DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election of the required species in the reply filed on 7/10/26 is acknowledged. Because 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)).
Claims 8-15 are withdrawn from consideration as they require non-elected species.
Claims 1-7 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/21/24 and 6/2/26 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 5 is objected to because of the following informalities: “the group of bacteria of interest consists in bacterial strains of a single species”. To place the claim in better form, it is suggested that it recite, “the group of bacteria of interest consists of bacterial strains of a single species”. Appropriate correction is required.
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 1-7 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.
Claim 1 recites the limitation "by each bacterium" in line 9. There is insufficient antecedent basis for this limitation in the claim.
Claim 1 recites, “A method for preparing a vector which contains no or only few restrictions sites of restriction enzymes…” and “…modifying the sequence of the vector, so as it comprises no more than 100…1 restriction site(s)…”. However, the modifying step of part (iii) indicates that at least 1 site is present in the vector, but the preamble states that the vector contains “no” restriction site. Therefore, it is unclear if a restriction site is permitted to be in the expression vector. Furthermore, it is unclear what the metes and bounds of “only few restriction sites” are since “only few” could be interpreted as 2, 5 or 10 or more. The specification does not elaborate on what the metes and bounds of “only few” are.
Claim 1 recites, “(iii) modifying the sequence of the vector, so as it comprises no more than 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 restriction site(s) recognized by the restriction enzymes encoded by each bacterium of the group of bacteria of interest”. However, the claim does not require a specific vector, which includes a plasmid, phage genome or phagemid. Furthermore, no specific bacterium is recited as the “bacteria of interest”. Therefore, it is unclear which number of restriction sites of the undefined vector are to be recognized and thus be modified by an undefined restriction enzyme by an undefined bacteria of interest or group of bacteria of interest. Without the vector being specifically identified and the bacteria of interest being identified, the number of restriction sites would be unclear.
Claims 2-7 are also rejected because they depend from claim 1, but do not remedy these deficiencies.
Claim Rejections - 35 USC § 102
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(s) 1-6 are rejected under 35 U.S.C. 102a1 as being anticipated by Murray et al. (Nature, Vol. 251, 1974).
The claimed invention is drawn to a method for preparing a vector which contains no or only few restriction sites of restriction enzymes encoded by a group of bacteria of interest, wherein the method comprises: (i) selecting a group of bacteria of interest; (ii) based on the vector sequence, identifying the restriction sites recognized by the restriction enzymes encoded by the group of bacteria of interest; (iii) modifying the sequence of the vector, so as it comprises no more than 100, 90, 80, 70, 60, 50, 40, 30, 20, 10, 9, 8, 7, 6, 5, 4, 3, 2, 1 restriction site(s) recognized by the restriction enzymes encoded by each bacterium of the group of bacteria of interest; and (iv) preparing the modified vector.
In step (ii), the frequency of the restriction enzymes in the group of bacteria of interest is determined, and, in step (iii), the sequence of the vector is modified to remove at least one restriction site of the restriction enzymes frequently encoded by the group of bacteria of interest.
The modified vector of step (iv) is prepared by nucleic acid synthesis or by mutation of the vector.
The vector is a bacteriophage genome or a phagemid and the group of bacteria of interest consists in bacterial strains of a single species.
The vector also comprises a sequence of interest. This limitation is interpreted as including any sequence, including a phage genome.
The specification states that modification of the sequence of the vector and its restriction site can include: “By modification of a restriction site is intended that the modified sequence of the restriction site present at least one nucleotide difference with its non-modified sequence and that the restriction enzyme cannot recognized the restriction site anymore. Modification of a restriction site can be done by deletion of a part or of the totality of the restriction site or by nucleotide substitution of at least one nucleotide of the restriction site.” [see page 25, lines 25-30] In view of the guidance pertaining to modifications to the sequence of the vector, restriction sites can be removed by any means known at the time of applicant’s earliest priority date.
Murray et al. teach “Bacteriophage lambda with its extensively studied genetics and biochemistry could be a particularly useful alternative vehicle for applications of this sort. The DNA of phage lambda however, has five targets for R.EcoRp5, so our first problem was to construct derivatives of lambda, whose chromosomes have only one target for this enzyme.” [see right column of page 1] The bacteria associated with the restriction enzyme is E. coli. [see page 1] Murray et al. summarize variants of their phage Lambda with different numbers of R.EcoRI restriction sites in figure 2 and they teach their process of generating these modified pha ge Lamba on pages 476 and 477. Murray et al. further teach that phage lambda strain b538 lacks a genetic region in an inessential part of the genome, which decreases the restriction site targets by two. [see first paragraph of page 477]
Therefore, Murray et al. anticipate the instant 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, 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.
Claim(s) 7 is rejected under 35 U.S.C. 103 as being unpatentable over Murray et al. as applied to claims 1-6 above, and further in view of Bikard et al. (US PGPub 2018/0200342).
The claimed invention also requires the sequence of interest encoding a Cas protein.
The teachings of Murray et al. are summarized above. While they teach phage lambda can accommodate about 10% more than its normal complement of DNA these deletions permit the insertion of DNA equivalent to about 15 genes. [see left column of page 481], Murray et al. do not teach that the sequence of interest encodes a Cas protein.
Bikard et al. teach the generation of phages (including phage lambda) or phagemids that encode endonuclease proteins, such as Cas nuclease. [see paragraphs 45 and 66]
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Murray et al. in order to additionally encode a Cas protein. One would have been motivated to do so, given the suggestion by Murray et al. that the method be used to generate a recombinant phage lambda that lacks restriction sites and that phage can be further modified to include insertions of sequences of up to 10% of its genome size. There would have been a reasonable expectation of success, given the knowledge that phage lambda can encode endonucleases, including Cas nucleases, as taught by Bikard et al. Thus the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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