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 .
DETAILED ACTION
Response to Amendment
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/17/2026 has been entered.
Newly amended Claims 1-2, 4-8, 10-13, 15, and 36-39 are pending in the application.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied and constitute the complete set presently being applied to the instant application.
Response to Applicant’s Arguments
Applicant argues Lee is “totally silent about post-operative pain, let alone severe pain (pain intensity (PI) score of 7 to 10))”. Applicant’s argument is fully considered but not persuasive because Lee suggests pain can vary in terms of type and severity (Col 120, Lines 57+; Col 27, Lines 20-27). Further, applicant concedes “there may be an ‘inflammatory’ component to post-operation pain”. Therefore, one of skill in the art would reasonably expect the Lee compound to treat post-operative pain. Even if that treatment were only limited to “inflammatory pain”, said treatment would constitute treatment of post-operative pain, the scope of which is established by applicant (Remarks 6/03/2025). Regarding applicant’s limitation of the scope of Claim 1 to exclusively “severe pain,” the scope of applicant’s arguments are not commensurate in scope with the present amendments. Paragraphs 84-85 do not establish a clear and limiting definition which defines severe pain as pain having a PI of 7 or greater. The language “common severity cutpoints are…” does not clearly indicate that a PI of 6 or lower for example cannot be considered severe, only that a PI of 7 or greater is often considered to be severe. The limitation that severe pain is necessarily reflective of a PI of 7 or more cannot be read into the claims.
Applicant argues that in patients with limited responsiveness to non-opioid analgesics exhibiting severe pain of a PI>7, VVZ-149 results in significant reduction of pain as compared to a placebo. This difference in pain is significant as compared to a patient group with a PI>4 (Remarks Pages 12-13; Figs. 16A and 16B). Further, the total pain AUC for patients with severe pain with PI>7 receiving VVZ-149 was significantly less than the placebo, suggesting VVZ-149 is more effective than a placebo; however, no comparison to a moderate pain group of PI>4 is provided (Page 13; Figs 17A). Applicant states these results are surprising. The arguments are fully considered but not persuasive because the scope of the results are not commensurate in scope with the claims for three reasons:
The patient population of the cited figures are patients with limited responsiveness to non-opioid analgesics. This subpopulation is not claimed.
The results are directed to patients with severe pain, wherein said pain is characterized by a PI>7. This definition of severe pain is not incorporated into the claims or defined in the specification.
The results offered are reflective of a single compound of the claimed genus of Formula (I), VVZ-149. No other compound is tested. No evidentiary declaration is filed to suggest that a plurality of compounds encompassed within the genus of Formula (I) would be expected to have similar “surprising” effects. The scope of Formula (I) as claimed is significantly broader than experiment testing the single compound.
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.
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.
Claims 1-2, 5-8, 10-13, 15, and 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (US9359346, published in 2016, cited in 12/09/2021 IDS) in view of Stroissnig (US20110294843, published 2011).
Lee teaches the following benzamide compound of Formula 6 (Col 10):
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in which the following definitions of examined Formula (I) apply: R1 is NR5R6, wherein both R5 and R6 are alkyl, methyl; R2 and R4 are each alkyl, methyl; and R3 is alkyl, butyl. The same compound is depicted in instant Claim 7 and the HCl salt is described in Claim 15. The benzamide compound is useful for the treatment or prevention of pain in a human patient as required by examined Claim 2 (Abstract; Col 26, Lines 33-37). Several other compounds encompassed by claimed Formula (I) are taught in Lee Claim 3 for the same purpose: Formulae 35, 38, 41, 43, 44, at least (Claims 3 and 5). Also, additional compounds encompassed by examined Formula (I) are taught for the same purpose in the specification:
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, inter alia (Col. 16-18). Said pain can vary in terms of type and severity, which includes severe pain (Col 120, Lines 57+; Col 27, Lines 20-27).
