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 .
Priority
This application claims foreign priority to INDIA 202211027609 (05/13/2022).
Status
Claims 1-5, 7-10 are pending.
Rejections not reiterated in this office action are withdrawn.
New 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 1-10 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 was amended to read:
A stable ophthalmic composition consisting of Loteprednol, … wherein the composition comprises Loteprednol having a particle size D50<1 um and D90 < 3 um.”
which is confusing because the “composition” has both “comprises” and “consisting of” which has conflicting meaning with respect to whether the composition is open or closed with respect to additional elements. MPEP 2111.03. One of skill in the art would find the claim ambiguous as to whether how the claim is open or closed-ended based on these terms. Thus, the claim and those that depend therefrom are rejected as indefinite.
For purposes of examination, the “comprises” language is interpreted as “wherein the Loteprednol comprises a particle size D50<1 um and D90 < 3 um.”
New 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.
(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.
Claims 1-2, 4-5, 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Popov et al. (US20150125539).
Popov teaches an ophthalmic composition of loteprednol etabonate (claim 1’s loteprednol), a (poly(ethylene oxide))-(poly(propylene oxide))-(poly(ethylene oxide)) triblock copolymer (claim 1’s suspending agent), Pluronic (claim 1’s excipient, claim 2’s surfactant), glycerin (claim 1’s excipient, claim 2’s viscosity modifier), sodium chloride (claim 1’s excipient, claim 2’s tonicity agent), EDTA (claim 1’s excipient, claim 2’s chelating agent) (Popov claim 28; [0464]: “aqueous suspension containing about 2-20% loteprednol etabonate (coarse or micronized crystals), about 0.2-20% Pluronic® F127, about 0.5-3% glycerin, about 0.1-1% sodium chloride, and about 0.001-0.1% EDTA was milled in the presence of milling media to produce a nanosuspension of loteprednol etabonate particles sized in the range of 200-300 nm.”). Regarding claim 1’s new limitation of particle size, Popov teaches the range of 200-300 nm (claim 44; [0464]).
Thus claims 1-2 are anticipated.
Regarding claim 4, Popov teaches the viscosity modifier is glycerin ([0464]).
Regarding claim 5, Popov teaches the surfactant is Pluronic, a poloxamer ([0464]).
Regarding claim 7, Popov teaches “a substantially neutral pH (e.g., about pH 7)” ([0350]).
New 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.
Claims 1-5, 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Popov et al. (US20150125539) in view of Shawer et al. (US20160213609).
Popov teaches an ophthalmic composition of loteprednol etabonate (claim 1’s loteprednol), a (poly(ethylene oxide))-(poly(propylene oxide))-(poly(ethylene oxide)) triblock copolymer (claim 1’s suspending agent), Pluronic (claim 1’s excipient, claim 2’s surfactant), glycerin (claim 1’s excipient, claim 2’s viscosity modifier), sodium chloride (claim 1’s excipient, claim 2’s tonicity agent), EDTA (claim 1’s excipient, claim 2’s chelating agent) (Popov claim 28; [0464]: “aqueous suspension containing about 2-20% loteprednol etabonate (coarse or micronized crystals), about 0.2-20% Pluronic® F127, about 0.5-3% glycerin, about 0.1-1% sodium chloride, and about 0.001-0.1% EDTA was milled in the presence of milling media to produce a nanosuspension of loteprednol etabonate particles sized in the range of 200-300 nm.”). Popov teaches particle sizes in the range of 200-300 nm (claim 44; [0464]). Popov teaches “a substantially neutral pH (e.g., about pH 7)” ([0350]).
Shawer teaches a stable ophthalmic suspensions comprising loteprednol etabonate (claim 15: “loteprednol etabonate at 0.38 wt %”), a carboxyvinyl polymer (claim 7: “wherein the suspending agent comprises a carboxyvinyl polymer.”), glycerin and propylene glycol (claim 13), poloxamer 407, sodium chloride, edetate sodium ([0075], [0084]-[0088]). Shawer teaches the composition includes “a non-ionic cellulose derivative as a supplemental suspending agent” ([0073]). Shawer teaches “ the ophthalmic active ingredient is present as particles having Dv90<3 μm and Dv50<1 μm.” (claim 18). Shawer teaches the suspension “is storage stable for at least one year.” (claim 2). Shawer teaches a formulation without HPMC, i.e. Soluplus ([0118]).
One of ordinary skill in the art following the combined teaching of Popov and Shawer in the same field of endeavor ophthalmic suspensions of loteprednol etabonate would have considered combining the teachings of the prior art to in formulating stable ophthalmic suspensions. One of ordinary skill in the art would have considered routine substituting equivalent elements such as Shawer’s supplemental suspension agent for the equivalent of caboxyvinyl polymer (see Shawer [0009]). One of ordinary skill in the art would consider such substitution routine in the art of formulation and arrive at the claimed invention with a reasonable expectation of success.
Furthermore, one of ordinary skill in the art would have been motivated by each of the prior art’s teaching of the need to optimize the formulation stability and have an expectation to arrive at a stability of more than a year as taught by Shawer.
One of ordinary skill in the art would have considered further optimization of the formulation to improve the pharmaceutical properties including stability, penetration and absorption (Popov [0005], [0079], [0093], [0094]; Shawer [0069]-[0072], [0078]) through routine experimentation similar to as was performed in the prior art.
In addition, as per MPEP 2144.05:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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 reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In reKulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was “unexpectedly good”); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
In view of the desired to optimize the pharmaceutical properties as disclosed by Popov and Shawer, it would have been routine optimization to arrive at the claimed invention. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range because as taught by Popov and Shawer, the ratios and particle size are results effective variables that our routinely use to improve formulations.
Response to Applicant Remarks
Applicant argues that that it was surprising that the particle size D90< 3um did not show any sign of instability on long term storage.
The prior art teaches the same benefit from a proper formulation including small particle size to improve stability and effectiveness (Shawer [0069][0071], claims 2 and 18; Popov [0005], [0010], Examples).
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626