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 .
Current Status of 18/741,475
This Office Action uses the amended claims of 6/29/2026.
Election/Restrictions
Applicant’s election without traverse of Group II (Claims 13 and 16-22) in the reply filed on 06/29/2026 is acknowledged.
Claims 13 and 16-22 read on the elected species (Naloxone, clonidine, and laryngospasm).
Priority
This application has priority claimed to 18/154,752 (abandoned), 17/266,960 (abandoned), PCT/US2019,045786, filed on 08/08/2019, which claims priority to 62/828,914, filed on 04/03/2019, and 62/716,291, filed on 08/08/2018.
The claims find support from PCT/US2019,045786. Therefore, 08/08/2019 is assigned as the instant application’s effective filing date.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 06/12/2026, are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Objections
Claim 13, is objected to because of the following informalities: Claim 13 says “a α2-adrenergic”. Applicants should revise claims to replace “a” with -- an -- . Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 21 and 22 are 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 21 recites the broad recitation “0.4 mg to 4 mg” of naloxone, and the claim also recites 0.4 mg to 2mg or 1 mg to 4 mg of naloxone which is the narrower statement of the range/limitation. Claim 22 also does this multiple ranges for clonidine. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
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.
Claims 13, and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over:
BENNETT (Bennett et al., “Difficult or impossible ventilation after sufentanil-induced anesthesia is caused primarily by vocal cord closure”, Anesthesiology, 1997 Nov), previously supplied by applicants
In view of
FDA (“Narcan”, FDA, reference number: 51-022523-00, 4/19/2003), previously supplied by applicants
In view of
JERUSSI (Jerussi et al., “Reversal of opioid-induced muscular rigidity in rats: Evidence for alpha-2 Adrenergic involvement”, Pharmacology Biochemistry and Behavior, Vol. 28, Issue 2, October 1987), previously supplied by Applicants,
And in view of
COLEMAN (US 2008/0146549 A1), previously supplied by applicants.
BENNETT teaches that administration of opioids caused vocal cord closure (abstract’s results). Furthermore, BENNETT teaches that vocal cord closure makes it difficult to breath (abstract’s conclusion).
BENNETT teaches that opioid-based anesthetic regimens are often complicated by muscular rigidity and difficult ventilation (breathing) (page 1070 right col).
BENNETT teaches that a muscle relaxant was given after vocal cord closure/difficulty in breathing occurred (page 1071 right col). This helps teach identifying the subject (person) as having vocal cord closure before administering the treatment of claim 13 and claim 18.
FDA teaches that naloxone (elected species of mu opioid receptor antagonist) is prevents or reverses the effects of opioids including respiratory depression (page 2 first paragraph). Examiner interprets “respiratory depression” as a condition which makes it difficult to breath (which would include vocal cord closure). This helps teach a method of preventing or reversing effects of opioids.
FDA teaches that naloxone (brand name Narcan) (page 1) will produce withdrawal symptoms for someone who is physically dependent on opioids (page 2 third paragraph). FDA further teaches that withdrawal symptoms may appear within minutes of naloxone administration and subside in about 2 hours (page 2 third paragraph). FDA lists withdrawal symptoms on the last paragraph of page 6 to the top of page 7, including fever, increased blood pressure, and tachycardia. This helps teach a motivation for why an artisan would be interested in administering a second compound (a compound which aids in opioid withdrawal) in the method of reversing vocal cord closure of claim 13.
JERUSSI teaches that clonidine reversed fentanyl induced muscular rigidity (abstract). This helps teach a motivation for why an artisan would be interested in administering a second compound (a compound which reverses muscle rigidity such as vocal cord closure). This helps teach claim 17 (fentanyl induced muscular rigidity).
COLEMAN teaches a method of administering to a subject a medication that relieves opioid withdrawal symptoms such as clonidine (paragraph [0013]).
COLEMAN teaches a patient addicted to oxycontin (opioid) being administered Valium, Zyprexa, Ultram, a clonidine patch (for a week), an intravenous administration of naloxone, and an implanted sustained release pellet of naltrexone (paragraph [0040]). COLEMAN teaches a treatment of clonidine, applicants’ elected A2AR agonist, and naloxone, applicants’ elected Mu opioid receptor antagonist (paragraph [0040]). This helps teach combined treatment of clonidine and naloxone in claim 13, and 16.
COLEMAN teaches the use of a carrier in the intravenous administration (paragraph [0034]). COLEMAN administers the composition intravenously and “the choice of carrier will depend upon the route of administration of the composition” (paragraphs [0040] and [0034]). COLEMAN teaches parenteral administration where the pharmaceutical composition of the present invention is combined with a sterile aqueous solution, containing sodium chloride, glycine (paragraph [0031]). The examiner interprets the above COLEMAN’s teaching as requiring a carrier for parenteral administration (paragraph [0031]). This helps teach the carrier of claim 13.
COLEMAN administers the treatment for an opioid addicted human patient (para [0040]). This helps teach the subject is human of claim 19.
While BENNETT teaches that administration of opioids caused vocal cord closure (abstract’s results), and teaches that a muscle relaxant was given after vocal cord closure/difficulty in breathing occurred (page 1071 right col), BENNETT does not teach the instant claim 13.
While FDA teaches that naloxone is prevents or reverses the effects of opioids including respiratory depression (page 2 first paragraph), and that naloxone will quickly produce withdrawal symptoms for someone who is physically dependent on opioids (page 2 third paragraph), FDA does not teach clonidine or vocal cord closure.
While JERUSSI teaches that clonidine reversed opioid induced muscular rigidity (abstract), JERUSSI does not teach the instant claims.
