DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 12/22/2025 has been entered. Claims 1-44 are pending in this application. Claims 3 and 11-44 are withdrawn. Claims 1, 2, and 4-10 are currently under examination.
Priority
This application is a 371 of PCT/CA2021/050769 filed on 06/04/2021 and claims benefit of US PRO 63/035,017 filed on 06/05/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 63/035,017, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1, 2, and 4-10 recite “if the cannabinoid is CBD and the one or more derivatization sites is a primary hydroxyl group, the spacer is not O”, “the spacer is selected from the group consisting of: O; a linear or branched, substituted or unsubstituted alkyl chain or unsaturated carbon chain; C=O; O=C-C=O; O=C-(CH2)nC=O, where n is any integer number; O=C-(CR2)nC=O, where R is independently H, alkyl, halide, CN, NH2, OH, or COOH; NH-CO; NH-alkyl; substituted or unsubstituted alkyl-C=O, alkyl-NHC=O, alkenyl-C=O, alkenyl -C=O, alkenyl-NH-C=O, alkenyl-C=O, alkynyl-C=O, alkynyl-C=O, alkenyl-NH-C=O, and alkynyl-C=O; cycloalkyl, cycloalkenyl, and heterocyclic structures; azole derivatives; and triazole, optionally substituted with alkyl, carbonyl, or alkoxy moieties”, “degree of covalent conjugation”, “synergistic compound is selected from the group consisting of: non-steroidal anti-inflammatory drugs (NSAIDs ), functional fatty acids (FA), amino acids (AA), oligosaccharides, sugars, and vitamins (or diclofenac sodium, oleic acid, stearic acid, linolenic acid, palmitic acid, caproic acid, arachidonic acid, anandamide, phosphatidylethanolamine, leucine, isoleucine, lysine, valine, glucosamine, and vitamin C)”, and/or “chondroitin sulfate, chitosan, polyacrylic acid carboxypolymethylene, carboxymethylcellulose, and hyaluronate”, which are not disclosed or supported by the prior-filed Application No. 63/035,017. Thus, the priority date of claims 1, 2, and 4-10 is 06/04/2021.
Election/Restrictions
Applicant's election with traverse of Group I invention (claims 1-13) and species (Compound 1(a):
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, the polysaccharide backbone is hyaluronic acid, the spacer is NHCO, and the cannabinoid is CBD-A) in the reply filed on 12/22/2025 is acknowledged. The traversal is on the ground(s) that “there is no discussion of how the cannabinoid is "incorporated", much less any suggestion of creating a conjugate. There is no reference back to the prodrug section or discussion of a "linking moiety"… There is no indication in Bevier that HA is particularly suitable over any of the others in the long list of polymers… it would require impermissible hindsight with knowledge of the invention as disclosed in the present application, for a person skilled in the art to assemble the teachings from these three different sections of Bevier to arrive at the technical feature” (p. 17, para. 4; p. 18, para. 1 to 2). This is not found persuasive because the disclosures “chemically modified cannabinoid receptor binding agent comprises a cannabinoid receptor binding agent linked to a polymer via a linking moiety, where the linking moiety is capable of hydrolysis, such as by an oral hydrolase” and “Natural polymers may include glycosaminoglycans such as hyaluronic acid, chondroitin sulfate A, chondroitin sulfate C, dermatan sulfate, keratan sulfate, keratosulfate, chitosan, and derivatives thereof” by Bevier of record, made in the Requirement for Restriction/Election mailed on 07/03/2025, indicate that hydrolysis of a covalent bond, including an ester bond, requires an oral hydrolase and the listed glycosaminoglycans are encompassed by the claimed “a polysaccharide backbone of hyaluronic acid or an analog or derivative thereof”. “Lack of unity of invention may be directly evident “ a priori ,” that is, before considering the claims in relation to any prior art, or may only become apparent “ a posteriori ,” that is, after taking the prior art into consideration. For example, independent claims to A + X, A + Y, X + Y can be said to lack unity a priori as there is no subject matter common to all claims. In the case of independent claims to A + X and A + Y, unity of invention is present a priori as A is common to both claims. However, if it can be established that A is known, there is lack of unity a posteriori, since A (be it a single feature or a group of features) is not a technical feature that defines a contribution over the prior art.“ (see MPEP § 1850 [R-01.2024], 37 CFR 1.475, II). Claims 3 and 11-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Thus, claims 1, 2, and 4-10 are currently under examination.
The requirement is still deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 09/13/2023 has been considered.
