DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-4, 16, 17, 21-27, 29-41 are pending in the instant application.
Applicant's election with traverse of Invention 1 in the reply filed on 11/24/2025 is acknowledged. The arguments have been considered but are not persuasive. As previously stated, Inventions 1-9 do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Schmidt et al. (ENVIRONMENTAL MICROBIOLOGY, BLACKWELL SCIENCE, GB, vol. 11, no. 6, 10 February 2009 (2009-02-10), pages 1422-1437; IDS filed 07/30/2024) teaches the promoter of the prnABCD operon of Burkholderia which would hybridize under stringent conditions to any of SEQ ID NOs: 7-10 of the instant application. Lefebre et al. (APPLIED AND ENVIRONMENTAL MICROBIOLOGY, AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 68, no. 12, 1 December 2002 (2002-12-01), pages 5956-5964; IDS filed 07/30/2024) teaches the promoter of the S7 ribosomal gene from
Burkholderia which would hybridize under stringent conditions to any of SEQ ID NOs: 7-10 of the instant application. Further, the combination of the references teachings of Schwager Stephan Alois Michael("The use of non-mammalian infection models to study the pathogenicity of members of the genus Burkholderia and Pseudomonas aeruginosa", 1 January 2012 (2012-01-01), XP093177831, Universitat Zurich, see attached EP4296362 Provisional opinion 08-07-2024; PTO 892) in view of JP2019205402A (12/05/219; PTO 892), Accession A0A1Y1BW10 (30-AUG-2017; PTO 892), Accession X70354 (07-OCT-1993; PTO 892) render obvious Invention 1 as stated below in the rejection of claims 1, 2, 16, 17, 21, 35, 38, 39 are rejected under 35 U.S.C. 103. Thus, the same or corresponding technical feature was known in the prior art and therefore cannot make a contribution over the prior art. Since the inventions lack the same or corresponding special technical feature, then Inventions 1-9 are not so linked as to form a single general inventive concept under PCT Rule 13.1.
Claims 3, 4, 22-27, 29-34, 36, 37, 40, 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention. The requirement is still deemed proper and is therefore made FINAL.
Claims 1, 2, 16, 17, 21, 35, 38, 39, drawn to a method for producing a protein encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus Burkholderia, wherein the bacterium lacks BSFP_068740, are under consideration in this Office Action.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ) 2nd Paragraph
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, 2, 16, 17, 21, 35, 38, 39 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.
Claim 1 recites the phrase “the bacterium lacks one or more genes selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720,” which renders the claim vague and indefinite since the specific nucleotide sequence and structure of the genes cited as BSFP_068740, BSFP_068730, and BSFP_068720 are not known and not recited in the claim. Dependent claims 2, 16, 17, 21, 35, 38, 39 are also rejected because they do not correct the defect. For examination purposes the genes cited as BSFP_068740, BSFP_068730, and BSFP_068720 will not be limited to a specific nucleotide sequence and structure.
Claims 1, 17 recites the phrase “capable of hybridizing under stringent conditions” which renders the claim vague and indefinite since the specific hybridization conditions are not known and not recited in the claim. For examination purposes the claims will not be limited to any hybridization conditions.
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 2, 16, 17, 21, 35, 38, 39 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 claims are drawn to a genus of methods for producing a genus of proteins encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus of Burkholderia bacteria, wherein the bacterium lacks one or more genus of genes of any nucleotide sequence and structure selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720, or has inhibited expression of the genes or proteins encoded by the genes, where the BSFP_068740 comprises any genus of DNA capable of hybridizing under any stringent conditions to DNA consisting of a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO: 1, wherein a protein encoded thereby has a function of decreasing a copy number of an expression construct in the bacterium; any genus of DNA consisting of a nucleotide sequence derived from the nucleotide sequence of SEQ ID NO: 1 by the deletion, substitution, or addition of one or a few bases, wherein a protein encoded thereby has a function of decreasing a copy number of an expression construct in the bacterium; any genus of DNA consisting of a nucleotide sequence having at least 80% or higher sequence identity to SEQ ID NO: 1, wherein a protein encoded thereby has a function of decreasing a copy number of an expression construct in the bacterium; any genus of DNA capable of hybridizing under stringent conditions to DNA consisting of a nucleotide sequence encoding a protein consisting of the amino acid sequence of SEQ ID NO: 2, wherein a protein encoded thereby has a function of decreasing a copy number of an expression construct in the bacterium; or any genus of DNA consisting of a nucleotide sequence encoding a protein consisting of an amino acid sequence derived from the amino acid sequence of SEQ ID NO: 2 by the deletion, substitution, or addition of one or a few amino acids, wherein the protein has a function of decreasing a copy number of an expression construct in the bacterium; any genus of DNA consisting of a nucleotide sequence encoding a protein consisting of an amino acid sequence having at least 80% or higher sequence identity to SEQ ID NO: 2, wherein the protein has a function of decreasing a copy number of an expression construct in the bacterium. The claims are drawn to said genus of methods for producing a genus of proteins encoded by a target gene, where the target gene encodes any genus of esterases wherein target gene comprises any genus of DNA capable of hybridizing under stringent conditions to DNA consisting of a nucleotide sequence complementary to a nucleotide sequence of any one of SEQ ID NOs: 11 to 13, wherein a protein encoded thereby has esterase activity; any genus of DNA consisting of a nucleotide sequence derived from a nucleotide sequence of any one of SEQ ID NOs: 11 to 13 by the deletion, substitution, or addition of one or a few bases, wherein a protein encoded thereby has esterase activity; any genus of DNA consisting of a nucleotide sequence having at least 80% or higher sequence identity to a nucleotide sequence of any one of SEQ ID NOs: 11 to 13, wherein a protein encoded thereby has esterase activity. According to MPEP 2163:
“For each claim drawn to a genus: 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 (see i)(A), above), reduction to drawings (see i)(B), above), 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 (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014)…”
According to MPEP 2163.02:
“The courts have described the essential question to be addressed in a description requirement issue in a variety of ways. An objective standard for determining compliance with the written description requirement is, "does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed." In re Gosteli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989). Under Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991), to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed. The test for sufficiency of support in a parent application is whether the disclosure of the application relied upon "reasonably conveys to the artisan that the inventor had possession at that time of the later claimed subject matter." Ralston Purina Co. v. Far-Mar-Co., Inc., 772 F.2d 1570, 1575, 227 USPQ 177, 179 (Fed. Cir. 1985) (quoting In re Kaslow, 707 F.2d 1366, 1375, 217 USPQ 1089, 1096 (Fed. Cir. 1983)).”
The reference of Prather et al. (Curr Opin Biotechnol. 2008 Oct;19(5):468-74; IDS filed 01/12/2024) teaches numerous challenges associated with constructing de novo metabolic pathways, including selection of the appropriate enzymes in a multi-step pathway, compatibility of the enzymes with the expression host and with each other, and the requirement to engineer one or more of the enzymes to achieve the desired activity on a given substrate [see p. 472, columns 1-2]. Prather et al. specifically teach that “while synthetic biology provides a complementary framework for de novo pathway design, it is unclear how well some of the core principles, for example, Abstraction, can be implemented [see p. 472, column 2, top]. The reference of Kizer et al. (Appl Environ Microbiol. 2008 May;74(10):3229-41; IDS filed 01/12/2024), which teaches that producing complex chemicals using synthetic metabolic pathways in microbial hosts is often complicated by deleterious interactions between pathway intermediates and the host cell metabolism [see p. 3229, abstract], noting that “… embedding a novel biochemical pathway in the metabolic network of a host cell can disrupt the subtle regulatory mechanisms that the cell has evolved over the millennia" [see p. 3229, column 1] and “[w]hile it can be relatively simple to determine that an engineered synthetic biochemical pathway is not functioning in the heterologous host, it is often a far more challenging task to determine exactly what is causing the problem” [p. 3237, column 2]. The reference of Chica et al. (Curr Opin Biotechnol. 2005 Aug;16(4):378-84; IDS filed 01/12/2024) teaches that the complexity of the structure/function relationship in enzymes has proven to be the factor limiting the general application of rational enzyme modification and design, where rational enzyme modification and design requires in-depth understanding of structure/function relationships. The reference of Singh et al. (Curr Protein Pept Sci. 2017, 18, 1-11; IDS filed 01/12/2024) reviews protein engineering methods including directed evolution, rational design, semi-rational design, and de-novo design; and states that despite the availability of a growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see entire publication especially Figs.1 and 3, and page 7, left column, lines 8-17). However, such rational design and directed evolution techniques only provide guidance for searching and screening for the recited DNA wherein a protein encoded thereby has a function of decreasing a copy number of an expression construct in the bacterium; and the recited DNA wherein a protein encoded thereby has esterase activity
The specification as originally filed does not disclose a representative number of species of bacteria having any chemical and/or biological properties and capable of producing any target gene encompassed by the claimed invention by actual reduction to practice. The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which nucleotide sequences, amino acid sequences, and/or structures correlate with the biological functions of the protein encoded thereby that has a function of decreasing a copy number of an expression construct in the bacterium.
