DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election without specifying traverse of Group I in the reply filed on 7/15/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)). The requirement is still deemed proper and is therefore made FINAL.
Claim 23 ais withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Applicant’s election without specifying traverse of a single composition in the reply filed on 7/15/2026 is also acknowledged.
The elected species read upon claims 1-2, 6-8, 10 and 15. Claims 17 and 19-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
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.
Claims 2, 6-8 and 10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 2 recites “[t]he pharmaceutical composition... wherein the amino acid is an amino acid... [is] preferably alanine, 4-aminobutyric acid...” and so on.
The phrase “preferably” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 6-8 and 10 similarly recite the phrase “preferably”.
Accordingly, claims 2, 6-8 and 10 are rejected as indefinite.
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.
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 1-2, 6-10 and 15 are rejected under 35 U.S.C. 103(a) as being unpatentable over Huang et al (WO 2020/259675 – based on US 2022/0380393 as the English language equivalent; of record) in view of Wan et al (EP 2 464 230 B1, 2010).
Claim 1 is drawn to a pharmaceutical composition, comprising:
(A) a compound of formula I or a pharmaceutically acceptable salt thereof:
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; and
(B) a stabilizer selected from an amino acid and/or a saccharide (more specifically, wherein the stabilizer is arginine (claims 2 and 15)).
Huang et al teach “a new NK1 [neurokinin-1 receptor] antagonist prodrug” of rolapitant (Paragraph 0006), specifically disclosing the instantly claimed compound of formula I (Paragraphs 0101-0110, Example 1, Compound 4), and “a pharmaceutically acceptable salt thereof” (Abstract), specifically disclosing the N-methyl-D-glucamine salt of said compound (Paragraphs 0110, Example 1, Compound 5), as well as “a pharmaceutical composition comprising a therapeutically effective amount of at least one of the aforementioned compounds or pharmaceutically acceptable salt thereof, as well as a pharmaceutically acceptable carrier, diluent or excipient” (Paragraph 0064), which “shows excellent pharmacokinetic data of rolapitant in rats, which indicates that the compound of Example 1 has been metabolized to rolapitant in vivo” (Paragraph 0221).
As such, the composition of Huang et al differ from the instantly claimed compositions in that Huang et al do not teach the inclusion of arginine.
Yet, as further taught by Huang et al, regarding “the pharmaceutically acceptable salt”, “[t]he compound according to the present disclosure is reacted with a base such as N-methyl-D-glucamine... to form the corresponding salt” wherein “[s]aid base can be selected from the group consisting of... arginine” (Paragraph 0068).
Similarly, Wan et al teach structurally related prodrugs of rolapitant, including “[i]n a more preferred embodiment of the prodrug” the N-methyl-D-glucamine salt of:
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(Paragraph 0037) wherein, as further taught by Wan et al, “[t]he preferred... salts are selected from, for example... salts with organic bases such as N-methyl-D-glucamine... [or] amino acids such as arginine” (Paragraph 0038).
Additionally, Wan et al teach “parenteral formulations comprising” rolapitant and “a pharmaceutically acceptable vehicle” (Paragraph 0014) wherein “[t]he term ‘pharmaceutically acceptable vehicle’... [is] selected from... amino acids” wherein “positively charged amino acids... complex with a negatively charged portion of [rolapitant] and neutralize it and reduce exposure of the compound to red blood cells” (Paragraph 0015).
At minimum, it would have been prima facie obvious to utilize arginine in formulating “a pharmaceutically acceptable salt” of Compound 4 taught by Huang et al as opposed to as N-methyl-D-glucamine with a reasonable expectation of success. It would have been obvious to do so considering that Huang et al and Wan et al explicitly teaches arginine, in addition to N-methyl-D-glucamine, as a suitable amino acid cation for forming salts of the instantly claimed compound and structurally related phosphate-derivative rolapitant prodrugs. And, in doing so, it is necessarily the case that some free arginine would be present in the composition.
Additionally, based on Wan et al, it would have been further obvious to include arginine as a pharmaceutically acceptable excipient in the pharmaceutical composition of Huang et al comprising said compound. It would have been obvious to do so in the reasonable expectation that the association of arginine with the intact prodrug and/or released rolapitant would reduce exposure to red blood cells.
In view of either or all of the foregoing, claims 1-2 and 15 are rejected as prima facie obvious.
Claim 6 is drawn to the composition according to claim 1, wherein the pharmaceutical composition further comprises water.
As discussed above, Huang et al teach “a pharmaceutical composition comprising a therapeutically effective amount of at least one of the aforementioned compounds or pharmaceutically acceptable salt thereof, as well as a pharmaceutically acceptable carrier, diluent or excipient” (Paragraph 0064). As further taught by Huang et al, “[t]he compound of... the present disclosure has better solubility than that of the parent drug... and is thus suitable for intravenous administration” (Paragraph 0021; see also Page 31, Table 1: Example 1 is water soluble at greater than 10 mg/ml at pH 5). Moreover, Huang et al specifically teach “[a] certain amount of the compounds of Example 1... were weighed and prepared into a pH=4.0 solution by using 20 mmol/L sodium dihydrogen phosphate” (Paragraph 0215) which is understood to contain water as the solvent.
Additionally, as taught by Wan et al, regarding the formulations of the structurally related prodrugs of rolapitant for intravenous administration, “[t]he pharmaceutical composition can be diluted prior to administration with a suitable aqueous diluent(s) such as... dextrose filtered water” (Paragraph 0093).
As such, it would have been obvious to a person of ordinary skill in the art to include water in formulating the composition of Huang et al suitable for intravenous administration.
