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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is
eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e)
has been timely paid, the finality of the previous Office action has been withdrawn pursuant to
37 CFR 1.114. Applicant's submission filed on 02/02/2026 has been entered.
Receipt is acknowledged of an amendment, filed on 02/02/2026, in which claims 123 and 129 were amended and claims 125, 127, 130-133, 135, 137-139 and 143-145 were previously presented.
Claims 123, 125, 127, 129-133, 135 137-139 and 143-145 are currently under examination.
Priority
Acknowledgment is made of applicant's claim for priority based on a provisional application filed as 62/931, 795 on 11/06/2019.
All claims are given the priority date of 11/06/2019.
Specification
The previous objection to the specification has been withdrawn in view of applicant amendment to the specification filed 02/02/2026.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 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.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 123, 125, 127, 129-133 and 135 are rejected under 35 U.S.C. 103 as being unpatentable over Yosef et al (WO 2016/084088 Al) in view of Leon et al (WO 2020/257715 Al, provisionally filed 6/21/2019; Claims priority to provisional application 62/865,085 referenced from herein as 085). This rejection was made in the Office action mailed 10/31/2025.
Regarding claims 123, 125 and 129-132, Yosef teaches a system comprising a nucleic acid sequence comprising a spacer and a CRISPR complex comprising at least one cas gene and at least one CRISPR array (Abstract; Page 18, paragraph 2; Page 20, Paragraphs 2-3). Yosef teaches that phages are used as a genetic tool to increase bacterial susceptibility to antibiotics such as in gram negative bacteria (Page 3; Paragraph 1). Yosef teaches a genetically modified lytic bacteriophage, such as T7 Enterobacteria phage, comprising an engineered CRISPR (i.e., exogenous CRISPR) wherein the CRISPR spacer that targets a nucleic acid sequence comprised within an essential gene of a lytic bacteriophage, such as a phage specific for Pseudomonas aeruginosa (Page 7; Paragraph 3, Page 15, paragraph 1 and Page 18 bridging Page 19). Yosef teaches systems of the invention for use in targeting and eliminating pathogenic genes in bacteria such as Pseudomonas aeruginosa (Page 55, Paragraph 2). Yosef teaches the recombinant DNA construct comprising the polynucleotides that encode the cas-CRISPR system of the invention (Page 68, Paragraph 2). Yosef teaches the CRISPR-cas Type I system which also comprises the cas3 gene (Page 47 last paragraph bridging page 48 first paragraph). Yosef teaches the conjugation and integration of the CRISPR cas system into the genome of the Pseudomonas bacterium by teaching genetically modified bacteriophage (Page 16, Paragraph 2). Yosef teaches a lytic bacteriophage undergoes viral replication leading to lysis of the cell membrane, destruction of the cell, and release of progeny bacteriophage particles capable of infecting other cells (Page 16, Paragraph 1).
Yosef does not teach where the bacteriophage comprises the type I-C Pseudomonas
CRISPR cascade complex and targets an essential gene within the Pseudomonas bacterium.
Leon teaches a recombinant bacteriophage comprising one or more polynucleotides
encoding the crRNA and one more Type I-C CRISPR-Cas3 system (which includes the Type I-C
CRISPR-Cascade complex of Cas5d, Cas8c polypeptide, and Cas7 polypeptide) from
Pseudomonas aeruginosa (WO [0071, 0111]; 085 [0094]). Leon teaches the system can be used
in Pseudomonas bacteria (WO [0105 and 0120-0121]; 085 [0088 and 0103-0104]). Leon teaches
that the system can be used for large scale deletions in genome editing with high efficiency as
well as higher genome editing efficiency (WO [0045-0046]; 085 [0033-0034]). Leon teaches the targeting of the rplQ, an essential gene in the Pseudomonas bacteria, using the I-C CRISPR Cas system (WO [0134]; 085 [0026]). Leon teaches the CRISPR system comprises a crRNA containing a spacer sequence of 32-37 nucleotides in length that is complementary to the genomic site being targeted as well as the spacer sequence being flanked by repeat sequences (WO [0093]; 085 [0076]). Leon teaches the methods and compositions are used to target cells, in vitro or in vivo, for destruction or genomic modification by directing an exogenous I-C CRISPR-Cas3 system to specific genomic or extragenomic targets [0082]. Leon teaches the repeat sequence of the instant application listed as SEQ ID: 24 as SEQ ID: 1 with 100% identity (WO Page 2, lines 30-32 and [0093]; 085 Page 60 and [0076]).
