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
Acknowledgment is made of Applicant's claim for priority from U.S. Provisional Application No. 63/067,271, filed on August 18, 2020.
Response to Amendment
Applicant’s amendment filed on October 17, 2025 amending claims 74, 86, 94, and 98; and canceling claims 305 and 306 has been entered. Claims 1, 107, 136, 170, 216 and 285 are withdrawn. Claims 2-73, 75-85, 87-93, 95-97, 99-106, 108-135, 137-169, 171-215, 217-284 and 286-304 were previously canceled. Claims 74, 86, 94, and 98 are currently presented for examination.
Response to Arguments
Due to Applicant’s amendments to the claims, the previous rejection of claims 74, 86, 94, 98, 305 and 306 under 35 U.S.C. 112(b) is hereby withdrawn.
Due to Applicant’s amendments to the claims, the previous rejection of claims 74, 94, 98 and 305 under 35 U.S.C. 102(a)(1) over Small-Howard et al. is hereby withdrawn.
Applicant's arguments filed October 17, 2025 with respect to the remaining rejection under 35 USC 103 have been fully considered but they are not persuasive.
Applicant argues that the instantly claimed composition comprises less than 5 wt.% CBN and greater than 70 wt.% CBDV, neither of which are values encompassed by Small-Howard. Applicant argues that the claimed ratio demonstrates a statistically significant anti-inflammatory response for CD4+ and CD8+ T cells in cytokine release syndrome, while presenting no statistically significant pro-nor anti-inflammatory influence at plasmacytoid dendritic cells (pDC) nor monocytes (Mq). Applicant argues that this representative cannabinoid-based therapeutic mixture targets T cells while preserving plasmacytoid dendritic cell and monocyte responses to virus/bacteria.
Applicant argues that the Office has not provided any evidence that claim 74 as originally filed, nor as currently amended, would have been obvious to a person having ordinary skill in the art at the time of filing of the instant application.
These arguments are found not persuasive since Applicant has not adequately demonstrated criticality for their claimed ratio. Applicant points to one figure (24B) which shows the results for one composition wherein the ratio of CBDV to CBN is as claimed. However, Applicant does not compare this data to any other ratios outside of the ratio claimed. Furthermore, Applicant does not provide any additional data demonstrating that these results lead to any practical advantage, such as a nonobvious improvement in the treatment or prevention of any disease or disorder. It is Applicant’s burden to demonstrate unexpected results over the prior art. See MPEP 716.02, also 716.02 (a) - (g). Furthermore, the unexpected results should be demonstrated with evidence that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance. Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). Thus Applicant’s data merely demonstrates that the claimed composition has some activity. However, this is not relevant to the issue of nonobviousness of the claimed subject matter and provides no objective evidence thereof.
Furthermore, Applicant’s argument that the instantly claimed composition comprises less than 5 wt.% CBN and greater than 70 wt.% CBDV is found not persuasive because the claims of the instant application are drawn to a molar ratio of CBDV to CBN of 100:1. Small-Howard et al. specifically demonstrates that the best neuroprotection was achieved with 1 mM cannabinol (CBN) as the major cannabinoid and with 100 mM of cannabidivarin (CBDV) as the minor cannabinoid (Figure 1A). Thus the teachings of Small-Howard et al. suggest that lower concentrations of CBN combined with higher concentrations of CDBV would produce improved results for improving neuroprotection. Accordingly, it would have been obvious to a person of ordinary skill in the art to combine CBDV and CBN at said concentrations with a reasonable expectation of improved neuroprotection which would arrive at the 100:1 ratio as claimed. Thus the teachings of Small-Howard et al. specifically suggests combining CBDV and CBN at a molar ratio of 100:1 as claimed in the instant claims with a reasonable expectation of providing improved neuroprotection. It is not necessary that the prior art suggests the same advantage or result discovered by applicant when the steps of the claim are the same as those described or suggested by the prior art. See, e.g., In re Kahn, 441 F.3d 977, 987 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323 (Fed. Cir. 2005) (“One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings.”); In re Lintner, 458 F.2d 1013 (CCPA 1972); In re Dillon, 919 F.2d 688 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). Therefore, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Thus, it is maintained that the amounts and molar ratio as claimed overlap with the amounts and molar ratio as taught and suggested in the prior art. Thus Applicant’s amendments and arguments do not overcome the rejection of record under 35 USC 103. Accordingly the previous rejection under 35 USC 103 is hereby maintained, however said rejection has been modified in view of Applicant’s amendments to the claims. This action is FINAL.
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.
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 74, 86, 94 and 98 are rejected under 35 U.S.C. 103 as being unpatentable over Small-Howard et al. U.S. Publication No. 2018/0098948 A1.
