DETAILED ACTION
Claims 1-6, 8-18, 20-38 and 56-71 are pending. Of these, claims 56-57 are withdrawn as directed to a nonelected invention. Therefore, claims 1-6, 8-18, 20-38, and 58-71 are under consideration on the merits.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/26/26 was filed prior to the mailing date of a Final Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, it was considered by the Examiner.
Status of the Rejections
The claim objections are withdrawn in view of the amendment.
The 112(b) rejections are withdrawn in view of the amendment, but a new rejection was necessitated by the amendment.
The 103 rejections are withdrawn as to cancelled claims 7 and 19, revised in view of the amendment as to the remaining claims, and expanded to include newly added claims.
The double patenting rejections are withdrawn as to cancelled claims 7 and 19 and maintained and expanded to include the newly added claims.
Claim Rejections - 35 USC § 112
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 67 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as 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.
Newly added claim 67 is indefinite because it depends from claim 19, which is canceled. Clarification is required.
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: Claim Rejections - 35 USC § 112
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.
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 1-6, 8-18, 20-38, and 58-71 are rejected under 35 U.S.C. 103 as unpatentable over Shaw et al. (US Pat. Pub. 2009/0004262) in view of Bhattacharya et al. (WO 2020/234781; of record in IDS).
As to claims 1-6, 8-18, 20-38, and 58-71, Shaw teaches that it is very difficult to formulate dosage forms for drugs having low aqueous solubility, and discloses a solution for this problem in the form of nanoparticulate formulations of drugs having an aqueous solubility of less than 1 mg/ml at a pH of about 7.4, and which have enhanced stability and pharmacokinetic properties to optimize between pharmacodynamic effects and side effect profiles (paragraphs 2-3). The nanoparticulate formulation comprises particles of the drug having a surface stabilizer adsorbed on its surface such as sodium lauryl sulfate (the elected species of surfactant of claims 1, 3-5, 8-9, 13, and 65) or a copolymer of polyvinylpyyrolidone and vinyl acetate (the elected species of “binder” of claim 1)(paragraphs 112, 198, 225). The surface stabilizer is present in the amount of 3-70 wt% (paragraph 24), which reads on the amounts of claim 65 and is viewed as reading on the “about 0.1 to about 2.5%” range recited by claim 36 due to the use of the term “about” and the closeness of 2.5 wt% and 3 wt% such that the use of either amount would be expected to result in no significant change in the properties of the composition. 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). Shaw further teaches that the nanoparticulates may be layered onto inert beads (“inert substrate” of claims 1, 4-5) using a spray granulation method (claim 5)(paragraphs 181, 183), wherein the inert substrate may be the elected species, i.e., mannitol (claims 6 and 58-59)(paragraph 211). The binder is present in the amount of 20-70%, which overlaps the range of claim 34 (paragraphs 204-205). The composition may be in the form of granules (paragraph 187).
As to claims 14-17 and 66, the particles have a median diameter of 50-500 nm, which overlaps the recited ranges (paragraph 12).
As to claims 20-23, 31, 35, 67-68, the composition further may comprise additional excipients so as to form an external phase relative to the inert beads (claim 18) such as fillers/diluents such as calcium carbonate, lactose, or calcium phosphate, or sodium phosphate (“fillers” of claims 18, 20) or mannitol or cellulose (“fillers” of claims 20, 23, 67)(paragraphs 195-196) and wherein the cellulose may be microcrystalline cellulose of claim 68 (paragraph 52), disintegrants such as corn starch or alginic acid (claim 21)(paragraph 202), and lubricating agents such as magnesium stearate, stearic acid, or talc (claims 22-23)(paragraph 206). Shaw also discloses embodiments comprising silicified microcrystalline cellulose filler in the amount of 37 wt% which is within the range of claim 31 and magnesium stearate lubricant in the amount of 0.5 wt% which is within the range of claim 35 (Example 29).
Regarding claims 25-29 and 70, the final dosage form comprising the composition may be a tablet such as a film coated tablet or a capsule (paragraphs 228, 314).
As to claim 32, the disintegrating agent may be used in the amount of 1-11 wt%, which encompasses the claimed range (paragraph 201).
As to claims 37-38 and 71, the drug may be present in the amount of, for example, 100-500mg, which encompasses amounts recited by these claims (paragraph 216).