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to substitute the Type I CRISPR complex of Yosef to include the specific Type I-C CRISPR cascade complex in Pseudomonas bacterium taught by Leon because Yosef teaches it is within the ordinary skill in the art to use the Type I CRISPR system in gram negative bacteria and Leon teaches increased genome-editing efficiency when using the specific Type I-C CRISPR system in Pseudomonas bacterium.
One would have been motivated to make such a modification in order to receive the
expected benefit of large-scale deletions resulting in higher efficiency genome editing as taught
by Leon.
Regarding claims 127, 133 and 135, Yosef teaches the CRISPR-cas Type I system which also comprises the cas3 gene (Page 47 last paragraph bridging page 48 first paragraph). Yosef teaches the bacteriophage is a lytic phage (Page 7; Paragraph 3). Yosef teaches that the lytic
bacteriophages means that it is capable of viral replication in order to produce lysis of the cell membrane and destruction of the cell which would then release the progeny bacteriophages to
continue the infection (Page 16, Paragraph 1).
Claims 137-139 and 143-145 are rejected under 35 U.S.C. 103 as being unpatentable over Yosef et al (WO 2016/084088 Al) in view of Leon et al (WO 2020/257715 Al, provisionally filed 6/21/2019; Claims priority to provisional application 62/865,085 referenced from herein as 085), as applied to claims 123, 125, 127, 129-133 and 135, and in further view of Takos et al (EP 4170036 Al). This rejection was made in the Office action mailed 10/31/2025.
The teachings of Yosef and Leon are described above and applied as before.
Regarding claims 137-139 and 143-145, Leon teaches the use of the promoter to drive crRNA, antianti-CRISPR or 1-C CRISPR -Cas3 gene expression in prokaryotic cells (WO [0055]; 085 [0043]). Leon teaches the promoter is operably linked to the Type 1-C CRISPR array and spacer (WO [0077]; 085 [0063]). Leon teaches that the CRISPR system uses a cas3 polypeptide (WO [0129]; 085 [0112]). Leon teaches the Type I-C CRISPR cas system uses three cas genes that effectively make up the crRNA guided Cascade complex (WO [0131]; 085 [0125]).
Leon does not teach the specific sequence of the promoter identified as any one of SEQ ID NOS: 1-11.
Takos teaches a nucleic acid for introduction into a host cell where the vector comprises a
first nucleotide sequence encoding a Type I cas3 and a second nucleotide sequence encoding one or more Cascade proteins where the sequences are under control of one or more promoters for
the expression of the proteins in the cell [0004]. Takos teaches the promoter as SEQ ID: 13 used
as a promoter in a DNA construct vector with 100% identity to SEQID: 4 in the instant application (Page 51; line 12). Takos teaches that the promoter upstream of the Cascade operon
allows crRNA-directed DNA binding without cleavage (Page 6; lines 1-5). Takos teaches that
the use of a medium strength promoter and/or repressed promoter is beneficial for minimizing
Cas toxicity while culturing to the maximum amplification and yielding the DNA/vector (Page
11 bridging Page 12).
It would have been obvious to one of ordinary skill in the art before the effective filing
date of the claimed invention to modify the teachings of Yosef and Leon to include the specific promoter as identified as SEQ ID NO: 13 taught by Takos because Yosef and Leon teach it is within the ordinary skill in the art to use the Type I-C CRISPR cas system in the Pseudomonas bacterium with the use of a promoter to drive expression of CRISPR system components and Takos teaches the use of the promoter in other gram-negative bacteria such as E. coli and Pseudomonas.
