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 .
Priority
This application is a 371 of PCT/EP2023/054159, filed 2/20/2023. This application claims benefit to foreign application UNITED KINGDOM 2202777.5, filed 3/01/2022. Claims 1-33 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-19 and 27-30, in the reply filed on 6/2/2026 is acknowledged. Claims 20-26 and 31-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Claims 1-19 and 27-30 have been examined on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 10, 12, 19 and 27-28 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.
The term “substantially” in claim 10, line 3, is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Hence, claim 10 is rejected under 35 U.S.C. 112(b) as being indefinite.
The term “substantially” in claim 12, line 2, is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Hence, claim 10 is rejected under 35 U.S.C. 112(b) as being indefinite.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 19 recites the broad recitation “the RNA-precipitating agent is selected from the group consisting of calcium chloride, lithium chloride, and tripotassium citrate”, and the claim also recites “preferably calcium chloride” which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 27, the phrase "such as" in line 3 renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Claim 28 depends from claim 27 but does not resolve the indefiniteness; hence, claims 27-28 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4-6, 15 and 27-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hitchcock et al., 2010 (NPL cite 9, IDS, 6/12/2024) in light of “Plasmidselect Xtra information page” (cite U, attached PTO-892).
Hitchcock teaches a method for separating supercoiled DNA from a liquid sample comprising loading an alkaline lysis of an RNAse-treated cell culture harvest comprising plasmid DNA into a low-pressure anion-exchange chromatography (AEX) medium, eluting the plasmid DNA from the AEX medium, diluting the eluted plasmid DNA with an (NH4)2SO4 solution to adjust the eluate to 2.1 M (NH4)2SO4, adding the liquid sample to a second chromatography medium comprising the thiophilic aromatic adsorption ligand, 2-mercaptopyridine (see “Plasmidselect Xtra information page”, page 3), eluting open-circle plasmid DNA, then, eluting the supercoiled plasmid DNA (scDNA); concentrating the scDNA, exchanging the buffer to a pharmaceutically-acceptable buffer and filter sterilizing the scDNA solution wherein the scDNA >> 95% pure (pp. 50-51, “Streamlining Existing Plasmid DNA Purification Platform with PlasmidSelect Xtra Resin:”; p. 54, “Anion-Exchange Chromatography:”, “Plasmid Select Xtra Chromatography:”, “Buffer Exchange By Tangential Flow Filtration (TFF):”; Figs. 3-6; Table 1), i.e., the method comprising the steps of: (a) adding a liquid sample comprising pDNA to a first chromatography material comprising (i) an anion exchange chromatography ligand for binding to pDNA and (ii) a support material allowing convective flow through the first chromatography material, wherein the liquid sample originates from a cell culture harvest and has been subjected to a step of removing RNA before step (a); (b) eluting a liquid sample, comprising a purified mixture of supercoiled pDNA and open circular pDNA, from the first chromatography material; (c) adding the liquid sample from step (b) to a second chromatography material comprising a ligand that binds to pDNA and enables selective separation of supercoiled pDNA from open circular pDNA, wherein the ligand is 2-mercaptopyridine; (d1) eluting the open circular pDNA from the second chromatography material. (d) eluting the purified supercoiled pDNA from the second chromatography material; (e1) concentrating the supercoiled pDNA to a pharmaceutically relevant dose, (e2) replacing a buffer applied in step (d) of claim 1 with a pharmaceutically acceptable buffer, and (e3) sterilizing the supercoiled pDNA, thereby obtaining a composition comprising pharmaceutical grade supercoiled pDNA wherein the supercoiled pDNA eluted in step (d) has a purity degree of at least 95% without use of any further chromatography material than said first and second chromatography materials anticipating claims 1, 4-6, 15 and 27-30.
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.
Claims 1-7, 10-12, 15 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hitchcock in view of Zurbriggen et al., US 2022/0145283 (cite A, attached PTO-892; herein “Zurbriggen”).
The discussion of Hitchcock regarding claims 1, 4-6, 15 and 27-30 set forth in the rejection above is incorporated herein.
Hitchcock teaches that their method of purifying scDNA to a purity of >95% comprises only an AEX chromatography step and a Plasmid Select Xtra® chromatography step [0081], i.e., a thiophilic aromatic adsorption with 2-mercaptopyridine step, with no other chromatography steps, but Hitchcock does not disclose the ligand for the AEX chromatography. However, a person of ordinary skill in the art at the time of filing would have found it obvious to the AEX ligand to be a strong quaternary amino group AEX ligand or a weak diethyl aminoethyl (DEAE) AEX ligand in view of the disclosure of Zurbriggen.
Zurbriggen, like Hitchcock, teaches methods of separating scDNA from a liquid sample, comprising purifying scDNA to a purity of >95% [0044] with only an AEX chromatography step [0051-60] and a Plasmid Select Xtra® chromatography step [0081], i.e., a thiophilic aromatic adsorption with 2-mercaptopyridine step, with no other chromatography steps required. Zurbriggen teaches that the AEX ligand can be, inter alia, a strong quaternary amino group AEX ligand [0057]; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the anion exchange chromatography ligand to be a strong anion exchange chromatography ligand; therefore, claim 2 is prima facie obvious.
Zurbriggen teaches that the AEX ligand can be, inter alia, a weak diethyl aminoethyl (DEAE) AEX ligand [0057], hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the anion exchange chromatography ligand to be a weak anion exchange chromatography ligand; therefore, claim 3 is prima facie obvious.
