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 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-22 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.
Claims 1 and 15 recite the phrase “in a fluid conducting manner” before “to at least one inlet”, “to at least one outlet for the target”, and “to at least one outlet for the permeate”. The term “in a fluid conducting manner” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Given the indefiniteness of the phrase, the examiner will proceed the phrase to be interpreted as if the phrase was removed from the claims, as it appears redundant, given the phase of the components of the filtration has already been limited to a fluid earlier in claims 1 and 15.
Regarding claim 14, the phrase "-like" renders the claim(s) indefinite because the claim(s) include(s) elements not actually disclosed (those encompassed by "-like"), thereby rendering the scope of the claim(s) unascertainable. See MPEP § 2173.05(d).
Claims 2-13 and 16-22 are rejected due to their dependency of independent claims 1 and 15 above.
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.
Claim(s) 1-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kruse (“An alternative downstream process based on aqueous two-phase extraction for the purification of monoclonal antibodies”), in view of Leuthold (US20190030486A1).
Regarding claim 1, Kruse teaches a separation system configured to process a fluid containing a plurality of components, {Abstract re. aqueous two-phase extraction & removal of phase forming components} wherein at least one component of the plurality of components of the fluid is a target {Section 1, top of left column page 2 re. mAb can be extracted into the target phase} and wherein the separation system comprises: an aqueous-two phase extraction unit for aqueous-two phase extraction of the fluid {Section 2.2 re. aqueous two-phase extraction and a centrifuge for phase separation}
a separation unit for separating a target phase obtained after aqueous-two phase extraction, {Section 2.4 re. benchtop crossflow system for diafiltration} wherein the target phase contains the target component; {Section 1, top of left column page 2 re. mAb in target phase}
and a crossflow diafiltration unit for continuous diafiltration of the separated target phase for obtaining a retentate and a permeate. {Section 2.4 re. benchtop crossflow system for diafiltration, retentate, and permeate}
Kruse is silent to continuous diafiltration, however teaches the use water as a feed component, which is an integral part of continuous filtration. Thus Kruse, while silent to the claimed terminology, teaches the claimed limitation.
Kruse further teaches a first filter material, and a second filter material. {Section 2.4 re. two ultrafiltration cassettes}
While Kruse does not explicitly teach wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate; an argument can be made regarding the inherency of these component given what is taught by Kruse; however, the examiner believes for clarity of the record and compact prosecution, Leuthold teaches these limitations more clearly, and thus will map to Leuthold to follow.
Leuthold drawn to the extraction of biological components in a crossflow diafiltration system {Leuthold, [0016]} teaches wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; {[0010] re. diafiltration channel, a retentate channel, and a permeate channel}
wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, {[0010] re. diafiltration channel to the inlet for the diafiltration medium} the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate {[0010] re. retentate channel to the target phase inlet and retentate outlet} and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate. {[0010] re. permeate channel to the permeate outlet}
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate; as Leuthold, similarly to Kruse, teaches a continuous diafiltration system with retentate, permeate, and diafiltration medium, specifically with biological components {Leuthold, [0002] & [0016]} Doing so would improve efficiency of the system, as this would provide separate flow paths for each fluid, preventing cross contamination.
Kruse fails to teach that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, and the second filter material delimits the retentate channel and the permeate collection channel from one another.
Leuthold teaches that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, {[0010] re. the first filter delimits the diafiltration and retentate channels} and the second filter material delimits the retentate channel and the permeate collection channel from one another, {[0010] re. the second filter delimits the retentate and permeate collection channels}
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, and the second filter material delimits the retentate channel and the permeate collection channel from one another as doing so would improve the quality of the fluid being separated as these filters help with the separation of the branch points between the flow paths, thus decreasing contamination between them.