While COLEMAN teaches a method of administering to a subject a medication that relieves opioid withdrawal symptoms such as clonidine (paragraph [0013]), a carrier in the intravenous administration (paragraph [0034]), and administration to an opioid addicted human patient (para [0040]), COLEMAN does not teach the instant claim 13.
The instant claims 13, and 16-19 are prima facie obvious in light of the combination of references BENNETT, FDA, JERUSSI, and in view of COLEMAN.
The artisan would have been motivated to administer both naloxone and clonidine in a method of preventing and reversing vocal cord closure (elected species of opioid or opiate effect). Examiner will refer to vocal cord closure as VCC henceforth.
Naloxone is a known treatment for opioid overdose (FDA page 2). The artisan would have been motivated and expected to administer naloxone before vocal cord closure (VCC) began in order to prevent it (BENNTT Abstract’s results and FDA page 2).
The artisan would have been motivated to identify the subject (person) as having vocal cord closure before administering an overdose treatment. BENNETT teaches that a muscle relaxant was given after vocal cord closure/difficulty in breathing occurred (page 1071 right col). The artisan expects to give a treatment to a person after identifying/seeing symptoms that the person is in need of said treatment. This helps teach of claim 13 and claim 18.
The artisan would have been motivated to add clonidine for two reasons. First, BENNETT reverses VCC with a muscle relaxant (page 1071). JERUSSI teaches that clonidine reversed fentanyl induced muscular rigidity (abstract). The Examiner understands vocal cord closure as muscles closing the airway (BENNETT’s Abstract’s results, background, and page 1070). The artisan would expect that vocal cord muscles to be relaxed in the same way that the muscles of opioid induced muscular rigidity that were relaxed by clonidine. The artisan would expect that clonidine in relaxing the vocal cord muscles to reverse vocal cord closure (BENNETT page 1071). This helps teach a method of reversing VCC with clonidine. This also teaches reversing fentanyl induced muscular rigidity of claim 17.
Second, the artisan would have been motivated to administer clonidine to prevent the sudden withdrawal symptoms caused by naloxone, especially in subjects who are physically dependent on opioids (FDA page 2 third paragraph). The artisan would expect that clonidine relieves opioid withdrawal symptoms (COLEMAN paragraph [0013]). This helps teach a method of reversing VCC with clonidine.
The artisan would be further motivated and expected to use a pharmaceutically acceptable carrier (paragraph [0034]) in the combination treatment of naloxone and clonidine. The artisan would also expect that the combination treatment to be safe to administer to a human patent (COLEMAN paragraph [0040]). This teaches claims 13. This also teaches claims 16 (naloxone and clonidine), and 17 (fentanyl-induced muscle rigidity).
The artisan would have been motivated to identify the subject (person) as having vocal cord closure before administering an overdose treatment. BENNETT teaches that a muscle relaxant was given after vocal cord closure/difficulty in breathing occurred (page 1071 right col). The artisan expects to give a treatment to a person after identifying/seeing symptoms that the person is in need of said treatment. This teaches claim 18.
The artisan would be motivated to give the combined naloxone and clonidine treatment to humans. The artisan would also expect that the combination treatment to be safe to administer to a human patent (COLEMAN paragraph [0040]). This teaches claim 19.
Claim(s) claims 13, 16-19, and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over
BENNETT (Bennett et al., “Difficult or impossible ventilation after sufentanil-induced anesthesia is caused primarily by vocal cord closure”, Anesthesiology, 1997 Nov), previously supplied by applicants,
In view of
FDA (“Narcan”, FDA, reference number: 51-022523-00, 4/19/2003), previously supplied by applicants,
In view of
JERUSSI (Jerussi et al., “Reversal of opioid-induced muscular rigidity in rats: Evidence for alpha-2 Adrenergic involvement”, Pharmacology Biochemistry and Behavior, Vol. 28, Issue 2, October 1987), previously supplied by Applicants,
in view of
COLEMAN (US 2008/0146549 A1), previously supplied by applicants,
as evidenced by
FDA (“Guidance for Industry: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers”, FDA, July 2005),
And in view of
Adapt Pharma (“NARCAN® (naloxone HCl) Nasal Spray 2mg Approved by U.S. Food and Drug Administration (FDA)”, PR Newswire provided by Adapt Pharma, January 25, 2017).
Claims 13 and 16-19 are taught above.
Adapt Pharma teaches the dosage for naloxone is 2mg (page 1).
Adapt Pharma does not teach a dosage for clonidine.
JERUSSI teaches that clonidine reversed fentanyl induced muscular rigidity (abstract). JERUSSI teaches a dosage of clonidine between 0.0001 mg/kg to 0.035 mg/kg (table 5); these doses were effective in reversing fentanyl induced muscular rigidity (table 5).
FDA is relied upon for the beneficial teaching that an average human is 60 kg (page 7 under table 1). Assuming a 60 kg person, Examiner calculates a dosage range of clonidine from 0.006 mg to 2.1 mg.
The artisan would have been motivated to optimize the dosage of naloxone and clonidine. Adapt Pharma and Jerussi (as evidenced by FDA) teaches dosages which fall within the instant claims’ ranges. Generally, 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. See MPEP 2144.05(II)A. Examiner has reviewed the instant specification and claims and has not found evidence that the dosage is critical. Thus, the artisan would be motivated and expected to optimize the dosage of naloxone and clonidine. This teaches claims 21-22.
Conclusion
No claims are allowed as written.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GILLIAN A HUTTER whose telephone number is (571)272-6323. The examiner can normally be reached M-F 7:30-5.
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/G.A.H./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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