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 . 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.
Priority
The instant application is a continuation of US application no. 14/914,516 filed on 02/25/2015, which is a 371 of PCT/US2014/053425 filed on 08/29/2014 and has a US provisional application no. 61/871,554 filed on 08/29/2013.
Status of the Claims
The claim amendments and remarks filed on 07/23/2025 is acknowledged. Claims 40 and 48-49 are amended. Claims 1-39, 42-43, and 46-47 are cancelled.
Accordingly, claims 40-41, 44-45, and 48-49 are pending and being examined on the merits herein.
Withdrawn Objections/Rejections
35 USC 112(b) rejection for claims 46-47 are withdrawn in view of claims 46-47 being cancelled.
35 USC 112(b) rejection and 35 USC 101 rejection for claims 48-49 are withdrawn in view of claims 48-49 now reciting only product claims.
35 USC 102 rejection over Allison et al. (Nature, 2011 cited in parent app. no. 14/914,516 in IDS filed on 05/25/2017) for claims 40 and 48-49 are withdrawn in view of amended claim 40 reciting the new limitation “wherein the at least one metabolite or compound of the metabolic pathway is fumarate and the therapeutically effective amount of fumarate is at least 11 mM or greater”.
35 USC 103 rejection over Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516) in view of Fraimow et al. (Journal of Bacteriology, 1991 cited in IDS filed on 01/04/2023 as well IDS filed on 02/25/2016 of parent app. no. 14/914,516) and Taber et al. (Microbiological Reviews, 1987 cited in IDS filed on 01/04/2023 as well IDS filed on 02/25/2016 of parent app. no. 14/914,516) for claims 40-47 are withdrawn in view of claims 42-43 and 46-47 being cancelled as well as amended claim 40 reciting the new limitation “wherein the at least one metabolite or compound of the metabolic pathway is fumarate and the therapeutically effective amount of fumarate is at least 11 mM or greater”.
Claim Objections
Claim 48 is objected to because of the following informalities:
Claim 48 recites “… the composition is formulated for the treatment of a chronic or persisting a bacterial infection.” (emphasis added). The recited “persisting a bacterial infection” is suggested to be changed to “a persisting bacterial infection” for proper grammar.
Appropriate correction is required.
New Rejections Necessitated by the Amendments filed on 07/23/2025
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 44-45 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 44 recites “... the at least one metabolite or compound of the metabolic pathway is succinate, citrate, oxaloacetate, ribose, arabinose, gluconate, or propionate.”. Claims 44-45 depend from claim 40, and claim 40 recites “… wherein the at least one metabolite or compound of the metabolic pathway is fumarate …”. Claim 44 recites “... the at least one metabolite or compound of the metabolic pathway is succinate, citrate, oxaloacetate, ribose, arabinose, gluconate, or propionate.”.
Claim 44 does not include the “fumarate” recited in claim 40 for the recited “at least one metabolite or compound of the metabolic pathway”. Therefore, claim 44 fails to include all of the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 40, and 48-49 are rejected under 35 U.S.C. 103 as being unpatentable over Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023) in view of Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892) and Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892).
Allison et al. discloses a method for treating E. coli and S. aureus biofilms and chronic infection in a mouse urinary tract infection model by administering aminoglycosides together with a metabolic stimulus (a proton motive force stimulating compound) as an adjuvant, which generates (stimulates) a proton motive force (PMF) and facilities aminoglycoside uptake (see Abstract and section “Methods Summary”). Allison et al. discloses that this aminoglycoside uptake via a metabolic stimulus does not rely on growth resumption and is effective in both aerobic and anerobic conditions (see Abstract). Allison et al. discloses that 20 mM pyruvate was administered as the metabolic stimulus as well other metabolites such as 10 mM gluconate, 12 mM arabinose, and 12 mM ribose (see section “Methods Summary”), which are metabolites of the TCA cycle and metabolites recited in instant claim 44. Allison et al. demonstrates in Figure 1 that gentamycin in combination with a metabolite significantly reduced survival of bacteria compared to gentamicin alone (see Figure 1 on page 217). Allison et al. discloses that the metabolite-enabled eradication of persisters was general to the aminoglycoside class of antibiotics by further testing kanamycin and streptomycin (see page 216, left col., 4th paragraph). Allison et al. discloses that the addition of a terminal electron acceptor nitrate at 10 mM boosted PMF through anaerobic respiration and further improved aminoglycoside killing by an additional order of magnitude in anaerobic environments (see additional Supplementary Information of Allison et al. in PTO-892, page 8 first paragraph and Supplementary Figure 17 on page 39).
