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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12 May 2026 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application (371 of PCT/IB2021/052739, filed 04/01/2021, which has PRO 63/009,080, filed 04/13/2020) under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Response to Amendments
Applicant’s amendments filed 12 May 2026 have been entered.
Claims 1-4 and 18 have been amended; Claim 17 has been canceled; and Claims 19 and 20 were previously withdrawn. Claims 1-16, 19, and 20 are pending.
Regarding the rejections of Claims 1, 4-6, 12, and 13 under 35 U.S.C. 102 as being anticipated by XENOPOULOS et al. (US 2015/0133636 A1) with evidentiary support from KOZLOV et al. (US 2013/0245139 A1), Applicant’s amendments are persuasive; the 35 U.S.C. §102 rejections have been withdrawn. However, upon further consideration, new grounds of rejection have been made for Claim(s) 1, 4-6, 12, 13, and 18 under 35 U.S.C. 103 as obvious over XENOPOULOS et al. (US 2015/0133636 A1) with evidentiary support from KOZLOV et al. (US 2013/0245139 A1) in view of COLAK ATAN et al. (US 2019/0194250 A1).
Please note the added rejections of Claims 1-16 and 18 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite.
Please note the added rejections of Claims 12-16 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form.
Response to 37 CFR 1.132 Affidavit
The affidavit/declaration under 37 CFR 1.132 filed 12 May 2026 is insufficient to overcome the rejection of Claims 1, 4-6, 12, and 13 based upon 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over XENOPOULOS et al. (US 2015/0133636 A1) with evidentiary support from KOZLOV et al. (US 2013/0245139 A1) as set forth in the last Office action.
The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992). "[A]ppellants have the burden of explaining the data in any declaration they proffer as evidence of non-obviousness." Ex parte Ishizaka, 24 USPQ2d 1621, 1624 (Bd. Pat. App. & Inter. 1992). Evidence of unexpected properties may be in the form of a direct or indirect comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980) and MPEP § 716.02(d) - § 716.02(e).
While Applicant has shown evidence (e.g., comparing Comparative Example 2 with Examples 2a-c of the as-filed Specification, see especially Tables 5-8) between comparative examples with buffer exchange and examples of the as-disclosed invention without buffer exchange between contacting with salt-tolerant anion exchange filters and cation exchange porous filters, the objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support. The showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (MPEP 716.02(d)).
The provided evidence compares the purification of a target monoclonal antibody (mAb), i.e., mAbA (pg. 43, par. 2), and removal of high molecular weight species (HMW) to compare host cell protein (HCP) concentration, % HMW composition, % HMW removed, and % monomeric mAbA yield (Tables 5-8, respectively). Even further, the as-disclosed invention used FE-L loaded plates as anion exchange filter elements (pg. 43, par. 6; a guanindinyl ligand-functionalized nylon membrane, pg. 41, par. 4) and FE-J, FE-K, and FE-F loaded plates as cation exchange filter elements, which are nylon membranes grafted with an IEM-glycine sodium salt/IEM-phenylalanine sodium salt monomer solution, an IEM-glycine sodium salt monomer solution, and a VDM-GABA sodium salt/VDM-phenylalanine sodium salt monomer solution, respectively. As summarized by Applicant, the disclosed evidence compares the “state-of-the-art primary amine containing AEX filter (Sartobind STIC) to our guanidinyl-containing filter (Examples 2a, 2b, and 2c)” (Affidavit, par. 7).
However, the claimed inventions are far broader than the evidence shown purporting nonobviousness. Claim 1 only requires a “target molecule”, i.e., “a protein”; comparatively, the disclosed evidence recites monoclonal antibodies, specifically mAbA. Further, Claim 1 only requires a “salt-tolerant anion exchange nonfibrous porous filter element” which is recited to include “a nonfibrous porous filter element comprising a porous membrane” and “immobilized cationic nitrogen-containing ligands”; comparatively, the disclosed evidence recites FE-L loaded plates as anion exchange filter elements (pg. 43, par. 6; a guanindinyl ligand-functionalized nylon membrane, pg. 41, par. 4). Finally, Claim 1 only requires a “cation exchange nonfibrous porous filter element” which is recited to include a “nonfibrous porous support”, and a plurality of pendant groups comprising at least one acidic group or salt thereof with a spacer group of at least 6 catenated atoms; comparatively, the disclosed evidence recites FE-K, and FE-F loaded plates as cation exchange filter elements, which are nylon membranes grafted with an IEM-glycine sodium salt/IEM-phenylalanine sodium salt monomer solution, an IEM-glycine sodium salt monomer solution, and a VDM-GABA sodium salt/VDM-phenylalanine sodium salt monomer solution, respectively. None of the claimed limitations even recite “guanidinyl groups” as ligands for the AEX filter element. As such, the objective evidence of nonobviousness is hardly commensurate in scope with the claims which the evidence is offered to support.
Furthermore, in the filed affidavit, Applicant contends with the Office action’s dismissal that the prior art XENOPOULOS disclosing in p0348 a pH change from neutral to pH 5.0 as a mere preferred embodiment (Affidavit, par. 8) arguing that the prior art “is clearly recounting the state-of-the-art filters… in concert with all the rest of his examples… Xenopoulos does not have a single example where the pH is not adjusted…” (Affidavit, par. 8). Applicant concludes, arguing that “It is not reasonable to assume the pH adjustment step is optional, when it is included in every single example disclosed in Xenopoulos” (Affidavit, par. 8).
The Examiner respectfully disagrees. 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)). In further paragraphs of the filed Affidavit, Applicant cites select examples from the prior art illustrating that such examples are indeed preferred embodiments, e.g., “In some preferred embodiments, the anion-exchange adsorber device is…” (Affidavit, par. 9, citing p0246 of XENOPOULOS), “the use of a flow-through cation-exchange step may necessitate a reduction of solution pH” (Affidavit, par. 10, citing p0255), and “typically, cation exchange flow-through chromatography requires the sample to be…” (Affidavit, par. 10, citing p0348) (all emphases added). Applicant concludes stating that “Accordingly, the pH of the sample has to be changed from about neutral pH to about pH 5.0” (Affidavit, par. 10; emphasis Applicant). There is no disclosure by XENOPOULOS requiring this buffer exchange as Applicant argues.
While the filed affidavit is insufficient to overcome the pending rejections, the claimed invention requires more specificity pertaining to the limitations of the AEX and CEX ligands. It is noted that Claims 14 and 15 do recite that the cationic ligands of the salt-tolerant anion exchange nonfibrous porous filter element comprise guanidinyl-containing ligands, which renders the scope of the claimed AEX ligands as commensurate with the provided evidence with respect to the AEX ligands. However, the claimed cation exchange nonfibrous porous filter element remains broader in scope than the evidence argued.
Response to Arguments
Applicant’s arguments filed 12 May 2026 have been fully considered.
Regarding Applicant’s arguments pertaining to “§3) Rejection of the Claims Under 35 U.S.C. § 102” (pg. 13-17), Applicant’s arguments are moot in light of the withdrawn rejections under 35 USC 102.
Regarding Applicant’s arguments pertaining to “§4) Rejection of the Claims Under 35 U.S.C. § 103(a)” subsection “(a) Rejection of Claims 2, 3, and 7-11 under 35 U.S.C. § 103(a) over Xenopoulos in view of Bothof” (pg. 17-23), Applicant’s arguments are moot as they are directed toward XENOPOULOS and BOTHOF as not teaching certain deficiencies; the as-amended claims are now rejected over XENOPOULOUS in view of COLAN ATAK and further in view of BOTHOF. COLAN ATAK discloses or makes obvious the recited “deficiencies” as summarized in the subsequent prior art rejections.
Regarding the subsection “(b) Rejection of Claims 14 and 15 under 35 U.S.C. § 103(a) over Xenopoulos in view of Rasmussen” (pg. 23-24), Applicant argues that RASMUSSEN “does not teach or suggest a flow-through process for purifying target molecules—period” (pg. 24, first lines).
The Examiner respectfully disagrees. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, RASMUSSEN was not relied upon to teach “a flow-through process for purifying target molecules” – such a limitation has already been addressed by the parent prior art.
