DETAILED ACTION
Status of the Application
Claims 1-17 are pending.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election with traverse of Group I, claims 1-13, 16, drawn in part to a modified Bacillus licheniformis host cell, and a single genetic modification to increase the expression of a single gene, wherein said gene is a degQ gene, as submitted in a communication filed on 5/6/2026 is acknowledged.
Applicant’s traverse is on the grounds that the cited reference does not teach or suggest the modified host cell with the genetic modification elected below. Therefore, Applicant is of the opinion that the technical feature makes a contribution over the cited reference. Applicant’s arguments have been fully considered but not deemed persuasive to withdraw the restriction requirement. The examiner acknowledges the election made. However, it is noted that the claims are not limited to the elected modification to the elected gene. The claims are directed to a Bacillus licheniformis that has been modified by one or more modifications as set forth in parts (a), (b) and (c) of claim 1. As previously indicated, the technical feature linking the inventions of Groups I and II is a genetically modified Bacillus licheniformis, which is shown by Borgmeier et al. to lack novelty or inventive step since Borgmeier et al. teach a genetically modified Bacillus licheniformis wherein the expression of the degU gene is induced by a heterologous promoter that is induced by IPTG. The genetically modified Bacillus licheniformis of Borgmeier et al. anticipates claim 1. Therefore, contrary to Applicant’s assertions, the cited prior art reference shows that the technical feature does not make a contribution over the prior art and the claimed inventions do not meet the requirement of unity of invention under PCT Rule 13.2. The requirement is deemed proper and therefore is made FINAL.
While claim 6 requires a modification to increase the expression of the degQ gene, this claim also requires increased autophosphorylation of the DegS protein or reduced activity of the DegS protein. As such, claim 6 is directed to a non-elected combination of modifications since the elected combination is limited to a modification to increase the expression of the degQ gene. Claims 7-8 are directed to a non-elected invention in view of the fact that they require non-elected modifications, namely increased autophosphorylation of the DegS protein and reduced phosphatase activity of the DegS protein.
Claims 6-8, 14-15, 17 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 5/6/2026.
Claims 1-5,9-13, 16 are at issue and will be examined only to the extent they encompass the elected invention.
Specification
The specification is objected to for the following reasons. The tables in the specification are not numbered sequentially in the order in which they are presented. For example, Tables 3 are 4 are displayed before Tables 1 and 2. Applicant is advised that if the numbering of the Tables is amended, references to the corresponding Tables in the specification would have to be amended to reflect changes in the numbering of the Tables. Appropriate correction is required.
The specification is objected to for the following reasons. While Table 3 refers to SEQ ID NO: 33, 35-36, 39-40 as related to genes, it is noted that SEQ ID NO: 33 is an oligonucleotide of 20 nucleotides (not a forD gene), SEQ ID NO: 35 is an amino acid sequence (not a degQ gene), SEQ ID NO: 36 is an amino acid sequence that has been disclosed in the sequence listing as corresponding to B. licheniformis formosin (not a degQ gene), SEQ ID NO: 39 is a nucleotide sequence that according to the sequence listing is the CDS of a degQ gene (not a degS gene), and SEQ ID NO: 40 is an amino acid sequence of 46 amino acids (not a degS gene). Also, while Table 4 refers to SEQ ID NO: 34, 37-38, 41-46 as related to proteins, SEQ ID NO: 34 is a nucleotide sequence (not a protein), SEQ ID NO: 37 is a nucleotide sequence (not a protein), SEQ ID NO: 41 is an amino acid sequence corresponding to a DegQ protein according to the sequence listing (not a DegS protein), SEQ ID NO: 42 is an amino acid sequence of a DegQ protein according to the sequence listing (not a DegS protein), SEQ ID NO: 43 is a nucleotide sequence (not a protein), SEQ ID NO: 45 is a nucleotide sequence (not a protein). Applicant is reminded that no new matter should be introduced in any amendment filed in response to this objection. Amendments made should be accompanied by the corresponding support in the specification as originally filed. Appropriate correction is required.
The specification is objected to for the following reasons. The specification states that the B. licheniformis DegU protein has the amino acid sequence of SEQ ID NO: 54. However, the sequence listing states that SEQ ID NO: 54 is a B. pumilus protein and the prior art discloses that SEQ ID NO: 54 is that of a B. subtilis DegQ protein. Appropriate correction is required.
