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
Acknowledgement is hereby made of receipt and entry of the communication filed on June 24, 2026 and Feb. 22, 2024. Claims 1-8, 10-20 and 22 are pending. Claims 10-11, 15, 17-20 and 22 are withdrawn. Claims 1-8, 12-14 and 16 are currently examined.
Election/Restrictions
Applicant's election Group I (claims 1-8 and 10-17) in the reply filed on June 24, 2026, is acknowledged.
As for the species election, Applicant elected claim 8 among claims 8, 10 and 11, and elected claim16 among claims 15-17.
Accordingly, claims 18-20 and 22 are withdrawn as being directed to a non-elected group. Claims 10-11, 15 and 17 are withdrawn as being directed to non-elected species.
Although applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8, 12-14 and 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “stably” in the base claim 1 is a relative term which renders the claim indefinite. The term “stably” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim1 recites a phrase “wherein said production bacterial cell is from a bacterial species or strain different from the bacterial species or strain from which said first type of bacteriophage comes from and/or that said first type of bacteriophage targets” that renders the claim indefinite because it is unclear if the “first type of bacteriophage” is the same as the “a first type of bacteriophage” in the claim.
Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
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, 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.
Claims 1, 8 and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Haaber et al. (US 2019/0160120 A1, published on May 30, 2019, hereinafter, “Haaber”).
The base claim 1 is directed to a production bacterial cell for producing phage particles or phage- derived delivery vehicles, which comprising at least one phage structural gene and at least one phage DNA packaging gene, said phage structural gene(s) and phage DNA packaging gene(s) being derived from a first type of bacteriophage, wherein the expression of at least one of said phage structural gene(s) and/or at least one of said phage DNA packaging gene(s) in said production bacterial cell is controlled by at least one induction mechanism, and wherein said production bacterial cell is from a bacterial species or strain different from the bacterial species or strain from which said first type of bacteriophage comes from and/or that said first type of bacteriophage targets.
Haaber teaches the production of phage and transduction particles using DNAs ( eg, plasmids and helper phage, mobile genetic elements (MGEs) or plasmids with chromosomally integrated helper phage genes), as well as the phage, helper phage, kits, compositions and methods involving these (See Abstract), where the DNAs comprise all phage structural protein genes required to produce a packaged phage particle comprising a copy of the first DNA (See [0011]) and are introduced into a host bacterial cells (See e.g., [0025]). Also, Haaber teaches a method of making a plurality of transduction particles comprising producing host cells whose genomes comprise nucleic acid encoding structural proteins necessary to produce transduction particles that can package first DNA, wherein the genomes are devoid of a phage packaging signal, wherein the expression of the proteins is under the control of inducible promoter(s) (See [0070] and [0071]).
Accordingly, Haaber teaches a production bacterial cell for producing phage particles where the bacterial cells comprise the phage structural gene and packaging gene of the first type of phage DNA and the expression of the phage DNA is under an inducible promoter.
As for the limitation on the bacterial cell is from a bacterial species or strain that is different from the host bacteria or target bacteria of the first type of bacteriophage, Haaber teaches that a bacterial host cell comprising nucleic acid under the control of one or more inducible promoters and that the host cell is of a different species than that of the target cell (or “second cells”) (See e.g., [0058]), and also discloses that a shuttle vectors that can be replicated in first bacteria, wherein the vectors can further be replicated and packaged into first phage in second bacteria (host bacteria) in the presence of the helper phage, wherein the first bacteria are of a strain or species that is different to the strain or species of the host bacteria (See [0155]).
As for the limitation on “…said production bacterial cell stably comprising at least one phage structural gene and at least one phage DNA packaging gene…”, although Haaber does not explicitly use the term “stably comprising”, however, Haaber teaches that “the DNA is integrated in the genome of a host bacterial cell” (See e.g., [0272]), and “the phage chromosome can be integrated into the bacterial chromosome” (See e.g. [0324]). Here it is obvious that the a “stably comprising” can be achieved by the chromosome integration.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 8, Haaber teaches a bacterial host cell comprising an MGE, vector or particle of the invention and nucleic acid under the control of one or more inducible promoters, wherein the nucleic acid encodes all structural proteins necessary to produce a transduction particle that packages a copy of the MGE or plasmid (See [0058]), which teaches that the phage structural gene(s) and the phage DNA packaging gene(s).can be expressed by inducing a same “one or more inducible promoters”.
Regarding claim 12, Haaber teaches that the invention relates to the production of phage using DNAs (eg, plasmids and helper phage, or plasmids with chromosomally integrated helper phage genes), as well as the phage, helper phage, kits, compositions and methods involving these (See [0003]), where the phage DNA is introduced into the bacterial cells including the structural gene encoding the structure protein and packaging DNA to package the phage particles (See e.g., [0086]).
