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 1-12, 15-19 and 23-25 are pending and are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/16/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application is a U.S. National phase application under 35 U.S.C 371 of PCT application PCT/IB2022/054640, filed 5/18/2022, which claims priority under 35 U.S.C 119 (e) from provisional application serial No. 63269675, filed 3/21/2022 and serial no. 63191293, filed 05/20/2021.
Claim Rejections - 35 USC § 112
The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
Claim 16 is rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 16 is vague and indefinite in that the metes and bounds of the “aqueous suspension ” are unclear and there is no clear and positive prior antecedent basis for the term “aqueous suspension” in the claim because claim 1 upon which it depends do not define the composition as aqueous suspension. It would be remedial to amend the claim to provide a clear antecedent basis for the term “aqueous suspension”.
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, 8-9,15 , 17, 18, 19 and 23-25 are rejected under 35 U.S.C. 102 (a) (1) and under 35 U.S.C 102(a)(2) as being anticipated Boss et al (US 2022/0064164, Priority date 11/29/2019)
Instant claims are drawn to a formulation comprising 3-((3-(4-(2-(isobutylsulfonyl)phenoxy)-3- (trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5,5-dimethyl-1-(2- morpholinoethyl)imidazolidine-2,4-dione or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and a method of lowering a subject's meibum melting temperature and/or increasing meibum outflow from a subject's meibomian glands or method of reducing obstruction of meibum outflow from a subject's meibomian gland or a method for the treatment of dry eye disease or Meibomian gland dysfunction (MGD) in a subject in need of treatment thereof, comprising administering a therapeutically effective amount of the said formulation.
Boss et al., discloses the instantly claimed compound 3-((3-(4-(2-(isobutylsulfonyl)phenoxy)-3- (trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5,5-dimethyl-1-(2- morpholinoethyl)imidazolidine-2,4-dione [0133] (claim 21) and pharmaceutical compositions comprising the compound with a pharmaceutically acceptable carrirers, (claim 23, [0584][0608-0609], [0612]). Boss et al. discloses that their inventive compound is present in the pharmaceutical composition for topical administration at a concentration of at least about 0.5% w/w, at least about 1.0% w/w, at least about 1.5% w/w, at least about 2.0% w/w [0595-0596]. They disclose that their composition can be formulated for ophthalmic or topical administration [0586] for administration topically to the eyelid, or eyelid margin [0587]. They disclose their pharmaceutical composition as having a viscosity in a range from about 50 cps to about 1000 cps, about 50 cps to about 500 cps, about 50 cps to about 200 cps, or about 60 cps to about 120 cp and non-aqueous carrier may comprise an oil such as vegetable oil and may include a monomeric polyol such as, glycerol, propylene glycol, and ethylene glycol, polymeric polyols such as polyethylene glycol, dextran such as dextran 70; water soluble proteins such as gelatin, polymers such as polyvinyl alcohol, polyvinylpyrrolidone, and povidone; carbomers, such as carbomer 934P. carbomer 941, carbomer 940 and carbomer 974P; and gums such as HP-guar[0588]. Boss et al. further disclose additional excipients in their formulation to include tonicity enhancers such as ionic tonicity enhancers such as Sodium Chloride and nonionic tonicity enhancing agents such as mannitol or propylene glycol and the pharmaceutical compositions may have an osmolality of about 280 to about 320 mOsm [0591] , Solubilizers such as tyloxapol, fatty acid glycerol polyethylene glycol esters, fatty acid polyethylene glycol esters, polyethylene glycols, glycerol ethers, or cyclodextrins [0593]. For the adjustment of pH , they disclose use of physiological pH buffers such as boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, tris(hydroxymethyl)aminomethane (TRIS), and various mixed phosphate buffers to maintain the pH from about 6.5 to 7.8 [0590]. Boss et al. discloses that pharmaceutical compositions are delivered to the surface of the eye or the eyelid one to four times a day, depending on the routine discretion of the skilled clinician. [0601] , Boss et al. discloses that their composition results In a decrease of at least about 10%, at least about 15%, at least about 20%, or at least about 30% in the symptoms and/or signs of meibomian gland dysfunction, including one or more of ocular dryness, ocular discomfort or pain, eye itchiness, blurry vision, heavy or fatigued eyes, watery eyes, ocular hyperemia, ocular burning or stinging, grittiness or foreign body sensation, or photophobia or light sensitivity, crusty or red or swollen eyelids or eyelid margins, sensitivity to environmental factors such as wind or low humidity, or loss of tolerability to contact lens use [0603]. Boss et al. discloses that the administration of their composition thereof, results in a decrease in the melting temperature of meibum in the subject[0643], decreases the signs and/or symptoms of meibomian gland dysfunction or dry eye disease or ocular surface disease (claim 51, [0644]) and that their inventive compound robustly upregulate SCD1 protein production in SZ95 cells and in turn increase the desaturation index of the lipids these cells produce, thereby , the viscosity of meibum may be lowered leading to better meibum outflow in vivo and ameliorating the signs and symptoms of Meibomian gland dysfunction and evaporative dry eye disease [0986].
