DETAILED ACTION
Claims 1-29, 32-35, 37-68, 70-72, 74-76, were stand cancelled. Claims 30-31, 36, 69, 73 and 77-93 are pending.
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 is a DIV of 16/955,659 (06/18/2020; PAT 11,826,467) which is a 371 of PCT/US18/66235 (12/18/2018) which claims benefit of 62/607,429 (12/19/2017) and claims benefit of 62/728,564 (09/07/2018) as reflected in the filing receipt issued February 15 2024.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62607429 and 62728564, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
The claims as amended September 4 2026 recite methods comprising administering a pharmaceutical composition comprising a mucoadhesive polymer comprising chitosan and pregabalin or a pharmaceutically acceptable salt there. As well as claiming a reduction of internal pressure of one or both eyes of at least 30% by administering this composition as well as the cumulative amount of pregabalin released is determined using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes. The prior filed applications provide no discussion on bioadhesion or the release rate. While these prior filed applications mention chitosan and mention pregabalin. The disclosures fail to provide support for a composition comprising just these two ingredients nor do they provide support for a reduction of internal pressure of at least 30% or measurement via fast micro-equilibrium dialysis with semi-permeable regenerated cellulose membranes. These prior filed applications only ever teach the mucoadhesive polymer which could be chitosan as part of a microemulsion. A description which renders the claim invention obvious does not satisfy the written description requirement (p 1172, Ariad v. Eli Lilly, 598 F3d 1336, 94 USPQ2d 1161, citing Lockwood v. Am. Airlines). MPEP 2163.
Therefore, the effective filing date of claims 30-31, 36, 69, 73 and 77-93 is December 18 2018 as all of these claim limitations recite a composition comprising pregabalin and chitosan without more. While support for the express limitation in claims 31, 36, 73, 77-78 and 89-90 is found in the prior filed applications, since these claims depend from a claim requiring chitosan and pregabalin they also do not find support in the prior filed applications.
Claims 79-80 recite the combination of pregabalin and chitosan but with additional limitations not supported (higher degree of bioadhesion) and at least about 90%.
Regarding claims 81-84, the prior filed applications recite a broader range. However, since there is no evidence of an unexpected effect of the upper limit (about 1.2%), these limitations are deemed supported. But they require the unsupported limitations of chitosan and pregabalin.
Regarding claims 85-88 and 91, support for these limitations is not found.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on January 18 2024, April 30 2024, June 15 2026 and September 8 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Indefiniteness
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.
Claim 73 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 73 recites the limitation "the inhibitor" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 73 depends from claim 69 which was amended to remove any recitation to an inhibitor. The recitation pregabalin which is now recited in claim 69 is not the same scope as inhibitor.
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 of this title, 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 30-31, 36, 69, 73, 77-90 and 92-93 are rejected under 35 U.S.C. 103 as being unpatentable over Chintalapudi et al. (Nature Communications, 2017, cited on PTO Form 1449) in view of de Oliveira Fulgêncio et al. (Journal of Ocular Pharmacology and Therapeutics, 2012).
Applicant Claims
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject.
The instant application claims a method for reducing intraocular pressure in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby reducing intraocular pressure in the subject
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject, wherein the pharmaceutical composition achieves a higher degree of bioadhesion to mucin on one or both eyes as compared to a pharmaceutical composition comprising a mucoadhesive polymer comprising sodium alginate or carbomer.
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject, wherein the cumulative amount of pregabalin released from the pharmaceutical composition following administration is at least about 90%.
The instant application claims a method of improving bioadhesion of a topical ophthalmic pharmaceutical composition comprising pregabalin, wherein the method comprises combining pregabalin and chitosan to form the topical ophthalmic pharmaceutical composition.
