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
This office action is in response to applicant’s reply filed on July 9, 2026.
Status of Claims
Amendment of claims 1, 3 and 6, and cancellation of claim 27 is acknowledged
Claims 1, 3-6, 8, 10-11, 16, 18-19, 21, 23, 25, 28, 36, 47 and 49-51 are currently pending and are the subject of this office action.
Claims 1 and 6 were withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 27, 2025.
Claims 16, 18-19, 21, 23, and 25-26 are further withdrawn since they do not encompass the elected species: visceral pain.
Claims 3-5, 8, 10-11, 28, 36, 47 and 49-51 are presently under examination.
Priority
The present application is a 371 of PCT/US04/25336 filed on 08/04/2004 and claims priority to provisional application No. 60/492,367 filed on 08/04/2003.
Rejections and/or Objections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Rejections and/or Objections) or newly applied (New Rejections and/or Objections, Necessitated by Amendment or New Rejections and/or Objections not Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Responses to Applicant’s arguments have been addressed immediately after the corresponding rejections, or in the section: Withdrawn Rejections and/or Objections, if the rejection was withdrawn.
Claim Rejections - 35 USC § 103 (Modified Rejection Necessitated by Amendment).
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.
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 INTERPRETATION:
The humans in need thereof (of reducing the dose of an opioid analgesic) are being considered humans suffering from pain that are being administered a composition comprising an opioid and compound A
Claim(s) 3-5, 8, 10-11, 28, 36, 47 and 49-51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ehrlich et. al. (Expert Opinion on Therapeutic Targets (2019) 23:315-326, published online 03/15/2019), Koller et. al. (Expert Opinion on Pharmacotherapy (2019) 20:1993-2005, published online 08/16/2019), Vernier et. al. (US 8,993,593, cited in previous office action), and Cooke et. al. (WO 2010/085848, 08/05/2010, cited in previous office action).
For claim 3, the prior art teaches that opioid analgesics are effective in treating pain in humans (see Ehrlich et. al and see Koller et. al.). Ehrlich and Koller further teach the oral administration of opioids (see Ehrlich page 318, right column, section 3.2, line 18 from the top; and see Koller page 1993, right column, section 1.2, first paragraph)
Neither Ehrlich nor Koller teach the treatment of pain comprising the oral administration of an effective amount of Compound A (Encukalner or Azetukalner or XEN1101):
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However, Vernier teaches that compound A:
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(see abstract, column 30, lines 8-18, and column 31, lines 55-64) is a KCNQ 2/3 (Kv7 2/3) modulator like for example retigabine:
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(see column 2, lines 22-48).
Compound A, like retigabine is effective in treating pain (see column 1, lines 35-38, column 31, lines 46-48) and column 32, lines 7-8). Vernier further teaches that Compound A is superior to retigabine since the KCNQ1 potassium channel is unaffected (see column 2, lines 22-48; column 29, line 61 through column 30, line 21 and column 31, line 33 through column 32, line 8). Vernier also teaches the oral administration of compound A (see column 30, lines 25-36).
Further, Cooke teaches a method of treating pain in a human in need thereof comprising the administration of a composition comprising the KCNQ 2/3 (Kv7 2/3) modulators retigabine or flupirtine, and an opioid (see abstract, see page 1 under FIELD, see claims 1 and 6). Cooke further teaches that this combination reduces the risk of opioid abuse (see page 1 last paragraph and page 2 until the end). Cooke teaches the oral administration of the composition (see page 21, last paragraph and page 22, line 3),
Before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to treat pain combining two compositions (an opioid and any KCNQ 2/3 (Kv7 2/3) modulator, like compound A) each of which is taught by the prior art to be useful for the same purpose (treating pain), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
The skilled in the art will be further motivated to treat pain with a combination comprising an opioid and the KCNQ 2/3 (Kv7 2/3) modulator, like compound A, since the prior art (Cooke) already teaches that the oral administration of compositions comprising opioids and KCNQ 2/3 (Kv7 2/3) modulators (like retigabine or flupirtine) are already proven to be effective in treating pain.
The prior art is silent regarding “reducing the dose of opioid analgesic administered to a human in need thereof”. However, it will be obvious that the amount of opioid needed to effectively treat pain in the presence of another agent (i.e. compound A) which is also effective in treating pain, will be less that if the pain had been treated with the opioid analgesic alone.
All this will result in the practice of claim 3, with a reasonable expectation of success.
