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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 38-54) in the reply filed on 7/10/2026 is acknowledged.
Claims 55-57 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/10/2026.
The election is made FINAL.
Status of Claims
Claims 38-54 are under examination on the merits.
Claims 55-57 are withdrawn without traverse.
Claim Interpretation
The instant specification describes callus as comprising “a plurality of pluripotent (totipotent) cells, being able to regenerate the whole plant body” (page 10, lines 9-12). The instant specification defines pluripotent cells as slowly dividing cells giving rise to daughter cells that can either differentiate to new tissues and organs or remain stem-cells (page 10, lines 19-21). In light of the specification’s broad definition of pluripotent cells and the use of totipotent as an interchangeable term with pluripotent in the specification, claims 38-54 have been examined under the interpretation that totipotent cells read on pluripotent cells.
The claims require pluripotent undifferentiated cells (claim 38, lines 2-4). The plain language reading of this requirement is that the preparation requires intact cells, because a cell fraction or lysate or other composition comprising parts of a cell would not be capable of giving rise to daughter cells, as required by the limitation that the cells are pluripotent. However, the claims have been broadly interpreted here to encompass extracts and fractions of pluripotent cells in alignment with the working example in the specification of a preparation of a liposomal extract wherein the whole cell broth is subjected to high-pressure homogenization (page 34, line 4-page 14), which pursues destruction of cell membranes to release extractable substances and liposomes contain the fat and water soluble fractions of the cells (page 34, lines 25-28).
In claim 53 (line 3) a “sterile Cannabis explant” is interpreted as an explant free from microbial contamination and not an explant from a Cannabis plant with reduced fertility.
Claim Objections
Claim 39, 40, 48 & 53 are objected to because of the following informalities:
Claim 39 (line 2): L. should not be italicized.
Claim 39 (lines 1-2): “the Cannabis” should read --the plant of the genus Cannabis--.
Claim 40 (line 1): “claims” should read --claim--.
Claim 40 (line 3): “and” should read --or--. Although treatment of claims reciting alternatives is not governed by the particular format used (e.g., alternatives may be set forth as "a material selected from the group consisting of A, B, and C" or "wherein the material is A, B, or C"), claim 40 is not written in Markush format, which would require --the group consisting of-- in order to present a closed group of options. See MPEP 2117(I) for guidance on Markush formatting.
Claim 48 (line 3): “CBN” should be in parentheses.
Claim 48 (line 5): cannabigervarin and cannabigerovarin are both given the abbreviation “CBGV”. For clarity, each distinct cannabinoid should have a distinct abbreviation.
Claim 53 (lines 3, 4, 6, 8, 10): periods should not be used within a claim except for abbreviations. See MPEP 608.01(m). An alternative format like --a)-- would be acceptable.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
Indefiniteness
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 41-44 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. All dependent claims are included in the rejections below.
Claim 41 recites a concentration “from about 0.001% to about 25% w/w” (lines 2-3). The instant specification defines “about” as “within a range of normal tolerance in the art” and states that about can be understood as within ±10 through ±0.01% (page 9, lines 28-32). Because the range of values that could be encompassed by “about 0.001% to about 25%” is not clearly defined the specification, the limitation of the claims is indefinite.
Claims 42-44 are indefinite in claiming both a product, the skin care preparation, and a method of making it. Claim 42 requires the active step that the cells “are cultured in a medium” (line 2). Claim 43 further requires that the cell suspension “is maintained under conditions inducing or enhancing the production of at least one secondary metabolite” (lines 2-3). When a claim mixes statutory classes, it is unclear when direct infringement occurs. See MPEP 2173.05(p) II. Editing the language to --have been cultured-- in claim 42, and --has been maintained-- in claim 43 to remove the active steps could resolve the indefiniteness.
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 51-52 & 54 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a preparation or a method of producing a preparation wherein part of the callus-derived cells are encapsulated in nanoparticles, does not reasonably provide enablement for a preparation wherein pluripotent Cannabis callus-derived stem cells are encapsulated in or formulated in a form of a nanoparticle. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
Claims 51 & 52 are drawn to a plant-based skin care preparation comprising callus-derived undifferentiated cells of a plant of the genus Cannabis, wherein said preparation is formulated in a form of a nanoparticle. Claim 54 is drawn to a plant-based skin care preparation wherein the preparation is produced by a method comprising the step of encapsulating all or part of the callus-derived cells by means of nanoparticles.