Regarding Claims 8, 13, and 39, the compounds of the invention are taught to be administered in amounts of 12.5, 25, 50, 100 mg/kg to various patients via various routes including intravenously (Col 119, Lines 23-33; Col 120, Example 4; Col 27, Lines 7-18). Opiates are also taught as analgesics which induce severe and painful side effects: e.g., vomiting, pruritus, and constipation (Col 1; Lines 28-66). The benzamide compounds, which act as antagonists of GlyT2 and 5HT2A, counter pruritis while relieving pain (Col 2, Lines 16-30; Col 3, Lines 29-37). Therefore, the compounds of Lee are opioid-sparing by virtue of countering pruritic, an opiate side effect.
Lee does not teach the reduction of opioid administration alongside the administration of the benzamide compounds for post-operative pain. Lee also fails to teach specific dosing regimens.
Stroissnig teaches post-operative pain is usually treated with morphine which possesses several side effects like nausea and vomiting, affecting patient compliance and safety (Page 1, Para 3-4). Regarding Claims 10-12 and 36-38, Stroissnig teaches post-operative pain can be treated via the administration of an analgesic medicament prior to, concomitantly, or after an operation, induction of anesthesia, or post-operative recovery phase (Page 10, Claims 11-16 and 18). Regarding Claim 5, the medicament for pain relief is specifically administered within 48 hours following the completion of the operation (Page 10, Claim 18, Step b). Regarding Claim 6, the opiates are taught to be commonly administered via patient-controlled analgesia (PCA) (Page 2, Para 27).
A human patient receiving a standard opiate analgesic following an operation would benefit from the intravenous coadministration of the Lee benzamide HCl salt because the Lee compound is taught to be opioid-sparing, or to reverse side effects like pruritus associated with the standard method of opioid-based analgesia. Further, the benzamide compound is taught to reduce pain, functioning as an analgesic thereby reducing the necessary opioid to be administered via PCA to a patient. The reduction in pain and painful opioid side effects is desirable for patients who are prone pain after an operation. The method is expected to be advantageous for pain which ranges from moderate to severe because Lee teaches the use of Formula 6 and other compounds for an array of pain severity. The treatment of post-operative pain is not precluded by Lee. The administration of either analgesic may be performed before, during, or after an operation to prevent or treat the postoperative pain while also reducing opioid-induced side effects, either directly or through reduced opiate requirement for pain relief.
Lee teaches the benzamide compounds are to be administered in amounts of 12.5, 25, 50, 100 mg/kg (Col 119, Lines 23-33; Col 120, Example 4). A dose of 12.5mg/kg in a 70-90kg human patient, for example, is 875-1125mg, squarely within the effective range of examined Claim 1. Lee embraces various patient body weight (Col 27, Lines 19-27). The exact dosing and timing of the administration of opioids and benzamide compounds are not taught by either Stroissnig or Lee. However, one of skill in the art would appreciate the vast and diverse genus of medical procedures encompassed by the word “operation”. It is obvious to one of skill in the art that to accommodate factors like pain severity of the patient as well as different types of operations, the medicaments must be administered at different times and manners to optimize the reduction of pain and opiate analgesic necessary following a procedure. Again, Lee teaches “pain can vary in terms of type and severity (Col 120, Lines 57+; Col 27, Lines 20-27) and the compounds of Lee are taught to be administered different amounts via various routes including intravenously (Col 119, Lines 23-33; Col 120, Example 4; Col 27, Lines 7-18).” The MPEP states the following:
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. "[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 Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See MPEP 2144.05 II (A).
Claims 5, 8, 10-13, and 36-39 specify optimal variables such as amount, timing, and delivery route achieved through routine experimentation, but do not suggest such adjustments are critical or yield unexpected results as compared to the routes taught by the prior art. Because the general conditions of amount, timing, and delivery route are taught by Lee, the claims are not inventive thereover for merely having discovered “the optimum or workable ranges by routine experimentation”, especially considering the breadth of operations, the pain of which an ordinary artisan would seek to reduce with an optimal regimen.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Lee in view of Stroissnig as applied to Claims 1-2, 5-8, 10-13, 15, and 36-39 in further view of Chou (The Journal of Pain, Vol 17, No 2, 2016: pp 131-157).
