DETAILED ACTION
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 Continuation of US application 17/228,753 filed 13 April 2021. Acknowledgement is made of the Applicant’s claim of domestic priority to provisional US applications 63/014,277 filed 23 April 2020 and 63/009,623 filed 14 April 2020.
Claim Objections
Claim 44 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 29. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 26, 28-33, 36, 38-40, and 43-51 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al. (WO 2018194356 A1) in view of Winter et al. (US 2011/0281912) in view of DeWeer et al. (US 2015/0224199).
Oh teaches pharmaceutical compositions comprising the mesylate salt of N-(5-(4-(4-((dimethylamino)methyl)-3-phenyl-1H-pyrazol-1-yl)pyrimidine-2-ylamino)-4-methoxy-2-morpholinophenyl)acrylamide and the novel crystalline form thereof (abstract, formula 1 and 2) [46-60]. The compound is made in an aqueous process, thus implying the hydrated form is prepared [86]. The compound is useful for inhibiting the activity of protein kinase-mediated disorders and potentially is effective in patients with advanced non-small cell lung cancer [5-6]. The compound is in crystalline form and has PXRD peaks at 5.614, 12.394, 14.086, 17.143, 18.020, 19.104, 21.585, 22.131, and 22.487, all ±0.2 [52]. The crystalline form further has an endothermic transition peak value at 210 to 230 ºC, preferably 217±2 ºC [53]. The pharmaceutical composition may be in the form of a tablet, capsule, elixir, suppository, sterile solution or suspension, lotion, gel, ointment, or cream [75]. Oh teaches that the dose/dosage of the mesylate varies depending on the weight of the weight of the patient and that in general the dosage of active agent ranges from about 10 mg/day to about 1000 mg/day [76]. The composition can comprise pharmaceutically acceptable additives such as at least one diluent or excipient, disintegrant, lubricant, binder, and surfactant [77]. The pharmaceutically acceptable additive may include sugar/sugar cane, polysaccharide such as lactose or glucose, synthetic mineral powder (highly dispersed silicic acid and silicate), emulsifier (lignin, sulfite liqueur, methylcellulose, starch, polyvinylpyrrolidone), magnesium stearate, and others [78].
Oh does not teach further comprising hydrophobic colloidal silicon dioxide, microcrystalline cellulose, or a sugar.
DeWeer teaches tablets [0043] of kinase inhibitor active agents [0020] wherein the composition can comprise a glidant [0087]. A glidant is used to promote powder flow by reducing interparticle friction and cohesion and is commonly used in combination with a lubricant which has no ability to reduce die wall friction [0087]. A commonly used glidant is hydrophobic colloidal silica, also known as AEROSIL, and can be used in 0.1-1% by weight [0152-0153; 0306].
Winter teaches an oral dispersible tablet comprising a sugar or sugar alcohol along with microcrystalline cellulose (abstract). It was found that the ratio of sugar to cellulose was important for establishing a low friability and good tablet hardness [0009]. The desired range of sugar to MCC is from 1:0.60 to 1:3.00 (which is a ratio of MCC to sugar range of from 1:1.6 to 1:0.33) [0009]. The tablet can be prepared by direct compression (which is a dry blend with no solvent) [0009]. The sugar can be mannitol [0014] and the lubricant can be magnesium stearate [0025]. In one example, Winter suggests using a range of sugar from 60-240 mg, a range of MCC from 60-240 mg, and a range of active from 0-50 mg [0049]. That being said, Winter teaches that there is no particular limitation on the amount of or choice of active agents used [0047-0048].
It would have been prima facie obvious to prepare the composition of Oh which is a tablet comprising a kinase inhibitor and a lubricant and further include a glidant (0.1-1% by weight), such as hydrophobic colloidal silicon dioxide, based on the teachings of DeWeer wherein the glidant is used in conjunction with lubricant in a tablet to provide die wall friction reduction. Moreover, it would have been obvious to use hydrophobic colloidal silicon dioxide (silica) in 0.5% by weight based on the range taught by DeWeer, as required in instant claims 26, 28-29, 38-40, and 43-44. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).
Moreover, it would have been prima facie obvious to prepare the tablet wherein the tablet further comprises excipients such as disintegrants, lubricants, and binders. Oh does not specify which additives are required, therefore it would have been obvious to look to Winter, which teaches that the binding agent microcrystalline cellulose (MCC) when used in combination with a sugar alcohol such as mannitol provides a tablet with a desired friability and hardness. The low point in the range of Winter is a ratio of 1:0.33 of MCC to mannitol, which is reasonably close to the range in instant claim 33. 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). MPEP 2144.05 (I). Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (See MPEP 2131.03 (III)). The inclusion of MCC and mannitol in a ratio of 1:0.33 renders obvious instant claims 30-33.
Regarding the lubricant, it would have been obvious to use magnesium stearate, which is taught in Oh [78] and also as a lubricant in Winter, addressing instant claim 36. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).
Regarding the ratio of active to diluents, Oh does not teach this ratio thus it would have been obvious to look to Winter, which provides an example wherein the active agent can be used in 50 mg and the diluents in a combined 120 mg, which is a ratio of 1:2.4 of active to diluents, as required in instant claims 45-46.