Regarding the subsection “(c) Rejection of Claims 17 and 18 under 35 U.S.C. § 103(a) over Xenopoulos in view of Colak Atan” (pg. 24-25), Applicant argues “Colak Atan is entirely silent about a nonfibrous porous filter element comprising a porous membrane comprising immobilized cationic nitrogen-containing ligands. Thus, Colak Atan does not cure the deficiencies of Xenopoulos” (pg. 25, par. 1).
The Examiner respectfully disagrees. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, COLAK ATAN was not relied upon to teach the “immobilized cationic nitrogen-containing ligands” – such a limitation has already been addressed by the parent prior art.
Claim Interpretation
The claimed invention recites the phrase “buffer exchange(s)”. Applicant has defined “exchange” in the disclosure as (pg. 6, lines 29-33):
"exchange" does not require changing the buffer. Although a buffer exchange may include a complete change in buffers (i.e., change of one buffer for another buffer) by known methods (e.g., Tangential Flow Filtration or Crossflow Filtration), an "exchange" can also include modifying a buffer by, e.g., changing the pH, changing the conductivity, and/or diluting the sample of interest. It may also be referred to as a buffer change or a buffer adjustment.
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(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.
Claims 1-16 and 18 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.
Regarding Claim 1, there is insufficient antecedent basis for “porous nonfibrous membrane” in the limitation “disposed on the porous nonfibrous membrane”. Presumably, Applicant is referencing the cation exchange nonfibrous porous filter element (based on context and on the limitations of now-canceled Claim 17); however, the only “porous membrane” introduced is associated with the “salt-tolerant anion exchange nonfibrous porous filter element”. Claims 5-16 and 18 are also rejected due to their dependence on Claim 1.
Similarly, regarding Claim 2, there is insufficient antecedent basis for “porous nonfibrous membrane” in the limitation “disposed on the porous nonfibrous membrane”. Presumably, Applicant is referencing the cation exchange nonfibrous porous filter element (based on context and on the limitations of now-canceled Claim 17); however, the only “porous membrane” introduced is associated with the “salt-tolerant anion exchange nonfibrous porous filter element”.
Similarly, regarding Claim 3, there is insufficient antecedent basis for “porous nonfibrous membrane” in the limitation “disposed on the porous nonfibrous membrane”. Presumably, Applicant is referencing the cation exchange nonfibrous porous filter element (based on context and on the limitations of now-canceled Claim 17); however, the only “porous membrane” introduced is associated with the “salt-tolerant anion exchange nonfibrous porous filter element”.
Similarly, regarding Claim 4, there is insufficient antecedent basis for “porous nonfibrous membrane” in the limitation “disposed on the porous nonfibrous membrane”. Presumably, Applicant is referencing the cation exchange nonfibrous porous filter element (based on context and on the limitations of now-canceled Claim 17); however, the only “porous membrane” introduced is associated with the “salt-tolerant anion exchange nonfibrous porous filter element”.
Regarding Claim 18, it is unclear which “nonfibrous porous filter element” is being referenced in line 2. Claim 1 has introduced two “nonfibrous porous filter element”, i.e., “a salt-tolerant anion exchange nonfibrous porous filter element” and “a cation exchange nonfibrous porous filter element”. The Examiner will assume Applicant is referencing the latter.
Claims 12-16 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.
Regarding Claim 12, the instant limitations do not further limit the subject matter of the claim upon which it depends, i.e., all instantly cited limitations have already been introduced in Claim 1. Claims 13-16 are also rejected due to the dependence on Claim 12.
Regarding Claim 13, the instant limitations do not further limit the subject matter of the claim upon which it depends, i.e., all instantly cited limitations have already been introduced in Claim 1. Claims 14 and 15 are also rejected due to the dependence on Claim 13.
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
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.
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.
Claim(s) 1, 4-6, 12, 13, and 18 is/are rejected under 35 U.S.C. 103 as obvious over XENOPOULOS et al. (US 2015/0133636 A1) with evidentiary support from KOZLOV et al. (US 2013/0245139 A1) in view of COLAK ATAN et al. (US 2019/0194250 A1).
Regarding Claims 1 and 4, XENOPOULOS discloses a method for purifying a target molecule from a sample; the method comprises depth filtration to remove one or more impurities and flow-through purification using two or more media (i.e., a flow-through process for purifying a target molecule from a biological solution in a sample that includes the target molecule; p0014; p0021; p0173-0179; see Table 1 on pg. 13). The target molecule is an antibody, e.g., monoclonal antibody (i.e., the target molecule comprises a protein; p0018), and the sample comprises cell culture (i.e., a biological solution in a sample; p0026).
