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 without traverse of Group I (claims 1-6, 11-19) and Species 1 (claim 6): Corynebacterium tuberculostrearicum in the reply filed on 07/02/2026 is acknowledged.
The restriction requirement of Species 1 (claim 6) has been reconsidered as there is no longer a burden to examine the invention of species 1. The restriction requirement of Species 1 is hereby withdrawn.
In view of the above noted withdrawal of the restriction requirement of Species 1,
applicant is advised that if any claim presented in a divisional application is anticipated
by, or includes all the limitations of, a claim that is allowable in the present application,
such claim may be subject to provisional statutory and/or nonstatutory double patenting
rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are
no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32
(CCPA 1971). See also MPEP § 804.01.
Claim Status
Claims 1-6, 11-19, and 38-42 are pending and under review. Claims 7-10 and 20-37 are cancelled.
Claim Objection
Claims 1, 5, 6,11-15,18,38, 41, and 42 recite Corynebacteria spp., the genus name of the organism is Corynebacterium. Appropriate correction is required.
Claim 38 recites Corynebacteria spp. comprises C. tuberculostrearicum, “spp.” indicates more than one species and is plural, however the claim further states one organism. 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 3, 5 and 11 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 3 (lines 4-5) recites “…other high velocity projectile” – the statement is a relative term, which renders the claim indefinite. The applicant does not have any number or degree as to what constitutes high velocity, additionally regarding this limitation it is not clear what accounts for a point of reference of comparison that is acceptable to assess said measure of velocity. The term(s) are not defined by the claim; the specification does not provide a standard for ascertaining what constitutes “…other high velocity projectile” and therefore, one of ordinary skill in the art would not reasonably be apprised of the scope of the invention.
Claim 5 (line 2) recites “naturally low levels of…” – the statement is a relative term, which renders the claim indefinite. The applicant does not have any number of what constitutes naturally low levels, additionally regarding this limitation it is not clear what accounts for a point of reference of comparison that is acceptable to assess said levels. The term(s) are not defined by the claim; the specification does not provide a standard for ascertaining what constitutes “naturally low levels of…” and therefore, one of ordinary skill in the art would not reasonably be apprised of the scope of the invention.
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) 1,2, 3, 6, 11-13, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ramsey M.M. et al. Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species. Frontiers in Microbiology. 2016; (7:1230); pp. 1-15 and evidenced by Zygmunt, W.A. Susceptibility of Coagulase-negative Staphylococci to Lysostaphin and Other Antibiotics. Applied Microbiology. 1968. 1168-1173.
Regarding claims 1,2, 3, and 6 Ramsey et al., discloses exposure to an effective amount of Corynebacterium striatum to decrease S. aureus, in a penetrating wound that is a subcutaneous abscess model for diabetic foot infections (DFIs) which resulted in a less successful pathogen (page 10, Figure 5).
Regarding claims 11 and 12, Ramsey et al., exposed subjects to a culture-free conditioned medium (CFCM) that is heat-inactivated (95°C for 15 minutes) from C. striatum cultures (pages 4-5, paragraph 5-cont.), where cells were removed through filtration using an 0.2µm filter and the CFCM was further heat-inactivated rendering any residual cells non-viable and/or replication deficient.
Regarding claim 13, Ramsey et al., discloses cultures prepared with 5 x106 CFU in 10µl of C. striatum (page 3, paragraph 4) and further discloses subcutaneous injection with ~ 106 CFU (page 6, ‘In vivo Murine Abscess Growth’)
Regarding claim 16, Ramsey et al., discloses S. aureus sensitive cells are lysed with lysostaphin (page 3, paragraph 2) to extract genomic material; S. aureus has a long-standing history of selective susceptibility to lysostaphin as a coagulase positive Staphylococcal species, further evidenced by Zygmunt et al., (page 1169, Table 3).
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.
Claim(s) 4,5, 14, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Ramsey M.M. et al., Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species. Frontiers in Microbiology. 2016; (7:1230); pp. 1-15. as applied to claims 1,2, 3, 6, 11-13, and 16 and further in view of Peral, M.C. Bacteriotherapy with Lactobacillus plantarum in burns. International Wound Journal. 2009; (6:1); pp. 73-81 as evidenced by Gao, Z. et al., Quantitation of Major Human Cutaneous Bacterial and Fungal Populations. Journal of Clinical Microbiology. 2010; (48:10); pp. 3575-3581.
The teachings of Ramsey M.M. et al are previously discussed.
Ramsey et al., further teaches administering commensal Corynebacterium species to a wound and describes Corynebacterium species as common flora of the human skin microbiota and teaches the benefit of administering and colonization by Corynebacterium resulting in decreased S. aureus virulence expression (page 2, ‘Introduction’, paragraphs 1 and 4; page 8, paragraph 1).
