DETAILED ACTION
This action is in response to the RCE with amendments and remarks filed 01/07/2026, in which claims 13 and 24 have been amended, claim 25 has been newly added; and claims 13 and 16-25 are pending and ready for examination.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/07/2026 has been entered.
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, 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) a fibrous substrate, Patel discloses making molecularly imprinted polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers to form the MIP nanofiber (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 polymer into nanofibers via electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers 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.)
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 Patel for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising fibers of electrospun crosslinked hydrogel, 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].
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.
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, 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) a fibrous substrate, Patel discloses making molecularly imprinted polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers to form the MIP nanofiber (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 polymer into nanofibers via electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers 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.)
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 Patel for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising fibers of electrospun crosslinked hydrogel, 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, 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) a fibrous substrate, Patel discloses making molecularly imprinted polymer electrospun nanofibers for extractions and separations, including hemoperfusion, where the molecular imprinting may be accomplished during electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers to form the MIP nanofiber (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 polymer into nanofibers via electrospinning a solution of monomers, imprinting molecule/target, and crosslinkers as disclosed by Patel because this involves the simple substitution of known means of forming molecularly imprinted polymers into nanosized absorbent media for removing toxins from patient fluids to obtain the expected results of successful filtration. 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 Patel for forming their nanoparticles, i.e. such as in [0009]-[0016] and [0075]. Thus resulting in the fibrous substrate comprising electrospun fibers, 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 01/07/2026 have been fully considered but they are not persuasive.
In response to Applicants’ argument that one of skill in the art reading Patel would be led away from a crosslinked electrospun fibrous substrate; the Examiner disagrees. Applicants argue that “Patel establishes that MIPs are not well-established and can only "envisage" future developments of hybrid electrospun-MIP nanofibers which would lead one of skill in the art away from crosslinked electrospun fibers”. However, Patel also discloses many working examples of electrospun-MIP nanofibers, and teaches one of skill in the art what parameters should be optimized. Optimization of these parameters is routine in the art, and while potentially difficult, the benefits of such electrospun-MIP nanofibers are also disclosed, including that 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.). Patel teaches the combination of nanofiber and MIPs “are extremely promising for large-scale manufacturing applications and hence certainly deserving of attention” (Sec. 2), that “[t]he range of applications for which these composite materials can be used has been amply demonstrated, spanning from drug delivery, sensing/diagnostics, separation/filtration, bioremediation and waste removal, all the way up to tissue engineering and regenerative medicine” (Sec. 5) and “[s]tarting from the examples discussed here, possible solution strategies can be envisaged to overcome the challenges for integrating MIPs and electrospinning, thus generating a library of new commercially exploitable MIP hybrid nanomaterials for next-level applications” (Sec. 5). Thus overall the disclosure of Patel is motivating one of skill in the art to pursue making MIP nanofibers, and not dissuading one of skill in the art from the combination as proposed in the rejection.
Applicants further argue that “Patel explains problems with crosslinking of the fibers after electrospinning”. 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. Notably Patel concludes by saying that “careful optimization of the grafting conditions should be performed”; where optimization of know result effective variables has been held to be obvious; See MPEP § 2144.05 (B).
In response to Applicants’ argument that it would require non-routine experimentation merely to determine a viable method for producing suitable crosslinked electrospun fibers the Examiner disagrees. Applicants argue “Patel's treatment of crosslinked electrospun fibers is entirely preliminary: it identifies the concept, highlights significant unresolved challenges, and expressly calls for future experimentation, but does not provide substantive experimental data or workable protocols on which one of skill in the art could reasonably rely.” However, Patel discloses all the parameters that need to be optimized and provides guidance on potential problems to plan for precisely to direct one of skill in the art how to successfully make the nanofiber MIPs. Further, as discussed in the rejection, Hoshino discloses the materials that are known to form the MIP which provide known working starting point for the MIPS, and thus there is an expectation that they will provide MIP nanofibers after optimization of the spinning and crosslinking parameters as directed by Patel. There is not seen to be evidence that the experimentation is non-routine; to the contrary Patel discloses it is known and routine to optimize these parameters. Further, it should be noted that Applicants claims are significantly broader than the specific nanofibers disclosed in the original disclosure, and therefore if finding the parameters necessary to produce nanofibers other than specifically disclosed through working examples would require non-routine experimentation then the instant claims would suffer from a scope of enablement problem as the claims are so board as to contain materials Applicant’s do not enable to one of skill in the art to make; see MPEP 2164.01(a). It is however the Examiner position that the experimentation needed is routine, without further evidence to the contrary. With regard to predictability, See MPEP § 2143.02, which states that “neither a conclusive proof of efficacy nor absolute predictability of success is required to show a reasonable expectation of success.”
Overall Patel concludes that nanofiber MIPS are a promising new technology, and while not fully explored in the literature, directed one of skill in the art in how to be successful in making electrospun-MIP nanofibers through routine experimentation.
Conclusion
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/ERIC J MCCULLOUGH/ Examiner, Art Unit 1773
/BENJAMIN L LEBRON/ Supervisory Patent Examiner, Art Unit 1773