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 .
Status of Claims
Claims 1-4 are pending as of the response and amendments filed on 3/16/26.
Claims 1-4 were previously rejected under 35 USC 103 as being unpatentable over Berger in view of Pietra. Applicants’ reasons for traversal and the 1.132 declaration filed on 3/16/26 are addressed below.
Applicants have argued the reference don’t support a prima facie case of obviousness over claims 3-4 because they do not teach “means for inducing therapeutic levels of netupitant in vivo”. Applicants have further argued the examiner has interpreted “means for inducing therapeutic levels of netupitant in vivo” in claim 3 simply as “netupitant” but this definition ignores the requirement that the means recited in claim 3 “induce therapeutic levels of netupitant in vivo”. Applicants have further argued none of the references describe how much netupitant must be injected to produce a therapeutic effect, i.e., how much netupitant must be injected to treat CINV. Applicants have argued Berger doesn’t disclose anything about netupitant injectable doses, and Pietra’s dosing teachings are limited to doses effective for the treatment of pain and irritable bowel syndrome. Applicant has stated with respect to pain and IBS, Pietra teaches doses well below those required to treat CINV, and have referred to para [059] in Pietra, i.e., for treating pain via injection, Pietra teaches a dose of netupitant of 4 to 120 mg. Applicants have also referred to para [066] in Pietra with respect to treatment of IBS, i.e., a dose of less than 0.7 mg. for a 70 kg patient. Applicants have continued to argue these doses are far less than the dose required to treat CINV, and as explained in the 1.132 declaration of Roberta Cannella, the injectable fosnetupitant dose approved by the FDA for treating CINV is 235 mg, which is equivalent to 197 mg. netupitant.
Applicants’ arguments are not persuasive. It is noted that the claims under examination are drawn to a formulation, not to a method of treatment. Regarding claims 3-4, these claims are drawn to an injectable formulation comprising: means for inducing therapeutic levels of netupitant in vivo; palonosetron or a pharmaceutically acceptable salt thereof, and a pH adjusting means. As discussed in the previous office action, “means for inducing therapeutic levels of netupitant in vivo” as recited by claim 3 has been interpreted by the examiner as an effective amount of netupitant, and this interpretation is maintained. There is nothing in the specification to define “means for inducing therapeutic levels of netupitant in vivo” to be specifically limited to the dose for treating CINV, as argued by Applicants. The examiner notes claim 1 as amended recites “An injectable formulation comprising: a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof for the treatment of CINV”, however, as the claim is drawn to a product and not a method of treatment, “for the treatment of CINV” is interpreted as a statement of intended use of the formulation. If a statement of intended use limits the structure of the formulation, it represents a claim limitation; however, if the body of a claim fully sets forth all of the limitations of the formulation, the statement of intended use doesn’t further limit the claim. See MPEP 2111.02(II): If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). Moreover, the dose of 197 mg netupitant is not recited in any of the claims. Applicants’ argument Berger doesn’t disclose anything about netupitant injectable doses is not persuasive, because Pietra was relied upon for the teaching of combination of netupitant with palonosetron. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although the 1.132 declaration has been considered by the examiner, it is not found persuasive to overcome the 103 rejection of record because while the declaration refers to netupitant based drug products for the treatment of CINV, the claims are not drawn to a method of treating CINV. Rather, the claims are drawn to a product, i.e., an injectable formulation comprising a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof; palonosetron or a pharmaceutically acceptable salt thereof; and a pH adjusting means. As discussed above, “for the treatment of CINV” as recited in amended claim 1 has been interpreted as a statement of intended use of the formulation, and does not further structurally limit the formulation.
For the reasons above, the 103 rejection over Berger in view of Pietra is maintained. This rejection will be reiterated with modification to address the claim amendments.
Claims 1-4 were previously rejected for nonstatutory double patenting over claims 15-16 of US ‘523 in view of Berger and Pietra. Applicants’ reasons for traversal are summarized and addressed below.
Applicants have argued none of the cited references teach or suggest an injectable dose of netupitant suitable for the treatment of CINV. Applicants have further argued Berger doesn’t disclose any netupitant doses, and Pietra discloses doses well below those required to treat CINV. Applicants have also argued US ‘523 only discloses preferred oral doses of netupitant and doesn’t inform a dose that would be appropriate for injection.
