DETAILED ACTION
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 .
Priority
This application is a national stage entry of PCT/CN2021/141009 filed on 12/24/2021.
Acknowledgment is made of applicant's claim for foreign priority based on applications filed in CHINA (202011559059.6 and 202111066727.6) on 12/25/2020 and 09/13/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
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 1-10, 12 and 13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 12,421,260 B2 in view of Yan et al. CN-103520725 A (Google Machine English Translation provided).
Claims 1-10, 12 and 13 of the instant application claim a method for preventing or treating nausea and/or vomiting in a patient in need thereof, comprising administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, as well as a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, and one or more pharmaceutically acceptable carriers, wherein the compound of formula (I) is
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known as fosrolapitant.
Claims 1-7 of ‘260 claim a compound of formula (III) such as
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and a composition thereof for use in a method of treating nausea and vomiting.
The claims of ‘260 do not claim combining the compound with a 5-HT3 receptor antagonist in the dosages as claimed for treating chemotherapy induced nausea and vomiting.
Yan et al. teaches a pharmaceutical composition containing a neurokinin 1 (NK-1) receptor antagonist, a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist and adrenocortical hormone (abstract, claims 1-12 and page 4). Yan et al. teaches that the composition can be used to prevent and treat nausea and vomiting caused by cancer radiotherapy, chemotherapy, and surgery and that the invention aims to develop a more convenient and effective pharmaceutical composition formulation for preventing and treating vomiting using the NK-1 receptor antagonist, 5HT-3 receptor antagonist, and adrenocortical hormone, thereby improving patient compliance (abstract and claim).
Yan et al. teaches that nausea and vomiting (CINV) caused by chemotherapy is very common clinically and CINV is often divided into three categories according to the time when vomiting occurs: acute (occurs within the first 24 hours after chemotherapy starts), delayed (occurs at least 24 hours after chemotherapy starts) and anticipation (conditional reflex, occurs before chemotherapy) (page 5).
Yan et al. teaches that selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, by antagonizing the 5-HT3 receptors in peripheral vagal nerve endings and central chemoreceptor area, block the vomiting reflex that promotes intestinal chromaffin cells to release 5-hydroxytryptamine because of factors such as chemotherapy and surgery, and the excited vagal afferent nerve causes (page 5). The 5-HT3 receptor antagonists used clinically are granisetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride, palonosetron hydrochloride and dolasetron mesylate (page 5).
Yan et al. teaches that tachykinins, such as substance P (SP), are peptide ligands of neurokinin receptors and neurokinin receptors, such as NK-1, NK-2, and NK-3, participate in many biochemical processes (page 5). Yan et al. teaches that Neurokinin 1 receptor antagonists (NKIRAs) have antidepressant and antianxiety effects and are effective in treating chemotherapy-induced nausea and vomiting and combining them with other antiemetics can better control delayed vomiting and postoperative vomiting (page 5).
Yan et al. teaches the pharmaceutical composition comprises the NK-1 receptor antagonist, the 5HT-3 receptor antagonist, and the corticosteroid as active ingredients, and is combined with a combination of excipients of specific types and proportions (page 6). The NK-1 receptor antagonist is selected from aprepitant, netupitant, and rolapitant; the 5-hydroxytryptamine 3 receptor antagonist is selected from granisetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride, palonosetron hydrochloride, and dolasetron mesylate; and the corticosteroid is selected from hydrocortisone, cortisone acetate, dexamethasone, and betamethasone (page 6 and claims 2-4).
Yan et al. teaches the dosage of the NK-1 receptor antagonist is 50-500 mg per unit preparation, preferably 200-400 mg; the dosage of the 5HT-3 receptor antagonist is 0.25-10 mg per unit preparation, preferably 0.25-1 mg; and the dosage of the adrenocortical hormone is 1.0-50 mg per unit preparation, preferably 5.0-20 mg (page 7). Yan et al. teaches that when the 5HT-3 receptor antagonist is palonosetron hydrochloride, its dosage is preferably 0.5 mg per unit preparation (page 7).
