DETAILED ACTION
This action is in response to the amendments and remarks filed 06/18/2026, in which claims 13 and 23-24 have been amended, claims 26-28 have been newly added; and claims 13 and 16-28 are pending and ready for examination.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 18 JUNE 2026 is/are in compliance with the provisions of 37 CFR 1.97 and has/have been considered. An initialed copy of Form 1449 is enclosed herewith.
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 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.
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.
Claims 13, 16-21 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over US 2012/0097613 A1 (hereinafter “Hoshino”) in view of K. D. Patel, H.-W. Kim, J. C. Knowles, A. Poma, Molecularly Imprinted Polymers and Electrospinning: Manufacturing Convergence for Next-Level Applications. Adv. Funct. Mater. 2020, 30, 2001955. (hereinafter “Patel”) and US 2012/0097613 A1 (hereinafter “Hyde”).
Regarding Claim 13 Hoshino discloses a method of removing a substance from fluids of a patient, [0007]-[0042], comprising:
withdrawing a fluid (blood) sample from the patient; and
contacting the fluid sample with an extracorporeal filtration device, the extracorporeal filtration device comprising
a nanoparticle substrate, the nanoparticle substrate comprising a synthetic polymer, wherein the synthetic polymer exhibits binding specificity with the substance to be removed; and
returning filtered fluids to the patient, [0022];
wherein the synthetic polymer comprises a polymer comprising at least two monomers (i.e. wherein two monomers would be a copolymer and then three monomers a terpolymer, etc.) selected from the group consisting of N-t-butylacrylamide (TBAm), acrylic acid (AAc), N-isopropylacrylamide (NIPAm), N,N'-methylenebis(acrylamide) (MBAm), N,N'ethylenebis( acrylamide) (EBAm), acrylamide (AAm), I-vinyl imidazole (VI), N-(3- aminopropyl)acrylamide (APAm), N-phenyl acrylamide (PAm), N-[2-[5-(Dimethylamino)-1- naphthalenyl ]sulfonyl ]-amino ]ethyl ]-2-methyl-Z-propenamide (DANSMAm), fluorescein omethacrylate (FMAc) and polyethylene glycol dimethacrylate (PEGDMAc ), [0010].
Hoshino does not disclose (1) the substrate is fibrous comprising electrospun fibers of a hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, or (2) wherein the substance to be removed comprises an oncological marker comprising at least one of CD63, annexin A6, and mesothelin.
However, with regard to (1) an electrospun fibrous hydrogel substrate, Patel discloses making molecularly imprinted synthetic polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers and the imprinting molecule/target to form the MIP nanofiber, and wherein it is further disclosed that the fibers may be crosslinked, including after electrospinning of the fibers (Secs. 1., 2., 3.1., 4.4., Fig. 2).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino by forming the molecularly imprinted synthetic polymer into nanofibers via electrospinning, and crosslinking the polymer nanofibers after electrospinning as disclosed by Patel because nanofibers provide extremely high surface area to volume, coupled with improved mechanical performance, high porosity and adjustable pore-size distribution and ultimately versatility for the surface decoration with specific chemical moieties which can guarantee extremely high biocompatibility/biodegradability, essential in the case of healthcare and drug-delivery applications (Sec. 1), and “the conjugation of MIP technology with electrospinning to produce micro/nanofibers embedded with inherent specific recognition capacity is certainly extremely attractive, especially for specific separation purposes, sensing applications or even tissue engineering and drug delivery” (Sec. 2.), and because crosslinking post-electrospinning allows “achieving not only a stabilization of the recognition cavities, but also an overall increase of mechanical strength of the final fiber mats” (Sec. 3.1.)
Thus resulting in a (nano)fibrous substrate comprising the imprinted (co)polymer. Where specifically, in the combined invention, it would have been obvious to try electrospinning the same monomer/target/crosslinker solutions as used in Hoshino for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising electrospun fibers of hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, and wherein the fibers exhibit binding specificity with the substance to be removed, as claimed.
With regard to (2) an oncological marker comprising at least one of CD63, annexin A6, and mesothelin, Hoshino discloses the target may be those associated with tumors, including CD20 [0023], [0041], [0052], i.e. oncological markers, but does not disclose the specific oncological markers as claimed. However Hyde discloses devices, systems and methods of controlling the level of one or more target cell types in the blood fluid and/or lymph fluid of a vertebrate subject, where the targets may be those associated with a tumor cell, and include CD20 as well as mesothelin; Abstract, [0040]-[0042], [0084]-[0085].
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino in view of Patel by substituting for the target oncological marker, i.e. substance to be removed, mesothelin, as discleod by Hyde because this involves the simple substitution of known oncological markers known to be desirably removed from blood to achieve the predictable result of removing oncological markers from blood.