Applicants’ arguments are not persuasive. As discussed previously, the claims are drawn to a product formulation, not to a method of treating CINV, and the statement in the preamble of claim 1, “for the treatment of CINV” has been interpreted as a statement of intended use of the formulation, and does not further structurally limit the formulation. While rejected claims 15-16 of US ‘523 recite oral dosage form comprising netupitant and palonosetron, the references of Berger and Pietra were applied for an injectable formulation. Applicants’ argument Berger doesn’t disclose any netupitant doses is not persuasive because the rejection was based on Berger and Pietra, not just Berger. The nonstatutory double patenting rejection is maintained and reiterated, with modification to address the amended claims.
Claims 1-4 were examined and are rejected.
Claim Objection
Claim 1 objected to because of the following informalities: the claim refers to “CINV”, but this abbreviation is not mentioned anywhere in the specification. For the sake of clarity, it is suggested the claim be amended to recite “chemotherapy induced nausea and vomiting” with “CINV” in parenthesis. Appropriate correction 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:
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.
Claim(s) 1-4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Berger et. al., US 5202333, patented 4/13/1993, in view of Pietra et. al., WO 2013057554 A2, publ. 4/25/2013. Berger and Pietra are of record.
The terms “means for inducing therapeutic levels of netupitant in vivo” as recited by claim 3 has been interpreted by the examiner as an effective amount of netupitant.
Claim 1 as amended recites “An injectable formulation comprising: a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof for the treatment of CINV”, however, as the claim is drawn to a product and not a method of treatment, “for the treatment of CINV” is interpreted as a statement of intended use of the formulation. If a statement of intended use limits the structure of the formulation, it represents a claim limitation; however, if the body of a claim fully sets forth all of the limitations of the formulation, the statement of intended use doesn’t further limit the claim. See MPEP 2111.02(II): If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). As the body of the claim fully sets forth the structural limitations, “for the treatment of CINV” has been interpreted as a statement of intended use of the formulation and not further structurally limiting the claimed formulation.
Berger teaches tricyclic 5-HT3 receptor antagonists of the following structural formula (title & abstract; col. 1, lines 9-16; col. 2, line 17-col. 3, line 15):
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. Berger teaches the compounds to have activity as anti-emesis agents for the treatment of nausea and vomiting caused by chemotherapy and radiotherapy (col. 1, lines 32-41; col. 3, lines 19-24; col. 4, lines 42-45; col. 10, lines 6-13). Berger exemplifies (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, which is structurally identical to palonosetron (col. 27, Ex. 10). Berger teaches pharmaceutical compositions comprising a compound as described above for various routes of administration, including intravenous or subcutaneous injection, as well as in the form of solutions or suspensions (col. 12, lines 25-52). Berger exemplifies an intravenous formulation comprising citric acid monohydrate (an acidifying agent) and NaOH as pH adjusting agents (col. 29, lines 1-12). Berger also teaches a compound of formula (I) as discussed previously can be combined with another therapeutic agent (col. 12, lines 1-7).
Berger doesn’t explicitly teach or suggest the composition further comprises netupitant.
Pietra teaches the combination of netupitant and palonosetron for the treatment of pain and irritable bowel syndrome (title & abstract; para [001]). Palonosetron is a selective 5-HT3 antagonist, and netupitant is a selective NK1 receptor antagonist (para [002], [004]). It is also taught that the combination of a 5-HT3 receptor antagonist and a NK1 receptor antagonist exhibits significantly increased efficacy towards CINV (chemotherapy induced nausea and vomiting) (para [006]). Pietra teaches the combination of palonosetron and netupitant as synergistic (para [016], [045]). Therapeutically effective amounts of the agents are taught (para [038]; p. 27, claim 1). Pietra teaches the combination in a pharmaceutical composition in solid or liquid form, for oral, parenteral, or intravenous administration; preferred routes of administration are injectable or oral (para [067-068], [071]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the claimed injectable formulation comprising netupitant, palonosetron, and a pH adjusting agent in consideration of the combined teachings of Berger and Pietra. Berger teaches injectable formulations comprising palonosetron and pH adjusting agents, including NaOH and citric acid; additionally, Berger teaches the inclusion of an additional therapeutic agent. Pietra teaches the combination of netupitant and palonosetron for providing a synergistic therapeutic effect, while also teaching the combination in a pharmaceutical composition, in which injection is included as a preferable route of administration. As such, one of ordinary skill in the art would have been motivated to have incorporated palonosetron and netupitant into the injectable composition taught by Berger, in order to provide a therapeutic synergistic effect, and have had a reasonable expectation of success.