The instant application claims a method of improving the duration of release of a topical ophthalmic pharmaceutical composition comprising pregabalin, wherein the method comprises combining pregabalin and chitosan to form the topical ophthalmic pharmaceutical composition.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Chintalapudi et al. is directed to systems genetics which identifies a role of Cacna2d1 regulation in elevated intraocular pressure and glaucoma susceptibility. Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Elevated intraocular pressure (IOP) is one of the most significant risk factors contributing to visual field loss in this disease. Because IOP can be medically controlled, IOP reduction is the first-line therapeutic option in glaucoma (page 2, left column, first paragraph). Taught is that Cacna2d1 modulates IOP and block the function of its gene product with pregabalin reduces IOP in a dose-dependent and haplotype-specific manner (page 2, left column, last paragraph). Shown in Figure 5 is the IOP-lowering potency of pregabalin. Taught are single application of pregabalin from 0.3 to 1.2%. A single dose of pregabalin eye drops (0.9%) lowers IOP by 22.1% wherein reductions up to 30% are shown (page 7).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Chintalapudi et al. teaches the treatment of POAG by reducing intraocular pressure with eye drops of pregabalin, Chintalapudi et al. does not expressly teach chitosan. However, this deficiency is cured by de Oliveira Fulgêncio et al.
de Oliveira Fulgêncio et al. is directed to a new mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate an in vivo evaluation. High levels of intraocular pressure (IOP) represent recognized key risk factor in the development of glaucoma. Timolol maleate is one of the main options for the medical treatment of open-angle glaucoma. Drugs administered in conventional topical ophthalmologic formulation tend to present a poor bioavailability. The majority of ophthalmic preparations can be found in the form of aqueous solutions and suspensions. These liquid forms are quickly drained from the conjunctival sac to the nasolacrimal duct leading to low availability of the drug at the target site, systemic side effects and bad patient compliance (page 350). Chitosan is a polycationic biopolymer. Chitosan is able to develop molecular attraction forces through electrostatic interactions with mucus negative charges, giving way to the mucoadhesion process. Biodegradability, biocompatibility and nontoxicity are included in favorable biological properties that allow for their use as vehicles for ophthalmic formulations. The efficacy of topical delivery system depends on the interaction of the ocular mucosa, slow degradation, and the release of the drugs within the ocular tissues. Chitosan hydrogels when compared with commercial drug solutions have shown higher corneal residence times. Taught is a suitable and mucoadhesive system consisting of the drug (TM) and chitosan as a prolonged treatment device (page 351, left column). The amount of drug released from chitosan films was shown in Fig. 3. In 2 weeks 85% of the drug was released whose total in vitro content was released within 4 weeks (page 353, left column).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Chintalapudi et al. and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin. One skilled in the art would have been motivated to utilize chitosan due to its mucoadhesive properties. Since de Oliveira Fulgêncio et al. teaches the efficacy of topical delivery system depends on the interaction of the ocular mucosa, slow degradation, and the release of the drugs within the ocular tissues and chitosan hydrogels when compared with commercial drug solutions have shown higher corneal residence times provides motivation to utilize chitosan with any drug desired to be delivered topically.
Regarding claims 30, 69 and 89-90, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Chintalapudi et al. and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin to treat glaucoma. One skilled in the art would have been motivated to administer the composition to reduce intraocular pressure with both Chintalapudi et al. and de Oliveira Fulgêncio et al. recognize is a key factor in glaucoma. One skilled in the art would have been motivated to administer the composition topically to one or both eyes as both Chintalapudi et al. and de Oliveira Fulgêncio et al. suggest this type of administration. One skilled in the art would have been motivated to administer the composition in the particular time frame necessary to achieve the desired treatment. Depending on the concentration of the drug and the release rate, one skilled in the art would recognize that the frequency of delivery would have to be varied to ensure effective treatment.
Regarding claim 31, Chintalapudi et al. teaches POAG.
Regarding claim 36 and 73, Chintalapudi et al. teaches topical application via eye drops. de Oliveira Fulgêncio et al. teaches chitosan hydrogels, when compared with commercial drug solutions, have shown higher corneal residence times (page 351, left column). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Chintalapudi et al. and de Oliveira Fulgêncio et al. and utilize a hydrogel of chitosan and pregabalin as eye drops. One skilled in the art would have been motivated to utilize this form as it is a common method of application of ophthalmic solutions.
