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 .
Applicants’ amendment of 4/25/2024 has been acknowledged. Claims 1-15 have been canceled. New claims 16-35 have added.
Claim Status
Claims 16-35 are pending in this application.
Drawings
4. The drawings submitted 10/26/2023 are accepted by the examiner.
Priority
This application, Serial No. was filed 10/26/2023. This application is a 371 of PCT/EP 2022/061000 filed on 4/26/2022, which claims foreign priority of European Patent Application (EPO) 21305543.7 filed on 04/27/2021. The certified copy of the application has been submitted by the applicants, however, the priority document EP21305543 does not mention or exemplify the antibiotic mupirocin. For the subject-matter of claims comprising mupirocin, namely claims 23, 26, 27, 30 and 31, the date of priority is not valid. Additionally, the word concomitant is not disclosed in the first application within the meaning of present claim 15. The word 'concomitant' is effectively mentioned in page 9, line 32. However, for indicating the simultaneous action of administering the combination (in any of the disclosed ways: either simultaneously, separately or sequentially') at the same time when the bacterial infection is treated. The word 'concomitantly' is not disclosed in the context of the administration of the combination (see above). Hence, it cannot replace the ways of administering, namely 'simultaneous, separate or sequential, that are defined in page 6. Should the administration be 'simultaneously', then this word should be used in claim 1 and interpreted in the light of the definition of page 6 in order to comply with the requirements of clarity. In regard to priority, the Office will give priority to the date of the 371 application which is 4/26/2022.
Specification
The disclosure is objected to because of the following informalities:
Specification is missing priority statement in the first page. Appropriate correction is required.
Information Disclosure Statement
7. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejection - 35 U.S.C. § 112 – Scope of Enablement
8. The following is a quotation 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.
9. Claims 16-35 are rejected under 35 U.S.C. § 112(a), because the specification, while enabling for a method for testing different bacteria and antibiotics in vitro on Staphylococcus aureus bacteria that are resistant to an antibiotic, it does not reasonably provide enablement for preventing emergence of Staphylococcus aureus bacteria that are resistant to an antibiotic when treating a colonization and/or an infection caused by a S. aureus bacterium that is susceptible to said antibiotic.
Further, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with the claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands, 8 USPQ2d 1400 (CAFC 1988). The court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation.’” (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary; (2) the amount or direction or guidance presented; (3) the presence or absence of working examples; (4) the nature of the invention; (5) the state of the prior art; (6) the relative skill of those in the art; (7) the predictability or unpredictability of the art; and (8) the breadth of the claims. While all these factors are considered, a sufficient number are discussed below so as to create a prima facie case.
Independent claim 16 is directed to:
A method for preventing emergence of Staphylococcus aureus bacteria that are resistant to an antibiotic when treating a colonization and/or an infection caused by a Staphylococcus aureus bacterium that is susceptible to said antibiotic, said method comprising the concomitant administration of said antibiotic and of at least one non-pathogenic bacterium from the Corynebacterium genus that is resistant to said antibiotic.
With regard to the “prevention” limitation within claim 16, while the person of ordinary skill in the art would have a reasonable expectation of successfully preventing emergence of Staphylococcus aureus bacteria that are resistant to an antibiotic when treating a colonization and/or an infection caused by a Staphylococcus aureus bacterium that is susceptible to said antibiotic, said method comprising the concomitant administration of said antibiotic and of at least one non-pathogenic bacterium from the Corynebacterium genus that is resistant to said antibiotic.
Prevention of emergence of resistant bacteria (e.g., infection via colonization), for the purpose of examination, is taken in the absolute sense. The skilled artisan would view the prevention of such colonization of Staphylococcus aureus as highly unlikely since all cases would not be preventable by the administration of a pharmaceutical composition that comprises at least one Corynebacterium sp., and an antibiotic. Thus, it would be highly unpredictable to prevent emergence of Staphylococcus aureus that resistant to an antibiotic. Rather, it would be more appropriate to limit the claims to a method of screening for a composition comprising a non - pathogenic corynebacterium genus and an antibiotic.
