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
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/09/2025 has been entered.
Response to Amendment
Acknowledgment is made of the receipt and entry of the amendment filed on 04/09/2025, wherein independent claim 25 is amended and new claims 53-59 are added.
Independent claim 25 is amended to recite limitation “the dosage form is in the form of a tablet, capsule, pill, troche, lozenge, pastille, cachet, pellet, granule, gummy, cream, salve, tincture, paste, gelatin suppository, crystal, ointment, jelly, e-juice, powder, syrup, drop, patch, or chewing gum”. Please note powder and tincture are considered as natural dosage form that do NOT add significant more to the natural product of cannabinol.
Status of Claims
Claims 25, 28, 32, 34-38, 49, 51 and 53-59 are pending and currently under examination in this office action.
Response to Declaration
The Declaration under 37 CFR 1.132 by Vaugh Hartung filed 04/09/2025 is fully considered, but it’s NOT persuasive to overcome the rejection of claims based upon Bray in view of Barr under 35 U.S.C. 103.
Hartung Declaration focused on Barr’s process of preparing high purity cannabinol (CBN). Hartung Declaration argues cannabinol (CBN) is difficult to synthesize in high purity, especially on an industrial scale… The process disclosed by Barr for synthesizing high purity cannabinol is not economical or practical because Barr process includes many purification steps (fractional distillation) and expensive crystallization solvent (e.g. isooctane) (Para 8-15), and “A person in the cannabinoid field would not have considered using the processes disclosed by Barr to produce cannabinol, especially on an industrial scale, because these methods are uneconomical and impractical. Therefore, I believe it is unlikely that a skilled chemist would incorporate the cannabinol from the method disclosed by Barr into the oral composition disclosed by Bray or the soft gel capsule disclosed by Nuleaf” (Para 16).
RESPONSE: Instant claims are product claims, NOT process claims. Even for product-by-process claims, the process of producing the product is given no patentable weight since it does not impart novelty to a product when the product is taught by the prior art. As stated in MPEP 2113 I: "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). In instant case, a skilled artisan would have known high purity cannabinol could be made as taught by Barr, thus the product of high purity cannabinol is NOT novel.
Please note Barr (US 2022/0274942 A1) is now US Patent No.12338223B2 (granted on 06/24/2025). Barr teaches the one-pot synthesis of high purity CBN is commercially scalable because it does not require chromatographic purification which is advantageous compared with known multiple-steps synthesis requiring lengthy chromatography (See [0067]). Please note fractional distillation and recrystallization are common/routine technique in pharmaceutical industry, especially in the art of natural product. Barr also teaches the high-purity CBN is crystalline CBN which could be more advantageous compared to other forms of CBN, including amorphous CBN, in terms of chemical and physical stability, storage, processing, compatibility, and bioavailability (See [0070]).
Regarding the motivation to use high-purity synthetic cannabinol, use of high-purity component to maximize the potency of the drug and minimize unwanted side-effect of impurities would be prima facie obvious and common sense even without express teaching in the prior art. See Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293 ( Fed. Cir. 2007) (“[o]rdinarily, one expects a concentrated or purified ingredient to retain the same properties it exhibited in a mixture, and for those properties to be amplified when the ingredient is concentrated or purified; isolation of interesting compounds is a mainstay of the chemist’s art. If it is known how to perform such an isolation, doing so is likely the product not of innovation but of ordinary skill and common sense”).
It's general knowledge in the art that THC has unwanted psychoactive side-effect as taught by robBray and Barr and acknowledged in instant disclosure (See [0005]). Bray and Barr teach cannabinol composition exhibit minimal psychoactive effects, which makes this compound potentially useful as treatment for a variety of diseases or conditions. As such, it’s logical and prima facie to incorporate Barr’s high-purity cannabinol into pharmaceutical composition for treating disease/disorder.
Action Summary
Applicant's remarks filed 04/09/2025 have been fully considered, but they are NOT persuasive to overcome rejections under 35 U.S.C. 101 on the record.
Applicant’s argument regarding rejections over Neurogan, NCT05344170 under 35 U.S.C. §102/103, and Nuleaf under 35 U.S.C. §/103 are moot.
