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 .
Formal Matters
This Office Action is in response to the claim set filed on December 01, 2023. Claims 1-13 are pending. Claims 1-13 are under consideration in the instant office action.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The US effective filing date of the instant application is determined to be June 04, 2021 the filing date of the foreign application EP 21177809.7.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 01, 2023 are noted and the submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
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 1-13 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 1 recites the limitation "the core tablet" in claim 1. There is insufficient antecedent basis for this limitation in the claim.
In instant claim 1 the phrase “a coating in an amount of 2.5% to 35% w/w in relation to the core tablet weight comprising a water soluble pH independent gelling control release polymer” is indefinite because it is unclear if the amount is referring to the amount of a water soluble pH independent gelling control release polymer in the coating or the amount is referring to the amount of the coating relative to the total amount of the controlled release pharmaceutical tablet. Appropriate clarification is requested. For prior art rejection purpose the examiner interpreted the claim by affording the broadest reasonable interpretation of wherein the amount of 2.5% to 35% w/w is referring to the amount of a water soluble pH independent gelling control release polymer in the coating.
Claims 2-13 are included in the rejection for depending from an indefinite base claim.
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.
Claim(s) 1-8 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by NIETO et al. (WO2019/224058, IDS reference of 12/01/23).
Regarding the recited core, NIETO et al. disclose a controlled release pharmaceutical tablet comprising: a) An inner tablet comprising tofacitinib or a pharmaceutically acceptable salt thereof and a pH independent gelling control release polymer; b) An outer tablet surrounding said inner tablet comprising a pH independent gelling control release polymer; wherein said outer layer does not contain tofacitinib or a pharmaceutically acceptable salt thereof (see claim 1). NIETO et al. disclose the tablet-into-tablet system of the present invention combines two controlled release structures or mechanisms: there are two tablets comprising pH independent gelling control release polymer. Dissolution can be modulated to achieve the desired profile by choosing among these polymers; the inner tablet contains the tofacitinib or a salt thereof, preferably the citrate salt, and a pH independent gelling control release polymer. Covering this inner tablet there is an outer tablet that acts as external layer formulated as a placebo, this external layer contains a pH independent gelling control release polymer which determines the resulting lag time of the dissolution profile (see pages 4-5).
NIETO et al. disclose in Table 1 as follows:
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The examiner notes that Methocel K100 LV has a viscosity of 100 cP (as evidenced by Applicant’s own disclosure Examples 1-3. In the present invention the inner tablet contains at least one pH independent gelling control release polymer. The term pH independent gelling control release polymer means a control release polymer that forms a gel when in contact with water independently of the pH of the water. Such polymers are known in the art and include polyethylene oxide (for example (MW:900.000 g/mol; Polyox® 1105 WSR), hydroxypropyl methylcellulose (for example Methocel® K100 Premium low viscosity (LV) grade), hydroxypropyl cellulose, polyvinyl alcohol (for example Parteck® SRP 80), guar gum, carrageenan and combinations thereof. A preferred pH independent gelling control release polymers are soluble polymers such a polyethylene oxide, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinyl alcohol more preferably hydroxypropyl methyl cellulose and polyethylene oxide, even more preferably hydroxypropyl methyl cellulose. The amount of the pH independent gelling control release polymer in the inner tablet is preferably in an amount from 10% to 50%, more preferably from 20% to 40%, even more preferably 25% to 35% by weight based on the total inner tablet weight. The pH independent gelling control release polymer of the present invention has preferably a viscosity of 10 cP or more, more preferably 25cP or more, even more preferably between 20 and 500cp, most preferred 24 to 300cP in a solution containing 2% of the polymer in distilled water at 22.5±0.5°C, measured using a Fungilab viscosimeter. The inner tablet contains additional excipients such as diluents, lubricants, binders or buffering agents (see pages 5-6). In the case that the inner tablet is made by granulation process these excipients can be present intragranularly or extragranularly. Diluents are excipients that are used to increase the bulk volume of a tablet. By combining a diluent with the active pharmaceutical ingredient, the final product is given adequate weight and size to assist in production and handling. Binders hold the excipients that are present in a tablet together. Binders ensure that tablets and granules can be formed having the desired or required mechanical strength. The inner tablet of the present invention preferably contains at least one diluent.
