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 .
Priority
Acknowledgement is made of Applicants’ claim for benefit to prior filed US Provisional application 63/163,375 (filed on 03/19/2021).
Claim Status
A preliminary amendment was received on 12/20/2023. Claims 74-93 are pending, all of which have been considered on the merits.
Claim Rejections - 35 USC § 112
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 74-93 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 some embodiments, does not reasonably provide enablement for all embodiments.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
The breadth of claims 74-93 encompass a method of treating a skin condition of a subject by detecting a population of microorganisms in a skin sample and then administering a bacteriophage or fungal virus capable of lysing a detected microorganism. Embodiments that treat a skin condition that is caused by a bacteria or fungus are enabled as being treatable by a bacteriophage or fungal virus, respectively The level of skill in the art is high and would include, e.g., Ph.D. level scientists. Embodiments that treat other skin conditions (e.g. viral or mite caused, autoimmune, etc.) are not enabled as being treatable by the administration of a bacteriophage or fungal virus.
The specification provides examples of treating acne caused by acne causing bacteria (Cutibacterium spp.) but does not provide any working examples or reasonable direction in treating skin conditions not caused by bacteria or fungus (Examples 1-3 and Figure 4).
Clokie, et al. (Bacteriophage. 2011 Jan;1(1):31-45., hereinafter “Clokie”) provides a review of the state of the art in bacteriophages and Bozarth (Environ Health Perspect. 1972 Oct;2:23-39.) provides a review of the state of the in fungal viruses. Bacteriophages can only infect and lyse bacteria (Clokie, Abstract) while fungal viruses can only infect fungi (Bozarth, pg. 23). Bozarth and Clokie demonstrate that the ability to lyse bacteria or infect fungi is not reasonable predictive of the ability of the virus to lyse other microorganisms, such as mites, viruses, etc., or the ability to treat conditions that are not caused by bacteria or fungi, including autoimmune skin conditions such as psoriasis, lupus (cutaneous), scleroderma, dermatomyositis, vitiligo, etc., …. (Clokie Abstract and Bozarth pg. 23).
In view of the breadth of the claims, the limited teachings of the specification and the examples regarding the treatment of skin conditions not caused by bacteria or fungi, the state of the art, and the low predictability with regard to the ability of bacteriophage or fungal viruses to treat skin conditions not caused by bacteria or fungi, it would require undue experimentation to practice the claimed methods. Amendment to the claims to require the skin condition treated to be caused by bacteria or fungi would overcome the rejection.
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.
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.
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 74-79 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard, et al. (Sci Rep 6, 39491 (2016)., hereinafter “Barnard”) and as evidenced by Lomholt, et al. (Anaerobe. 2017 Oct;47:57-63, hereinafter “Lomholt).
Regarding claim 74, 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.
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.
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.
Claim 80 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard as applied to claims 74-79 above, and further in view of Bruggeling, et al. (bioRxiv 2020.08.25.267641., hereinafter “Bruggeling”).
As discussed above, claims 74-79 were rendered prima facie obvious over Barnard.
Regarding claim 80, Barnard does 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 for shotgun metagenomic sequencing in order to treat skin conditions with specific 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 and Bruggeling because they 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.
Claim 81 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Bruggeling as applied to claim 80 above, and further in view of Hardwick, et al. (Nat Commun. 2018 Aug 6;9(1):3096, hereinafter “Hardwick”).
As discussed above, claim 80 was rendered prima facie obvious over Barnard and Bruggeling.
Regarding claim 81, Barnard 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 and Bruggeling for shotgun metagenomic sequencing using isolated DNA samples with human DNA removed in order to treat skin conditions with specific 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, Bruggeling, and Hardwick because they all 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.
Claim 82 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard as applied to claims 74-79 above, and further in view of Davis, et al. (Microbiome. 2018 Dec 17;6(1):226, hereinafter “Davis”).
As discussed above, claims 74-79 were rendered prima facie obvious over Barnard.
Regarding claim 82, Barnard does 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 for shotgun metagenomic sequencing in order to treat skin conditions with specific 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 and Davis because they 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.
Claims 83-87 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard as applied to claims 74-79 above, and further in view of Chouvarine, et al. (PLoS One. 2016 Oct 19;11(10):e0165015., hereinafter “Chouvarine”) as evidenced by Partridge, et al. (Clin Microbiol Rev. 2018 Aug 1;31(4):e00088-17, hereinafter “Partridge”) and Li, et al. (Microbiome. 2021 Feb 17;9(1):47., hereinafter “Li”).
As discussed above, claims 74-79 were rendered prima facie obvious over Barnard.
Regarding claim 83, Barnard does 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 does 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 for shotgun metagenomic sequencing in order to treat skin conditions with specific 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 and Chouvarine because they 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.
Claims 88-90 and 92-93 are rejected under 35 U.S.C. 103 as being unpatentable over Barnard as applied to claims 74-79 above, and further in view of Weinstock, et al. (WO 2019/113,066 A1 FOR-IDS, filed, 01/13/2024, hereinafter “Weinstock”) as evidenced by Lomholt.
As discussed above, claims 74-49 were rendered prima facie obvious over Barnard.
Regarding claim 88, 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).
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.
Regarding claim 92, Weinstock teaches that the bacteriophage composition only comprises bacteriophages against P. acnes, Weinstock further teaches that the bacteriophage do not affect P. granulosum (¶10 and 47). Lomholt evidences that the genus Propionibacterium is the same as the genus Cutibacterium.
Regarding claim 93, Weinstock teaches that the two bacteriophages collectively prevent the development of resistance to P. acnes strains in a culture tube (¶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.
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.
Claim 91 is rejected under 35 U.S.C. 103 as being unpatentable over Barnard and Weinstock as applied to claims 74-79 and 88-89 above, and further in view of Dagnelie, et al. (Acta Derm Venereol. 2018 Feb 7;98(2):262-267., hereinafter “Dagnelie”) as evidenced by Lomholt.
As discussed above, claims 74-49 were rendered prima facie obvious over Barnard and claims 88-89 were rendered 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.
Conclusion
NO CLIAMS ARE ALLOWED
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/CASSANDRA SENN GRIZER/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672