Claims 25, 28, 32, 34-38, 49, 51 and 53-59 are rejected over Bray under 35 U.S.C. 102/103;
Claims 25, 28, 32, 34-38, 49, 51 and 53-59 are rejected under 35 U.S.C.§103 as being unpatentable over Bray in view of Barr, Corroon and NCT05344170. Please note obviousness analysis is based on the combined teachings of prior art, together with general knowledge of cannabinoid and treatment for sleep disorder. Applicant’s argument against individual reference on the record are addressed accordingly.
Priority
The instant application filed on 02/16/2024 claims priority to U.S. Provisional Patent Application No. 63/523,786 filed on 06/28/2023. It’s noted that provisional application No. 63/523,786 discloses dosage form comprising about 40 mg to about 60 mg cannabinol CBN (See [0003][0045]-[0046]). Example 1 in provisional application No. 63/523,786 discloses cannabinol CBN at 25 mg, 50 mg and 100 mg daily oral dose.
Claim interpretation
Instant claim 25 recites “a dosage form comprising a dose of cannabinol or a pharmaceutically acceptable salt thereof in an amount of about 40 mg to about 60 mg, wherein the cannabinol or pharmaceutically acceptable salt thereof, has a purity of at least about 95%”. Instant specification (See [0059]) discloses “The pharmaceutical compositions provided herein can be provided in unit dosage forms or multiple-dosage forms… A multiple-dosage form is a plurality of identical unit-dosage forms packaged in a single container to be administered in segregated unit-dosage form”. Thus, instant claims are construed under broadest reasonable interpretation BRI as dosage form comprising cannabinol or a pharmaceutically acceptable salt thereof in single dose unit or multiple dose units, e.g. 50 mg of cannabinol in one dose unit or 50 mg in two dose units of 25 mg per unit that can be administered at the same time. Please note administering 50mg in one dose unit verse two x 25mg dose unit at one time are both considered as administering a dose of 50mg at one time.
Claim 59 recites cannabinol dosage form of claim 25, with limitation “the cannabinol is prepared by a method comprising: “admixing a catalyst, cannabidiol, and an oxidizing agent…”. Claim 59 is constructed as product-by-process claim. Please note in product-by-process type claims, the process of producing the product is given no patentable weight since it does not impart novelty to a product when the product is taught by the prior art. See In re Thorpe, 227 USPQ 964 (CAFC 1985); In re Marosi, 218 USPQ 289, 292-293 (CAFC 1983) and In re Brown, 173 USPQ 685 (CCPA 1972). Consequently, even if a particular process used to prepare a product is novel and unobvious over the prior art, the product per se, even when limited to the particular process, is unpatentable over the same product taught in by the prior art. See In re King, 107 F.2d 618, 620, 43 USPQ 400, 402 (CCPA 1939); In re Merz, 97 F.2d 599, 601, 38 USPQ 143-145 (CCPA 1938); In re Bergy, 563 F.2d 1031, 1035, 195 USPQ 344, 348 (CCPA 1977) vacated 438 US 902 (1978); and United States v. Ciba-Geigy Corp., 508 F. Supp. 1157, 1171, 211 USPQ 529, 543 (DNJ 1979).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 25, 28, 32, 34-38, 53-54, 56 and 58 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural products without significantly more.
Instant claims recite natural product cannabinol CBN, which is present in natural plant. Instantly claimed cannabinol CBN with certain purity is not markedly different from its naturally occurring counterpart because there is no indication that purity has caused the compound to have any characteristics that are markedly different from the naturally occurring counterpart. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP § 2106 sets forth the Subject Matter Eligibility Test to determine if a claim is directed to patent eligible subject matter. Step 1 asks if a claim is directed to a statutory category of invention. Applicant’s claims are directed to a product; thus, the answer to Step 1 is Yes.
The analysis then moves to Step 2A, Prong One, which asks if a claim recites to a product of nature. In this case, instant claims are directed to dosage form comprising cannabinol or pharmaceutically acceptable salt which can be found in nature (plant), and therefore patent ineligible judicial exceptions (natural products) under 35 USC 101.
MPEP § 2106.04(b) states that “When a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation and determine the answer to Step 2A.”
MPEP § 2106.04(c)(I) states that “if the nature-based product limitation is not naturally occurring, for example due to some human intervention, then the markedly different characteristics analysis must be performed to determine whether the claimed product limitation is a product of nature exception…”. To perform the markedly different characteristic analysis, MPEP § 2106.04(c)(II) states “The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties…”.
