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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-16 and 19-20 in the reply filed on 3/27/2026 is acknowledged.
Claims 17, 18, and 21-27, 30, 34, and 36-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-8 and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Adielsson et al (WO 2013/130001 A1) in view of Maloisel et al (US PGPub 2019/0111419 A1).
Examiner notes that Maloisel is the US publication corresponding to the CN 108883394 A reference cited on the 10/24/2023 IDS. The US publication is cited in this action for convenience.
With respect to claims 1 and 2, Adielsson teaches chromatography media including beads with a core-shell structure (an inner porous core with ligands and an outer porous layer without) with pores for size exclusion separation (pores employed to exclude certain molecules from the inner layer) [Abs]. The media may be made of synthetic polymer [pg. 4 line 21]. Regarding the average pore size, Adielsson teaches that it may be selected depending upon the material being excluded (i.e. for excluding materials of a target molecular weight e.g. 100 kDa or even up to 700 kDa or more for very large proteins) [pg. 3 line 31-pg. 4 line 8], such that optimization of the pore size for a given application represents an obvious engineering choice for one of ordinary skill in the art. Adielsson similarly teaches that the pore size may be the same in the core and shell regions i.e. having a homogeneous pore structure. Adielsson does not particularly limit the particle size of the beads, although it is suggested that the shell layer may have a thickness of 7 microns [pg. 7], such that the beads would necessarily be larger than this dimension. Further, regarding the requirement that the core and shell layers have different functionality or at least different densities of functionality, Adielsson is silent to this feature unless it is considered that a density value of zero on the outer layer satisfies the claim requirement.
However, Maloisel teaches separation matrices for biomacromolecules of a core-shell structure [Abs] and teaches that the design is beneficial because smaller particle size media are good for separation resolution while larger particle size media are good for reducing column back pressure and thus cost [0002], such that the combined core-shell geometry facilitates both benefits [0006]. Maloisel suggests a volume-weighted media diameter may be in a range of e.g. 50-100 microns [0028]. Further, regarding functionalities, Maloisel suggests that while the shell may be devoid of ligands (e.g. to facilitate simple size exclusion separations) it may also be useful to functionalize the shell with different types of ligands to facilitate a broad range of chromatographic techniques such as anion/cation exchange groups, hydrophobic groups, affinity groups, and the like [0033], while the core region contains a grafted polymer which is specifically not attached to the shell region (as the shell region grafting sites are inactivated before grafting the core) [0007-0012].
It would have been obvious to one of ordinary skill in the art to modify the beads taught by Adielson in view of the guidance of Maloisel to employ beads with a median diameter if e.g. 50-100 microns because, as in Maloisel, this size is useful for separations with good resolution while also maintaining lower back pressures (and thus cost) in columns, and further to modify the beads to include different functionalities on the shell layer because, as in Maloisel, this layer can be modified in various ways to facilitate other types of chromatographic separations.
Regarding the particle size distribution of the beads, Adielson and Maloisel do not discuss this parameter. However, given the back pressure considerations and thus motivation to select an appropriate bead size taught by Maloisel, optimization of the size distribution would similarly have been obvious to one of ordinary skill in the art, to ensure consistent operation of the column without large fluctuations in packing and pressure behavior. See further MPEP 2144.05 II.A; "[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
With respect to claim 3, as above Adielson and Maroisel teach core-shell structures i.e. those having two layers, with the porous structures potentially being essentially the same at least as discussed by Adielson, with the core and shell having the same pore size.
With respect to claim 4, as above at least Maroisel teaches a broad variety of ligands may be incorporated including hydrophobic interaction groups, ionic (anionic/cationic) groups, affinity groups, and the like.
With respect to claim 5, as above at least Maroisel teaches a median particle diameter in a range of 1-500 microns (specifically 50-100 microns as a suggested range).
With respect to claims 6-8 and 10, the claims represent product-by-process limitations; see MPEP 2113. The product described by such claims is not limited by the manipulations of the recited steps, only the structure implied by such steps. Because the modified beads of Adielson and Maroisel have structural features consistent with the claim requirements as discussed above, absent evidence of a structural difference, the product is considered the same as that implied by the claim limitations regardless of the process steps employed.
With respect to claim 11, the media discussed by Adielson and Maroisel both include at least the feature (T1) i.e. a core-shell structure, with the core representing a first layer and the shell a second layer. Additionally, Adeilson suggests e.g. hydrophobic moieties (multimodal mines which are capable of binding endotoxins, as an example) for the core [pg. 8, calims 5-6]. As above, Maroisel suggests any of various functionalities to the shell, such as hydrophobic, cationic/anionic, affinity, or the like. Thus, the combination would similarly render obvious at least features (T7) and (T8). Examiner further notes that several of the proposed features represent an intended use of the claimed media which would not distinguish structurally.
With respect to claim 12, as above Maroisel suggests the use of affinity ligands.
With respect to claim 13, Maroisel suggests that Protein A/L/G affinity ligands may be useful [0033] and, as above, Adielson suggests functionalizing the core to bind to particular target molecules. As such, providing a modified media in which the specific affinity groups suggested by Maroisel are provided in the core for binding in the manner suggested by Adielson would have been obvious to one of ordinary skill in the art.
With respect to claims 14 and 15, as above Adielson suggests shell thickness of e.g. about 7 microns, and given a total median diameter of 50-100 microns (as suggested by Maroisel), this would represent a ratio of thicknesses of about 7-14%. Maroisel additionally discuses a thickness ratio of 0.5-6% and shell region thickness of about 1-15 microns [0028]. In either case, the claimed thickness and ratio would have been obvious over the prior art.
With respect to claim 16, both Adielson and Maroisel discuss employing shell layers with essentially no functional groups, i.e. a density of zero; this would imply a ratio of D1/D2 being larger than 1.05 (i.e. nearly infinite). Further, even when present, Maroisel teaches that the density of ligands on the shell can vary depending on the application [0033] such that optimization of the amount present to facilitate the desired functions is nevertheless obvious to those of ordinary skill in the art.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Adielsson et al in view of Maloisel et al, further in view of Lawrence et al (US PGPub 2019/0015815 A1).
Adielsson and Maloisel teach as above but are silent to rod- or disk-shaped media. However, Lawrence discusses chromatographic media [Abs] of core-shell geometry [0008] including monolithic porous materials [0010] and teaches that, in addition to typical spherical core morphologies, the materials can instead employ rod morphologies or variations thereof [0059-0060]. See MPEP 2144.04 IV.B; changes in shape are generally obvious to those of ordinary skill in the art, and in view of Lawrence it would be recognized that such shape changes to e.g. rod-shapes nevertheless may still produce useful structures for core-shell chromatographic media. As such, the claimed configuration would have been obvious to one of ordinary skill in the art.
Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Adielsson et al in view of Maloisel et al, further in view of Koontz et al (WO 98/32790 A1).
Adielsson and Maloisel teach chromatography media as above, but are silent to materials to which a detectable label of e.g. a protein or enzyme is bound.
However, Koontz teaches various porous articles and uses thereof [Abs] e.g. chromatography media, and teaches that the media may be used for diagnostic assays [pg. 66] and may be labeled using a detectable label [pg. 69, first paragraph]; in other contexts, Koontz suggests that labels useful for assays may include reporter groups such as enzyme reporter groups [pg. 67, last paragraph]. As such, binding a material such as an enzyme which is known to be useful as a reporter group/label would have been an obvious use for the modified media of Adielsson and Maloisel, because as in Koontz this may be useful for diagnostic purposes.
Conclusion
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/BRADLEY R SPIES/Primary Examiner, Art Unit 1777
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