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
Amended claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 (dated 12/18/2024) are pending and is now under consideration for examination.
Priority
Applicants’ claim for the benefit of priority under 35 U.S.C. 119(e). This application is a 371 of PCT/US2022/082294 filed on 12/22/2022, which claims the benefit of priority under 35 U.S.C. 119(e) to the US Provisional application 63/295,278 filed on 12/30/2021.
Information disclosure statement
The information disclosure statement (IDS) submitted on 09/19/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS statement is considered and initialed by the examiner.
Objections to Abstract/Specification
The Abstract of the disclosure is objected to because, Abstract should be on a separate sheet of paper. The abstract of the disclosure is objected to because the abstract is presented as part of the first page of a WO publication. The abstract should be presented as a single sheet apart from all other bibliographic material including the information included on the first page of a WO publication. If EFS is used to submit a replacement abstract, the appropriate abstract (ABST) document code should be used for the one-page document. Correction is required. See MPEP § 608.01 (b).
Objections to Claims
Claim 1 and claims 2-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 depending therefrom are objected to, due to the following informality: Claims 1-3, 10, 20, 22 and 28 recite abbreviations “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” in the claims; abbreviations unless otherwise obvious and/or commonly used in the art, should not be recited in the claims without at least once reciting the entire phrase for which the abbreviation is used. Examiner suggests expanding the abbreviation to recite the full form of what the abbreviation stands for; As written, the term appears to be generic to any microorganism and not limited to a particular species or specific strain of bacteria/E. coli. While the gene nomenclature used may be appropriate for specific strain of bacteria/E. coli, the use of this nomenclature for genes encoding proteins of identical function in other microorganism may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. For example, the ARO4 gene of Candida albicans encodes a DAHP synthase whereas the E. coli counterpart is the AroF gene. See Sousa et al. (Microbiology, 2002, Vol. 148: 1291-1303; reference not enclosed). As such, the use of gene terminology which is applicable to some microorganisms and not to others is confusing since the claims use this gene nomenclature with respect to any microorganism. For examination purposes, the term phrase “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” will be interpreted as “phosphotransferase system” involved in the tricarboxylic acid (TCA) cycle/carbon-nitrogen metabolism. If applicant wishes to retain the gene nomenclature used, it is suggested that the protein encoded by said gene or the structure be placed in parentheses next to the recited gene. Clarification and correction is required.
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 1 and claims 2-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 depending therefrom 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 pre-AIA the applicant regards as the invention.
Claims 1-3, 10, 20, 22 and 28 recite the phrase “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” in the claims; for the following reasons. As written, the term appears to be generic to any microorganism and not limited to a particular species or specific strain of bacteria/E. coli. While the gene nomenclature used may be appropriate for specific strain of bacteria/E. coli, the use of this nomenclature for genes encoding proteins of identical function in other microorganism may not be accurate. As known in the art, genes encoding proteins of identical function in two different organisms may use different designations. For example, the ARO4 gene of Candida albicans encodes a DAHP synthase whereas the E. coli counterpart is the AroF gene. See Sousa et al. (Microbiology, 2002, Vol. 148: 1291-1303; reference not enclosed). As such, the use of gene terminology which is applicable to some microorganisms and not to others is confusing since the claims use this gene nomenclature with respect to any microorganism. For examination purposes, the term phrase “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” will be interpreted as “phosphotransferase system” involved in the tricarboxylic acid (TCA) cycle/carbon-nitrogen metabolism. If applicant wishes to retain the gene nomenclature used, it is suggested that the protein encoded by said gene or the structure be placed in parentheses next to the recited gene. Clarification and correction is required.
Claim Rejections: 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(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 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. For a broad generic claim, the specification must provide adequate written description to identify the genus of the claim.
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus.”). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the biomolecule, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule.”
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice . . ., reduction to drawings . . ., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” MPEP 2163.
Furthermore, a “‘representative number of species’ means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure ‘indicates that the patentee has invented species sufficient to constitute the gen[us].’ See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (‘[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.’). ‘A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.’ In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).” MPEP 2163.