XENOPOULOS teaches a solution change to adjust solution pH (i.e., conducting a buffer exchange with the sample; p0034) or to add a precipitant to aid in impurity removal during depth filtration (p0113, p0119, p0180). The flow-through purification employs an anion exchange chromatography step (i.e., contacting the sample with a salt-tolerant anion exchange… filter element; p0237) utilizing a porous membrane comprising polymeric materials, e.g., porous membrane sheets (i.e., anion exchange nonfibrous porous filter element comprising a porous membrane; p0240-0241), and coated with suitable monomers/polymer ligands having appropriate moieties (p0242-245). XENOPOULOS further discloses exemplary AEX media include ligands such as those based on quaternary ammonium ions and weak anion exchangers based on primary, secondary, and tertiary amines (i.e., immobilized cationic nitrogen-containing ligands; p0239). The flow-through purification further employs an additional step, specifically a cation exchange chromatography step (i.e., immediately thereafter, contacting the sample with a cation exchange… filter element; p0247, p0253); said step employs a solid support containing one or more cation exchange binding groups (p0253). XENOPOULOS references Application No. 13/783941 (published KOZLOV et al. US 2013/0245139 A1 is referenced herein) for further details regarding the flow-through CEX process; KOZLOV discloses such solid supports for CEX include porous media, including polymeric porous membranes functionalized with negatively charged ionic binding groups (i.e., a cation exchange nonfibrous porous filter element; p0100-p0104; p0109-0110, p0114). XENOPOULOS is deficient in disclosing the instant limitations directed toward the cation exchange nonfibrous porous filter element.
COLAK ATAN discloses processes for separating target proteins in a biological solution (abstract), e.g., monoclonal antibodies from a protein solution (p0006), utilizing filter media comprising porous substrate membranes functionalized with negatively charged binding groups (p0008; p0077). These filter media include a porous substrate (p0008); the porous substrate includes porous membranes (i.e., a nonfibrous porous substrate; differentiated from nonwoven and woven webs and fibers; p0149). A polymer is grafted onto the porous substrates and includes a hydrocarbon backbone and a plurality of pendant groups attached to the hydrocarbon backbone; said pendant groups including at least one acidic group or salt thereof and a spacer group that directly links the at least one acidic group or salt thereof to the hydrocarbon backbone by a chain of at least six catenated atoms (p0008-0010). At the time of the filing of the invention, one of ordinary skill in the art would have found it obvious to include the filter media taught by COLAK ATAN as the cation exchange nonfibrous porous filter element disclosed by XENOPOULOS. The nature of the problem to be solved would have led one of ordinary skill in the art to combine 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). It is further noted that the COLAK ATAN prior art constitutes Applicant-admitted prior art as it pertains to cation exchange membrane filters that “can be made using standard techniques” as disclosed by Applicant (see Specification, pg. 20, lines 24-26).
Although XENOPOULOS further discloses in p0255 the use of a pH adjustment to buffer solutions prior to the CEX step, XENOPOULOS teaches such a step as optional: “The use of a flow-through cation-exchange step (CEX) may necessitate a reduction of solution pH to increase affinity and capacity for impurities” (emphases added), i.e., a pH adjustment step is not required depending on the desired separation outcome. Indeed, the prior art further states in p0235: “In some embodiments… in-line static mixers… may be used”, i.e., buffer exchanges are optional and not required by the prior art. Furthermore, as noted earlier by the prior art, “[b]y reducing or eliminating steps, such as intermediate washing, the application of continuous chromatography for higher titers (target protein concentrations) is enabled… [and] simplifies the timing required for all titer conditions during continuous chromatography” (p0216). Thus, the prior art provides sufficient motivation for one of ordinary skill in the art to exclude a buffer exchange step between the AEX step and the CEX step.
Regarding Claim 5, modified XENOPOULOS makes obvious the flow-through process of Claim 1. XENOPOULOS further discloses the target molecule is an antibody, e.g., monoclonal antibody (p0018).
