DETAILED ACTION
Election/Restrictions
Applicant’s election of carvacrol, ester that is enzymatically cleavable and EDTA in the reply filed on July 21 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
Claims 1-36, 40, 42, 45, 48-49, 54, 58, 61, 64 and 70-102 were/stand cancelled. Claims 37-39, 41, 43-44, 46-47, 50-53, 55-57, 59-60, 62-63, 65-69 and 103-107 are pending in the application. Claims 51-53, 55-57, 59-60, 62-63 and 65-69 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention (species), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 21 2026. Accordingly, claims 37-39, 41, 43-44, 46-47, 50 and 103-107 are being examined on the merits herein.
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
This application is a DIV of 16/981,072 (09/15/2020) which is a 371 of PCT/US2019/022408 (03/15/2019) which claims benefit of 62/644,219 (03/16/2018) as reflected in the filing receipt issued on April 15 2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 21 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 43 is objected to because of the following informalities: the recitation “cyclohexane 1,2,4,-5, tetracarboxylic acid” is written incorrectly. The chemical name should be written as “cyclohexane 1,2,4,5-tetracarboxylic acid”. Appropriate correction is required.
Claim 107 is objected to because of the following informalities: there are two step (c) in the claim. 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 37-39, 41, 43-44, 46-47, 50 and 103-107 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 50 recites the pro-payload molecule is dicarvacrol-EDTA. While the structure is not indefinite as Figure 4 clearly shows the structure. As evidenced by the registry number entry for this compound in CAS Scifinder, this molecule is water soluble at a pH of 10. Therefore, the scope of water-insoluble is unclear. There is no definition of this term in the instant specification. Is the scope interpreted to encompass chemical compounds in which in any aspect of pH or temperature or concentration the compound is water-insoluble? The metes and bounds of the recitation “water-insoluble” is unclear.
Therefore, in light of this confusion, the claims are indefinite as the claims all recite the pro-payload is water-insoluble.
Claim Rejections - 35 USC § 112
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 37-39, 41, 43-44, 46-47 and 103-107 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The specification discloses chemicals, such as dicarvacrol-EDTA, dicarvacrol-cyclohexane which meet the written description and enablement provisions of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. However, claim(s) 37-39, 41, 43-44, 46-47 and 103-107 is(are) directed to encompass any payload molecule linked to any scaffolding molecule that forms a water-insoluble pro-payload molecule which only correspond in some undefined way to specifically instantly disclosed chemicals. None of these payload molecule and scaffolding molecule meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus encompassed by the claim. Note: MPEP 2163.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, (Fed. Cir. 1991), makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886, 1892 (CAFC 2004), further supports this by stating that:
The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice…. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added).
With the exception of the above specifically disclosed chemical structures, the skilled artisan cannot envision the detailed chemical structure of the encompassed pro-payload, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The chemical structure itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (Fed. Circ. 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016, (Fed. Cir. 1991). In Fiddes v. Baird, 30 USPQ2d 1481, 1483, (Bd. Pat. App. & Int. 1993), claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404, 1405 (Fed. Cir. 1997) held that:
...To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.
Furthermore, to the extent that a functional description can meet the requirement for an adequate written description, it can do so only in accordance with PTO guidelines stating that the requirement can be met by disclosing “sufficiently detailed, relevant identifying characteristics,” including “functional characteristics when coupled with a known or disclosed correlation between function and structure.” Univ. of Rochester v. G.D. Searle, 68 USPQ2d 1424, 1432 (DC WNY 2003).
Looking to the instant specification, the description of Fig. 2 states that it is a diagram depicting the claimed method of creating water-insoluble pro-payload molecules (Fig. 2A). Looking to Fig. 2A states that the payload is water soluble:
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. This Figure indicates that attachment of a backbone converts a water soluble payload into a water-insoluble payload. However, this is going to depend on the particular factors of each material. The instant claims do not limit the payload or scaffold (aka backbone) to require one to be water-insoluble. Thus the claims encompass payload and scaffolding molecules which are both water soluble. Looking to the elected species, carvacrol is water insoluble and EDTA is only slightly or sparingly soluble at lower pH. The CAS entry of the instantly elected pro-payload (dicarvacrol-EDTA) is shown as being water insoluble up to pH 9. However, the predicted solubility at pH 10 is it is water soluble (see page 2, mass solubility).