The claims recite the following broadly claimed genera: Claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 recite genera of enzymes in the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
As described, claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 encompasses any enzyme with no structural limitations, including wild-type enzymes and enzymes heavily mutated from known wild-type enzymes, with the sole functional proviso being that “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage”. The structural elements recited in claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 are not sufficient structure and having no specific structural elements of any kind and having associated function, genera of enzymes in the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation). There in inherent unpredictability in regards to which amino acid sequences may have the associated function and possibly fall within the claims and those amino acid sequences that do not have the associated function/activity. As such, claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 recite genera of biomolecules described only by a functional characteristic i.e. PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” without any disclosed correlation between function and structure of the biomolecule, it is not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed biomolecule. Due to the literal unlimited structural scope of the claims, it is not possible to provide for a representative number of species that adequately described are representative of the entire genus having no fixed structural outer boundaries. Further, such genera of altered enzymes as recited lack “a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” And without any required structure that is sufficient for providing the recited enzyme activity, the recited genera lack disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. The claims lack adequate written description in the as-filed specification for the reasons stated.
No information, beyond the characterization of a single species of mutagenized E.coli strain comprising a mutation in ptsP gene of phosphotransferase system/operon, and expressing a heterologous protein of interest/antibody fragment expression construct Fab 1; see ¶ [0039-0062], Examples 1-9, pages 15-22 of the specification, has been provided by the applicants’, which would indicate that they had possession of the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation).
The claimed genera of enzymes in the claimed genera of prokaryotic organisms, encoded polypeptides and encoding polynucleotides is an extremely large structurally and functionally variable genus. While the argument can be made that the recited genus of polypeptides and the encoding polynucleotides is adequately described by the disclosure of the structures of the amino acid sequences of SEQ ID NO: 1 encoding the phosphotransferase (PTS) system of E. coli having the associated activity/function, since one could use structural homology to isolate those encoding polypeptides recited in the claims. The art also teaches, even highly structurally homologous polypeptides do not necessarily share the same function and conversely functionally similar molecules do not necessarily have similar structures. For example proteins having similar structure have different activities; Witkowski et al., (Biochemistry 38:11643-11650, 1999) teaches that one conservative amino acid substitution transforms a b-ketoacyl synthase into a malonyl decarboxylase and completely eliminates b-ketoacyl synthase activity. Similarly, Wishart et al., (J. Biol. Chem., 1995, Vol. 270(10): 26782-26785) teach that a single mutation converts a novel phosphotyrosine binding domain into a dual-specificity phosphatase. The art also teaches that functionally similar molecules have different structures; Kisselev L., (Structure, 2002, Vol. 10: 8-9) teach that polypeptide release factors in prokaryotes and eukaryotes have same function but different structures.
Specifically regarding phosphotransferase (PTS) system in prokaryotes, the following references disclose significant differences in the PTS operon of E.coli and other prokaryotes; see in gram negative bacteria there are two common PTS variants, see Abstract and Introduction, col.1-2, page10234 in (i) Sánchez-Cañizares et al., (PNAS., 2020, Vol. 17(19): 10234-10245); and (ii) structural differences in E.coli PTS system as compared to other prokaryotes; see Abstract and entire document of Sharma et al., (J. Bacteriol., 2016, Vol. 198(13): 1868-1882). Examiner takes the position that a skilled artisan requires and be provided with specific structures and specific cellular context to practice the invention.
Hence, the recited genera of polypeptides and the encoding polynucleotides are interpreted to have widely variable structures, since minor changes may result in changes affecting function and no additional information correlating structure with function has been provided. As the claimed genera of polypeptides having widely variable structure and associated function, since minor changes in structure may result in changes affecting function and no additional information (species/variant/mutant) correlating structure with function has been provided. Furthermore, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features” (See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895).
Therefore, one skilled in the art cannot reasonably conclude that applicant had possession of the claimed invention at the time the instant application was filed. Applicants are referred to the revised guidelines concerning compliance with the written description requirement of under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, published in the Official Gazette and also available at www.uspto.gov.
Enablement
Claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification is enabling for the characterization of a single species of mutagenized E.coli strain comprising a mutation in ptsP gene of phosphotransferase system/operon, and expressing a heterologous protein of interest/antibody fragment expression construct Fab 1; see ¶ [0039-0062], Examples 1-9, pages 15-22 of the specification. However, specification does not reasonably provide enablement for claimed genera of enzymes in the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claim(s).
Claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 are so broad as to encompass: a claimed genera of enzymes in the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation). The scope of the claim is not commensurate with the enablement provided by the disclosure with regard to the extremely large number of encoded polypeptides broadly encompassed by the claims in a genera of prokaryotes. Since the amino acid sequence of a protein encoded by a polynucleotide determines its structural and functional properties, predictability of which changes can be tolerated in a protein's amino acid sequence and obtain the desired activity requires a knowledge of and guidance with regard to which amino acids in the protein's sequence and the respective codons in its polynucleotide, if any, are tolerant of modification and which are conserved (i.e., expectedly intolerant to modification), and detailed knowledge of the ways in which the encoded proteins' structure relates to its function. However, in this case the disclosure is limited to the characterization of a single species of mutagenized E.coli strain comprising a mutation in ptsP gene of phosphotransferase system/operon, and expressing a heterologous protein of interest/antibody fragment expression construct Fab 1; see ¶ [0039-0062], Examples 1-9, pages 15-22 of the specification. It would require undue experimentation of the skilled artisan to make and use the claimed polypeptides/enzymes in a genera of prokaryotes. The specification but provides no guidance with regard to the making of variants and mutants or with regard to other uses. In view of the great breadth of the claims, amount of experimentation required to make and use the claimed polypeptides, the lack of guidance, working examples, and unpredictability of the art in predicting function from a polypeptide primary structure, the claimed invention would require undue experimentation. As such, the specification fails to teach one of ordinary skill how to use the full scope of the polypeptides/enzymes encompassed by the claims in a genera of prokaryotes. However, claims reading on significant numbers of inoperative embodiments would render claims non-enabled when the specification does not clearly identify the operative embodiments and undue experimentation is involved in determining those that are operative.” Atlas Powder Co. v. E.I. duPont de Nemours & Co., 750 F.2d 1569, 1577, 224 USPQ 409, 414 (Fed. Cir. 1984); In re Cook, 439 F.2d 730, 735, 169 USPQ 298, 302 (CCPA 1971); MPEP 2164.08(b). Here, the claims read on a significant number of inoperative embodiments.
The specification does not support the broad scope of the claims which encompass: claimed genera of enzymes in the claimed genera of prokaryotic organisms i.e., “PtsP pathway; PTS operon; ptsl, ptsO, ptsN, ptsP, or manX gene; AscpA-argK-scpBC; AaraEp::J23104; mutation in the araBAD operon; and ParaC in operable linkage to araC, PprpR in operable linkage to prpR, and ParaBAD in operable linkage” having no specific structural elements including variants, mutants and homologs of undefined and unlimited structures having the associated biochemical properties/function (also see claims objections and 35 U.S.C. 112(b) for claims interpretation), because the specification does not establish: (A) a rational and predictable scheme for modifying specific amino acid residues in any enzyme having no specific structural elements and an expectation of obtaining the desired biological/biochemical function in a genera of prokaryotes; (B) defined core regions/motifs involved in the desired catalytic activity of encoded polypeptide; (C) the tertiary structure of the molecule and folding patterns that are essential for the desired activity and tolerance to modifications; and (D) the specification provides insufficient guidance as to which of the essentially infinite possible choices is likely to be successful.
While as discussed above, the specification provides guidance with regard to the characterization specific structures and specific mutants, specific amino acid sequences, see paragraphs [0069-0073], Table 2-4, pages 17-23 of the specification, however, the scope of claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 is so broad and the lack of guidance either in the specification or in the prior art, the claims remains not commensurate in scope with the enabled invention and therefore for the rejected claims, this would clearly constitute undue experimentation. While enablement is not precluded by the necessity for routine screening, if a large amount of screening is required, the specification must provide a reasonable amount of guidance with respect to the direction in which the experimentation should proceed. Such guidance has not been provided in the instant specification or in the prior art.
Thus, applicants’ have not provided sufficient guidance to enable one of ordinary skill in the art to make and use the claimed invention in a manner reasonably correlated with the scope of the claims broadly including polypeptides with an enormous number of modifications. The scope of the claim must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1975)). Without sufficient guidance, determination of polypeptides/enzymes having the desired biological characteristics in a genera of prokaryotes is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988).
Although the claims are examined in the light of the specification, specification cannot be read into the claims, i.e., the limitations of the specification cannot be read into the claims (see MPEP 2111 R-5).
Claim Rejections: 35 USC § 102 (AIA )
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
I. Claims 1-3, 6-7, 10, 24 and 33 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Pfluger et al., (J. Bacteriol., 2008, Vol. 190 (9): 3374-3380, in IDS) when given the broadest reasonable interpretation.
Regarding claims 1-3, 6-7, 10, 24 and 33, Pfluger et al., (J. Bacteriol., 2008, Vol. 190 (9): 3374-3380, in IDS) disclose inactivation of the ptsP gene in Pseudomonas putida by chromosomal insertion of a kanamycin resistance cassette (Abstract; Table 1, page 3375; and entire document). A reporter plasmid pVLTptsNtag was transferred to the ptsP strain (page 3376, right column and Fig. 1). Therefore, the reference of Pfluger et al., (J. Bacteriol., 2008, Vol. 190 (9): 3374-3380, in IDS) is deemed to anticipate claims 1-3, 6-7, 10, 24 and 33 as written and when given the broadest reasonable interpretation and rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
II. Claims 1-3, 6-7, 10, 24 and 33 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sánchez-Cañizares et al., (PNAS., 2020, Vol. 117 (19): 10234-10245) when given the broadest reasonable interpretation.