Claims 74, 86, 94 and 98 of the instant application claim an active pharmaceutical ingredient comprising: cannabidivarin (CBDV) and cannabinol (CBN) and a method of making said active ingredient; wherein the molar ratio of CBDV to CBN is 100:1 such as 1 mM CBDV and 0.01 mM CBN.
Small-Howard et al. teaches a pharmaceutically active ingredient comprising at least a first major cannabinoid; at least a first minor cannabinoid; and optionally, at least a first selected terpene, wherein in some embodiments, the first major cannabinoid is cannabinol (CBN) [0013] [0070]. Small-Howard et al. further teaches, in some embodiments, the first minor cannabinoid is cannabidivarin [0014] [0071].
Small-Howard et al. teaches that “Major cannabinoid” means cannabidiol (CBD) or cannabinol (CBN), and the major cannabinoid can be obtained by chemical synthesis, chemical modification, or obtained from plant materials derived from one or more Cannabis plants [0049]. Small-Howard et al. teaches that “Minor cannabinoid” means cannabichromene, cannabigerol, or cannabidivarin wherein the minor cannabinoid can be obtained by chemical synthesis, chemical modification, or obtained from plant materials derived from one or more Cannabis plants [0050].
Small-Howard et al. teaches that in certain currently preferred embodiments, the first major cannabinoid is cannabinol (CBN), and the first minor cannabinoid is cannabidivarin [0077].
Small-Howard et al. teaches that in certain embodiments, the major cannabinoids collectively constitute 5-10 wt. % of the active ingredient, 10-15 wt. % of the active ingredient, 15-20 wt. % of the active ingredient, 20-25 wt. % of the active ingredient, 25-30 wt. % of the active ingredient, 30-35 wt. % of the active ingredient, or 35-40 wt. % of the active ingredient [0089]. In certain embodiments, the major cannabinoids collectively constitute at least 5 wt. %, at least 10 wt. %, at least 15 wt. %, at least 20 wt. %, at least 25 wt. %, at least 30 wt. %, at least 35 wt. %, but each case no more than 40 wt. %, of the active ingredient [0089]. Thus Small-Howard et al. teaches that the major cannabinoid which is CBN comprises at least 5 wt. % of the active ingredient.
Small-Howard et al. teaches that in typical embodiments, the minor cannabinoids collectively constitute 5-70% by weight of the active ingredient [0090]. Small-Howard et al. teaches that in certain embodiments, the minor cannabinoids collectively constitute at least 55 wt. %, at least 60 wt. %, at least 65 wt. %, but in each case less than 70 wt. %, of the active ingredient [0091]. Thus Small-Howard et al. teaches that the minor cannabinoid which is CBDV comprises at most 70 wt. % of the active ingredient.
In some embodiments, the pharmaceutically active ingredient is prepared by mixing chemically pure major cannabinoids, minor cannabinoids, and optional selected terpenes to desired final concentrations [0117]. Each of the major cannabinoids, minor cannabinoids, and selected terpenes can independently be chemically synthesized, either by total synthesis or by synthetic modification of an intermediate, purified from a compositional mixture such as a Cannabis sativa extract, or purchased commercially [0117].
In typical embodiments, the active ingredient is present in the pharmaceutical composition at a concentration of at least 0.01 mg/ml, at least 0.1 mg/ml, at least 0.5 mg/ml, or at least 1 mg/ml. In certain embodiments, the active ingredient is present in the pharmaceutical composition at a concentration of at least 1 mg/ml, 2 mg/ml, 3 mg/ml, 4 mg/ml, 5 mg/ml, 10 mg/ml, 15 mg/ml, 20 mg/ml, or 25 mg/ml. In certain embodiments, the active ingredient is present in the pharmaceutical composition at a concentration of at least 30 mg/ml, 35 mg/ml, 40 mg/ml, 45 mg/ml or 50 mg/ml [0126].
In various embodiments, the unit dosage form is a vial, ampule, bottle, or pre-filled syringe and in some embodiments, the unit dosage form contains 0.01 mg, 0.1 mg, 0.5 mg, 1 mg, 2.5 mg, 5 mg, 10 mg, 12.5 mg, 25 mg, 50 mg, 75 mg, or 100 mg of the cannabinoid composition [0140]. In some embodiments, the unit dosage form contains 125 mg, 150 mg, 175 mg, 200 mg, or 250 mg of the cannabinoid composition [0140]. In typical embodiments, the pharmaceutical composition in the unit dosage form is in liquid form. In various embodiments, the unit dosage form contains between 0.1 mL and 50 ml of the pharmaceutical composition, such as 1 ml, 2.5 ml, 5 ml, 7.5 ml, 10 ml, 25 ml, or 50 ml of pharmaceutical composition [0141]. In particular embodiments, the unit dosage form is a vial containing 1 ml of the cannabinoid composition at a concentration of 0.01 mg/ml, 0.1 mg/ml, 0.5 mg/ml, or 1 mg/ml [0142]. In some embodiments, the unit dosage form is a vial containing 2 ml of the cannabinoid composition at a concentration of 0.01 mg/ml, 0.1 mg/ml, 0.5 mg/ml, or 1 mg/ml [0142].
