DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Information Disclosure Statement
The twelve information disclosure statements (IDS) submitted on 12/20/2023 have been considered by the examiner.
Crossed out references have not been considered because no publication year listed or an English copy was not available.
Status of the Claims
The claims filed 12/20/2023 are under consideration.
Claims 1, 5-29, 33-58, and 62-90 are pending.
Applicant’s election of Group I, claims 1, and 5-28 in the reply filed on 03/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 29, 33-58, and 62-90 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 03/23/2026.
Applicant’s election of 25 mg dose of esmethadone as species A in the reply filed on 03/03/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Applicant indicates claims 1, 5-8, 15, 23, and 26 read on the elected species.
Claims 9-14, 16-22, 24-25 and 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/23/2026.
Claims 1, 5-8, 15, 23, and 26 are treated on the merits in this action.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 8 includes the limitation of the formulation of esmethadone in claim 1 as modified release formulations, including a hydrogel formulation.
The phrase "including a hydrogel formulation" renders the claim indefinite because it is unclear whether the limitation(s) following “including” are part of the claimed invention. See MPEP § 2173.05(d).
Clarification 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 of this title, 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, 5-7, 15, 23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Manfredi, US 20180214395 A1 and Morella, US 5202128.
The limitation of “including a 25 mg dose of esmethadone” is interpreted to mean the modified release formulation contains 25 mg esmethadone.
Morella teaches and claims a modified release methadone formulation, i.e., sustained release pharmaceutical composition wherein the active ingredient is methadone (Morella, e.g., claim 4). Morella teaches the formulations have a significant decrease in Cmax values relative to an immediate release solution and a significant increase in Tmax times relative to an immediate release solution (Morella, e.g., c18:12-51). The modified release composition has the same structure claimed. Therefore, the properties claimed are necessarily present. See MPEP, 2112.01. The numbers in the reference indicate at least the decrease in Cmax is greater than 10 % (Morella, e.g., c18:21-31).
It is noted that Morella teaches methadone and this is considered to be racemic methadone which is understood as containing both esmethadone and levomethadone since esmethadone and levomethadone are enantiomers present in the racemic methadone mixture.
The modified release formulation technique addresses the known problem of dose dumping when formulating agents having high solubility in water (Morella, e.g., c1:12-31). The technique stabilizes the plasma concentration of the agent thereby reducing the risk of toxicity and normalizing diurnal plasma concentrations of active agents (Morella, e.g., c1:12-31). The technique is also useful for addressing the known problem of compromised bioavailability by food (Morella, e.g., c1:32-36). The technique may be used to optimize dose and dosing interval for individual patients (Morella, e.g., c1:51-63). Normalizing plasma concentrations lowers the peak and raises the trough plasma concentrations which are associated with side effects and inadequate therapeutic potency, and extends duration of therapeutic effects (Morella, e.g., ¶ bridging c1-c2).
Morella does not expressly teach a modified release formulation containing 25 mg of esmethadone.
Manfredi teaches formulations containing 25 mg of esmethadone (Manfredi, e.g., 0303, example 4: 0466-0478, example 5: 0479-0483, example 7: 0489-0494). Manfredi teaches esmethdone has a number of useful applications including treating pain (Manfredi, entire document, e.g., 0379 and claim 20, and claim 22).
Manfredi does not expressly teach a modified release formulation of esmethadone.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to combine the teachings of Manfredi and Morella to arrive at a formulation within the scope of the present claims with a reasonable expectation of success.
Starting from Morella, the skilled artisan would have been motivated to modify Morella’s modified release formulations by including esmethadone with a reasonable expectation of success. The skilled artisan would have seen this modification as the substitution of one known methadone agent for another to achieve predictable results. That is, the skilled artisan understood from Manfredi that the esmethadone, d-enantiomer of methadone, was known and used for treating pain like racemic methadone. Thus, the skilled artisan would have seen this as a substitution of one equivalent methadone agent for another to predictably arrive at a modified release formulation for treating pain having improved pharmacokinetic profile, improved therapeutic efficacy, and reduced side effects.
Alternatively, starting from Manfredi, the skilled artisan would have been motivated to use modified release formulation techniques known from Morella to improve pain treatment methods using methadone to improve esmethadone treatments in the same way. The skilled artisan would have been motivated to apply techniques known from Morella to optimize bioavailability, improve therapeutic effect, and reduce side effects of Manfreidi’s esmethadone formulations in the same way with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of success since methadone in Morella’s formulations contains esmethadone, which means the skilled artisan understood that Morella had already reported effectiveness for formulations containing esmethadone.
The skilled artisan would have understood from Morella that modified release formulation techniques were useful to optimize the Cmax for reduced side effects. The skilled artisan understood from Morella that modified release formulation techniques were useful to optimize the Cmin for optimal therapeutic effectiveness, e.g., effective pain relief. The skilled artisan understood that modified release formulation techniques were useful to optimize the time to reach peak blood concentration (Tmax) for therapeutic duration (Morella, e.g., c19:46-53 and ¶ spanning c1-c2).
Accordingly, the subject matter of claims 1, 5-7, 15, 23 and 26 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Manfredi, US 20180214395 A1 and Morella, US 5202128 as applied to claims 1, 5-7, 15, 23 and 26 above, and further in view of Cruz, US 20050158382.
The combined teachings of Manfredi and Morella teach a formulation within the scope of claim 1 but do not expressly teach the formulation comprising a hydrogel.
Cruz teaches controlled release formulations of opioids (Cruz, e.g., Abstract, title, claims), wherein the formulation includes a hydrogel (Cruz, e.g., 0182 and 0186). Cruz teaches the hydrogel modified release formulations enable optimizing pharmacokinetic parameters (Cruz, e.g., 0123, 0241, 0248, and 0250). Cruz suggests the hydrogel formulations are effective for methadone (Cruz, e.g., 0042, 0140, 0143, claim 74).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention to modify a modified release formulation of esmethadone suggested by Manfredi and Morella by incorporating a hydrogel as taught by Cruz with a reasonable expectation of success. Since Cruz teaches hydrogel containing formulations may be used to optimize pharmacokinetic parameters for opioids, the skilled artisan would have found it obvious to formulate a modified release esmethadone formulation using a hydrogel to achieve desirable pharmacokinetic parameters, e.g., cmax, tmax, and cmin, for improved therapeutic efficacy with a reasonable expectation of success. The skilled artisan would have had a reasonable expectation of success since Cruz expressly teaches hydrogel containing modified release dosage forms effective for methadone.
Accordingly, the subject matter of claim 8 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A WAX can be reached on 571-272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615
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