The instant specification defines nanoparticles as particles between 1 and 250 nanometers in size (page 22, lines 11-15). The instant specification teaches an example of a preparation of a liposomal extract wherein the whole cell broth is subjected to high-pressure homogenization (page 34, line 4-page 14). The specification teaches that high-pressurization pursues destruction of cell membranes to release extractable substances and liposomes contain the fat and water soluble fractions of the cells (page 34, lines 25-28). The specification teaches a method of producing a skin care preparation comprising fractions of callus-derived Cannabis cells encapsulated in liposomes but does not teach any example of a preparation comprising cells encapsulated in a nanoparticle.
Cannabis cells in suspension culture can vary in size. Abedini et al (2024) Journal of Photochemistry and Photobiology B: Biology. 254. 112902. (available 3/29/2024 after the effective filing date of the instant application) teaches that UVB illumination treatments led to cultured Cannabis suspension cells with a width as low as 6µm, or a length of 50µm (figure 2). Even if round cells of 6µm in diameter had been observed, such cells would still be 6000 nanometers in size, far larger than the definition of nanoparticles in the instant specification.
Given the size of Cannabis suspension cells, and given the teachings of the instant specification, one of ordinary skill in the art would not reasonably know how to encapsulate callus-derived Cannabis cells within a nanoparticle according to the definition of the instant specification. One of ordinary skill in the art would be required to conduct undue experimentation to attempt to create Cannabis cells of a size capable of being formulated as a nanoparticle, if it is even possible to generate a Cannabis cell of that size. Thus, claims 51, 52 & 54 are not enabled over the full scope of the claims.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 38-40, 42-46, 48, 50 & 53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bimonte et al WO 2020/127056 A1 (published 6/25/2020, hereafter Bimonte; copy provided by Applicant).
Claims 38-40, 42-46, 48, 50 & 53 are drawn to a plant-based skin care preparation comprising callus-derived undifferentiated cells of a plant of the genus Cannabis.
Bimonte discloses that molecules present in Cannabis plants have important physiological functions such as antioxidant, anti-inflammatory, anti-cancer, anti-tumor, anxiolytic, analgesic, and immune-stimulating properties (page 2, lines 16-20).
Bimonte discloses that production of Cannabis extracts from cultivated plants has disadvantages, including cultivated plants are subject to varying environmental and seasonal conditions that may compromise plant growth and significantly affect the production of secondary metabolites, leading to a variable content of cannabinoids in an extract (page 3, lines 19-25). Bimonte also discloses that cultivated plants may be contaminated by toxic substances such as pesticides or fertilizers or by pathogens (page 3, line 26-page 4, line 4).
Bimonte discloses that complete plant regeneration via organogenesis from callus cultures of Cannabis has been established in the art (page 4, lines 10-15) and that the culture cells of the claimed method are totipotent and capable of expressing a wider variety of compounds, in particular secondary metabolites, compared to that present in a differentiated tissue (page 8, lines 20-30).
Bimonte discloses a composition for use in the prevention and treatment of inflammation, or for a cosmetic use, comprising an extract derived from a culture of Cannabis sativa cells at a hydrophilic solvent, including wherein the composition comprises between 0.0001 and 10% of the cell culture extract by weight on the total weight of the composition (page 6, line 15-page 7, line 4). Bimonte discloses that the levels of tetrahydrocannabinol (THC) and cannabinol (CBN) in the extract are preferably comprised between 0.1 and 0.005 ug/g of extract dry weight to produce an optimal inhibitory effect (page 8, line 31 - page 9, line 3). Bimonte discloses that phytocannabinoids such as THC and CBN are produced by Cannabis plants (page 1, lines 12-25). Because the effects produced by cannabinoids appear to be dose-dependent, Bimonte discloses a motivation to modify the dose of cannabinoids in a preparation to change its biological effect (page 1, line 26-page 2, line 15).
Bimonte discloses that the composition can be a cosmetic formulation comprising a cosmetically acceptable vehicle, in the form of a cream, gel, or lotion for skin application (page 7, lines 11-15) and that the extract from the culture of Cannabis sativa cells is capable of preventing or treating neurogenic inflammation, which plays an important role in pathogenesis of skin diseases like hypersensitivity, psoriasis, eczema, rosacea and vitiligo (page 7, line 22-page 8, line 9). Example 5 discloses the capacity of the extract to reduce inflammation in human keratinocyte cells, which are skin cells (page 18, lines 11-21). Bimonte also discloses a pharmaceutical composition comprising the extract with acceptable vehicles for an oral preparation in the form of a powder (page 12, line 29-page 13, line 4).
Bimonte discloses a method comprising placing pieces of wounded leaves on solid substrate and growing in the dark until calluses are obtained (page 14, lines 1-10). Then, calluses are placed in flasks containing culture medium without agar and with kinetin and placed on a shaker until density was reached to carry out cultivation scale up (page 14, lines 12-18). Then, cells were collected through filters to remove the culture medium and the cells were washed (page 14, lines 20-22). Cells were homogenized in ethanol, the homogeneous lysate was centrifuged, and the filtered supernatant was distilled to recover a concentrated extract (page 14, line 24-page 15, line 5).
A plant-based skin care preparation for humans, which reads on a mammalian subject, comprising callus-derived undifferentiated Cannabis sativa cell matter, including in a cosmetic formulation comprising a cosmetically acceptable vehicle in the form of a cream, gel, or lotion for skin application, which reads on a dermatologically acceptable carrier, is therefore disclosed by Bimonte. In light of the definition and use of the term “pluripotent” in the instant specification, the totipotent cells of Bimonte read on the pluripotent cells of the instant invention. Thus, Bimonte anticipates a composition which reads on claims 38 & 39.
The composition was capable of reducing inflammation in human skin cells, which reads on promoting or maintaining health of mammalian skin cells (claim 40). An oral preparation with a powder formulation reads on a preparation in a form of a dry powder (claim 50).
The method of culturing callus-derived cells taught by Bimonte comprises the steps of and therefore anticipates the method of producing a preparation of instant claim 53 and a preparation wherein the cells are cultured in a medium, forming a cell suspension (claim 42), and wherein the cells are separated from the medium (claim 44).
The preparation of Bimonte comprises the secondary metabolites THC and CBN, which are endogenous to Cannabis sativa (instant claims 45, 46, 48). Because the secondary metabolites were produced during the culture of the cell suspension, this reads on and anticipates the cell suspension being maintained under conditions that induce the production of at least one secondary metabolite (claim 43).
Claims 38-40, 42-46, 48, 50 & 53 are anticipated by Bimonte.
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.
Claim(s) 38-46 & 48-54 are rejected under 35 U.S.C. 103 as being unpatentable over Bimonte et al WO 2020/127056 A1 (published 6/25/2020, hereafter Bimonte; copy provided by Applicant) in view of Morus et al (2014) Acta Poloniae Pharmaceutica. 71(5): 701-707 (published September 2014, hereafter Morus; copy provided by Applicant)
Claim 41 is drawn to a preparation wherein the concentration of the cells is from about 0.001% to about 25% w/w based on a dry weight of the total weight of the preparation. Claims 51, 52 & 54 require that the preparation is formulated in a nanoparticle or the cells are encapsulated by means of nanoparticles. Claim 49 is drawn to the preparation wherein the pluripotent cells comprise WUS transcription factors.
The teachings of Bimonte are presented above and incorporated herein. Bimonte does not teach a composition comprising intact pluripotent cells. Bimonte does not teach that the cells comprise WUSCHEL transcription factors.
Morus teaches that the ability of plant stem cells for dedifferentiation into pluripotent cells is used in the production of care preparations or cosmetic procedures including for the elimination of human skin aging symptoms (page 703, right column, paragraph 3). Morus teaches a commercial product including stem cells from the Uttwiler Spatlauber apple tree (page 705, left column, paragraph 3) which is produced by mixing the culture in a suspension including liposomes and subjecting to high-pressure homogenization, wherein stem cell components are released and closed inside liposomes or dissolved in a water phase (page 704, right column, paragraph 3). Morus teaches the use of the extract in the oil in water emulsion in a cream for treating crow’s feet (page 706, left column, paragraphs 2-3). Morus teaches another product which is a powder made from stem cells using biomass homogenization and that the biomass processing step depends on the product type and target designation (page 704, right column, paragraph 3). Morus teaches that new plant cell lines may be generated (page 704, left column, paragraph 3) and teaches multiple species of plants which are used for plant cell culture (page 704, left column, paragraph 1).
Morus teaches that proliferation and differentiation of plant stem cells are controlled by factors such as the gene expression product WUSCHEL, which affects an increase of stem cell numbers (page 703, left column, paragraph 3). WUSCHEL protein is responsible for turning somatic cells back into stem cells (page 703, right column, paragraph 2).
Before the filing date of the instant application, it would have been obvious to one of ordinary skill in the art to modify the composition of Bimonte to use the formulation of Morus, wherein the stem cell culture is processed so that the stem cell components are closed inside liposomes. One of ordinary skill in the art would have been motivated to use the formulation taught by Morus in order to form a cream preparation. One of ordinary skill in the art would have reasonable expectation of success, because Morus teaches that the final step of processing the plant stem cell lines depends on the product type desired.
