DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
Applicant’s claim for the benefit of a prior-filed application (371 of PCT/SE2013/051493, filed 12 December 2013) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority (SE1251422-0, filed 14 December 2012) under 35 U.S.C. 119 (a)-(d).
Claim Interpretation
Claim 1 recites the following “by flowing a first cleaning liquid upwards… followed by repacking the cleaned liquefied bed” (emphasis added). Although the claim is seemingly open-ended because of the use of the “comprising the steps of” transitional phrase in the preamble, the phrase “followed by” is interpreted to indicate that the step of “flowing a first cleaning liquid upwards” must directly precede the step of “repacking the cleaned liquefied bed”, i.e., there are no other steps that can be practiced between these two steps. Arguments filed by the Applicant on 17 March 2020 have indicated this difference between the inventive method and that of the prior art DICKSON: “The removal of a reslurried media is not recited by the Applicant’s claims, and, as a result, the Applicant’s claims are not taught or suggested by the cited art, including Dickson” (pg. 2, bottom) and “The removal of the Dickson’s reslurried media before the addition of a second sample prevents the reference from teaching or suggesting the Applicant’s independent claims” (pg. 3, middle). Thus, the inventive method is interpreted to not be as broad as the preamble would suggest and requires a specific order of steps without additional steps to be practiced during the liquefying and cleaning steps.
It is further noted that the limitation “by flowing a first cleaning liquid upwards… followed by repacking the cleaned liquefied bed” does not restrict the claimed process to other steps prior to “flowing a first cleaning liquid upwards”, e.g., flowing other cleaning liquids, because the claim utilizes open-ended transitional phrases (i.e., “A process for chromatographic separation… comprising the steps of…”).
Even further, the limitation “a first cleaning liquid” does not necessarily indicate that such a cleaning liquid is the initial cleaning liquid to be used in the process, e.g., the claim is broadly constructed such that a second cleaning liquid or multiple other fluids may be introduced to the column prior to the flowing of a first cleaning liquid through the compressed bed. The claim only requires that a “first” cleaning liquid be flowed upward through the compressed bed and does not restrict this to be the only liquid to be flowed.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1, 3-7, 9, 11, 14-22, and 24 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over DICKSON (US 6,740,241) in view of LEIJON (US 6,706,191), EDBLAD (US 2011/0073213 A1), and GJERDE et al. (US 6,485,648) with evidentiary support from GUPTA (Expanded Bed Affinity Chromatography, 2002) and ATODIRESEI et al. (Journal of Magnetism and Magnetic Materials, 2004, vol. 272-276, pg. 2359-2361).
Regarding Claim 1, DICKSON discloses a method for packing a column, separating a mixture of interest, and cleaning the column in place (c6/45-c7/44) utilizing a chromatography column as exemplified in FIG. 1. Said column comprises a hollow cylindrical housing (i.e., an axial chromatography column), a lower fixed cell assembly (i.e., a bottom end), and an upper adjustable cell assembly 13 (i.e., a top end, an adaptor at the top end; c4/10-20); a filter mesh is provided in the lower distribution cell 6 (i.e., a support net at the bottom end; c7/34-37). Chromatography media 14 is first packed within the column being retained in the column by the distribution cell of the upper adjustable cell assembly 13 (i.e., the column comprising a compressed bed of separation matrix particles confined between a support net at the bottom end and a movable adaptor at the top end, wherein the compressed bed is in contact with the adaptor; c6/45-52). A mixture of interest (e.g., pharmaceuticals; i.e., a first target biomolecule; c1/30-32) is fed to the column through an upper slurry valve 11 for separation (i.e., applying the sample to the compressed bed and separating a first target biomolecule from at least one contaminant on the column; c6/66-c7/5). After separating, a cleaning solution is introduced into the column through a bottom slurry valve 11 to allow for the contents of the column to “re-slurry” (i.e., liquefying and cleaning the compressed bed in the column to form a cleaned liquefied bed of the column by flowing a first cleaning liquid upwards through the compressed bed to form a liquefied bed; c7/6-10, 24-26, 38-42). Finally, once cleaned, the column is repacked for subsequent separations (c8/5-11).
