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 .1
Status of Claims and Priority
Claims 1-3 and 5-10 are pending. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant’s election without traverse of the species of distinct excipient species in the reply filed on Aug 26 2025 is acknowledged. Examination is proceeding based on the elected species (lactose as diluent, povidone, aka PVP as the binder, isopropyl alcohol as the solvent and the lubricant magnesium stearate). Claims 1-3 and 5-10 read upon the elected species.
Information Disclosure Statements
The information disclosure statement (IDS) submitted on Nov 2 2022 is in compliance with the provisions of 37 CFR § 1.97. Enclosed with this Office Action is a return-copy of the PTO-1449 Forms with the Examiner's initials and signature indicating those references that have been considered.
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 1-3 and 5-10 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2014/147526 (WO 526) in view of Martin 2014, aka Martin, L.M., Rajabi-Siahboomi, A.R. (2014). Applications of Polyethylene Oxide (POLYOX) in Hydrophilic Matrices. [Chapter 5] In: Timmins, P., Pygall, S., Melia, C. (eds) Hydrophilic Matrix Tablets for Oral Controlled Release. AAPS Advances in the Pharmaceutical Sciences Series, vol 16. Springer, New York, NY.
WO 526 is cited on Applicant’s Nov 2, 2022 IDS as reference BE. Martin 2014 is cited on the accompanying PTO-892 form.
In terms of claim interpretation, the specification states the invention is directed to a “non-osmotic an extended release composition of Tofacitinib or salt thereof is used in the treatment of Rheumatoid Arthritis. . . . “ See abstract. The specification states “there is need in the art to provide a simple cost effective commercial feasible non[-]osmotic extended release [oral] tablet of Tofacitinib and which also avoids, minimizes problems associated with osmotic drug delivery system [sic] like Gastro intestinal obstruction. . . . [etc.]” See page 4, 4th full paragraph. “Osmotic drug delivery devices are composed of an osmotically active drug core, which is surrounded by a rate controlling semipermeable membrane.” See page 7, last paragraph.
Similar to the goals of the claimed invention, WO 526 is directed to achieve the goal of treating Rheumatoid arthritis with a sustained release oral composition of tofacitinib, with a desirable sustained pharmacokinetic release profile as defined therein. See paragraph 1, page 1. See also abstract and claim 1.
Note that the art recognized terms, polyethylene oxide, poly (ethylene oxide), PEO and POLYOX will be used interchangeably throughout this office action.
Claim 1 is directed to an extended release composition comprising
a) tofacitinib or a pharmaceutically acceptable salt thereof;
b) a mixture of two or more polyethylene oxides wherein the molecular weight of each of the polyethylene oxide ranges from 20,000 g/mol to 10,000,000 g/mol; and
c) one or more pharmaceutically acceptable excipients.
Regarding claim 1 WO 526 discloses a once daily pharmaceutical dosage form comprising tofacitinib, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said dosage form is a sustained release dosage form, and when administered to a subject has a mean area under the plasma
concentration versus time curve following administration as defined therein. See claim 1
WO 526 teaches a sustained release pharmaceutical dosage form of its claim 1, wherein said tofacitinib is embedded in a matrix which releases tofacitinib by eroding. See claim 48. Note, like the claimed invention, that disclaims an osmotic drug delivery system, this particular embodiment of WO 526 of claim 48, is distinguished from the osmotic drug delivery systems of WO 526’s claims 28-47.
Regarding the limitation of claim 1 and polyethylene oxide, WO 526 teaches sustained release pharmaceutical dosage form of claim 48, wherein the matrix of the dosage form comprises poly (ethylene oxide) aka PEO. See claim 50. Note that WO 526 teaches an equivalent interchangeable substitute to polyethylene oxide polymer matrix is a hydroxypropyl methylcellulose (HPMC) matrix, see claim 49, as both PEO and HPMC can be used interchangeably with WO 526 composition of claim 48.
See also page 16, first paragraph that notes “release modifying agents which can be optionally be formulated into the matrix include water-soluble polymers such as . . . hydroxypropyl methyl cellulose (HPMC) . . . methyl cellulose [ aka METHOCEL] [and its equivalents] poly (N-vinyl-2- pyrrolidinone) (PVP) [aka povidone], [and] poly(ethylene oxide) (PEO) [aka POLYOX]. . . .” See page 16, first paragraph.
As required by claim 1 and the suggestion of two or more polyethylene oxides, WO 526 teaches that for its sustained release matrix systems, a mixture of tofacitinib with one or more excipients selected to form a matrix capable of limiting the dissolution rate of the tofacitinib into a medium. See bottom page 15 bridging to top of page 16. As required by claim 1 such matrix materials include multiple polymers, such as poly (ethylene oxide) (PEO). See page 16, middle of page. The mixture of polymers of WO 526 suggests a mixture of two more PEOs as claimed.
As required by claim 1, WO 526 teaches a “one or more” additional pharmaceutically acceptable excipient, i.e., “polyacrylic acid.” See claim 51. See also Table 11, page 81, where a hydrophilic matrix tablet composition formulation comprising tofacitinib citrate and the following additional pharmaceutically acceptable excipients: the PEO equivalent Methocel (methyl cellulose) as matrix polymer, lactose monohydrate and magnesium stearate(s), is taught.