Regarding claims 1-3, 6-7, 10, 24 and 33, Sánchez-Cañizares et al., (PNAS., 2020, Vol. 117 (19): 10234-10245) disclose inactivation of the ptsP gene in Rhizobium leguminosarum strain by chromosomal insertion of a kanamycin resistance cassette by conjugations and transductions with bacteriophage RL38 (Abstract; Methods, col. 1, page 10243; Fig. 1-4; and entire document). A reporter plasmid comprising inducible promoter expressing reporter b-galactosidase and luxCDABE cassette was transferred to the ptsP strain (Methods, col. 1, page 10243; Fig. 1-4). Therefore, the reference of Sánchez-Cañizares et al., (PNAS., 2020, Vol. 117 (19): 10234-10245) is deemed to anticipate claims 1-3, 6-7, 10, 24 and 33 as written and when given the broadest reasonable interpretation and rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
III. Claims 1-3, 6-7, 10-13, 24-25 and 33 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Sharma et al., (J. Bacteriol., 2016, Vol. 198 (13): 1868-1882) and as evidenced by Blattner et al., (Science, 1997, Vol. 277: 1453-1462) and Touchon et al., (PLoS Genet., 2009, Vol. 5: E1000344-E1000344).
Regarding claims 1-3, 6-7, 10-13, 24-25 and 33, Sharma et al., (J. Bacteriol., 2016, Vol. 198 (13): 1868-1882) disclose inactivation of the ptsN gene of the phosphotransferase (PTS) system in an E. coli strain by chromosomal insertion of a kanamycin resistance cassette by conjugations and transductions with bacteriophage RL38 (Abstract; Introduction, col. 1, page 1869; Materials and Methods; TABLE 1, col. 1-2, page 1869; and entire document). A reporter plasmid comprising inducible promoter expressing reporter b-galactosidase cassette was transferred to the ptsP strain and expressing a heterologous Ycgo gene (Methods, col. 1, page 10243; Fig. 1-4); regarding claims 11-13 and as evidenced by Blattner et al., (Science, 1997, Vol. 277: 1453-1462) and Touchon et al., (PLoS Genet., 2009, Vol. 5: E1000344-E1000344) disclosing the structure of ptsP operon (SEQ ID NO: 1) including mutations in ptsP operon (substitutions in the amino acid sequence of SEQ ID NO: 1). Therefore, the reference of Sharma et al., (J. Bacteriol., 2016, Vol. 198 (13): 1868-1882) and as evidenced by Blattner et al., (Science, 1997, Vol. 277: 1453-1462) and Touchon et al., (PLoS Genet., 2009, Vol. 5: E1000344-E1000344) is deemed to anticipate claims 1-3, 6-7, 10-13, 24-25 and 33 as written and when given the broadest reasonable interpretation and rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
Since the Office does not have the facilities for examining and comparing applicants’ organism with the organism of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed organism and the organism of the prior art (i.e., that the organism of the prior art does not possess the same material structural and functional characteristics of the organism of the instant invention). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Claim Rejections: 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
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 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.
Claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 are rejected under 35 U.S.C. 103(a) as being unpatentable over by (i) Pfluger et al., (J. Bacteriol., 2008, Vol. 190 (9): 3374-3380, in IDS); (ii) Sánchez-Cañizares et al., (PNAS., 2020, Vol. 117 (19): 10234-10245); and (iii) Sharma et al., (J. Bacteriol., 2016, Vol. 198 (13): 1868-1882) and as evidenced by Blattner et al., (Science, 1997, Vol. 277: 1453-1462) and Touchon et al., (PLoS Genet., 2009, Vol. 5: E1000344-E1000344) as applied to claims 1-3, 6-7, 10-13, 24-25 and 33 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Masuda et al., (US 2011/0111458 A1) and Patterson et al., (WO 2020/069011 A1).
