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 .
Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/14/26 has been entered.
Claim Status
Claims 2-7, 9, 13 and 14 are cancelled.
Claims 1, 8, 10-12 and 15-26 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/14/26 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn rejections
Applicant's amendments and arguments filed 5/14/26 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn. Claims 12, 24 and 25 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. Applicant has amended the claims to overcome the rejection.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
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.
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, 8, 10-12, 15 and 22-26 are rejected under 35 U.S.C. 103 as being unpatentable over Pelletier et al. (WO2015069956).
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103, the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103.
Applicant claims, for example:
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a pharmaceutical research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from pharmaceutical formulation methods, pharmaceutical excipients and pharmaceutical laboratory techniques— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1, 8 and 15, Pelletier et al. disclose a solid pharmaceutical composition comprising the compound of formula I and meglumine (Claims 1, 11-13, 17, 36 and 50, for example) that is suitable for reconstitution if lyophilized (Claims 17 and 19). Thus, a solid lyophilized composition is reasonably taught by Pelletier et al. It is the Examiner’s position that after freeze-drying process of lyophilization, the artisan has in their hands a composition with ≤3% w/w water. Pelletier et teach adding “one or more bulking agents which may provide adequate structure to the lyophilized cake, e.g., one or more of mannitol, lactose, sucrose, trehalose, sorbitol, glucose, raffinose, arginine, glycine, histidine, dextran ( e.g., dextran 40), polyvinylpyrrolidone, polyethylene glycol, and polypropylene glycol, e.g., one or more of mannitol, glucose, sucrose, lactose, trehalose, and dextran ( e.g., dextran 40).” (Page 21, 1.35; see also page 62, 1.36-1.39) in an amount of wherein the composition comprises 5 or 10 or 50 mg to
2 or 5 g of one or more bulking agents, e.g., from about 50 or 100 mg to 200, 300,
500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking agents (Page 21, 1.36). Consequently, Pelletier et al. teach and suggest adding lyophilization excipients such as one or more of sucrose, trehalose and lactose to the composition. Pelletier et al. teach a specific embodiment with meglumine in claim 50:
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Regarding claim 1, since Pelletier et al. disclose 20-500 mg of the compound of Formula I and from 60 and 500 mg of meglumine, then, for example 500 mg of the compound of Formula I and 500 mg of meglumine is a ratio of 1:1 and within the claimed ranges. Pelletier et al. also disclose ratios of at least 1:2 and 1:4 (Claim 16).
Regarding claim 1, Pelletier et al. teach that the composition is stable at room temperatures for months with < 1 % N-[3,5-
bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. (Claim 55).
Regarding claims 10, 12, 24 and 25, Pelletier et al. disclose adding pH adjusting agents such as tris(hydroxymethyl)aminomethane, sodium citrate and Na2HPO4 (Claim 47-49). While Pelletier et al. teach that after admixing the pH is between pH 7 and pH 10.5, such as 8.5 (Claims 4, 28 and 38), which falls overlaps or falls within the claimed range of 7.5 to 9.5 or 8.0-9.0 or about 8.5 for solutions of the composition, it would still be obvious add such solid pH adjusting agents prior to the solid composition prior to dissolution. See MPEP 2144.04 IV: “In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).”
