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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 20 November 2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application (CON of 14/669,930, filed 26 March 2015, which has PRO 61/972,827, filed 31 March 2014) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Response to Amendments
Applicant’s amendments filed 20 November 2025 have been entered.
Claims 46, 70, and 71 have been amended; Claim 82 has been canceled; and new Claims 83-92 have been added. Claims 46-53, 58-62, 64-71, 76-79, 81, and 83-92 are pending.
In view of the amendments to Claim 46 incorporating the limitations of now-canceled Claim 82, the prior art rejection of Claim 46 under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1) with evidentiary support from GUAN et al. (Artificial Organs, 2012, Vol 36, Issue 10; pg. 894-900), and further in view of KORIN (US 5,137,637) is withdrawn. New grounds of rejection are made further in view of PALL (US 4,033,881).
In view of the new Claims 83-92, Claims 88-92 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
Response to Arguments
Applicant’s arguments filed 20 November 2025 have been fully considered.
Regarding the rejections of Claims 46-53, 58-62, 64-71, 76-79, 81, and 82 under 35 U.S.C. 103 as being unpatentable over various combinations of DAVIDNER et al. (US 2005/0277863 A1), WARD et al. (CA 2967094 A1) with evidentiary support from GUAN et al. (Artificial Organs, 2012, Vol 36, Issue 10; pg. 894-900), and further in view of KORIN (US 5,137,637), KOBAYASHI et al. (US 2013/0108715), SZETO et al. (US 2009/0221514 A1), HOCHAREON et al. (US 2012/0302995 A1), HONARD et al. (EP 0132534), PALL (US 4,033,881), and HYDE et al. (2010/0217172), Applicant traverses the rejections and requests withdrawal based on the following arguments: none of the cited references alone or in combination teach or suggest the features of Claim 46, in particular, the recitation of “filtering the removed blood from the first portion of the circuit through a filter comprising one or more conical cylinders at a blood flow rate of 10 L per hour or more to selectively remove blood components” and “exerting a centrifugal force on the blood to selectively retain the blood components in the one or more conical cylinders” (pg. 9, par. 1). Applicant further focuses on KORIN, arguing that “the spiral wound membrane in Korin is not described as including cylinders, nor ‘conical cylinders’” and that “[n]owhere does Korin mention blood or blood components, and the use of centrifugal force in Korin relates to the feedstream” (pg. 9, par. 2).
Applicant then argues that Claim 46 is patentable over the cited references and that the dependent claims are also patentable for the same reasons (pg. 9, par. 3).
The Examiner respectfully disagrees.
Applicant’s arguments have been considered but are not persuasive because they are directed to grounds of rejection that have been withdrawn. Furthermore, Applicant has selectively focused only on the KORIN reference as failing to teach the recited “conical cylinders”, blood, or blood components, only disclosing spiral wound membranes, and only teaching centrifugal force as being applied to the feedstream. However, it must be noted that the rejection of Claim 46 is predicated on a combination of references, not just KORIN alone. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As noted in the subsequent 35 U.S.C. 103 rejection of Claim 46, PALL teaches modifying filter sheet materials into the shape of a conical cylinder (c5/38-41). Advantageously, such a conical shape increases the surface area of the filter allowing for higher throughput (c5/41-43). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to modify the cylindrical filters of modified DAVIDNER to have a conical shape as taught by PALL.
Applicant’s argument that KORIN teaches exerting centrifugal force on a feedstream and not on blood is perplexing. KORIN teaches that a sample to be treated, i.e., the feed, is subjected to centrifugal forces such that flux is enhanced. The disclosed “feed” is interpreted to be the recited “blood from the subject” and the “blood from a patient” disclosed by DAVIDNER. The relevant recited limitation requires “exerting a centrifugal force on the blood”. There is no other component that the centrifugal force taught by KORIN acts upon other than the “feed”.
Thus, Applicant’s arguments have been addressed; the pending claims remain rejected under 35 U.S.C. 103 as follows.
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.
Claims 88-92 are 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.
Regarding Claim 88, there is insufficient antecedent basis for “the filter material”. No “filter material” has been introduced in Claim 88 or parent Claim 46. Claims 89-92 are also rejected due to their dependence on Claim 88.
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.