As to claims 1-6, 8-18, 20-38, and 58-71, Shaw does not further expressly disclose that the drug is N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claims 1-2) and which is present in amounts within the weight percent range of claim 30, and in the weight ratio with respect to the binder as recited by claims 10 and 60-61 or with respect to the binder and surfactant (claims 11 and 62-63) or the weight percent of the binder with respect to the active (claims 12 and 64), or the weight of the surfactant with respect to that of the active (claim 13) or the weight percent of the external phase (claims 24, 69) or of the inert substrate (claim 33). Nor does Shaw teach the use of cellulose and sodium carbonate (claim 23).
Bhattacharya discloses pharmaceutical compositions comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide as the active ingredient in free form (claim 2)(page 3, 1st paragraph). The composition further may comprise surfactants and binders (page 8, 2nd full paragraph), and may be in the form of granules (page 19, 1st full paragraph). The composition further may comprise additional excipients such as diluents such as mannitol, cellulose, and sodium carbonate, disintegrants such as corn starch or alginic acid), and lubricating agents such as magnesium stearate, stearic acid, or talc (page 19, 1st full paragraph). The final dosage form comprising the composition may be a tablet or a capsule such as a soft capsule (page 19, 1st full paragraph). Regarding claims 37-38, the active compound may be dosed in amounts within the recited ranges such as 10-200mg, such as 10 mg (page 22).
As to claims 1-6, 8-18, 20-38, and 58-71, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the Shaw composition by selecting the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claim 2) and which is present in amounts within the ranges of claims 37-38 as the drug as taught by Bhattacharya for incorporation into the Shaw nanoparticulate formulation because the skilled artisan would recognize that N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide is a nonpolar drug with virtually no solubility in water and Shaw teaches that it is very difficult to formulate dosage forms for drugs having low aqueous solubility, but that the nanoparticulate formulations disclosed therein can successfully be used to formulate poorly water soluble drug, and result in a dosage form having enhanced stability and pharmacokinetic properties, such that the skilled artisan reasonably would have expected that the Shaw nanoparticulate formulation could be used to successfully formulate a dosage form comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide having enhanced stability and pharmacokinetic properties.
As to claims 1, 10-13, 24, 60-64, and 69, it further would have been prima facie obvious to select a weight ratio of the active with respect to the binder as recited by claims 1, 10, and 60-61 or with respect to the binder and surfactant (claims 11 and 62-63) or the weight percent of the binder with respect to the active (claims 12 and 64), or the weight percent of the surfactant with respect to that of the active (claim 13) or the weight percent of the external phase (claims 24, 69) with a reasonable expectation of success, because Shaw and Bhattacharya teach amounts of the binder, surfactant, active, as well as amounts of the ingredients in the external phase (i.e., filler, disintegrating agent, and lubricating agent) that read on the ranges for these ingredients as recited by the claims as discussed above, such that the presently claimed weight ratios are encompassed by the ranges taught for these ingredients by the cited references. Differences in concentration generally 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). Here, there is no evidence of record of any unexpected criticality of the claimed weight ratios.
As to claim 23, it further would have been prima facie obvious to incorporate mannitol, cellulose, and sodium carbonate as excipients for the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide, because Bhattacharya expressly teaches these compounds as excipients that are suitable for use in a pharmaceutical formulation comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide as the active.
As to claim 30, it further would have been prima facie obvious to select a weight % amount of the active that is within the recited range with a reasonable expectation of success because the amount of an active is a result effective variable that will affect the therapeutic efficacy of the composition, and because Bhattacharya teaches amounts of the active in terms of milligrams that are within the ranges recited by present claims 37-38 and further teaches the use of the active to treat the same disorder recited by the claims (i.e., Bhattacharya teaches the use of the active to treat Sjogren’s syndrome (see Title and Abstract) and the present disclosure also teaches the use of the active to treat this disorder (see, e.g., withdrawn claim 57). “[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).
As to claim 33, it further would have been prima facie obvious to select an amount of the inert substrate that is within the recited range with a reasonable expectation of success because the purpose of the inert substrate is the same in Shaw as in the present invention (i.e., to serve as a carrier), and because Shaw and Bhattacharya teach amounts of the other ingredients in the composition that are within the presently claimed ranges as discussed above, such that the composition of Shaw and Bhattacharya as combined supra reasonably would be expected to require an amount of the inert substrate carrier that is similar to the amount of carrier required by the claimed invention. Discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)..
Claims 1-9, 14-17, 19-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71 are rejected under 35 U.S.C. 103 as unpatentable over Shaw et al. (US Pat. Pub. 2009/0004262) in view of Angst et al. (US Pat. No. 9,512,084).