Regarding claim 11, Pelletier et al. disclose adding NaH2PO4 and/or
Na2HPO4, which together form a phosphate buffer, as well as sodium hydroxide (Claim 30).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Pelletier et al. is that Pelletier et al. do not expressly teach wherein the weight ratio of 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate to lyophilization excipient is 1:1-10, or 1:2.5-7.5, or 1:5 and wherein the pharmaceutical composition comprises ≤ 1 % of N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after 6 months at room temperature.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to have a weight ratio of the compound claimed with the lyophilization excipient of 1:1-10 or 1:21.5-6.7 or 1:5 and wherein the pharmaceutical composition comprises ≤ 1 % of N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after 6 months at room temperature, and produce the instant invention. However, Pelletier et al. teach and suggest a lyophilized cake with one or more of mannitol, lactose, sucrose, trehalose (Page 21, 1.35) and provides amounts to employ such as in an amount of wherein the composition comprises 5 or 10 or 50 mg to
2 or 5 g of one or more bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking agents (Page 21, 1.36). Since Pelletier et al. teach that the compound of formula I is present in an amount of 10 to 600 mg (Claim 2), then it is then merely routine optimization to determine the optimal amount of lyophilization excipient/bulking agent to add to arrive at the claimed ratio of 1:1-10 with a reasonable expectation of success. For example, the artisan can choose 500 mg of the compound of Formula I and 500 mg of a lyophilization excipient/bulking agent for a 1:1 ratio. The artisan can even select 500 mg of the compound of Formula I and 5 grams of a lyophilization excipient/bulking agent for a 1:10 ratio without any undue experimentation whatsoever. See MPEP 2144.05 (II) (A): “[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). It is the Examiner’s position that the same combination of active agent, meglumine an lyophilization excipients in the solid lyophilized pharmaceutical composition of Pelletier et al. naturally results in and wherein the pharmaceutical composition comprises ≤ 1 % of N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide after 6 months at room temperature. The Examiner's finding is based on the principle that products of identical chemical compositions cannot have mutually exclusive properties. This is a well settled principle in patent law. See In re Papesch, 315 F.2d 381,391 (CCPA 1963) ("From the standpoint of patent law, a compound and all of its properties are inseparable; they are one and the same thing."). Where patentability rests upon a property of the claimed material not disclosed within the art, the USPTO has no reasonable method of determining whether there is, in fact, a patentable difference between the prior art materials and the claimed material. In re Best, 562 F.2d 1252, 1255 (CCPA 1977). Therefore, where the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the USPTO can require an applicant to prove that the prior art products do not necessarily possess the characteristics of his claimed product. Id. In addition, the Examiner notes that Pelletier et al. observe “about 1 % of N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide over a four month period at room temperature” [00140], where “about 1%” allows for less than 1% and the composition did not have meglumine or a lyophilization agent. Thus, there is an expectation of very low amounts of the degradation product.
The difference between the instant application and Pelletier et al. is that Pelletier et al. do not expressly teach hydrochloric acid or citric acid pH adjusting agents. However, Pelletier et al. do suggest adjusting the pH to the desired pH [0052] and Pelletier et al. suggest sodium citrate. The conjugate acid to sodium citrate is citric acid. Thus, citric acid is an obvious pH adjusting agent when too much sodium citrate has been used and the pH needs adjusting. Similarly, hydrochloric acid is a common strong acid that can be used to adjust pH with a reasonable expectation of success by the pharmaceutical formulation researcher. Especially if the artisan over adjusts the pH with sodium hydroxide and desires a less alkaline pH, then a strong acid like hydrochloric acid can be used to titrate the solution to a less alkaline pH. Thus, the ordinary artisan would employ the pH adjusting agents citric acid and hydrochloric acid to produce the instant invention with a reasonable expectation of success.
Response to Arguments:
Applicant’s remarks filed on 5/14/26 have been carefully considered but are not persuasive.
Applicant asserts: “That meglumine in particular with the specific lyophilization excipients and the specific amounts claimed could be used to provide enhanced stability of formula (I) could not have been predicted from Pelletier.” Respectfully, that assertion is difficult to believe because Pelletier et al. teach an embodiment with a compound of formula I and meglumine and with amounts that read upon the claimed ratio range (Claim 50) and Pelletier et al. teach and suggest the same lyophilization excipients to provide adequate structure to the lyophilized cake (Page 21, 1.35) and Pelletier et al. provide an expectation of stability for months at room temperature with < 1 % N-[3,5-
bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide. Applicant’s argument is not persuasive.