The teachings of Lee and Stroissnig are set forth above and incorporated by reference herein.
Lee and Stroissnig do not teach the subject exhibits pain catastrophizing.
Chou teaches the assessment of preoperative pain and psychiatric comorbidities associated therewith like pain catastrophizing are critical to developing an appropriate plan for managing postoperative pain (Page 135, Para 1). One of ordinary skill in the art, seeking to minimize miserable side effects of opiate analgesics which worsen postoperative pain in subjects prone to catastrophizing said pain, would attempt to treat pain and expect successful analgesia in the subject experiencing pain catastrophizing upon administering the compounds of Lee to reduce necessary opioid administration taught in Stroissnig, thereby lessening severe side effects and pain catastrophizing in said subject.
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.
NONPROVISIONAL:
Claims 1-2, 4-8, 10-13, 15, and 36-39 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-5 of U.S. Patent No. 9359346 (hereinafter referred to as Vivozon) in view of Hyun Lee (US20140336378), Stroissnig (US20110294843), and Chou (The Journal of Pain, Vol 17, No 2, 2016: pp 131-157).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to compounds, including
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, directed to the treatment of pain. Vivozon teaches additional compounds encompassed within claimed Formula (I):
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, e.g.
Regarding the claims directed to compositions of matter, In AbbVie Inc. v. Kennedy Institute of Rheumatology Trust, 764 F.3d 1366, 112 USPQ2d 1001 (Fed. Cir. 2014), the court explained that it is also proper to look at the disclosed utility in the reference disclosure to determine the overall question of obviousness in a nonstatutory double patenting context. See Sun Pharm. Indus., Ltd. v. Eli Lilly & Co., 611 F.3d 1381, 95 USPQ2d 1797 (Fed. Cir. 2010). See MPEP 804 (II) (B) (1).
Vivozon teaches the following claimed benzamide compound of Formula 6 in Claim 3:
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.
The same compound is depicted in instant Claim 7 and the HCl salt is described in Claim 15. The benzamide compound is useful for the treatment or prevention of pain in a human patient as required by Claim 2 (Abstract; Col 26, Lines 33-37). Said pain can vary in terms of type and severity, which includes severe pain (Col 120, Lines 57+; Col 27, Lines 20-27). Other compounds encompassed by examined Formula (I) are taught for the same purpose:
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, inter alia (Claim 3).
Hyun Lee teaches regarding Claims 8, 13, and 39, the compounds of Vivozon are taught to be administered for the same purpose in amounts of 12.5, 25, 50, 100 mg/kg to various patients via various routes including intravenously (Page 63, Example 4; Page 14, Para 85). Opiates are also taught as analgesics which induce severe and painful side effects: e.g., vomiting, pruritus, and constipation (Page 1, Para 7). The benzamide compounds, which act as antagonists of GlyT2 and 5HT2A, counter pruritis while relieving pain (Page 2, Para 16; Page 4, Para 52). Therefore, the compounds of Vivozon and Hyun Lee are opioid-sparing.
Stroissnig teaches post-operative pain is usually treated with morphine which possesses several side effects like nausea and vomiting, affecting patient compliance and safety (Page 1, Para 3-4). Regarding Claims 10-12 and 36-38, Stroissnig teaches post-operative pain can be treated via the administration of an analgesic medicament prior to, concomitantly, or after an operation, induction of anesthesia, or post-operative recovery phase (Page 10, Claims 11-16 and 18). Regarding Claim 5, the medicament is specifically administered within 48 hours following the completion of the operation (Page 10, Claim 18, Step b). Regarding Claim 6, the opiates are taught to be commonly administered via patient-controlled analgesia (PCA) (Page 2, Para 27).