With respect to the purity limitation of the cannabinol product , there is no indication that instant claimed cannabinol with different purity as a whole changes the structure, function, or other properties of the cannabinol in any marked way in comparison with the closest naturally occurring counterpart from natural plant. Please note psychoactive effect is the property of THC, CBD or other impurities of cannabinoid, NOT property of natural-occurred cannabinol. In other word, the alleged diminished or completely absent psychoactive effect of high purity cannabinol is considered as the characteristics/property of natural-occurred cannabinol. The purification and/or chemical synthesized cannabinol has not resulted in any structural changes to cannabinol molecule and other properties thereof compared to its natural counterpart(s). High-purity cannabinol is structurally and functionally identical to the naturally occurring cannabinol and there are no markedly different characteristics. Therefore, the answer to Step 2A, Prong One, is Yes.
Thus, the analysis must move to Step 2A, Prong Two, which asks if the claim recites additional elements that integrate the judicial exception into a practical application. As discussed in MPEP § 2106.04(d)(2) this evaluation is performed by identifying whether there are additional elements recited in the claim beyond the judicial exception and evaluating these additional elements to determine whether the claim as a whole integrates the exception into a practical application. The additional element “dosage form” as naturally occurred form (tincture, powder, etc.) is not sufficient to integrate the judicial exception into a practical application. Thus, the answer to Step 2A, Prong Two, is No.
Thus, the analysis must move to Step 2B which asks if claims recite additional elements that amount to significantly more than the judicial exception. MPEP § 2106.05 states that this evaluation is performed by “Evaluating additional elements to determine whether they amount to an inventive concept requires considering them both individually and in combination to ensure that they amount to significantly more than the judicial exception itself.” Instant claim 28 recites additional element “pharmaceutical excipient”. However, the unspecified pharmaceutical excipient might be other natural products and does not amount to an inventive concept. Thus, the answer to Step 2B is No.
Most importantly , instant claims are directed to product claims. As discussed in MPEP § 2106.05(I)(A), “Generally linking the use of the judicial exception to a particular technological environment or field of use” is not considered to be enough to qualify as significantly more. An intended use of a claimed composition only generally links the exception to the field of use and the additional elements are not considered to amount to significantly more than the judicial exception.
As elaborated above, instant claims do not provide any limitations beyond the judicial exceptions or provide anything that adds significantly more to the judicial exceptions. Consequently, the claims are not directed to patent eligible subject matter.
Response to Arguments
Applicant argues “ Independent claim 25 is amended to recite limitation “the dosage form is in the form of a tablet, capsule, pill, troche, lozenge, pastille, cachet, pellet, granule, gummy, cream, salve, tincture, paste, gelatin suppository, crystal, ointment, jelly, e-juice, powder, syrup, drop, patch, or chewing gum” (Remarks, page 6/22).
Please note powder and tincture are considered as natural dosage form that do NOT add significant more to the natural product of cannabinol. As discussed in the interview on 02/24/2025, the applicant is advised to add limitations of non-natural dosage form (e.g. soft gel capsule, tablet) and/or non-natural excipient that add significantly more to overcome 101 rejection.
Claim Rejections - 35 USC § 102/103
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.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed 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.
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 25, 28, 32, 34-38, 49, 51 and 53-59 are rejected under 35 U.S.C. 102 (a)(1) and 102(a)(2) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Bray et al.(WO 2014/200350 A1, Applicant’s IDS dated 07/03/2024).
Regarding the active ingredient cannabinol CBN, Bray teaches cannabinol composition exhibit minimal psychoactive effect compared with other cannabinoid (e.g. THC), thus potentially useful as treatment for a variety of diseases or conditions (See page 8, lines 17-21). Bray teaches composition comprising cannabinol (enriched natural cannabinol extract or pure synthetic cannabinol), optionally with other excipients for use in the treatment of neurobehavioral disorders (e. g. sleep disorder including insomnia) (See page 3, lines 11-17; page 4, lines 23-25 ; page 5, lines 14-16; Examples 1-5).
