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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/23/26 has been entered.
Status of Claims
Claims 1-4 are pending as of the response and amendments filed on 6/23/26.
The objection to claim 1 is withdrawn in view of the amendments. The 103 rejection of claims 1-4 over Berger in view of Pietra is withdrawn in view of the amendments. The nonstatutory obviousness type double patenting rejection over the claims of US 11559523 B2 in view of Berger and Pietra is withdrawn based on the amended claims.
A new 103 rejection, and a new nonstatutory double patenting rejection are made based on the amended claims, discussed below.
Claims 1-4 were examined and are rejected.
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 and 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ottoboni et. al., WO 2014093907 A1, publ. 6/19/2014.
The terms “means for inducing therapeutic levels of netupitant in vivo for the treatment of CINV” as recited by claim 3 has been interpreted by the examiner as an effective amount of netupitant for treating CINV.
Ottoboni teaches a pharmaceutical formulation that provides sustained release for the combination of a 5-HT3 receptor antagonist and a NK1 receptor antagonist, for the treatment of disorders including chemotherapy-induced nausea and vomiting (CINV) (title & abstract; para [0002], [0006]). Ottoboni further teaches an embodiment wherein the 5-HT3 receptor antagonist and NK1 receptor antagonist are in a single formulation, formulated for subcutaneous injection (para [0008]). Other modes of delivery, including intravenous are also taught (para [0050]). Netupitant is included as an exemplary NK1 receptor antagonist (para [0010], [0108]), and palonosetron is included as an exemplary 5-HT3 receptor antagonist (para [0017], [0104]). Ottoboni teaches a therapeutically effective amount of both the NK1 receptor antagonist, and 5-HT3 receptor antagonist (para [0007], [0044], [0072]). Ottoboni teaches administering the composition comprising the combination therapy to a subject in need thereof to treat CINV (para [0075]). Ottoboni provides an example wherein the formulation includes a phosphate buffer (para [0092-0093]), thereby meeting a pH adjusting means.
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 treated CINV in a human subject comprising administering via subcutaneous injection a formulation comprising a therapeutically effective amount of netupitant for the treatment of CINV, and a therapeutically effective amount of palonosetron for the treatment of CINV; and a phosphate buffer, in view of Ottoboni. Ottoboni teaches the combination of a 5-HT3 receptor antagonist and a NK1 receptor antagonist in a single formulation for the treatment of CINV, and subcutaneous injection to a subject in need is exemplified. Ottoboni further teaches therapeutically effective amounts of the 5-HT3 receptor antagonist and a NK1 receptor antagonist, with netupitant included as an exemplary NK1 receptor antagonist, and palonosetron included as an exemplary 5-HT3 receptor antagonist. While treatment of a human is not explicitly taught, humans are well-known in the art to comprise the patient population afflicted with CINV. As such, the claimed method of treatment would have been prima facie obvious to a person of ordinary skill in the art, based on the teachings of Ottoboni, and have had a reasonable expectation of success.
Claim(s) 2 and 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ottoboni et. al., WO 2014093907 A1, publ. 6/19/2014 as applied to claims 1 and 3 above, and further in view of Berger et. al., US 5202333, patented 4/19/1993 (of record).
The disclosure of Ottoboni as discussed previously is incorporated herein. Although a phosphate buffer is taught, Ottoboni doesn’t explicitly teach the inclusion of an acidifying agent.
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).
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 incorporated an acidifying agent such as citric acid monohydrate into the composition administered for treating CINV as taught by Ottoboni, in view of Berger. Ottoboni teaches administering, either intravenously or subcutaneously a formulation comprising a 5-HT3 receptor antagonist such as palonosetron, and a NK1 receptor antagonist such as netupitant, to a subject in need of treatment for CINV. Although an acidifying pH adjusting agent is not explicitly taught by Ottoboni, Berger teaches an acidifying agent such as citric acid monohydrate as a suitable excipient for intravenous formulations comprising palonosetron. As such, it would have been routine for a person of ordinary skill in the art to have incorporated an acidifying agent such as citric acid monohydrate into the combination formulation administered for treating CINV as taught by Ottoboni.
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 1-4 and 8-11 of U.S. Patent No. 11559523 B2 (US ‘523) in view of Ottoboni et. al., WO 2014093907 A1, publ. 6/19/2014; and Berger et. al., US 5202333, patented 4/19/1993.
Claims 1-4 and 8-11 of US ‘523 are drawn to a method of treating emesis in a patient comprising orally administering a solid oral 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. Additionally, treatment of emesis induced by cancer chemotherapy is also recited by the patented claims (see claims 2-3 & 8-9). Although the instant claims are drawn to treating CINV by administering the combination of netupitant and palonosetron in an injectable formulation rather than an oral solid 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 in view of Ottoboni and Berger. Ottoboni teaches a pharmaceutical formulation that provides sustained release for the combination of a 5-HT3 receptor antagonist and a NK1 receptor antagonist, for the treatment of disorders including chemotherapy-induced nausea and vomiting (CINV) (title & abstract; para [0002], [0006]). Ottoboni further teaches an embodiment wherein the 5-HT3 receptor antagonist and NK1 receptor antagonist are in a single formulation, formulated for subcutaneous injection (para [0008]). Other modes of delivery, including intravenously are also taught (para [0050]). Netupitant is included as an exemplary NK1 receptor antagonist (para [0010], [0108]), and palonosetron is included as an exemplary 5-HT3 receptor antagonist (para [0017], [0104]). Ottoboni teaches a therapeutically effective amount of both the NK1 receptor antagonist, and 5-HT3 receptor antagonist (para [0007], [0044], [0072]). Ottoboni teaches administering the composition comprising the combination therapy to a subject in need thereof to treat CINV (para [0075]). Ottoboni provides an example wherein the formulation includes a phosphate buffer (para [0092-0093]), thereby meeting a pH adjusting means. 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).
Therefore, one of ordinary skill in the art would have been motivated to have modified the solid oral composition administered in the method 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 routes such as intravenously or subcutaneously, 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.
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
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