The difference between Allison et al. and the claimed invention is that Allison does not disclose a composition comprising fumarate.
Bryan et al. discloses the mechanism of aminoglycoside antibiotic resistance in anaerobic bacteria (see Abstract). Bryan et al. demonstrates that anaerobic bacterial species, B. fragilis and C. perfringens, did not uptake streptomycin or gentamicin without the addition of hemin, menadione, and fumarate (see Fig. 1 on page 12 and Abstract), whereas B. fragilis exhibited decreased resistance to aminoglycosides and had a time-dependent uptake of dihydrostreptomycin at 500 ug/mL when grown with hemin, menadione, and fumarate (see Fig. 1 on page 12 and Abstract). Bryan et al. demonstrates that anaerobic bacteria are unable to carry out oxygen- or nitrate-dependent electron transport and are therefore resistant to streptomycin and gentamicin because of failure to transport aminoglycosides (see Abstract). Bryan et al. concludes that a satisfactory electron acceptor must be present and exemplifies fumarate as a satisfactory electron acceptor to enable significant anaerobic electron transport (see left column page 13).
Sinclair et al. discloses the effect of nitrate, fumarate, and oxygen on the formation of the membrane-bound electron transport system of Haemophilus parainfluenza (see Abstract). Sinclair et al. discloses that fumarate acts as a terminal electron acceptor for the anaerobic growth of H. parainfluenza (see right column page 368), and demonstrates in Fig. 5A that 20 mM fumarate was a sufficient concentration to function as the terminal electron acceptor (see Fig. 5A on page 369).
It would have been prima facie obvious to combine Allison with Bryan and Sinclair before the effective filing date of the claimed invention by substituting the 10 mM nitrate disclosed in Allison with the fumarate disclosed in Bryan et al. and further modifying the concentration of fumarate to 20 mM as disclosed in Sinclair et al. to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria.
Claims 41 and 44-45 are rejected under 35 U.S.C. 103 as being unpatentable over Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516) in view of Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892) and Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892), as applied to claim 40 above, and further in view of Fraimow et al. (Journal of Bacteriology, 1991 cited in parent app. no. 14/914,516 in IDS filed on 02/25/2016)
Allison in view of Bryan and Sinclair teach the composition of claim 40 as described above.
However, the teachings of Allison, Bryan, and Sinclair do not disclose tobramycin as the aminoglycoside antibiotic.
Fraimow et al. discloses that aminoglycosides such as streptomycin and tobramycin must traverse the bacterial cytoplasmic membrane prior to initiating lethal effects and that transport of aminoglycoside is regulated by proton motive force (see Abstract).
It would have been prima facie obvious to combine Allison, Bryan, and Sinclair with Fraimow before the effective filing date of the claimed invention by substituting the gentamicin disclosed in Allison with the tobramycin disclosed in Fraimow to arrive at the claimed invention. One of ordinary skill in the art would have made this substitution with a reasonable expectation of success because Allison provides guidance that proton motive force facilities aminoglycoside uptake and demonstrates that metabolite-enabled eradication of persisters was general to the aminoglycoside class of antibiotics by further testing kanamycin and streptomycin, and Fraimow also establishes that aminoglycosides such as streptomycin and tobramycin can also be transported by proton motive force.
Response to Arguments
Applicant’s arguments in the response filed on 07/23/2025 have been fully considered in so far
as they apply to the rejections of the instant office action, but were not persuasive.
Applicant states that claim 40 was amended to require fumarate at a concentration of 11 mM or greater, and further states that none of the cited references teach or suggest a composition comprising fumarate at 11 mM or greater.