Claim Rejections-Nonstatutory 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 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-16 of U.S. Patent No. 11559523 B2 (US ‘523) in view of Berger et. al., US 5202333, patented 4/13/1993, in view of Pietra et. al., WO 2013057554 A2, publ. 4/25/2013.
As noted above, claim 1 as amended recites “An injectable formulation comprising: a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof for the treatment of CINV”, however, as the claim is drawn to a product and not a method of treatment, “for the treatment of CINV” is interpreted as a statement of intended use of the formulation. If a statement of intended use limits the structure of the formulation, it represents a claim limitation; however, if the body of a claim fully sets forth all of the limitations of the formulation, the statement of intended use doesn’t further limit the claim. See MPEP 2111.02(II): If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). As the body of the claim fully sets forth the structural limitations, “for the treatment of CINV” has been interpreted as a statement of intended use of the formulation and not further structurally limiting the claimed formulation.
Claims 15-16 of US ‘523 are drawn to an orally administered dosage form comprising a therapeutically effective amount of palonosetron or a pharmaceutically acceptable salt thereof, and a therapeutically effective amount of netupitant or a pharmaceutically acceptable salt thereof. Although the instant claims are drawn to an injectable formulation rather than an oral formulation, and the patented claims don’t recite the inclusion of a pH adjusting agent as required by the instant claims, such modifications to the patented formulation would have been prima facie obvious. Berger teaches tricyclic 5-HT3 receptor antagonists of the following structural formula (title & abstract; col. 1, lines 9-16; col. 2, line 17-col. 3, line 15):
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. Berger teaches the compounds to have activity as anti-emesis agents for the treatment of nausea and vomiting caused by chemotherapy and radiotherapy (col. 1, lines 32-41; col. 3, lines 19-24; col. 4, lines 42-45; col. 10, lines 6-13). Berger exemplifies (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-2,3,3a,4,5,6-hexahydro-1H-benz[de]isoquinolin-1-one, which is structurally identical to palonosetron (col. 27, Ex. 10). Berger teaches pharmaceutical compositions comprising a compound as described above for various routes of administration, including intravenous or subcutaneous injection, as well as in the form of solutions or suspensions (col. 12, lines 25-52). Berger exemplifies an intravenous formulation comprising citric acid monohydrate (an acidifying agent) and NaOH as pH adjusting agents (col. 29, lines 1-12). Berger also teaches a compound of formula (I) as discussed previously can be combined with another therapeutic agent (col. 12, lines 1-7).
Berger doesn’t explicitly teach or suggest the composition further comprises netupitant.
Pietra teaches the combination of netupitant and palonosetron for the treatment of pain and irritable bowel syndrome (title & abstract; para [001]). Palonosetron is a selective 5-HT3 antagonist, and netupitant is a selective NK1 receptor antagonist (para [002], [004]). It is also taught that the combination of a 5-HT3 receptor antagonist and a NK1 receptor antagonist exhibits significantly increased efficacy towards CINV (chemotherapy induced nausea and vomiting) (para [006]). Pietra teaches the combination of palonosetron and netupitant as synergistic (para [016], [045]). Pietra teaches the combination in a pharmaceutical composition in solid or liquid form, for oral, parenteral, or intravenous administration; preferred routes of administration are injectable or oral (para [067-068], [071]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the claimed injectable formulation comprising netupitant, palonosetron, and a pH adjusting agent in consideration of the combined teachings of Berger and Pietra. Berger teaches injectable formulations comprising palonosetron and a pH adjusting agent, including NaOH and citric acid; additionally, Berger teaches the inclusion of an additional therapeutic agent. Pietra teaches the combination of netupitant and palonosetron for providing a synergistic therapeutic effect, while also teaching the combination in a pharmaceutical composition, in which injection is included as a preferable route of administration. As such, one of ordinary skill in the art would have been motivated to have modified the composition of the patented claims by the addition of a pH adjusting agent such as NaOH or citric acid monohydrate, for injection delivery, since both palonosetron and netupitant are taught in the prior art to be administered via injection, and have had a reasonable expectation of success. The instant and patented claims are as such obvious variants of each other and are not patentably distinct.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627