For claim 4, Koller teaches opioid analgesics like: buprenorphine and methadone (see page 1993, under 1.2), and Cooke teaches that the opioid can be selected from the group consisting of oxycodone, hydromorphone, morphine, hydrocodone, etc. (see page 8, second paragraph),
All this thus will result in the practice of claim 4 with a reasonable expectation of success.
For claims 5 and 8, Vernier teaches that compound A “can affect the opening of, or otherwise modulate, voltage-gated potassium channels” (see abstract). Vernier further teaches that compound A is a KCNQ 2/3 (Kv7 2/3) activator (See column 72, lines 33-35), thus resulting in the practice of claims 5 and 8 with a reasonable expectation of success.
For claims 10-11 and 49-51, Cooke teaches that the pain being treated can be a nociceptive pain (see page 14, third paragraph) wherein the nociceptive pain is visceral pain (see page 14, last paragraph).
All this will result in the practice of claims 10-11 and 49-51 with a reasonable expectation of success.
For claims 28 and 36, Vernier teaches the administration of 10 mg up to 2000 mg per day (see column 29, lines 46-50) which overlaps with the instantly claimed ranges (2 mg to 200 mg per day and 5 mg to 1000 mg per day).
MPEP 2144.05 states: In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Even a slight overlap in range establishes a prima facie case of obviousness. In re Peterson, 65 USPQ2d 1379, 1382 (Fed. Cir. 2003).
"A prior art reference that discloses a range encompassing a somewhat narrower claimed range is sufficient to establish a prima facie case of obviousness." In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003). >See also In re Harris, 409 F.3d 1339, 74 USPQ2d 1951 (Fed. Cir. 2005).
All this will result in the practice of claims 28 and 36 with a reasonable expectation of success.
For claim 47, the prior art does not teach that the compound should be administered 30 minutes before to about 2 hours after eating a meal. However, dose regimen optimization is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize given the guidance of the prior art. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. As such, before the effective filing date of the claimed invention it would have been prima facie obvious for a person of ordinary skill in the art to determine the optimal dose regimen to achieve the best result for a particular patient, thus resulting in the practice of claim 47 with a reasonable expectation of success.
Response to Applicant’s arguments related to the above rejection
Applicants’ arguments have been fully considered but are not persuasive.
Since a new rejection was issued (see above), only those arguments presented by Applicant that are relevant to the new rejection are being considered.
Examiner’s response:
First, the Cooke reference is not a starting point for this rejection. The starting points for the above 103 rejection are: Ehrlich et. al. Koller et. al. and Vernier et. al.: Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to treat pain combining two compositions (an opioid and any KCNQ 2/3 (Kv7 2/3) modulator, like compound A) each of which is taught by the prior art (Ehrlich et. al. and Koller et. al. teach methods of treating pain comprising the oral administration of opioids, and Koller teaches a method of treating pain comprising the oral administration of Compound A) to be useful for the same purpose (treating pain), in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art (see MPEP 2144.06). In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See also: In re Diamond, 360 F.2d 214, 53 C.C.P.A. 1172, 149 U.S.P.Q. 562 (C.C.P.A. 1966).
The above suffice to make a 103 rejection.
The Cooke reference simply states that combinations of an opioid and a KCNQ 2/3 modulators like retigabine are effective in treating pain, regardless of the dysphoric and sedating effects of the KCNQ 2/3 modulator retigabine. Even if the KCNQ 2/3 modulator Compound A was not a sedative or dysphoric, the skilled in the art will still be further motivated to treat pain with a mixture of an opioid and any KCNQ 2/3 modulator, including Compound A, since Cook already teaches that such combinations are already known to be effective in treating pain. The fact that Cooke teaches that the combinations are effective to deter abuse FDC (Fixed Dose Combination) does not negate that the combination (of an opioid and a KCNQ 2/3 modulator) is still effective in treating pain.
Second, it will be expected that the amount of an opioid analgesic required to treat pain in combination with another drug which is effective to treat pain will be lower that if the treatment were with the opioid alone. This is expected. If Applicant believes that the administration of an opioid in combination with Compound A is synergistic (i.e. unexpected result), then Applicant should provide experimental evidence, otherwise the rejection stands.
Conclusion
No claims are allowed.
Applicants’ 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 extension fee 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 date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is
(571) 270-3498. The examiner can normally be reached Flexing M-F 7 AM-7 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached on 571 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARCOS L SZNAIDMAN/ Primary Examiner, Art Unit 1628 July 31, 2026.
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