Regarding the dose amount, Bray teaches approximately 25 mg of cannabinol-rich (>80%) extract provides relaxation and induce good sleep for patients with insomnia (See Example 2). Bray teaches 20 mg of pure synthetic cannabinol exhibit similar potent sleep-inducing effect in subjects suffering from insomnia (See page 7, Example 3). Bray teaches 25 mg cannabinol-rich extract for treating anxiety and managing attention deficit disorder (ADHD) symptoms (See Example 4). Bray also teaches pharmacokinetics study of pure cannabinol at a variety of amount/concentration ( e.g. 0.01mg/kg -0.5mg/kg) orally administrated to mice models that is equivalent to sleep test on humans, wherein CBN0 was prepared with 50 mg of cannabinol in 10 mL of olive oil (See page 8, Example 5; page 9, line 12; page 10, Table 1)(which reads on the dose amount of instant claims 25, 32). Bray teaches all 5 doses tested increased significantly the number of mice sleeping 30 minutes after administration of cannabinol at 3 consecutive days, indicating cannabinol can be used to enhance sleep(See Figure 4; page 12, lines 25-29).
Regarding the excipient limitation of instant claim 28, Bray teaches synthetic cannabinol formulated with terpene and/or phenol, or optionally other excipients, for use in the treatment of neurobehavioral disorders(See page 5, lines 14-16; claim 12).
Regarding the dosage form limitation recited in instant claims 25, 49, 51, 55 and 57, Bray teaches variety of dosage/formulation forms, e.g. powders, tablets, capsules for oral administration or other administration route( See page 3, line 4, 25; claim 11).
Regarding the purity limitation, Bray teaches the CBN embodiments comprises at least 80% w/w non—psychoactive cannabinol (See page 4, line 1; page 6, line 32) and essentially free of tetrahydrocannabinol(THC) (See page 4, line 20). Bray teaches the amount of psychoactive cannabinoids in the composition is below a predetermined threshold for having a psychoactive effect related to cannabinoids such as THC which is regarded as an undesirable side effect(See page 4, lines 14-19). Bray teaches preferred CBN embodiment wherein psychoactive cannabinoids can be reduced below a predetermined threshold by further chemical purification techniques including chromatography, extraction, recrystallization, vacuum distillation and sublimation, etc. ( page 6, lines 20-25).
As elaborated, Bray teaches pharmaceutical composition comprising pure cannabinol substantially free of THC and other cannabinoid at various amount (e.g. 25 mg, 50mg ) that could be formulated with excipient in capsule for treating variety of disease (e.g. sleep disorder).
Bray is silent about specific purity of cannabinol (CBN) compound (at least about 95% or 98%, etc. ). Please note the USPTO office does not have the facilities and resources to provide factual evidence needed in order to establish that the product of the prior art does not possess the same material with the same purity, structural and functional characteristics of the claimed product. “In the absence of evidence to the contrary, the burden is on the applicant to prove that the claimed product is different from those taught by the prior art and to establish patentable differences.” See In re Best 562F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray 10 USPQ 2d 1922 (PTO Bd. Pat. App. & Int. 1989).
Even if instantly claimed percentage of purity or dose amount in one single dosage form are not explicitly taught by the prior art , those differences appear to be only slight differences within the meaning of obviousness under 35 U.S.C. 103. It would be generally obvious to use pure drugs (as much as possible) to avoid the unwanted side effects of contaminants and maximize the potency of the drug. The exploration/optimization of active ingredient dose amount is within the knowledge of an ordinary skilled in the art. MPEP 2144.05 states, 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. It would have been obvious to one of the ordinary skill in the art to explore the dose/amount of pure cannabinol thereof based on the teachings of prior art and general knowledge of cannabinol/cannabinoid through experimentation/ optimization and arrive at instantly claimed invention.
RESPONSE TO ARGUMENTS
Applicant argues claim 25 is amended to recite that the dosage form comprises "a dose of cannabinol or a pharmaceutically acceptable salt thereof in an amount of about 40 mg to about 60 mg." As described in paragraph [0032] of the application as filed, a "dose" means the measured quantity
of an active agent to be taken at one time by a patient. Bray is silent as to a dose amount in the
range of 40 mg to 60 mg. Further, Bray is silent as to other limitations added in claim 25, including that the dosage form is substantially free of cannabidiol and THC” (Remarks, page 10/22).
RESPOSNE: Applicant’s argument about “dose” is NOT persuasive. Under broadest reasonable interpretation, administering 50mg in one dose unit verse two x 25mg dose unit at one time are both considered administering a dose of 50mg at one time.