Regarding claim 4, Kruse teaches wherein the target component is contained in the retentate after diafiltration. {Section 3.2.3 re. mAb in the retentate}
Regarding claim 5, Kruse teaches wherein the separated target phase is directly applied to the crossflow diafiltration unit. {Section 3.2.3 re. how the retentate was applied in the diafiltration process}
Regarding claims 6-7, Kruse fails to teach wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 6) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase. (Claim 7)
Leuthold teaches wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 6) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase. (Claim 7) {[0058] teaches relationships of flow rates of both the diafiltration medium and the retentate (target phase) to a supplied feed fluid. With the relationships taught, the relationship of diafiltration medium to the retentate (target phase) can be determined as 0.1 to 300 times the volume flow rate of one another}
If the rate of supplied feed fluid stays constant, the medium can be anywhere from 0.1 to 15x the speed, and the target phase can be from 0.05 to 10x the speed. When comparing lower and upper ranges of medium liquid to target liquid flow rates, you get anywhere from 0.1/10=0.01 to 15/0.05=300.0 . Which can be rewritten as the volume flow rate of the diafiltration medium is 0.01 to 300 times the volume flow rate of the retentate (target phase)
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 6) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase (Claim 7) as continuous diafiltration is a process that does not have to be interrupted, and the flow rates taught by Leuthold, are compatible with this process. Doing so makes it possible to run the unit in an efficient and economical manner. {Leuthold, [0015]}
Regarding claims 8, Kruse teaches wherein a concentration of the target component in the separated target phase is from 0.5 g/L to 10 g/Line. {Table 3 re. mAb concentration at after ATPE 2.4 +/- 0.1 mg/mL (converts to 2.4 g/L)} and
Regarding claim 9, Kruse teaches wherein a concentration of the target component in the retentate after diafiltration is from 0.5 g/L to 10 g/L.{Table 3 re. mAb concentration at after phase separation 2.4 +/- 0.1 mg/mL (converts to 2.4 g/L)}
Regarding claim 10, Kruse teaches wherein the first filter material and the second filter material are identical. {Section 2.4 re. two ultrafiltration cassettes (Sartocon Slice 200). Note that given Kruse recites the same model for both cassettes, it teaches that each cassette is identical}
Regarding claim 11, Kruse teaches wherein the pH of the diafiltration medium is from 2.0 to 12.0. {Section 2.4 re. KPi as a DF-buffer with a pH of 7.0}
Regarding claim 12, Kruse teaches wherein the diafiltration medium is selected from the group consisting of KPi buffer, sodium phosphate buffer, sodium acetate buffer, PBS, glycine, citrate buffer, Tris buffer, BIS-Tris buffer, HEPES buffer, and water. {Section 2.4 re. KPi as a DF-buffer}
Regarding claim 13, Kruse teaches wherein a composition for the aqueous-two phase extraction comprises, based on a total amount of the composition; from 4.0 to 25.0 wt.% of polyethylene glycol having an average molecular weight of from 300 to 20000; {Section 2.2 re. PEG (polyethylene glycol) with molecular weight of 400 g/mol}
from 5.0 to 40 wt.% first salt selected from a phosphate salt, a citrate salt and a sulfate salt, or polymer. {Section 2.2 re. 40 weight % phosphate buffer}
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention because the range of Kruse teaches the claimed range in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP § 2144.05(I)
Kruse further teaches 0 to 10.0 wt.% second salt; {Table 1 re. 4% weight NaCl} 10.0 to 50.0 wt.% fluid containing the target component; {Table 1 re. 19% weight PEG400} and the balance being water. {Table 1 re. 36% weight feed & Section 2.4 re. water as the feed component}
Regarding claim 14, Kruse teaches wherein the target component is selected from proteins, monoclonal antibodies, hormones, vaccines, nucleic acids, exosomes, viruses, and virus-like particles. {Title re. monoclonal antibodies}
Regarding claim 15, Kruse teaches a method for purifying a target component included in a fluid, wherein the method comprises the steps of:
(a) subjecting the fluid to aqueous two-phase extraction; {Abstract re. aqueous two-phase extraction & removal of phase forming components}
(b) separating a target phase containing the target component from the other phase obtained after aqueous-two phase extraction; {Section 2.r re. the LP being diafiltrated, inferring that the LP (target fluid) had to have been separated after the centrifugation process in the two-phase extraction step}
and (c) subjecting the separated target phase to diafiltration using a crossflow diafiltration unit; {Section 2.4 re. diafiltration}
a first filter material, and a second filter material. {Section 2.4 re. two ultrafiltration cassettes}
While Kruse does not explicitly teach wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate; an argument can be made regarding the inherency of these component given what is taught by Kruse; however, the examiner believes for clarity of the record and compact prosecution, Leuthold teaches these limitations more clearly, and thus will map to Leuthold to follow.
Leuthold drawn to the extraction of biological components in a crossflow diafiltration system {Leuthold, [0016]} teaches wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; {[0010] re. diafiltration channel, a retentate channel, and a permeate channel}
wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, {[0010] re. diafiltration channel to the inlet for the diafiltration medium} the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate {[0010] re. retentate channel to the target phase inlet and retentate outlet} and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate. {[0010] re. permeate channel to the permeate outlet}
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings wherein the crossflow diafiltration unit at least comprises a diafiltration channel, a retentate channel, and a permeate collection channel; wherein the diafiltration channel is connected in a fluid conducting manner to at least one inlet for a diafiltration medium, the retentate channel is connected in a fluid conducting manner to at least one inlet for the target phase and to at least one outlet for the retentate and the permeate collection channel is connected in a fluid conducting manner to at least one outlet for the permeate; as Leuthold, similarly to Kruse, teaches a continuous diafiltration system with retentate, permeate, and diafiltration medium, specifically with biological components {Leuthold, [0002] & [0016]} Doing so would improve efficiency of the system, as this would provide separate flow paths for each fluid, preventing cross contamination.
Kruse fails to teach that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, and the second filter material delimits the retentate channel and the permeate collection channel from one another.
Leuthold teaches that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, {[0010] re. the first filter delimits the diafiltration and retentate channels} and the second filter material delimits the retentate channel and the permeate collection channel from one another, {[0010] re. the second filter delimits the retentate and permeate collection channels}
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings that the first and second filters are arranged in such a way that the first filter material delimits the diafiltration channel and the retentate channel from one another, and the second filter material delimits the retentate channel and the permeate collection channel from one another as doing so would improve the quality of the fluid being separated as these filters help with the separation of the branch points between the flow paths, thus decreasing contamination between them.
Regarding claim 16, Kruse teaches wherein the target component is contained in the retentate after diafiltration. {Section 3.2.3 re. mAb in the retentate}
Regarding claim 17, Kruse teaches wherein the separated target phase is directly applied to the crossflow diafiltration unit. {Section 3.2.3 re. how the retentate was applied in the diafiltration process}
Regarding claims 18-19, Kruse fails to teach wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 18) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase. (Claim 19)
Leuthold teaches wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 18) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase. (Claim 19) {[0058] teaches relationships of flow rates of both the diafiltration medium and the retentate (target phase) to a supplied feed fluid. With the relationships taught, the relationship of diafiltration medium to the retentate (target phase) can be determined as 0.1 to 300 times the volume flow rate of one another}
If the rate of supplied feed fluid stays constant, the medium can be anywhere from 0.1 to 15x the speed, and the target phase can be from 0.05 to 10x the speed. When comparing lower and upper ranges of medium liquid to target liquid flow rates, you get anywhere from 0.1/10=0.01 to 15/0.05=300.0 . Which can be rewritten as the volume flow rate of the diafiltration medium is 0.01 to 300 times the volume flow rate of the retentate (target phase)
It would be obvious to one of ordinary skill prior to the effective filing date of the claimed invention to modify Kruse with Leuthold’s teachings wherein a volume flow rate of the diafiltration medium is 0.5 to 20 times the volume flow rate of the target phase; (Claim 18) and wherein the volume flow rate of the diafiltration medium is 5.0 to 7.0 times the volume flow rate of the target phase (Claim 19) as continuous diafiltration is a process that does not have to be interrupted, and the flow rates taught by Leuthold, are compatible with this process. Doing so makes it possible to run the unit in an efficient and economical manner. {Leuthold, [0015]}
Regarding claim 20, Kruse teaches wherein a concentration of the target component in the separated target phase is from 0.5 g/L to 10 g/L. {Table 3 re. mAb concentration at after ATPE 2.4 +/- 0.1 mg/mL (converts to 2.4 g/L)}
Regarding claim 21, Kruse teaches wherein a concentration of the target component in the retentate after diafiltration is from 0.5 g/L to 10 g/L. {Table 3 re. mAb concentration at after phase separation 2.4 +/- 0.1 mg/mL (converts to 2.4 g/L)}
Regarding claim 22, Kruse teaches wherein the first filter material and the second filter material are identical. {Section 2.4 re. two ultrafiltration cassettes (Sartocon Slice 200). Note that given Kruse recites the same model for both cassettes, it teaches that each cassette is identical}
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Kopf (US20110309018A1) directed to an apparatus with retentate, permeate, diafiltration medium, continuous crossflow filtration, biological components, and channels connecting the flow paths within.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CONNOR J ROTONDI whose telephone number is (571)272-2058. The examiner can normally be reached M-F 8:00am-4:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Benjamin Lebron can be reached at (571)272-0475. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CONNOR J ROTONDI/ Examiner, Art Unit 1773 /JOSEPH W DRODGE/Primary Examiner, Art Unit 1773
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