Regarding the ratio of active agent overall, Winter provides an example wherein 50 mg of active agent would be approximately 8.4% by weight of the tablet. While this one example is a lower mass of API (active pharmaceutical ingredient) than in the instant claims, Winter does teach that the amount of active is not limited and Oh teaches using up to 1000 mg per day. That being said and in lieu of objective evidence of unexpected results, the amount of active can be viewed as a variable which achieves the recognized result of successfully treating a specific patient. The optimum or workable range of active agent can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980). As such, the concentrations of instant claims 47-50 would have been obvious based on optimization.
Regarding instant claim 51, the hydrophobic silicon dioxide is used as a glidant in the powder prior to tableting and the MCC along with mannitol is used to impart hardness to the tablet during tableting process. As such, it would have been obvious to include the silicon dioxide prior to the MCC. That being said, it is obvious to change the sequence of adding ingredients, thus any order would have been obvious (see MPEP 2144.04 (IV)C).
The resulting tablet renders obvious instant claims 26, 28-33, 36, 38-40, and 43-51.
Claims 26 and 28-51 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al. (WO 2018194356 A1) in view of Winter et al. (US 2011/0281912) in view of Luckhart et al. (US 2016/0151380).
Oh, DeWeer, and Winter, as applied supra, are herein applied in their entirety for the teachings of a composition comprising the claimed active agent which is a protein kinase inhibitor.
Oh does not teach further comprising croscarmellose sodium.
Luckhart teaches a pharmaceutical composition that can comprise a protein kinase inhibitor that can further comprise magnesium stearate as a lubricant and croscarmellose sodium as a disintegrant [0043].
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07). Thus, it would have been prima facie obvious to prepare the composition of Oh and Winter and further include croscarmellose sodium as the disintegrant taught by Oh. Regarding the concentration, disintegrants are known in the art for providing disintegration properties to a tableted formulation. That being said and in lieu of objective evidence of unexpected results, the concentration of disintegrant can be viewed as a variable which achieves the recognized result of successfully preparing a tablet with desired disintegration properties. The optimum or workable range of disintegrant can be accordingly characterized as routine optimization and experimentation (see MPEP 2144.05 (II)B). “[Discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art.” In re Boesch, 617 F.2d 272, 276 (CCPA 1980).
Regarding claims 41-42, Winter provides an example wherein active can be included up to 50 mg, however Oh teaches including up to 1000 mg of the active. Winter further teaches using the sugar and MCC blend in from 120-500 mg, filler up to 80 mg, and lubricant up to 10 mg. These broad ranges do not match those of instant claims 41-42, however, in lieu of evidence of an unexpected result or critical range, the concentration of each agent present in the prior art can be adjusted based on routine optimization and experimentation (See MPEP 2144.05 (II)B). Accordingly, claims 26 and 28-51 are rejected as obvious over the prior art above.
Claims 26-51 are rejected under 35 U.S.C. 103 as being unpatentable over Oh et al. (WO 2018194356 A1) in view of Winter et al. (US 2011/0281912) in view of Luckhart et al. (US 2016/0151380) in view of Jonat et al. (Powder Technology 141 (2004) 31-43) as evidenced by Nitert et al. (US 2022/0112220).
Oh, DeWeer, Winter, and Luckhart, as applied supra, are herein applied in their entirety for the teachings of a composition comprising the claimed active agent which is a protein kinase inhibitor.
Oh does not teach wherein the hydrophobic colloidal silicon dioxide (AEROSIL) is a fumed silica that is treated with dimethyldichlorosilane.
Jonat teaches that glidants are incorporated into solid dosage forms to improve the flow properties of powders and granulates (pg 31, ¶1). When applied to tablets, glidants improve flow into the hopper and the die cavities of the tablet press, increase tablet weight, decrease the weight variation, and minimize the tendency of the powder or granules to separate or segregate (id). Glidants used in pharmaceutical compositions include colloidal silicon dioxide which are the most efficient (pg 31, ¶2). In order to improve the handling of colloidal silicon dioxide, special mechanical processes were developed resulting in the production of AEROSIL R972, which is a hydrophobic silicon dioxide with dimethyl silyl groups chemically bound to the silica surface (id). Furthermore, AEROSIL R972 gives superiority over water-wettable conventional colloidal silicon dioxides in pharmaceutical applications (id). AEROSIL R972 is a fumed silica that is after-treated with dimethyldichlorosilane, as evidenced by Nitert [0019].
It would have been prime facie obvious to prepare the composition of Oh, DeWeer, Winter, and Luckhart and modify the hydrophobic colloidal silicon dioxide, as taught generically as AEROSIL in DeWeer, with the AEROSIL R972 of Jonat. Substitution of the R972 product would have been obvious due to the beneficial properties associated with the compound that make it a superior glidant in pharmaceutical tablets than other glidants. Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (see MPEP § 2144.07).
The resulting composition renders obvious instant claims 26-51.
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 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 26-51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,138,351. Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘351 claims, in claim 15, require colloidal silicon dioxide to be included in the composition of Lazertinib, cellulose, and sugar or polyol. The dependent claims further require the inclusion of MCC, croscarmellose sodium, and magnesium stearate wherein the Lazertinib is the mesylate salt with the same crystalline properties of the instant claims. The concentrations and ratios of ‘351 read on those of the instant claims.
Conclusion
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/ANDREW S ROSENTHAL/Primary Examiner, Art Unit 1613
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