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
Status of claims
The response filed on August 11, 2026 is acknowledged. Claims 1-9 are under examination in the instant office action.
Applicants' arguments, filed on August 11, 2026, have been fully considered but they are not deemed to be persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Responses are limited to Applicants' arguments relevant to either reiterated or newly applied rejections.
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.
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.
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.
Claims 1-2 and 4-9 are rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0086602 (hereafter, Egashira’602) in view of US 2003/0065020 (hereafter, Gale and US 20110021974, hereafter Shantha).
As to claim 1, Egashira’602 teaches a pharmaceutical composition comprising statin-loaded nanoparticles, which allows local delivery of statin and thus improves therapeutic efficacy of several kind of diseases treatable by statin (abstract and claim 1). Egashira’602 further teaches a method for treating diseases and/or conditions treated by statins or condition associated with HMG-CoA reductase, wherein said method comprises administering to warm-blood animal in need thereof the pharmaceutical composition comprising statin-loaded nanoparticles ([0054] and claim 13). Egashira’602 also teaches that the statin-loaded nanoparticles may show prolonged intracellular release of statin in a specific tissue and a therapeutic effect stimulating neovascularization without potential side effects such as rhabdomyolysis and hepatic disorder ([0008]).
As to claims 2 and 4-5, Egashira’602 teaches statin inhibits HMG-CoA reductase, which is a rate-determining enzyme in biosynthesis of cholesterol at the liver and includes pitavastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, and rovastatin ([0002] and claim 2-3). Egashira further teaches that the nanoparticles comprises a biocompatible polymer such as PLGA ([0033]). Egashira specifically discloses pitavastatin-loaded PLGA nanoparticles and pitavastatin-loaded PEG/CS-PLGA nanoparticles wherein the loading amounts of pitavastatins were 5.5% (w/v) in the nanoparticles and 2.3% (w/v) in the PEG/CS-PLGA nanoparticles ([0060]). The weight percentage of statin falls within the range recited in claim 4.
As to claim 6, Egashira’602 teaches that the statin-loaded nanoparticles have an average particle size of less than 1,000 nm, preferably 2.5 to 1,000 nm, more preferably 5 to 500 nm, still more preferably 25 to 300 nm, most preferably 50 to 200 nm by number when determined by the light scattering method ([0037]). The range (50 to 200 nm) falls within that of the instant claim 6.
As to claim 7, Egashira’602 teaches that the pharmaceutical composition may comprise 0.1% to 99%, especially about 1% to about 50%, preferably 1 to 20% by weight of the active ingredient ([0055]). The range (1 to 20% by weight) overlaps that of the instant claim 7.
As to claim 8, Egashira’602 teaches a therapeutically effective amount typically varies in the range from 0.01 mg/kg to about 1000 mg/kg, preferably from about 0.1 mg/kg to about 200 mg/kg, and most preferably from about 0.2 mg/kg to about 20 mg/kg, in one or more dose administrations daily, for one or more days ([0057]). The range overlaps that of the instant claim 8.
As to claim 9, Egashira’602 teaches the administration is made by injection such as intravenous injection (claim 14 and [0055]).
While Egashira’602 teaches the use of statin-loaded nanoparticles for treating a disease or condition treated by statins or condition associated with HMG-CoA reductase, Egashira’602 does not specifically disclose retinitis pigmentosa as one of such diseases or conditions.
However, retinitis pigmentosa was taught to be a disease or condition treated by statins or condition associated with HMG-CoA reductase as evidenced by Gale and Shantha.
Gale teaches a method of treating or preventing macular degeneration or degenerative diseases of the retina such as retinitis pigmentosa in a patient, the method comprising administering an HMG-CoA reductase inhibitor to the patient (abstract and [0020]). Gale further teaches the HMG-CoA reductase inhibitor comprises a statin selected from the group consisting of: fluvastatin (Lescol), cerivastatin (Baycol), atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol), lovastatin (Mevacor) and rosuvastatin (ZD 4522) ([0012]).