Therefore, the conditions at which the water solubility is measured matters for compounds like the elected species.
Other scaffolding molecules taught include polyamidoamines, such as taught by Shadrack et al. (Molecules 2018), enhance solubility of small molecules. Therefore, use of this particular scaffolding with other highly soluble molecules like nucleic acids would be expected to produce a water-soluble pro-payload not a water insoluble pro-payload.
Since the poly(aminoamine) can be large molecules (see Shadrack et al.), even if the payload is water insoluble there is no expectation that the resulting pro-payload is necessarily water-insoluble.
Even if the payload and/or scaffolding is water insoluble, if the other is water soluble, the joining of the two does not necessarily result in a water-insoluble pro-payload.
The only way to ensure a water-insoluble payload is to select both a water-insoluble payload and a water-insoluble scaffold but this is not required by the claims.
Therefore, only the above chemically structurally defined chemicals, but not the full breadth of the claim(s) meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. The species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC § 112 is severable from its enablement provision. (See page 1115.)
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claim 37-39, 41, 43-44, 46-47, 50 and 103-107 are rejected under 35 U.S.C. 103 as being unpatentable over Abrey et al. (WO2016124927) in view of Zhou et al. (Journal of Food Protection, 2007), Klahn et al. (Nat. Prod. Rep., 2017) and Uhrich et al. (WO2008128193).
Applicant Claims
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system; and (c) administering to a subject the particulate delivery system under conditions that permit internalization of the particulate delivery system in a cell of the subject, cleavage of the cleavable linker, and release and delivery of the payload molecule within the cell of the subject.
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system; and (c) administering the particulate delivery system to a subject under conditions that permit release and delivery of the payload molecule in the subject.
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system;(c) formulating the particulate delivery system as a pharmaceutically acceptable composition; and(c) administering the pharmaceutically acceptable composition to a subject under conditions that permit release and delivery of the payload molecule in the subject.
As elected the pro-payload molecule is dicarvacrol-EDTA.
The examiner notes that the recitation “optionally” is interpreted as not being required. Therefore the BRI of all the claims that contain the word optionally is that the limitations following the recitation optionally are not required.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Abrey et al. is directed to the encapsulation of high potency active agents. Claimed is a composition comprising a microparticle component and a highly potent active agent encapsulated in the microparticle (claim 1). As claimed the composition can be co-encapsulated with a second active agent (claim 37) which can be carvacrol (claim 39). The microparticles are hollow glucan particles including hollow cell wall particles (claims 51-52). As claimed the cell wall particle can comprise 75-85% w/w glucan (claim 61) and the amount of beta 1,3-glucan is from about 25 to about 90 w/w% (claim 62) including about 25-35 % beta 1,3-glucan (claim 63). Claimed is a method of delivering a highly potent active agent to a recipient comprising the steps of (i) providing a microparticle component; (ii) contacting the microparticle with a highly potent active agent component wherein the highly potent active agent component becomes, at least partially, encapsulated within the microparticle; (iii) contacting the recipient with the microparticle (claim 82). The recipient can be a mammal (claim 83). Claimed is a method of delivering a fragrance comprising administering an effective amount of a highly potent active agent in the form of a composition for formulation comprising a highly potent active agent component encapsulated in a microparticle composition wherein the highly potent active agent comprises a fragrance (claim 112). The same method with a flavoring is claimed (claim 113). Abrey et al. teaches that glucan particles are readily available, biodegradable and substantially spherical. Preparation of such particles are known in the art (page 13). A key attribute of these hollow microparticles is that they may contain more than 10% lipid w/w and are very effective at absorbing active agents (page 15). Hollow glucan particles are generally formed from relatively inert materials and are porous (page 19).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Abrey et al. suggest actives can be encapsulated in yeast cell wall particles with active agents which include carvacrol and the particles can be used to deliver the material to a recipient, Abrey et al. does not expressly teach a pro-payload molecule with is dicarvacrol-EDTA. However, this deficiency is cured by Zhou et al., Klahn et al. and Uhrich et al.
