DETAILED ACTION
Claims 1-14, submitted on June 6, 2023, are pending in the application and are rejected for the reasons set forth below. No claim is allowed.
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions of the Leahy-Smith America Invents Act (AIA ), Public Law 112-29, 125 Stat. 284. 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.
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.
Claims 2-3 and 12 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
In claim 2, the “control” is undefined. In claims 2-3, the “increased cytotoxicity and/or cytostasis” and “normal basal level” appear to be matters of opinion that would necessarily vary from person to person. Applicant’s specification does not provide some standard for measuring or otherwise determining whether these things are “increased” or “above the normal basal level.” See MPEP 2173.05(b) (relative terminology). The examiner therefore concludes that these two claims are indefinite.
In claim 12, it is unclear whether the claim is limited to cells “of human origin.” “Description of examples or preferences is properly set forth in the specification rather than the claims.” See MPEP 2173.05(d) (exemplary claim language).
Claim Rejections – 35 USC § 102/103
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.
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 1-6 and 12-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated, or in the alternative, under 35 U.S.C. 103 as prima facie obvious over Liu et al., Int. J. Oncol. 2016;49(2):793-802.
Liu (cited in applicant’s IDS1) discloses that “naltrexone exhibits non-cytotoxic anticancer activities and as such, may be best combined with other modalities and combination schedules that maximise the individual action of each partner” (p. 793). “[C]ells pre-treated with LDN [low dose naltrexone] were more sensitive to the cytotoxic effects of a number of common chemotherapy agents” (see abstract). This reference describes an in vitro screening assay that includes co-incubating A549 (immortalized human lung cancer) and HCT116 (immortalized human colorectal cancer) cells with LDN and a target chemotherapy agent, followed by measuring the cytotoxic effects of the chemotherapy agent (p. 794). The concentration of the LDN was 10 nM and 10 μm (p. 794), which appears, as discussed in detail below, to be “an amount sufficient to increase the concentration of OPRK1 above the normal basal levels expected in the specific cancer cell type” as recited in instant claim 3. The assay is conducted in phases, with the first phase including priming with LDN followed by treatment the target anti-cancer agent (p. 794), which meets the limitation of claim 4, although it is implicit that they could be administered simultaneously within the meaning of claim 6.
Liu describes many genes that are induced by treatment with naltrexone (see, e.g., Table I at p. 795 and the discussion thereof). The present invention appears to represent yet another gene that is affected by naltrexone, namely, the opioid receptor kappa-1 (OKRK1). The discovery, however, of such a previously unappreciated property of the prior art, or of a scientific explanation for the prior art’s functioning, does not render it patentably new to the discoverer. The claiming of a new use, new function, or unknown property that is inherently present in the prior art, although not specifically disclosed therein, does not necessarily make the instant claims patentable. See MPEP 2112(I) (something old does not become patentable upon the discovery of a new property).
The claims implicate OPRK1 in two ways: (1) “administration with a second agent that increases the expression of opioid receptor kappa-1 (OPRK1)” (see instant claim 1) and (2) “an amount sufficient to increase the concentration of OPRK1 above the normal basal levels expected in the specific cancer cell type” (see claim 3). Liu appears to disclose both of these limitations. First, Liu clearly discloses using naltrexone; and claim 1 states that “the second agent is … naltrexone.” Therefore, the disclosure of naltrexone in Liu necessarily meets the limitations of item “(1).” That is, Liu inherently discloses “administration with a second agent that increases the expression of opioid receptor kappa-1 (OPRK1),” even though it does not specifically disclose that naltrexone has any effect on OPRK1. Second, example concentrations taught by Liu include 10 nM naltrexone and 10 μM naltrexone (see the footnote below Table I of Liu at p. 795). Naltrexone has a molecular weight of 341 g/mol, so 10 nM and 10 μM as taught by Liu are, respectively, equivalent to 3.41 ng/mL and 3410 ng/mL. Applicant’s own specification explains (p. 12, para. 0041) that suitable concentrations of such a compound is “about 0.34 ng/ml to about 3,400 ng/ml.” The examiner therefore concludes that “10 nM naltrexone” and “10 μM naltrexone” as taught by Liu are within the meaning of an “an amount sufficient to increase the concentration of OPRK1 above the normal basal levels expected in the specific cancer cell type” as recited in claim 4.
The examiner therefore concludes that Liu seems to be identical to the instant claims, except it is silent as to a mechanism of action that is mediated, at least in part, by OPRK-1. See MPEP 2112(V) (once a reference teaching a product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant). The burden of showing a patentable difference—if any—between the teachings of Liu and the instant claims now falls to applicant.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 11,885,796 B2. Although the claims at issue are not identical, they are not patentably distinct from each other. Claim 1 of the ‘796 Patent, of which the present application is a continuation, is directed to an in vitro method for identifying an anti-cancer agent, the therapeutic efficacy of which is enhanced upon administration with a second agent that increases the expression of opioid receptor kappa-1 (OPRK1), comprising the steps of: a) co-incubating a population of cells with a target anti-cancer agent and said second agent; and b) measuring the cytotoxicity and/or cytostasis in the population of cells; wherein the therapeutic efficacy of the target anti-cancer agent is enhanced if the cytotoxicity and/or cytostasis of the target anti-cancer agent is increased compared to a control, and wherein the second agent is 6-β-naltrexol or a pharmaceutically acceptable salt thereof and is provided in an amount sufficient to increase the concentration of OPRK1 by at least 10% above the normal basal levels expected in the population of cells.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Theodore R. Howell whose telephone number is (571)270-5993. The examiner can normally be reached Monday - Thursday, 7:00 am - 6:00 pm (Eastern Time).
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THEODORE R. HOWELL
Primary Examiner
Art Unit 1628
/THEODORE R. HOWELL/ Primary Examiner, Art Unit 1628
December 19, 2025
1 See the information disclosure statement (IDS) submitted on June 6, 2023. For a convenience, a courtesy copy of this reference is included with this communication.