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 .
Maintained rejections
All rejections set forth in the office action mailed on 2/17/26 are maintained. Reply to arguments presented by applicant on 5/14/26 follow the repeated text of the rejection of record.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 1-15 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for methods of treatment of bacterial infection, does not reasonably provide enablement for prevention of bacterial infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
A conclusion of lack of enablement means that, based on the evidence regarding each of the factors below, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
These factors include:
(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.
The breadth of the claims
Claims 1-15 are directed to a method of preventing a bacterial infection in a subject comprising administering an imidazole based antifungal agent. A limited list of said antifungal agents is presented in claim 3.
The state of the prior art
Prior art recognizes treatment of resistant bacteria by administration of an imidazole based agent and an antibacterial agent. Young (US 8,614,179) discloses a method of treating vancomycin resistant and methicillin resistant S. aureus (VRSA and MRSA) in an infected patient. The method comprises administration of miconazole (imidazole-based antifungal agent) in combination with Fosfomycin (antibiotic).
The level of one of ordinary skill
The skilled artisan in this field is that of an MD and/or a PhD skilled in the development and treatment of bacterial infections.
The level of predictability in the art
The examiner acknowledges the probability and predictability that the instantly claimed agents have applicability in treating bacterial infection. There is not seen sufficient data to substantiate the assertion that bacterial infection may be prevented by the compounds of the instant invention. One skilled in this art would not predict from the disclosure provided that bacterial infection can be prevented in view of the data and examples provided.
The amount of direction provided by the inventor.
The instant specification is not seen to provide adequate guidance, which would allow the skilled artisan to extrapolate from the same to establish enablement for the prevention of bacterial infection. There is not seen guidance as to how the skilled artisan would formulate the requisite active agents and use it in methods for the prevention of the claimed diseases.
There is not seen sufficient guidance, which would teach the skilled artisan how to administer, said active agents in methods for preventing bacterial infection. To treat said diseases appears to be the limit of the applicability of the claimed compounds.
The existence of working examples
There are no working examples provided in the specification that demonstrate prophylactic efficacy of the claimed agents.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Indeed, in view of the information set forth supra, the instant disclosure is not seen to be sufficient to enable the prevention of any disease or conditions and the skilled artisan would not extrapolate preventive efficacy from the compounds instantly claimed. Nor is this data alone recognized in the art, as sufficient data to assert compounds with a specific activity would be expected to prevent bacterial infection.
Claim Rejections - 35 USC § 102
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 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, 3-9, 16, 18 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Young et al (US 8,614,179).
Claim 1 - Young discloses a method of treating vancomycin resistant and methicillin resistant S. aureus (VRSA and MRSA) in an infected patient. The method comprises administration of miconazole (imidazole-based antifungal agent) in combination with Fosfomycin (antibiotic). (column 11, lines 36-62).
Claims 3 and 18 – Young discloses miconazole
Claim 4 – The claim is directed to PMF inhibitor (miconazole) being administered in an amount effective to at least partially inhibit PMF in the bacterial cells. Since no minimal amount required to achieve the stated limitation, Examiner will interpret therapeutically effective amount as described by Young to meet the limitation of claim 4.
Claims 5, 6, 9 – Young discloses treatment of vancomycin resistant SA which examiner is interpreting as meeting the limitations of claim 5 and 6 directed to fraction of cells that are resistant within bacterial population. In VRSA all cells are resistant to vancomycin.
Claims 7 and 20 – Young discloses S. aureus.
Claim 8 – Young co-administers miconazole with Fosfomycin (antibiotic).
Claim 16 – The sole active step of contacting antibiotic resistant bacterial cell with imidazole based antifungal agent is disclosed by Young in column 11, lines 36-62.
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.
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(s) 1, 3-16, 18 and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Young et al (US 8,614,179).
Scope of prior art
Young discloses a method of treating vancomycin resistant and methicillin resistant S. aureus (VRSA and MRSA) in an infected patient. The method comprises administration of miconazole (imidazole-based antifungal agent) in combination with Fosfomycin (antibiotic). (column 11, lines 36-62).
In column 7, lines 55-62, Young teaches equivalency between miconazole and econazole as imidazole-based agent. In column 9, lines 35-40, Young teaches equivalency between Fosfomycin and D-cycloserine (glycylcycline) and colistin as antibiotic agents.
Ascertaining the difference
Young recites a method of treating where miconazole and fosfomycin are administered. While econazole, D-cycloserine and colistin are recited as alternatives to the miconazole and fosfomycin, a method of treatment limited to these agents is not recited.
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application would have found it obvious to practice the method of treating an infection of VRSA or MRSA with a combination treatment comprising miconazole and D-cycloserine or colistin, or combination comprising econazole and fosfomycin. D-cycloserine, colistin, and econazole are taught by Young to be equivalents to miconazole and fosfomycin and a skilled artisan would expect them to be interchangeable with retention of antibiotic activity.
Regarding claims 16 and 19, since Young teaches a method of administering econazole, it is inherent that the bacterial cells are re-sensitized to an antibacterial because administration of econazole is the sole active step which is met by Young.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Young et al (US.8,614,179) in view of Pietschmann et al (Vet Res Commun, 2009, 33, 489-505).
Scope of prior art
Young teaches a method of treating vancomycin resistant and methicillin resistant S. aureus (VRSA and MRSA) in an infected patient. The method comprises administration of miconazole (imidazole-based antifungal agent) in combination with Fosfomycin (antibiotic). Young also teaches that the antibiotic can be polymyxin B (col. 9, lines 51-56).
Ascertaining the difference
Young is directed to treatment of infection with gram-positive bacteria, while claims 2 and 17 are directed to gram-negative bacteria.
Secondary reference
Pietschmann teaches that combination of polymyxin B and miconazole is synergistic against both gram-positive and gram-negative strains (page 494, “antibiotic susceptibility”, Table 1).
Obviousness
A person of ordinary skill in the art, prior to the earliest effective filing date of the current application, would have found it obvious to apply the method of treating bacterial infection as described by Young for gram-positive bacteria to a subject infected with gram-negative bacteria. Pietschmann demonstrates that the combination of miconazole and polymyxin B is synergistic against both gram-positive and gram-negative strains. In view of Pietschmann, a skilled artisan would have found it obvious to try treating gram-negative bacteria in a subject by administering to said subject the combination of miconazole and polymyxin B. There is reasonable expectation of success because Pietschmann provides experimental data clearly showing that miconazole alone is not active against E. coli, but in combination with polymyxin B provides a lower MIC than polymyxin B alone.
Reply to applicant’s remarks
Remarks filed on 5/14/26 have been fully considered and found to be not persuasive to overcome the rejections of record.
35 USC § 112
Applicants have traversed this rejection on the grounds that specification defines treatment to include prevention. Applicants are correct. If specification did not define treatment to include prevention the Examiner would not have made this rejection. The rejection argues that applicants have not enabled prevention, not that there is no written description for prevention.
Applicants further rely on the examples to provide evidence of preventing bacterial infection. The examples relied upon add econazole into bacterial cells. This example provides support for treatment of bacteria, but does not provide support that econazole can prevent penetration of bacterial cells into an organism thereby causing infection. Furthermore, from the example it appears that econazole sensitizes bacteria to antibiotics, but does not eradicate bacteria as a sole agent. In this sense even treatment of bacterial infection with econazole alone is not enabled.
There are no examples in the specification where econazole is demonstrated to prevent bacterial infection.
35 USC § 102 and 35 USC § 103
With regards to rejections over art, applicants are arguing that art (Young or Pietschmann) fails to disclose activity of the imidazole-based antifungal agent that is dissipation of bacterial PMF by depolarization of a cytoplasmic membrane of bacterial cells. This argument is not persuasive.
REJECTION UNDER 35 U.S.C. 102/103 CAN BE MADE WHEN THE PRIOR ART PRODUCT SEEMS TO BE IDENTICAL EXCEPT THAT THE PRIOR ART IS SILENT AS TO AN INHERENT CHARACTERISTIC
Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103, expressed as a 102/103 rejection. “There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102.” In re Best,562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic. Therefore, a 35 U.S.C. 102/103rejection is appropriate for these types of claims as well as for composition claims.
Dissipation of bacterial PMF by depolarization of a cytoplasmic membrane of bacterial cells is an activity derived from the structure of the imidazole-based antifungal agent. Since Young discloses the claimed antifungal agent, the activity claimed by the applicant is inherently accomplished when the agent is contacted with bacterial cell.
The fact that applicant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter.1985).
It is a general rule that merely discovering and claiming a new benefit of an old process cannot render the process again patentable. In re Woodruff. 16 USPQ2d 1934, 1936 (Fed. Cir. 1990).
Conclusion
Claims 1-20 are pending
Claims 1-20 are rejected
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to YEVGENY VALENROD whose telephone number is (571)272-9049. The examiner can normally be reached Mon-Fri 9am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628
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