Applicant has provided no direction for the claimed method t for preventing emergence of Staphylococcus aureus bacteria that are resistant to an antibiotic when treating a colonization and/or an infection caused by a Staphylococcus aureus bacterium that is susceptible to said antibiotic, said method comprising the concomitant administration of said antibiotic and of at least one non-pathogenic bacterium from the Corynebacterium genus that is resistant to said antibiotic.
Therefore, the above claims are not enabled by the instant specification.
Claim Rejection - 35 U.S.C. § 103
10. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 non-obviousness.
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.
11. Claims 16, 19-28 and 30-35 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu, George WO 2009/117310 A2 [referred to as Liu I] in view of Liu et al. (U.S. PGPUB 2011/0008303; 2011) [referred to as Liu et al.II], further in view of Kaye et al. (GB vol. 9, no.3, pp. 547-559, 1995).
Liu I disclose (example 3,4, abstract, claims 1-22) the colonizing efficacy of three non- pathogens, including one strain of Corynebacterium. From day 5 to day 7, afte1 antibiotic administration, each of the non-pathogens are inoculated intra-nasal at a dose of 5 x 108 CFU for three days. Liu I further disclose that the non-pathogenic bacteria are applied to the host surface at least 48 hours after terminating application of the antibiotic (claims 9,22) and also that the method of treatment for MRSA is advantageous in that may eliminate or at the least substantially reduce the population of MRSA from the host surface for a prolonged period of time, may not induce resistance (since non-pathogens known to coexist with Staphylococcus aureus) and may be reapplied if necessary. Liu I discloses the use of non- pathogen Corynebacterium in combination with mupirocin and Liu I indicate that the co-administration of probiotics during antibiotic therapy is a valid approach to prevent antibiotic resistance (page 4 of Liu I). Liu I teach limitations claims 23, 26, 27, 28, 30, 31 (mupirocin and Fosfomycin) see page 2, 4, 5 and claims 5,16. Liu I teach limitations claims 19., 20 (103 to 109 CFU) see examples.
Additionally, Liu et al. II teach method for preventing methicillin-resistant Staphylococcus aureus (MRSA) and/or methicillin-sensitive Staphylococcus aureus (MSSA) colonization with a non-pathogenic bacterium (Abstract; paragraphs 16 and 20). Liu et al. II teach that the non-pathogenic bacteria can be that the non-pathogenic bacteria can be Corynebacterium (paragraph 23), may obstruct subsequent colonization by MRSA, thus eliminating or at the least substantially reducing the colonization, transmission and infection of MRSA (paragraph 22). Liu et al. II teach that after pretreating with an antibiotic, the subject is treated with non-pathogenic bacteria such as Corynebacterium by applying the bacteria to the subject (paragraph 20). Liu et al. II also teach limitations 32-35, administering the composition to the nares of the subject (i.e., topically) in need thereof (paragraphs 34). The surface the composition can be applied to can also be the skin of the subject (paragraph 13).
Regarding claims 19-20, Liu et al. II teach that the composition comprises non-pathogenic bacteria at 5×108 cfu per dose (paragraph 36).
Furthermore, Kaye et al. discloses that mupirocin is highly effective against S. aureus, and that mupirocin is inactive against normal skin flora such as Corynebacterium sp. so its use does not compromise much of the skin's natural flora. The problem of mupirocin resistance in chronic dermatologic conditions and for nasal S. aureus carriage has been reported in Kaye et al. (see abstract, pages 548, 549, 551. 552. 553, 554, 555, 556).
It would have obvious for the skilled person in view of the teaching of references to obtain the instant invention. Liu I disclose the use of non-pathogen Corynebacterium in combination with mupirocin, Fosfomycin which indicate that the co-administration of probiotics during antibiotic therapy to prevent antibiotic resistance. The skilled person would therefore use resistant strains with simultaneous administration as taught by Kaye et al. with naturally resistant Corynebacterium strains or non-resistant strains of Corynebacterium, just as taught by iLiu I and II or Kaye et al. should the administration of the non-pathogen and the antibiotic be separated in time. The concomitant administration of the two components simultaneously, sequentially or separated does not seem to provide any effect that requires inventive skills.
A person of ordinary skill in the art would have been motivated to combine the teachings of, where Liu also teaches that the probiotic can be Corynebacterium that can be utilized.
It is submitted that based on the above, the use of antimicrobial non-pathogenic bacterial compositions to treat Staphylococcus aureus resistance. The idea of combining them flows logically from there having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980) (citations omitted; MPEP2144.06).
In view of the above, regardless, it is noted that generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (MPEP § 2144.05(II)(A).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 103
12. Claims 16, 26, 27 and 29 and 30-35 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu, George WO 2009/117310 A2 or Liu I in view of Liu et al. (U.S. PGPUB 2011/0008303; 2011) or Liu et al. II, further in view of Kaye et al. (GB vol. 9, no.3, pp. 547-559, 1995) and Damon et al. (Antimicrobial Agent and Chemotherapy, vol.42, no. 10, pp.2590-2594, 1998).
The teachings of claims 16, 26 and 27 have been mentioned above. Liu I discloses the use of non- pathogen Corynebacterium in combination with mupirocin and Liu I indicate that the co-administration of probiotics during antibiotic therapy is a valid approach to prevent antibiotic resistance (page 4 of Liu I). Liu I teach limitations claims 25, 26, 27, 28, 30, 31 ( mupirocin and Fosfomycin) see page 2, 4, 5 and claims 5,16.
The above references do not teach rifampicin limitations of claims 26, 27 and 29.
As to rifampicin, Damon et al. bacterial resistance to rifampicin and rifampicin resistance mutants ( see abstract and page 2591).
It would have obvious for the skilled person in view of the teaching of references to obtain the instant invention. Liu I disclose the use of non- pathogen Corynebacterium in combination with mupirocin, Fosfomycin and indicate that the co-administration of probiotics during antibiotic therapy is a valid approach to prevent antibiotic resistance (page 4 ). Damon et al. bacterial resistance to rifampicin and rifampicin resistance mutants ( see abstract and page 2591).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 103
13. Claims 16-18 are rejected under 35 U.S.C. § 103 as being unpatentable over Liu, George WO 2009/117310 A2 or Liu I in view of Liu et al. (U.S. PGPUB 2011/0008303; 2011) or Liu et al. II, further in view of Kaye et al. GB vol. 9, no.3, pp. 547-559, 1995 in view of Ouwehand et al. Annals of Medicine vol. 48, no.4, pp. 246-255, 2016 ) art of record search report).
The teachings of claims 16 has been mentioned above. Liu I discloses the use of non- pathogen Corynebacterium in combination with mupirocin and Liu I indicate that the co-administration of probiotics during antibiotic therapy is a valid approach to prevent antibiotic resistance (page 4 of Liu I). Liu I teach limitations claims 25, 26, 27, 28, 30, 31 ( mupirocin and Fosfomycin) see page 2, 4, 5 and claims 5,16.
The above references do not teach rifampicin limitations of claims 17-18.
As to limitations of claim 17-18, Ouwehand et al. teach genetically modified bacteria, non-pathogenic bacteria , nucleotide mutations and non-transferable genes ( see abstract, pages 247, 248 and 251).
It would have obvious for the skilled person in view of the teaching of references to obtain the instant invention. Liu I disclose the use of non- pathogen Corynebacterium in combination with mupirocin, Fosfomycin and indicate that the co-administration of probiotics during antibiotic therapy is a valid approach to prevent antibiotic resistance (page 4 ). Ouwehand et al. teach genetically modified bacteria, non-pathogenic bacteria , nucleotide mutations and non-transferable genes ( see abstract, pages 247, 248 and 251).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
14. No claims are allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHATOL S SHAHNAN SHAH whose telephone number is (571)272-0863. The examiner can normally be reached on Mon-Tue, Thurs-Fri 12pm-8pm.
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/Khatol S Shahnan-Shah/
Examiner, Art Unit 1645
November 15, 2025 /JANA A HINES/Primary Examiner, Art Unit 1645