Yan et al. teaches that the pharmaceutical composition can significantly improve acute or delayed vomiting caused by middle and high risk chemotherapy regimens of emetics (page 7).
Yan et al. specifically demonstrates administration of the combination including palonosetron prior to the administration of cisplatin chemotherapy wherein the combination suppressed retching and vomiting induced by cisplatin for at least 3 days (examples starting on page 13). Therefore, Yan et al. teaches the preferred prescription of the pharmaceutical composition is aprepitant 300 mg+ palonosetron hydrochloride 0.5mg+ dexamethasone 15mg, which is orally given half an hour in advance on chemotherapy first day (page 17). Yan et al. teaches that the pharmaceutical composition can be administered 1 time and can reach a continuous antiemetic effect, wherein the therapeutic effect is maintained for more than 3 days, greatly facilitating the patient, and effectively improving patient compliance (page 17). Thus claims 5 and 6 of the instant application are rendered obvious since the effect is maintained for more than 3 days and thus administration once a week as claimed is rendered obvious.
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of the claims of ‘260 which claim a compound of formula (III) such as
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(fosrolapitant) and a composition thereof for use in a method of treating nausea and vomiting with the teachings of Yan et al. which teaches a method for treating or preventing nausea and vomiting in patient in need thereof comprising administering a pharmaceutical composition containing a neurokinin 1 (NK-1) receptor antagonist and a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist, wherein the NK-1 receptor antagonist may be selected as rolapitant which is structurally similar to the compound as claimed in ‘260. Thus an ordinary skilled artisan would have been motivated to combine fosrolapitant (the compound as claimed in ‘260) with a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist in the same manner as Yan et al. teaches combining rolapitant with a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist, in view of their structural and functional similarities, with a reasonable expectation of improved treatment of nausea and vomiting.
Thus the cited claims of the instant application are rendered obvious over the cited claims of ‘260 in view of the cited prior art teachings and thus are deemed not patentably distinct.
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 (i.e., changing from AIA to pre-AIA ) 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 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 1-10, 12 and 13 are rejected under 35 U.S.C. 103 as being obvious over Yan et al. CN-103520725 A (Google Machine English Translation provided) in view of U.S. Publication No. 2022/0380393 A1 (Provided on IDS) (effective filing date June 28, 2019).
The applied reference has a common Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claims 1-10, 12 and 13 of the instant application claim a method for preventing or treating nausea and/or vomiting in a patient in need thereof, comprising administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, as well as a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, and one or more pharmaceutically acceptable carriers, wherein the compound of formula (I) is
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known as fosrolapitant.
Yan et al. teaches a pharmaceutical composition containing a neurokinin 1 (NK-1) receptor antagonist, a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist and adrenocortical hormone (abstract, claims 1-12 and page 4). Yan et al. teaches that the composition can be used to prevent and treat nausea and vomiting caused by cancer radiotherapy, chemotherapy, and surgery and that the invention aims to develop a more convenient and effective pharmaceutical composition formulation for preventing and treating vomiting using the NK-1 receptor antagonist, 5HT-3 receptor antagonist, and adrenocortical hormone, thereby improving patient compliance (abstract and claim).
Yan et al. teaches that nausea and vomiting (CINV) caused by chemotherapy is very common clinically and CINV is often divided into three categories according to the time when vomiting occurs: acute (occurs within the first 24 hours after chemotherapy starts), delayed (occurs at least 24 hours after chemotherapy starts) and anticipation (conditional reflex, occurs before chemotherapy) (page 5).
Yan et al. teaches that selective 5-hydroxytryptamine 3 (5-HT3) receptor antagonists, by antagonizing the 5-HT3 receptors in peripheral vagal nerve endings and central chemoreceptor area, block the vomiting reflex that promotes intestinal chromaffin cells to release 5-hydroxytryptamine because of factors such as chemotherapy and surgery, and the excited vagal afferent nerve causes (page 5). The 5-HT3 receptor antagonists used clinically are granisetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride, palonosetron hydrochloride and dolasetron mesylate (page 5).
