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 .
Claims 1-4, 7, 10-12, 14, 18, 20, 22, 25, 27-30, 32 and 33 are presented for examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/07/2026 has been entered.
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) 1-4, 7, 10-12, 14, 18, 20, 22, 25, 27-29, 30, 32 and 33 is/are rejected under 35 U.S.C. 103 as
being unpatentable over Lewis et al. (US 5986122) in view of Holm et al. (US 20060267352) and further
in view of Cohen et al. (Evaluation of clinical outcomes in patients with dry eye disease using lubricant
eye drops containing polyethylene glycol or carboxymethylcellulose)
The claims are drawn to a method of stabilizing a polyether compound in an aqueous formulation,
comprising mixing a chelate compound with the polyether compound, wherein the chelate compound is
thiosulfate, and the polyether compound is at least one selected from the group consisting of poloxamer
and polyethylene glycol, a composition comprising a polyether compound and a chelate compound,
wherein the composition is an aqueous formulation, the chelate compound is thiosulfate, and the
polyether compound is at least one selected from the group consisting of poloxamer and polyethylene
glycol, and a method for improving solubility of a poorly soluble compound upon the preparation of an
aqueous formulation which comprises the poorly soluble compound, comprising combining a
hydrophobic polyoxy aliphatic moiety- containing polyether compound and a hydratable compound with the aqueous formulation, wherein the hydrophobic polyoxy aliphatic moiety-containing polyether
compound is poloxamer, and the hydratable compound is polyethylene glycol.
Lewis et al. as it relates to claims 1-4, 7 and 10 teach the use of ascorbic and citric acid, their salts,
ethers, acid esters and mixtures thereof in a method for the prevention of peroxide formation, and/or
for decomposing peroxides already formed in polyethers. Lewis et al. teach that the polyethers are
made reactive to hydrosilylation by silanes and hydrosiloxanes. When the polyether treatment is done
with mixtures of ascorbic acid and sodium ascorbate and allyl polyethers, the hydrosilylation product contains reduced levels of propanol. See the Abstract and claim 1. Lewis et al. teach that addition of Antioxidants to already made polyether prevents peroxide formation and improve storage stability of polyether. This method also permits the recovery and use of poorly reacting polyether. The method arrests the formation of propanol as a by- product in copolymers made with allyl polyethers, thereby contributing to low odor and low viscosity in the resulting products. See (39). The formula of polyether is taught in claims 7 and 14. Lewis does not teach the use of thiosulfate as a chelating/antioxidant compound, the molecular weights of poloxamer and polyethylene glycol, and the use of mannitol or BHT. Such deficiencies are taught by Holm et al. Holm teaches the use of sodium thiosulfate in a composition comprising polyethylene glycol and poloxamer, which can be used as a stabilizing agent. See Para [0059]. The use of mannitol is taught in Para [0054].
Holm et al. as relates to claims 11, 12, 14, 18, 20, 22, 25, 27, 29, 30, 32 and 33 teach tacrolimus is a macrolide compound with useful immunosuppressive activity, antimicrobial activity and other pharmacological activities and is of value for the treatment or prevention of rejection reactions by transplantation of organs or tissues, graft versus host diseases, autoimmune diseases and infectious diseases. See Para [0004]. Holm further teaches that a modified release tacrolimus-containing pharmaceutical composition having the active ingredient dissolved or dispersed in a hydrophilic or water-miscible vehicle as described herein, preferably a vehicle selected among polyethylene glycols, polyoxyethylene oxides, poloxamers, polyoxyethylene stearates, poly-epsilon caprolactone, polyglycolized glycerides such as Gelucireo, and mixtures thereof, more preferably polyethylene glycol optionally in mixture with a poloxamer. A specific example of a useful mixture is a mixture of 70 w/w % polyethylene glycol 6000 (PEG6000) and 30 w/w % poloxamer 188. See Para [0048]. Holm teaches that In a preferred embodiment the vehicle is a polyethylene glycol (PEG), in particular a PEG having an average molecular weight of at least 1500, preferably at least 3000, more preferably at least 4000, especially at least 6000. The polyethylene