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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 February 05, 2026 has been entered.
Priority
Acknowledgment is made of applicant’s claim for foreign priority (JP2020-083505, filed on May 11, 2020) under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Interpretation
Claim 1 recites the limitation “a first hollow fiber membrane having a sieving coefficient of not less than 0.12 nor more than 0.28 for dextran having a molecular weight of not less than 300 kDa nor more than 1000 kDa.” The instant Specification explains that the recited sieving coefficient is realized when the first hollow fiber membrane has first pores, that the sieving coefficient can be adjusted by changing the water/organic-solvent mixing ratio in the internal coagulation liquid, and that a sieving coefficient is “an index of the filtration ratio of a solute” (¶[0043]; ¶[0046]; ¶[0057]). Under the broadest reasonable interpretation, the recited dextran sieving coefficient defines the first hollow fiber membrane by the resulting filtration behavior produced by its pore/transport structure when evaluated using dextran in the recited molecular-weight range, rather than limiting the membrane to a particular pore morphology, pore-size distribution, pore connectivity, dense-layer configuration, or other specific structural arrangement.
Claim Rejections - 35 USC § 112
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.
Claim 5 is 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 5 recites the limitation “a second hollow fiber membrane.” The limitation is indefinite because the claim does not specify how the second hollow fiber membrane is structurally arranged relative to the first hollow fiber membrane of Claim 1 within the claimed hollow fiber membrane module. Although the Specification describes a hollow fiber membrane bundle in which the first hollow fiber membrane and the second hollow fiber membrane are mixed (¶[0044]), Claim 5 does not recite whether the first and second hollow fiber membranes are mixed in one bundle, arranged in series, arranged in parallel, or otherwise positioned in the module. As a result, the structural arrangement and desired outcome of the claimed two-membrane product are unclear.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3, and 4 are rejected under 35 U.S.C. 103 as being unpatentable over OHIRA et al. (JP2008173163A, hereinafter OHIRA).
Regarding Claim 1, OHIRA discloses a hollow fiber membrane module for blood purification including hollow fiber membranes made of a polyester polymer alloy (PEPA) primarily composed of polyarylate resin (PAR) and polyethersulfone resin (PES). The PEPA membrane has excellent mechanical strength, heat resistance, chemical resistance, and biocompatibility, and exhibits high blocking ability against pyrogens such as endotoxins in dialysis fluid (¶[0004]).
In performance testing, when a 1000 EU/L endotoxin solution is filtered through the PEPA membrane under blood purification conditions, the endotoxin concentration in the filtrate is reduced to 1.0 EU/L or less (¶[0010]).
The membrane is a hollow fiber formed from a polymer alloy of polyarylate and polyethersulfone by extruding a membrane-forming solution into a coagulation liquid together with a core liquid using a double-tube spinneret (¶¶[0036]–[0037]).
The resulting hollow fiber membrane includes dense layers on the inner and outer surfaces and a support layer with coarser pores between them. The inner dense layer has a pore size of 2–80 nm, and the outer dense layer has a pore size of 10–100 nm. These pore sizes are adjustable by changing the resin mixing ratio, with preferred ranges of 5–50 nm and 15–70 nm, respectively. This pore configuration enhances both permeability and pyrogen-blocking performance. The membrane exhibits sieving coefficients of approximately 0.5 for a 35 kDa solute, 0.05 for a 70 kDa solute, and near zero for solutes of 100 kDa or greater (¶[0038]).
Regarding the limitation “a first hollow fiber membrane having a sieving coefficient of not less than 0.12 nor more than 0.28 for dextran having a molecular weight of not less than 300 kDa nor more than 1000 kDa,” this limitation (1) reflects a performance value based on the solute used in testing, and (2) is considered a result-effective variable that depends on tunable membrane parameters.
(1) Dextran is not part of the claimed hollow fiber membrane module and merely serves as the material worked upon to generate permeability data. As such, the dextran test material does not itself define a structural feature of the membrane module and is not entitled to patentable weight (In re Casey, 370 F.2d 576 (CCPA 1967); In re Otto, 312 F.2d 937 (CCPA 1963)).
(2) The recited sieving coefficient is tied to the membrane pore structure, and the instant Specification explains that the recited sieving coefficient is realized by the first pores. As discussed above, OHIRA’s PEPA hollow fiber membrane includes an inner dense layer having pores of 2–80 nm and an outer dense layer having pores of 10–100 nm, with pore size adjustable to obtain permeability and pyrogen-blocking performance. It would have been obvious to a person skilled in the art to adjust and optimize the pore size and dense-layer structure to obtain the desired dextran sieving coefficient, with a predictable change in permeability and sieving behavior while preserving pyrogen-blocking performance in the known PEPA membrane system (In re Aller, 220 F.2d 454, 456–57 (CCPA 1955)).
Regarding the limitation “wherein the endotoxins enter pores of the first hollow fiber membrane and adhere to inner wall surfaces of the pores,” this limitation describes the endotoxin-retention mechanism of the PEPA hollow fiber membrane. As discussed above, OHIRA’s PEPA hollow fiber membrane retains endotoxins, and the pore-entry/adherence language does not define a distinct structure over the known PEPA hollow fiber pore structure.
Regarding Claim 3, OHIRA makes obvious the hollow fiber membrane module of Claim 1. OHIRA discloses filtration of endotoxins through the PEPA membrane under blood purification conditions (¶[0010]).
