DETAILED ACTION
This detailed action is in response to the amendments and arguments filed on 10/30/25, and any subsequent filings.
Notations “C_”, “L_” and “Pr_” are used to mean “column_”, “line_” and “paragraph_”.
Claims 10-11 are canceled. Claims 1-9, 14, and 21-28 are pending.
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 .
Response to Arguments
Claim Rejections - 35 USC § 103
The Applicant argues that none of Plotz, Protein or Nikolaev teach albumin covalently attached to a surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of plurality of the beads, and that Plotz teaches 30 to 50 mg albumin per gram of wet weight of beads (pg. 8). This argument is unpersuasive because this is directed towards the amended claim.
Response to Amendment
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.
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 1-9, 14 and 21-27 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication US20150290380A1 (‘Welzel’) in view of Publication Bilirubin Removal from Human Plasma with Albumin Immobilised Magnetic Poly(2-hydroxyethyl methacrylate) Beads (‘Rad’, Macromol. Biosci. 2003, 3, 471–476) and in further view of Publication CNBr-activated resin to immobilize ligands for affinity chromatography (‘Protein’, a file of the publicly available webpage was provided with a previous office action) and in further view of Publication Removing Substances from Blood by Affinity Chromatography: I. REMOVING BILIRUBIN AND OTHER ALBUMIN-BOUND SUBSTANCES FROM PLASMA AND BLOOD WITH ALBUMIN-CONJUGATED AGAROSE BEADS (‘Plotz’, J Clin Invest. 1974;53(3):778-785) and in further view of Publication Deliganding Carbonic Adsorbents for Simultaneous Removal of Protein- Bound Toxins, Bacterial Toxins and Inflammatory Cytokines (‘Nikolaev’, S. Mikhalovsky and A. Khajibaev (eds.), Biodefence, NATO Science for Peace 289 and Security Series A: Chemistry and Biology, DOI 10.1007/978-94-007-0217-2_29).
The Applicant’s claims are directed towards an apparatus.
Regarding Claims 1-9, 14 and 21-27, Welzel teaches a device (abstract) operable to remove one or more toxin molecules ([0016]) from a stream of blood ([0059]), the device comprising:
a housing (Fig. 3, [0035], housing 13) having a receiving space (Fig. 3, [0035], space 15);
at least one hollow fiber (Fig. 3, [0035], hollow fiber membrane 14) extending longitudinally through at least a portion of the receiving space of the housing (Fig. 3, [0035]), the at least one hollow fiber operable to receive the stream ([0035]) of blood (fluid ([0035]) is blood ([0059])), the stream of blood including one or more cellular elements ([0025] and [0060], liver toxins. [0008], blood cells.) and one or more plasma elements ([0036]); and
a plurality of beads (Fig. 3, [0017], particles 22) disposed within the receiving space ([0017]) and external to the at least one hollow fiber ([0015], [0025], [0052] and [0057]), wherein,
the at least one hollow fiber includes a plurality of pores ([0046]),
the plurality of pores has an average diameter from about 100 nanometers to about 1 micron ([0046]) and are operable to retain the one or more cellular elements of the stream of blood within the at least one hollow fiber ([0008], plasma separation membranes retain blood cells and large protein molecules) and to allow the one or more plasma elements of the stream of blood to pass from the at least one hollow fiber to the receiving space of the housing ([0008] and [0047], plasma separation membranes exhibit high permeability for plasma proteins and lipoproteins),
and the plurality of beads is configured to receive a toxin molecule from the one or more plasma elements ([0057], removal of target substances, such as liver toxins, from the fluid to be treated).
Welzel does not teach that the plurality of beads includes a cyanate ester group and comprises albumin covalently attached to a surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of the plurality of the beads, and that the toxin molecule is indoxyl sulfate.
Rad also relates to a device operable to remove one or more toxin molecules (pg. 471) from a stream of blood (pg. 473, left column), the device comprising:
a plurality of beads including a cyanate ester group (beads are coupled to human serum albumin via cyanogen bromide, pg. 472, right column, Pr3, resulting in a cyanate ester group. See Protein, figure titled Activation of resin with cyanogen bromide),
the plurality of beads comprises albumin covalently attached (pg. 472, right column, last Pr) to a surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of the plurality of the beads (pg. 471 and 474, left column).
Additional Disclosures Included:
Claim 2: the one or more cellular elements comprises at least one selected from the group consisting of red blood cells (Welzel, [0008]), white blood cells, and platelets, and
the one or more plasma elements comprises at least one selected from the group consisting of free toxin molecules (Welzel, [0062]), amino acids, proteins (Welzel, [0059]), glucose, and lipids.
Claim 3: the one or more plasma elements comprises a protein (Welzel, [0059]).
Claim 4: the one or more plasma elements is albumin (Welzel, [0016]).
Claim 5: each of the plurality of beads includes a chemical moiety capable of receiving the toxin molecule (Rad, pg. 471), and
the toxin molecule is bound to the one or more plasma elements (Rad, pg. 471).
Claim 6: the chemical moiety is characterized by a greater chemical affinity toward the toxin molecule than a chemical affinity exhibited by the plasma element to the toxin molecule to which it is bound (Plotz, abstract, albumin binds protein-bound substances. Welzel, [0036], the dialysate is enriched with albumin which serves for binding liver toxins from a fluid consisting of plasma comprising albumin bound liver toxins. Thus, it is being interpreted that the albumin has a greater chemical affinity towards toxins than towards the plasma).
Claim 7: the one or more plasma elements includes a plasma protein bound to the toxin
molecule (Plotz, abstract, albumin-bound toxins), and
each of the plurality of beads is configured to receive the toxin molecule from the plasma protein (Plotz, abstract).
Claim 8: each of the plurality of beads comprises one or more chemical moieties (Rad, pg. 471), and
each of the one or more chemical moieties have a chemical affinity for the toxin molecule that is greater than or equal to the chemical affinity of the plasma protein for the toxin molecule (Plotz, abstract, albumin binds protein-bound substances. Welzel, [0036], the dialysate is enriched with albumin which serves for binding liver toxins from a fluid consisting of plasma comprising albumin bound liver toxins. Thus, it is being interpreted that the albumin has a greater chemical affinity towards toxins than towards the plasma).
Claim 9: the plasma protein is albumin (Welzel, [0036]).
Claim 14: the at least one hollow fiber comprises a hollow fiber array (Welzel, [0016-0017], Fig. 3, bundle of hollow fiber membranes 14).
Claim 21: the average diameter is from about 650 nanometers to about 1 micron (Welzel, [0046]).
Claim 22: average diameter is from about 400 nanometers to about 700 nanometers (Welzel, [0046]).
Regarding Claims 23-28, Welzel teaches a device (abstract) operable to remove one or more toxin molecules ([0016]) from a stream of blood ([0059]), the device comprising:
a housing (Fig. 3, [0035], housing 13) having a receiving space (Fig. 3, [0035], space 15);
at least one hollow fiber (Fig. 3, [0035], hollow fiber membrane 14) extending longitudinally through at least a portion of the receiving space of the housing (Fig. 3, [0035]), the at least one hollow fiber operable to receive the stream ([0035]) of blood (fluid ([0035]) is blood ([0059])), the stream of blood including one or more cellular elements ([0025] and [0060], liver toxins. [0008], blood cells.) and one or more plasma elements ([0036]); and
a plurality of beads (Fig. 3, [0017], particles 22) disposed within the receiving space ([0017]) and external to the at least one hollow fiber ([0015], [0025], [0052] and [0057]), wherein,
the at least one hollow fiber includes a plurality of pores ([0046]),
the plurality of pores operable to retain the one or more cellular elements of the stream of blood within the at least one hollow fiber ([0008], plasma separation membranes retain blood cells and large protein molecules) and to allow the one or more plasma elements of the stream of blood to pass from the at least one hollow fiber to the receiving space of the housing ([0008] and [0047], plasma separation membranes exhibit high permeability for plasma proteins and lipoproteins),
the plurality of beads are configured to receive a toxin molecule bound to the one or more plasma elements ([0057], removal of target substances, such as liver toxins, from the fluid to be treated).
Welzel does not teach that the plurality of beads includes a cyanate ester group and comprises albumin covalently attached to a surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of the plurality of the beads, and that the toxin molecule is indoxyl sulfate.
Rad also relates to a device operable to remove one or more toxin molecules (pg. 471) from a stream of blood (pg. 473, left column), the device comprising:
a plurality of beads including a cyanate ester group (beads are coupled to human serum albumin via cyanogen bromide, pg. 472, right column, Pr3, resulting in a cyanate ester group. See Protein, figure titled Activation of resin with cyanogen bromide),
the plurality of beads comprises albumin covalently attached (pg. 472, right column, last Pr) to a surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of the plurality of the beads (pg. 471 and 474, left column).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the plurality of beads of Welzel can include a cyanate ester group, as demonstrated by Rad and Protein, to remove albumin-bound substances (Plotz, pg. 778, right column, last Pr-pg. 779, left column, Pr1), including indoxyl sulfate (Nikolaev, pg. 290-291, see section 29.1 Protein Bound Uremic and Hepatic Toxins and Table 29.1, indoxyl sulfate is moderately bound to albumin). It would have been obvious for the plurality of beads of Welzel to comprise albumin covalently attached to the surface of each of the plurality of beads in an amount of about 10 mg of albumin per gram of the plurality of beads, as demonstrated by Rad, as the extent of albumin immobilization can be changed (Rad, pg. 472, right column, last Pr).
Additional Disclosures Included:
Claim 24: the cyanate ester group is characterized by a greater chemical affinity toward the toxin molecule than the chemical affinity exhibited by the plasma element to the toxin molecule to which it is bound (Plotz, abstract, albumin binds protein-bound substances. Welzel, [0036], the dialysate is enriched with albumin which serves for binding liver toxins from a fluid consisting of plasma comprising albumin bound liver toxins. Thus, it is being interpreted that the albumin has a greater chemical affinity towards toxins than towards the plasma).
Claim 25: the plurality of pores has an average diameter from about 100 nanometers to about 1 micron (Welzel, [0046]).
Claim 26: the plurality of pores has an average diameter from about 650 nanometers to about 1 micron (Welzel, [0046]).
Claim 27: the plurality of pores has an average diameter from about 400 nanometers to about 700 nanometers (Welzel, [0046]).
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication US20150290380A1 (‘Welzel’) in view of Publication Bilirubin Removal from Human Plasma with Albumin Immobilised Magnetic Poly(2-hydroxyethyl methacrylate) Beads (‘Rad’, Macromol. Biosci. 2003, 3, 471–476) and in further view of Publication CNBr-activated resin to immobilize ligands for affinity chromatography (‘Protein’, a file of the publicly available webpage was provided with a previous office action) and in further view of Publication Removing Substances from Blood by Affinity Chromatography: I. REMOVING BILIRUBIN AND OTHER ALBUMIN-BOUND SUBSTANCES FROM PLASMA AND BLOOD WITH ALBUMIN-CONJUGATED AGAROSE BEADS (‘Plotz’, J Clin Invest. 1974;53(3):778-785) and in further view of Publication Deliganding Carbonic Adsorbents for Simultaneous Removal of Protein- Bound Toxins, Bacterial Toxins and Inflammatory Cytokines (‘Nikolaev’, S. Mikhalovsky and A. Khajibaev (eds.), Biodefence, NATO Science for Peace 289 and Security Series A: Chemistry and Biology, DOI 10.1007/978-94-007-0217-2_29) as applied to claim 1 above, and further in view of U.S. Publication US20150273127A1 (‘Flieg’).
The Applicant’s claim is directed towards an apparatus.
Regarding Claim 28, the combination of Welzel, Rad, Protein, Plotz and Nikolaev teaches the device of Claim 1, including one or more ports fluidly coupled to the receiving space (Welzel, Fig. 3, [0017], inlet 18 and outlet 20), except that the one or more ports are movable between an open position and a closed position to provide access to the receiving space.
Flieg also relates a device operable to remove one or more toxin molecules from a stream of blood (abstract), the device comprising one or more ports (Fig. 2, [0063] and [0076], ports, 8b, 10b and 11b) that are movable between an open position and a closed position ([0063] and [0076]) to provide access to the receiving space ([0025] and [0063]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention for the one or more ports of the combination of Welzel, Rad, Protein, Plotz and Nikolaev to be movable between an open position and a closed position, as demonstrated by Flieg, in order to feed and remove fluid as desired (Flieg, [0017] and [0025]).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BOI-LIEN THI NGUYEN whose telephone number is (703)756-4613. The examiner can normally be reached Monday to Friday, 8 am to 6 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bobby Ramdhanie can be reached at (571) 270-3240. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BOI-LIEN THI NGUYEN/Examiner, Art Unit 1779
/Bobby Ramdhanie/Supervisory Patent Examiner, Art Unit 1779