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 Status
Claims 21-26 are new.
Claims 5, 6, 13 and 14 are cancelled.
Claims 1-4, 7-12 and 15-26 are pending. Applicant’s amendments have necessitated new grounds of rejection. Accordingly, this Action is FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/3/25 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Withdrawn rejections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 11/3/25 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 Any rejection and/or objection not specifically addressed below is herein withdrawn.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 5, 9, 11 and 12 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph; Claims 16-20 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph; and claim(s) 1-6 and 10-15 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pelletier et al. (WO2015069956). Applicant has amended the claims to overcome these rejections. Claims 1-6 and 10-14 were provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 88-92 of copending Application No. 18492750. The copending application is directed to an aqueous solution while the instantly claimed subject matter is a lyophilized solid. Claims 1-6 and 16-18 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 10, 12-15, 18, 19 and 23 of U.S. Patent No. 11117909. The patent teaches admixing the crystalline form of the compound in a liquid. Thus, the pharmaceutical composition made is a solution and not a solid lyophilized composition.
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 § 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.
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.
Claims 12, 24 and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being 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. Claim 1 is directed to a solid lyophilized compositions. Claims 12, 24 and 25 are directed to pH values of the composition. However, pH is only measured in aqueous solution as pH is defined by the hydrogen ion and hydroxide ion concentrations in a water-based solution and claim 1 requires a solid lyophilized composition. A solid is not a solution and the pH cannot be measured. Therefore, the claims are indefinite. Correction is required. Claims 12, 24 and 25 will not be further treated on the merits.
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(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) 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 1-4, 7-11, 15, 22-23 and 26 are rejected under 35 U.S.C. 103(a) 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(a), 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(a).
Applicant claims, for example:
PNG
media_image1.png
240
794
media_image1.png
Greyscale
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, 7, 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 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, 1.46-1.49). Consequently, Pelletier et al. teach and suggest adding lyophilization excipients to the composition. Pelletier et al. teach a specific embodiment with meglumine in claim 50:
PNG
media_image2.png
260
954
media_image2.png
Greyscale
Regarding claims 2-4, 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 10, 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). It is then merely routine optimization to determine the optimal amount of lyophilization to add with a reasonable expectation of success. 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 11/3/25 have been carefully considered but are not persuasive.
Applicant asserts that their lyophilized product comprises ≤ 1 % of N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide (formula (II)) even after 6 months at room temperature and directs the Examiner to Examples 15 and 17 of Pelletier et al. for teaching compositions with about 1% of the degradation product over a 4 month period at RT. Applicant asserts the meglumine in particular could not have been predicted to provide enhanced stability of formula (1) from the teachings of Pelletier et al. Respectfully, the Examiner has a different perspective. As noted above, Example 17 lacked the presence of meglumine. Pelletier et al. teach and suggest a specific embodiment with the compound of formula 1 and meglumine (Claim 50). Any stability imparted by the meglumine is naturally present in the composition of Pelletier et al. and a latent benefit of admixing the components. It appears that all Applicant has done it measured the stability of that embodiment of Pelletier et al. Based on the evidence of record, it is reasonable to shift the burden of proof to Appellant to show that the functional limitations regarding stability is not inherent in the composition made obvious by prior art. In re Best, 562 F.2d 1252, 1254--55, (CCPA 1977) (quoting In re Swinehart, 439 F.2d 210, 212-13 (CCPA 1971 )) ("' [M]ere recitation of a newly discovered function or property, inherently possessed by things in the prior art, does not cause a claim ... to distinguish over the prior art. Additionally, where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on.'"). Respectfully, Applicants 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:
PNG
media_image3.png
244
756
media_image3.png
Greyscale
PNG
media_image4.png
184
752
media_image4.png
Greyscale
PNG
media_image5.png
380
804
media_image5.png
Greyscale
PNG
media_image6.png
98
718
media_image6.png
Greyscale
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:
PNG
media_image7.png
318
628
media_image7.png
Greyscale
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 11/3/25 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. 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:
PNG
media_image8.png
502
672
media_image8.png
Greyscale
PNG
media_image9.png
124
488
media_image9.png
Greyscale
(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, the scope of the solid composition includes lyophilized products with lyophilization agents (Column 14, lines 61-column 15, line 2; column 15, lines 39-40). See MPEP 804: “The portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim.” 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. 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):
PNG
media_image10.png
652
544
media_image10.png
Greyscale
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, the patent does suggest a lyophilized compound of Formula I (Claim 11) and it is then obvious to add common and conventional lyophilization agents, such as those claimed, and optimize the amount added to achieve the desired lyophilized product. 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 11/3/25 have been carefully considered but are not persuasive. With regard to the ‘254 patent, Applicant asserts that the embodiment with lyophilization agent dextrose is a solution and not a solid lyophilized pharmaceutical composition. Respectfully, the Examiner has a different perspective. As discussed above, the scope of the solid composition includes lyophilized solids thus rendering obvious solid lyophilized compositions with the lyophilization agents claimed. With regard to the ‘255 patent, Applicant also asserts that the embodiment with lyophilization agent dextrose is a solution and not a solid lyophilized pharmaceutical composition. Applicant acknowledges that claim 11 recites that Formula I is lyophilized. The kit of claim 11 is dependent upon claim 3 which comprises one or more containers comprising the compound of Formula I and one or more Bronsted bases (Claim 3) that is meglumine (Claim 9) and can be in the same container (Claim 13) as a solid (Claim 14). Thus, a solid lyophilized composition the compound of Formula I and meglumine is obvious. It is then obvious to add lyophilization agents to Formula I prior to lyophilization for the benefit provided by such agents with a reasonable expectation of success. Respectfully, Applicant’s arguments are not persuasive.
Conclusion
No claims are allowed.
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.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERNST V ARNOLD/Primary Examiner, Art Unit 1613