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
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/EP2022/064237 (filed 05/25/2022). Acknowledgement is made of Applicants’ claim for priority to foreign application EP21175871.9 (filed 05/26/2021).
Claim Rejections - 35 USC § 103
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.
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 10-19 are rejected under 35 U.S.C. 103 as being unpatentable over Eshoo and Duncan (US 2012/171685) in view of Gregoire (US 2019/0054112).
Eshoo and Duncan (hereinafter Eshoo) teaches buffers for the stabilization of nucleic acid molecules (Abstract).
Gregoire teaches compositions and methods for the preparation, manufacture, and therapeutic use of renal polynucleotides (Abstract).
Regarding claim 10-14, 17-19: Eshoo teaches a method for storing nucleic acid comprising mixing a storage solution comprising a chelator and a synthetic oligonucleotide, wherein the storage solution is stored at -20°C to freeze the solution; the solution may be thawed again (par. 0013); the chelator may be EDTA, BAPTA, DTPA, TPEN (par. 0031), and the synthetic oligonucleotide may be RNA (par. 0023, 0033). This reads on the preparing a composition comprising RNA and a metal binding chelator and freezing the composition limitations recited in claim 10.
Eshoo does not teach the RNA as in vitro transcribed and having a 5’ CAP-1 structure, as required by the remaining limitation recited in claim 10.
However, Gregoire teaches a nucleic acid molecule encoding one or more renal peptide(s) of interest (par. 0021), disclosing an embodiment wherein the nucleic acid is a renal in vitro transcribed (IVT), modified mRNA polynucleotide (pars. 0023-0024). Gregoire teaches an embodiment wherein the modification comprises a 5’-Cap1 structure (par. 0118); formulations of the renal polynucleotide may further comprise metal cations, e.g., Zn2+, Ca2+, Cu2+, Mg2+ (par. 0141). Thus, the renal polynucleotide of Gregoire reads on the remaining wherein the RNA is in vitro transcribed and has a 5’ CAP-1 structure limitation recited in claim 10.
It would have been prima facie obvious to have modified the method of Eshoo by substituting the RNA with the renal polynucleotide of Gregoire. This conclusion of obviousness is based on the ‘substitution rationale’. The use of the renal polynucleotide in place of the RNA is a predictable use of prior art elements according to their established functions as nucleic acid molecules, leading to the predictable result of storing the molecule; further, as Gregoire teaches the renal polynucleotide may be stored between -20°C and -80°C (par. 0422), one skilled in the art would have more than a reasonable expectation of success. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
As the modified method carries out the same active steps, the effect of reducing and/or preventing the formation of RNA aggregates is necessarily achieved.
In addition to rendering obvious the limitations recited in claim 10, the modified method of Eshoo as set forth above reads on:
the wherein the composition further comprises divalent metal ions limitation recited in claim 11;
the wherein the metal binding chelator is capable of binding divalent metal ions limitation recited in claim 12;
the wherein the divalent metal ions are selected from: Ca2+ ions, Cu²+ ions, Fe²+ ions, Zn2+ ions, or Mg2+ ions limitations recited in claim 13;
the wherein the divalent metal ions are Mg2+ ions limitation recited in claim 14;
the wherein the metal binding chelator is BAPTA (1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid), EDTA (ethylenediaminetetraacetic acid), DPTА (diethylenetriaminepentaacetic acid), or TPEN (N'- Tetrakis(2-pyridylmethyl)ethylenediamine) limitations recited in claim 17;
the wherein freezing the composition comprises freezing the composition at a temperature of -20°C or less limitation recited in claim 18; and
the further comprising thawing the composition limitation recited in claim 19.
Regarding claims 16-17: Following the above discussion, the modified method of Eshoo does not teach the limitations recited in the instant claims. However, Eshoo teaches chelators form complexes with metal ions so they can't participate or interact normally with other elements, ions or molecules (par. 0030). Many enzymes (e.g., nucleases) require a metal ion for activity; additionally, metal ions themselves can attack and degrade biological molecules, e.g., nucleic acids (par. 0030). Thus, a chelator can be used to sequester the metal ions from interacting with enzyme polypeptides, therefore eliminating, inhibiting, or minimizing enzyme activity, or to maintain the integrity of a nucleic acid in solution (par. 0030).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have further modified the method of Eshoo by formulating the storage solution so the concentration of chelator is equimolar to or higher than equimolar to the concentration of divalent metal ions. This conclusion is based on the ‘teaching, suggestion, or motivation rationale’; one would be thus motivated in order to provide sufficient chelator to sequester any metal ions to prevent degradation of the nucleic acid and maintain its integrity. Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical; see MPEP 2144.05(II)(A).
This renders obvious the limitations recited in claims 15 and 16.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Eshoo and Duncan (US 2012/171685) in view of Gregoire (US 2019/0054112), as evidenced by Qiagen® (“Supplementary Protocol”; 2019).
The teachings of Eshoo and Gregoire are set forth above.
Regarding claim 20: Following the above discussion, the modified method of Eshoo does not explicitly teach thawing the storage solution comprising the renal polynucleotide at a temperature from about 20°C to 30°C, as required by the limitation recited in claim 20. However, regarding the thawing temperature, as per MPEP 716.02, any differences between the claimed invention and the prior art may be expected to result in some difference in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d1091.231 USPQ 375 (Fed. Cir. 1986). Furthermore, the ordinary artisan would have known the prior art recognized room temperature (~25°C) as an appropriate temperature for thawing biological material, e.g., nucleic acids, as evidenced by the supplementary protocol taught by Qiagen® (pg. 2; pars. 2, 4).
Thus, the modified method of Eshoo renders obvious the limitation recited in claim 20.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA PRONZATI whose telephone number is (571)270-5725. The examiner can normally be reached Monday - Friday 9:00a - 5:00p ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, CHRISTOPHER BABIC can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633