKOY whose telephone number is (703)756-4598. The examiner can normally be reached Monday - Thursday 8:00 - 6:00.
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/QUINCY A. MCKOY/
Patent Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626