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 was filed on 05/21/2024 and does not claim any priority status.
Information Disclosure Statement
This application does not have an IDS filed and no IDS was submitted before the mailing of the first office action.
Claim Objections
Claims 1, 6, and 14 are objected to with regards to the language “consisting the steps of”. The language is grammatically malformed and not consistent with the terminology of transitional terms within MPEP §2111.03 “Transitional Phrases”. The language should be reflective of “…the steps consisting of” to be consistent with transitional language.
Claims 1, 6, and 14 are objected to with regards to the language of “treating drug addict”. The language is inconsistent regard the use of the phrase. The term of “drug addict” is not clearly and/or explicitly stated in a definition within the specification. It would be unclear as to whether the intent of the language was to be specific to “someone with drug addiction” [097] or broader to read as “anyone in need of treatment…consisting of…”.
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.
Claim(s) 1, and 3-5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jordan et al. (Naloxone. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441910/ and further in view of Rodney (US 2024/0342137 A1)..
Jordan et al teaches the administration of naloxone as an opioid receptor agonist in hospital and pre-hospital medicine. Specifically, Jordan et al teaches the administration of naloxone:
Intravenously between .04-.1 mg (‘Administration: Adult dose’);
Intravenous infusion (prehospital) of 1-2mg (‘Administration: Adult dose’);
Intramuscular 1-2mg (‘Administration: Adult dose’);
Subcutaneous 1-2mg (‘Administration: Adult dose’).
Jordan et al does not teach where naloxone is administered with atipamezole.
Rodney teaches that atipamezole is an Alpha-2 antagonists that binds to receptors to prevent the activation of adrenergic alpha-2 agonist to include but not limited to xylazine, medetomidine, brimonidine and clonidine (¶012). The reference teaches that atipamezole is primarily for veterinary use with limited dosing information regarding humans, however data from human exposure demonstrates safely using up to a 100 mg dose to be safe (¶0039-40). Additionally, Rodney also recites where atipamezole has been tested in combination with naltrexone (opioid agonist) in white tail deer to reverse the effects of alpha-2 agonists.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where a drug addict would be administered a therapeutic amount of naloxone and atipamezole to a person needing treatment for drug addiction.
Regarding claims 1 and 3-5, where Jordan et al recites that naloxone is a known opioid receptor agonist, commonly used in a prehospital overdose incident setting but can also be utilized in a hospital setting. Given the number of overdoses increase in recent years and where opioids (specifically fentanyl) is often co-laced with xylazine (known veterinary use alpha-2 blocker) as recited by Rodney (¶3 and ¶11), it would be reasonable to conclude that one skilled in the art would combine an opioid receptor agonist (naloxone) and an alpha-2 agonist (atipamezole) because the inclusion of an alpha-2 agonist such as atipamezole would counteract the sedative and respiratory effects of xylazine which would not be counteracted by naloxone alone.
Claim 2 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Jordan et al. (Naloxone. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441910/ and further in view of Rodney (US 2024/0342137 A1) and Rowe et al. (Handbook of Pharmaceutical Excipients; (2006) 5th ed).
Jordan teaches the administration of naloxone in all forms as disclosed (see previous rejection), however does not specifically disclose where the compound is administered topically and does not disclose chelating agents or excipients of the compound.
Rodney teaches the administration where the administration of atipamezole as stated in the previous rejection in all forms (as instant claims 1 and 3-5), and further discloses excipients such as ethanol-water and propylene glycol water (¶044). However, Rodney does not specifically teach where an excipient is a chelating agent.
Rowe et al. teaches where Disodium Edetate (aka EDTA) is a known excipient and chelating agent as referenced in the instant specification (p278-279). Specifically, EDTA is widely used in pharmaceutical formulations that include topical, oral and parenteral administration (p.256, Safety, ¶1). Where, EDTA “…forms stable water-soluble complexes (chelates) with alkaline earth and heavy-metal ions.” and known to sequester (remove) ions from a solution. Additionally, is also used therapeutically as an anti-coagulant as it will chelate with calcium and prevent coagulation in blood.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where a drug addict would be administered a therapeutic amount of naloxone and atipamezole to a person needing treatment for drug addiction where the administered form comprises a chelating agent because it would be obvious to administer the compounds with a chelating agent to increase stability and to prevent interactions with substances (such as alkalines/heavy-metal ions) when administered parenterally: intravenous (as in claim 3), intramuscularly (as in claim 4), and subcutaneously (as in claim 5). Finally, it would be further obvious to use EDTA as a chelating agent due to the wide usage of EDTA in multiple forms that include topical, oral and parenteral routes and anti-coagulant properties.
Claim(s) 6-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Myers et al (US Patent 11,135,216) and further in view of Rodney (US 2024/0342137 A1) and Rowe et al (Handbook of Pharmaceutical Excipients, 5th edition (2006), p278).
Myers et al. teaches where naloxone is combined with another therapeutic drug (buprenorphine- an opioid partial agonist) as an oral treatment for narcotic dependence (pdf p7, col 2, lines 25-30). Myers et al. recites where the treatment is administered as an orally dissolving film (pdf p8, col 2, lines 22-46) to prevent being able to easily removed from the oral cavity by the user (as in claim 13). Additionally, the combination of naloxone/buprenorphine is evaluated as Example 2: Absorption Studies for Suboxone products, for both film and tablet products (pdf p 14, col 2 lines 56 through p15, col 1 line 33). Finally, (as reference claim 9), Myers et al. recites where “A method for treating opioid dependence in a patient in need thereof comprising sublingual or buccally administering the mucoadhesive film of claim 1 to a sublingual or buccally mucosal tissue of the patient to treat the opioid dependence” (pdf p18, col2, lines 32-36).
