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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 submissions filed on 2/12/2026 and 4/10/2026 have been entered.
DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Amendments after Final office action filed on 2/12/2026 and 4/10/2026 are acknowledged.
3. Claim filed on 2/12/2026 is acknowledged.
4. Claims 2-8, 10, 12, 14, 16, 18, 20-24 and 27-50 have been cancelled.
5. New claims 53-61 have been added.
6. Claims 1, 9, 11, 13, 15, 17, 19, 25, 26 and 51-61 are pending in this application.
7. Claims 9, 11, 13, 15, 17, 53, 54, 60 and 61 remain/are withdrawn from consideration as being drawn to non-elected species. In the instant case, Applicant elected subject having leptin resistance as a single disclosed species of subject in the replies filed on 4/30/2025 and 6/2/2025, which is not the same as a subject that is not obese recited in instant claims 53 and 60.
8. Applicant elected without traverse Group 1 (claims 1, 7, 9, 11, 13, 15, 17, 19, 25-27, 38, 46 and 49) and elected without traverse of subject having leptin resistance as species of subject; intranasal administration as species of route of administration; post-surgical administration recited in instant claim 26 as species of administration scheme; and increase in minute ventilation recited in instant claim 19 as species of effect of the treatment from claims 9, 11, 13, 15, 17 and 19 in the replies filed on 4/30/2025 and 6/2/2025.
Restriction requirement was deemed proper and made FINAL in the previous office actions. Group 1 is drawn to a method of treating or inhibiting opioid-induced respiratory depression in a subject in need thereof, wherein the method comprises: (1) administering to a subject that is (i) recovering from surgery-induced stress and (ii) in need of pain management a therapeutically effective amount of an opioid; and (2) intranasally administering to the subject a therapeutically effective amount of leptin; and a method of treating or inhibiting opioid-induced respiratory depression in a subject, the method comprising: intranasally administering to a subject that is (i) recovering from surgery-induced stress and (ii) receiving an opioid for pain management the subject a therapeutically effective amount of leptin. A search was conducted on the elected species; and prior art was found. Claims 9, 11, 13, 15, 17, 53, 54, 60 and 61 remain/are withdrawn from consideration as being drawn to non-elected species. Claims 1, 19, 25, 26, 51, 52 and 55-59 are examined on the merits in this office action.
Please note: As stated in the previous office action, subject having leptin resistance as the elected species of subject is not explicilty recited in the pending claims.
Withdrawn Objections
9. Objection to the drawings is hereby withdrawn in view of Applicant’s amendment to the drawings.
Maintained/Revised Objections
10. (Revised due to Applicant’s amendment to the claim) Claim 1 remains objected to for the following minor informality: First, claim 1 needs to end with a period. Second, Applicant is suggested to amend claim 1 as “…wherein the method comprises: (1) administering a therapeutically effective amount of an opioid to a subject that is (i) recovering from surgery-induced stress and (ii) in need of pain management; and (2) intranasally administering to the subject a therapeutically effective amount of leptin”.
Response to Applicant's Arguments
11. In the instant case, Applicant fails to address all the minor issue in claim 1 and Applicant’s amendment to claim 1 introduces additional minor issues. Therefore, the objection is deemed proper and is hereby maintained.
New Objections
12. Claim 55 is objected to for the following minor informality: Applicant is suggested to amend claim 55 as “A method of treating or inhibiting opioid-induced respiratory depression in a subject that is (i) recovering from surgery-induced stress and (ii) receiving an opioid for pain management, wherein the method comprises intranasally administering to the subject a therapeutically effective amount of leptin”.
Maintained/Revised Rejections
Claim Rejections - 35 U.S.C. § 103
13. 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.
14. 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 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.
15. (Revised due to Applicant’s amendment to the claim) Claims 1, 19, 25, 26, 51, 52 and 55-59 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Berger et al (Am J Respir Crit Care Med, 2019, 199, pages 773-783, originally published in press as DOI: 10.1164/rccm.201805-0879OC on October 12, 2018, cited and enclosed in the previous office actions) in view of Angel et al (Anesthesiology, 2018, 128, pages 984-991, filed with IDS) and Golder et al (Respiratory Physiology & Neurobiology, 2013, 189, pages 395-402, cited and enclosed in the previous office actions).
The instant claims 1, 19, 25, 26, 51, 52 and 55-59 are drawn to a method of treating or inhibiting opioid-induced respiratory depression in a subject in need thereof, wherein the method comprises: (1) administering to a subject that is (i) recovering from surgery-induced stress and (ii) in need of pain management a therapeutically effective amount of an opioid; and (2) intranasally administering to the subject a therapeutically effective amount of leptin; and a method of treating or inhibiting opioid-induced respiratory depression in a subject, the method comprising: intranasally administering to a subject that is (i) recovering from surgery-induced stress and (ii) receiving an opioid for pain management the subject a therapeutically effective amount of leptin.