On page 7 of remarks, Applicant points to examples 2, 3 and 6 for room temperature stability in the presence of meglumine. However, Pelletier et al. already teach and suggest similar ratios of the claimed compound and meglumine and an expectation of stability for months. Consequently, it is merely routine optimization of the disclosure of Pelletier et al. Example 15 of Pelletier is not relevant because ethanolamine is not a claimed excipient and Pelletier specifically provides for the combination with meglumine. Thus, meglumine is not a fleeting thought to combine with the compound of Formula I, but rather a solid embodiment of Pelletier. Applicant’s testing of various components in Examples 7-8 is noted but Pelletier already direct the artisan to meglumine which naturally imparts any enhanced stability to the composition. It appears all that Applicant has done is verify what was taught by Pelletier. Applicant’s arguments are not persuasive.
Claims 16-21 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pelletier et al. (WO2015069956) and Lyophilization: A Primer ([online] retrieved on 11/12/25 from: https://www.pharmtech.com/view/lyophilization-primer; Pharmaceutical Technology 2013;37(5):15 pages).
Applicant claims:
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Regarding the “optionally” limitation, the MPEP provides, “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure.” See M.P.E.P § 2111.04; see also M.P.E.P §§ 2103(C) and 2173.05(h).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 16-20, Pelletier et al. teach methods of making a salt solution of the compound of Formula I by admixing with meglumine (Claim 83). Pelletier et al. also teach methods of making the pharmaceutical composition comprising the compound of Formula I by admixing with a pharmaceutically acceptable excipient (Claim 57; see also claims 1, 3 and 13). Pelletier et al. teach using sterile water for injection (Claim 20). Pelletier et al. specifically teach pharmaceutical compositions with between 25-450 mg of the compound of Formula I and between about 20 and 900 mg of meglumine (Claim 50). Pelletier et al. teach adding pH adjusting agents such as tris(hydroxymethyl)aminomethane, sodium citrate and Na2HPO4 (Claim 47-49) and wherein after admixing the pH is between pH 7 and pH 10.5 (Claim 38). Pelletier et al. also suggest lyophilization (Claim 19) and adding one or more of the lyophilization agents sucrose, lactose and trehalose (Page 21, 1.35, 1.39). Pelletier et al. teach sterile filtration to remove particles and microbes (Page 40, 1.97; page 81, 1.97).
Regarding claim 21, Pelletier et al. teach lyophilizing with freezing, primary drying and secondary drying (Page 22, 1.42-1.43; Page 63, 1.42).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and Pelletier et al. is that Pelletier et al. do not expressly taking water for injection, temperatures and lyophilization steps as claimed. However, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to prepare the pharmaceutical composition as claimed by performing the claimed method steps and produce the instant invention. First of all, typical room temperatures ranges from 20-25 °C, so having the water for injection at room temperature is obvious. The order of dissolving the components is obvious in the absence of any criticality. See MPEP 2144.04 IV: “See also In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946) (selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results); In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious.).” Adding to the portion of water for injection meglumine first and dissolving until clear and then slowly adding the compound, optional components such as lyophilization agents and pH adjusting agents and the remainder of water for injection is then obvious to the pharmaceutical artisan in this art. Cooling to 20° C can simply be in an air-conditioned room. Sterile filtering is an obvious step to remove any bacterial contaminants such that the subject receiving the formulation is not infected and Pelletier et al. teach sterile solutions (Claim 20) and sterile filtering as discussed above. While Pelletier et al. do not describe the claimed lyophilizing process, Pelletier et al. suggest lyophilization with freezing, primary drying and secondary drying as discussed above. It is then merely routine optimization of the lyophilization process steps of claims 19 and 21 to obtain a lyophilized product and bring it to room temperature of 25° C in the absence of evidence to the contrary. Especially when the artisan is aware that lyophilization proceeds through a primary drying of the frozen material at very low level of pressure to allow the solvents to sublime (Page 4) and a secondary drying desorption process to remove any solvent after the primary drying where the temperature is raised and the pressure reduced to a minimum in a process that could last several days (Page 5) as taught by the Lyophilization: A Primer. See also Figure 3 showing a simplified freeze-drying chart of the lyophilization cycle with steps in the cycle:
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In addition, the Primer teaches that the freeze-drying cycles are optimized with regard to the formulation and freeze drying equipment to achieve optimum efficiency in manufacturing (Page 8). Thus, the artisan recognizes the freeze-drying process as something to optimize. Consequently, in the absence of any unexpected results, the result is the same: a lyophilized product. See MPEP 2144.05 (II) (A): “[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). Therefore, all the decreasing of shelf temperatures, within certain time periods and maintained for certain time periods followed by an increase in shelf temperature for a certain time period followed by decreasing slab temperature and maintained for a time period with a vacuum below 0.2 mbar and further decreasing the shelf temperature within a time period and maintained for another time period before raising the shelf temperature in steps under ultimate vacuum to dry at 25 °C for 12 hours as described in claims 19 and 21 are well within the skill of the ordinary artisan in this art optimizing the freeze-drying cycle for optimum efficiency in manufacturing.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the combined 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 at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments:
Applicant’s remarks filed on 5/14/26 have been carefully considered but are not persuasive.
Applicant asserts that Pelletier does not describe a solid lyophilized product as claimed and therefore does not teach or suggest a method of preparing the solid lyophilized product. Respectfully, the Examiner does not agree for the reasons provided supra.
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 1-4, 7-11, 15-18, 22, 23 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11801254 in view of Pelletier et al. (WO2015069956). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent also teaches a pharmaceutical composition comprising:
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(Claim 1) and meglumine (Claim 10) in a ratio of at least 1:2 (Claim 11); that is suitable for dissolution, hence a solid, with an aqueous solution to form an injection (Claim 2) with sterile water for injection comprising the lyophilization agent dextrose (Claim 12) and at a pH between 8 and 8.5 (Claims 3-5). The composition comprises less than 1% of the impurity after one week (Claim 6). Methods of admixing the Formula I compound and an amine are disclosed (Claim 15).
The patent does not expressly teach a lyophilized solid with lyophilizing agents in the ratios claimed. However, Pelletier et al. teach and suggest a lyophilized cake with one or more of mannitol, lactose, sucrose, trehalose (Page 21, 1.35) and provides amounts to employ such as in an amount of wherein the composition comprises 5 or 10 or 50 mg to 2 or 5 g of one or more bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking agents (Page 21, 1.36). Since Pelletier et al. teach that the compound of formula I is present in an amount of 10 to 600 mg (Claim 2), then it is then merely routine optimization to determine the optimal amount of lyophilization excipient/bulking agent to add to arrive at the claimed ratio of 1:1-10 with a reasonable expectation of success. For example, the artisan can choose 500 mg of the compound of Formula I and 500 mg of a lyophilization excipient/bulking agent for a 1:1 ratio. The artisan can even select 500 mg of the compound of Formula I and 5 grams of a lyophilization excipient/bulking agent for a 1:10 ratio without any undue experimentation whatsoever. Consequently, it would be obvious to add the common and conventional claimed lyophilization agents and optimize the amount to arrive at the ratios claimed to make a solid lyophilized product with ≤ 3% w/w water.
The patent does not expressly teach a weight ratio of 1:0.6~1. However, the “~” denotes variability and includes values greater than 1 such that the disclose ratio of 1:2 renders the claimed ratio obvious.
The patent does not expressly teach adding a pH adjusting agent to the solid lyophilized composition as claimed. However, the patent does suggest a range of pH values and the ordinary artisan would employ the common and conventional pH adjusting agents such as sodium hydroxide, phosphate buffer, hydrochloric acid or citric acid to achieve the desired pH within the ranges upon dissolution.