Myers et al does not teach where naloxone is administered in combination with atipamezole or specifically disclose an immediate release tablet, sublingual tablet, orally disintegrating tablet effervescent tablet or gelling tablet.
Rodney teaches that atipamezole is an Alpha-2 antagonists that binds to receptors to prevent the activation of adrenergic alpha-2 agonist to include but not limited to xylazine, medetomidine, brimonidine and clonidine (¶012). The reference teaches that atipamezole is primarily for veterinary use with limited dosing information regarding humans, however data from human exposure demonstrates safely using up to a 100 mg dose to be safe (¶0039-40). Additionally, Rodney also recites where atipamezole has been tested in combination with naltrexone (opioid agonist) in white tail deer to reverse the effects of alpha-2 agonists.
Rowe et al teaches examples excipients for the formulation of the following routes of administration:
Capsule/tablet formulation (p112);
Effervescent tablets (p208);
Gelling tablets (p309).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where a drug addict would be orally administered a therapeutic amount of naloxone and atipamezole to a person needing treatment for drug addiction.
Regarding claims 6-13, where Myers et al. recites the current combination of naloxone/ buprenorphine (formulated as suboxone) is administered orally for the treatment of narcotic dependence, and administered orally as a disintegrating tablet or film, it would be reasonable to conclude that one skilled in the art would combine an opioid receptor agonist (naloxone) and an alpha-2 agonist (atipamezole) because the inclusion of an alpha-2 agonist such as atipamezole would counteract the sedative and respiratory effects of xylazine or similar acting substances commonly co-laced with and opioid such as fentanyl (Rodney, ¶03 and ¶11), which would not be counteracted by naloxone alone as a treatment method for drug addiction. Additionally, while not specifically stated, the combination of naloxone/atipamezole could be administered as a capsule, tablet or film through disintegration (as in claims 7/9/13), sublingual (as in claims 8/10), effervescent (as in claim 11) or gelling tablets (as claim 12) as dictated by the needs/response of the patient or as determined by the physician.
Claim(s) 14-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jordan et al. (Naloxone. [Updated 2024 May 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441910/ above, and further in view of Aungst et al. (”Enhancement of naloxone penetration through human skin in vitro using fatty acids, fatty alcohols, surfactants, sulfoxides and amides”; Inter Jour Pharm, 33 (1986) 225-234) and Patruska & Trent (WO 2017/079734 A1).
The teachings of Jordan et al are set forth above and incorporated by reference herein.
Jordan et al teaches the administration of naloxone as an opioid receptor agonist in hospital and pre-hospital medicine. Specifically, Jordan et al teaches the administration of naloxone as a Trans-nasal spray/solution 3-8mg (‘Administration: Adult dose’). Jordan et al does not teach where naloxone is administered with atipamezole in combination or in a formulation for topical administration.
Aungst et al. teaches where naloxone is an opioid agonist and the advantages to transdermal drug delivery systems. In addition to the treatment of narcosis, naloxone has additional potential uses to include cardiovascular shock, chronic constipation, Alzheimer’s and topically has anti-pruritic effects (pp 226, cont’d ¶1). Additionally, naloxone was prepared in multiple vehicles to include solutions and gel components (Table 1, pp228).
Petruska & Trent teaches where the use of atipamezole is demonstrated in veterinary procedures where animals received alpha-2 sedation as in Example 1 (¶74) where demonstrated post-procedural paralysis/paresis can occur where in some embodiments the sedation included the use of xylazine. Additionally, the prior art discloses where the administration can occur via injections, IV, spray and topically (¶90) and within Claim 38 of the prior art. Petruska & Trent further disclose where the composition can generically consist of “…solutions, suspension and other dosage forms for topical administrations.” and where “…the compositions may also be suspensions, viscous or semi-viscous gels, or other types of solid or semi-solid compositions.” (¶80) with additional specific excipients disclosed (¶85).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing dated of the claimed invention, to arrive at the instantly claimed invention where a drug addict would be administered a therapeutic amount of naloxone and atipamezole as a topical to a person needing treatment for drug addiction.
Regarding claims 16-19, where Jordan et al. recites where naloxone is a known opioid receptor agonist, commonly used in a prehospital overdose incident setting but can also be utilized in a hospital setting and provides mechanisms that are typically used in the administration of naloxone in multiple vehicles to include as a nasal spray solution (as instant claims 16 and 18). Aungst recites the advantages of using naloxone in a transdermal delivery system; such as i) avoidance of first pass metabolism associated with oral dosing and ii) sustained constant dosing concentrations of drugs (as instant claims 14 and 17). Additionally, the use of topical naloxone can extend into additional treatment needs such as the treatment of cardiovascular shock, chronic constipation (known side effects of opioid abuse), and as an anti-pruritic. Petruska & Trent demonstrated that atipamezole is an alpha-2 agonist that can be used in the treatment of prolonged topical anesthetic/NSAIDs use to prevent toxicity in multiple topical forms such as solutions and gels (as instant claims 17-19). From the previous teachings as recited in prior rejections, it would be reasonable to conclude that one skilled in the art would combine the compounds of naloxone and atipamezole in a topical composition because both compounds can be administered topically and used for the treatment of opioids and to reverse to toxicity effects of sedations (such a xylazine). Additionally, both compounds have been shown to tolerate similar compositions as solutions or gel.
Summary of the Claims
Claims 1-19 are pending.
Claims 1-19 are rejected.
No claims are in condition for allowance.
Conclusion
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/S.H.D./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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