Bray teaches variety amount of cannabinol, e.g. 20 mg of pure synthetic cannabinol exhibit similar potent sleep-inducing effect as 25 mg of cannabinol-rich extract in subjects suffering from insomnia (See Example 2 and 3). Bray also teaches pharmacokinetics study of pure cannabinol at a variety of amount/concentration orally administrated to mice models that is equivalent to sleep test on humans, wherein CBN 0 is prepared with 50 mg of cannabinol in 10 mL of olive oil, which is considered as read on instantly claimed dose amount.
Alternatively, even if the instantly claimed dose amount in one single dosage form or percentage of purity are not explicitly taught by the prior art, those differences appear to be only slight differences within the meaning of obviousness under 35 U.S.C. 103 as elaborated above.
Applicant repeated argument about the unexpected result of 50mg over 25 mg or 100 mg as presented in previous communication and in response to NCT 05344170 under 35U.S.C.102/103 (Remarks, page 8-9/22): “Office Action appears to mischaracterize the results of the PROMIS™ Sleep study. The 50 mg CBN product offered a statistically significant and clinically meaningful improvement in sleep quality. However, the lower dose of CBN (25 mg) and higher dose of CBN (100 mg), while also leading to sleep quality improvement over placebo, did not result in statistically significant differences from placebo. See paragraph [00189] of the application as filed. Therefore, the Office Action's statement that "there is no statistically significant difference between dose of 25 mg, 50 mg, and 100 mg" is not accurate” .
RESONSE:
First, independent claim 25 recites a dose range of 40-60mg. MPEP 716.02(d) states: To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). As shown in Figure 5 and Table 5, lower dose of CBN (25 mg) and higher dose of CBN (100 mg) also led to greater sleep quality improvement over placebo and there is no statistically significant difference between dose of 25 mg , 50 mg and 100 mg. Thus, instantly claimed dose range of 40-60 mg CBN is not considered as critical and there is no unexpected result associated with dose amount of 40-60 mg of CBN over prior art.
As for alleged unexpected result of 50mg dose, a higher dose of active compound in general is expected to produce higher response/effect in the subject. Bray already taught 25mg CBN-enriched embodiments provides relaxation and induce good sleep for patients with insomnia (See Example 2), and 20 mg of pure synthetic cannabinol exhibit similar potent sleep-inducing effect in subjects suffering from insomnia (See page 7, Example 3). As such, higher dose of 50mg CBN exhibiting improvement on sleep quality is NOT unexpected to an ordinary skilled in the art.
It’s noted the PROMIS™ Sleep Disturbance Survey question as shown in Fig 3 and 4 are subjective. The treatment outcome evaluation as shown in Figure 5 tend to fluctuate based on subjective answers of patients.
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As seen from Figure 5, the treatment outcome of different dose fluctuate depending on the time of evaluation. For example, 25 mg CBN shows better activity than 50mg CBN around week 2. 100mg CBN exhibit the same activity as 50mg CBN around week 3. In absence of objective outcome measurement using tradition polysomnography on sleep study, Applicant’s alleged unexpected 50 mg CBN product a statistically significant and clinically meaningful improvement in sleep quality compared with 25mg or 100mg is NOT fully established and NOT persuasive.
Alternatively, even if instantly claimed 50 mg of cannabinol has slight better result than 25mg taught by prior art which is NOT unexpected, As stated in MPEP 2144.05, " It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions".
Claim Rejections - 35 USC § 103
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.
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 25, 28, 32, 34-38, 49, 51 and 53-59 are rejected under 35 U.S.C. 103 as being unpatentable over Bray et al.(WO 2014/200350 A1, Applicant’s IDS dated 07/03/2024), in view of Barr et al.( US 2022/0274942 A1), Corroon (Cannabis and Cannabinoid Research, October 2021,6(5):366-371, Applicant’s IDS dated 07/03/2024, “Cannabinol and Sleep: Separating Fact from Fiction”) and NCT 05344170 (V1, posted 04/19/2022, Cannabinol Use in Patients With Insomnia Disorder (CUPID), V7 posted 06/20/2023 is disclosed in Applicant’s IDS dated 07/03/2024).
