Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Applicant’s Arguments and Amendments
In the response submitted by the Applicant the following 35 U.S.C. 112 rejections are withdrawn:
Claim 1 rejected under, 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The following 35 USC 102 rejections are withdrawn:
Claims 14-16 are withdrawn;
The following 35 USC 103 rejections are withdrawn:
Claims 14-16 are withdrawn
The Applicant’s amendments necessitated the above 35 USC 112 rejection withdrawals. The Applicant has pointed out that the method of Hebel et al. has holding tanks and therefore cannot be “substantially continuous” as defined in the Specification on pg. 6-7. This definition state:
The term "continuous" or "substantially continuous" as used in reference to the processes described herein refers to a continuous flow of materials ( or solution or dispersion) between each step of the purification process to each subsequent step, starting from the beginning of the purification process up until the step of loading the ion-exchange chromatography column.
It is understood that holding tanks in Hebel et al. fill, then settle to clarify the lysate prior to filtering with an ion exchange membrane. This filling/settling steps breaks the continuity between the steps limited in these claims.
All arguments drawn to these rejections are now considered moot.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 1-12 remain rejected under pre-AIA 35 U.S.C. 102b as being anticipated by Hebel et al. (EP 1628749).
Hebel et al. teach a continuous method for the purification of plasmids from bacterial cells comprising [0034, 0042]:
Producing a lysate solution by mixing a bacterial cell suspension (Fig 2, 202,) and lysis solution (Fig 2, 201) in a high-shear, in line mixer (Fig 2, #205) [0096-0099] for about 5 mins [0099, last line];
Mixing a neutralizing solution (Fig 2, #208) with the lysate solution in the bubble column mixer (Fig 2, #207) to produce a crude lysate solution comprising neutralized lysate and precipitate (e.g. debris) which is then sent to a settling tank Fig 2, #211) [0100] for a period of time to remove the precipitate/debris [0107] from the solution before it is filtered as seen in Figure 4;
The crude neutralized lysate in the settling tank #211 or #401 is then continuously passed through two filters, a primary and a secondary, (Fig. 4, #404, #405) and this clarified lysate is collected in a holding tank #406 [0109];
The clarified lysate is then passed through an ion exchange membrane to produce an ion exchange elute comprising the plasmid (Fig 5, [0112-0113], this ion exchange membrane is a anion exchange membrane [0116];
The ion exchange elute is further purified with a hydrophobic interaction membrane to produce a hydrophobic interaction solution comprising the plasmid [0113-0114];
The hydrophobic interaction solution is subject to ultrafiltration/diafiltration to concentrate the plasmid [0114]; and
The solution with the plasmid from step f) is then subjected to sterile filtration for pharmaceutical applications [0115].
Therefore the invention as a whole is anticipated by the reference.
Response To Applicant’s Arguments
Applicant's arguments have been fully considered but they are not persuasive. Applicant argues that Hebel et al. does not teach “a large scale process in which the product is continuously produced” Initially the argument that the process must be continuously produced is not commensurate in scope with the claims 1-12. This limitation does not appear until claims 14-15.
The Specification states (see pg. 6 lines 15-20):
The term "large scale" as used in reference to the described processes refers to purification processes that produce from bacterial cells or a suspension of bacterial cells quantities of at least one biologically active molecules, particularly DNA plasmid, of about 1 gram or greater and/or purification processes that requires lysis of quantities of bacterial cell
paste of about 1 kilogram or greater.
This can be rephrased that a large scale process purifies at least one biologically active molecule of about 1 gram or greater from bacterial cells. This reads as the intended result of the claim. Hebel et al. clearly teach that their method produces 3100 mg of total plasmid (see Example 3) or 2700 mg of plasmid DNA (see Example 2). Therefore it appears that Hebel et al. has achieved the intended result of the Applicant’s definition.
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 negated by the manner in which the invention was made.
Claims 1-13 remain rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Hebel et al. (EP 1628749) in view of Blanche et al. (WO2005026331, in IDS 2/8/23).
Hebel et al. teach a continuous method for the purification of plasmids from bacterial cells comprising [0034, 0042]:
Producing a lysate solution by mixing a bacterial cell suspension (Fig 2, 202,) and lysis solution (Fig 2, 201) in a high-shear, in line mixer (Fig 2, #205) [0096-0099] for about 5 mins [0099, last line];
Mixing a neutralizing solution (Fig 2, #208) with the lysate solution in the bubble column mixer (Fig 2, #207) to produce a crude lysate solution comprising neutralized lysate and precipitate (e.g. debris) which is then sent to a settling tank Fig 2, #211) [0100] for a period of time to remove the precipitate/debris [0107] from the solution before it is filtered as seen in Figure 4;
The crude neutralized lysate in the settling tank #211 or #401 is then continuously passed through two filters, a primary and a secondary, (Fig. 4, #404, #405) and this clarified lysate is collected in a holding tank #406 [0109];
The clarified lysate is then passed through an ion exchange membrane to produce an ion exchange elute comprising the plasmid (Fig 5, [0112-0113], this ion exchange membrane is a anion exchange membrane [0116];
The ion exchange elute is further purified with a hydrophobic interaction membrane to produce a hydrophobic interaction solution comprising the plasmid [0113-0114];
The hydrophobic interaction solution is subject to ultrafiltration/diafiltration to concentrate the plasmid [0114]; and
The solution with the plasmid from step f) is then subjected to sterile filtration for pharmaceutical applications [0115].
What Hebel et al. does not teach is performing their hydrophobic interaction separation with butyl hydrophobic interaction chromatography. This is obvious in view of Blanche et al. who teach that plasmid purification from bacterial with hydrophobic interaction chromatography (HIC) can use many resins including those with ether, phenyl, butyl, and hexyl chains (Blanche, pg. 35 lines 9-25). One of ordinary skill in the art would recognize that using butyl side chains in their HIC membrane would be obvious to purify plasmids from bacteria because this is simply substitution a known technique for plasmid purification. (MPEP 2141 III (B)).
Therefore the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicants rely on the arguments used in traversing the above rejection to also traverse this rejection without additional arguments. However, as explained above, the previous rejection stands. Therefore, the response set forth above to arguments also applies to this rejection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,453,855 . Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to a similar method with similar scope with the following steps:
a) producing a lysate solution by mixing a bacterial cell suspension with a lysis solution in a high shear, in-line mixer for about 5 mins;
b) neutralizing said lysate solution by mixing it with a neutralizing solution to in a bubble mixer to produce a dispersion that comprises neutralized lysate solution and debris;
c) filtering the dispersion through at least one filter, or a primary then secondary filter to produce a crude lysate;
d) performing anion exchange separation on said neutralized lysate solution to produce an anion exchange eluate;
e) performing hydrophobic interaction separation on said anion exchange eluate to produce a hydrophobic interaction solution;
f) ultrafiltration of the hydrophobic interaction solution; and
g) sterile filtering the ultrafiltrated hydrophobic interaction solution to recover a sterile plasmid;
The method steps can be substantially continuous.
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.
In response to this office action the applicant should specifically point out the support for any amendments made to the disclosure, including the claims (MPEP 714.02 and 2163.06).
CONTACT INFORMATION
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THANE E UNDERDAHL whose telephone number is (303) 297-4299. The examiner can normally be reached Monday through Thursday, M-F 8-5 MST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fereydoun Sajjadi can be reached at (571) 272-3311.The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/THANE UNDERDAHL/Primary Examiner, Art Unit 1699