Berger et al, throughout the literature, teach a method of treating upper airway obstruction and alveolar hypoventilation (syndromes of obesity-related sleep disordered breathing (SDB)) in diet-induced obesity (DIO) mice, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the DIO mice, and wherein intranasal leptin bypasses leptin resistance and significantly attenuates sleep-disordered breathing independently of body weight, for example, Abstract; and Figures 1-3. It reads on intranasal administration as the elected species of route of administration. Berger et al further teach leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice, for example, Abstract; page 780, the paragraph bridging the middle and the right columns; and Figure 2. It reads on increase in minute ventilation as the elected species of effect of the treatment; and meets the limitations of instant claims 19 and 56. Berger et al also teach humans and rodents with DIO are leptin resistant owing, at least in part, to limited permeability of the blood–brain barrier (BBB) to leptin, for example, page 774, the Section “At a Glance Commentary”; and the paragraph bridging the middle and the right columns. It reads on subject having leptin resistance as the elected species of subject. Furthermore, Berger et al teach “Previous investigations in humans and animals showed that leptin is involved in the pathogenesis of SDB through central regulation of respiratory pump muscles and upper airway patency…Leptin deficient obese ob/ob mice have suppressed hypercapnic ventilatory response (HCVR) and are hypercapnic while awake, mimicking human OHS”; and “This study provides a proof of principle for novel human pharmacotherapy for obesity associated sleep-disordered breathing”, for example, page 774, right column, the 2nd paragraph; and page 782, Section “Conclusions and Clinical Implications”. Therefore, in view of the teachings of Berger et al as a whole, one of ordinary skilled in the art would immediately envision a method of treating upper airway obstruction and alveolar hypoventilation in DIO mice or DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the DIO mice or DIO human, wherein the DIO mice or DIO human is leptin resistant, and wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human.
The difference between the reference and instant claims 1, 19, 25, 26, 51, 52 and 55-59 is that the reference does not explicilty teach the DIO mice or DIO human has opioid-induced respiratory depression and is a subject recited in instant claims 1 and 55; post-surgical administration as the elected species of administration scheme; and the limitations of instant claims 25, 26, 51, 52 and 57-59.
However, Angel et al, throughout the literature, teach opiate-induced respiratory depression is associated with increased risk among subjects who are obese; buprenorphine (one type of opioid) decreases minute ventilation in mice with diet-induced obesity; and leptin signaling contributes to the buprenorphine-induced decrease in minute ventilation, for example, Abstract; page 984, left column, the 1st paragraph; Figures 2, 3 and 5; and page 989, Section “Conclusions”. Therefore, in view of the combined teachings of Berger et al and Angel et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treating or inhibiting opiate-induced respiratory depression in DIO mice or DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the DIO mice or DIO human, wherein the DIO mice or DIO human is leptin resistant, and wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human.
Furthermore, Golder et al teach postoperative patients receive opioids for pain management; drug-induced respiratory depression (DIRD) is a common problem encountered post-operatively and can persist for days after surgery; and patients who are housed on usual patient floors for routine post operative care are at greatest risk for opioid-induced respiratory depression from postoperative day 1 through day 5, for example, Abstract; page 395, left column, the 1st paragraph in Section “1. Introduction”; and page 396, left column, the 1st paragraph. Furthermore, with regards to the limitation “recovering from surgery-induced stress” recited in instant claims 1 and 55, the instant specification fails to define it. Thus, in the broadest reasonable interpretation, a postoperative patient receiving opioids for pain management is the subject recited in instant claims 1 and 55.
Therefore, it would have been obvious to one of ordinary skilled in the art to combine the teachings of Berger et al, Angel et al and Golder et al to develop a method of treating or inhibiting opiate-induced respiratory depression in postoperative DIO mice or postoperative DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the postoperative DIO mice or postoperative DIO human, wherein the postoperative DIO mice or postoperative DIO human is leptin resistant and is a subject receiving a therapeutically effective amount of opioids for pain management and a subject recovering from surgery-induced stress, wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human, and wherein the leptin is administered in combination with the opioid for up to 5 days following surgery. It reads on post-surgical administration as the elected species of administration scheme.
Furthermore, one of ordinary skilled in the art would have been motivated to optimize the administration scheme of leptin for efficiently treating or inhibiting opiate-induced respiratory depression in postoperative DIO mice or postoperative DIO human, including repeating the administering step every 6 hours or repeating the administering step at least once every 12 hours. And, the MPEP states the following: 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. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (see MPEP § 2144.05 II A).