Zurbriggen teaches that the support material for the AEX chromatography can be a monolith, a membranous material or beads of an average diameter with linkers, i.e., extenders [0057-59]. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the AEX chromatography support material to be a monolith, a membranous structure or spherical particles with extenders; therefore, claims 7 and 10 are prima facie obvious.
A person of ordinary skill in the art at the time of filing would have found it obvious to use similar support material for the second chromatography step, i.e., for the second chromatography support material to also be a monolith, a membranous structure or spherical particles with extenders; therefore, claims 11-12 are prima facie obvious.
Claims 1-15 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hitchcock in view of Zurbriggen and Park et al., 2014 (cite U, attached PTO-892; herein “Park”).
The discussion of Hitchcock and Zurbriggen regarding claims 1-7, 10-12, 15 and 27-30 set forth in the rejection above is incorporated herein.
Neither Hitchcock nor Zurbriggen teach that the membrane support for the chromatography steps comprises a membranous structure comprising a nonwoven web of electrospun polymer nanofibers; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the membrane supports for either chromatography step to be a membranous structure comprising a nonwoven web of electrospun polymer nanofibers in view of Park.
Park teaches producing electrospun nonwoven webs of polymer nanofibers for anion exchange membranes (Abst.) and teaches that the process can be extended to other polymers and different ligands (Abst.); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the membrane supports for either chromatography step to be a membranous structure comprising a nonwoven web of electrospun polymer nanofibers; therefore, claims 8-9 and 13-14 are prima facie obvious.
Claims 1-6, 15-16, 19 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hitchcock in view of Bhikhabhai, US 6410274 (US Patent document cite 1, IDS, 6/12/2024; herein “Bhikhabhai”).
The discussion of Hitchcock regarding claims 1, 4-6, 15 and 27-30 set forth in the rejection above is incorporated herein.
Hitchcock mentions precipitation of RNA from the lysate (p. 48, ¶4) but does not specifically recite that RNA is removed from the lysate by precipitation with calcium chloride (CaCl2); however, a person of ordinary skill in the art at the time of filing would have found it obvious to remove RNA from the lysate with CaCl2 before purifying the scDNA with chromatography steps in view of the disclosure of Bhikhabhai.
Bhikhabhai teaches large scale purification of plasmid DNA wherein most of the RNA and chromosomal DNA from the alkaline lysis is precipitated with calcium chloride, followed by clarification by filtration (Abst.; col. 3, l. 65 – col. 4, l. 32), thereby removing most RNA and chromosomal DNA before loading the lysate onto AEX chromatography matrix. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Hitchcock wherein pretreating the liquid sample comprises (a1-a) subjecting the cell culture harvest to cell lysis, (a1-b) precipitation of RNA in the presence of an RNA-precipitating agent wherein the RNA-precipitating agent is calcium chloride; and (a1-c) clarification; therefore, claims 15-16 and 19 are prima facie obvious.
Regarding claim 2, Hitchcock discloses that the method for separating scDNA comprises making an alkaline lysate of the cells expressing the pDNA, purifying the plasmid DNA by AEX chromatography, then purifying scDNA by thiophilic aromatic adsorption chromatography with the ligand 2-mercaptopyridine, but does not specifically teach that the AEX chromatography ligand is a strong anion exchange chromatography ligand. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the AEX chromatography ligand in the method of Hitchcock to be a strong anion exchange chromatography ligand because Bhikhabhai teaches that the anion exchange chromatography ligand can comprise quaternary amino groups (col. 4, l. 56-62); therefore, claim 2 is prima facie obvious.
Regarding claim 3, Hitchcock discloses that the method for separating scDNA comprises making an alkaline lysate of the cells expressing the pDNA, purifying the plasmid DNA by AEX chromatography, then purifying scDNA by thiophilic aromatic adsorption chromatography with the ligand 2-mercaptopyridine, but does not specifically teach that the AEX chromatography ligand is a weak anion exchange chromatography ligand. However, a person of ordinary skill in the art at the time of filing would have found it obvious for the AEX chromatography ligand in the method of Hitchcock to be a weak anion exchange chromatography ligand because Bhikhabhai teaches that the anion exchange chromatography ligand can comprise diethyl aminoethyl groups (col. 4, l. 56-62); therefore, claim 3 is prima facie obvious.
Claims 1-6, 15-19 and 27-30 are rejected under 35 U.S.C. 103 as being unpatentable over Hitchcock in view of Bhikhabhai and Blanche et al., US 2007/0213289 (cite B, attached PTO-892; herein “Blanche”).
The discussion of Hitchcock and Bhikhabhai regarding claims 1-6, 15-16, 19 and 27-30 set forth in the rejection above is incorporated herein.
Neither Hitchcock nor Bhikhabhai teach that the alkaline lysis comprises subjecting the cell culture harvest to cell lysis by mixing the cell culture harvest with a lysis solution using a static mixer wherein the cell culture harvest is contacted with said lysis solution to form a combined composition, and said combined composition is allowed to flow through said static mixer to achieve mixing thereof. However, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Hitchcock in view of Bhikhabhai wherein a static mixer is used to perform the alkaline lysis in view of Blanche.
Blanche teaches a static mixer and methods for using the static mixer to lyse cell culture compositions for the purification of plasmid DNA because using the static mixer to lyse the culture compositions greatly reduces the shear forces involved in mixing the solutions (Abst; [0012]; Figs. 1-2).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Hitchcock in view of Bhikhabhai wherein the cell culture harvest is subjected to cell lysis by mixing the cell culture harvest with a lysis solution using a static mixer wherein the cell culture harvest is contacted with said lysis solution to form a combined composition, and said combined composition is allowed to flow through said static mixer to achieve mixing thereof; therefore, claims 17-18 are prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651