Zhou et al. is directed to the synergistic effect of thymol and carvacrol combined with chelators and organic acids against Salmonella Typhimurium. Salmonella Typhimurium is a major concern and represents one of the most important Salmonella serovars implicated in gastroenteritis outbreaks (page 1704). Carvacrol has found to be synergistic with preservative systems. Chelators such as EDTA also has been reported to be synergistic with other antimicrobials (page 1704, last paragraph). Carvacrol plus EDTA was found to be synergistic (page 1707; table 3, page 1708 2nd-3rd paragraph).
Klahn et al. is directed to bifunctional antimicrobial conjugates and hybrid antimicrobials. The hybridization of two antimicrobial drugs can be associated with several advantages. The dual targeting can lead to an enhanced antibacterial potency due to synergistic effects of the single components. Hybrid antimicrobials can surpass the efficacy of their component drugs, either alone or in combination, by maintaining their antibacterial activity against pathogens that are resistant to ne or both components of the hybrid antimicrobial and they can decrease the frequency of resistant mutations. The covalent linkage of two or more antimicrobial drugs makes the pharmacokinetic and dynamic properties of the resulting hybrid antimicrobial more predictable compared the administration of the single antimicrobial component in a combination therapy page 834, section 3). Ester bonds are taught as being metabolically labile (page 850, right column). Ester bonds are taught as being cleaved by intracellular esterases (page 866, left column, second paragraph). Hybrid antimicrobials are shown Fig. 1 wherein Drug A is covalently linked to Drug B.
Uhrich et al. is directed biodegradable polyanhydrides with natural bioactive molecules. Claimed is a compound of formula IIb wherein R1-X and R2-X are each independently a residue of a biologically active molecule and X is O, S or NRa wherein Ra can be hydrogen (claim 35).
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As shown in Table 4, the combination of carvacrol and EDTA completely prevented biofilm formation. Carvacrol is specifically taught as a biologically active molecule (page 4, lines 11-12). The compositions are effective against Salmonella (page 13). How to synthesize dicarvacrol-EDTA is shown (Scheme 3).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 37, 43, 46-47, 50, 103 and 107:
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Abrey et al., Zhou et al., Klahn et al. and Uhrich et al. and form a hybrid antimicrobial of EDTA and carvacrol. One skilled in the art would have been motivated to covalently link EDTA and carvacrol as both are known antimicrobial agents and are known to be synergistic as taught by Zhou et al. Since hybrid antimicrobials, e.g. those which are covalently linked, have advantages as taught by Klahn et al., one skilled int eh art would have been motivated to covalently link EDTA and carvacrol. There is a reasonable expectation of success as Uhrich et al. teaches the formation of compounds which are specifically dicarvacrol-EDTA and that polymers made from these compounds are also antimicrobial.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Abrey et al., Zhou et al., Klahn et al. and Uhrich et al. and incorporate the hybrid antimicrobial with an extracted yeast cell wall particle to encapsulate the antimicrobials. One skilled in the art would have been motivated to utilize these particles as Abrey et al. teaches they are readily available, biodegradable and substantially spherical and that a key attribute of these hollow microparticles is that they may contain more than 10% lipid w/w and are very effective at absorbing active agents. Therefore, one skilled in the art would have been motivated to utilize these particles in order to deliver the antimicrobials. There is a reasonable expectation of success as Abrey et al. teaches the active agent which can be encapsulated includes carvacrol. Regarding the claimed yeast cell wall particle, Abrey et al. teaches they comprise an internal space and beta glucan.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Abrey et al., Zhou et al., Klahn et al. and Uhrich et al. and administer the particle with the antimicrobials encapsulated. One skilled in the art would have been motivated to administer the particles as Abrey et al. expressly teaches the particles can be administered. Covalent linkages of esters which are suggested by Klahn et al. and Uhrich et al. are taught by Klahan et al. as being capable of being cleaved by esterases. This cleavage, based on the teachings of Klahan et al. and Ulrich et al. would be expected to release both EDTA and carvacrol at the same site.
