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 .
Claims 1-21 have been presented for examination on the merits.
NOTE: In claim 6, line 2there is typographical error. The claim recites “encoding a a mutant…”.
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 1-21 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 1 and 11 are indefinite for reciting a concentration range of between about 1 and about 40% w/v without indicating what the basis for the said percentages is. That is, it is not recited if the said percentages are based on the solid medium, the parental strain or else.
Claims 2 and 13 are indefinite for reciting a concentration range of between about 5 and about 20% w/v without indicating what the basis for the said percentages is. That is, it is not recited if the said percentages are based on the solid medium, the parental strain or else. Further, if the base is the solid medium, it is not clear why the unit is w/v (volume).
Claim 4 recites the limitation "the solid agar medium" in the method of claim 1. There is insufficient antecedent basis for this limitation in the claim. Method of claim 1 does not support an agar medium.
Remaining claims are rejected for depending on claims 1 and 11.
Applicant’s claim 1 is directed to a method of identifying a Paenibacillus sp. mutant derivative strain with decreased viscosity in a liquid culture compared to a Paenibacillus sp. parental strain, the method comprising: mutagenizing the Paenibacillus sp. parental strain to produce mutant isolates; culturing the mutant isolates and the Paenibacillus sp. parental strain on a solid medium comprising a sugar at a concentration of between about 1% (w/v) and about 40% (w/v), wherein the Paenibacillus sp. parental strain has a mucoid morphology on the solid medium; and visually screening the mutant isolates on the solid medium to identify a Paenibacillus sp. mutant derivative strain with a non-mucoid morphology indicative of decreased viscosity in a liquid culture.
Claim 11 is directed to a method of generating the said Paenibacillus sp. mutant derivative strain.
Claims 20-21 are drawn to a fermentation product comprising Paenibacillus sp. mutant derivative strain identified with the method according to claim 1.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 and 18 of U.S. Patent No. 12,173,278.
An obviousness-type double patenting rejection is appropriate because while the conflicting claims are not identical, the examined claims are not patentably distinct from the reference claims because the examined claims would have been obvious over the reference claims.
The examined claims are drawn to a method of identifying a Paenibacillus sp. mutant derivative strain with decreased viscosity in a liquid culture, a method of generating the said strain and a fermentation product comprising the said strain. Examined claim 6 is drawn to the method of claim 1, further comprising sequencing deg U and/or degS in the Paenibacillus sp. mutant derivative strain to identify a sequence encoding a mutant DegU lacking a functional receiver domain or a functional DNA binding domain and/or a mutant DegS lacking a functional single binding domain or a functional ATPase domain.
The reference claims are drawn to a composition comprising a biologically pure culture of a fusaricidin-producing Paenibacillus sp. strain comprising a mutant DegU lacking a functional receiver domain or a functional DNA binding domain and/or a mutant DegS lacking a functional single binding domain or a functional ATPase domain, wherein the mutant DegU and/or the mutant DegS result in a liquid culture of the Paenibacillus sp. strain with decreased viscosity compared to a liquid culture of a Paenibacillus sp. strain comprising a wild-type DegU and a wild-type DegS.
The difference is that the examined claims are drawn to a method of identifying or a method of generating a Paenibacillus sp. mutant derivative strain with decreased viscosity and a composition comprising the said strain, while the reference claims are drawn to a composition comprising a Paenibacillus sp. strain.
Regarding the claims directed to a method of identifying or a method of generating a Paenibacillus sp. mutant derivative strain with decreased viscosity, the claims would have been obvious over the reference claims because the same composition is provided and claimed by the reference claims as identified or generated by the examined claims. That is, the claimed methods would have led one of ordinary skill in the art to the compositions in reference claims.
Regarding claims 2021, both sets of the claims are directed to a composition comprising a Paenibacillus sp. mutant derivative strain with decreased viscosity. Thus, the examined claims are the same and as such are anticipated by the reference claims.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Beau et al (US 20160278388),
Beau et al teach a composition comprising a biologically pure culture of a fungicidal Paenibacillus sp. strain comprising a variant fusaricidin synthetase lacking a functional adenylation domain in the third module, and methods of treating a plant to control a plant disease with the disclosed compositions (See abstract).
