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 .
Priority
This application, filed 22 April, 2022, is a national stage application of PCT/GB2020/052679, filed 23 October, 2020, which claims foreign benefit of Application GB1915514.2, filed 25 October, 2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 16 September, 2025, is acknowledged and has been considered.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 25 September, 2025, in the matter of Application N° 17/771,190. Said documents have been entered on the record.
Claims 1 and 9 are amended. Claims 10-11 are canceled. Claims 12-15 are new. No new matter was introduced.
Thus, Claims 1-9 and 12-15 represent all claims currently under consideration.
Drawings
The set of colored drawings were received on 25 September, 2025. These drawings are acceptable.
Specification
The disclosure remains objected to because it still contains an embedded hyperlink and/or other form of browser-executable code (Pg. 2, Para 0013.) Applicant merely replaced “http://” with “www.”, however, the Specification still recites a full active link “www.fda.gov/regulatory-information/search-fda-guidancedocuments/development-new-stereoisomeric-drugs” (instant Specification, Para 0014.)
Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code (e.g., example.com, fda.gov, etc.) See MPEP § 608.01.
Response to Amendment
Claims 10-11 have been canceled. Therefore, the rejections of these claims under 35 U.S.C. 112(a) and 112(b) are moot.
Below can be found new grounds of rejection necessitated by amendments.
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.
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 1-9 and 12-15 are 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.
Claims 1 and 9 recite the phrase “as a sole active agent” in the context of a method of treating epilepsy or a pharmaceutical composition. However, the term “active” lacks antecedent basis or a clear definition within the claim or specification. It is unclear whether “active” refers to activity for treating epilepsy, for any physiological effect, or relative to other components that may or may not be present.
Furthermore, because the claim uses the transitional phrase “comprising”, it remains unclear whether other agents may be included in the composition or method, and if so, whether they are considered “inactive”, “non-therapeutic”, or otherwise outside the scope of the phrase “sole active agent.” As such, the metes and bounds of the claim are ambiguous, and a person of ordinary skill in the art would not be reasonably apprised of the scope of the claim with respect to what constitutes the “sole active agent.”
Claims 2-8 and 12-15, which depend upon Claim 1, fail to cure the deficiencies as stated above.
Response to Arguments
Applicant's arguments filed 26 September, 2025, regarding the rejections of 35 U.S.C. § 103 and Double Patenting have been fully considered but they are not persuasive.
Regarding the phrase “as sole active agent” (Remarks, Pg. 8), Applicant contends this phrase distinguishes the claims from Gedo (of previous record), which discloses a plant extract containing multiple enantiomers, including the presently claimed one. However, this argument is not persuasive because Gedo expressly teaches the use of the compound and its enantiomers, diastereomers, and racemates, and such language reasonably encompasses the claimed enantiomer whether or not it exists in a mixture. Moreover, the claim employs the open transitional term “comprising,” which does not exclude the presence of other compounds or active components. The phrase “as a sole active agent” is ambiguous and fails to clearly define whether it limits activity to the treatment of epilepsy or any other physiological effect. Accordingly, this amendment does not meaningfully distinguish the claimed method from the teachings of Gedo.
Regarding the motivation to combine with Martin (Remarks, Pg. 8-9), Applicant argues that Martin (of previous record) does not provide motivation to go beyond the natural enantiomer taught by Gedo. This is also not persuasive. Martin identifies the existence of four total stereoisomers of the same compound and describes known differences among them, including activity, potency, and behavioral effects, while recognizing a need for further study. As discussed in the prior office action, such disclosure provides a clear reason to explore all four isomers as part of routine optimization of biologically active compounds. A person of ordinary skill in the art would have been motivated to evaluate each of the known stereoisomers, particularly in light of the data showing differing potency ratios (up to 100:1) and activity thresholds (e.g., minimum effective dose of 30 mg/kg). Such investigation represents a predictable variation within the scope contemplated by Gedo and does not require inventive skill.
Regarding the evidence of unexpected results (Remarks, Pg. 9), Applicant’s assertion of unexpected results is not supported by the record. While Applicant refers to data showing the claimed enantiomer’s activity relative to a control, the evidence does not include a direct comparison between the claimed enantiomer and the other enantiomers disclosed in Martin or in the co-pending applications. In accordance with MPEP §2144.09, a showing of unexpected results must be based on comparative data between claimed species and the closest art species – here, the other enantiomers known in the art. Because no such comparison is provided, applicant’s evidence is insufficient to rebut the prima facie case of obviousness.