Regarding claim 13, it requires that the production bacterial cell according to claim 1, wherein said production bacterial cell further comprises at least one gene, derived from a second type of bacteriophage, involved in phage excision/insertion, phage DNA replication, and/or phage regulation, said second type of bacteriophage coming from and/or targeting bacterial species or strain different from the bacterial species or strain from which said first type of bacteriophage comes from and/or that said first type of bacteriophage targets.
Haaber teaches that the invention relates to the production of phage including one or more second DNAs that is devoid of a nucleotide sequence (eg, a packaging signal) required for packaging the second DNA into phage particles, wherein the DNAs are operable when co-existing in a host bacterium for producing packaged phage that comprise the first DNA, wherein the phage require the second DNA for replication thereof to produce further phage particles (See [0005]-[0015]), where the second DNA can be comprised by a vector (eg, a plasmid or shuttle vector), helper phage ( eg, a helper phagemid) or is integrated in the genome of a host bacterial cell (See [0104]). Here the descriptions teach that the second phage DNA is involved in the phage replication as claimed.
As for the differences of the targeting/host bacterial strain/species between the first phage and second phage, Haaber teaches that in an example, the second DNA is comprised by an M13 or M13-based helper phage (See [0092]), and in another embodiment, the second DNA is comprised by a vector (eg, a plasmid or shuttle vector), helper phage ( eg, a helper phagemid) or is integrated in the genome of a host bacterial cell (See [0104]), where in an example, the helper phage are E coli phage and the first phage are E coli, C Streptococcus, Klebsiella, Pseudomonas, Acitenobacter, Enterobacteracea, Firmicutes or Bacteroidetes phage (See [0126]), which indicates that the second phage and the first phage can be from the different host/target bacterial cells, for example, the second phage is from a M13 phage and the first phage is a phage of Pseudomonas. Here the description of Haaber also teaches the claim 14 at the “production bacterial cell is from the same bacterial species or strain as the bacterial species or strain from which said second type of bacteriophage comes from and/or that said second type of bacteriophage targets”, for example, the second phage is a E coli helper phage (See [0126]) and the host and/or target bacteria is an E. coli (eg, 0157: H7) host (See, page 11, [0288]).
Claims 2-7 are rejected under 35 U.S.C. 103 as being unpatentable over Haaber et al. (US 2019/0160120 A1, published on May 30, 2019, hereinafter, “Haaber”) as applied to claims 1, 8 and 12-14 above, as evidenced by Traore et al. (Dis Model Mech. 2025 Sep 1;18(9): dmm052393, hereinafter, “Traore”).
Regarding claim 2, it requires that the bacterial cell further comprises a payload to be packaged into said phage particles or phage-derived delivery vehicles.
Haaber teaches that a "non-self-replicative transduction particle" refers to a particle, ( eg, a phage or phage-like particle; or a particle produced from a genomic island ( eg, a SaPI) or a modified version thereof) capable of delivering a nucleic acid molecule encoding an antibacterial agent or component into a bacterial cell, but does not package its own replicated genome into the transduction particle (See [0336]), where the “a nucleic acid molecule encoding an antibacterial agent or component” is reasonably to be considered as a “payload” as claimed although Haaber does not explicitly use the term ‘payload”. This can be evidenced by Traore’s study. Traore teaches that the concept of engineered phages with antibacterial payloads (see poster, ‘Technologies based on engineered phages’ panel, ‘Phages as antimicrobial agents’) aims to overcome limitations associated with traditional phage therapy, such as the emergence of phage-resistant bacteria and narrow host spectrum, by enhancing antimicrobial efficacy through the delivery of heterologous antimicrobial effectors (See page 5, right column, paragraph 3).
Regarding claim 3, Haaber teaches that a bacterial host cell comprising a first phage and a MGE, vector or particle of the invention, wherein the agent is toxic to cells of the same species as the host cell, and wherein the host cell has been engineered so that the agent is not toxic to the host cell (See [0054]), where the agent is a antibacterial agent encoded by a nucleic acid or MGE that is comparable to the “nucleic acid payload” as claimed (See [0042] and [0045]). Here the first phage-encoded proteins are expressed and MGE copies are packaged by first phage proteins to produce a plurality of transduction particles (See [0053]).
At the same time, Haaber teaches an antibacterial composition comprising a plurality of non-self-replicative transduction particles comprising a nucleic acid encoding an antibacterial agent or component, where the nucleic acid comprises a packaging signal comprising a pac, cos or a homologue thereof that is operable with the first phage to package the nucleic acid in non-self-replicative transduction particles (See page 89, claim 12), where a Cos packaging site is SEQ ID NO: 3 (See [0801]).
Regarding claim 4, Haaber teaches that a composition comprising a plurality of transduction particles, wherein each particle comprises a MGE or vector according to the invention, wherein the transduction particles are capable of transferring the MGEs, or nucleic acid encoding the agent or component, or copies thereof into target bacterial cells (See [0045]), where the agent or component is the payload as claimed.
Regarding claim 5, Haaber teaches that in an embodiment, the phage particle of (i) is capable of infecting a target bacterium, the phage comprising a nucleotide sequence of interest (NSI) that is capable of expressing a protein or RNA in the target bacterium, or wherein the NSI comprises a regulatory element that is operable in the target bacterium (See [0098]).
Regarding claims 6 and 7, Haaber teaches that a bacterial host cell comprising a first phage and a MGE, vector or particle of the invention, wherein the agent is not toxic to the host cell, but the agent is toxic to second cells of a species or strain that is different from the species or strain of the host cell, wherein the MGE is mobilizable in transduction particles producible by the host cell that are capable of transferring the MGE or a copy thereof into a said second cell, whereby the second cell is exposed to the antibacterial agent (See [0056]), where the second cell is the target cell that are killed by the antibacterial agent (See [0046]) or is sensitized to an antibiotic (See [0048]).
Claim16 is rejected under 35 U.S.C. 103 as being unpatentable over Haaber as applied to claims 1, 8 and 12-14 above in view of Brede et al. (Appl Environ Microbiol. 2005 Dec;71(12):8077-84).
Claim 16 is required the production bacterial cell is a P. freudenreichii bacterial cell.
Relevance of Haaber is set forth above. However, it is silent on that the production bacterial cell is a P. freudenreichii bacterial cell.
Brede teaches that heterologous bacteriocin production in Propionibacterium freudenreichii is described in their study. They developed an efficient system for DNA shuttling between Escherichia coli and P. freudenreichii using vector pAMT1. It is based
on the P. freudenreichii rolling-circle replicating plasmid pLME108 and carries the cml(A)/cmx(A) chloramphenicol resistance marker. Introduction of the propionicin T1 structural gene (pctA) into pAMT1 under the control of the constitutive promoter (P4) yielded bacteriocin in amounts equal to those of the wild-type producer Propionibacterium thoenii 419. The P. freudenreichii clone showed propionicin T1 activity in coculture, killing 90% of sensitive bacteria within 48 h. The pamA gene from P. thoenii 419 encoding the protease-activated antimicrobial peptide (PAMP) was cloned and expressed in P. freudenreichii, resulting in secretion of the
pro-PAMP protein. The P4 and Ppamp promoters directed constitutive gene expression, and activity of both promoters was enhanced by elements upstream of the promoter core region (See Abstract).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to introduce the efficient system for DNA shuttling between E. coli and P. freudenreichii of Brede into Haaber’s invention and arrive at an invention as claimed. One would have been motivated to do so for the gain of propagating the vector in two different species of bacterial cells such as E. coli. and P. freudenreichii. There would be a reasonable expectation of success to develop such a production bacterial cell such as P. freudenreichii as claimed by combining the teachings of Brede and Haaber because Brede teaches that an efficiency expression of the propionicin T1 in P. freudenreichii (See page 8981, left column, paragraph 2), and Haaber teaches a shuttle vectors that can be replicated in first bacteria, wherein the vectors can further be replicated and packaged into first phage in second bacteria (host bacteria) in the presence of the helper phage, wherein the first bacteria are of a strain or species that is different to the strain or species of the host bacteria (See [0155]).
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-7, 12-14 and 16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of US patent 11697802B2.
Although the conflicting claims are not identical, they are not patentably distinct from each other. Both sets of claims are directed to a production bacterial cell for producing phage particles or phage-derived delivery vehicles, said production bacterial cell stably comprising phage structural genes and phage DNA packaging genes of a first type of bacteriophage.
The US patent 11697802B2 anticipates the instant claims as the follows:
The patent claim 1 anticipates the instant base claim 1 and the instant claims 13, 14 and 16.
The patent claims 2-7 anticipates the instant claims 2-7.
The patent claim 8 anticipates the instant claims 12.
Accordingly, claims 1-7, 12-14 and 16 of the instant application are unpatentable on the ground of nonstatutory double patenting over claims 1-8 of US patent 11697802B2.
Conclusion
No claims are allowed.
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/RUIXUE WANG/ Examiner, Art Unit 1672
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