Claim(s) 46-48, 50-53, 58, 61, 62, 64, 66-68, 70, 71, 81, and 87 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1) with evidentiary support from GUAN et al. (Artificial Organs, 2012, Vol 36, Issue 10; pg. 894-900), and further in view of KORIN (US 5,137,637) and PALL (US 4,033,881).
Regarding Claim 46, DAVIDNER discloses a hemoconcentrator/filter system used to remove target molecules from the blood of a patient (p0048) suffering from inflammatory diseases, such as ischemic stroke (i.e., a method for treating or preventing ischemia in a subject; passing the removed blood… through a filter… to selectively remove blood components; p0022). The hemoconcentrator/filter is capable of removing blood proteins and cell mediators (p0070); such mediators include inflammatory mediators, such as TNF-α, IL-6, IFNγ, MCP-1, C3-a, and other endotoxins (i.e., blood components comprising one or more of… cytokines, interleukins, tumor necrosis factor α… interferon-γ, monocyte chemoattractant protein-1…; p0096). In operation, the apparatus removes blood from a patient, filters blood through the hemoconcentrator/filter, and returns the filtered blood to the patient (i.e., removing blood from a subject, comprising moving the blood from the subject through a first portion of a circuit comprising a first portion of tubing; returning the filtered blood to the subject, comprising passing the filtered blood to the subject via a second portion of the circuit comprising a second portion of tubing; p0012; FIG. 1) at a blood flow rate of 100 mL/min (p0018).
Furthermore, DAVIDNER teaches that the transmembrane pressure (TMP) of the hemoconcentrator/filter is used to determine the appropriate blood flow rates for a desired performance (p0028); the TMP is dependent on a number of factors, including blood hematocrit and blood flow rate (p0052). DAVIDNER then discloses a condition wherein a TMP of greater than 76 mmHg and blood flow rate of 100 mL/min allows for the sufficient processing of blood with greater than 36% HCT (p0053).
While it is noted that DAVIDNER discloses a hemoconcentrator having a pore size of 70-90 kD (p0070) and that the pro-inflammatory and anti-inflammatory mediators removable by the disclosed system have molecular weights of 10-90 kD, e.g., TNF-α being 45-55 kD (p0045), DAVIDNER nevertheless discloses that “50-75% of immune system mediators will be removed from blood” (p0045) and that the hemoconcentrator unit “is capable of removing blood proteins and cell mediators whose molecular weight is less than about 85 kD” (p0070). Indeed, as evidenced by GUAN et al. (Artificial Organs, 2012, Vol 36, Issue 10; pg. 894-900), hemoconcentrators are capable of removing at least some fraction of smaller inflammatory mediators including IL-6, IL-1β, and TNF-α (abstract; Table 2; pg. 899, bottom col. 1 and top col. 2; §Conclusion). While not considered as effective as other methods, hemoconcentrators can apparently remove up to 5% of inflammatory mediators from blood (pg. 899, col. 1 bottom). Thus, while DAVIDNER teaches the overall hemoconcentrator/filter system discloses the removal of 50-75% of mediators from blood, at least some fraction of that percentage is due to the hemoconcentrator 106. Broadly interpreted, the instantly claimed invention does not require a removal efficiency or effectiveness of the claimed filter; the claim only requires that “a filter… selectively remove[s] blood components”. Thus, DAVIDNER’s disclosure of a hemoconcentrator—despite having a pore size larger than the molecular weights of the inflammatory mediators—reads on the claimed invention.
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DAVIDNER is deficient in explicitly disclosing “filtering the removed blood from the first portion of the circuit through a filter at a blood flow rate of 10 L per hour or more”.
WARD discloses the removal of cytokines or pathogens from blood by contacting the blood with a solid substrate for their selective removal (pg. 5, middle). WARD further discloses that such extracorporeal blood circuits maintain a sufficiently high flow rate to advantageously avoid blood clots or high transmembrane pressures/pressure drops (pg. 5, bottom). Such flow rates include at least 150 mL/minute (i.e., 9 L/hr; pg. 6, top), which overlaps with the claimed rate of 10 L per hour or more and therefore, establishes a case of prima facie obviousness (MPEP 2144.05). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to execute the claimed method at a flow rate of 10 L per hour or more as suggested by WARD in the method disclosed by DAVIDNER.
Modified DAVIDNER is deficient in explicitly disclosing exerting a centrifugal force on the blood during the filtering of the removed blood.
KORIN discloses a spiral wound membrane module for separating at least part of one component of a feed; said module comprises a rotatable shaft (abstract, lines 1-5). The disclosed membrane further includes one or more spiral channels wound together in a cylindrical module (c4/29-31). As feed enters the module, rotation of the module around its axis exerts a centrifugal force on the feed (i.e., exerting a centrifugal force on the blood; c4/35-42). Advantageously, such a module increases flux and reduces membrane fouling (c4/41-42). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to modify the filter of the method made obvious by modified DAVIDNER such that the filter would be capable of rotating to exert a centrifugal force on incoming feed, e.g., blood, as taught by KORIN.
Modified DAVIDNER is deficient in disclosing the filter comprises one or more conical cylinders.
PALL discloses filter tubes or cartridges for filtering fluids (abstract). PALL teaches that the filter sheet materials of these filter tubes are in the shape of a conical cylinder (c5/38-41). Advantageously, such a conical shape increases the surface area of the filter allowing for higher throughput (c5/41-43). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to modify the cylindrical filters of modified DAVIDNER to have a conical shape as taught by PALL.
The recited limitation “to selectively retain the blood components in the one or more conical cylinders” is directed toward an inherent property or characteristic resulting from the practice of the claimed method. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). DAVIDNER discloses a hemofilter system that filters blood to remove target molecules whereby blood proteins and cell mediators are captured by the hemoconcentrator; KORIN and PALL further disclose that such a filter can be a spiral wound membrane shaped into a conical cylinder and subject to centrifugal forces to advantageously increase flux and maximize filter surface area. Thus, the prior art expressly discloses capturing and removing such target molecules from blood utilizing filters and centrifugal forces, which necessarily requires that such target molecules are “selectively retain[ed]” by the disclosed filters under centrifugal forces.
Regarding Claim 47, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses the interleukins include IL-1β, IL-6, and IL-10 (p0096).
Regarding Claim 48, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses inflammatory mediators include ICAM-1 (Table 1, p0006).
Regarding Claim 50, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses inflammatory mediators include C3-a (p0096).
Regarding Claim 51, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses vascular access via catheter (i.e., the removing of the blood from the subject comprises using a catheter inserted into the patient’s body for use in carrying or extracting the blood; p0028, p0058, p0092).
Regarding Claims 52 and 53, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses an oxygenator connected between the blood source (patient) and the filter device to oxygenate the blood received from the source (i.e., oxygenating the blood prior to returning the filtered blood to the subject (Claim 52); [using] an oxygenator in supplying oxygen to be added to the blood (Claim 53); p0019).
Regarding Claim 58, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses reducing free radicals in the removed blood (i.e., the selectively removing the blood components comprises removing free radicals; p0023).
Regarding Claim 61, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses the hemoconcentraor/filter is capable of removing blood proteins and cell mediators (p0070) and the device comprises a computer with a color LCD display and touch screen (i.e., passing the removed blood through a therapeutic device comprising the filter, the circuit connects the device and the subject; p0088).
Regarding Claim 64, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses at least one pump for moving blood (i.e., using at least one pump for pumping the blood; p0018).
Regarding Claims 66 and 67, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses the use of a heat exchanger to warm or cool blood temperature prior to reintroduction into the patient (i.e., returning cooled blood to the subject (Claim 66); using a blood temperature regulator… [and] returning cooled blood to the subject (Claim 67); p0092). The limitation “inducing therapeutic hypothermia of the subject” is considered an inherent property or characteristic resulting from the practice of the recited method step of “returning cooled blood to the subject”. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). Because DAVIDNER discloses a heat exchanger cools blood temperature prior to reintroduction to the patient, the reintroduced blood will be at an effectively lower temperature and thereby necessarily induce some degree of “therapeutic hypothermia” as recited.
Regarding Claim 68, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses removing a number of inflammatory mediators considered pathological targets in blood (p0096). While DAVIDNER is deficient in explicitly disclosing these mediators are “soluble or secreted blood components”, such a claim is directed toward the properties of said blood components and is considered inherent. The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable (In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). The disclosed inflammatory mediators are produced by surrounding cells and are secreted into a pateint’s bloodstream; hence, these chemicals are inherently considered to be “soluble or secreted blood components” as recited.
Regarding Claim 70, modified DAVIDNER makes obvious the methods of Claim 68. DAVIDNER discloses a hemoconcentrator/filter having a cylindrical form (p0070). However, modified DAVIDNER is deficient in disclosing the filter comprises a base and one or more conical cylinders with a larger opening of the one or more conical cylinders oriented away from the base (Claim 70) or that the filter comprises one or more conical cylinders (Claim 82).
As noted earlier, PALL discloses filter tubes or cartridges for filtering fluids (abstract). PALL teaches that the filter sheet materials of these filter tubes are in the shape of a conical cylinder (c5/38-41) and the conical filter tubes are supported in a tubular or cylindrical element to increase resistance to fluid pressure and closed off by end caps (i.e., the filter comprises a base and one or more conical cylinders; support: c5/48-56; end caps: c5/18-22). Advantageously, such a conical shape increases the surface area of the filter allowing for higher throughput (c5/41-43).
Modified DAVIDNER is deficient in disclosing that a larger opening of the one or more conical cylinders is oriented away from the base. However, such a claimed orientation would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed inventio because it is a simple rearrangement of parts (i.e., either the larger opening of the conical cylinders is oriented toward the based or away from the base). Absent a showing of significance or unexpected results, the claimed locations of the components are prima facie obvious and do not modify the operation of the invention and further, do not add patentable significance (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950); MPEP §2144.04).
Regarding Claim 62, modified DAVIDNER makes obvious the method of Claim 70. DAVIDNER further discloses the device comprises a computer with a color LCD display and touch screen (i.e., passing the removed blood through the therapeutic device; the therapeutic device displays information on a screen; p0088).
Regarding Claim 71, modified DAVIDNER makes obvious the method of Claim 70. The limitation “to send the blood into or through the one or more conical cylinders along a spiral path to selectively retain the blood components in the one or more conical cylinders” is directed toward an inherent property or characteristic resulting from the practice of the claimed method. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). Because KORIN discloses applying a centrifugal force to a spiral wound membrane and PALL further discloses shaping such cylindrical membranes into conical shaped cylinders to advantageously increase flux and filter surface area, the resulting effect on the blood components is to necessarily be captured or retained on a spiraling path along the disclosed spiral wound conically-shaped filter subject to centrifugal force.
Regarding Claim 81, modified DAVIDNER makes obvious the method of Claim 46. While DAVIDNER is deficient in disclosing the claimed “biocompound-specific adhesion”, WARD disclose the use of selectively adsorbent molecules, biomolecules or chemical groups for selectively removing cytokines and/or pathogens (i.e., filtering the removed blood from the first portion of the circuit through the filter to filter the blood using biocompound-specific adhesion; pg. 4, bottom). Advantageously, the use of such selective biomolecules lessens or eliminates the spread of disease (pg. 4, bottom); thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to provide the additional functionality of selective adsorption by biocompound-specific adhesion as suggested by WARD for the method disclosed by DAVIDNER.
Furthermore, such biocompound-specific adhesion capabilities taught by WARD and the size-selective separation capabilities taught by DAVIDNER would have been obvious to one of ordinary skill in the art prior to the effective filing date because the added layer of selectivity would ensure a higher effective removal of undesired cytokines and inflammatory mediators. All claimed elements were known in the prior art and one of ordinary skill in the art could have combined the elements as claimed by known methods with no change in their respective, individual functions, and the combination would have yielded nothing more than predictable results (MPEP §2143.01 A).
Even further, WARD explicitly discloses that the use of selective biomolecules addresses the issue of large pressure drops and low flow rates commonly encountered with other types of extracorporeal blood circuits, i.e., diffusion-based transport (pg. 6-7). Thus, the use of “biocompound-specific adhesion” would have been obvious because the technique for improving the size-selective diffusion process of DAVIDNER was part of the capabilities of one of ordinary skill in the art prior to the effective filing date of the claimed invention and would have led to otherwise predictable results (MPEP §2143.01 C).