In summary, Applicant’s arguments regarding the amended claims have been considered but are not persuasive. The newly added language, including “as a sole active agent,” fails to meaningfully distinguish the claims from the prior art, does not introduce functional limitations that overcome the teachings of Gedo, and remains indefinite in scope. Martin continues to provide sufficient motivation for a person of ordinary skill in the art to evaluate known stereoisomers, including the presently claimed one, as part of routine optimization. Applicant’s evidence of unexpected results is insufficient, as it lacks direct comparison between the claimed and unclaimed enantiomers.
Accordingly, the previous rejections under §103 have been revised to reflect the amended claim language, but the underlying rationale remains unchanged. The obviousness-type double patenting rejections previously applied are likewise maintained in substance, and have been updated to reference the same art cited under §103 to reflect the common scope and motivation across the co-pending applications.
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.
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.
Claims 1-9 and 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Gedo (WO 2019180706 A1, published 26 September, 2019) and further in view of Martin et al. (“BEHAVIORAL COMPARISONS OF THE STEREOISOMERS OF TETRAHYDROCANNABINOLS”. Life Sciences, Vol. 29, pp. 565-574, 1981, cited in IDS), hereinafter Martin.
Regarding Claim 1, Gedo teaches a method for treating epilepsy or a disorder associated therewith comprising administering to a subject in need thereof a therapeutically effective amount of a cannabinoid combination comprising Δ9-tetrahydrocannabinol (Δ9-THC), or an enantiomer, diastereomer, or racemate thereof (‘706, Pg. Abstract and Pg. 3, Para 011.)
Regarding Claims 2-3, Gedo teaches Δ9-THC may be extracted from the cannabis plant using any suitable extraction or purification method known in the art (Pg. 7, Para 033.)
Regarding Claim 4-6, Gedo teaches Δ9-THC may be extracted from the cannabis plant using any suitable extraction or purification method known in the art (Pg. 7, Para 033) and alternatively, each of these cannabinoids may be synthesized following any one of the procedures disclosed in the literature. (Pg. 7, Para 034.)
Regarding Claim 7, Gedo teaches the cannabis extract or control (vehicle solution) was injected at 150 mg/kg (‘706, Pg. 24, Para 0146, Example 1.)
Regarding Claim 8, Gedo teaches a dose of Δ9-THC is about 0.5 mg/kg (‘706, Pg. 13, Para 064.)
Regarding Claim 9, Gedo teaches a pharmaceutical composition, further comprising a pharmaceutically acceptable carrier (‘706, Pg. 13, Para 045) and may comprise one or more pharmaceutically acceptable excipients (‘706, Pg. 13, Para 057.)
Regarding Claims 12-15, Gedo teaches an anti-convulsive effect, significantly increasing latency to first tonic-clonic seizures, and lowering the % of mice developing tonic-clonic seizures (‘706, Pg. 4, and Fig. 1.)
Gedo explicitly discloses the compound as a racemic mixture or as a mixture of enantiomers and diastereomers, but fails to specifically identify (+)-cis-THC as one of the potential enantiomers or diastereomers. Gedo also fails to disclose specific purity levels (w/w%) of (+)-cis-THC.
However, Martin (1981) teaches that (-)-trans-THC is the principal active ingredient in marijuana and that its isomers include: (+)-trans-Δ9-THC, (-)-cis-Δ9-THC, and (+)-cis-Δ9-THC. Martin uses stereospecific syntheses to prepare the four optically-pure stereoisomers of THC and reports the pharmacological test findings. For example, Martin discloses that the potency of (+)-cis-Δ9-THC in the dog static-ataxia test was comparable to that of (+)-trans-Δ9-THC (Pg. 565, Summary and Pg. 571, Table 2.) Martin further teaches that the unnatural isomers, both cis and trans, were less effective than the corresponding natural isomer at all doses tested (Pg. 573, Para 1.) In addition, Martin concludes that the minimal active dose of (+)-trans-Δ9-THC in a subject was 30 mg/kg, resulting in a potency ratio between the isomers of about 100 to 1. While Martin does teach results demonstrating differences between the stereoisomers, it also discloses limitations in some findings suggesting further testing is advised.