Regarding claims 38-39, 41 a covalent linkage is taught as being an ester which can be cleaved by esterases (i.e. enzymatic hydrolysis).
Regarding claim 44, Abrey et al. claims the cell wall particle can comprise 75-85% w/w glucan (claim 61) and the amount of beta 1,3-glucan is from about 25 to about 90 w/w% (claim 62) including about 25-35 % beta 1,3-glucan (claim 63).
Regarding claims 104-106, Abrey et al. teaches administration of a composition comprising the particle and the payload. Uhrich et al. teaches inhibiting biofilm formation on an area comprising contacting the area with the composition. The area includes a body (claim 29) which is taught as being the skin of a mammal such as a human (page 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Abrey et al., Zhou et al., Klahn et al. and Uhrich et al. and administer the composition topically to areas in need to of the antimicrobials in order to deliver the antimicrobials to the area where the biofilm is present. It would have been obvious to one of ordinary skill in the art to administer the composition in any customary manner to the site where the biofilm is present as suggested by Abrey et al. and Uhrich et al.
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.
Claims 37-39, 41, 43-44, 46-47, 60 and 103-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 10638750 in view of Zhou et al. (Journal of Food Protection, 2007), Klahn et al. (Nat. Prod. Rep., 2017) and Uhrich et al. (WO2008128193). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system; and (c) administering to a subject the particulate delivery system under conditions that permit internalization of the particulate delivery system in a cell of the subject, cleavage of the cleavable linker, and release and delivery of the payload molecule within the cell of the subject.
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system; and (c) administering the particulate delivery system to a subject under conditions that permit release and delivery of the payload molecule in the subject.
The instant application claims a method of delivering a payload molecule to a subject, comprising a) linking a payload molecule to a scaffolding molecule via a cleavable linker to form a water-insoluble pro-payload molecule;(b) contacting an extracted yeast cell wall particle (YCWP) with the water-insoluble pro- payload molecule, wherein the extracted YCWP comprises an internal space and beta glucan, and wherein the water-insoluble pro-payload molecule is at least partially enclosed within the internal space, thereby forming a particulate delivery system;(c) formulating the particulate delivery system as a pharmaceutically acceptable composition; and(c) administering the pharmaceutically acceptable composition to a subject under conditions that permit release and delivery of the payload molecule in the subject.
As elected the pro-payload molecule is dicarvacrol-EDTA.
Patent ‘750 claims a composition comprising a glucan particle or cell wall particle from which the soluble components have been removed, said particle encapsulating a terpene component, wherein the glucan particle or cell particle comprises a hollow central cavity suitable for encapsulating the terpene component, wherein the lipid content of the glucan particle or cell wall particle is 5% w/w or greater with respect to the weight of the glucan particle or the cell wall particle, and wherein the glucan particle or cell wall particle has been autolyzed prior to encapsulating the terpene. Yeast cell walls are claimed. Yeast extract manufacturing process is claimed. Eugenol Is claimed. Surfactant is claimed. Carvacrol is claimed.
While Patent ‘750 claims a carvacrol component, Patent ‘750 does not claim a payload scaffolding molecule (EDTA as elected) operably linked to the payload molecule (carvacrol) through a chemical linker (ester). However, this deficiency is cured by Zhou et al., Klahn et al. and Uhrich et al.
Zhou et al. is directed to the synergistic effect of thymol and carvacrol combined with chelators and organic acids against Salmonella Typhimurium. Salmonella Typhimurium is a major concern and represents one of the most important Salmonella serovars implicated in gastroenteritis outbreaks (page 1704). Carvacrol has found to be synergistic with preservative systems. Chelators such as EDTA also has been reported to be synergistic with other antimicrobials (page 1704, last paragraph). Carvacrol plus EDTA was found to be synergistic (page 1707; table 3, page 1708 2nd-3rd paragraph).