Regarding Claim 87, modified DAVIDNER makes obvious the method of Claim 46. PALL further discloses that the conical filter element is supported by an external support that encloses the exterior of the filter element with a supporting material so as to closely abut the filter sheet material throughout its surface area (i.e., the filter material is disposed on an inner surface of the one or more cylinders; c5/48-56). This advantageously provides increased mechanical support for the filter sheet material to fluid pressure or back pressure (c5/48-50).
Claim(s) 49 and 59 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claims 46 and 52 above, respectively, and further in view of KOBAYASHI et al. (US 2013/0108715 A1).
Regarding Claim 49, modified DAVIDNER makes obvious the method of Claim 46. While DAVIDNER discloses the removal or reduction of free radicals (p0023), modified DAVIDNER fails to disclose the free radicals comprise at least one of free iron radicals and free oxygen radicals.
However, as disclosed by KOBAYASHI, free radicals in blood include oxygen radicals that can negatively cause cell injury during ischemia (i.e., at least one of free iron radicals and free oxygen radicals; p0002). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would find it obvious to remove oxygen free radicals as disclosed by KOBAYASHI to advantageously prevent cell injury during ischemia and infarctions in patients during the treatment method made obvious by modified DAVIDNER.
Regarding Claim 59, modified DAVIDNER makes obvious the method of Claim 52. While DAVIDNER discloses the removal or reduction of free radicals (p0023), modified DAVIDNER fails to disclose the removal of blood components comprises removing oxygen free radicals.
However, as disclosed by KOBAYASHI, free radicals in blood include oxygen radicals that can negatively cause cell injury during ischemia (i.e., oxygen free radicals; p0002). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would find it obvious to remove oxygen free radicals as disclosed by KOBAYASHI to advantageously prevent cell injury during ischemia and infarctions in patients during the treatment method made obvious by modified DAVIDNER.
Claim(s) 60 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 52, and further in view of SZETO et al. (US 2009/0221514 A1).
Regarding Claim 60, modified DAVIDNER makes obvious the method of Claim 52. While DAVIDNER discloses the removal or reduction of inflammatory mediators (p0096), modified DAVIDNER is deficient in explicitly disclosing removing heme oxygenase-1.
However, as disclosed by SZETO, heme oxygenase-1 is known to cause oxidative damage (p0267). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would find it obvious to remove a number of inflammatory mediators, including heme oxygenase-1 as disclosed by SZETO, in the method made obvious by modified DAVIDNER.
Claim(s) 65 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 52 above, and further in view of HOCHAREON et al. (US 2012/0302995 A1).
Regarding Claim 65, modified DAVIDNER makes obvious the method of Claim 52. DAVIDNER further discloses a heat exchanger to warm or cool blood temperature prior to reintroduction into the patient (p0092). However, modified DAVIDNER is deficient in disclosing inducing therapeutic hypothermia of the subject prior to removing blood from the subject.
HOCHAREON discloses that mild hypothermia with reperfusion therapy advantageously provides significant improvement to tissue protection when compared with reperfusion therapy alone (p0009). In an embodiment related to cardiac arrest, HOCHAREON discloses first cooling a target tissue (in this case, an organ) prior to reperfusion (i.e., inducing therapeutic hypothermia of the subject prior to removing blood from the subject); this advantageously maximizes cell salvaging (p0120). Thus, prior to the effective filing date of the claimed invention one of ordinary skill in the art would find it obvious to induce therapeutic hypothermia to the subject prior to removing blood from the subject as disclosed by HOCHAREON in the method made obvious by modified DAVIDNER.
Claim(s) 69 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 68 above, and further in view of HONARD et al. (EP 0132534 B1).
Regarding Claim 69, modified DAVIDNER makes obvious the method of Claim 68. DAVIDNER discloses a hemoconcentrator/filter having a cylindrical form (p0070). However, modified DAVIDNER is deficient in disclosing the filter comprises a hydrogel layer to which one or more molecules capable of binding one or more of the blood components has been immobilized.