Regarding claim 79, as set forth above, treating glaucoma with pregabalin and chitosan is obvious. The recitation “wherein the pharmaceutical composition achieves a higher degree of bioadhesion to mucin on one or both eyes as compared to a pharmaceutical composition comprising a mucoadhesive polymer comprising sodium alginate or carbomer” is the result of using chitosan. Since the use of chitosan is obvious for the reasons set forth above and the reference does not teach sodium alginate or carbomer, the wherein clause merely limits the composition to a structure with chitosan which is taught by the cited prior art.
Regarding claim 80, de Oliveira Fulgêncio et al. teaches total in vitro content was released within 4 weeks.
Regarding claims 81-84, Chintalapudi et al. teaches single application of pregabalin from 0.3 to 1.2% which overlaps the instant claims. In the case where the claimed ranges "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). Note MPEP 2144.05.
Regarding claims 85-88, Chintalapudi et al. teaches a single dose of pregabalin eye drops (0.9%) lowers IOP by 22.1% wherein reductions up to 30% are shown.
Regarding claim 92, combining pregabalin and chitosan is obvious for the reasons set forth above. Regarding “improving bioadhesion of a topical ophthalmic pharmaceutical composition”, when reading the preamble in the context of the entire claim, the recitation improving bioadhesion is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As set forth above, de Oliveira Fulgêncio et al. teaches chitosan is mucoadhesive thus inclusion of chitosan would be expected to improve bioadhesion of a topical ophthalmic pharmaceutical composition.
Regarding claim 93, de Oliveira Fulgêncio et al. teaches that the use of chitosan improves the duration of release.
Claim 91 is rejected under 35 U.S.C. 103 as being unpatentable over Chintalapudi et al. in view of de Oliveira Fulgêncio et al. as applied to claims 30-31, 36, 69, 73, 77-90 and 92-93 above and in further view of Hitzman et al. (Journal of Pharmaceutical Sciences, 2005).
Applicant Claims
The instant application claims wherein the cumulative amount of pregabalin released is determined using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Chintalapudi et al. and de Oliveira Fulgêncio et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While measuring drug release is discussed, measuring using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes is not expressly taught. However, this deficiency is cured by Hitzman et al.
Hitzman et al. is directed to measurement of drug release from microcarriers by microdialysis. It is taught that drug release can be readily obtained by microdialysis (abstract). The microdialysis is taught as using a cellulose membrane (page 1459). The concentration-time profiles obtained by microdialysis sampling were precise. The two curves are close to being symmetrical and show that equilibrium is reached after 5-6 h (page 1461, right column, last paragraph).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Chintalapudi et al., de Oliveira Fulgêncio et al. and Hitzman et al. and utilize microdialysis to determine release rate. As taught by Hitzman et al. release rates can be readily obtained by microdialysis. Thus, it would have been obvious to utilize known standard practice to measure the release rate. Reading the claimed semi-permeable cellulose membrane, Hitzman et al. teaches a cellulose membrane to filter and thus is clearly semipermeable. Reading the claimed fast equilibrium, Hitzman et al. teaches microdialysis reaches equilibrium quickly in 5-6 hr.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 30-31, 36, 69, 73 and 77-93 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 30-31, 36, 69, 73 and 77-93 of copending Application No. 18920652 (USPGPUB No. 20250041219). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Copending claim 30 recites the exact same scope as instant claim 30.
Both claim recite a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject. The claims are word for word the same.
The remaining claims are all exactly the same as instantly claimed except for claim 73. Instant claim 73 recites “the inhibitor” whereas copending claim 73 recites “the composition”. Since the recitation “the inhibitor” lacks antecedent basis, it is the examiner position that the scope is exactly the same because the proper antecedent basis would be for the composition.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 30-31, 36, 69, 73, 77-90 and 92-93 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 11826467. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The examiner notes that while the instant application in the priority claim is listed as a DIV of 16955659 (US Patent 11826467), as set forth in the notice of Allowance the restriction requirement was withdrawn and the provisions of 35 USC 121 are no longer applicable.
