Detailed Action
The present office action is in response to the remarks filed 20 Jan 2026.
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
Claims 1, 4-8, 10, 18-19, and 22-29 of the pending application have been examined on the merits. Acknowledgement is made of the amendments filed on 20 Jan 2026. Acknowledgement is made of the cancellation of claims 2-3, 9, 11-17, and 20-21.
Priority
The effective filing date remains March 15, 2019.
Response to Arguments
Examiner acknowledges applicant amendments and reply filed on 20 Jan 2026.
The rejections of claims 12 and 16 are rendered moot following the cancellation of claims 12 and 16.
The rejection of claims 6 and 26 under 35 USC § 112(b) is rendered moot by applicant amendments.
The rejection of claims 1, 4-8, 10, and 22 under 35 USC § 103 is rendered moot by applicant amendments.
The rejection of claims 1, 4-8, 10, 18-19, and 22-27 under 35 USC § 103 is rendered moot by applicant amendments. However, upon further consideration, a new ground(s) of rejection (see below) is made under 35 U.S.C. § 103 over WO 2015/189597, Romano et al. (Phytomed, 2014, 21:631-639), Aviello et al. (J Mol Med, 2012, 90:925-934), Ramer et al. (FASB, 2012, 26:1535-1548), Ramer et al. (Pharm Res, 2010, 27:2162-2174), Viudez-Martinez et al. (Bri J Pharmacol, 2018, 175:3369-3378), Scott et al. (Anticancer Res, 2013, 33:4373-4380), Bergamaschi et al. (Curr Drug Saf, 2011, 6:237-249), and Guzman et al. (Br J Cancer, 2006, 95:197-203). This rejection is necessitated by applicant amendments.
Claim Objections
Claim 18 is objected to because of the following informalities: the phrase “perkilogram” should be “per kilogram.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 22 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 22 contains the limitation, “A pharmaceutical preparation comprising: (a) an amount between 0.9 mg and 6.8 mg of: (i) naltrexone, or (ii) 6-β-naltrexol, or (iii) methylnaltrexone, or (iv) a pharmaceutically acceptable salt of one of naltrexone, 6-β-naltrexol, and methylnaltrexone…” However, the range of mass of 0.9 mg and 6.8 mg was not found in the specification on the application filing date. The only mass found for naltrexone and metabolites of naltrexone is up to 3 mg per day in total (Specification, pg. 7, lines 29-30). Applicant may overcome this objection by amending the claim to cancel the new matter.
Claim Rejections - 35 USC § 112(b)
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 8 and 29 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.
Claim 8 recites the limitation "wherein the pharmaceutical composition comprises naltrexone and/or 6-β-naltrexol." Claim 1 limits the pharmaceutical composition to “naltrexone, or 6-β-naltrexol, or methylnaltrexone” and does not include basis for both naltrexone and 6-β-naltrexol. There is insufficient antecedent basis for this limitation in the claim.
Claim 29 recites the limitation "wherein the alkylating agent is oxaliplatin and/or the antimetabolite is gemcitabine." Claim 1 limits the chemotherapeutic agent to an antimetabolite or an alkylating agent, but does not include the administration of both an antimetabolite and an alkylating agent. There is insufficient antecedent basis for this limitation in the claim.
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.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4-8, 10, 18-19, and 22-29 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2015/189597 (provided in IDS 09/09/21), hereinafter Dalgleish, further in view of Romano et al. (Phytomed, 2014, 21:631-639), hereinafter Romano, Ramer et al. (Pharm Res, 2010, 27:2162-2174), hereinafter Ramer, Scott et al. (Anticancer Res, 2013, 33:4373-4380), hereinafter Scott, Bergamaschi et al. (Curr Drug Saf, 2011, 6:237-249), hereinafter Bergamaschi, WO 2019/207319, hereinafter ‘319, and Guzman et al. (Br J Cancer, 2006, 95:197-203; provided in the office action dated 09/05/24), hereinafter Guzman.
The instant claims are drawn to a method of treating lung or colon cancer by administering in a first phase naltrexone, 6-β-naltrexol, methylnaltrexone, or pharmaceutically acceptable salt thereof at a dose of 0.03 mg/kg to 0.08 mg/kg. Following the first phase, the treatment consists of administering between 200 mg and 1000 mg of a cannabinoid selected from a Markush group which includes cannabidiol. After the second phase, applicant claims administering a therapeutically effective amount of a chemotherapeutic agent where the agent is either an antimetabolite or alkylating agent (claim 1). Applicant further adds limitations regarding the components administered to the subject (claims 8, 10, and 29), the length and spacing of the first and second treatment phases (claims 4, 7, 23-25, and 27), and an additional recovery phase between the first and second treatment phases (claims 5-6, 26, and 28). Applicant also claims a method of treating cancer which includes the limitations of claim 1 and further requires a tumor biopsy to measure CB2 levels in the subject (claims 18-19). Applicant finally claims a pharmaceutical preparation comprising 0.9-6.8 mg of naltrexone, 6-β-naltrexol, methylnaltrexone, or pharmaceutically acceptable salt thereof; 200-1000 mg of a cannabinoid selected from a Markush group; and a therapeutically effective amount of a chemotherapeutic agent which is either an antimetabolite or an alkylating agent (claim 22).