The collective teachings of Bray are elaborated in preceding 102/103 rejection and applied as before. Bray collectively teaches composition comprising pure cannabinol substantially free of THC and other cannabinoid at various amount (e.g. 25 mg, 50mg ) that could be formulated with excipient in capsule for treating variety of disease (e.g. sleep disorder).
Bray is silent about specific purity of cannabinol CBN at least about 95%, 98%, etc. which is within the meaning of obviousness under 35 U.S.C. 103 as elaborated in preceding 102/103 rejection.
Barr teaches the potential therapeutic value of CBN in the treatment of diseases has stimulated research and development in formulating CBN for use in pharmaceutical compositions (See [0070]). Barr teaches preparation of high-purity synthetic cannabinol CBN in high yield, formulation comprising high-purity synthetic cannabinol and pharmaceutical salt thereof and excipient/diluent that can be used for treating various disease responsive to CBN's affinity to cannabinoid receptors(e.g. pain, anxiety, etc.) (See abstract, [0136]-[0138], [0142], claims 1-35).
Regarding the purity limitation “at least about 95%” or “at least about 98%”... , Barr teaches the synthetic cannabinol (CBN) has a purity >97% or above 99% and embodiments with higher purity at about 99.1 %, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9% or higher (See [0067],[0119]- [0120], [0123], claim 25, 28).
Regarding limitations “substantially free of” cannabidiol and THC , Barr teaches embodiments substantially free from another chemical compound, solid form or composition that contains less than about 0.1 %, 0.05%, or 0.01 % by weight of the other compound or solid forms (See [0079], [0082]). Barr’s embodiment comprising high-purity of cannabinol(>99.9%) is construed as “substantially free of” cannabidiol, THC,
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, or any other additional cannabinoids recited in instant claims 25, 35-38, and 53-54.
Barr teaches the commercially scalable one-pot synthesis of high purity CBN crystalline in high yield does not require chromatographic purification which is advantageous compared with known multiple-steps synthesis requiring lengthy chromatography (See [0067]. Barr teaches embodiments CBN oil produced in >97% purity following the oxidation and subsequent hydrolysis step without need for column chromatography, and embodiments fractionally distilled to remove low level impurities and residual solvents to achieve purity>99%(See [0067]). Barr also teaches the high-purity CBN crystalline could be more advantageous in one or more respects compared to other forms of CBN, including amorphous CBN, in terms of chemical/ physical stability, storage, processing, compatibility, and bioavailability (See [0070]).
Regarding the excipient and dosage form limitation, Barr teaches pharmaceutical formulations comprising API (e.g. CBN) having the desired degree of purity mixed with one or more pharmaceutically acceptable excipients/diluents, wherein the amount of CBN in a single dosage form vary depending upon the host treated and the particular mode of administration e.g. a time-release formulation intended for oral administration to humans may contain approximately 1 to 1000 mg of active material (e.g. CBN) (See [0142], [0149], [0153]). Barr teaches the formulations may be packaged in unit-dose or multi-dose containers, e.g. tablet, powders, etc.( (See [0154]).
Barr collectively teaches pharmaceutical formulation/ dosage form comprising high-purity cannabinol (e.g. >99.9%) substantially free of THC , CBD and other psychoactive cannabinoid that could be formulated with excipient in variety of dosage form (e.g. tablet) for treating variety of disease/disorder.
Regarding cannabinol use in patients with sleep/ insomnia disorder, Corroon systemically reviewed cannabinol CBN (history, regulation, phytochemistry/ pharmacognosy, etc.) and its sleep-promoting effects on human subject, including pre-clinical and clinical research investigation (See whole article). Corroon and its incorporated references teach various dose of CBN (e.g. 25mg, 50 mg, 100mg, 20-200 mg) was administered to human subjects in various dosage form /administration route in variety of study (See abstract, Table 1, Results on page 369-370 ). For example, 25 mg or 50 mg of CBN was orally administered in Kamiol study (See Table 1; page 369, left column). 100 mg of CBN was orally administered in Gong study (See Table 1). Corroon warns misleading marketing materials/ product labels about cannabinol CBN's sedative properties ( e.g. “up to 10 times stronger than those of prescription and over-the-counter sleeping drugs”) (See Introduction) and recommends to use cannabinol dosages significantly higher than those found in currently commercially available cannabis products and evaluate CBN’s effects on sleep through polysomnography or validated sleep questionnaires (See abstract, Discussion page 370-371).
