DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 07/23/2024, 11/12/2024, 01/02/2025, and 11/06/2025 have been considered by the examiner.
Claim Objections
Claims 11, 14, and 15 are objected to because of the following informalities:
(i) Claim 11 recites “wherein the average particle size “between 7 µm to 8 µm” which is grammatically improper. It is respectfully suggested to amend the limitation to “wherein the average particle size “is between 7 µm and 8 µm.”
(ii) Claim 14 recites “between 1 mm to 2.1 mm” in line which is grammatically improper. It is respectfully suggested to amend the limitation to “between 1 mm and 2.1 mm” or “from 1 mm to 2.1 mm.”
(iii) Claim 15 recites “between 15 to 50 mm” in line 2 which is grammatically improper. It is respectfully suggested to amend the limitation to “between 15 mm and 50 mm” or “from 15 mm to 50 mm.”
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2-12 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 2-12 depend from claim 1, which is directed to “A chromatographic column comprising,” but claims 2-12 are directed to “The particle of claim 1”, instead of “The chromatographic column according to claim 1”. Claims 2-12 improperly change the claimed subject from the chromatographic column of claim 1 to a particle. Although claim 1 recites particles as components of the chromatographic column, claims 2-12 do not recite “The chromatographic column of claim 1, wherein each particle...” or similar language that limits the column. Also, claims 2-12 fail to properly specify a further limitation of the subject matter claimed in claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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 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.
Claims 1-4 and 9-19 are rejected under 35 U.S.C. 103 as being unpatented over Brousmiche et al., (US 2019/0322783 A1, hereinafter as “Brousmiche”) in view of Wirth (US 2014/0316108 A1, hereinafter as “Wirth”) and DeLano et al., (US 2022/0118443 A1, hereinafter as “DeLano”).
Regarding claim 1, Brousmiche teaches a chromatographic column comprising (¶ [0069]): a column chromatographic packing particles for bioseparation applications (¶ [0069-0073]), each particle of the plurality of particles comprising:
a non-porous polymer particle (¶ [0010]) having a poly(styrene-divinylbenzene) nucleus;
a hydrophilic outer surface layer comprising poly(glycidyl methacrylate-co-ethylene dimethylacrylate)[poly(GMA/EDMA)] surrounding the polymer core (¶ [0010, 0089]);
Brousmiche further discloses monodisperse particles having average particle size of 0.5-100 µm (p. 19, claim 23). Since the claimed average particle size of 1.0 µm and 10 µm encompassed by the average particle size of 0.5-100 µm taught by Brousmiche, the range recited in claim 1 is considered prima facie obvious. See MPEP 2144.05.
But Brousmiche does not explicitly disclose one or more molecules of streptavidin conjugated to the hydrophilic surface of the particle and the column body formed of a metal or a metal alloy.
However, Wirth teaches affinity chromatography matrices having a hydrophilic surface coating and a binding ligand attached thereto, wherein the binding ligand may comprise streptavidin (¶ [0024]). Wirth discloses that affinity chromatography employs ligands immobilized on chromatographic particles to selectively bind biomolecules and further discloses that hydrophilic polymer coatings including glycidyl methacrylate-containing coatings suitable for immobilization of ligands such as streptavidin (¶ [0024-0025]).
DeLano teaches chromatographic system 100 including metallic chromatographic column 125 (Fig. 1, ¶ [0054]) and wetted metallic flow-path components configured for biomolecule chromatography (¶¶ [0002-0003; 0009-0011]).
Brousmiche, Wirth and DeLano are analogous arts because each addresses biomolecular liquid chromatography using engineered stationary-phase or wetted-flow path surfaces to control ligand binding, non-specific adsorption, and analyte recovery, specifically, Brousmiche teaches hydrophilic polymer chromatography particles for bioseparation, Wirth teaches hydrophilic affinity-chromatography supports bearing ligands such as streptavidin for selective biomolecule capture, and DeLano teaches hydrophilic/organosilane-coated liguid chromatography flow path surfaces to reduce secondary interactions with biomolecules, making each reference from the same field of endeavor and reasonably pertinent to the claimed streptavidin-functionalized low-adsorption chromatographic column.
Therefore, before the effective filing date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to modify the hydrophilic chromatographic particles of Brousmiche with streptavidin ligands as taught by Wirth because streptavidin-functionalized hydrophilic chromatographic supports selectively bind biotinylated biomolecules for affinity chromatography applications (Wirth: ¶ [0024]); the modification merely applies known affinity-ligand functionality to the known chromatographic particles of Brousmiche to obtain predictable affinity-separation performance (Wirth: ¶ [0031]); and it would have been obvious to use the modified particles within a metallic chromatographic column body as taught by DeLano because metallic chromatographic flow paths and column hardware were known for high-pressure biomolecule chromatography systems and provides mechanically robust chromatographic systems (DeLano: ¶ [0003]).
In regard to claim 2, Brousmiche discloses that the polymer particles may have a gradient composition between the core and outer regions of the particle (¶¶ [0010, 0022]).
In regard to claim 3, Brousmiche discloses polymer particles formed using styrene and DVB 80 divinylbenzene crosslinker (Table 1 shows synthesis of polymer materials with DVB80 and styrene crosslinkers (¶¶ [0086-0089]).
In regard to claim 4, Brousmiche discloses the hydrophilic surface selected from glycidol (Table 15, ¶ [0144]) and glycerol triglycidyl ether (Table 15, ¶ [0147]).
In regard to claim 9, Brousmiche in view Wirth as applied to claim 1 discloses chromatographic particles having an average particle size of 0.5-100 µm (p. 19, claim 23). Since the claimed particle size that is between 2 µm and 5 µm encompassed by the average particle size of 0.5-100 µm (p. 19, claim 23) taught by Brousmiche, the range recited in claim 9 is considered prima facie obvious. See MPEP 2144.05.
In regard to claim 10, Brousmiche in view Wirth as applied to claim 9 discloses chromatographic particles having an average particle size of 0.5-100 µm (p. 19, claim 23). Since the claimed average particle size of 3.5 µm is within the range of the particle size 0.5-100 µm (p. 19, claim 23) as taught by Brousmiche, the range recited in claim 10 is considered prima facie obvious. See MPEP 2144.05.
In regard to claim 11, Brousmiche, in view Wirth as applied to claim 1, discloses chromatographic particles having an average particle size of 0.5-100 µm (p. 19, claim 23). between 7 µm and 8 µm. Since the claimed average particle size between 7 µm and 8 µm is encompassed by the particle size of 0.5-100 µm (p. 19, claim 23) as taught by Brousmiche, the range recited in claim 11 is considered prima facie obvious. See MPEP 2144.05.
In regard to claim 12, Wirth teaches affinity chromatography matrices utilizing streptavidin ligands for selective binding of biomolecules, including proteins and nucleic-acid related biomolecules. It would have been obvious to bind biotinylated oligonucleotides, antibodies, or antigen-binding fragments to streptavidin because streptavidin-biotin binding was a well-known and predictable affinity interaction routinely used in biomolecule immobilization and affinity purification systems as evidenced by Kukolka et al., (Covalent Coupling of DNA Oligonucleotides and Streptavidin, In: Niemeyer,C.M., (eds), Bioconjugation Protocols: Strategies and Methods, Methods in Molecular Biology, 2004, Chapter 12, vol. 283, pp. 181- 196; p. 181, Introduction section, first paragraph, lines 1-8; p. 184, first paragraph lines 1-11).
In regard to claim 13, Brousmiche, in view Wirth as applied to claim 1, does not disclose one or more molecules of streptavidin conjugated to the hydrophilic the surface coverage of 2-6 µg/mg particle.
With respect to the surface coverage of the streptavidin molecules conjugated to the hydrophilic surface, experimental preparation of this prior art in order to ascertain optimum surface reaction conditions fail to render applicant’s claims patentable in the absence of unexpected results. In re Aller, 105 USPQ 222. Brousmiche, in view of Wirth, does not disclose surface coverage of the streptavidin molecules conjugated to the hydrophilic surface with surface coverage of 2-6 µg/mg particle; however, one of ordinary skill in the art would have been motivated to prepare the molecules of streptavidin conjugated to the hydrophilic to have the surface coverage as claimed since optimization of streptavidin surface ligand-loading density was a recognized result-effective variable that influence affinity-binding capacity and chromatographic performance (Wirth: ¶ [0025]). A prima facie case of obviousness may be rebutted, however, where the results of the optimizing variable, which is known to be result-effective, are unexpectedly good. In re Boesch and Slaney, 205 USPQ 215.
In regard to claim 14, DeLano discloses internal portions of the column 125 and chromatographic hardware suitable for high-performance biomolecular chromatography systems 100 (Fig. 1, ¶ [0057]). But DeLano does not disclose internal diameter of column body that is between 1 mm and 2.1 mm.
With respect to the internal diameter of the column body, device internal diameter configuration of this prior art in order to ascertain optimum operating conditions fail to render applicant’s claims patentable in the absence of unexpected results. In re Aller, 105 USPQ 222. DeLano does not disclose internal diameter of column body that is between 1 mm and 2.1 mm; however, one of ordinary skill in the art would have been motivated to design internal diameter of the column body between 1 mm and 2.1 mm as claimed since internal diameters are optimized based on the type of manufactured polymeric resin constructed in the flow paths and be able to withstand high pressure at increasingly fast flow rates to obtain favorable yields of retention times in chromatography systems (DeLano: [0003, 0007]). A prima facie case of obviousness may be rebutted, however, where the results of the optimizing variable, which is known to be result-effective, are unexpectedly good. In re Boesch and Slaney, 205 USPQ 215.
In regard to claim 15, Brousmiche teaches high-performance chromatographic particles intended for rapid chromatographic separation using compact chromatographic columns and Wirth discloses a chromatography column 125, including fluidic flow path length to diameter ratio of at least 20, at least 25, at least 35, or at least 40 (Fig 1, ¶ (0054]). But Brousmiche and Wirth do not disclose the length of the column body between 15 to 50 mm.
With respect to the length of the column body, device length configuration of this prior art in order to ascertain optimum operating conditions fail to render applicant’s claims patentable in the absence of unexpected results. In re Aller, 105 USPQ 222. Brousmiche and Wirth do not disclose length of the column body that is between 15 to 50 mm; however, one of ordinary skill in the art would have been motivated to design length of the column body between 15 to 50 mm since selecting the right column length is an obvious optimization for flow paths because it directly impacts both the efficiency of the separation and the practicality of the system, balancing resolution, speed, and pressure constraints as taught by DeLano (¶¶ [003, 0014, 0144]). A prima facie case of obviousness may be rebutted, however, where the results of the optimizing variable, which is known to be result-effective, are unexpectedly good. In re Boesch and Slaney, 205 USPQ 215.
In regard to claim 16, DeLano teaches coating wetted interior chromatographic surfaces with organosilane (i.e., a broad class of organosilicon compounds including alkylsilyl compounds) coatings to provide a hydrophilic and /or non-ionic surface (Abstract, ¶ [0010]).
In regard to claim 17, DeLano discloses frits coated with organosilane material (i.e., a broad class of broad class of organosilicon compounds including alkylsilyl compounds) (¶¶ [0159-0160]).
In regard to claim 18, DeLano teaches hydrophilic non-ionic polyethylene glycol silane coatings on chromatographic flow-path surfaces (¶ [0012]).
Claim 19 is rejected under 35 U.S.C. 103 as being unpatented over Brousmiche in view of Wirth and DeLano.
In regard to claim 19, DeLano teaches chromatographic systems comprising (Fig. 1,
¶¶ [0137, 0054]:
the chromatographic column was addressed by Brousmiche, in view of Wirth and DeLano, as set forth in the discussions regarding claim 1;
DeLano discloses a column injector 135 positioned upstream of the chromatographic column, and
tubing 110 in fluidic connection with and located downstream of the chromatographic column,
wherein a portion of an internal surface of the column injector and a portion of an internal surface of the tubing are coated with organosilica material (i.e., a broad class of organosilicon compounds including alkylsilyl compounds) ((Fig. 1, ¶¶ [0137, 0054]; ¶ [0060]).
Claims 5-8 are rejected under 35 U.S.C. 103 as being unpatented over Brousmiche in view of Wirth and DeLano as applied to claim 1, and in further view of Nakamura et al., (JP2017083363A, please refer to the English translation document, hereinafter as “Nakamura”).
Regarding claim 5, Brousmiche teaches chromatographic polymer particles having hydrophilic glycidyl methacrylate-containing surface layers suitable for functionalized and biomolecule chromatography (¶ [0019]). Wirth teaches affinity chromatography matrices comprising hydrophilic surfaces coatings (i.e., glycidoxyl methacrylate groups) configured for immobilization of affinity ligands including streptavidin (¶ [0024]).
But Brousmiche and Wirth do not teach conjugating streptavidin to the hydrophilic particle surface using an epoxy linker.
However, Nakamura teaches affinity chromatography carriers activated with polyethylene glycol diglycidyl ether and related epoxy/glycidyl linker compounds for immobilization of proteins and affinity ligands onto chromatography carriers (p. 6, lines 9-14).
Brousmiche, Wirth and Nakamura are analogous arts because each are directed to affinity chromatography using hydrophilic functionalized stationary-phase surfaces and covalent ligands immobilization chemistry; specifically, Brousmiche hydrophilic polymer chromatography particles for bioseparations, Wirth teaches streptavidin-functionalized affinity chromatography matrices for selective biomolecule capture, while Nakamura teaches epoxy/PEG-diglycidyl linker activation of affinity chromatography carriers for protein immobilization, making each reference pertinent to improving ligand-functionalized chromatographic particle systems for biomolecule separation.
Therefore, before the effective filing date of the claimed invention, it would have been prima facie obvious to one of ordinary skill in the art to use the epoxy linker chemistry of Nakamura to conjugate the streptavidin ligand of Wirth into the hydrophilic polymer surface of Brousmiche because the epoxy/glycidyl linker compounds provide reactive functional groups for improving flow rate characteristics and target substance trapping characteristics thereby predictably improving ligand attachment stability and affinity chromatography performance as taught by Nakamura (p. 2, lines 2-9).
In regard to claim 6, Nakamura discloses polyethylene glycol diglycidyl ether compounds used as a linker compound in affinity chromatography carriers, including varying polyethylene glycol chain lengths (Fig. 7, p. 6, lines 9-14).
In regard to claim 7, Nakamura discloses the n of the polyethylene glycol diglycidyl ether formula is 9 (Fig. 7, p. 6, lines 9-14).
In regard to claim 8, Nakamura does not expressly disclose the n of the polyethylene glycol diglycidyl ether formula is 1.
With respect to the n of the polyethylene glycol diglycidyl ether formula, experimental n selection of this prior art in order to ascertain target n of the linker length fail to render applicant’s claims patentable in the absence of unexpected results. In re Aller, 105 USPQ 222. Nakamura does not expressly disclose the claimed n of the polyethylene glycol diglycidyl ether formula is 1; however one of ordinary skill in the art would have been motivated to adjust the polyethylene glycol diglycidyl ether formula is 1 as claimed since selection of the claimed linker length represented by “n” would have been obvious optimization of a known result-effective variable because linker chain lengths are varied to control affinity-carrier performance as taught by Nakamura (p. 2, lines 2-9). A prima facie case of obviousness may be rebutted, however, where the results of the optimizing variable, which is known to be result-effective, are unexpectedly good. In re Boesch and Slaney, 205 USPQ 215.
Conclusion
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, In Suk Bullock can be reached on 571-272-5954. The fax phone number for the organization where this application or processing is assigned is 571-273-8300.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, In Suk Bullock can be reached on 571-272-5954. The fax phone number for the organization where this application or processing is assigned is 571-273-8300.
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/WILSON GALLARDO MENDOZA/Examiner, Art Unit 1772
/YOUNGSUL JEONG/Primary Examiner, Art Unit 1772
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