It would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to modify the methods of Gedo, which comprise THC, its enantiomers, diastereomers, and racemates thereof, to isolate and purify the individual stereoisomers of THC taught by Martin, including the claimed (+)-cis-THC isomer. One would have been motivated to select a specific stereoisomer because stereochemical variants of biologically active compounds are routinely explored to optimize efficacy, selectivity, and stability, and Gedo already contemplates the inclusion of these stereoisomers. In addition, the selection of a specific w/w% purity of (+)-cis-THC would have been an obvious optimization of known extraction and purification techniques, which are routinely used to enrich specific stereoisomers.
Furthermore, under MPEP 2113, product-by-process claims (such as with instant Claims 4-6) are evaluated based on the structure and properties of the resulting product, not the process used to obtain it, unless the process imparts a novel characteristic. Here, the claims do not describe any unexpected structural or functional properties of the purified (+)-cis-THC isomer compared to what is inherently present in Gedo’s extract. Purification alone does not render a composition nonobvious when the starting material (the extract) and its components were already known, as evidenced by Martin, and standard techniques would have predictably resulted in the claimed purity level.
While Martin is suggestive, but limited, in its comparative findings regarding (+)-cis-THC, it nonetheless provides rationale for further investigating individual enantiomers, making it clear that a person of skill in the art would have been prompted to explore their effects in the known method of Gedo. One would have had a reasonable expectation of success because, despite Martin identifying areas not fully explored in some of the studies, it still establishes that differences exist among the stereoisomers, which would lead one skilled in the art to anticipate some variation in activity or effect. Given that stereoisomeric effects are well understood and predictable in the field, one skilled in the art would have reasonably expected that isolating a specific stereoisomer, and purifying it for use in the method described by Gedo would yield results within an expected range of possibilities based on known principles of stereochemistry.
Furthermore, under MPEP 2144.09, when a reference discloses a compound and explicitly mentions its enantiomers, it would have been routine optimization for a person of ordinary skill in the art to resolve, isolate, or otherwise obtain a specific enantiomer, particularly where the four stereoisomers of THC and enantiomer separation techniques are well known at the time of filing, as is the case here.
While the Applicant has provided experimental data suggesting unexpected properties for the claimed enantiomer, these comparisons were made only against known drugs and not against the other enantiomers of the same compound. To successfully rebut a prima facie case of obviousness, unexpected properties must be shown relative to the closest prior art which are the corresponding isomers, or at least the known (-)-trans-THC of Gedo which is effective in treating epilepsy. Because Applicant has not provided such comparative data, the current evidence does not sufficiently establish that the claimed enantiomer exhibits an unexpected result compared to what a skilled artisan would have reasonably expected.
Accordingly, the claimed enantiomer remains prima facie obvious, as the prior art provides both the motivation to isolate enantiomers and a reasonable expectation of success in doing so.
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 1-9 and 12-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-9 and 12-15 of copending Application No. 17/771,184 and over Claims 1-9 and 12-15 of copending Application No. 17/771,190 in view of Kupper (WO 2006133941 A2), and further in view of Martin (“BEHAVIORAL COMPARISONS OF THE STEREOISOMERS OF TETRAHYDROCANNABINOLS”. Life Sciences, Vol. 29, pp. 565-574, 1981, of previous record.)
Kupper (2006) teaches a method for treating pain and epilepsy comprising administering to a mammal in need of such treatment an effective amount of a pharmaceutical composition (‘941, Pg. 14, Lines 6-16), comprising crystalline trans-(±)-Δ9-tetrahydrocannabinol (‘941, Pg. 8, Lines 19-20.) Kupper teaches trans-(-)-Δ9-THC can be extracted and purified from Cannabis sativa plant material, as well as hashish (‘941, Pg. 32, Lines 14-15.) The plant extracts may contain trans-(-)-Δ9-THC as well as impurities such as cannabinoid isomers (‘941, Pg. 33, Line 27 and Pg. 34, Line 1.) Kupper teaches methods for making compositions comprising at least 98%, at least 99%, at least 99.5% or at least 99 .9% by weight of trans-(-)-Δ9-THC based on the total amount of cannabinoids (‘941, Pg. 34, Lines 7-9.) Kupper teaches trans-(-)-Δ9-THC can be chemically synthesized according to methods disclosed in the art (‘941, Pg. 33, Lines 4-5.) Kupper teaches the effective dosage amount ranges from about 0.01 mg/kg of body weight to about 0.8 mg/kg of body weight about every 4 hours, which at its highest range would equate to 4.8 mg/kg/day (‘941, Pg. 75, Lines 4-6.) Kupper teaches a pharmaceutical composition comprising crystalline trans-(± ) Δ9-THC and a pharmaceutically-acceptable carrier or excipient (‘941, Pg. 9, Lines 13-15.)
