DETAIL 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 .
Election/Restrictions
Applicant’s election without traverse of Group I comprising claims 1-10 in the reply filed on 12/03/2025 is acknowledged.
The election is made FINAL.
Claim Status
Claims 1-20 pending.
Claims 11-20 are withdrawn, as being drawn to non-elected inventions.
Claims 1-20 are being examined.
Claim Rejections - 35 USC § 112(a)
Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6, 9 and 10 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for only photosynthetic bacteria, does not reasonably provide enablement for all or any bacteria that do not photosynthesize. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The specification describes methods of enhancing a rate of adaptive mutation, more particularly to achieving increases in photosynthesis and growth of cyanobacterial species (Spec, para 2, line 1-2). The Applicant does not describe or provide any example of transforming a non-photosynthetic bacteria into photosynthetic ones, using the claimed method. Current status of art also does not teach any method to transform a non-photosynthetic bacteria into a photosynthetic one.
Undue trial and error experimentations would be needed to introduce the trait of photosynthesis in a non-photosynthetic bacteria.
Based on breadth of the claims, lack of any working example, lack of guidance in the instant description or in prior art, the specification at the time of the application filed would not have taught one skilled in the art how to make and use the full scope of the claimed invention without performing undue experiments.
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.
Claims 1-10 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.
Claim 1 recites, “… enhancing at least one of photosynthetic rate and photosynthetic efficiency…”. However, the Applicant defines the two terms “photosynthetic rate” and “photosynthetic efficiency” to be the same. Instant specification defines, “”The term “enhanced photosynthetic rate and/or efficiency” refer(s) to a measure of photosynthesis of a modified organism relative to the wild-type or otherwise unmodified organism”” (spec, page 8, para 00046). It is unclear what is the difference between the two terms, “photosynthetic rate” vs “photosynthetic efficiency”, as used by the Applicant. All the claims directly or indirectly depending from claim 1, inherit the indefiniteness of the claim 1.
Claim 9 recites “…. High throughput screening….based on modeling” which renders the claim indefinite. The instant specification does not define “modeling”. It is also unclear what types of screens are encompassed by “high throughput screening for sucrose production”. Specification recites the term “high throughput” in several instances but does not define the term. It is unclear what other screens/assays are encompassed by this limitation. In other words, it is not clear when a screening qualifies as “high throughput”.
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.
Claims 1-8 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Emlyn-Jones et al. (Nitrogen-Regulated Hypermutator Strain of Synechococcus sp. for Use in In Vivo Artificial Evolution, 2003, Applied and Environmental Microbiology, 69:6427–6433) in view of Roberts et al. (US 10654901 B2), in evidence of Foster, P. (Stress-Induced Mutagenesis in Bacteria, 2007, Crit Rev Biochem Mol Biol., 42: 373–397).
Claim 1 is drawn to a method of identifying a genetic mutation capable of enhancing photosynthetic rate and/or photosynthetic efficiency by modifying bacterial cells to enhance mutation rate relative to wild-type organisms in presence of an environmental stressor.
Emlyn-Jones et al. teaches that inactivation of mutS gene greatly increased mutation rate in cyanobacteria (abstract). Emlyn-Jones et al. describes an inducible expression system using the nirA promoter in Synechococcus sp. strain PCC 7942 (as recited in claim 8) by inactivating or repressing the mutS gene which is in the DNA mismatch repair pathway (as recited in claim 6) (abstract). Such hypermutator strains play a role in evolutionary adaptation to a new environment (page 6431, right column, para 1, line 5-7) and reads on to “adaptive mutation”, as recited in claim 2. Emlyn-Jones et al. also describes a vector comprising the nirA promoter (page 6429, right column, para 1, line 1-4, and line 33-34; Fig. 3). The recombinant vector comprising the nirA promoter was transformed into wild type cyanobacteria (Synechocystis sp. strain PCC 7942) to form modified cells (page 6429, right column, para 2, line 1-2), as recited in claim 5. Emlyn-Jones et al. also teaches that the PnirA-mutS system will make a useful addition to the toolbox of molecular genetic techniques available for the study and manipulation of cyanobacteria (p. 6432, left col., 4th paragraph).
However, Emlyn-Jones et al. does not describe photosynthetic rate/efficiency/capacity or screening cyanobacterial mutants based on its ability to have increased photosynthetic rate/efficiency and/or increased production of sucrose.
Roberts et al. describes a method of increasing photosynthetic capacity by downregulating activity of the RpaB pathway in cyanobacterial cells (as recited in claim 7) including in Synechococcus elongatus PCC7942 (as recited in claim 8) and also genetically modified cyanobacterial cells (abstract; column 11, line 2-3). Roberts et al. describes that increased photosynthetic capacity can increase total carbon fixation, production of carbon containing compounds, and growth (biomass accumulation) (column 9, line 24-26). Hence, the term “photosynthetic capacity” is interpretated by the Examiner as synonymous to “photosynthetic rate” and “photosynthetic efficiency” (as recited in claim 1) as all these terms are “a measure of photosynthesis”. Each of the parameters (i.e., increase total carbon fixation, production of carbon containing compounds, and growth or biomass accumulation) are interpreted as markers of enhanced photosynthetic rate/efficiency.
Roberts et al. also describes culturing the photosynthetic microorganism in specific medium (column 13, line 42-49; column 19, line 37-39 and line 48-67; column 20, line 26-32) and selecting genetically modified cyanobacterial cells (column 22, line 62-65) with increased photosynthetic capacity as compared to wild type photosynthetic microorganism of the same species (column 23, line 2-5). Growth (i.e., increased or enhanced biomass accumulation) of the bacterial cells including the modified bacterial cells are measured by optical density (column 2, line 21-22), as recited in claim 10.