The pharmaceutical composition can be in any form appropriate for human or veterinary medicine, including a liquid, an oil, an emulsion, a gel, a colloid, an aerosol or a solid [0127].
Small-Howard et al. specifically exemplifies an active ingredient comprising cannabidivarin (CBDV) and cannabinol (CBN), see ENT1, ENT3, ENT6, ENT8-12 which all contain cannabidivarin (CBDV), and are combined with cannabinol (CBD) (see figures 2 and 3A).
Claims 1, 3 and 4 of Small-Howard et al. claim a pharmaceutically active ingredient, comprising: at least a first major cannabinoid; at least a first minor cannabinoid; and optionally, at least a first selected terpene, wherein the first major cannabinoid is cannabinol (CBN) and the first minor cannabinoid is cannabidivarin. Claim 20 of Small-Howard et al. claims the active ingredient of claim 1, wherein the major cannabinoids collectively constitute 5-40% by weight of the active ingredient; the minor cannabinoids collectively constitute 5-70% by weight of the active ingredient; and the selected terpenes collectively constitute 0-70% by weight of the active ingredient. Claim 22 of Small-Howard et al. claims a method of making a pharmaceutically active ingredient, comprising steps, in any order, of mixing: at least a first major cannabinoid; at least a first minor cannabinoid; and optionally, at least a first selected terpene.
Thus Small-Howard et al. teaches an active pharmaceutical ingredient, comprising: cannabidivarin (CBDV) and cannabinol (CBN). Small-Howard et al. further teaches and a method of making said active ingredient comprising mixing the cannabinoids which are chemically synthesized, either by total synthesis or by synthetic modification of an intermediate, purified from a compositional mixture such as a Cannabis sativa extract, or purchased commercially. Small-Howard et al. also teaches in typical embodiments, the active ingredient is present in the pharmaceutical composition at a concentration of at least 0.01 mg/ml and the pharmaceutical composition can be in any form appropriate for human or veterinary medicine, including a liquid, an oil, an emulsion, a gel, a colloid, an aerosol or a solid [0126]-[0127].
Small-Howard et al. does not specifically teach the molar ratio of CBDV and CBN is 100 parts CBDV to 1 part CBN. Small-Howard et al. does not specifically teach that CBDV is present in an amount sufficient to achieve a mean peak concentration (Cmax) in plasma or target tissue of at least 0.01 mM when administered.
Although Small-Howard et al. does not specifically teach the same molar ratio of CBDV to CBN as claimed, as detailed above, Small-Howard et al. teaches that the major cannabinoid which is CBN comprises at least 5 wt. % of the active ingredient and the minor cannabinoid which is CBDV comprises at most 70 wt. % of the active ingredient. Thus Small-Howard et al. teaches that CBDV can comprise the majority of the active ingredient as compared to CBN. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("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."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
With respect to currently amended claim 86 of the instant application which claims a unit dosage form comprising the active pharmaceutical ingredient of claim 74, wherein CBDV is present in an amount sufficient to achieve a mean peak concentration (Cmax) in plasma or target tissue of at least 0.01 mM when administered, Small-Howard et al. specifically demonstrates that the best neuroprotection was achieved with 1 mM cannabinol (CBN) as the major cannabinoid and with 100 mM of cannabidivarin (CBDV) as the minor cannabinoid (Figure 1A). Thus the teachings of Small-Howard et al. suggest that lower concentrations of CBN combined with higher concentrations of CDBV would produce improved results for improving neuroprotection. Accordingly, it would have been obvious to a person of ordinary skill in the art to combine CBDV and CBN at said concentrations with a reasonable expectation of improved neuroprotection which would arrive at the 100:1 ratio as claimed. Thus the teachings of Small-Howard et al. specifically suggests combining CBDV and CBN at a molar ratio of 100:1 as claimed in the instant claims with a reasonable expectation of providing improved neuroprotection. Therefore, since Small-Howard et al. specifically suggests using the combination as claimed in the same molar ratio as claimed, the effect of CBDV in the composition as claimed will necessarily occur. Thus by following the teachings and suggestions of Small-Howard et al. and combining the cannabinoids in the same molar ratio as claimed, CBDV will necessarily be present in an amount sufficient to achieve a mean peak concentration (Cmax) in plasma or target tissue of at least 0.01 mM when administered as claimed in instant claims 86.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 74, 86, 94, 98, are rejected. Claims 1, 107, 136, 170, 216 and 285 are withdrawn. Claims 2-73, 75-85, 87-93, 95-97, 99-106, 108-135, 137-169, 171-215, 217-284 and 286-306 are canceled. No claims are allowed.
THIS ACTION IS MADE FINAL. 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 KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM