DETAILED ACTION
Status of Application
Claims 156-175 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claims 156, 161-171 and cancellation of claims 1-155 as submitted in a communication filed on 04/17/2026 is acknowledged.
Applicant’s election without traverse of Group I, claims 156-161, drawn to a method of preparing an enzyme loaded nanoparticle, as submitted in communication filed on 02/17/2026 is acknowledged.
Claims 162-175 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/17/2026.
Claims 156-161 are at issue and will be examined to the extent they encompass the elected invention.
Priority
Acknowledgment is made of applicant’s claim for domestic priority under 35
U.S.C. 119 (e) to provisional Application No. 63221827 filed on 07/14/2021.
This is the US national application which entered the national stage from Application No. PCT/US22/73650 filed on Date 07/12/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/08/2024 and 8/15/2024 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner
Drawings
The drawings submitted on 01/08/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Claim Objections
Claim 159 is objected to due to the recitation of “…polylactic acid (PLA), or poly-e-caprolactone (PCL)…..polypropylene oxide (PPO), or polyhydroxybutyrate…”, due to the two “or” in the list of alternatives. To enhance clarity, and to be consistent with commonly used claim language, the term should be amended to recite “…polylactic acid (PLA), poly-e-caprolactone (PCL)….polypropylene oxide (PPO), or polyhydroxybutyrate…”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 156-161 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 156 (claims 157-161 dependent thereon) is indefinite in the recitation of “first enzyme”, for the following reason: The term “first” implies there is a second, third, or fourth enzyme involved in the method, and no subsequent enzymes have been mentioned. Therefore, it is unclear how many enzymes are needed for the steps in this case. For examination purposes, no patentable weight will be given to the term “first enzyme”. Correction is required.
Claim Rejections - 35 USC § 102 (AIA )
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 156-157 and 159-161 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yoo et al. (Journal of pharmaceutical sciences 90.2 : 194-201 Published 02/02/2001) (hereby “Yoo”).
Claims 156-157 and 159-161 as interpreted are directed in part to a method of preparing enzyme-loaded nanoparticles, the method comprising: preparing a hydrophobic ion pairing complex comprising: mixing, within a solution, a hydrophobic ion and a first enzyme to form the hydrophobic ion pairing complex; and separating the hydrophobic ion pairing complex from the solution; mixing a hydrophobic polymer with the hydrophobic ion pairing complex within a solvent to form a mixture, wherein the hydrophobic ion pairing complex comprises an enzyme and a hydrophobic ion; adding the mixture to an aqueous solution to form the enzyme-loaded nanoparticles;
and separating the enzyme-loaded nanoparticles from the aqueous solution, thereby preparing the enzyme-loaded nanoparticles, wherein the hydrophobic polymer comprises polylactic co-glycolic acid (PLGA), polylactic acid (PLA), or poly-e-caprolactone (PCL), ethyl cellulose (EC), polybutylcyanoacrylate (PBCA), polypropylene oxide (PPO), or polyhydroxybutyrate (PHB), wherein the mixing comprises vortexing, stirring, homogenization, or sonication, wherein the separating of the enzyme- loaded nanoparticles is by centrifuging.
Yoo teaches a protein-fatty acid complex which is a hydrophobic ion pairing complex made of lysozyme and oleate (Page 195, left column, last paragraph). Yoo teaches making nanoparticles with PLGA (Page 196, left column, last paragraph). Yoo teaches making nanoparticles under vigorous stirring conditions (Page 196, right column, first paragraph). Yoo teaches dissolving the ion-pairing complex in a water-miscible organic solvent into biodegradable nanoparticles based on a spontaneous emulsion solvent diffusion method (Page 195, right column, first paragraph). Yoo teaches mixing lysozyme with oleate in tris or acetate buffer to get the hydrophobic ion pairing complex, and centrifugation to recover the complex (Page 195, right column, paragraph 3).
Therefore, the teachings of Yoo anticipate the instant claims as written/interpreted.
Claim Rejections - 35 USC § 103 (AIA )
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.
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.
Claim 158 is rejected under 35 U.S.C. 103 as being unpatentable over Yoo et al. (Journal of pharmaceutical sciences 90.2 : 194-201 Published 02/02/2001) (hereby “Yoo”) in view of Suk et al. (Advanced drug delivery reviews 99 (2016): 28-51) (hereby “Suk”).
The teachings of Yoo have been discussed above. Yoo does not teach the use of polyethylene glycol (PEG). Suk teaches that coating the surface of nanoparticles with polyethylene glycol (PEG), or “PEGylation”, is a commonly used approach for improving the efficiency of drug and gene delivery.