Regarding Claim 6, modified XENOPOULOS makes obvious the flow-through process of Claim 1. Prior to the flow-through purification steps, XENOPOULOS discloses viral inactivation of the depth filtered cell culture solution (p0228-0233).
Regarding Claims 12 and 13, modified XENOPOULOS makes obvious the flow-through process of Claim 1. XENOPOULOS further discloses exemplary AEX media include ligands such as those based on quaternary ammonium ions and weak anion exchangers based on primary, secondary, and tertiary amines (p0239).
Regarding Claim 18, modified XENOPOULOS makes obvious the flow-through process of Claim 1. COLAK ATAN further discloses the polymer disposed on the porous substrate includes interpolymerized units of at least one monomer (p0055), i.e., copolymerized with other monomers having other types of ligands to advantageously adjust binding capacities and/or to achieve special properties (p0135-0138).
Claim(s) 2, 3, and 7-11 is/are rejected under 35 U.S.C. 103 as being unpatentable over XENOPOULOS et al. (US 2015/0133636 A1) with evidentiary support from KOZLOV et al. (US 2013/0245139 A1) in view of COLAK ATAN et al. (US 2019/0194250 A1), as applied to Claim 1 above, and further in view of BOTHOF et al. (US 8,846,203 B2).
Regarding Claims 2 and 3, as applied to the rejection of Claim 1 modified XENOPOULOS makes obvious a flow through process for purifying a target molecule from a biological solution. XENOPOULOS further discloses that although the overall disclosed method includes four steps, i.e., clarification, bind and elute chromatography, virus inactivation, and flow-through purification, any of these process steps can be removed without affecting other process steps (p0099). Furthermore, XENOPOULOS notes “[b]y reducing or eliminating steps, such as intermediate washing, the application of continuous chromatography for higher titers (target protein concentrations) is enabled… [and] simplifies the timing required for all titer conditions during continuous chromatography” (p0216). Thus, absent showings of criticality or non-obviousness beyond the advantage disclosed by XENOPOULOS, one of ordinary skill in the art would find it obvious to perform depth filtration immediately followed by anion exchange and immediately followed by cation exchange as cited in Claim 2 or to include a buffer exchange after the step of depth filtration as cited in Claim 3.
Modified XENOPOULOS is deficient in disclosing the adsorptive depth filter is an anion exchange adsorptive depth filter.
BOTHOF discloses the functionalization of porous substrates with ligands for use in selectively binding and removing biological materials from biological samples (c1/17-21). Such ligands have an affinity for binding negatively charged biomaterials (c2/28-29). Advantageously, compared with non-modified porous substrates, the functionalization of such porous substrates with these ligands enhances the affinity for negatively charged biological materials, such as host cell proteins, DNA, RNA, and viruses and more importantly allows for the positively charged materials, especially antibodies, to be purified (c4/24-28). The nature of the problem to be solved would have led one of ordinary skill in the art to combine 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). It is further noted that the BOTHOF prior art constitutes Applicant-admitted prior art as it pertains to grafted ligand-functional polymers disclosed by Applicant (see Specification, pg. 8, lines 29-32).
Regarding Claim 7, modified XENOPOULOS discloses or makes obvious the flow-through process of Claim 1. While XENOPOULOS teaches the use of depth filters having graded layers of polymeric non-woven fibers with an anisotropic pore distribution to filter cellular debris and particulate matter from cell culture (e.g., p0174-0176, p0178), the prior art is deficient in disclosing the depth filter further comprises immobilized anion exchange ligands.
BOTHOF discloses the functionalization of porous substrates with ligands for use in selectively binding and removing biological materials from biological samples (c1/17-21). Such ligands have an affinity for binding negatively charged biomaterials (c2/28-29). Advantageously, compared with non-modified porous substrates, the functionalization of such porous substrates with these ligands enhances the affinity for negatively charged biological materials, such as host cell proteins, DNA, RNA, and viruses and more importantly allows for the positively charged materials, especially antibodies, to be purified (c4/24-28). The nature of the problem to be solved would have led one of ordinary skill in the art to combine 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). It is further noted that the BOTHOF prior art constitutes Applicant-admitted prior art as it pertains to grafted ligand-functional polymers disclosed by Applicant (see Specification, pg. 8, lines 29-32).