Claim Objections
Claims 1, 2, 4-6, and 10 are objected to because of the following informalities: In claim 1, spell out the abbreviated “CBD” (line 6) to “cannabidiol (CBD)”. In claim 2, insert the missing word “each” immediately before the recitation “R is” (line 4) because there are two R; delete the redundant “alkenyl-C=O,” (line 6, two occurrences), “alkynyl-C=O,” (lines 6 to 7, two occurrences), and “alkenyl-NH-C=O,” (line 7), which have been recited in the preceding clause; insert the conjunction “or” immediately before the recitation “alkynyl-C=O” (line 6); and change the incorrect recitation “and heterocyclic” (line 7) to “or heterocyclic”. In claim 4, change the incorrect recitation “claim 2, comprising” (line 1) to “claim 2, wherein the conjugate comprises” to become proper dependent claim format; and replace the incorrect conjunction “and” (line 2) with “and/or” because the amide-based spacer and the ester-based spacer are present alone or together in the conjugate. In claim 5, change the incorrect conjunction “and” (line 2) to “and/or” because the amide-based spacer and the ester-based spacer are present alone or together in the conjugate. In claim 6, change the incorrect recitation “claim 2, comprising” (line 1) to “claim 2, wherein the conjugate further comprises” to become proper dependent claim format and to indicate that synergistic compound is further attached in addition to the cannabinoid. In claim 10, delete the redundant recitations “cannabigerol (CBG),” (line 4) and one of “cannabichromenic acid (CBCA),” (line 8), which have been recited in the preceding clause; and delete the recitation “, mixture” (line 21), which is redundant with “combinations” (line 21). Appropriate correction is required.
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, and 4-10 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 2, 4, and 6-8 depend from claim 1.
Claims 1, 9 and 10 recite “derivatives” (line 2 of claims 1 and 9; line 21 of claim 10), which is not defined and thus the scope is not clear. Applicant is advised to insert the word “structural” immediately before the recitation “derivatives” specifying the scope to structural modification.
The term “high degree” or “low degree” in claim 5 is a relative term which renders the claim indefinite. The term “high degree” or “low degree” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant is advised to change the above recitations to “suitable degree”.
Claim 9 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: The recitations “polyacrylic acid” and “carboxypolymethylene” do not have a polysaccharide backbone and thus do not meet the requirement of a polysaccharide backbone in the preceding claim 1. Applicant is advised to delete the above recitations.
Claim Rejections - 35 USC § 102
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.
Claims 1, 2, 4, 5, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Peet et al. (US 2017/0362195, Dec. 21, 2017, hereinafter referred to as Peet ‘195).
With regard to structural limitations “a cannabinoid-hyaluronic acid conjugate, comprising a polysaccharide backbone of hyaluronic acid or an analog or derivative thereof, having a cannabinoid attached by way of a spacer (or C=O; or O=C-(CR2)nC=O, where each R is independently H, alkyl, or NH2; or one or more amide-based and/or ester-based spacers) to one or more derivatization sites of the polysaccharide backbone selected from the group consisting of: a primary hydroxyl group, a secondary hydroxyl group, and a carboxyl group, wherein the spacer is not O if CBD is attached to the primary hydroxyl group of the polysaccharide backbone (or the cannabinoid is delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), or cannabidiolic acid (CBDA))” (claims 1, 2, 4, 5, and 10):
Peet ‘195 disclosed a cannabinoid prodrug according to Formula Ia (
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) and Formula Ila (
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), synthesized by contacting a compound according to Formula I (
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) or Formula II (
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) with an activated-Y-Z reagent. For Formula I or Formula II compounds R is -H, substituent R1 is -H, -COOR, or -COO(C1-C5)alkyl, R2 is a group selected from (C1-C10)alkyl, (C2-C10)alkenyl, (C2-C10)alkynyl, (C3-C10)cycloalkyl, (C3-C10)cycloalkylalkylene, (C3-C10)aryl, and (C3-C10)arylalkylene, and substituent R3 is -H, or (C1-C5)alkyl. For cannabinoid compounds, alternatively, -Y -Z is an oligosaccharide. In one embodiment, -Y-Z is a -Y-oligosaccharide. Illustrative "Y" groups include a L-amino acid residue, a D-amino acid residue, a ß-amino acid residue, or a γ-amino acid residue. Exemplary activated forms of a carboxylic acid include acid halides, acid anhydrides, alkyl esters, and aryl esters. In some instances, a first compound having a carboxylic acid or an activated form of a carboxylic acid couples to a second compound having an amine or hydroxyl group using one or more coupling reagents (pages 2/25 to 3/25, [0006-0008 and 0015]; page 6/25, [0052]). Illustrate of the category of oligosaccharide prodrugs are mannose, N-acetyl glucosamine (GlcNAc), galactose, and sialic acid (page 7/25, [0070]).
Thus, these teachings of Peet ‘195 anticipate Applicant’s claims 1, 2, 4, 5, and 10 because (a) the oligosaccharide of Peet ‘195 is encompassed by the claimed analog or structural derivative of hyaluronic acid polysaccharide backbone, and (b) the activated carboxylic acid of an oligosaccharide, an oligosaccharide containing N-acetyl glucosamine or sialic acid, or amino acid-oligosaccharide would reacts with OR, R is H, of Formula I or Formula II to form linkage of O-C=O or O=C-(CR2)nC=O, where each R is independently H, alkyl, or NH2.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, and 4-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bellini et al. (US 8,575,129, Nov. 5, 2013, hereinafter referred to as Bellini ‘129) in view of Svarovsky et al. (US 2021/0332004, Oct. 28, 2021, US filed on Apr. 13, 2021 and benefitted from Provisional application No. 63/014,471, filed on Apr. 23, 2020, hereinafter referred to as Svarovsky ‘004).