Priority
Acknowledgment is made of a claim for foreign priority under 35 U.S.C. 119(a)-(d) to EUROPEAN PATENT OFFICE (EPO) 21181349.8 filed on 6/24/2021. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
This is the US national application which entered the national stage from PCT/EP2022/067439 filed on 06/24/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/23/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings submitted on 12/21/2023 have been reviewed and are accepted by the Examiner for examination purposes.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 1-5, 9-13, 16 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 1-2, 4-5, 9-10, 16 (claims 3, 11-13 dependent thereon) are indefinite in the recitation of “degQ”, “degU”, “degS”, “degR”,. “phrG”, “DegU”, “DegQ”, “DegS”, “DegR”, and “PhrG” for the following reasons. The terms as written, appear to be generic and not limited to a specific organism. While the gene/protein nomenclature used may be appropriate for B. licheniformis genes and proteins encoded by B. licheniformis genes, the use of this nomenclature for (i) genes encoding proteins of identical function in other organisms, or (ii) proteins of identical function from other organisms 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 the abstract of Sousa et al. (Microbiology 148(Pt5):1291-1303, 2002). As such, the use of gene/protein terminology which is applicable to some organisms and not to others as used herein is confusing since one cannot determine if by using this nomenclature, the claims are limiting the organism from which these genes/proteins derive to those that use the same nomenclature. For examination purposes, the term “degQ” will be interpreted as a gene encoding a positive regulator of a quorum sensing system and the term “DegQ” will be interpreted as a positive regulator of a quorum sensing system. Correction is required.
Claims 1-5, 13 (claims 9-12 and 16 dependent thereon) is indefinite in the recitation of “compared to an unmodified control cell” and “compared to an unmodified Bacillus licheniformis control cell” for the following reasons. The claims do not require the comparison to be made with the corresponding unmodified Bacillus licheniformis but rather allows for the comparison to be made with a genus of cells. The term “unmodified control cell” encompasses any cell that lacks the genetic modifications recited. The term “unmodified Bacillus licheniformis control cell” encompasses any strain of Bacillus licheniformis and is not limited to the same strain having the modification. The basis for comparison is variable, thus making the determination as to what is included or excluded from the scope of the claims impossible. A Bacillus licheniformis cell may or may not be within the scope of the claim depending on what is used as the basis for comparison. For example, Bacillus licheniformis Z may be encompassed by the claim if the comparison is made with wild-type B. subtilis X that lacks the genetic modifications recited but may not meet the limitations recited if the comparison is made with wild type B. subtilis Y that lacks the genetic modifications recited. For examination purposes, no patentable weight will be given to the terms “compared to an unmodified control cell” and “compared to an unmodified Bacillus licheniformis control cell”. Correction is required.
Claims 9-10 are indefinite in the recitation of “..wherein the degQ gene encodes a DegQ protein comprising an amino acid sequence with at least 80%….identity to SEQ ID NO: 37” for the following reasons. According to the sequence listing, SEQ ID NO: 37 is a nucleotide sequence. Therefore, there is no amino acid sequence that has SEQ ID NO: 37. For examination purposes, no patentable weight will be given to the term. Claims 9-10 will be interpreted as duplicates of claim 1. Correction is required.
Claim 12 is indefinite in the recitation of “such as an enzyme selected from the group ….and cellulase” for the following reasons. The phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). No patentable weight will be given to the term “such as an enzyme selected from the group ….and cellulase”. Correction is required.
Claim 16 is indefinite in the recitation of “wherein the host cell is a host cell overexpressing at least one of the genes selected from…” for the following reasons. The term “overexpressing” is a relative term and the claim fails to provide the basis for comparison to determine if overexpression is present (i.e., overexpressed compared to what?). For examination purposes, it will be assumed that the claim reads “wherein the host cell is a host cell that expresses at least one of the genes selected from…”. Correction is required.
When amending the claims, applicant is advised to carefully review all examined claims and make the necessary changes to ensure proper antecedent basis and dependency.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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 1-5, 9-13, 16 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.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. Claims 1-5, 9-13, 16 are directed in part to a genus of genetically modified B. licheniformis cells that have been modified by any means to increase the expression of a genus of genes encoding positive regulators of a quorum sensing system having any structure, wherein said genetically modified cells also have an increased level of phosphorylation of the endogenous DegU protein and a reduced level of an endogenous formosin D protein. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “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”. As indicated in MPEP § 2163, 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 that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that 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 claims require a potentially large genus of (i) genes encoding positive regulators of a quorum sensing system having any structure, and (ii) unknown modifications that can be made to any B. licheniformis cell to increase the expression of said genes of (i). In addition, the claims also require unknown modifications that can be made to any B. licheniformis cell to increase phosphorylation of an endogenous DegU protein and to reduce the level of formosin D. While the specification discloses increasing the copy number of a degQ gene from B. licheniformis as the only method to increase the expression of a degQ gene and increase the phosphorylation of the DegU protein, and the deletion of an endogenous forD gene to reduce the levels of formosin D, the specification is silent with regard to the structural features required in any gene that encodes a positive regulator of a quorum sensing system. Furthermore, while the claims require unknown modifications to increase the expression of any gene encoding a positive regulator of a quorum sensing system, the specification is silent with regard to other genetic modifications that can be made to a B. licheniformis cell to increase the expression of said gene in said cell, such as mutations in the regulatory region of said gene, the expression of unknown inducers of the expression of said gene, or the expression of antisense molecules that could block the expression of repressors of said gene. Similarly, while some of the claims require a reduction in the levels of formosin D, the specification is silent with regard to other methods to reduce the levels of an endogenous protein beyond a disruption of the gene encoding said protein. Such undisclosed methods encompass, for example, structural modifications to the regulatory regions of said genes, the expression of proteins that could act as inhibitors of transcription, antisense molecules to block expression of the desired gene, or structural modifications to the coding region of the gene. The specification fails to provide a structure/function correlation that would allow one of skill in the art to recognize those genes that encode positive regulators of a quorum sensing system and the genetic modifications required in any B. licheniformis cell to obtain the desired increase in expression, phosphorylation, or reduction in formosin D.
A sufficient written description of a genus of genes/proteins may be achieved by a recitation of a representative number of genes/proteins defined by their nucleotide/amino acid sequence or a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature and there is no art-recognized correlation between structure and function which would provide those unknown structural features. In addition, while one could argue that sequences disclosed in the prior art are representative of the structure of all the members of the genus of genes/proteins required, it is noted that the art teaches several examples of differences in activity even when there is little structural variability. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013;) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. Therefore, since minor structural differences may result in different function, and no additional information correlating structure with the desired activity has been provided, one cannot reasonably conclude that the genes/proteins of the prior art are representative of all the members of the genus of genes/proteins required by the claims.
Due to the fact that the specification only discloses a very limited number of genes encoding positive regulators of a quorum sensing system, and an very limited number of modifications to increase the expression of a gene, increase the phosphorylation of DegU and reduce the production of an endogenous protein, one of skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1-5, 9-13, 16 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a B. licheniformis cell that has been genetically modified by transforming it with a B. licheniformis degQ gene placed under the control of a heterologous promoter, wherein said B. licheniformis cell further comprises a deletion in the endogenous forD gene, does not reasonably provide enablement for a B. licheniformis cell that has been modified by any means to increase the expression of any gene encoding a positive regulator of a quorum sensing system having any structure, to increase the level of phosphorylation of an endogenous DegU protein and to reduce the level of an endogenous formosin D protein. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or 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, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of 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 claims. The factors that have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims. Claims 1-5, 9-13, 16 broadly encompass a B. licheniformis cell that has been modified by any means to increase the expression of any gene encoding a positive regulator of a quorum sensing system having any structure, to increase the level of phosphorylation of an endogenous DegU protein and to reduce the level of an endogenous formosin D protein. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
The enablement provided is not commensurate in scope with the claims due to the large number of unknown genes encoding a positive regulator of a quorum sensing system required by the claims, and the large number of unknown genetic modifications one could make to a B. licheniformis cell so that the expression of genes encoding a positive regulator of a quorum sensing system can be increased, the phosphorylation of a DegU protein can be increased, and the production of formosin D can be reduced. In the instant case, the specification enables a B. licheniformis cell that has been genetically modified by transforming it with a B. licheniformis degQ gene placed under the control of a heterologous promoter, wherein said B. licheniformis cell further comprises a deletion in the endogenous forD gene
The amount of direction or guidance presented and the existence of working examples. The specification discloses a B. licheniformis cell that has been genetically modified by transforming it with a B. licheniformis degQ gene placed under the control of a heterologous promoter, wherein said B. licheniformis cell further comprises a deletion in the endogenous forD gene, as a working example.
