DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Application
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 9/19/25 has been entered.
Claims 1-51, 64-68 have been cancelled. Claims 52-63 are pending. Claim 52 has been amended. Claims 52-63 are examined herein.
The terminal disclaimers filed on 9/19/25 disclaiming the terminal portion of any patent granted on this application, which would extend beyond the expiration date of US Patents 10,716,784 and 12,064,423 have been reviewed and accepted. The terminal disclaimers have been recorded. The obviousness double patenting rejections are hereby withdrawn.
Applicant’s arguments have been fully considered but found not persuasive. The rejection of the last Office Action is maintained for reasons of record and modified below as a result of the new claim amendments.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 52-63 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Babul et al. (US2010/0249045 A1, of record) as evidenced by PubChem CID5462351, of record.
Babul et al. teaches oral pharmaceutical compositions of opioid agonists, extended release pharmaceutical compositions of opioid agonist an extended release abuse resistant pharmaceutical composition [abstract and entire document]. The composition is directed to an oral abusable drug pharmaceutical composition that provide extended release delivery of the drug and the use for the treatment of pain [0060 and 0064]. The compositions and methods include (i) one or more abusable drugs (i.e., one or more opioid agonist); and (ii) ADER and (iii) optionally other therapeutic agents in immediate or extended release form, ect. [0091]. The term "abusable drugs”, are limited to one or more "opioid agonist” or “opioid receptor agonist” [0061]. All pain states are contemplated by this invention regardless of etiology, mechanism, duration, prior treatment response and anatomic location, including acute pain, inflammatory pain, chronic pain, cancer pain, visceral pain and neuropathic pain [0332]. All modes of co-administration are contemplated including oral route [0339]. The "abusable drugs" is consider an opioid agonists for the prevention or treatment of diseases and disorders amenable to prevention or treatment with opioids [0380]. Opioids agonist include morphine, levallorphan and pharmaceutical acceptable salts such as morphine sulfate [0385, example 15 and 17]. The amount of abusable drug in the dosage form is about 0.01µg to 1500 mg or about 1mg to about 500mg [0361]. The ratio between abusable drug and ADER is about 1:10,000 to about 10,000: 1 by weight, about 1:1000 to about 1000:1 by weight or about 1:250 to about 250:1 [0363]. The ADER, other abuse deterrent or abuse resistant substances include one or more aversive agents such as bittering agents [0408]. Bittering agents include quinidine [0414]. The aversive agent in the dosage form may be about 0.00000000001 mg to about 2000 mg [0410]. A co-administered drug (in the same or different dosage form, by any route if administration) may be used to provide additive, complementary, superadditive or synergistic therapeutic analgesic effects including NMDA receptor antagonist such as dextromethorphan [0438]. The amount of pharmacologic antagonist to the abusable drug in the oral dosage form will vary for a variety of reasons, including the choice of abusable drug, the potency of the abusable drug, the potency of the antagonist, the oral bioavailability of the abusable drug and the antagonist, the safety, tolerability of the antagonist, the degree of block sought to the effects of the abusable drug, the patients prior to exposure to the abusable drug and the nature of the formulation, pharmacodynamics and physicochemical characteristics of the abusable drug and the antagonist [0273]. The pharmacologic antagonist to the abusable drug is about 0.00001mg to 1000 mg, or about 0.01 to about 200mg [0274]. “Pharmaceutically acceptable salts” are well known in the art and include those of inorganic acids, such as hydrochloride, sulfate, hydrobromide and phosphate; and those of organic acids, such as formate, tartrate [0052]. For example, in some other embodiments, the dosage form of the abusable drug of the invention contains one or more aversive agents in releasable or partially releasable form, said dosage form not aversive when taken at medically approved doses or at doses consistent with the manufacturers prescribing information, said dosage form producing an aversive effect when taken in excess of medically approved doses or the manufacturers prescribing information [0316].
With regard to the limitation regarding “fast-dissolving film,” attention is drawn to paragraph 00369 in Babul, which teaches that the oral pharmaceutical dosage forms can include transmucosal films and fast disintegrating dosage forms.
Pubchem CID 5462351 is cited to demonstrate the dextromethorphan hydrobromide is a synonym of dextromethorphan hydrobromide monohydrate [see chemical names/synonym].
Babul et al. does not teach wherein the ratio of dextromethorphan: quinidine: morphine is 1:1:1 [claim 53], wherein dextromethorphan hydrobromide monohydrate [claim 62], and wherein the quinidine is quinidine gluconate or quinidine sulfate [claim 63].