Yan et al. teaches that tachykinins, such as substance P (SP), are peptide ligands of neurokinin receptors and neurokinin receptors, such as NK-1, NK-2, and NK-3, participate in many biochemical processes (page 5). Yan et al. teaches that Neurokinin 1 receptor antagonists (NKIRAs) have antidepressant and antianxiety effects and are effective in treating chemotherapy-induced nausea and vomiting and combining them with other antiemetics can better control delayed vomiting and postoperative vomiting (page 5).
Yan et al. teaches the pharmaceutical composition comprises the NK-1 receptor antagonist, the 5HT-3 receptor antagonist, and the corticosteroid as active ingredients, and is combined with a combination of excipients of specific types and proportions (page 6). The NK-1 receptor antagonist is selected from aprepitant, netupitant, and rolapitant; the 5-hydroxytryptamine 3 receptor antagonist is selected from granisetron hydrochloride, ondansetron hydrochloride, ramosetron hydrochloride, tropisetron hydrochloride, palonosetron hydrochloride, and dolasetron mesylate; and the corticosteroid is selected from hydrocortisone, cortisone acetate, dexamethasone, and betamethasone (page 6 and claims 2-4).
Yan et al. teaches the dosage of the NK-1 receptor antagonist is 50-500 mg per unit preparation, preferably 200-400 mg; the dosage of the 5HT-3 receptor antagonist is 0.25-10 mg per unit preparation, preferably 0.25-1 mg; and the dosage of the adrenocortical hormone is 1.0-50 mg per unit preparation, preferably 5.0-20 mg (page 7). Yan et al. teaches that when the 5HT-3 receptor antagonist is palonosetron hydrochloride, its dosage is preferably 0.5 mg per unit preparation (page 7).
Yan et al. teaches that the pharmaceutical composition can significantly improve acute or delayed vomiting caused by middle and high risk chemotherapy regimens of emetics (page 7).
Yan et al. specifically demonstrates administration of the combination including palonosetron prior to the administration of cisplatin chemotherapy wherein the combination suppressed retching and vomiting induced by cisplatin for at least 3 days (examples starting on page 13). Therefore, Yan et al. teaches the preferred prescription of the pharmaceutical composition is aprepitant 300 mg+ palonosetron hydrochloride 0.5mg+ dexamethasone 15mg, which is orally given half an hour in advance on chemotherapy first day (page 17). Yan et al. teaches that the pharmaceutical composition can be administered 1 time and can reach a continuous antiemetic effect, wherein the therapeutic effect is maintained for more than 3 days, greatly facilitating the patient, and effectively improving patient compliance (page 17). Thus claims 5 and 6 of the instant application are rendered obvious since the effect is maintained for more than 3 days and thus administration once a week as claimed is rendered obvious.
Yan et al. does not teach a compound of formula I as the NK-1 receptor antagonist.
However, Yan et al. specifically teaches that the NK-1 receptor antagonist may be selected as rolapitant (claim 3) having the following structure:
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.
Huang et al. teaches that in order to solve the problem of the low solubility of the compound of formula I (rolapitant) at physiological pH, researchers have used a co-solvent-based formulation containing Captisol, propylene glycol and ethanol to significantly improve the solubility of compound 1, but the co-solvent-based formulation has significant hemolytic effect after intravenous administration [0005]. Huang et al. further teaches that even if the compound of formula I is prepared as a prodrug containing phosphates, the hemolytic effect of the pharmaceutical composition is still not completely resolved [0005]. Thus Huang et al. teaches a new NK1 antagonist prodrug compound that is effective in treating various physiological disorders, conditions and diseases and has minimal side effects [0006]. Huang et al. specifically teaches new rolapitant prodrugs including
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[0061]. Huang et al. teaches that the compound has higher solubility and better in vivo conversion compared with known compounds and the compound has low hemolytic effect and reduced side effects after drug administration, and is beneficial to improve patient compliance with the drug administration [0063]. Huang et al. further teaches that these prodrugs like rolapitant are used for treating vomiting and nausea [0067].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Yan et al. which teaches a method for treating or preventing nausea and vomiting in patient in need thereof comprising administering a pharmaceutical composition containing a neurokinin 1 (NK-1) receptor antagonist and a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist, wherein the NK-1 receptor antagonist may be selected as rolapitant, with the teachings of Huang et al. which teaches rolapitant prodrugs such as fosrolapitant that has higher solubility and better in vivo conversion compared with known compounds as well as low hemolytic effect and reduced side effects after drug administration resulting in improved patient compliance. Thus an ordinary skilled artisan would have been motivated to substitute fosrolapitant for rolapitant in the combination of Yan et al. based on the teachings of Huang et al. which teaches improved properties for the prodrug fosrolapitant as compared to rolapitant with a reasonable expectation of improved and predictable results.