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DICKSON further teaches removing the chromatographic media for cleaning after separation (c7/6-8) prior to repacking for subsequent separations (c8/5-11). However, this is distinguished from the claimed inventive method, which requires that during the liquefying and cleaning steps, the compressed bed is cleaned by flowing a first cleaning liquid upward through the compressed bed to form a liquefied bed, followed by repacking the cleaned liquefied bed to create a second compressed bed.
However, such a limitation of first cleaning a fluidized bed followed by repacking the fluidized bed is recognized as a cleaning-in-place process well-known in the art. LEIJON discloses chromatographic processes utilizing fluidized beds (c1/22-46); after a column separation using adsorbent particles, the adsorbent particles are subjected to cleaning-in-place in fluidized mode (c2/20-29). Advantageously, as GUPTA teaches, the washing of expanded bed adsorbents (e.g., wherein adsorbent beads are in motion, much like in fluidized beds) is critical and provides a quicker and vigorous wash to the bed (§6.2, par. 1; §6.3, par. 1). Thus, the basic technique of cleaning-in-place as taught by LEIJON yields no more than a predictable outcome and results in an improved system as that taught by DICKSON which one of ordinary skill in the art would have expected to achieve (MPEP §2143.01 D).
Even further, while DICKSON is deficient in explicitly disclosing that the first and second target biomolecules are different, LEIJON teaches that in a typical cyclic chromatographic process carried out on packed/fluidized beds comprising a capture step, a wash step, and a regeneration step, “one or more compounds present in a liquid sample” are captured (c1/22-46), e.g., such compounds include proteins and peptides ((i.e., the first and the second target biomolecules, independently, comprise a protein, a peptide, or a virus; c7/66-c8/12). The subsequent use of the same packed bed for the separation of the same or a different compound present in a liquid sample is indeed known in the art and would be obvious to any one of ordinary skill to practice. Such a repeated process, albeit for a second target biomolecule different from the first target biomolecule, is obvious because this particular known technique is recognized as part of the capabilities of one of ordinary skill in the art (MPEP §2143.01 D).
Modified DICKSON is deficient in explicitly disclosing a movable adaptor at the top end and raising the adaptor by at least 25% of the height of the compressed bed.
EDBLAD discloses a column packing and unpacking method utilizing a movable adaptor to determine optimal packing conditions for a chromatography bed. EDBLAD teaches compacting a column bed by lowering the adapter to produce a packed bed (p0034) and unpacking the bed by raising the adapter to allow the bed to expand past the point of an uncompressed bed (p0037).
While EDBLAD discloses a packing method different from the packing process taught by DICKSON, wherein top/bottom valves of top/bottom distributors are open/closed to allow for media to be delivered to optimal packing conditions, EDBLAD discloses that the movable adaptor method can be combined with a process similar to the method taught by DICKSON: “Another possible solution is to combine this packing method with a moveable adapter. The column can be packed as described above…” (p0029). This “packing method” that EDBLAD references is similar to that of DICKSON: “the adapter is placed at the intended final packed bed height and the column is filled and packed at the same time through the nozzle in the top of the column…[w]hen the correct amount of slurry has been delivered from the slurry tank to the column, the packing pump can be shut off” (p0028).
Thus, while DICKSON may have disclosed packing without a movable adaptor, EDBLAD discloses that the use of a movable adaptor could be combined with such a packing method. Further, EDBLAD recognized that conventional packing methods, such as that disclosed by DICKSON, results in a sub-optimal bed pack; EDBLAD teaches that after filling a column with the desired amount of slurry/media, a movable adaptor can advantageously fill/squeeze out any remaining gaps and voids, properly consolidate/pack the bed, and thereby prevent unwanted bed expansion (p0030). Thus, at the time of the invention, one of ordinary skill in the art would have found it obvious to apply the movable adaptor of EDBLAD to the method of bed packing taught by modified DICKSON.