HONARD discloses a device for the extracorporeal treatment of blood diseases (pg. 2, lines 5-6) involving the removal of whole blood, the separation of soluble blood substances, and the infusion of treated whole blood (pg. 2, lines 47-49). HONARD further discloses that the treating means for treating blood comprises a biospecific polymer bound to a support member (pg. 4, lines 28-29); the treating means further comprises a porous reticulated foam with the biospecific polymer coated thereon (pg. 5, lines 9-10), said foams being known in the art as hydrogels (i.e., the filter comprises a hydrogel layer to which one or more molecules capable of binding one or more of the blood components has been immobilized; pg. 6, lines 1-10). Advantageously, the use of such hydrogels offers not only a support for covalently bound biospecific polymers but also biocompatibility which tend not to cause adverse effects when in contact with body fluids (pg. 6, lines 1-9). The asserted claims involve a combination of familiar elements according to known methods that does no more than yield predictable results. Because both prior arts teach methods for removing soluble blood components/substances, it would have been prima facie obvious to one of ordinary skill in the art to substitute one method for the other with a reasonable expectation of success. Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious (MPEP §2143.01 B). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to substitute the hydrogel-based filter taught by HONARD with the polysulfone hollow fiber filler made obvious by modified DAVIDNER given the same expectation of success, i.e., the removal of soluble blood components from blood.
Claim(s) 76-79 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 46 above, and further in view of HYDE et al. (US 2010/0217172 A1).
Regarding Claims 76 and 79, modified DAVIDNER makes obvious the method of Claim 46. Modified DAVIDNER is deficient in disclosing adjusting flow rate through the filter based on information about a type or amount of one or more soluble or secreted blood components in the blood (Claim 76) or adjusting flow rate through the filter to maintain IL-6 below a toxicity threshold (Claim 79).
HYDE teaches an extracorporeal device for controllably reducing inflammatory mediators in a subject (abstract, p0059; extracorporeal: p0083). Sensors and controllers in the device control the levels of inflammatory mediators to reach a target value (p0008) – such mediators include IL-6 (p0009). HYDE further discloses that the controller compares current levels of IL-6 with desired concentrations of IL-6 and, as appropriate, diverts all or part of the whole blood to one or more treatment chambers to treat the blood to achieve the desired target value of IL-6 (p0180). The diversion of blood is disclosed to be the control of flow of blood through the treatment chamber, i.e., controlling flow rate (p0006). Such an ability to accurately reduce inflammatory mediators to a desired toxicity level would advantageously provide greater control over patient therapy. Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to provide improved control over the method of modified DAVIDNER by adjusting the flow rate of blood through the filter to achieve a specific toxicity threshold, e.g., for IL-6, as taught by HYDE.
Regarding Claim 77, modified DAVIDNER makes obvious the method of Claim 46. Modified DAVIDNER is deficient in disclosing adjusting flow rate through the filter based on information about a type or amount of one or more soluble or secreted blood components to be filtered in 30 minute intervals.
HYDE teaches an extracorporeal device for controllably reducing inflammatory mediators in a subject (abstract, p0059; extracorporeal: p0083). Sensors and controllers in the device control the levels of inflammatory mediators to reach a target value (p0008). HYDE further discloses that the controller compares current inflammatory mediator levels with desired concentrations and, as appropriate, diverts all or part of the whole blood to one or more treatment chambers to treat the blood to achieve the desired target value (p0180). The diversion of blood is disclosed to be the control of flow of blood through the treatment chamber, i.e., controlling flow rate (p0006). Such an ability to accurately reduce inflammatory mediators to a desired toxicity level would advantageously provide greater control over patient therapy. Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to provide improved control over the method of modified DAVIDNER by adjusting the flow rate of blood through the filter to achieve a specific toxicity threshold as taught by HYDE.
HYDE further discloses that the treatment can be conducted at different times over the course of inflammatory response, e.g., in real-time (p0084), or at specific time points (p0101), to reduce the levels of inflammatory mediators down to a desired level. While HYDE is deficient in explicitly disclosing a 30 minute interval as claimed, such a specific interval would be obvious to one of ordinary skill in the art absent showings such an interval provides unexpected results. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation absent unexpected results or evidence indicating such optimum or workable ranges are critical (In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); MPEP§2144.05).
Regarding Claim 78, modified DAVIDNER makes obvious the method of Claim 46. DAVIDNER further discloses that pump flow can be regulated using transmembrane pressure measurements (p0063). Modified DAVIDNER is deficient in disclosing using pressure-driven automatic flow control in adjusting flow rate through the filter based on information about a nature or amount of one or more soluble or secreted blood components below a toxicity threshold.