A human patient receiving a standard opiate analgesic following an operation would benefit from the intravenous coadministration of the Vivozon and Hyun Lee benzamide HCl salt because the compound is taught to be opioid-sparing, or to reverse side effects like pruritus associated with the standard method of opioid-based analgesia. Further, the benzamide compound is taught to reduce pain, functioning as an analgesic thereby reducing the necessary opioid to be administered via PCA to a patient. The reduction in pain and painful opioid side effects is expected to be advantageous for pain which ranges from moderate to severe because Hyun Lee teaches the use of Formula 6 and other compounds for an array of pain severity. The treatment of post-operative pain is not precluded by Hyun Lee. The administration of either analgesic may be performed before, during, or after an operation or use of an anesthetic therefor to prevent or treat the postoperative pain while also reducing opioid-induced side effects.
Hyun Lee teaches the benzamide compounds are to be administered in amounts of 12.5, 25, 50, 100 mg/kg (Page 62, Para 573; Page 63, Example 4). A dose of 12.5mg/kg in a 70-90kg human patient, for example, is 875-1125mg, squarely within the effective range of examined Claim 1. Hyun Lee embraces various patient body weights (Page 14, Para 86). The exact dosing and timing of the administration of opioids and benzamide compounds are not taught by either Stroissnig or Hyun Lee. However, one of skill in the art would appreciate the vast and diverse genus of medical procedures encompassed by the word “operation”. It is obvious to one of skill in the art that to accommodate factors like pain severity of the patient as well as different types of operations, the medicaments must be administered at different times and manners to optimize the reduction of pain and opiate analgesic necessary following a procedure. Again, Vivozon and Hyun Lee teach pain can vary in terms of type and severity (Vivozon: Col 120, Lines 57+; Col 27, Lines 20-27; and Hyun Lee: Page 14, Para 86). The same compounds of Vivozon and Hyun Lee are taught to be administered different amounts via various routes including intravenously (Hyun Lee: Page 63, Example 4; Page 14, Para 85). The MPEP states the following:
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. "[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 Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See MPEP 2144.05 II (A).
Claims 5, 8, 10-13, and 36-39 specify optimal variables such as amount, timing, and delivery route achieved through routine experimentation, but do not suggest such adjustments are critical or yield unexpected results as compared to the general routes taught by the prior art. Because the general conditions of amount, timing, and delivery route are taught by Vivozon and Hyun Lee, the claims are not inventive thereover for merely having discovered “the optimum or workable ranges by routine experimentation”, especially considering the breadth of operations, the pain of which an ordinary artisan would seek to reduce with an optimal regimen.
Chou teaches the assessment of preoperative pain and psychiatric comorbidities associated therewith like pain catastrophizing are critical to developing an appropriate plan for managing postoperative pain (Page 135, Para 1). One of ordinary skill in the art, seeking to minimize miserable side effects of opiate analgesics which worsen postoperative pain in subjects prone to catastrophizing said pain, would attempt to treat and expect successful analgesia in the subject with pain catastrophizing upon administering the compounds of Vivozon and Hyun Lee to reduce necessary opioid administration taught in Stroissnig, thereby lessening pain catastrophizing in said subject.
One of skill in the art seeking to apply the Vivozon composition as taught for therapeutic use would, in view of the teachings of Hyun Lee, Strossnig, and Chou, would find it obvious to treat a patient with post-operative pain to reduce the coadministered opioid to reduce side effects associated therewith and expect success in doing so because Vivozon and Hyun Lee teach the exact same compounds as claimed with anti-opioid-side-effect capabilities for analgesic use.
Since both claim sets teach the same compounds for the same therapeutic purpose, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of Vivozon.
Conclusion
No claim is allowable.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Richard G. Peckham whose telephone number is (703)756-4621. The examiner can normally be reached 7:30am - 4:30pm.
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
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