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 .
Response to Amendment
The amendment filed 26 June 2026 in which claims 74 and 88 were amended, claims 92-93 were cancelled, and claims 94-95 were added has been entered/
Claims 74-91, and 94-95 are under examination on the merits.
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous rejection, withdrawn as to claims 74-93 due to amendment to claim 74 and cancellation of claims 92-93). Claims 74-93 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. Applicant’s amendment of claim 74 and cancellation of claims 92-93 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
(Previous rejection withdrawn as to claims 74-79 due to amendment of claim 74). Claims 74-79 were rejected under 35 U.S.C. 103 as being unpatentable over Barnard as evidenced by Lomholt. Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claim 80 due to amendment of claim 74). Claim 80 was rejected under 35 U.S.C. 103 as being unpatentable over Barnard and further in view of Bruggeling. Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claim 81 due to amendment of claim 74). Claim 81 was rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Bruggeling and further in view of Hardwick. Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claim 82 due to amendment of claim 74). Claim 82 was rejected under 35 U.S.C. 103 as being unpatentable over Barnard and further in view of Davis Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claims 83-87 due to amendment of claim 74). Claims 83-87 were rejected under 35 U.S.C. 103 as being unpatentable over Barnard and further in view of Choivarine as evidenced by Partridge and Li. Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claims 88-90 and 92-93 due to amendment of claim 74 and cancellation of claims 92-93). Claims 88-90 and 92-93 were rejected under 35 U.S.C. 103 as being unpatentable over Barnard and in further view of Weinstock as evidenced by Lomholt. Applicant’s amendment of claim 74 and cancellation of claims 92-93 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(Previous rejection withdrawn as to claim 91 due to amendment of claim 74). Claim 91 was rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock and further in view of Dagnelie as evidenced by Lomholt. Applicant’s amendment of claim 74 submitted 26 June 2026 have overcome the rejection previously set forth in the Non-Final Office Action mailed 23 February 2026.
(New rejection, necessitated by amendment to claim 74). Claims 74-79 and 88-90 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard and in further view of Weinstock as evidenced by Lomholt.
Regarding claims 74 and 88, Barnard teaches using strain-specific phage-based treatment to target specific acne causing bacterial strains on a subject’s skin (pg. 8 ¶3). Barnard also teaches determining a subject’s skin microbiota by detecting the population of microorganisms in a skin sample using shotgun metagenomic sequencing (pg. 2 ¶1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the separate teachings of Barnard for identifying a subject’s skin microbiome using shotgun metagenomic sequencing and for the strain-specific phage-based treatments targeting acne causing microorganisms to have created a method for treating the skin condition of acne with a specific phage treatment after first identifying the microorganisms needing treatment by shotgun metagenomic sequencing. Barnard provides motivation by teaching the shotgun metagenomic sequencing allows for deeper insight into the skin microbiome, allowing for a more targeted phage therapy (pg. 1 ¶4). One of ordinary skill in the art would have had reasonable expectation of success at combining both teachings of Barnard because both teachings rely on identifying the skin microbiota.
Barnard further teaches using a microorganism specific phage to treat acne (pg. 8 ¶3), but does not teach the type of bacteriophage to be used. However, Weinstock teaches using a composition comprising two bacteriophages to treat conditions related to P. acnes and that both of the bacteriophages are lytic (¶10). Weinstock further teaches that combining bacteriophages delays the time until the appearance of a resistant mutant P. acnes (¶0180-0182). Lomholt evidences that the genus Propionibacterium is the same as the genus Cutibacterium.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Barnard for a method of treating a skin condition with bacteriophages after determining the bacteria in involved with shotgun metagenomic sequencing with the teachings of Weinstock for a bacteriophage composition comprising two lytic bacteriophages. Weinstock provides motivation by teaching that combining bacteriophages delays the time until the appearance of a resistant mutant P. acnes (¶0180-0182). One of ordinary skill in the art would have had reasonable expectation of success at combining Barnard and Weinstock because they both teach using bacteriophage compositions to treat acne.
Regarding claim 75, Barnard teaches that the average number of mappable reads per sample was 7.2 million (pg. 9 ¶4).