The teachings of Shaw are relied upon as discussed above.
As to claims 1-6, 8-9, 14-17, 20-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71,, Shaw does not further expressly disclose that the drug is N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claim 2).
Angst discloses a compound that is the active recited by present claim 1, i.e., free form N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide (see claim 11 of Angst). The compound may be formulated as a pharmaceutical composition in the form of a tablet or capsule (column 14, lines 4-11) that comprises a binder (claim 1), diluents such as lactose or mannitol (claim 20), lubricants such as magnesium stearate, stearic acid, or talc (claim 22), and disintegrating agents such as alginic acid (claim 21)(column 13, line 34 through column 14, line 2).
As to claims 1-6, 8-9, 14-17, 20-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the Shaw composition by selecting the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claim 2) and which is present in amounts within the ranges of claims 37-38 as the drug as taught by Angst for incorporation into the Shaw nanoparticulate formulation because the skilled artisan would recognize that N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide is a nonpolar drug with virtually no solubility in water and Shaw teaches that it is very difficult to formulate dosage forms for drugs having low aqueous solubility, but that the nanoparticulate formulations disclosed therein can successfully be used to formulate poorly water soluble drug, and result in a dosage form having enhanced stability and pharmacokinetic properties, such that the skilled artisan reasonably would have expected that the Shaw nanoparticulate formulation could be used to successfully formulate a dosage form comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide having enhanced stability and pharmacokinetic properties.
Claims 1-6, 8-9, 14-17, 20-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71 are rejected under 35 U.S.C. 103 as unpatentable over Shaw et al. (US Pat. Pub. 2009/0004262) in view of Angst et al. (US Pat. No. 10,457,647).
The teachings of Shaw are relied upon as discussed above.
As to claims 1-6, 8-9, 14-17, 20-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71, Shaw does not further expressly disclose that the drug is N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claim 2).
Angst discloses a compound that is the active recited by present claim 1, i.e., free form N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide (see claim 8 of Angst). The compound may be formulated as a pharmaceutical composition in the form of a tablet or capsule (column 13, lines 29-31) that comprises a binder (claim 1), diluents such as lactose or mannitol (claim 20), lubricants such as magnesium stearate, stearic acid, or talc (claim 22), and disintegrating agents such as alginic acid (claim 21)(column 13, line 39 through column 14, line 8).
As to claims 1-6, 8-9, 14-17, 20-22, 25-29, 31-32, 34-38, 58-59, 67-68, and 70-71, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the Shaw composition by selecting the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide that is in its free form (claim 2) and which is present in amounts within the ranges of claims 37-38 as the drug as taught by Angst for incorporation into the Shaw nanoparticulate formulation because the skilled artisan would recognize that N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide is a nonpolar drug with virtually no solubility in water and Shaw teaches that it is very difficult to formulate dosage forms for drugs having low aqueous solubility, but that the nanoparticulate formulations disclosed therein can successfully be used to formulate poorly water soluble drug, and result in a dosage form having enhanced stability and pharmacokinetic properties, such that the skilled artisan reasonably would have expected that the Shaw nanoparticulate formulation could be used to successfully formulate a dosage form comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide having enhanced stability and pharmacokinetic properties.
Response to Applicant’s Arguments
Applicant argues that Shaw, Battacharya, and the Angst references do not suggest a composition comprising the active and polyvinylpyrollidone-vinyl acetate copolymer in the recited weight ratios, and that Shaw merely discloses polyvinylpyrollidone-vinyl acetate copolymer as a binder among a long list of candidates but without any teaching specifically of its use.
In response, the mere fact that a reference suggests a multitude of possible combinations does not in and of itself make any one of those combinations less obvious. See Merck v. Biocraft, 10 USPQ2d 1843, 1846 (Fed Cir 1985); In re Corkill, 771 F.2d 1496, 1500, 226 USPQ 1005, 1008 (Fed.Cir. 1985) (obviousness rejection of claims affirmed in light of prior art teaching that “hydrated zeolites will work” in detergent formulations, even though “the inventors selected the zeolites of the claims from among ‘thousands’ of compounds”); In re Susi , 440 F.2d 442, 445, 169 USPQ 423, 425 (CCPA 1971) (obviousness rejection affirmed where the disclosure of the prior art was “huge, but it undeniably include[d] at least some of the compounds recited in appellant's generic claims and it is of a class of chemicals to be used for the same purpose as appellant's additives”).