Disclosed is a composition comprising a biologically pure culture of a fungicidal Paenibacillus sp. strain comprising a variant fusaricidin synthetase lacking a functional adenylation domain in the third module (FusA-A3), wherein the lack of a functional FusA-A3 inhibits synthesis of fusaricidins with a tyrosine or a phenylalanine at amino acid residue (3) compared to synthesis of fusaricidins by a Paenibacillus sp. strain comprising a wild-type fusaricidin synthetase. In certain aspects, the variant fusaricidin synthetase comprises a deletion in FusA-A3 of at least one or ten amino acid residues that determine substrate specificity. The amino acid residues are selected from the group consisting of Asp235, Ala236, Ser239, Thr278, Leu299, Ala301, Ala/Gly322, Val330, Cys331, Lys517, and combinations thereof (See [0011]). The amino acid residues are located at positions 3203, 3204, 3207, 3246, 3267, 3269, 3290, 3298, 3299, and/or 3486 of SEQ ID NO: 11. The variant fusaricidin synthetase comprises a deletion in FusA-A3 of Asp235, Ala236, Ser239, Thr278, Leu299, Ala301, Ala/Gly322, Val330, and Cys331. The variant fusaricidin synthetase comprises SEQ ID NO: 10 (See [0012]).
Beau et al teach a method of treating a plant to control a disease, wherein the method comprises applying an effective amount of the said composition to the plant, to a part of the plant and/or to a locus of the plant. The said composition is a fermentation product of the Paenibacillus sp. strain NRRL B-50972, Paenibacillus sp. strain NRRL B-67129, or a fungicidal mutant strain thereof. The method comprises applying the composition to foliar plant parts. In yet other aspects, the composition is applied at about 1×1010 to about 1×1012 colony forming units (CFU) of Paenibacillus sp. strain NRRL B-50972, Paenibacillus sp. strain NRRL B-67129, or a fungicidal mutant strain thereof per hectare (See [0041]).
Beau et al teach that the plant disease is caused by a fungus, including powdery mildew or downy mildew, wheat leaf rust, leaf rust of barley, etc. The said fungus is selected from the group consisting of Alternaria alternata, Alternaria solani, Botrytis cinerea, Colletotrichum lagenarium, etc, (See [0042]-[0043]).
Additionally, it is disclosed that the plant disease may be caused by bacteria including Xanthomonas campestris, Pseudomonas syringae, and Erwinia carotovora (See [0044]-[0045]).
Beau et al teach that a sequence alignment of Spo0A orthologs from endospore-forming bacteria indicating the nucleotide change in the Paenibacillus sp. strain NRRL B-67129 coding sequence results in a single amino acid substitution in a conserved region. The aligned Spo0A ortholog sequences are: Paenibacillus terrae Spo0A (SEQ ID NO: 14), Paenibacillus sp. strain NRRL B-50972 Spo0A (SEQ ID NO: 15), Paenibacillus sp. strain NRRL B-67129 Spo0A (SEQ ID NO: 16), Paenibacillus polymyxa Spo0A (SEQ ID NO: 17), Bacillus subtilis Spo0A (SEQ ID NO: 18), Bacillus cereus Spo0A (SEQ ID NO: 19), and Clostridium pasteurianum Spo0A (SEQ ID NO: 20) (See [0061]).
Beau et al also disclose the Paenibacillus sp. strain NRRL B-50972 or a fungicidal mutant (strain) derived therefrom. It has been found that the Paenibacillus sp. strain NRRL B-50972 has a broad spectrum of activity against phytopathogens (See [0063]).