However, the specification fails to disclose (i) the structure and/or identity of additional genes encoding positive regulators of a quorum sensing system, (ii) other genetic modifications to increase the expression of a gene beyond increasing the copy number of the gene, (iii) additional modifications to increase phosphorylation of a DegU protein or (iv) additional modifications to reduce the production of an endogenous protein beyond deleting the gene encoding said protein. As indicated above, the claims encompass genetic modifications such as mutations in the regulatory region of the recited genes, the expression of unknown inducers of the expression of said genes, or the expression of antisense molecules that could block the expression of repressors of said genes. Also, the specification is silent with regard to other methods to reduce the levels of an endogenous protein beyond a disruption of the gene encoding said protein. Such undisclosed methods encompass, for example, structural modifications to the regulatory regions of said genes, the expression of proteins that could act as inhibitors of transcription, antisense molecules to block expression of the desired gene, or structural modifications to the coding region of the gene. No structure/function correlation has been provided that would allow one of skill in the art to determine those genes that encode positive regulators of a quorum sensing system and the genetic modifications required in any B. licheniformis cell to obtain the desired increase in expression, phosphorylation, or reduction in formosin D.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The coding region of a polynucleotide determines the structure and function of the protein encoded by said polynucleotide. Neither the specification nor the art provide a correlation between structure and function such that one of skill in the art can envision the structure of any positive regulator of a quorum sensing system (or its coding gene) that could be used in the claimed B. licheniformis cell. In addition, the art does not provide any teaching or guidance as to which genetic modifications can be made to any B. licheniformis cell so that the expression of any gene encoding a positive regulator of a quorum sensing system can be increased, the phosphorylation of a DegU protein can be increased, and the level of formosin D can be reduced.
While the argument can be made that the structure/identity of those positive regulators and their corresponding genes can be obtained by structural homology, the art clearly teaches that (i) there is a high level of unpredictability associated with accurate functional annotation of proteins based solely on structural homology, and (ii) modification of a protein’s amino acid sequence to obtain the desired activity without any guidance/knowledge as to which amino acids in a protein are tolerant of modification and which ones are conserved is highly unpredictable. For example, Singh et al. (Current Protein and Peptide Science 19(1):5-15, 2018) disclose different protein engineering approaches and state that despite the availability of an ever-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 (page 11, left column, last paragraph). Sadowski et al. (Current Opinion in Structural Biology 19:357-362, 2009) teach that much of the problem in assigning function from structure comes from functional convergence, where although a stable structure is required to perform many functions it is not always necessary to adopt a particular structure to carry out a particular function (page 357, right column, first full paragraph). Sadowski et al. further explain that the unexpected and significant difficulties of predicting function from structure show that the potential of structural models for providing novel functional annotations has not yet fully realized. Sadowski et al. also states that while a few successes have been achieved which required manual intervention, the ability to vary the requirements for specificity in prediction means that it is difficult to determine how useful the end result may be for the user (page 361, left column, first full paragraph). The teachings of Singh et al. and Sadowski et al. are further supported by the teachings of Witkowski et al., Tang et al. and Seffernick et al. already discussed above, where it is shown that even small amino acid changes result in enzymatic activity changes.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of isolating polypeptides and genes were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an infinite number of proteins/genes and determine which ones have the desired activity or encode a protein with the desired activity. Similarly, it was not routine in the art to screen by a trial and error process for an infinite number of genetic modifications, proteins that can act as expression regulators, or antisense molecules that could block expression of the desired genes. In the absence of (a) a rational and predictable scheme for identifying which proteins and their genes are more likely to have the desired activity, (b) a correlation between structure and activity, (c) a rational and predictable scheme for identifying those genetic modifications most likely to result in the desired increase in expression and phosphorylation, and (d) some knowledge or guidance as to which genetic modifications can result in a decrease of formosin D production, one of skill in the art would have to test an essentially infinite number of proteins, nucleic acids, and modifications to determine which genetic modifications would lead to the desired outcome, and which proteins have the desired activity.
Therefore, taking into consideration the extremely broad scope of the claims, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and function, and the high degree of unpredictability of the prior art in regard to function determination based on structural homology, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
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.
Claims 1-4, 9-13, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Borgmeier et al. (Journal of Biotechnology 159:12-20, 2012; cited in the prior Office action).