A person of ordinary skill in the art at the time of the invention would have found it prima facie obvious to develop a pharmaceutical composition comprising dextromethorphan, quinidine and morphine sulfate because Babul et al. teaches pharmaceutical compositions that contain one or more opioids, an abuse resistant substances such as quinidine and other therapeutic agents in immediate or extended release form such as dextromethorphan for the treatment of pain and deterring abuse by drug addicts. The skilled artisan would have been motivated to incorporate morphine, dextromethorphan and quinidine in a pharmaceutical composition because Babul et al. taught that morphine, dextromethorphan and quinidine can be used together in a pharmaceutical composition for treating pain since morphine is an abusable drug, dextromethorphan is used as synergistic therapeutic analgesic effects and quinidine is used as aversive agent. Thus, the skilled artisan would have found motivation and instruction to develop the instantly claimed pharmaceutical dosage since Babul et al. taught Babul et al. taught that morphine, dextromethorphan and quinidine can be used together in a pharmaceutical composition for treating pain since morphine is an abusable drug, dextromethorphan is used as synergistic therapeutic analgesic effects and quinidine is used as aversive agent.
The skilled artisan would have been motivated to use opioid pharmaceutical salts such as morphine sulfate because Babul et al. taught that opioid salts such as morphine sulfate, are suitable salts that can be incorporate in the composition. The skilled artisan would have been motivated use quinidine sulfate because Babul et al. incorporates quinidine salts such as a sulfate in a pharmaceutical composition comprising one or more opioids and dextromethorphan hydrobromide.
In regards to the limitation wherein the ratio of dextromethorphan to quinidine to opioid agonist is about 1:1:1 as recited in claim 53. Babul et al. demonstrates a combination therapy of opioid (morphine), dextromethorphan, and quinidine for the treatment of pain. Babul et al. teaches an amount of abusable drug in the dosage form is about 0.01µg to 1500 mg or about 1mg to about 500mg. The ratio between abusable drug and ADER is about 1:10,000 to about 10,000: 1 by weight, about 1:1000 to about 1000:1 by weight or about 1:250 to about 250:1. In addition, the reference discloses that the abusable drug and the dextromethorphan can be co-administer in the same dosage. Further, Babul et al. teaches that the aversive agent in the dosage form may be about 0.00000000001 mg to about 2000 mg and pharmacologic antagonist is about 0.00001mg to 1000 mg, or about 0.01 to about 200mg. The skilled artisan would have been motivated to include composition comprises about 10 mg, about 20 mg, about 30 mg, about 40 mg, about 50 mg or about 60 mg of the opioid agonist because Babul et al. taught that the opioid agonist can be present in amounts of about 0.01µg to 1500 mg or about 1mg to about 500mg for the treatment of pain. The skilled artisan would have been motivated to use the instantly ratio of dextromethorphan to quinidine to opioid agonist is about 1:1:1 because Babul et al. taught that the abusable drug in the dosage form is about 0.01µg to 1500 mg or about 1mg to about 500mg, aversive agent in the dosage form may be about 0.00000000001 mg to about 2000 mg and pharmacologic antagonist to the abusable drug is about 0.00001mg to 1000 mg, or about 0.01 to about 200mg in a pharmaceutical composition for the treatment of pain. Such amount disclosed by Babul et al. render obvious to the instantly claimed ratio of 1:1:1. In addition, Babul et al. demonstrates that the ratio between abusable drug and ADER is about 1:10,000 to about 10,000: 1 by weight, about 1:1000 to about 1000:1 by weight or about 1:250 to about 250:1. Given the teachings of Babul et al. the skilled artisan would have had motivation and instruction to arrive at the instantly claimed invention ratio since such amount disclosed overlap and can be safely administer to a subject in need. 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) See MPEP 2144.05 (I).
It would, therefore, have been prima facie obvious to a person of ordinary skill in the art to modify the teachings disclosed by Babul et al., with reasonable expectation of success. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was made.
Response to Arguments
Applicant argues that Babul does not teach or suggest pharmaceutical dosage forms which are fast-dissolving films.
This is not persuasive because Babul clearly teaches which teaches that the oral pharmaceutical dosage forms can include transmucosal films and fast disintegrating dosage forms (paragraph 00369).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam 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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/Yong S. Chong/Primary Examiner, Art Unit 1623