Ramsey et al., does not teach:
administration directly to an open wound (claim 4),
at anatomic areas that are naturally low levels of Corynebacterium species (claim 5),
where the Corynebacterium species is topically administered (claim 14), or
where the subject is human (claim 19).
However, regarding claims 4, 14, and 19, Peral, et al., teaches biotherapy: administration of microbes directly to an open burn wound (claim 4) that are a topical treatment (claim 14) (page 73, Abstract); and uses a beneficial microbe of L. plantarum as a treatment for human patients (claim 19) to minimize S. aureus infection (page 78, paragraph 1).
Further regarding claim 5, Peral et al., teaches burn wound locations for patients include legs and arms among other physiological locations (page 75, Table 1) which as evidenced by Gao, et al are at a naturally lower level for Corynebacterium species compared with the axilla of the body (page 3578, Figure 2).
It would have been obvious to a person of ordinary skill in art at the effective date of filing to have combined the teachings of Ramsey et al., with Peral, et al. since Ramsey et al. teaches treating wounds with commensal/beneficial Corynebacterium species to minimize S. aureus infection and Peral, et al. teaches the direct addition of commensal/beneficial organisms to open wound(s), as a topical treatment, to human appendages (i.e. arms and/or legs, regions with lower levels of Corynebacterium species) , to minimize S. aureus infection.
The motivation to combine Ramsey et al., with Peral et al., would be to directly apply bacteriotherapy/ antivirulence therapy, using Corynebacterium species as a topical treatment, to an open wound, at an efficacious amount, to minimize S. aureus infection and promote wound healing while also further minimizing the propagation of therapy resistant pathogens.
An ordinary artisan would have expected success since the combined art teaches the same Corynebacterium species added directly to open wounds, as a topical treatment and limits the development of an S. aureus infection in a human patient at sites which harbor low levels of Corynebacterium species.
Claim(s) 17,38- 42, are rejected under 35 U.S.C. 103 as being unpatentable over Ramsey M.M. et al., Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species. Frontiers in Microbiology. 2016; (7:1230); pp. 1-15. and Peral, M.C. Bacteriotherapy with Lactobacillus plantarum in burns. International Wound Journal. 2009; (6:1); pp. 73-81 as evidenced by Gao, Z. et al., Quantitation of Major Human Cutaneous Bacterial and Fungal Populations. Journal of Clinical Microbiology. 2010; (48:10); pp. 3575-3581, and further in view of Jo, H.W. et al., (KR102334454B1; 2021-12-03).
The teachings of Ramsey et al., and Peral et al., are previously disclosed.
Ramsey et al. further teaches that the traits of inhibiting S. aureus virulence and infection are observed by Corynebacterium species (C. amycolatum, C. accolens, C. pseudodiphtheriticum, and C. glutamicum) and therefore prospectively conserved across the genus (page 8, paragraph 1).
Note, Ramsey et al., modified by Peral et al., previously teaches:
Claim 39, the method of administering, while the wound is open (Peral et al., page 73, Abstract).
Claim 41, the method of topical administration (Peral et al., page 73, Abstract).
Note, Ramsey et al., previously teaches:
Claim 40, the method of limiting S. aureus infection of the wound (Ramsey et al., page 10, Figure 5).
Claim 42, the method of administering to the wound about 104 and about 1012 CFU (Ramsey et al., page 3, paragraph 4).
Ramsey et al., modified by Peral et al., do not teach:
administering compounds that benefit Corynebacterium (claim 17) or
a composition comprising C. tuberculostrearicum (claim 38).
However, regarding claim 17 and 38, Jo et al. teaches a composition combined with fructose (page 4, paragraph 0045) of Corynebacterium species, that includes C. tuberculostrearicum (page 1, paragraph 0005) for “skin disease” that are skin wounds (page 3, paragraph 0034).
It would have been obvious to a person of ordinary skill in art at the effective date of filing to combine the teachings of Ramsey et al modified by Peral et al., in view of Jo et al., to administer fructose with C. tuberculostrearicum to benefit growth; to further apply C. tuberculostrearicum to an open wound, topically, to treat an infection caused by S. aureus, while administering the composition at a result effective concentration range.
The motivation to add fructose to the composition described by Ramsey et al., modified by Peral et al., in view of Jo et al., is to introduce a sugar to support C. tuberculostrearicum growth and cultivate the strain for further application. Secondly, the motivation to introduce C. tuberculostrearicum into a topical treatment composition for an open wound, are the conserved infection controlling traits of the genus Corynebacterium as previously taught by Ramsey et al. Thirdly, the prescribed concentration(s) are accordingly able to limit S. aureus in an infected wound at a result optimized concentration.
One would have expected success, as the combined prior art teaches the same organism(s), sugar(s) supplements for supporting Corynebacterium species, along with C. tuberculostrearicum topical application into an open wound, to minimize a S. aureus infection, and at the appropriate concentrations to minimize wound infection through the same genus-level Corynebacterium mechanisms which render S. aureus deficient of functional virulence factor(s).
Claim 18, is rejected under 35 U.S.C. 103 as being unpatentable over Ramsey M.M. et al., Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species. Frontiers in Microbiology. 2016; (7:1230); pp. 1-15. as applied to claims 1,2, 3, 6, 11-13, and 16 and Peral, M.C. Bacteriotherapy with Lactobacillus plantarum in burns. International Wound Journal. 2009; (6:1); pp. 73-81 as evidenced by Gao, Z. et al., Quantitation of Major Human Cutaneous Bacterial and Fungal Populations. Journal of Clinical Microbiology. 2010; (48:10); pp. 3575-3581 and further in view of Hillebrand, G et al., WO2019108715A1 (published 2019-06-06).
The teachings of Ramsey et al., and Peral et al., are previously discussed.
Further, Ramsey teaches cryogenic preservation of CFCM in a 10% glycerol solution (page 4, paragraph 4).
Ramsey et al., modified by Peral et al., does not teach pharmaceutical composition comprising 10-50% glycerol and chitosan (claim 18).
However, Hillebrand et al., teaches a pharmaceutical composition (page 4, paragraph 0025) containing glycerin (i.e. glycerol) and chitosan (page 11, paragraph 0055) in a composition with Corynebacterium species used to treat inflammatory skin conditions along with preventing pathogenic organisms from colonizing the skin surface and causing disease (page 1, paragraph 0004).
Therefore, it would have been obvious to an artisan of ordinary skill in the art at the effective date of filing, to combine the teachings of Ramsey et al., modified by Peral et al., with Hillebrand et al., to include glycerol and/or chitosan to formulate a pharmaceutical composition containing Corynebacterium species. Ramsey et al. teaches 10% glycerol as a cryogenic preservation method and Hillebrand et al., further teaches glycerin (i.e. glycerol) and chitosan in a pharmaceutical composition. The formulation of a concentration of glycerol and chitosan between 10-50% is not specified by Hillebrand et al but is a result effective optimization of said compounds, relative to the composition.
Accordingly, the motivation to combine the teachings of Ramsey et al., modified by Peral et al., with Hillebrand et al., is to formulate a pharmaceutically compatible composition (using an appropriate concentration of glycerol and chitosan) to suspend and/or maintain the composition, for therapeutic delivery to open cutaneous wounds, using Corynebacterium species to limit the development of an S. aureus infection.
A skilled artisan would have reasonably expected success in the combination since the combined art teaches the application of Corynebacterium species, as a pharmaceutical formulation, with said compounds, applied to cutaneous disease conditions, topically, to limit the development of opportunistic pathogen S. aureus, in open cutaneous wounds.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Ramsey M.M. et al. Staphylococcus aureus Shifts toward Commensalism in Response to Corynebacterium Species. Frontiers in Microbiology. 2016; (7:1230); pp. 1-15 as applied to claims 1,2, 3, 6, 11-13, and 16 above, and further in view Chang, C. et al., Genetic manipulations of Corynebacterium diphtheriae and other Corynebacterium species. Curr Protoc Microbiol. 2020; 58(1). pp 1-26.
The teachings of Ramsey is described above. Regarding claim 15, Ramsey et al., teaches Corynebacterium sp. that inactivate virulent factors in S. aureus (page 8, paragraph 1).
Ramsey et al., does not specifically state the Corynebacterium sp. strain is genetically modified.
However, Chang et al teaches a method of genetic modification for Corynebacterium species, through a series of multiple protocols that include gene deletion, mutagenesis and/or complementation of a mutant strain. Chang et al., teaches methods for selection of gene deletion mutants using a protocol that generates in-frame, markerless, gene deletion, in Basic Protocol 1 (pages 2-11; Basic Protocol 1: Gene Deletion in C. diphtheriae’).
It would have been obvious to an artisan of ordinary skill in the art at the effective date of filing to combine Ramsey et al., with Chang et al., to assess the commensal Corynebacterium species strains used to attenuate S. aureus in a DFI model and to inactivate virulence factor(s) in said strain(s), resulting in a genetically modified strain for wound application. The motivation to modify Ramsey et al., with Chang et al., is to produce Corynebacterium strains that are a-virulent yet able to function as agents of antivirulence therapy, able to attenuate S. aureus and therefore treat wound infection. One would have expected success, as the combined methods result in markerless, in-frame gene deletions which can be applied broadly to Corynebacterium species and virulence associated genes, which allow for genetically modified Corynebacterium strain(s) that retain the ability to attenuate S. aureus and inactivate virulence genes, and render virulence genes of Corynebacterium species non-functional in the wound environment.
Conclusion
No claims are currently deemed patentable.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ENUSHA KARUNASENA whose telephone number is (571)272-3972. The examiner can normally be reached Monday-Friday 7:30am-5pm.
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/ENUSHA KARUNASENA/Examiner, Art Unit 1653
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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