Claims 1-4, 9-13, 16 as interpreted are directed in part to a Bacillus licheniformis cell that has a genetic modification to increase the expression of a degU gene compared to the corresponding Bacillus licheniformis cell lacking the genetic modification, wherein said Bacillus licheniformis cell also comprises an expression cassette that encodes a protein of interest, wherein the protein of interest is an enzyme. It is noted that the limitation of claim 9 regarding the % sequence identity of the DegU protein has not been given any patentable weight in view of the fact that SEQ ID NO: 54 is not the sequence associated with a DegU protein. See extensive explanation above under Specification. Also, it is noted that claim 10 is further limiting claim 1 by merely providing a limitation for the degQ gene and is not limiting claim 10 to a genetic modification to the degQ gene. As such, claim 10 still encompasses a genetic modification to increase the expression of a degU gene. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Borgmeier et al. teach a Bacillus licheniformis cell that has been genetically modified to insert a fragment that comprises a degU gene which has been operably linked to an IPTG-inducible promoter and further comprises additional genes including a lacZ gene (page 16, Figure 3a, right column, Results), which encodes a β-galactosidase (an enzyme). According to the specification, it is asserted that increased expression of a degU gene results in reduced production of the formosin D protein. As such, the Bacillus licheniformis cell would also have reduced production of the formosin D protein. Therefore, the teachings of Borgmeier et al. anticipate the instant claims as written/interpreted.
Claims 1-5, 9-13, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Qiu et al. (Applied Microbiology and Biotechnology 103:4003-4015, 2019; hereinafter “Qiu 1”) as evidenced by Qiu et al. (Applied Microbiology and Biotechnology 98:8895-8903; 2014, hereinafter “Qiu 2”).
Claims 1-5, 9-13, 16 as interpreted are directed in part to a Bacillus licheniformis cell that has a genetic modification to increase the expression of a degQ gene compared to the corresponding Bacillus licheniformis cell lacking the genetic modification, wherein said Bacillus licheniformis cell also comprises an expression cassette that encodes a protein of interest, wherein the protein of interest is an enzyme. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Qui 1 teaches a B. licheniformis cell (WX02-Psrflch; Abstract) that has been genetically engineered such that the lch operon has been placed under the control of the promoter Psrf (Table 1, Strains, WX02-Psrflch). Qui 1 states that this strain was previously described by Qiu 2 (page 4004, right column, Bacterial strains and plasmids). As evidenced by Qiu 2, this strain was obtained by homologous recombination with a plasmid that replaces the native promoter Plch with the Psrf promoter (Figure 1, caption). The lch operon comprises the genes lchAA, lchAB, and lchAC genes which encode the subunits of a lichenysin synthetase and the lchA-TE gene that encodes a thioesterase (8895, right column, last 4 lines- page 8896, left column, line 1). Therefore, B. licheniformis cell WX02-Psrflch comprises an expression cassette that encodes an enzyme (protein of interest). Qiu 1 teaches that the expression levels of the degQ gene were the highest in the B. licheniformis cell WX02-Psrflch when compared to the control B. licheniformis cell WX02 that lacks the genetic modification that places the lch operon under the control of the Psrflch promoter (Figure 4a; page 4008, right column, second full paragraph). Therefore, the genetic modification that places the lch operon under the control of the Psrflch promoter is a genetic modification that results in an increase in the expression of the degQ gene. According to the specification, it is asserted that increased expression of a degQ gene results in reduced production of the formosin D protein and an increase in the phosphorylation of the DegU protein in B. licheniformis. As such, the B. licheniformis cell of Qiu 1 would also have a reduced production of formosin D and an increase in the phosphorylation of the DegU protein. Therefore, the teachings of Qiu 1 anticipate the instant claims as written/interpreted.
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 1-5, 9-13, 16 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 8-10 of copending Application No. 18/572,974. Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 1-5, 9-13, 16 of the instant application as interpreted are directed in part to a Bacillus licheniformis cell that has a genetic modification to increase the expression of a degQ gene compared to the corresponding Bacillus licheniformis cell lacking the genetic modification, wherein said Bacillus licheniformis cell also comprises an expression cassette that encodes a protein of interest, wherein the protein of interest is an enzyme. See Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA ) for claim interpretation.
Claims 8-10 of copending Application No. 18/572,974 are directed in part to a Bacillus cell which has a genetic modification to increase the expression of a degQ gene compared to the corresponding Bacillus cell lacking the genetic modification. The specification of copending Application No. 18/572,974 as evidenced by claims 11-13 discloses a B. licheniformis cell which comprises an expression cassette that encodes an enzyme as a preferred embodiment of the genus of Bacillus cells of claims 8-10. Therefore, the Bacillus licheniformis cell of claims 1-5, 9-13, 16 of the instant application is deemed an obvious variation of the Bacillus cell of claims 8-9 of copending Application No. 18/572,974 in view of the preferred embodiments disclosed.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to DELIA M RAMIREZ, Ph.D., whose telephone number is (571) 272-0938. The examiner can normally be reached on Monday-Friday from 8:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B. Mondesi, can be reached at (408) 918-7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/DELIA M RAMIREZ/Primary Examiner, Art Unit 1652
DR
May 12, 2026
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