Klahn et al. is directed to bifunctional antimicrobial conjugates and hybrid antimicrobials. The hybridization of two antimicrobial drugs can be associated with several advantages. The dual targeting can lead to an enhanced antibacterial potency due to synergistic effects of the single components. Hybrid antimicrobials can surpass the efficacy of their component drugs, either alone or in combination, by maintaining their antibacterial activity against pathogens that are resistant to one or both components of the hybrid antimicrobial and they can decrease the frequency of resistant mutations. The covalent linkage of two or more antimicrobial drugs makes the pharmacokinetic and dynamic properties of the resulting hybrid antimicrobial more predictable compared the administration of the single antimicrobial component in a combination therapy page 834, section 3). Ester bonds are taught as being metabolically labile (page 850, right column). Ester bonds are taught as being cleaved by intracellular esterases (page 866, left column, second paragraph). Hybrid antimicrobials are shown Fig. 1 wherein Drug A is covalently linked to Drug B.
Uhrich et al. is directed biodegradable polyanhydrides with natural bioactive molecules. Claimed is a compound of formula IIb wherein R1-X and R2-X are each independently a residue of a biologically active molecule and X is O, S or NRa wherein Ra can be hydrogen (claim 35).
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As shown in Table 4, the combination of carvacrol and EDTA completely prevented biofilm formation. Carvacrol is specifically taught as a biologically active molecule (page 4, lines 11-12). The compositions are effective against Salmonella (page 13). How to synthesize dicarvacrol-EDTA is shown (Scheme 3).
Regarding claims 37, 43-44, 46-47, 50, 103 and 107:
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘750, Zhou et al., Klahn et al. and Uhrich et al. and form a hybrid antimicrobial of EDTA and carvacrol. One skilled in the art would have been motivated to covalently link EDTA and carvacrol as both are known antimicrobial agents and are known to be synergistic as taught by Zhou et al. Since hybrid antimicrobials, e.g. those which are covalently linked, have advantages as taught by Klahn et al., one skilled int eh art would have been motivated to covalently link EDTA and carvacrol. There is a reasonable expectation of success as Uhrich et al. teaches the formation of compounds which are specifically dicarvacrol-EDTA and that polymers made from these compounds are also antimicrobial.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘750, Zhou et al., Klahn et al. and Uhrich et al. and incorporate the hybrid antimicrobial with an extracted yeast cell wall particle to encapsulate the antimicrobials. One skilled in the art would have been motivated to utilize these particles as Patent ‘750 claims the same yeast cell wall particles with carvacrol.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘750, Zhou et al., Klahn et al. and Uhrich et al. and administer the particle with the antimicrobials encapsulated. Covalent linkages of esters which are suggested by Klahn et al. and Uhrich et al. are taught by Klahan et al. as being capable of being cleaved by esterases. This cleavage, based on the teachings of Klahan et al. and Ulrich et al. would be expected to release both EDTA and carvacrol at the same site. Therefore, one skilled in the art would have been motivated to administer the particles with the antimicrobial.
Regarding claims 38-39, 41 a covalent linkage is taught as being an ester which can be cleaved by esterases (i.e. enzymatic hydrolysis).
Regarding claims 104-106, Uhrich et al. teaches inhibiting biofilm formation on an area comprising contacting the area with the composition. The area includes a body (claim 29) which is taught as being the skin of a mammal such as a human (page 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘750, Zhou et al., Klahn et al. and Uhrich et al. and administer the composition topically to areas in need to of the antimicrobials in order to deliver the antimicrobials to the area where the biofilm is present. It would have been obvious to one of ordinary skill in the art to administer the composition in any customary manner to the site where the biofilm is present as suggested by Uhrich et al.
Claims 37-39, 41, 43-44, 46-47, 60 and 103-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10729130 in view of Zhou et al., Klahn et al. and Uhrich et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘130 claims a nematocidal composition comprising a hollow glucan particle encapsulating a terpene component, wherein the terpene component is an active agent, and wherein the hollow glucan particle has a β-1,3-glucan content from 24% to 35% w/w. Terpenes claimed include carvacrol, eugenol and geraniol. The hollow glucan particles are yeast cell walls. Extract manufacturing process is claimed. Water is claimed. Surfactants are claimed.
