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 .
Status of the Application
The amendment and remarks of 16 March 2026 are entered.
Claims 2, 3, and 5 have been canceled. Claims 1 and 5-16 are pending. Claims 4, 12-14, and 16 are withdrawn with traverse. Claims 1, 5-11, and 15 are being examined on the merits.
The election requirement remains in effect.
The objection to claim 16 as being a substantial duplicate of claim 15 is withdrawn in light of the amendment filed 16 March 2026.
The rejection of claims 1, 6-11, 15, and 16 under 35 U.S.C. 103 as being unpatentable over ‘106 and Zanos is withdrawn in light of the amendment filed 16 March 2026.
The rejection of claim 5 under 35 U.S.C. 103 as being unpatentable over ‘106 and Zanos in view of Mogri is withdrawn in light of the cancellation of said claim in the amendment of 16 March 2026.
New grounds of rejection are provided in response to Applicants’ amendment filed 16 March 2026.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1, 6-11, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Pedersen et al. (US 2013/0085106 A1, published 4 April 2013), Zanos et al. (British J. Pharmacology 175:2809-2824, published July 2018) and Mogri et al. (Chest 133:1484-1488, published June 2008, hereafter referred to as Mogri).
The ‘106 art discloses treatment of a medical disorder in a subject by administering oxytocin receptor agonists (see e.g. claim 1). The disorder can be a dependence disorder including patients with opioid addiction (see e.g. claims 3 and 5). The oxytocin receptor agonist can be oxytocin (see e.g. claim 20). A pharmaceutical composition is disclosed comprising oxytocin for treating opioid withdrawal symptoms including those in treatment for pain relief and having opioid dependence (see e.g. claims 22 and 34-37). When discussing various disorders the ‘106 art discloses sleeping disorders including breathing-related sleep disorders for treatment (see e.g. [0081]).
The difference between ‘106 and the claimed invention is that ‘106 does not explicitly show treatment of opioid-induced respiratory depression by administering oxytocin in a subject diagnosed with or having sleep apnea or obstructive sleep apnea.
Oxytocin was known in the art as a potential treatment for obstructive sleep apnea (as evidence, see e.g. Jain et al. Am. J. Physiol. Lung Cell Mol. Physiol. 313:L825-L833, published 10 August 2017).
Zanos discusses the use of oxytocin as a candidate for treatment of opioid addiction and depression-addiction co-morbidities (see e.g. Abstract). Zanos discusses that the oxytocin effect on opioid tolerance in those receiving opioid replacement therapy and cautions that oxytocin may reduce tolerance to the respiratory depressant effects of opioid, such that a higher risk may exist for opioid overdose (see e.g. p.2817 Col.2).
Mogri discloses patients who are on opioid for pain management where significant sleep apnea developed as a result of treatment, including worsening of previous obstructive sleep apnea (see e.g. Objectives).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the treatment of those with opioid addiction of ‘106 by administration of oxytocin could have been modified by utilizing oxytocin to treat co-morbidities as taught in Zanos including the suggestion that oxytocin could alter the respiratory depressant effects of opioids and as a result offer a method of reducing opioid-induced respiratory depression in subjects with opioid addiction through administration of oxytocin. The rationale comes from ‘106 already suggesting treatment of those with opioid addiction with oxytocin as well as discussing breathing issues as being targeted, and Zanos suggesting that oxytocin is useful to alter respiratory depressive effects of opioids in those having opioid addiction. As a result, one of ordinary skill would seek to administer oxytocin to those patients and have a reasonable expectation that it would reduce the opioid-induced respiratory depression in said patients. There would have been a reasonable expectation of success because administration of oxytocin to those patients at risk for opioid-induced respiratory depression was already provided by the above art, with Zanos providing a disclosure that leads one of ordinary skill to expect that a reduction in respiratory depressive effects of opioids would be achieved. Furthermore, given the disclosure of Mogri it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of ‘106 and Zanos was such that there would have been an expectation that the patients with opioid addiction would have had sleep apnea. The rationale comes from ‘106 already suggesting treatment of sleep-related breathing disorders, encompassing sleep apnea, and Mogri showing that patients on opioid treatment for pain frequently develop or exacerbate sleep apnea during the course of treatment. Additionally, as noted above there was evidence the prior art already recognized oxytocin for treatment of sleep apnea from Jain et al. There would have been a reasonable expectation of success because ‘106 already suggests treatment in a genus encompassing sleep apnea, ‘106 and Zanos suggest treatment of patients on opioid treatment, and Mogri confirms that such patients frequently develop or exacerbate sleep apnea. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claims 6 and 7, as set forth above ‘106 provides for treatment of patients that are already undergoing opioid administration for pain management. By necessity those patients are identified as need in treatment before the administration step.