Regarding Claim 16 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, the extracorporeal filtration device comprising a flow channel (i.e. a column); Hoshino [0019]-[0021], [0039], [0055], [0059].
Regarding Claim 17 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 16, wherein the fibrous substrate is disposed within the flow channel, (i.e. a column); Hoshino [0019]-[0021], [0039], [0055], [0059].
Regarding Claim 18 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, the substance comprising a toxic substance; Hoshino [0052].
Regarding Claim 19 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, the substance comprising an oncological/tumor marker; Hoshino [0052].
Regarding Claim 20 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, the substance comprising an agent responsible for the growth and/or spread of a cancer (i.e. hormones); Hoshino [0052].
Regarding Claim 21 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, wherein the binding specificity is provided by utilizing an imprinted synthetic polymer, i.e. based on conformational promiscuity; Hoshino [0007]-[0010], [0027]-[0034].
Regarding Claim 26 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 17, wherein the flow channel (i.e. the column, Hoshino [0019]-[0021], [0039], [0055], [0059]) inherently comprises an inner surface, and wherein the fibrous substrate would obviously be used to fill the column, so it would have been obvious and/or inherent that the fibrous substrate lines the inner surface of the flow channel, as occurs when the fiber are packed into the column.
Regarding Claim 27 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, wherein Patel discloses the MIP nanofibers are often formed into mats or membranes for use (Patel Secs. 3.1., 3.2., 4.1., 4.2., 4.4.).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino in view of Patel and Hyde by forming the nanofibers into membranes or mats as disclosed by Patel in order to use the nanofibers in fluid filters.
Where nanofiber membrane or mats are considered “porous monoliths”, and while the pore size of the membranes/mats is not disclosed, it is disclosed that the pore size may be controlled (Sec. 1.), and it is further well-known that pore size effects filtration performance such as what size particles are removed and flow restriction through the filter, thus nanofiber membrane/mat pore size is thus a variable which achieves a recognized result, and it would therefore have been obvious for one of skill in the art to optimize this variable through routine experimentation, by using values including those within the scope of the present claims, so as to produce desired end results. See MPEP § 2144.05 (B).
Claims 22 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Hoshino in view of Patel and Hyde and further in view of CN 107694347 A (hereinafter “Liu”).
Regarding Claim 22 Hoshino in view of Patel and Hyde discloses the method of removing a substance from fluids of a patient of claim 13, and wherein Patel discloses that after extracting nilotinib by adsorbing onto the nanofiber, the nilotinib is desorbed from the membrane and its amount determined via spectrofluorimetric measurement (Abstract, “Selecting a desorbing solvent and desorption time”), but does not disclose further comprising visualizing the substance bound in the fibrous substrate using a visualization element, wherein the visualization element comprises a fluorescent dye.
However Liu discloses using a membrane to extract specific tumor cells from fluids from a patient (liquid biopsy fluid; “Background technique” sec. pgs. 1-2) wherein the cells are labeled with a fluorescent dye and visualized bound on the membrane’s surface to investigate the morphology of the cells, how they are captured by and interact with the membrane investigate how they are captured and interact with the membrane (pg. 5, last two para.).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino in view of Patel and Hyde by visualizing the removed substance bound in the fibrous substrate using a fluorescent dye as disclosed by Liu in order to quantify the amount of removed substance and/or investigate the morphology of the removed substance, how they are captured by and interact with the membrane.
Regarding Claim 25 Hoshino in view of Patel, Hyde and Liu discloses the method of removing a substance from fluids of a patient of claim 22, wherein, as above, the cells are labeled with a fluorescent dye (i.e. the visualization element) and are visualized bound on the membrane’s surface, thus the fluorescent dye (i.e. the visualization element) is considered bonded to the membranes surface, which is the fibrous substrate of the combined invention, because the dye is labeled (i.e. bonded) to the cell and the cell is bonded to the surface, thus the dye is bonded to the surface. Note: the term “bonded” is not limited to covalent chemical bonds.
Regarding Claim 25 Hoshino in view of Patel, Hyde and Liu discloses the method of removing a substance from fluids of a patient of claim 22, but does not specifically disclose wherein the visualization element further comprises a specific binding element. However Liu uses reactive dyes to label the cells (Example 4), and while it is not disclosed specifically how the dye labels the cell, it would have been obvious to provide an element that specifically binds the cells being labeled, i.e. so the dye does not attach to materials other than the cell being labeled and attaches well to the cells.
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Hoshino in view of Patel.