Clinical trial NCT 05344170 CUPID V1 (2022) discloses a randomized, double-blind, placebo-controlled pilot study investigating the effects of cannabinol (CBN) 30 mg and 300 mg on sleep architecture and next-day function in insomnia disorder(See Official Title). NCT 05344170 V1 (2022) discloses participants receive single dose oral liquid 30 mg cannabinol (CBN), 300 mg CBN, and matched placebo and undergo sleep assessment to examine CBN-related changes to sleep parameters in three overnight treatment sessions(See Study Description). NCT 05344170 V1 teaches objective evaluation of treatment outcome based on traditional polysomnographic (PSG) measures, e.g. Wake After Sleep Onset (WASO), Sleep Onset Latency (SOL) (See Outcome Measure).
It would have been obvious to one of the ordinary skilled in the art before the effective filing date of instant claimed invention to further explore cannabinol use in subjects with sleep/ insomnia disorder based on the combined beneficial teachings of Bray, Barr, Corroon and NCT 05344170, together with general knowledge of cannabinoid and sleep disorder treatment, and arrive at instantly claimed invention with reasonable expectation of success. At the time the instant invention was made, it was already known that composition comprising pure cannabinol at various amount (e.g. 20 mg, 50mg etc.) could be prepared and used for treating sleep disorder (e.g. insomnia) as taught by Bray. Bray also teaches pharmacokinetics study of pure cannabinol at various amount/concentration orally administrated to mice models that is equivalent to sleep test on humans. It was also known high-purity cannabinol (e.g. >99.9%) substantially free of THC , CBD and other cannabinoid could be prepared and formulated with excipient in variety of dosage form for treating variety of disease/disorder as taught by Barr. Corroon and NCT 05344170 further investigate CBN’s promoting effect on sleep in human subjects and teach various dose of CBN (e.g. 20-200 mg, 25mg, 50mg, 100mg, etc.). NCT 05344170 further teaches 30mg dose of CBN and objective evaluation of treatment outcome with traditional polysomnographic (PSG).
It would also be generally obvious and common sense to use pure drugs (as much as possible) to avoid the unwanted side effects of contaminants and maximize the potency of the drug. See Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293 ( Fed. Cir. 2007) (“[o]rdinarily, one expects a concentrated or purified ingredient to retain the same properties it exhibited in a mixture, and for those properties to be amplified when the ingredient is concentrated or purified; isolation of interesting compounds is a mainstay of the chemist’s art. If it is known how to perform such an isolation, doing so is likely the product not of innovation but of ordinary skill and common sense.”)
It's general knowledge in the art of cannabinoid that THC has unwanted psychoactive side-effect as taught by Bray and other prior art. Bray and other prior art teach the cannabinol composition exhibit minimal psychoactive effects, which makes this compound potentially useful as treatment for a variety of diseases or conditions. It would be obvious and logical for an ordinarily skilled in the art to explore cannabinol composition comprising highpurity of cannabinol free of THC as taught Barr to maximize the potency of cannabinol and avoid unwanted side effect of THC, CBD or other cannabinoid for study of CBN in human subjects. Bray, Corroon and NCT 05344170 teach various dose of CBD including instantly claimed dose of 50mg. Dosage adjustment for treating disease/disorder is within the knowledge of an ordinary skilled in the art as demonstrated in Bray and Corroon. 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. MPEP 2144.05.
The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to further explore dosage form of cannabinol composition comprising higher purity of cannabinol free of THC. A skilled artisan would be motivated to combined the teaching of Bray, Barr, Corroon and NCT 05344170 because all teachings refer to composition comprising cannabinol as the active ingredient and use thereof , and the combined teachings of prior art, together with exploration/optimization based on general knowledge of cannabinoid would provide a dosage form comprising high-purity cannabinol at optimal amount with minimal side-effect for treating sleep disorder (e.g. insomnia) in human subject. The commercial success of sleep aid comprising cannabinol in the market would also provide motivation for an ordinary skilled in the art to further explore CBN dosage form comprising high-purity CBN for sleep disorder.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art and general knowledge of cannabinoid(e.g. CBN, CBD, THC, etc.) and sleep treatment . Therefore, the invention as a whole is 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.