With respect to claim 8, ‘106 offers intranasal administration routes (see e.g. claim 23).
With respect to claim 9, ‘106 suggests as-needed treatment (see e.g. [0111]).
With respect to claim 10, again given that the patients are those with opioid addiction in both ‘106 and Zanos, by necessity the treatment must occur before, during, or after administration of an opioid.
With respect to claim 11, ‘106 suggests that carbetocin can be utilized as an oxytocin receptor agonist (see e.g. [0076]).
With respect to claim 15, the ‘106 art suggests inclusion of opioid receptor antagonists such as naltrexone (see e.g. [0116]).
Response to Arguments:
The Applicants provide a summary of the legal basis for determining obviousness.
The Examiner finds no issues with the summary as provided.
The Applicants summarize the rejection of claim 5. The Applicants argue disclosure of patients on opioids for pain management developing sleep apnea does not provide guidance or suggestion for the claimed invention.
The Examiner finds no issues with the summary as provided. The Examiner disagrees that the ‘106, Zanos, and Mogri art fails to provide guidance to treating patients having sleep apnea with oxytocin to prevent, reverse, or reduce opioid-induced respiratory depression in those subjects. As argued above, ‘106 and Zanos provide disclosures leading to treating patients on opioids with oxytocin for managing opioid-induced respiratory depression. The Mogri art provides for patient populations within those utilizing opioids for pain management that would require the same intervention in the case of having sleep apnea. Further as discussed above, the Jain art provides evidence that oxytocin was also utilized to treat sleep apnea, i.e. extension to the patients utilizing opioids would have been a reasonable application of oxytocin as already provided by ‘106 and Zanos. Further supporting this is Geller A (Cleveland Clinic J. of Medicine 84:91-94, published February 2017) indicating that in patients with chronic opioid usage the incidence of sleep apnea can be as high as 90% of patients. Given this, there would have been a reasonable expectation that the patients of ‘106, Zanos, and Mogri would have sleep apnea.
The Applicants argue improper hindsight, and that the only way to arrive at the claimed invention is through using the claimed subject matter as a blueprint for the combination of ‘106, Zanos, and Mogri. The Applicants argue this is clear because the only arguable combination alleged by the Office is based upon the limitation from claim 5 regarding sleep apnea patients.
The Examiner disagrees. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). In this case, the art as noted above discloses that oxytocin is useful for treating respiratory depression as in ‘106 and Zanos. The Mogri art indicates that patients utilizing opioids are more likely to experience sleep apnea. The Geller art as cited above provides further evidence that patients having chronic opioid usage are very likely to have sleep apnea. The Jain art as cited above further indicates that oxytocin was known for treatment of sleep apnea. Given the accumulated prior art and evidence therein, there is a more than reasonable combination of ‘106, Zanos, and Mogri for treatment of those same patients and an expectation that oxytocin would be a useful therapeutic. The mere citation of the sleep apnea patients as part of a difference statement required for obviousness analysis is not an admission of hindsight but a requirement under the Deere analysis.
The Applicants arguments have been considered but are not persuasive. The rejection is modified in light of Applicants’ amendment.
Conclusion
No claims are allowed.
Applicant's 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Z.J.M/Patent Examiner, Art Unit 1658 /SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658