Regarding Claim 23 Hoshino discloses a method of removing a substance from fluids of a patient, [0007]-[0042], comprising:
withdrawing a fluid (blood) sample from the patient; and
contacting the fluid sample with an extracorporeal filtration device, the extracorporeal filtration device comprising
a nanoparticle substrate, the nanoparticle substrate comprising a synthetic polymer, wherein the synthetic polymer exhibits binding specificity with the substance to be removed; and
returning filtered fluids to the patient, [0022];
wherein the synthetic polymer comprises a polymer comprising at least two monomers (i.e. wherein two monomers would be a copolymer and then three monomers a terpolymer, etc.) selected from the group consisting of N-t-butylacrylamide (TBAm), acrylic acid (AAc), N-isopropylacrylamide (NIPAm), N,N'-methylenebis(acrylamide) (MBAm), N,N'ethylenebis( acrylamide) (EBAm), acrylamide (AAm), I-vinyl imidazole (VI), N-(3- aminopropyl)acrylamide (APAm), N-phenyl acrylamide (PAm), N-[2-[5-(Dimethylamino)-1- naphthalenyl ]sulfonyl ]-amino ]ethyl ]-2-methyl-Z-propenamide (DANSMAm), fluorescein omethacrylate (FMAc) and polyethylene glycol dimethacrylate (PEGDMAc ), [0010].
Hoshino does not disclose (1) the substrate is fibrous comprising electrospun fibers of a hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, or (2) wherein the substance to be removed comprises an oncological marker comprising at least one of CD63, annexin A6, and mesothelin.
However, with regard to (1) an electrospun fibrous hydrogel substrate, Patel discloses making molecularly imprinted synthetic polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers and the imprinting molecule/target to form the MIP nanofiber, and wherein it is further disclosed that the fibers may be crosslinked, including after electrospinning of the fibers (Secs. 1., 2., 3.1., 4.4., Fig. 2).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino by forming the molecularly imprinted synthetic polymer into nanofibers via electrospinning, and crosslinking the polymer nanofibers after electrospinning as disclosed by Patel because nanofibers provide extremely high surface area to volume, coupled with improved mechanical performance, high porosity and adjustable pore-size distribution and ultimately versatility for the surface decoration with specific chemical moieties which can guarantee extremely high biocompatibility/biodegradability, essential in the case of healthcare and drug-delivery applications (Sec. 1), and “the conjugation of MIP technology with electrospinning to produce micro/nanofibers embedded with inherent specific recognition capacity is certainly extremely attractive, especially for specific separation purposes, sensing applications or even tissue engineering and drug delivery” (Sec. 2.), and because crosslinking post-electrospinning allows “achieving not only a stabilization of the recognition cavities, but also an overall increase of mechanical strength of the final fiber mats” (Sec. 3.1.)
Thus resulting in a (nano)fibrous substrate comprising the imprinted (co)polymer. Where specifically, in the combined invention, it would have been obvious to try electrospinning the same monomer/target/crosslinker solutions as used in Hoshino for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising electrospun fibers of hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, and wherein the fibers exhibit binding specificity with the substance to be removed, as claimed.
Regarding Claim 24 Hoshino discloses a method of removing a substance from fluids of a patient, [0007]-[0042], comprising:
withdrawing a fluid (blood) sample from the patient; and
contacting the fluid sample with an extracorporeal filtration device, the extracorporeal filtration device comprising
a nanoparticle substrate, the nanoparticle substrate comprising a synthetic polymer, wherein the synthetic polymer exhibits binding specificity with the substance to be removed; and
returning filtered fluids to the patient, [0022];
wherein the synthetic polymer comprises a polymer comprising at least two monomers (i.e. wherein two monomers would be a copolymer and then three monomers a terpolymer, etc.) selected from the group consisting of N-t-butylacrylamide (TBAm), acrylic acid (AAc), N-isopropylacrylamide (NIPAm), N,N'-methylenebis(acrylamide) (MBAm), N,N'ethylenebis( acrylamide) (EBAm), acrylamide (AAm), I-vinyl imidazole (VI), N-(3- aminopropyl)acrylamide (APAm), N-phenyl acrylamide (PAm), N-[2-[5-(Dimethylamino)-1- naphthalenyl ]sulfonyl ]-amino ]ethyl ]-2-methyl-Z-propenamide (DANSMAm), fluorescein omethacrylate (FMAc) and polyethylene glycol dimethacrylate (PEGDMAc ), [0010].
Hoshino does not disclose (1) the substrate is fibrous comprising electrospun fibers of a hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, or (2) wherein the substance to be removed comprises an oncological marker comprising at least one of CD63, annexin A6, and mesothelin.
However, with regard to (1) an electrospun fibrous hydrogel substrate, Patel discloses making molecularly imprinted synthetic polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers and the imprinting molecule/target to form the MIP nanofiber, and wherein it is further disclosed that the fibers may be crosslinked, including after electrospinning of the fibers (Secs. 1., 2., 3.1., 4.4., Fig. 2).
Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino by forming the molecularly imprinted synthetic polymer into nanofibers via electrospinning, and crosslinking the polymer nanofibers after electrospinning as disclosed by Patel because nanofibers provide extremely high surface area to volume, coupled with improved mechanical performance, high porosity and adjustable pore-size distribution and ultimately versatility for the surface decoration with specific chemical moieties which can guarantee extremely high biocompatibility/biodegradability, essential in the case of healthcare and drug-delivery applications (Sec. 1), and “the conjugation of MIP technology with electrospinning to produce micro/nanofibers embedded with inherent specific recognition capacity is certainly extremely attractive, especially for specific separation purposes, sensing applications or even tissue engineering and drug delivery” (Sec. 2.), and because crosslinking post-electrospinning allows “achieving not only a stabilization of the recognition cavities, but also an overall increase of mechanical strength of the final fiber mats” (Sec. 3.1.)
Thus resulting in a (nano)fibrous substrate comprising the imprinted (co)polymer. Where specifically, in the combined invention, it would have been obvious to try electrospinning the same monomer/target/crosslinker solutions as used in Hoshino for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising electrospun fibers of hydrogel synthetic polymer, wherein the synthetic polymer is crosslinked after electrospinning, and wherein the fibers exhibit binding specificity with the substance to be removed, as claimed.
With further regard to the diameter of the electrospun fibers, Patel discloses the nanofibers diameter may be controlled and may range from “tens of nanometers up to micrometers” (Sec. 1). Therefore, before the effective filing date, it would have been prima facie obvious to one of ordinary skill in the art to modify the method of Hoshino in view of Patel by forming the molecularly imprinted polymer nanofibers to have a diameter of from tens of nanometers up to micrometers as disclosed by Patel because this is a known useful size of MIP nanofibers.
Response to Arguments
Applicant's arguments filed 06/18/2026 have been fully considered but they are not persuasive.
Regarding Applicants’ argument that Patel teaches away from crosslinking after electrospinning; the Examiner disagrees. Applicants argue that Patel teaches away from crosslinking after electrospinning MIP polymer fibers because they note that imprinting during electrospinning is “complicated and difficult to achieve” and “amongst the least popular” approaches and the crosslinking “needs to be carefully optimized” or it could lead to disadvantages. However, while Patel does note post-crosslinking may be difficult, the advantages are also noted, i.e. stabilization of the recognition cavities and overall increase in mechanical strength of the final fiber mats (Sec. 3.1.). Some potential pitfalls to the process would not outweigh the potential benefits and would still motivate one of skill in the art to pursue the advantages, as evidenced by the prior art cited in Patel of using this strategy. Patel also notes disadvantages of each different process, such as in Sec. 3.2 where discussing the “alternative approach” for production of MIP-enabled electrospun fibers, i.e. placing MIP on separately formed electrospun support, including grafting to and from, it is noted that “a drawback of this extremely simple procedure is represented by the potential low physico-chemical robustness and potential susceptibility of the recognition layer to degradation, particularly if intended for long-term applications”, and “[u]nfortunately, this method usually does not allow depositing a sufficient amount of polymer onto the surface of the support. Moreover, at the same time, uncontrolled bulk polymerization might take place in solution” and “Although both approaches [grafting to and from] have been exploited and demonstrated for the formation of MIP membranes as well as core-shell micro/nanoparticle architectures;[35,39–40] unfortunately, no reports are available in the case of electrospun fiber mats. This could be due to the challenges of achieving post-electrospinning chemical modifications of the materials.”
Overall Patel is a review article that discusses the known options available for combing MIPs and electrospinning, none of which are free from disadvantages. As disadvantages of each process are noted it cannot be concluded that Patel teaches away from each One of skill in the art would thus be left to weigh between the advantages and disadvantages of each of the different processes as it applies to their desired goals. Thus any of the processes noted would have been obvious to use, with no indication that one specific process would be either fully unsuitable nor clearly the best.
… “[t]he disclosure of desirable alternatives does not necessarily negate a suggestion for modifying the prior art to arrive at the claimed invention” (MPEP 2143.01) and the “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed” (MPEP 2123).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 Eric J. McCullough whose telephone number is (571)272-8885. The examiner can normally be reached Monday-Friday 10:00-6:00.
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/ERIC J MCCULLOUGH/ Examiner, Art Unit 1773
/BENJAMIN L LEBRON/ Supervisory Patent Examiner, Art Unit 1773
