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 .
DETAILED ACTION
Claims 1-30 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-10, and the species of compound 3, M3, and a gaseous mixture comprising CO2 and H2 in the reply filed on 3/3/2026 is acknowledged. The traversal is on the ground that there is no serious search burden to examine all the claims. This is not found persuasive because the restriction is a 371 lack of unity restriction and search burden is not a requirement in a 371 of lack of unity restriction. Furthermore, examination of the additional groups, especially Group III, which is drawn to a chemical compound, would require extensive search of the chemical arts. In contrast, search and examination of Group I, which is drawn to a genetically modified microorganism, does not require searching the chemical arts.
The requirement is still deemed proper and is therefore made FINAL.
Claims 11-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 3/3/2026.
Claims 1-10 are examined herein.
Claim Rejections - 35 USC § 112
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 4-7 and 9 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.
Claims 4 and 6-7 are indefinite because the claims recite a % sequence identity without reference to any sequence. Note that a gene name (e.g. phaC) is not a sequence. In addition, it is unclear whether the sequence identity threshold is a nucleotide sequence identity or amino acid sequence identity.
Claim 4 is further indefinite because Pseudomonadaceae is a taxonomic family, not a genus. Thus, it is unclear whether the claim scope is the Pseudomonas genus of the Pseudomonadaceae family of bacteria.
Claim 5 is rejected for depending from a rejected base claim without rectifying the source of indefiniteness discussed above.
Claim 9 recites “wherein the carbon source is selected from the group
consisting of: a gaseous mixture comprising CO2 and H2, formic acid, acetic acid, fructose, sucrose, or salts thereof.” There are at least two different reasonable interpretations of the claim, rendering the claim indefinite. In one interpretation, the microorganism is capable of producing a PHA polymer comprising a carbon atom metabolized from CO2. In a second interpretation, the microorganism is capable of producing a PHA polymer under a gaseous mixture comprising CO2 and H2 and the PHA polymer also comprises a carbon atom metabolized from CO2. Thus, the ambiguity lies in the fact that CO2 is a carbon source but H2 is not, leaving the claim subject to multiple interpretations with respect to the significance of the H2 in the gaseous mixture.
In addition, claim 9 recites “selected from the group consisting of a gaseous mixture comprising CO2 and H2, formic acid, acetic acid, fructose, sucrose, or
salts thereof,” which is not a closed group of alternatives. Applicant may consider replacing the conjunction “or” in the list of alternatives with “and” to obviate this aspect of the rejection.
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, 4, and 6-7 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 4 recites a genus of variants of phaC gene with at least 80% sequence identity to a PHA synthase (phaC) gene from a bacterium of the Pseudomonadaceae genus.
Claim 6 recites a genus of variants of isocaprenoyl-CoA:2-hydroxyisocaproate CoA-transferase (hadA) gene with at least 80% sequence identity to a gene from Clostridium difficile.
Claim 7 recites a propionate CoA-transferase (pct) gene that has at least 80% sequence identity to a gene from Clostridium propionicum.
Claims 4 and 6-7 are interpreted as requiring at least 80% amino acid sequence identity to the translated phaC, pct, or hadA genes.
The specification discloses a single UniProt sequence for each gene: Q9L3F7 _CLOPR (pct), Q188l3_PEP06 (hadA) and B9WOT0_9PSEO (phaC): see [0078] of the specification. The specification also discloses a limited number of mutations in each gene: V193A for pct540 and El300, S325T, S477G, and Q481K for phaC1437 ([0078]). Thus, a limited number of species of the genus of pct genes and phaC genes is disclosed and no variants of hadA are disclosed. The majority of the phaC sequences are roughly 560 amino acids long (see SEQ ID NO: 1-13). Thus, at least 80% identity corresponds to as many as 112 amino acid substitutions.
Fig. 5A-5M are sequences of additional phaC genes and Fig. 6A-6E illustrate the alignment of the amino acid sequences of PHA synthase, Fig. 7A-7G show amino acid sequences of hydroxyl-CoA transferases (pct). However, it is unclear whether any of the other sequences have been functionally characterized or whether they are merely assigned function by sequence homology. For example, UniProt G3XCV5_PSEAE, corresponding to Fig. 5D, is a predicted protein (see G3XCV5_PSEAE website, “protein”). Likewise, PHAC1_ECTOL is a protein inferred from homology (see the PHAC1_ECTOL website, “protein”). Thus, the additional sequences and the alignment are insufficient to establish a structure-function correlation because the function has not been demonstrated for each of these proteins.
Chek et al. (Applied Microbiology and Biotechnology (2019) 103:1131–1141) teaches that phaC from Chromobacterium sp. USM2 and Cupriavidus necator have been crystallized (Abstract). Table 1 of Chek highlights a limited number of species of PhaC variants from Cupriavidus necator, Aeromonas caviae, Chromobacterium sp.
USM2, and Pseudomonas sp. 61–3, with possible impacts of the mutations. There are seven point mutations made individually for Pseudomonas sp. 61–3 phaC and none of the point mutations are tested in combination.
With respect to the genus of pct variants, Selmer et al. (European journal of biochemistry 269.1 (2002): 372-380) teaches a glutamate 324 at the active site (Abstract). Fig. 3 illustrates a sequence alignment of the active site region of various propionate CoA-transferases. However, Selmer does not generate any variants of pct and the significance of the remaining amino acids outside of the active site region is unclear. For example, amino acids outside of the active site may be involved in stabilizing the three-dimensional structure of the protein and indirectly contribute to enzyme activity.
