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 .
Withdrawn Rejections:
Applicant's amendments and arguments filed on 04/28/2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
The application is examined in view of polymer from methyl 2-fluoroacrylate (monomer, MFA) and Pentaerythritol triallyl ether (cross-coupling agent, APE). Claims 5-7 and 10 are on the elected species and are under examination.
Claims 1-2, 4-7, 10-15, 18-20, 23-32 are pending; claims 5-7 and 10 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/07/2026 is being considered by the examiner.
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.
Claims 5-7 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Young et al. (US20150183908) in view of Bromberg et al. (US20030152623).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Young et al. teaches crosslinked cation-binding polymers comprising monomers containing carboxylic acid groups and pKa decreasing groups, wherein the polymer contains i) calcium cations that are counterions to about 5% to about 75% of the carboxylic acid groups in the polymer; or ii) calcium cations and magnesium cations that are counterions to about 5% to about 75% of the carboxylic acid groups in the polymer, wherein the magnesium cations are counterions to no more than about 35% of the carboxylate groups in the polymer (abstract). In some embodiments, the crosslinked cation-binding polymer is a crosslinked polymer comprising monomers containing carboxylic acid groups and pKa-decreasing groups such as electron-withdrawing substituents (e.g., a halide atom such as F). For example, the polymer (e.g., polyfluoroacrylic acid or polymethyl-fluoroacrylate polymer) may be crosslinked with about 0.025 mol % to about 3.0 mol % crosslinker. Additionally, for example, the polymer (e.g., polyfluoroacrylic acid) may be crosslinked with about 4.0 mol % to about 20.0 mol of one or more crosslinkers ([0010]). Polymers of the present disclosure are crosslinked. Any crosslinker known in the art may be used. Crosslinking agents contemplated for use in the present disclosure, include, for example, diethelyeneglycol diacrylate (diacryl glycerol), triallylamine, tetraallyloxyethane, allylmethacrylate, 1,1,1-trimethylolpropane triacrylate (TMPTA), divinylglycol, divinylbenzene (DVB), ethylene bisacrylamide, N,N′-bis(vinylsulfonylacetyl) ethylene diamine, 1,3-bis (vinylsulfonyl) 2-propanol, vinylsulfone, N,N′-methylenebisacrylamide, epichlorohydrin (ECH), 1,7-octadiene (ODE), 1,5-hexadiene (HDE), or a combination thereof ([0028]). Monomers contemplated for use in the present disclosure include those monomers that comprise carboxylic acid groups and pKa decreasing groups such as electron-withdrawing substituents. Most preferably, the electron-withdrawing group is fluoride and is attached to the carbon atom alpha to the acid group, for example, 2-fluoroacrylic acid or its salts, methyl-2-fluoroacrylate, difluoromaleic acid or its salts, or an anhydride thereof ([1657]). The crosslinked intermediate polymer, which is then subjected to hydrolysis conditions to convert the ester functionality to carboxylic acid functionality by means known in the art. In another example a crosslinked methyl-2-fluoroacrylate polymer can hydrolyzed with base to form the 2-fluoroacrylate polymer. In another example, acrylonitrile is graft polymerized to starch with a crosslinker as necessary to form a crosslinked starch-graft intermediate polymer, which is then treated with aqueous base to hydrolyze the nitrile functionality to carboxylic acid functionality ([1659]). Exemplary crosslinkers are one or more compounds having (in one molecule) 2-4 groups selected from the group consisting of CH2═CHCO—, CH═C(CH3)CO— and CH2═CH—CH2—, for example and without limitation: diacrylates and dimethacrylates of ethylene glycol, glycerol, diethylene glycol, triethylene glycol, tetraethyleneglycol, propylene glycol, dipropyleneglycol, tripropyleneglycol, tetrapropyleneglycol, polyoxyethylene glycols and polyoxypropylene glycols, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, neopentyl glycol, trimethylol propane, and pentaerythritol; triacrylates and trimethacrylates of trimethylolpropane and pentaerythritol; highly ethoxylated trimethylol propane triacrylate; tetracrylate and tetramethacrylate of pentaerythritol; allyl methacrylate, triallylamine, triallylcitrate and tetraallyloxyethane ([1673]). The polymerization can be carried out in a 1 L three-neck Morton-type round bottom flask equipped with an overhead mechanical stirrer with a Teflon paddle and a water condenser. An organic