One would have been motivated to make such a modification in order to receive the
expected benefit of minimizing the Cas toxicity while maximizing amplification of the vector as
taught by Takos.
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claims 123, 125, 127, 129-133 and 135 under 35 U.S.C. 103 as being unpatentable over Yosef et al (WO 2016/084088 Al) in view of Leon et al (WO 2020/257715 Al, provisionally filed 6/21/2019; Claims priority to provisional application 62/865,085 referenced from herein as 085) have been maintained. Applicant’s arguments in remarks filed on 02/02/2026, have been considered but are not found fully persuasive.
The previous rejection of claims 137-139 and 143-145 under 35 U.S.C. 103 as being unpatentable over Yosef et al (WO 2016/084088 Al) in view of Leon et al (WO 2020/257715 Al, provisionally filed 6/21/2019; Claims priority to provisional application 62/865,085 referenced from herein as 085), as applied to claims 123, 125, 127, 129-133 and 135, and in further view of Takos et al (EP 4170036 Al) have been maintained. Applicant’s arguments in remarks filed on 02/02/2026, have been considered but are not found fully persuasive.
All arguments of the two 103 rejections have been addressed together below as they were addressed in the response.
Applicant’s arguments states that the office has not identified a reference teaching a lytic bacteriophage having a CRISPR array targeting an essential Pseudomonas gene and a Type I-C CRISPR-cascade complex integrated into the genome, as claimed and the combined teachings of the cited references would not lead one of the skills to produce the claimed recombinant lytic bacteriophages. Specifically, Applicant argues that the Yosef alone as well as in combination with Leon does not teach the claimed invention of a lytic bacteriophage having a CRISPR-Cas system. Applicant continues that the combined teachings of Yosef and Leon would not have been prima facia obvious to one of ordinary skill in the art.
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Yosef and Leon in combination teaches the claimed invention of claim 123. Yosef teaches a genetically modified lytic bacteriophage, such as T7 Enterobacteria phage, comprising an engineered CRISPR (i.e., exogenous CRISPR) wherein the CRISPR spacer that targets a nucleic acid sequence comprised within an essential gene of a lytic bacteriophage, such as a phage specific for Pseudomonas aeruginosa (Page 7, Paragraph 3, Page 15, paragraph 1 and Page 18 bridging Page 19). Yosef does not teach where the bacteriophage comprises the type I-C Pseudomonas CRISPR cascade complex and targets an essential gene within the Pseudomonas bacterium. Whereas, Leon teaches a recombinant bacteriophage comprising one or more polynucleotides encoding the crRNA and one more Type I-C CRISPR-Cas3 system (which includes the Type I-C CRISPR-Cascade complex of Cas5d, Cas8c polypeptide, and Cas7 polypeptide) from Pseudomonas aeruginosa (WO [0071, 0111]; 085 [0094]). Leon teaches the targeting of the rplQ, an essential gene in the Pseudomonas bacteria, using the I-C CRISPR Cas system (WO [0134]; 085 [0026]). Therefore, in combination, Yosef and Leon teach the claimed invention.
Applicant continues to argue that the combination of references would change the principle operations of the primary reference. Specifically, Applicant argues that the substitution of the Type I CRISPR complex of Yosef to include the specific Type I-C CRISPR cascade complex in Pseudomonas bacterium taught by Leon would teach away due to their interpretation of Yosef teaching the CRISPR cas system for the means of enrichment rather than killing.
However, this is not persuasive due to Yosef not teaching the Type I CRISPR complex in combination of the lytic bacteria for enrichment but rather for targeting and elimination of bacterial genes leading to the elimination of the bacteria (including Pseudomonas bacteria) (Page 55, Paragraph 2). Leon is only used in combination to specifically identify that the substitution of one Type I CRISPR cascade for another Type I CRISPR cascade that was specific to the Pseudomonas bacteria and therefore, would not change the intended method of the invention only the specific target bacteria.
Therefore, the reasons stated above, the arguments are not persuasive and the rejections of record are maintained.
Conclusion
No claims are allowed.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637