With respect to claim 10 of the instant application which claims the pharmaceutical composition is packaged, although Yan et al. does not specifically recite the composition is packaged, this limitation is rendered obvious since pharmaceutical formulations must be prepared and stored in a package such as a container for oral dosage forms or a bottle or bag for liquid dosage forms.
Thus in view of the cited prior art teachings claims 1-10, 12 and 13 are rendered obvious.
Claims 1-3, 5-10, 12 and 13 are rejected under 35 U.S.C. 103 as being obvious over Wan et al. U.S. Patent No. 9,101,615 B2 (Provided on IDS) in view of U.S. Publication No. 2022/0380393 A1 (Provided on IDS) (effective filing date June 28, 2019).
The applied reference has a common Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Claims 1-3, 5-10, 12 and 13 of the instant application claim a method for preventing or treating nausea and/or vomiting in a patient in need thereof, comprising administering to the patient an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, as well as a pharmaceutical composition comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof and a 5-HT3 receptor antagonist, and one or more pharmaceutically acceptable carriers, wherein the compound of formula (I) is
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known as fosrolapitant.
Wan et al. teaches pharmaceutical compositions for intravenous administration comprising the compound of Formula I
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or pharmaceutically acceptable salts, hydrates or prodrugs thereof as well as methods for treating nausea and/or emesis with the pharmaceutical compositions (abstract). Wan et al. teaches the compound of formula I is classified as a tachykinin compound and is an antagonist of neuropeptide neurokinin-1 (NK-1) receptors (column 1 lines 50-52). Wan et al. teaches that NK-1 receptor antagonists have been shown to be useful therapeutic agents, for example, in the treatment of pain, inflammation, migraine, nausea, emesis (vomiting), and nociception (column 2 lines 12-15). Wan et al. further teaches the use of a prodrug of formula I (column 7 line 31-column 8 line 65).
Wan et al. further teaches that the intravenous formulations may be used in combination with other antiemetic and antinausea medications; anti-inflammatory or steroidal agents (e.g. dexamethasone) and with chemotherapeutic agents (column 11 lines 60-64). Such other medications include ondansetron and other known 5HT3 antagonists (column 11 lines 66-67). Thus, Wan et al. teaches that a compound of formula I and salts thereof for injection may be utilized with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy including, for example, treatment with cisplatin (column 11 line 67-column 12 line 5). Wan et al. teaches that a compound of formula I and salts thereof for injection may also be utilized with other antiemetic agents for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy, and in addition to treatment with cisplatin, other anticancer agents that are administered in this combination dosing regimen include etoposide, flurouracil, gemcitabine, vinorelbine, paclitaxel, cyclophosphamide, doxorubicin, docetaxel and can also include temozolomide (column 12 lines 6-14; column 23 lines 30-55). Wan et al. teaches that the treatment with a compound of formula I should begin thirty minutes before chemotherapy treatment on day 1 of such treatment (column 12 lines 15-19).
Wan et al. teaches a method of treating a patient in need of treatment thereof with an intravenous formulation comprising a compound of Formula I or a pharmaceutically acceptable salt thereof wherein the dosage ranges from 100 to 200 mgs of such compound and the formulation is administered to the patient as a single dose once prior to a chemotherapy or radiation cycle or once prior or post-surgery to treat CINV (Chemotherapy Induced Nausea and Vomiting), PONV (Post Operative Nausea and Vomiting) or RINV (Radiation Induced Nausea and Vomiting) (column 20 lines 20-29).