With regard to structural limitations “a cannabinoid-hyaluronic acid conjugate, comprising a polysaccharide backbone of hyaluronic acid or an analog or derivative thereof (or hyaluronate or chitosan), having a cannabinoid attached by way of a spacer (or one or more amide-based and/or ester-based spacers; or further comprising synergistic compound, selected from functional fatty acids (FA) or stearic acid, attached by way of a spacer) to one or more derivatization sites of the polysaccharide backbone selected from the group consisting of: a primary hydroxyl group, a secondary hydroxyl group, a carboxyl group, and an acetamido group, wherein the spacer is not O if CBD is attached to the primary hydroxyl group of the polysaccharide backbone (or elected Compound 1(a):
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, the polysaccharide backbone is hyaluronic acid, the spacer is NHCO, and the cannabinoid is CBD-A)” (claims 1, 2, and 4-10):
Bellini ‘129 disclosed amides of hyaluronic acid and derivatives thereof having the following general formula:
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, wherein R= NR6R7, or alcoholic group of the aliphatic series, OH, O, alcoholic group of hyaluronic acid, amino group of deacylated hyaluronic acid; R1, R2, R3, R4,= H, SO3, acyl group derived from a carboyxylic acid of the aliphatic series, -CO-(CH2)2-COOY; Y= negative charge, or H; R5= -CO-CH3, H, SO3, acyl group derived from a carboxylic acid of the aliphatic series, acylic group of hyaluronic acid; R6 is H or a aliphatic group, substituted or unsubstituted; R7 is H or a aliphatic group, substituted or unsubstituted; wherein at least one of R or R5 forms an amide group. Of particular interest are the forms for the transport and release of substances or of biologically active substances. Other polysaccharide polymers include chitin, chitosan, glycosaminoglycan (page 5/13, col. 2, lines 34-67; page 7/13, col. 5, lines 20-22 and 45-48). Example 1, Preparation of Partially N-Deacetylated Hyaluronic Acid in the Form of Sodium Salt (DHA/Na). One gram of sodium hyaluronate, with a mean molecular weight of 600 Kda, is solubilized in 50 ml of a 1% solution of hydrazine sulphate in hydrazine monohydrate. Example 2, Preparation of the Salt of Hyaluronic Acid Partially N-Deacetylated with Tetrabutylammonium (DHA/TBA). Example 6, Preparation of p-NO2-Phenylester of Stearic Acid (Acylating Agent). Example 11, Preparation of Partially N-Acylated Hyaluronic Acid (with the Derivative of Stearic Acid). One gram (1.6 mmol) of DHA/TBA (26% deacetylation) is solubilized in 50 ml of NMP, after which 6 ml of a 10% solution of p-NO2-phenylester of stearic acid (prepared according to example 6) in NMP is added.
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(page 8/13, col. 7, lines 29-34; col. 8, lines 1-4; page 9/13, col. 9, lines 15-19; page 10/13, col. 11, lines 1-24).
Bellini ‘129 did not explicitly disclose the limitations “Compound 1(a):
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”, required by claims 1, 2, 4, 5, and 10.
Svarovsky ‘004 disclosed use of mPEG-amine instead of mPEG-alcohol for improving the physiological stability of the mPEG-drug conjugate (e.g. amide instead of an ester bond). Cannabinoid is made more water soluble by attaching ester PEG, once in the body the ester bond is cleaved by endogenous esterases to release native cannabinoid. In embodiments, the acidic version of cannabinoid molecules is used for linkage with PEG. Reaction between the carboxyl group on the cannabinoid acid and another function group on the PEG linker, such as an amine group, is easier to create. The result also preserves the cannabinoid molecule, in particular the functional groups on the cannabinoid molecules. In the cannabidiolic acid (
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) molecule, the carboxylic group is not part of the cannabidiol molecule (pages 11/29 to 13/29, [0086, 0090, and 0091]). In embodiments, a cannabinoid-PEG linked molecule may also be a trifunctional cannabinoid-PEG linked molecule. Direct conjugation of CBDA with PEG-7 is achieved by reacting CBDA with mPEG7-amine in 72% yield. Synthesis of CBDA-PEG7 through CBDA-NHS (
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) Ester Preparation: CBDA-NHS ester reacts with mPEG7-amine in a dioxane solution buffered by pH 10 borate buffer. NHS is returned to its original state as N-Hydroxysuccinimide (page 16/29, [0107]; pages 19/29 to 20/29, [0122 0123, and 0126-0128]).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine the Partially N-Acylated Hyaluronic Acid (with the Derivative of Stearic Acid) of Bellini ‘129 with amide linkage of CBDA in view of Svarovsky ‘004 to achieve stable dual or multiple releases of active substances from the polymer or hyaluronic acid, as described above. Also, one of skill in the art would have a reasonable expectation that by combining the Partially N-Acylated Hyaluronic Acid (with the Derivative of Stearic Acid) of Bellini ‘129 with amide linkage of CBDA in view of Svarovsky ‘004, one would achieve Applicant’s claims 1, 2, and 4-10.
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691