RESPONSE TO ARGUMENT:
Regarding Bray reference, please see response to argument presented under 35 USC 102/103.
Regarding Barr reference, similar as Hartung Declaration, Applicant argues against the process of preparing high-purity synthetic cannabinol taught by Barr in comparation with Applicant’s application 18/403,509, and argues “One having ordinary skill in the art would not have been motivated to incorporate the preparation of high-purity synthetic cannabinol as disclosed by Barr into the oral composition disclosed by Bray for treating sleep disorder” (Remarks, page 11-14/22).
As stated in Response to Declaration, instant claims are product claims, NOT process claims. In instant case, a skilled artisan would have known high purity cannabinol could be made as taught by Barr, thus instantly claimed product of high purity cannabinol is NOT novel. It's general knowledge in the art that THC has unwanted psychoactive side-effect as taught by Bray and Barr. Bray and Barr teach cannabinol composition exhibit minimal psychoactive effects, which makes this compound potentially useful as treatment for a variety of diseases or conditions. As such, it’s logical and prima facie to incorporate Barr’s high-purity cannabinol into pharmaceutical composition to maximize potency of CBN for treating disease/disorder and minimize side effect of THC and other cannabinoid.
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 25, 28, 32, 34-38, 49, 51 and 53-59 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14-16 ,19, 22 and 24 of copending U.S. Patent No. 12371412 B2 in view of Bray (WO 2014/200350).
Reference claims are directed to a method of preparing cannabinol, or a pharmaceutically acceptable salt thereof comprising steps that are the same as recited in instant claim 59.
References claim 14 and 24 recite the cannabinol, or a pharmaceutically acceptable salt thereof, has a purity of about 90% or more, about 95% or more, or about 99% or more. Reference claim 15 and 16 recites the cannabinol, or a pharmaceutically acceptable salt thereof, is substantially free of Δ(8,9)-tetrahydrocannabinol and Δ(9,10)-tetrahydrocannabinol.
Reference claims are silent about dosages form comprising about 40-60mg dose of cannabinol.
The collective teachings of Bray is elaborated in preceding 102/103 and 103 rejection. Bray collectively teaches composition comprising pure cannabinol substantially free of THC and other cannabinoid at various amount (e.g. 25 mg, 50mg ) that could be formulated with excipient in capsule for treating variety of disease (e.g. sleep disorder).
It would have been obvious to one of the ordinary skilled in the art to incorporate the high-purity cannabinol prepared by the method of reference claims into Bray dosage form for treating sleep disorder, together with general knowledge of cannabinoid and sleep disorder treatment. It's general knowledge in the art that THC has unwanted psychoactive side-effect as taught by Bray. It’s logical and prima facie obvious to incorporate high-purity cannabinol taught by reference into Bray’s pharmaceutical composition to maximize potency of CBN for treating disease/disorder and minimize side effect of THC and other cannabinoid. Dosage adjustment for treating disease/disorder is within the knowledge of an ordinary skilled in the art as demonstrated in Bray. 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. MPEP 2144.05.
The instant application shares at least one common inventor/applicant with reference application. The instant application is not related to reference application on the record and thus no 35 USC 121 shield exists.
Claims 25, 28, 32, 34-35, 49, 51 and 53-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 27-29 of copending U.S. Patent Application No. 18/403,664 in view of Bray (WO 2014/200350). This is a provisional nonstatutory double patenting rejection.
Reference claims are directed to a method of treating a neurodegenerative disease or condition in a subject, comprising administering a therapeutically effective amount of a cannabinoid to the subject. Reference claim 21and 29 recite the cannabinoid is cannabinol. Reference claims 27 and 28 recited cannabinoid is substantially free of THC / Δ9(10)-THC.
Reference claims are silent about dosages form comprising about 40-60mg dose of cannabinol.
The collective teachings of Bray is elaborated in preceding 102/103 and 103 rejection. Bray collectively teaches composition comprising pure cannabinol substantially free of THC and other cannabinoid at various amount (e.g. 25 mg, 50mg ) that could be formulated with excipient in capsule for treating variety of disease (e.g. sleep disorder).
It would have been obvious to one of the ordinary skilled in the art to further explore treating neurodegenerative disease or condition in a subject with dosage form of pure cannabinol based on the combined beneficial