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 .
Information Disclosure Statement
Three information disclosure statement (IDS) submitted: one on 07/25/2024; one on 10/14/2024; and one on 04/07/2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Specification
The description of Figure 1A-F (see page 18, [0094]) refers to patient 1 (P1) and patient 2 (P2), however, the figures show P2 and P3.
Drawings
The drawings are objected to because of discrepancies between the specification and the Figures themselves – see objections to spec. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Status of the Claims
Claims 1-16 are pending in this application.
Claim Interpretation
[0014] of the spec. defines “estrogen” as all forms of estrogen or estrogen-like molecules including, without limitation, endogenous estrogens (e.g., estrone, 17β-estradiol, estriol, estetrol, estradiol), phytoestrogens/biosynthetic estrogens (e.g., genistein, zearalenone), and other exogenous estrogens whether or not biosynthetic or synthetic estrogens or stimulatory estrogen receptor ligands (e.g., ethinylestradiol, estradiol valerate, 17β-estradiol, mestranol, estropipate, tamoxifen, etc.).
Regarding claim 10, the limitation: “an amount of exogenous estrogen to reach in vivo amount of estrogen that is therapeutically acceptable” will be interpreted as “administered a therapeutically acceptable amount”.
Examiner Notes
NSDP rejections over US Patent No. 12,097,211 B2 (US ‘211) have not been raised herein because the instant application is a DIV of US ‘211 which resulted from a restriction. See MPEP 804.01.
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 1-2, 5-6, and 8 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.
Claim 1 is unclear because step b (III) reads: “determining that the patient is producing an effective amount of estrogen”. Thus, it is unclear if, with step b. (III), Applicant intends to claim the method of treatment comprising administering an effective amount of CE (step a), wherein the patient has already been determined to be producing an effective amount of estrogen; OR the method of treatment comprising administering an effective amount of CE (step a) despite the patient’s estrogen status, then ‘determining’ whether or not the patient is producing an effective amount of estrogen”. If the latter is the case, this raises a question as to what the intended course of action is for patients who are not producing an effective amount of estrogen versus those who are producing an effective amount of estrogen. . . Will patients not producing an effective amount of estrogen be administered an effective amount of estrogen so as to bring estrogen levels up? Will patients who are producing an effective amount of estrogen also be administered additional estrogen or will they not be administered additional estrogen? If they will not be administered additional estrogen, then, for that population of patients who are producing an effective amount of estrogen and not receiving additional estrogen, will only the CE be administered as part of the claimed method of treatment?
For the purposes of applying art, the claim will be interpreted as follows:
“A method of treating an estrogen sensitive cancer in a patient, the method comprising: determining whether or not the patient is producing an effective amount of estrogen;
if the patient is producing effective amount of estrogen, then administering to said patient an effective amount of cannabis extract (CE), wherein the CE comprises about 50% to about 99.9% by weight cannabidiol (CBD);
if the patient is not producing an effective amount of estrogen, then administering an effective amount of estrogen to said patient, or administering an amount of estrogen to said patient to bring the total estrogen levels within the patient to an effective amount, then administering to said patient an effective amount of the CE.”
Claims 2, 5-6, and 8 are rejected for depending upon the limitations of claim 1 without resolving the ambiguities raised by the claim language.
Regarding claim 8, the claim recites: “ensuring that the effective amount of estrogen is not adversely affected by antiestrogen therapy”. It is unclear what this “ensuring” step entails. Will the ‘ensuring’ take place before ‘administration of the effective amount of estrogen/ determining the patient is producing an effective amount of estrogen’ by discontinuing any existing antiestrogen therapy? Or will the ‘ensuring’ happen after ‘administration of the effective amount of estrogen/ determining the patient is producing an effective amount of estrogen,’ while the patient still receives antiestrogen therapy? If the latter is the case, why would antiestrogen therapy be continued if endogenous production of estrogen/ in vivo levels of estrogen is desired/ beneficial for treatment? The metes and bounds of the claim are unclear.
For the purposes of applying art, claim 8 will be interpreted as meaning to say that all antiestrogen therapies were discontinued prior to administering the claimed treatment.
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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); and Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
Regarding claims 1 and 10, Meiri discloses their unexpected finding that a composition comprising their CBG-derivatives of Formula I or II in combination with an ER activation inhibitor (e.g. tamoxifen (TAM) – reading on ‘estrogen’ as defined in the instant spec. – see claim interpretation) increased apoptosis % of cancer cells by more than 40% compared to tamoxifen alone ([009], page 3), and discloses methods of treating a subject afflicted with an ER-related disease (such as breast, ovarian, and endometrial cancers – see [031]), and of increasing the efficacy of an ER-activation inhibitor in a subject comprising administration of their CBG-derivatives ([010] to [015]). Meiri teaches their composition may further comprise an additional cannabinoid [017]), such as THC, CBN, and CBD [077].
In Figures 1C-D below, Meiri discloses the % cell death of MCF7 cells (breast cancer cells) treated with THC: CBD and high CBD content, respectively, with and without TAM (see results below for CANN21 and CANN29 in particular, which show a synergistic increase in %cell death when treated with a combination with TAM versus the CBD: THC or CBD alone.
Meiri further teaches while single cannabinoids have been shown to exert biological activity, cannabis synergy, also known as “entourage effect,” markedly increased the activity of primary endogenous cannabinoids [006].
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(Fig. 1C-D)
Furthermore, Dobovisek, also cited herein, discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1).
Therefore, regarding claims 1 and 10, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer a cannabis extract (CE) comprising 50-99.9% CBD (or 70:40 to about 99.9:0.1 CBD) in combination with an effective amount of ‘estrogen’, such as TAM – see claim interpretation – and other cannabinoids, such as THC and CBN, in view of Meiri and Dobovisek. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Meiri discloses their unexpected effect after combining THC:CBD and CBD compositions with TAM in %cell death (see figures above); further because Dobovisek discloses the additive effects of CBD with TAM in the cell viability of an ER+ breast cancer cell line. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, in view of Meiri and Dobovisek, to arrive at the instant invention.
Regarding claim 3, Meiri discloses their “administration” may be done orally, etc. ([0154], line 10).
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claim 6, Dobovisek discloses ER+ cancer (reading on estrogen receptor positive cancer).
Regarding claim 8, since TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering Meiri’s and Dobovisek’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of Meiri and Dobovisek.
Regarding claims 9 and 12, Meiri discloses their compositions may comprise carriers such as phosphate buffer solutions (reading on excipients – claim 12), and buffering agents and pH adjusting agents ([0100] and [0101]). Furthermore, Meiri discloses administration of additional cannabinoids in their compositions (‘plurality of cannabinoids’ – see [064]) – with each cannabinoid reading on an additional chemotherapy. Furthermore, Dobovisek discloses palbociclib, trastuzumab, and cisplatin as chemotherapies used for ER+ breast cancer.
Therefore, regarding claim 9, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to administer Meiri’s and Dobovisek’s treatment comprising CBD and TAM, further comprising additional chemotherapies, such as other cannabinoids, palbociclib, trastuzumab, and/or cisplatin, in view of Meiri’s and Dobovisek’s disclosures. Applicant is advised that, with respect to a mixture of the two claimed reagents, the courts have found that “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art (In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).” See MPEP2144.06. It is therefore obvious to provide a mixture of the two or more agents.
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from Meiri and Dobovisek, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount, since Meiri and Dobovisek disclose an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; and further in view of Dobovisek’s results of CBD in combination with TAM; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s and Dobovisek’s disclosures. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp. Note: MPEP 2143(E) KSR,550 U.S. at 421, 82 USPQ2d at 1397.
Further regarding claim 13, both Meiri and Dobovisek disclose a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9% or 70:40 to about 99.9:0.1 CBD; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is advised that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. See In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). The courts have also found that 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. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05-II. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claims 6 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); and Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”); as applied to claims 1-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of Meiri and Dobovisek are disclosed above and incorporated herein.
Meiri discloses their methods of treatment and compositions for the treatment of endometrial cancer (claim 16, and [031]).
While Meiri and Dobovisek don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with Meiri and Dobovisek’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Meiri and Dobovisek disclose their methods and compositions for treating ER-dependent cancers, including endometrial cancer, with their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
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.
The teachings of Meiri et al. – applied to the Non-Statutory Double Patenting rejections below – are summarized here to avoid repetition in the record below.
Meiri discloses their unexpected finding that a composition comprising their CBG-derivatives of Formula I or II in combination with an ER activation inhibitor (e.g. tamoxifen (TAM) – reading on ‘estrogen’ as defined in the instant spec. – see claim interpretation) increased apoptosis % of cancer cells by more than 40% compared to tamoxifen alone ([009], page 3), and discloses methods of treating a subject afflicted with an ER-related disease (such as breast, ovarian, and endometrial cancers – see [031]), and of increasing the efficacy of an ER-activation inhibitor in a subject comprising administration of their CBG-derivatives ([010] to [015]). Meiri teaches their composition may further comprise an additional cannabinoid [017]), such as THC, CBN, and CBD [077].
In Figures 1C-D below, Meiri discloses the % cell death of MCF7 cells (breast cancer cells) treated with THC: CBD and high CBD content, respectively, with and without TAM (see results below for CANN21 and CANN29 in particular, which show a synergistic increase in %cell death when treated with a combination with TAM versus the CBD: THC or CBD alone.
Meiri further teaches while single cannabinoids have been shown to exert biological activity, cannabis synergy, also known as “entourage effect,” markedly increased the activity of primary endogenous cannabinoids [006].
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Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,654,171 B2 (US ‘171) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘171 claims a method of treating ovarian cancer (an estrogen-sensitive cancer – reading on claim 6) comprising administration of a CE comprising between 50-99% CBD with a pH of 3.5-6 (reading on claims 9 and 12) and another chemotherapeutic agent, such as paclitaxel (reading on claim 9), wherein the CE composition is administered intravaginally (reading on claim 3) (US ‘171’s claim 1). US ‘171 also claims their method comprising administration of the CE, wherein the CE further comprises additional cannabinoids, such as THC, CBN, etc. (reading on claim 10) (US ‘171’s claim 3).
While US ‘171 does teach administration of an estrogen with their CE composition; the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘171’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of ovarian cancer, or other ER-positive cancers. One of ordinary skill would have been motivated to do so because US ‘171 discloses their method of treating ovarian cancer comprising administration of CE and an additional chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘171 and Meiri, to arrive at the instant invention.
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, both Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,654,171 B2 (US ‘171) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘171 and Meiri are disclosed above and incorporated herein.
While US ‘171 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘171 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘171 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 11,654,171 B2 (US ‘171) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘171 and Meiri are disclosed above and incorporated herein.
While US ‘171 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘171 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘171 and Meiri disclose their methods and compositions for treating ER-dependent cancers, with Meiri specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,793,847 B2 (US ‘847) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘847 claims a method of treating endometrial cancer (an estrogen-sensitive cancer – reading on claim 6) comprising administration of a CE comprising between 50-99% CBD with a pH of 3.5-6 (reading on claims 9 and 12) and another chemotherapeutic agent, such as paclitaxel (reading on claim 9), wherein the CE composition is administered intravaginally (reading on claim 3) (US ‘847’s claim 1). US ‘847 also claims their method comprising administration of the CE, wherein the CE further comprises additional cannabinoids, such as THC, CBN, etc. (reading on claim 10) (US ‘847’s claim 4).
While US ‘847 does teach administration of an estrogen with their CE composition; the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘847’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of ovarian cancer, or other ER-positive cancers. One of ordinary skill would have been motivated to do so because US ‘847 discloses their method of treating endometrial cancer comprising administration of CE and an additional chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘847 and Meiri, to arrive at the instant invention.
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, both Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,793,847 B2 (US ‘847) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘847 and Meiri are disclosed above and incorporated herein.
While US ‘847 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘847 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘847 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,793,847 B2 (US ‘847) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘847 and Meiri are disclosed above and incorporated herein.
While US ‘847 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘847 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘847 and Meiri disclose their methods and compositions for treating ER-dependent cancers, specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,251,411 B2 (US ‘411) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘411 claims a method of treating endometrial cancer (an estrogen-sensitive cancer – reading on claim 6) comprising administration of a CE comprising between 50-99% CBD with a pH of 3.5-6 (reading on claims 9 and 12) and another chemotherapeutic agent, such as paclitaxel (reading on claim 9), wherein the CE composition is administered intravaginally (reading on claim 3) (US ‘411’s claim 1). US ‘847 also claims their method comprising administration of the CE, wherein the CE further comprises additional cannabinoids, such as THC, CBN, etc. (reading on claim 10) (US ‘411’s claims 5-6).
While US ‘411 does teach administration of an estrogen with their CE composition; the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘411’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of ovarian cancer, or other ER-positive cancers. One of ordinary skill would have been motivated to do so because US ‘411 discloses their method of treating endometrial cancer comprising administration of CE and an additional chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘411 and Meiri, to arrive at the instant invention.
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, both Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,251,411 B2 (US ‘411) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘411 and Meiri are disclosed above and incorporated herein.
While US ‘411 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘411 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘411 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 12,251,411 B2 (US ‘411) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘411 and Meiri are disclosed above and incorporated herein.
While US ‘411 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘411 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘411 and Meiri disclose their methods and compositions for treating ER-dependent cancers, specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 15-16 of U.S. Patent No. 12,440,528 B2 (US ‘528) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘528 claims a method of treating ovarian cancer (an estrogen-sensitive cancer – reading on claim 6) comprising administration of a CE comprising between 50-99% CBD with a pH of 3.5-6 (reading on claims 9 and 12) and another chemotherapeutic agent, such as paclitaxel (reading on claim 9), wherein the CE composition is administered intravaginally (reading on claim 3) (US ‘528’s claim 1). US ‘528 also claims their method comprising administration of the CE, wherein the CE further comprises additional cannabinoids, such as THC, CBN, etc. (reading on claim 10) (US ‘528’s claim 15-16).
While US ‘528 does teach administration of an estrogen with their CE composition; the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘528’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of ovarian cancer, or other ER-positive cancers. One of ordinary skill would have been motivated to do so because US ‘528 discloses their method of treating ovarian cancer comprising administration of CE and an additional chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘528 and Meiri, to arrive at the instant invention.
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, both Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 15-16 of U.S. Patent No. 12,440,528 B2 (US ‘528) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘528 and Meiri are disclosed above and incorporated herein.
While US ‘528 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘528 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘528 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 and 15-16 of U.S. Patent No. 12,440,528 B2 (US ‘528) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘528 and Meiri are disclosed above and incorporated herein.
While US ‘528 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘528 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘528 and Meiri disclose their methods and compositions for treating ER-dependent cancers, with Meiri specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 12,011,451 B2 (US ‘451) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘451 claims a method of treating a gynecological disease (reading on ovarian and endometrial cancers – ER positive cancers in view of Meiri – reading on claim 6) comprising administration of a CE comprising between 50-99.0% CBD and a flavonoid (reading on another chemotherapeutic agent, reading on claim 9), (US ‘451’s claim 10).
While US ‘451 does teach: (i) administration of an estrogen with their CE composition or the treatment of estrogen-sensitive cancers (claims 1 and 10); (ii) routes of administration (claims 3 and 15); (iii) wherein the CE comprises other cannabinoids besides CBD; (iv) administration comprising additional excipients (claim 12); or (v) estrogen receptor positive cancers, such as endometrial cancer (claim 6); the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, regarding claims 1 and 10, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘451’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of gynecological ER-positive cancers, such as endometrial cancer. One of ordinary skill would have been motivated to do so because US ‘451 discloses their method of treating gynecological conditions comprising administration of CE and an additional flavonoid chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM for the treatment of ER-positive cancers, such as endometrial cancer, and that combination resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘451 and Meiri, to arrive at the instant invention.
Regarding claim 3, Meiri discloses their “administration” may be done orally, etc. ([0154], line 10).
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claim 6, Meiri discloses ER positive cancers and endometrial cancer.
Regarding claim 12, Meiri discloses their compositions may comprise carriers such as phosphate buffer solutions (reading on excipients – claim 12), and buffering agents and pH adjusting agents ([0100] and [0101]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 12,011,451 B2 (US ‘451) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘451 and Meiri are disclosed above and incorporated herein.
While US ‘451 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘451 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘451 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 12,011,451 B2 (US ‘451) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘451 and Meiri are disclosed above and incorporated herein.
While US ‘451 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘451 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘451 and Meiri disclose their methods and compositions for treating gynecological, ER-dependent cancers, with Meiri specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,318,399 B2 (US ‘399) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”).
Regarding instant claims 1-7 and 9-15, US ‘399 claims a method of treating a gynecological disease (reading on ovarian and endometrial cancers – ER positive cancers in view of Meiri – reading on claim 6) comprising administration of a CE comprising between 50-100% CBD and a flavonoid (reading on another chemotherapeutic agent, reading on claim 9), (US ‘399’s claim 1).
While US ‘399 does teach: (i) administration of an estrogen with their CE composition or the treatment of estrogen-sensitive cancers (claims 1 and 10); (ii) routes of administration (claims 3 and 15); (iii) wherein the CE comprises other cannabinoids besides CBD; (iv) administration comprising additional excipients (claim 12); or (v) estrogen receptor positive cancers, such as endometrial cancer (claim 6); the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, regarding claims 1 and 10, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer US ‘399’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of gynecological ER-positive cancers, such as endometrial cancer. One of ordinary skill would have been motivated to do so because US ‘399 discloses their method of treating gynecological conditions comprising administration of CE and an additional flavonoid chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM for the treatment of ER-positive cancers, such as endometrial cancer, and that combination resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of US ‘399 and Meiri, to arrive at the instant invention.
Regarding claim 3, Meiri discloses their “administration” may be done orally, etc. ([0154], line 10).
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claim 6, Meiri discloses ER positive cancers and endometrial cancer.
Regarding claim 12, Meiri discloses their compositions may comprise carriers such as phosphate buffer solutions (reading on excipients – claim 12), and buffering agents and pH adjusting agents ([0100] and [0101]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,318,399 B2 (US ‘399) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of US ‘399 and Meiri are disclosed above and incorporated herein.
While US ‘399 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering US ‘399 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of US ‘399 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
Claims 6 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,318,399 B2 (US ‘399) in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of US ‘399 and Meiri are disclosed above and incorporated herein.
While US ‘399 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with US ‘399 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because US ‘399 and Meiri disclose their methods and compositions for treating gynecological, ER-dependent cancers, with Meiri specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
Claims 1-7 and 9-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 19/055,241 (Co. ‘241); in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”)
Regarding instant claims 1-7 and 9-15, Co. ‘241 claims a method of treating endometrial cancer (an estrogen-sensitive cancer – reading on claim 6) comprising administration of a CE comprising between 50-99.9% CBD with a pH of 3.5-6 (reading on claims 9 and 12) and another chemotherapeutic agent, such as paclitaxel (reading on claim 9), wherein the CE composition is administered orally, intravaginally, etc. (reading on claim 3) (Co. ‘241’s claims 1 and 9). Co. ‘241 also claims their method comprising administration of the CE, wherein the CE further comprises additional cannabinoids, such as THC, CBN, etc. (reading on claim 10) (Co. ‘241’s claims 4-5 and 12-13).
While Co. ‘241 does teach administration of an estrogen with their CE composition; the teachings of Meiri are relied upon for these disclosures. The teachings of Meiri are disclosed above and incorporated herein.
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the instant application to administer Co. ‘241’s CE comprising CBD in combination with TAM (an estrogen as defined in the instant spec. – see claim interpretation), in view of Meiri, for the treatment of ovarian cancer, or other ER-positive cancers. One of ordinary skill would have been motivated to do so because Co. ‘241 discloses their method of treating endometrial cancer comprising administration of CE and an additional chemotherapeutic agent; further because Meiri discloses CBD-containing cannabinoid mixtures in combination with TAM resulted in synergistic augmentation of the % cancerous cell death. One would have been further motivated to use a cannabis extract in view of Meiri’s disclosure of the entourage effect, which is a known property of cannabinoids that results in synergy and augmented properties. Thus, one of ordinary skill would have been motivated to use a CE comprising CBD and other cannabinoids, such as THC, CBN, and CBG, etc., in combination with TAM, and an additional chemotherapeutic in view of Co. ‘241 and Meiri, to arrive at the instant invention.
Regaring claim 4, Meiri discloses their pharmaceutical composition comprising their CBG-derivative may be formulated with the ER activation inhibitor (TAM) in the same composition ([038]).
Regarding claims 7, 11, and 13, It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter shown to be in the prior art does not possess the characteristic relied on” (205 USPQ 594, second column, first full paragraph).
Further regarding claim 7, in the present case, in view of the teachings from US ‘171 and Meiri, there is a reasonable expectation that the CBD containing compositions obtained from these disclosures will produce the claimed outcomes after administration of an effective amount in combination with TAM, since Meiri discloses an increase in cancer cell death after administration of their combination therapy.
Further regarding claim 11, in view of Meiri’s results after administering cannabinoid compositions comprising CBD and TAM led to greater than additive augmentation of activity (reading on synergy), and their guidance on the “entourage effect” of cannabinoid mixtures; one of ordinary skill would have been motivated to, with a reasonable expectation of success, administer an amount of CBD-containing CE in combination with TAM in amounts that will yield synergistically augmented results. These studies of optimizing amounts administered are routine in the art, as can be seen from Meiri’s disclosure. Thus, a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Further regarding claim 13, both Meiri discloses a reduction in cancer cell viability after treatment with their CBD compositions and TAM (see Figures 1C-D above, for example).
Regarding claim 15, Meiri discloses their cannabinoid composition and the ER activation inhibitor (TAM) may be in separate compositions (see [036]) and that their compositions can be administered via oral, buccal, lingual, sub lingual, parenteral
(e.g. subcutaneous, intravenous, or intramuscular), intratracheal, intrabronchial, intraalveolar,
topical, intraperitoneal, and intranasal [0154] – thus, it would have been prima facie obvious to one of ordinary skill prior to the effective filing of the claimed invention to administer the CE and TAM separately via any of these routes, with a reasonable expectation of success. Applicant is reminded that a person with ordinary skill has good reason to pursue known options within his or her technical grasp.
Regarding: (i) the ranges of CBD in the CE administered ranging from 50-99.9%; (ii) and the effective amounts of estrogen serum levels being ≥ 300 pg/mL, 600-150000 pg/mL, or 30-20000 pg/mL, as recited in claims 2, 5, 10, and 14; Applicant is reminded that the courts have stated where the claimed ranges overlap or lie inside the ranges disclosed by the prior art and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that 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. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
This is a provisional nonstatutory double patenting rejection.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 19/055,241 (Co. ‘241); in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Dobovisek et al. (Advances in Cancer Biology – Metastasis, 4, 2022, 100038, 7 pages - Available online 4 April 2022) (“Dobovisek”).
The teachings of Co. ‘241 and Meiri are disclosed above and incorporated herein.
While Co. ‘241 in view of Meiri does not specifically teach or suggest ensuring the effective amount of estrogen is not adversely affected by antiestrogen therapy; the teachings of Dobovisek are relied upon for these disclosures.
Dobovisek discloses that CBD and TAM had an additive negative effect on cell viability in ER+ T-47D breast cancer (abstract; Fig. 3; and section 3.3.1); however, fulvestrant (a SER degrader – reading on antiestrogen therapy) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek).
Regarding claim 8, TAM (a SERM) administration resulted in unexpected results when combined with cannabis compositions comprising CBD, as reported by both Meiri and Dobovisek, and fulvestrant (a SERD) did not show the same additive results as TAM when combined with CBD (see Fig. 4B of Dobovisek), then it would have been prima facie obvious to one of ordinary skill to stop antiestrogen therapy prior to administering Co. ‘241 and Meiri’s treatment regimen. One of ordinary skill would have been motivated to do so with a reasonable expectation of success in view of the teachings of Co. ‘241 and Meiri’s disclosure of a CE + TAM treatment regimen for estrogen-receptor positive cancers; and Dobovisek’s teachings of the effects of combining TAM + CBD versus fulvestrant + CBD.
This is a provisional nonstatutory double patenting rejection.
Claims 6 and 16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of copending Application No. 19/055,241 (Co. ‘241); in view of Meiri et al. (WO 2022/144878 A1 – Int. Filing Date: Dec. 27th, 2021 – cited in IDS) (“Meiri”); as applied to claims 1-7 and 9-15; in view of Wan et al. (Sci. Rep., 2016, 6, Article 39744, 7 pages) (“Wan”).
The teachings of Co. ‘241 and Meiri are disclosed above and incorporated herein.
While Co. ‘241 in view of Meiri don’t specifically teach type 1 or 2 endometrial cancer; the teachings of Wan are relied upon for these disclosures.
Wan teaches the majority of type 1 (96%) and type 2 (82%) endometrial cancers were estrogen and progesterone receptor positive (abstract).
Therefore, it would have been prima facie obvious to one of ordinary skill prior to the effective filing date of the claimed invention to treat type 1 endometrial cancer with Co. ‘241 and Meiri’s method, in view of Wan. One of ordinary skill would have been motivated to do so with a reasonable expectation of success because Co. ‘241 and Meiri disclose their methods and compositions for treating ER-dependent cancers, specifically disclosing endometrial cancer, by administering their CBD and TAM combination; further because Wan discloses most type 1 and 2 endometrial cancers are estrogen receptor positive.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/JACKSON J HERNANDEZ/Examiner, Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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