While WO 526 teaches the claimed tofacitinib comprising polyethylene oxide as a matrix and at least one additional pharmaceutically acceptable carrier, it does not teach polyethylene oxide excipients with the claimed MW weight ranges from 20000 g/mol to 10000000 g/mol.
To address this Martin and Rajabi - Siahboomi 2 (aka Martin 2014), teaches that polyethylene oxide (PEO, aka POLYOX) is an alternative to HPMC in hydrophilic matrices, where the physical and chemical properties make it a suitable candidate for use on its own or in combination with other polymers in hydrophilic matrix formulations. See Section 5.1 Introduction, page 12. With regard to the particular range MW range of 20000 to 10000000 g/mol of PEO, Martin 2014 teaches PEO, aka POLYOX compounds in weights that overlap the claimed range.3 See Tables 5.2 pages 124 bottom of page, reproduced below.
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Also note Figure 5.4 on top of page 130 noting different release profile for different weights of POLYOX (900000 MW, 40000000 MW, 7000000MW) providing a suggestion to one of ordinary skill in the art to mix and match various polyethylene oxides, to order to achieve desirable drug release profiles over time.
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In fact, Fig 5.4, with its varying drug release profiles suggests to a person having ordinary skill in the art (PHOSITA), that mixtures of PEO combined would result in adjustments of release profiles as each PEO of Fig. 5.4 has a unique profile, see WSR 1105 vs WSR-303.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the primary reference WO 526 to modify tofacitinib extended release formulations with combinations of polyethylene oxide matrices and other excipients with the secondary reference Martin 2014 in order to arrive at formulation of the claimed PEO, or POLYOX, molecular weights.
The PHOSITA would have had a reasonable expectation of success because the cited prior art note the necessity of formulating extended release tablet formulations of tofacitinib to treat rheumatoid arthritis (RA), in non-osmotic forms, with interchangeable polymer matrix systems of PEO mixtures in the MW weight ranges that overlap with the range of MW from 20000 to 10000000 g/mol.
Regarding claim 2, WO 526 discloses a non-osmotic drug delivery system, see above.
As required by the limitations of claim 3 where dose is to 11mg or 22 mg, WO 526 discloses: wherein the dosage is 11 mg of tofacitinib (see claim 23) and wherein the dose is 22 mg of tofacitinib (see claim 25). See also Table 11 disclosing a 22 mg tofacitinib tablet.
Regarding claim 5 and the limitation of a range where the two PEO mixture is from 1:0.1 to 1:100, while such range is not explicitly recited in WO 526, given that there would be only two PEO mixtures within the composition and the bottom limit of the range (0.1 :1 or 0.1%) would be the bare minimum of one PEO combined with a second PEO, where a value of 100:1 would approach the top upper limit of just below 100% of total combined PEO of the two PEO mixture, a PHOSITA would routinely optimize two PEO mixtures in concentration ratio between above 0.1% and under 100% as claimed.
Regarding claim 6 and the limitations of dosage forms claimed therein, WO 526 discloses its sustained release formulations are meant to include tablets, capsules, multiparticulates or beads. See page 11, first full paragraph. See also Table 11 on page 81 disclosing a 22 mg tofacitinib tablet.
Regarding claim 7 and the disclosed dissolution profile claimed therein, as the claimed composition is taught by the prior art, such dissolution profile is necessarily present. See MPEP 2112.01 II. 4
As required by claims 8-9 and the limitations of a diluent (lactose, microcrystalline cellulose, mannitol); binder (povidone aka polyvinylpyrrolidone aka PVP, hydroxy propyl cellulose (aka HPC)) solvent (isopropyl alcohol or water) and magnesium stearate as lubricant, these are taught in WO 526 as follows. Table 11 at page 81 of WO 526, teaches a tablet formulation relying on Methocel (PEO equivalent as a gel former providing controlled release), lactose as a filler and magnesium stearate as lubricant. WO 526 teaches solvents such as water and isopropanol at page 17, first paragraph, last line. WO 526 teaches binders including PVP and HPC. See page 35, 3rd paragraph.
As required by claim 10’s limitations of techniques, WO 526 teaches tofacitinib multiparticulates can be formed by techniques known in the art (said to be previously discussed with reservoir systems but NOT limited to) such as extrusion and spheronization, wet granulation and fluid bed (dry) granulation. See page 61, last paragraph.
Conclusion
In summary no claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/
Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a 371 of PCT/IB2021/054195 05/17/2021
FOREIGN APPLICATIONS
INDIA 202021020825 05/18/2020
This application has published as US 20230172934
2 Martin, L.M., Rajabi-Siahboomi, A.R. (2014). Applications of Polyethylene Oxide (POLYOX) in Hydrophilic Matrices. In: Timmins, P., Pygall, S., Melia, C. (eds) Hydrophilic Matrix Tablets for Oral Controlled Release. AAPS Advances in the Pharmaceutical Sciences Series, vol 16. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1519-4_5
3 See MPEP 2144.05 with regard to prima facie obviousness with overlapping ranges.
4 II. COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
"Products of identical chemical composition can not 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.").