Wan et al. teaches combinations of the iv formulations with another anti-emetic agent such as a serotonin 5-HT3 receptor antagonist, a corticosteroid or a substituted benzamide can be used to treat other forms of emesis including acute emesis induced by chemotherapy, radiation, motion and/or alcohol (ethanol), and post-operative nausea and vomiting wherein examples of 5-HT3 antagonists include palosetron, dolasetron, ondansetron and granisetron or pharmaceutically acceptable salts thereof (column 23 lines 18-26).
Wan et al. teaches that the formulations are useful in the prevention and treatment of nausea and vomiting associated with radiation therapy for cancer treatment; chemotherapy therapy for cancer treatment and with post operative associated nausea and vomiting, wherein the course of therapy comprises a single dose of the formulation comprising a compound of Formula I or salt thereof on day one before the initiation of chemotherapy followed by once a day dosing on days two and three (column 47 lines 1-16). The course of therapy also comprises a single dose administration on day 1 wherein the iv solution can be in the form of a 2 mg/ml solution with 50 ml necessary to deliver 100 mg to the patient in need of treatment thereof (column 47 lines 1-16). The formulation can be a ready to go premixed solution or a concentrate which can be diluted before use (column 47 lines 1-16). The formulation may also be a lyophilized formulation in the form of a powder which is mixed with saline or appropriate buffer solution before use (column 47 lines 1-16).
Wan et al. does not teach a compound of formula I as the NK-1 receptor antagonist.
However, Wan et al. specifically teaches that the NK-1 receptor antagonist is rolapitant having the following structure:
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as well as prodrugs thereof.
Huang et al. teaches that in order to solve the problem of the low solubility of the compound of formula I (rolapitant) at physiological pH, researchers have used a co-solvent-based formulation containing Captisol, propylene glycol and ethanol to significantly improve the solubility of compound 1, but the co-solvent-based formulation has significant hemolytic effect after intravenous administration [0005]. Huang et al. further teaches that even if the compound of formula I is prepared as a prodrug containing phosphates, the hemolytic effect of the pharmaceutical composition is still not completely resolved [0005]. Thus Huang et al. teaches a new NK1 antagonist prodrug compound that is effective in treating various physiological disorders, conditions and diseases and has minimal side effects [0006]. Huang et al. specifically teaches new rolapitant prodrugs including
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[0061]. Huang et al. teaches that the compound has higher solubility and better in vivo conversion compared with known compounds and the compound has low hemolytic effect and reduced side effects after drug administration, and is beneficial to improve patient compliance with the drug administration [0063]. Huang et al. further teaches that these prodrugs like rolapitant are used for treating vomiting and nausea [0067].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Wan et al. which teaches a method for treating or preventing nausea and vomiting in patient in need thereof comprising administering a pharmaceutical composition comprising rolapitant or prodrugs thereof and a 5-hydroxytryptamine 3 (5HT-3) receptor antagonist, with the teachings of Huang et al. which teaches rolapitant prodrugs such as fosrolapitant that have higher solubility and better in vivo conversion compared with known compounds as well as low hemolytic effect and reduced side effects after drug administration resulting in improved patient compliance. Thus an ordinary skilled artisan would have been motivated to substitute fosrolapitant for rolapitant or the prodrugs disclosed therein in the combination of Wan et al. based on the teachings of Huang et al. which teaches improved properties for the prodrug fosrolapitant as compared to rolapitant and other known prodrugs with a reasonable expectation of improved and predictable results.
With respect to claim 10 of the instant application which claims the pharmaceutical composition is packaged, although Wan et al. does not specifically recite the composition is packaged, this limitation is rendered obvious since pharmaceutical formulations must be prepared and stored in a package such as a container for solid dosage forms or a bottle or bag for liquid dosage forms.
Thus in view of the cited prior art teachings claims 1-10, 12 and 13 are rendered obvious.
Conclusion
Claims 1-10, 12 and 13 are rejected. Claim 11 is canceled. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571)270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM