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 .
Claim Status
Claim 15 is rejected.
No claims are allowed.
New Claim Objections
Claim 15 is objected to because of the following informalities: the term “A emulsion system” should be written as “An emulsion system.” Further, in line three, the term “become” should be written as “becomes.” Additionally, the claim should indicate that the abbreviation MEG-3 stands for. Appropriate correction is required.
New Claim Rejections - 35 USC § 112(b)
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.
Claim 15 is 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.
Claim 15 recites the limitation optionally, a single-stranded nucleic acid between 20 and 5000 nucleotides in length; and water, wherein the molar ratio of MEG-3 to the water insoluble protein is 2 to 20. The claim is indefinite since it is unclear which of the limitations following the term optionally are optional, and which limitations, if any, required.
New 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.
1. Claim 15 rejected under 35 U.S.C. 103 as being unpatentable over Putnam et al., (A gel phase promotes condensation of liquid P granules in Caenorhabditis elegans embryos, published March 04, 2019) (cited by Applicant on IDS 06/21/2024) (hereinafter Putnam) as evidenced by Saha et al., (Polar positioning of phase-separated liquid compartments in cells regulated by an mRNA competition mechanism, September 08, 2016) (cited by Applicant on IDS 06/21/2024) (hereinafter Saha).
Putnam discloses that RNA granules are subcellular compartments that are proposed to form by liquid–liquid phase separation (LLPS), a thermodynamic process that partitions molecules between dilute liquid phases and condensed liquid phases. P granules are RNA granules that form in the posterior of Caenorhabditis elegans embryos and spontaneous LLPS of the RNA-binding protein PGL-3 with RNA drives the assembly of P granules. The PGL-3 phase is intrinsically labile and requires a second phase for stabilization in embryos. The second phase is formed by gel-like assemblies of the disordered protein MEG-3 that associate with liquid PGL-3 droplets in the embryo posterior (Abstract). To examine P granule protein dynamics in live embryos, a meg-3 and pgl-3 loci were tagged with green fluorescent protein (GFP) or mCherry (page 220, Results). Embryos co-expressing PGL-3::mCherry and MEG-3::GFP were filmed and the eggshell of the embryo was punctured to release cellular contents into an aqueous buffer (i.e., water). Consistent with a liquid phase, PGL-3::mCherry diffused immediately on dilution into the buffer. By contrast, MEG-3::GFP persisted in the granule phase, as the granules flowed out of the embryo into the dilute buffer. These observations suggest that the MEG-3 phase is not an irreversible aggregate, but a stable, gel-like phase. By contrast, the PGL-3 phase behaves like a liquid (i.e., emulsion system) (pages 221-222, The MEG-3 phase is gel-like). To determine whether the distinct properties of MEG-3 and PGL-3 observed in vivo are intrinsic to these proteins, condensates in vitro using purified MEG-3 and PGL-3 were generated. Recombinant MEG-3 and PGL-3 were previously shown to phase separate with RNA under pH and salt conditions in the physiological range so MEG-3, PGL-3, and C. elegans RNA (i.e., a single-stranded nucleic acid) were introduced together in condensate buffer. After 1 minute MEG-3 and PGL-3 initially formed separate condensates, but after 5 min of incubation, co-assemblies were observed and by 30 min the majority of condensates contained both MEG-3 and PGL-3 (pages 222-223, In vitro reconstitution of a minimal P granule). For in vitro condensation experiments, the concentrations of MEG-3, PGL-3 and mRNA have been estimated at 11 ± 4 nM, 680 ± 200 nM and 100 nM (50 ng µl−1), respectively. These estimates were derived from pooled, mixed-stage embryos and thus are likely to be underestimates for MEG-3 and PGL-3. Further, MEG-3/PGL-3 condensates form over a wide range of concentrations as long as the ratio of RNA to MEG-3 is kept high to prevent co-assemblies of PGL-3 and MEG-3 from aggregating (page 228, second paragraph).
As evidenced by Saha, in physiological buffer, purified PGL-3-mEGFP phase separates into two phases: one containing PGL-3 at ~50 fold higher concentration compared to the bulk phase and drops of PGL-3 settle down by gravity indicating that they are denser compared to the surrounding bulk phase (i.e., becomes insoluble at increased concentrations) (page 1573, Results). Further, PGL-3 phase separates from the water-like solvent (i.e., is water insoluble) (e6, C ) Fit of the theory to experimental data).
Thus, Putnam discloses MEG-3 in a stable, gel-like phase and a PGL-3 (i.e., a water insoluble protein) phase that behaves like a liquid (i.e., emulsion system) in an aqueous buffer (i.e., water) (pages 221-222, The MEG-3 phase is gel-like). Together these would provide a composition as claimed instantly. The prior art is not anticipatory insofar as Putnam does not disclose wherein the MEG-3 is present at 500nM and wherein the molar ratio of MEG-3 to the water insoluble protein is 2 to 20. However, as discussed above, Putnam estimates the concentration of PGL-3 (i.e., water insoluble protein) to be about 680 ± 200 nM and teaches that the PGL-3 (i.e., water insoluble protein) phase is intrinsically labile and requires a second phase formed by gel-like assemblies of the disordered protein MEG-3 for stabilization in embryos and MEG-3/PGL-3 condensates form over a wide range of concentrations as long as the ratio of RNA to MEG-3 is kept high to prevent co-assemblies of PGL-3 and MEG-3 from aggregating. Accordingly, one of ordinary skill in the art would have arrived at the claimed amount of MEG-3 through routine experimentation depending on the amount of MEG-3 phase necessary to effectively stabilize the PGL-3 (i.e., water insoluble protein) phase while preventing aggregation of the co-assemblies. After arriving at this amount, a ratio between these two amounts is obtained. Therefore, since the ratio is based on desired effects, the claimed ratio would have been obvious based on the desired effect of MEG-3. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A).
2. Claim 15 rejected under 35 U.S.C. 103 as being unpatentable over Putnam et al., (A gel phase promotes condensation of liquid P granules in Caenorhabditis elegans embryos, published March 04, 2019) (cited by Applicant on IDS 06/21/2024) (hereinafter Putnam) in view of Seydoux (The P Granules of C. elegans: A Genetic Model for the Study of RNA–Protein Condensates, Aug. 08, 2018) (cited by Applicant on IDS 06/21/2024) (hereinafter Seydoux).
As discussed above, Putnam makes obvious the limitations of claim 15 but does not disclose wherein the optional RNA (i.e., single-stranded nucleic acid) is between 20 and 5000 nucleotides in length.
However, Seydoux discloses that experiments with recombinant proteins revealed that MEG-3 and PGL-3 form condensates in vitro under physiological salt concentrations (150 mM KCl or 150 mM NaCl). For both MEG-3 and PGL-3, addition of RNA stimulates phase separation. Addition of short (30 nt) poly-U oligonucleotides increased the number and sizes of MEG-3 condensates (page 4704, A Competition for RNA Localizes P Granules in Zygotes).
As discussed above, Putnam discloses wherein MEG-3 and PGL-3 form condensates in embryos (i.e., in vitro) and were shown to phase separate with RNA. Thus, it would have been prima facie obvious to one of ordinary skill in the art to have added the RNA as short (30 nt) poly-U oligonucleotides to increase the number and sizes of MEG-3 condensates, as taught by Seydoux.
Response to Applicant’s Arguments
Applicant’s arguments have been considered but are moot because new rejections necessitated by Applicant’s amendments have been made.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/S.J.K./Examiner, Art Unit 1614
/TRACY LIU/Primary Examiner, Art Unit 1614