Kupper discloses a composition of both (-)-trans-THC and (+)-trans-THC isomers in the treatment of pain and epilepsy, but fails to disclose (-)-cis-THC or (+ )-cis-THC specifically or teach a dose of greater than 100 mg/kg/day.
However, Martin (1981) teaches that (-)-trans-THC is the principal active ingredient in marijuana and that its isomers include: (+)-trans-Δ9-THC, (-)-cis-Δ9-THC, and (+)-cis-Δ9-THC. Martin uses stereospecific syntheses to prepare the four optically-pure stereoisomers of THC and reports the pharmacological test findings. For example, Martin discloses that the potency of (+)-cis-Δ9-THC in the dog static-ataxia test was comparable to that of (+)-trans-Δ9-THC (Pg. 565, Summary and Pg. 571, Table 2.) Martin further teaches that the unnatural isomers, both cis and trans, were less effective than the corresponding natural isomer at all doses tested (Pg. 573, Para 1.) In addition, Martin concludes that the minimal active dose of (+)-trans-Δ9-THC in a subject was 30 mg/kg, resulting in a potency ratio between the isomers of about 100 to 1 (Pg. 578, Para 4.) While Martin does teach results demonstrating differences between the stereoisomers, it also discloses limitations in some findings suggesting further testing is advised.
It would have been prima facie obvious to one skilled in the art before the effective filing date of the claimed invention to modify the methods of Kupper, which comprises isomers of THC, to isolate and purify the individual stereoisomers of THC taught by Martin. One would have been motivated to select a specific stereoisomer because stereochemical variants of biologically active compounds are routinely explored to optimize efficacy, selectivity, and stability, and Kupper already contemplates the inclusion of stereoisomers.
In addition, while the claimed dose of greater than 100 mg/kg/day of (-)-cis-THC is not explicitly disclosed in Kupper, Martin teaches that the unnatural isomers, both cis and trans, were less effective than the corresponding natural isomer at all doses tested (Pg. 573, Para 1.) In addition, Martin concludes that the minimal active dose of (+)-trans-Δ9-THC (another unnatural isomer) in a subject was 30 mg/kg, resulting in a potency ratio between the isomers of about 100 to 1 (Pg. 578, Para 4.) This provides clear guidance and a predictable performance trend, making it obvious to test and optimize dosage within a range above the minimum effective amount. As explained in MPEP 2144.05 and In re Aller, where 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.
Furthermore, under MPEP 2113, product-by-process claims (such as with instant Claims 4-6) are evaluated based on the structure and properties of the resulting product, not the process used to obtain it, unless the process imparts a novel characteristic. Here, the claims do not describe any unexpected structural or functional properties of the purified individual isomers compared to what is inherently present in Kupper’s extract. Purification alone does not render a composition nonobvious when the starting material (the extract) and its components were already known, as evidenced by Martin, and standard techniques would have predictably resulted in the claimed purity level.
While Martin is suggestive, but limited, in its comparative findings, it nonetheless provides rationale for further investigating individual enantiomers, making it clear that a person of skill in the art would have been prompted to explore their effects in the known method of Kupper. One would have had a reasonable expectation of success because, despite Martin identifying areas not fully explored in some of the studies, it still establishes that differences exist among the stereoisomers, which would lead one skilled in the art to anticipate some variation in activity or effect. Given that stereoisomeric effects are well understood and predictable in the field, one skilled in the art would have reasonably expected that isolating a specific stereoisomer, and purifying it for use in the method described by Kupper would yield results within an expected range of possibilities based on known principles of stereochemistry.
Furthermore, under MPEP 2144.09, when a reference discloses a compound and explicitly mentions its enantiomers, it would have been routine optimization for a person of ordinary skill in the art to resolve, isolate, or otherwise obtain a specific enantiomer, particularly where the four stereoisomers of THC and enantiomer separation techniques are well known at the time of filing, as is the case here.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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 Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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, Kortney Klinkel can be reached on 571-270-5239. 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.
/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627