HYDE teaches an extracorporeal device for controllably reducing inflammatory mediators in a subject (abstract, p0059; extracorporeal: p0083). Sensors and controllers in the device controls the levels of inflammatory mediators to reach a target value (p0008). HYDE further discloses that the controller compares current inflammatory mediator levels with desired concentrations and, as appropriate, diverts all or part of the whole blood to one or more treatment chambers to treat the blood to achieve the desired target value (p0180). The diversion of blood is disclosed to be the control of flow of blood through the treatment chamber, i.e., controlling flow rate (p0006). Such an ability to accurately reduce inflammatory mediators to a desired toxicity level would advantageously provide greater control over patient therapy. Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to provide improved control over the method of modified DAVIDNER by adjusting the flow rate of blood through the filter to achieve a specific toxicity threshold as taught by HYDE.
The limitation requiring “automatic flow control” is not sufficient to distinguish the invention over the prior art. Broadly providing an automatic or mechanical means to replace an otherwise manual activity that accomplishes the same result is not sufficient to distinguish the invention over the prior art (MPEP §2144.04 III).
Claim(s) 83-86 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 46 above, and further in view of BROWN et al. (WO 2013/022995 A2).
Regarding Claims 83-86, modified DAVIDNER makes obvious the method of Claim 46. Modified DAVIDNER is deficient in disclosing the filtering comprises exerting a centrifugal force of between 10,000 and 100,000 G on the blood (Claim 83), between 20,000 and 80,000 G on the blood (Claim 84), between 25,000 and 75,000 G on the blood (Claim 85), and 50,000 G on the blood (Claim 86).
BROWN discloses methods for characterizing and analyzing circulating biomarkers (p0012), said biomarkers including a protein selected from, e.g., CRP, iC3b, IL-1beta, IL6, GM-CSF, and p53 (p0014), from a biological sample, e.g., bodily fluid (p0098) including blood (p0119), such that the circulating biomarker is isolated from the sample (p0098). BROWN discloses filtration of the circulating biomarkers by filtering the biological sample through a filtration module at “centrifugal speeds” of less than 50,000 ×g (p0165). Said filtration module includes regenerated cellulose membrane filters welded to conical devices (p0170) such that retentate comprising the isolated circulating biomarker is collected on the filters (i.e., to selectively retain the blood components in the one or more conical cylinders; p0171). Thus, BROWN discloses a range of “centrifugal speeds” that overlap with or border the recited centrifugal forces of Claims 83-86 and therefore, establishes cases of prima facie obviousness (MPEP 2144.05). Prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to apply the recited centrifugal forces as suggested by BROWN for the method made obvious by modified DAVIDNER because such centrifugal force ranges were recognized as part of the capabilities of one of ordinary skill in the art (MPEP §2143.01 D).
Claim(s) 88-91 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), and PALL (US 4,033,881), as applied to Claim 46 above, and further in view of SCHILTHUIZEN et al. (US 2010/0100027 A1).
Regarding Claim 88, modified DAVIDNER makes obvious the method of Claim 46. As noted earlier, KORIN discloses that as feed enters the module, rotation of the module around its axis exerts a centrifugal force on the feed (i.e., exerting the centrifugal force on the blood; c4/35-42). Modified DAVIDNER is deficient in disclosing the filter material comprises a surface activated filtering agent to enhance chemical attraction of the filter material to one or more compounds.
SCHILTHUIZEN discloses a sorption filter device and method for the removal of toxic substances from blood or blood plasma, including toxic molecules and proteins (abstract, p0015, p0051). The sorption filter device comprises a sorbent material that includes nanofibers and nanoparticles (p0019-p0024). SCHILTHUIZEN further discloses that selective absorbing agents can be utilized to advantageously further enhance the selectivity of the sorption filter device for toxic proteins, e.g., by loading the sorbent material with specific molecule receptors (i.e., the filter material comprises a surface activated filtering agent to enhance chemical attraction of the filter material to one or more compounds; p0142). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to provide the recited surface activated filtering agent as taught by SCHILTHUIZEN for the method made obvious by modified DAVIDNER.
Furthermore, the recited limitation “to cause the blood components to contact the filter material comprising the surface activated filtering agent to selectively retain the blood components in the one or more conical cylinders” is directed toward an inherent property or characteristic resulting from the practice of the claimed method. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). Because SCHILTHUIZEN discloses the use of selective absorbing agents to further enhance the selectivity of the device for toxic proteins, the resulting effect of “caus[ing] blood components to contact the filter material… to selectively retain the blood components” is necessarily expected.