Regarding the truncation of SEQ IDs, it is disclosed that “FIG. 13 presents a multiple sequence alignment of a segment of the FusA fusaricidin synthetase expressed by the following Paenibacillus strains: Paenibacillus peoriae A (SEQ ID NO: 1), Paenibacillus polymyxa A (SEQ ID NO: 2); Paenibacillus polymyxa PKB1 (GenBank ABQ96384.2; SEQ ID NO: 3); Paenibacillus polymyxa E681 (GenBank ADM67985.1; SEQ ID NO: 4); Paenibacillus polymyxa B (SEQ ID NO: 5); Paenibacillus polymyxa SQR (GenBank AHM63812.1; SEQ ID NO: 6); Paenibacillus polymyxa C (SEQ ID NO: 7); Paenibacillus polymyxa M1 (GenBank CCC83015.1; SEQ ID NO: 8); Paenibacillus polymyxa SC2 (GenBank ACA09733.2; SEQ ID NO: 9); Paenibacillus sp. strain NRRL B-50972 (SEQ ID NO: 10); and Paenibacillus sp. strain A (SEQ ID NO: 11). The amino acid residues that determine substrate specificity are identified with a black outline (see also Table 1). These amino acid residues are located at positions 3203, 3204, 3207, 3246, 3267, 3269, 3290, 3298, 3299, and 3486 of SEQ ID NOs: 1-5 and 11 and at positions 3204, 3205, 3208, 3247, 3268, 3270, 3291, 3299, 3300, and 3487 of SEQ ID NOs: 6-9” (See [0058]).
Further disclosed is that the Paenibacillus sp. strain comprises a DNA sequence exhibiting at least 75% sequence identity, at least 96% sequence identity, at least 97% sequence identity, at least 98% sequence identity, or at least 99% sequence identity to SEQ ID NO: 10 (See [0068]).
It is disclosed that the mutant or a fermentation product thereof controls (as an identifying functional characteristic) fungi, Oomycetes and/or bacteria at least as well as the parent Paenibacillus sp. strain NRRL B-50972. Such mutants may be genetic variants having a genomic sequence that has greater than about 85%, greater than about 90%, or greater than about 99% sequence identity to Paenibacillus sp. strain NRRL B-50972. The fungicidal Paenibacillus sp. strain comprises a DNA sequence exhibiting at least 90% sequence identity to SEQ ID NO: 10 (See [0066] and claim 5).
Dahl et al (The phosphorylation state of the DegU response regulator acts as a molecular switch allowing either degradative enzyme synthesis or expression of genetic competence in Bacillus subtilis),
Dahl et al teach that two classes of mutations were identified in the DegS and DegU regulatory genes of Bacillus subtitis, leading either to deficiency of degradative enzyme synthesis (degS or degU mutations) or to a pleiotropic phenotype which includes overproduction of degradative enzymes and the loss of genetic competence (degB(Hy) or degU(Hy) mutations) (See Abstract).
In the experiment performed it is disclosed that one fragment was generated by polymerase chain reaction using chromosomal DNA of strain QB136 (carrying mutation degU32) as a template, in which a SacI site was introduced 72 bp upstream from the DegU start codon. The DNA sequence of the polymerase chain reaction fragments cloned in plasmid pMD409, pMD410, or pMD418 was verified, showing that degS220, degS200, or degU32 was the only mutation present (See page 14510, 2nd col).
Dahl et al stet that “the purification and study of the properties of the corresponding mutationally altered proteins, DegS220, DegU146, and DegU32 were described. The purified DegU146 protein, containing a D56N amino acid substitution modifying the putative phosphoryl acceptor site was shown to no longer be phosphorylatable by the DegS protein kinase. This result is comparable to the data showed that the CheY D57N, SpoOA D56N, and VirG D52N response regulators modified at equivalent positions are no longer phosphorylated by their cognate protein kinases. The DegU146 protein has lost the capacity to stimulate degradative enzyme synthesis but still allows expression of late competence genes such as comG. This is in sharp contrast with mutants in which the degU gene is disrupted, leading to absence of competence” (See Page 14513, 2nd col).
It is also disclosed that “Mutations in DegS leading to the inability to phosphorylate the DegU response regulator have a phenotype which is comparable to that of the degUl4~ mutant. An example of such a mutant is DegS42, encoding a modified protein with an E300K amino acid substitution. Tanaka et al. (24) recently showed that the DegS42 protein is deficient for both autophosphorylation and phosphorylation of the DegU response regulator. The DegS220 protein described in this paper is also deficient in DegU phosphorylation activity. However, an interesting difference between the DegS42 and DegS220 proteins is that DegS220 retains autophosphorylation activity. The reduced DegU phosphorylation activity is presumably the reason that the degS220 mutation was initially identified as an extragenic suppressor of the hyperproduction phenotype of the degU32 mutant. Indeed, the DegU32 protein remained unphosphorylated when incubated with the DegS220 kinase in the presence of ATP (results not shown)” (See page 14513, 2nd col).
