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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 2/9/2026 has been entered.
Claim Status
Claims 1-25 are pending. Claims 7 and 13 have been amended. Claims 7-8, 10, 12-13 and 15-16 are being examined in this application. In the response to the restriction requirement, Applicants elected morphine, Tyr-c[D-Lys-Trp-Phe-Glu]-Gly-NH2 (ZH853), and wherein the subject has not been treated previously with another agent. Claims 1-6, 9, 11, 14 and 17-25 are withdrawn as being drawn to a nonelected species.
Claim Rejections - 35 USC § 103
The rejection of claims 7-8, 10, 12-13 and 15-16 under 35 U.S.C. 103 as being unpatentable over Neale et al. in view of Zadina et al. is withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
This is a new rejection.
Claims 7-8, 10, 12-13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zadina et al. (US 2017/0369531).
With respect to claims 7-8, 10 and 12, Zadina et al. teach a method for providing analgesia, providing relief from a gastrointestinal disorder, or providing therapy for a drug dependence comprising administering to a patient an effective amount of a cyclic peptide of formula I (H-Z-c[X1-X2-X3-X4]-X5) (claim 11), wherein the patient has a history of substance abuse (claim 14).
Zadina et al. also teach that “[B]eyond the value of high mu agonist selectivity (i.e., exclusion of potential side-effects resulting from activation of multiple receptors), delta antagonism is expected to attenuate opioid-induced tolerance, dependence, and reward. As first shown in 1991 and supported in numerous studies since, delta antagonists can reduce morphine induced tolerance and dependence, while maintaining or enhancing analgesia. Recent studies have also shown reduced rewarding properties of mu agonist/delta antagonists as reflected in the conditioned place preference (CPP) test described below. The activity of the peptides of Formula I (e.g., Compound 1) as mu agonists/delta antagonists as well as at mu/delta receptor dimers indicate that the peptides will produce effective analgesia with reduced tolerance, dependence, and reward” (para [0068]).
Zadina et al. further teach that “[E]xplanations for the tolerance and opioid induced hypersensitivity include the possibility that activation of glia, a reflection of an inflammatory response, results in an increased release of substances that activate or sensitize neuronal transmission of nociceptive signals. Specifically, enhanced release of "pronociceptive" cytokines and chemokines are thought to mediate the enhanced pain sensitivity sometimes observed after chronic exposure to opioids. In addition, several studies have linked this phenomenon to opioid tolerance based on the concept that increasing doses of opioids are required to overcome the increased pronociceptive effects of the released compounds. Described below are the unexpected findings that: (1) Compounds 1, 2 and 5 produce significantly less tolerance relative to morphine, and (2) in direct comparison to morphine, and in contrast to morphine and most clinically used opioids, the analogs do not induce an inflammatory glial activation response after chronic administration” (para [0078]).
Zadina et al. additionally teach that the peptide is Tyr-c[D-Lys-Trp-Phe-Glu]-Gly-NH2 (SEQ ID NO: 3) (para [0017]), which corresponds to the elected species.
With respect to the claimed “discontinued chronic exposure to an opioid”, it is noted that any subject using opioids must necessarily discontinue exposure between one dose and another.
Therefore, since Zadina et al. teach administering the instantly claimed peptide for the treatment of subjects with chronic exposure to opioids, the withdrawal symptoms associated with said exposure to opioids would inherently be prevented (see MPEP 2112.01).
With respect to claim 13, Zadina et al. teach that the mu opioid receptor agonist is morphine (paras [0075]-[0076]; passim).
With respect to claim 15, Zadina et al. teach that the peptide is administered intravenously (paras [0019], [0049], [0069] and [0072]).
Response to Arguments
Applicant’s arguments filed on 2/9/2026 have been fully considered but they are not persuasive.
Applicant argues that Zadina does not teach or suggest any opioid agonist that prevents withdrawal symptoms induced by discontinued chronic exposure to an opioid.
Applicant’s arguments are not persuasive because, as discussed in the rejction above, Zadina et al. clearly teach administering the instantly claimed peptide for the treatment of subjects with chronic exposure to opioids.
The withdrawal symptoms associated with said exposure to opioids would inherently be prevented.
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.
This is a new rejection.
Claims 7-8, 10, 12-13 and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Zadina et al. (US 2017/0369531).
The teachings of Zadina et al. with respect to claims 7-8, 10, 12-13 and 15 have been discussed above.
Please note that the instant specification teaches that “[T]he term "analgesic ED50", as used herein with respect to a peptide of Formula I, refers to a dose of the peptide which provides 50% analgesia as determined for alleviation of intradermal capsaicin-induced pain by the Dixon sequential up-down method (see, e.g., Wong 2014). The analgesic ED50 dose may be different for different methods of administration (e.g., oral, intravenous, intrathecal, subcutaneous, transdermal, and the like), as is well known in the pharmaceutical arts. In rats, a suitable model for determining a dose response curve and an ED50 for antinociception (an animal model for analgesia) is the tail flick test (see Zadina 2016). Based on tail flick studies, the antinociceptive ED50 for ZH853 in rats is about 2 mg/Kg” (para [0053]).
Therefore, instant claim 16 relates to a dose of about 1 mg/Kg.
Zadina et al. do not teach the claimed dose.
However, Zadina et al. teach that the dosage of the effective amount of the peptides can vary depending upon the age and condition of each individual patient to be treated. However, suitable unit dosages typically range from about 0.01 to about 100 mg (para [0058]).
A prima facie case of obviousness necessarily exists when the prior art range overlaps or touches a claimed range, such as in the instant rejection (MPEP § 2144.05).
Furthermore, the MPEP 2144.05 A states that “[G]enerally, 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)”.
Since Applicant has not disclosed that the specific limitations recited in the instant claims are for any particular purpose or solve any stated problem, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum dosage by normal optimization procedures known in the pharmaceutical art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SERGIO COFFA whose telephone number is (571)270-3022. The examiner can normally be reached M-F: 6AM-4PM.
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/SERGIO COFFA Ph.D./
Primary Examiner
Art Unit 1658
/SERGIO COFFA/Primary Examiner, Art Unit 1658