phase is prepared by mixing methyl-2-fluouracrylate (54 g), divinyl benzene (0.02 g), 1,7-octadiene (0.02 g) and lauroyl peroxide (0.6 g). An aqueous phase is prepared by dissolving PVA (3 g) and NaCl (11.25 g) in water (285.75 g). The organic and aqueous phases are then mixed in the flask and stirred at 300 rpm under nitrogen. The flask is then immersed in a 70° C. oil bath for 5 hours and then cooled to room temperature. The internal temperature during reaction is about 65° C. The solid product is then washed with water and collected by filtration. The white solid is then freeze-dried, affording dry solid beads. The polymethyl-2-fluoroacrylate beads are hydrolysed and converted to the sodium salt by suspending the beads in a NaOH solution (400 g, 10 wt. %) and stirring at 200 rpm. The mixture is heated in a 95° C. oil bath for 20 hours and then cooled to room temperature. The solid product is then washed with water and collected by filtration. After freeze-drying, beads of the sodium salt of poly2-fluoroacrylate sodium are obtained. Similarly, the potassium salt of poly2-fluoroacrylate can be prepared using the same method except for using a KOH solution rather than a NaOH solution for hydrolysis (for example, 500 g of a 10 wt % solution of KOH for 48.93 g of polymethylfluoroacrylate). Likewise, beads of the sodium salt of polyacrylic acid can be prepared from methacrylate monomer by adjusting the amount of monomer for the difference in molecular weight (e.g. 45 g of methacrylate rather than 54 g of methyl-2-fluoroacrylate). Similarly, copolymers of methylacrylate and 2-fluoroacrylate monomers can be prepared by adjusting the amount of monomer for the difference in molecular weight of methylacrylate and poly-2-fluoroacrylate ([1844]).
Bromberg et al. teaches A responsive microgel is provided which responds volumetrically and reversibly to a change in one or more aqueous conditions selected from the group consisting of (temperature, pH, and ionic conditions) comprised of an ionizable network of covalently cross-linked homopolymeric ionizable monomers wherein the ionizable network is covalently attached to an amphiphilic copolymer to form a plurality of ‘dangling chains’ and wherein the ‘dangling chains’ of amphiphilic copolymer form immobile micelle-like aggregates in aqueous solution (abstract). Examples of cross-linkers of this type, which are normally used as crosslinkers in polymerization reactions, are N,N′-methylenebisacrylamide, polyethylene glycol diacrylates and polyethylene glycol dimethacrylates which are derived in each case from polyethylene glycols with a molecular weight of from 106 to 8500, preferably 400 to 2000, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, ethylene glycol diacrylate, propylene glycol diacrylate, butanediol diacrylate, hexanediol diacrylate, hexanediol dimethacrylate, diacrylates and dimethacrylates of block copolymers of ethylene oxide and propylene oxide, polyhydric alcohols such as glycerol or pentaerythritol which are esterified two or three times with acrylic acid or methacrylic acid, triallylamine, tetraallylethylenediamine, divinylbenzene, diallyl phthalate, polyethylene glycol divinyl ethers of polyethylene glycols with a molecular weight of from 126 to 4000, trimethylolpropane diallyl ether, butanediol divinyl ether, pentaerythritol triallyl ether and/or divinylethyleneurea. Water-soluble crosslinkers are preferably used, e.g. N,N′-methylenebisacrylamide, oligoethylene glycol diacrylates and oligoethylene glycol dimethacrylates derived from adducts of 2 to 400 mol of ethylene oxide and 1 mol of a diol or polyol, vinyl ethers of adducts of 2 to 400 mol of ethylene oxide and 1 mol of a diol or polyol, ethylene glycol diacrylate, ethylene glycol dimethacrylate or triacrylates and trimethacrylates of adducts of 6 to 20 mol of ethylene oxide and one mol of glycerol, pentaerythritol triallyl ether and/or divinylurea ([0120]). A method of prevention or treatment of a tumor is provided comprising administering a therapeutically effective amount of a responsive microgel which comprises at least one therapeutic entity to a patient wherein the patient is either at risk of developing a tumor or already exhibits a tumor ([0140]).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Young et al. is that Young et al. do not expressly teach crosslinking agent Pentaerythritol triallyl ether. This deficiency in Young et al. is cured by the teachings of Bromberg et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Young et al., as suggested by Bromberg et al., and produce the instant invention.