The patent does not expressly teach taking water for injection, cooling to 15°C~25°C, adding meglumine and dissolving until clear, slowly adding 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof;
b) Adding the lyophilization excipient and optionally, adding other components;
c) Adding water for injection;
d) Sterile filtering and lyophilizing the product obtained in step (c).
However, optional steps need not be performed and determination of the amount of water to mix the component in at room temperature is conventional laboratory work for the ordinary artisan in this art. Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter.
Claims 1-4, 7-12, 15-18, 22, 23 and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10894055 in view of Pelletier et al. (WO2015069956). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent also teaches a solid lyophilized pharmaceutical composition (Claims 1 and 11) and methods of making (Claim 2):
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The base is meglumine (Claim 9). The patent teaches sterile water for injection and sterile solutions comprising lyophilization agent dextrose (Claims 15-17). The patent teaches lyophilized compound (Claim 11) and dissolved compound and bases in aqueous solution (Claim 18).
The patent does not teach the claimed lyophilization agents or the ratio of compound to lyophilization agent. However, Pelletier et al. teach and suggest a lyophilized cake with one or more of mannitol, lactose, sucrose, trehalose (Page 21, 1.35) and provides amounts to employ such as in an amount of wherein the composition comprises 5 or 10 or 50 mg to 2 or 5 g of one or more bulking agents, e.g., from about 50 or 100 mg to 200, 300, 500, or 800 mg, or 1, 1.5, 2, 3, 4, or 5 g of one or more bulking agents (Page 21, 1.36). Since Pelletier et al. teach that the compound of formula I is present in an amount of 10 to 600 mg (Claim 2), then it is then merely routine optimization to determine the optimal amount of lyophilization excipient/bulking agent to add to arrive at the claimed ratio of 1:1-10 with a reasonable expectation of success. For example, the artisan can choose 500 mg of the compound of Formula I and 500 mg of a lyophilization excipient/bulking agent for a 1:1 ratio. The artisan can even select 500 mg of the compound of Formula I and 5 grams of a lyophilization excipient/bulking agent for a 1:10 ratio without any undue experimentation whatsoever. It the Examiner’s position that the lyophilized product has less than or equal to 3% w/w water.
The patent does not expressly teach the weight ratio of compound to meglumine. However, it is merely routine optimization to determine the optimal ratio of compound to meglumine.
The patent does not expressly teach a pH adjusting agent as claimed. However, the patent suggest a pKa between 8-10 and the ordinary artisan would employ the claimed pH adjusting agents to achieve the desired pH within the ranges upon dissolution of the solid. The ordinary artisan would add common and conventional pH adjusting agents such as sodium hydroxide, phosphate buffer, hydrochloric acid or citric acid to keep the pH in that range to achieve the desired pH within the ranges upon dissolution of the solid composition.
The patent does not expressly teach all the steps of the method of claim 16 by taking water for injection, cooling to 15°C~25°C, adding meglumine and dissolving until clear, slowly adding 2-((3,5-bis(trifluoromethyl)phenyl)carbamoyl)-4-chlorophenyl dihydrogen phosphate or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof;
b) Adding the lyophilization excipient and optionally, adding other components;
c) Adding water for injection;
d) Sterile filtering and lyophilizing the product obtained in step (c).
However, optional steps need not be performed and determination of the amount of water to mix the component in at room temperature is conventional laboratory work for the ordinary artisan in this art. Furthermore, the steps of claim 16 appear to be nothing more than routine optimization of the lyophilization process to obtain a lyophilized product. Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the patented subject matter.
Response to Arguments:
Applicant’s remarks filed on 5/14/26 have been carefully considered but are not persuasive. The patents specifically claim meglumine and provide an expectation of enhanced stability with meglumine combined with lyophilization agents given the teachings of the references. The examples that applicant discusses are unavailing. Applicant’s arguments are not persuasive.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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/ERNST V ARNOLD/Primary Examiner, Art Unit 1613
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