Therefore the composition and method disclosed by Boss et al. fully anticipates instant claims 1-2, 8-9,15 , 17, 18, 19 and 23-25.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 3-7 and 10-12 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Boss et al. (US 2022/0064164, Priority date 11/29/2019) as applied to claims 1-2, 8-9,15 , 17, 18, 19 and 23-25 (in the above anticipation rejection) further in view of
Instant claims 3-7 and 10-12 are drawn to various excipients such as castor oil, carbomer, sodium chloride, glycerine, mannitol and HCl or tromethamine or NaOH for pH adjustment.
The teachings of Boss et al. is reiterated below:
Boss et al., discloses the instantly claimed compound 3-((3-(4-(2-(isobutylsulfonyl)phenoxy)-3- (trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5,5-dimethyl-1-(2- morpholinoethyl)imidazolidine-2,4-dione [0133] (claim 21) and pharmaceutical compositions comprising the compound with a pharmaceutically acceptable carrirers, (claim 23, [0584][0608-0609], [0612]). Boss et al. discloses that their inventive compound is present in the pharmaceutical composition for topical administration at a concentration of at least about 0.5% w/w, at least about 1.0% w/w, at least about 1.5% w/w, at least about 2.0% w/w [0595-0596]. They disclose that their composition can be formulated for ophthalmic or topical administration [0586] for administration topically to the eyelid, or eyelid margin [0587]. They disclose their pharmaceutical composition as having a viscosity in a range from about 50 cps to about 1000 cps, about 50 cps to about 500 cps, about 50 cps to about 200 cps, or about 60 cps to about 120 cp and non-aqueous carrier may comprise an oil such as vegetable oil and may include a monomeric polyol such as, glycerol, propylene glycol, and ethylene glycol, polymeric polyols such as polyethylene glycol, dextran such as dextran 70; water soluble proteins such as gelatin, polymers such as polyvinyl alcohol, polyvinylpyrrolidone, and povidone; carbomers, such as carbomer 934P. carbomer 941, carbomer 940 and carbomer 974P; and gums such as HP-guar[0588]. Boss et al. further disclose additional excipients in their formulation to include tonicity enhancers such as ionic tonicity enhancers such as Sodium Chloride and nonionic tonicity enhancing agents such as mannitol or propylene glycol and the pharmaceutical compositions may have an osmolality of about 280 to about 320 mOsm [0591] , Solubilizers such as tyloxapol, fatty acid glycerol polyethylene glycol esters, fatty acid polyethylene glycol esters, polyethylene glycols, glycerol ethers, or cyclodextrins [0593]. For the adjustment of pH , they disclose use of physiological pH buffers such as boric acid, sodium borate, potassium citrate, citric acid, sodium bicarbonate, tris(hydroxymethyl)aminomethane (TRIS), and various mixed phosphate buffers to maintain the pH from about 6.5 to 7.8 [0590]. Boss et al. discloses that pharmaceutical compositions are delivered to the surface of the eye or the eyelid one to four times a day, depending on the routine discretion of the skilled clinician. [0601] , Boss et al. discloses that their composition results In a decrease of at least about 10%, at least about 15%, at least about 20%, or at least about 30% in the symptoms and/or signs of meibomian gland dysfunction, including one or more of ocular dryness, ocular discomfort or pain, eye itchiness, blurry vision, heavy or fatigued eyes, watery eyes, ocular hyperemia, ocular burning or stinging, grittiness or foreign body sensation, or photophobia or light sensitivity, crusty or red or swollen eyelids or eyelid margins, sensitivity to environmental factors such as wind or low humidity, or loss of tolerability to contact lens use [0603]. Boss et al. discloses that the administration of their composition thereof, results in a decrease in the melting temperature of meibum in the subject[0643], decreases the signs and/or symptoms of meibomian gland dysfunction or dry eye disease or ocular surface disease (claim 51, [0644]) and that their inventive compound robustly upregulate SCD1 protein production in SZ95 cells and in turn increase the desaturation index of the lipids these cells produce, thereby , the viscosity of meibum may be lowered leading to better meibum outflow in vivo and ameliorating the signs and symptoms of Meibomian gland dysfunction and evaporative dry eye disease [0986].