Additionally, and as discussed in the rejection it would have been prima facie obvious to select a weight ratio of the active with respect to the binder as recited by the claims with a reasonable expectation of success, because Shaw and Bhattacharya teach amounts of the binder and active that read on the ranges for these ingredients as recited by the claims as discussed above, such that the presently claimed weight ratios are encompassed by the ranges taught for these ingredients by the cited references. Additionally, differences in concentration generally 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).
Applicant also argues that Example 1 shows that a composition containing a higher ratio of PVP-vinyl acetate copolymer showed the best re-suspendability leading to higher in vivo e3xposure in dogs thus overcoming the problematic gelling issue associated with the recited active.
In response, this argument is not persuasive because Examiner has reviewed the working examples but could not locate any disclosure comparing inventive compositions having a ratio of the copolymer within the recited range to a comparative composition that is outside the recited range, and showing that the inventive composition possesses superior re-suspendabilitiy and higher in vivo exposure.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-6, 8-18, 20-38, and 58-71 are rejected on the ground of nonstatutory double patenting as unpatentable over claims 1-15 of Angst (US Pat. No. 9,512,084) and in view of Shaw et al. (US Pat. Pub. 2009/0004262) and/or Bhattacharya et al. (WO 2020/234781) where indicated below.
The teachings of the cited secondary references are relied upon as discussed above.
Reference claim 2 is drawn to a compound that may be the active recited by present claim 1, i.e., N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide.
Although the reference claim does not recite a pharmaceutical composition for oral administration comprising a granule particle comprising the active, a binder that is a copolymer of polyvinylpyyrolidone and vinyl acetate, and an inert substrate comprising mannitol and a surfactant that is sodium lauryl sulfate layered onto the inert substrate and an external phase comprising mannitol as filler, a disintegrating agent such as corn starch or alginic acid and lubricating agents such as magnesium stearate, stearic acid, or talc and wherein these ingredients are present in the claimed amounts, it would have been prima facie obvious to formulate the active into a dosage form comprising these ingredients because Shaw teaches that a nanoparticulate formulation comprising these ingredients in such amounts is useful for formulating a poorly water soluble drug and the skilled artisan would recognize that N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide is a poorly water soluble drug.
Although the reference claims do not recite the particle size of the drug particles or that the composition is in the form of a tablet or capsule, it further would have been prima facie obvious to select such sizes because Shaw teaches particle sizes within the claimed ranges as suitable for use in its nanoparticulate formulations and to formulate as a tablet or capsule because Bhattacharya teaches that such forms are suitable for N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide.
The reference claims do not recite that the active is present in amounts within the ranges of the claims, and in the weight ratio with respect to the binder as recited by the claims or with respect to the binder and surfactant or the weight percent of the binder with respect to the activ , or the weight of the surfactant with respect to that of the active or the weight percent of the external phase or of the inert substrate).
It would have been prima facie obvious, however, to select a weight ratio of the active with respect to the binder as recited by the claims or with respect to the binder and surfactant or the weight percent of the binder with respect to the active, or the weight percent of the surfactant with respect to that of the active, or the weight percent of the external phase with a reasonable expectation of success, because Shaw and Bhattacharya teach amounts of the binder, surfactant, active, as well as amounts of the ingredients in the external phase (i.e., filler, disintegrating agent, and lubricating agent) that read on the ranges for these ingredients as recited by the claims as discussed above, such that the presently claimed weight ratios are encompassed by the ranges taught for these ingredients by the cited references. Differences in concentration generally 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). Here, there is no evidence of record of any unexpected criticality of the claimed weight ratios.
It further would have been prima facie obvious to select an amount of the inert substrate that is within the recited range with a reasonable expectation of success because the purpose of the inert substrate is the same in Shaw as in the present invention (i.e., to serve as a carrier), and because Shaw and Bhattacharya teach amounts of the other ingredients in the composition that are within the presently claimed ranges as discussed above, such that the composition of Shaw and Bhattacharya as combined supra reasonably would be expected to require an amount of the inert substrate carrier that is similar to the amount of carrier required by the claimed invention. Discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It further would have been prima facie obvious to incorporate mannitol, cellulose, and sodium carbonate as excipients for the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide, because Bhattacharya teaches that these compounds as conventional excipients that are suitable for use in a pharmaceutical formulation comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide as the active.
The claims are directed to an invention not patentably distinct from the claims of the copending application. Specifically, see above.
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application of common ownership (see 37 CFR 42.411). The copending application, discussed above, would be prior art to the noted claims under 35 U.S.C. 102(a)(2) if the patentably indistinct inventions were not commonly owned or deemed to be commonly owned as of the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned as of the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case.