The specification as originally filed does not provide a correlation between function and structure to enable one of ordinary skill in the art to predict which nucleotide sequences, amino acid sequences, and/or structures correlate with the esterase enzymatic activity.
Hence, the specification does not provide sufficient written description to inform one of ordinary skill in the art that applicants at the time the application was filed were in possession of the claimed genus of methods for producing a genus of proteins encoded by a target gene, and said genus of methods for producing a genus of proteins encoded by a target gene where the target gene encodes any genus of esterases.
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 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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schwager Stephan Alois Michael ("The use of non-mammalian infection models to study the pathogenicity of members of the genus Burkholderia and Pseudomonas aeruginosa", 1 January 2012 (2012-01-01), XP093177831, Universitat Zurich, see attached EP4296362 Provisional opinion 08-07-2024; PTO 892).
For the reasons stated above, the recited genes will be not limited to a specific nucleotide sequence sequence and structure.
Michael teach bacteria of the genus Burkholderia that lack plasmid 3, the virulence plasmid. Since BSFP_068740, BSFP_068730 and BSFP_068720 are all located on plasmid 3, said bacteria of the genus Burkholderia disclosed lack all said genes. Said bacteria are cultured and used for infection experiments. Since said bacteria further produce undefined target genes during culture or during infection, Michael also teaches a method for producing a protein encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus Burkholderia, wherein the bacterium lacks one or more genes selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720, or has inhibited expression of the genes or proteins encoded by the genes. (see attached EP4296362 Provisional opinion 08-07-2024; PTO 892). Thus, the reference teachings anticipate the claimed invention.
Claim Rejections - 35 USC § 103
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 of this title, 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 16, 17, 21, 35, 38, 39 are rejected under 35 U.S.C. 103 as being unpatentable
over Schwager Stephan Alois Michael("The use of non-mammalian infection models to study the pathogenicity of members of the genus Burkholderia and Pseudomonas aeruginosa", 1 January 2012 (2012-01-01), XP093177831, Universitat Zurich, see attached EP4296362 Provisional opinion 08-07-2024; PTO 892) in view of JP2019205402A (12/05/219; PTO 892), Accession A0A1Y1BW10 (30-AUG-2017; PTO 892), Accession X70354 (07-OCT-1993; PTO 892).
Michael teach bacteria of the genus Burkholderia that lack plasmid 3, the virulence plasmid. Since BSFP_068740, BSFP_068730 and BSFP_068720 are all located on plasmid 3, said bacteria of the genus Burkholderia disclosed lack all said genes. Said bacteria are cultured and used for infection experiments. Since said bacteria further produce undefined target genes during culture or during infection, Michael also teaches a method for producing a protein encoded by a target gene, comprising the step of expressing the target gene in a bacterium of the genus Burkholderia, wherein the bacterium lacks one or more genes selected from the group consisting of BSFP_068740, BSFP_068730, and BSFP_068720, or has inhibited expression of the genes or proteins encoded by the genes. (see attached EP4296362 Provisional opinion 08-07-2024; PTO 892).
The teachings of the reference differ from the claims in that the reference does not teach that the target gene encodes esterase.
JP2019205402A teaches methods using Burkholderia stabilis as host for recombinant production of proteins and enzymes including cholesterol esterase and lipase, constitutive promoter that enables high-level, inducer free expression, and vectors introduced into Burkholderia stabilis for transformation (see attached English language translation description and claims especially claims 1-9).
Accession A0A1Y1BW10 teaches a protein having 89.9% identity to SEQ ID NO: 2 and encoding polynucleotide (see attached record).
Accession X70354 teaches polynucleotide having 99.8% identity to SEQ ID NO: 12 encoding lipase (see attached record).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify and/or combine the reference teachings to make the claimed invention by transforming the bacteria of the genus Burkholderia to express the polynucleotide encoding lipase of Accession X70354, and use the transformed bacteria in the method of JP2019205402A to produce the esterase. Further, it would have been obvious to modify the Burkholderia stabilis of JP2019205402A by deleting the BSFP_068740 as taught by Michael, transforming the Burkholderia stabilis to express the polynucleotide encoding lipase of Accession X70354, and use the transformed bacteria in the method of JP2019205402A to produce the esterase. One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to do this in order to obtain a simple and efficient method for producing desired proteins in Burkholderia stabilis. One of ordinary skill in the art at the time the invention was made would have a reasonable expectation of success because genetically modifying Burkholderia stabilis to produce desired proteins are known in the art as shown by reference teachings. Hence, the claimed invention as a whole is prima facie obvious.
Conclusion
No claims are allowed.
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/CHRISTIAN L FRONDA/Primary Examiner, Art Unit 1652