Regarding Claim 89, modified DAVIDNER makes obvious the method of Claim 88. SCHILTHUIZEN further discloses the nanostructured sorption material of the sorption filter is functionalized to exhibit improved sorbing properties of toxic substances (p0082). This advantageously provides for very high sorption efficiency (p0082). Nanostructured materials particularly suitable for such use include nanofibers (i.e., the surface activated filtering agent comprises nanofibers; p0096) and nanoparticles (p0096-0097).
Furthermore, the recited limitation “to cause the blood components to contact the filter material comprising the surface activated filtering agent comprising the nanofibers to selectively retain the blood components in the one or more conical cylinders” is directed toward an inherent property or characteristic resulting from the practice of the claimed method. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). Because SCHILTHUIZEN discloses the use of selective absorbing agents to further enhance the selectivity of the device for toxic proteins, the resulting effect of “caus[ing] blood components to contact the filter material… to selectively retain the blood components” is necessarily expected.
Regarding Claim 90, modified DAVIDNER makes obvious the method of Claim 89. SCHILTHUIZEN further discloses the nanofibers further include carbonaceous nanomaterial, including carbon nanotubes (i.e., the surface activated filtering agent comprises carbon nanofibers; p0104, p0106).
Furthermore, the recited limitation “to cause the blood components to contact the filter material comprising the surface activated filtering agent comprising the carbon nanofibers to selectively retain the blood components in the one or more conical cylinders” is directed toward an inherent property or characteristic resulting from the practice of the claimed method. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). Because SCHILTHUIZEN discloses the use of selective absorbing agents to further enhance the selectivity of the device for toxic proteins, the resulting effect of “caus[ing] blood components to contact the filter material… to selectively retain the blood components” is necessarily expected.
Regarding Claim 91, modified DAVIDNER makes obvious the method of Claim 88. As noted earlier, SCHILTHUIZEN discloses that nanostructured materials particularly suitable for such use include nanofibers (p0096) and nanoparticles (p0096-0097). SCHILTHUIZEN further discloses that carbon nanotubes are prepared from the decomposition of carbon-containing gases over selected catalytic metal surfaces, which is well-known to one of ordinary skill in the art as chemical vapor deposition (i.e., exposing the filter material to chemical vapor deposition to yield nanofiber-supported nanoparticles; p0106).
Furthermore, the recited limitation “to enhance a surface area of the filter material” is directed toward an inherent property or characteristic resulting from the practice of the claimed CVD step. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II). As is well-known to one of ordinary skill in the art, chemical vapor deposition significantly enhances available surface area; because the prior art discloses chemical vapor deposition, such a recited result is necessarily expected.
Claim(s) 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over DAVIDNER et al. (US 2005/0277863 A1) in view of WARD et al. (CA 2967094 A1), KORIN (US 5,137,637), PALL (US 4,033,881), and SCHILTHUIZEN et al. (US 2010/0100027 A1), as applied to Claim 88 above, and further in view of BARTHOLOMEW et al. (US 2011/0257008 A1).
Regarding Claim 92, modified DAVIDNER makes obvious the method of Claim 88. Modified DAVIDNER is deficient in disclosing sintering nanoparticles to a surface of the filter.
BARTHOLOMEW discloses methods for making high surface area, high porosity, stable metal oxides useful as adsorbents in filters (abstract). Briefly, the method entails sintering nanoparticles on a surface to yield a highly porous, stable metal oxide with a pore structure (abstract). Advantageously, sintering affords the production of high surface area mesoporous metal oxide structures (i.e., to enhance a surface area of the filter material; p0040, p0052) and enables greater control over pore size distribution, stability (p0043, p0045). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to sinter nanoparticles to a surface as recited as taught by BARTHOLOMEW for the method made obvious by modified DAVIDNER.
Furthermore, the recited limitation “to enhance a surface area of the filter material” is directed toward an inherent property or characteristic resulting from the practice of the claimed sintering step. “[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.” (Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004); MPEP §2112 II).
Conclusion
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/Ryan B Huang/Primary Examiner, Art Unit 1777
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