Shantha teaches that HMG-CoA reductase inhibitors can be used to treat retinitis pigmentosa (RP) to prevent the oxidative damage, clear the linear fatty deposits in the Bruch's membrane so that it can actively participate in the photoreceptors physiological function, and prevent photoreceptors apoptosis seen in this condition ([0264]). Shantha further teaches that HMG-CoA reductase inhibitors are selected from the group consisting of: fluvastatin (Lescol), cerivastatin (Baycol), atorvastatin (Lipitor), simvastatin (Zocor), pravastatin (Pravachol), lovastatin (Mevacor) and rosuvastatin (ZD 4522) ([0264]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the statin-loaded nanoparticles for treating retinitis pigmentosa because of the following reasons. Egashira’602 already teaches and suggests the use of statin-loaded nanoparticles for treating diseases treatable by statin because the statin-loaded nanoparticle allows local delivery of statin and thus improves therapeutic efficacy. While Egashira’602 does not specifically discloses retinitis pigmentosa as a disease treatable by statin, it was known in the art that HMG-CoA reductase inhibitors such as statin are useful for treating retinitis pigmentosa as evidenced by Gale and Shantha. Thus, one of ordinary skill in the art would have been motivated to use a statin such as pitavastatin in the form of nanoparticles as taught by Egashira’602 for treating a statin-treatable disease such as retinitis pigmentosa on the reasonable expectation that the statin-loaded nanoparticles would be more efficient by allowing delivery of the statin to the local area (e.g., retinal area) and thus improving therapeutic efficacy of the statin in the treatment of retinitis pigmentosa.
As to the percentage range of the statin-loaded nanoparticles in the pharmaceutical composition in claim 7 and the dose range in claim 8, Egashira’602 teaches the ranges overlapping those claimed. 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). “A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379,1382-83 (Fed. Cir. 2003). See 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 re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); 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 re Hoeschele, 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.). See MPEP 2144.05 IIA.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over US 2010/0086602 (hereafter, Egashira’602; cited in the IDS filed on 10/3/2024) in view of US 2003/0065020 (hereafter, Gale) and US 20110021974, (hereafter Shantha) in further view of US 2010/0086615 (hereafter, Egashira’615).
Egashira, Gale and Shantha as applied supra are herein applied for the same teachings in their entirety.
Egashira does not specifically disclose pitavastatin calcium.
However, hereafter, Egashira’615 teaches the use of a salt of HMG-CoA reductase inhibitor such as pitavastatin for preparing nanoparticles wherein a particularly preferable salt is a calcium salt or a sodium salt and specifically discloses that pitavastatin calcium was used for preparing pitavastatin-loaded PLGA nanoparticles (NPs) ([0026]-[0029], [0044], [0048], and Examples 1-2).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use pitavastatin calcium for preparing pitavastatin-loaded nanoparticles of Egashira because it was well known salt form of pitavastatin and has been used for preparing the same nanoparticles. Thus, one of ordinary skill in the art would have been motivated to do so on the reasonable expectation that calcium salt of pitavastatin would provide similar nanoparticles which is useful for treating the same disease as its base form.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the forgoing discussion, it is concluded that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the reference, especially in the absence of evidence to the contrary.
Response to Applicants’ argument:
Applicants argued that the combination of prior art references does not suggest using statin-loaded nanoparticles to target the retina. Applicants argued that because a person of ordinary skill in the art would understand that drug delivery to the retina would be completely different compared with drug delivery to peripheral tissues, there would not be a reasonable expectation of success from Egashira'602 that an effective amount of statin-encapsulated nanoparticles would reach the retina, which is the lesion site of retinitis pigmentosa. Applicants further stated that Gale and Shantha fail to disclose or suggest using nanoparticles for drug delivery, and Egashira'61 also fails to suggest nanoparticles crossing the blood-retinal barrier, thus the combination of cited references provide no teaching or suggestion of the claimed method. Also, Applicant argued that Gale does not disclose any data showing an effect on retinitis pigmentosa (RP) while Gale related to the use of statins for age-related macular degeneration (AMD). In addition, Applicant argued that while Shantha relates to the treatment of retinitis pigmentosa by ophthalmic administration and/or IGF-I and describes HMG-Co-A reductase inhibitors as combination drugs, Shantha also does not discloses any data showing an effect of HMG-CoA reductase inhibitor on retinitis pigmentosa.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). It is important to note that in an obvious rejection, it is not necessary that one reference addresses any limitation in a particular claim but that the references, when combined, do so.