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject.
The instant application claims a method for reducing intraocular pressure in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby reducing intraocular pressure in the subject
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject, wherein the pharmaceutical composition achieves a higher degree of bioadhesion to mucin on one or both eyes as compared to a pharmaceutical composition comprising a mucoadhesive polymer comprising sodium alginate or carbomer.
The instant application claims a method for treating glaucoma in a subject in need thereof, comprising topically administering to one or both eyes of the subject an effective amount of a pharmaceutical composition comprising pregabalin or a pharmaceutically acceptable salt thereof and a mucoadhesive polymer comprising chitosan, thereby treating glaucoma in the subject, wherein the cumulative amount of pregabalin released from the pharmaceutical composition following administration is at least about 90%.
The instant application claims a method of improving bioadhesion of a topical ophthalmic pharmaceutical composition comprising pregabalin, wherein the method comprises combining pregabalin and chitosan to form the topical ophthalmic pharmaceutical composition.
The instant application claims a method of improving the duration of release of a topical ophthalmic pharmaceutical composition comprising pregabalin, wherein the method comprises combining pregabalin and chitosan to form the topical ophthalmic pharmaceutical composition.
Patent ‘467 claims a method for treating glaucoma in a subject in need thereof, comprising administering to the subject an effective amount of a microemulsion, wherein administering the microemulsion reduces the intraocular pressure of the subject. As claimed the microemulsion comprising: (a) a discontinuous internal phase comprising an aqueous solution encompassed within an internal emulsifier, wherein the aqueous solution comprises pregabalin; (b) a continuous oil phase encompassing the internal phase; (c) an external emulsifier encompassing the oil phase; and
(d) an aqueous phase surrounding the external emulsifier and comprising a hydrogel comprising a mucoadhesive polymer, wherein the microemulsion is a water-in-oil-in-water microemulsion and comprises globules formed by (a)-(c) that are between about 1 nm and about 50 nm in diameter. As claimed the mucoadhesive polymer is chitosan. The microemulsion is administered to one or both eyes of the subject. The administration is done once per day. Topical formulation is claimed. The concentration of the aqueous solution is 0.5-35% w/w.
While Patent ‘467 claims the mucoadhesive polymer can be chitosan, Patent ‘467 does not expressly claim the combination.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize chitosan as the mucoadhesive polymer. It would have been obvious to one of ordinary skill in the art to try any of the specifically taught mucoadhesive polymers as a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2141 KSR International CO. v. Teleflex Inc. 82 USPQ 2d 1385 (Supreme Court 2007).
Regarding claims 81-84, Patent ‘467 claims the pregabalin is part of the aqueous solution and the aqueous solution is taught in an overlapping amount. In the case where the claimed ranges "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). Note MPEP 2144.05.
Regarding claims 85-88, while Patent ‘467 claims the composition reduces the internal pressure of one or both eyes, Patent ‘467 is silent to the degree of reduction. One skilled in the art would manipulate the concentration of the pregabalin in order to achieved the desired level of reduction of internal pressure in order to treat glaucoma.
Regarding claim 92, combining pregabalin and chitosan is obvious for the reasons set forth above. Regarding “improving bioadhesion of a topical ophthalmic pharmaceutical composition”, when reading the preamble in the context of the entire claim, the recitation improving bioadhesion is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As set forth above, Patent ‘467 teaches chitosan is mucoadhesive thus inclusion of chitosan would be expected to improve bioadhesion of a topical ophthalmic pharmaceutical composition.
Regarding claim 93, the only method step claimed is combining pregabalin and chitosan. Since the use of chitosan is obvious for the reasons set forth above, the instantly claimed method step is claimed.
Claims 91 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-39 of U.S. Patent No. 11826467 as applied to claims 30-31, 36, 69, 73, 77-90 and 92-93 above in view of Hitzman et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims wherein the cumulative amount of pregabalin released is determined using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes.
The teachings of Patent ‘467 are set forth above.