glycol may advantageously be mixed with one or more other hydrophilic or water-miscible vehicles, for example a poloxamer, preferably in a proportion of between 1:3 and 10:1, preferably between 1:1 and 5:1, more preferably between and 3:2 4:1, especially between 2:1 and 3:1, in particular about 7:3. A specific example of a useful mixture is a mixture of PEG6000 and poloxamer 188 in the ratio 7:3. See Para [0107]. Holm teaches that for polyethylene glycols (PEG), the melting point (freezing point or pour point) increases as the average molecular weight increases. For example, PEG 400 is in the range of 4-8.degree. C., PEG 600 is in the range of 20-25.degree. C., PEG1500 is in the range of 44-48.degree. C., PEG2000 is about .degree. C., PEG 4000 is about 9.degree. C., PEG 6000 is about 65.degree. C. and PEG 8000 are about degree. C as claimed in claim 10 of the instant application. See Para [0108], claims 18, 20 and 22. Holm teaches useful poloxamers are for example poloxamer 188, poloxamer 237, poloxamer 338 or poloxamer 407 or other block copolymers of ethylene oxide and propylene oxide such as the Pluronic. and/or Tetronic. RTM. series. Suitable block copolymers of the Pluronic X series include polymers having a molecular weight of about 3,000 or more such as, e.g. from about 4,000 to about 20,000 and/or a viscosity (Brookfield) from about 200 to about 4,000 cps such as, e.g., from about 250 to about 3,000 cps as claimed in claim 7 of the instant application. See Para[0109]. The use of a buffering agent and a pH adjusting agent is taught in Para [0118]. Holm teaches that at least about 50% w/w of the total amount of tacrolimus and/or an analogue thereof is released about 24 hours, within about 22 hours, within about 20 hours, within about 18 hours, within 15 hours, within 12 hours, when tested in an in vitro dissolution test and employing a dissolution medium comprising a buffer having pH 7.5. See Para [0081]. The use of cyclodextrin and sodium carboxy methyl cellulose is taught in claim 16. Oral administration is taught in Para [0220] and examples. Topical administration is taught in Paras [0129] and [0149]. Holm teaches that any of the tacrolimus-containing dosage forms, compositions, dispersions or solutions of the invention may improve treatment of conditions that respond to tacrolimus treatment. See Para [0221]. Regarding claims 32 and 33 Cohen et al. teach the use of polyethylene glycol in an eye drop for the treatment of dry eye. See the abstract. Cohen et al. teach Systane Gel Drops (polyethylene glycol 400 0.4% and propylene glycol 03% were associated with significantly better corneal staining scores versus Refresh Liquigel Sodium carboxymethyl cellulose eye drops in patients with dry eye. Supportive efficacy outcomes were not significantly different between groups. Both treatments were well tolerated. It would have been obvious to a person skilled in the art to use the polyethylene glycol and poloxamer at the claimed molecular weight motivated by the teachings of Holm, which teaches the use of polyethylene glycol and poloxamer at the claimed molecular weight in combination with a hydratable compound as old and well known. The use of components, such as cyclodextrin and carboxymethyl cellulose is also taught by Holm. The topical and oral administration is also taught by Holm. The atmospheric pressure of claim 22 is related to a process of making and not the composition. The selection of a poorly soluble compound as claimed in claim 20, is considered to be within the skill of artisan in the absence of evidence to the contrary. The use of a polyether compound in an eye drop is taught by Cohen et al. The relied upon references in combination make clear that polyether compounds have been previously stabilized by the use of a chelating agent and they have been used in combination with a macromolecule pharmaceutical formulation in order to increase the stability of such compositions. The molecular weights of polyethylene glycol and poloxamer is also taught by the relied upon references. The mode of administration and their use in an eye dop is also taught by the relied upon references. Applicant has presented no evidence to establish the unexpected or unobvious nature of the claimed invention and as such claims 1-4, 7, 10-12, 14, 18, 20, 22, 25, 27-30 and 32-33 are properly rejected under35 U.S.C. 103(a).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617
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