The disclosures of (i) Pfluger et al., (ii) Sánchez-Cañizares et al., and (iii) Sharma et al., as applied to claims 1-3, 6-7, 10-13, 24-25 and 33 is described above (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2). However, (i) Pfluger et al., (ii) Sánchez-Cañizares et al., and (iii) Sharma et al., are silent regarding wherein the prokaryotic organism comprises an intracellular environment that is more oxidizing than a wild-type prokaryotic organism of the same species… comprising ahpCA, trxB, gor, AscpA-argK-scpBC, and at least one inactivating mutation in the araBAD operon (as in claims 14-15 and 20); further comprising AaraEp::J23104 (as in claim 22); wherein the inducible promoter is ParaBAD…further comprising at least one chaperone coding region or gene (as in claims 26, 28 and 30); wherein the expressible coding region or gene encodes an antibody chain, an antibody fragment thereof, or a chimeric antigen receptor (as in claim 32).
Regarding claims 1-3, 6-7, 10-13, 24-25 and 33, Masuda et al., (US 2011/0111458 A1) also provide teaching, suggestion and motivation for deleting/mutating chromosomal DNA comprising PTS operon including the genes ptsl, ptsO, ptsN, ptsP, or manX gene in E. coli cellular context and the use of said mutated E. coli cellular context in producing useful chemicals and proteins of interest (see Abstract; ¶ [0014], [0018], [0306], [0325]; and entire document).
Regarding claims 14-15, 20, 22, 26, 28, 30 and 32 the following reference Patterson et al., (WO 2020/069011 A1), provide teaching, suggestion and motivation for the choice of wherein the prokaryotic organism comprises an intracellular environment that is more oxidizing than a wild-type prokaryotic organism of the same species… comprising ahpCA, trxB, gor, AscpA-argK-scpBC, and at least one inactivating mutation in the araBAD operon; further comprising AaraEp::J23104; wherein the inducible promoter is ParaBAD…further comprising at least one chaperone coding region or gene; wherein the expressible coding region or gene encodes an antibody chain, an antibody fragment thereof (see Abstract; claims and entire document); oxidizing cytoplasm (page 4, lines 5-23); inducible promoter is ParaBAD, co-expression of chaperones; and gene encodes an antibody chain, an antibody fragment thereof (page 10, lines 9-33 to page 11, lines 1-24; page 17, lines 24-34 to page 18, lines 1-11; page 19, lines 14-34 to page 20, lines 1-28; page 22, lines 5-34 to page 29, lines 1-21; Table 2, pages 34-35; page 35, lines 1-25 to page 36, lines 1-4; and entire document).
As such, disclosure of strategy and methods for “wherein the prokaryotic organism comprises an intracellular environment that is more oxidizing than a wild-type prokaryotic organism of the same species… comprising ahpCA, trxB, gor, AscpA-argK-scpBC, and at least one inactivating mutation in the araBAD operon; further comprising AaraEp::J23104; wherein the inducible promoter is ParaBAD…further comprising at least one chaperone coding region or gene; and wherein the expressible coding region or gene encodes an antibody chain, an antibody fragment thereof” as in claims 14-15, 20, 22, 26, 28, 30 and 32 of the instant invention, such as that of reference of Patterson et al., teaching the advantages of said modifications, clearly suggests to a skilled artisan to modify the teachings of (i) Pfluger et al., (ii) Sánchez-Cañizares et al., and (iii) Sharma et al. and incorporate the structural and functional elements of Masuda et al., and Patterson et al., in the claimed prokaryotic organism comprising a defective PtsP pathway and a heterologous expressible coding region or gene as claimed in the instant invention. One of ordinary skill in the art would have a reasonable expectation of success, since the prokaryotic organism comprising a defective PtsP pathway and a heterologous expressible coding region or gene are well known in the art.
Therefore, claims 1-3, 6-7, 10-15, 20, 22, 24-26, 28, 30 and 32-33 are rejected under 35 U.S.C. 103(a) as being unpatentable over by (i) Pfluger et al., (J. Bacteriol., 2008, Vol. 190 (9): 3374-3380, in IDS); (ii) Sánchez-Cañizares et al., (PNAS., 2020, Vol. 117 (19): 10234-10245); and (iii) Sharma et al., (J. Bacteriol., 2016, Vol. 198 (13): 1868-1882) and as evidenced by Blattner et al., (Science, 1997, Vol. 277: 1453-1462) and Touchon et al., (PLoS Genet., 2009, Vol. 5: E1000344-E1000344) as applied to claims 1-3, 6-7, 10-13, 24-25 and 33 (see 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) rejection above) and further in view of Masuda et al., (US 2011/0111458 A1) and Patterson et al., (WO 2020/069011 A1).
Allowable Subject Matter/Conclusion
None of the claims are allowable.
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/GANAPATHIRAMA RAGHU/ Primary Examiner, Art Unit 1652
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