Patent ‘467 does not claim a step of measuring drug release using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes is not expressly taught. However, this deficiency is cured by Hitzman et al.
Hitzman et al. is directed to measurement of drug release from microcarriers by microdialysis. It is taught that drug release can be readily obtained by microdialysis (abstract). The microdialysis is taught as using a cellulose membrane (page 1459). The concentration-time profiles obtained by microdialysis sampling were precise. The two curves are close to being symmetrical and show that equilibrium is reached after 5-6 h (page 1461, right column, last paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Patent ‘467 and Hitzman et al. and utilize microdialysis to determine release rate. As taught by Hitzman et al. release rates can be readily obtained by microdialysis. Thus, it would have been obvious to utilize known standard practice to measure the release rate. Reading the claimed semi-permeable cellulose membrane, Hitzman et al. teaches a cellulose membrane to filter and thus is clearly semipermeable. Reading the claimed fast equilibrium, Hitzman et al. teaches microdialysis reaches equilibrium quickly in 5-6 hr.
Claims 30-31, 36, 69, 73, 77-90 and 92-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10-11 and 24-28 of copending Application No. 18686086 (USPGPUB No. 20240423937) in view of de Oliveira Fulgêncio et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘086 claims a method of treating ocular pain in a subject, the method comprising topically administering to one or both eyes of the subject in need thereof an effective amount of an ocular pharmaceutical composition comprising pregabalin (PRG). As claimed the ocular composition contains about 0.001% to about 1.2% of pregabalin (PRG). As claimed, the composition is administered via eye drop and administered once per day. As claimed the subject has glaucoma.
While copending ‘086 claims administering to the same subject (i.e. subject with glaucoma) the same drug (i.e. pregabalin), copending ‘086 does not expressly claim the inclusion of chitosan in the composition. However, this deficiency is cured by de Oliveira Fulgêncio et al.
de Oliveira Fulgêncio et al. is directed to a new mucoadhesive chitosan film for ophthalmic drug delivery of timolol maleate an in vivo evaluation. High levels of intraocular pressure (IOP) represent recognized key risk factor in the development of glaucoma. Timolol maleate is one of the main options for the medical treatment of open-angle glaucoma. Drugs administered in conventional topical ophthalmologic formulation tend to present a poor bioavailability. The majority of ophthalmic preparations can be found in the form of aqueous solutions and suspensions. These liquid forms are quickly drained from the conjunctival sac to the nasolacrimal duct leading to low availability of the drug at the target site, systemic side effects and bad patient compliance (page 350). Chitosan is a polycationic biopolymer. Chitosan is able to develop molecular attraction forces through electrostatic interactions with mucus negative charges, giving way to the mucoadhesion process. Biodegradability, biocompatibility and nontoxicity are included in favorable biological properties that allow for their use as vehicles for ophthalmic formulations. The efficacy of topical delivery system depends on the interaction of the ocular mucosa, slow degradation, and the release of the drugs within the ocular tissues. Chitosan hydrogels when compared with commercial drug solutions have shown higher corneal residence times. Taught is a suitable and mucoadhesive system consisting of the drug (TM) and chitosan as a prolonged treatment device (page 351, left column). The amount of drug released from chitosan films was shown in Fig. 3. In 2 weeks 85% of the drug was released whose total in vitro content was released within 4 weeks (page 353, left column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘086 and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin. One skilled in the art would have been motivated to utilize chitosan due to its mucoadhesive properties. Since de Oliveira Fulgêncio et al. teaches the efficacy of topical delivery system depends on the interaction of the ocular mucosa, slow degradation, and the release of the drugs within the ocular tissues and chitosan hydrogels when compared with commercial drug solutions have shown higher corneal residence times provides motivation to utilize chitosan with any drug desired to be delivered topically.
