DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/24/2024 is acknowledged and has been considered except where lined through.
Claim Objections
Claims 44-46, 48-49 and 51 are objected to because of the following informalities:
Both claims 46 and 48 limit the cannabinoid of claim 43 to cannabidiol (CBD) or a CBD analogue, wherein the CBD analogue includes CBD. As such, it is suggested that Applicants amend the claims to remove inclusion of CBD within the selection of analogues.
Claim 51 lists a number of esterification agents and “combination the same”. In the instant case, it is unclear what “of same” means. It is suggested that Applicants amend to recite “combinations thereof”.
Claims 44-45 and 49 both refer to a compound of formula (II). However, the chemical structure represented by formula II are different in claims 44-45 vs. claim 49.
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 43-62 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.
Regarding claim 43, recites a specific formula for a cannabinoid-phospholipid conjugate having the general formula (I):
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, wherein A is a cannabinoid and PL is a phospholipid, but also recites a conjugate in more generic terms, e.g. wherein the cannabinoid (A) is covalently linked, via a cleavable linker, to a polar head group of the PL. As such, it is unclear whether
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is the cleavable linker or there is some other cleavable linker that is present. Moreover, it is unclear whether the “oxygen” of the ester is part of the cannabinoid or whether it is from the maleic anhydride. For example, cannabidiol contains two hydroxyl groups (see claims 44 and 45) and it appears that the conjugation is through one of these oxygens (see claim 53). If this is the case, claim 43 is confusing since it could be interpreted that the oxygen is coming from the maleic anhydride vs. the cannabinoid.
Regarding claims 45-46, both claims 45-46 recite the conjugate of claim 43, wherein said cannabinoid (A) is linked to said linker at either position C2a or C6a of thereof according to a numbering in free cannabidiol (CDB) of formula II. However, it is unclear whether the claims are limited to cannabidiol or if it is a generalized reference to cannabinoid “numbering”. Additionally, it is unclear whether the “link” occurs at the C2a or C6a carbon or actually at the hydroxyl groups already present at those positions. If the latter is correct, it is unclear whether the resulting linker would be a O-O bond? For prior art purposes, the examiner is interpreting the compound to be CBD and the bond occurs through the O of the cannabinoid.
Regarding claims 49 and 51, claim 49 recites “…wherein said PL has the general formula II:
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Thus, it appears that the PL can be linked to the cleavable linker directly through an oxygen or via a polar head group. As such, the oxygen and polar headgroup appear to be distinct from one another. However, claim 43, from which claim 49 depends, does not recite that the cleavable linker is linked to PL via an oxygen with no polar headgroup. In contrast, claim 43 limits the cleavable linker to being attached through the polar headgroup of the PL.
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 43-49 and 56-62 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 43 recites a cannabinoid-phospholipid conjugate having the general formula (I):
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, wherein A is a cannabinoid and PL is a phospholipid and wherein the cannabinoid (A) is covalently linked, via a cleavable linker, to a polar head group of the PL. As such, the claims encompass a genus of polar headgroups.
The specification teaches that the cannabinoid is linked to the polar headgroup of the phospholipid via a linking portion/segment, referred to herein as the linker portion. To allow this linkage, the polar headgroup of the phospholipid is one that is capable of, accordingly to some examples of the present disclosure, reacting with maleic anhydride (page 9, lines 6-9). Moreover, the specification teaches that the polar head group is selected from the group consisting of serine, ethanolamine, inositol or glycerol (page 9, lines 13-15). The specification further provides a specific example, wherein DLPE (which contains an ethanolamine) is maleic anhydride and further conjugated to cannabidiol creating a compound having the formula
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. While the specification provides this single example, the specification appears to be silent on any other polar headgroups other than those listed which are capable of reacting with maleic anhydride.
The state of the art at the time of filing recognizes that cyclic anhydrides are powerful tools for bioconjugation and smart delivery. For example, Spanedda et al. (Bioconjugate Chemistry 2021; 32; 482-496) teach that cyclic anhydrides including maleic anhydride are potent tools for bioconjugation and therefore, they are broadly used in the functionalization of biomolecules and carriers (abstract). In particular, Spanedda et al. teach that cyclic anhydrides are generally reactive with amines, alcohols and phenols (page 483, Scheme 1). Thus, Spanedda et al provides guidance for the reactivity of cyclic anhydrides with amines, alcohols and phenols, Spanedda is silent on the incorporation of these functional groups into polar headgroups of phospholipids.
Thus, while the claims encompass broadly, polar headgroups, the specification only appears to provide written description for polar head group of phospholipids selected from the group consisting of serine, ethanolamine, inositol or glycerol.
Conclusion
Therefore, No claim is allowed.
The compounds encompassed by claims 43-62 appear to be free of the prior art. The closest prior art at the time of filing can be considered to be Diverse Biotech INC (WO2020/263893A1, 2020-12-30) or Integrated Nanotherapeutics INC (WO2020/191477A1, 2020-10-01, IDS) or Ramot At. Tel-Aviv University LTD (WO2021/205459A1, 2021-10-14, IDS). Diverse Biotech INC teaches multifunctional conjugate molecules in which at least one therapeutic agent is covalently linked to a cannabinoid (abstract). Regarding the cannabinoid, Diverse Biotech teaches a number of example Cannabinoids such as:
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, but generally teaches that the cannabinoid component can be provided by any cannabinoid that contains a hydroxy or carboxylic acid group to which the therapeutic agent component can be attached (paragraphs 44 and 45). While Diverse Biotech teach a number of cannabinoid conjugates, the conjugates encompass at least one additional therapeutic agent and not the phospholipid or maleic acid linker as presently claimed. Similarly, Integrated Nanotherapeutics INC teaches a number of cannabinoid conjugated to lipids having the following structures:
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(page 103). However, the prior art differs from the claimed invention in the use of maleic anhydride to form a linker between the cannabinoid and phospholipid, as well as, conjugation of cannabinoids to phospholipids through the polar head group and there is no suggestion or motivation to make these two substitutions. Ramot At. Tel-Aviv University teaches CBD-phospholipid moieties having the formula:
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, wherein A or B is L-P, wherein L is a linking moiety and P is a phospholipid (page 21, lines 9-17). The prior art does not specifically teach that L is
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and P is linked to L via the polar headgroup of P. Moreover, considering that that
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has an ester linkage and CBD does not contain a reactive functional group at A or B, one would have to add additional reactive functional group. However, the prior art does not teach or suggest such modification, nor does the prior art teach conjugation with the linker through a polar headgroup or said linker.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRANDON J FETTEROLF whose telephone number is (571)272-2919. The examiner can normally be reached M-F 6AM-4PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey S Lundgren can be reached at 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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BRANDON J. FETTEROLF, PHD
Primary Patent Examiner
Art Unit 1626
/BRANDON J FETTEROLF/Primary Examiner, Art Unit 1626
Prosecution Insights