Kim et al. (The FEBS Journal 272.2 (2005): 550-561) teaches hadA and its activity (Fig. 2). Kim teaches that hadA is a highly specific class III 2-hydroxyisocaproate CoA-transferase using (R)-2-hydroxyisocaproyl-CoA and (E)-isocaprenoate as well as isocaproate as substrates (page 556, left column, Discussion, bottom paragraph). Kim also teaches the nucleotide sequences around the ribosome binding site and start codons of the hadA gene (Fig. 3). However, Kim does not teach the structure-function correlation of hadA nor does Kim teach any variants of hadA that retain enzymatic activity.
Based on the limited number of species disclosed in the specification and taught by the prior art, as well as a lack of structure-function correlation for the protein encoded by each gene, the person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genera of phaC variants, hadA variants, or pct variants.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-2, 4-5, 7, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park et al. (Metabolic engineering 20 (2013): 20-28).
Regarding claims 1-2, Park teaches genetically engineered Ralstonia eutropha (synonym for Cupriavidus necator) comprising the Clostridium propionicum pct540 gene and Pseudomonas sp. MBEL6–19 phaC1437 gene (Abstract). The genetically engineered R. eutropha is capable of producing a PHA polymer (Abstract).
Regarding claims 4-5, Park teaches heterologously expressing the Pseudomonas sp. MBEL6–19 phaC1437 gene in R. eutropha (Abstract). Thus, the gene is 100% identical to a PHA synthase (phaC) gene from a bacterium of the Pseudomonadaceae genus, as acknowledged in claim 5.
Regarding claim 7, Park teaches heterologously expressing the Clostridium propionicum pct540 gene in R. eutropha (Abstract), thus the gene has at least 80% sequence identity to a gene from Clostridium propionicum.
Regarding claim 10, the microorganism is necessarily capable of producing the claimed polymer because the structure of the microorganism is identical to the microorganism of the instant application (i.e. the microorganism contains the required enzymes). Note that the ability of the microorganism to produce the claimed polymer is a function of the structure of the microorganism only, since the culture conditions (substrates) are not part of the claimed microorganism.
Claim 3 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park et al. (Metabolic engineering 20 (2013): 20-28) as evidenced by Raberg et al. (PLoS One 9.5 (2014): e95907).
See discussion of Park above, which is incorporated into this rejection as well.
Regarding claim 3, Park teaches replacing phaC with Pseudomonas
sp.6-19 phaC1437 gene (Fig. 1 caption). There are only two phaC genes in R. eutropha H16, phaC1 and phaC2, and only phaC1 is transcribed in H16 as evidenced by Raberg (page 4, left column, Results, Sequence analysis of the phaCAB operon of the PHB negative mutant R. eutropha PHB-4, paragraph 1). Therefore, Park’s genetically engineered R. eutropha is a ΔphaC1 mutant of Cupriavidus necator because the original R. eutropha phaC1 has been replaced.
Claims 1, 4-7, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al. (Nature communications 9.1 (2018): 79).
Regarding claims 1, 4-5, and 7, Yang teaches a genetically engineered E. coli comprising phaC from the Pseudomonas sp. MBEL 6–19 and C. propionicum pct gene (page 7, right column, Methods, Plasmids and construction of bacterial strains, paragraph 2), so the E. coli comprises a phaC gene with 100% identity to a phaC from Pseudomonas sp. MBEL 6–19 and a pct gene with 100% identity to a C. propionicum pct gene. The genetically modified E. coli is capable of producing PHA polymers (page 2, right column, bottom paragraph).
Regarding claim 6, Yang teaches a genetically engineered E. coli comprising Clostridium difficile isocaprenoyl-CoA:2-hydroxyisocaproate CoA-transferase (hadA) and evolved polyhydroxyalkanoate (PHA) synthase (phaC) genes (Abstract and Fig. 1), so the E. coli comprises a hadA gene with 100% identity to a hadA from Clostridium difficile. The genetically engineered E. coli is capable of producing PHAs (Abstract and Introduction, left column, paragraph 1).
Regarding claim 10, Yang teaches that the genetically engineered E. coli is capable of producing Poly(3HB-co-PhLA) (see Fig. 3b), which is an embodiment of the compound of formula (I). Poly(3HB-co-PhLA is the embodiment of claim 1 in which n is N1 and m is M1 (see specification [061] and [063]-[0064]), corresponding to X1 is absent, X2 is alkylene, X3 is absent, and X4 is a substituted alkylene (see [0061] and [0064] of the specification). Yang teaches that the genetically engineered E. coli comprising hadA and phaC1437 is able to produce poly(52.1 mol% 3HB-co-47.9 mol% D-phenyllactate), so n is greater than zero and n and m sum to 100 mol% (page 5, right column, top paragraph).
Claims 8-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park et al. (Metabolic engineering 20 (2013): 20-28) as evidenced by Shimizu et al. (BMC microbiology 13.1 (2013): 169).
See discussion of Park above, which is incorporated into this rejection as well.
Regarding claims 8-9, R. eutropha is a chemoautotroph that is capable of incorporating CO2 into PHAs even when grown in heterotrophic conditions as evidenced by Shimizu (Abstract Results). Thus, the R. eutropha is necessarily capable of converting the carbon from CO2 into the PHA polymer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
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