In response to these arguments, new 35 USC 103 rejection over Allison et al in view of Bryan et al. and Sinclair et al. makes obvious a composition requiring the fumarate at 11 mM or greater because as described above, Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Furthermore, Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria.
Amended Rejections Necessitated by the Amendments filed on 07/23/2025
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 40-41, 44-45 and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11,382,883 (‘883) in view of Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516), Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892) and Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892)
Claim 1 of ‘883 recites a method for treating a chronic or persisting bacterial infection by administering an effective amount of aminoglycoside and fumarate or succinate as an adjuvant to potentiate the aminoglycoside antibiotic. Claim 20 of ‘883 recites the method of claim 1, wherein the aminoglycoside antibiotic is tobramycin and is administered with fumarate. Claim 22 of ‘883 recites a method of inhibiting or delaying biofilm formation by administering an aminoglycoside and fumarate or succinate. Claim 25 of ‘883 recites the composition containing the aminoglycoside and fumarate or succinate is administered by inhalation or intravenously.
The difference between the claims of ‘883 and the claimed invention is that the claims of ‘883 do not recite fumarate having a concentration of 11 mM or greater..
The independent teachings of Allison, Bryan, and Sinclair are as described above.
It would have been prima facie obvious to combine the claims of ‘883 with Allison, Bryan, and Sinclair before the effective filing date of the claimed invention by combining the succinate with fumarate at 20 mM as disclosed in Allison, Bryan, and Sinclair to arrive at the claimed invention. One of ordinary skill in the art would have made this modification with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as the succinate recited in the claims of ‘883. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria.
Claims 40-41, 44-45 and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-48 of U.S. Patent No. 9,480,696 (‘696) in view of Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516), Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892), and Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892).
Claim 1 of ‘696 recites a method for treating a chronic or persisting bacterial infection, the method comprising administering to a subject having or at risk for a chronic or persisting bacterial infection an effective amount of an aminoglycoside antibiotic and an effective amount of at least one proton motive force (PMF) stimulating compound selected from fructose and pyruvate as an adjuvant. Claim 3 of ‘696 recites wherein the aminoglycoside antibiotic is streptomycin, gentamicin, kanamycin A, tobramycin, …, or lividomycin. Claim 13 of ‘696 recites topical, intravenously, intramuscularly, or oral administration of their composition.
The claims of ‘696 differ from that of the instantly claimed invention in that ‘696 does not recite a composition comprising fumarate at 11 mM or greater.
The independent teachings of Allison, Bryan, and Sinclair are as described above.
It would have been prima facie obvious to combine ‘696 with Allison, Bryan, and Sinclair before the effective filing date of the claimed invention by selecting tobramycin recited in claim 3 of ‘696 and further administering either 20 mM fumarate as a terminal electron acceptor as suggested by Allison, Bryan, and Sinclair for the composition of ‘696 to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria.
Claims 40-41, 44-45 and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 10,080,766 (‘766) in view of Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516), Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892), Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892), and Fraimow et al. (Journal of Bacteriology, 1991 cited in parent app. no. 14/914,516 in IDS filed on 02/25/2016)
Claim 1 of ‘766 recites a method for treating a bacterial infection associated with a urinary catheter, comprising: administering to a subject in need thereof, by intravenous administration, an effective amount of an aminoglycoside antibiotic selected from the group consisting of gentamicin and amikacin, and an effective amount of pyruvate as a proton-motive force stimulating metabolite.
The claims of ‘766 differ from that of the instantly claimed invention in that ‘766 does not recite a composition comprising tobramycin and fumarate at 11 mM or greater.
The independent teachings of Allison, Bryan, Sinclair, and Fraimow are as described above.
It would have been prima facie obvious to combine ‘766 with Allison et al., Bryan, Sinclair, and Fraimow before the effective filing date of the claimed invention by modifying the composition of ‘766 with tobramycin as the aminoglycoside as disclosed in Fraimow and further including 20 mM fumarate as a terminal electron acceptor as suggested by Allison, Bryan, and Sinclair to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria. Additionally, Allison provides guidance that proton motive force facilities aminoglycoside uptake and demonstrates that metabolite-enabled eradication of persisters was general to the aminoglycoside class of antibiotics by further testing kanamycin and streptomycin, and Fraimow also establishes that aminoglycosides such as streptomycin and tobramycin can also be transported by proton motive force.
Claims 40-41, 44-45 and 48-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 10,660,911 (‘911) in view of Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516), Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892), and Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892).
Claim 1 of ‘911 recites a method for treating a chronic or persisting bacterial infection, the method comprising administering to a subject having or at risk for a chronic or persisting bacterial infection an effective amount of an aminoglycoside antibiotic selected from the group consisting of: kanamycin and streptomycin and an effective amount of pyruvate as an adjuvant. Claim 5 of ‘911 recites the route of administration of the aminoglycoside antibiotic and pyruvate is selected from the group consisting of: intravenous, intramuscular, and topical. Claim 10 of ‘911 recites the aminoglycoside antibiotic is selected from the group consisting of: streptomycin, … , tobramycin, … , and paromoycin.
The claims of ‘911 differ from that of the instantly claimed invention in that ‘911 does not recite a composition comprising fumarate at 11 mM or greater.
The independent teachings of Allison, Bryan, and Sinclair are as described above.
It would have been prima facie obvious to combine ‘911 with Allison, Bryan, and Sinclair before the effective filing date of the claimed invention by selecting tobramycin recited in claim 10 of ‘911 and further administering 20 mM fumarate as a terminal electron acceptor as suggested by Allison, Bryan, and Sinclair to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria.
Claims 40-41, 44-45 and 48-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 10, 33-39, and 44-45 of copending Application No. 17/425,438 (‘438) in view of Allison et al (Nature, 2011 cited in IDS filed on 01/04/2023 as well IDS filed on 05/25/2017 of parent app. no. 14/914,516), Bryan et al. (Antimicrobial agents and chemotherapy, 1979 in PTO-892), Sinclair et al. (Journal of Bacteriology, 1970 in PTO-892), and Fraimow et al. (Journal of Bacteriology, 1991 cited in parent app. no. 14/914,516 in IDS filed on 02/25/2016)
Claim 1 of ‘438 recites a pharmaceutical composition comprising a first D-amino acid, a carbon source, an antibiotic, and a pharmaceutically acceptable carrier. Claim 4 of ‘438 recites that the antibiotic can be an aminoglycoside antibiotic, and claim 33 recites several carbon sources such as arabinose, pyruvate, gluconate, and fumarate. Claim 10 of ‘438 recites a method for treating a bacterial infection by administering the pharmaceutical composition.
The claims of ‘438 differ from that of the instantly claimed invention in that ‘438 does not recite a composition comprising tobramycin and fumarate at 11 mM or greater.
The independent teachings of Allison, Bryan, Sinclair, and Fraimow are as described above.
It would have been prima facie obvious to combine ‘438 with Allison, Bryan, Sinclair, and Fraimow before the effective filing date of the claimed invention by selecting tobramycin as disclosed in Fraimow et al. for the aminoglycoside antibiotic and further including arabinose or gluconate along with 20 mM fumarate as disclosed by Allison, Bryan, and Sinclair to arrive at the claimed invention. One of ordinary skill in the art would have made these modifications with a reasonable expectation of success because Allison et al. establishes that the addition of a terminal electron acceptor further enhanced aminoglycoside killing enabled by a metabolite stimulus such as pyruvate, arabinose, ribose, or gluconate. Bryan et al. provides guidance that the addition of fumarate as an electron acceptor was necessarily in order for anaerobic bacteria to transport and uptake aminoglycosides, and Sinclair et al. establishes that 20 mM fumarate was sufficient as a terminal electron acceptor in anaerobic bacteria. Additionally, Allison provides guidance that proton motive force facilities aminoglycoside uptake and demonstrates that metabolite-enabled eradication of persisters was general to the aminoglycoside class of antibiotics by further testing kanamycin and streptomycin, and Fraimow also establishes that aminoglycosides such as streptomycin and tobramycin can also be transported by proton motive force.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowable.
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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/D.H.C./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693