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 § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 2,7, 11-13, 18, 21, 24, 26, 27 and 33-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 27 recites the following elements which does not appear to have support in the original disclosure:
fiber has an outside diameter of 200 µm to 300 µm
an albumin sieving coefficient of less than 0.01
said outer surface has a polyvinylpyrrolidone concentration of at least 3.6%
The disclosure defines the OD as: “A basic dimensional parameter of interest is the outside diameter of the fiber, because a dialysis fiber should have an outside diameter of about 200 to 300 microns” in [00106.] While OD range is described as “200 to 300 microns” in [0066,] there is no single data point in the entire disclosure that meets all the claim 27 requirements. Albumin sieving coefficient is met only by F3, which does not meet the OD and wall thickness requirements. In fact, F13 is disclosed as undesirable in [00107]: “A fiber outside diameter of >350 microns is undesirable for present applications.” The outside PVP concentration of at least 3.6% is met only by F16, but this does not meet the albumin sieving coefficient and the OD requirement. The fibers that meet the OD requirement are F10 to F-13, which have no other data, but listed as inferior for morphology in Table 2, which also would not meet claim 33 requirements.
The information for claim 27 appears to have been taken from dissimilar results from the disclosure. Therefore, it appears that applicant did not have possession of the invention claimed in claim 27 at the time of filing this application.
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, 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.
Claims 2, 7, 11-13, 18, 21, 24, 26, 27 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over Ying et al (US 9,352,283) in view of Lahib et al (US 10, 369,263) and Xu et al, “Polyethersulfone (PES) hollow fiber ultrafiltration membranes prepared by PES/non-solvent/NMP solution,” Journal of Membrane Science 233 (2004) 101·· 111, and with further evidence from applicant’s own admission of prior arts.
Independent Claim 27 recites a dialyzer cartridge having a microporous asymmetric hollow fiber membrane made of PS and PVP with skin layer on the outside to aid filtration outside-in. The hollow fiber is characterized by its albumin sieving coefficient, at “less than approximately 0.01,” water permeability at least approximately 6 mL/(h.mmHg.m2), and presence of elongated macrovoids. Claim 27 also recites the dimensions of the hollow fiber, and details of the cartridge.
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Cartridge details are depicted in fig. 2 of Ying, which are self-explanatory. Cartridge 200 has hollow fiber 208 terminating in the end barriers 206. Housing 202, with inlet and outlet 212. Lumen inlet and outlet 210. First and second plenums 204. Regarding the cross-sectional areas between the blood inlet/outlet vs. that of the mid-section which Yin does not teach in Fig.2, see Lahib, fig. 5B, which applicant incorporates by reference in spec. at [0029]. This design is also very common as seen from the references applicant submitted in an IDS.) Applicant thus uses an existing design, already known, and thus this element of the claims is not patentable.
Col. 9, lines 8-15 shows that the blood is circulated through the shell-side of the hollow fiber cartridge, that is blood flowing between the outside of the hollo fibers inside the housing wall.
Ying teaches such a membrane: see the figures 4A-C, abstract, and example 1A. The membrane has outside skin layer (col. 16, lines 25-30), macrovoids are clearly visible in the figures. Albumin sieving coefficient is seen in Table II, which is significantly below the range of “less than approximately 0.01,” with two data points actually <<0.01. Compare this to applicant’s Table 4, which shows a wide berth for the term “approximate”.
Ying teaches the actual water permeability in Fig. 8. Using Fig. 8, and harvesting the data for the sample cartridge, vise, 10 fibers, 11 mm long, and 780 micron OD from the different locations in Ying, the calculated flux is >> than the 6mL/(h.mmHg.m2.). Since Ying’s is a similar membrane (hollow fiber made of PS and PVP, with similar characteristics,) inherently, the water permeability would be in the range claimed. Evidence that such membranes would have water permeability and albumin sieving coefficient in the claimed range is readily seen in the Xu reference – see table 5. The fibers include external skinned membranes in examples 1W-6W. Applicant also admits in the specification at [0045] - [0052] that similar membranes (citing Gorsuch) have high flux.
Ying teaches thickness and diameter in the claimed range: see example 1A, col. 16, lines 5-8. OD at 330 micron is close to the 200-300 micron range claimed, and thickness at 45 micron would fall withing the range ‘about 20-40 microns.’. Additionally, this reference in the same example teaches different diameters and thickness, which indicate that the thickness and diameter are not critical. Applicant also admits in the specification by citing references that the thickness and diameters are known in the art (for example, see the cited reference in [0043], Krause et al US 8,596,467, example 3.)
With respect to figure 5B, Lahib teaches that the cartridges are designed to have demonstrated … long service lives which are helpful for flow geometry(col. 12, lines 11-16,) and blood can flow at least partially traversely [sic] (col. 12 lines 35-40.) Therefore, it would have been obvious to one of ordinary skill to use the teaching of Lahib in the teaching of Yin to have improved flow geometry.
Applicant’s disclosure in Table 2 also has significant variation in the fiber diameter, and only one data point (F3) has BSA sieving coefficient <0.01, which does not meet the diameter and thickness, whereas only (F6) actually falls within the claimed range for thickness, showing lack of any criticality.
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Regarding the PVP being at a higher concentration at the outer surface: this appears to be a common and inherent feature in this type of membranes from applicant’ disclosure – see [00165]. Both the prior art Fresenius (commercially used) and applicant’s membrane show PVP content on the outer surface from FTIR spectra of outer surface. Such would be expected because PVP is required as a compatible material for blood.
Evidence: applicant’s figures 18 A and B are copied herein. This is the only result in the application disclosure showing the PVP content on the outer surface, and that is 3.69% of F16 and 4.12% in F8HPS (from N%, which is PVP.) It is noted that the fiber F16 does not fall in the claimed fibers because, at the last, it does not meet the diameter requirement and the albumin sieving coefficient of the claims (see applicant’s table 2 showing F16 OD as 322 microns, and Table 4 showing F16 albumin sieving coefficient as 0.09.) F8HPS is a commercially available dialysis membrane by Fresenius.
Dependent claims 2 and 7 on macrovoids: these claims recite structure and approximate dimension ranges of the macrovoids. Finger-shaped macrovoids are commonly present in such asymmetric membranes, as taught by Ying (figures) as well as Xu. Macrovoids open into the lumen in some of the Ying membranes (see figures) while some other membranes have a lumen skin layer with specific pore sizes, like 0.5-3 microns. Macrovoids are commonly known, and known to make the membrane structurally weak, but it is difficult to find a reference that actually quantifies the dimensions of such macrovoids. The office is also not equipped to figure out the dimensions of the macrovoids from such references. The claimed dimensions are broad, and do not appear to be critical. Applicant does not show any particular reason why they are beneficial, when reference membrane structures that do not teach such voids perform equally well or better (applicant’s specification at [0045]). Therefore, they are unpatentable unless otherwise shown.
Claim 11-13 recite thickness, pore size, molecular weight cut-off and surface roughness of the selective layer. Ying teaches pore size at less than 7 nm (abstract, claims), lumen layer at 0.5-3 micron pores, molecular weight cut-off at 60 or 70KDa (col. 9 line 15: see also albumin sieving coefficient that matches this.) Ying is silent on the selective layer thickness, but the outer layer appears to be in a similar range of thickness in fig. 4B. Applicant also discloses in [0136] significant variation in this thickness with no attributable controlling variable.
Claims 18 and 24 are directed at the composition of the polymers in the hollow fiber. All the cited references teach the same. Ying teaches the compositions in Table 1. Regarding the derivative of polysulfone in claim 25, applicant’s own admission in [0053] that it is known.
Claim 26 recites sieving coefficient of beta-2-microglobulin at least approx. 0.7: while the references do not have this data, this value would have been an inherent property of the membrane, based on other characteristics like albumin sieving coefficient, and molecular weight cut-off.
Claim 33: surface roughness is disclosed as related to the surface pore size, which is the same in Yin as that of applicants’. Yin also inherently would have the same hydrophilicity or contact angle as that of applicant’s because of PVP, which is in fact more in the Yin membrane (higher concentration in the dope). Regarding thickness of the skin layer, this also would have been inherently the same since the membrane is made similarly. See example 1A: there is no air gap and the dope is extruded directly into the coagulation bath, compared to applicant’s 6 mm air gap with “shower,” which, the examiner believes, assures a very thin external skin layer external. Compare with example 1B, the standard procedure, which produced smooth internal (lumen) skin with nm sized pores. The Xu reference also provides evidence to that fact.
Claim 34: housing structure is the same in Yin in view of Lahib.
Claims 2, 7, 11-13, 18, 21, 24, 26, 27 and 33-34 are rejected under 35 U.S.C. 103 as being unpatentable over, Lahib et al (US 10, 369,263), with added evidence from Yin as cited in rejection 1 and applicant’s own admission of prior arts.
Lahib has a prior publication date of 2015 (PGPUB) [underlined for emphasis], and is therefore a 102(a1) reference.
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As seen in this fig. 5B, teaching of the cartridge with all its details as claimed is clearly seen. This picture is the same as applicant’s fig. 2d, and this reference is incorporated by reference in spec. at [0029.] This also anticipates claim 34.
Regarding the details of the hollow fiber, materials are PES and PVP (col. 4 lines 61-67.) (This is also as in claim 16.) For dimensions, see col. 16, lines 12-15 and col. 33 lines 6-12, which meet the claimed ranges. Pore diameters of 2-7 nm and mol. Wt cut off at 50,000D, shows that the albumin sieving coefficient of less than 0.01 would be inherent (MPEP 2112). See also col. 4 lines 37-42: “retaining … especially albumin.” Water permeability – see UF coefficient of 5-100 ml.hr/m2/mmHg, which means the water permeability will be more than 6 as claimed and the exterior surface is hemocompatible – col. 14, lines 57-67. (Compare with applicant’s table 2, which has KUf at twice the permeability, whereas Lahib teaches KUf the same as permeability – compare the units.)
Regarding the PVP being at a higher concentration at the outer surface: this appears to be a common and inherent feature in this type of membranes from applicant’ disclosure – see [00165] – and meant for hemocompatibility. While Lahib teaches having the outside surface hemocompatible (col. 7, lines 27-34,) it is silent on an increased concentration of PVP on the outer surface. Therefore, having a higher concentration of PVP on the outer surface would have been obvious to one of ordinary skill. Both the prior art Fresenius F8HPS (which is admitted as commercially widely used for the purpose: spec. at [00166]) and applicant’s membrane show PVP content on the outer surface from FTIR spectra of outer surface. Such would be expected because PVP is required as a compatible material for blood. More details are incorporated from rejection 1 above.
Claims 11 and 33: selective layer thickness and surface roughness in Lahib would be inherently the same as claimed because the same membrane is used, with the same hemocompatible (unspecified by applicant) coating. Lahib also teaches that smoothness is consistent with general filtration practice (col. 15, lines 51-55) and is a result of the choices of formulations, etc. (col. 16, lines 40-48.) See also applicant’s [0052] describing that the selective layer thickness of 0.5 micron is known in the art.
Claims 2 and 7: the membrane in Lahib appears the same as that of applicant’s. Therefore, these structural details also will be the same, and are common in asymmetric membranes. See also rejection 1 in this regard.
Claims 12 and 13: pore size and mol. Wt. cut-off already shown in claim 27 above.
Claims 18 and 21: PES/PVP ratio – while Lahib does not teach the actual ratio, it can be optimized as taught in col. 16, lines 35-47. Other details are inherent – same type of membrane.
Claim 24: added polyethylene glycol – see col. 28, lines 43-55.
Claim 26: Please also see rejection 1 which details the teaching of Yin and other secondary references, for the PES-PVP hollow fiber membrane with outside-in blood flow. The characteristics of this type of membrane are inherent, if not expressly stated in the references.
Response to Arguments
Applicant's arguments filed 11/13/25 have been fully considered but they are not persuasive. They are addressed in the rejection.
Arguments citing the Saito reference and its relation to Yin is unpersuasive. Arguments are directed to the intended use of the hollow fiber. Yin teaches the hollow fiber structurally substantially same as what are claimed, and has same or better performance in terms of dialysis parameters, and expressly useful for artificial kidneys – a synonym for dialysis machines.
The outside diameter and thickness of the claimed membranes appear to be non-critical (see applicant’s table 2 which list all working and good hollow fibers as having diameters >300 microns), since applicant’s disclosed examples do not have the claimed parameters together in even a single example.
Arguments in general are also not commensurate in scope with the rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISHNAN S MENON whose telephone number is (571)272-1143. The examiner can normally be reached Flexible, but generally Monday-Friday: 8:00AM-4:30PM.
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/KRISHNAN S MENON/ Primary Examiner, Art Unit 1777