One of ordinary skilled in the art would have been motivated to combine the teachings of Berger et al, Angel et al and Golder et al with routine optimization to develop a method of treating or inhibiting opiate-induced respiratory depression in postoperative DIO mice or postoperative DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the postoperative DIO mice or postoperative DIO human, wherein the postoperative DIO mice or postoperative DIO human is leptin resistant and is a subject receiving a therapeutically effective amount of opioids for pain management and a subject recovering from surgery-induced stress, wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human, wherein the leptin is administered in combination with the opioid for up to 5 days following surgery, and wherein the administering step is repeated every 6 hours or at least once every 12 hours, because Angel et al, throughout the literature, teach opiate-induced respiratory depression is associated with increased risk among subjects who are obese; buprenorphine (one type of opioid) decreases minute ventilation in mice with diet-induced obesity; and leptin signaling contributes to the buprenorphine-induced decrease in minute ventilation. Therefore, in view of the combined teachings of Berger et al and Angel et al, it would have been obvious to one of ordinary skilled in the art to develop a method of treating or inhibiting opiate-induced respiratory depression in DIO mice or DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the DIO mice or DIO human, wherein the DIO mice or DIO human is leptin resistant, and wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human. And Golder et al teach postoperative patients receive opioids for pain management; drug-induced respiratory depression (DIRD) is a common problem encountered post-operatively and can persist for days after surgery; and patients who are housed on usual patient floors for routine post operative care are at greatest risk for opioid-induced respiratory depression from postoperative day 1 through day 5. Furthermore, one of ordinary skill in the art would have been motivated to optimize the administration scheme of leptin for efficiently treating or inhibiting opiate-induced respiratory depression in postoperative DIO mice or postoperative DIO human, including repeating the administering step every 6 hours or repeating the administering step at least once every 12 hours. And the MPEP states the following: 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).
A person of ordinary skilled in the art would have reasonable expectation of success in combining the teachings of Berger et al, Angel et al and Golder et al with routine optimization to develop a method of treating or inhibiting opiate-induced respiratory depression in postoperative DIO mice or postoperative DIO human, wherein the method comprises administering a therapeutically effective amount of leptin intranasally to the postoperative DIO mice or postoperative DIO human, wherein the postoperative DIO mice or postoperative DIO human is leptin resistant and is a subject receiving a therapeutically effective amount of opioids for pain management and a subject recovering from surgery-induced stress, wherein leptin treatment increases minute ventilation (VE), when compared to an untreated DIO mice or DIO human, wherein the leptin is administered in combination with the opioid for up to 5 days following surgery, and wherein the administering step is repeated every 6 hours or at least once every 12 hours.
Response to Applicant's Arguments
16. Applicant argues about each of the cited prior art references individually. Applicant further argues that the three paragraphs at the end of the rejection are mere conclusion statements without explicit analysis.
17. Applicant's arguments have been fully considered but have not been found persuasive.
In response to Applicant's arguments about instant rejection:
First, the Examiner agrees that none of the cited references individually teaches or suggests the methods recited in instant claims 1, 19, 25, 26, 51, 52 and 55-59; and none of the cited references anticipates the methods recited in instant claims 1, 19, 25, 26, 51, 52 and 55-59. However, the Examiner would like to point out that instant claims 1, 19, 25, 26, 51, 52 and 55-59 are rejected under 35 U.S.C. 103 (obviousness type), and the rejection is based on the combined teachings of Berger et al, Angel et al and Golder et al with routine optimization. Therefore, it is not necessary for each of the cited references to teach all the limitations of instant claims. Furthermore, in the instant case, the combined teachings of Berger et al, Angel et al and Golder et al with routine optimization as set forth in Section 15 above teach each and every limitation recited in instant claims 1, 19, 25, 26, 51, 52 and 55-59. The postoperative DIO mice or postoperative DIO human that is leptin resistant, a subject receiving a therapeutically effective amount of opioids for pain management and a subject recovering from surgery-induced stress in the method developed in Section 15 above is a subpopulation of the subject recited in instant claimed methods. In addition, as stated in the previous office action, the Examiner would like to point out that the MPEP states "One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references…" (see MPEP § 2145 IV).
Second, the Examiner would like to point out that the fact that Berger et al fail to teach the subject recited in instant claims does not disqualify Berger et al as a prior art reference for rejection under 35 U.S.C. 103.
Third, the Examiner would like to point out that the three paragraphs at the end of the rejection are based on the teachings of the cited prior art references with routine optimization set forth in the rejection. In the instant case, the rejection set forth on pages 6-12 above is not limited to the three conclusion paragraphs only. Therefore, it is unclear to the Examiner why and/or how the conclusion paragraphs should not be conclusive statements, and what kind of explicit analysis is required by Applicant. Further clarification is required.
Taken all these together, the rejection is deemed proper and is hereby maintained.
Conclusion
No claim is allowed.
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/LI N KOMATSU/Primary Examiner, Art Unit 1658
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