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 .
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) 1, 2, 5-13, 21-22, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chawathe et al., “Biodegradable Hydralese (PGSU) (poly(glycerol sebacate) urethane) Microspheres for Controlled Drug Delivery,” 2020 AAPS PharmSci 360 Meeting, Virtual, October 26-November 5, 2020, as cited by the Applicant in their IDS file dated 02/23/2023. (hereinafter Chawathe).
Regarding claims 1, 2, 5-7, 9-13, 21 and 22, Chawathe teaches a PGSU microsphere obtained by first obtaining a dispersed phase by mixing a pre-polymer of poly(glycerol sebacate) (PGS) in an amount of 20-50wt%, a crosslinker of hexamethylene diisocyanate (HDI), and a tin catalyst in an acetone solvent along with acetaminophen and 2’-deoxydenosine. (page 2). The dispersed phase meets the claimed first composition. The dispersed phase is then emulsified in mineral oil with a sorbitan trioleate (Span 85) emulsifier (page 2), which meets the continuous fluid phase, and is further heated to form the PGSU microspheres with a drug loading of acetaminophen and 2’-deoxydenosine. The above is microspheres are separated and dried at 40 deg C under vacuum. (page 2) with a size of 45-106 microns. (Fig. 5).
Regarding claim 8, as cited above and incorporated herein, Chawathe teaches claim 1. Chawathe also teaches 20-50 wt% of PSG in acetone solvent is in the dispersed phase, with the continuous phase of mineral oil with a sorbitan trioleate.
One skilled in the art would have a reasonable expectation for the above emulsion to have to have the claimed viscosity ratio of the first composition to the viscosity of continuous fluid phase properties of the claimed invention because Chawathe teaches a substantially identical emulsion to the claimed invention such as 20-50 wt% of the PGS resin in an acetone solvent as the dispersed phase and a mineral oil and Span 85 as the continuous phase as the Applicant’s examples, and it is known in the art that it is the amount of polymer/materials in a solvent that determines the viscosity of each the dispersed phase and continuous phase. See MPEP 2112.01. (Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977)).
Claim(s) 1, 2, 9-13, 21-22, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Frydrych et al., “Thermoresponsive, stretchable, biodegradable and biocompatible poly(glycerol sebacate)-based polyurethane hydrogels,” Polymer Chemistry, Vol. 6, pp. 7974-7987, (2015), (hereinafter Frydrych), and attached Electronic Supplementary Material (ESI), page 1-15, (hereinafter ESI).
Regarding claims 1, 2, 5-7, 9-13, 21 and 22, Frydrych teaches a PGSU microspheres with a size range of 42 to 289 microns (page 7985), obtained by an oil-in-oil solvent evaporation technique process as shown in the Electronic Supplementary Material (ESI), and the Li reference. (page 7985). Specifically, the mixture of glycerol, HDI in dioxane with a tin catalyst is mixed with a pre-PGS solution with tin to form a PEU solvent mixture that is then dispersed and emulsified in a mineral oil with a sorbitan trioleate (Span 85) emulsifier (page 2-3 of ESI), which meets the continuous fluid phase. The above is heated and the solvent is evaporated and the obtained microspheres are separated and dried. (page 2-3 of ESI). As cited above, Frydrych specifically cites using the microencapsulation process as described in the Li reference. (See footnote 61).
Claim(s) 1, 2, 9-13, 21-22, is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by JP 2021-053594 A to Nakagama et al. (hereinafter Nakagama).
Regarding claims 1, 2, 9-13, 21-22, Nakagama teaches a microcapsule having a core part and a shell art (See abstract). The microcapsule is obtained by reacting sebacic acid with glycerin (i.e. glycerol) to form a biodegradable polymer (para 112), which meets the claimed PGS resin. The sebacic acid- glycerin polymer is then mixed with tolylene diisocyanate and tetrahydrofuran solvent to form an oil-phase, (para 113), which meets the claimed first composition of the PSG and isocyanate crosslinker. Next, an aqueous solution of a polyvinyl alcohol was prepared as an aqueous phase, (para 114), which meets the claimed continuous fluid phase. 2.6 parts of the above oil-phase is then added and dispersed in 30.7 parts of the aqueous phase to form an oil-in-water emulsion and 66.7 parts of additional aqueous polyvinyl alcohol is added to the emulsion and stirred and warmed to form a microcapsule aqueous dispersion with a 2 mass% amount of microcapsules to the total mass of the microcapsule aqueous dispersion, wherein the microcapsules have a mean size of 20 microns (para 115). The above microcapsule aqueous dispersion is centrifuged and separated from the liquid (para 116), and dried (para 119-120), which meets the claimed process of claims 1, 2, 9-13, 21-22.
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.
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.
Claim(s) 14-20, 23, and 24, is/are rejected under 35 U.S.C. 103 as being unpatentable over Frydrych and ESI, as applied to claim 1, and in further view of Varde et al., “Microspheres for controlled release drug delivery,” Expert Opinion on Biological Therapy, vol. 4(1), pp. 35-51 (2004). (hereinafter Varde).
Regarding claims 14-20, 23, and 24, as cited above and incorporated herein, Frydrych teaches claim 1. Frydrych further teaches that the PEU can be formed into microspheres and such microspheres are also known to be obtained by methods as cited in footnote 62, which is the Varde reference. (page 7985).
Varde teaches known methods for forming microparticles for controlling the release rates of encapsulated drugs. (See abstract), which is in the same field of methods of forming microparticles of the Applicant’s invention. Varde teaches that there are several types of processes commonly used for the fabrication of polymer microspheres and three basic classes of fabrication methods include polymerization, emulsion-solvent extraction/evaporation and extrusion (Figure 1),
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(page 37-38). In the extrusion method, a polymer solution of the microsphere constituents are forced through an orifice or nozzle. (page 39). Varde teaches known extrusion methods such as where the aqueous polymer solution is passed through a porous membrane with well-defined pore sizes to an oil phase (i.e. continuous phase) to form a water-in-oil emulsion to form microspheres of 4-12 microns, extrusion through a nozzle into a stabilizing solution, and/or a dual nozzle system with a polymer solution stream and an aqueous carrier stream, wherein the above droplets are hardened in a manner analogous to the traditional emulsion-solvent extraction/evaporation by collecting the droplets in the continuous phase. (page 39-40). The above meets the claimed process cited in claims 14, 15, 19, 20, 23, and 24.
It would have been obvious to one ordinarily skilled in the art before the effective date of the claimed invention to use the methods for forming microparticles of Varde to form the PEU microspheres of Frydrych because Varde teaches the same field of methods of forming microparticles of the Applicant’s invention, and Frydrych directly teaches forming the PEU into microspheres and directly cites the Varde reference as a known method for forming microparticles.
Allowable Subject Matter
Claims 3-4 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: The above prior art does not teach the isocyanate crosslinker present in the continuous phase.
Conclusion
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/HA S NGUYEN/Primary Examiner, Art Unit 1766