Regarding claims 30, 69 and 85-90, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘086 and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin to treat glaucoma as copending ‘086 specifically claims treating glaucoma. Regarding the reduction in intraocular pressure, copending ‘086 is silent however as claimed is administration of the same drug (pregabalin) in the same amount. One skilled in the art would have been motivated to administer the composition topically to one or both eyes as both copending ‘086 and de Oliveira Fulgêncio et al. suggest this type of administration. One skilled in the art would have been motivated to administer the composition in the particular time frame necessary to achieve the desired treatment. Depending on the concentration of the drug and the release rate, one skilled in the art would recognize that the frequency of delivery would have to be varied to ensure effective treatment.
Regarding claim 36 and 73, copending ‘086 claims topical application via eye drops. de Oliveira Fulgêncio et al. teaches chitosan hydrogels, when compared with commercial drug solutions, have shown higher corneal residence times (page 351, left column). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘086 and de Oliveira Fulgêncio et al. and utilize a hydrogel of chitosan and pregabalin as eye drops. One skilled in the art would have been motivated to utilize this form as it is a common method of application of ophthalmic solutions.
Regarding claim 79, as set forth above, treating glaucoma with pregabalin and chitosan is obvious. The recitation “wherein the pharmaceutical composition achieves a higher degree of bioadhesion to mucin on one or both eyes as compared to a pharmaceutical composition comprising a mucoadhesive polymer comprising sodium alginate or carbomer” is the result of using chitosan. Since the use of chitosan is obvious for the reasons set forth above and the reference does not teach sodium alginate or carbomer, the wherein clause merely limits the composition to a structure with chitosan which is taught by the cited prior art.
Regarding claim 80, de Oliveira Fulgêncio et al. teaches total in vitro content was released within 4 weeks.
Regarding claims 81-84, Copending ‘086 claims the same amount.
Regarding claim 92, combining pregabalin and chitosan is obvious for the reasons set forth above. Regarding “improving bioadhesion of a topical ophthalmic pharmaceutical composition”, when reading the preamble in the context of the entire claim, the recitation improving bioadhesion is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As set forth above, de Oliveira Fulgêncio et al. teaches chitosan is mucoadhesive thus inclusion of chitosan would be expected to improve bioadhesion of a topical ophthalmic pharmaceutical composition.
Regarding claim 93, de Oliveira Fulgêncio et al. teaches that the use of chitosan improves the duration of release.
Claims 30, 36, 69, 73, 77-90 and 92-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18022252 (USPGPUB No. 20240041808) in view of de Oliveira Fulgêncio et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection.
The instant claims are set forth above.
Copending ‘252 claims a method of treating glaucoma in a subject, the method comprising administering to the subject in need thereof an effective amount of an ocular composition comprising pregabalin (PRG), wherein the glaucoma is normal tension glaucoma.
While copending ‘252 claims administering to the same subject (i.e. subject with glaucoma) the same drug (i.e. pregabalin), copending ‘252 does not expressly claim the inclusion of chitosan in the composition. However, this deficiency is cured by de Oliveira Fulgêncio et al.
The teachings of de Oliveira Fulgêncio et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘252 and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin. One skilled in the art would have been motivated to utilize chitosan due to its mucoadhesive properties. Since de Oliveira Fulgêncio et al. teaches the efficacy of topical delivery system depends on the interaction of the ocular mucosa, slow degradation, and the release of the drugs within the ocular tissues and chitosan hydrogels when compared with commercial drug solutions have shown higher corneal residence times provides motivation to utilize chitosan with any drug desired to be delivered topically.
Regarding claims 30, 69 and 85-90, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘252 and de Oliveira Fulgêncio et al. and utilize a composition of chitosan and pregabalin to treat glaucoma. Regarding the claimed reduction in intraocular pressure de Oliveira Fulgêncio et al. recognize is a key factor in glaucoma. Since the same drug claimed is administered, there is a reasonable expectation that administration of the pregabalin of copending ‘252 would result in the claimed reduction in intraocular pressure. One skilled in the art would have been motivated to administer the composition topically to one or both eyes de Oliveira Fulgêncio et al. suggest this type of administration. One skilled in the art would have been motivated to administer the composition in the particular time frame necessary to achieve the desired treatment. Depending on the concentration of the drug and the release rate, one skilled in the art would recognize that the frequency of delivery would have to be varied to ensure effective treatment.