Regarding Claims 8-11, modified XENOPOULOS makes obvious the flow-through process of Claim 7. BOTHOF further discloses the ligand-functionalized substrates comprises a number of components including (a) a grafted photoinitiator group extending from the surface of the base substrate; (b) one or more ligand monomers of Formula II (see column 3 middle); (c) optionally one or more monomers having at least one acryloyl group; and (d) optionally one or more hydrophilic monomers (c4/35-43), e.g., of the form (c13/23-32):
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Such a formula is disclosed by BOTHOF to include cationic nitrogen-containing ligands, including a number of primary amines and quaternary ammonium salts (Formula X; c16/31-55).
Regarding Claim 16, modified XENOPOULOS makes obvious the flow-through process of Claim 12. Modified XENOPOULOS is deficient in explicitly disclosing the salt-tolerant anion exchange nonfibrous porous filter element comprises a nonfibrous porous filter element and a ligand-functional polymer grafted thereto having the claimed formula.
BOTHOF discloses the functionalization of porous substrates with ligands for use in selectively binding and removing biological materials from biological samples (c1/17-21). Such ligands have an affinity for binding negatively charged biomaterials (c2/28-29). Porous substrates include microporous membranes, e.g., those formed by thermally-induced phase separation (c5/48-52). These substrates are functionalized with grafted groups comprising a number of components including one or more ligand monomers of Formula II (see column 3 middle); (c) optionally one or more monomers having at least one acryloyl group; and (d) optionally one or more hydrophilic monomers (c4/35-43), e.g., of the form (c13/23-32):
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Ligand monomers of Formula II (column 3, middle):
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Advantageously, compared with non-modified porous substrates, the functionalization of such porous substrates with these ligands enhances the affinity for negatively charged biological materials, such as host cell proteins, DNA, RNA, and viruses and more importantly allows for the positively charged materials, especially antibodies, to be purified (c4/24-28).
The nature of the problem to be solved would have led one of ordinary skill in the art to combine 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). It is further noted that the BOTHOF prior art constitutes Applicant-admitted prior art as it pertains to salt-tolerant membrane filters that are “made using standard techniques” as disclosed by Applicant (see Specification, pg. 18, lines 21-23).
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over XENOPOULOS et al. (US 2015/0133636 A1) in view of COLAK ATAN et al. (US 2019/0194250 A1), as applied to Claim 13 above, and further in view of RASMUSSEN et al. (US 10,239,828 B2).
Regarding Claims 14 and 15, modified XENOPOULOS makes obvious the flow-through process of Claim 13. Modified XENOPOULOS is deficient in explicitly disclosing the cationic nitrogen-containing ligands of the salt-tolerant anion exchange nonfibrous porous filter element comprises guanidinyl-containing ligands (Claim 14) or that the ligands further comprise interpolymerized monomer units comprising a guanidinyl-containing ligand monomer, an amide monomer, an oxy monomer (selected from epoxy and alkyl ether functional monomer units), and a polyalkylene oxide monomer (Claim 15).
RASMUSSEN discloses guanidino-functional polymers used to bind negatively charged biomaterials for the separation and purification of various target biomaterials (c1/50-53; c1/33-47). The polymers are represented by the general formula (column 3, top):
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wherein R1 is selected from hydrogen, alkyl, aryl, and combinations thereof; R2 is selected from hydrocarbylene, heterohydrocarbylene, and combinations thereof; each R3 is independently selected from hydrogen, hydrocarbyl, heterohydrocarbyl, and combinations thereof; R4 is selected from hydrogen, hydrocarbyl, heterohydrocarbyl (for example, R4 can comprise -R2-NH-C(=NR3)-N(R3)2, so as to provide a compound having more than one guanidino moiety), and combinations thereof; and R5 is selected from hydrocarbylene, heterohydrocarbylene, and combinations thereof (c3/12-26). The nature of the problem to be solved would have led one of ordinary skill in the art to combine 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). It is further noted that the RASMUSSEN prior art constitutes Applicant-admitted prior art as it pertains to salt-tolerant membrane filters that “can be made using standard techniques” as disclosed by Applicant (see Specification, pg. 18, lines 21-23).
Conclusion
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/Ryan B Huang/Primary Examiner, Art Unit 1772
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