Regarding Claim 4, OHIRA makes obvious the polyester polymer alloy membrane of Claim 1. OHIRA discloses that the membrane is a hollow fiber formed from a polymer alloy of polyarylate (i.e., Chemical 1) and polyethersulfone (i.e., Chemical 2), produced by extruding a membrane-forming solution into a coagulation liquid together with a core liquid using a double-tube spinneret (¶¶[0036]–[0037]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over OHIRA as applied to claim 1 above, and further in view of MEADA et al. (Efficacy of hemofiltration with PEPA membrane for IL-6 removal in a rat sepsis model, 2017, hereinafter MAEDA).
Regarding Claim 5, OHIRA makes obvious the hollow fiber membrane module of Claim 1. However, OHIRA does not explicitly disclose “a second hollow fiber membrane having a sieving coefficient of not less than 0.64 nor more than 0.80 for dextran having a molecular weight of not less than 20 kDa nor more than 30 kDa, wherein the second hollow fiber membrane adsorbs interleukin 6.”
MAEDA discloses a PEPA membrane used for continuous hemofiltration in a rat sepsis model for cytokine removal (Abstract). The study used mini-modules fabricated from commercial PEPA hollow fiber membranes and compared against cellulose triacetate (CTA) membranes. Continuous hemofiltration was performed in rats after lipopolysaccharide (LPS) injection to induce sepsis. Plasma interleukin-6 (IL-6) levels were monitored over time, and filtrate samples were collected to evaluate membrane removal properties (§ Materials and Methods).
As a result, plasma IL-6 concentrations in the PEPA membrane group were significantly lower than in the CTA membrane group throughout the circulation period. IL-6 was not detected in the filtrate of the PEPA group, whereas it was consistently present in the CTA group. The accumulated amount of IL-6 adsorbed to the PEPA membrane increased steadily, reaching 244,000 pg after 3 hours (§ Results). The study attributes this behavior to PEPA’s inherent protein-adsorbing properties, driven by hydrophobic interactions and membrane structure, and concludes that PEPA membranes are well-suited for cytokine adsorption in blood purification applications (§ Discussion).
The IL-6 removal by the PEPA hollow fiber membrane disclosed by MAEDA is attributed to PEPA’s protein-adsorbing properties, including hydrophobic interaction and membrane structure (§ Discussion). This indicates that PEPA hollow fiber membranes are suitable for removing lower molecular weight cytokines such as interleukin 6 in addition to higher molecular weight endotoxins. In view of OHIRA’s PEPA hollow fiber membrane module, a person skilled in the art would have included an additional PEPA hollow fiber membrane adjusted to adsorb IL-6, with the predictable result of removing IL-6 through PEPA’s known protein-adsorbing properties.
Regarding the limitation “a sieving coefficient of not less than 0.64 nor more than 0.80 for dextran having a molecular weight of not less than 20 kDa nor more than 30 kDa,” this limitation is considered a result-effective variable that depends on tunable membrane parameters. As discussed for Claim 1, the recited sieving coefficient is tied to membrane pore structure, and MAEDA’s experimentation shows PEPA hollow fiber membranes adsorb IL-6. It would have been obvious to a person skilled in the art to optimize the pore size and dense-layer structure to obtain the desired dextran sieving coefficient, with predictable changes in permeability and IL-6 adsorption.
Therefore, it would have been obvious to a person having ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate a PEPA hollow fiber membrane configured for interleukin 6 adsorption, as disclosed by MAEDA, as the second hollow fiber membrane in the hollow fiber membrane module by OHIRA.
Response to Arguments
Applicant’s arguments, see Remarks filed on January 29, 2026, have been fully considered but are not persuasive. The rejection of Claims 1, 3–5 under 35 U.S.C. § 103 over OHIRA and MAEDA is updated and maintained.
Applicant’s argument that pore size and sieving coefficient are not synonymous is acknowledged, but does not overcome the rejection. The rejection does not require pore size and sieving coefficient to be identical. Rather, as discussed above, the recited sieving coefficient is tied to the membrane pore structure, and OHIRA discloses a PEPA hollow fiber membrane with adjustable pore structure for obtaining permeability and pyrogen-blocking performance.
Applicant’s argument that OHIRA’s membrane blocks endotoxins only at the surface is not persuasive. Sieving coefficient measures passage into filtrate, not whether endotoxins enter a pore region and are retained. The recited pore-entry and adherence language describes the endotoxin-retention mechanism and does not define a distinct structure over OHIRA’s PEPA hollow fiber pore structure.
Applicant’s reliance on PEPA-A testing is also not persuasive. The data may show performance differences among tested PEPA membranes, but Claim 1 does not recite the particular pore morphology, dense-layer structure, or preparation condition responsible for PEPA-A’s alleged performance. The showing is therefore not commensurate with the scope of Claim 1 and does not establish criticality of the claimed sieving coefficient range.
MAEDA remains properly relied upon for Claim 5 because it shows that PEPA hollow fiber membranes adsorb IL-6 through PEPA’s protein-adsorbing properties. Thus, adding an additional PEPA hollow fiber membrane adjusted for IL-6 adsorption would have been obvious for the reasons set forth above.
Conclusion
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/TAK L. CHIU/Examiner, Art Unit 1777
/KRISHNAN S MENON/Primary Examiner, Art Unit 1777
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