Claim 158 is directed in part to the method of claim 156, wherein the polymer comprises a hydrophobic polymer and polyethylene glycol (PEG).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate PEG in the method taught by Yoo. A person of ordinary skill in the art is motivated to incorporate PEG in the method taught by Yoo to improve efficiency of nanoparticle drug and gene delivery. One of ordinary skill in the art has a reasonable expectation of success at arriving to using a polymer that comprises a hydrophobic polymer and polyethylene glycol (PEG) because all that is required is adding PEG to the nanoparticle preparation method taught by Yoo. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 156-161 are rejected under 35 U.S.C. 103 as being unpatentable over White et al. (cited in IDS published 06/01/2017) (hereby “White”) in view of Ristroph et al. (cited in IDS published 2019) (hereby “Ristroph”).
Regrading claim 156, White teaches a method of preparing conjugates and particles comprising these conjugates, including polymeric nanoparticles, self-assembling particles, conjugate/surfactant and conjugate/block co-polymers mixed micelles, composite nanoparticles formed by conjugates, surfactants and phospholipids or block co-polymers, or polyaminoacids, or proteins, inorganic nanoparticles, and pharmaceutical formulations thereof (Page 1 [0006]-[0007]). White teaches that the conjugates and particles may comprise hydrophobic ion pairing complexes (Page 105 [277]-[278]). White teaches a method of preparing conjugates and particles comprising these conjugates for nanoparticle formation (Page 108 [0301]). White teaches a method of preparing conjugates and particles comprising these conjugates comprising mixing the complex in a solution (Page 137 [0568]-[0572]). White teaches a method of preparing conjugates and particles comprising these conjugates comprising centrifuging the solution to separate the hydrophobic ion pairing complex (Page 194 [0763]). White teaches a method of preparing conjugates and particles comprising these conjugates comprising mixing polymer with the hydrophobic ion pairing complex (Page 113 [0329]). White teaches a method of preparing conjugates and particles comprising these conjugates comprising mixing polymer wherein the polymers are loaded in nanoparticles (Page 115 [0346]).
Regrading claim 157-159, White teaches the use of a hydrophobic polymer (Page 107 [0288]).White discloses that the polymers may contain one more of the following polyesters: homopolymers including glycolic acid units, referred to herein as “PGA”, and lactic acid units, such as poly-L-lactic acid, poly-D-lactic acid, poly-D,L-lactic acid, poly-L-lactide, poly-D-lactide, and poly-D,L-lactide, collectively referred to herein as “PLA”, and caprolactone units, such as poly(ε-caprolactone), collectively referred to herein as “PCL”; and copolymers including lactic acid and glycolic acid units, such as various forms of poly(lactic acid-co-glycolic acid) and poly(lactide-co-glycolide) characterized by the ratio of lactic acid:glycolic acid, collectively referred to herein as “PLGA”; and polyacrylates, and derivatives thereof. Exemplary polymers also include copolymers of polyethylene glycol (PEG) and the aforementioned polyesters, such as various forms of PLGA-PEG or PLA-PEG copolymers, collectively referred to herein as “PEGylated polymers”(Page 106-107 [0286]-[0287]).
Regrading claim 160-161, White teaches the use of a high-pressure homogenizer or probe sonicator to mix polymer with the complex (Page 136 [0538]).
White alone does not explicitly teach the remaining claim limitations. White does not explicitly teach the use of an enzyme to form the hydrophobic ion pairing complex with the hydrophobic ion.
Ristorph teaches that hydrophobic ion pairing is a useful tool for complexing and encapsulating small molecules, peptides, protein fragments, and full proteins such as antibodies and enzymes into nano-scale delivery vehicles (Page 4230; left column; last paragraph). Ristorph teaches that hydrophobic ion pairing has emerged as a method to modulate the solubility of charged hydrophilic molecules (Page 4207; Abstract). Ristorph teaches that hydrophobic ion pairing improve encapsulation efficiencies up to 100% and drug loadings up to 30% (Page 4207; Abstract).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use an enzyme to form the hydrophobic ion pairing complex as taught by Ristorph with the method of White. A person of ordinary skill in the art is motivated to combine the teachings of White and Ristorph to prepare enzyme loaded nanoparticles to improve encapsulation efficiencies of loaded nanoparticles. One of ordinary skill in the art has a reasonable expectation of success at arriving to using an enzyme for hydrophobic ion pairing because all that is required is substituting the conjugates used White for an enzyme that can form hydrophobic ion pairing complexes. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is in condition for allowance.
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/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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