Claims 1-6, 8-18, 20-38, and 58-71 are rejected on the ground of nonstatutory double patenting as unpatentable over claims 1-13 of Angst (US Pat. No. 11,180,460) and in view of Shaw et al. (US Pat. Pub. 2009/0004262) and/or Bhattacharya et al. (WO 2020/234781) where indicated below.
The teachings of the cited secondary references are relied upon as discussed above.
Reference claim 8 is drawn to a compound that may be the active recited by present claims 1-6, 9-18, 20-38, and 58-71, i.e., N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide.
Although the reference claims do not recite a pharmaceutical composition for oral administration comprising a granule particle comprising the active, a binder that is a copolymer of polyvinylpyyrolidone and vinyl acetate, and an inert substrate comprising mannitol and a surfactant that is sodium lauryl sulfate layered onto the inert substrate and an external phase comprising mannitol as filler, a disintegrating agent such as corn starch or alginic acid and lubricating agents such as magnesium stearate, stearic acid, or talc and wherein these ingredients are present in the claimed amounts, it would have been prima facie obvious to formulate the active into a dosage form comprising these ingredients because Shaw teaches that a nanoparticulate formulation comprising these ingredients in such amounts is useful for formulating a poorly water soluble drug and the skilled artisan would recognize that N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide is a poorly water soluble drug.
Although the reference claims do not recite the particle size of the drug particles or that the composition is in the form of a tablet or capsule, it further would have been prima facie obvious to select such sizes because Shaw teaches particle sizes within the claimed ranges as suitable for use in its nanoparticulate formulations and to formulate as a tablet or capsule because Bhattacharya teaches that such forms are suitable for N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide.
The reference claim does not recite that the active is present in amounts within the ranges of the claims and in the weight ratio with respect to the binder as recited by the claims or with respect to the binder and surfactant, or the weight percent of the binder with respect to the active, or the weight of the surfactant with respect to that of the active, or the weight percent of the external phase or of the inert substrate.
It would have been prima facie obvious, however, to select a weight ratio of the active with respect to the binder as recited by the claims or with respect to the binder and surfactant or the weight percent of the binder with respect to the active, or the weight percent of the surfactant with respect to that of the active or the weight percent of the external phase with a reasonable expectation of success, because Shaw and Bhattacharya teach amounts of the binder, surfactant, active, as well as amounts of the ingredients in the external phase (i.e., filler, disintegrating agent, and lubricating agent) that read on the ranges for these ingredients as recited by the claims as discussed above, such that the presently claimed weight ratios are encompassed by the ranges taught for these ingredients by the cited references. Differences in concentration generally 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). Here, there is no evidence of record of any unexpected criticality of the claimed weight ratios.
It further would have been prima facie obvious to select an amount of the inert substrate that is within the recited range with a reasonable expectation of success because the purpose of the inert substrate is the same in Shaw as in the present invention (i.e., to serve as a carrier), and because Shaw and Bhattacharya teach amounts of the other ingredients in the composition that are within the presently claimed ranges as discussed above, such that the composition of Shaw and Bhattacharya as combined supra reasonably would be expected to require an amount of the inert substrate carrier that is similar to the amount of carrier required by the claimed invention. Discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
It further would have been prima facie obvious to incorporate mannitol, cellulose, and sodium carbonate as excipients for the N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide, because Bhattacharya teaches that these compounds as conventional excipients that are suitable for use in a pharmaceutical formulation comprising N-(3-(6-Amino-5-(2-(N-methylacrylamido)ethoxy)pyrimidin-4-yl)-5-fluoro-2-methylphenyl)-4-cyclopropyl-2-fluorobenzamide as the active.
The claims are directed to an invention not patentably distinct from the claims of the copending application. Specifically, see above.
The USPTO may not institute a derivation proceeding in the absence of a timely filed petition. The U.S. Patent and Trademark Office normally will not institute a derivation proceeding between applications or a patent and an application of common ownership (see 37 CFR 42.411). The copending application, discussed above, would be prior art to the noted claims under 35 U.S.C. 102(a)(2) if the patentably indistinct inventions were not commonly owned or deemed to be commonly owned as of the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned as of the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case.
Response to Applicant’s Arguments
Applicant advances the same arguments made against the 103 rejections, but these arguments are not persuasive for the reasons discussed above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, 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 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.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/ Primary Examiner, Art Unit 1600
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