In this case, Egashira’602 already teaches and suggests the use of statin-loaded nanoparticles for treating diseases treatable by the statin because the statin-loaded nanoparticle allows local delivery of statin and thus improves therapeutic efficacy. The term "local" administration in Egashira’602 means not only the topical administrations such as transdermal or ophthalmic administration, but also an oral administration to cause the drug substance delivered selectively to, for example, ischemic tissues and other tissues to be locally treated (see [0008]). Thus, the local delivery in Egashira’602 encompasses any target tissue to be locally treated, including retina. While the working examples in Gale relate to macular degeneration, Gale explicitly teaches that their method and treatment is applied to the treatment of particularly degenerative diseases of the retina such as retinitis pigmentosa (see [0020]) and retinal pigment abnormalities are considered the earliest retinal manifestations of macular degeneration and consist of increased retinal pigmentary degeneration and atrophy in the plane of the retinal pigment epithelium (see [0044]). Also, Gale teaches and suggests oral, topical or parenteral administration of statin can be effectively used for treating retinal disorders, which include AMD and RP. Thus, one of ordinary skill in the art would have recognized that AMD and RP share similar clinical features and the same lesion site (retina) and thus reasonably expected that the statin would be also effective for treating RP as well as AMD via reaching the same target site (i.e., retina) as taught by Gale. In addition, Shantha explicitly teaches that oral intake of HMG-CoA reductase inhibitors can be used to treat RP to prevent the oxidative damage, clear the linear fatty deposits in the Bruch's membrane so that it can actively participate in the photoreceptors physiological function, and prevent photoreceptors apoptosis seen (see [0264]). Further, it should be noted that the instant claim 1 is not limited to systemic or oral administration, which requires transfer of drug from the circulating blood to the blood-aqueous barrier and the blood retinal barrier. Actually, the instant claim 1 encompasses local or direct ophthalmic delivery, which does not need cross such barriers. Thus, Applicant’s argument based on the blood-aqueous barrier and the blood retinal barrier are not commensurate with the scope of the claims.
As to the Tomi & Hosoya reference Applicant cited, the reference is not related to statin treatment and does not provide any evidence that the statin-loaded nanoparticles cannot cross blood-retinal barrier. In the absence of such evidence that one of ordinary skill in the art would have been motivated to use a statin such as pitavastatin in the form of nanoparticles as taught by Egashira’602 for treating a known statin-treatable disease such as retinitis pigmentosa as well as AMD on the reasonable expectation that the statin-loaded nanoparticles would allow the delivery of the statin to the local area (e.g., retinal area) and thus improving therapeutic efficacy of the statin in the treatment of retinitis pigmentosa as stated above.
As to arguments regarding the lack of efficacy data in the treatment of RP, efficacy is not a requirement for prior art enablement. A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation." ImpaxLabs. Inc. v. Aventis Pharm . Inc., 468 F.3d 1366, 1383, 81 USPQ2d 1001, 1013 (Fed. Cir. 2006). See also MPEP § 2122. Also, it should be noted that a reference is not limited to its working examples, but must be evaluated for what it teaches those of ordinary skill in the art. In re Boe, 355 F.2d 961, 148 USPQ 507 (C.C.P.A 1966). In re Chapman, 357 F.2d 418, 148 USPQ 711 (C.C.P.A. 1966).
“[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. The motivation to combine may be implicit and may be found in the knowledge of one of ordinary skill in the art, or, in some cases, from the nature of the problem to be solved. Id. at 1366, 80 USPQ2d at 1649. “[A]n implicit motivation to combine exists not only when a suggestion may be gleaned from the prior art as a whole, but when the improvement’ is technology-independent and the combination of references results in a product or process that is more desirable, for example because it is stronger, cheaper, cleaner, faster, lighter, smaller, more durable, or more efficient. Because the desire to enhance commercial opportunities by improving a product or process is universal-and even common-sensical-we have held that there exists in these situations a motivation to combine prior art references even absent any hint of suggestion in the references themselves. In such situations, the proper question is whether the ordinary artisan possesses knowledge and skills rendering him capable of combining the prior art references.” Id. at 1368, 80 USPQ2d at 1651.
The examiner recognizes that obviousness can only be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988) and In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992). It is also noted that "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
For the foregoing reasons, Applicant’s arguments have not been found to be persuasive.
Conclusion
No claims are allowed.
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 extension fee 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 date of this final action.
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/BONG-SOOK BAEK/Primary Examiner, Art Unit 1611