While Patent ‘130 claims a carvacrol component, Patent ‘130 does not claim a payload scaffolding molecule (EDTA as elected) operably linked to the payload molecule (carvacrol) through a chemical linker (ester as elected). However, this deficiency is cured by Zhou et al., Klahn et al. and Uhrich et al.
The teachings of Zhou et al., Klahn et al. and Uhrich et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘130, Zhou et al., Klahn et al. and Uhrich et al. and incorporate the hybrid antimicrobial with an extracted yeast cell wall particle to encapsulate the antimicrobials. One skilled in the art would have been motivated to utilize these particles as Patent ‘130 claims the same yeast cell wall particles with carvacrol.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘130, Zhou et al., Klahn et al. and Uhrich et al. and administer the particle with the antimicrobials encapsulated. Covalent linkages of esters which are suggested by Klahn et al. and Uhrich et al. are taught by Klahan et al. as being capable of being cleaved by esterases. This cleavage, based on the teachings of Klahan et al. and Ulrich et al. would be expected to release both EDTA and carvacrol at the same site. Therefore, one skilled in the art would have been motivated to administer the particles with the antimicrobial.
Regarding claims 38-39, 41 a covalent linkage is taught as being an ester which can be cleaved by esterases (i.e. enzymatic hydrolysis).
Regarding claims 104-106, Uhrich et al. teaches inhibiting biofilm formation on an area comprising contacting the area with the composition. The area includes a body (claim 29) which is taught as being the skin of a mammal such as a human (page 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘130, Zhou et al., Klahn et al. and Uhrich et al. and administer the composition topically to areas in need to of the antimicrobials in order to deliver the antimicrobials to the area where the biofilm is present. It would have been obvious to one of ordinary skill in the art to administer the composition in any customary manner to the site where the biofilm is present as suggested by Uhrich et al.
Claims 37-39, 41, 43-44, 46-47, 60 and 103-107 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10004229 in view of Zhou et al., Klahn et al. and Uhrich et al. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘229 claims a method of killing nematodes, said method comprising the step of applying an effective amount of a nematocidal composition comprising an active agent, the nematocidal composition comprising a hollow glucan particle encapsulating a terpene component, wherein the terpene component is the active agent. Carvacrol is claimed. The hollow glucan particles are yeast cell walls derived from Baker’s yeast cells.
While Patent ‘229 claims a carvacrol component, Patent ‘229 does not claim a payload scaffolding molecule (EDTA as elected) operably linked to the payload molecule (carvacrol) through a chemical linker (ester as elected). However, this deficiency is cured by Zhou et al., Klahn et al. and Uhrich et al.
The teachings of Zhou et al., Klahn et al. and Uhrich et al. are set forth above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘229, Zhou et al., Klahn et al. and Uhrich et al. and incorporate the hybrid antimicrobial with an extracted yeast cell wall particle to encapsulate the antimicrobials. One skilled in the art would have been motivated to utilize these particles as Patent ‘229 claims the same yeast cell wall particles with carvacrol.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘229, Zhou et al., Klahn et al. and Uhrich et al. and administer the particle with the antimicrobials encapsulated. Covalent linkages of esters which are suggested by Klahn et al. and Uhrich et al. are taught by Klahan et al. as being capable of being cleaved by esterases. This cleavage, based on the teachings of Klahan et al. and Ulrich et al. would be expected to release both EDTA and carvacrol at the same site. Therefore, one skilled in the art would have been motivated to administer the particles with the antimicrobial.
Regarding claims 38-39, 41 a covalent linkage is taught as being an ester which can be cleaved by esterases (i.e. enzymatic hydrolysis).
Regarding claims 104-106, Uhrich et al. teaches inhibiting biofilm formation on an area comprising contacting the area with the composition. The area includes a body (claim 29) which is taught as being the skin of a mammal such as a human (page 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to Patent ‘229, Zhou et al., Klahn et al. and Uhrich et al. and administer the composition topically to areas in need to of the antimicrobials in order to deliver the antimicrobials to the area where the biofilm is present. It would have been obvious to one of ordinary skill in the art to administer the composition in any customary manner to the site where the biofilm is present as suggested by Uhrich et al.
Conclusion
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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