Dalgleish teaches treating cancer using naltrexone in a first treatment phase lasting between 1 and 7 days, no treatment in a recovery phase lasting at least 1 day, and a subsequent treatment phase lasting at least 1 day comprising a small-molecule signaling inhibitor chosen from either a PI3-kinase inhibitor, an AKT inhibitor, a taxane, an antimetabolie, an alkylating agent, or a cell cycle inhibitor (pg. 11, line 9 to pg. 13, line 16), including a specific example of treating HCT116 (human colon cancer) cells are treated with low-dose naltrexone and either cyclophosphamide, gemcitabine, or oxaliplatin (pg. 21, Example 3). Dalgleish further teaches that a preferred embodiment is treatment of lung or colorectal cancer (pg. 19, lines 32-35; Example 1). Dalgleish teaches administering naltrexone in a low dose of, most preferably, between 0.04 mg/kg and 0.05 mg/kg (pg. 19, lines 5-9). However, Dalgleish does not teach the inclusion of a cannabinoid in the treatment of cancer.
Romano teaches treatment of colon cancer cells and xenograft models of colon cancer with cannabidiol (Abstract). Romano teaches that cannabidiol inhibited colorectal cancer cell proliferation (Abstract).
Ramer teaches that cannabidiol causes a profound inhibition of A549 (human lung cancer) cells. Ramer also teaches that treating mice xenografted with A549 cells with 5 mg/kg of cannabidiol significantly reduces tumor size (pg. 2169, column 2).
Scott teaches that phytocannabinoids possess anticancer activity and that sequencing of administration of the cannabinoids with anticancer drugs is important to the success of the anticancer effects seen (pg. 369, column 1). Scott teaches treating CEM and HL60 cells with treatments that include swapping the order of administration of cannabinoids and antileukemia drugs and also include adding recovery phases to the treatments (pg. 370, column 2).
Bergamaschi teaches that cannabidiol can be administered patients with increasing doses up to 1,500 mg/day with no adverse effects reported (pg. 3, column 2).
‘319 teaches that a cannabidiol preparation may depend on a variety of factors known in the medical arts and that one having ordinary skill in the art will be readily able to determine appropriate dosages based on the relevant factors (paragraph [00201]). ‘319 further teaches that appropriate doses or amounts to be administered may be extrapolated from in vitro or animal model test systems (paragraph [00201]). ‘319 further teaches that specific dosage regimens should be adjusted over time according to the individual need and that the dose of cannabidiol may be up to 2000 mg of CBD (paragraphs [00207]-[00208]).
Guzman teaches taking a tumor biopsy pre- and post-treatment and measuring the CB2 concentration to show THC treatment decreases cell viability by activating CB2 receptors (Fig. 1). Guzman teaches measuring CB2 concentration of pre- and post-treatment tumors to look for links to tumor growth inhibition (pg. 200, column 2, second paragraph under heading “THC action on tumor cells”).
It would be prima facie obvious to one having ordinary skill in the art to combine the composition of low dose naltrexone at a dosage of 0.04-0.05 mg/kg and a therapeutically effective amount of gemcitabine, as taught in Dalgleish, with the composition of cannabidiol, as taught in Romano and Ramer, to create a third composition for the treatment of colon and lung cancer with a reasonable expectation of success. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980)
The artisan would further experiment with the order, dosage, and recovery phase of the composition, as taught in Dalgleish and Scott, to arrive at the instant invention. The artisan would change the order, dosage, and recovery phase because the order of the cannabidiol is important to ensuring the maximal anticancer effect is seen, as taught in Scott. The artisan would have a reasonable expectation of success that there would be no adverse effects when modifying dosages of cannabidiol up to 1,500 mg/day. By making this modification, the references would show possession of a pharmaceutical composition of 0.04-0.05 mg/kg of naltrexone, up to 1,500 mg of cannabidiol, and an effective amount of gemcitabine.
By combining the treatment of Dalgleish, Romano, and Ramer with the method of measuring CB2 concentration of Guzman, it would have been obvious to a person having ordinary skill in the art to measure CB2 concentration in tumors. The artisan would be motivated to make this measurement to look for links to tumor growth inhibition.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976). In light of the foregoing discussion, the examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Aviello et al. (J Mol Med, 2012, 90:925-934) is considered pertinent for teaching that CBD inhibits colon cancer cell proliferation. Ramer et al. (FASEB, 2012, 26:1535-1548) is considered pertinent for teaching that CBD inhibits lung cancer cell invasion. Viudez-Martinez et al. (Bri J Pharmacol, 2018, 175:3369-3378) is considered pertinent for teaching co-administration of naltrexone and cannabidiol to animal models of alcohol consumption.
Conclusion
No claim is 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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jonathan D. Mahlum whose telephone number is (703)756-4691. The examiner can normally be reached 8:30 AM - 5:00 PM ET, M-F.
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/J.D.M./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625