Claim 7 is drawn to the composition according to claim 1, wherein the weight ratio of the compound of formula I or the pharmaceutically acceptable salt thereof to stabilizer is 1:0.1-1:20.
At the outset, as stated by MPEP 2144.05, “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical” (see also In re Aller (220 F.2d 454 (CCPA): “where 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 fact, as further discussed by the court, “[s]uch experimentation is no more than the application of the expected skill of the [ordinarily skilled artisan] and failure to perform such experiments would, in our opinion, show a want of the expected skill”; see also In re Peterson, 315 F.3d at 1325 (Fed. Cir. 2005): “[t]he normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages” and “[o]nly if the ‘results of optimizing a variable’ are ‘unexpectedly good’ can a patent be obtained for the claimed critical range” (quoting In re Antonie (559 F.2d 618 (CCPA 1977))).
In the instant case, the concentrations of active ingredient and counter-ion and/or vehicle (and thus, the ratio thereof) is clearly a result-effective variable. Indeed, indicated by the court in Ariosa Diagnostics, Inc. v. Sequenom, Inc., 809 F.3d 1282, 1293 (Fed. Cir. 2015), every ordinary artisan in medicine performs “merely routine optimization of drug dosage to maximize therapeutic effect.”
Accordingly, at minimum, it would have been customary for an artisan of ordinary skill in the art to determine the optimal concentration of the compound of Example 1 and arginine (and, thus, the ratio thereof) in order to best achieve the desired results.
Furthermore, Huang et al teach mixing “Compound 4 (111 mg...) and meglumine (59.6 mg...)” which entails a weight ratio of 1:0.54.
As such, claim 7 is also rejected as prima facie obvious.
Claim 8 is drawn to the composition according to claim 1, wherein the compound of formula I or pharmaceutically acceptable salt thereof has a mass volume percentage of 0.01% to 30%.
As discussed above, Huang et al specifically teach “[a] certain amount of the compounds of Example 1... were weighed and prepared into a pH=4.0 solution by using 20 mmol/L sodium dihydrogen phosphate” (Paragraph 0215). As further taught by Huang et al, “[t]he drug was administered by intravenous bolus injection... administration dose of 2 mg/kg, administration concentration of 0.4 mg/ml and administration volume of 5 ml/kg” (Paragraph 0217), which equates to a mass volume percentage of 0.04%.
As such, claim 8 is also rejected as prima facie obvious.
Claim 10 is drawn to the composition according to claim 1, wherein the pharmaceutical composition further comprises a buffer (e.g., citrate buffer), chelating agent (e.g., EDTA) and/or a 5-HT3 antagonist (e.g., ondansetron).
As taught by Wan et al, regarding the intravenous formulations, “preservatives (EDTA), etc.” may be added (Paragraph 0034), “[t]he pharmaceutical composition may also comprise at least one buffer... such as... citrate buffers (pH 2-6)” (Paragraph 0077), and the “intravenous formulations may be used in combination with other antiemetic and antinausea medications” such as “ondansetron and other known 5HT3 antagonists” (Paragraph 0051).
As such, it would have been obvious to a person of ordinary skill in the art to include a buffer, chelating agent and/or a 5HT3 antagonist in formulating the composition of Huang et al suitable for intravenous administration.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 1-2, 6-10 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12,421,260 in view of Wan et al (EP 2 464 230 B1, 2010).
Although the claims at issue are not identical, they are not patentably distinct from each other. Claims 1-2 of the ‘260 Patent are drawn to the instantly claimed compound of formula (I) or a pharmaceutically acceptable salt thereof. And claim 3 recites “[a] pharmaceutical composition... wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier, diluent or excipient”.
Wan et al teach structurally related prodrugs of rolapitant, including “[i]n a more preferred embodiment of the prodrug” the N-methyl-D-glucamine salt of:
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(Paragraph 0037) wherein, as further taught by Wan et al, “[t]he preferred... salts are selected from, for example... salts with organic bases such as N-methyl-D-glucamine... [or] amino acids such as arginine” (Paragraph 0038).
Additionally, Wan et al teach “parenteral formulations comprising” rolapitant and “a pharmaceutically acceptable vehicle” (Paragraph 0014) wherein “[t]he term ‘pharmaceutically acceptable vehicle’... [is] selected from... amino acids” wherein “positively charged amino acids... complex with a negatively charged portion of [rolapitant] and neutralize it and reduce exposure of the compound to red blood cells” (Paragraph 0015).
Accordingly, for the same reasons as discussed above, based further on Wan et al, it would have been prima facie obvious to include arginine in the ‘260 composition.
At minimum, it would have been prima facie obvious to utilize arginine in formulating “a pharmaceutically acceptable salt” of the ‘260 compound with a reasonable expectation of success. It would have been obvious to do so considering that Wan et al explicitly teaches arginine as a suitable amino acid cation for forming salts of the instantly claimed compound and structurally related phosphate-derivative rolapitant prodrugs. And, in doing so, it is necessarily the case that some free arginine would be present in the composition.
Additionally, based on Wan et al, it would have been further obvious to include arginine as a pharmaceutically acceptable excipient in the pharmaceutical composition of Huang et al comprising said compound. It would have been obvious to do so in the reasonable expectation that the association of arginine with the intact prodrug and/or released rolapitant would reduce exposure to red blood cells.
Claims 2, 6-10 and 15 are rejected for the same reasons as discussed above.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CRAIG D RICCI whose telephone number is (571) 270-5864. The examiner can normally be reached on Monday through Thursday, and every other Friday, 7:30 am - 5:00 pm ET. 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, Bethany Barham can be reached on (571) 272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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