Roberts et al. describes various inducible promoters (column 13, line 1-5 and line 42-50) including the ones induced by osmotic stress (by increasing salinity of the culture) (column 13, line 48-49) and described salt tolerant strains capable of growth in water or media having a salinity (column 7, line 10-24), mostly made of Sodium Chloride (NaCl) (column 6, last line) (as recited in claim 4) in the range of 2.0% (i.e., 341 mM NaCl concentration) to 3.0% (column 7, line 27-29) (i.e., about 512 mM NaCl concentration, as recited in claim 3). Roberts et al. also describes the nirA promoter (as recited in claim 5) to control e xpression of different coding sequences (column 13, line 24, line 28; column 14, line 41-44, line 52-60).
It would have been obvious to an ordinarily skilled artisan to repress the mutS gene in a cyanobacteria using the NH4 salt (as a nitrogen source in the medium) inducible nirA promoter (repressed by NH4 salt) to enhance the rate of mutation on the genome of the cyanobacteria, as described by Emlyn-Jones et al., and culturing the modified bacterial cells in a medium comprising salt (NaCl) stress as observed in salt/saline water and brackish water (reads on to “an environmental stressor”) with a realistic goal to select the modified salt-tolerant cyanobacterial cells capable to grow and able to do photosynthesis, as described by Roberts et al. It is known in the art that bacterial cells try to overcome specific stress(es) by initiating stress-induced mutagenesis (SIM) or directed mutations (rather than relying solely on pre-existing random mutations) and selecting specific mutation(s) as the cells grow and divide in the medium under the specific stress(es) (Foster, P., abstract; page 1, para 1-2). Inactivation or repression of mutS gene under the control of inducible nirA promoter in the modified bacterial cells would only increase the rate of genetic mutation compared to unmodified wild type cells under specific stress including salt stress. The modified cells, which are able to grow in high salt containing medium, would have increased photosynthetic rate/efficiency/capacity, compared to unmodified, non-mutated cyanobacterium, and as cyanobacterial growth is heavily dependent on photosynthesis.
An ordinarily skilled artisan would have been motivated to repress the mutS gene in a cyanobacteria using the inducible nirA promoter to enhance the rate of mutation on the genome of the cyanobacteria and culturing the modified bacterial cells in a medium comprising salt stress with a realistic goal to select the modified salt-tolerant cyanobacterial cells capable to grow by having increased photosynthesis rate/efficiency/capacity as compared to unmodified wild type cells.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Roberts et al. in view of Emlyn-Jones et al., as applied to claims 1-8 and 10 above, and further in view of Liang et al. (Freshwater Cyanobacterium Synechococcus elongatus PCC 7942 Adapts to an Environment with Salt Stress via Ion-Induced Enzymatic Balance of Compatible Solutes, 2020, Applied and Environmental Microbiology, 86: e02904-19).
Claim 9 is drawn to the method of claim 1, wherein identifying the modified cells comprises a high throughput screening for cells displaying enhanced biomass accumulation as measured by optical density.
Roberts et al. in view of Emlyn-Jones et al. describes a method of identifying a genetic mutation capable of enhanced biomass accumulation by enhancing photosynthetic rate/efficiency/capacity in presence of salt stress (an environmental stressor), as discussed above.
However, Roberts et al. in view of Emlyn-Jones et al. does not describe any screening for sucrose production.
Liang et al. teaches cyanobacteria opted for the “salt-out” strategy to adopt in a high salt environment (page 2, para 1, line 12-13). Liang et al. describes that freshwater cyanobacterium Synechococcus elongatus PCC 7942 (Syn7942) exclusively accumulates sucrose as a compatible solute upon salt stress and is thus an ideal model microorganism for studying the metabolism of compatible solute dynamics (abstract). Cyanobacterial species with low salt tolerance (up to 0.7 M NaCl, equivalent to 4.1% salinity) produce sucrose (page 2, para 3, line 6-7). Liang et al. teaches that direct photosynthetic production of sucrose by cyanobacteria is also considered a potential strategy to provide abundant sugar feedstock for biorefineries (page 2, para 3, last 3 lines). Liang et al. also describes up-regulation of sucrose phosphate synthase (SPS) gene, a key enzyme catalyzing the rate limiting step of sucrose biosynthesis in cyanobacteria (page 4, para 3, line 1-2), by up to 4.3 times in presence of 300mM NaCl in the media (page 4, para 4, line 1-5). Liang et al. also describes an assay to determine sucrose in bacterial cells (page 11, para 4, line 1-6).
It would have been obvious to an ordinarily skilled artisan to modify the method described by Roberts et al. in view of Emlyn-Jones et al. to include the assay to determine sucrose in modified cyanobacterial cells, as described by Liang et al. with a realistic objective to get genetically modified cyanobacterial cells capable to grow under at least 300mM NaCl salt stress and able to produce sucrose. The term “high throughput” is not defined in the specification.
Conclusion
No claim is allowed.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAY CHATTERJEE whose telephone number is (703)756-1329. The examiner can normally be reached (Mon - Fri) 8.30 am to 5.30 pm..
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/Jay Chatterjee/Examiner, Art Unit 1662
/BRATISLAV STANKOVIC/Supervisory Patent Examiner, Art Units 1661 & 1662