While EDBLAD is deficient in explicitly disclosing raising the adapter by at least 25% of the height of the compressed bed as claimed, absent a showing of criticality, the “at least 25%” limitation would have been obvious to one of ordinary skill in the art at the time of the invention. As noted earlier, EDBLAD teaches that the bed can be expanded by running the adapter upward to allow the bed to expand past the point of the uncompressed bed (p0037). Such an action allows the process to operate at “the best unpacking conditions” and to advantageously achieve desired slurry concentrations (p0037, p0038). Furthermore, the degree to which the adaptor would have to be raised to allow for sufficient unpacking would be dependent on the type of adsorption media, slurry density, and column operating conditions, which could be determined by one of ordinary skill in the art as noted by EDBLAD (p0037). 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). Thus, the claimed parameter, i.e., the relative adaptor height, is also recognized as a result-effective variable and can be optimized through routine experimentation (MPEP §2144.05 II B), and the claimed range, i.e., "at least 25% of the height of the consolidated bed", would have been obvious. At the time of the invention, one of ordinary skill in the art would have found it obvious that the upper adjustable cell assembly of DICKSON in view of LEIJON would have to be raised as taught by EDBLAD to advantageously allow for the fluidization of the packed bed for sufficient cleaning.
While modified DICKSON is deficient in explicitly disclosing repacking the cleaned liquefied bed of the column in the column to create a second compressed bed and lowering the adaptor such that it contacts the second compressed bed and optionally compresses it or a subsequent step e) of applying a second sample to the top of the chromatography column and separating a second target biomolecule from at least one contaminant on the column, these limitations are directed toward repeated process steps, namely the packing of separation matrix particles and the separation of a target compound. Because modified DICKSON makes obvious such steps as described, and further discloses the optional continued operation of the column for another separation (i.e., DICKSON c8/9-11), absent new or unexpected results would be produced, these instant limitations have no patentable significance because they would have been obvious to one of ordinary skill in the art to practice to properly separate a target biomolecule of interest. Furthermore, such limitations are considered obvious and typically practiced by one of ordinary skill in the art. Chromatography columns are typically cleaned, repacked, and prepared for further separations; in the normal use and operation of a column, such as that made obvious by modified DICKSON, the limitations of repacking and compressing and running a subsequent sample are expected.
Modified DICKSON is deficient in disclosing the cleaning liquid is alkaline with a pH value of at least 10 or that wherein any cleaning liquid that first contacts the compressed bed is alkaline, with a pH value of at least 10.
GJERDE teaches the separation of biomolecules using a chromatography column packed with stationary phase separation media (c4/58-c5/4); GJERDE further discloses the need to clean accumulated residue from the stationary phase due to gradual fouling by using a highly effective cleaning solution to advantageously restore the separation media to a fully effective state (c13/16-26). GJERDE discloses that at the end of each run, cleaning solutions are routinely injected into the system to regenerate and clean the separation media surfaces (c14/25-28) and lists suitable cleaning solutions designed for removal of particular materials in Table A (c14-c15), including sodium EDTA solutions having a pH up to 13 (c15/10-11). Such a disclosure of a pH up to 13 overlaps with the claimed range of a pH value of at least 10 and therefore, establishes a case of prima facie obviousness (MPEP 2144.05). Thus, at the time of the invention, one of ordinary skill in the art would have found it obvious to utilize alkaline cleaning liquid to first contact the compressed bed as taught or suggested by GJERDE in the method made obvious by modified DICKSON.
It is noted that although GJERDE primarily discloses that the method of cleaning accumulated residue is directed toward removing DNA residue, i.e., “For removing DNA residues, sodium EDTA solutions having a pH up to 13…” (c15/10-11), such a disclosure is directed toward an exemplary embodiment. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use” (In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994); MPEP §2123 II). GJERDE further discloses in Table A that sodium EDTA is useful as a cleaning solution reagent for removing proteins and peptides in addition to DNA (i.e., the first and the second target biomolecules, independently, comprise a protein, a peptide, or a virus; c14/45-c15/9). Thus, one of ordinary skill in the art would have found it obvious to apply the disclosed cleaning liquid to remove protein or peptide residues from a column—ostensibly from a separation of proteins or peptides from a solution—because the prior art discloses such alternative capabilities of the cleaning solution. The claim would have been obvious to one of ordinary skill in the art because the substitution of one known element for another would have yielded predictable results (MPEP §2143.01 B).
Modified DICKSON is deficient in explicitly disclosing the compressed bed having a yield stress higher than about 100 Pa, or the liquefied bed having a yield stress lower than about 50 Pa.
However, as evidenced by ATODIRESEI, the yield stress levels in stabilized and fluidized beds are dependent on the fluid velocity; as an increasing fluid velocity is imparted in a vertical, fluidized glass column, the yield stress within the bed decreases (FIG. 2; §3, pg. 2360, col. 2, par. 1-2). For example, LEIJON discloses a 1000-mm bed depth and a liquid velocity of 300 cm/h (c9/14-21); as recognized by ATODIRESEI, as the superficial fluid velocity (Ub) increases relative to the minimum fluidization velocity (Umf), the yield stress in the bed decreases from over 250 Pa to around 50 Pa (FIG. 2). For higher velocities, it is expected that the bed yield stress would continue to decrease, i.e., yield stress is an inherent property of a packed or fluidized bed and is primarily dependent on fluid velocity . Thus, although not explicitly disclosed by DICKSON, LEIJON or EDBLAD, the yield stress of a compressed, non-fluidized bed is expected to be high, e.g., over 250 Pa as evidenced by ATODIRESEI, and that of a liquefied, fluidized bed is expected to continually decrease, e.g., below about 50 Pa as evidenced by ATODIRESEI. 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). Therefore, the specified “yield stress higher than about 100 Pa” and “yield stress lower than about 50 Pa” limitations would have been obvious to one of ordinary skill in the art absent showings of criticality to such ranges. Furthermore, even if not explicitly disclosed by the prior art, fluidized beds are expected to have low yield stresses and non-fluidized beds are expected to have relatively higher yield stresses. Applicant has not shown why the claimed yield stress ranges are critical to the invention; such ranges are therefore obvious to one of ordinary skill in the art.
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Regarding Claims 3-5, modified DICKSON makes obvious the process of Claim 1. The instant claim limitations are directed toward additional steps of conveying a second cleaning liquid after step b) (Claim 3), conveying a third cleaning liquid after step e) (Claims 4 and 5), and further repeating steps b), b'), e), and e’) (Claim 5) and are construed as duplications of step d). The mere duplication of parts has no patentable significance unless a new and unexpected result is produced (In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960); MPEP §2144.04).
Regarding Claim 6, modified DICKSON makes obvious the process of Claim 1. The instant claim limitation of “storing the column for at least one week” has no patentable significance or effect on the claimed chromatographic separation or column cleaning. While the disclosure of the invention describes column storage (pg. 8, lines 1-7), no special significance or relatable effect to chromatographic separation or cleaning is afforded such a step. Therefore, absent a showing of significance or unexpected results, this limitation is considered inconsequential to the practice of this invention and would be obvious to one of ordinary skill in the art.
Similarly, regarding Claim 21, the claim limitations “removing a sample of the cleaned liquefied bed of the column and analyzing the sample with respect to purity" have no patentable significance or effect on the claimed chromatographic separation and column cleaning. The claimed steps have no discernable effect and would not result in any manipulative difference. Furthermore, if one of ordinary skill in the art would be so inclined to test whether the cleaning process was performed to an acceptable purity, a sample would have obviously been taken.
Similarly, regarding Claim 22, the claim limitations “recovering the second target biomolecule and, optionally after further purification, using it in a pharmaceutical formulation” have no patentable significance or effect on the claimed chromatographic separation and column cleaning. The claimed steps have no discernable effect and would not result in any manipulative difference. Furthermore, regarding the limitation “recovering the second target biomolecule”, because GU already teaches the recovery of a target biomolecule, the mere duplication of a method step has no patentable significance unless a new and unexpected result is produced (In re Harza, 274 F.2d 669, 124 USPQ 378 (CCPA 1960); MPEP §2144.04).
Regarding Claim 7, modified DICKSON makes obvious the process of Claim 1. DICKSON further discloses that cleaning liquid is introduced by pump through the bottom of the column to fluidize the column media (c7/24-37). This fluidization step naturally agitates the fluidized bed (i.e., agitating the liquefied bed in step d)). Furthermore, such a limitation is considered an intended result of the claimed liquefying step d). Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. A “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003); MPEP §2111.04). Where a reference discloses the terms of the recited method steps, and such steps necessarily result in the desired and recited effect, the fact that the reference does not describe the recited effect in haec verba is of no significance because the reference meets the claim under the doctrine of inherency.
Regarding Claim 9, modified DICKSON makes obvious the process of Claim 7. DICKSON further discloses a port 1 from which cleaning liquid is introduced into the column (i.e., wherein the agitation comprises agitation by jets from one or more nozzles; c7/24-27).
Regarding Claims 11, 14-18, 20, and 24, modified DICKSON makes obvious the process of Claim 1. The prior art is deficient in explicitly disclosing the separation matrix particles have a density of about 1.0-1.4 g/mL (Claim 11) or 1.0-1.1 g/mL (Claim 24), a column inner diameter of at least 2.5 cm (Claim 14), a compressed bed height of about 5-50 cm (Claim 15), a ratio between the inner diameter of the chromatography column to the compressed bed height of at least 0.4 (Claim 16), an average matrix particle diameter of at least 20 µm (Claim 17), a matrix particle size coefficient of variation of about 10-50% (Claim 18), or a first cleaning liquid viscosity being about 1.0-1.5 mPa·s (Claim 20).
However, these limitations are considered choices or options related to column dimensions or particle bed dimensions readily available to one of ordinary skill in the art. Absent a showing of significance or non-obvious results, claims to these dimensions in the claimed inventive process would not meaningfully affect the practice of the process or result in any manipulative differences other than the separation of a target biomolecule. Because the prior art teaches all method steps, whether applied to a specifically claimed column or a different column, the end result would be a regenerated bed and a purified target molecule. If a prior art process is capable of performing the intended use as recited and does not result in a manipulative difference, then it meets the limitation of the claim (MPEP §2111.02 II).
Regarding Claim 19, modified DICKSON makes obvious the process of Claim 1. GJERDE further discloses the chromatography stationary phase can comprise different materials including polysaccharides (i.e., the composition of the matrix particles being a polysaccharide support; c4/19-25). Absent any evidence of unexpected results or criticality to such a limitation, the limitation requiring the composition of the matrix particles be a polysaccharide is taught by JOHANSSON and would be obvious to use in the method made obvious by modified DICKSON. 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).
Claims 8, 10, and 12 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over DICKSON (US Patent 6,740,241) in view of LEIJON (US 6,706,191), EDBLAD (US 2011/0073213 A1), and GJERDE et al. (US 6,485,648), as applied to Claims 1 and 7 above, and further in view of GU (WO 2012/072029 A1; English equivalent publication, US 2013/0248430 A1, is referenced).
Regarding Claims 8 and 10, modified DICKSON makes obvious the process of Claim 7. The prior art is deficient in disclosing the agitation comprises vibrating or sonicating the liquefied bed or separation matrix particles or wherein the agitation comprises an oscillating flow.
GU teaches a process for the separation of a target molecule and the cleaning of a chromatography column (p0028). GU further discloses a clean-in-place regeneration step wherein a cleaning solution is circulated through the column (p0298-0299; FIG. 8f) utilizing a distributor along the bottom of the column (p0033) for ensuring flow distribution and sufficient recirculation throughout the column (i.e., agitating the liquefied bed, wherein the agitation comprises vibrating the liquefied bed; p0034, p0046). Said distributor arms oscillate periodically (i.e., wherein the agitation comprises an oscillating flow; p0218). At the time of the invention, one of ordinary skill in the art would have found it obvious to provide an agitation step as disclosed by GU with vibration and oscillating flow in the process of chromatographic separation and cleaning made obvious by modified DICKSON because such an agitation step advantageously provides even flow distribution inside the column for more efficient cleaning (GU, p0218).
Regarding Claim 12, modified DICKSON makes obvious the process of Claim 1. The prior art is deficient in disclosing using separation matrix particle ligands that include Protein A, Protein G, Protein L, single chain camelid antibodies or functional varieties thereof.
However, DICKSON discloses the use of the process for purifying pharmaceuticals (c1/27-32). As is well-known to one of ordinary skill in the art, Protein A, Protein G, and Protein L ligands are commonly used in biomolecular separations, especially for pharmaceutical or antibody separations. While the prior art may not have explicitly disclosed the claimed specific ligands, one of ordinary skill in the art would find it obvious that specific ligands would be required for the capture of specific target biomolecules. In this case, as evidenced by GU, Protein A ligands are commonly used for antibody purifications (Example 1, p0355-0360). Therefore, absent a showing of unexpected results or criticality, the choice of Protein A, Protein G, Protein L single chain camelid antibodies or functional varieties thereof would have been obvious to one of ordinary skill in the art of biomolecular chromatography.
Claims 11 and 24 is/are alternatively rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over DICKSON (US 6,740,241) in view of LEIJON (US 6,706,191), EDBLAD (US 2011/0073213 A1), and GJERDE et al. (US 6,485,648), as applied to Claim 1 above, and further in view of BERGSTROM et al. (US 6,572,766).
Regarding Claims 11 and 24, modified DICKSON makes obvious the process of Claim 1. The prior art is deficient in disclosing a separation matrix particle density of about 1.0-1.4 g/mL or 1.0-1.1 g/mL.
BERGSTROM teaches particulate matrices useful in separation applications, including fluidized beds (abstract, c1/42-55). BERGSTROM further discloses that the density of the particulate matrices are typically at least 1.02 g/cm3 or a density different from the liquid medium to be treated (c5/45-63). Absent a showing of unexpected or significant results, the claimed separation matrix particle density ranges of about 1.0-1.4 g/mL and 1.0-1.1 g/mL would be considered obvious to one of ordinary skill in the art. 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). At the time of the invention, one of ordinary skill in the art would have found obvious to use a separation matrix particle density of about 1.0-1.4 g/mL or 1.0-1.1 g/mL as taught by BERGSTROM in the chromatographic separation made obvious by modified DICKSON because such a particle density, especially if different from the liquid medium that is being treated, would enhance the separation efficiency. All claimed elements were known in the prior art and one of ordinary skill in the art could have combined the elements as claimed with no change in their respective, individual functions, and the combination would have yielded nothing more than predictable results (MPEP §2143.01 A).
Response to Arguments
No amended claims were filed.
Applicant’s arguments/remarks filed 16 October 2025 have been fully considered but are not persuasive.
Applicant states that LEIJON discloses a capture step that “can capture two or more different compounds in a single ‘capture step’” and cites column 2, lines 5-10 of the prior art; Applicant argues that such a disclosure is contrary to the claimed method requiring two steps instead of one to separate two different target biomolecules, i.e., the claimed dual-step separation process is not taught or suggested by LEIJON and LEIJON would not have been modified by one of ordinary skill in the art to include a dual-step separation process (pg. 6-7 Arguments/Remarks). Further, Applicant argues that by separating the single ‘capture step’ of LEIJON into two steps, the principle of operation of the method disclosed by LEIJON would be impermissibly changed (pg. 8).
The Examiner respectfully disagrees.
First, Applicant’s citation of col. 2, lines 5-10 is referencing an embodiment of LEIJON. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments (In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971)). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use” (In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994); MPEP §2123 II). LEIJON’s disclosure that a capture step “may mean capture of two or more compounds” does not require or even imply LEIJON teaches such a step. Rather, Applicant should consider the teachings of LEIJON as a whole. Earlier in the disclosure, LEIJON teaches a step b: “capturing one or more compounds present in a liquid sample” among other steps a through f (see col. 1, lines 22-38). LEIJON then states that a typical cyclic chromatography process involves multiple cycles where the step b of capture is repeated in a sequence (col. 1, lines 38-46). Even further, LEIJON teaches multiple capture steps being performed cyclically in their disclosed invention; see the table in col. 4 indicating different capture steps in Step 1 and Step 2. As such, it is evidently clear as explicitly disclosed by LEIJON that multiple capture steps are preferred and taught—therefore, LEIJON’s method is not “impermissibly changed” as argued.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/Ryan B Huang/Primary Examiner, Art Unit 1777