Diluents are preferably used in an amount of from 10% to 75% more preferably 20 to 65% even more preferably 25% to 50% by weight based on the total weight of the inner tablet. Suitable examples of diluents to be used in accordance with the present invention include lactose, starch, pregelatinized starch, microcrystalline cellulose(MCC), phosphates, and combinations thereof. In a preferred embodiment of the present invention, the diluents to be used are lactose, microcrystalline cellulose or mixtures thereof. Binders which are suitable for use in accordance with the present invention include povidone, hydroxypropyl methylcellulose, hydroxy propylcellulose, and sodium carboxyl methylcellulose. Binders are preferably used intragranularly in an amount of from 1% to 5% by weight based on the total weight of the composition. A preferred binder is hydroxypropyl cellulose, povidone or co-povidone. The inner tablet may also contain a lubricant and/or a glidant. Lubricants are generally used in order to reduce sliding friction. In particular, to decrease friction at the interface between a tablet’s surface and the die wall during ejection, and reduce wear on punches and dies. Suitable lubricants to be used in accordance with the present invention include magnesium stearate, calcium stearate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, and sodium stearyl fumarate. Lubricants preferably are used in a total amount of from 0.05% to 5% by weight based on the total weight of the inner tablet. A preferred lubricant is magnesium stereate. Glidants enhance product flow by reducing interparticulate friction. A suitable example is colloidal silicon dioxide. Glidants preferably are used in a total amount of from 0.05% to 5% by weight based on the total weight of the inner tablet. The inner tablet may also contain one or more buffering agents. Buffering agents are generally used in order to maintain the pH constant. They may be acidic or basic agents. Suitable acidic buffering agents are tartaric acid, malic acid, maleic acid and citric acid. Suitable basic buffering agents are sodium carbonate, sodium acetate and potassium citrate (see pages 6-8). Regarding the coating, NIETO et al. disclose in the present invention the outer tablet contains at least one pH independent gelling control release polymer. The pH independent gelling control release polymer in the outer tablet may be the same as or different from the pH independent gelling control release polymer in the inner tablet. In a preferred embodiment the pH independent gelling control release polymer is the same for the inner and outer tablet. As with the inner tablet the preferred polymer is a soluble polymer, more preferably hydroxypropyl methyl cellulose. The amount of the pH independent gelling control release polymer in the outer tablet is preferably in an amount from 3% to 35% more preferably from 5% to 25%, even more preferably 10% to 20%, most preferably 12% to 18% by weight to the total outer tablet. The inner tablet mainly alters the dissolution profile after 2 hours time. The content of the controlled release in the inner tablet modulates the dissolution rate of the active ingredient. The inner tablet comprises the whole dose of tofacitinib. The word tofacitinib is used herein to refer to tofacitinib free base as well as its pharmaceutically acceptable salts. A preferred salt to be use is the citrate salt. Tofacitinib free base as well as its pharmaceutically acceptable salts, preferably tofacitinib citrate is preferably used in an amount of 10 to 80%, more preferably 15% to 70%, even more preferably 20 to 60% by weight based on the total inner tablet weight. In the present invention tofacitinib is released from the formulation, in a controlled fashion so that at least 60% of tofacitinib is released at 4 hours and at least 80% of tofacitinib is released after 6 hours. In a preferred embodiment of the present invention, the diluents to be used are lactose, microcrystalline cellulose or mixtures thereof (see claim 6). Binders which are suitable for use in accordance with the present invention include povidone, hydroxypropyl methylcellulose, hydroxy propylcellulose, and sodium carboxyl methylcellulose. Binders are preferably used intragranularly in an amount of from 1% to 5% by weight based on the total weight of