Cairns et al (An alternate route to phosphorylating DegU of Bacillus subtilis using acetyl phosphate),
Cairns et al teach in Bacillus subtilis, the DegS-DegU two-component system controls transcription of target genes in a manner dependent on the level of the phosphorylated response regulator, DegU. Previous work has tentatively indicated that DegU, and DegU H12L, a DegU variant which displays enhanced stability of the phosphoryl moiety, can be phosphorylated in the absence of the kinase, DegS (See abstract).
The data presented here reveal that DegU H12L requires aspartic acid 56 (D56), the identified DegU phosphorylation site, for its activity. By indirectly measuring the level of DegU ~ P in the cell by assessment of several well recognized DegU regulated processes it was shown that DegU H12L retains its activity in the absence of DegS, and that mutation of D56 produced an inactive protein. Further experiments designed to raise the level of acetyl phosphate within the cell suggest that DegU can be phosphorylated by acetyl phosphate in the absence of DegS. Additionally, the phenotypic and biochemical experiments presented indicate that DegU H12L can reliably mimic high levels of phosphorylated DegU. The ability of acetyl phosphate to modify DegU, and indeed DegU H12L, reveal an additional layer of regulation for DegU phosphorylation that will be relevant when the level of DegS is low or in the absence of DegS. Given the number of processes that DegU can activate or inhibit, extensive regulation at a number of levels is required to ensure that the system is not inappropriately stimulated. DegS has both kinase and phosphatase activity and our findings demonstrate that the phosphatase activity of DegS is essential to control the level of DegU phosphate. Overall, we contribute to our understanding of how the intricate signalling pathway DegS-DegU is regulated in B. subtilis (See abstract).
Cairns et al disclose that “understanding of the mechanisms behind the regulation of DegU ~ P controlled processes has been aided by the use of several point mutations in the coding regions of both DegS and DegU that have been harnessed to test the effects of (i) inhibiting the phosphorylation of DegU or (ii) promoting phosphorylation of DegU. For example, the DegU (D56N) (also known as degU146) allele encodes for the DegU D N protein variant where the aspartic acid phosphorylation site is mutated to asparagine 56. Additionally, other studies use the DegU (H12L) (also known as degUhy32) allele where histidine at position 12 is mutated to leucine (DegU H L). This variant of DegU exhibits a dephosphorylation rate that is seven times slower than that of phosphorylated wild-type 12 DegU and has therefore been used to test the effects of increasing levels of DegU ~ P on multiple DegU controlled outputs. However, it is important to note that recent work has suggested that an inability of DegU H L to interact with the SwrA protein may explain its inhibitory effect on flagellar motility, rather than this being the result of high levels of DegU ~ P per se. The authors suggest that motility is retained when the levels of wild-type DegU ~ P are elevated using variants of DegS that lack dephosphorylation activity. Therefore, it was concluded that use of the DegU H L variant may not directly mimic high levels of DegU ~ P in the cell (See page 2).
Cairns et al state that they utilised strains where the 12 degU (H12L) coding region was integrated at a non-essential location on the chromosome of strains that carried either an insertion in the native degU gene or a deletion of both the degS and de gU coding regions. Production of the exopolymer γ-PGA was assessed by the presence or absence of a mucoid colony morphology after growth on LB agar. An increase in the level of DegU ~ P results in enhanced transcription of genes required for the synthesis and export of γ-PGA, culminating in the generation of a mucoid colony morphology. Induction of degU (H12L) expression with IPTG in the absence of the native copy of the degU gene resulted in a mucoid colony morphology. Induction of degU (H12L) in a strain lacking the native copies of both degS and degU also produced a mucoid colony morphology. These data indicate that DegU H L is able to stimulate γ-PGA production regardless of whether DegS is present or not (See par. Bridging pages 5 and 6).
Claims 1-21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mina Haghighatian whose telephone number is (571)272-0615. The examiner can normally be reached M-F, 7-5 EST.
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/Mina Haghighatian/
Mina Haghighatian
Primary Examiner
Art Unit 1616