Young et al. teaches a crosslinked polymer from monomer methyl 2-fluoroacrylate and crosslinking agent such as triallylamine, and pentaerythritol having 2-4 allyl groups (CH2═CH—CH2—) (which encompassing Pentaerythritol triallyl ether)
One of ordinary skill in the art would have been motivated to choose Pentaerythritol triallyl ether as crosslinking agent to prepare crosslinked polymer from monomer methyl-2-fluoroacrylate because Pentaerythritol triallyl ether is a suitable crosslinker. MPEP 2144.05. Under guidance from Young et al. teaching crosslinker pentaerythritol having 2-4 allyl groups (CH2═CH—CH2—) (which encompassing Pentaerythritol triallyl ether), Bromberg et al. teaching Pentaerythritol triallyl ether as suitable crosslinker for polymer, it is obvious for one of ordinary skill in the art to choose Pentaerythritol triallyl ether as crosslinking agent to prepare crosslinked polymer from monomer methyl-2-fluoroacrylate and prepare instant claimed invention with reasonable expectation of success.
One of ordinary skill in the art would have been motivated to choose Pentaerythritol triallyl ether as crosslinking agent to prepare crosslinked polymer from monomer methyl-2-fluoroacrylate because this is simple substitution of one known crosslinker for another to obtain predictable results. MPEP 2143, it is prima facie obviousness for simple substitution of one known element for another to obtain predictable results. Under guidance from Young et al. teaching crosslinker triallyamine, Bromberg et al. teaching Pentaerythritol triallyl ether as alternative to triallylamine as crosslinker, it is obvious for one of ordinary skill in the art to choose Pentaerythritol triallyl ether as crosslinking agent to prepare crosslinked polymer from monomer methyl-2-fluoroacrylate and produce instant claimed invention with reasonable expectation of success.
Regarding claims 5-7 and 10, prior art teaches crosslinked polymer from methyl 2-fluoroacrylate and Pentaerythritol triallyl ether, same as applicant’s claimed crosslinked polymer, and Young et al. teaches substantially same polymerization procedure as applicant’s example 1 (see the following Fig.) the prior art crosslinked polymer is expected to have same structure as the polymer in example 1 of applicant’s specification. Young et al. also teaches hydrolysis to have carboxylic acid as well as Ca2+ and Mg2+ salt.
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In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Declaration:
The declaration under 37 CFR 1.132 filed 04/28/2026 is insufficient to overcome the rejection of claims 5-7 and 10 based upon Young et al. (US20150183908) in view of Bromberg et al. (US20030152623) as set forth in the last Office action because:
Applicants argue that polymer prepared from APE crosslinker is more stable than polymer prepared from TMPTA.
In response to this argument: this is not persuasive. This is only show during the hydrolysis of methyl 2-fluoroacrylate moiety (last step of preparation), APE is more stable than TMPTA in strong basic condition for hydrolysis. Once synthesis of the polymer completes, there is no evidence to show the polymer with crosslinker APE with any superior properties than polymer with crosslinker TMPTA. Since this is product claim, the differences of process are not sufficient to overcome the 103 rejection. Furthermore, Young et al. teaches the preparation of polymer from 2-fluoroacrylic acid ([01874]) and no hydrolysis step is required. Therefore, the 103 rejection is still proper.
Applicants argue that polymer with crosslinker TAIC not safe.
In response to this argument: this is not persuasive. Polymer crosslinked with TAIC is expected to be unsafe because TAIC is known for toxic issue and general for synthetic rubber, flame retardant and agrochemical, and not biocompatible as evidenced by Zeiger (“Triallyl Isocyanurate”, TOXICOLOGICAL SUMMARY FOR TRIALLYL ISOCYANURATE, July 1998). Thus, no unexpected results has been demonstrated, and the 103 rejection is still proper.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Response to Argument:
Applicants argue the same as declaration.
In response to this argument: this is not persuasive. Since the declaration is not sufficient to overcome the 103 rejection, the same arguments based on declaration is not sufficient to overcome the 103 rejection, either.
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after weighing all the evidence, the Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts which is more convincing than the evidence which has been offered in opposition to it.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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/JIANFENG SONG/Primary Examiner, Art Unit 1613
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