Regarding claim 36 and 73, de Oliveira Fulgêncio et al. teaches chitosan hydrogels, when compared with commercial drug solutions, have shown higher corneal residence times (page 351, left column). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘252 and de Oliveira Fulgêncio et al. and utilize a hydrogel of chitosan and pregabalin as eye drops. One skilled in the art would have been motivated to utilize this form as it is a common method of application of ophthalmic solutions.
Regarding claim 79, as set forth above, treating glaucoma with pregabalin and chitosan is obvious. The recitation “wherein the pharmaceutical composition achieves a higher degree of bioadhesion to mucin on one or both eyes as compared to a pharmaceutical composition comprising a mucoadhesive polymer comprising sodium alginate or carbomer” is the result of using chitosan. Since the use of chitosan is obvious for the reasons set forth above and the reference does not teach sodium alginate or carbomer, the wherein clause merely limits the composition to a structure with chitosan which is taught by the cited prior art.
Regarding claim 80, de Oliveira Fulgêncio et al. teaches total in vitro content was released within 4 weeks.
Regarding claims 81-84, copending ‘252 claims administering an effective amount of pregabalin. Therefore, one skilled in the art would manipulate the amount of pregabalin in order to determine the effective amount.
Regarding claim 92, combining pregabalin and chitosan is obvious for the reasons set forth above. Regarding “improving bioadhesion of a topical ophthalmic pharmaceutical composition”, when reading the preamble in the context of the entire claim, the recitation improving bioadhesion is not limiting because the body of the claim describes a complete invention and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claim(s) is not considered a limitation and is of no significance to claim construction. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02. As set forth above, de Oliveira Fulgêncio et al. teaches chitosan is mucoadhesive thus inclusion of chitosan would be expected to improve bioadhesion of a topical ophthalmic pharmaceutical composition.
Regarding claim 93, de Oliveira Fulgêncio et al. teaches that the use of chitosan improves the duration of release.
Claim 91 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5-8, 10-11 and 24-28 of copending Application No. 18686086 (USPGPUB No. 20240423937) in view of de Oliveira Fulgêncio et al. as applied to claims 30-31, 36, 69, 73, 77-90 and 92-93 above and in further view of Hitzman et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
The claims of copending ‘086 are set forth above.
Copending ‘086 does not claim a step of measuring drug release using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes is not expressly taught. However, this deficiency is cured by Hitzman et al.
The teachings of Hitzman et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘086, de Oliveira Fulgêncio et al. and Hitzman et al. and utilize microdialysis to determine release rate. As taught by Hitzman et al. release rates can be readily obtained by microdialysis. Thus, it would have been obvious to utilize known standard practice to measure the release rate. Reading the claimed semi-permeable cellulose membrane, Hitzman et al. teaches a cellulose membrane to filter and thus is clearly semipermeable. Reading the claimed fast equilibrium, Hitzman et al. teaches microdialysis reaches equilibrium quickly in 5-6 hr.
Claim 91 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18022252 (USPGPUB No. 20240041808) in view of de Oliveira Fulgêncio et al. as applied to claims 30, 36, 69, 73, 77-90 and 92-93 above and in further view of Hitzman et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
The claims of copending ‘252 are set forth above.
Copending ‘252 does not claim a step of measuring drug release using fast micro-equilibrium dialysis with semipermeable regenerated cellulose membranes is not expressly taught. However, this deficiency is cured by Hitzman et al.
The teachings of Hitzman et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of copending ‘252, de Oliveira Fulgêncio et al. and Hitzman et al. and utilize microdialysis to determine release rate. As taught by Hitzman et al. release rates can be readily obtained by microdialysis. Thus, it would have been obvious to utilize known standard practice to measure the release rate. Reading the claimed semi-permeable cellulose membrane, Hitzman et al. teaches a cellulose membrane to filter and thus is clearly semipermeable. Reading the claimed fast equilibrium, Hitzman et al. teaches microdialysis reaches equilibrium quickly in 5-6 hr.
Conclusion
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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