Boss et al. discloses that their pharmaceutical compositions comprise ophthalmologically acceptable preservatives, surfactants, viscosity enhancers, penetration enhancers, buffers, sodium chloride, and water to form an aqueous, sterile ophthalmic suspension or solution [0598] and further .explicitly discloses that methods of preparing various pharmaceutical composition are known to those of skill in the art and may be described in, for example, in the Handbook of Pharmaceutical Excipients, American Pharmaceutical Association (current edition); Pharmaceutical Dosage Forms Tablets (Lieberman, Lachman and Schwartz, editors) current edition, published by Marcel Dekker, Inc., as well as Remington's Pharmaceutical Sciences (Arthur Osol, editor), 1553-1593 (current edition) [0585]. Boss et al. discloses their composition to be in the form of suspensions [0598]
In addition, Boss et al. while teaching the inclusion of vegetable oil and solubilizers in their composition , fails to specifically recite the polyoxyl 40 hydrogenated castor oil and the amount present in the composition , while teaching the inclusion of carbomer in their composition fails to teach the specific carbomer homopolymer type B and the amount in the composition, while teaching inclusion of NaCl as tonicity enhancer, fails to teach NaCl as a carrier and the amount present, while teaching humectant, fails to teach glycerin and amount present, while they teach mannitol and propylene glycol, fails to teach amount present and the exact formulation claimed in instant claim 12 is not taught by Boss et al. Boss et al. also teach that the amount and type of excipient added is in accordance with the particular requirements and is generally in the range of from approximately 0.0001 to approximately 90% by weight [0594].
Boss et al. teaches the key excipients that goes into an ophthalmic formulations which are instantly claimed , vegetable oil which includes instantly claimed castor oil, NaCl as a tonicity enhancer which could also function as a carrier, Mannitol and propylene glycol as carriers as noted above. Further, excipients used in the ophthalmic compositions and formulation of ophthalmic compositions are well known in the pharmaceutical arts. As such it would have been prima facia obvious to a person of ordinary skill in the art to arrive at the instant claims motivated and guided by teachings of Boss et al. and what is well known in the art.
Further it is recognized that pharmaceutical excipients may perform more than one function, and are therefore characterized as having different uses depending on the particular application. While the use of an excipient in the context of a particular formulation may determine the function of the excipient, the inclusion of any particular excipient into any one or more category as set forth above is not meant to limit the function of that excipient.
With regards to claim 16, Boss et al. teaches suspension formulation of the instantly claimed compound and formulating suspensions in pharmaceutical arts is well known in the art and it is also well know to optimize the particle size in the suspension for maximum absorption, absence of evidence to the contrary.
With regards to instant claim 19, it will be well within the purview of an ordinary skilled artisan to develop an ophthalmic formulation of the compound taught by Boss et al. without hydroxyethylcellulose.
Boss et al, provides a clear motivation and suggestions to formulate an ophthalmic composition with the instantly claimed compound suitable for administration to the eyes for the purpose it serves. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. Thus, absent some demonstration of unexpected results from the claimed parameters, the optimization of ingredient amounts would have been obvious at the time of applicant's invention. With regards to the amount of each of the excipient added to the composition. it would be within the skill of an ordinary artisan to be able to optimize the concentrations of each of the excipient to maximize its effect and utility in the composition. It is noted that "[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). An ordinarily skilled artisan would arrive at the instantly claimed concentration while conducting routine optimization testing to achieve this goal. As such a person of ordinary skill in the art would be imbued with a reasonable expectation of success in formulating the instantly claimed composition , absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 2 and 23-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 8, 14-15 U.S. Patents 11,427,586 (‘586)
Instant claims are drawn to a formulation comprising 3-((3-(4-(2-(isobutylsulfonyl)phenoxy)-3- (trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5,5-dimethyl-1-(2- morpholinoethyl)imidazolidine-2,4-dione or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and a method of lowering a subject's meibum melting temperature and/or increasing meibum outflow from a subject's meibomian glands or method of reducing obstruction of meibum outflow from a subject's meibomian gland or a method for the treatment of dry eye disease or Meibomian gland dysfunction (MGD) in a subject in need of treatment thereof, comprising administering a therapeutically effective amount of the said formulation.
Claims 1-5, 7, 8, 14-15 of ‘589 recites the instantly claimed composition comprising 3-((3-(4-(2-(isobutylsulfonyl)phenoxy)-3- (trifluoromethyl)phenyl)-1,2,4-oxadiazol-5-yl)methyl)-5,5-dimethyl-1-(2- morpholinoethyl)imidazolidine-2,4-dione or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable carriers and a method for the treatment of dry eye disease or Meibomian gland dysfunction (MGD) in a subject in need of treatment thereof, comprising administering a therapeutically effective amount of the said formulation.
As such the claims of ‘586 anticipates instant claims.
Instantly claimed method of lowering a subject's meibum melting temperature and/or increasing meibum outflow from a subject's meibomian glands or method of reducing obstruction of meibum outflow from a subject's meibomian gland would inherently occur in the method of ’586 and is therefore anticipated.
Conclusion
Claims 1-12, 15-19 and 23-25 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Dierdre (Renee) Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SAVITHA M RAO/Primary Examiner, Art Unit 1691