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 .
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 allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). 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, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 04/15/2026 has been entered.
Status of the Application
Claims 1-58 are pending and are under current examination.
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 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 of this title, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
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 1-12, 16-44 and 54-58 are rejected under 35 U.S.C. 103 as being unpatentable over Scorza (US 20160024139 A1; effective filing date 03/15/2013), Beckert (RNA Methods and protocols; 2011; Chapter 3; pages 29-42; as provided by the applicant on IDS dated 11/20/2025) and Azarani (Nucleic acids Research, 2000, vol 29, N02e7; as provided by the applicant on IDS dated 11/20/2025) in combination.
Determining the scope and contents of the prior art
Scorza teaches a method of purification of RNA from a mixture comprising DNA impurity, comprising providing a DNA encoding the RNA; transcribing DNA to yield a solution of RNA in in vitro transcription (IVT), wherein RNA may be circular or linear, preferably linear and concentrating (desired fragment) using TFF and/or diafiltration (removal or separation of components) using TFF and/or purification of RNA using one or more steps of TFF, for example hollow fibers, with a preferred molecular weight cut off of 500kDa using buffer comprising sodium chloride (aqueous salt solution) with no phenol/CHCl3 extraction or RNA precipitation (paragraphs 0026, 0042-0048, 0050-0054, 0061). Paragraph 0051 teaches that the retentate of TFF (is performed using buffer comprising NaCl) may be re-circulated or re-filtered (i.e. C2, and C3 steps of TFF of diafiltration (diafiltration also results purification and concentration or vice versa) or purification) using TFF and MW cut off of a TFF filter may be selected based on molecule of interest. Paragraph 0056 teaches that the TFF process may be carried out by using any suitable filter membrane and further provides examples of polysulfone (PS), polyether sulfone (PES) and modified PES (mPES). Paragraph 008, 0012-0015, 0018, 0020 and 0022 teaches that the purification of RNA through TFF may be combined with other purification steps such as first step of core bead flow-through chromatography using buffer (aqueous salt solution); second step of hydroxyapatite chromatography and then a third TFF step or first step of TFF (using NaCl) second step of hydroxyapatite chromatography and then a third TFF step (using NaCl) and TFF steps may be repeated (paragraph 0020-0021, 0051). Paragraph 187, further teaches a step of reverse phase chromatography and the purity of sample which is higher than the impure mixture of step B having DNA fragment along with desired RNA.
Ascertaining the differences between the prior art and the claims at issue
Scorza teaches applicant’s process of purification of RNA using any TFF with an example of hollow membrane, but fails to teach the step A1 of linearizing the plasmid DNA--- and terminating the linearization reaction; the method using TFF membrane cassette filter; cellulose derivate membrane with MWCF of about 100 kDa.
Resolving the level of ordinary skill in the pertinent art
With regard to the difference of teach the step A1 of linearizing the plasmid DNA--- and terminating the linearization reaction- Scorza teaches getting RNA sample using in vitro transcription (IVT) but fails to teach any particular step of IVT such as A1 of the instant claims. The Examiner notes that A1 step is a well-known step for IVT and is routinely used in molecular biology for obtaining sample of RNA, for example as detailed by Beckert (chapter 3, pages 29-42, in particular pages 30-32).
Thus, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that the impure RNA sample may be obtained by performing steps of IVT, i.e. linearizing the plasmid DNA--- and terminating the linearization reaction as it is a well-known process of transcription and has been in routine use in the art as taught by Beckert. Thus, the cited prior art meets limitation of the instant claims.
With regard to the difference of using TFF hollow membrane vs TFF membrane cassette filter - Scorza teaches using TFF method by using any apparatus available for the practice of TFF. However, Scorza only gives example with the hollow membrane. Thus, with the guidance provided by Scorza, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that the other commercially available apparatus such as TFF cassettes may be substituted for hollow membrane of Scorza for practicing TFF process.
Further, Case law has established that it is prima facie obvious to substitute one known element for another to obtain predictable results. KSR Int'I Co. v. Teleflex, Inc., 550 U.S. 398 (2007). Thus, the cited prior art meets limitation of the instant claims.
With regard to the difference of cellulose derivate membrane with MWCF of about 100 kDa- Scorza teaches that any suitable filter membrane with desired MW cut off may be selected based on molecule of interest. Thus, with the guidance provided by Scorza, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that the other commercially available suitable filter membrane with desired MW cut off may be selected based on molecule of interest. Thus, the cited prior art meets limitation of the instant claims.
With regard to the difference of removing solvents from the reverse phase chromatography step - Scorza teaches a step of reverse phase chromatography and the purity of sample which is higher than the impure mixture of step B having DNA fragment along with desired RNA. However, the cited prior art is silent about removing solvent from the fractions eluted from reverse phase chromatography. The Examiner notes that reverse phase chromatography is a routine chromatography technique of purification and analysis and it is routine to remove any undesired organic solvents used in the mobile phase of the chromatography from the desired eluted fraction. It may be used as analytical technique for standardization of a purification technique or for an analysis. For example, as detailed by Azarani (Nucleic acids Research, 2000, vol 29, N02e7).
Since Scorza reverse chromatography for analysis, it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that same kind of column as in the instant claims but larger for purification purposes under same solvent conditions of Scorza may be additionally added to the steps of purification if higher purification and/ or a particular desired fraction from analytical HPLC is desired followed by a routine technique of getting rid of unwanted organic solvent from the desired fraction as it is a well-known process of RNA purification and has been in routine use in the art as taught by Azarani. Thus, the cited prior art meets limitation of the instant claims.
Based on the above established facts, it appears that the combination of teachings of above cited prior art read applicants’ process.
Therefore, all the claimed elements were known in the prior art and one skilled person in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Considering objective evidence present in the application indicating obviousness or nonobviousness
To establish a prima facie case of obviousness, three basic criteria must be met: (1) the prior art reference must teach or suggest all the claim limitations; (2) there must be some suggestion or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings; and (3) there must be a reasonable expectation of success; and (MPEP § 2143).
In this case, Scorza teaches applicant’s process of purification of RNA using any TFF with an example of hollow membrane, Beckert teaches routine IVT steps well known in the art such as step A1 and A2 of the instant claims and Azarani teaches reverse phase chromatography as routinely useful technique in RNA purification and removal of undesired solvents.
So, the combination of prior art read applicants claims.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” (Id. At 1395). See MPEP 2143 - Examples of Basic Requirements of a Prima Facie Case of Obviousness [R-9].
In this case at least prong (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success would apply.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. Further, there is a reasonable expectation of success that the impure RNA sample to be purified via TFF may be obtained by performing well-known routine steps of IVT, i.e. linearizing the plasmid DNA--terminating the linearization reaction and purification step using reverse phase chromatography by combination of the above cited prior art.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited references and to make the instantly claimed process with a reasonable expectation of success. Modifying such parameters is prima facie obvious because an ordinary artisan would be motivated to develop an alternative process for economic reasons or convenient purposes from a known individual reaction steps, and to arrive applicants process with a reasonable expectation of success, since it is within the scope to modify the process through a routine experimentation.
Allowable Subject Matter
Claims 13-15 and 45-53, presents allowable subject matter over the cited prior art.
Objection
Claim 13-15 and 45-53 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PANCHAM BAKSHI whose telephone number is (571)270-3463. The examiner can normally be reached M-Thu 7-4.30 EST.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623
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