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 .
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.
Claims 1-3, 7, 9, 13, 14, 16, 26-29, 41, 52 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Williams, III et al. US 12,076,328 B2, in view of Temtem et al. US 20170209372 A1 and Hom-ma et al. US 6,274,174 B1.
Williams teaches a pharmaceutical composition comprising niclosamide, and optionally an excipient for inhalation. See Abstract and Claims. Compositions comprising up to 90% by weight of niclosamide is found in column 12, lines 40-49. Niclosamide includes a salt such as an ethanolamine or piperazine salt is found in column 12, lines 50-52. Niclosamide includes co-crystal of niclosamide may be used in the pharmaceutical compositions may include co-crystals of niclosamide with 2-aminothiazole, benzamide, isoniazid, acetamide, caffeine, urea, p-aminobenzoic acid, theophylline, nicotinamide, or isonicotinamide is found in column 12, lines 54-65. Naclosamide having the claims particle diameter is found in column 13. Nacloside particle having a high surface area, a low tapped density, or a low bulk density, including surface area of greater than 10 m2/g, greater than 25 m2/g, or greater than 50 m2/g; bulk density of the pharmaceutical compositions may be less than 1 g/mL, less than 0.5 g/mL, or less than 0.25 g/mL; and tapped density of the pharmaceutical compositions may be less than 0.1 g/cm3, 0.05 g/cm3, or 0.025 g/cm3. See column 13, last paragraph through column 14. The use of noclosamide for the treatment similar to that of the present claims is found in columns 16-17. The composition further comprises the claimed excipients/carriers. See columns 18-21. The claimed method is found in columns 22-24.
While Williams teaches the amount of niclosamide of about 90% w/w, Williams does not expressly teach the amount of at least 90% w/w.
Temtem teaches a composition comprising a particulate amorphous solid dispersion comprising 5 to 95% (w/w) of the pharmaceutically active compound and 95 to 5% (w/w) of the stabilizing agent. See paragraph 0019. Active compound including niclosamide is found in paragraph 0074.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to optimize the teaching in Williams to include at least 90% w/w of the active agent in the particle with the expectation of at least similar result in view of the teaching of Temtem. This is because Temtem teaches the desirability for having high drug load composition is known in the art, and this is because Temtem teaches including niclosamide in a composition having drug load of up to 95% is known and desired.
It is noted that the cited references do not teach the claimed specific surface area of niclosamide. However, it is known in the art to increase specific surface area of a low water-soluble drugs to increase the drug bioavailability. See for example the teaching in Hom-ma, see Abstract: The present inventors have made studies for the purpose of establishing a process for preparing controlled-release preparations which can rapidly release 99% or more of a slightly soluble medicament (which has by itself shows a slow dissolution rate) in the upper part of the small intestine. As a result, the inventors have succeeded in establishing a process comprising carrying a slightly soluble medicament which has a slow intestinal dissolution rate on aggregates of the spherical microparticles of a multivalent metal alginate, in which each of the secondary particles (i.e., the aggregates) has a specific surface area ranging from 1 to 280 m2/g. This success leads to the accomplishment of the present invention. Hom-ma teaches conventional pharmaceutical preparations for oral administration which contains a slightly soluble medicament, the medicament shows a small dissolution rate in the digestive tract. Therefore, the amount of the dissolved medicament per a certain time of period is small, the absorption of the medicament through the digestive tract is delayed, and the amount of the medicament absorbed through the digestive tract per hour becomes small, resulting in slow absorption in a living body and a low bioavailability. In these situations, improvement in solubility of the slightly soluble medicament has been desired for effective manifestation of the efficacy and the quick-acting nature of the medicament. See column 1.
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to, by routine experimentation optimize the teaching in Williams in view of the teaching in Hom-ma to obtain a niclosamide particle having a specific surface area that falls within the claimed range. This is because Hom-ma teaches a composition with improved dissolution rate of a poorly water-soluble active agent. Hence, one of ordinary skill in the art would have been motivated to, by routine experimentation making a composition comprises niclosamide with specific surface area that falls within the claimed range given the teaching of Williams in view of the teaching in Hom-ma. This is because Williams teaches the desirability to obtain a composition with improved solubility for the delivery of niclosamide, this is because niclosamide is known in the art to suffer from low solubility. See column 2 in the Williams reference. Advantageously, Hom-ma teaches a composition suitable for the delivery of a poorly water-soluble active agent that provides improved solubility, dissolution, and bioavailability of a poor water-insoluble active agent.
Response to Arguments
Applicant's arguments filed 09/23/2026 have been fully considered but they are not persuasive.
The Declaration under 37 CFR 1.132 filed 09/23/2026 is insufficient to overcome the 103 rejection based upon Williams, III et al. US 12,076,328 B2, in view of Temtem et al. US 20170209372 A1 and Hom-ma et al. US 6,274,174 B1 as set forth in the last Office action.
The Declaration and Applicant’s Remarks argue that none of the examples in Williams provide any teaching or suggestion of the bulk density or tapped density of any of the low percentage niclosamide particles produced. Furthermore, Applicant argues that the processes disclosed in Williams could not be used to produce the claimed composition.
However, Applicant’s arguments are not persuasive for the following reasons:
In response to Applicant’s argument that none of the examples in Williams provide any teaching or suggestion of the bulk density or tapped density of any of the low percentage niclosamide particles produced, it is noted that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). "A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use." In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have "relatively acceptable dimensional stability" and "some degree of flexibility," but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since "Gurley asserted no discovery beyond what was known in the art." Id. at 554, 31 USPQ2d at 1132.). Here, the teaching of compositions comprising up to 90% by weight of niclosamide is found in column 12, lines 40-49;
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). Here, Williams was cited in view of Temtem for the teaching of a composition comprising a particulate amorphous solid dispersion comprising 5 to 95% (w/w) of the pharmaceutically active compound and 95 to 5% (w/w) of the stabilizing agent. See paragraph 0019. Active compound including niclosamide is found in paragraph 0074. Therefore, one of the ordinary skill in the art would have been motivated to, by routine experimentation select a niclosamide amount that falls within the claimed range in view of the teaching in Temtem because Temtem teaches composition comprising niclosamide of upto 95% is known in the art. This is also because optimization of range is obvious in the art when the composition is used for similar purposes. 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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In 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.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.");
Applicant’s attention is called to teaching 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));
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. "The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed."); and
Furthermore, in response to Applicant’s argument that the processes disclosed in Williams could not be used to produce the claimed composition, Applicant’s attention is called to the teaching that "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Here, the rejected claims are directed to a composition claims, not a process of making claims.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSAN T TRAN whose telephone number is (571)272-0606. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm.
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/SUSAN T TRAN/Primary Examiner, Art Unit 1615