In light of Morus, a preparation wherein the method of producing it comprises the steps of encapsulating part of the callus-derived cells by means of nanoparticles and incorporating the nanoparticles into the preparation is obvious (instant claim 54) as is the preparation formulated in the form of a liposome nanoparticle (instant claims 51 & 52). It would also be obvious for the cells to comprise WUSCHEL transcription factors (instant claim 49) because WUS is responsible for the proliferation of stem cells, and stem cells must be cultured in medium for the preparation.
Bimonte’s composition comprises between 0.0001 and 10% of the cell culture extract by weight on the total weight of the composition, which overlaps with and makes obvious a concentration of about 0.001% to about 25% w/w based on dry weight of the total weight of the preparation (claim 41). Claims 38-40, 42-46, 48, 50 & 53 are obvious over Bimonte as presented above.
Claim(s) 38-48, 50 & 53 are rejected under 35 U.S.C. 103 as being unpatentable over Bimonte et al WO 2020/127056 A1 (published 6/25/2020, hereafter Bimonte; copy provided by Applicant) in view of Sayre et al CN 111465700 A (published 7/28/2020, attached with an English translation of the description; hereafter Sayre).
Claim 47 is drawn to the skin care preparation wherein the preparation comprises at least 0.05% total cannabinoids out of the total dry weight of the callus-derived pluripotent cells.
The teachings of Bimonte are presented above. They do not teach 0.05% total cannabinoids out of the total dry weight of the callus-derived pluripotent cells.
Sayre teaches a method of producing sterile plant cell suspension cultures and introducing genetic modifications which allow the plants to transiently modify the chemical structure of cannabinoid compounds, which can accumulate at concentrations higher than natural levels without causing harm to cultured yeast and/or plant cells and can be harvested and administered for pharmaceutical applications (paragraph [0031]).
Sayre teaches the motivation to transform Cannabis cell cultures, because cannabinoids are cytotoxic; the inability to store cannabinoids outside the cells in trichomes in cannabis cell cultures means that accumulation of cannabinoids will be toxic to the cultured cells and hamper the scale up of cultures to industrial production levels (paragraph [0021]).
Sayre teaches modification of Cannabis cell culture, including introduction of one or more exogenous glycosyltransferases from tobacco or other non-cannabis plants to saccharify cannabinoids in vivo (paragraph [0132]), genetically modifying the cannabinoid synthase gene to remove or destroy the extracellular N-terminal target so that the synthase can be retained in the place cell (paragraph [0156]), or overexpression of at least one Myb transcription factor (paragraph [0169]). Sayre demonstrates that glycosylation and hydroxylation of cannabinoids is possible in Cannabis sativa by performing Agrobacterium infiltration of constructs into various strains of Cannabis sativa and observing synthesis and accumulation of hydroxylated and glycosylated cannabinoids (paragraph [0206], table 8).
Sayre teaches that the invention may include topical formulations for transdermal delivery of water-soluble cannabinoids (paragraph [0251], Sayre claim 591). Additionally, Sayre teaches that the specific dosage for a patient depends on various factors and that the concentration of the therapeutic active ingredient in the formulation may be about 0.1-100% by weight (paragraph [0196]). Specifically, Sayre teaches a cannabinoid liniment comprising water, isopropyl alcohol solution, and cannabinoids, wherein the composition comprises about 0.5-2.5% by weight of cannabinoids (Sayre claims 630, 633).
Before the filing of the instant application, one of ordinary skill in the art would have been motivated to modify the method of Bimonte to increase the cannabinoid content produced by cultured Cannabis cells. One of ordinary skill in the art would have been motivated to modify the Cannabis cells to increase the total cannabinoids out of the total weight of the cells because Sayre teaches therapeutic formulations applied to the skin in which the active ingredient cannabinoids are about 0.1-100% by weight, higher than the requirement of the instant claims. One of ordinary skill in the art would have had reasonable expectation of success, because the expression of the transgenes of Sayre in C. sativa leaves lead to accumulation of hydroxylated and/or glycosylated cannabinoids. Thus, claim 47 would have been obvious to one of ordinary skill in the art.
Bimonte’s composition comprises between 0.0001 and 10% of the cell culture extract by weight on the total weight of the composition, which overlaps with and makes obvious a concentration of about 0.001% to about 25% w/w based on dry weight of the total weight of the preparation (claim 41). Claims 38-40, 42-46, 48, 50 & 53 are obvious over Bimonte as presented above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Victoria L DeLeo whose telephone number is (703)756-5998. The examiner can normally be reached M-F 8:00am-4pm EDT.
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/VICTORIA L DELEO/Examiner, Art Unit 1662
/Anne Kubelik/Primary Examiner, Art Unit 1663