the composition. A preferred binder is hydroxypropyl cellulose, povidone or co-povidone. The inner tablet may also contain a lubricant and/or a glidant. Lubricants are generally used in order to reduce sliding friction. In particular, to decrease friction at the interface between a tablet's surface and the die wall during ejection, and reduce wear on punches and dies. Suitable lubricants to be used in accordance with the present invention include magnesium stearate, calcium stearate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, and sodium stearyl fumarate. Lubricants preferably are used in a total amount of from 0.05% to 5% by weight based on the total weight of the inner tablet. A preferred lubricant is magnesium stereate. Glidants enhance product flow by reducing interparticulate friction. A suitable example is colloidal silicon dioxide. Glidants preferably are used in a total amount of from 0.05% to 5% by weight based on the total weight of the inner tablet. The inner tablet may also contain one or more buffering agents. Buffering agents are generally used in order to maintain the pH constant. They may be acidic or basic agents. Suitable acidic buffering agents are tartaric acid, malic acid, maleic acid and citric acid. Suitable basic buffering agents are sodium carbonate, sodium acetate and potassium citrate (see page 7). In the present invention the outer tablet contains at least one pH independent gelling control release polymer. The pH independent gelling control release polymer in the outer tablet may be the same as or different from the pH independent gelling control release polymer in the inner tablet. In a preferred embodiment the pH independent gelling control release polymer is the same for the inner and outer tablet. As with the inner tablet the preferred polymer is a soluble polymer, more preferably hydroxypropyl methyl cellulose. The amount of the pH independent gelling control release polymer in the outer tablet is preferably in an amount from 3% to 35% more preferably from 5% to 25%, even more preferably 10% to 20%, most preferably 12% to 18% by weight to the total outer tablet. The outer tablet may further contain additional pharmaceutical excipients as described above for the inner tablet, such as diluents, binders et cetera. In a preferred embodiment at least one diluent as described above for the inner tablet is present in the outer tablet. Diluents are preferably used in an amount of from 10% to 95%, more preferably 30% to 90%, even more preferably 50% to 90% by weight based on the total weight of the outer tablet. In a preferred embodiment of the present invention, the diluents to be used are lactose, microcrystalline cellulose or mixtures thereof. The outer tablet can also contain a lubricant and/or glidant as described above for the inner tablet (see page 7-8).
The inner tablet comprises based on total weight of the inner tablet: a. Tofacitinib citrate in an amount of from 20 to 60% by weight; b. pH independent gelling control release polymer, preferably Hydroxypropyl methylcellulose, in an amount of from 20 to 40% by weight; c. Diluents in an amount of from 25% to 50%by weight; and wherein said outer tablet comprises based on total weight of the outer tablet: a. pH independent gelling control release polymer, preferably Hydroxypropyl methylcellulose in an amount of from 10% to 20% by weight; b. Diluents in an amount of from 50 to 90% by weight. In a more preferred embodiment the inner tablet and the outer tablet have the following compositions.
The inner tablet comprises based on total weight of the inner tablet: a. Tofacitinib citrate in an amount of from 20 to 60% by weight; b. pH independent gelling control release polymer, preferably Hydroxypropyl methylcellulose, in an amount of from 20% to 40% by weight; c. MCC in an amount of from 10 to 40% by weight; d. Lactose in an amount of from 10 to 40% by weight; e. Optionally other pharmaceutical excipients; and wherein said outer tablet comprises based on total weight of the outer tablet: a. pH independent gelling control release polymer, preferably Hydroxypropyl methylcellulose in an amount of from 10% to 20% by weight; b. MCC in an amount of from 25 to 45% by weight; c. Lactose in an amount of from 25 to 45% by weight; d. Optionally other pharmaceutical excipients (see page 9).
A controlled release pharmaceutical tablet according to claim 1 wherein tofacitinib is in the form of tofacitinib citrate (see claim 2). A tablet according to any one of the claims 1 to 3 wherein said tofacitinib is present in an amount of from 20 to 60% by weight based on the total inner tablet weight (see claim 4). A tablet according to any one of the claims 1 to 4 wherein said pH independent gelling control release polymer is present in the outer tablet in an amount from 10% to 20% by weight to the total outer tablet weight (see claim 5). A tablet according to any one of the claims 1 to 4 wherein said pH independent gelling control release polymer is present in the inner tablet in an amount from 20 to 40% by weight to the total inner tablet weight (see claim 6). A tablet according to any one of the claims 1 to 6 wherein said pH independent gelling control release polymer in said inner tablet and in said outer tablet are each independently selected from the group consisting of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene oxide, polyvinyl alcohol, and combinations thereof (see claim 7). A tablet according to claim 6, wherein said pH independent gelling control release polymer in said inner tablet comprises hydroxypropyl methylcellulose (see claim 8). A tablet according to claim 5, wherein said pH independent gelling control release polymer in said outer tablet comprises hydroxypropyl methylcellulose (see claim 9). A tablet according to any one of the claims 1 to 9 wherein said inner tablet further comprises a diluent in an amount from 25-50% by weight based in the total weight of the inner tablet (see claim 10). A tablet according to any one of the claims 1 to 10 wherein said outer tablet further comprises a diluent in an amount from 50-90% by weight based in the total weight of the outer tablet (see claim 11). A tablet according to claim 10 and/or 11 wherein said diluent is selected from the group comprising microcrystalline cellulose, lactose, phosphates, hydroxypropyl cellulose, starch and combinations thereof (see claim 12). Claim 14 discloses a tablet according to any one of the claims 1 to 12 wherein said inner tablet and/or said outer tablet further comprises a lubricant (see claim 13). A tablet according to any one of the claims 1 to 13; wherein said inner tablet comprises based on total weight of the inner tablet:
a. Tofacitinib citrate in an amount of from 20 to 60% by weight;
b. Hydroxypropyl methylcellulose in an amount of from 20% to 40% by weight;
c. Diluents in an amount of from 25% to 50% by weight;
and wherein said outer tablet comprises based on total weight of the outer tablet:
a. Hydroxypropyl methylcellulose in an amount of from 10% to 20% by weight;
b. Diluents in an amount of from 50 to 90% by weight.
A tablet according to claim 14 wherein the diluents are microcrystalline cellulose, lactose or combination thereof (see claim 15).
The examiner reminds Applicant that "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). 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. Id. (Applicant argued that the claimed composition was a pressure sensitive adhesive containing a tacky polymer while the product of the reference was hard and abrasion resistant. "The Board correctly found that the virtual identity of monomers and procedures sufficed to support a prima facie case of unpatentability of Spada’s polymer latexes for lack of novelty.")
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 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over NIETO et al. (WO2019/224058, IDS reference of 12/01/23).
Applicant Claims
Applicant claims a controlled release pharmaceutical tablet comprising the ingredients as recited.
Determination of the Scope and Content of the Prior Art (MPEP §2141.01)
The teachings of NIETO et al. are described in detail above and are herein incorporated by reference.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
NIETO et al. teach the limitations of claims 9-13 in obvious manner NIETO et al. teach the amounts in overlapping ranges. It is addressed by the prima facie arguments set forth below.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to produce the instant invention by following the teachings of NIETO et al. because NIETO et al. teach all of the claimed limitations as described in detail above and are incorporated herein by reference. With regard to the amount of active and other ingredients in the case where the claimed amounts"overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985). Furthermore, differences in concentration or amount will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955). It is within the purview of one of ordinary skill in the art to optimize the amounts absent evidence to the contrary. One of ordinary skill in the art would have had a reasonable chance of success in producing the instant invention by following the teachings of NIETO et al. because NIETO et al. teach substantially identical product.
In light of the forgoing discussion, one of ordinary skill in the art would have concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusions
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIGABU KASSA whose telephone number is (571)270-5867. The examiner can normally be reached on 8 AM-5 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIGABU KASSA/
Primary Examiner, Art Unit 1619