Regarding claim 76, Barnard teaches that bacteria, viruses, and fungi can be found in skin samples (Figure 1).
Regarding claims 77-79, Barnard teaches that P. acnes, a bacteria associated with acne, redness, and inflammation, was found in the skin samples (Figure 1). Lomholt evidences that the genus Propionibacterium is the same as the genus Cutibacterium.
Regarding claims 89-90, Weinstock teaches that the two bacteriophages lyse two different P. acnes strains, giving them two different host ranges (¶10). Lomholt evidences that the genus Propionibacterium is the same as the genus Cutibacterium.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
(New rejection, necessitated by amendment to claim 74). Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock as applied to claims 74-79 and 88-90 above, and further in view of Bruggeling.
As discussed above, claims 74-79 and 88-90 were rendered prima facie obvious over Barnard and Weinstock.
Regarding claim 80, Barnard and Weinstock do not teach removing human DNA from DNA isolates. However, Bruggeling teaches reducing and removing host DNA, including human DNA, from DNA isolation samples before metagenomic shotgun sequencing to improve analysis of the bacterial content (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Barnard and Weinstock for shotgun metagenomic sequencing in order to treat skin conditions with two specific lytic phages with the teachings of Bruggeling for removing host DNA from DNA isolates. Bruggeling provides motivation by teaching that removing host DNA improves the analysis of the bacterial content (Abstract). One of ordinary skill in the art would have had reasonable expectation of success at combining Barnard, Weinstock, and Bruggeling because Barnard and Weinstock both teach shotgun metagenomic sequencing.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
(New rejection, necessitated by amendment to claim 74). Claims 81 and 94-95 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard, Weinstock, and Bruggeling as applied to claim 80 above, and further in view of Hardwick.
As discussed above, claim 80 was rendered prima facie obvious over Barnard, Weinstock, and Bruggeling.
Regarding claim 81, Barnard, Weinstock, and Bruggeling do not teach adding internal standards into the isolated DNA. However, Hardwick teaches internal synthetic DNA standards to add to the DNA samples before library preparation to undergo sequencing with the DNA samples (Abstract).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Barnard, Weinstock, and Bruggeling for shotgun metagenomic sequencing using isolated DNA samples with human DNA removed in order to treat skin conditions with two specific lytic phages with the teachings of Hardwick for internal DNA standards. Hardwick provides motivation by teaching that internal DNA standards are used to measure fold change differences in the size and structure of accompanying microbial communities, and perform quantitative normalization between samples (Abstract). One of ordinary skill in the art would have had reasonable expectation of success at combining Barnard, Weinstock, Bruggeling, and Hardwick because Barnard, Bruggeling, and Hardwick teach shotgun metagenomic sequencing.
Regarding claims 94-95, Barnard, Weinstock, and Bruggeling do not teach determining the abundance of isolated NA and absolute quantity of microorganisms using the internal DNA standard. However, Hardwick teaches using the internal DNA standard “sequins” to determine both the relation and absolute abundance of microorganisms in a sample by determining the amount of isolate DNA in the sample. (Figure 4c)
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
(New rejection, necessitated by amendment to claim 74). Claim 82 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock as applied to claims 74-79 and 88-90 above, and further in view of Davis.
As discussed above, claims 74-79 and 88-90 were rendered prima facie obvious over Barnard and Weinstock.
Regarding claim 82, Barnard and Weinstock do not teach identifying one or more background sequence reads isolated from a negative control sample and eliminating said sequence reads from the set of sequence reads. However, Davis teaches identifying sequences found in negative controls and removing those sequences from the set of sequence reads to remove contaminants, this can be done using an R package (Abstract, Background).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Barnard and Weinstock for shotgun metagenomic sequencing in order to treat skin conditions with two specific lytic phages with the teachings of Davis for cleaning of sequence reads by removing contaminants found in negative controls. Davis provides motivation by teaching that removing contaminants improves the quality of shotgun metagenomic sequencing. (Abstract, Conclusion). One of ordinary skill in the art would have had reasonable expectation of success at combining Barnard, Weinstock, and Davis because Barnard and Davis both teach shotgun metagenomic sequencing.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
(New rejection, necessitated by amendment to claim 74). Claims 83-87 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock as applied to claims 74-79 and 88-90 above, and further in view of Chouvarine as evidenced by Partridge and Li.
As discussed above, claims 74-79 and 88-90 were rendered prima facie obvious over Barnard and Weinstock.
Regarding claim 83, Barnard and Weinstock do not teach normalizing counts of the sequence read set to generate a set of normalized sequence reads. However, Chouvarine teaches normalizing sequence reads to remove errors from GC bias, fragmentation bias, etc. (pg. 2¶ 1).
Regarding claim 84, Barnard and Weinstock do not teach clustering the normalized sequence reads. However, Chouvarine teaches clustering sequence reads to filter out hits that are most likely located on genomic islands originating from horizontal transfer rather than innate to the bacteria itself (Pg. 2 ¶1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have combined the teachings of Barnard and Weinstock for shotgun metagenomic sequencing in order to treat skin conditions with two specific lytic phages with the teachings of Chouvarine for normalizing sequence reads. Chouvarine provides motivation by teaching that normalization removes errors caused by sequencing factors such as GC bias, fragmentation vias, and sequence protocol (pg. 2 ¶1). One of ordinary skill in the art would have had reasonable expectation of success at combining Barnard, Weinstock, and Chouvarine because Barnard and Chouvarine both teach shotgun metagenomic sequencing.
Regarding claims 85-87, Barnard teaches comparing sequence reads to the NCBI BLAST database (pg. 10 ¶1). Li evidences that the NCBI BLST database comprises sequences of microorganisms isolated from skin samples (pg. 12, column 1) and Partridge evidences that the NCBI BLAST database comprises sequences of mobile genetic elements (pg. 29, ¶4).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
(new rejection, necessitated by amendment to claim 74). Claim 91 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock as applied to claims 74-79 and 88-90 above, and further in view of Dagnelie as evidenced by Lomholt.
As discussed above, claims 74-79 and 88-90 were rendered prima facie obvious over Barnard and Weinstock.
Regarding claim 91, Barnard and Weinstock teach a bacteriophage composition containing two lytic bacteriophages with different host ranges (¶10) but do not teach that on one of the host ranges is C. namnatense. However, Dagnelie teaches that C. namnatense is known to also cause acne (pg. 266 column 1). Lomholt evidences that the genus Propionibacterium is the same as the genus Cutibacterium.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have substituted a bacteriophage against C. namnatense for one of the bacteriophages against P. acnes in the bacteriophage composition taught by Barnard and Weinstock. Dagnelie teaches that both C. namnatense and P. acnes are known causes of acne (pg. 264, column 1). Barnard further teaches using strain-specific bacteriophages after identification of the bacteria causing a subject’s acne (pg. 8 ¶3). One of ordinary skill in the art would have had a reasonable expectation of success at substituting a bacteriophage for C. namnatense strain taught by Dagnelie for one of the bacteriophages in the composition taught by Barnard and Weinstock as both bacteria are known to both cause acne and are both in the same genus.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evident to the contrary.
Response to Arguments
Applicant contends of pages 6-10 of the Remarks submitted 26 June 2026 that Barnard does not teach, disclose, or even suggest administering to a subject a bacteriophage or fungal virus formulation comprising a first and second bacteriophage or fungal virus to lyse a microorganism of a population of microorganisms to reduce resistance of the microorganism to the formulation, a limitation of claim 74, and all other claims are dependent on claim 74.
In response: Applicant’s arguments with respect to the claims have been fully considered but are moot because the argument is towards a new limitation added to the claim after the mailing of the Non-Final Office action and therefore requires a new ground of rejection which does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument. Claim 74 now includes a limitation of a bacteriophage or fungal virus formulation comprising two bacteriophages or fungal viruses which are lytic and reduce the resistance of the microorganisms to the bacteriophage or fungal viruses. This limitation is taught by Weinstock which teaches bacteriophage compositions with 2 lytic bacteriophages and further teaches that combining bacteriophages into a single formulation delays the time until the appearance of a resistant mutant P. acnes.
Conclusion
NO CLAIMS ARE ALLOWED
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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